CN102030718B

CN102030718B - Preparation method of 3,4-dichloro-5-cyan-isothiazole

Info

Publication number: CN102030718B
Application number: CN200910272294A
Authority: CN
Inventors: 温素姐; 洪蕾; 彭金平; 谢贤俊
Original assignee: HUBEI CHENGYU PHARMACEUTICAL CO Ltd
Current assignee: HUBEI CHENGYU PHARMACEUTICAL CO Ltd
Priority date: 2009-09-28
Filing date: 2009-09-28
Publication date: 2012-09-05
Anticipated expiration: 2029-09-28
Also published as: CN102030718A

Abstract

The invention provides a preparation method of 3,4-dichloro-5-cyan-isothiazole. The 3,4-dichloro-5-cyan-isothiazole is an important midbody of a series of isothiazole pesticides and medicines. The invention also discloses a green preparation method, comprising the following steps of: suspending sodium cyanide in dimethylformamide, dropping carbon disulfide at 20-30 DEG C, reacting for 3h at 60 DEG C, introducing chlorine in a reaction mixture, reacting for 3h at 60 DEG C, decompressing and recycling dimethylformamide, adding ethyl acetate in residue for backflow and dissolution, cooling and then filtering to remove undissolved substances, recycling ethyl acetate, cooling, crystallizing, filtering to obtain a first product, adding water to the mother liquor and distilling to obtain a second product, wherein the water for filtering the product can be circularly used. The invention avoids waste water emission in the whole production process. The yield ranges from 50-60%, the melting point ranges from 80 to 84 DEG C and the purity is 98% above.

Description

3, the preparation method of 4-two chloro-5-cyanic acid-isothiazole

The present invention relates to 3, the preparation method of 4-two chloro-5-cyanic acid-isothiazole.3,4-two chloro-5-cyanic acid-isothiazole are important intermediate of a series of isothiazole class agricultural chemicals and medicine, and molecular formula is C4C12N2S, and molecular weight is 179.03.

Background technology

Relevant 3, the preparation method of 4-two chloro-5-cyanic acid-isothiazole, report is all seldom both at home and abroad.German patent DE 2231097 adopts Trichloroacetonitrile or 2 with DE2231098, and 3-dichloro Malaysia dintrile and excessive sulphur react in 200 to 300 ℃ tube sealing and prepares.This needs autoclave equipment, and operation is trouble comparatively.U.S. Pat 3341547 adopts sodium cyanide and the dithiocarbonic anhydride reaction that is suspended in the N with US 5240951, and then prepares 3,4-two chloro-5-cyanic acid-isothiazole with chlorine reaction.All reaction solution is joined in a large amount of water after these two pieces of patent reactions finish, separate out bullion, bullion is further refining to obtain 3,4-two chloro-5-cyanic acid-isothiazole.Contain that organic waste water such as by product again can serious environment pollution in N and the reaction in a large number like this.German patent DE 102005031348A1 steams except that N after adopting logical chlorine, and with the alcohol dissolving, heat filters and contains 3 of impurity; 4-two chloro-5-cyanic acid-isothiazole alcoholic solutions; Avoided the generation of waste water, but after concentrating, contained in the product and be difficult to the impurity removed in a large number; Product purity is lower, is difficult to sell as commodity.

Summary of the invention

The objective of the invention is to adopt sodium cyanide, dithiocarbonic anhydride and chlorine preparation 3,4-two chloro-5-cyanic acid-isothiazole.

Technical scheme of the present invention is achieved in that

Provide a kind of 3, the preparation method of 4-two chloro-5-cyanic acid-isothiazole at first is suspended in anhydrous sodium cyanide in the N, drips dithiocarbonic anhydride in 20-30 ℃ down in the water-bath cooling, again in 60 ℃ of reactions, separates out solid after placement is spent the night after the stirring at room.Stir down that solid dispersed imports 40% chlorine in reaction solution under 20-30 ℃ of temperature, import other 60% chlorine after stirring 1 hour at 50 ℃, too fierce and make temperature of reaction be difficult to control to avoid importing in the chlorine process reaction.Chlorine has imported the back and has continued reaction 2-3 hour in 60 ℃.Feed nitrogen and drive unnecessary chlorine away.Temperature control is lower than the N of 75 ℃ of following reclaim under reduced pressure 90-95%, adds ethyl acetate backflow in the residue and extracts, and cooled and filtered is removed insolubles (being mainly sulphur and sodium-chlor), reclaims ETHYLE ACETATE postcooling crystallization, gets product.Mother liquor behind the crystallization adds water and carries out steam distillation, and the product that remains in the mother liquor is all reclaimed.The water cycle of having filtered behind the product is used, and production whole process does not like this have waste water to form, no matter be crystallization obtain 3,4-two chloro-5-cyanic acid-isothiazole or mother liquor add water distill obtain 3,4-two chloro-5-cyanic acid-isothiazole, purity all reaches more than 98%.Can preserve transportation and sale easily.

Embodiment

Embodiments of the invention are described below, but are not limited to present embodiment:

Embodiment 1:

The N that adds 500 milliliters in 1 liter the four-hole bottle; Stir the sodium cyanide that adds 49 grams (1 mole) down; With the water-bath cooling, make reacting liquid temperature drop to 20 ℃, begin to drip the about 1.05 moles dithiocarbonic anhydride of 79.8 grams; The control rate of addition remains between 20-30 ℃ reacting liquid temperature.Drip to finish, continue under the room temperature to stir 1 hour, be heated to 60 ℃, 60 ℃ of insulated and stirred 3 hours.Place and separate out a large amount of solids more than 12 hours.Stir, let solid dispersed in reaction solution, with the icy salt solution cooling, import 35 gram chlorine, between the introduction period, the color of reaction solution becomes redness by burgundy at chlorine, becomes burgundy again, becomes redness then again, and is orange, become again brown, burgundy, light brown.Be heated to 50 ℃ with heating jacket, insulated and stirred reaction 1 hour continues under agitation to import 50 gram chlorine.Be warmed up to 60 ℃, insulated and stirred 3 hours.Feed nitrogen 1 hour to drive unnecessary chlorine away.Under 60-70 ℃, the N that reclaim under reduced pressure is 450 milliliters adds 400 milliliters of ETHYLE ACETATE in the residue.Stirring and refluxing 10 minutes, cool to room temperature filters, and filter cake is used the ETHYLE ACETATE washes clean, drains, and the burgundy filter cake discards.Filtrating is arrived at 60 ℃ of reclaim under reduced pressure ETHYLE ACETATE and is done, and cooling back crystallization filters, and dries, and gets brown solid 45 grams, and fusing point 80.3-83.6 ℃, purity 98.2%.

Mother liquor adds 200 ml waters, air distillation, and product steams with water, when steaming product-free and taking out of, stops distillation.After the cooling, filter, dry, get off-white color solid 7 grams, mp80.1-83.4 ℃, purity 99.0%.

Be total to such an extent that product 52 restrains productive rate 58.1%.

Embodiment 2:

The N that adds 500 milliliters in 1 liter the four-hole bottle; Stir the sodium cyanide that adds 49 grams (1 mole) down; With the water-bath cooling, make reacting liquid temperature drop to 20 ℃, begin to drip the dithiocarbonic anhydride of 79.8 grams (1.05 moles); The control rate of addition remains between 20-30 ℃ reacting liquid temperature.Drip to finish, continue under the room temperature to stir 1 hour, be heated to 60 ℃, 60 ℃ of insulated and stirred 3 hours.Place and separate out a large amount of solids more than 12 hours; Stir, let solid dispersed in reaction solution, cool off with icy salt solution, import 31 gram chlorine, between the introduction period, the variation same with routine 1 takes place in the color of reaction solution at chlorine.Be heated to 50 ℃ with heating jacket, insulated and stirred reaction 1 hour continues under agitation to import 50 gram chlorine.Be warmed up to 60 ℃, insulated and stirred 3 hours.Under 60-70 ℃, the N that reclaim under reduced pressure is 440 milliliters adds 500 milliliters of ETHYLE ACETATE in the residue.Stirring and refluxing 10 minutes, cool to room temperature filters, and filter cake is used the ETHYLE ACETATE washes clean, drains, and the burgundy filter cake discards.Filtrating is arrived at 60 ℃ of reclaim under reduced pressure ETHYLE ACETATE and is done, and cooling back crystallization filters, and dries, and gets brown solid 41 grams.

Mother liquor adds 200 ml waters, air distillation, and product steams with water, when steaming product-free and taking out of, stops distillation.After the cooling, filter, dry, get off-white color solid 7 grams.

Be total to such an extent that product 48 restrains productive rate 53.6%.

Comparing embodiment 3:

The N that adds 500 milliliters in 1 liter the four-hole bottle; Stir the sodium cyanide that adds 49 grams (1 mole) down; With the water-bath cooling, make reacting liquid temperature drop to 20 ℃, begin to drip the dithiocarbonic anhydride of 79.8 grams (1.05 moles); The control rate of addition remains between 20-30 ℃ reacting liquid temperature.Drip to finish, continue under the room temperature to stir 1 hour, be heated to 60 ℃, 60 ℃ of insulated and stirred 3 hours.Place and separate out a large amount of solids more than 12 hours.Stir, let solid dispersed in reaction solution, cool off with icy salt solution, import 31.5 gram chlorine, between the introduction period, the variation same with routine 1 takes place in the color of reaction solution at chlorine.Be heated to 50 ℃ with heating jacket, insulated and stirred reaction 1 hour continues under agitation to import 61 gram chlorine.Be warmed up to 60 ℃, insulated and stirred 3 hours cools to 25 ℃, feeds nitrogen and drives unnecessary chlorine in 1 hour away.Be cooled to 20 ℃, be added drop-wise in the 1.5L frozen water, separate out brown solid, filter, filter cake joins in the 2L flask, adds water and carries out steam distillation, when steaming product-free and steaming till.Overhead product is cooled to 5 ℃ of after-filtration, dries, and gets off-white color solid 40 grams, fusing point 80.1-83.4 ℃.Productive rate 44.7%.Purity 99.0%.

Though preceding text have shown detailed embodiment of the present invention, obvious, those skilled in the art revises and changes can carry out part under prerequisite of the present invention; The content that the description of preceding text is mentioned not is as limitation of the present invention only as illustrative case; Have 3 of technical characterictic described herein, the preparation method of 4-two chloro-5-cyanic acid-isothiazole all falls into this patent protection domain.

Claims

1. one kind 3; The preparation method of 4-two chloro-5-cyanic acid-isothiazole is characterized in that: at first anhydrous sodium cyanide is suspended in the N, under the water-bath cooling, drips dithiocarbonic anhydride in 20-30 ℃; Again in 60 ℃ of reactions, after spending the night, placement separates out solid after the stirring at room; Solid dispersed imports 40% chlorine under stirring under 20-30 ℃ of temperature in reaction solution, imports other 60% chlorine after 1 hour 50 ℃ of stirrings, and chlorine has imported the back in 60 ℃ of continuation reactions 2-3 hour, and feeding nitrogen is driven unnecessary chlorine away; Temperature control is lower than the N of 75 ℃ of reclaim under reduced pressure 90-95%, adds ethyl acetate backflow in the residue and extracts, and cooled and filtered is removed insolubles, reclaims ETHYLE ACETATE postcooling crystallization, gets product; Mother liquor behind the crystallization adds water and carries out steam distillation, and the product that remains in the mother liquor is all reclaimed.