CN108299229A - A kind of preparation method of 3,4,5- trimethoxybenzoyls hydrazine - Google Patents

Abstract

The present invention provides one kind 3,4, the preparation method of 5 trimethoxybenzoyl hydrazines, this method is with 3,4,5 trimethoxybenzoic acids and hydrazine hydrate are raw material, with H β type solid acid sieve peg-raking catalysts, hydrazidesization reaction is carried out at a certain temperature and prepares 3,4,5 trimethoxybenzoyl hydrazines, keep 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, the reaction time is shortened, reaction yield is improved.Compared with prior art, the method for the present invention is easy to operate, and one step of reaction is completed, high income, the recyclable reuse of catalyst, eliminates esterification, shortens processing step, production cost is reduced, the discharge of waste is reduced, is a kind of environmental type production technology.

Description

A kind of preparation method of 3,4,5- trimethoxybenzoyls hydrazine

Technical field

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

Background technology

3,4,5- trimethoxybenzoyl hydrazines are white crystalline solid, and fusing point is 159~160 DEG C, is dissolved in water and organic molten Agent.3,4,5- trimethoxybenzoyl hydrazines are to synthesize the intermediate of the heterocyclic compounds such as methoxybenzyl aminopyrimidine, and synthesize anti-height Blood pressure drug（Reserpine）Etc. the raw material of a variety of drugs.

Currently, the preparation 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 prepare 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, useless Gurry discharges less, production cost is low, energy-saving and environment-friendly 3,4,5- trimethoxybenzoyls hydrazine novel preparation method.

The technical solution adopted by the present invention is：Under the action of catalyst simultaneously by 3,4,5- trimethoxybenzoic acids and hydrazine hydrate Hydrazides being carried out at a certain temperature, 3,4,5- trimethoxybenzoyl hydrazines being obtained by the reaction, hydrazine hydrate mistake is kept in reaction system Amount, and the water that reaction generates constantly is separated from reaction system（To promote reaction balance to be moved to positive direction, shorten anti- Between seasonable, improve reaction yield）, excessive hydrazine hydrate is steamed by recycling, remaining solid using vacuum distillation after reaction Catalyst is recovered by filtration in substance after being dissolved with pure water, filtrate obtains 3,4,5- trimethoxies after being evaporated under reduced pressure and concentrating removing moisture Benzoyl hydrazine crude product, then washed with absolute ethyl alcohol, it is dry after obtain 3,4,5- trimethoxybenzoyl hydrazine finished products.Above-mentioned hydrazides Reaction catalyst used is H β type solid acid molecular sieves（Grain size is 1~2mm）, which can after regeneration treatment It reuses.

The specific processing step of the present invention is as follows：By 3,4,5- trimethoxybenzoic acids, hydrazine hydrate and H β type solid acids point Sub- sieve catalyst is put into the reaction kettle with rectifying column, is opened stirring, reflux is heated to, when steam enters rectifying column Afterwards, it in 98 DEG C~100 DEG C extraction vapor of tower top temperature, reacts 4~6 hours at a reflux temperature, when rectifying tower top frozen-free It reacts and terminates after water outflow, remaining hydrazine hydrate is steamed by recycling using vacuum distillation, hydrazine hydrate is added suitable after all being steamed Amount pure water fully dissolves the solid matter in reaction kettle, H β type solid acid molecular sieve catalysts is then recovered by filtration, by filtrate It is evaporated under reduced pressure after concentration removes moisture and obtains 3,4,5- trimethoxybenzoyl hydrazine crude products, then washed with absolute ethyl alcohol, after drying Obtain 3,4,5- trimethoxybenzoyl hydrazine finished products.

In above-mentioned steps, the mass ratio of 3,4,5- trimethoxybenzoic acids and hydrazine hydrate is 1: 1~1.5, H β type solid acids The dosage of 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 with 3,4,5- trimethoxybenzoic acids and hydrazine hydrate for raw material, with H β type solid acid sieve peg-raking catalysts, Hydrazidesization reaction is carried out under certain temperature and prepares 3,4,5- trimethoxybenzoyl hydrazines, and this method is easy to operate, and one step of reaction is complete At high income（With 3,4,5- trimethoxybenzoic acid rate of collecting 95% or more）, post-processing is simple, the recyclable repetition of catalyst It uses, eliminates esterification, shorten processing step, reduce production cost, reduce the discharge of waste, be a kind of green Color environment-friendly production process.

Specific implementation mode

Embodiment 1

3,4,5- trimethoxybenzoic acids 212g, the hydrazine hydrate 265g and H β type solid acid molecular sieves 22g that content is 80% are put into With stirring, thermometer, rectifying column four-hole boiling flask in, open stirring, reflux is heated to, when steam enters rectifying column Afterwards, it in 98 DEG C~100 DEG C extraction vapor of column top temperature, reacts 4~6 hours at a reflux temperature, when rectifying capital frozen-free Reaction was completed after water outflow, remaining hydrazine hydrate in flask is steamed recycling with vacuum distillation, hydrazine hydrate adds after all being steamed Enter appropriate pure water fully to dissolve the solid matter in flask, then solution is poured out, filters recycling H β type solid acid molecular sieves Catalyst, filtrate, which is transferred in cucurbit, is evaporated under reduced pressure concentration, and 3,4,5- trimethoxybenzoyl hydrazine crude products are obtained after removing moisture, It washed again with absolute ethyl alcohol, obtain 3,4,5- trimethoxybenzoyl hydrazine finished products 215.8g after drying.

Embodiment 2

3,4,5- trimethoxybenzoic acids 212g, the hydrazine hydrate 295g and H β type solid acid molecular sieves 32g that content is 90% are put into With stirring, thermometer, rectifying column four-hole boiling flask in, open stirring, reflux is heated to, when steam enters rectifying column Afterwards, it in 98 DEG C~100 DEG C extraction vapor of column top temperature, reacts 4~6 hours at a reflux temperature, when rectifying capital frozen-free Reaction was completed after water outflow, remaining hydrazine hydrate in flask is steamed recycling with vacuum distillation, hydrazine hydrate adds after all being steamed Enter appropriate pure water fully to dissolve the solid matter in flask, then solution is poured out, filters recycling H β type solid acid molecular sieves Catalyst, filtrate, which is transferred in cucurbit, is evaporated under reduced pressure concentration, and 3,4,5- trimethoxybenzoyl hydrazine crude products are obtained after removing moisture, It washed again with absolute ethyl alcohol, obtain 3,4,5- trimethoxybenzoyl hydrazine finished products 218.1g after drying.

Embodiment 3

3,4,5- trimethoxybenzoic acids 212g, the hydrazine hydrate 320g and H β type solid acid molecular sieves 42g that content is 99% are put into With stirring, thermometer, rectifying column four-hole boiling flask in, open stirring, reflux is heated to, when steam enters rectifying column Afterwards, it in 98 DEG C~100 DEG C extraction vapor of column top temperature, reacts 4~6 hours at a reflux temperature, when rectifying capital frozen-free Reaction was completed after water outflow, remaining hydrazine hydrate in flask is steamed recycling with vacuum distillation, hydrazine hydrate adds after all being steamed Enter appropriate pure water fully to dissolve the solid matter in flask, then solution is poured out, filters recycling H β type solid acid molecular sieves Catalyst, filtrate, which is transferred in cucurbit, is evaporated under reduced pressure concentration, and 3,4,5- trimethoxybenzoyl hydrazine crude products are obtained after removing moisture, It washed again with absolute ethyl alcohol, obtain 3,4,5- trimethoxybenzoyl hydrazine finished products 220.3g after drying.

Claims (1)

1. one kind 3,4, the preparation method of 5- trimethoxybenzoyl hydrazines, it is characterised in that include the following steps：By 3,4,5- tri- Methoxy benzoic acid, hydrazine hydrate and H β type solid acid molecular sieve catalysts are put into the reaction kettle with rectifying column, open stirring, It is heated to reflux, after steam enters rectifying column, in 98 DEG C~100 DEG C extraction vapor of tower top temperature, in reflux temperature Lower 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 Go out recycling, hydrazine hydrate is added appropriate pure water after all being steamed and fully dissolves the solid matter in reaction kettle, then filters back H β type solid acid molecular sieve catalysts are received, filtrate decompression is concentrated by evaporation after removing moisture and obtains 3,4,5- trimethoxybenzoyls Hydrazine crude product, then washed with absolute ethyl alcohol, it is dry after obtain 3,4,5- trimethoxybenzoyl hydrazine finished products；In above-mentioned steps, 3,4, The mass ratio of 5- trimethoxybenzoic acids and hydrazine hydrate is that the dosage of 1: 1~1.5, H β type solid acid molecular sieves is 3,4,5- front threes The 10%~20% of p-methoxybenzoic acid quality, the content of hydrazine hydrate is 80%~100%.