CN105601572B - A kind of preparation process of carbendazim - Google Patents

A kind of preparation process of carbendazim Download PDF

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Publication number
CN105601572B
CN105601572B CN201610042788.1A CN201610042788A CN105601572B CN 105601572 B CN105601572 B CN 105601572B CN 201610042788 A CN201610042788 A CN 201610042788A CN 105601572 B CN105601572 B CN 105601572B
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added dropwise
carbendazim
reaction
toluene
equivalents
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CN105601572A (en
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严家庆
许小祥
王琳
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JIANGSU BAOZONG BAODA PHARMACEUTICAL CO Ltd
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JIANGSU BAOZONG BAODA PHARMACEUTICAL CO Ltd
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D235/00Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/24Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
    • C07D235/30Nitrogen atoms not forming part of a nitro radical
    • C07D235/32Benzimidazole-2-carbamic acids, unsubstituted or substituted; Esters thereof; Thio-analogues thereof

Abstract

The invention discloses a kind of carbendazim preparation methods, it is characterised in that traditional synthesis technology is improved.(1)Using toluene and water two-phase solvent reaction system, product appearance is improved, makes product color in brilliant white, purity improves the grade of product up to more than 99.8%.(2)The method being added dropwise simultaneously using concentrated hydrochloric acid and Methyl cyanocarbamate cyclizing agent, product yield is up to more than 97.5%.Compared with existing traditional synthesis, this method biggest advantage is product yield height, and appearance luster is good, and purity is also higher, is a kind of method for producing high standard carbendazim.

Description

A kind of preparation process of carbendazim
Technical field
The present invention relates to the application fields of carbendazim preparation process two phase solvent system, and in particular to a kind of system of carbendazim Preparation Method.
Background technology
Carbendazim also known as carbendazol, carbendazol, chemical name:N-(2- benzimidazole bases)Carbamic acid first Ester.Carbendazim is a kind of broad-spectrum germicide, to various crop by fungi(Such as Fungi Imperfecti, more sac fungus)Caused disease has anti- Control effect.Available for foliar spray, seed treatment and soil treatment etc..Carbendazim is to be closed using o-phenylenediamine with cyclizing agent Ring is reacted come what is prepared, and o-phenylenediamine is to prepare the indispensable raw material of carbendazim, but cyclizing agent can there are many select.According to The difference of cyclizing agent prepares carbendazim and is segmented into lime nitrogen method, Thiourea-uv Method, urea method, rhodanate method etc..Scale metaplasia at present Production is mainly using lime nitrogen method, because cyclizing agent cost prepared by this method is minimum.The present invention is optimized for lime nitrogen method It improves, finds a kind of method that low cost prepares high standard carbendazim.Traditional lime nitrogen method is molten as single reaction using water Agent, since atropurpureus impurity does not dissolve in water, so the product package being easily precipitated and absorption, so as to cause product colour Relatively deep, purity is not also high.
Invention content
The purpose of the present invention is to provide a kind of preparation methods of high standard carbendazim, and this method is easy to operate, product color Pool is good, and purity is high, and production cost is low, and yield is also high.
(1)The preparation of cyclizing agent Methyl cyanocarbamate:The cyanamide aqueous solution of 10% content is added in reaction bulb, 0 Under the conditions of~5 DEG C, the sodium hydroxide that the methylchloroformate of 1.1 equivalents and 30% concentration of 2.2 equivalents is added dropwise simultaneously while stirring is molten Liquid, control pH value keeps the temperature 2 hours after being added dropwise for 8~9. during being added dropwise, you can it is water-soluble to obtain Methyl cyanocarbamate Liquid.
(2)The preparation of carbendazim:O-phenylenediamine is dissolved in reaction bulb with the toluene of 4 times of weight, in 55~60 DEG C of conditions Under, the concentrated hydrochloric acid of 1.2 equivalents 35% and the Methyl cyanocarbamate aqueous solution of 1.1 equivalents are added dropwise while stirring, is controlled during being added dropwise PH value processed is 4~5, and 3 hours are kept the temperature after being added dropwise.After reaction, 25 DEG C of suction filtration solid products, filter cake toluene are cooled to Washing, damp product, which are placed on to dry 8 hours in 70 DEG C of convection ovens, can obtain product.
By the use of toluene and water as the two phase solvent system of ring-closure reaction, product quality and appearance are improved with this;By cyclization Agent cyanamide base methyl formate and concentrated hydrochloric acid are added drop-wise in reaction system simultaneously, and the yield of product is improved with this.
Following formula is the synthetic route that the present invention uses.
The advantage of the invention is that:Product appearance color and luster is good, and purity is high, and production cost is low, high income, is suitble to extensive raw Production.
Specific embodiment
Following typical reaction is used for illustrating the present invention, and technical staff in the art is the present invention simple Replacement or improvement etc. are belonged within the technical solution that the present invention is protected.
Embodiment 1
(1)The preparation of cyanamide base methyl formate cyclizing agent
By the cyanamide aqueous solution 231.0g of 10% concentration(0.55mol)It adds in reaction bulb, control temperature is to 0~5 DEG C. 57.2g is added dropwise simultaneously under stirring(0.605mol)Methylchloroformate and 162.0g(1.21mol)30% concentration hydrogen-oxygen Change sodium water solution.Control pH value is 8~9 during being added dropwise, and after being added dropwise, 0~5 DEG C of insulation reaction obtains cyanogen ammonia in 2 hours Base methyl formate aqueous solution 450.0g.
(2)The preparation of carbendazim
By 54.0g o-phenylenediamines(0.5mol)It is dissolved in 216g toluene, raises the temperature to 55~60 DEG C, under stirring The cyclizing agent 450.0g that simultaneously prepared by a dropping step 1(0.55mol)And 62.5g(0.6mol)A concentration of 35% concentrated hydrochloric acid is added dropwise Control PH is 4~5 in the process.After being added dropwise, insulation reaction 3 hours under the conditions of 55~60 DEG C.After heat preservation, it is cooled to 25 DEG C or so, solid product is filtered, filter cake is eluted with 50.0g toluene.Earth tide product are put into 70 DEG C of convection ovens to dry within 8 hours It is dry, obtain product 93.6g, purity 99.9%, yield 98.0%(It is calculated with o-phenylenediamine).
Embodiment 2.
(1)The preparation of cyanamide base methyl formate cyclizing agent
By the cyanamide aqueous solution 1155.0g of 10% concentration(2.75mol)It adds in reaction bulb, control temperature is to 0~5 DEG C. 286.0g is added dropwise simultaneously under stirring(3.03mol)Methylchloroformate and 810.0g(6.05mol)30% concentration hydrogen-oxygen Change sodium water solution.Control pH value is 8~9 during being added dropwise, and after being added dropwise, 0~5 DEG C of insulation reaction obtains cyanogen ammonia in 2 hours Base methyl formate aqueous solution 2250g.
(2)The preparation of carbendazim
By 270.0g o-phenylenediamines(2.5mol)It is dissolved in 1080g toluene, raises the temperature to 55~60 DEG C, stirring The lower cyclizing agent 2250.0g that simultaneously prepared by a dropping step 1(2.75mol)And 312.5g(3.0mol)A concentration of 35% concentrated hydrochloric acid, Control PH is 4~5 during being added dropwise.After being added dropwise, insulation reaction 3 hours under the conditions of 55~60 DEG C.It is cold after heat preservation But to 25 DEG C or so, solid product is filtered, filter cake is eluted with 250.0g toluene.It is small that earth tide product are put into 70 DEG C of convection ovens 8 When dry, obtain product 467.0g, purity 99.9%, yield 97.8%(It is calculated with o-phenylenediamine).
Embodiment 3.
(1)The preparation of cyanamide base methyl formate cyclizing agent
By the cyanamide aqueous solution 2310.0g of 10% concentration(5.5mol)It adds in reaction bulb, control temperature is to 0~5 DEG C. 572.0g is added dropwise simultaneously under stirring(6.05mol)Methylchloroformate and 1620.0g(12.1mol)30% concentration hydrogen Aqueous solution of sodium oxide.Control pH value is 8~9 during being added dropwise, and after being added dropwise, 0~5 DEG C of insulation reaction obtains cyanogen in 2 hours Methyl carbamate aqueous solution 4500.0g.
(2)The preparation of carbendazim
By 540.0g o-phenylenediamines(5.0mol)It is dissolved in 2160.0g toluene, raises the temperature to 55~60 DEG C, stir shape The cyclizing agent 4500.0g that simultaneously prepared by a dropping step 1 under state(5.5mol)And 625.0g(6.0mol)A concentration of 35% dense salt Acid, control PH is 4~5 during being added dropwise.After being added dropwise, insulation reaction 3 hours under the conditions of 55~60 DEG C.Heat preservation terminates Afterwards, 25 DEG C or so are cooled to, filters solid product, filter cake is eluted with 500.0g toluene.Earth tide product are put into 70 DEG C of air blast to dry Case is dried for 8 hours, obtains product 940.8g, purity 99.9%, yield 98.5%(It is calculated with o-phenylenediamine).
The present invention is using cyanamide aqueous solution, methylchloroformate, sodium hydroxide, o-phenylenediamine, concentrated hydrochloric acid as raw material, by contracting The carbendazim of high standard is prepared in conjunction, cyclization two-step reaction.In the condensation reaction for preparing cyclizing agent Methyl cyanocarbamate, adopt The decomposition of methylchloroformate is reduced with the reaction temperature lower than traditional handicraft, raw material availability is improved, reduces cost.It is making In the ring-closure reaction of standby carbendazim, o-phenylenediamine is oxidized easily generation atropurpureus impurity.Traditional lime nitrogen method is made using water For single reaction solvent, since atropurpureus impurity does not dissolve in water, so the product package being easily precipitated and absorption, so as to Cause product colour deeper, purity is not also high.The method of the present invention uses water and toluene two-phase reaction system, and atropurpureus impurity is molten Solution will not be precipitated product package and absorption, so as to improve product color, improve product purity in toluene phase, and Toluene will not dissolved product and influence yield.The present invention by being added drop-wise to reactant simultaneously by Methyl cyanocarbamate and concentrated hydrochloric acid The method of system shortens Methyl cyanocarbamate residence time in acid system, reduces decomposition amount, improves its utilization rate, finally Improve the yield of product.The high standard carbendazim prepared using the method for the present invention, color brilliant white, purity up to more than 99.8%, Product yield is up to more than 97.5%.

Claims (2)

1. a kind of preparation method of carbendazim, it is characterised in that this method carries out as follows:
(1)The preparation of cyclizing agent Methyl cyanocarbamate:The cyanamide aqueous solution of 10% content is added in reaction bulb, 0~5 Under the conditions of DEG C, the methylchloroformate of 1.1 equivalents and the sodium hydroxide solution of 30% concentration of 2.2 equivalents is added dropwise simultaneously while stirring, Control pH value keeps the temperature 2 hours after being added dropwise for 8~9. during being added dropwise, you can obtains Methyl cyanocarbamate aqueous solution;
(2)The preparation of carbendazim:O-phenylenediamine is dissolved in reaction bulb with the toluene of 4 times of weight, under the conditions of 55~60 DEG C, side It stirs side and the concentrated hydrochloric acid of 1.2 equivalents 35% and the Methyl cyanocarbamate aqueous solution of 1.1 equivalents is added dropwise, control PH during being added dropwise It is 4~5 to be worth, and 3 hours are kept the temperature after being added dropwise;After reaction, 25 DEG C of suction filtration solid products are cooled to, filter cake is washed with toluene It washs, damp product, which are placed on to dry 8 hours in 70 DEG C of convection ovens, can obtain product;Mother liquor is realized by layering, distillation procedure to first Benzene solvent recovery;By the use of toluene and water as the two phase solvent system of ring-closure reaction;By cyclizing agent cyanamide base methyl formate and Concentrated hydrochloric acid is added drop-wise in reaction system simultaneously.
2. according to a kind of preparation method of carbendazim described in claim 1, it is characterised in that:The synthesis side that carbendazim uses Formula is
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CN106083730A (en) * 2016-06-21 2016-11-09 如皋市光华科技创业服务有限公司 A kind of carbendazim preparation
CN106565609B (en) * 2016-09-28 2019-04-23 江苏扬农化工集团有限公司 A kind of preparation method of carbendazim
CN107778253A (en) * 2017-11-08 2018-03-09 安徽东至广信农化有限公司 A kind of technique of hydrogen chloride synthesis carbendazim
CN109053586A (en) * 2018-09-11 2018-12-21 安徽东至广信农化有限公司 A kind of production method of carbendazim
CN109467535A (en) * 2018-11-14 2019-03-15 江苏宝众宝达药业有限公司 A kind of preparation method of Fenbendazole
CN109760162A (en) * 2019-01-24 2019-05-17 深圳市至霸化工有限公司 A kind of bamboo and wood rattan willow herb mildew and insect proof fungicide

Citations (5)

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US3997553A (en) * 1969-06-25 1976-12-14 E. I. Du Pont De Nemours And Company 2-Benzimidazolecarbamic acid esters by the cyanamide process
CN102070535A (en) * 2011-02-23 2011-05-25 江苏蓝丰生物化工股份有限公司 Preparing method for synthesizing sanmate from calcium cyanamide
CN102850278A (en) * 2012-10-09 2013-01-02 江苏宝众宝达药业有限公司 Method for decoloring imidazole anthelmintics
CN103058932A (en) * 2013-02-01 2013-04-24 黄河三角洲京博化工研究院有限公司 Synthetic method of N-(2-benzimidazolyl)-methyl carbamate
CN104910077A (en) * 2015-06-08 2015-09-16 常州佳灵药业有限公司 Preparation method and application of albendazole

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3997553A (en) * 1969-06-25 1976-12-14 E. I. Du Pont De Nemours And Company 2-Benzimidazolecarbamic acid esters by the cyanamide process
CN102070535A (en) * 2011-02-23 2011-05-25 江苏蓝丰生物化工股份有限公司 Preparing method for synthesizing sanmate from calcium cyanamide
CN102850278A (en) * 2012-10-09 2013-01-02 江苏宝众宝达药业有限公司 Method for decoloring imidazole anthelmintics
CN103058932A (en) * 2013-02-01 2013-04-24 黄河三角洲京博化工研究院有限公司 Synthetic method of N-(2-benzimidazolyl)-methyl carbamate
CN104910077A (en) * 2015-06-08 2015-09-16 常州佳灵药业有限公司 Preparation method and application of albendazole

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