Patent GB-858903-A (GB)
Title: Tertiary-amino substituted amides
IPC: C07C233/12
Filed: 1957-05-06
Abstract: The invention comprises amides of the general formula: <FORM:0858903/IV(b)/1> wherein n represents an integer from 2 to 6 inclusive, - CnH2n-represents an alkylene radical having at least two carbon atoms between the valencies, R1 and R2 each represent an alkyl radical having not more than 8 carbon atoms or when taken together with the nitrogen atom represent a pyrrolidino or an alkyl-substituted pyrrolidino radical, R3 and R4 each represent an alkyl radical having not more than 8 carbon atoms or when taken together with the nitrogen atom represent an alkyl substituted pyrrolidino radical and in which the phenyl nucleii may be optionally substituted by unreactive substituents such as alkyl or alkoxy radicals each having not more than 8 carbon atoms or halogen, or an acid addition or quaternary ammonium salt thereof, or an amine oxide derivative thereof or an acid addition salt of said amine oxide, and the preparation of the above amides by reacting a tertiary amine of the formula <FORM:0858903/IV(b)/2> wherein R1 and R2 have the above significance with a compound of the general formula: <FORM:0858903/IV(b)/3> wherein R7 represents hydrogen, and reacting the resulting compound in the presence of an alkali metal amide with the compound of the general formula: <FORM:0858903/IV(b)/4> wherein R8 represents a halogen and n, R3 and R4 have the above significance, and by reacting a tertiary amine having the general formula: <FORM:0858903/IV(b)/5> wherein R1 and R2 have the above significance with an acid chloride of the general formula:  <FORM:0858903/IV(b)/6> wherein n, R3 and R4 have the above significance.  The acid addition salts such as those derived from hydrochloric, hydrobromic, sulphuric, phosphoric, lactic, citric, tartaric, benzoic, salicylic, succinic and acetic acids, and the quaternary salts such as those derived from methyl bromide, are prepared by the usual methods.  The amine oxides are prepared by treating the amides of the above general formula with hydrogen peroxide.  The alkyl substituted pyrrolidino radical may be a 2, 2-dimethyl-, 2-methyl, or a 2, 2, 4-trimethylpyrrolidino radical.  In the examples the following compounds are prepared: 5-diethylaminoN, N-dimethyl-2, 2-diphenyl-valeramide, 1-(4-diethylamino-2, 2-diphenylbutyryl)-pyrrolidine and -2-methylpyrrolidine, 4-diethylamino-N, N-dimethyl (and disopropyl)-2, 2-diphenylbutyramide, N, N-diisopropyl-2, 2, 4-trimethyl-a , a -diphenyl-1-pyrrolidinebutyramide, 4-dimethylamino (and diisopropylamino)-N, N-dimethyl-2, 2-diphenyl-butyramide, N, N, 2, 2, 4-pentamethyl-a , a -diphenyl-1-pyrrolidine-butyramide, 1-[2, 2-diphenyl-4-(2, 2-dimethylpyrrolidino) butyryl]-pyrrolidine and 2-methyl-1-[2, 2-diphenyl-4-(2, 2-dimethylpyrrolidino)-butyryl] pyrrolidine and the hydrochlorides and methobromides of all these compounds, and N, N, 2, 2-tetramethyl-a , a -diphenyl-1-pyrrolidine-butyramide and the hydrochloride and methobromide thereof and the N-oxide and N-oxide hydrobromide thereof.  Amides of the general formula:  <FORM:0858903/IV(b)/7> wherein the phenyl radicals and R1 and R2 have the above significance, are prepared by reacting the required carboxylic acid chloride and tertiary amine.  In the examples 1-diphenylacetylpyrrolidine, N, N-diisopropyl-a , a -diphenylacetamide and 1-diphenylacetyl-2-methyl-pyrrolidine are prepared.  5-Diethylamino-2, 2-diphenyl-valeric acid sulphate is prepared by treating 5-diethylamino -2, 2-diphenylvaleronitrile with concentrated sulphuric acid.  Other acid sulphates of carboxylic acids corresponding to the acid chlorides of the above general formula may be prepared by a similar method.  5-Diethylamino-2, 2-diphenylvaleryl chloride is prepared by treating the above acid with thionyl chloride.  Other acid chlorides of the above general formula may be prepared by similar methods.  1-(2-Chloroethyl)-2, 2, 4-trimethylpyrrolidine hydrochloride is prepared by treating 2, 2, 4-trimethyl-1-pyrrolidine-ethanol with gaseous hydrogen chloride using benzene as the reaction solvent. Specification 790,102 is referred to.