Summary of Chemitry doctoral thesis: Developing of novel methods for synthesis 1,3-benzazole using sulfur

The research objectives of the thesis: Successfully studied a new multi-component reaction to synthesize 1,3- benzothiazoles using a sulfur agent; new reaction for synthesis of 1,3-benzoxazoles using a sulfur catalyst.
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Summary of Chemitry doctoral thesis: Developing of novel methods for synthesis 1,3-benzazole using sulfur MINISTRY OF EDUCATION VIETNAM ACADEMY OF AND TRAINING SCIENCE AND TECHNOLOGY GRADUATE UNIVERSITY SCIENCE AND TECHNOLOGY ----------------------------- Nguyen Le Anh PROJECT NAME Developing of novel methods for synthesis 1,3-benzazole using sulfur Major: Organic Chemistry Code: 9 44 01 14 SUMMARY OF CHEMITRY DOCTORAL THESIS Ha noi– 2021 INSTRODUCTION 1. The urgency of the thesis Benzazoles is one of the important compounds, representing a group of heterocyclic compounds with many interesting biological activities. 1,3-benzazoles derivatives have been shown to be active against cancer, bacteria and mold [1, 2] ... In recent years, research into new methods of synthesizing derivatives of 1,3- benzazoles has attracted the attention of many scientists in the world. Up to now, most of the 1,3-benzazoles synthesis methods have been based on a condensation oxidation reaction that uses the oxidizing effect of oxygen and is catalyzed with different metals. However, the use of oxygen as an oxidizer has some drawbacks, such as the often poorly selective reaction, requiring the presence of a metal catalyst, sometimes expensive, and the complicated catalytic-type product refining process. The manipulation of gaseous oxygen requires special reactors, especially at high temperatures and high pressures. Recently, sulfur is being studied for use in many condensation oxidation reactions. Using sulfur as a condensate oxidation reaction agent or catalyst has several advantages such as sulfur as a solid, non- hygroscopic, durable, and non-toxic. Compared to oxygen, it is easy to use the exact amount of sulfur in a reaction even at high temperatures. In addition, reactions with sulfur can be catalyzed with inexpensive metals and no significant toxicity such as iron, molybdenum. With the above advantages, sulfur chemistry is an appropriate method with a green, environmentally friendly approach. Therefore, in order to research and develop some new simple, environmentally friendly methods using sulfur, we have implemented the thesis with the name ‘‘Developing of novel methods for synthesis 1,3-benzazole using sulfur’’. 2. The research objectives of the thesis - Successfully studied a new multi-component reaction to synthesize 1,3- benzothiazoles using a sulfur agent. - New reaction for synthesis of 1,3-benzoxazoles using a sulfur catalyst. 3. Research content - Construction of conditions and optimization of 1,3-benzothiazole fusion from o-chloronitrobenzen, aldehydes, sulfur. - Synthesis of different derivatives of 1,3-benzothiazole under optimal conditions. - Construction of conditions and optimization of new reaction for synthesis 1,3-benzoxazoles from o-aminophenol, aldehyde, sulfur. - Synthesis of various derivatives 1,3-benzoxazole. - Applied to the scale of 10 mmol and 100 mmol in the synthesis of 1,3- benzoxazoles with the new optimized reaction. 1 - Reaction products are cleaned by column chromatography. The structure of the product is determined by modern spectroscopic methods such as: NMR, HR-MS, X-ray. CHAPTER 1. OVERVIEW 1.1. Overview of benzazole compounds 1.2. Benzazole compounds in nature 1.2.1. Benzazole compounds were extracted from Streptomyces 1.2.2. Benzazole compounds were isolated from marine organisms 1.3. The compounds contain semi-synthetic benzazole frames 1.4. Benzazole synthesis methods do not use sulfur 1.4.1. Methods of benzoxazole synthesis 1.4.1.1. Synthesis of benzoxazole with condensation of o-Aminophenol and Aldehyde or diketone 1.4.1.2. Synthesis of benzoxazole from o-Aminophenol and carboxylic acid or ester 1.4.1.3. Synthesis of benzoxazole from o-aminophenol with diaryl acetylene 1.4.1.4. Synthesis of benzoxazole from anilines compounds 1.4.1.5. Synthesis of benzoxazole from aryne 1.4.1.6. Synthesis of benzoxazole from Schiff base 1.4.1.7. Multi-component reaction for synthesis of benzoxazole 1.4.2. Synthesis of benzothiazole 1.4.2.1. Synthesis of benzothiazole from o-aminothiophenol with aldehyde, ketone, carboxylic acid and acyl chloride 1.4.2.2. Synthesis of benzothiazole from 2-aminothiophenol with CO2 1.5. Synthesis benzazole use sulfur 1.5.5. Synthesis of benzoxazole 1.5.5.1. From o-nitrophenol 1.5.5.2. From o-aminophenol CHAPTER 2. EXPERIMENT 2.1. Chemicals and equipment 2.1.1. Chemicals 2.1.2. Equipment 2.2. Method of determining the cleanliness and studying the structure of the product 2.2.1. Thin layer chromatography 2.2.2. Column chromatography 2.2.3. Method of determining structures 2.3. Synthesis of benzothiazoles 2.4. Synthesis of benzoxazoles CHAPTER 3. RESULTS AND DISCUSSION 3.1. Synthesis of benzothiazoles Figure: 2 We constructed a reaction model in which three starting materials o- chloronitrobenzene 109a, aldehyde 110a and elemental sulfur were used with equal equivalent. N-methylmorpholine (4 eq) is used as a base because it is believed to be suitable for this purpose in previous studies [121a, b]. We selected the ratio of the starting substances o-chloronitrobenzene: S: aldehyde: N-methylmorpholine (1: 1: 1: 4) to optimize the reaction conditions around this ratio. Response time is 16 hours. 3.1.1. Optimization of the benzothiazole synthesis * Survey reaction temperature Bảng 3.1. Effect of temperature on the reaction efficiency of the synthesis 2- Phenylbenzo[d]thiazole Nhiệt độ (°C) Hiệu suất % ...