Reduction of pyrazoles

A -Pyrazolines are obtained by the reduction of pyrazoles with sodium and alcohol, by catalytic hydrogenation on palladium or by electrochemical means (B-76MI40402). In some cases the reduction proceeds further yielding pyrazolidines and open-chain compounds. 

Rosenmund reduction of pyrazole acid chlorides to aldehydes never causes reduction of the ring.834,635,744,745 Attempts to prepare the aldehydes by the sodium amalgam reduction of the anilides, however, gave only traces of the required products,635 but the fate of the pyrazole ring is not recorded. It is the authors experience that pyrazoles unsubstituted on nitrogen are usually unaffected by sodium and alcohol, although the reduction to pyrazoline by sodium and alcohol at 130° and 20 atmospheres pressure has been patented.746 Reduction of Ar-phonyIpyrazoles is somewhat easier sodium and alcohol reduce them to A-phenylpyrazolines,77,78, 207,235, 447,567,... 

Only two topics are of importance for this section the reduction of pyrazolium salts and 3-pyrazolin-5-ones by complex hydrides, and the nucleophilic photosubstitution of pyrazoles and indazoles. 

Besides the salts (458) and (459) previously described, aminopyrazolium salts can be obtained from the reaction between amines and chloropyrazolium salts (Section 4.04.2.3.7(ii)) or by quaternization of iminopyrazplines as in (461)—> (462) (72BSF2807). The lithium aluminum hydride reduction of the salt (462) affords mixtures of reduced and open-chain pyrazoles (Figure 23 Section 4.04.2.1.6(i)). 

Ravindranath and co-workers studied the electrochemical behavior of 5-amino-2-phenyl-4-arylazo-l,2-dihydro-3//-pyrazol-3-one (90UC864) and 5-methyl-4-arylazo-2-(pyridin-2-ylcarbonyl)-2,4-dihydro-3//-pyrazol-3-(Mie (90IJC895). Similar studies were undertaken by Jain and Damodharan of pyrazol-3-ones 408a-f (95CJC176) (Scheme 94). The underlying rationale for this study on the electrochemical reduction of these biologically important pyrazol-3-ones is that it can lead to information on the reaction routes and mechanisms of biological redox reactions. 

Makriyannis and Liu claimed a series of pyrazole analogues in a patent application published in 2003 [272]. Of the 29 compounds specifically exemplified in the patent application, compound (389) was demonstrated to reduce lever presses when administered to rats that were trained to expect delivery of a food pellet as the outcome. It was proposed that the reduction in lever pressing was the result of decreased appetite brought about by CBi receptor antagonism. 

Literature reports on diazaquinones derived from o-benzoquinone are very rare. Compound 74 was suggested to be a common intermediate formed during heating of 2,5-bis(diazo)-3,4-diketoadipate 73 with isopropanol and with various bases (76T269). Direct reduction of the intermediate with isopropanol provided pyridazine 75. A base-catalyzed benzilic acid rearrangement of 74 followed by decarboxylation of 76 afforded pyrazole 77 (Scheme 18). 

Bis(pyrazolyl)borate copper complex 47 has been employed as a catalyst in the homogeneous and heterogeneous styrene epoxidation reactions <00JCS(CC)1653>. Pyrazole palladacycles 48 have proven to be stable and efficient catalysts for Heck vinylations of aryl iodides <00JCS(CC)2053>. An asymmetric borane reduction of ketones catalyzed by N-hydroxyalkyl-/-menthopyrazoles has been reported <00JHC983>. 

As mentioned above, iridium complexes are also active in the formation of amines via the hydrosilylation/protodesUylation of imines. In the presence of 2 equiv. of HSiEts, the cationic complex [lr bis(pyrazol-l-yl)methane (CO)2][BPh4] (C4) catalyzes the reduction of various imines, including N-alkyl and N-aryl imines and both aldimines and ketimmes. Excellent conversions directly to the amine products were achieved rapidly at room temperature in a methanol solution (Scheme 14.7) [53]. 

USP482361). Compound 184 is converted into the pyrazolo[4,3- /]-pyrimidine derivative 185 by formamide. Amines convert 184 into carboxamide 186, which affords 187 upon treatment with formamide (78MI1). Reduction of 181 in the presence of formic acid gives the pyrazole derivative 183, which when treated with DMF affords the pyrazolo[4,3-d]pyrimidine derivative 182 (81USP4822361 83FES369). 

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