CN115433143B

CN115433143B - Method for synthesizing isothiazolinone compound

Info

Publication number: CN115433143B
Application number: CN202110621338.9A
Authority: CN
Inventors: 余正坤; 李云龙
Original assignee: Dalian Institute of Chemical Physics of CAS
Current assignee: Dalian Institute of Chemical Physics of CAS
Priority date: 2021-06-03
Filing date: 2021-06-03
Publication date: 2023-10-13
Anticipated expiration: 2041-06-03
Also published as: CN115433143A

Abstract

The invention discloses a synthetic method for cyclizing copper oxide N, S-ketal compounds into isothiazolinone compounds, belonging to the field of synthesis of pyrrole compounds. The invention takes N, S-ketal compounds as raw materials, and generates copper oxidation self-cyclization reaction at high temperature to generate isothiazolinone compounds. The synthesis method has the advantages of easily available raw materials, simple and convenient operation, mild synthesis reaction conditions, high efficiency, wide substrate adaptability, diversity of functional groups and the like.

Description

Method for synthesizing isothiazolinone compound

Technical Field

The invention belongs to the technical field of organic synthesis, and particularly relates to a method for synthesizing an isothiazolinone compound by cyclizing a copper oxide N, S-ketal compound.

Background

The isothiazolinone compound is a broad-spectrum, efficient, low-toxic and non-oxidative biocide, can kill bacteria, fungi, mildew and mildew, and the sterilization principle mainly depends on the active part on heterocycle to destroy DNA molecules in the thallus, so that the thallus is deactivated, and the isothiazolinone compound has the characteristics of high sterilization efficiency, good degradability, no residue, safe operation, good compatibility, strong stability and the like. Isothiazolinone bactericides have been widely used in the industries such as oil field, paper making, pesticides, cutting oil, leather, inks, dyes, leather making, etc. (z.k.yu, et al chem. Eur. J.2018,24, 14368-14372.). Therefore, research and development of a synthetic method of isothiazolinone compounds with mild reaction conditions and high efficiency is an important subject to be researched urgently.

Disclosure of Invention

In view of the above, the present invention aims to provide a method for synthesizing copper oxide N, S-ketal compounds into isothiazolinone compounds by cyclization. In order to achieve the above object, the technical scheme of the present invention is as follows:

an isothiazolinone compound, the molecular structural formula of which is shown as the following formula:

R ¹ 、R ² selected from C ₁ -C ₁₈ C containing substituent(s) of alkyl group(s) ₁ -C ₁₈ Alkyl, C of (2) ₆ -C ₁₈ Or C containing substituents ₆ -C ₁₈ The substituent is one or more than two of fluorine, chlorine, bromine, iodine, methyl, tertiary butyl, phenyl, methoxy, cyano and acetoxy.

In the above technical solution, further, R ¹ 、R ² Selected from C ₁ -C ₁₈ C containing substituents, straight-chain alkyl groups of (2) ₁ -C ₁₈ Straight chain alkyl, C ₆ -C ₁₈ Or C containing substituents ₆ -C ₁₈ Aryl, wherein the substituent is one of fluorine, chlorine, bromine, iodine, methyl, tertiary butyl, phenyl, methoxy, cyano and acetoxy, and the substituent-containing C ₆ -C ₁₈ Aryl is aryl wherein the substituents are ortho, meta or para monosubstituted.

The invention further aims to provide a synthesis method of the isothiazolinone compound, which uses copper salt as an oxidant, and under the condition of alkali, the N, S-ketal compound (2) undergoes self cyclization in a reaction solvent, and after the reaction is finished, the product is separated and characterized by a separation and purification method, so that the isothiazolinone compound (1) is generated in one step;

the reaction formula is as follows:

in the above technical solution, further, the copper salt is one or two of copper bromide and copper chloride.

In the above technical scheme, further, the alkali is selected from one or more than two of lithium carbonate, sodium carbonate, potassium carbonate, sodium acetate, potassium acetate, lithium acetate, sodium tert-butoxide, potassium tert-butoxide or lithium tert-butoxide.

In the above technical scheme, further, the molar ratio of the N, S-ketene acetal compound (2) to the oxidant is 10:1-1:10; the molar ratio of the N, S-ketene compound (2) to the alkali is 10:1-1:10.

In the above technical scheme, the reaction solvent is one or more than two of N, N-dimethylformamide, dichloroethane, dioxane, pyridine, acetic acid and benzene.

In the above technical scheme, the reaction atmosphere is one or two of air, oxygen, nitrogen and argon.

In the technical scheme, the reaction temperature is 85-150 ℃ and the reaction time is 0.5-12 h.

In the above technical scheme, further, the molar ratio of the N, S-ketene compound (2) to the oxidant is 1:3.

In the above technical scheme, further, the molar ratio of the N, S-ketene compound (2) to the alkali is 1:3.

In the above technical scheme, further, the reaction temperature is 120 ℃.

In the above technical scheme, further, the reaction time is 2h.

Compared with the prior art, the invention has the following beneficial effects: according to the method, the N, S-ketal compounds are used as raw materials, and the N, S-ketal compounds are utilized to undergo self cyclization reaction of copper oxidation at high temperature to synthesize the isothiazolinone compounds of different types, so that the obtained product has functional group diversity, the prepared raw materials are easy to obtain, the operation is simple and convenient, the synthesis reaction condition is mild, and the efficiency is high. Provides important guarantee for the wide application of isothiazolinone compounds in industries such as oil fields, papermaking, pesticides, cutting oil, leather, printing ink, dye, leather making and the like.

Detailed Description

The invention is further illustrated below with reference to specific examples. The present invention will be further understood by the following examples, but the content of the present invention is not limited thereto.

The invention synthesizes isothiazolinone compounds from N, S-ketal compounds. The reaction scheme for the preparation of raw material (2 a) in the examples below is prepared as described in the specific experimental procedure reference (J.org.chem.2014, 79, 10553-10560).

Example 1

A synthetic method of isothiazolinone compounds has the following reaction formula:

the specific process is as follows: 1-methylsulfanyl-1-benzylamine-1-butene-3-phenyl-3-thione (2 a) (90 mg,0.3 mmol), copper bromide (201 mg,0.9 mmol) and lithium t-butoxide (72 mg,0.9 mmol) were weighed into a 10mL reaction tube, 3mL of N, N-dimethylformamide was added, and the mixture was stirred at 120℃for 2 hours. After the completion of the reaction, volatile components were removed under reduced pressure, followed by separation by silica gel column chromatography (petroleum ether (60-90 ℃) in ethyl acetate, v/v=20:1 as eluent) to give the objective product (1 a) as a yellow liquid (56 mg, yield 70%). The target product was confirmed by nuclear magnetic resonance spectroscopy.

Data on characterization of the Compounds

Isothiazolinone compound (1 a) is a yellow liquid, ¹ H NMR(400MHz,CDCl ₃ )δ7.43(m,5H),7.36(m,5H),6.52(s,1H),4.98(s,2H). ¹³ C{ ¹ H}NMR(100MHz,CDCl ₃ )δ169.24,156.37,136.38,131.01,130.30,129.37,129.00,128.53,128.43,125.89,110.12,47.49。

example 2

the reaction procedure and operation were the same as in example 1, except that the oxidant was cupric chloride. The reaction was stopped, and the desired product (1 a) (51 mg, yield 63%) was obtained by working up.

Example 3

the reaction procedure and operation were as in example 1, except that the base was sodium t-butoxide. The reaction was stopped, and the desired product (1 a) (39 mg, yield 49%) was obtained by working up.

Example 4

the reaction procedure and operation were as in example 1, except that the base was potassium carbonate. The reaction was stopped, and the desired product (1 a) (46 mg, yield 57%) was obtained by working up.

Example 5

the reaction procedure and operation were as in example 1, except that the base was sodium carbonate. The reaction was stopped, and the desired product 1a (37 mg, yield 46%) was obtained by working up.

Example 6

The procedure was as in example 1, except that the molar ratio of 1-methylsulfanyl-1-benzylamine-1-butene-3-phenyl-3-thione (2 a) to copper bromide was 2.5:1. The reaction was stopped, and the desired product 1a (52 mg, yield 65%) was obtained by working up.

Example 7

The procedure was as in example 1, except that the molar ratio of 1-methylsulfanyl-1-benzylamine-1-butene-3-phenyl-3-thione (2 a) to lithium t-butoxide was 1:2. The reaction was stopped, and the desired product (1 a) (41 mg, yield 51%) was obtained by working up.

Example 8

The reaction procedure and operation were as in example 1, except that the reaction time was 1h. The reaction was stopped, and the desired product (1 a) (47 mg, yield 59%) was obtained by working up.

Example 9

The reaction procedure and operation were as in example 1, except that the reaction time was 1.5h. The reaction was stopped, and the desired product (1 a) (50 mg, yield 62%) was obtained by working up.

Many possible variations and modifications of the disclosed technology can be made by anyone skilled in the art without departing from the scope of the technology, or the technology can be modified to be equivalent. Therefore, any simple modification, equivalent variation and modification of the above embodiments according to the technical substance of the present invention shall still fall within the scope of the technical solution of the present invention.

Claims

1. A synthetic method of isothiazolinone compounds is characterized in that copper salt is used as an oxidant, and N, S-ketal compounds (2) undergo cyclization reaction in a reaction solvent under the condition of alkali to generate the isothiazolinone compounds (1) in one step;

the reaction formula is as follows:

R ¹ is phenyl, R ² Is benzyl;

the copper salt is one or two of copper bromide and copper chloride;

the reaction atmosphere is one or two of air and oxygen;

the alkali is selected from one or more of lithium carbonate, sodium carbonate, potassium carbonate, sodium acetate, potassium acetate, lithium acetate, sodium tert-butoxide, potassium tert-butoxide or lithium tert-butoxide;

the reaction solvent is one or more than two of N, N-dimethylformamide, dichloroethane, dioxane, pyridine, acetic acid and benzene.

2. The synthesis method according to claim 1, wherein the molar ratio of the N, S-ketene compound (2) to the oxidizing agent is 10:1-1:10; the molar ratio of the N, S-ketene compound (2) to the alkali is 10:1-1:10.

3. The method according to claim 1, wherein the reaction temperature is 85-150 ℃ and the reaction time is 0.5-12 h.

4. The synthesis method according to claim 2, wherein the molar ratio of the N, S-ketene compound (2) to the oxidant is 1:3, and the molar ratio of the N, S-ketene compound (2) to the base is 1:3.

5. A synthetic method according to claim 3, characterized in that the reaction temperature is 120 ℃.

6. The method of claim 5, wherein the reaction time is 2h.