Patent GB-733425-A (GB)
Title: Secondary amines and method for preparing the same
Inventor: BRUCE WILLIAM FAUSSET
Filed: 1952-04-15
Abstract: The invention comprises secondary amines having the formula <FORM:0733425/IV (b)/1> where R represents a methylenedioxy radical or at least one alkyl, alkoxy or hydroxy radical and the acid addition salts thereof.  It also comprises a process for forming secondary amines by reacting an isopropyl magnesium halide with a benzaldehyde of the formula <FORM:0733425/IV (b)/2> wherein R represents a methylenedioxy radical or at least one alkyl or alkoxy radical, hydrolysing the complex formed to obtain a secondary alcohol, reacting the said secondary alcohol with hydrogen cyanide to form a formylamine and then reducing said formylamine with a metallic hydride in order to obtain the secondary amine.  As a modification the secondary amine is dehydrated to the corresponding olefine and the latter is then reacted with an inorganic cyanide and water to form the formylamine.  Dehydration may be effected using sulphonic acids such as benzene, toluene or naphthalene sulphonic acids, sulphamic acid or either phosphoric or sulphuric acid on vermiculite or other carrier.  Reduction of the formylamine may be effected in ether solution with, for example, sodium, potassium, lithium, calcium or aluminium hydride or, preferably, sodium borohydride or lithium aluminium hydride.  In the formation of the formylamine from the secondary alcohol gaseous hydrogen cyanide or metal cyanides with an acid such as sulphuric, phosphoric, chlorosulphonic, sulphamic or sulphonic acids may be used.  The solvent for the reactants may be an alkyl mono-carboxylic acid of not more than 5 carbon atoms.  Alkoxy and methylene dioxy derivatives can be hydrolysed to the corresponding mono- and di-hydroxy derivatives.  Salts mentioned are those of hydrochloric, sulphuric, phosphoric, lactic, tartaric, oleic and palmitic acids.  In examples (1) anisaldehyde and isopropyl magnesium chloride are reacted to give 1,1 - dimethyl - 2 - hydroxy - 2 - (p - methoxyphenyl) ethane which is dehydrated by heating with sulphuric acid on vermiculite to give the olefine p-CH3O.C6H4.CH = C(CH3)2. Treatment of the latter with sodium cyanide and concentrated sulphuric acid in glacial acetic acid followed by the addition of the reaction mixture to water gives the corresponding formylamine which is reduced with lithium aluminium hydride to give N-methyl-o -(p-methoxyphenyl) - tert. butylamine; (2) the product of example (1) is hydrolysed with hydrobromic acid to give N-methyl-o -(p-hydroxyphenyl)-tert. butylamine; (3) similarly to (1), the alcohol 1,1-dimethyl-2-hydroxy-2-(3,4 - dioxymethylenephenyl) ethane is prepared from piperonal and isopropyl magnesium chloride.  The alcohol is treated with cooling with sodium cyanide and sulphuric acid and the product, after dilution and isolation, is reduced with lithium aluminium hydride to give N - methyl - o  - (3,4 - dioxymethylenephenyl)-tert. butylamine; (4) the product of (3) is treated with hydrobromic acid under non-oxidizing conditions to give N-methyl-omega-(m, p-dihydroxyphenyl)tert. butylamine.  Reference has been directed by the Comptroller to Specifications 670,991 and 688,129.