In 1960,Gundermann, Karl Dietrich; Thomas, Rainer published 《Mercaptoacrylic acid derivatives. VII. The effect of thioether groups on the stabilization of 1-pyrazoline-3-carboxylic acid derivatives》.Chemische Berichte published the findings.Product Details of 15366-34-4 The information in the text is summarized as follows:
cf. CA 54, 289b. 3-Alkylthio-1-pyrazoline-3-carboxylic acid esters, readily obtained from α-alkylthioacrylic acid esters and CH2N2, split off mercaptans at room temperature to yield pyrazole-3-carboxylic acid esters, but N at 50° to give mixtures of 1-alkylthiocyclopropane-1-carboxylic acid esters and α-alkylthiocrotonic acid esters. Pyrazoline derivs, from α-alkylthioacrylonitriles and CH2N2 underwent only a stabilization reaction with the elimination of N. CH2:C(SMe)CO2Me (21.4 g.) in 200 cc. Et2O treated with CH2N2 from 25 g. H2NCON(NO)Me (I) in 200 cc. Et2O, kept overnight, filtered, evaporated in vacuo at 30°, the resulting light yellow, oily pyrazoline derivative added dropwise to a flask preheated to 90-100°, heated about 0.5 hr. on the steam bath, and fractionated gave 19.8 g. 3:1 mixture of the Me ester (II) of 1-methylthiocyclopropane-1-carboxylic acid (III) and Me α-(methylthio)crotonate (IV), b15 70-82°, n20D 1.4835. (III-IV mixture (15 g.) and 50 cc. 20% HCl refluxed about 6 hrs., evaporated in vacuo, and the residue (7.7 g.) recrystallized from 20% HCl gave III, m. 65-6°, b0.2 84-6°, Rf 0.90 (4:1:5 BuOH-glacial AcOH-H2O), colorless prisms; III with CH2N2 gave 100% pure II, b14 74°, n20D 1.4823. II treated room temperature with concentrated NH4OH and evaporated yielded the amide of III, prisms, m. 89° (petr. ether). Crude pyrazoline derivative from CH2:C(SMe)CO2Me and CH2N2 kept 1 week at room temperature and filtered gave the Me ester of pyrazole-3-carboxylic acid (V), m. 140° (aqueous MeOH), which was saponified to V, m. 212°. II-III mixture (3 g.) treated about 24 hrs. at room temperature with liquid NH3 gave 0.6 g. MeCH(NH2)-CH(SMe)CO2H, Rf 0.64; saponification of the nonbasic portion of the product gave 1.7 g. III. Me3CSH (45 g.) added dropwise with stirring to 60 g. CH2:CClCO2Me and 2.3 g. NaOMe at 45-50°, kept overnight, diluted with Et2O, washed, dried, and fractionated gave 68.7 g. Me3CSCH2CHClCO2Me (VI), b0.4 85-6°, b0.2 77-8°, n20D 1.4790. VI (42 g.), 26.2 g. powd. KBr, 22.2 g. Et3N, and 170 cc. HCONMe2 gave in the usual manner 22.8 g. Me2CSC(:CH2)CO2Me (VII), b12 92-3°. n20D 1.4795. VII (8.6 g.) in 70 cc. Et2O treated with CH2N2 from 10 g. I in 100 cc. Et2O, the product decomposed at 85-90°, and fractionated gave 7.0 g. oil, b12 83-5°, n20D 1.4803; the oil refluxed 1 hr. on the steam bath with 2 volumes 20% aqueous NaOH and 1 volume MeOH, filtered, acidified, and the product isolated with Et2O gave 3.8 g. 1-tert-butylthiocyclopropane-1-carboxylic acid, b0.2 93-4°, n22D 1.4955. The crude product from VII and CH2N2 kept 8 days at room temperature yielded 90% Me ester of V. CH2:C(SMe)CN (8 g.) in 80 cc. Et2O treated with CH2N2 from 12 g. I, the crude product dropped at 80-90° into a flask, and the residue fractionated yielded 6.85 g. 4:1 mixture of the nitrile of III and MeCH:C(SMe)CN, b11 67-9°, n20D 1.4900; the mixture heated 4 hrs. with a 5-fold amount 1:1 glacial AcOH-HCl, evaporated, the residue extracted with Me2CO, and the extract worked up gave 60% III. CH2:C(SCH2Ph)CN (11.5 g.) and CH2N2 from 11 g. I yielded similarly 10.53 g. 4:1 mixture of 1-benzylthio-1-cyanocyclopropane and MeCH:C(SCH2Ph)CN, b0.15 104-6°, n20D 1.5676; a 10-g. portion in 100 g. AcOH-HCl heated 7 hrs. on the steam bath and evaporated, the residue treated with Et2O and aqueous NaHCO3, and the aqueous phase acidified gave 5.55 g. 1-benzylthiocyclopropane-1-carboxylic acid, prisms, m. 132-3° (C6H6-petr. ether). MeCH:C(SMe)CO2Me (10 g.) in 100 cc. Et2O treated with CH2N2 from 10 g. I in 100 cc. Et2O, 1 g. of the resulting crude pyrazoline ester kept at room temperature, and filtered gave 0.51 g. Me 4-methylpyrazole-3-carboxylate (VIII), m. 172° (aqueous MeOH). Crude pyrazoline ester (12 g.) added dropwise to a flask at 110-13° gave 5.5 g. VIII, m. 172°; the residue from the petr. ether washings gave 2.65 g. unidentified oil, b15 88-91°, n20D 1.4902, which by acid hydrolysis gave MeSH. In the experiment, the researchers used many compounds, for example, Methyl 1H-pyrazole-3-carboxylate(cas: 15366-34-4Product Details of 15366-34-4)
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.Product Details of 15366-34-4
Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics