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HYDROFLUMETHIAZIDE

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HYDROFLUMETHIAZIDE Basic information

Product Name:
HYDROFLUMETHIAZIDE
Synonyms:
  • dihydroflumethazide
  • dihydroflumethiazide
  • diucardin
  • diuredemina
  • diurometon
  • elodrin
  • elodrine
  • finuret
CAS:
135-09-1
MF:
C8H8F3N3O4S2
MW:
331.29
EINECS:
205-173-8
Product Categories:
  • DIUCARDIN
  • Amines
  • Heterocycles
  • Intermediates & Fine Chemicals
  • Isotope Labelled Compounds
  • Pharmaceuticals
  • Sulfur & Selenium Compounds
Mol File:
135-09-1.mol
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HYDROFLUMETHIAZIDE Chemical Properties

Melting point:
272-273
Boiling point:
531.6±60.0 °C(Predicted)
Density 
1.5955 (estimate)
storage temp. 
Keep in dark place,Sealed in dry,2-8°C
solubility 
DMSO (Slightly), Methanol (Sparingly)
form 
Solid
pka
8.9, 8.2(at 25℃)
color 
White
Water Solubility 
329.9mg/L(room temperature)
EPA Substance Registry System
2H-1,2,4-Benzothiadiazine-7-sulfonamide, 3,4-dihydro-6-(trifluoromethyl)-, 1,1-dioxide (135-09-1)
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Safety Information

Hazard Codes 
Xn,Xi
Risk Statements 
42/43
Safety Statements 
36
WGK Germany 
2
RTECS 
DK9625000
Hazard Note 
Irritant
HS Code 
2935904000
Hazardous Substances Data
135-09-1(Hazardous Substances Data)
Toxicity
LD50 in mice (mg/kg): >8000 orally, 750 i.v., 6280 i.p. (Piala)

MSDS

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HYDROFLUMETHIAZIDE Usage And Synthesis

Chemical Properties

White Solid

Originator

Saluron,Bristol,US,1959

Uses

Labelled Hydroflumethiazide. Antihypertensive; diuretic.

Definition

ChEBI: Hydroflumethiazide is a benzothiadiazine consisting of a 3,4-dihydro-HH-1,2,4-benzothiadiazine bicyclic system dioxygenated on sulfur and carrying trifluoromethyl and aminosulfonyl groups at positions 6 and 7 respectively. A diuretic with actions and uses similar to those of hydrochlorothiazide. It has a role as a diuretic and an antihypertensive agent. It is a benzothiadiazine and a thiazide.

Manufacturing Process

(a) Preparation of 5-Trifluoromethylaniline-2,4-Disulfonyl Chloride: 113 ml of chlorosulfonic acid was cooled in an ice-bath, and to the acid was added dropwise while stirring 26.6 grams of α,α,α-trifluoro-m-toluidine. 105 grams of sodium chloride was added during 1 to 2 hours, whereafter the temperature of the reaction mixture was raised slowly to 150° to 160°C, which temperature was maintained for 3 hours. After cooling the mixture, ice-cooled water was added, whereby 5-trifluoromethylaniline-2,4-disulfonyl chloride separated out from the mixture.
(b) Preparation of 5-Trifluoromethyl-2,4-Disulfamylaniline: The 5- trifluoromethylaniline-2,4-disulfonyl chloride obtained in step (a) was taken up in ether and the ether solution dried with magnesium sulfate. The ether was removed from the solution by distillation, the residue was cooled to 0°C and 60 ml of ice-cooled, concentrated ammonia water was added while stirring. The solution was then heated for one hour on a steam bath and evaporated in vacuo to crystallization. The crystallized product was 5-trifluoromethyl-2,4- disulfamylaniline, which was filtered off, washed with water and dried in a vacuum exsiccator over phosphorus pentoxide. After recrystallization from a mixture of 30% ethanol and 70% water the compound had a MP of 247° to 248°C.
(e) Preparation of 6-Trifluoromethyl-7-Sulfamyl-3,4-Dihydro-1,2,4- Benzothiadiazine-1,1-Dioxide: 3.2 grams of 5-trifluoromethyl-2,4- disulfamylaniline was added to a solution of 0.33 gram of paraformaldehyde in 25 ml of methyl Cellosolve (2-methoxy ethanol) together with a catalytic amount of p-toluenesulfonic acid, and the mixture was boiled with reflux for 5 hours. The solvent was then distilled off in vacuo, and the residue triturated with 30 ml of ethyl acetate. 6-trifluoromethyl-7-sulfamyl-3,4-dihydro-1,2,4- benzothiadiazine-1,1-dioxide crystallized out. After recrystallization from methanol/water the substance had a MP of 272° to 273°C.

Therapeutic Function

Diuretic, Antihypertensive

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