Synthesis Of1-methyl-3-trifluoromethyl-4-pyrazole Carboxylic Acid

4-Amide-aryl-pyrazol is an effective HPPD inhibitor which is environmentally-friendly as well as has high activity and low toxicity.1-methyl-3-trifluromethyl-4-pyrazole carboxylic acid is an important intermediate in the synthesis of the herbicide mentioned above and the new pyrazole herbicide which contains fluorine. The fluorine-containing amide pyrazol derivatives which gains from1-methyl-3-tri-fluromethyl-4-pyrazole carboxylic acid are also important antiseptic. Fluorine-containing amide pyrazol derivatives are increasingly becoming hot issues because of excellent activity in sterilizing and weeding.This project put forward an improved synthetic method of1-methyl-3-trifluro-methyl-4-pyrazole carboxylic acid and made some optimizations on the basis of the proposed route reported. The improved synthetic technology was first started from the preparation of N-(methoxymethylene)-N,N-dimethylaminium methyanesulfate followed by the reaction with sodium cyanoacetate to afford3-(dimethylamino)acry-lonitrile. Then3-(dimethylamino)acrylonitrile reacts with trifluoroacetyl chloride by acylation to give2-((dimethylamino)methylene)-4,4,4-trifluoro-3-oxobutanenitrile. The following step is cyclization using the last product and methylhydrazine to yield1-methyl-3-(trifluoromethyl)-pyrazole-4-carbonitrile. Eventually,1-methyl-3-triflur-omethyl-4-pyrazole carboxylic acid was prepared by hydrolysis.Appropriate reaction conditions were obtained by the research of the influences of reaction solvents, reaction time, temperature and feed ratio on the yield. The condensation reaction where ethanol was used in replace of CH2Cl2was carried out at40-50℃for5hours, with the molar ratio of sodium cyanoacetate to N-(methoxymethylene)-N,N-dimethyaminium methanesulfate being1:2.5, and the yield was93.7%. In acylation, TEA was used as acid-capturer and trifluoroacetyl chloride was used instead of phosgene as allylation reagent, and78.6%yield was obtained with the molar ratio of3-(dimethylamino)acrylonitrile, trifluoroacetyl- chloride and TEA being1:1.5:2. The cyclization reaction was carried out in a mixed sovlent of methanol and water(Vmethanol:Vwater=2:1), and the product was obtained in74.3%yield with the molar ratio of2-((dimethylamino)methylene)-4,4,4-trifluoro-3-oxobutanenitrile to methylhydrazine being1:1.5. In hydrolysis, the molar ratio of1-methyl-3-(trifluoromethyl)-pyrazole-4-carbonitrile to NaOH is1:1.8and the volume ratio of ethanal to water is2:1with the yield being87.2%.This proposed synthetic process is much of industrial value because of the high yield, cheap and easily gained materials, the moderate reaction conditions and the convenient operation. The melting point obtained was found to be the conformity of those reported in literatures, and the structure of the title compound by1H-NMR.