阅读说明：本技术 一种5-氯-烷基异噻唑啉酮的制备方法 (Preparation method of 5-chloro-alkyl isothiazolinone ) 是由 不公告发明人 于 2019-10-29 设计创作，主要内容包括：本发明涉及一种5-氯-烷基异噻唑啉酮的制备方法,包括如下步骤：(1)在有机溶剂中加入过渡金属卤化物和冠醚作为催化剂以及底物二烷基-3,3-二硫代二丙酰胺,然后通入氯气,进行闭环反应,反应温度＜0℃,反应时间为1-3h；(2)向上述反应中通入氯气和惰性气体组成的混合气体,温度控制在-10-10℃,反应时间为1-3h；(3)当底物在反应体系中的占比≤10％时,停止反应。通过本发明制备而成的5-氯-烷基异噻唑啉酮,产率显著高于现有报道中的多氯烷基异噻唑啉酮的产率,并且对真菌的抑制率,与目前市场上主流杀菌剂成分4,5-二氯-辛基异噻唑啉酮相当。这一制备方法,在多个领域中的杀菌剂和防腐剂配方中具有广泛应用。(The invention relates to a preparation method of 5-chloro-alkyl isothiazolinone, which comprises the following steps: (1) adding transition metal halide and crown ether as catalyst and dialkyl-3, 3-dithiodipropionamide as substrate into organic solvent, then introducing chlorine gas to carry out ring-closing reaction at the reaction temperature of less than 0 ℃ for 1-3 h; (2) introducing mixed gas consisting of chlorine and inert gas into the reaction, controlling the temperature at-10-10 ℃ and the reaction time to be 1-3 h; (3) when the ratio of the substrate in the reaction system is less than or equal to 10 percent, the reaction is stopped. The yield of the 5-chloro-alkyl isothiazolinone prepared by the invention is obviously higher than that of the polychlorinated-alkyl isothiazolinone reported in the prior art, and the inhibition rate of the 5-chloro-alkyl isothiazolinone on fungi is equivalent to that of the 4, 5-dichloro-octyl isothiazolinone which is the main bactericide component in the market at present. The preparation method has wide application in the formulas of bactericides and preservatives in various fields.)

1. A preparation method of 5-chloro-alkyl isothiazolinone is characterized by comprising the following steps:

(1) adding transition metal halide and crown ether as catalysts and dialkyl-3, 3-dithiodipropionamide as a substrate into an organic solvent, introducing chlorine gas, and carrying out a ring-closing reaction at the reaction temperature of less than 0 ℃ for 1-3 h;

(2) introducing mixed gas consisting of chlorine and inert gas into the reaction, controlling the temperature at-10-10 ℃ and the reaction time to be 1-3 h;

(3) when the ratio of the substrate in the reaction system is less than or equal to 10 percent, the reaction is stopped.

2. The method of preparing 5-chloro-alkylisothiazolinone according to claim 1, wherein the transition metal halide is selected from the group consisting of ferric chloride, nickel chloride, cobalt chloride, cupric chloride, zinc chloride, palladium chloride, ferric bromide, nickel bromide, cobalt bromide, cupric bromide, zinc bromide, palladium bromide, ferric iodide, nickel iodide and cobalt iodide.

3. The method for preparing 5-chloro-alkylisothiazolinone according to claim 1, wherein the number of carbon atoms of the alkyl group is an integer of 1 to 22.

4. The method for preparing 5-chloro-alkylisothiazolinone according to claim 1, wherein the transition metal halide is 0.01 to 0.1 wt% of the substrate.

5. A method of preparing 5-chloro-alkylisothiazolinone according to claim 1, characterized in that the crown ether is selected from 15-crown-5, 18-crown-6 or dicyclohexyl-18-crown-6.

6. The method for preparing 5-chloro-alkylisothiazolinone according to claim 1, wherein the crown ether is 0.005 to 0.05 wt% of the substrate.

7. The method for preparing 5-chloro-alkylisothiazolinone according to claim 1, wherein the rate of introducing chlorine gas in the step (1) is 1 to 10m³/h。

8. The method of preparing 5-chloro-alkylisothiazolinone according to claim 1, wherein the ratio of the inert gas to the chlorine gas in the mixed gas in the step (2) is 1:1 to 1:10 (v/v).

9. The method of preparing 5-chloro-alkylisothiazolinone according to claim 1, wherein the mixed gas is introduced at a rate of 2 to 20m in the step (2)³/h。

10. The method of preparing 5-chloro-alkylisothiazolinone according to claim 1, wherein the reaction is stopped by adding an alkali solution.

Technical Field

The invention belongs to the field of organic synthesis, and particularly relates to a preparation method of 5-chloro-alkyl isothiazolinone.

Background

The alkyl isothiazolinone is a broad-spectrum antiseptic, has good effect of inhibiting the growth of microorganisms, and can inhibit the growth of bacteria, fungi, mold and mildew. The chloro-alkyl isothiazolinone as an important derivative of the alkyl isothiazolinone has more obvious effect on killing fungi and algae. Therefore, the chloro-alkyl isothiazolinone is widely applied to antifouling paint, emulsion paint, cutting fluid and wood paint as a preservative or bactericide.

The current mainstream preparation process of chloroalkylisothiazolinone is as follows: preparing an amide intermediate by ester-ammonia exchange, for example, the method for preparing the amide intermediate disclosed in Chinese patents CN102786455A, WO2007/112613A1 and the like, and then carrying out ring closure on the amide intermediate through reaction with chlorine; and further reacting with excessive chlorine to obtain the final product chloroalkyl isothiazolinone. The disadvantage of this preparation is (1) that the chloroalkylisothiazolinones obtained are usually mixtures of dichloro, trichloro or tetrachloro products, the proportions of which are almost equivalent in the crude product, due to the difficult control of the reaction of the amide intermediate with chlorine during the ring closure. Therefore, further purification is required to obtain pure dichloroalkylisothiazolinone or tetrachloroalkylisothiazolinone, which causes additional cost and also results in low yield of the product; (2) polychlorinated alkylisothiazolinones mean that more chlorine gas is required to react with the same equivalent of alkylisothiazolinones than monochloroalkylisothiazolinones, which is too inefficient for chlorine gas as a raw material.

As is clear from the above, it has not been possible to obtain monochlorinated alkylisothiazolinones by the conventional methods. In fact, in the monochloro alkyl isothiazolinone compound, only one chlorine atom is substituted, so the chlorine dosage can be greatly reduced compared with polychlorinated alkyl isothiazolinone; and researches show that the monochloro alkyl isothiazolinone has the preservative effect equivalent to that of polychlorinated alkyl isothiazolinone, so that the monochloro alkyl isothiazolinone is more ideal preservative and bactericide.

The prior art has few reports on the preparation method of the monochloro alkyl isothiazolinone, and the yield of the method is not high, so that an industrial method for efficiently preparing the monochloro alkyl isothiazolinone is urgently needed.

Disclosure of Invention

The invention aims to provide a preparation method of monochloro alkyl isothiazolinone, which overcomes the defect that in the prior art, a plurality of polychlorinated products are generated due to side reactions, so that alkyl isothiazolinone with less monochloro can not be generated or can only be generated.

The monochloro alkyl isothiazolinone of the invention has a chemical name of 5-chloro-alkyl isothiazolinone, and is represented by the following chemical general formula:

wherein R is selected from C1-C22 alkyl groups, and when the number of carbon atoms of the alkyl groups is more than or equal to 3, the alkyl groups are straight chains, branched chains or cyclic chains. When chlorine and alkyl isothiazolinone generate chlorination reaction, hydrogen atom on 5 th position of five-membered ring of alkyl isothiazolinone is substituted preferentially. It is therefore desirable to find a suitable preparation process in which the chlorination reaction is controlled in this step, while suppressing further polychlorination reactions.

The technical scheme of the invention is realized by the following technical means.

A preparation method of 5-chloro-alkyl isothiazolinone, comprising the following steps:

(1) adding transition metal halide and crown ether as catalysts and dialkyl-3, 3-dithiodipropionamide as a substrate into an organic solvent, introducing chlorine gas, and carrying out a ring-closing reaction at the reaction temperature of less than 0 ℃ for 1-3 h;

(2) introducing mixed gas consisting of chlorine and inert gas into the reaction, controlling the temperature at-10-10 ℃ and the reaction time to be 1-3 h;

(3) when the ratio of the substrate in the reaction system is less than or equal to 10 percent, the reaction is stopped.

The reaction in the step (1) is a ring-closure reaction of dialkyl-3, 3-dithiodipropionamide, and the reaction temperature and time need to be strictly controlled, so that the ring-closure reaction can be smoothly carried out, and polychlorinated byproducts cannot be further generated. The reaction can be monitored by GC-MS, if necessary. The step (2) is a key step of the 5-chloro-alkyl isothiazolinone, and the mixed gas of chlorine and inert gas is adopted for two purposes, wherein the purity of the reactant chlorine is controlled, and the inert gas can effectively reduce the reaction activity of the chlorination reaction, namely the reaction activity of the chlorination reaction is controlled between the monochloro reaction and the polychlorinated reaction, so that the polychlorinated alkyl isothiazolinone, namely the 5-chloro-alkyl isothiazolinone, can be obtained as much as possible. Both of the above objects are effective in suppressing the production of polychlorinated alkylisothiazolinone as a by-product.

Further, the transition metal halide is selected from the group consisting of iron chloride, nickel chloride, cobalt chloride, copper chloride, zinc chloride, palladium chloride, iron bromide, nickel bromide, cobalt bromide, copper bromide, zinc bromide, palladium bromide, iron iodide, nickel iodide, and cobalt iodide.

In theory, the transition metal halide can catalyze the ring-closing reaction, and nickel chloride, cobalt chloride, copper chloride, zinc chloride and palladium chloride are preferred.

Further, the number of the alkyl carbon atoms is an integer of 1 to 22.

The alkyl has the main function of ensuring that the generated product is used in a bactericide formula and can be compatible with other components of the bactericide, so that the length of the alkyl can be adjusted by a person skilled in the art according to the experience of the person and the conditions of different bactericide formulas.

Further, the transition metal halide is present in an amount of 0.01 to 0.1 wt% based on the substrate.

Further, the crown ether is selected from 15-crown-5, 18-crown-6 or dicyclohexyl-18-crown-6.

Further, the crown ether is present in an amount of 0.005 to 0.05% by weight of the substrate.

Further, the rate of introducing chlorine gas in the step (1) is 1-10m³/h。

Further, in the step (2), the ratio of the inert gas to the chlorine gas in the mixed gas is 1:1 to 1:10 (v/v).

Further, the velocity of the mixed gas introduced in the step (2) is 2-20m³/h。

The above control of the rate of the chlorine gas or the mixed gas aims at controlling the reaction activity of the reaction, so that more monochloro pairs are obtained as much as possible to inhibit polychlorinated alkylisothiazolinone, namely 5-chloro-alkylisothiazolinone.

Further, the reaction was stopped by adding an alkali solution.

The alkali solution is selected from sodium carbonate solution or potassium carbonate solution.

The invention has the following beneficial effects:

the invention discloses a preparation method of 5-chloro-alkyl isothiazolinone, which adopts dialkyl-3, 3-dithiodipropionamide as a substrate and transition metal halide and crown ether as catalysts to carry out monochloro substitution reaction of alkyl isothiazolinone by a one-pot method, and overcomes the defects that only polychlorinated alkyl isothiazolinone can be obtained and the yield of main products of the polychlorinated alkyl isothiazolinone, such as dichloroalkyl isothiazolinone, is low in the preparation method of the chloroalkyl isothiazolinone in the prior art. The yield of the 5-chloro-alkyl isothiazolinone prepared by the invention is obviously higher than that of the polychlorinated-alkyl isothiazolinone reported in the prior art, and the inhibition rate of the 5-chloro-alkyl isothiazolinone on fungi is equivalent to that of the 4, 5-dichloro-alkyl isothiazolinone which is the main bactericide component in the market at present. The preparation method greatly reduces the industrial production cost of the chloroalkyl isothiazolinone serving as the bactericide component, and has wide application in bactericide and preservative formulations in a plurality of fields.

Detailed Description