5-Aminopyrazole

Pyrazolines substituted at position 4 or 5 with hydroxy or amino groups readily eliminate a molecule of water or amine yielding pyrazoles. The 4-substituted derivatives are relatively more stable than the 5-substituted ones, because for the last group the lone pair at N-1 assists the elimination (407) -> (408) -> (409). The sulfonyl group at position 1 is also easily eliminated and this property is taken advantage of in Dorn s elegant synthesis of 3-aminopyrazole (Section 4.04.3.3.1). 

The tautomeric equilibria of 5-hydroxy-3-aminopyrazoles 226 are affected by the substituent R" (Scheme 77) [76AHC(S1), p. 467]. While structure 226b is usually the major form, for some compounds of type 226 (R = COMe, COPh) the equilibrium content of 226c may reach 60% (74BSF291). 

I.3.3.I. Reaction of 2-Lithiomethylpyridine 88.11, 1-Lithiomethylisoquinoline 85.12,2-Lithiomethylthiozole 85.14/thiazolidine 85.15,3-Aminopyrazole 85.17 with 6 A New General Method for Bridgehead Heterocycles... 

The 3-aminopyrazole 85.17 also reacted with 6 to yield the corresponding pyrazolo[a] pyrimidines 111 (19 examples) exclusively as sole regioisomers in excellent yields. Similarly the condensed variants 112 and 113 were prepared in high yields <90T577>. 

Aminopyrazole has been prepared by a Curtius degradation of pyrazole-3(5)-carboxylic acid hydrazide,2 3 by saponification and decarboxylation of ethyl 3-aminopyrazole-4-carboxy-late 4 obtained from ethyl ethoxymethylenecyanoacetate and hydrazine, and by the present procedure.6,6... 

With chlorinated quinones. New heterocycles containing 1,2-dihydro-imidazo [l,2- ]imidazol-3-one 405 or 1/7-imi-dazo[l,2- ]pyrazole moieties were obtained via charge-transfer interaction of creatinine or 3-aminopyrazole with some 7i-deficient compounds such as 2,3-dichloro-5,6-dicyano-l,4-benzoquinone, 2,3,5,6-tetrachloro-l,4-benzoquinone, 2,3-dichloro- or 2,3-dicyano-1,4-naphthoquinone, and 3,4,5,6-tetrachloro-l,2-benzoquinone (Equation 183) C1996BSB159, 2001HC0541, 2000PS1>. 

Aminopyrazoles 257 substituted at the C-4 and C-5 positions react with a variety of imidate hydrochlorides giving iV-hydroxyamidines 258, that after tosylation and intramolecular cyclization afford the corresponding pyrazolo[ 1,5-4 )-[l,2,4]triazole derivatives 259 (Scheme 21) <1998CPB287, 1998CPB69>. 

A typical cyclization reaction starting from a 3-aminopyrazole is the transformation of 255 <2000BML821 >. This compound was treated first with ethoxycarbonyl isothiocyanate followed by sodium methoxide to yield a cyclic intermediate which was methylated by methyl iodide to give the stable product 256. In the cases of the synthesis of 257 <1995PHA675>, the dimeric 258 <2005JHC975>, the azo-substituted 259 <2001JCM439>, and the diaryl... 

The reaction of 3-aminopyrazole and EMME at 100°C for 30 min gave 10% of pyrazolo[l,5-a]pyrimidinecarboxylate (64) and 25% of 3-pyrazolylaminomethylenemalonate (70CB3252). When the reaction was carried out in boiling acetic acid for 3 hr, pyrazolo[l,5-n]pyrimidinecar-boxylate (64) was isolated in 60% yield (62CPB620 70CB3252). Heating of the reaction mixture of 5-substituted 2-amino-1,3,4-oxadiazoles and EMME at 130-140°C for 2-3 hr afforded N-(5-substituted 1,3,4-oxadiazol-2-yl)aminomethylenemalonates (65) in 40-92% yields [88IJC (B)293]. 

Pyrazolo[l,5-a]pyrimidine-6-carboxylates (1402) were prepared in 70% yields in the reaction of 3-aminopyrazoles and diethyl amino(trichloro-methyl)methylenemalonate in boiling ethanol in the presence of sodium ethoxide for 6 hr (78JPR533). 

Herz salts (89) made from 3-aminopyrazoles (Section 4.11.8.5) give pyrazolo[3,4-r/]-l,2,3-thia-diazoles (90) when subjected to reduction by sodium dithionite followed by nitrozation (Equation (12)) <84JOCl224>. If the reduction is carried out in an inert atmosphere the disulfide (91) is formed which upon nitrozation gives (90) in 63% yield. Notably, benzo-fused Herz salts give benzo-1,2,3-thiadiazoles simply on treatment with nitrozating mixture <84CHEC-I(6)916>. 

Numerous patents78,79 have recorded the preparation of malonates (71 X = C02Et), which afforded 4-hydroxy or 4-chloro derivatives (72 R3 = OH, Cl) when refluxed with diphenyl ether or phosphorous oxychloride. The reaction has provided 2-substituted isomers80,81 from 3-aminopyrazoles and, by using the appropriate reagent (70 X = COR), the corresponding 5-ketones (72) can be obtained.82-87... 

Unsubstituted isoxazolium salts (72) react with hydrazines to yield 3-aminopyrazoles (73 X = H, N02, Hal, COMe, C02Et, R3 = H, Me, Ph, CONH2) (88S203). 

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