58-94-6

Crystals; white powder.

Alkaline aqueous solutions will decompose on standing or heating .

Insoluble in water.

Flash point data for this chemical are not available; however, CHLOROTHIAZIDE is probably combustible.

Chlorothiazide is a first-in-class thiazide diuretic initially discovered from its ability to inhibit carbonic anhydrase in vitro. As an antihypertensive agent, this thiazide increases renal excretion of sodium, potassium, chloride, and bicarbonate ions by inhibiting tubular reabsorptive mechanisms.

Off-White Solid

Diuril,Merck Sharp and,US,1957

Chlorthiazide is a diuretic that causes the body to excrete excess fluid. This drug exhibits strong diuretic action during both acidosis and alkalosis. It is used for arterial hypertension, in edematous syndromes of various genesis, congestive effects in cardiovascular insufficiency, nephrosis and nephritis, and toxicosis. It is especially recommended for hypertonic illnesses. It lowers intraocular pressure in a number of cases.

ChEBI: 4H-1,2,4-benzothiadiazine 1,1-dioxide in which the hydrogen at position is substituted by chlorine and that at position 7 is substituted by a sulfonamide group. A diuretic, it is used for treatment of oedema and hypertension.

(A) m-Chloroaniline (64 g, 0.5 mol) was added dropwise with stirring to 375 ml of chlorosulfonic acid in a 3-liter round bottom, 3-necked flask cooled in an ice bath. Sodium chloride (350 g) was added portionwise over a period of 1 to2 hours and the mixture then heated gradually in an oil bath to 150°C. After 3 hours at 150° to 160°C, the flask was cooled thoroughly in an ice bath and the contents treated with a liter of cold water. The product was extracted with ether and the extract washed with water and dried over sodium sulfate.
After removal of ether on the steam bath, the residual 5-chloroaniline-2,4- disulfonyl chloride, which may be crystallized from benzene-hexane MP 130° to 132°C, was cooled in an ice bath and treated with 150 ml of 28% ammonium hydroxide in a 2-liter Erlenmeyer flask. The mixture was heated on the steam bath for 1 hour, cooled and the product collected on the filter, washed with water and dried. Upon crystallization from dilute alcohol 5- chloro-2,4-disulfamylaniline was obtained as colorless needles, MP 251° to 252°C.
(B) A solution of 88 g of 5-chloro-2,4-disulfamylaniline in 1.1 liters of 88% formic acid was heated under reflux for 2 hours. After removal of 200 ml of solvent by distillation, one liter of water was added and the product collected, washed with water and dried. Crystallization from dilute alcohol afforded 6- chloro-7-sulfamyl-1,2,4-benzothiadiazine-1,1-dioxide as colorless needles, MP 342.5° to 343°C, as described in US Patent 2,809,194.

Diuril (Ovation).

The diuretic action of chlorothiazide, like other drugs of this series, is caused by reduced absorption of sodium and chloride ions by the kidneys during their simultaneous, intense excretion from the organism.

Chlorothiazide, 1,1-dioxide 6-chloro-2H-1,2,4-benzothiadiazin-7-sulfonamide (21.3.3) is synthesized in the exact same manner, is all thiazide diuretics. 3- Chloroaniline (or 3-trifluoromethylaniline) undergoes sulfoylchlorination by chlorosulfonic acid, forming 4,6-sulfonochloride-3-chloroaniline (21.3.1), the reaction of which with ammonia gives 4,6-sulfonylamido-3-chloroaniline (21.3.2). Heating this with formamide leads to formation of chlorothiazide (21.3.3).

In veterinary medicine, furosemide has largely supplanted the use of thiazides as a general diuretic (edema treatment). Thiazides are still used for the treatment of systemic hypertension, nephrogenic diabetes insipidus, and to help prevent the recurrence of calcium oxalate uroliths in dogs.
Chlorothiazide is approved for use in dairy cattle for the treatment of post parturient udder edema, but the veterinary labeled product has been discontinued in the USA.