CN108409597A - A method of synthesis 3,4,5- trimethoxybenzoyl hydrazines - Google Patents

Abstract

The present invention provides a kind of methods of 3,4,5 trimethoxybenzoyl hydrazines of synthesis, and this method is with 3,4,5 trimethoxybenzoic acids and hydrazine hydrate are raw material, make catalyst with 5 acidic zeolites of ZSM, hydrazides is carried out at a certain temperature, and 3,4,5 trimethoxybenzoyl hydrazines are obtained by the reaction.It keeps hydrazine hydrate excessive in the reaction system, and the water that reaction generates constantly is separated from reaction system, to effectively promote the progress of hydrazidesization reaction, shortens the reaction time, improve reaction yield.Compared with prior art, the method of the present invention is simple for process, react step completion, high income, the recyclable reuse of catalyst, eliminate esterification, processing step is shortened, production cost is reduced, does not generate acid waste water and salt-containing organic wastewater, the discharge for reducing waste is a kind of environmental type production technology.

Description

A method of synthesis 3,4,5- trimethoxybenzoyl hydrazines

Technical field

The invention belongs to chemosynthesis technical fields, and in particular to a kind of side of 3,4,5- trimethoxybenzoyl hydrazines of synthesis Method.

Background technology

3,4,5- trimethoxybenzoyl hydrazines are white crystalline solid, and fusing point is 159~160 DEG C, soluble easily in water and organic Solvent.3,4,5- trimethoxybenzoyl hydrazines are to synthesize the intermediate of the heterocyclic compounds such as methoxybenzyl aminopyrimidine, and synthesis is anti- Hypertension agents（Reserpine）Etc. the raw material of a variety of drugs.

Currently, the synthetic method of 3,4,5- trimethoxybenzoyl hydrazines is mainly with 3,4,5- trimethoxybenzoic acids, first It is raw material that alcohol and water, which closes hydrazine, by two-step reaction（Esterification and hydrazinolysis reaction）Obtain 3,4,5- trimethoxybenzoyl hydrazines： It is that raw material is heating back using the concentrated sulfuric acid as catalyst that first step esterification, which is with 3,4,5- trimethoxybenzoic acids and methanol, After flowing down esterification 10 hours, 3,4,5- trimethoxy-benzenes will be obtained after reaction solution crystallisation by cooling, filtering, drying and recrystallization Methyl formate；The reaction of second step hydrazinolysis is being heated to reflux for raw material with 3,4,5- tri-methoxybenzoates and hydrazine hydrate Lower reaction 5~6 hours, reaction solution obtains 3,4,5- trimethoxybenzoyl hydrazines after crystallisation by cooling, filtering, drying, recrystallization. It is of the existing technology the disadvantage is that：（1）Catalyst is made using the concentrated sulfuric acid in the esterification reaction, there are corrosivity by force, is wanted to equipment It asks high, will produce a large amount of acidic organic wastewaters, become the very high organic wastewater of salt content, environmental hazard after being handled with alkali neutralization Greatly, the problems such as wastewater treatment difficulty is costly greatly；（2）Using two-step reaction synthesis 3,4,5- trimethoxybenzoyls hydrazine there is also Operating procedure is more, and technique is cumbersome, and process is complicated, and high energy consumption, side reaction impurity is more, and total recovery is low（Only 80~90%）, it is produced into The problems such as this is high.

Invention content

In order to overcome disadvantages mentioned above of the existing technology, the present invention provides it is a kind of it is simple for process, reaction yield is high, raw Produce at low cost, waste discharge is few, it is energy-saving and environment-friendly synthesis 3,4,5- trimethoxybenzoyl hydrazines new method.

The technical solution adopted by the present invention is：With 3,4,5- trimethoxybenzoic acids and hydrazine hydrate for raw material, with ZSM-5 acid Property zeolite molecular sieve make catalyst, at a certain temperature carry out hydrazides 3,4,5- trimethoxybenzoyl hydrazines are obtained by the reaction. Keep hydrazine hydrate excessive in reaction system, and the water that reaction generates constantly is separated from reaction system（To promote to react It balances and is moved to positive direction, shorten the reaction time, improve reaction yield）, use vacuum distillation by excessive water after reaction It closes hydrazine and steams recycling, ZSM-5 acidic zeolite catalyst, filtrate is recovered by filtration in remaining solid matter after being dissolved with pure water 3,4,5- trimethoxybenzoyl hydrazine crude products are obtained after being evaporated under reduced pressure and concentrating removing moisture, then is washed with absolute ethyl alcohol, is dry After obtain 3,4,5- trimethoxybenzoyl hydrazine finished products.The grain size of ZSM-5 acidic zeolites used is 1~2mm, the molecule Sieve catalyst is reusable after regeneration treatment.

The specific processing step of the present invention is as follows：By 3,4,5- trimethoxybenzoic acids, hydrazine hydrate and ZSM-5 acid zeolites Molecular sieve is put into the reaction kettle with rectifying column, is opened stirring, is heated to reflux, after steam enters rectifying column, 98 DEG C~100 DEG C extraction vapor of tower top temperature, react 4~6 hours at a reflux temperature, when rectifying tower top evaporated condensation water flows out Reaction terminates afterwards, remaining hydrazine hydrate is steamed recycling using vacuum distillation, appropriate pure water is added after all being steamed in hydrazine hydrate Solid matter in reaction kettle is fully dissolved, ZSM-5 acidic zeolite catalyst is then recovered by filtration, filter cake is in right amount Filtrate decompression is concentrated by evaporation after removing moisture and obtains 3,4,5- trimethoxybenzoyl hydrazine crude products by pure water, then with anhydrous 3,4,5- trimethoxybenzoyl hydrazine finished products are obtained after ethyl alcohol washing, drying.

In above-mentioned steps, the mass ratio of 3,4,5- trimethoxybenzoic acids and hydrazine hydrate boils for 1: 1~1.5, ZSM-5 acidity The dosage of stone molecular sieve is the 10%~20% of 3,4,5- trimethoxybenzoic acid quality, and the content of hydrazine hydrate is 80%~100%.

Above-mentioned hydrazides reaction equation is as follows：

Compared with prior art, beneficial effects of the present invention and advantage are as follows：

The present invention, for raw material, is catalyzed with 3,4,5- trimethoxybenzoic acids and hydrazine hydrate using ZSM-5 acidic zeolites Agent carries out hydrazides and 3,4,5- trimethoxybenzoyl hydrazines is obtained by the reaction at a certain temperature, and this method is easy to operate, reaction one Step is completed, high income（With 3,4,5- trimethoxybenzoic acid rate of collecting 95% or more）, post-processing is simple, and catalyst is recyclable It reuses, eliminates esterification, shorten processing step, reduce production cost, reduce the discharge of waste, be one Kind environmental type production technology.

Specific implementation mode

Embodiment 1

By 3,4,5- trimethoxybenzoic acids 212g, the hydrazine hydrate 265g and ZSM-5 acidic zeolite 22g that content is 80% Be put into stirring, thermometer, rectifying column four-hole boiling flask in, open stir, reflux is heated to, when steam enters rectifying After column, in 98 DEG C~100 DEG C extraction vapor of column top temperature, react 4~6 hours at a reflux temperature, when rectifying capital is without cold Reaction was completed after condensate outflow, remaining hydrazine hydrate in flask is steamed recycling with vacuum distillation, after hydrazine hydrate is all steamed Appropriate pure water is added fully to dissolve the solid matter in flask, then solution is poured out, recycling ZSM-5 acidity boiling is filtered by vacuum Stone molecular sieve catalyst, the appropriate pure water of filter cake, filtrate, which is transferred in cucurbit, is evaporated under reduced pressure concentration, is obtained after removing moisture 3,4,5- trimethoxybenzoyl hydrazine crude products, then washed with absolute ethyl alcohol, it is dry after obtain 3,4,5- trimethoxybenzoyl hydrazines Finished product 215.7g.

Embodiment 2

By 3,4,5- trimethoxybenzoic acids 212g, the hydrazine hydrate 295g and ZSM-5 acidic zeolite 32g that content is 90% Be put into stirring, thermometer, rectifying column four-hole boiling flask in, open stir, reflux is heated to, when steam enters rectifying After column, in 98 DEG C~100 DEG C extraction vapor of column top temperature, react 4~6 hours at a reflux temperature, when rectifying capital is without cold Reaction was completed after condensate outflow, remaining hydrazine hydrate in flask is steamed recycling with vacuum distillation, after hydrazine hydrate is all steamed Appropriate pure water is added fully to dissolve the solid matter in flask, then solution is poured out, recycling ZSM-5 acidity boiling is filtered by vacuum Stone molecular sieve catalyst, the appropriate pure water of filter cake, filtrate, which is transferred in cucurbit, is evaporated under reduced pressure concentration, is obtained after removing moisture 3,4,5- trimethoxybenzoyl hydrazine crude products, then washed with absolute ethyl alcohol, it is dry after obtain 3,4,5- trimethoxybenzoyl hydrazines Finished product 218.9g.

Embodiment 3

By 3,4,5- trimethoxybenzoic acids 212g, the hydrazine hydrate 324g and ZSM-5 acidic zeolite 42g that content is 98% Be put into stirring, thermometer, rectifying column four-hole boiling flask in, open stir, reflux is heated to, when steam enters rectifying After column, in 98 DEG C~100 DEG C extraction vapor of column top temperature, react 4~6 hours at a reflux temperature, when rectifying capital is without cold Reaction was completed after condensate outflow, remaining hydrazine hydrate in flask is steamed recycling with vacuum distillation, after hydrazine hydrate is all steamed Appropriate pure water is added fully to dissolve the solid matter in flask, then solution is poured out, recycling ZSM-5 acidity boiling is filtered by vacuum Stone molecular sieve catalyst, the appropriate pure water of filter cake, filtrate, which is transferred in cucurbit, is evaporated under reduced pressure concentration, is obtained after removing moisture 3,4,5- trimethoxybenzoyl hydrazine crude products, then washed with absolute ethyl alcohol, it is dry after obtain 3,4,5- trimethoxybenzoyl hydrazines Finished product 220.2g.

Claims (1)

1. a kind of method of 3,4,5- trimethoxybenzoyl hydrazines of synthesis, it is characterised in that include the following steps：By 3,4,5- tri- Methoxy benzoic acid, hydrazine hydrate and ZSM-5 acidic zeolites are put into the reaction kettle with rectifying column, are opened stirring, are added Heat is warming up to reflux, after steam enters rectifying column, in 98 DEG C~100 DEG C extraction vapor of tower top temperature, at a reflux temperature Reaction 4~6 hours, reacts after rectifying tower top evaporated condensation water flows out and terminates, and is steamed remaining hydrazine hydrate using vacuum distillation Recycling, hydrazine hydrate are added appropriate pure water after all being steamed and fully dissolve the solid matter in reaction kettle, be then recovered by filtration Filtrate decompression is concentrated by evaporation after removing moisture and obtains by ZSM-5 acidic zeolite catalyst, the appropriate pure water of filter cake 3,4,5- trimethoxybenzoyl hydrazine crude products, then washed with absolute ethyl alcohol, it is dry after obtain 3,4,5- trimethoxybenzoyl hydrazines Finished product；In above-mentioned steps, the mass ratio of 3,4,5- trimethoxybenzoic acids and hydrazine hydrate is 1: 1~1.5, ZSM-5 acid zeolites The dosage of molecular sieve is that the grain size of 10%~20%, the ZSM-5 acidic zeolites of 3,4,5- trimethoxybenzoic acid quality is 1 ~2mm, the content of hydrazine hydrate is 80%~100%.