Phenoxybenzamine hydrochloride

Chemical Name N-(2-chloroethyl)-N-(1-methyl-2-phenoxyethyl)benzenemethanamine hydrochloride 

Trade Name Manufacturer Country Year Introduced 

Step 1 In a 500 ml flask equipped with gas inlet tube, dropping funnel and reflux condenser is placed 139 grams of 1-phenoxy-2-propanol. A stream of dry air is bubbled through the alcohol while 55 grams of thionyl chloride is added dropwise with external cooling. 

The stream of dry air is continued for about six hours or until most of the hydrogen chloride has been expelled and then another 55 grams of thionyl chloride is added. The reaction mixture is allowed to stand twenty-four hours, a few drops of pyridine are added and the mixture heated 4 hours on the steam bath. The cooled reaction mixture is poured into water, the crude product is washed with dilute sodium bicarbonate solution and finally taken up in benzene. The benzene is distilled at ordinary pressure and the residue distilled in vacuo to yield 60-70% of Tphenoxy-2-chloropropane, BP 93°-94°C/5 mm. 

Step 2 To 494 grams of ethanolamine, heated to approximately 150°C in a 500 ml flask equipped with stirrer, condenser and dropping funnel, is added 465 grams of 1-phenoxy-2-chloropropane with mechanical stirring. The reaction mixture is then heated to reflux for 3 hours, cooled and poured into a liter of water. The organic layer is extracted into ether and the ether solution is extracted with dilute hydrochloric acid. The aqueous acid solution is then made alkaline with 40% sodium hydroxide solution and the organic base is extracted into ether. Removal of the ether leaves N-(phenoxyisopropyl)-ethanolamine which, after recrystallization from hexane, melts at 70.5°-72°C. 

Step 3 To 43 grams of N-(phenoxyisopropyl)ethanolamine dissolved in 500 ml of alcohol in a 1,000 ml flask equipped with stirrer and condenser is added 28 grams of benzyl chloride and 18.5 grams of sodium bicarbonate. The mixture is stirred and refluxed for 10 hours and then approximately half the alcohol is removed by distillation. The remaining solution is poured into 500 ml of water and the organic material extracted with 3 100-ml portions of ether. The combined ether extracts are washed with water, dried over anhydrous potassium carbonate and filtered. After removal of the ether, the residue is distilled in vacuo to yield N-(phenoxyisopropyl)-N-benzylethanolamine, BP 163°-168°C/0.2 mm. 

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Phenoxyacetic acid herbicides (see Chlorophenoxy herbicides) Phenoxybenzamine hydrochloride... 

Soluble 1 in 25 of water, 1 in 9 of ethanol, and 1 in 9 of chloroform practically insoluble in ether. Neutral and alkaline solutions are unstable. Caution. Phenoxybenzamine hydrochloride in powder form should not be allowed to come into contact with eyes or skin, as it may cause irritation. 

Infra-red Spectrum. Principal peaks at wavenumbers 1240, 750, 698, 1494, 1598, 1586 (phenoxybenzamine hydrochloride, KBr disk). 

Dose. 10 to 60 mg of phenoxybenzamine hydrochloride daily up to 200 mg daily has been given. 

Phenoxyacetamidopenicillanic acid, 887 Phenoxybenzamine, 887 Phenoxybenzamine hydrochloride, 887 Phenoxybutyramidopenicillanic acid, 935 Phenoxyethylpenicillin, 877 Phenoxyisopropylnorsuprifen, 693 Phenoxymethylpenicillin, 887 Phenoxymethylpenicillin calcium, 888 Phenoxymethylpenicillin potassium, 888 Phenoxyphenylpropionic acid, 615 Phenoxypropazine, xvii Phenoxypropionamidopenicillanic acid, 877 Phenoxypropylpenicillin, 935 Phenprobamate, 888 Phenprocoumon, 889 Phenpropamine, 332... 

It is a potent alpha-adrenoceptor (ai and 02) blocking agent with a prolonged duration of action. Phenoxybenzamine hydrochloride has been employed intravenously in the treatment of shock. It also finds its application in the treatment ofpulmonary oedema. 

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