Chemistry of Heterocyclic Compounds, Vol. 40, No. 10, 2004
POLYFUNCTIONAL PYRAZOLES.
3.* SYNTHESIS OF 3-(3-ARYL-4-FORMYL-
1-PYRAZOLYL)PROPIONIC ACIDS AND THEIR AMIDES
M. K. Bratenko1, V. A. Chornous1, and M. V. Vovk2
3-(3-Aryl-4-formyl-1-pyrazolyl)propionic acids were synthesized by the reaction of 3-aryl-1-(2-
cyanoethyl)-4-formylpyrazoles with concentrated hydrochloric acid. They were converted into the
corresponding amides by the carbodiimide method.
Keywords: amides, dicyclohexylcarbodiimide, 3-(4-formyl-1-pyrazolyl)propionic acids, 1-(2-cyanoethyl)-
4-formylpyrazoles, hydrolysis.
Earlier [2] we described the synthesis of 3-aryl-1-(2-cyanoethyl)-4-formylpyrazoles and the
corresponding thiosemicarbazides. On the basis of the last reactions with monochloroacetic acid and maleic
anhydride unsymmetrical azines with 3-aryl-1-(2-cyanoethyl)-4-methylidenepyrazole and 2-thiazolidinylen-4-
one fragments having antimicrobial activity were obtained [3].
The present communication presents the results from selective modification of the 2-cyanoethyl
substituent in the 4-formylpyrazoles 1a-e to a 2-carboxyethyl substituent. We showed that during the action of
boiling concentrated hydrochloric acid the nitrile group of compounds 1a-e is readily hydrolyzed and forms
3-(3-aryl-4-formyl-1-pyrazolyl)propionic acids 2a-e with yields of 78-93%. It is remarkable that cleavage of the
C–N bond of neither the β-cyanoethyl nor the β-carboxyethyl substituent with the nitrogen atom of the pyrazole
ring was observed under the reaction conditions [4].
CHO
CHO
CHO
Ar
Ar
Ar
R1R2NH
DCC
H2O / HCl
CN
N
N
N
N
N
N
O
COOH
3a–e R2R1N
2a–e
1a–e
1, 2 а Ar = Ph, b Ar = 4-FC6H4, c Ar = 4-ClC6H4, d Ar = 4-BrC6H4, e Ar = 4-MeOC6H4;
3a,b,d-g R1 = H, c R1R2 = (CH2)2O(CH2)2; a Ar = Ph, R2 = 2-methyl-5-quinolinyl;
b Ar = 4-FC6H4, R2 = 4-MeOC6H4; c Ar = 4-FC6H4,; d Ar = 4-ClC6H4, R2 = 5-quinolinyl;
e Ar = 4-BrC6H4, R2 = 4-MeC6H4; f Ar = 4-BrC6H4, R2 = 3-pyridyl;
g Ar = 4-MeOC6H4, R2 = Ph
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* For Communication 2, see [1].
__________________________________________________________________________________________
1
Bukovinian State Medical Academy, Chernovtsy, Ukraine; e-mail: chornous@chv.ukrpack.net.
2
Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Kiev, Ukraine; e-mail:
hetfos@ukrpack.net. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1483-1486, October,
2004. Original article submitted May 15, 2001.
0009-3122/04/4010-1279©2004 Springer Science+Business Media, Inc.
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