In 1947,Owen, L. N.; Somade, H. M. Babatunde published 《Olefinic acids. II. Reactivity of α-bromoacrylic acid and some related compounds》.Journal of the Chemical Society published the findings.Electric Literature of C5H6N2O2 The information in the text is summarized as follows:
cf. C.A. 39, 4589.1. BrCH2CHBrCO2H (I) (24 g.) in 20 cc. MeOH and 11 cc. 3.76 N MeOH-MeONa, refluxed 7 hrs., gives 1.1 g. β-methoxyacrylic acid (II), m. 102°, absorption maximum at 2280 A. (ε 14,100); it yields malonic semialdehyde 2,4-dinitrophenylhydrazone (III), lemon-yellow, m. 136° (decomposition); aqueous NaOH gives a deep red solution I (90 g.) in H2O, neutralized with N NaOH at 0°, treated with an equal volume N NaOH, and kept at room temperature 1 hr., gives 87% CH2:CBrCO2H (IV), m. 72°, stable for several months. IV (15 g.) in 40 cc. MeOH and 35 cc. 3.67 N MeOH-MeONa, refluxed 3 hrs., give a liquid acid containing some II; with MeI and Ag2O in ether, refluxed 0.5 hr., the acid yields MeOCH2CHBrCO2Me containing some MeOCH2CH(OMe)CO2Me. IV (10 g.) and 45 cc. 2 N EtOH-EtONa, refluxed 20 hrs., give 1 g. EtOCH:CHCO2H, m. 109°, absorption maximum at 2300 A. (ε 14,700); ether extraction of the aqueous solution gives 5.1 g. of a liquid halogen-free acid which, with EtI and Ag2O, gives 1.5 g. Me α,β-diethoxypropionate, b11 87°, nD21 1.4130. IV (7.5 g.) in 60 cc. iso-PrOH and 5 g. K in 60 cc. iso-PrOH, refluxed 24 hrs., give 7 g. of mainly β-isopropoxyacrylic acid (probably containing 12% iso-PrOCH:C(OPr-iso)CO2H), b0.001 55°, nD15 1.4425, absorption maximum at 2340 A., ε 14,000; 2,4-(O2N)2C6H3NHNH2 gives III; neither acid could be purified. IV (15.2 g.) in 20 cc. tert-BuOH and 10 g. K in 200 cc. tert-BuOH, refluxed 24 hrs., give 4.9 g. β-tert-butoxyacrylic acid, m. 86.5°, absorption maximum at 2370 A., ε 15,400. CH2:C(OMe)CO2Me (b15 58-60°, absorption maximum at 2280 A., ε 7300) (2.1 g.) and 15 cc. 2 N NaOH, heated 1.5 hrs. at 100°, give 1.2 g. α-methoxyacrylic acid (V), m. 52°, absorption maximum at 2280 A., ε 6000; V is unchanged on refluxing 6 hrs. with N MeOH-MeONa; EtOCH:CHCO2H behaves similarly. IV (5 g.), added to 5 cc. AcSH cooled in ice and heated 15 min. on the steam bath, gives 6.9 g. α-bromo-β-(acetylmercapto)-propionic acid, m. 85-6°; the α-Cl analog m. 75°; under the same conditions MeCH:CBrCO2H (VI) is unchanged. IV (0.5 g.), 0.5 cc. C5H5N, and 1 cc. PhCH2SH, heated 15 min. on the steam bath, give β-(benzylmercapto)-acrylic acid, m. 162-3°, absorption maximum at 2740 A., ε 15,500. IV (2 g.) in excess CH2N2 in ether, kept 5 days at 20° and the liquid residue heated to 60°, gives 0.9 g. Me 3-pyrazolecarboxylate (VII), m. 141°; CH2:CClCO2H gives the same product; VI gives the 4-Me derivative of VII, m. 170°. Me2C:CBrCO2H (2 g.) and CH2N2 give 1.8 g. Me α-bromo-β,β-dimethylacrylate, b9 76°, nD21 1.4909; NH4OH gives α-bromo-β,β-dimethylacrylamide, m. 129°. CH2:CBrCO2Me (1 g.) and 2 g. N2CHCO2Me in petr. ether (b. 80-100°), refluxed 15 hrs., give 1.3 g. di-Me 3,5-pyrazoledicarboxylate, m. 152°. The Me ester of VI (1 g.) and 1 g. N2CHCO2Me in petr. ether, refluxed 24 hrs., give 0.15 g. di-Me 4-methyl-3,5-pyrazoledicarboxylate, m. 128-9°. Me2C:CBrCO2H does not react with N2CHCO2Me. CH2:C(OMe)CO2Me (VIII) and CH2N2 in ether, kept 4 days at 20°, give a liquid b. about 135°; NH4OH gives 1-methoxy-1-cyclopropanecarboxamide, m. 117°. VIII in MeOH, saturated with dry HCl at 0°, gives MeC(OMe)2CO2Me.Methyl 1H-pyrazole-3-carboxylate(cas: 15366-34-4Electric Literature of C5H6N2O2) was used in this study.
Methyl 1H-pyrazole-3-carboxylate(cas: 15366-34-4) belongs to pyrazoles. The application of pyrazole derivatives in the development of anticancer agents has been thoroughly investigated and verified. Moreover, the medicinal features of a number of natural products incorporating pyrazole moiety such as pyrazofurin, pyrazofurin B, pyrazole-3(5)-carboxylic acid and 4-methylpyrazole-3(5)-carboxylic acid have been reported.Electric Literature of C5H6N2O2
Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics