Preparation of Antidotes for Anticholinesterase Poisoning Iii. Esters of 1-Arylcycloalkanecarboxylic Acids

Abstract

In preceding papers of this series (1, 2) the preparation of several analogues of 5'-diethylaminoethyl 1-phenylcyclopentanecarboxylate hydrochloride (Parpanit) and certain of their quaternary salts was described. These coinpounds were required for evaluation of their efficacy as substitutes for, or adjuncts to, atropine in the treatment of sari11 poisoning (3-5). T h e preparation of fifteen additional analogues of Parpailit and four N-methyl-4'-piperidyl 1-arylcycloall~anecarboxylate hydrochlorides required for extensioil of these studies is reported herein. The compounds prepared and their properties are listed in Tables I to VI, and representative preparations are described in the Experimental section.The majority of the Parpanit analogues (Table IV) was prepared by the interaction of potassiuin 1-phenylcyclopentanecarboxylate \\-it11 the appropriate diall;ylai~~inoalkyl chloride, followed by treatment with dry hydrogen chloride netho hod F) in ethanol ( 1 , 6 , 7 ) .This was the most useful synthetic method when the requisite internlediate dialliylaminoalliyl chloride hydrochloride could be readily prepared, or ~vhen prepared, could be brought into reaction. 3'-Diethylaminopropyl 1-phenylcyclopentanecarboxylate hydrochloride, for example, was obtained in 62y0 yield from 3-diethylaminopropyl chloride and potassium 1-phenylcyclopentanecarboxylate, whereas the interaction of 3'-cl~loropropyl 1-phenylcyclopentanecarboxylate with diethylamine according to the general method of Weston (8) furnished only a 30% yield (nlethod 13).The potassiuin salt method proved impractical for the synthesis of 3'-quinuclidinyI 1-phenylcyclopentanecarboxylate hydrochloride. 3-Quinuclidinyl chloride hydrochloride is readily prepared by the action of thionyl chloride upon 3-quinuclidinol (9). 3-Quinuclidinyl chloride (lo), however, could not be induced to react with potassium 1-phenj lcyclopentanecarboxylate, presuinably because the rigidity of the ring system prevents the SKI reaction by inhibiting carbonium ion formation and also shields the 3-position fro111 SN2 attack. This compound was therefore prepared by interaction of l-phenylcyclopentanecarbonyl chloride and 3-quinuclidinol in anhydrous benzene (cf. refs. 1, 8 , 11-13; method I<), or by transesterification of methyl 1-phenylcyclopentanecarboxylate with 3-quinuclidinol in toluene using a catalytic amount of sodium, followed by treatment with dry hydrogen chloride (cf. refs. 13, 14, 16; method J ) . Transesterification of 3-quinuclidinol with ethyl 1-phenylcyclopentanecarboxylate (17) was unsuccessf~~l. 2'-t-ButylmethyIaminoethyl 1-phenylcyclopentanecarboxylate hydrochloride was prepared by the interaction of 2'-t-butylaminoethyl 1-phenylcyclopentanecarboxylate with ethyl iodide in benzene, folIo\ved by ion exchange (method G).T h e N-methyl-4-piperidyl hydrochloride esters of 1-phei~ylc~~clopentanecarboxylic, 1-phenylcyclobutanecarboxylic, 1-p-n~ethylphen~~lcyclobutanecarboxylic, and l-p-methoxyphen~~lcyclobutanecarboxylic acids were prepared by treatment of the appropriate...

Hydrophilic Quaternary Ammonium Type Ionic Liquids. Systematic Study of the Relationship among Molecular Structures, Osmotic Pressures, and Water-Solubility

“…However, they instantly absorbed H 2 O after exposure to air to change to transparent liquids like RTILs. The DSC or TG/DTA results of these bromides show their melting points and decomposition points all corresponding to the reported values (90–300 °C). ,, The melting points of 1 , 2 , 5 , and 9 are below 100 °C but higher than room temprature. They are classified in ILs but not in RTILs .…”

Plasma membrane permeabilisation by ionic liquids: a matter of charge

“…Spectral data for 1 H and 13 C NMR were identical to the previously reported ones. [36][37][38][39][40][41] For all tested ionic liquids, the 1-octanol/water distribution coefficients (log D) of isolated cations (for 1-alkyl-3-methylimidazolium chlorides and alkyl-(2hydroxyethyl)-dimethylammonium bromides) or anions (for cholinium alkanoates) were calculated using Chemicalize.org software (http://www.chemicalize.org) by using ChemAxon.…”

Preparation and characterization of some unsymmetrical 2-(dialkylamino)ethanethiols

“…Most of the 2-(dialkylamino)ethyl chlorides have been already described 17,18 , only for the derivatives 2b and 2d has there not been found any reference. These chlorides have been prepared by the treatment of the corresponding alcohols 1b 22 and 1d 19 with thionyl chloride in chloroform.…”