ARTICULOS PUBLICADOS

TECNOLÓGICO NACIONAL DE MÉXICO INSTITUTO TECNOLÓGICO DE TIJUANA

Centro de Graduados e Investigación en Química

Maestría en Ciencias en Química

No. de reg. CONACyT: 000261

ARTICULOS PUBLICADOS

LGAC: Síntesis de productos naturales y no naturales biológicamente activos.

La productividad de esta línea de investigación en cuanto a artículos publicados durante el periodo 2012-2017 fue de 55 artículos científicos,

A continuación se da el detalle de los artículos.

1) Rocha Alonso, F.*; Chávez, D.; Ochoa Terán, A.; Morales-Morales, D.; Velázquez-Contreras, E. F.; Parra-Hake, M. A Novel Synthesis of 1,2,3-Benzotriazinones from 2-(o-Aminophenyl)oxazolines. J. Chem. 2017, http://dx.doi.org/10.1155/2017/2384780.

2) Ramírez-Zatarain, S. D.; Ochoa-Terán, A.*; Reynoso-Soto, E. A.; Miranda-Soto, V.; Félix-Navarro, R. M.; Pina-Luis, G.; Yatsimirsky, A. K. “Selective interaction of N,N-bis(aminobenzyl)naphthalenediimides with fluoride anion”, Supramol. Chem., 2017, 29, 446-454.

3) Ramírez M., Ochoa-Terán A., Somanathan R., Gerardo Aguirre. “Synthesis of cis-enamide macrocycles via ring-closing metathesis” Arkivoc 2017, iv, 194-209.

4) Cruz, H.; Aguirre, G.; Madrigal, D.; Chávez, D.; Somanathan, R. Enantioselective nitromethane addition to brominated and fluorinated benzaldehydes (Henry reaction) catalyzed by chiral bisoxazoline-copper(II) complexes. Tetrahedron: Asymmetry 2016, 27, 1217-1221.

5) J. L. Gómez-López, D. Chávez, M. Parra-Hake, A. T. Royappa, A. L. Rheingold, D. B. Grotjahn*, V. Miranda-Soto*. “Synthesis and Reactivity of Bi(protic N-heterocyclic carbene)iridium(III) Complexes”. Organometallics, 2016, 36, 3148-3153.

6) Navarrete Guitérrez A., Aguirre Hernández G., Bernés S. “Crystal structures of p-substitutes derivatives of 2,6-dimethylbromobenzene with 1/2 Z’4”. Acta Crystallogr

E Crystallogr Commun. 2016, E72, 1762-1767.

7) Hernández Linares M. G., Carrasco-Carballo A., Guerrero-Luna G., Bernés S. Aguirre Hernández G. “(25R)-3b,16b-Diacetoxy-23-acetyl-22,26-epoxycholesta-5,22-diene n-hexane 0.8-solvate”. Acta. Cryst. 2016, 1, 160622.





8) Correa-Ayala, E.; Valle-Delgado, A.; Ríos-Moreno, G.; Chávez, D.; Morales-Morales, D.; Hernández-Ortega, S.; García, J. J.; Flores-Álamo, M.; Miranda-Soto*, V.; Parra-Hake*, M. Synthesis, Structures and Catalytic Activity of 1,3-bis(aryl)triazenide (p-cymene)ruthenium(II) Complexes. Inorg. Chim Acta. 2016, 446, 161-168.

9) Somanathan, R.; Chávez, D.; Servín, F. A.; Romero, J. A.; Aguirre, G.* Application of mono- and bis-sulfonamides in asymmetric catalysis. Curr. Top. Cat. 2016, 12, 29-51.

10) Vite-Caritino, H.; Méndez-Lucio, O.; Reyes, H.; Cabrera, A.; Chávez, D.; Medina-Franco, J. L.* Advances in the Development of Pyridinone Derivatives as Non-Nucleoside Reverse Transcriptase Inhibitors. RSC Adv. 2016, 6, 2119-2130.

11) Pech-Puch, D.; Cruz-López, H.; Canche-Ek, C.; Campos-Espinosa, G.; García, E.; Mascaro, M.; Rosas, C.; Chávez-Velasco, D.; Rodríguez-Morales, S.* Chemical Tools of Octopus maya during Crab Predation Are Also Active on Conspecifics. PLoS ONE 2016, 11(2): e0148922. doi:10.1371/journal.pone.0148922.

12) Lopez-Sanchez, J. A.; Cornejo-Bravo, J. M.; Luque, P. A.*; Madrigal-Peralta, D.; Olivas, A. Synthesis and comparative study of n-isopropylacrylamide (NIPAAm) hydrogel and n-isopropylacrylamide-methyl-methacrylate (NIPAAm-MMA) gel. Dig. J.

Nanomater. and Biostruct. 2015, 10, 161–167.

13) Báez-Castro, A.; Baldenebro-López, J.; Glossman-Mitnik, D.; Höpfl, H.; Cruz-Enriquez, A; Miranda-Soto, V.; Parra-Hake, M.; Campos-Gaxiola, J. J.* Novel synthesis, structural analysis, photophisical properties and theoretical study of 2,4,5-tris(2-pyridyl)imidazole. J. Mol. Struct. 2015, 1099, 126-134.

14) Servín, F.A.; Madrigal, D.; Romero, J.A.; Chávez, D.; Aguirre, G.; Anaya de Parrodi, C.; Somanathan, R.* Synthesis of C2-symmetric 1,2-diamine-functionalized organocatalysts: mimicking enzymes in enantioselective Michael addition reactions. Tetrahedron Lett.2015, 56, 2355-2358.

15) Cabrera, A.; Miranda, L. D.; Reyes, H.; Aguirre, G.; Chávez, D.* Crystal structure of ethyl 2,4-dichloroquinoline-3-carboxylate. Acta Cryst. 2015, E71, o939.

16) Romero, J. A.; Aguirre, G.; Bernès, S.* Anomalous halogen bonds in the crystal structures of 1,2,3-tribromo-5-nitrobenzene and 1,3-dibromo-2-iodo-5-nitrobenzene. Acta. Cryst. E Cryst. Commun. 2015, E71, 960-964.

http://www.researchtrends.net/tia/title.asp?id=23&type=3





17) Rojas, H.; Huelgas, G.; Hernández, J. M.; Walsh, P. J.; Somanathan, R.; Anaya de Parrodi, C.* Homochiral L-prolinamido-sulfonamides and their use as organocatalysts in aldol reactions. Tetrahedron: Asymmetry 2015, 26, 163-172.

18) Kovacic, P.*; Somanathan, R.; Abadjian, M.-C. Z. Natural monophenols as therapeutics, antioxidants and toxins; electron transfer, radicals and oxidative stress. Nat. Products J. 2015, 5, 142-151.

19) Kovacic, P.*; Somanathan, R. Irinotecan: Electron transfer mechanism in CNS disorders: electron affinity, ROS, and SAR. Open J. Med. 2015, 3, 1-15.

20) Báez-Castro, A.; Baldenebro-López, J.; Cruz-Enríquez, A.; Höpfl, H.; Glossman-Mitnik, D.; Miranda-Soto, V.; Parra-Hake, M.*; Campos-Gaxiola, J. J.* Synthesis, structure, characterization and photophysical properties of copper(I) complexes containing polypyridyl ligands. RSC Adv. 2014, 4, 42624-42631.

21) Báez-Castro, A.; Peinado-Guevara, H.; Guerrero-Álvarez, J.; Cruz-Enríquez, A.; Parra-Hake, M.; Campos Gaxiola, J. J.* Síntesis, caracterización y propiedades luminiscentes de nuevos complejos de Eu(III) y Tb(III) con el ligando tripiridil imidazolina. Rev. Iberoamericana Cien. 2014, 1, 89-95.

22) Romero, J. A.; Navarrete, A.; Servín, F. A.; Madrigal, D.; Cooksy, A. L.; Aguirre, G.; Chávez, D.; Somanathan*, R. Oxygen–chlorine interactions in the transition state of asymmetric Michael additions of carbonyl compounds to -nitrostyrene. Tetrahedron:

Asymmetry 2014, 25, 997–1001.

23) Sert, Y.*; Doğan, H.; Navarrete, A.; Somanathan, R.; Aguirre, G.; Çırak, Ç. Experimental FT-IR, Laser-Raman and DFT spectroscopic analysis of 2,3,4,5,6-Pentafluoro-trans-cinnamic acid. Spectrochim. Acta, A 2014, 128, 119-126.

24) Aguirre, G.*; Somanathan, R.; Bernès, S. Pelanserin: 3-[3-(4-phenylpiperazin-1-yl)propyl]quinazoline-2,4(1H,3H)-dione. Acta Crystallogr. 2014, E70, 878.

25) Kovacic, P*.; Somanathan, R. Nitroaromatic compounds: Environmental toxicity, carcinogenicity, mutagenicity, therapy and mechanism. J. Appl. Toxicol. 2014, 34, 810-824.

26) Kovacic, P.*; Somanathan, R. Toxicity of imine–iminium dyes and pigments: electron transfer, radicals, oxidative stress and other physiological effects. J. Appl. Toxicol.

2014, 34, 825-834.





27) Kovacic, P.*; Somanathan, R. Melatonin and circadian rhythm: Aging, cancer, and mechanism. Open J. Prev. Med. 2014, 4, 545-560.

28) Kovacic, P.*; Somanathan, R. New developments in the mechanism of drug action and toxicity of conjugated imines and iminiums, including related alkaloids. Open J.

Prev.Med. 2014, 4, 583-597.

29) Kovacic, P.*; Somanathan, R. Unifying effectors of circadian rhythm: Protein N-acetylation, phosphorylation, sulfation and other electrical effects. J. Electrostat.

2014, 72, 198-202.

30) Kovacic, P.*; Somanathan, R. Cardiovascular diseases: Electron transfer, reactive oxygen species, oxidative stress, toxicity, antioxidants and arrhythmia. Open J. Med.

2014, 3, 1-34.

31) Kovacic, P.*; Somanathan, R. Cannabinoids (CBD, CBDHQ and THC): Metabolism, physiological effects, electron transfer, reactive oxygen species and medical use. Nat.

Products J. 2014, 4, 47-53.

32) Kovacic P., Somanathan R. Recent developments in the mechanism of teratogenesis-Electron transfer, reactive oxigen species, and antioxidants. Chapter 26. Systems biology of free radicals and antioxidants. 2014

33) Huelgas, G.; Rojas Cabrera, H.; Madrigal, D.; Somanathan, R.; Guzmán, P.; Ortiz, A.; Anaya de Parrodi, C*. Synthesis of new chiral monosulfonamides prepared from (11R,12R)-11,12-diamino-9,10-dihydro-9,10-ethanoanthracene and their use as ligands for asymmetric catalysis. J. Mex. Chem. Soc. 2013, 57, 54-60.

34) Cortez, N. A.; Aguirre, G.; Parra-Hake, M.; Somanathan, R.* Synthesis of (R)-tembamide and (R)-Aegeline via asymmetric transfer hydrogenation in water. Tetrahedron: Asymmetry 2013, 24, 1297-1302.

35) Quiroa-Montalván, C. M.; Chávez, D.; Reyes-Martínez, R.; Morales-Morales, D.; Parra-Hake, M.* N-{1,2-Bis(pyridin-3-yl)-2-[(E)-(pyridin-3-yl)methylideneamino]-ethyl}-nicotinamide. Acta Crystallogr. 2013, E69, o691-o692.

36) Campos-Gaxiola, J. J.*; Cruz-Enríquez, A; Höpfl, H.; Parra-Hake, M. (1RS,2RS )-4,4_-(1-Azaniumyl-2-hydroxyethane-1,2-diyl)dipyridinium tetrachloridoplatinate(II) Chloride. Acta Crystallogr. 2013, E69, m157-m158.





37) Campos-Gaxiola, J. J.*; A. Báez-Castro, Cruz-Enríquez, A.; Höpfl, H.; Parra-Hake, M. Bis[(1RS,2RS)-4,4-‘-(1-azaniumyl-2-hydroxyethane-1,2-di-yl)dipyri-dinium]-tris-[tetrachloridopalladate(II)]. Acta Crystallogr. 2013, E69, m65–m66.

38) Reyes, H.; Aguirre, G.; Chávez, D.* 4-Hydroxy-6-methylpyridin-2(1H)-one. Acta

Crystallogr. 2013, E69, o1534.

39) Navarrete, A.; Somanathan, R.; Aguirre, G.* 2,3,4,5,6-Pentafluoro-trans-cinnamic acid. Acta. Crystallogr. 2013, E69, 1519.

40) Kovacic, P.*; Somanathan, R. Broad overview of oxidative stress and its complications in human health. Open J. Prev. Med. 2013, 3, 32-41.

41) Kovacic, P.*; Somanathan, R. Sugar toxicity-fundamental molecular mechanisms: -dicarbonyl, electron transfer, and radicals. J. Carbohydr. Chem. 2013, 32, 105-119.

42) Kovacic, P.*; Somanathan, R. Cell signaling receptors, electrical effects and therapy in circadian rhythm. J. Recept. Signal Transduct. 2013, 33, 267-275.

43) Kovacic P., Somanathan R. Nanoparticles: Toxicity, Radicals, electron transfer and antioxidans. Oxidative Stress and Nanotechnology 2013, 1028.

44) Vargas B., Olivas A., Aguirre G. Madrigal D.* (2-tert-butyl-5-hidroxymethyl-1,3-dioxan-5-yl) metanol. Acta Crystallographica Section E, 2012, E68, o2049.

45) Somanathan R.*, Z Flores-López L, Chávez D., Parra-Hake M., Aguirre G. Immobilized organocatalysts and their application in asymmetric aldol reaction. Current Topics in Catalysis, 2012, 10 1-16.

46) Cruz Enríquez A., Figueroa Pérez M.G., Almaral Sánchez J.L., Höpfl H., Parra-Hake M., Campos-Gaxiola J.J.* Supramolecular networks in organic-inorganic hybrid materials from perchlorometalate (II) salts and 2,4,5-tr(4-pyridyl)imidazole. CrystEngComm, 2012, 14, 6146-6151.

47) Campos-Gaxiola J.J.*, Morales-Morales D., Höpfl H., Parra-Hake M., Reyes-Martínez R. Two coordination modes of CuII in a binuclear complex with N-(pyridine-2-yl-carbonyl) pyridine-2-carboxamidate ligands. Acta Crystallographica Section E 2012, E68, m1280.

48) Somanathan R.*, Chávez D., Servín F. A., Romero J. A., Navarrete A., Parra-Hake M., Aguirre G., Anaya de Parrodi C., González J. Bifunctional organocatalysts in the





Asymmetric Michael Additions of Carbonylic Compounds to Nitroalkenes. Current

Organic Chemistry 2012, 16, 2440-2461.

49) Madrigal D.*, Cooksy A.L.,* Somanathan R., Theoretical calculations on rhodium(III)-Cp* catalyzed asymmetric transfer hydrogenation of acetophenone using monosulfonamide ligands derived from (1R,2R)-diaminocyclohexane. Computational

and Theorical Chemistry 2012, 999, 105-108.

50) Cruz-Enriquez A., Baez-Castro A., Höpfl H., Parra-Hake M., Campos-Gaxiola J.J.*, Tetrakis (-acetato-k2O:O’)-bis[(3-pyridinecarboxaldehyde-kN’)]-dicopper(II)(Cu---Cu). Acta Crystallographica Section E 2012, E68, m1339-m1340.

51) Kovacic P.,* Somanathan R. Mechanism of taste; electrochemistry, receptors and signal transduction. Journal of Electrostatics 2012, 70, 7-14.

52) Quiroa-Montalván C.M., Aguirre G., Parra-Hake M.* 1,3,5-Tris(pyridin-3-yl)-2,4-diazapenta-1,4-diene. Acta Crystallographica Section E 2012, E68, o746.

53) Báez-Castro A., Höpfl H., Parra-Hake M., Cruz-Enríquez, A., Campos-Gaxiola J.J.* Dichloridobis(metanol-kO)[cis-(±)-2,4,5-tris(pyridin-2-yl)-2-imidazoline-k3 N2, N3, N4]ytterbium(III) chloride. Acta Crystallographica Section E 2012, E68, m815-m816.

54) Campos-Gaxiola J.J.,* Höpfl H., Aguirre G., Parra-Hake M. 2,4,5-Tris(pyridin-4-yl)-4,5-dihydro-1,3-oxazole”Acta Crystallographica Section E 2012, E68, o1873.

55) Rocha-Alonzo F.,* Morales-Morales D., Hernández-Ortega S., Reyes-Martínez R., Parra-Hake M. “3-[(R)-1-Hydroxybutan-2-yl]-1,2,3-benzo-triazin-4(3H)-one. Acta

Crystallographica Section E 2012, E68, o3240-o3241.

Research ArticleA Novel Synthesis of 1,2,3-Benzotriazinones from2-(o-Aminophenyl)oxazolines

Fernando Rocha-Alonzo,1 Daniel Chávez,2 Adrián Ochoa-Terán,2 David Morales-Morales,3

Enrique F. Velázquez-Contreras,1 and Miguel Parra-Hake2

1Departamento de Ciencias Quımico Biologicas, Universidad de Sonora, Hermosillo, SON, Mexico2Centro de Graduados e Investigacion en Quımica, Instituto Tecnologico de Tijuana, Tijuana, BC, Mexico3Instituto de Quımica, Universidad Nacional Autonoma de Mexico, Ciudad de Mexico, Mexico

Correspondence should be addressed to Fernando Rocha-Alonzo; [email protected]

Received 29 September 2016; Accepted 13 December 2016; Published 19 January 2017

Academic Editor: Hakan Arslan

Copyright © 2017 Fernando Rocha-Alonzo et al.This is an open access article distributed under theCreative CommonsAttributionLicense, which permits unrestricted use, distribution, and reproduction in anymedium, provided the originalwork is properly cited.

1,2,3-Benzotriazinones were synthesized in excellent yields by the reaction of 2-(o-aminophenyl)oxazolines and isoamyl nitrite inmethanol. The crystal structure of the acetyl derivative of one of the 1,2,3-benzotriazinones provided additional support for thespectroscopic structural characterization of the title compounds.

1. Introduction

1,2,3-Benzotriazinones are compounds widely investigateddue to their interesting biological and chemical proper-ties. These heterocyclic compounds have been studied asanaesthetic [1], anti-inflammatory [2], anticancer [3, 4], andantitumoral [5, 6] agents. In organic synthesis, triazinonesare used as an activating moiety in coupling agents for thepreparation of peptides and amino acids [7–9]. As a resultof their biological and synthetic importance, there is stillinterest in the development of methods for the synthesis ofcompounds which contain the 1,2,3-triazinone moiety.

In general, 1,2,3-benzotriazinones are prepared via intra-molecular cyclization through diazonium ion condensationwith an adjacent nucleophilic function. Using this strategy,1,2,3-triazinones have been obtained from aminobenzamides[10–12], aminonitriles [13, 14], and triazenes [15–17]. Otherworkers have reported the synthesis of 1,2,3-benzotriazinonesby the oxidation of indazol-3-amines with hydrogen peroxidein the presence of sodium carbonate, though in low yields,and by the cyclization of 2-azido-N-4-toluoylbenzamide inmoderate yields [18].

In this report, we describe facile access to the title com-pounds from chiral and nonchiral 2-(o-aminophenyl)oxa-zolines. Since racemization is not possible during the reac-tion, this method allows the preparation of enantiopure 1,2,3-benzotriazinones in excellent yields.

2. Results and Discussion

The first step for the synthesis of 1,2,3-benzotriazinones wasthe preparation of 2-(o-aminophenyl)oxazolines 3a–3c (see(1)). These oxazolines were prepared in high yields (58–80%) by cyclization of anthranilonitrile with ethanolaminesunder basic conditions in a mixture of glycerol and ethyleneglycol, following the methodology reported by Gomez andcoworkers [19]. In the literature, it has been reported thatoxazolines 3a and 3b were obtained as oils, whereas in ourwork both were isolated as solids; we believe this fact is dueto problems in the purification process in the previous report.Nevertheless, NMR and IR spectroscopic and mass spec-trometry data are consistent with those previously reported[20].

HindawiJournal of ChemistryVolume 2017, Article ID 2384780, 5 pageshttps://doi.org/10.1155/2017/2384780

https://doi.org/10.1155/2017/2384780

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Supramolecular Chemistry

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Selective interaction of N,N-bis(aminobenzyl)naphthalenediimides withfluoride anion

Sandy D. Ramírez-Zatarain, Adrián Ochoa-Terán, Edgar A. Reynoso-Soto,Valentín Miranda-Soto, R. M. Félix-Navarro, Georgina Pina-Luis & Anatoli K.Yatsimirsky

To cite this article: Sandy D. Ramírez-Zatarain, Adrián Ochoa-Terán, Edgar A. Reynoso-Soto, Valentín Miranda-Soto, R. M. Félix-Navarro, Georgina Pina-Luis & Anatoli K. Yatsimirsky(2017) Selective interaction of N,N-bis(aminobenzyl)naphthalenediimides with fluoride anion,Supramolecular Chemistry, 29:6, 446-454, DOI: 10.1080/10610278.2016.1266360

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DOI: http://dx.doi.org/10.3998/ark.5550190.0018.400 Page 194 ©ARKAT USA, Inc

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for Organic Chemistry Paper

Archive for

Organic Chemistry Arkivoc 2017, part iv, 194-209

Synthesis of cis-enamide macrocycles via ring-closing metathesis

Moisés Ramírez, Adrián Ochoa-Terán, Ratnasamy Somanathan, and Gerardo Aguirre*

Centro de Graduados e Investigación en Química. Instituto Tecnológico de Tijuana. Blvd. Alberto Limón Padilla

S/N, Mesa de Otay, 22510 Tijuana, B.C. México

E-mail: [email protected]

Received 01-12-2017 Accepted 02-25-2017 Published on line 05-21-2017

Abstract

Herein we report the synthesis of 13-, 14- and 15-membered cyclic lactams, using Grubbs’ RCM method in 25,

52 and 46% yields respectively. The cis-enamide functional group was successfully introduced into these cyclic

lactams by syn sulfoxide elimination The synthetic cyclic lactams resemble natural cyclic peptides. Our

synthetic methodology provides a simple route to making medium-sized cyclic lactams that could be used as

models to mimic the β-turn in natural proteins, an important marker in understanding their biological activity.

R1

R2

O

H

OH

R1

R2

O

HN

S

On

nO

R1

R2HN O

R1 = H, Br

R2 = H, Brn= 2-4

Keywords: cyclopeptide alkaloids, ring closing metathesis, sulfoxide elimination

http://dx.doi.org/10.3998/ark.5550190.0018.400

mailto:[email protected]

Enantioselective nitromethane addition to brominated andfluorinated benzaldehydes (Henry reaction) catalyzed by chiralbisoxazoline–copper(II) complexes

Harold Cruz, Gerardo Aguirre ⇑, Domingo Madrigal, Daniel Chávez, Ratnasamy Somanathan ⇑Centro de Graduados e Investigación del Instituto Tecnológico de Tijuana, Apartado Postal 1166, Tijuana, B.C. 22510, Mexico

a r t i c l e i n f o

Article history:Received 4 June 2016Accepted 3 October 2016Available online 27 October 2016

a b s t r a c t

The successful enantioselective Henry reaction of nitromethane to brominated and fluorinated benzalde-hydes was achieved using a chiral bisoxazoline (unbridged)–Cu(II) complex as a catalyst. Nitroalcoholswere obtained in excellent yields (up to 99%) and with enantioselectivities up to >99%. Theoretical calcu-lations support the idea that the unbridged bisoxazoline–Cu(II) complex behaves similarly to the privi-leged bisoxazolines as catalysts in the Henry reaction.

� 2016 Elsevier Ltd. All rights reserved.

1. Introduction

The Henry reaction (nitroaldol) is a versatile carbon–carbonbond forming reaction in organic chemistry (Scheme 1). The result-ing nitroalcohols can be readily converted into synthetically usefulintermediates, such as b-amino alcohols, aldehydes, a-hydroxyketones, azides, carboxylic acids and other synthetically usefulcompounds.1 The reduction of b-nitro alcohols to chiral b-aminoalcohols have found widespread application as ligands in asym-metric catalysis, and as important building blocks in the construc-tion of natural products as well as pharmaceuticals.2 b-Aminoalcohols continue to find application as antiarrhythmics, antihypo-tonics, antiasthmatics, rhinologics, ophthalmics and vasoconstric-tors. There have been many prior reports of enantioselectivesynthesis leading to these b-amino alcohols.3

In recent years, fluorinated b-amino alcohols have attractedmuch attention in the design of new drugs. Fluorine can providemany beneficial properties when incorporated into a molecule,such as the pKa of functional groups proximal to a fluorinesubstituent, increased membrane penetration at physiological

pH, fluorinated arenes are more lipophilic than their non-fluori-nated counterparts, and can be used as an isostere for hydrogenin medicinal chemistry, and also in transition state inhibitors.4

Herein our aimwas to explore an efficient route to enantioenrichedfluorinated nitroalcohols, which can be subsequently reduced touseful b-amino alcohols. Various metal catalysts and organocata-lyst have been used in the asymmetric Henry reactions involvingnitro alkanes, aldehydes and ketones.5 Herein we report the useof Cu(II)–oxazoline (with no methylene bridge) complexes to cat-alyze the enantioselective addition of nitromethane to halogenatedbenzaldehydes.

2. Results and discussion

Commonly used ligand–Cu(II) complexes for the Henry reactioncontain the privileged bisoxazoline chiral ligands 1 (Fig. 1), whichare also known to complex a wide variety of metals and catalyze anumber of reactions with excellent enantioselectivities.6 The

H

OCH3NO2

chiral catalystNO2

HO H

Scheme 1. Enantioselective Henry reaction.N N

O O

R2 R2

R1 R1

R R

1a = R = R1 = H, R2 = CH2Ph1b = R = CH3, R1 = H, R2 = tBut1c = R = H, R1 = R2 = Ph1d = R = R1 = H, R2 = tBu1e = R = CH3, R1 = H, R2 = CH2Ph

1 2

2 R = Ph

N

O

N

O

R R

Figure 1. Oxazoline ligands used in Henry reactions.

http://dx.doi.org/10.1016/j.tetasy.2016.10.0070957-4166/� 2016 Elsevier Ltd. All rights reserved.

⇑ Corresponding authors.

Tetrahedron: Asymmetry 27 (2016) 1217–1221

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Synthesis and Reactivity of Bis(protic N‑heterocycliccarbene)iridium(III) ComplexesJessica L. Gomez-Lopez,† Daniel Chavez,† Miguel Parra-Hake,† Arun T. Royappa,‡ Arnold L. Rheingold,‡

Douglas B. Grotjahn,*,§ and Valentín Miranda-Soto*,†

†Centro de Graduados e Investigacion en Química, Instituto Tecnologico de Tijuana, Tijuana, Baja California 22000, Mexico‡Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California 92093-0385, United States§Department of Chemistry and Biochemistry, San Diego State University. 5500 Campanile Drive San Diego, California 92182, UnitedStates

*S Supporting Information

ABSTRACT: A nonfunctionalized bis(imidazole) ligand precursor hasbeen directly metalated using IrCp*(OAc)2, leading to a mixture ofbis(protic N-heterocyclic carbene) (bisPNHC) complexes (2a,b).Treatment of 2a,b with HCl gas in CH2Cl2 gave a bisPNHC complex(3a), which has been transformed into a hydride bisPNHC complex.Complex 3a underwent ligand and counterion exchange reactions toafford acetonitrile and ethylamine bisPNHC complexes (5 and 6).Furthermore, these bisPNHC complexes have been tested as catalysts intransfer hydrogenation reactions of ketones and unsaturated ketones.

■ INTRODUCTIONN-heterocyclic carbenes (NHCs) are well-known ancillaryligands that provide important properties to a coordinatedmetal center in terms of stability and/or activation, mainly dueto NHC steric and electronic factors.1 During the past decade,an increasing number of protic NHC (PNHC) complexes havebeen reported.2 In contrast to typical NHCs, PNHCs could actas reactive ligands activating and/or recognizing substrates byhydrogen bonding.3 However, PNHC complexes have beenscarcely studied due to their more difficult synthesis, since thereaction of an imidazole with a metal tends to give an N-coordinated tautomer instead of a PNHC complex.4 Relativelyfew methods of syntheses have been reported, and a morelimited number of articles relate to PNHC reactivity andcatalysis.5

In general, the syntheses of PNHCs require more than onestep,5g,6 with the use of acids,7 bases,5h,8 other reagents,9 ordonor-functionalized azoles.5a,b,d−f,10 With donor-functionalizedazoles, where the PNHC is obtained by tautomerization, to thebest of our knowledge, there are only two reports on bisPNHCcomplexes that have been synthesized by this method.5a,10e Afacile way to synthesize PNHC complexes could lead to a betterunderstanding of these compounds, especially their potentialbifunctional behavior. Here we report a one-pot synthesis of afacially oriented bisPNHC complex by direct metalationstarting with a nonfunctionalized bis(imidazole) (1), as wellas its reactivity and catalytic activity in transfer hydrogenation.

■ RESULTS AND DISCUSSIONThe equimolar reaction of 1 with IrCp*(OAc)2 in benzene at70 °C led to CH activation, giving two species according to

NMR spectra (eq 1). The isolated product (51% total yield)was analyzed by 1H NMR spectroscopy in CD2Cl2 and D2O,

giving signals for two species with a ratio of 4:1. This reactionwas also carried out in toluene and THF with similar results.The observed Ir−C signals by 13C{1H} NMR at δ 152.2 and151.5 are consistent with protic carbene formation in bothspecies. The major species is 2a, which shows a weak and broadNH signal at δ 12.46 and an AB system of diastereotopic CH2hydrogens (J = 12.8 Hz). However, the analysis of 2a,b byHRMS (ESI-TOF) showed only 2a with a peak at m/z647.2929 amu.The structure of 2b was proposed to have two acetate

counterions and a coordinated aquo ligand, the presence ofwhich is most likely due to the hygroscopic nature ofIrCp*(OAc)2 instead of the sensitivity of 2a to the presenceof water. Rather surprisingly, a control experiment in which the4:1 mixture of 2a and 2b was treated with water (2.6 equiv,CDCl3, 70 °C, 20 h) did not increase the amount of 2b.The crystallization of the crude product led to a sample

containing two species with a similar ratio according to NMR

Received: June 17, 2016Published: September 13, 2016

Article

pubs.acs.org/Organometallics

© 2016 American Chemical Society 3148 DOI: 10.1021/acs.organomet.6b00501Organometallics 2016, 35, 3148−3153

pubs.acs.org/Organometallics

http://dx.doi.org/10.1021/acs.organomet.6b00501

1762 http://dx.doi.org/10.1107/S2056989016017485 Acta Cryst. (2016). E72, 1762–1767

research communications

Received 20 October 2016

Accepted 1 November 2016

Edited by H. Ishida, Okayama University, Japan

Keywords: crystal structure; bromoarenes; Z0;

hydrogen bond; molecular symmetry.

CCDC references: 1513710; 1513709;

1513708; 1513707

Supporting information: this article has

supporting information at journals.iucr.org/e

Crystal structures of p-substituted derivatives of2,6-dimethylbromobenzene with 1

2 �� Z000 �� 4

Angelica Navarrete Guiterrez,a Gerardo Aguirre Hernandeza* and Sylvain Bernesb

aCentro de Graduados e Investigacion en Quımica, Instituto Tecnologico de Tijuana, Apartado Postal 1166, 222000

Tijuana, B.C., Mexico, and bInstituto de Fısica, Benemerita Universidad Autonoma de Puebla, Av. San Claudio y 18 Sur,

72570 Puebla, Pue., Mexico. *Correspondence e-mail: [email protected]

The crystal structures of four bromoarenes based on 2,6-dimethylbromobenzene

are reported, which are differentiated according the functional group X placed

para to the Br atom: X = CN (4-bromo-3,5-dimethylbenzonitrile, C9H8BrN), (1),

X = NO2 (2-bromo-1,3-dimethyl-5-nitrobenzene, C8H8BrNO2), (2), X = NH2 (4-

bromo-3,5-dimethylaniline, C8H10BrN), (3) and X = OH (4-bromo-3,5-

dimethylphenol, C8H9BrO), (4). The content of the asymmetric unit is different

in each crystal, Z0 = 12 (X = CN), Z0 = 1 (X = NO2), Z0 = 2 (X = NH2), and Z0 = 4 (X

= OH), and is related to the molecular symmetry and the propensity of X to be

involved in hydrogen bonding. In none of the studied compounds does the

crystal structure feature other non-covalent interactions, such as �–�, C—H� � ��or C—Br� � �Br contacts.

1. Chemical context

Our group is interested in the design of chemical model

systems for studying polar–� interactions (Cozzi et al., 2008).

In order to achieve this objective, it is necessary to prepare a

variety of arylboronic esters as suitable substrates for Suzuki–

Miyaura cross-coupling reactions (Ishiyama et al., 1995; Kotha

et al., 2002). We obtained these boronic derivatives starting

from functionalized bromoarenes. The present communica-

tion is about the synthesis and crystallography of a series of

such bromoarenes, namely, para-substituted derivatives of 2,6-

dimethylbromobenzene, for which the p-substituent is X = CN

(1), X = NO2 (2), X = NH2 (3), or X = OH (4).

The crystallized molecules are closely related to one

another from the chemical and structural points of view.

However, very different crystal structures were obtained, with

different compositions for the asymmetric units. Once again,

this evidences that small chemical modifications for a given

compound may induce dramatic changes in its crystal struc-

ture, even in the case of hydrogen/deuterium exchange, which

is the smallest possible modification of a molecule (Vasylyeva

ISSN 2056-9890

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data reports

IUCrData (2016). 1, x160622 http://dx.doi.org/10.1107/S2414314616006222 1 of 3

(25R)-3b,16b-Diacetoxy-23-acetyl-22,26-epoxy-cholesta-5,22-diene n-hexane 0.8-solvate

Marıa-Guadalupe Hernandez Linares,a Alan Carrasco-Carballo,a Gabriel Guerrero-

Luna,a Sylvain Bernesb* and Gerardo Aguirre Hernandezc

aLaboratorio de Investigacion del Jardın Botanico, Instituto de Ciencias, Benemerita Universidad Autonoma de Puebla,

Edif. 113 Complejo de Ciencias CU, San Manuel, 72570 Puebla, Pue., Mexico, bInstituto de Fısica, Benemerita

Universidad Autonoma de Puebla, Av. San Claudio y 18 Sur, 72570 Puebla, Pue., Mexico, and cCentro de Graduados e

Investigacion del Instituto Tecnologico de Tijuana, Apdo. Postal 1166, 22500 Tijuana, B.C., Mexico. *Correspondence

e-mail: [email protected]

In the title solvate, C33H48O6�0.8C6H14, the steroid presents a conformation

almost identical to that of its previously characterized benzene monosolvate

[Sandoval-Ramırez et al. (1999). Tetrahedron Lett. 40, 5143–5146]. The n-hexane

solvent of crystallization is agglomerated in channels parallel to [100] in the

crystal. The solvent molecule is disordered over two sites in the asymmetric unit,

with occupancies of 0.46 and 0.34. A minor disorder for the carbonyl O atom of

the acetyl substituent at position 16 in the steroid was also introduced, with two

sites having occupancies of 0.7 and 0.3.

Structure description

The crystallization process for the title steroid afforded a hexane solvate (Fig. 1), which

crystallizes in an orthorhombic cell close to that previously reported for the benzene

monosolvate (Sandoval-Ramırez et al., 1999; Refcode HOSKAB in the CSD). In both

structures, the steroidal molecule adopts the same conformation. HOSKAB was reported

and deposited with the wrong configuration; however, after inversion, a fit with the

steroid reported here gives an r.m.s. deviation between the two molecules of 0.058 A

(Macrae et al., 2008). The pyran ring C22–C26/O5 in the title structure also adopts the

same twisted conformation found in related steroids bearing this ring (Sandoval-Ramırez

et al., 1999; Castro-Mendez et al., 2002; Perez-Dıaz et al., 2010).

Once the steroid is placed in the asymmetric unit, the refinement converges to R1 =

0.073 (observed data), but ca 24% of the cell volume is unoccupied. Difference maps

show that residual density is present in these voids, which may be modelled as two

Received 31 January 2016

Accepted 13 April 2016

Edited by P. Bombicz, Hungarian Academy of

Sciences, Hungary

Keywords: crystal structure; steroid; diosgenin;

solvate.

CCDC reference: 1473880

Structural data: full structural data are available

from iucrdata.iucr.org

ISSN 2414-3146


Synthesis, structures and catalytic activity of 1,3-bis(aryl)triazenide(p-cymene)ruthenium(II) complexes

Erick Correa-Ayala a, Aida Valle-Delgado a, Gustavo Ríos-Moreno b, Daniel Chávez a,David Morales-Morales c, Simón Hernández-Ortega c, Juventino J. García d, Marco Flores-Álamo d,Valentín Miranda-Soto a,⇑, Miguel Parra-Hake a,⇑aCentro de Graduados e Investigación, Instituto Tecnológico de Tijuana, Apartado Postal 1166, Tijuana, B.C. 22000, MexicobUnidad Académica de Ciencias Químicas, Universidad Autónoma de Zacatecas, Campus Siglo XXI, Carretera a Guadalajara Km. 6, Ejido La Escondida, Zacatecas 98160, Mexicoc Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior Cd, Universitaria Coyoacán, México D.F. 04510, Mexicod Facultad de Química, Universidad Nacional Autónoma de México, Circuito Exterior Cd, Universitaria Coyoacán, México D.F. 04510, Mexico


Article history:Received 13 January 2016Received in revised form 1 March 2016Accepted 3 March 2016Available online 10 March 2016

Keywords:Triazenide ligandsRuthenium complexesTransfer hydrogenationIntramolecular hydrogen bondChemoselective hydrogenationTriazenes

a b s t r a c t

The synthesis, characterization, crystal structures and catalytic activity of four new 1,3-bis(aryl)tri-azenide(p-cymene)ruthenium(II) complexes bearing methoxycarbonyl (5), hydroxymethyl (6), acetyl-phenyl (7) in the ortho position, and methyl in the para position (8) of the bis(aryl)triazenide ligandare reported. These complexes were used as catalysts in the transfer hydrogenation reactions of ketonesand alkenone with good to excellent yields of the corresponding alcohol. Remarkable differences in yieldswere obtained with those complexes with ortho substituents on the aryl group of the triazenide ligand(5–7) compared to that without ortho substituent (8). Good selectivity was also observed in the reductionof the alkenone towards the carbonyl group.

� 2016 Elsevier B.V. All rights reserved.

1. Introduction

For the last decades, coordination and organometallic chemistryhave focused on the design and development of alternative ligandsto stabilize metal complexes and control their reactivity. With thisin mind we have directed our attention to ligands of the type 1,3-bis(aryl)triazenide, since they exhibit a variety of bonding modeswith distinct properties [1,2]. Triazenide ligands can act as mon-odentate binding through a terminal [3,4] or central nitrogen[5,6] as bidentate to form a chelate [7,8], bidentate bridging twometal centers [9,10] or tricoordinate bridges [11] and tetracoordi-nate bridges [12] (Fig. 1).

It can be expected that incorporation of donor groups at theortho position of the 1,3-bis(aryl)triazenide would produce a mark-edly different coordination chemistry. Thus we have turned ourattention to the application of 1,3-bis(aryl)triazenide ligands bear-ing Lewis basic ortho substituents [13–17], expecting that theyinfluence the electronic and steric properties of their complexes,which in turn determine their catalytic activity.

On the other hand, p-cymene complexes of ruthenium with1,3-bis(aryl)triazenide as supporting ligands are attracting cur-rent interest from the point of view of their synthesis and struc-ture, as catalysts in hydrogenation of enones, and anticanceractivity. In this context, Strähle and coworkers reported thesynthesis and structure of the first complex of this type, [RuCl(g2-1,3-ClC6H4NNNC6H4Cl)(g6-p-cymene)] [18]. More recently,Albertin and coworkers, reported neutral complexes [RuCl(g2-1,3-ArNNNAr)(g6-p-cymene)], their structures and catalytic activityon hydrogenation of 2-cyclohexen-1-one and cinnamaldehydeunder H2 pressure [19]. Košmrlj, Osmak and coworkers havereported a series of 1,3-bis(aryl)triazenide(p-cymene)ruthenium(II) complexes with a high in vitro anticancer activity as thefirst study on the biological properties of this class of complexes[20].

Here we report on the synthesis of four complexes offormula [RuCl(g2-1,3-ArNNNAr)(g6-p-cymene)] (Ar = o-COOCH3,o-CH2OH, o-COCH3 and p-tolyl) and their X-ray molecular struc-tures. The catalytic activity of these complexes in the transferhydrogenation of ketones and enones was evaluated with excel-lent results.

http://dx.doi.org/10.1016/j.ica.2016.03.0040020-1693/� 2016 Elsevier B.V. All rights reserved.

⇑ Corresponding authors.

Inorganica Chimica Acta 446 (2016) 161–168


Inorganica Chimica Acta

journal homepage: www.elsevier .com/locate / ica

Advances in the development of pyridinonederivatives as non-nucleoside reverse transcriptaseinhibitors†

Hugo Vite-Caritino,a Oscar Mendez-Lucio,b Hector Reyes,c Alberto Cabrera,c

Daniel Chavezc and Jose L. Medina-Franco*a

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are part of a structurally diverse family with

distinct features attractive for the treatment of AIDS that continues to be a major health problem.

NNRTIs are highly selective to HIV-1 reverse transcriptase and have, in general, high selectivity and lower

toxicity than other anti-AIDS drugs. However, non-optimal pharmaceutical properties and resistance

mutations highlight the need to continue identifying and developing novel NNRTIs. Derivatives of

pyridin-2(1H)-one are promising NNRTs under pre-clinical development. Herein, we survey the evolution

of the pyridin-2(1H)-one class over the past 25 years: from the first generation of compounds with weak

inhibitory activities against mutant strains to advanced generations with improved activity profiles against

clinically relevant mutants. Crystallographic structures, structure-based and ligand-based computational

analysis, and medicinal chemistry efforts have worked in synergy to develop this important chemical

class. We also discuss recent trends and future directions that can further improve the activity of pyridin-

2(1H)-ones against clinically relevant mutant strains.

1. Introduction

Acquired Immune Deciency Syndrome (AIDS) continues to bea major health problem. According to the World and HealthOrganization WHO, in 2014 there were 36.9 million peopleliving with the human immunodeciency virus (HIV). In thesame year, there were 2.0 million new infections and 1.2million people died from AIDS.1 Drugs available today for thetreatment of HIV-1 infections can be classied into thefollowing classes: reverse transcriptase (RT) inhibitors: nucle-oside (nucleotide) (NRTIs) and non-nucleoside (NNRTIs); HIVprotease inhibitors, integrase inhibitors, a fusion inhibitor (toprevent the fusion of the viral envelope with the host-cellmembrane), and a C–C chemokine receptor type ve (CCR5)inhibitor (to block the interaction of the virus with this receptorat the host cell).2 These drugs are administered through theHighly Active Antiretroviral Therapy or HAART in variouscombinations and administration schedules. Current

treatments require the combination of at least two or threeactive drugs from at least two different classes. For instance,Atripla and Complera are combinations of two NRT inhibitorsand one NNRTI. HAART has been helpful to reduce the viralloads in patients, reducing the incidence of opportunisticinfections and death in AIDS patients. However, treatmentseventually fail due to the emergence of resistance. Resistance isprimarily associated with the development of mutations in RT,integrase, and HIV protease.

In this paper we survey the progress on the development ofNNRTIs with a special emphasis on the pyridine-2(1H)-onechemical class. Pyridinone derivatives were one of the stchemical classes to be investigated as anti-HIV compounds.Similar to other NNRTIs, due to the emergence of resistance,several groups around the globe have been working on theoptimization of pyridinone derivatives using a wide range ofexperimental and computational tools. This manuscript isorganized in ve sections. Aer this introduction, a brief over-view of the structure of RT is presented in Section 2. Section 3discusses the current status of NNRTIs including the majorstrategies that are being pursued to overcome resistance. It isalso presented an overview of the chemical classes that arebeing developed. Section 4 describes the development andcurrent status of pyridine-2(1H)-one derivatives as NNRTIs.Contributions of computational methods to develop pyridin-2(1H)-one derivatives and current trends to further develop thischemical class are also discussed. Finally, concluding remarksare presented in Section 5.

aFacultad de Quımica, Departamento de Farmacia, Universidad Nacional Autonoma

de Mexico, Avenida Universidad 3000, Mexico City 04510, Mexico. E-mail:

[email protected]; [email protected]; Tel: +52-55-5622-3899 ext.

44458bUnilever Centre for Molecular Science Informatics, Department of Chemistry,

University of Cambridge, Lenseld Road, Cambridge CB2 1EW, UKcCentro de Graduados e Investigacion en Quımica del Instituto Tecnologico de Tijuana,

Apdo. Postal 1166, 22500, Tijuana, B.C., Mexico

† Electronic supplementary information (ESI) available. See DOI:10.1039/c5ra25722k

Cite this: RSC Adv., 2016, 6, 2119

Received 3rd December 2015Accepted 16th December 2015

DOI: 10.1039/c5ra25722k

www.rsc.org/advances

This journal is © The Royal Society of Chemistry 2016 RSC Adv., 2016, 6, 2119–2130 | 2119

RSC Advances

REVIEW

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RESEARCH ARTICLE

Chemical Tools of Octopus maya during CrabPredation Are Also Active on ConspecificsDawrin Pech-Puch1, Honorio Cruz-López1, Cindy Canche-Ek1, Gabriela Campos-Espinosa1, Elpidio García2, Maite Mascaro3, Carlos Rosas3, Daniel Chávez-Velasco4,Sergio Rodríguez-Morales1*

1 Unidad de Química-Sisal, Facultad de Química, Universidad Nacional Autónoma de México, Sisal,Yucatán, México, 2 Departamento de Bioquímica, Facultad de Química, Universidad Nacional Autónoma deMéxico, México, D.F., México, 3 Unidad Multidisciplinaria Docencia e Investigación, Facultad de Ciencias,Universidad Nacional Autónoma de México, Sisal, Yucatán, México, 4 Centro de Graduados e InvestigaciónQuímica, Instituto Tecnológico de Tijuana, Tijuana, Baja California Norte, México

* [email protected]

AbstractOctopus maya is a major socio-economic resource from the Yucatán Peninsula in Mexico.

In this study we report for the first time the chemical composition of the saliva ofO.mayaand its effect on natural prey, i.e. the blue crab (Callinectes sapidus), the crown conch snail

(Melongena corona bispinosa), as well as conspecifics. Salivary posterior glands were col-

lected from octopus caught by local fishers and extracted with water; this extract paralyzed

and predigested crabs when it was injected into the third pereiopod. The water extract was

fractionated by membrane ultrafiltration with a molecular weight cut-off of 3kDa leading to a

metabolic phase (>3kDa) and a neurotoxic fraction (<3kDa). The neurotoxic fraction

injected in the crabs caused paralysis and postural changes. Crabs recovered to their initial

condition within two hours, which suggests that the effects of the neurotoxic fraction were

reversible. The neurotoxic fraction was also active onO.maya conspecifics, partly paralyz-ing and sedating them; this suggests that octopus saliva might be used among conspecifics

for defense and for reduction of competition. Bioguided separation of the neurotoxic fraction

by chromatography led to a paralysis fraction and a relaxing fraction. The paralyzing activity

of the saliva was exerted by amino acids, while the relaxing activity was due to the presence

of serotonin. Prey-handling studies revealed thatO.maya punctures the eye or arthrodial

membrane when predating blue crabs and uses the radula to bore through crown conch

shells; these differing strategies may helpO.maya to reduce the time needed to handle its

prey.

IntroductionThe Mexican red octopus, Octopus maya, is a large endemic species of the Yucatan Peninsulawhere it is of social and economic importance [1]. It occurs mainly in shallow waters near theshore between 2 and 25 m depth along the continental shelf of the Yucatan Peninsula. Octopus

PLOSONE | DOI:10.1371/journal.pone.0148922 February 19, 2016 1 / 22

OPEN ACCESS

Citation: Pech-Puch D, Cruz-López H, Canche-Ek C,Campos-Espinosa G, García E, Mascaro M, et al.(2016) Chemical Tools of Octopus maya during CrabPredation Are Also Active on Conspecifics. PLoSONE 11(2): e0148922. doi:10.1371/journal.pone.0148922

Editor: Erik V. Thuesen, The Evergreen StateCollege, UNITED STATES

Received: October 5, 2015

Accepted: January 23, 2016

Published: February 19, 2016

Copyright: © 2016 Pech-Puch et al. This is an openaccess article distributed under the terms of theCreative Commons Attribution License, which permitsunrestricted use, distribution, and reproduction in anymedium, provided the original author and source arecredited.

Data Availability Statement: All relevant data arewithin the paper and its Supporting Information files.

Funding: This work was supported by grants fromthe Dirección General de Asuntos del PersonalAcadémico (DGAPA)-UNAM (PAPIIT TA200314),from Consejo Nacional de Ciencia y Tecnología(CONACyT) and the Yucatán government (FOMIX-YUCATAN 107350).

Competing Interests: The authors have declaredthat no competing interest exist.

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Novel synthesis, structural analysis, photophysical properties andtheoretical study of 2,4,5-tris(2-pyridyl)imidazole

Alberto B�aez-Castro a, Jesús Baldenebro-L�opez a, Daniel Glossman-Mitnik b,Herbert H€opfl c, Adriana Cruz-Enríquez a, Valentín Miranda-Soto d, Miguel Parra-Hake d,Jos�e J. Campos-Gaxiola a, *

a Facultad de Ingeniería Mochis, Universidad Aut�onoma de Sinaloa, Fuente de Poseid�on y Prol. A. Flores S/N C.U. Los Mochis, Sinaloa, 81223, Mexicob Centro de Investigaci�on en Materiales Avanzados, S.C., Miguel de Cervantes 120, Complejo Industrial Chihuahua, Chihuahua, 31136, Mexicoc Centro de Investigaciones Químicas, Instituto de Ciencias B�asicas e Ingeniería, Universidad Aut�onoma de Morelos, Av. Universidad 1001, Cuernavaca,62209, Mexicod Centro de Graduados e Investigaci�on, Instituto Tecnol�ogico de Tijuana, Apartado Postal 1166, Tijuana, B.C., 22000, Mexico


Article history:Received 24 December 2014Received in revised form22 May 2015Accepted 22 May 2015Available online 17 June 2015

Keywords:Imidazole derivativePolypyridyl compoundNon-covalent interactionsX-ray structurePhotophysical propertiesTheoretical calculations

a b s t r a c t

2,4,5-Tris(2-pyridyl)imidazole has been successfully synthetized by a novel synthetic route and fullycharacterized by FT-IR,UVeVis and fluorescence spectroscopy, one- and two-dimensional NMR spec-troscopy (1H, 13C{1H} ATP, 1He1H COSY, NOESY 1He13C HSQC and HMBC) high-resolution, mass spec-trometry (HR-FABþ), and single-crystal X-ray diffraction analysis. Additionally, the molecular geometry,vibrational frequencies and infrared intensities were calculated by density functional theory using theM06/6-31G(d) level of theory, showing good agreement with the experimental results. The title com-pound showed interesting photophysical properties, which were studied experimentally in solution andin the solid state by UVeVis and fluorescence spectroscopy, and theoretically using TD-DFT calculations.Natural and Mulliken atomic charges and the molecular electrostatic potential (MEP) have been mapped.

© 2015 Elsevier B.V. All rights reserved.

1. Introduction

In the field of heterocyclic chemistry, imidazole comprises afive-membered N-containing aromatic ring structure with a varietyof interesting properties. Imidazole-related drugs have excellenttherapeutic properties, which has encouraged medicinal chemiststo synthesize a large number of novel active pharmaceutical in-gredients (APIs) [1]. In this context addition and substitution re-actions of imidazole and its derivatives continue receivingconsiderable attention not only for the preparation of biologicallyactive compounds [2], but also for the design of new materials [3].Imidazoles are also useful ligands in coordination chemistry andconstitute still today an important area of scientific investigation[4,5]. Pyridine-substituted imidazole-based ligands are of specialinterest for research in the field of crystal engineering, particularlyin form of polypyridine-type tectons (building blocks), which can

be easily protonated in an acidic medium to produce, frequently incombination with metal complexes, supramolecular networksthrough non-covalent interactions [6].

Existing methodologies for the synthesis of imidazoles arelimited in terms of the starting materials, conversion and productselectivity [7e10]. There are some reports on synthetic proceduresbased on aromatic nitriles as starting materials. Among them,Vijendra and co-workers reported the synthesis of 2,4,5-tris(2-pyridyl)imidazole, which was prepared from a 1:2 mixture of 2-picolyamine and 2-cyanopyridine [11]. To overcome low conver-sions employing traditional synthetic methods and tominimize theamount of reaction byproducts and undesired impurities, the use ofcatalysts is a potentially useful strategy, which even promotes theformation of more complex imidazole derivatives by incorporationof additional functionalities [12]. Siamaki and Arndsten havedescribed a palladium-catalyzed (5% mol) process for the synthesisof tetra-substituted imidazoles, involving two imines and an acidchloride under CO atmosphere. However, the corresponding im-idazoles were obtained only in low to moderate yields [13]. Other* Corresponding author.

E-mail address: [email protected] (J.J. Campos-Gaxiola).


Journal of Molecular Structure

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Journal of Molecular Structure 1099 (2015) 126e134

Synthesis, structure, characterization andphotophysical properties of copper(I) complexescontaining polypyridyl ligands†

Alberto Baez-Castro,a Jesus Baldenebro-Lopez,a Adriana Cruz-Enrıquez,a

Herbert Hopfl,b Daniel Glossman-Mitnik,c Miranda-Soto Valentın,d Miguel Parra-Hake*d and Jose J. Campos-Gaxiola*a

Two novel photoluminescent copper(I) complexes having the compositions [CuI(L1)(PPh3)2]NO3$3CHCl3(1)

and [CuI(L2)(PPh3)2]NO3$H2O(2) with PPh3 ¼ triphenylphosphine, L1 ¼ cis-(�)-2-(2,5-di(pyridin-2-yl)-4,5-

dihydro-1H-imidazol-4-yl)pyridine and L2¼ 2,4,6-tris(2-pyridyl)triazine have been successfully synthesized

and characterized by IR and 1H-NMR spectroscopy, FAB+ mass spectrometry and single-crystal X-ray

diffraction analysis. Both complexes showed interesting photophysical properties, which were studied

experimentally in solution and in the solid state by UV-Vis and fluorescence spectroscopy and

theoretically using TD-DFT calculations.

Introduction

In the past decades, inorganic photochemistry has focused onmolecular systems that possess low-lyingmetal-to-ligand chargetransfer excited states capable of electron and energy transfer.In this context, ruthenium(II), osmium(II), and rhenium(II)complexes have received special attention because of theirfascinating properties and potential applications for chemicalsensing, display devices, probes of biological processes, pho-totherapy, and solar energy conversion schemes.1,2

At the same time, the strong appealing possibility of usingcostless and nontoxic metals such as copper or zinc, as substi-tutes of the above-mentioned more expensive heavy metal ions,has stimulated further research in this eld.3 Copper(I) formspseudotetrahedral complexes with polypyridine ligands. A fewcoordination polymers of Cu(I) and mixed-valence Cu(I)–Cu(II)

complexes of 2,4,6-tris(2-pyridyl)triazine (L2) with a four coor-dinated metal center have been reported.4 There is a number ofcomplexes which are susceptible of uorescent light emission.Cu(I) complexes prepared from phosphines and polypyridineligands were rst studied more than three decades ago, whichresulted potentially useful as sensors due to their long lifetimesupon light excitation.

We are interested in exploring the coordination chemistry ofCu(I) complexes with phosphines and polypyridine ligandsbecause of their promising photoluminescence properties andintriguing coordination architectures.3,5

In previous studies regarding the coordination behaviour ofpolypyridyl ligands, we analysed the inuence of non-covalentinteractions on the supramolecular structure of metalcomplexes.6 In this contribution, we report on two new Cu(I)complexes with triphenylphosphine and cis-(�)-2,4,5-tris(2-pyridyl)imidazoline (L1) and 2,4,6-tris(2-pyridyl)triazine (L2)ligands for which we explored their photophysical properties,both experimentally and theoretically.

aFacultad de IngenierıaMochis, Universidad Autonoma de Sinaloa, Fuente de Poseidon

y Prol. A. Flores S/N, C.P. 81223, C.U. Los Mochis, Sinaloa, Mexico. E-mail:

[email protected]; Fax: +52 668 8127641; Tel: +52 668 8127641bCentro de Investigaciones Quımicas, Universidad Autonoma del Estado de Morelos,

Av. Universidad 1001, C.P. 62209, Cuernavaca, Morelos, Mexico. E-mail: hhop@

uaem.mx; Fax: +52 777 3297997; Tel: +52 777 3297997cCentro de Investigacion en Materiales Avanzados, S.C., Miguel de Cervantes 120,

Complejo Industrial Chihuahua, Chihuahua 31190, MexicodCentro de Graduados e Investigacion, Instituto Tecnologico de Tijuana, Apartado

Postal 1166, C.P. 22000, Tijuana, Baja California, Mexico. E-mail: miguelhake@

yahoo.com; Fax: +52 664 623 40 43; Tel: +52 664 623 37 72

† Electronic supplementary information (ESI) available: Experimental andtheoretical IR spectral data of complexes 1 and 2, Table of hydrogen bondinggeometries of compounds 1 and 2, TD-DFT assessment data, 1H-NMR and 31P{1H} NMR spectra and thermograms of compounds 1 and 2. CCDC969083–969084. For ESI and crystallographic data in CIF or other electronicformat see DOI: 10.1039/c4ra06512c

Cite this: RSC Adv., 2014, 4, 42624

Received 1st July 2014Accepted 27th August 2014

DOI: 10.1039/c4ra06512c

www.rsc.org/advances

42624 | RSC Adv., 2014, 4, 42624–42631 This journal is © The Royal Society of Chemistry 2014

RSC Advances

PAPER

Revista Iberoamericana de Ciencias ISSN 2334-2501

ReIbCi – Julio 2014 – www.reibci.org

Síntesis, caracterización y propiedades luminiscentes de nuevos complejos de Eu(III) y

Tb(III) con el ligandotripiridil imidazolina Alberto Báez-Castro1, Hector Peinado-Guevara1,Jorge Guerrero-Alvarez2, Adriana Cruz-Enríquez1, Miguel

Parra-Hake3, José J. Campos-Gaxiola1* Facultad de Ingeniería1, Centro de Investigaciones Químicas2, Centro de Graduados e Investigación3

Universidad Autónoma de Sinaloa1, Universidad Autónoma del Estado de Morelos2, Instituto Tecnológico de Tijuana3

Los Mochis, Sinaloa, México1; Cuernavaca, Morelos, México2; Tijuana B.C. México3

[email protected]

Abstract—Two novel photoluminescent complexes have been successfully synthesized. Both complexes where characterized by IR spectroscopy, thermal analysis and EDS. Additionally one complex was characterized by 1H-RMN, 13C-RMN and FAB+ mass spectrometry suggesting they have the formula [EuIII(L)(CH3OH) (CH3CN)(H2O)Cl3] and [TbIII(L)(CH3OH)2(H2O)Cl3] where L=cis-(±)2,4,5-tri(pyridin-2-yl) imidazoline. The photophysical proprieties of both complexes were studied experimentally by UV-Vis and fluorescence spectroscopy in solution and solid state.

Keyword—Lanthanide, europium, terbium, complex, photophysical proprieties.

Resumen— Se han sintetizado satisfactoriamente dos nuevos complejos fotoluminiscentes. Ambos complejos fueron caracterizados por espectroscopia de infrarrojo, análisis térmico y EDS. Adicionalmente uno de los complejos fue caracterizado por 1H-RMN, 13C-RMN y espectrometría de masas FAB+ sugiriendo que su fórmula es[EuIII(L)(CH3OH)(CH3CN)(H2O)Cl3] y [TbIII(L)(CH3OH)2(H2O)Cl3] donde L=cis-(±)2,4,5-tri(2-piridil) imidazolina. Las propiedades fotofísicas de ambos compuestos fueron analizadas experimentalmente por espectroscopia de UV-Vis y fluorescencia en solución y en estado sólido.

Palabras clave—Lantánido, europio, terbio, complejo, propiedades fotofísicas.

I. INTRODUCCIÓN Las propiedades de los lantánidos han fascinado a los investigadores durante las últimas décadas[1-

4],debido a sus múltiples aplicaciones en diversas áreas, destacando su uso como material contrastante en estudios biomédicos [5], en la obtención de materiales con propiedades magnéticas [6]y especialmente en el diseño y construcción de dispositivos fotoluminiscentes [7-9], siendo europio y terbio los más comúnmente utilizados debido a sus bandas de emisión finas y definidas [10-12]. Debido a que los iones lantánidos sufren de una débil absortividad molar, y la luminiscencia no sólo es proporcional al rendimiento cuántico sino también a la cantidad de radiación absorbida, su intensidad de luminiscencia es débil [13]. Este problema puede ser sobrellevado mediante el llamado efecto antena, el cual se observa en complejos de lantánidos con ligandos orgánicos donde se aprecia una gran intensidad de emisión centrada en el metal al excitar las bandas de absorción de los ligandos.

Uno de los principales intereses de nuestro grupo de investigación ha sido el diseño, síntesis y caracterización de complejos de coordinación con iones metálicos y ligandos polipiridínicos[14-17], así como el estudio de sus aplicaciones potenciales.

II. EXPERIMENTAL Todos los reactivos fueron utilizados tal como se recibieron sin ninguna purificación. La síntesis del

ligando L fue realizada de acuerdo a la metodología reportada [18] y la síntesis de los complejos se realizó en condiciones ambientales. Los espectros de Infrarrojo se obtuvieron en un espectrofotómetro de infrarrojo FT-IR marca Tensor 27 Brucker formando comprimidos con KBr. El análisis térmico se

Open Journal of Preventive Medicine, 2014, 4, 583-597 Published Online July 2014 in SciRes. http://www.scirp.org/journal/ojpm http://dx.doi.org/10.4236/ojpm.2014.47068

How to cite this paper: Kovacic, P. and Somanathan, R. (2014) New Developments in the Mechanism of Drug Action and Toxicity of Conjugated Imines and Iminiums, including Related Alkaloids. Open Journal of Preventive Medicine, 4, 583-597. http://dx.doi.org/10.4236/ojpm.2014.47068

New Developments in the Mechanism of Drug Action and Toxicity of Conjugated Imines and Iminiums, including Related Alkaloids Peter Kovacic1*, Ratnasamy Somanathan1,2 1Department of Chemistry and Biochemistry, San Diego State University, San Diego, CA, USA 2Centro de Graduados e Investigación del Instituto Tecnológico de Tijuana, Tijuana, Mexico Email: *[email protected] Received 29 May 2014; revised 30 June 2014; accepted 21 July 2014

Copyright © 2014 by authors and Scientific Research Publishing Inc. This work is licensed under the Creative Commons Attribution International License (CC BY). http://creativecommons.org/licenses/by/4.0/

Abstract This review deals with mechanism and physiological activity of conjugated imine and iminium species, including those in the alkaloid category. An appreciable number can be found in the Merck Index. There is focus in mode of action on electron transfer (ET), reactive oxygen species (ROS), oxidative stress (OS) and reduction potential in the prior review. These aspects can be involved in both therapeutic action and toxicity. A unifying mechanistic approach involving ET-ROS-OS is applied to synthetic drugs and alkaloids in the imine-iminium category in relation to both beneficial and adverse effects. Insight at the basic, molecular level can aid in practical pharmaceutical design.

Keywords Mechanism of Drug, Alkaloids

1. Introduction Electron transfer (ET) functionalities that received the most attention in earlier years are quinone (and phe-

*Corresponding author.

http://www.scirp.org/journal/ojpm

http://dx.doi.org/10.4236/ojpm.2014.47068

http://dx.doi.org/10.4236/ojpm.2014.47068

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54 J. Mex. Chem. Soc. 2013, 57(1) Gabriela Huelgas et al.

Synthesis of New Chiral Monosulfonamides Prepared from (11R,12R)-11,12-Diamino-9,10-dihydro-9,10-ethanoanthracene and their Use as Ligands for Asymmetric CatalysisGabriela Huelgas,1 Haydee Rojas Cabrera,1 Domingo Madrigal,3 Ratnasamy Somanathan,3 Pilar Guzmán,1,2 Aurelio Ortiz,2 and Cecilia Anaya de Parrodi1*

1 Departamento de Ciencias Químico-Biológicas, Universidad de las Américas-Puebla, Sta. Catarina Mártir, 72820 Cholula, México. Telephone: +(55)222-2292005; [email protected].

2 Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, 72570 Puebla, Puebla. México.3 Centro de Graduados e Investigación, Instituto Tecnológico de Tijuana, Apartado Postal 1166, 22000 Tijuana, B. C., México.

Received August 1, 2011; accepted April 1, 2013

J. Mex. Chem. Soc. 2013, 57(1), 54-60© 2013, Sociedad Química de México

ISSN 1870-249XArticle

Abstract. New chiral monosulfonamides 6-16 containing (11R,12R)-diamino-9,10-dihydro-9,10-ethanoanthracene as carbon skeleton were prepared. Compounds 6-12, 15 and 16 were used as optically active ligands in the enantioselective ethylation of benzaldehyde. Moreover, the monosulfonamides 6-10 were tested in the asymmetric transfer hydrogenation (ATH) of acetophenone with Rh(Cp*)L* complex.Key words: Monosulfonamide, asymmetric catalysis, enantioselec-tive addition.

Resumen. Nuevas monosulfonamidas quirales 6-16 teniendo a la (11R,12R)-diamino-9,10-dihidro-9,10-etanoantraceno como esqueleto carbonado fueron preparadas. Los compuestos 6-12, 15 y 16 se utiliza-ron como ligantes ópticamente activos en la etilación enantioselectiva de benzaldehído. Además, las monosulfonamidas 6-10 se probaron en la reducción asimétrica por transferencia de hidrógeno (ATH) de acetofenona con Rh(Cp*)L* utilizándolos como catalizadores.Palabras clave: Monosulfonamida, catálisis asimétrica, adición enan-tioselectiva.

Introduction

Chiral secondary alcohols are important structures present in natural products and in many pharmaceutical compounds, and are also precursors for many other complex organic molecules [1]. Hence, there is need to develop new methods for making chiral secondary alcohol. Asymmetric catalysis has been a pow-erful tool to obtain enantiomerically pure or enriched alcohols, mainly by nucleophilic additions to carbonyl compounds [2]. Several and efficient chiral ligands have been used, alone or in the presence of Lewis acids. These include amino alcohols [3-6], α-hydroxy acids [7], α-amino amides [8], α-hydroxy amides [9], and hydroxysulfonamides [10-14].

Our group has recently reported the preparation of bis(sulfonamide) 1, containing (11R,12R)-11,12-diamino-9,10-dihydro-9,10-ethanoanthracene as carbon skeleton [15]. The bis(sulfonamide) 1 was used as ligand in the asymmetric alkylation of prochiral ketones with diethyl zinc in high yield and enantioselectivities up to 99% ee (Figure 1).

Subsequently, König et al. [16] described the synthesis of novel tetradentate sulfonamide ligands and used them in the catalytic asymmetric alkylation of aldehydes with diethylzinc. Quantitative yields of the corresponding secondary alcohol and good asymmetric induction (70% yield and 74% ee) were ob-tained with ligands 2a-b.

Somanathan et al. [17-18] reported the use of monosul-fonamide ligand 3a-b, derived from trans-(1R,2R)-cyclohex-ane-1,2-diamine, in the asymmetric transfer hydrogenation of aromatic ketones. Enantioselectivities ranged from 70 to 99% and good yields for the synthesis of 1-phenylpropanol deriva-tives were achieved.

Recently Hirose [19] and co-workers described the synthe-sis of chiral 1,3-amino sulfonamides, 4, 5.

They were prepared from (-)-cis-2-benzamidocyclohexan-ecarboxylic acid and studied by tested as ligands for catalytic enantioselective addition of diethyl zinc to aldehydes. They provided secondary alcohols in quantitative yields and in good to excellent enantioselectivities (up to 98% ee).

These reports prompted us to prepare the monosulfon-amides 6-12, 15 and 16 and to test their catalytic activity. First,

Fig. 1. Chiral sulfonamides used in asymmetric catalysis.

N H 2

3a, b

1

N N

N H H NSO 2S O 2

R R

2a, bR = a: p-M eC 6H 4- b : C 6H 5-

N H N

NH

4 5

N HO 2S

M eM e

N HO 2S

M eM eO H

O H R = a : p-M eC 6H 4 b : C 6H 5

N HO 2S

SO OR

N M e2

R = a: 4 -M eC 6H 4-

SO

OR

R = b: 4 -M eC 6H 4-

R

Synthesis of New Chiral Monosulfonamides Prepared from (11R,12R)-11,12-Diamino-9,10-dihydro-9,10-ethanoanthracene 55

the ethylation of benzaldehyde was performed in the presence of diethylzinc. Second, monosulfonamides 6-10 were tested in the asymmetric induce hydrogenation (ATH) of acetophenone with Rh(Cp*)L* complex.

Results and Discussion

The synthesis of monosulfonamides 6-12 were achieved from enantiopure (11R,12R)-diamino-9,10-dihydro-9,10-ethanoan-thracene [20]. (11R,12R)-Diamine (1 equiv) was treated with sulfonyl chlorides (1 equiv) in DCM at 0 oC in the presence of triethylamine. Monosulfonamides 6-12 were obtained in good yields (62-90%) after column chromatography purification on silica gel [Hexane:EtOAc; 1:5]. (Table 1).

Preparation of monosulfonamides 13-16

The reaction of (11R,12R)-diamine 17 with (S)-camphorsulfo-nyl chloride, under the same reaction conditions, afforded ke-tone 13 in 70% yield. The reduction of ketone 13 with NaBH4, gave a mixture of two diastereomeric alcohols in a 5.3:1.0 ratio exo-exo:exo-endo in 69% yield. The major diastereomer 15 was isolated in 58% yield by flash chromatography purifica-tion (Scheme 1).

On the other hand, the preparation of ketone 14 was per-formed using (11S,12S)-diamine-18 and (S)-camphorsulfonyl chloride. After purification by column chromatography, the desired ketone was obtained in 76% yield. Ketone 14 was reduced with NaBH4 to provide a mixture of alcohols in a dia-stereomeric ratio of 8.0:1.0. The major exo-exo alcohol 16 was isolated in 67% yield, after flash chromatography purification (Scheme 2).

Enantioselective addition of diethylzinc to benzaldehyde

Chiral monosulfonamides 6-12, 15 and 16 were tested as li-gands in the enantioselective addition of diethylzinc to benzal-dehyde. The reaction was performed using 5 mol% of the cor-responding optically active ligands in the presence of toluene as solvent and under solvent-free conditions. The chiral zinc cata-lyst was generated in situ upon the addition of 2.0 equivalents of diethylzinc to the corresponding chiral monosulfonamide. 1-Phenylpropan-1-ol was obtained in moderate to good yields (in toluene 55-95%, under solvent free conditions 47-92%) and low to moderate enantioselectivities (in toluene 4-52%, under solvent free conditions 8-56%). We found that the presence or

Table 1. Synthesis of the monosulfonamide ligands derived from (11R,12R)-diamino-9,10-dihydro-9,10-ethanoanthracene.

C lS O2R E t3N, C H2C l2, 0 °C

1 eq

+

NH2

NHO2S

R

62 - 90%, 5 hNH2

NH2

(11R,12R)-17 6 - 12

Entry Monosulfonamide R Yield (%)a

1 6 p-(t-Bu)-C6H4- 85

2 7 C6H5-CH2- 75

3 8 2,4,6-(i-Pr)3-C6H2

- 904 9 p-FC6H4

- 815 10 CH3 626 11 p-CF3C6H4

- 667 12 p-CH3C6H4

- 68a Yields were measured after column chromatography on silica gel (Et3N/SiO2 = 2.5% v/w, (hexane/EtOAc; 15:1 as eluent).

Scheme 1. Synthesis of ligand 15.

+ OC lO 2SN Et3

C H 2C l2, r.t

70% y ie ld

1 .0 equ iv

1 .0 equ iv

(1 .0 equ iv)

(11R,12R)-S-13(11R,12R)-17

N H 2 N H 2

1) N aB H 4 (7 equ iv)

TH F :E tO H 4 :1 , r.t 69% y ie ld d r = 5 .3 :1 .02) flash chrom atography 58% y ie ld

N H 2 N HO 2S

OM eM e

N H 2

N HO 2S

M eM eO H

(S)

(11R,12R)-S-15

Scheme 2. Synthesis of the ligand 16.

OC lO 2S

N Et3

C H 2C l2, r.t76% y ie ld

1.0 equ iv

(1 .0 equ iv)

1 .0 equ iv(11S,12S)-18

+

(11S,12S)-S-14

N H 2

N H 2

N H

N H 2

O 2S

OM e

1) N aBH 4 (7 equ iv)

TH F :E tO H (4 :1), r.t 75% y ie ld d r = 8 :12) flash chrom atography 67% y ie ld

N H

N H 2

O 2S

M eO H

(S)

(11S,12S)-S-16

M e

M e


absence of solvent did not lead to significant improvements. Monosulfonamide 8 (Table 2) gave the best yields and enan-tioselectivities (entries 5 and 6) (Table 2). Monosulfonamides 6-12 provided (R)-1-phenylpropan-1-ol as major enantiomer; however monosulfonamides 15 and 16 afforded the alcohol with the opposite configuration (Table 2). The transition state

for alkylation of benzaldehyde with diethylzinc is show in (Figure 2) [23].

Asymmetric induced hydrogenation with rhodium complex as ligands 6-10

Next, we performed the catalytic enantioselective reduction reaction using ligands 6-10, in the asymmetric induced hy-drogenation of acetophenone with a rhodium complex (Table 3). A mixture of the metal precursor [RhCl2(Cp*)]2 and the monosulfonamide was heated in water to form the Rh(Cp*)L* complex. Then sodium formate and acetophenone were added to form the 1-phenyl-1-ethanol. The reaction proceeded with low to moderate results (10-34% yield and 3-42% ee). Best enantioselectivity was achieved with ligand 10 (42% ee, entry 5) (Table 3). The transition state for ATH of aromatic ketones is show in (Figure 3).

In our previous study [21, 22] we found that the dihedral angle N-C-C-N is critical in obtaining maximum overlap, in order to get good yields and enantioselectivities. The dihedral angle calculations were carried out by B3LYP density func-tional level of theory, using a cc-pVDZ basis set calculations. The angles N-C-C-N of ligands 6, 7, 8, 9, and 10 were found to be in the range of 114.16 to 116.96°, compared to 59° observed for monosulfonamide of 1,2-cyclohexane diamine.

Table 2. Diethylzinc addition of benzaldehyde catalyzed by monosul-fonamides 6 - 12 and 15 - 16 under different reaction conditions.

+ E t2Zn 1) L igand (5 m ol% )

2) PhM e, 25 °C , 20 h3) H 2O1 eq

H

O

2 eq

O H

Entry Ligand Solvent Yield (%)a

ee

(%)b

1 6 Toluene 75 18 (R)2 Solvent-free 47 22 (R)3 7 Toluene 95 4 (R)4 Solvent-free 53 8 (R)5 8 Toluene 94 52 (R)6 Solvent-free 92 56 (R)7 9 Toluene 55 8 (R)8 Solvent-free 51 26 (R)9 10 Toluene 85 12 (R)10 Solvent-free 54 19 (R)11 11 Toluene 56 28 (R)12 Solvent-free 63 24 (R)13 12 Toluene 72 28 (R)14 Solvent-free 68 24 (R)15 15 Toluene 81 44 (S)16 Solvent-free 55 18 (S)17 16 Toluene 85 18 (S)18 Solvent-free 69 26 (S)

a Yields were measured after column chromatography on silica gel (Et3N/SiO2 = 2.5% v/w, (hexane/EtOAc; 15:1 as eluent).b The enantiomeric excess was determined by HPLC on a chiral OD column. Absolute configuration was assigned by comparing the specific rotation with literature values.

Fig. 2. Transition states for alkylation of benzaldehyde with diethyl-zinc.

NH 2N

S

H

Zn

O

H

OO

R

Zn

H 2C

EtE t

NH 2N

S

H

Zn

O

H

OO

R

Zn

H 2C

E tE t

C H 3 C H 3

Table 3. Asymmetric transfer hydrogenation of acetophenone cata-lyzed by Rh(Cp*)L* complexes with ligands 6-10.

[R h IIIC l2(C p*)]2 , ligand

H C O O - N a+ / H 2OP h

O

P h H

M e O H

Entry Ligand Yield (%)a ee (%)b

1 6 26 31 (R)2 7 21 18 (R)3 8 18 3 (R)4 9 34 30 (R)5 10 10 42 (R)

a Yields were measured after column chromatography on silica gel (Et3N/SiO2 = 2.5% v/w, (hexane/EtOAc; 15:1 as eluent).b The enantiomeric excess was determined by GC analysis of the acetylated alcohol with chiral capillary column β-DEX 120.

Fig. 3. Transition states for ATH of acetophenone.

NN

R h

H

H

SO

OR

HO

P h

NN

R h

H

H

SO

OR

HO

P h


Conclusion

In conclusion, we have described an easy and simple synthesis of different chiral monosulfonamides from (11R,12R)-diamino-9,10-dihydro-9,10-ethanoanthracene in good yields (62-90%). They have been used as zinc-based catalysts in the enantiose-lective addition of diethylzinc to benzaldehyde with high yield (94%) and moderate ee (56%).

We also evaluated the potential of these ligands as cata-lysts in the asymmetric enantioselective reduction in the ATH of acetophenone with Rh(Cp*)L* complex. We observed low conversion (10-34%) and low enantioselectivities (3-42%).

These results clearly indicate that the monosulfonamides derived from (1R,2R)-cyclohexane-1,2-diamine are more stere-oselective than those prepared with (11R,12R)-diamino-9,10-dihydro-9,10-ethanoanthracene. Based on these results, we are working on the design of new chiral sulfonamides based ligands that display better stereoinduction.

Experimental

All manipulations involving diethylzinc were carried out under argon atmosphere. Benzaldehyde was distilled prior to use. NMR spectra were obtained on a Varian 200 MHz. Fourier transform spectrometer. 1H NMR spectra were referenced to tetramethylsilane; 13C{1H} NMR spectra were referenced to residual solvent.

General procedure for synthesis of monosulfonamides 6-14

To a solution of enantiopure 11,12-diamino-9,10-dihydro-9,10-ethanoanthracene (300 mg, 1.3 mmol) in CH2Cl2 (10 mL) and triethylamine (0.5 mL, 1.3 mmol) at 0 °C a sulfonyl chloride solution was added dropwise (300 mg, 1.3 mmol) in CH2Cl2 (10 mL) over 60 min. After the addition was completed, the mixture was allowed to warm to room temperature. After be-ing stirred for 5 h, the mixture was washed with water (3 x 50 mL). The organic phase was separated and dried over NaSO4. The solution was filtered and the solvent was removed under vacuum, the crude product was purified by flash chromatogra-phy on silica gel, (Hexane/EtOAc 1:5 as eluent).

(4-tert-Butylbenzenesulfonamido)-(11R,12R)-diamino-9,10-dihydro-9,10-ethanoanthracene (6)Affording a white solid (85% yield): mp 188-190 °C; [α]D20 = -6.6 (c 1.0, CHCl3). 1H NMR (CDCl3, 200 MHz) δ 1.36 (s, 9H), 1.42 (s, 3H), 2.81-2.84 (m, 1H), 3.07-3.10 (m, 1H), 3.95 (d, 1H, J = 2.6 Hz), 4.04 (d, 1H, J = 3.0 Hz), 7.07-7.27 (m, 8H), 7.54 (d, 2H, J = 8.8 Hz), 7.80 (d, 2H, J = 8.4 Hz). 13C NMR (50 MHz, CDCl3) δ 31.8, 50.0, 52.2, 61.1, 63.6, 124.1, 124.2, 125.6, 125.9, 126.2, 126.3, 126.7, 126.8, 137.2, 137.5, 138.6, 139.6, 141.5, 156.2. IR-FT (KBr) νmax/ cm-1: 3344, 3277, 3072, 2958, 2874, 2799, 2754, 1595, 1575, 1464, 1398, 1368, 1335,

1268, 1228, 1199, 1162, 1109, 1088, 1021, 930, 902, 836, 792, 757, 641, 582, 555, 525, 406. HRMS-FAB+: m/z [M+H]+ calcd. for C26H29O2N2S: 433.1950; found: 433.1942.

(Phenylmethanesulfonamido)-(11R,12R)-diamino-9,10-dihydro-9,10-ethanoanthracene (7)Affording a white solid (75% yield): mp 185-186 °C; [α]D20 = -26.0 (c 1.0, CHCl3). 1H NMR (CDCl3, 200 MHz) δ 1.25 (broad, 2H), 2.74-2.76 (m, 1H), 2.91 (broad, 1H), 4.00-4.01 (m, 1H), 4.04-4.10 (m, 2H), 4.28 (s, 2H), 7.06-7.42 (m, 13H). 13C NMR (CDCl3, 50 MHz) δ 51.0, 52.8, 60.2, 61.4, 64.0, 124.1, 124.2, 125.7, 125.9, 126.2, 126.4, 126.7, 128.5, 129.1, 130.5, 137.2, 138.3, 139.6, 141.4. IR-FT (KBr) νmax/cm-1: 3341, 3278, 3066, 3041, 2951, 2924, 2880, 2753, 1947, 1800, 1603, 1578, 1487, 1459, 1410, 1378, 1322, 1257, 1228, 1200, 1149, 1123, 1099, 1069, 1030, 960, 935, 909, 872, 847, 824, 782, 758, 696, 635, 603, 564, 543, 509, 462, 347. HRMS-FAB+: m/z [M+H]+ calcd. for C23H23O2N2S: 391.1480; found: 391.1478.

(2,4,6-Triisopropylbenzenesulfonamido)-(11R,12R)-diamino-9,10-dihydro-9,10-ethanoanthracene (8)Affording a white solid (90% yield): mp 183-184 °C; [α]D20 = -8.6 (c 1.0, CHCl3). 1H NMR (CDCl3, 200 MHz) δ 1.19-1.27 (m, 18H), 2.80-2.93 (m, 3H), 3.17-3.24 (m, 1H), 4.01-4.27 (m, 6H), 7.08-7.31 (m, 10H). 13C NMR (CDCl3, 50 MHz) δ 24.3, 25.5, 30.2, 34.7, 50.3, 52.1, 61.0, 63.7, 123.5, 124.2, 125.6, 125.9, 126.2, 126.3, 126.7, 132.9, 137.4, 138.6, 139.7, 141.6, 149.5, 152.4. IR-FT (KBr) νmax/ cm-1: 3343, 3275, 3074, 2958, 2873, 1599, 1572, 1462, 1420, 1361, 1324, 1256, 1227, 1195, 1158, 1104, 1066, 1037, 932, 903, 881, 788, 757, 660, 546. HRMS-FAB+: m/z [M+H]+ calcd. for C31H39O2N2S: 503.2732; found: 503.2737.

(4-Fluorobenzenesulfonamido)-(11R,12R)-diamino-9,10-dihydro-9,10-ethanoanthracene (9)Affording a white solid (81% yield): mp 178-179 °C; [α]D20 = -13.5 (c 1.0, CHCl3). 1H NMR (CDCl3, 200 MHz) δ 2.72-2.74 (m, 1H), 2.98-3.0 (m, 1H), 3.87 (d, 1H, J = 3.0 Hz), 3.94 (d, 1H, J = 2.6 Hz), 5.18 (s, 3H), 6.97-7.21 (m, 10H), 7.82 (dd, 2H, J = 5.2, 5.2 Hz).. 13C NMR (50 MHz, CDCl3) δ 50.1, 52.4, 60.9, 63.5, 116.0, 116.5, 124.2, 125.6, 126.0 126.2, 126.4, 126.7, 129.5, 129.7, 136.7, 136.7, 137.1, 138.4, 139.4, 141.5, 161.9, 166.9. IR-FT (KBr) νmax/cm-1 3359, 3298, 3070, 3029, 2948, 2867, 2746, 1591, 1491, 1463, 1407, 1330, 1291, 1233, 1158, 1091, 1020, 980, 925, 892, 840, 788, 758, 669, 635, 579, 551. HRMS-FAB+: m/z [M+H]+ calcd. for C22H20O2N2F1S: 395.1230; found: 395.1234.

(Methansulfonamido)-(11R,12R)-diamino-9,10-dihydro-9,10-ethanoanthracene (10)Affording a white solid (62% yield): mp 112-113 °C; [α]D20 = -8.7 (c 1.0, CHCl3). 1H NMR (CDCl3, 200 MHz) δ 2.02 (s, 3H), 2.94 (broad, 1H), 3.10 (s, 3H), 3.26 (broad, 1H), 4.10 (broad, 1H), 4.28 (d, 1H, J = 2.6 Hz), 7.14-7.40 (m, 8H). 13C


NMR (CDCl3, 50 MHz) δ 42.1, 50.8, 53.0, 61.0, 62.8, 124.0, 124.3, 125.8, 126.0, 126.3, 126.4, 126.5, 126.6, 137.3, 138.1, 139.8, 141.3. IR-FT (KBr) νmax/cm-1: 3349, 3281, 3070, 3042, 3023, 2954, 2930, 2872, 1629, 1588, 1463, 1411, 1323, 1227, 1149, 1116, 1068, 1023, 982, 868, 845, 823, 762, 718, 671, 636, 603, 563, 519, 459. HRMS-FAB+: m/z [M+H]+ calcd. for C17H19O2N2S: 315.1167; found: 315.1171.

(4-Trifluoromethanbenzenesulfonamido)-(11R,12R)-diamino-9,10-dihydro-9,10-ethanoanthracene (11)Affording a white solid (66% yield): mp 190-191 °C; [α]D20 = -10 (c 1.0, CHCl3). 1H NMR (CDCl3, 200 MHz) δ 2.33 (broad, 3H), 2.71-2.74 (m, 1H), 3.04 (s, 1H), 3.94-3.95 (m, 2H), 6.96-7.21 (m, 8 H), 7.71 (d, 2H, J = 8.4 Hz), 7.94 (d, 2H, J = 8.0 Hz). 13C NMR (CDCl3, 50 MHz) δ 50.2, 52.5, 60.8, 63.5, 98.2, 124.0, 124.1, 125.6, 126.0, 126.2, 126.5, 126.7 127.3, 137.2, 138.1, 138.3, 139.4, 141.4, 144.3. IR-FT (KBr) νmax/cm-1: 3349, 3281, 3065, 3033, 2950, 2929, 2872, 2750, 1583, 1491, 1460, 1415, 1323, 1226, 1203, 1152, 1124, 1068, 1026, 951, 901, 849, 785, 758, 728, 698, 636, 604, 543, 508, 450. HRMS-FAB+: m/z [M+H]+ calcd. for C23H20O2N2F3S: 445.1198; found: 445.1202.

(4-Methylbenzenesulfonamido)-(11R,12R)-diamino-9,10-dihydro-9,10-ethanoanthracene (12)Affording a white solid (68% yield): mp 166-168 °C; [α]D20 = -23.5 (c 1.0, CHCl3). 1H NMR (CDCl3, 200 MHz) δ 1.3 (broad, 3H), 2.44 (s, 3H), 2.79 (t, 1H, J = 2.6 Hz), 4.03 (d, 1H, J = 2.6 Hz), 3.92 (d, 1H, J= 2.6 Hz), 4.03 (d, 1H, J = 2.6 Hz), 7.06-7.35 (m, 10 H), 7.76 (d, 2H, J = 8.4 Hz). 13C NMR (CDCl3, 50 MHz) δ 22.3, 50.0, 52.1, 61.0, 63.6, 124.1, 124.1, 125.6, 125.9, 126.2, 126.3, 126.7, 126.9, 129.5, 137.2, 137.6, 138.5, 139.6, 141.5, 143.2. IR-FT (KBr) νmax/cm-1: 3339, 3262, 3069, 3023, 2959, 2878, 1739, 1593, 1492, 1460, 1327, 1295, 1224, 1154, 1091, 1022, 975, 923, 889, 842, 818, 791, 760, 710, 666, 636, 601, 578, 552, 532. HRMS-FAB+: m/z [M+H]+ calcd. for C23H23O2N2S: 391.1480; found 391.1485.

[7,7-Dimethyl-2-oxobicyclo[2.2.1]heptan-1-methylsulfonamido](11R,12R)-diamino-9,10-dihydro-9,10-ethanoanthracene (13)Affording a white solid (70% yield): mp 218-219 °C; [α]D20 = +13.2 (c 1.0, CHCl3). 1H NMR (CDCl3, 200 MHz) δ 0.91 (s, 3H), 1.02 (s, 3H), 1.36-1.48 (m, 2H), 1.74-2.47 (m, 7H), 2.94 (d, 1H, J = 15 Hz) 2.99-3.01 (m, 1H), 3.25-3.29 (m, 1H), 3.57 (d, 1H, J = 15 Hz), 4.11 (d, 1H, J = 2.6 Hz), 4.30 (d, 1H, J = 2.6 Hz), 4.80 (d, 1H, J = 8 Hz), 7.08-7.36 (m, 8H). 13C NMR (CDCl3, 50 MHz) δ 20.3, 20.6, 26.5, 27.6, 43.2, 43.3, 48.9, 50.4, 51.0, 52.5, 59.3, 61.4, 63.9, 124.2, 125.5, 125.9, 126.2, 126.3, 126.7, 137.3, 138.7, 139.8, 141.6, 215.0. IR-FT (KBr) νmax/cm-1: 3354, 3297, 3073, 3029, 2950, 2929, 2911, 2884, 2807, 2764, 1742, 1593, 1456, 1414, 1389, 1330, 1279, 1235, 1202, 1149, 1098, 1067, 1051, 1026, 975, 937, 913, 888, 850, 785, 765, 748, 637, 602, 571, 527, 500. HRMS-FAB+: m/z [M+H]+ calcd. for C26H31O3N2S: 451.2055; found: 451.2059.

[7,7-Dimethyl-2-oxobicyclo[2.2.1]heptan-1-methylsulfonamido](11S,12S)-diamino-9,10-dihydro-9,10-ethanoanthracene (14)Affording a white solid (76% yield): mp 225-226 °C; [α]D20 = +32.1 (c 9.2, CHCl3). 1H NMR (CDCl3, 200 MHz) δ 0.92 (s, 3H), 0.98 (s, 3H), 1.31-1.44 (m, 2H), 1.80-2.39 (m, 7H), 2.91-2.94 (m, 1H), 3.04 (d, 1H, J = 15.0 Hz), 3.26-3.30 (m, 1H), 3.76 (d, 1H, J = 15.4 Hz), 4.02 (d, 1H, J = 2.6 Hz), 4.32 (d, 1H, J = 2.6 Hz), 4.90 (d, 1H, J = 8.6 Hz), 7.10-7.38 (m, 8H). 13C NMR (CDCl3, 50 MHz) δ 20.2, 20.6, 27.3, 27.7, 43.1, 43.4, 49.2, 51.5, 51.8, 53.9, 59.7, 61.0, 63.5, 123.9, 124.4, 126.0, 126.3, 126.5, 126.6, 137.4, 138.3, 140.4, 141.5, 215.6. IR-FT (KBr) νmax/cm-1: 3363, 3264, 3070, 3021, 2952, 2899, 1732, 1585, 1442, 1390, 1326, 1276, 1209, 1135, 1060, 1032, 1020, 989, 941, 900, 864, 821, 781, 752, 710, 663, 606, 555, 519, 503, 423, 387, 353, 329, 297. HRMS-FAB+: m/z [M+H]+ calcd. for C26H31O3N2S: 451.2055; found: 451.2051

General procedure for synthesis of ligands 15 and 16In a 100 mL flask ketone (300 mg, 0.67 mmol) was dissolved in a mixture solvent (40 mL, MeOH/ THF = 4:1). Next NaBH4 (180 mg, 4.6 mmol, 7 equiv) was added slowly. The mixture was stirred for another 4 h. The reaction mixture was quenched with saturated aqueous ammonium chloride, and the solid was filtered. The filtrate was extracted with CH2Cl2 (3 × 50 mL). The organic phase was washed with water and was dried over NaSO4. The solvent was removed under vacuum; the crude product was purified by flash chromatography on silica gel (Hexane/EtOAc 7:3 as eluent).

[2-(S)-Hydroxy-7,7-dimethylbicyclo[2.2.1]heptan-1-methylsulfonamido](11R,12R)-diamino-9,10-dihydro-9,10-ethanoanthracene (15)Affording a white solid (58% yield): mp 128-129 °C; [α]D20 = +6.1 (c 1.0, CHCl3). 1H NMR (CDCl3, 200 MHz) δ 0.81 (s, 3H), 0.96 (s, 3H), 1.61-1.89 (m, 5H), 2.21-2.27 (m, 5H), 2.79-2.82 (m, 1H), 2.93 (d, 2H, J = 14.4 Hz), 3.13-3.20 (m, 1H), 3.72 (d, 1H, J = 14.6 Hz), 3.92-4.00 (m, 2H), 4.50 (d, 1H, J = 2.6 Hz), 7.11-7.42 (m, 8H). 13C NMR (CDCl3, 50 MHz) δ 20.6, 21.3, 28.0, 29.9, 41.3, 44.6, 49.4, 50.3, 51.3, 51.7, 54.0, 60.9, 62.6, 74.6, 123.9, 124.7, 126.0, 126.3, 126.5, 126.6, 126.8, 136.9, 137.5, 140.1, 141.1. IR-FT (KBr) νmax/cm-1: 3459, 3377, 3304, 3146, 3072, 3043, 3021, 2954, 2931, 2892, 1585, 1460, 1415, 1392, 1320, 1280, 1207, 1139, 1062, 1027, 988, 955, 887, 848, 817, 789, 753, 713, 638, 582, 560, 506, 450, 347. HRMS-FAB+: m/z [M+H]+ calcd. for C26H33O3N2S: 453.2212; found: 453.2218.

[2-(S)-Hydroxy-7,7-dimethylbicyclo[2.2.1]heptan-1-methylsulfonamido](11S,12S)-diamino-9,10-dihydro-9,10-ethanoanthracene (16)Affording a white solid (68% yield): mp 217-219 °C; [α]D20 = +19.7 (c 9.0, CHCl3). 1H NMR (CDCl3, 200 MHz) δ 0.81 (s, 3H), 0.96 (s, 3H), 1.15-1.28 (m, 2H), 1.68-1.87 (m, 6H), 2.78-2.81 (m, 1H), 2.93 (d, 2H, J = 14.4 Hz), 3.16-3.19 (m, 1H), 3.71 (d, 1H, J = 14.4 Hz), 3.90-4.00 (m, 4H), 4.50 (d,


1H, J = 2.6 Hz), 7.12-7.42 (m, 8H). 13C NMR (CDCl3, 50 MHz) δ 20.9, 21.5, 28.2, 30.2, 41.5, 44.8, 49.6, 50.6, 51.5, 52.0, 54.2, 61.0, 62.9, 74.8, 124.1, 124.9, 126.3, 126.6, 126.7, 126.8, 127.0, 127.1, 137.2, 137.7, 140.3, 141.4. IR-FT (KBr) νmax/cm-1: 3457, 3377, 3136, 2954, 2927, 2890, 1459, 1414, 1398, 1356, 1317, 1272, 1137, 1061, 1024, 986, 954, 885, 848, 814, 790, 748, 710, 638, 602, 581, 557, 529, 502, 447, 421, 394, 344, 317. HRMS-FAB+: m/z [M+H]+ calcd. for C26H33O3N2S: 453.2212; found: 453.2220.

General procedure for the asymmetric diethylzinc addition to benzaldehydeThe ligands 6-12, 15 and 16 (5 mol %) were weighed into the re-action vessel that was then purged with nitrogen, and dissolved in toluene (3 mL). Diethylzinc (1.0 M in hexane, 2.0 equiv, 0.94 mL) was then added at rt. After 10 min, benzaldehyde (1.0 equiv, 0.47 mmol) was added. The homogeneous reaction mixture was stirred at rt, after 20 h the reaction was quenched with water (5 mL), extracted with EtOAc (2 × 40 mL) and the combined organic layers were washed with brine, dried over NaSO4 and concentrated in vacuo. The residue was purified by flash chromatography on deactivated silica gel (Et3N/SiO2 = 2.5% v/w, Hexane/EtOAc 95:5) to afford 1-phenyl-1-propanol. The enantiomeric excess of the product was determined by HPLC analysis using a Chiracel OD column, 254 nm UV de-tector, 95:5 Hexane/i-propanol, flow rate 0.5 mL min, retention time (R): 14 min, retention time (S): 15 min. Specific rotations of the secondary alcohols were measured and compared with those reported on the literature to assign configuration [23].

General procedure for the asymmetric diethylzinc addition to benzaldehyde under solvent-free conditionsThe ligands 6-12, 15 and 16 (5 mol %) were weighed into the reaction vessel and diethylzinc (1.0 M in hexane, 2.0 equiv, 0.94 mL) was then added at rt. After 10 min, benzaldehyde (1.0 equiv, 0.47mmol) was added. The homogeneous reaction mixture was stirred at rt. After 20 h the reaction was quenched with water (5 mL), extracted with EtOAc (2 × 40 mL) and the combined organic layers were washed with brine, dried over NaSO4 and concentrated in vacuo. The residue was purified by flash chromatography on deactivated silica gel (Et3N/SiO2 = 2.5% v/w, Hexane/EtOAc 95:5) to afford 1-phenyl-1-pro-panol.

The enantiomeric excess of the product was determined by HPLC analysis using a Chiracel OD column, 254 nm UV detec-tor, 95:5 Hexane/i-propanol, flow rate 0.5 mL min, retention time (R): 14 min, retention time (S): 15 min. Specific rotations of the secondary alcohols were measured and compared with those reported on the literature to assign configuration [24].

General procedure for the asymmetric transfer hydrogenation of acetophenone in waterA mixture of the metal precursor [RhCl2(Cp*)]2 (0.0039 mmol) and chiral ligand (0.00075 mmol) was heated in water (2 mL) at 40 °C for 1 h in air. HCOONa (5.7 mmol) and the substrate

were subsequently added (1.14 mmol). The reaction mixture was stirred at 40 °C in air. The reaction mixture was extracted with ether (3 × 10 mL). The ether layers were combined, dried over anhydrous NaSO4, filtered and concentrated under vacu-um. The residue containing the alcohol was acetylated using acetic anhydride. The enantiomeric excess of the product was determined by GC analysis of the acetylated alcohol with chiral capillary column β-DEX 120.

Specific rotations of the secondary alcohols were measured and compared with those reported on the literature to assign configuration [23].

Acknowledgments

This work was supported by CONACYT, Consejo Nacional de Ciencia y Tecnología (Project No. 153594. and P. Guzmán Grants No. 207757). We thank F. J. Perez. L. Velasco, E. Gar-cia Ríos, E. Huerta, R. Patiño, and M. A. Peña (Instituto de Química, UNAM) for their technical assistance.

References

1. (a) Wang, G.; Liu, X.; Zhao, G. Tetrahedron: Asymmetry 2005, 16, 1873-1879; (b) Zhu, D.; Mukherjee, C.; Hua, L. Tetrahedron: Asymmetry 2005, 16, 3275-3278; (c) Reilly, M.; Anthony, D. R.; Gallagher, C. Tetrahedron Lett. 2003, 44, 2927-2930; (d) Okano, K.; Murata, K.; Ikariya, T. Tetrahedron Lett. 2000, 41, 9277-9280; (e) Soai, K.; Niwa, S. Chem. Rev. 1992, 92, 833-856.

2. (a) Ojima Iwao, Catalytic Asymmetric Synthesis (2nd ed.) Wiley Interscience, New York 2000; (b) Pu. L.; Yu, H. B. Chem. Rev. 2001, 101, 757-824.

3. (a) Wu, X. Y.; Liu, X. Y.; Zhao, G. Tetrahedron: Asymmetry 2005, 16, 2299-2305; (b) Park, J. K.; Lee, H. G.; Bolm, C.; Kim, B. M. Chem. Eur. J. 2005, 11, 945-950; (c) Cobb, A. J. A.; Marson, C. M. Tetrahedron 2005, 61, 1269-1279; (d) Tseng, S. L.; Yang, T. K. Tetrahedron: Asymmetry 2004, 15, 3375-3380; (e) Sibi, M. P.; Stanley, L. M. Tetrahedron: Asymmetry 2004, 15, 3353-3356; (f) Mao, J. C.; Wan, B. S.; Wang, R. L.; Wu, F.; Lu, S. W. J. Org. Chem. 2004, 69, 9123-9127; (g) Da, C. S.; Han, Z. J.; Ni, M.; Ynag, F.; Liu, D. X.; Zhou, Y. F.; Wang, R. Tetrahedron: Asymme-try 2003, 14, 659-665; (h) Wu, Y. J.; Yun, H. Y.; Wu, Y. S.; Ding, K. L.; Zhou, Y. Tetrahedron: Asymmetry 2000, 11, 3543-3552; (i) Dosa, P. I.; Fu, G. C. J. Am. Chem. Soc. 1998, 120, 445-446.

4. (a) Ji, J. X.; Wu, J.; Au-Yeung, T. L.; Yip, C. W.; Haynes, R. K.; Chan, A. S. C. J. Org. Chem. 2005, 70, 1093-1095; (b) Panda, M.; Phuan, P. W.; Kozlowski, M. C. J. Org. Chem. 2003, 68, 564-571; (c) Cimarelli, C.; Palmieri, G.; Volpini, E. Tetrahedron: Asymmetry 2002, 13, 2417-2426; (d) Lu, J.; Xu, X.; Wang, S. Z.; Wang, C. D.; Hu, Y. F.; Hu, H. W. J. Chem. Soc., Perkin Trans. 1 2002, 2900-2903.

5. (a) Scarpi, D.; Lo Galbo, F.; Occhiato, E. G.; Guarna, A. Tetra-hedron: Asymmetry 2004, 15, 1319-1324; (b) García Martínez, A.; Teso Vilar, E.; García Fraile, A.; de la Moya Cerero, S.; Lora Maroto, B. Tetrahedron: Asymmetry 2003, 14, 1959-1963; (c) Hanyu, N.; Aoki, T.; Mino, T.; Sakamoto, M.; Fujita, T. Tetrahe-dron: Asymmetry 2000, 11, 2971-2979.

6. (a) Kitamura, M.; Suga, S.; Kawai, K.; Noyori, R. J. Am. Chem. Soc. 1986, 108, 6071; (b) Noyori, R.; Kitamura, M. Angew. Chem.; Int. Ed. 1991, 30, 49-69.


7. (a) Bauer, T.; Gajewiak, J. Tetrahedron 2004, 60, 9163; (b) Bauer, T.; Tarasiuk, J. Tetrahedron Lett. 2002, 43, 687-689.

8. Burguete, M. I.; Collado, M.; Escorihuela, J.; Galindo, F.; García-Verdugo, E.; Luis, S. V.; Vicent, M. J. Tetrahedron Lett. 2003, 44, 6891-6894.

9. Blay, G.; Fernández, I.; Hernández-Olmos, V.; Marco-Aleixandre, A.; Pedro, J. R. Tetrahedron: Asymmetry 2005, 16, 1953-1958.

10. (a) Mino, T.; Oishi, K.; Yamashita, M. Synlett 1998, 965; (b) Fleischer, R.; Braun, M. Synlett 1998, 1441-1443.

11. Bauer, T.; Gajewiak, J. Tetrahedron 2003, 59, 10009-10012. 12. (a) Guo, C.; Qui, J.; Zhang, X. M.; Verdugo, D.; Larter, M. L.;

Christie, R.; Kenney, P.; Walsh, P. J. Tetrahedron 1997, 53, 4145-4148; (b) Qiu, J.; Guo, C.; Zhang, X. M. J. Org. Chem. 1997, 62, 2665-2668.

13. Zhang, X. M.; Guo, C. Tetrahedron Lett. 1995, 36, 4947-4474. 14. Ito, K.; Kimura, Y.; Okamura, H.; Katsuki, T. Synlett 1992, 573-

574. 15. Huelgas, G.; LaRochelle, L.; Rivas, L.; Loutchinina, Y.; Toscano,

R. B.; Carroll, P. J.; Walsh, P. J.; de Parrodi C. A. Tetrahedron 2011, 67, 4467-4474.

16. Hechavarría, M. F.; Eibler, E.; Zabel, M.; Hönig, B. Tetrahedron: Asymmetry 2003, 14, 1989-1994.

17.Cortez, N. A.; Aguirre, G.; Parra-Hake, M.; Somanathan, R.; Arita, A, J.; Coksy, A L.; de parrodi, C. A.; Huelgas, G. Synth. Com-mun.2011, 41, 73-84.

18. Cortez, N. A.; Aguirre, G.; Parra-Hake, M.; Somanathan, R. Tet-rahedron Lett. 2007, 48, 4335-4338.

19. Hirose, T.; Sugawara, K.; Kodoma, K. J. Org. Chem. 2011, 76, 5413-5428.

20. Fox, M. E.; Gerlach, A.; Lennon, I. C.; Meek, G.; Praquin, C. Synthesis 2005, 3196-3198.

21. Cortez, N. A.; Aguirre, G.; Parra-Hake, M.; Somanathan, R. Tet-rahedron: Asymmetry 2008, 19, 1304-1309.

22. Barrón-Jaime, A.; Aguirre, G.; Parra-Hake, M.; Chávez, D.; Mad-rigal, D.; Sanders, B.; Cooksy, A. L.; Somanathan, R. J. Mex. Chem. Soc. 2011, 55, 16-20.

23. Vidal-Ferran, A.; Moyano, A.; Pericàs, M. A.; Riera, A. Tet. Lett, 1997, 38, 8773-8776.

24. Sosa-Rivadeneyra, M.; Muños-Muñis, O.; de Parrodi, C. A.; Quin-tero, L.; Juaristi, E. J. Org. Chem. 2003, 68, 2369-2375.

Synthesis of (R)-tembamide and (R)-aegeline via asymmetric transferhydrogenation in water

Norma A. Cortez, Gerardo Aguirre, Miguel Parra-Hake, Ratnasamy Somanathan ⇑Centro de Graduados e Investigación del Instituto Tecnológico de Tijuana, Apartado Postal 1166, Tijuana B.C. 22510, Mexico


Article history:Received 11 July 2013Accepted 28 August 2013Available online 14 October 2013

a b s t r a c t

The synthesis of (R)-tembamide and (R)-aegeline via asymmetric transfer hydrogenation involving enan-tioenriched monosulfonamide–RhCp⁄ complex in aqueous sodium formate as hydride donor is described.

� 2013 Elsevier Ltd. All rights reserved.

1. Introduction

The b-aminoalcohol functionality is a rich resource in organicand medicinal chemistry1–15 This functional group is often foundnot only in the structural unit of many building blocks, chiral aux-iliaries, and ligands in organic transformations, but also in thestructural motif of many biologically active compounds. Opticallyactive b-aminoalcohols are important structural elements in chiraldrugs, such as a- or b-adrenergic blockers and agonists in the treat-ment of cardiovascular disease, cardiac failure, asthma, antidepres-sant, and glaucoma.1–15 We have developed a simple and efficientroute to various chiral b-aminoalcohols involving the enantioselec-tive addition of trimethylsilylcyanide to prochiral aryl aldehydescatalyzed by chiral Schiff base-titanium complexes to give enanti-omerically pure cyanohydrins in good yields and enantioselectivi-ties.16–19 The trimethylsilylcyanohydrins can subsequently bereduced to give enantiopure b-aminoalcohols in good yields usingdiborane. Using this technique, we synthesized and reported X-raystructures of the naturally occurring (R)-(�)-tembamide and(R)-(�)-aegeline, isolated form Fagara hyemalis (St. Hill) Englerand Aegele marmelos (Correa), respectively, belonging to the familyRutaceae.20

b-Hydroxyamides 1 are important biosynthetic intermediatesin plants; they are also used in traditional Indian medicine andhave been shown to have good hypoglycemic activity. We havediscussed a possible biosynthetic pathway to enamides 2 and oxaz-olines 320–22 (Scheme 1).

Following our work, various other methods leading to the syn-thesis of optically active (R)-(�)-tembamide and (R)-(�)-aegelinehave been reported. Kumar et al. reported on a synthesis employ-ing the Sharpless asymmetric dihydroxylation as the source ofchirality.23 Lainé et al. reported the synthesis of (R)-tembamide,(R)-aegeline, and (R)-pronethalol via the diastereoselectiveoxy-Michael addition of delta lactol anions to nitro olefins as the

key step.24 Kamal et al. enantioselectively reduced and resolvedthe b-azido alcohol from ketoazides using NaBH4/lipase enzymes,and subsequent reduction and coupling led to the desired chiraltembamide and aegeline.25 Here we report another route to

HN

H

O

HN

H

OH3CO H3CO

HO HO

(R)-(-)-tembamide (R)-(-)-aegeline

0957-4166/$ - see front matter � 2013 Elsevier Ltd. All rights reserved.http://dx.doi.org/10.1016/j.tetasy.2013.08.014

⇑ Corresponding author. Tel.: +52 (664) 623 3772; fax: +52 (664) 623 4043.E-mail address: [email protected] (R. Somanathan).

HN

OH

O

RHN

O

RO

N

R

12 3

Scheme 1. Pathway to enamides and oxazolines.

Tetrahedron: Asymmetry 24 (2013) 1297–1302


Tetrahedron: Asymmetry

journal homepage: www.elsevier .com/locate / tetasy

N-{1,2-Bis(pyridin-3-yl)-2-[(E)-(pyridin-3-yl)methylideneamino]ethyl}nicotinamide

Claudia M. Quiroa-Montalvan,a Daniel Chavez,a Reyna

Reyes-Martınez,b David Morales-Moralesb and Miguel

Parra-Hakea*

aCentro de Graduados e Investigacion del Instituto Tecnologico de Tijuana, Apdo.

Postal 1166, 22500 Tijuana, BC, Mexico, and bInstituto de Quımica, Universidad

Nacional Autonoma de Mexico, Circuito exterior, Ciudad Universitaria, Mexico, DF,

04510, Mexico

Correspondence e-mail: [email protected]

Received 10 February 2013; accepted 28 March 2013

Key indicators: single-crystal X-ray study; T = 298 K; mean �(C–C) = 0.005 A;

disorder in main residue; R factor = 0.071; wR factor = 0.198; data-to-parameter

ratio = 12.2.

In the title compound, C24H20N6O, the pyridin-3-yl groups on

the ethylene fragment are found in a trans conformation with a

C(py)—C(e)—C(e)—C(py) (py = pyridine, e = ethylene)

torsion angle of 179.2 (3)�. The dihedral angle between the

pyridine rings is 3.5 (1)�. In the crystal, N—H� � �N and C—

H� � �O C interactions form a layer arrangement parallel to

the bc plane. The compound displays disorder of the ethylene

fragment over two positions with an occupancy ratio of

0.676 (7) to 0.324 (7) that extends into the amide section of the

nicotinamide moiety.

Related literature

For supramolecular structures, see: Nyburg & Wood (1964);

House & Sadler (1973); Kocak (2000). For a related enanti-

oselective catalyst, see: Jacobsen et al. (1990); Corey & Kuhnle

(1997); Corey et al. (1989). For coordination compounds with

polypyridine ligands related to the title compound, see: Parra-

Hake et al. (2000); Cruz Enrıquez et al. (2012). For the

synthesis of analogous compounds, see: Proskurnina et al.

(2002); Tu et al. (2009); Irving & Parkins (1965).

Experimental

Crystal data

C24H20N6OMr = 408.46Monoclinic, P21=ca = 11.4868 (17) Ab = 8.7275 (13) Ac = 21.105 (3) A� = 99.857 (3)�

V = 2084.6 (5) A3

Z = 4Mo K� radiation� = 0.08 mm�1

T = 298 K0.28 � 0.26 � 0.14 mm

Data collection

Bruker SMART APEX CCDdiffractometer

Absorption correction: multi-scan(SADABS; Bruker, 2007Tmin = 0.984, Tmax = 0.992

17508 measured reflections3821 independent reflections2371 reflections with I > 2�(I)Rint = 0.050

Refinement

R[F 2 > 2�(F 2)] = 0.071wR(F 2) = 0.198S = 1.023821 reflections312 parameters48 restraints

H atoms treated by a mixture ofindependent and constrainedrefinement

��max = 0.34 e A�3

��min = �0.25 e A�3

Table 1Hydrogen-bond geometry (A, �).

D—H� � �A D—H H� � �A D� � �A D—H� � �A

N8—H8� � �N25i 0.84 (3) 2.33 (3) 3.168 (4) 174 (3)C28—H28� � �O1ii 0.93 2.25 3.163 (16) 169

Symmetry codes: (i) �xþ 1; y� 12;�zþ 1

2; (ii) �xþ 1;�yþ 1;�z.

Data collection: SMART (Bruker, 2007); cell refinement: SAINT

(Bruker, 2007); data reduction: SAINT; program(s) used to solve

structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine

structure: SHELXTL (Sheldrick, 2008); molecular graphics:ORTEP-

3 for Windows (Farrugia, 2012) and DIAMOND (Brandenburg,

2006); software used to prepare material for publication: SHELXTL

and PLATON (Spek, 2009).

This work was supported by the Direccion General de

Educacion Superior Tecnologica (DGEST) (grant No.

2785.09-P). Support from the Consejo Nacional de Ciencia y

Tecnologıa (CONACyT) in the form of a graduate scholarship

for CMQM is gratefully acknowledged. DMM would like to

acknowledge Dr Alfredo Toscano for technical assistance.

Supplementary data and figures for this paper are available from theIUCr electronic archives (Reference: ZL2533).

organic compounds

Acta Cryst. (2013). E69, o691–o692 doi:10.1107/S1600536813008544 Quiroa-Montalvan et al. o691

Acta Crystallographica Section E

Structure ReportsOnline

ISSN 1600-5368

(1RS,2RS)-4,4000-(1-Azaniumyl-2-hydroxy-ethane-1,2-diyl)dipyridinium tetra-chloridoplatinate(II) chloride

Jose J. Campos-Gaxiola,a* Jorge L. Almaral-Sanchez,a

Adriana Cruz-Enrıquez,a Herbert Hopflb and Miguel

Parra-Hakec

aFacultad de Ingenieria Mochis, Universidad Autonoma de Sinaloa, Fuente Poseidon

y Prol. A. Flores S/N, CP 81223, C.U. Los Mochis, Sinaloa, Mexico, bCentro de

Investigaciones Quimicas, Universidad Autonoma del Estado de Morelos, Av.

Universidad 1001, CP 62210, Cuernavaca, Morelos, Mexico, and cCentro de

Graduados e Investigacion en Quımica del Instituto Tecnologico de Tijuana, Blvd.

Industrial S/N, Col. Otay, CP 22500, Tijuana, B.C., Mexico


Received 5 February 2013; accepted 12 February 2013


R factor = 0.038; wR factor = 0.091; data-to-parameter ratio = 13.4.

The title compound, (C12H16N3O)[PtCl4]Cl, consists of a 4,40-(1-azaniumyl-2-hydroxyethane-1,2-diyl)dipyridinium trica-

tion, a square-planar tetrachloridoplatinate(II) dianion and a

chloride ion. In the cation, the pyridinium rings attached to

the central 1-azaniumyl-2-hydroxyethane fragment have an

anti conformation, as indicated by the central C—C—C—C

torsion angle of �166.5 (6)�, and they are inclined to one

another by 63.5 (4)�. In the crystal, the cations and anions are

linked through N—H� � �Cl and O—H� � �Cl hydrogen bonds.

There are also �–� contacts [centroid–centroid distances =

3.671 (4) and 3.851 (4) A] and a number of C—H� � �Clinteractions present, consolidating the formation of a three-

dimensional supramolecular structure.

Related literature

For potential applications of organic-inorganic hybrid mate-

rials with magnetic, optical and electrical properties, see: Yao

et al. (2010); Sanchez et al. (2011); Pardo et al. (2011); Piecha et

al. (2012). For related tetrachloroplatinate(II) compounds,

see: Fusi et al. (2012); Adarsh et al. (2010); Campos-Gaxiola et

al. (2010); Adams et al. (2005). For the synthesis of the title

ligand, see: Campos-Gaxiola et al. (2012).

Experimental

Crystal data

(C12H16N3O)[PtCl4]ClMr = 590.62Triclinic, P1a = 7.636 (2) Ab = 8.082 (2) Ac = 14.599 (4) A� = 88.689 (4)�

� = 84.240 (4)�

� = 70.148 (4)�

V = 843.1 (4) A3


T = 100 K0.50 � 0.26 � 0.12 mm

Data collection

Bruker SMART CCD area-detectordiffractometer

Absorption correction: multi-scan(SADABS; Sheldrick, 1996)Tmin = 0.092, Tmax = 0.408


Refinement



��max = 2.34 e A�3

��min = �1.98 e A�3


D—H� � �A D—H H� � �A D� � �A D—H� � �A

O1—H10� � �Cl1i 0.84 (6) 2.49 (7) 3.250 (6) 152 (6)N1—H1A� � �Cl5ii 0.86 (7) 2.32 (6) 3.148 (6) 162 (7)N1—H1B� � �Cl5iii 0.86 (5) 2.30 (6) 3.097 (7) 154 (7)N1—H1C� � �Cl2 0.86 (5) 2.50 (5) 3.214 (6) 141 (6)N1—H1C� � �Cl3 0.86 (5) 2.58 (7) 3.242 (6) 134 (6)N2—H20 � � �Cl5iv 0.84 (4) 2.45 (7) 3.088 (6) 134 (7)N2—H20 � � �Cl5v 0.84 (4) 2.69 (6) 3.272 (6) 128 (7)N3—H30 � � �Cl1vi 0.84 (6) 2.50 (6) 3.275 (6) 155 (6)N3—H30 � � �Cl4vi 0.84 (6) 2.72 (7) 3.286 (7) 127 (7)C1—H1� � �Cl1vii 0.98 2.71 3.660 (8) 163C5—H5� � �Cl3iii 0.93 2.71 3.604 (8) 162C10—H10� � �Cl3i 0.93 2.73 3.459 (8) 136C10—H10� � �Cl5v 0.93 2.74 3.308 (7) 120C11—H11� � �Cl2viii 0.93 2.64 3.449 (8) 145

Symmetry codes: (i) x� 1; yþ 1; z; (ii) x; y; z� 1; (iii) �xþ 1;�yþ 1;�zþ 1; (iv)x; yþ 1; z� 1; (v) �x;�yþ 2;�zþ 1; (vi) �xþ 1;�y;�zþ 1; (vii) x; yþ 1; z; (viii)�xþ 1;�yþ 1;�z.

Data collection: SMART (Bruker, 2000); cell refinement: SAINT-

Plus-NT (Bruker 2001); data reduction: SAINT-Plus-NT; program(s)

used to solve structure: SHELXS97 (Sheldrick, 2008); program(s)

used to refine structure: SHELXL97 (Sheldrick, 2008); molecular

graphics: ORTEP-3 for Windows (Farrugia, 2012) and Mercury

(Macrae et al., 2008); software used to prepare material for publica-

tion: publCIF (Westrip, 2010).

This work was supported financially by the Universidad

Autonoma de Sinaloa (PROFAPI 2012/032).

Supplementary data and figures for this paper are available from theIUCr electronic archives (Reference: SU2560).

metal-organic compounds

Acta Cryst. (2013). E69, m157–m158 doi:10.1107/S160053681300425X Campos-Gaxiola et al. m157



ISSN 1600-5368

electronic reprint

Bis[(1RS,2RS)-4,4000-(1-azaniumyl-2-hydroxyethane-1,2-diyl)dipyridinium]tris[tetrachloridopalladate(II)]

Jose J. Campos-Gaxiola,a* Alberto Baez-Castro,a Adriana

Cruz-Enriquez,a Herbert Hopflb and Miguel Parra-Hakec





Graduados del Instituto Tecnologico de Tijuana, Blvd. Industrial S/N, Col. Otay,

CP 22500, Tijuana, B.C., Mexico


Received 10 December 2012; accepted 13 December 2012



The asymmetric unit of the title compound, (C12H16N3O)2-

[PdCl4]3, consists of a 4,40-(1-azaniumyl-2-hydroxyethane-1,2-

diyl)dipyridinium dication and one and a half tetra-

chloridopalladate(II) anions; the latter has inversion

symmetry. In the cation, the pyridinium rings attached to the

central 1-azaniumyl-2-hydroxyethane fragment show an anti

conformation, as indicated by the central C—C—C—C torsion

angle of �178.1 (4)�, and they are inclined to one another by

25.7 (2)�. In the crystal, the cations and anions are linked

through N—H� � �Cl and O—H� � �Cl hydrogen bonds. There

are also �–� contacts [centroid–centroid distance =

3.788 (3) A] and a number of C—H� � �O and C—H� � �Clinteractions are present, consolidating the formation of a

three-dimensional structure.

Related literature

For potential applications of organic–inorganic hybrid mate-

rials with magnetic, optical and electrical properties, see: Yao

et al. (2010); Sanchez et al. (2011); Pardo et al. (2011). For

related tetrachloridopalladate(II) compounds, see: Kumar et

al. (2006); Adams et al. (2005, 2006); Maris (2008). For the

synthesis of the ligand, see: Campos-Gaxiola et al. (2012).

Experimental

Crystal data

(C12H16N3O)2[PdCl4]3Mr = 1181.16lTriclinic, P1a = 7.6970 (7) Ab = 7.7339 (7) Ac = 15.7254 (13) A� = 84.541 (2)�

� = 81.314 (2)�

� = 78.717 (1)�

V = 905.40 (14) A3


T = 100 K0.29 � 0.22 � 0.17 mm

Data collection




Refinement



��max = 1.23 e A�3

��min = �0.48 e A�3


D—H� � �A D—H H� � �A D� � �A D—H� � �A

O1—H10� � �Cl5 0.84 (4) 2.22 (4) 3.047 (3) 168 (4)N1—H1A� � �Cl3i 0.86 (3) 2.62 (2) 3.355 (4) 145 (4)N1—H1A� � �Cl4i 0.86 (3) 2.54 (4) 3.203 (4) 135 (4)N1—H1B� � �Cl6ii 0.86 (4) 2.49 (5) 3.310 (4) 160 (4)N1—H1C� � �Cl1ii 0.86 (2) 2.22 (2) 3.080 (3) 177 (6)N2—H20 � � �Cl2iii 0.84 (4) 2.35 (4) 3.137 (4) 157 (4)N3—H30 � � �Cl5iv 0.84 (4) 2.44 (4) 3.150 (4) 143 (4)N3—H30 � � �Cl6iv 0.84 (4) 2.71 (5) 3.353 (4) 135 (3)C4—H4� � �Cl5v 0.95 2.64 3.406 (5) 139C6—H6� � �O1vi 0.95 2.54 3.454 (6) 161C9—H9� � �Cl3ii 0.95 2.78 3.599 (5) 145C10—H10� � �Cl2vii 0.95 2.75 3.649 (5) 159C11—H11� � �Cl1 0.95 2.61 3.486 (5) 154C11—H11� � �Cl1viii 0.95 2.80 3.422 (5) 124

Symmetry codes: (i) x� 1; yþ 1; z; (ii) x� 1; y; z; (iii) x; y� 1; z; (iv) �x;�yþ 2;�z;(v) �x;�yþ 1;�z; (vi) x; yþ 1; z; (vii) �x;�yþ 1;�zþ 1; (viii)�xþ 1;�yþ 1;�zþ 1.


Plus (Bruker, 2001); data reduction: SAINT-Plus; program(s) used to

solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to

refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics:

ORTEP-3 (Farrugia, 2012) and Mercury (Macrae et al., 2008); soft-

ware used to prepare material for publication: publCIF (Westrip,

2010).

This work was financially supported by the Universidad

Autonoma de Sinaloa (PROFAPI 2012/032).



Acta Cryst. (2013). E69, m65–m66 doi:10.1107/S1600536812050817 Campos-Gaxiola et al. m65



ISSN 1600-5368

electronic reprint

4-Hydroxy-6-methylpyridin-2(1H)-one

Hector Reyes, Gerardo Aguirre and Daniel Chavez*

Centro de Graduados e Investigacion del Instituto Tecnologico de Tijuana, Apdo.

Postal 1166, 22500, Tijuana, B.C., Mexico


Received 15 July 2013; accepted 29 August 2013



In the crystal structure of the title compound, C6H7NO2, N—

H� � �O and O—H� � �O hydrogen bonds link the molecules,

forming a zigzag array along [001] and a layer structure

parallel to the ab plane.

Related literature

For the potential of related compounds in anti-HIV treatment,

see: De Clercq (2005); Dolle et al. (1995); Medina-Franco et al.

(2007).

Experimental

Crystal data

C6H7NO2

Mr = 125.13Monoclinic, P21=na = 4.7082 (5) A

b = 12.2988 (8) Ac = 10.0418 (7) A� = 91.303 (7)�

V = 581.32 (8) A3


T = 298 K0.65 � 0.20 � 0.18 mm

Data collection

Bruker P4 diffractometerAbsorption correction: scan

(XSCANS; Siemens, 1996)Tmin = 0.216, Tmax = 0.259

2445 measured reflections1701 independent reflections

1269 reflections with I > 2�(I)Rint = 0.0263 standard reflections every 97reflectionsintensity decay: 9.4%

Refinement

R[F 2 > 2�(F 2)] = 0.050wR(F 2) = 0.160S = 1.061701 reflections

82 parametersH-atom parameters constrained��max = 0.32 e A�3

��min = �0.25 e A�3


D—H� � �A D—H H� � �A D� � �A D—H� � �A

N1—H1A� � �O1i 0.86 1.98 2.835 (2) 175O2—H2B� � �O1ii 0.82 1.79 2.609 (2) 180

Symmetry codes: (i) �x þ 2;�y þ 2;�z þ 1; (ii) x � 12;�y þ 3

2; z � 12.

Data collection: XSCANS (Siemens, 1996); cell refinement:

XSCANS; data reduction: XSCANS; program(s) used to solve


structure: SHELXL97 (Sheldrick, 2008); molecular graphics:

SHELXTL (Sheldrick, 2008); software used to prepare material for

publication: SHELXTL.

We gratefully acknowledge support for this project by the

Direccion General de Educacion Superior Tecnologica

(DGEST grants 2535.09P and 3604.10-P).

Supplementary data and figures for this paper are available from theIUCr electronic archives (Reference: IM2437).

References

De Clercq, E. (2005). J. Med. Chem. 48, 1297–1313.Dolle, V., Fan, E., Nguyen, C. H., Aubertin, A.-M., Kirn, A., Andreola, M. L.,

Jamieson, G., Tarrago-Litvak, L. & Bisagni, E. (1995). J. Med. Chem. 38,4679–4686.

Medina-Franco, J. L., Martinez-Mayorga, K., Juarez-Gordiano, C. & Castillo,R. (2007). ChemMedChem, 2, 1141–1147.

Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.Siemens (1996). XSCANS. Siemens Analytical X-ray Instruments Inc.,

Madison, Wisconsin, USA.

organic compounds

o1534 Reyes et al. doi:10.1107/S1600536813024240 Acta Cryst. (2013). E69, o1534



ISSN 1600-5368

electronic reprint

(2-tert-Butyl-5-hydroxymethyl-1,3-dioxan-5-yl)methanol

Berenice Vargas,a Amelia Olivas,b Gerardo Aguirrea and

Domingo Madrigala*

aCentro de Graduados e Investigacion del Instituto Tecnologico de Tijuana, Apdo.

Postal 1166, 22500, Tijuana, B.C., Mexico, and bCentro de Ciencias de la Materia

Condensada, Universidad Nacional Autonoma de, Mexico. Km. 107 Carretera

Tijuana-Ensenada, Ensenada, BC, CP 22800, Mexico


Received 26 May 2012; accepted 4 June 2012



In the title compound, C10H20O4, the dioxane ring adopts a

chair conformation. The tert-butyl group occupies an equa-

torial position, and is staggered with respect to the O atoms of

the dioxane ring. In the crystal, molecules are connected by

O—H� � �O hydrogen-bonds into zigzag chains of R44(8) and

R22(12) ring motifs that run parallel to the a axis.

Related literature

For background information on the synthesis and properties

of 1,3-dioxanes, see: Anderson (1967); Bailey et al. (1978);

Juaristi et al. (1987, 1989); Vazquez-Hernandez et al. (2004).

For the crystal structure of a similar compound, see: Zhang et

al. (2010).

Experimental

Crystal data

C10H20O4

Mr = 204.26Triclinic, P1a = 5.8337 (10) Ab = 6.1408 (9) A

c = 17.941 (3) A� = 81.468 (12)�

� = 87.335 (14)�

� = 62.606 (13)�

V = 564.16 (15) A3


T = 298 K0.73 � 0.63 � 0.20 mm

Data collection

Siemens P4 diffractometerAbsorption correction: empirical

(using intensity measurements)(XEMP in SHELXTL; Sheldrick,2008)Tmin = 0.335, Tmax = 0.466

3581 measured reflections

3283 independent reflections2593 reflections with I > 2�(I)Rint = 0.0133 standard reflections every 97

reflectionsintensity decay: 5.8%

Refinement



��min = �0.29 e A�3


D—H� � �A D—H H� � �A D� � �A D—H� � �A

O3—H3A� � �O4i 0.82 1.94 2.7346 (14) 162O4—H4A� � �O3ii 0.82 1.91 2.6878 (15) 159

Symmetry codes: (i) �x;�yþ 1;�z; (ii) xþ 1; y; z.




structure: SHELXL97 (Sheldrick, 2008); molecular graphics: XP in

SHELXTL (Sheldrick, 2008) and Mercury (Macrae et al., 2006);

software used to prepare material for publication: SHELXL97.

Support for this work from the Direccion General de

Educacion Superior Tecnologica (DGEST) Grant 2574.09P, is

gratefully acknowledged.

Supplementary data and figures for this paper are available from theIUCr electronic archives (Reference: PK2419).

References

Anderson, J. E. (1967). J. Chem. Soc. B pp. 712–716.Bailey, W. F., Connon, H., Eliel, E. L. & Wiberg, K. B. (1978). J. Am. Chem.

Soc. 100, 2202–2209.Juaristi, E., Gordillo, B., Martinez, R. & Toscano, R. A. (1989). J. Org. Chem.

54, 5963–5967.Juaristi, E., Martinez, R., Mendez, R., Toscano, R. A., Soriano-Garcia, M.,

Eliel, E. L., Petsom, A. & Glass, R. S. (1987). J. Org. Chem. 52, 3806–3811.Macrae, C. F., Edgington, P. R., McCabe, P., Pidcock, E., Shields, G. P., Taylor,

R., Towler, M. & van de Streek, J. (2006). J. Appl. Cryst. 39, 453–457.Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.Siemens (1996). XSCANS Siemens Analytical X-ray Instruments Inc.,

Madison, Wisconsin, USA.Vazquez-Hernandez, M., Rosquete-Pina, G. A. & Juaristi, E. (2004). J. Org.

Chem. 69, 9063–9072.Zhang, M., Yuan, X.-Y. & Ng, S. W. (2010). Acta Cryst. E66, o2917.

organic compounds

Acta Cryst. (2012). E68, o2049 doi:10.1107/S160053681202541X Vargas et al. o2049



ISSN 1600-5368

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Supramolecular networks in organic–inorganic hybrid materials fromperchlorometalate(II) salts and 2,4,5-tri(4-pyridyl)imidazole{

Adriana Cruz Enrıquez,a Marely G. Figueroa Perez,a Jorge L. Almaral Sanchez,a Herbert Hopfl,b

Miguel Parra-Hakec and Jose J. Campos-Gaxiola*a

Received 1st April 2012, Accepted 11th May 2012

DOI: 10.1039/c2ce25476j

Three organic–inorganic hybrid compounds have been prepared by combination of the tripyridinium

imidazole of cation [2,4,5-tri(4-pyridyl)imidazole] (L) and a series of perhalometallate anions to give,

namely [H3L(CuCl4)]Cl (1), [(H3L)2(PdCl4)3]?4H2O (2) and [(H3L)2(PtCl4)3]?4H2O (3), which have

been structurally characterized by single-crystal X-ray diffraction analysis, showing that the hydrogen

bonding interactions of the resulting 1D, 2D, and 3D networks contain at least one of the following

synthons: X–H…ClnM2 [X = C, N, N+; n = 0,1,2; M = Cu(II), Pd(II), Pt(II)] The dimensions are

enhanced further by strong X–H…Cl2 (C, N+) and OH…ClnM2 [n = 1,2; M = Pd(II), Pt(II)]

hydrogen bonds. Additional weak C–H…O, p–p stacking and Cl…Cl interactions stabilize the crystal

structures further.

1. Introduction

The engineering of novel materials via non-covalent synthesis has

emerged as a very attractive potential area of research because

of their fascinating assemblies and range of applications. The

field of crystal engineering, a sub-discipline of supramolecular

chemistry, is concerned with the construction of crystalline

materials from molecules or ions using non-covalent interac-

tions.1 For the synthesis of crystal structures by design, the

assembly of molecular units in predefined arrangements is a key

goal.2 The means to reach this goal is the identification and

application of reliable synthons, which can control molecular

aggregation and lead to crystal structures with at least partly

controlled structures containing sheets, ribbons and other

desired motifs in the pattern.3 Hydrogen bonds are the principal

interactions used in this strategy, because they are strong and

directional.4 Deliberate syntheses of hydrogen bond-based

organic–inorganic hybrid materials have also gained widespread

interest because of their structural, magnetic, optical and

electrical properties.5 Hydrogen bonding interactions with metal

salts to control the crystal structure product have also recently

received attention.6 Brammer and Orpen and co-workers have

contributed to this area utilizing supramolecular synthons such

as charge-assisted N–H…Cl hydrogen bonds to form organic–

inorganic hybrid crystalline solids containing organic cations

and anionic metal complexes.7,8 In these assemblies, the cations

are usually protonated nitrogen bases with peripheral functional

groups, such as bipyridinium moieties, and the anionic metal

complexes generally refer to the primary coordination sphere of

metal ions containing halogens. Typical bond acceptors are, for

example, [MCl4]22 and [MCl6]22. Since then, deliberate efforts

have been made to construct intriguing supramolecular assem-

blies using metal halide-based hydrogen bonds. In these studies,

organic molecules containing protonated ring nitrogens +N–H

(either aromatic or alicyclic) and inorganic perhalometallate salts

(MX4; M = transition metals, X = halogen, mainly Cl) have been

used as hydrogen-bond donors and acceptors, respectively.9

For further understanding of the structure formation princi-

ples that direct the interaction of pyridinium derivatives with

metal perhalides, we have aimed to prepare and characterize a

range of crystalline hybrid materials using triply-protonated

2,4,5-tri(4-pyridyl)imidazole L as the organic component,

[H3L]3+, and inorganic perchlorometallate salts derived from

Cu(II), Pd(II) and Pt(II), [MCl4]22, as the inorganic component.

The organic tecton [H3L]3+ offers the possibility of incorporating

approximate 3-fold symmetry into the hydrogen-bonded net-

work, and it can be expected that it acts as three-connected node

based on exotopic pyridinium functions. The imidazole nitrogen

aFacultad de Ingenierıa Mochis, Universidad Autonoma de Sinaloa, Fuentede Poseidon y Prol. A. Flores S/N, C.P. 81223, C.U. Los Mochis, Sinaloa,Mexico. E-mail: [email protected]; Fax: (52) 668 8127641;Tel: (52) 668 8127641bCentro de Investigaciones Quımicas, Universidad Autonoma del Estado deMorelos, Av. Universidad 1001, C.P. 62209, Cuernavaca, Morelos,Mexico. E-mail: [email protected]; Fax: (52) 777 329 79 97;Tel: (52) 777 329 79 97cCentro de Graduados e Investigacion, Instituto Tecnologico de Tijuana,Apartado Postal 1166, C.P. 22000, Tijuana, Baja California, Mexico.E-mail: [email protected]; Fax: (52) 664 623 40 43;Tel: (52) 664 623 37 72{ Electronic supplementary information (ESI) available: ORTEP dia-grams showing the structures of compounds 1, 2 and 3, table of selectedbond lengths and angles of compounds 1, 2 and 3, table of hydrogenbonding geometries, figure showing the 3D supramolecular networks of 2and 3, figure showing TGA graphs of compounds 1–3. CCDC referencenumbers 873200–873202. For ESI and crystallographic data in CIF orother electronic format see DOI: 10.1039/c2ce25476j

CrystEngComm Dynamic Article Links

Cite this: CrystEngComm, 2012, 14, 6146–6151

www.rsc.org/crystengcomm PAPER

6146 | CrystEngComm, 2012, 14, 6146–6151 This journal is � The Royal Society of Chemistry 2012

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ishe

d on

17

May

201

2. D

ownl

oade

d by

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ity o

f Pi

ttsbu

rgh

on 3

1/10

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http://pubs.rsc.org/en/journals/journal/CE

http://pubs.rsc.org/en/journals/journal/CE?issueid=CE014019

Two coordination modes of CuII in abinuclear complex with N-(pyridin-2-yl-carbonyl)pyridine-2-carboxamidateligands

Jose J. Campos-Gaxiola,a* David Morales-Morales,b

Herbert Hopfl,c Miguel Parra-Haked and Reyna

Reyes-Martınezb

aFacultad de Ingenierıa Mochis, Universidad Autonoma de Sinaloa, Fuente de

Poseidon y Prol. Angel Flores, 81223 Los Mochis, Sinaloa, Mexico, bInstituto de

Quımica, Universidad Nacional Autonoma de Mexico, Circuito exterior, Ciudad

Universitaria, Mexico, D.F., 04510, Mexico, cCentro de Investigaciones Quımicas,

Universidad Autonoma del estado de Morelos, Av. Universidad 1001, 62209

Cuernavaca, Morelos, Mexico, and dCentro de Graduados e Investigacion del

Instituto Tecnologico de Tijuana, Apdo. Postal 1166, 22500 Tijuana, BC, Mexico


Received 2 August 2012; accepted 6 September 2012



In the title dinuclear complex, (acetonitrile-1�N)[�-N-(pyri-

din-2-ylcarbonyl)pyridine-2-carboxamidato-1:2�5N,N0,N00:-

O,O0][N-(pyridin-2-ylcarbonyl)pyridine-2-carboxamidato-

2�3N,N0,N00]bis(trifluoromethanesulfonato-1�O)dicopper(II),

[Cu2(C12H8N3O2)2(CF3O3S)2(CH3CN)], one of the CuII ions is

five-coordinated in a distorted square-pyramidal N3O2

environment provided by two N-(pyridin-2-ylcarbonyl)-

pyridine-2-carboxamidate (bpca) ligands, while the second

CuII ion is six-coordinated in a distorted octahedral N4O2

environment provided by one bpca ligand, two trifluoro-

methansulfonate ligands and one acetonitrile molecule. Weak

intermolecular C—H� � �O and C—H� � �F hydrogen bonds and

�–� stacking interactions with centroid–centroid distances of

3.6799 (15) and 3.8520 (16) A stabilize the crystal packing and

lead to a three-dimensional network.

Related literature

For complexes of divalent metal ions with the N-(pyridin-2-

ylcarbonyl)pyridine-2-carboxamidate (bpca) ligand, see:

Chowdhury et al. (2007); Folgado et al. (1988); Ha (2010,

2011); Halder et al. (2010); Miguel et al. (2009). For complexes

of trivalent metal ions with the bpca ligand, see: Li et al.

(2011); Sugimoto et al. (2002); Wocadlo et al. (1993). For

electrochemical and magnetic studies for example complexes

of Cu(II), see: Cangussu de Castro Gomes et al. (2008);

Kajiwara et al. (2002). For the synthesis of the ligand, see:

Larter et al. (1998).

Experimental

Crystal data

[Cu2(C12H8N3O2)2(CF3O3S)2-(C2H3N)]

Mr = 918.70Triclinic, P1a = 8.9726 (7) Ab = 10.0569 (8) Ac = 18.3689 (15) A� = 82.573 (1)�

� = 83.802 (1)�

� = 82.222 (1)�

V = 1621.6 (2) A3


T = 100 K0.32 � 0.24 � 0.18 mm

Data collection


Absorption correction: multi-scan(SADABS; Bruker, 2001)Tmin = 0.638, Tmax = 0.768


Refinement


497 parametersH-atom parameters constrained�max = 0.83 e A�3

�min = �0.50 e A�3


D—H� � �A D—H H� � �A D� � �A D—H� � �A

C2—H2� � �O9i 0.95 2.57 3.448 (3) 154C4—H4� � �O1ii 0.95 2.53 3.210 (4) 128C10—H10� � �F5iii 0.95 2.54 3.239 (3) 130C21—H21� � �O1iv 0.95 2.48 3.257 (3) 140C21—H21� � �O2iv 0.95 2.37 3.203 (3) 147C22—H22� � �O10v 0.95 2.48 3.400 (3) 163

Symmetry codes: (i) xþ 1; y� 1; z; (ii) �xþ 2;�y;�zþ 1; (iii)�x þ 1;�yþ 2;�zþ 1; (iv) �xþ 2;�yþ 1;�zþ 1; (v) xþ 1; y; z.





SHELXTL (Sheldrick, 2008) and DIAMOND (Brandenburg, 2006);

software used to prepare material for publication: SHELXTL and

PLATON (Spek, 2009).

This work was supported by the Universidad Autonoma de

Sinaloa, Mexico (DGIP.PROFAPI-2010–024).

Supplementary data and figures for this paper are available from theIUCr electronic archives (Reference: WM2669).


m1280 Campos-Gaxiola et al. doi:10.1107/S1600536812038330 Acta Cryst. (2012). E68, m1280–m1281



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2440 Current Organic Chemistry, 2012, 16, 2440-2461

Bifunctional Organocatalysts in the Asymmetric Michael Additions of Carbonylic

Compounds to Nitroalkenes

Ratnasamy Somanathan,1* Daniel Chávez,

1 Felipe Antonio Servín,

1 José Alfonso Romero,

1 Angélica

Navarrete,1 Miguel Parra-Hake,

1 Gerardo Aguirre,

1 Cecilia Anaya de Parrodi,

2 and Jorge González

3

1Centro de Graduados e Investigación, Instituto Tecnológico de Tijuana, Apartado Postal 1166, Tijuana, B. C. 22000 México

2Departamento de Ciencias Químico-Biológicas, Universidad de las Américas-Puebla, Ex Hacienda Santa Catarina Mártir s/n

Cholula, Puebla, 72810, México

3Facultad de Ciencias Químicas, Universidad de Colima, Km 9 Carretera Coquimatlán, Colima, Coquimatlán, Col. 28400, México

Abstract: In the past decade, the organocatalytic asymmetric Michael addition has emerged as one of the most important carbon-carbon

bond forming reactions in organic chemistry. As an example, the conjugated addition of ketones to nitroolefins has received extensive at-

tention, since the resulting nitroalkanes are versatile intermediates in which the nitro group can be transformed into various useful func-

tional groups. Furthermore, the reaction has the ability to introduce two vicinal stereogenic centers in a single step. Stimulated by the

seminal work of List, Barbas and coworkers, several research groups have focused on the development of novel bifunctional organocata-

lysts bearing amine and hydrogen donor functionalities.

This review will focus on the development of multifunctional chiral organocatalysts derived from proline, pyrrolidine, cinchona alka-

loids, thioureas and sulfonamides in the asymmetric Michael addition to nitroalkenes.

Keywords: Asymmetric, Bifunctional, Ketones, Michael Additions, Nitroalkenes, Organocatalysts.

INTRODUCTION

The asymmetric conjugate addition is one of the most powerful

bond-forming reactions to construct enantioenriched, highly func-

tionalized carbon skeletons for the total synthesis of natural bio-

logically active compounds [1,2]. Since this reaction often leads to

the formation of a stereogenic center, considerable effort has been

devoted to the development of efficient stereoselective methods [3].

Its strategic importance is evident by considering that Michael addi-

tion can represent the initiating step of more complex inter-and

intramolecular tandem process [4-8]. Among the different possible

strategies (Scheme 1), diasteroselective additions to chiral Michael

acceptors have been firmly established [3]. Similarly, Michael addi-

tion of chirally modified nucleophile to prochiral acceptor has also

been studied with chiral organometallic compounds bearing chiral

ligands e.g., chiral cuprates [3]. Finally, Michael addition involving

a catalyst, such as organometallic (transition metal-chiral ligand) or

organocatalysts (small organic molecules) has received much atten-

tion in recent years [9-20].

Among the various organocatalysts discovered, hydrogen-

bonding catalysts have recently emerged as an important strategy in

the asymmetric aldol and Michael reactions. Many hydrogen-

bonding catalysts have been designed based on inspiration drawn

from molecular recognition processes exhibited in enzyme cata-

lyzed reactions [21]. Enzymes are conformationally flexible, in

contrast, the vast majority of hydrogen-bonding catalysts reported

to date are derived from rigid chiral backbones in order to reduce

the number of distinct possible diasteromeric transition states that

can be involved [12, 15, 21-24].

* Address correspondence to this author at the Centro de Graduados e Investigación,

Instituto Tecnológico de Tijuana, Apartado Postal 1166, Tijuana, B. C. 22000 México;

Tel: +52 664 6233772; Fax: +52 664 6234043; E-mail: [email protected]

R'

EWG Nu

R'EWG

Nu

*

** chiral

R'

EWGNu-ML

R'

EWG

Nu

*

* chiral

R'

EWGNu

R'

EWG

Nu

*achiral

achiral

MX* or L*

Catalytic enantioselective Michael addition using a chiral catalyst

Diasteroselective Michael addition to a chiral acceptor

Enantioselective Michael addition of a chiral donor

*

Scheme 1. Steroselective additions to Michael acceptors.

Since a tremendous amount of literature exists on asymmetric

Michael addition using organocatalysts, for the reader’s conven-

ience we have categorized the reactions according to the type of

catalyst used.

I. Proline, proline derived amides, and peptides.

II. Pyrrolidine derived amines and other amines

III. Cinchona alkaloids

IV. Thioureas

V. Sulfonamides

VI. Immobilized organocatalysts

1875-5348/12 $58.00+.00 © 2012 Bentham Science Publishers

Theoretical calculations on rhodium(III)-Cp� catalyzed asymmetric transferhydrogenation of acetophenone using monosulfonamide ligands derived from(1R,2R)-diaminocyclohexane

Domingo Madrigal a,⇑, Andrew L. Cooksy b,⇑, Ratnasamy Somanathan a

a Centro de Graduados e Investigación, Instituto Tecnológico de Tijuana. Apartado Postal 1166, Tijuana, BC 22000, Mexicob Department of Chemistry and Biochemistry, San Diego State University, San Diego, CA 92182-1030, United States


Article history:Received 22 June 2012Received in revised form 8 August 2012Accepted 19 August 2012Available online 29 August 2012

Keywords:Density functional theoryAsymmetric transfer hydrogenationCatalysisRhodium and ruthenium complex

a b s t r a c t

Chiral secondary alcohols are valuable synthetic intermediates in the pharmaceutical industry in makingcomplex biologically active molecules. Noyori’s ATH of aromatic ketones using Ru(II)-monotosylated dia-mine complexes are catalyst is one the useful methods to induce high yields and enantioselectivities inthe formation of the secondary alcohol. Using Ru(II) as catalyst, the calculated energy difference betweenthe Re and Si transition state were found to be 2.1 kcal/mol. We found Rh(III)Cp�-monotosylated diaminecomplexes gave better results in aqueous conditions compared to the Ru(II) complexes in the ATH of aro-matic ketones. Here we show a similar calculation for the transition state involving Rh(III), which givesthe energy difference between the Re and Si to be 3.9 kcal/mol.


1. Introduction

Chiral secondary alcohols are valuable intermediates in the syn-thesis of physiologically active pharmaceuticals [1], agrochemical[2] and flavor ingredients [3]. In response to the increasing demandfor optically pure secondary alcohols, Noyori et al. reported the useof monotosylated diamines and 1,2-aminoalcohols as ligands forthe ruthenium(II) catalyzed asymmetric transfer hydrogenation(ATH) of ketones, using isopropanol as the hydride source (Eq.(1)) [4]. Since this discovery, a significant number of new-ligandruthenium(II), rhodium(III), and iridium(I) complexes have beenused as catalysts in the ATH of ketones using isopropanol/KOH,aqueous sodium formate and formic acid as proton donors [5–9].

R

R1

OR

R1

OH

H

lC hRH2N

N Ts

isopropanol/KOH

HCOOH/NEt3or aq NaOOCH

RuH2N N SO2ArCl Ru

H2N O

Me Ph

Cl

ð1Þ

Noyori et al. also reported a detailed theoretical study using abinitio MO calculation at the MP4/MP2 level to predict the mecha-nism involving chiral Ru(II)-arene diamine-complex and acetophe-none shown in Scheme 1 [10]. Their experimental and theoreticalfindings showed the transfer hydrogenation takes place by a novelbifunctional mechanism, where neither the carbonyl oxygen nor analcoholic oxygen interacts with the metallic center throughout thehydrogen transfer. The authors used RuCl[(S,S)-NTs(C6H5)NH2](g6-arene), 2-propanol/KOH base system to reduce acetophenone.The hydridic RuH and protic NH are simultaneously delivered tothe C@O via a six-member pericyclic mechanism, to give S-phenylethanol.

The origin of the enantioselctivity comes from the Ru(II)-arenering proton interacting with the p cloud of the phenyl ring of theacetophenone in the Re enantiomer, which is absent when themethyl and phenyl are reversed (Fig. 1). The energy differencebetween the TS of the favored Re and the TS of the unfavored Siis calculated to be 2.1 kcal/mol.

2. Results and discussion

Recently a number of reports have appeared where ATH can becarried out in aqueous media using sodium formate as the hydridesource in conjunction with Ru(II), Rh(III) and Ir(III)–complexed tochiral monosulfonamide ligands [9]. Interestingly, in aqueous so-dium formate the rate of the ATH reaction was accelerated. Xiaoet al. reported that water molecule (in aqueous sodium formate)plays a role by complexing to the Ru(II)monosulfonamide-

2210-271X/$ - see front matter � 2012 Elsevier B.V. All rights reserved.http://dx.doi.org/10.1016/j.comptc.2012.08.021

⇑ Corresponding authors. Tel.: +1 619 594 5571; fax: +1 619 594 4634 (A.L.Cooksy).

E-mail address: [email protected] (A.L. Cooksy).

Computational and Theoretical Chemistry 999 (2012) 105–108

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http://dx.doi.org/10.1016/j.comptc.2012.08.021

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Tetrakis(l-acetato-j2O:O000)-bis[(3-pyridinecarboxaldehyde-jN000)]-dicopper(II)(Cu—Cu)

Adriana Cruz-Enriquez,a Alberto Baez-Castro,a Herbert

Hopfl,b Miguel Parra-Hakec and Jose J. Campos-Gaxiolaa*





Graduados del Instituto Tecnologico de Tijuana, Blvd. Industrial S/N Col. Otay,

CP 22500, Tijuana, B.C., Mexico


Received 27 September 2012; accepted 30 September 2012



The binuclear title compound, [Cu2(CH3CO2)4(C6H5NO)], is

located about a center of inversion. The CuII atoms are

connected [Cu—Cu = 2.6134 (5) A] and bridged by four

acetate ligands. Their distorted octahedral coordination

geometry is completed by a terminal pyridine N atom of a

3-pyridincarboxaldehyde ligand. In the crystal, the complex

molecules are linked by C—H� � �O hydrogen bonds, forming

two-dimensional networks lying parallel to the ab plane. These

networks are linked via C—H� � �O hydrogen bonds involving

inversion-related 3-pyridinecarboxaldehyde ligands, forming a

three dimensional supramolecular architecture.

Related literature

For related paddle-wheel structures, see: Aakeroy et al. (2003);

Sieron (2004); Fairuz et al. (2011); Trivedi et al. (2011). For

Cu� � �Cu separations in related structures, see: Seco et al.

(2004); Asem et al. (2011).

Experimental

Crystal data

[Cu2(C2H3O2)4(C6H5NO)]Mr = 577.48Triclinic, P1a = 7.4099 (6) Ab = 8.4298 (7) Ac = 10.0254 (8) A� = 100.353 (1)�

� = 108.975 (1)�

� = 98.679 (1)�

V = 567.61 (8) A3


T = 100 K0.48 � 0.21 � 0.17 mm

Data collection




Refinement



��min = �0.36 e A�3


D—H� � �A D—H H� � �A D� � �A D—H� � �A

C3—H3� � �O1i 0.93 2.43 3.262 (4) 148C6—H6� � �O3ii 0.93 2.56 3.449 (4) 159C8—H8B� � �O3iii 0.96 2.60 3.542 (3) 168C10—H10C� � �O2iv 0.96 2.48 3.420 (4) 167

Symmetry codes: (i) �xþ 2;�y þ 2;�zþ 1; (ii) �xþ 2;�yþ 1;�zþ 2; (iii)�x þ 1;�y;�zþ 2; (iv) x� 1; y; z.


Plus-NT (Bruker, 2001); data reduction: SAINT-Plus-NT;

program(s) used to solve structure: SHELXS97 (Sheldrick, 2008);

program(s) used to refine structure: SHELXL97 (Sheldrick, 2008);

molecular graphics: ORTEP-3 (Farrugia, 2012) and Mercury (Macrae

et al. 2008); software used to prepare material for publication:

publCIF (Westrip, 2010).

This work was supported financially by the Universidad

Autonoma de Sinaloa (PROFAPI 2011/033). ABC thanks the

Consejo Nacional de Ciencia y Tecnologia (CONACYT) for

support in the form of a scholarship.


References

Aakeroy, C. B., Beatty, A. M., Desper, J., O’Shea, M. & Valdes-Martınez, J.(2003). Dalton Trans. pp. 3956–3962.

Asem, S., Buchanan, R. M. & Mashuta, M. S. (2011). Acta Cryst. E67, m1892–m1893.

Bruker (2000). SMART. Bruker AXS Inc., Madison, Wisconsin, USA.Bruker (2001). SAINT-Plus-NT. Bruker AXS Inc., Madison, Wisconsin, USA.Fairuz, Z. A., Aiyub, Z., Abdullah, Z., Ng, S. W. & Tiekink, E. R. T. (2011).

Acta Cryst. E67, m1636.Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849–854.Macrae, C. F., Bruno, I. J., Chisholm, J. A., Edgington, P. R., McCabe, P.,

Pidcock, E., Rodriguez-Monge, L., Taylor, R., van de Streek, J. & Wood,P. A. (2008). J. Appl. Cryst. 41, 466–470.


Acta Cryst. (2012). E68, m1339–m1340 doi:10.1107/S1600536812041074 Cruz-Enriquez et al. m1339



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Review

Mechanism of taste; electrochemistry, receptors and signal transduction

Peter Kovacic a,*, Ratnasamy Somanathan a,b

aDepartment of Chemistry and Biochemistry, San Diego State University, San Diego CA 92182, USAbCentro de Graduados e Investigación del Instituto Tecnológico de Tijuana, Apdo postal 1166, Tijuana, B.C. Mexico


Article history:Received 10 January 2011Received in revised form28 September 2011Accepted 28 September 2011Available online 17 October 2011

Keywords:TasteMechanismReceptorCell signalingNeurons

a b s t r a c t

This report describes a novel mechanistic approach based on electrochemistry, receptors and signaltransduction. Part A presents limited correlation between dipole moments and associated electrostaticfields (EFs), and taste. For Part B, binding of the tastant to the receptor results in interaction of the ligandEF with those of the protein receptor. Part C addresses passage of the message by the altered EF to thegustatory neurons, involving electrical effects and signal transduction. Insight is gained from externalelectrical stimulus. Part D represents the final step in which the electrical signal is converted to perceivedtaste in the brain.


1. Introduction

Recent reviews document the contribution of important invol-vement of the combination of receptors, cell signaling and elec-trochemistry in many aspects of biology and medicine [1e9]. It isreasonable to apply this approach, as an extension, to the mecha-nism of taste based on extensive evidence. Although there has beenconsiderable research involving these elements in the gustatorysystem, the proposed theory represents a novel, unifying mecha-nistic framework. Electrochemistry plays an important role inliving systems, withmost attention centered on the central nervoussystem (CNS). Recently, electrical effects were proposed to beinvolved in cell signaling [4] and receptoreligand activity [5]. In thereceptor case, electrostatic fields introduced by ions and dipoles ofthe ligands are designated as important elements in the commu-nication system.

When nature finds a useful theme, it is usually made use ofrepeatedly. For example, consider functional groups: amide (protein),acetal (carbohydrate), ester (lipid), the steroid skeleton (hormones)and the isoprene unit (terpenes and natural rubber), as well asreaction processes, such as, involvement of electrostatics, electrontransfer, enzymes, cell signaling and reactive oxygen species. Theliterature is rife with examples.

With the process of evolution, the chemical sense of animalsdifferentiated into gustatory and olfactory senses [10]. Thus, it isreasonable that the gustatory organ is very similar to the olfactoryone in function. The mechanisms of reception in the two organs arefundamentally very similar. This view is buttressed by a recentreview on smell, based similarly on electrochemistry, receptors andcell signaling [11].

In addition to providing novel insight, the framework is inter-disciplinary based on interaction of elements known to play vitalroles in living systems. Since action mode is often multifaceted,other factors may also participate. References are often represen-tative. Various original references may be found in the reviews andarticles cited.

2. Part A. Tastant molecules and electromagnetic fields (EFs):limited correlation

There is some correlation between molecular dipoles withassociated EFs, and taste. Molecules with no dipoles, such ashydrogen, oxygen and nitrogen exhibit no taste. Appreciable dipolemoments (DMs) (Table 1) [12] are linked to substances in the maintaste classes. For example, in the case of sour taste, acetic acid(vinegar) has DM of 1.70. The data for sweetness are also as follows:sugars, e.g., sucrose (Fig. 1) (alcohols 1.58e1.69 DM; aldehyde, 2.75DM; ketone, 2.88 DM; ether, 1.10 DM; saccharin (Fig. 2) amide, 3.68DM; aspartame (Fig. 3) carboxyl, 1.70 DM; amine, 1.19 DM; amide3.68 DM; ester, 1.72 DM; toluene, 0.27 DM; bitter taste (quinine,

* Corresponding author. Tel.: þ1 619 594 5595; fax: þ1 619 594 4634.E-mail address: [email protected] (P. Kovacic).

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Journal of Electrostatics 70 (2012) 7e14


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1,3,5-Tris(pyridin-3-yl)-2,4-diazapenta-1,4-diene

Claudia M. Quiroa-Montalvan, Gerardo Aguirre and

Miguel Parra-Hake*

Centro de Graduados e Investigacion del Instituto Tecnologico de Tijuana, Apdo.

Postal 1166, 22500, Tijuana, B.C., Mexico


Received 5 December 2011; accepted 10 February 2012



In the solid state, the structure of the title compound,

C18H15N5, is stabilized by weak C—H� � �N interactions.

Molecules are arranged in layers parallel to the bc plane

forming an interesting supramolecular structure.

Related literature

For coordination polymers and supramolecular structures, see:

Itoh et al. (2005); Albrechet (2001); Leininger et al. (2000). For

potential applications in catalysis, gas storage, chirality, optics,

magnetism, nanotechnology and luminescence, see: James

(2003); Kitagawa et al. (2004); Masaoka et al. (2001); Rarig et

al. (2002); Yaghi et al. (2003); Wang et al. (2009). For the

preparation of this class of compound, see: Larter et al. (1998);

Lozinskaya et al. (2003); Bessonov et al. (2005); Fernandes et

al. (2007).

Experimental

Crystal data

C18H15N5

Mr = 301.35Monoclinic, Pca = 5.7174 (11) Ab = 8.0934 (10) Ac = 16.972 (4) A� = 99.690 (18)�

V = 774.1 (3) A3


T = 298 K0.42 � 0.18 � 0.12 mm

Data collection

Bruker P4 diffractometer3235 measured reflections2874 independent reflections1159 reflections with I > 2�(I)

Rint = 0.0613 standard reflections every 97

reflectionsintensity decay: 11.5%

Refinement

R[F 2 > 2�(F 2)] = 0.070wR(F 2) = 0.135S = 0.982874 reflections209 parameters

2 restraintsH-atom parameters constrained��max = 0.17 e A�3

��min = �0.17 e A�3


D—H� � �A D—H H� � �A D� � �A D—H� � �A

C18—H18A� � �N1i 0.93 2.74 3.552 (7) 146C17—H17A� � �N3ii 0.93 2.66 3.456 (7) 144

Symmetry codes: (i) x;�y þ 1; z� 12; (ii) x; y þ 1; z.




structure: SHELXL97 (Sheldrick, 2008); molecular graphics:

ORTEP-3 (Farrugia, 1997) and Mercury (Macrae et al., 2006); soft-

ware used to prepare material for publication: SHELXS97.

This work was supported by Direccion General de Educa-

cion Superior Tecnologica (DGEST) (grant No. 2785.09-P).

Support from Consejo Nacional de Ciencia y Tecnologıa

(CONACyT) in the form of a graduate scholarship for CMQM

is gratefully acknowledged.

Supplementary data and figures for this paper are available from theIUCr electronic archives (Reference: RK2325).

References

Albrechet, M. (2001). Chem. Rev. 101, 3457–3498.Bessonov, I. V., Lozinskaya, N. A., Katachova, V. R., Proskurnina, M. V. &

Zefirov, N. S. (2005). Russ. Chem. Bull. Int. Ed. 54, 211–214.Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565.Fernandes, C., Horn, A. Jr, Howie, R. A., Schripsema, J., Skakle, J. M. S. &

Wardell, J. L. (2007). J. Mol. Struct. 837, 274–283.Itoh, M., Nakazawa, J., Maeda, K., Mizutani, T. & Kodera, M. (2005). Inorg.

Chem. 44, 691–702.James, S. L. (2003). Chem. Soc. Rev. 32, 276–288.Kitagawa, S., Kitaura, R. & Noro, S. (2004). Angew. Chem. Int. Ed. 43, 2334–

2375.Larter, M. L., Phillips, M., Ortega, F., Aguirre, G., Somanathan, R. & Walsh, P.

J. (1998). Tetrahedron Lett. 39, 4785–4788.Leininger, S., Olenyuk, B. & Stang, P. J. (2000). Chem. Rev. 100, 853–908.Lozinskaya, N. A., Tsybezova, V. V., Proskurnina, M. V. & Zefirov, N. S. (2003).

Russ. Chem. Bull. Int. Ed. 52, 674–678.Macrae, C. F., Edgington, P. R., McCabe, P., Pidcock, E., Shields, G. P., Taylor,

R., Towler, M. & van de Streek, J. (2006). J. Appl. Cryst. 39, 453–457.Masaoka, S., Furukawa, S., Chang, H.-C., Mizutani, T. & Kitagawa, S. (2001).

Angew. Chem. Int. Ed. 40, 3817–3819.Rarig, R. S. Jr, Lam, R., Zavalij, P. Y., Ngala, J. K., LaDuca, R. L. Jr, Greedan,

J. E. & Zubieta, J. (2002). Inorg. Chem. 41, 2124–2133.Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.Siemens (1996). XSCANS. Siemens Analytical X-ray Instruments Inc.,

Madison, Wisconsin, USA.Wang, L., Gu, W., Deng, J.-X., Liu, M.-L., Xu, N. & Liu, X.-Z. (2009). Z. Anorg.

Allg. Chem. 636, 1124–1128.Yaghi, O. M. O., Keeffe, M., Ockwig, N. W., Chae, H. K., Eddaoudi, M. & Kim,

J. (2003). Nature (London), 423, 705–714.

organic compounds

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Dichloridobis(methanol-jO)[cis-(�)-2,4,5-tris(pyridin-2-yl)-2-imidazoline-j3N2,N3,N4]ytterbium(III) chloride

Alberto Baez-Castro,a Herbert Hopfl,b Miguel Parra-

Hake,c Adriana Cruz-Enriqueza and Jose J. Campos-

Gaxiolaa*





Graduados del Instituto Tecnologico de Tijuana, Blvd. Industrial S/N, Col. Otay,

CP 22500, Tijuana, BC, Mexico


Received 7 May 2012; accepted 15 May 2012



In the crystal structure of the title complex, [YbCl2-

(C18H15N5)(CH3OH)2]Cl, the pseudo-pentagonal–bipyra-

midal coordination geometry of the YbIII cation is composed

of three N atoms from one cis-(�)-2,4,5-tris(pyridin-2-yl)-

imidazoline (HL) ligand, two O atoms from two methanol

molecules and two Cl� anions. Chains are formed along [010]

through N—H� � �Cl, O—H� � �Cl and O—H� � �N hydrogen

bonds.

Related literature

For background to the synthesis of HL, see: Later et al. (1998);

Fernandes et al. (2007). For metal complexes with HL, see:

Parra-Hake et al. (2000); Campos-Gaxiola et al. (2007, 2008,

2010). For related Yb (III) complexes, see: Li et al. (2007); Xu

et al. (2009); Stojanovic et al. (2010); Okawara et al. (2012). For

potential applications of polypyridyl chelating ligands in

magnetic, electronic and luminescent devices, see: Freidzon et

al. (2011); Maynard et al. (2009); Thomas et al. (2012).

Experimental

Crystal data

[YbCl2(C18H15N5)(CH4O)2]ClMr = 644.82Triclinic, P1a = 9.2401 (13) Ab = 9.8390 (14) Ac = 13.3765 (19) A� = 99.978 (2)�

� = 94.616 (2)�

� = 92.145 (2)�

V = 1192.2 (3) A3


T = 293 K0.34 � 0.29 � 0.24 mm

Data collection

Bruker APEX CCD area-detectordiffractometer



Refinement



��max = 1.10 e A�3

��min = �1.35 e A�3

Table 1Selected bond lengths (A).

Yb1—Cl1 2.5220 (19)Yb1—Cl2 2.5834 (18)Yb1—N1 2.268 (5)Yb1—N3 2.579 (5)

Yb1—N4 2.556 (6)Yb1—O1 2.289 (5)Yb1—O2 2.287 (5)


D—H� � �A D—H H� � �A D� � �A D—H� � �A

O1—H100� � �N5i 0.84 1.86 2.681 (3) 164O2—H200� � �Cl3i 0.84 2.19 2.956 (3) 152N2—H20 � � �Cl3 0.86 2.25 3.096 (3) 167

Symmetry code: (i) x; y� 1; z.


Plus-NT (Bruker 2001); data reduction: SAINT-Plus-NT; program(s)

used to solve structure: SHELXTL-NT (Sheldrick, 2008); program(s)

used to refine structure: SHELXTL-NT; molecular graphics:

SHELXTL-NT; software used to prepare material for publication:

publCIF (Westrip, 2010).


Acta Cryst. (2012). E68, m815–m816 doi:10.1107/S1600536812022052 Baez-Castro et al. m815



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2,4,5-Tris(pyridin-4-yl)-4,5-dihydro-1,3-oxazole

Jose J. Campos-Gaxiola,a* Herbert Hopfl,b Gerardo

Aguirrec and Miguel Parra-Hakec

aFacultad de Ingenierıa Mochis, Universidad Autonoma de Sinaloa, Fuente de

Poseidon y Prol. Angel Flores, 81223 Los Mochis, Sinaloa, Mexico, bCentro de

Investigaciones Quımicas, Universidad Autonoma del Estado de Morelos, Av.

Universidad 1001, 62209 Cuernavaca, Morelos, Mexico, and cCentro de Graduados

e Investigacion del Instituto Tecnologico de Tijuana, Apdo. Postal 1166, 22500

Tijuana, BC, Mexico


Received 26 March 2012; accepted 17 May 2012


disorder in main residue; R factor = 0.039; wR factor = 0.107; data-to-parameter

ratio = 11.8.

In the title compound, C18H14N4O, the molecules are

disordered about a crystallographic twofold axis, leading to

50:50 disorder of the O- and N-atom sites within the oxazole

ring. As a consequence, symmetry-related oxazole C—N and

C—O bonds are averaged. The oxazole ring makes a dihedral

angle of 6.920 (1)� with the pyridyl ring in the 2-position and

60.960 (2)� with the pyridyl rings in the 4- and 5-positions.

Related literature

For background to the synthesis of oxazoles see: Graham

(2010); Aspinall et al. (2011). For the use of pyridyloxazole

ligands in the construction of metal-organic complexes see:

Bettencourt-Dias et al. (2010, 2012). For the use of tripyridyl

ligands in the construction of metal-organic coordination

complexes and polymers, see: Campos-Gaxiola et al. (2007,

2008, 2010); Liang et al. (2008, 2009); Yang et al. (2010); Chen

et al. (2011).

Experimental

Crystal data

C18H14N4OMr = 302.33Orthorhombic, Pbcna = 15.9777 (13) Ab = 11.4504 (9) Ac = 7.7573 (6) A

V = 1419.21 (19) A3


T = 293 K0.43 � 0.38 � 0.34 mm

Data collection


Absorption correction: multi-scan(SADABS; Bruker, 2001)Tmin = 0.962, Tmax = 0.969


Refinement



��min = �0.23 e A�3





SHELXTL (Sheldrick, 2008); software used to prepare material for

publication: SHELXTL.

This work was supported by the Secretarıa de Educacion

Publica (PROMEP, UAS-PTC-033) and the Universidad

Autonoma de Sinaloa (DGIP, PROFAPI2011/033).

Supplementary data and figures for this paper are available from theIUCr electronic archives (Reference: PK2402).

References

Aspinall, H. C., Beckingham, O., Farrar, M. D., Greeves, N. & Thomas, C. D.(2011). Tetrahedron Lett. 52, 5120–5123.

Bettencourt-Dias, A., Barber, P. S. & Bauer, S. (2012). J. Am. Chem. Soc. 134,6987–6994.

Bettencourt-Dias, A., Barber, P. S., Viswanathan, S., Lill, D. T., Rollett, A.,Ling, G. & Altun, S. (2010). Inorg. Chem. 49, 8848–8861.

Bruker (2000). SMART. Bruker AXS Inc., Madison, Wisconsin, USA.Bruker (2001). SAINT-Plus and SADABS Bruker AXS Inc., Madison,

Wisconsin, USA.Campos-Gaxiola, J. J., Hopfl, H. & Parra-Hake, M. (2007). J. Mex. Chem. Soc.

51, 27–32.Campos-Gaxiola, J. J., Hopfl, H. & Parra-Hake, M. (2008). Inorg. Chim. Acta,

361, 248–254.Campos-Gaxiola, J. J., Hopfl, H. & Parra-Hake, M. (2010). Inorg. Chim. Acta,

363, 1179–1185.Chen, H., Xiao, D., Fan, L., He, J., Yan, S., Zhang, G., Sun, D., Ye, Z., Yuan, R.

& Wang, E. (2011). CrystEngComm, 13, 7098–7107.Graham, T. H. (2010). Org. Lett. 12, 3614–3617.Liang, X.-Q., Xiao, H.-P., Liu, B.-L., Li, Y.-Z., Zuo, J.-L. & You, X.-Z. (2008).

Polyhedron, 27, 2494–2500.Liang, X.-Q., Zhou, X.-H., Chen, C., Xiao, H.-P., Li, Y.-Z., Zuo, J.-L. & You,

X.-Z. (2009). Cryst. Growth Des. 9, 1041–1053.Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.Yang, F. L., Li, B., Hanajima, T., Einaga, Y., Huang, R. B., Zheng, L. S. & Tao, J.

(2010). Dalton Trans. 39, 2288–2292.

organic compounds

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3-[(R)-1-Hydroxybutan-2-yl]-1,2,3-benzo-triazin-4(3H)-one

Fernando Rocha-Alonzo,a* David Morales-Morales,b

Simon Hernandez-Ortega,b Reyna Reyes-Martınezb and

Miguel Parra-Hakec*

aDepartamento de Ciencias Quımico Bilogicas, Universidad de Sonora, Hermosillo,

Sonora, 83000 Mexico, bInstituto de Quımica, Universidad Nacional Autonoma de

Mexico, Circuito exterior, Ciudad Universitaria, Mexico D.F., 04510 Mexico, andcCentro de Graduados e Investigacion, Instituto Tecnologico de Tijuana, Tijuana,

B.C., 22500 Mexico

Correspondence e-mail: [email protected],

[email protected]

Received 21 October 2012; accepted 22 October 2012



The crystal structure of the title compound, C11H13N3O2, is

stabilized by O—H� � �O hydrogen bonds, which link the

molecules into chains along [100].

Related literature

For biological and synthetic applications of benzo-1,2,3-tria-

zinones, see: Caliendo et al. (1999); Zheng et al. (2005); Vais-

burg et al. (2004); Chollet et al. (2002); Le Diguarher et al.

(2003); Clark et al. (1995); Carpino et al. (2004); Janout et al.

(2003); Gierasch et al. (2000). For structures of benzo-1,2,3-

triazinones, see: Hjortas et al. (1973); Hunt et al. (1983);

Reingruber et al. (2009). For bond-length data, see: Allen et al.

(1987). For the synthesis, see: Gomez et al. (2005).

Experimental

Crystal data

C11H13N3O2

Mr = 219.24Orthorhombic, P212121

a = 8.9668 (13) A

b = 10.1506 (15) Ac = 12.0238 (17) AV = 1094.4 (3) A3

Z = 4

Mo K� radiation� = 0.09 mm�1

T = 298 K0.32 � 0.10 � 0.10 mm

Data collection

Bruker SMART APEX CCD area-detector diffractometer

9057 measured reflections

2000 independent reflections1700 reflections with I > 2�(I)Rint = 0.044

Refinement

R[F 2 > 2�(F 2)] = 0.034wR(F 2) = 0.076S = 0.932000 reflections149 parameters1 restraint


��max = 0.11 e A�3

��min = �0.15 e A�3


D—H� � �A D—H H� � �A D� � �A D—H� � �A

O2—H2� � �O1i 0.85 (1) 2.03 (1) 2.8712 (19) 171 (2)

Symmetry code: (i) xþ 12;�yþ 3

2;�zþ 2.

Data collection: SMART (Bruker, 2007); cell refinement: SAINT

(Bruker, 2007); data reduction: SAINT; program(s) used to solve

structure: SHELXTL (Sheldrick, 2008); program(s) used to refine

structure: SHELXTL; molecular graphics: SHELXTL; software used

to prepare material for publication: SHELXTL.

We gratefully acknowledge support for this project by the

Consejo Nacional de Ciencia y Tecnologıa (CONACyT grant

36435-E) and Consejo del Sistema Nacional de Educacion

Tecnologica (COSNET) grant 486–02-P. The authors are

indebted to Adrian Ochoa Teran and Ignacio Rivero Espejel

for their analytical support of this work.

Supplementary data and figures for this paper are available from theIUCr electronic archives (Reference: ZJ2097).

References

Allen, F. H., Kennard, O., Watson, D. G., Brammer, V., Orpen, A. G. & Taylor,R. (1987). J. Chem. Soc. Perkin Trans. 2, pp. S1–19.

Bruker (2007). SAINT and SMART. Bruker AXS Inc., Madison, Wisconsin,USA.

Caliendo, G., Fiorino, F., Grieco, P., Perissutti, E., Santagada, V., Meli, R.,Mattace-Raso, G., Zanesco, A. & De Nucci, G. (1999). Eur. J. Med. Chem.34, 1043–1051.

Carpino, L. A., Xia, J., Zhang, C. & El-Faham, A. (2004). J. Org. Chem. 69, 62–71.

Chollet, A. M., Le Diguarher, T., Kucharczyk, N., Oynel, A., Bertrand, M.,Tucker, G., Guilbaud, N., Burbridge, M., Pastoureau, P., Fradin, A., Sabatini,M., Fauchere, J.-L. & Casara, P. (2002). Bioorg. Med. Chem. 10, 531–544.

Clark, A. S., Deans, B., Stevens, M. F. G., Tisdale, M. J., Wheelhouse, R. T.,Denny, B. J. & Hartley, J. A. (1995). J. Med. Chem. 38, 1493–1504.

Gierasch, T. M., Chytil, M., Didiuk, M. T., Park, J. Y., Urban, J. J., Nolan, S. P. &Verdine, G. L. (2000). Org. Lett. 2, 3999–4002.

Gomez, M., Jansat, S., Muller, G., Aullon, G. & Maestro, M. A. (2005). Eur. J.Inorg. Chem. pp. 4341–4351.

Hjortas, J. (1973). Acta Cryst. B29, 1916–1922.Hunt, W. E., Schwalbe, C. H. & Vaughan, K. (1983). Acta Cryst. C39, 738–740.Janout, V., Jing, B., Staina, I. V. & Regen, S. L. (2003). J. Am. Chem. Soc. 125,

4436–4437.Le Diguarher, T., Chollet, A. M., Bertrand, M., Henning, P., Raimbaud, E.,

Sabatini, M. N., Guilbaud, N., Pierre, A., Tucker, G. C. & Casara, P. (2003). J.Med. Chem. 46, 3840–3852.

organic compounds

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