The reaction of an aromatic heterocycle with a proton is called a protonation. One of articles about this theory is 《Syntheses in the heterocyclic series. IV. Syntheses of heterocyclic aldehydes. 4-Pyrimidinecarboxaldehyde》. Authors are Bredereck, Hellmut; Sell, Ruediger; Effenberger, Franz.The article about the compound:1H-Pyrazole-5-carbaldehydecas:948552-36-1,SMILESS:O=CC1=CC=NN1).Safety of 1H-Pyrazole-5-carbaldehyde. Through the article, more information about this compound (cas:948552-36-1) is conveyed.
cf. CA 59, 10054b. A series of heterocyclic aldehyde acetals and aldehydes was prepared from the appropriate bifunctional compounds with an aldehyde acetal group. Me2NCH:CHCOCH(OEt)2 (I) and HN:CHNH2.AcOH (II) yielded 4-pyrimidinecarboxaldehyde di-Et acetal (III) and from this the free 4-pyrimidinecarboxaldehyde (IV). AcCH2COCH(OEt)2 (V), b10 101-3°, b0.001 48-50°, was prepared in 65% yield by the method of Panizzi (CA 38, 35003). AcCH(OAc)CH(OMe)2 (8.0 g.), b10 98-104°, in 50 cc. absolute MeOH refluxed 45 min. with 2 cc. 2% NaOMeMeOH yielded 5.0 g. AcCH(OH)CH(OMe)2 (VI), b8 87°, n20D 1.4302. AcCH(OMe)2 (29.2 g.) and 29.4 g. Me2NCH(OEt)2 heated 20 h. at 80° gave 32 g. I, b0.001 115-20°, n20D 1.5210, m. 25-30°. N2H4.H2SO4 (16.3 g.) in 100 cc. 10% aqueous NaOH treated dropwise at ∼15° with stirring with 23.5 g. V and the mixture stirred 1 h. at 15° yielded 20.5 g. (crude) 5(3)-methylpyrazole-3(5)-carboxaldehyde di-Et acetal (VII), b0.001 94-6°, n20D 1.4744. VII (4.0 g.), 0.85 cc. concentrated HCl, and 31 cc. H2O kept 10 h. at room temperature yielded 2.25 g. 5(3)-methylpyrazole-3(5)-carboxaldehyde (VIII), m. 188-9° (decomposition); oxime m. 171° (H2O); semicarbazone m. 193-8° (decomposition) (H2O); phenylhydrazone m. 184° (50% aqueous EtOH). VIII (0.5 g.) in 50 cc. concentrated NH4OH yielded during 3 days 0.4 g. 3(5)-methyl-5(3)-aminomethylenepyrazole, decomposed 170-3°. VIII (1.1 g.) and 2 cc. dry piperidine heated 3 h. at 80-90° gave 1.15 g. 3(5)-methyl-5(3)-piperidinomethylenepyrazole, m. 228-9° (decomposition). VIII (0.5 g.) in 30 cc. N2H4.H2O kept 3 days gave 0.3 g. 5(3)-methylpyrazole-3(5)-aldehyde azine, pale yellow. N2H4.H2SO4 (6.5 g.) in 40 cc. 10% aqueous NaOH treated dropwise with stirring at room temperature with 10 g. I, and the mixture stirred 2 h. and kept overnight gave 7.1 g. pyrazole-3-carboxaldehyde di-Et acetal (IX), b0.001 86°, n20D 1.4746; phenylhydrazone m. 199-201°. IX (4.0 g.) in 1% HCl kept several hrs. at room temperature gave 1.8 g. pyrazole-3-carboxaldehyde, m. 146-7° (H2O). HN:C(NH2)2 carbonate (3.1 g.) in 1 cc. concentrated H2SO4 and 5 cc. H2O treated with 5.67 g. Ba(OH)2 in 50 cc. H2O, the mixture filtered, concentrated to 10 cc., and treated 3 days with 5.0 g. VI, and the crude product (5.5 g.) treated in MeOH with picric acid in MeOH gave 5.5 g. (crude) picrate of 2-amino-4(5)-methylimidazole-5(4)-carboxaldehyde di-Me acetal (X), m. 229-30° (MeOH). VI (7.4 g.), 6.3 g. MeSC(:NH)NH2.HCl (XI.HCl), and 25 cc. absolute EtOH treated during 1 h. at room temperature with 1.15 g. Na in 25 cc. absolute EtOH, kept 3 days, and the oily product (2.0 g.) treated with saturated picric acid in MeOH gave 0.1 g. picrate, decomposed 163-5°, of the 2-MeS analog of X. VI (7.4 g.) and 7.8g. PhC(:NH)NH2.HCl gave 3.7 g. (crude) 2-Ph analog of X, m. 144-5° (AcOBu); picrate m. 239-40° (decomposition) (MeOH). V (75.2 g.), 72.4 g. XI, and 160 cc. H2O treated dropwise with stirring at room temperature during 0.5 h. with 29.2 g. KOH in 40 cc. H2O gave 49 g. di-Et acetal (XII) of 2-methylthio-6-methyl-4-pyrimidinecarboxaldehyde (XIII), yellowish oil, b0.001, 100-3°, n20D 1.5229; oxime m. 218-19° (decomposition)(EtOH); semicarbazone, light yellow, m. 215-20° (EtOH); phenylhydrazone, yellow, m. 182° (EtOH). XII (10.0 g.), 100 cc. 50% EtOH, and 1 cc. concentrated HCl refluxed 1 h. gave 5.7 g. XIII, m. 87° (petr. ether), b0.001 93-7°. XII (22.4 g.) in 400 cc. EtOH refluxed 2 h. with ∼100 g. Raney Ni gave 11.8 g. di-Et acetal (XIV) of 6-methylpyrimidine-4-carboxaldehyde (XV), b0.001 61-5°, n20D 1.4655; oxime m. 150° (H2O); semicarbazone m. 217° (EtOH); phenylhydrazone, yellow, m. 120-1° (50% EtOH). XIV (50 g.) in 50 cc. 50% EtOH and 0.5 cc. concentrated HCl refluxed 1 h. gave 3.4 g. XV, m. 53° (petr. ether). V (19 g.), 18.8 g. MeC(:NH)NH2.HCl, and 42 g. K2CO2 in 150 cc. H2O kept 3 days yielded 9.9 g. 2,6-dimethylpyrimidine-4-carboxaldehyde di-Et acetal (XVI), b0.001 50-9°, n20D 1.4712-1.4737; oxime m. 213° (1:3 EtOH-H2O). I (15 g.) and 15.6 g. PhC(:NH)NH2.HCl in 40 cc. H2O treated dropwise with stirring at 30° with 5.6 g. KOH in 20 cc. H2O and kept 2 days yielded 5.0 g. 2-Ph analog of XVI, viscous, yellow oil, b0.001 110-19°; oxime m. 165-6°(50% EtOH). I (20.5 g.), 18.3 g. XI, and 60 cc. H2O treated dropwise during 0.5 h. at room temperature with 7.3 g. KOH in 25 cc. H2O, stirred 1 h. at 50°, and kept several days yielded 14.3 g. pale yellow di-Et acetal (XVII) of 2-methylthiopyrimidine-4-carboxaldehyde (XVIII), b0.001, 112-16°, n20D 1.5190; oxime m. 165° (50% EtOH); semicarbazone, yellowish, m. 224° (50% EtOH); phenylhydrazone, yellow, m. 192-4° (EtOH). XVII (6.0 g.) in 60 cc. 50% EtOH refluxed 40 min. with 0.9 cc. concentrated HCl gave 2.8 g. XVIII, m. 68° (petr. ether), b0.001 110-12°. I (31.2 g.) and 40.2 g. II heated 2.5 h. at 115° gave 27 g. III, b0.001 63-5°, n20D 1.4683. XVII (20 g.) in 400 cc. EtOH refluxed 2 h. with ∼90 g. Raney Ni gave 5.7 g. III, b0.001 65-7°, n20D 1.4683. III gave in air III.H2O, m. 93° (sublimed at 70-80°/8 mm.); oxime m. 153-4°; semicarbazone m. 212° (decomposition); phenylhydrazone, yellow, m. 168-9° (50% EtOH). I (15 g.), 10.8 g. MeC(:NH)NH2.HCl, and 20 cc. absolute EtOH treated with stirring at 40° with 2.6 g. Na in 40 cc. EtOH, and the mixture stirred 2 h. at 40° and refluxed 15 min. gave 10.8 g. 2-Me derivative (XIX) of III, b7 104°, n20D 1.4719, phenylhydrazone m. 172° (50% EtOH). XIX (5.8 g.), 80 cc. H2O, and 0.35 cc. concentrated H2SO4 heated 3 h. at 60° and 1 h. at 70° yielded 5.5 g. 2-Me derivative of IV.H2O, m. 66° (sublimed in vacuo at 30°). PhC(:NH)NH2.HCl (15.5 g.), 20 g. I, and 20 cc. absolute EtOH treated dropwise at room temperature with 2.3 g. Na in 60 cc. absolute EtOH, and the mixture stirred 1 h. and kept overnight gave 15.7 g. 2-Ph derivative (XX) of III, b0.002 123°, n20D 1.5506; oxime m. 138°; phenylhydrazone m. 211° (EtOH). XX (5.2 g.), 30 cc. 50% EtOH, and 0.45 g. concentrated HCl refluxed 40 min. yielded 1.2 g. 2-Ph derivative of IV, m. 118° (cyclohexane). I (8.6 g.), 2.6 g. urea, and 0.99 g. Na in 40 cc. absolute EtOH refluxed 6 h. gave 1.4 g. 2-OH derivative of III, m. 143-4° (EtOH). HN:C(NH2)2 carbonate (1.12 g.) in the min. amount 1:5 H2SO4-H2O, treated with aqueous Ba(OH)2, filtered, concentrated to 10 cc., and treated 24 h. with 2.5 g. I yielded 0.80 g. 2-NH2 derivative of III, m. 137-8° (EtOH). IV (1.0 g.) in 5 cc. absolute EtOH treated with a few drops aqueous KCN yielded 0.60 g. pyrimidoin, orange-yellow, decomposed ∼239° (1:1 EtOH-Me2SO).
After consulting a lot of data, we found that this compound(948552-36-1)Safety of 1H-Pyrazole-5-carbaldehyde can be used in many types of reactions. And in most cases, this compound has more advantages.