Usage of Silicone Oil - Skilled Use

As an important industry in the field of fine chemicals, medicine has become the focus of development and competition in the past decade. With the progress of science and technology, many medicines have been continuously developed to benefit humanity. The synthesis of these medicines relies on the production of new high-quality pharmaceutical intermediates, which are protected by patents. However, the corresponding intermediates do not have such problems, Therefore, the domestic and international markets and application prospects of new pharmaceutical intermediates are very promising. There are many varieties of new pharmaceutical intermediates, and it is impossible to fully introduce them. This article briefly introduces the new pharmaceutical intermediates and some important new processes of pharmaceutical intermediates that have been studied and are worth paying attention to in China in recent years

1. 1- (6-neneneba methoxy-neneneea -2-naphthyl) ethanol

There are many synthetic methods for the nonsteroidal anti-inflammatory drug Naproxen, among which the carbonylation synthetic route is highly selective and environmentally friendly, making the carbonylation synthetic nonsteroidal anti-inflammatory drug superior to the traditional route. The key intermediate for the carbonylation synthesis of Naproxen is 1- (6-nenenebc methoxy-neneneec -2-naphthyl) ethanol. Hunan University in China uses 2-nenenebe methoxy naphthalene as raw material, and uses 1,3-dibromo-5,5-dimethyl Hydantoin hydrochloric acid to catalyze bromine Acetyl group Acetyl group and palladium Heterogeneous catalysis hydrogenation reduction under normal pressure, through intermediate products such as 1-bromo-2-nenenebc methoxy naphthalene, 5-bromo-6-nenenebd methoxy 2-nenenebe acetyl naphthalene, the final product is obtained.

2 α - Methylene cyclohexanone

α - Methylene cyclohexanone is an active center of many anticancer drugs, which contains α , β - Unsaturated ketones belong to the concealed group of the anticancer active group, and have become an important intermediate for the synthesis of many important cyclic anticancer drugs. There are three reported synthetic routes in the literature: 1) the Aldol condensation of cyclic ketones and formaldehyde; 2) Produced by Mannich reaction β - Dialkylamine methyl cycloketone, produced by amine or Quaternary ammonium cation geothermal decomposition α - Methylene cyclohexanone; 3) It is obtained by condensation of cyclohexanone with diethyl oxalate and reaction with formaldehyde α - Methylene cyclohexanone. Developed by Guangzhou Institute of Materia Medica, Chinese Academy of Sciences, Cyclopentanone, cyclohexanone and Isophorone react with diethyl oxalate respectively, and then the reaction products react with formaldehyde to obtain corresponding α - Methylene Cyclopentanone α - Methylene cyclohexanone and α - Methylene Isophorone, etc. The reaction shall be carried out in the presence of solvents, such as Dimethyl sulfoxide and tetrahydrofuran

3. 4,4 '- di Methoxy group Acetoacetic acid methyl ester

Methyl 4,4 '- di Methoxy group Acetoacetic acid is an intermediate of Nilvadipine, an important medicine for treating Cerebrovascular disease in geocentric regions. Nilvadipine is the second generation calcium antagonist developed by Fujisawa Pharmaceutical Company of Japan and listed in 1989. It is a leading medicine for treating cardiovascular and cerebrovascular diseases in the international market at present, and has not yet been produced in China. Glyoxylic acid is used as raw material to combine with Trimethyl orthoformate in the presence of concentrated sulfuric acid

The latter reacts with methyl acetate and Sodium methoxide to obtain 4,4 ′ - di Methoxy group Acetoacetic acid methyl ester

4. C3 chlorocephalenoic acid

C3 chlorocefenoic acid is an important intermediate of Cephalosporin Cefaclor. Cefaclor is the second generation of highly effective oral Cephalosporin developed by Lilly&Lyle. Because of its obvious curative effect and oral advantages, its sales in the United States in 2001 reached more than 80 million yuan, ranking second in antibiotic drugs. There are two synthetic routes of C3 chlorocefenoic acid. 1) Penicillin G salt undergoes oxidation, esterification, ring expansion, reduction, oxidation, reduction, oxidation, reduction, oxidation Multi step synthesis, such as Acetyl group removal and hydrolysis, has too many steps and low yield; 2) 7-ACA (7-ACA) is used as the raw material. When 7-ACA is undergoing the transformation of the 3-position earth mother core, because its 7-position amino group and 4-position carboxyl group are highly active, the first step is to protect them. The common method of 4-carboxyl group protection is to prepare them into tert butyl ester, diphenyl methyl ester and p-nitrobenzyl ester; 7-Amino ground protection can be protected by Silane based reagents such as phenoxymethyl, benzyl, and trimethylchloro Silane. Then nucleophilic substitution and reduction reactions are carried out. First, the ethoxy group is replaced by the nucleophilic reagent containing sulfur, such as ethyl xanthate, thiourea, or mercaptan, and then the nickel is used as a catalyst for hydrogenation to generate 3-cyclomethylenecephalosporanic acid; Then, external double bond oxidation and reduction are carried out. The oxidant is generally ozone, and the key is to control the oxidation depth. The commonly used reducing agents are Sulfurous acid, Dimethyl sulfide, sulfur dioxide and trimethylphosphate; The third step is chlorination, removal of Protecting group and hydrolysis reaction. The chlorination agent can be SOCl2, PCl3, POCl3, COCl3 or solid phosgene, which can be chlorinated, deacylated and hydrolyzed in one step to obtain C3l chlorocephaloenoic acid mother core

5. 2-Tetrahydronaphthone

2-tetrahydronaphthalene ketone is mainly used in medicine and liquid crystal industry. In recent years, the demand is strong at home and abroad. The conventional synthesis route is to replace Phenylacetic acid as raw material, first react with Thionyl chloride to generate acyl chloride, and then Acylation and cyclization of acyl chloride and olefin are carried out to synthesize 2-tetrahydronaphthalene ketone. This method is not economical and solvent is not easy to recover; Recently, a new one pot Acylation reaction was developed in China. Trifluoroacetic anhydride/phosphoric acid catalytic system was used to react substituted Phenylacetic acid with ethylene. In the reaction process, Trifluoroacetic acid can be converted into Trifluoroacetic anhydride for direct recycling, which is less corrosive to equipment and has a very promising application prospect

6. N-benzyl-N-methyl Ethanolamine

N-benzyl-N-methyl Ethanolamine is an important pharmaceutical intermediate, which can synthesize antiasthmatic and antiallergic drugs, Antihypertensive drug nicardipine and some new drugs for cardiovascular disease; In addition, it can also synthesize pesticides, herbicides, plant fungicides and metal preservatives. There are three routes for the synthesis of N-benzyl-N-methyl Ethanolamine: 1) N-benzyl-N-methylamine reacts with ethylene oxide; 2) It is a low-temperature reaction between N-benzyl-N-methylamine and chloroethanol; 3) 2-benzylamine ethanol is mixed with Paraformaldehyde and formic acid, heated to react, and then treated with excessive sodium hydroxide. The isomers are extracted and separated with ether and benzene