Potassium 2,5-dichlorobenzoate

Diuretics are drugs that increase the excretion of urine by the kidney, thereby decreasing body fluids. This alleviates the swelling of tissues that sometimes cause high blood pressure and heart, kidney, and liver failure. Furosemide is the most effective diuretic. It inhibits the readsorption of sodium in the kidney and promotes potassium excretion, two ions intimately involved in water retention for the body. It lowers blood pressure as well. The starting material for its synthesis is 2,4-dichlorobenzoic acid (formed by... 

Quinacrine Quinacrine, 6-chloro-9-(4-diethylamino-l-methylbntylamino)-2-methoxy-acridine (37.1.4.3), is synthesized from 6,9-dichloro-2-methoxyacridine (37.1.4.2) and aforementioned 4-diethylamino-l-methylbutylamine (37.1.1.2). The 6,9-dichloro-2-methoxyacridine (37.1.4.2) necessary for the synthesis is made in two stages. The initial reaction of 2,4-dichlorobenzoic acid and p-anizidine in the presence of copper dnst and potassium carbonate gives 2-(4-methoxyanilino)-4-chlorobenzoic acid (37.1.4.1), which upon reaction with phosphorus oxychloride turns into the necessary 6,9-dichloro-2-methoxyacridine (37.1.4.2) [33-38]. 

To a flask containing 45 ml (0.77 mole) of absolute ethanol is added portion-wise 2.5 gm (0.11 gm-atom) of sodium metal. While stirring vigorously and cooling, 9.55 gm (0.05 mole) of 2,2-dichlorobenzo-l,3-dioxolane in 25 ml of ether is added dropwise. After 18 hr the salt is filtered off, the filtrate diluted with ether, washed with cold water, dried over potassium carbonate, and fractionally distilled to afford 6.4 gm (60%), b.p. 123°C (15 mm), 1.4943. 

Tropine (34.24 g) is treated with anhydrous diethyl ether and ethereal hydrogen chloride and the precipitated hydrochloride is isolated by evaporation of the solvent. 3,5-Dichlorobenzoylchloride (51.7 g) is added and the mixture stirred at 140°C for 15 minutes during which time the mixture liquifies, evolves hydrogen chloride gas and resolidifies. After heating for a further 15 minutes the cooled solid is dissolved in water, an excess of an aqueous solution of potassium carbonate is added, and the base is extracted with ethyl acetate. Evaporation of the dried ethyl acetate solution yields a solid, which is recrystallized from aqueous methanol to yield 3,5-dichlorobenzoic acid 8-methyl-8-aza-bicyclo[3.2.1]oct-l-yl ester (endo). MP 95°C (51.8 g). 

Dobson et al. (48JCS123) constructed this ring system by using the Ullmann-amine coupling reaction between 7-aminoquinoline 1 and potassium 2,4-dichlorobenzoate, followed by cyclization of the resultant diaryl-... 

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