Patent GB-627139-A (GB)
Title: Improvements in and relating to the preparation of quaternary ammonium salts of substituted propanolamines, allylamines and propylamines
IPC: C07D211/08
Filed: 1947-05-28
Abstract: N - Trisubstituted - g ,g  - disubstituted - g -hydroxypropylammonium salts, allylammonium salts and propylammonium salts of the formul : <FORM:0627139/IV (b)/1> (where R1 and R2 are aryl, aralkyl or cycloalkyl, and may be substituted by alkyl or alkoxy groups; R3 and R4 are hydrogen or alkyl; R5 is hydrogen, alkyl, aryl or aralkyl; R6 and R7 are alkyl, alkenyl, cycloalkyl, aryl or aralkyl or -NR6R7 may be pyrrolidino-, morpholino-, or piperidino-; R8 is alkyl or aralkyl; R9 and R10 are alkyl, cycloalkyl, aryl, or aralkyl, or -NR9R10 is pyrrolidino, morpholino-, or piperidino-; and X is an acid radical such as chloride, bromide, iodide or methosulphate) are prepared by treating the corresponding tertiary-amines with a halide or salt R8X. It is preferred to use an excess of the compound R8X.  The reaction may be performed in a solvent, e.g. acetone, alcohol, or dioxan at room temperature, at the boiling point of the solvent, or at an intermediate temperature.  It is preferred either to use a solvent such that the quaternary salt crystallises out on cooling the reaction mixture, or to add a liquid, e.g. ether, in which the reaction product is insoluble until crystallisation takes place. Examples are given of the preparation of N-methyl - 3 - hydroxy - 3,3 - diphenylpropyl piperidinium iodide; N-methyl-3,3-diphenylprop-2-enyl piperidinium iodide; N-methyl3,3-diphenylpropyl piperidinium iodide; N-dimethyl - N - ethyl - 3 - hydroxy - 3,3 - diphenylpropyl ammonium iodide; N-dimethyl-N-propyl (or butyl)-3-hydroxy-3,3-diphenyl propyl ammonium bromide; N-dimethyl-N-benzyl - 3 - hydroxy - 3,3 - diphenylpropyl ammonium chloride; N-trimethyl-3,3-diphenylprop - 2 - enyl ammonium iodide; N - trimethyl - 3,3 - diphenylpropyl ammonium iodide; N-methyl-N-diethyl-3-hydroxy-3,3-diphenylpropyl ammonium iodide; N-methyl N - diethyl (or diallyl)-3,3-diphenylprop-2-enyl ammonium iodide; N-methyl-N-diethyl-3,3-diphenylpropyl ammonium iodide; N-methyl-N - dipropyl (or diallyl)-3,3-diphenyl-3-hydroxypropyl ammonium iodide; N-dimethyl-N-phenyl - 3,3 - diphenyl - 3 - hydroxypropyl ammonium iodide; the methiodide of 3-N-methyl - N - 21 - phenyl - 11 - methylethylamino-1,1 - diphenylpropan - 1 - ol; N - methyl-3,3 - diphenyl - 3 - hydroxypropyl pyrrolidinium iodide; methiodide of N-morpholino 1,1 - diphenylpropan - 1 - ol; methiodide of 3 - dimethylamino - 1,1 - diphenylbutan - 1-ol; methiodide of 3-dimethylamino-1,1-diphenylbutan - 1 - ol; methiodide of 3 - dimethylamino - 1,1 - diphenylbut - 1 - ene; methiodide of 3 - dimethylamino - 1,1 - diphenylbutane; methiodide of 3-diethylamino-1,1 - di - p - tolylpropan - 1 - ol; N - methyl-N - diethyl - 3,3 - di - p - tolylprop - 2 - enyl ammonium iodide; methiodide of 3-diethylamino - 1,1 - di - p - tolylpropane; methiodide of 4 - diethylamino - 1,2 - diphenylbutan - 2-ol; and N - methyl - N - diethyl - 3 - cyclohexyl - 3 - phenyl - 3 - hydroxypropyl ammonium iodide.  The N- disubstituted - g ,g  - disubstituted - g  - hydroxypropylamines are prepared by treating either a b -tertiary-aminopropionic ester or a b -tertiary-aminoethyl aryl ketone with a Grignard reagent, followed by hydrolysis.  The corresponding allylamines are then prepared by dehydration of the hydroxy compound, and the propylamines by reduction of the allylamines.