CN115433143B - Method for synthesizing isothiazolinone compound - Google Patents

Abstract

The invention discloses a synthesis method for cyclizing copper oxidized N, S-ketal compounds into isothiazolinone compounds, and belongs to the field of synthesis of pyrrole compounds. The present invention uses N, S-ketal compounds as raw materials, and undergoes a self-cyclization reaction of copper oxidation at high temperature to generate isothiazolinone compounds. The synthesis method of the present invention has the advantages of readily available raw materials, simple operation, mild synthesis reaction conditions, high efficiency, wide substrate adaptability, and diverse functional groups.

Description

A kind of synthesis method of isothiazolinone compounds

Technical field

The invention belongs to the technical field of organic synthesis, and specifically relates to a synthesis method for cyclization of copper oxidized N, S-ketal compounds into isothiazolinone compounds.

Background technique

Isothiazolinone compounds are broad-spectrum, high-efficiency, low-toxicity, non-oxidizing biocides that can kill bacteria, fungi, molds and molds. Its bactericidal principle mainly relies on the active part on the heterocyclic ring to destroy the DNA in the bacteria. The molecule inactivates the bacteria, has high biocidal efficiency, good degradability, no residue, safe operation, good compatibility, and strong stability. Isothiazolinone fungicides have been widely used in oil fields, papermaking, pesticides, cutting oil, leather, ink, dyes, tanning and other industries (Z.K.Yu, et al.Chem.Eur.J.2018,24,14368-14372 .). Therefore, research and development of a synthetic method for isothiazolinone compounds with mild reaction conditions and high efficiency has become an important topic that needs urgent research.

Contents of the invention

In view of this, the object of the present invention is to provide a synthetic method for cyclizing copper oxidized N,S-ketal compounds into isothiazolinone compounds. In order to achieve the above objects, the technical solutions of the present invention are as follows:

An isothiazolinone compound, its molecular structural formula is as follows:

R ¹ and R ² are selected from a C ₁ -C ₁₈ alkyl group, a C ₁ -C ₁₈ alkyl group containing a substituent, a C ₆ -C ₁₈ aryl group, or a C ₆ -C ₁₈ aryl group containing a substituent. , the substituent is one or more of fluorine, chlorine, bromine, iodine, methyl, tert-butyl, phenyl, methoxy, cyano and acetoxy.

In the above technical solution, further, R ¹ and R ² are selected from C ₁ -C ₁₈ linear alkyl groups, C ₁ -C ₁₈ linear alkyl groups containing substituents, C ₆ -C ₁₈ aryl groups or A C ₆ -C ₁₈ aryl group containing a substituent, the substituent being one of fluorine, chlorine, bromine, iodine, methyl, tert-butyl, phenyl, methoxy, cyano, and acetoxy, The C ₆ -C ₁₈ aryl group containing a substituent is an aryl group in which the substituent is ortho-, meta- or para-mono-substituted.

Another object of the present invention is to provide a method for synthesizing isothiazolinone compounds, using copper salt as an oxidizing agent, and under alkali conditions, N, S-ketal compounds (2) generate themselves in the reaction solvent. After the cyclization reaction, the product is separated and characterized using conventional separation and purification methods to generate isothiazolinone compounds (1) in one step;

The reaction formula is as follows:

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

In the above technical solution, further, the base is selected from one of lithium carbonate, sodium carbonate, potassium carbonate, sodium acetate, potassium acetate, lithium acetate, sodium tert-butoxide, potassium tert-butoxide or lithium tert-butoxide or A mixture of two or more.

In the above technical solution, further, the molar ratio of the N,S-ketal compound (2) to the oxidizing agent is 10:1-1:10; the molar ratio of the N,S-ketal compound (2) to the alkali The molar ratio is 10:1-1:10.

In the above technical solution, further, the reaction solvent is one or a mixed solvent of two or more types of N,N-dimethylformamide, dichloroethane, dioxane, pyridine, acetic acid, and benzene.

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

In the above technical solution, further, the reaction temperature is 85-150°C, and the reaction time is 0.5h-12h.

In the above technical solution, further, the molar ratio of the N,S-ketal compound (2) to the oxidizing agent is 1:3.

In the above technical solution, further, the molar ratio of the N,S-ketal compound (2) to the base is 1:3.

In the above technical solution, further, the reaction temperature is 120°C.

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

Compared with the prior art, the present invention achieves the following beneficial effects: the method of the present invention uses N,S-ketal compounds as raw materials, and utilizes the self-cyclization of N,S-ketal compounds to undergo copper oxidation at high temperatures. Different types of isothiazolinone compounds are synthesized through the reaction. The obtained products have functional group diversity, the raw materials are easily available, the operation is simple, the synthesis reaction conditions are mild, and the efficiency is high. It provides important guarantee for the wide application of isothiazolinone compounds in oil fields, papermaking, pesticides, cutting oil, leather, ink, dyes, tanning and other industries.

Detailed ways

The present invention will be further described below in conjunction with specific examples. The following examples are helpful to further understand the present invention, but the content of the present invention is not limited thereto.

The present invention starts from N,S-ketal compounds and synthesizes isothiazolinone compounds. The reaction formula for preparing the raw material (2a) in the following examples is as follows. The specific experimental steps are prepared by referring to the method of the literature (J.Org.Chem.2014, 79, 10553-10560).

Example 1

A synthesis method of isothiazolinone compounds, the reaction formula is as follows:

The specific process is: weigh 1-methylthio-1-benzylamine-1-butene-3-phenyl-3-thione (2a) (90 mg, 0.3 mmol) and copper bromide (201 mg, 0.9 mmol) and lithium tert-butoxide (72 mg, 0.9 mmol) in a 10 mL reaction tube, add 3 mL of N,N-dimethylformamide, and stir for 2 hours at 120°C. After the reaction is completed, the volatile components are removed under reduced pressure, and then separated by silica gel column chromatography (the eluent is petroleum ether (60-90°C)/ethyl acetate, v/v=20:1) to obtain the yellow liquid target Product (1a) (56 mg, yield 70%). The target product was confirmed by NMR spectroscopy.

Compound characterization data

Isothiazolinone compound (1a): 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 ) δ 169.24, 156.37, 136.38, 131.01, 130.30, 129.37, 129.00, 128.53, 128.43, 125.89, 110.12, 47.49.

Example 2

A synthesis method of isothiazolinone compounds, the reaction formula is as follows:

The reaction steps and operations are the same as those in Example 1, except that the oxidizing agent is copper chloride. The reaction was stopped, and the target product (1a) (51 mg, yield 63%) was obtained through post-treatment.

Example 3

A synthesis method of isothiazolinone compounds, the reaction formula is as follows:

The reaction steps and operations are the same as those in Example 1, except that the base is sodium tert-butoxide. The reaction was stopped, and the target product (1a) (39 mg, yield 49%) was obtained through post-treatment.

Example 4

A synthesis method of isothiazolinone compounds, the reaction formula is as follows:

The reaction steps and operations are the same as those in Example 1, except that the base is potassium carbonate. The reaction was stopped, and the target product (1a) (46 mg, yield 57%) was obtained through post-treatment.

Example 5

A synthesis method of isothiazolinone compounds, the reaction formula is as follows:

The reaction steps and operations are the same as those in Example 1, except that the base is sodium carbonate. The reaction was stopped, and the target product 1a (37 mg, yield 46%) was obtained through post-treatment.

Example 6

The reaction steps and operations are the same as in Example 1. The difference from Example 1 is that 1-methylthio-1-benzylamine-1-butene-3-phenyl-3-thione (2a) and copper bromide The molar ratio is 2.5:1. The reaction was stopped, and the target product 1a (52 mg, yield 65%) was obtained through post-treatment.

Example 7

The reaction steps and operations are the same as in Example 1. The difference from Example 1 is that 1-methylthio-1-benzylamine-1-butene-3-phenyl-3-thione (2a) and tert-butanol The molar ratio of lithium is 1:2. The reaction was stopped, and the target product (1a) (41 mg, yield 51%) was obtained through post-treatment.

Example 8

The reaction steps and operations are the same as those in Example 1. The difference from Example 1 is that the reaction time is 1 hour. The reaction was stopped, and the target product (1a) (47 mg, yield 59%) was obtained through post-treatment.

Example 9

The reaction steps and operations are the same as in Example 1. The difference from Example 1 is that the reaction time is 1.5 h. The reaction was stopped, and the target product (1a) (50 mg, yield 62%) was obtained through post-treatment.

For any person familiar with the art, without departing from the scope of the technical solution of the present invention, they can use the technical content disclosed above to make many possible changes and modifications to the technical solution of the present invention, or modify it into equivalent changes. Example. Therefore, any simple modifications, equivalent changes, and modifications made to the above embodiments based on the technical essence of the present invention without departing from the content of the technical solution of the present invention should still fall within the protection scope of the technical solution of the present invention.

Claims (6)

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.