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第五章、利用 α,β- 不飽和酮製備 3,5- 雙 取代衍生物. α,β- 不飽和酮的應用. α,β- 不飽和酮之文獻報導. Nafion-TMS mediated Mukaiyama aldol reaction of silyl enol ethers with aldehydes, obtained from mild oxidation of alcohols with polymer supported perruthenate (PSP), yielded α , β -unsaturated ketones. . - PowerPoint PPT Presentation
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第五章、利用 α,β- 不飽和酮製備 3,5- 雙 取代衍生物
NN
O
Ar
O
H
H
O
R'
NN
O
Ar
O
H
O
X
O
Y NN
O
Ar
O
O
Ar'
H
H
NN
O
Ar
O
NN
HR'
NN
O
Ar
O
NN
HX
O
Y
NN Ar'
H
NN
O
Ar
O
α,β- 不飽和酮的應用
NO
NN
C
O
.NH2NH2 H2O
NH2OH .HCl
α,β- 不飽和酮之文獻報導
Nafion-TMS mediated Mukaiyama aldol reaction of silyl enol ethers with aldehydes, obtained from mild oxidation of alcohols with polymer supported perruthenate (PSP), yielded α,β-unsaturated ketones.
OH
R
R
O
R'
R''
OTMS
NMe3+RuO4
-
CF2
SO O
OSi(CH3)3
R
R''
O
R'
Haunert, F.; Bolli, M. H.; Hinzen, B.; Ley, S. V. J. Chem. Soc.
Perkin Trans. I. 1998, 15, 2235.
α, β-unsaturated ketones obtained by base-catalysed condensation of aromatic aldehydes with substituted acetophenone
H3C
O
Ar'+NaOH
EtOH
O
HR
H
H
O
Ar'
R
★Powers, D. G.; Casebier, D. S.; Fokas, D.; Ryan, W. J. Troth,
J. R.; Coffen, D. L. Tetrahedron, 1998, 54, 4085.
★Vishnu Vardhan Reddy, K.; Sampath Rao, P.; Ashok, D.
Synth. Commun. 1998, 29, 2365.
★Pinto, D. C. G. A.; Silva, A. M. S.; Cavaleiro, J. A. S.
Tetrahedron. 1999, 55, 10187.
★ Holla, B. S.; Akberali, P. M.; Shivananda, M. K. IL
Farmaco. 2000, 55, 256.
★ Pathak, V. N.; Pathak, R.; Gupta, R.; Oza, C. K. Synth.
commun. 1997, 27, 1811.
α, β-unsaturated ketones obtained by base-catalysed condensation of aromatic aldehydes with substituted acetophenone
Preparation of starting materials
2a~2c
1a~1d
CH3COOCOCH3
HClO4
DMF
POCl3
NN
O
Ar
O
O
CH3
NN
O
Ar
O
H
NN
O
Ar
O
O
H
1a,2a : Ar = C6H5 1c,2c : Ar = p-CH3OC6H4
1b,2b : Ar = p-CH3C6H4 1d,2d : Ar = p-CH3CH2OC6H4
雪梨酮環取代的 α,β- 不飽和酮之合成1. 以 3- 芳香基 -4- 甲醯雪梨酮進行 Claisen － Schmidt
縮合反應。 N
NO
Ar
O
H
H
O
R'
NN
O
Ar
O
O
H
H3C
O
R'+NaOHEtOH
3a: Ar = p-CH3CH2OC6H4 , R' = CH3 , Yield: 52%
3b: Ar = p-CH3CH2OC6H4 , R' = C6H5, Yield: 60%
Syntheses of 5-Sydnonyl-4,5-dihydro-1H-
pyrazoles
H2O.
EtOH
NH2NH2
NN
O
Ar
O
H
H
O
R'
NN
O
Ar
O
O
H
H3C
O
R'+NaOHEtOH
NN
O
Ar
O
NN
HR'
1d 3a~3b
2. 以 3- 芳香基 -4- 甲醯雪梨酮與各種活性亞甲基 化合物進行 Knoevenagel 縮合反應。
+ X
O O
YN
NO
Ar
O
H
O
X
O
YNN
O
Ar
O
O
H
4a~4d 5aa~5dd1a~1d
4a: X = CH3 Y = CH3 4c: X = CH3 Y = OC2H5
4b: X = CH3 Y = C6H5 4d: X = OC2H5 Y = OC2H5
表 1. Knoevenagel 縮合產物 (5aa~5dd) 之收率 起始物 亞甲基化合物 產物 收率 *(%)1a ( Ar = C6H5 ) 4c 5ac 78
1b ( Ar = p-CH3C6H4 ) 4c 5bc 66
1c ( Ar = p-CH3OC6H4 ) 4c 5cc 76
1d ( Ar = p-CH3CH2OC6H4 ) 4c 5dc 63
1a ( Ar = C6H5 ) 4d 5ad 65
1b ( Ar = p-CH3C6H4 ) 4d 5bd 77
1c ( Ar = p-CH3OC6H4 ) 4d 5cd 70
1d ( Ar = p-CH3CH2OC6H4 ) 4d 5dd 68
* 再結晶收率
起始物 亞甲基化合物 產物 收率 *(%) 1a ( Ar = C6H5 ) 4a 5aa 74
1b ( Ar = p-CH3C6H4 ) 4a 5ba 78
1c ( Ar = p-CH3OC6H4 ) 4a 5ca 84
1d ( Ar = p-CH3CH2OC6H4 ) 4a 5da 80
1a ( Ar = C6H5 ) 4b 5ab 78
1b ( Ar = p-CH3C6H4 ) 4b 5bb 76
1c ( Ar = p-CH3OC6H4 ) 4b 5cb 74
1d ( Ar = p-CH3CH2OC6H4 ) 4b 5db 80
Syntheses of 5-sydnonyl-4,5-dihydro-1H-
pyrazoles
+ X
O O
YN
NO
Ar
O
H
OX
O
YNN
O
Ar
O
O
H
NH2NH2
EtOH
.H2ON
NO
Ar
O
NN
HX
O
Y
4a~4d 5aa~5dd1a~1d
3. 以 4- 乙醯 -3- 芳香基雪梨酮進行 Claisen－ Schmidt 縮合反應
NN
O
Ar
O
O
Ar'
H
HNN
O
Ar
O
O
CH3
H
O
Ar'+NaOHEtOH
2a~2c 6a~6d 7aa~7cd
2a : Ar = p-CH3C6H4 6a : Ar = C6H5 6c : Ar = p-CH3OC6H4
2b : Ar = p-CH3OC6H4 6b : Ar = p-CH3C6H4 6d : Ar = p-ClC6H4
2c : Ar = p-ClC6H4
表 2 、 1-(3- 芳香基雪梨酮 -4- 基 )-3- 芳香基 -
丙 -2- 烯 -1- 酮 (7aa~7cd) 之收率 起始物 芳香族醛 產物 收率 (%)*
2a ( Ar = p-CH3C6H4 ) 6a ( Ar' = C6H5) 7aa 64
2b ( Ar = p-CH3OC6H4) 6a ( Ar' = C6H5) 7ba 72
2c ( Ar = p-ClC6H4) 6a ( Ar' = C6H5) 7ca 55
2a ( Ar = p-CH3C6H4 ) 6b ( Ar' = p-CH3C6H4) 7ab 52
2b ( Ar = p-CH3OC6H4) 6b ( Ar' = p-CH3C6H4) 7bb 54
2c ( Ar = p-ClC6H4) 6b ( Ar' = p-CH3C6H4) 7cb 50
2a ( Ar = p-CH3C6H4 ) 6c ( Ar' = p-CH3OC6H4) 7ac 42
2b ( Ar = p-CH3OC6H4) 6c ( Ar' = p-CH3OC6H4) 7bc 45
2c ( Ar = p-ClC6H4) 6c ( Ar' = p-CH3OC6H4) 7cc 40
2a ( Ar = p-CH3C6H4 ) 6d ( Ar' = p-ClC6H4) 7ad 65
2b ( Ar = p-CH3OC6H4) 6d ( Ar' = p-ClC6H4) 7bd 79
2c ( Ar = p-ClC6H4) 6d ( Ar' = p-ClC6H4) 7cd 55
* 再結晶收率
圖一、 1-[3-(4- 甲苯基 ) 雪梨酮 -4- 基 ]-3-(4- 甲苯基 )- 丙 -2- 烯 -1- 酮 (7ab) 之分子結構圖
1H-pyrazoles 化合物的合成
1H- pyrazoles 化合物具有抗菌、抗發炎、抗過敏、止痛等特殊藥效，早已成為科學家們所熱衷於研究的對象。而近幾年來無論是其衍生物的合成或新合成方法的開發，甚至其藥理活性的探討研究已在世界各國如火如荼地展開
★ Satyanarayana, K.; Rao, M. N. A. J. Pharm. Sci. 1995, 84, 263.
★ Satyanarayana, K.; Rao, M. N. A. Eur J Med Chem. 1995, 30,
641.
★ Holla, B. S.; Akberali, P. M.; Shivananda, M. K. IL Farmaco.
2000, 55, 256.
Syntheses of 3-(3-arylsydnon-4-yl)-5-aryl
-4,5-dihydro-1H-pyrazoles
NN
O
Ar
O
O
Ar'
H
H
NN Ar'
H
NN
O
Ar
O
H2O.EtOH
NH2NH2
Method : 1. Starting material : Hydrazine hydrate = 0.5 mmole : 2 mmole
2. Solvent : 95% EtOH 3 mL
3. Heating 60 for 4~5 hrs ℃
表 3 、 3-(3- 芳香基雪梨酮 -4- 基 )-5- 芳香基 -4,5-
二氫 -1H-化合物 (8) 之收率化合物 Ar Ar' 收率 (%)
8aa p-CH3C6H4 C6H5 80
8ab p-CH3C6H4 p-CH3C6H4 60
8bb p-CH3OC6H4 p-CH3C6H4 55
8cb p-ClC6H4 p-CH3C6H4 54
8ac p-CH3C6H4 p-CH3OC6H4 81
8bc p-CH3OC6H4 p-CH3OC6H4 68
8cc p-ClC6H4 p-CH3OC6H4 62
8ad p-CH3C6H4 p-ClC6H4 72
8bd p-CH3OC6H4 p-ClC6H4 78
Furture Project and Development
NN
O
Ar
OO
N Ar'
NN
O
Ar
ONN
O
Ar
O
O
Ar'
H
H
N S
Ar'
NN
O
Ar
O
NN Ar'
ph
H2N SH
NH2OH
phNHNH2
.HCl
NN
O
Ar
O
NN
S
Ar'
NN Ar'
NN
O
Ar
O
NN
Ar'
NH2
NN
O
Ar
O
thiourea
HClNH2NH2 .
H2NC(=NH)NH2
NN
O
Ar
O
O
Ar'
H
H
