5-Amino-3-cyano-1 - pyrazole, hydration

A new efficient procedure has been proposed for the synthesis of 3-aryl-5-amino-l//-pyrazoles by reaction of a-chloro-/ -arylacrylonitriles with hydrazine hydrate <2004RJ01518>. Reaction of 2-(3,3-dicyano-2-propenylidene)-4,4,5,5-tetra-methyl-l,3-dioxolane 641 with hydrazine afforded 3-(2-hydroxy-l,l,2-trimethylpropoxy)pyrazole 642 (Equation 134) <2003RJ01016>. Treatment of ethyl 3,3-dicyano-2-methoxyacrylate with alkyl, aryl, heterocyclic, and sulfonyl hydrazines led to the synthesis of N-l-substituted 3-acyM-cyano-5-aminopyrazoles, which are versatile intermediates for the synthesis of many biologically active scaffolds <2006TL5797>. 2-Hydrazinothiazol-4(5//)-one reacted with a variety of cinnamonitrile derivatives and activated acrylonitriles to yield annelated pyrazolopyrano[2,3-rf thiazole <1998JCM730>. 

The hydration of 5-amino-3-cyano-l-(2,6-dichloro-4-trifluoromethylphenyl)-4-ethynylpyrazole was performed with p-toluenesulfonic acid monohydrate in acetonitrile (2 h, room temperature) to give the corresponding 4-acetyl derivative. An alkyl substituent at the triple bond decreases the rate of hydration the conversion of 5-amino-3-cyano-l-(2,6-dichloro-4-trifiuoromethylphenyl)-4-(prop-l-yn-l-yl) pyrazole to the 4-propanoylpyrazole was completed after 18 h (98INP9804530 99EUP933363). 

Hydrazine hydrate caused the formation of fused pyrazole-like rings as found in the conversions shown in Scheme 10. The reagent was observed to react more rapidly with the fragment H2NC=CC02Et as found in the conversion of cyano ester 149b to fused 2-amino-3-cyano-4//-pyran 45 (R1 = CN, R2 = Ph, R3 = Me, R4 = H) [86ZN(B)925]. 

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