CN102153490A

CN102153490A - Synthesis of ethyl hydrozino-formates

Info

Publication number: CN102153490A
Application number: CN2011100426458A
Authority: CN
Inventors: 牛吉峰
Original assignee: DONGYING CLEANWELL CHEMCIAL CO LTD
Current assignee: DONGYING CLEANWELL CHEMCIAL CO LTD
Priority date: 2011-02-16
Filing date: 2011-02-16
Publication date: 2011-08-17

Abstract

The invention relates to a synthesis technology of ethyl hydrozino-formates, in particular relates to synthesis of ethyl hydrozino-formates. The synthesis technology has the advantages of simple equipment and mild reaction condition. In the whole process, based on dialkyl carbonate, the conversion rate is up to above 94%, the selectivity is almost 99%. The synthesis technology comprises the following steps: adding quantitative hydrazine hydrate (40%) in the dialkyl carbonate in the presence of a catalyst to stir and react for 3-5 hours at the controlled temperature of 40-90 DEG C; concentrating a reaction liquid to 50-70% of original concentration under the vacuum condition, cooling the liquid, and naturally crystallizing at room temperature; and finally, carrying out centrifugal separation on a crystallized material so as to obtain a crude product with a purity of 96%, and drying or recrystallizing the crude product so as to obtain a product with a purity of 99%. In the method, a mother liquid can be recycled, equipment is simple and reaction condition is mild. Compared with the prior art, the method has the advantages of simplicity, safety, low cost, simple equipment and mild reaction condition.

Description

Synthesizing of carbazates class

One, technical field: the synthetic technology that the present invention relates to a kind of carbazates class.Especially synthesizing of a kind of carbazates class.

Two, background technology: along with the fast development of pharmaceutical industries to the carbazates demand, the synthetic technology of carbazates class has also obtained everybody concern.The carbazates production technique, can be by following several:

(1) hydrazine and phosgene reaction make;

(2) methyl-chloroformate reacts under hydrochloric acid catalysis with hydrazine hydrate and makes;

(3) reaction of carbonic diester and hydrazine hydrate is produced;

Wherein, method (1) will use the phosgene that has volatile hydrazine and severe toxicity to make raw material, and this still all is difficult to carry out industrial in the laboratory; The own toxicity of raw material methyl-chloroformate that method (2) is adopted is bigger, and all is obtained by the starting raw material phosgene of severe toxicity, so these two kinds of methods itself be we can say environmental hazard bigger; And method (3) the environmental protection technology newly developed that is us, its base mateiral is a methylcarbonate, methylcarbonate is described as " green " chemical industry foundation stone, methylcarbonate is arranged through synthetic other carbonic diester of ester-interchange method, and then reacts the carbazic acid methyl esters series products made from hydrazine hydrate.

Three, summary of the invention: purpose of the present invention is exactly the defective that exists at prior art, and a kind of convenience, safe, with low cost and equipment is simple is provided, the carbazates class of reaction conditions gentleness synthetic.Its technical scheme is: at first add carbazic acid methyl esters and hydrazine hydrate in reactor, adding appropriate amount of catalysts again mixes, control reaction temperature is at 70 ℃, about 2 hours of reaction times, reaction solution removes most of alcohols, water and the carbazic acid methyl esters that does not react through underpressure distillation then, will react also to be cooled to 0 ℃ of crystallization again, through filtration, alcohols drip washing, drying etc., finally obtain the white crystals product at last;

The peak optimization reaction condition is: in the carbohydrazide building-up reactions, carbazic acid methyl esters/hydrazine hydrate (40%)=1.5～1.75, this ratio is meant the mol ratio of methylcarbonate and hydrazine content, temperature of reaction: 70 ℃, reaction times: 2 hours, general 40% or 80%, 80% the hydrazine hydrate proportioning that adopts of the content of hydrazine hydrate: hydrazine hydrate consumption 2.3, diester consumption 1.3; Whole process is in carbonic diester, its transformation efficiency reaches more than 94%, and selectivity almost 99%, under the condition that catalyzer exists, quantitative hydrazine hydrate (40%) is joined in the methylcarbonate, be controlled under 40-90 ℃, stirring reaction 3-5 hour, reaction solution is concentrated into original 50-70% under vacuum state, the liquid cooling, spontaneous nucleation at room temperature, at last the crystallisate centrifugation can be got the thick product of purity 96%, thick product drying or recrystallize can obtain 99% product, the mother liquor reusable edible, and equipment is simple, the reaction conditions gentleness.The present invention has conveniently, safe, with low cost and equipment is simple, the advantage of reaction conditions gentleness compared with prior art.

Four, embodiment: at first in reactor, add carbazic acid methyl esters and hydrazine hydrate, adding appropriate amount of catalysts again mixes, control reaction temperature is at 70 ℃, about 2 hours of reaction times, reaction solution removes most of alcohols, water and the carbazic acid methyl esters that does not react through underpressure distillation then, will react also to be cooled to 0 ℃ of crystallization again, through filtration, alcohols drip washing, drying etc., finally obtain the white crystals product at last; The peak optimization reaction condition is: in the carbohydrazide building-up reactions, carbazic acid methyl esters/hydrazine hydrate (40%)=1.5～1.75, this ratio is meant the mol ratio of methylcarbonate and hydrazine content, temperature of reaction: 70 ℃, reaction times: 2 hours, general 40% or 80%, 80% the hydrazine hydrate proportioning that adopts of the content of hydrazine hydrate: hydrazine hydrate consumption 2.3, diester consumption 1.3; Whole process is in carbonic diester, its transformation efficiency reaches more than 94%, and selectivity almost 99%, under the condition that catalyzer exists, quantitative hydrazine hydrate (40%) is joined in the methylcarbonate, be controlled under 40-90 ℃, stirring reaction 3-5 hour, reaction solution is concentrated into original 50-70% under vacuum state, the liquid cooling, spontaneous nucleation at room temperature, at last the crystallisate centrifugation can be got the thick product of purity 96%, thick product drying or recrystallize can obtain 99% product, the mother liquor reusable edible, and equipment is simple, the reaction conditions gentleness.

Experimental data:

(1), 5 in the flask of testing installation: 500ml, one in stirrer, one of electronic balance, one of gas-chromatography, one of liquid chromatography, one in process furnace, one of water-bath, one in vacuum pump, glass adapter etc.

(2), reagent: distilled water, methylcarbonate, benzylalcohol, ethanol, the trimethyl carbinol, sodium hydroxide, potassium hydroxide, zinc chloride, cupric chloride, zinc oxide, cupric oxide.

Experiment (1) hydrazino benzyl formate

Methylcarbonate 100g, 99% benzylalcohol 325g, caustic alkali 5g, add in the flask of 500ml, heat up and be stirred to 100 ℃, back flow reaction 8 hours, underpressure distillation removes methylcarbonate and unnecessary benzylalcohol, the dimethyl benzyl crystal 2 35g of low temperature separation process adds the gained crystal in the flask of 500ml, adds zinc oxide 5g, add 80% hydrazine hydrate 80g, be warming up to 40-100 ℃ of reaction 2 hours, the underpressure distillation dehydration divides and hydrazine, and the benzylalcohol of by-product.Then, add distilled water wash, use the distilled water extractive crystallization at last, can product 108g, it is 98% above hydrazino benzyl formate product that liquid chromatographic detection purity is arranged.

Experiment (1) tert-butyl carbazate

Methylcarbonate 150g, 99% trimethyl carbinol 333g, caustic alkali 5g, add in the flask of 500ml, heat up and be stirred to 80 ℃, back flow reaction 8 hours, underpressure distillation removes the methylcarbonate and the unnecessary trimethyl carbinol, the dimethyl dicarbonate butyl ester 192g of rectifying adds products therefrom in the flask of 500ml, adds zinc oxide 5g, add 80% hydrazine hydrate 120g, be warming up to 40-100 ℃ of reaction 2 hours, the underpressure distillation dehydration divides and hydrazine, and the trimethyl carbinol of by-product.Then, rectifying can product 121g, it is 99% above tert-butyl carbazate product that liquid chromatographic detection purity is arranged.

Experiment (3) carbazic acid ethyl ester methylcarbonate 200g, 99% ethanol 272g, caustic alkali 5g, add in the flask of 500ml, heat up and be stirred to 80 ℃, back flow reaction 8 hours, underpressure distillation removes methylcarbonate and unnecessary ethanol, the diethyl carbonate 205g of rectifying adds products therefrom in the flask of 500ml, adds zinc oxide 5g, add 80% hydrazine hydrate 160g, be warming up to 40-100 ℃ of reaction 2 hours, the underpressure distillation dehydration divides and hydrazine, and the ethanol of by-product.Then, rectifying can product 168g, it is 99% above carbazic acid ethyl ester product that liquid chromatographic detection purity is arranged.

Claims

1. a carbazates class is synthetic, it is characterized in that: in reactor, add carbazic acid methyl esters and hydrazine hydrate, adding appropriate amount of catalysts again mixes, control reaction temperature is at 70 ℃, and in about 2 hours of reaction times, reaction solution is through underpressure distillation then, remove most of alcohols, water and the carbazic acid methyl esters that does not react, to react again and also be cooled to 0 ℃ of crystallization, through filtration, alcohols drip washing, drying etc., finally obtain the white crystals product at last.

2. synthesizing of carbazates class according to claim 1, it is characterized in that: the peak optimization reaction condition is: in the carbohydrazide building-up reactions, carbazic acid methyl esters/hydrazine hydrate (40%)=1.5～1.75, this ratio is meant the mol ratio of methylcarbonate and hydrazine content, temperature of reaction: 70 ℃, the reaction times: 2 hours, the content of hydrazine hydrate is general to adopt 40% or 80%, 80% hydrazine hydrate proportioning: hydrazine hydrate consumption 2.3, diester consumption 1.3.

3. synthesizing of carbazates class according to claim 2, it is characterized in that: quantitative hydrazine hydrate (40%) is joined in the methylcarbonate, be controlled under 40-90 ℃, stirring reaction 3-5 hour, reaction solution is concentrated into original 50-70% under vacuum state, the liquid cooling, spontaneous nucleation at room temperature, at last the crystallisate centrifugation can be got the thick product of purity 96%, thick product drying or recrystallize can obtain 99% product, the mother liquor reusable edible.