80-77-3

Usage

Uses

Used in Pharmaceutical Industry:
Chlormezanone is used as an anxiolytic for relieving moderate anxiety and stress. However, it has a number of side effects and is rarely used in practice due to the lack of advantage over other anxiolytics.
Used in Medical Treatment:
Chlormezanone is used to improve the emotional state of the patient, but its use is associated with large increases in the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis.

Originator

Trancopal,Winthrop-Breon,US,1958

Manufacturing Process

A solution of 4-chlorobenzaldehyde is reacted with beta-mercaptopropionic acid and with methylamine. The mixture is refluxed in benzene and water is removed from an overhead separator. The reaction mixture was cooled, washed with dilute ammonium hydroxide and water, and the benzene was removed by distillation in vacuo. The oily residue was taken up in ether from which it crystallized. The precipitate was recrystallized twice from ether to yield 2-(4-chlorophenyl)-3-methyl-4-metathiazanone. A solution of 11.2 g of potassium permanganate in 100 ml of warm water was added dropwise to a well stirred solution of 10 g of 2-(4-chlorophenyl)-3- methyl-4-metathiazanone in 50 ml of glacial acetic acid. The temperature was kept below 30°C with external cooling. An aqueous sodium bisulfite solution was then added to remove the manganese dioxide. The thick whitish oil which separated was taken up in chloroform and the extract was washed with water. Removal of the chloroform by distillation in vacuo yielded an oily residue which solidified. The solid was recrystallized from isopropyl alcohol to give 5 gof the product, 2-(4-chlorophenyl)-3-methyl-4-metathiazanone-1,1-dioxide, MP 116.2° to 118.6°C (corr.).

Therapeutic Function

Tranquilizer

World Health Organization (WHO)

Chlormezanone is a sedative with antianxiety properties and a central skeletal muscle relaxant effect. It had already been falling into obsolescence for several years.

Biological Activity

Anxiolytic and skeletal muscle relaxant that acts at the benzodiazepine site of GABA A receptors.

Synthesis

Chlormezanone, 2-(p-chlorophenyl)-tetrahydro-3-methyl-4H-1,3- tiazin-4-on-1,1-dioxide (5.2.8), is synthesized by joint condensation of mercaptopropionic acid, methylamine, and 4-chlorobenzaldehyde, evidently through the intermediate stage of formation of 4-chlorobenzylidenemethylamine, giving the aminothioacetal 2- (p-chlorophenyl)-tetrahydro-3-methyl-4H-1,3-tiazin-4-one (5.2.7). Oxidation of the sulfur atom using potassium permanganate gives chlormezanone (5.2.8) [62,63].

InChI:InChI=1/C11H12ClNO3S/c1-13-10(14)6-7-17(15,16)11(13)8-2-4-9(12)5-3-8/h2-5,11H,6-7H2,1H3

Upstream product

• 30897-26-8 2-(4-Chlorophenyl)-3-methyl-3,4,5,6-tetrahydro-2H-1,3-thiazin-4-on 
• 102818-66-6 (+)-2-(4-Chlorphenyl)-3-methyl-1,3-thiazinan-4-on-1,1-dioxid 
• 102818-67-7 (-)-2-(4-Chlorphenyl)-3-methyl-1,3-thiazinan-4-on-1,1-dioxid 

Downstream Products

• 102818-66-6 (+)-2-(4-Chlorphenyl)-3-methyl-1,3-thiazinan-4-on-1,1-dioxid 
• 102818-67-7 (-)-2-(4-Chlorphenyl)-3-methyl-1,3-thiazinan-4-on-1,1-dioxid 
• 77711-05-8 3-sulfinopropionic acid 
• 104-88-1 4-chlorobenzaldehyde 
• 74-89-5 methylamine 

Relevant academic research and scientific papers

Tranquillizer chlormezanone synthesis method

The invention discloses a tranquillizer chlormezanone synthesis method, which comprises: adding 2-(3-chloro-1,2-dihydroxyphenyl)-3-methyl-1,3-hydrothiazin-4-one and a chloromethyl methyl ether solution to a reaction container, carrying out controlled stirring, controlling the temperature of the solution, adding a 2-methyl-2,4-pentanediol solution, adding potassium ruthenate in batches, and continuously carrying out the reaction; and cooling the solution, adding a potassium carbonate solution in batches, layering the solution, taking out the oil layer, adding a benzenesulfonic acid solution, adjusting the pH value, extracting multiple times with a hexafluorobenzene solution, extracting multiple times with a dimethyl phosphate solution, washing with a 1,2-dibromobenzene solution, re-crystallizing in a polypropylene glycol solution, and dehydrating with a dehydrating agent to obtain the finished product chlormezanone.

Important pharmaceutical-chemical characteristics of the centrally acting muscle relaxant chlormezanone

The enantinomers of chlormezanone (1) may be achieved by enantioselective HPLC separation with a yield of 98% using a OD-Daicel column. Both enantiomers bind to human serum albumin (HSA) at pH 7,4 to a range of 11-12%. Binding to the globuline fractions is much less (2-4%, equilibrium dialysis, validation by ultrafiltration). It could be demonstrated by means of 1H-NMR spectroscopy that 1 binds to HSA with the benzene ring as well as with the thiazanone ring. The velocity of racemisation could be measured for the first time using a BSA column. The enantiomers undergo racemisation at pH 7.4 and 37 °C with a halflife of approx. 20.5 h.

Water dispersion containing ultrafine particles of organic compounds

A water-dispersible condensate of water-insoluble ultrafine particles of medicine or hormones having a particle size of at largest 4 μm prepared by the steps of heating the medicine or hormone in a vacuum vessel at a temperature of 30° C. higher than the boiling point and at a pressure between 0.01 Torr and 10 Torr to evaporate the medicine or hormone and condensing the medicine or hormone on a recovery plate to obtain the condensate.

FURTHER FUNCTIONAL GROUP OXIDATIONS USING SODIUM PERBORATE

Sodium perborate in acetic acid is an effective reagent for the oxidation of aromatic aldehydes to carboxylic acids, iodoarenes to (diacetoxyiodo)arenes, azines to N-oxides, and various types of sulfur heterocycles to S,S-dioxides.Nitriles are unaffected by the reagent in acetic acid, but undergo smooth hydration to amides when aqueous methanol is employed as solvent.