Green Synthesis Process Of Cyclopropylamine

Cyclopropylamine is the key intermediate in manufacture of the third and fourth generation of quinolone antibiotics,insect growth regulator cyromazine and herbicide cyprazine.The current synthesis route uses y-butyrolactone as starting materials,and requires 5 steps,involving process of ring-cleavage,esterification,ring closure,ammonolysis and Hofmann degradation.The conventional synthesis route has been limited by several problems.Present ring-cleavage process uses thionyl chloride and shows low atom economy with large sulfur dioxide emission and high solvents consumption;Ring closure process is energy and time consuming,along with generating by-products;Ammonolysis process in toluene leads to lower conversion of methyl cyclopropanecarboxylate and higher consumption of catalyst.Hofmann degradation process produces a great deal of salty wastewater.To solve the above problems,efforts are made to make conventional process greener,including(1)ring-cleavage of y-butyrolactone and esterification in CH3OH-HCl system;(2)ring closure of methyl 4-chlorobutyrate in octane;(3)solvent-free catalytic ammonolysis of methyl cyclopropanecarboxylate;(4)water recycling-based Hofmann degradation of cyclopropanecarboxamide.Study the one-pot synthesis of methyl 4-chlorobutyrate from y-butyrolactone in CH3OH-HCl system.Using HCl as ring-cleavage reagent instead of thionyl chloride solves the problem of sulfur dioxide emission and achieves high atom economy.HCl is bubbled into y-butyrolactone-methanol in batches in order to maintain high HCl concentration under the normal pressure,which accelerating the reaction velocity,reducing reaction time by 60%,and avoiding using inflating equipments.Compared with traditional water-wash and extraction treatments,improved process simplifies the product handling procedure with no solvents consumption and reducing wastewater discharge.Under optimized process conditions,the yield of methyl 4-chlorobutyrate is 98.1%.Introduce low methanol solubility solvents such as octane to methyl 4-chlorobutyrate,and develop the ring closure-azeotropic distillation process to prepare methyl cyclopropanecarboxylate.Using 30wt%CH3ONa-CH3OH solution for strong base.Octane is used instead of conventional toluene or xylene solvents.30wt%CH3ONa-CH3OH solution is dropped continuously to the solution of methyl 4-chlorobutyrate and CH3OH is distilled off continuously,then the by-product methyl 4-methoxybutanoate is inhibited.Octane-methanol azeotrope divides into two phase after condensation and shows high methanol separation efficiency.As a result,the solvent consumption reduces by 70%and 90%octane is recycled after distillation.Under optimized process conditions,the yield of methyl cyclopropanecarboxylate is 96.2%.Explore the solvent-free catalytic ammonolysis of methyl cyclopropanecarboxylate.Ammonolysis reaction without solvents makes the reaction conduct under high concentration,which can accelerate the ammonolysis velocity and reduce the reaction time by 20%-30%.Solvent-free condition contributes to reducing catalyst dosage by 50%,increasing reaction temperature by 15℃-20℃.Besides,solvent-free condition saves cost of separation equipments and improve the production efficiency.Under optimized process conditions,the yield of cyclopropanecarboxamide is 94.4%.Study water recycling-based Hofmann degradation of cyclopropanecarboxamide.Water phase after Hofmann degradation reaction is partly recycled by adding concentrated alkaline solution which is generated after the distillation of cyclopropylamine and wastewater dosage reduces by 40%.Through analysing the formation process of by-products and optimizing the reaction conditions,the yield of cyclopropylamine is 94.5%,improved by 9.8%.The products of the reactions are confirmed by MS,1H NMR and 13C NMR.In this paper,the process of ring closure of methyl 4-chlorobutyrate in octane and solvent-free catalytic ammonolysis of methyl cyclopropanecarboxylate are innovative processes;The one-pot synthesis of methyl 4-chlorobutyrate and water recycling-based Hofmann degradation of cyclopropanecarboxamide have a guiding significance for green production process.