Background and overview[1-2]
Chlorotoluene is an important fine chemical raw material. In recent years, the production of many new medicines, pesticides, dyes and other intermediates uses chlorotoluene as the starting material. These intermediates show very bright development prospects. Domestic The foreign market is unanimously optimistic, and many products have become hot development products. The huge development space in the downstream market has stimulated and promoted the production and development of chlorotoluene, and chlorotoluene will become the new favorite among organochlorine products. Many people in the industry believe that chlorotoluene will be the most potential basic intermediate for chlor-alkali companies to take the path of fine chemicals and build a chlorine product fine chemical product tree in the future. There are three isomers of chlorotoluene: p-, o-, and m-chlorotoluene, among which p-chlorotoluene is the most widely used. Para-chlorotoluene can prepare many important fine chemical intermediates and fine chemicals through side chain oxidation, ring oxidation, cyanation, halogenation, chlorination and other reactions. At present, more than 100 pesticides, medicines and dye products have been derived; o The application of chlorotoluene has been continuously expanded, and more than 30 derivative products have been developed; the production ratio of m-chlorotoluene is less than 1%, the output is small, and it is currently only used as a dye intermediate. O-chlorotoluene is also known as 2-chloro-1-methylbenzene. Colorless liquid. Molecular weight 126.59. Melting point -35.1℃. Boiling point 159.15℃. Relative density 1.0825 (20/4℃). Refractive index 1.5268. Flash point 47℃. Soluble in ethanol and benzene, miscible with ether, acetone, chloroform, carbon tetrachloride and heptane, slightly soluble in water. Can evaporate with water vapor. Toxic! Irritating. It is obtained by diazotization and replacement of o-toluidine.
Apply[2]
O-chlorotoluene is used as solvent, dye and pharmaceutical intermediate. Also used in other organic synthesis.
1) O-chlorobenzaldehyde. Its main industrial synthesis route is photocatalytic chlorination and hydrolysis of o-chlorotoluene. At present, there are nearly 20 major production plants including Zhejiang Lanxi Chemical Factory, Hangzhou Pesticide Factory, Lianyungang Jinping Chemical Factory, Wuhan Organic Industrial Co., Ltd., and Jiangsu Taizhou Chemical Factory. In 2002, my country's o-chlorobenzaldehyde production was approximately 7,000t, of which approximately 2,000t was exported. In the pesticide industry, o-chlorobenzaldehyde is mainly used to prepare the acaricide miticide; in the dye industry, it is used to produce a series of o-sulfobenzaldehyde sodium salt products; o-chlorobenzaldehyde is oximeted to prepare o-chlorobenzaloxime. Further chlorination can produce o-chlorobenzaldehyde chlorine. Both of these products are important pharmaceutical intermediates. In the pharmaceutical industry, o-chlorobenzaldehyde can also be used to synthesize chloroxime sodium, etc. With the continuous development of its downstream products, o-chlorobenzaldehyde has broad domestic and foreign market prospects. However, due to the rapid domestic construction speed in recent years, there has been an oversupply situation. Therefore, key enterprises have increased the scale of their equipment and increased the development of downstream products in order to Scale efficiency has become a very important means to participate in market competition.
2) O-chlorobenzoic acid. The production methods include: chlorination of o-chlorotoluene to o-chlorotrichlorotoluene, and then hydrolysis; there are also methods of direct oxidation of o-chlorotoluene using potassium permanganate or air. O-chlorobenzoic acid is used in the pharmaceutical industry to synthesize the antipyretic, analgesic and anti-inflammatory drugs flufenamic acid, aluminum flufenamic acid, mefenamic acid, etofenamate, the antipsychotic drugs chlorprothixol, thioridazine hydrochloride, Thioxanol, chloroxazolam, and drug intermediates m-chlorodiphenylamine, o-chlorobenzophenone, etc.; are mainly used in the synthesis of triphenylmethane dyes in the dye industry; used in the synthesis of high-efficiency pesticides in the pesticide industry Insecticides and various pesticide intermediates, such as mercaptobenzoic acid, sulfonate benzoic acid, o-chlorobenzoyl chloride. At present, there are nearly 10 major production plants including Changsha Organic Chemical Factory, Benxi Organic Chemical Factory, and Suzhou Auxiliary Factory. At present, the domestic output of o-chlorobenzoic acid is not large, the scale of enterprises is generally small, and the products have good development potential.
3) O-chlorophenylacetic acid. Using o-chlorotoluene as the starting material, o-chlorobenzyl chloride and o-chlorobenzyl acetonitrile are first synthesized and then reacted. This product is mainly used as an intermediate for the synthesis of highly effective anti-inflammatory drug diclofenac. There are nearly 10 major domestic production companies: Deyuan Fine Chemical Factory in Taixing City, Dongfeng Chemical Factory in Jintan City, Jiangsu Province, and Kangle Fine Chemical Factory in Gaoyou.
4) O-chlorobenzonitrile. To catalyze o-chlorotoluene to o-chlorobenzonitrile by air gas phase ammonia oxidation, the domestically developed OCN-98 fine particle catalyst and free turbulent fluidized bed reactor are used. This product can produce the disperse dye intermediate 2-cyano-4-nitroaniline after nitration and ammonolysis; it can also be made into the anti-malarial drug nitroquine. There is only production report of Jiangyin Suli Fine Chemical Co., Ltd. in China, with a production capacity of 1000t/a
O-Chlorophenylacetonitrile. It is obtained by using o-chlorobenzyl chloride as raw material and reacting with sodium cyanide. This product is a new type of fine chemical intermediate, mainly used for pharmaceutical synthesis. There are very few domestic companies carrying out small-scale production, and the products are mainly used for export.
5) O-chlorobenzoyl chloride. Using o-chlorotoluene as raw material, o-chlorobenzoic acid is first synthesized and then reacted to obtain o-chlorobenzoyl chloride. This product is used in the pharmaceutical industry to synthesize the general anesthetic ketamine hydrochloride and the non-narcotic antitussive drug Diflubenzuron; in the pesticide industry it is used to synthesize the insecticide diflubenzuron; in addition, it can also be used to synthesize dyes and fine chemical intermediates 4-Chlorobenzophenone. Country
6) O-chlorotrifluoromethylbenzene. Using o-chlorotoluene as raw material, in the presence of a catalyst, side chain photochlorination is performed to obtain o-chlorotrichlorotoluene, which is then fluorinated with hydrogen fluoride to obtain the product. The catalysts used in industrial production mainly include antimony pentachloride and trichloride. Phosphate. o-ChlorotrifluoromethylbenzeneIt is mainly used to synthesize the new drug Fluidol and a series of pesticides for the treatment of mental illness. In the past, only a few domestic companies produced it for their own pharmaceutical use, such as Northeast Pharmaceutical General Factory, Guangzhou No. 8 Pharmaceutical Factory, etc. As new uses are constantly being developed and export prospects are good, , currently produced by seven or eight companies including Zhejiang Yingguang Chemical Co., Ltd., Zhejiang Dongyang Chemical Factory No. 2, and Shandong Tianhao Chemical Group. The production capacity is very small. They are mainly produced according to foreign trade orders and the products are mainly exported.
7) 2-Chloro-5-bromotrifluoromethylbenzene. Use o-chlorotoluene as the raw material to synthesize o-chlorotrifluoromethylbenzene, then use iron powder as the catalyst, directly brominate with excess bromine, neutralize the excess bromine with sodium sulfite, steam distill the product, remove the water phase, and then The organic phase was distilled under reduced pressure to obtain the product. This product is mainly used to synthesize fluridol, a new drug for treating mental illness, and can also synthesize some herbicides and insecticides. At present, the domestic Fuxin Specialty Chemicals Co., Ltd. Research Institute has built a small-scale device
Preparation[1]
A preparation method for selective chlorination of toluene to synthesize o-chlorotoluene, which is characterized by following the following steps:
(1) Preparation of ionic liquid [Et3NH]Cl–nCuCl: Under N2 protection, under ice bath conditions, slowly add 2.7 mol of hydrochloric acid in a constant pressure funnel to 2.5 mol of triethylamine. into a 500mL three-neck flask with a condenser tube, stir and mix; after the reaction is completed, a thick milky white viscous liquid adheres to the inner wall of the flask, put the three-neck flask into a 90°C water bath and heat it for half an hour, and then heat it while it is hot. Pour into a beaker and cool to room temperature; under ice bath conditions, add an appropriate amount of water to the beaker containing the reaction product. After the product condenses and crystallizes, filter under reduced pressure to obtain the product. The product was washed with ethanol twice. Store in dry N2 atmosphere for later use. In N2 atmosphere, add 27.53g (0.2mol) intermediate and 19.80g (0.2mol) CuC into the three-necked flask, stir to disperse evenly, and react at 110°C for 2h; change the amount of CuCl to 39.60g (0.4mol) and 59.40g (0.6mol) to prepare [Et3NH]Cl–2CuCl and [Et3NH]Cl–3CuCl acidic ionic liquids.
(2) Toluene chlorination reaction step: Add a certain amount of ionic liquid catalyst [Et3NH]Cl–nCuCl to toluene, n=1, 2 or 3, stir to disperse evenly; then pass the solution into the system. Cl2 dried with concentrated sulfuric acid is reacted at a certain temperature for a certain time to obtain o-chlorotoluene. After the tail gas is condensed, the unreacted Cl2 is absorbed and removed by NaOH solution; the reaction is carried out under light-proof conditions. After the reaction is completed, the reaction product and the ionic liquid catalyst are separated using a separatory funnel, and the separated ionic liquid can be reused.
Main reference materials
[1] Concise Dictionary of Fine Chemicals
[2] Progress and application of chlorotoluene synthesis technology
[3] CN201510182767.5 A method for synthesizing o-chlorotoluene by selective chlorination of toluene
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