阅读说明：本技术 铜催化剂在1-噻唑基吲哚化合物、亚硝酸叔丁酯反应制备噻唑并喹唑啉酮衍生物中的应用 (Application of copper catalyst in preparation of thiazoloquinazolinone derivative through reaction of 1-thiazolylindole compound and tert-butyl nitrite ) 是由 邹建平 张栋梁 达莫拉·苏布 李成坤 陶泽坤 于 2018-03-01 设计创作，主要内容包括：本发明公开了铜催化剂在1-噻唑基吲哚化合物、亚硝酸叔丁酯反应制备噻唑并喹唑啉酮衍生物中的应用。本发明使用1-噻唑基吲哚化合物为起始物在空气中即可反应制备产物,原料易得,种类广泛；利用本发明方法得到的产物类型多样,用途广泛,既可直接使用,又可用于合成杀菌剂、除草剂和杀虫剂等具有药物活性的噻唑并喹唑啉酮衍生物；此外,本发明公开的方法步骤简单、反应条件温和、目标产物的收率高、污染小、反应操作和后处理过程简单,适合于工业化生产。(The invention discloses application of a copper catalyst in preparation of thiazoloquinazolinone derivatives through reaction of 1-thiazolyl indole compounds and tert-butyl nitrite. The 1-thiazolyl indole compound is used as an initiator and can react in the air to prepare a product, and raw materials are easy to obtain and wide in variety; the product obtained by the method has various types and wide application, can be directly used, and can also be used for synthesizing thiazoloquinazolinone derivatives with pharmaceutical activity, such as bactericides, herbicides, insecticides and the like; in addition, the method disclosed by the invention has the advantages of simple steps, mild reaction conditions, high yield of target products, small pollution, simple reaction operation and post-treatment process, and suitability for industrial production.)

1. the application of a copper catalyst in catalyzing a reaction of a 1-thiazolyl indole compound and tert-butyl nitrite to prepare a thiazoloquinazolinone derivative; the 1-thiazolyl indole compound is shown as the following chemical structural general formula:

wherein R is¹Selected from: one of hydrogen, alkyl, alkoxy, halogen, nitro, cyano and ester group;

wherein R is²Selected from: hydrogen, alkyl, alkoxy, halogen, nitro, cyano, trifluoromethyl, ester groupOne of (1);

the chemical formula of the copper catalyst is CuX_nWherein X is one of Cl, Br, I and OAc; n is 1 or 2.

2. Use according to claim 1, characterized in that: the reaction temperature is between room temperature and 100 ℃.

3. Use according to claim 1, characterized in that: the reaction was followed by thin layer chromatography until complete.

4. Use according to claim 1, characterized in that: the reaction is carried out in air.

5. Use according to claim 1, characterized in that: the 1-thiazolyl indole compound is selected from: 1- (thiazol-2-yl) indole, 1- (thiazol-2-yl) -5-methylindole, 1- (thiazol-2-yl) -6-methoxyindole, 1- (thiazol-2-yl) -7-fluoroindole, 1- (thiazol-2-yl) -6-chloroindole, 1- (thiazol-2-yl) -4-bromoindole, 1- (thiazol-2-yl) -5-cyanoindole, 1- (thiazol-2-yl) -5-nitroindole, 1- (thiazol-2-yl) -4-carboxyindole, 1- (4-methylthiazol-2-yl) indole, 1- (4-chlorothiazol-2-yl) indole, 1- (4-fluorothiazol-2-yl) indole, 1- (5-bromothiazol-2-yl) indole, 1- (4-methoxythiazol-2-yl) indole, 1- (5-nitrothiazol-2-yl) indole, 1- (4-cyanothiazol-2-yl) indole, 1- (4-trifluoromethylthiazol-2-yl) indole, 1- (5-carbomethoxythiazol-2-yl) indole.

Technical Field

The invention belongs to the technical field of preparation of organic compounds, and particularly relates to a copper catalyst catalytic preparation method of thiazoloquinazolinone derivatives and related derivative products.

Background

Quinazolinone derivatives exist in traditional Chinese medicines of evodiamine and rutaecarpine, and the traditional Chinese medicine has the effects of relieving pain and diminishing inflammation, losing weight, regulating heart, body temperature and bronchoconstriction and the like (tiarys, liubaylin, sinochang, pharmacological research progress of evodia and active ingredients thereof, traditional Chinese medicinal materials 2002, 10, 256-phase 259, Hulongping, Liyuejian, pharmacological research progress of evodiamine and rutaecarpine, Chinese pharmacological report, 2003, 19(10), 1084-phase 1987).

The 5H-thiazolo [2,3-b ] quinazolin-5-one derivative (structure shown as D) can be used as herbicide and plant growth regulator (Guenther S. Neuhofen, Bruno W. Otterstadt, U.S. Pat. No. 4,473,391, 1984).

Disclosure of Invention

The invention aims to provide a method for preparing thiazoloquinazolinone derivatives and related derivative products, which has the advantages of simple raw material source, mild reaction conditions, simple post-treatment, high yield and the like.

In order to achieve the purpose of the invention, the technical scheme adopted by the invention is as follows:

a process for the preparation of a thiazoloquinazolinone derivative comprising the steps of: dissolving a 1-thiazolyl indole compound, tert-butyl nitrite and a copper catalyst in a solvent, and reacting at room temperature-100 ℃ to obtain a thiazoloquinazolinone derivative;

the 1-thiazolyl indole compound is shown as the following chemical structural general formula:

wherein R is¹Selected from: one of hydrogen, alkyl, alkoxy, halogen, nitro, cyano and ester group;

wherein R is²Selected from: one of hydrogen, alkyl, alkoxy, halogen, nitro, cyano, trifluoromethyl and ester group;

the chemical formula of the copper catalyst is CuX_nWherein X is one of Cl, Br, I and OAc; n is 1 or 2;

in the technical scheme, the 1-thiazolyl indole compound is selected from 1- (thiazole-2-yl) indole, 1- (thiazole-2-yl) -5-methylindole, 1- (thiazole-2-yl) -6-methoxyindole, 1- (thiazole-2-yl) -7-fluoroindole, 1- (thiazole-2-yl) -6-chloroindole, 1- (thiazole-2-yl) -4-bromoindole, 1- (thiazole-2-yl) -5-cyanoindole, 1- (thiazole-2-yl) -5-nitroindole, 1- (thiazole-2-yl) -4-carbomethoxyindole, 1- (4-methylthiazol-2-yl) indole, 1- (4-chlorothiazol-2-yl) indole, 1- (4-fluorothiazol-2-yl) indole, 1- (5-bromothiazol-2-yl) indole, 1- (4-methoxythiazol-2-yl) indole, 1- (5-nitrothiazol-2-yl) indole, 1- (4-cyanothiazol-2-yl) indole, 1- (4-trifluoromethylthiazol-2-yl) indole, 1- (5-carbomethoxythiazol-2-yl) indole.

In the above technical scheme, the reaction is followed by Thin Layer Chromatography (TLC) until complete completion.

In the technical scheme, the molar ratio of the 1-thiazolyl indole compound to the tert-butyl nitrite to the copper catalyst is 1: 1-3: 0.05-0.15. Preferred conditions are: 1-thiazolyl indole compound, tert-butyl nitrite and copper catalyst are 1: 2: 0.1.

In the technical scheme, after the reaction is finished, the product is subjected to column chromatography separation and purification treatment.

The reaction process of the above technical scheme can be expressed as follows:

the invention also discloses application of the copper catalyst in catalyzing the reaction of the 1-thiazolyl indole compound and the tert-butyl nitrite or the reaction of preparing the thiazoloquinazolinone derivative.

In the technical scheme, the reaction temperature is room temperature-100 ℃.

In the above technical scheme, the reaction is followed by Thin Layer Chromatography (TLC) until complete completion.

Due to the application of the technical scheme, compared with the prior art, the invention has the following advantages:

1. the invention uses 1-thiazolyl indole compound as the starting material, the raw material is easy to get, the cost is low, and the variety is many.

2. The invention has wide application range.

3. The copper catalyst used in the invention is cheap and easy to obtain and has low cost.

4. The method disclosed by the invention has the advantages of mild reaction conditions, short reaction time, high yield of target products, simple reaction operation and post-treatment process, and suitability for industrial production.

Detailed Description

The invention is further described below with reference to the following examples: