2-Alkyl-substituted pyrazole 1-oxides

The aromatic 2-substituted pyrazole 1-oxides 74 are derived from pyrazoles 89 by appending an oxygen atom to the pyridine type ring nitrogen atom of the pyrazole nucleus. The second nitrogen atom of the pyrazole ring can be attached to an alkyl, aryl, hydroxy, or amino group. 

The 2-alkyl- or aryl-substituted pyrazole 1-oxides are usually stable, crystalline, semipolar, and slightly hygroscopic compounds. 2-Substituted pyrazole 1-oxides are weak bases, being subject to protonation at the negatively charged oxygen atom. 2-Hyd roxypyrazole 1-oxides 74 (R = OH) are acids, no pf(a values seem to have been reported. 

Substituted pyrazole 1-oxides 74 can be prepared by N-oxidation of 1-substituted pyrazoles 89, by A/-alkylation of 1 -hydroxypyrazoles 90, or by cyclization of 1,3-oximimines, conjugated oximenamines, or conjugated 1,3-nitrosoimines. 

N-Alkylation of 1-hydroxypyrazoles 90 produces 2-substituted pyrazole 1-oxides 91 (Scheme 26). Competing O-alkylation of the... 

Alkyl- or aryl-substituted pyrazole 1-oxides 94 can be obtained in acceptable yields by oxidative cyclization of O-silylated 3-oximimines like 1 -tert-hutyldimethyIsilyloxy-4-methylamino-1 -azab nta-1,3-diene 93 using copper(II) sulfate as the oxidant and pyridine and acetonitrile as the solvent. The oximimines are prepared from 1,3-dicarbonyl compounds 92 in a one-pot process. The method also gives access to 2-alkyl and aryl-pyrazole 1-oxides R=H devoid of substituents at the ring carbon atoms (94 Ri = R2=H) (1995JCS(P1)2773) (Scheme 27). 

Perhaps the most useful of these 4,5-dihydro-I/7-pyrazole based routes, however, are those where the intermediate is simply oxidized with manganese(IV) oxide. As in the synthesis of 3,3-dimethyl-l-nitro-2-phenylcyclopropene (5), this sometimes makes possible the synthesis of precursors not available by the diazoalkane to acetylene addition route. In other cases, man-ganese(IV) oxide oxidation gives yields which are at least as good and often better than the diazoalkane to acetylene addition route and this method has been applied to the synthesis of nitro-, cyano-, carboxymethyl-, phenyl-, and alkyl-substituted systems. ... 

Substituted imidazole 1-oxides 263 upon treatment with dimethyl or diethyl sulfate furnish l-alkoxy-3-subtituted imidazolium salts 283 that were converted to the tetrafluoroborate 283 (A- = BF4 ) or hexafluorophos-phates 283 (A = PF6-) by treatment with sodium tetrafluoroborate or hexa-fluorophosphate (2007ZN(A)295). The tetrafluoroborates 283 (A = BF4 ) reacted with cyanide ion to give 2-cyanoimidazoles 285 (1975JCS(P1)275). The reaction probably follows a mechanism similar to that suggested to be operative in the pyrazole series encompassing O-alkylation succeeded by nucleophilic addition and elimination of methanol (Scheme 85). 

Under conditions of C-H/N-H bond functionalization, aryl-, heteroaryl-, and alkenyl-substituted IH-pyrazoles underwent oxidative annulation with aryl and alkyl alkynes in high chemo- and regioselectivity in the presence of Ru(II)/AgSbFg catalyst (Eq. (7.28)) [36]. Aryl alkynes particularly bearing electron-donating substituents are more reactive in the present reaction system. A cationic ruthenium(II)-catalyzed reversible C-H bond metalation step was observed in the H/D exchange experiments. 

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