Synthetic Technology Study Of Chlorantraniliprole

A novel insecticidal chlorantraniliprole first marketed in 2007 in the Philippines,is anthranilic diamides broad-spectrum insecticide developed by Du Pont Company.Compared with the literature,a new synthetic route with lower cost higher yield which is more reasonable and suitable for industrial production is designed in this paper.Seven intermediates and chlorantraniliprole synthesized in this route are characterized by NMR,IR and MS.The synthesis steps are decreased to seven and the total yield is increased to 46.7%,instead of 14.5%using nine steps in literature.Some route improvements are summarized as follows:1.Synthesis of 3-Chloro-2-Hydrazypyridine（1）.Instead of refluxing for 35h with ethanol as solvent,the reaction time is shorten to 2h under higher pressure with hydrazine hydrate is 5 times much than 2,3-dichloropyridine.2.Synthesis of Ethyl 2-（3-chloro-2-pyridyl）-5-oxopyrazolidine-3-carboxyl ate（2）.The reaction mixture is concentrated to remove ethanol,dissolved with distilled water（recyclable）and neutralized to pH=7 with hydrochloric acid.The precipitate formed is filtered,dried in vacuum to get the intermediate 2（90%）,which has advanced greatly compared with the 30%～52%yield in literature.3.The synthesis of 3-Bromo-1-（3-chloro-2-pyridyl）-4,5-dihydro-1H-pyrazole-5-ethyl.When the mole ratio of 2 to POBr₃ is 3:2,the mixture is stirred and refluxing for 1h under nitrogen with acetonitril and the pure 3 is got after being extracted（ethyl acetate）,dried（Mg SO₄）and concentrated the same as literature except the whiter colour.4.Modified one-pot synthesis of 3-Bromo-1-（3-chloro-2-pyridyl）-1H-pyrazole-5-acid（5）is used.The reaction will come to an end after 2.5h refluxing with acetonitril as solvent and the 1:1.5:4 molar ratio of3/K₂S₂O₈/concentrated H₂SO₄.Neutralization undergoes with NaOH solution first and HCl last till pH=7,and the pale yellow compound 5 is got with 80%yield,which is better than the 60%yield of two-step synthesis.5.Instead of two-step synthesis method,2-Amino-N,3-Dimethyl-Benzamide（7）is synthesized with one-pot method beginning with 2-Amino-3-ethylbenzoic Acid.The reaction is finished in 35minutes’stirring at room temperature when the molar ratio of 2-Amino-3-Methylbenzoic Acid with bis（trichloromethyl）carbonate is 3:1 and the solvent is furanidine.The PH is regulated to 8～9 with saturated NaCO₃ aqueous solution,and then the excess methylamine aqueous solution are added to the reaction to finish the methylamine reaction.The remaining mixture is evaporated by rotary evaporator,washed with water,and dried with vacuum drier to get very clean white compound in 74.7%yield compared with the 42%yield in literature.6.Chlorination reaction:Using furanidine as the solvent instead of N,N-dimethylformamide,which has much higher boiling point,makes the technological procress dramatically be simplifier,the reprocessing much be easier which can be finished only by simple distillation and solvent extraction,and the yield up to be 96%.The total yield is 71.7%from 2-Amino-3-Methylbenzoic Acid,compared to the 31.5%in literature.7.Amidation reaction:Using paratoluensulfonyl chloride instead of methyl sulfonyl chloride as amidation reagent,technological operation is greatly simplified and the yield is improved to 96.5%from 84.9%.