ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 5, pp. 672−677. © Pleiades Publishing, Ltd., 2013.Original English Text © V.S. Fundamenskii, S.M. Ramsh, V.A. Brouskov, A.V. Smirnova, A.Yu. Yanichev, M. B. Fleisher, S.V. Belyakov, 2013, published in Zhurnal Organicheskoi Khimii, 2013, Vol. 49, No. 5, pp. 690−696.

672

To the memory of Professor G.I. Koldobskii

Study of the Structure of (Carbamimidoylsulfanyl)acetic (“Pseudothiohydantoic”) Acid by XRD and PM6 Methods

V. S. Fundamenskiia, S. M. Ramsha, V. A. Brouskova, A. V. Smirnovaa, A. Yu. Yanichevb, M. B. Fleisherb, and S. V. Belyakovb

aSt. Petersburg State Technological Institute, St. Petersburg,190013 Russiaе-mail: gsramsh@mail.wplus.net

bLatvian Institute of Organic Synthesis, Riga

Received February 22, 2013

Abstract—It was shown by the method of powder X-ray diffraction analysis that in the crystalline state the product of the reaction of thiourea with chloroacetic acid in water, (carbamimidoylsulfanyl)acetic acid, existed in the zwitter-ion tautomeric form. The structure consists of virtually planar infi nite layers normal to the c axis of the unit cell which are bound by van der Waals interactions. The layers are formed by infi nite rows elongated along the b axis of the unit cell consisting of materially planar zwitter-ionic molecules linked by strong bifurcated hydrogen bonds. The results of quantum-chemical calculations by PM6 method are in agreement with the XRD results: whereas an isolated molecule exists in nonzwitter-ionic tautomeric form, in the crystal only the zwitter-ionic tautomer is present.

DOI: 10.1134/S1070428013050060

(Carbamimidoylsulfanyl)acetic acid, the so-called “pseudothiohydantoic acid” (I), was prepared for the fi rst time from thiourea and chloroacetic acid [1]. It was erroneously assigned a structure of the isomeric “thiohy-dantoic acid,” and the melting or decomposition point of the compound obtained was not reported.

H2N

H2NS H2

+N

NH2

SO

OHCl

H2NNH

SOH

O

H2NNH2

SO

O

ClCH2COOH

_HCl

H2O

I

_

+

1

2

3

1

1

2

2

_

2

22 31

11

IBIA

It was however shown later that in the reaction of thiourea with monochloroacetic acid at room tempera-ture in water formed free acid I, whereas in acetone its hydrochloride was obtained: i.e., the primary formed

_______________1 Compound I was named in [3] “formamidinethiolacetic acid,” in

[4], “S-carboxymethylisothiourea.”

hydrochloride in water was totally hydrolyzed [2]. Ray et al. also did not report the melting point of acid I, it was only mentioned that the substance had no precise melting point and was “prone to decomposition,” evidently, at melting. Later these results were repeated in [3], and the measured melting point was 234°С (with decomposition).

One of us at the synthesis along procedure [3]1 isolated acid I as white fi nely dispersed powder [4].

Compound I possesses a feature very unusual for organic substances: It is practically insoluble in water and in common organic solvents (DMSO, DMF, HMPA, CCl4) [4] as has been shown by 1Н NMR spectroscopy. The sample of compound I melted at 230–240°С (with decomposition) [4].

The insolubility of acid I in water is the cause of the difference in the products of thiourea alkylation with monochloroacetic acid in water and acetone. The initially formed acid hydrochloride in the water solution suffers hydrolysis to free acid I that precipitates, therefore the hydrolysis occurs practically to the completion.

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673STUDY OF THE STRUCTURE OF (CARBAMIMIDOYLSULFANYL)ACETIC

Fig. 1. Packing of molecules of (carbamimidoylsulfanyl)acetic acid (I) in the unit cell according to XRD data. Hydrogen atoms (not shown in the fi gure) were localized by geometric calculations since they failed to be established from the difference Fourier synthesis.

Table 1. Experimental and calculated bond lengths and bond angles in the molecule of (carbamimidoylsulfanyl)acetic acid (I) in a crystal

Bondl, Å

Angleω, deg

XRD РМ6 XRD РМ6

С2–S1 1.802(7) 1.800 C2S1C3 103.0(3) 104.2

C3–S1 1.740(7) 1.779 S1C2C1 106.8(3) 102.6

C3–N2 1.34(1) 1.342 O1C1O2 125.0(4) 125.1

C3–N1 1.35(1) 1.351 O1C1C2 119.2(3) 117.5

C1–O1 1.281(4) 1.257 O2C1C2 115.7(3) 117.3

C1–O2 1.27(1) 1.259 S1C3N2 124.9(4) 122.1

C1–C2 1.530(3) 1.520 S1C3N1 112.5(4) 115.2

N2C3N1 122.4(5) 122.6

The insolubility of acid I in water and in organic solvents was ascribed to abnormally high for organic compound strength of intermolecular bonds in the solid state [4]. The aim of this study was the elucidation of the molecular form of acid I in the solid phase and of the fea-tures of the molecular packing underlying the abnormal strength of the intermolecular bonds in the solid state of this compound.

Since we were incapable to grow a single crystal the crystalline structure of substance I obtained by the pro-cedure [3] was subjected to the study by X-ray powder diffraction analysis. The results obtained are compiled in Tables 1, 2 and on Figs. 1, 2. [The image of the four-layer fragment (cluster) of the crystal structure of acid I containing (2 × 2 × 2) unit cells, 32 molecules in total, is available from the authors].

Nearly fl at molecules of acid I form infi nite rows due to strong hydrogen bonds HB1 N1...O1 and HB2

Table 2. Experimental and calculated lengths of inter-molecular hydrogen bonds and contacts in the crystal of (carbamimidoylsulfanyl)acetic acid (I)

Notation of intermolecular

HBа or a contact

Bond D–H⋯A

l (D⋯A), Å

XRD РМ6

HB1 N1⋯O1 2.852 2.923

HB2 N2⋯O2 2.838 2.746

HB3 N1⋯O1 2.994 3.026

HB4 N2⋯O2 2.785 2.831

Contact 1 N1⋯S1 3.175 3.118

Contact 2 C2⋯O2 3.262 3.068

Contact 3 C2⋯N2 3.282 3.267а Corresponds to the notation in Fig. 2, all HB shown in Fig. 1.

RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 5 2013

674 FUNDAMENSKII et al.

N2...O2 (Table 2) between the protonated carbamimidoyl (amidine) and deprotonated carboxy groups (bifurcated HB), as shown in Figs. 1, 2. Namely, in each row all molecules are uniformly oriented “head to tail”. Nitrogen atoms of the protonated amidine fragment act as donors of HB (D), oxygen atoms of the deprotonated carboxy fragments act as acceptors (A). Every molecule of acid I forms two bifurcated HB1 as the donor and the acceptor of HB, and two bifurcated HB2, also the donor and the acceptor of HB.

The infi nite rows form virtually fl at infi nite layers due to strong hydrogen bonds HB3 N1...O1 and HB4 N2...O2 (Table 2, Figs. 1, 2) between the protonated amidine and deprotonated carboxy groups of the neighbor rows, and each molecule is bound by two HB3 and two HB4 with

Fig. 2. Network of intermolecular hydrogen bonds (HB) N–H⋯O in the tentatively separated fragment of the crystal consisting of nine molecules of (carbamimidoylsulfanyl)acetic acid (I) according to XRD data. The notation of intermolecular HB correspond to Table 2. The circles mark the six-membered (1) and eight-membered (2, 3) “macrocycles.”

a couple of molecules in each neighbor row (Fig. 2). The layers are oriented normally to the c axis of the unit cell.

As a result each molecule of acid I take part in eight HB: in two bonds of HB1 type, two HB2, two HB3, and two HB4. The atom N1 is bound by HB1 and HB3 with two atoms O1, and the atom N2 is bound by HB2 and HB4 with two atoms O2; in its turn the atom O1 is bound by HB1 and HB3 with two atoms N1, and the atom O2, by HB2 and HB4 with two atoms N2. Evidently these hydroben bonds alongside the electrostatic interaction provide the extremely high strength to the crystal struc-ture of acid I.

The pattern of hydrogen bonding demonstrated on the Fig. 2 is possible only at the zwitter-ionic structure of the acid molecule IB. The obtained structural data (Table 2)

RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 5 2013

675STUDY OF THE STRUCTURE OF (CARBAMIMIDOYLSULFANYL)ACETIC

unambiguously prove that from two possible tautomeric forms of the acid, nonzwitter-ionic IA and zwitter-ionic IB, in the crystal the resonance-stabilized (delocalized) zwitter-ionic form IB is present. Actually, the insignifi cant difference in the lengths of bonds C–O: C1–O1 1.281, C1–O2 1.267 (intermediate between the lengths of an ordinary C–O 1.308 and double C=O 1.214 bonds in carboxylic acids; by 0.027–0.013 longer than the length of the delocalized bond C–O 1.254 in carboxylate anions [5]); and also insignifi cant difference in the bond lengths of C–N: C3–N1 1.352 Å, C3–N2 1.336 (about the bond distance of C–N 1.346 in thiourea, considerably longer than the length of the double bond C=N 1.313 in imidaz-ole [5] and of the delocalized bonds C–N 1.307 and 1.311 in bis(S-methylisothiuronium) sulfate [6]) shows a nearly symmetric resonance delocalization of the π-electron density in the carboxy and amidine fragments which is possible only at their ionization (the deprotonation of the former and protonation of the latter fragment).

The determined lengths of the other bonds (Table 1) also are well consistent with the published data: the lengths of bonds C2–S1 1.802 and C3–S1 1.740 are in agreement with the lengths of the corresponding bonds 1.786 and 1.746 in bis(S-methylisothiuronium) sulfate [6], the length of the C1–C2 bond 1.530, with the standard bond length С*–СОО– in carboxylate anions 1.520 [5].2

Formerly we obtained the product of reaction between ethylenethiourea with monochloroacetic acid, whose mol-ecule in DMSO-d6, according to NMR data also existed in a zwitter-ionic structure with the delocalized ion sites as symmetric resonance hybrids [7]. Regretfully, because of the abnormally low solubility of acid I we could not evaluate its structure in solution by the NMR method.

Beside the hydrogen bonds in the fl at layers contacts N1⋯S1 (Fig. 1, Table 2), C2⋯O2 and C2⋯N2 (Table 2) between adjacent chains were observed. Between the layers only van der Waals interactions are operating.

In every layer all rows of molecules are uniformly oriented, they are parallel to each other and are elongated approximately along the b axis; the neighbor rows are joined into layers by the second order screw axes (Fig. 1, 2). In the adjacent layers the molecules of acid I in the rows and consequently the rows proper are antiparallel oriented, namely, when in one layer they are oriented along the direction [010], in the neighbor layer, in the direction [0–10] (Fig. 2).______________2 In [5] with С* was designated the sp3-hybridized carbon atom

linked only to C and H atoms.

Owing to intermolecular HB it is possible to identify in the molecular structure hydrogen-bonded “macrocycles” of various sizes (Fig. 2): six-membered (1) and eight-membered (2, 3). In the six-membered “macrocycle” O1–C1–O2–N2–C3–N1 (1) the nitrogen and oxygen atoms are bound by two hydrogen bonds, HB1 and HB2. In the eight-membered “macrocycles” O2–N2–O2–C1–C2–S1–C3–N2 (2) and O1–N1–O1–C1–C2–S1–C3–N1 (3) the nitrogen and oxygen atoms are bound by three hydrogen bonds, one HB2 and two HB4 or one HB1 and two HB3 respectively.

The results of quantum-chemical calculations are consistent with the structural data obtained by XRD analysis (Table 2). According to ab initio calculation by Hartree-Fock method [8]) and to results of semiempiri-cal method PM6 [9], in the isolated form the nonzwitter-ionic tautomeric form IA is more favorable by energy (Fig. 3). It is known practically, that semiempirical methods based on NDDO approximation, in particular, method РМ6, give the values of enthalpy of formation closer to the experimental fi ndings than the ab initio calculations, therefore the values ΔHf –312.71 kJ mol–1 for the form IA and –200.01 kJ mol–1 for the form IB seem more reasonable.

For further calculations of the crystal structure method PM6 was chosen that provides a possibility of suffi -ciently precise calculation of organic crystals [9]. As the “zero approximation”, i.e., initial structure undergoing optimization in the course of calculations was taken the isolated molecule of the nonzwitter-ionic tautomer IA with the geometric parameters automatically taken by the calculation program. The calculation was carried out for the cluster model consisting of (2 × 2 × 2) unit cells of the crystal I.

In the course of the calculation optimization of the crystal structure a proton is eliminated from the atom O1 of the hydroxy group of one molecule and it is trans-ferred to the atom N1 of the imino group of the neighbor molecule, namely, a transition occurs from structure IA to structure IB. Simultaneously a redistribution (delocal-ization) of π-electron density and alternations (leveling) in bond lengths is observed in the carboxy and amidine fragments. The calculated geometric characteristics of these and the other bonds are in the reasonable agreement with the experimental values determined by the XRD analysis (Table 2): They correspond to nearly symmetric zwitter-ionic form IB. It should be noted however that the calculation afforded nearly standard bond lengths C1–O1 and C1–O2 in the deprotonated carboxy group,

RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 5 2013

676 FUNDAMENSKII et al.

1.257 and 1.259 respectively (1.254 in the carboxylate anions [5]), whereas the experimental values as was al-ready mentioned were somewhat larger, 1.281 and 1.267 respectively.

The calculated parameters of the hydrogen bonds system and of short contacts in the crystals are compiled in Table 2. The calculated system does not differ from the system found by XRD (Fig. 2).

The effective charges on atoms S1, O1, O2, N1, N2, C1, C2, and C3 in the molecule of acid I calculated by the Mulliken analysis of population [10] equal respectively 0.027, –0.774, –0.763, –0.461, –0.501, 0.790, –0.498, and 0.369. As seen, the largest negative charge in the molecules in the crystal is localized on the atom O1 of the deprotonated carboxy group, and the maximum positive charge, on the atom С1 of the same group.

Thus the calculation demonstrated that the nonzwitter-ionic form IA is characteristic only of the hypothetical isolated molecule. The simulation by PM6 method of the potential energy surface (PES) shows already for two molecules IA that in this system (dimer) the hydrogen atom of the carboxy group is transferred to the imino group, and therefore the fi nal state of the system consists

_____________3 The projection of the dimer of the zwitter-ionic tautomer IB

simulated by the method РМ6 and an animation presentation of the simulation of the tautomeric transition (IА) → (IB) in a dimer of compound I obtained by the method PM6 (in the formate *.avi) is available from the authors.

of two oppositely directed dipoles of the zwitter-ionic molecules IB. The transition from the tautomeric form IA into the tautomeric form IB simulated by the method PM6 may be schematically represented as follows3:

Dimer IA Dimer IB

N

NSO

O HH

HH

N

NS O

OHH

HH

N

NSO

O HH

HH

N

NS O

OHH

HH

_

... ...

...

...

_+

+

In calculating the PES of the dimeric system we have taken as the zero approximation two oppositely oriented molecules of the nonzwitter-ionic form IA. The calculation showed that fi rst the system overcame a potential barrier whose height (activation energy) was 29.01 kJ mol–1. Overcoming the barrier the system attains the energy minimum that corresponds to a dimer of the zwitter-ionic tautomeric form IB. The enthalpy of dimer formation was estimated from the depth of the minimum at–677.42 kJ mol–1, and calculated per one molecule of IB,–338.71 kJ mol–1. Accounting for the value of ΔHf of IA form (Fig. 3) the energy gain from such “dimerization” tautomerization equals 25.50 kJ mol–1.

The quantum-chemical calculation of the crystalline cluster (2 × 2 × 2, 32 molecules in total) recalculated per one molecule of acid I gives a value ΔHf –440.53 kJ mol–1. Hence in comparison with an isolated molecule IA (Fig. 3) at the transition from the gas phase to the crystal phase the energy gain reaches 127.32 kJ mol–1. Consequently, for the transition of a molecule of acid I from the crystal into a “free” (isolated) state an energy is required by the order of magnitude comparable with energy of the cleavage of an ordinary covalent bond [11]. Evidently this is the cause of the insolubility of these compounds in all known solvents. Apparently in the transition of acid I molecule from the crtystalline phase into the solution the solvation effects are unable to compensate the large energy loss for either of the possible tautomeric forms.

EXPERIMENTAL

IR spectrum was recorded on a spectrophotom-eter Shimadzu FTIR-8400S from pellets with KBr. Elemental analysis was carried out on an analyzer

IA IBΔHf –313.21 (PM6), –256.61 (ab initio)

ΔHf –200.34 (PM6), –203.64 (ab initio)

Fig. 3. Conformation of tautomers IA and IB corresponding to the energy minima, and their enthalpies of formation according to quantum-chemical calculations.

RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 5 2013

677STUDY OF THE STRUCTURE OF (CARBAMIMIDOYLSULFANYL)ACETIC

Leco CHNS(O) 942.A polycrystalline sample of compound I was investi-

gated at room temperature on a diffractometer Shimadzu A7000 (CuKα radiation, Ni-fi lter, 30 kV, 35 mA). The registering was carried out in a step mode in the angles range 2θ 5–120° with a step 0.02° and exposure of 10 s in the point. The peaks were approximated by the func-tion Pearson VII. The indexing and the evaluation of the unit cell parameters was performed using a program N-TREOR09 from the program package EXPO 2009 [12]. Compound I crystallizes in the monoclinic crystal system, space group P21/n. Parameters of the unit cell are as follows: a 9.7425(2), b 8.0864(1), c 6.9950(1) Å, β 106.913(1)°, V 527.914(2) Å3, ρcalc 1.615 g cm–3, Z 4. The structure was solved by the direct method and refi ned by Rietveld method till Rp 5.203, Rwp 7.131, Re 1.527, GOF 4.670. (Experimental and theoretical diffractograms of acid I are available from the authors).

All calculations were performed using EXPO 2009 software. The images of crystal structure are obtained applying Mercury 2.3 program [13].

Semiempirical quantum-chemical calculations were performed by PM6 method [9] using MOPAC2009 (ver-sion 9.069W) software [14]. The solid-state calculations were performed for a cluster model containing (2 × 2 × 2) unit cells of the crystal of acid I [key word of the program MERS=(2,2,2)]. The translation vectors were set by the positions of three auxiliary atoms having in the list of the initial data symbol marking “Tv” The optimization process of the system was terminated at reaching the threshold value of gradient norm (GNORM) equal 1.0.

The calculated unit cell parameters4 of compound I in the crystal and its density are as follows: a 9.815, b 7.971, c 6.308 Å, β85.11°, V 491.69 Å3, ρ1.812 g cm–3.

The ab initio quantum-chemical calculations were carried out by Hartree-Fock method [8] using a mini-mum basis. The use of an extended but unbalanced basis (employing d-functions only for sulfur atom) resulted in unnatural overestimation of the negative charge on the sulfur atom. The atomic functions were represented as the sum of Gaussians (basis 3-21G* was applied). The cal-culations were performed using GAMESS program [15].

(Carbamimidoylsulfanyl)acetic acid (I) was ob-tained by modifi ed procedure [3]. To a solution of 1.52 g (20 mmol) of thiourea in 10 ml of water was added at ____________4 The difference in the parameters of the a and с axes and consequently

of angle β from the parameters determined by XRD analysis was due by slightly another choice of the cell.

stirring a solution of 1.89 g (20 mmol) of monochloro-acetic acid in 10 ml of water, and the mixture was stirred for 3 h. After 24 h the separated precipitate was fi ltered off and several times was thoroughly washed with hot water. The product was dried in a vacuum desiccator over CaCl2. Yield 1.12 g (42%), mp 255°C (234°C [3]). IR spectrum (thin fi lm), ν, cm–1: 1119, 1150, 1230, 1366, 1406, 1434, 1439, 1585 (C–N, bending NH), 1682, 1686 (С=О), 2782 (CH2), 2948 (NH), 3082 sh, 3182, 3279, 3356 sh, 3544 sh. Found, %: C 26.56; H 4.58; N 20.23; S 23.79. C3H6N2O2S. Calculated, %: С 26.86; Н 4.51; N 20.88; S 23.90.

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6. Brand, H., Hubrich, C., Polborn, K., Schulz, A., and Villinger, A., Acta Cryst., Sect. E: Struct. Rep. Online., 2007, 63, no. 12, o4733.

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khimiyu (Introduction on Theoretical Organic Chemistry), Moscow: Vysshaya Shkola, 1974, p. 168.

12. Altomare, A., Camalli, M., Cuocci, C., Giacovazzo, C., Moliterni, A., and Rizzi, R., J. Appl. Cryst., 2009, vol. 42, p. 1197.

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14. Stewart, J.J.P., Program package MOPAC2009. http://OpenMOPAC.net

15. Schmidt, M.W., Baldridge, K.K., Boatz, J.A., Elbert, S.T., Gordon, M.S., Jensen, J.H., Koseki, S., Matsunaga, N., Nguyen, K.A., Su, S., Windus, T.L., Dupuis, M., and Mont-gomery, J.A., J. Comput. Chem., 1993, vol. 14, p. 1347; http://molecularmodelingbasics.blogspot.com/search/label/gamess.