阅读说明：本技术 2,2,4-三甲基-1,2-二氢化喹啉的制备方法 (Preparation method of 2,2, 4-trimethyl-1, 2-dihydroquinoline ) 是由 韦志强 江洋洋 付春 赵福宝 黄伟 于 2018-07-24 设计创作，主要内容包括：本发明属于精细化工技术领域,涉及2,2,4-三甲基-1,2-二氢化喹啉的制备方法。以酵母为生物催化剂,在特定的生物转化体系中,加入异丁醛或4-甲基-2,3-戊二酮,在0-50℃下,培养10-1000分钟,离心除去菌体,得到发酵液；在发酵液中加入溶剂萃取,之后再加入苯胺,加热至反应温度,反应一定时间后,蒸馏脱除溶剂,得到2,2,4-三甲基-1,2-二氢化喹啉。本发明不使用强酸做催化剂,无需液碱中和、分水的过程,即不产生废水,使用生物转化的方式,酵母可重复使用,同时替代原料丙酮在反应过程中易挥发的问题,降低反应温度,缩短反应时间,形成绿色环保的合成工艺。(The invention belongs to the technical field of fine chemical engineering, and relates to a preparation method of 2,2, 4-trimethyl-1, 2-dihydroquinoline. Adding isobutyraldehyde or 4-methyl-2, 3-pentanedione into a specific biotransformation system by using yeast as a biocatalyst, culturing at 0-50 deg.C for 10-1000 min, and centrifuging to remove thallus to obtain fermentation broth; adding a solvent into the fermentation liquor for extraction, then adding aniline, heating to the reaction temperature, reacting for a certain time, and distilling to remove the solvent to obtain the 2,2, 4-trimethyl-1, 2-dihydroquinoline. According to the invention, strong acid is not used as a catalyst, the processes of liquid alkali neutralization and water diversion are not needed, namely, no wastewater is generated, a biotransformation mode is used, the yeast can be reused, and the problem that the raw material acetone is volatile in the reaction process is solved, so that the reaction temperature is reduced, the reaction time is shortened, and the environment-friendly synthesis process is formed.)

1. A preparation method of 2,2, 4-trimethyl-1, 2-dihydroquinoline is characterized by comprising the following steps: adding isobutyraldehyde or 4-methyl-2, 3-pentanedione into a biotransformation system by using yeast as a biocatalyst, culturing at 0-50 deg.C for 10-1000 min, and centrifuging to remove thallus to obtain fermentation broth; adding a solvent into the fermentation liquor for extraction, then adding aniline, heating for reaction, and distilling to remove the solvent to obtain the 2,2, 4-trimethyl-1, 2-dihydroquinoline.

2. The method according to claim 1, wherein the yeast is selected from the group consisting of baker's yeast and brewer's yeast.

3. The method according to claim 1 or 2, wherein the bioconversion system catalyzes a reaction product by chemically converting isobutyraldehyde or 4-methyl-2, 3-pentanedione using an enzyme system specific to yeast.

4. The method according to claim 1, wherein the biotransformation system comprises a mixture of water, reducing sugars and phosphates together with yeast.

5. The method according to claim 4, wherein the reducing sugars are various carbon sources available to glucose and maltose.

6. The method according to claim 4, wherein the phosphate is selected from the group consisting of sodium hydrogen phosphate, sodium dihydrogen phosphate and dipotassium hydrogen phosphate.

7. The method according to claim 1, wherein the water is tap water or deionized water adjusted to pH 2 to 12.

8. The method as claimed in claim 1, wherein the centrifugation is performed at 0-50 ℃ and 1000-20000rpm for 10-600 min.

9. The method according to claim 1, wherein the solvent is selected from the group consisting of toluene, xylene, methylene chloride, and sulfolane.

10. The process according to claim 1, wherein the reaction temperature is 20 to 200 ℃ and the reaction time is 0.1 to 20 hours.

Technical Field

The invention relates to a preparation method of an anti-aging agent TMQ monomer 2,2, 4-trimethyl-1, 2-dihydroquinoline, which is an enzyme-chemical method for synthesizing 2,2, 4-trimethyl-1, 2-dihydroquinoline with low cost and high yield in a biocatalysis manner, is environment-friendly and relatively cheap, and belongs to the technical field of biocatalysis organic synthesis.

Background

2,2, 4-trimethyl-1, 2-dihydroquinoline is a monomer of an anti-aging agent TMQ, is mainly used for further polymerizing to obtain a di-, tri-or tetra-polymer (anti-aging agent TMQ) of the 2,2, 4-trimethyl-1, 2-dihydroquinoline, also called anti-aging agent RD, the anti-aging agent TMQ is a ketoamine anti-aging agent, is a faint yellow to ruined poise color particle or sheet, is mainly used as a rubber anti-aging agent, has the annual demand of 10 million tons in China, and is one of rubber anti-aging agent products with the largest demand in domestic and foreign markets,

the raw materials for synthesizing the 2,2, 4-trimethyl-1, 2-dihydroquinoline mainly comprise aniline and acetone, the condensation reaction is carried out under the action of an acid catalyst to directly obtain reaction liquid containing the 2,2, 4-trimethyl-1, 2-dihydroquinoline, and the reaction liquid is neutralized by liquid alkali and distilled to obtain the 2,2, 4-trimethyl-1, 2-dihydroquinoline with higher purity.

CN102010369 discloses a method for continuously preparing 2,2, 4-trimethyl-1, 2-dihydroquinoline, aniline and acetone are continuously fed into a reaction tower filled with a solid acid catalyst, and a reactant containing TMQ is overflowed and extracted. CN105348189A discloses a method for continuously preparing antioxidant RD monomer 2,2, 4-trimethyl-1, 2-dihydroquinoline. Adding aniline into a reactor, heating to 80-160 ℃, and reacting aniline, acetone and an acid catalyst according to a molecular ratio of 1-10: 5-100: 1, maintaining the temperature of the reactor at 80-160 ℃, and continuously extracting a condensation reaction liquid containing 2,2, 4-trimethyl-1, 2-dihydroquinoline from a discharge hole at the upper part of the reactor. The method also uses acid catalyst, especially hydrochloric acid, and has the disadvantages of high equipment corrosion and high three-waste treatment cost.

At present, the synthesis methods of 2,2, 4-trimethyl-1, 2-dihydroquinoline related at home and abroad do not relate to the improvement of intermediates in the reaction process, and the methods all use p-aniline and acetone as raw materials. Because the generation of 2,2, 4-trimethyl-1, 2-dihydroquinoline in the synthesis reaction depends on the generation of a key intermediate product 4-methyl-3-pentene-2-ketone obtained after condensation of two molecules of acetone, and the reaction speed of 4-methyl-3-pentene-2-ketone and aniline is very slow, the synthesis method can not completely eliminate the association of a plurality of unpredictable and interpretable side reactions caused by high temperature (120 ℃) and long reaction time and low-boiling point reaction raw material acetone which is too volatile and has low conversion rate and large acetone consumption and long-time high temperature, and is difficult to separate, the purity of the obtained 2,2, 4-trimethyl-1, 2-dihydroquinoline is not high, and 2 is further obtained, the content of TMQ finished products obtained by distilling and separating the 2, 4-trimethyl-1, 2-dihydroquinoline polymer is between 40 and 70 percent, and simultaneously, the defects that a large amount of waste water and waste residues need to be treated and the like are caused.

Disclosure of Invention

The invention aims to overcome the defects of the prior art, synthesize a key precursor in the condensation reaction with aniline, solve the problem that the substitute raw material acetone is volatile in the reaction process, reduce the reaction temperature, shorten the reaction time, form a green and environment-friendly synthesis process without using strong acid as a catalyst, and realize the environment-friendly production of 2,2, 4-trimethyl-1, 2-dihydroquinoline. By avoiding side reaction, the conversion rate of the aniline is greatly improved, so that the production cost of the product is reduced. As a corollary, another object of the present invention is to provide a process for reducing the aniline content in the reaction product to below 1% by weight, to achieve a content standard above 97% without rectification, for direct sale as a product or for the synthesis of high content of the antioxidant TMQ.

The invention provides a preparation method of 2,2, 4-trimethyl-1, 2-dihydroquinoline. The preparation method is realized by the following steps:

adding isobutyraldehyde or 4-methyl-2, 3-pentanedione into a specific biotransformation system by using yeast as a biocatalyst, culturing at 0-50 deg.C for 10-1000 min, and centrifuging to remove thallus to obtain fermentation broth; adding a solvent into the fermentation liquor for extraction, then adding aniline, heating to the reaction temperature, reacting for a certain time, and distilling to remove the solvent to obtain the 2,2, 4-trimethyl-1, 2-dihydroquinoline.

The biological conversion refers to a process of catalyzing isobutyraldehyde or 4-methyl-2, 3-pentanedione to generate a reaction product by using an enzyme system special for yeast at a certain temperature and under a certain pressure.

The yeast refers to yeast varieties such as baker's yeast and beer yeast. The biotransformation system is a mixture of water, reducing sugars and phosphate together with yeast.

The water system refers to tap water or deionized water with certain pH value regulated, and the pH value is within the range of 2-12.

The reducing sugars are various carbon sources that can be utilized by yeasts such as glucose and maltose.

The phosphate salts include various phosphate salts such as sodium hydrogen phosphate, sodium dihydrogen phosphate, and dipotassium hydrogen phosphate.

Further, the operation condition of the centrifugation is centrifugation for 10-600min at the rotation speed of 1000-20000rpm and at 0-50 ℃.

The solvent used may be toluene, xylene, methylene chloride, sulfolane and other organic solvents.

The reaction temperature is 20-200 ℃, and the reaction time is 0.1-20 hours.

Temperatures below 30 c, coupled with longer reaction times, may give higher yields than higher temperature, shorter time processes. A preferred time period for the synthesis of 2,2, 4-trimethyl-1, 2-dihydroquinoline to be substantially complete in the present invention is about 1 to 6 hours. After the synthesis of 2,2, 4-trimethyl-1, 2-dihydroquinoline, the reaction mixture was cooled and physically separated.

Has the advantages that: according to the invention, strong acid is not used as a catalyst, the processes of liquid alkali neutralization and water diversion are not needed, namely, no wastewater is generated, a biotransformation mode is used, the yeast can be reused, and the problem that the raw material acetone is volatile in the reaction process is solved, so that the reaction temperature is reduced, the reaction time is shortened, and the environment-friendly synthesis process is formed.

The conversion rate of the aniline is greatly improved by avoiding side reaction, the content of the aniline in the 2,2, 4-trimethyl-1, 2-dihydroquinoline is reduced to below 1 wt%, the content of a reaction product can reach more than 97% without rectification, the aniline can be directly sold as a product or used for a process for synthesizing a high-content anti-aging agent TMQ, and the production cost is greatly reduced.

Detailed Description

The present invention will be described in detail with reference to examples. It should be noted that the embodiments and features of the embodiments in the present application may be combined with each other without conflict.