346-18-9

Basic information

• Product Name: POLYTHIAZIDE (200 MG)
• Synonyms: ,2-trifluoroethyl)thio)methyl)-,1,1-dioxide;2,2-trifluoroethyl)thio)methyl)-,1,1-dioxide;2,2-trifluoroethyl)thio]methyl]-2h-1,2,4-6-chloro-4-dihydro-2-methyl-3-[[(2;2,2-trifluoroethylthiomethyl)-6-chloro-4-dihydro-2-methyl-7-sulphamoyl-3-(2;2H-1,2,4-Benzothiadiazine-7-sulfonamide, 6-chloro-3,4-dihydro-2-methyl-3-[[(2,2,2-trifluoroethyl)thio]methyl]-, 1,1-dioxide;2h-1,2,4-benzothiadiazine-7-sulfonamide,6-chloro-3,4-dihydro-2-methyl-3-(((2,;2h-1,2,4-benzothiadiazine-7-sulfonamide,6-chloro-3,4-dihydro-2-methyl-3-(((2,2;2h-benzo-1,2,4-thiadiazine1,1-dioxide
• CAS NO: 346-18-9
• Molecular Formula: C₁₁H₁₃ClF₃N₃O₄S₃
• Molecular Weight: 439.8818296
• EINECS: 206-468-4
• Mol File: 346-18-9.mol
• Article Data: 0

Chemical Properties

• Melting Point: 202.5°
• Boiling Point: 580.1°Cat760mmHg
• Flash Point: 304.7°C
• Appearance: /
• Density: 1.8346 (rough estimate)
• Vapor Pressure: 1.88E-13mmHg at 25°C
• Refractive Index: 1.6100 (estimate)
• Storage Temp.: Refrigerator
• Solubility: DMSO (Slightly), Methanol (Slightly, Heated)
• PKA: pKa 9.58(H2O,t =25) (Uncertain)
• CAS DataBase Reference: POLYTHIAZIDE (200 MG)(CAS DataBase Reference)
• NIST Chemistry Reference: POLYTHIAZIDE (200 MG)(346-18-9)
• EPA Substance Registry System: POLYTHIAZIDE (200 MG)(346-18-9)

Safety Data

• Hazardous Substances Data: 346-18-9(Hazardous Substances Data)

Usage

Description

Polythiazide exhibits a more pronounced antihypertensive effect than chlorothiazide and it may be used independently for the same indications as the aforementioned drugs. However, it is primarily used as an ingredient of a combination drugs intended for lowering pressure, in particular in minizide, which is a combination of prazozine and polythiazide.

Originator

Renese ,Pfizer, US ,1961

Uses

Polythiazide is a thiazide diuretic. Polythiazide is used in the treatment of hypertension as well as nephrotic syndrome, cirrhosis of the liver, and nutritional edema.

Manufacturing Process

(A) Preparation of trifluoroethylthioacetaldehyde dimethylacetal: To 4.6 g (0.2 mol) of metallic sodium dissolved in 75 ml of absolute methanol is rapidly added 24.4 g (0.2 mol) of mercaptoacetaldehyde dimethylacetal followed by dropwise addition of 42.0 g (0.2 mol) of trifluoroethyl iodide.The resulting reddish mixture is refluxed on a steam bath for one hour. One half of the alcohol is removed by concentration and the remainder diluted with several volumes of water and extracted with ether. The combined ether extracts are dried over sodium sulfate, the ether then removed at reduced pressure and the residue distilled to about 30 g (BP 82°C/25 mm).(B) Preparation of 4-Amino-2-Chloro-5-(Methylsulfamyl)Benzenesulfonamide: The 5-substituted-2,4-disulfamyl anilines may be prepared by procedures described in the literature, for example, the general procedures in Monatsch. Chem. vol. 48, p 87 (1927), which involves the treatment of a m-substituted aniline with from 10 to 20 parts by weight of chlorosulfonic acid followed by the gradual addition of from about 90 to 170 parts by weight of sodium chloride. The resultant mixture is heated at approximately 150°C for about 2hours after which the reaction mixture is poured into water and the resultant 5substituted aniline-2,4-disulfonyl chloride is filtered and is then treated with concentrated ammonium hydroxide or suitable amine by standard procedures to obtain the corresponding disulfonamide.(C) Preparation of 2-Methyl-3-(2,2,2-Trifluoroethyl)Thiomethyl-6-Chloro-7Sulfamyl-3,4-Dihydro-1,2,4-Benzothiadiazine-1,1-Dioxide: To 4.6 g (0.015 mol) of 4-amino-2-chloro5-(methylsulfamyl)benzenesulfonamide in 30 ml of the dimethyl ether of ethylene glycol is added 4.08 g (0.02 mol) of 2,2,2trifluoroethylmercaptoacetaldehyde dimethylacetal followed by 1 ml of ethyl acetate saturated with hydrogen chloride gas. The resulting solution is refluxed for 1.5 hours, cooled and then slowly added to cold water dropwise with stirring. The crude product is filtered, dried and recrystallized from isopropanol (3.2 g), MP 202° to 202.5°C. A second recrystallization from isopropanol raised the MP to 202° to 203°C.

Brand name

Renese (Pfizer).

Therapeutic Function

Diuretic

General Description

Crystals or white powder.

Air & Water Reactions

Its rate of decomposition in solution increases with an increase in pH. . Insoluble in water.

Reactivity Profile

POLYTHIAZIDE (200 MG) is a sulfonamide derivative. With strong reducing agents will produce hydrogen sulfide gas.

Fire Hazard

Flash point data for POLYTHIAZIDE (200 MG) are not available, but POLYTHIAZIDE (200 MG) is probably combustible.

Synthesis

Polythiazide, 1,1-dioxide 2-methyl-3-(2,2,2-trifluoroethylthiomethyl)-6- chloro-3,4-dihydro-2H-1,2,4-benzothiadiazin-7-sulfonamide (21.3.8), is also synthesized by an analogous scheme, which is by condensing 4-aminosulfonyl-5-chloro-2-methylaminosulfonylaniline (21.3.7) with 2,2,2-trifluoroethylthioacetaldehyde dimethylacetal.

InChI:InChI=1/C11H13ClF3N3O4S3/c1-18-10(4-23-5-11(13,14)15)17-7-2-6(12)8(24(16,19)20)3-9(7)25(18,21)22/h2-3,10,17H,4-5H2,1H3,(H2,16,19,20)