Adrenergic Blocking Agents. IV. β-Haloethylammonium Compounds¹

Abstract

@-HALOETHYLAMMONIUM COMPOUNDS AS ADRENERGIC BLOCKING AGENTS 5681resulting precipitate recrystallized from ethyl acetate-ethanol, giving 0.23 g. of the hydrochloride (60.5%), m.p. 184'. Reaction with Dry Acetic Acid-Sodium Acetate to Give dl-cis-2-Aminocyclohexanol.-The resulting solution by refluxing 5 g. of glacial acetic acid, 1 g. of acetic anhydride and 1 g. of fused sodium acetate was added to 2 g. of "Product A" ptoluenesulfonate and the mixture refluxed for four hours with exclusion of moisture. After cooling, the reaction mixture was poured into water, causing the separation of an oily product which could not successfully be crystallized. After extracting with ether, washing with water, 5% sodium carbonate solution and water and evaporating to dryness, the oily residue was added to 20 ml. of lO%hydrochloric acid and refluxed for two hours. After cooling, separated benzoic acid was filtered off and the filtrate was evaporated to dryness on a steam-bath. The solid residue so obtained weighed 0.7 g. (90.9%) and was recrystallized from ethyl acetate-ethanol, giving 0.55 g. (71.4%) of colorless crystals, m.p. 184-185'.A mixed m.p. with dl-cis-2aminocyclohexanol hydrochloride showed no depression.Reaction with Acetic Anhydride to Give dl-cis-2-Amino-cyclohexano1.-A mixture of 2 g. of "Product A" p-toluenesulfonate and 4 g. of acetic anhydride was refluxed. After cooling, and pouring of the reaction mixture into water the resulting oily product was extracted with ether and treated as previously described with dry AcOH-AcONa, giving 0.5 g. (65%) of dkk-2aminocyclohexanol hydrochloride.N-Ethylation of the 2-Aminocyclohexanols. dl-trans-2-Ethylaminocyclohexano1.-A mixture of 7.0 g. (1.3 mols) of ethyl bromide, 2.1 g. (1 mol) of sodium carbonate, 50 ml. of ethanol and 6 g. (1 mol) of dl-trans-2-aminocyclohexanol was refluxed on a steam-bath and after cooling the insoluble solid separated. The filtrate was concentrated to dryness, a small amount of water added and made alkaline with concd. sodium hydroxide. The resulting oil layer was extracted with ether, dried over fused sodium sulfate and distilled under reduced pressure: b.p. 104-105' (12 mm.) weight 5.5 g. (73%). Its hydrochloride melted at 156". which was identified with a sample obtained from ethylamine and cyclohexene oxide.6Anal. Calcd. for C8H170N.HCI: N, 7.82. Found: N, 7.62. dl-trans-2-Diethylaminocyclohexanol (a).-A mixture of 5 g. of ethyl bromide, 4 g. of potassium carbonate, 50 ml. of ethanol and 5 g. of dl-trans-2-ethylaminocyclohexanol was refluxed on a steam-bath for five hours and after cooling the precipitate filtered off. The filtrate was made alkaline with concd. sodium hydroxide and the resulting oil layer was extracted with ether, dried over fused sodium sulfate, evaporated to dryness and distilled under reduced pressure; the yieldwas4g.(67%), b.p. 11l0(15mm.), hydroch1oridem.p. 173'. A mixed melting point with the diethyl compound obtained from cyclohexene oxide and diethylamine did not depress.(b).-To one gram (1 mol) of dl-trans-2-amino...

Preparation of Antidotes for Anticholinesterase Poisoning: Ii. Tertiary and Quaternary Salts of Parpanit and Parpanit Analogues

“…Although the first of these is conlmonly used to prepare methiodides as derivatives for characterization of amines (11), the second has recently been used with increasing frequency for synthesis of alkyl, benzyl, and substituted benzyl quarternary ammonium salts (3-5, 7, 10, 12-21). Both methods have been conducted a t room temperature (14,16,19), a t the reflux temperature of the halide (21) or solvent (4,5,7,12,(14)(15)(16)(17)(18)20), or in sealed vessels a t elevated temperatures (3,13,16,(18)(19)(20). The solvent which has been used most frequently is benzene (7,12,(16)(17)(18), but ethanol (4, 10, 13, 16), ether (3, 7,14), illethyl ethyl ketone (3,4,20), methanol (13,15), nitromethane (10, 20), acetone (19), and chloroform (22) have also been employed.…”