Patent GB-491951-A (GB)
Title: Medicaments and process for the manufacture thereof
Filed: 1936-12-07
Abstract: Aromatic aminoalcohols of the formula <FORM:0491951/IV/1> wherein R denotes hydrogen or alkyl, are prepared by reacting with an arylmagnesium halide upon an aryl-aminoalkyl-ketone <FORM:0491951/IV/2> X representing aryl, in the molecular proportions of 2 : 1.  The aryl-aminoalkyl-ketones may first be formed from the corresponding aminoacidamides (i.e. wherein X in the above formula is an amino group) by interaction with arylmagnesium halides using the molecular proportions of 1 : 3 and then subjected to the further Grignard treatment.  Preferably, one or both aryl groups contains at least 8 carbon atoms.  The basic products, either as much, or in the form of their salts, e.g. the hydrochlorides or benzoates, are useful as local anaesthetics.  Examples describe the preparation of (1) diphenyl-dimethylaminomethylcarbinol from dimethylamino-acetophenone, magnesium and brombenzene in ethereal solution; (2) the same product as in (1), but in which the starting material is prepared by reacting dimethylaminoacetic acid dimethylamide with magnesium and brombenzene in ether; (3) bis-(2 : 5-dimethylphenyl)-dimethylaminomethylcarbinol from 2 : 5-dimethylphenyl - dimethylaminomethylketone, obtained from dimethylaminoacetic acid dimethylamide and 2-brom-p-xylene by the Grignard reaction, by treatment with magnesium and 2-brom-p-xylene in ethereal solution; (4) phenyl-2 : 5-dimethylphenyl-dimethylaminomethylcarbinol from dimethylaminoacetophenone, magnesium and 2-brom-p-xylene in ether. Reference is also made to the preparation of di-p-tolyl-dimethylaminomethylcarbinol from dimethylaminoacetic acid dimethylamide and p-bromtoluene by the Grignard reaction. The Specification as open to inspection under Sect. 91 also describes the treatment with arylmagnesium halides of starting materials of the above formula in which X represents an oxyalkyl group, i.e. aminoacid esters.  In addition, it includes examples of the preparation of (1) diphenyl-dimethylaminomethylcarbinol from dimethylglycine ester, magnesium and brombenzene; (2) dimethylaminoacetophenone from dimethylamino-diethylacetamide magnesium and brombenzene; (3) dimethylaminomethyl - 1 : 3 - dimethylphenylketone from dimethylamino - dimethylacetamide, magnesium and 1 : 3-dimethyl-4-brombenzene; (4) a  - dimethylaminopropiophenone from a  - dimethylamino - dimethylpropionamide, magnesium and brombenzene; (5) bis-(1 : 4-dimethylphenyl) - dimethylaminomethylcarbinol from ethyl dimethylaminoacetate, magnesium and 2-brom-p-xylene; (6) bis-(1 : 3-dimethylphenyl) - dimethylaminomethylcarbinol from dimethylglycine ester, magnesium and 1 : 3 - dimethyl - 4 - brombenzene; (7) bis - (1 : 2 - dimethylphenyl) - dimethylaminomethylcarbinol from dimethylaminoethyl acetate, magnesium and 1 : 2 - dimethyl - 4-bromxylene; (8) diethylaminoacetophenone from diethylamino - diethylacetamide, magnesium and brombenzene; (9) dimethylaminoacetophenone from dimethylamino-diethylacetamide, magnesium and brombenzene; (10) dimethylaminomethyl - 1 : 3 - dimethylphenylketone from dimethylamino - dimethylacetamide, magnesium and 1 : 3-dimethyl-4-brombenzene; (11) a -dimethylaminopropiophenone from a  - dimethylamino - dimethylpropionamide, magnesium and brombenzene.  The Specification further states that the p  diarylaminoalkyl-carbinols form readily soluble salts with mono- or poly-hydroxy-monocarboxylic acids and describes the combination of bis - (1 : 4 - dimethylphenyl) - dimethylaminomethylcarbinol with lactic acid in ethereal solution, with glycollic acid in aqueous solution, and with quinic acid by melting the components together; also the combination of bis - (1 : 3 - dimethylphenyl) - dimethylaminomethylcarbinol and bis-(p-methylphenyl)-dimethylaminomethylcarbinol with lactic acid. The application of the products is also described in further examples as follows:-(1) a mouthwash obtained by dissolving bis(2 : 4 - dimethylphenyl) - dimethylaminomethylcarbinol hydrochloride in water; (2) a dental tincture containing di-p-tolyl-dimethylaminomethylcarbinol hydrochloride, 90 per cent spirit and tincture myrrhae, to which menthol may be added; (3) a mouthwash tablet prepared by allowing sodium chloride to absorb an alcoholic solution of diphenyldimethylaminomethylcarbinol containing peppermint or eucalyptus oil; (4) an eyewash consisting of an aqueous solution of diphenyldimethylaminomethylcarbinol hydrochloride and sodium chloride; (5) an ointment prepared by working diphenyl-dimethylaminomethylcarbinol into lanolin; (6) a solution of di - p - tolyl - dimethylaminomethylcarbinol in olive oil for treating burns; (7) a basic soap to which di-p-tolyl-dimethylaminomethylcarbinol has been added; (8) an aqueous solution of di-p-tolyl-dimethylaminomethylcarbinol hydrochloride for sterilizing surgical instruments; (9) a solution of adrenaline to which bis - (2 : 3 - dimethylphenyl) - dimethylaminomethylcarbinol has been added, useful as a local anaesthetic; (10) glue or gelatine to which di-p-tolyl-dimethylaminomethylcarbinol has been added for protective purposes.  This subject-matter does not appear in the Specification as accepted.  Reference has been directed by the Comptroller to Specifications 24631/03, 11197/06, [both in Class 2]; and 307,304, [Class 2 (iii)], (as open to inspection under Sect. 91 of the Acts).ALSO:The Specification as open to inspection under Sect. 91 describes (1) a mouthwash obtained by dissolving bis-(2 : 4-dimethylphenyl) - dimethylaminomethylcarbinol hydrochloride in water; (2) a dental tincture containing-di-p-tolyl-dimethylaminomethylcarbinol hydrochloride, 90 per cent spirit and tincture myrrhae, to which menthol may be added; (3) a mouthwash tablet prepared by allowing sodium chloride to absorb an alcoholic solution of diphenyl - dimethylaminomethylcarbinol containing peppermint or eucalyptus oil; (4) an eyewash consisting of an aqueous solution of diphenyl - dimethylaminomethylcarbinol hydrochloride and sodium chloride; (5) an ointment prepared by working diphenyl-dimethylaminomethylcarbinol into lanolin; (6) a solution of di-p-tolyl-dimethylaminomethylcarbinol in olive oil for treating burns; (7) an aqueous solution of di-p-tolyl-dimethylaminomethylcarbinol hydrochloride for sterilizing surgical instruments; (8) a solution of adrenaline to which bis-(2 : 4-dimethylphenyl)-dimethylaminomethylcarbinol has been added, useful as a local anaesthetic.  This subject-matter does not appear in the Specification as accepted.  Reference has been directed by the Comptroller to Specifications 24631/03, 11197/06, [both in Class 2]; and 307,304, [Class 2 (iii)], (as open to inspection under Sect. 91 of the Acts).