Patent GB-742287-A (GB)
Title: Pyrrolidines
IPC: C07D295/084
Filed: 1953-11-11
Abstract: The invention comprises a pyrrolidine of the general formula <FORM:0742287/IV(a)/1> wherein R represents hydrogen or an alkyl radical containing from 1 to 8 carbon atoms, or an acid addition or quaternary salt thereof, and the preparation thereof by hydrogenating with hydrogen under pressure and in the presence of a hydrogenation catalyst a solution of a pyrrolidine of the general formula <FORM:0742287/IV(a)/2> or an acid addition salt thereof, R having the above significance and R1 representing hydrogen or the benzyl radical. Suitable reaction solvents are water and ethanol.  The hydrogenation may be effected at a pressure from about 30 to 80 pounds, a suitable reaction temperature being between about 20 DEG and 70 DEG  C.  Hydrogenation catalysts referred to are palladium charcoal, platinum and platinum oxide.  The acid addition salts may be derived from mineral, aliphatic and aromatic acids such as hydrochloric, hydrobromic, sulphuric, acetic, lactic, tartaric, succinic and benzoic acids, and strongly acidic phenols such as picric acid and the quaternary salts may be derived from alkyl and aralkyl halides and alkyl esters of aryl-sulphonic acids such as methyl bromide and iodide, cetyl bromide, myristyl iodide, lauryl bromide, benzyl chloride, allyl bromide and ethyl (p-toluene-sulphonate).  When an acid addition salt is prepared by the above process, the free base can be obtained by the addition of an alkali such as ammonium carbonate or hydroxide, sodium bicarbonate or hydroxide or potassium bicarbonate.  In the examples the following compounds are prepared: N-[b -hydroxy - b  - (3,4 - dihydroxyphenyl) - ethyl]-pyrrolidine and the hydrochloride, methiodide, methobromide, ethochloride and benzylchloride salts thereof, N-[a -methyl-b -hydroxy-b -(3,4-dihydroxyphenyl) -ethyl]-pyrrolidine and the hydrochloride, methiodide, methochloride, ethochloride and benzylchloride salts thereof, and N - [a  - ethyl - b  - hydroxy - b - (3,4 - dihydroxyphenyl)-ethyl]-pyrollidine and the hydrochloride thereof.  The Specification refers to a number of additional compounds as follows: the sulphate and benzoate salts of N-[b -hydroxy-b -(3,4 - dihydroxyphenyl) - ethyl] - pyrrolidine and the corresponding a -methyl compound, and compounds of the above general formula in which R represents the propyl radical (and the hydrochloride salt thereof) and the butyl, pentyl, hexyl, heptyl and octyl radicals.  Substituted pyrrolidines of the general formula <FORM:0742287/IV(a)/3> wherein R represents hydrogen or an alkyl radical containing 1 to 8 carbon atoms and R1 represents hydrogen or the benzyl radical, are prepared by reacting a solution of an a -halo-di-3,4 - dihydroxyacetophenone or an a  - halo-di - 3,4 - dibenzyloxyacetophenone with pyrrolidine.  The substituted pyrollidine can be converted into an acid addition salt, e.g. with hydrogen chloride or sulphuric acid.  Suitable reactants referred to are a -chloro- and a -bromo-3,4 - dihydroxyacetophenone, a  - chloro - 3,4-dihydroxypropiophenone and a  - bromo - 3,4-dibenzyloxypropiophenone.  The following compounds are prepared N - [b  - keto - b  - (3,4 - dihydroxyphenyl) - ethyl] - pyrrolidine and the hydrochloride, sulphate and benzoate salts thereof, and N - [b  - keto - b  - (3,4 - dibenzyloxyphenyl) - ethyl] - pyrrolidine and the corresponding a -methyl- and a -ethyl-substituted compounds and the hydrochloride salts thereof.  The following compounds are also referred to: N - [a  - methyl - b  - keto - b  - (3,4-dihydroxyphenyl) - ethyl] - pyrrolidine sulphate, N - [a  - ethyl - b  - keto - b  - (3,4 - dihydroxyphenyl) - ethyl - pyrrolidine and the corresponding a -propyl compound and the hydrochloride salts thereof, and N-[a -propyl-b  - keto - b  - (3,4 - dibenzyloxyphenyl) - ethyl]-pyrrolidine and the corresponding a -butyl compound and the hydrochloride salts thereof.