BENDROFLUMETHIAZIDE Chemical Properties
- Melting point:
- Boiling point:
- 602.1±65.0 °C(Predicted)
- 1.4711 (estimate)
- storage temp.
- Practically insoluble in water, freely soluble in acetone, soluble in ethanol (96 per cent).
- pKa 8.53±0.05(H2O t=25 I=0.2) (Uncertain)
- Crystals from MeOH/CHCl3
- Water Solubility
- 40mg/L(room temperature)
- EPA Substance Registry System
- 2H-1,2,4-Benzothiadiazine-7-sulfonamide, 3,4-dihydro-3-(phenylmethyl)-6-(trifluoromethyl)-, 1,1-dioxide (73-48-3)
BENDROFLUMETHIAZIDE Usage And Synthesis
Bendroflumethiazide may be used for the same indications as the aforementioned drugs; however, it is primarily used as an adjuvant agent for relieving edema associated with cardiac insufficiency, liver cirrhosis, and edema caused by taking corticosteroids.
ChEBI: A sulfonamide consisting of 7-sulfamoyl-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide in which the hydrogen at position 6 is substituted by a trifluoromethyl group and that at position 3 is substituted by a benzyl group.
The process is described in US Patent 3,392,168 as follows:
(A) Preparation of 5-Trifluoromethylaniline-2,4-Disulfonylchloride - 113 ml of chlorosulfonic acid is cooled in an ice bath, and to the acid is added dropwise while stirring 26.6 grams of α,α,α-trifluoro-m-toluidine. 105 grams of sodium chloride is added during 1-2 hours, where after the temperature of the reaction mixture is raised slowly to 150° - 160°C which temperature is maintained for three hours. After cooling the mixture, ice-cooled water is added, whereby 5-trifluoromethylaniline-2,4-disulfonyl chloride separates out from the mixture.
(B) Preparation of 5-Trifluoromethyl-2,4-Disulfamylaniline - The 5- trifluoromethylaniline-2,4-disulfonyl chloride obtained in step (A) is taken up in ether and the ether solution dried with magnesium sulfate. The ether is removed from the solution by distillation, the residue is cooled to 0°, and 60 ml of ice-cooled, concentrated ammonia water is added while stirring. The solution is then heated for one hour on a steam bath and evaporated in vacuo to crystallization. The crystallized product is 5-trifluoromethyl-2,4- disulfamylaniline, which is filtered off, washed with water and dried in a vacuum-desiccator over phosphorus pentoxide. After recrystallization from a mixture of 30% ethanol and 70% water, the compound has a MP of 247°- 248°C.
(C) Preparation of 3-Benzyl-6-Trifluoromethyl-7-Sulfarnyl-3,4-Dihydro-1,2,4- Benzothiadiazine-1,1-Dioxide - 6.4 grams of 5-trifluoromethyl-2,4- disulfamylaniline is dissolved in 12 ml of dioxane, 2.7 ml of phenylacetaldehyde and a catalytic amount of p-toluenesulfonic acid are added. After boiling for a short time under reflux, the reaction mixture crystallizes, and, after filtration and recrystallization from dioxane, the desired product is obtained with a MP of 224.5°-225.5°C.
(D) Alternative to (C) - 9.6 grams of 5-trifluoromethyl-2,4-disulfarnylaniline and 4.9 grams of ω-ethoxystyrene are dissolved in 35 ml of n-butanol. 0.5 grams of p-toluenesulfonic acid is added, and the mixture is heated on a steam bath while stirring. When the solution is clear, 55 ml of hexane is added, whereafter the mixture is heated further for one and a half hours. After cooling, the substance identical to that of Example (C) is filtered off and has a MP of 222°-223°C.
Sterile compositions containing Bendroflumethiazide for parenteral administration may be prepared as described in US Patent 3,265,573.
Poison by intravenous route.Human systemic effects by ingestion: convulsions andsomnolence. Mutation data reported. When heated todecomposition it emits toxic fumes of F-, SOx, and NOx.
Bendroflumethiazide, 1,1-dioxide 3-benzyl-6-(trifluoromethyl)- 3,4-dihydro-2H-1,2,4-benzothiadiazin-7-sulfonamide (21.3.6), is synthesized by the same scheme of making the aforementioned drugs using phenylacetaldehyde or its acetale as a carbonyl component, and using 2,4-disulfonamido-5-trifluoromethylaniline (21.3.5) as an o-aminosulfonamide component.
- BENDROFLUMETHIAZIDE IMPURITY A
- BENDROFLUMETHIAZIDE IMP. A (EP): 4-AMINO-6-(TRIFLUOROMETHYL)BENZENE-1,3-DISULPHONAMIDE
- BENDROFLUMETHIAZIDE USP(CRM STANDARD)
- BENDROFLUMETHIAZIDE EPB(CRM STANDARD)
- Benzenesulfonamide, 2-(methylamino)- (9CI)
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