Synthesis and Herbicidal Activity of 1,5-Diarylpyrazole Derivatives

interest in agrochemicals and drugs. Aryl group substituted pyrazoles and imidazoles, in particular, have been studied because their biological activities are strongly dependent on their substituents on the pyrazole ring system. 1,5-Diaryl substituted pyrazole (SR141716A, 1), which has a hydrazide group on the 3-position of the pyrazole ring, has recently been synthesized and identified as the first antagonist for the cannabinoid receptor. A 3-trifluoromethyl group substituted 1,5-diarypyrazole derivative (SC-558, 2) was reported to be a new class of selective inhibitors of cyclooxygenase-2 (cox2). As an agrochemical, 1-arylimidazole, which has a carboxylic ester group on the 4-position of the imidazole ring (3), was reported to be a herbicide antidote. 1,5-Diaryl substituted 1,2,4-triazole-3-carboxamide, previously known as flupoxam (4), is a selective herbicide against broadleaf weeds, and is completely safe against wheat (Fig. 1). We focused on the synthesis of 4-nonsubstituted or 4-chloro-substituted pyrazolecarboxamides (5 or 6), and 5-nonsubstituted or 5-chloro-substituted imidazole carboxamides (7 or 8) and sought to learn their herbicidal activities (Chart 1). It was speculated that 1,5-diarylpyrazoles could be synthesized by condensation of arylhydrazines and aroylpyruvates, which were prepared from acetophenone derivatives and dimethyl oxalate. An arylhydrazine having the same substituents as flupoxam (4) was synthesized as shown in Chart 2. 2-Chlorobenzyl chloride (9) was treated with potassium nitrate and sulfuric acid to give the nitro-form (10). Introduction of a 1,1,1,2,2-pentafluoropropyl group was performed with the reaction of compound 10, the corresponding alcohol, and potassium hydroxide. Reduction of the nitro group of compound 11, without cleavage of the benzylic ether moiety, was accomplished with zinc powder in 90% acetic acid to afford the aniline derivative (12). Conversion of amino group into hydrazine proceeded by diazotization, followed by reduction with stannous chloride, giving rise to the desired aryl hydrazine (13a) in good yield. With hydrazine in hand, compound 13a was condensed with benzoylpyruvate (15a), which was prepared from acetophenone (14a) and dimethyl oxalate, to give the desired 1,5-diarylpyrazole 16a in 93.1% yield, along with 1,3-diarylpyrazole 17a in 3.2% yield (Chart 3). These two isomers can be easily separated by silica gel column chromatography, and can be readily distinguished by their NMR spectra, because it is reported that the pyrazole C4 proton in the 1,5-diarylisomer always resonates in a higher field than that in the 1,3-diarylisomer. Conversion of the June 1999 Chem. Pharm. Bull. 47(6) 857—868 (1999) 857