Patent GB-431786-A (GB)
Title: Process for the production of diaminoalcohols of the aromatic series
IPC: C07C215/30
Filed: 1934-01-12
Abstract: Diaminoalcohols of the formula RCHOHCH (R<1>)NR<11>R<111>, in which R is an aromatic radicle of the benzene series, R<1> is hydrogen or methyl, R<11> is a dialkylaminoalkyl group, and R<111> is hydrogen or a hydrocarbon radicle, are prepared (1) by treating monoaminoalcohols of the formula RCHOHCH(R<1>)NHR<111> (or their salts) with dialkylaminoalkyl halides or sulphonates (or their salts) in the presence or absence of an acid-binding agent, or (2) by treating halogen ketones of the formula RCOCH(R<1>)X, where X is halogen, with diamines containing a dialkylaminoalkyl group, and subsequently reducing the keto group, or (3) by treating halogenalcohols of the formula RCHOHCH(R<1>)X with diamines containing a dialkylaminoalkyl p group; a modification of method (3) consists in starting from the ethers of the halogenalcohols and subsequently hydrolyzing the ether group.  Examples are given in which (1) l - 1 - phenyl - 2 - methylaminopropanol-1 and diethylaminoethyl chloride yield l - 1 - phenyl - 2 - (methyl) (diethylaminoethyl) aminopropanol-1, the dihydroiodide and diprimary phosphate of which are described; (2) 1 - p - methoxyphenyl - 2 - methylaminoethanol-1 and diethylaminoethyl benzenesulphonate yield 1-p-methoxyphenyl-2 (methyl) (diethylaminoethyl)aminoethanol - 1, the dihydrochloride of which is described; (3) racemic 1 - phenyl - 2 - aminopropanol - 1 and diethylaminoethyl p - toluenesulphonate yield racemic 1 - phenyl - 2 - diethylaminoethylaminopropanol - 1, the dihydroiodide of which is described; (4) a -bromopropiophenone and 1 - methylamino - 2 - diethylaminoethane yield 1 - phenyl - 2 - (methyl)(diethylaminoethyl) aminopropanone-1, which is converted into racemic 1 - phenyl - 2 - (methyl) (diethylaminoethyl)aminopropanol-1 (the dihydrochloride of which is described) by reduction with hydrogen at atmospheric temperature and slightly raised pressure in the presence of a palladium and barium sulphate catalyst; (5) 1 - phenyl - 1 - methoxy - 2 - bromopropane and 1 - methylamino - 2 - diethylaminoethane yield the methyl ether of 1 - phenyl - 2 - (methyl)(diethylaminoethyl)aminopropanol-1, which is heated with hydrobromic acid to hydrolyze the ether group; (6) 1 - phenyl - 2 - benzylaminopropanol-1 and diethylaminoethyl chloride yield 1 - phenyl - 2 - (benzyl)(diethylaminoethyl) aminopropanol-1, the dihydrochloride of which is described.  The products are of therapeutic value in the treatment of asthma.  The Specification as open to inspection under Sect. 91 states that in method (2) above the reaction of the halogenketones with the diamines and the reduction of the keto group may proceed simultaneously.  Further, it includes additional examples of the methods described above in which (1) d - 1 - phenyl - 2 - methylaminopropanol - 1 and diethylaminoethyl chloride yield d - 1 - phenyl - 2 - (methyl)(diethylaminoethyl)aminopropanol-1, the dihydroiodide of which is described; (2) l - 1 - phenyl - 2 - methylaminopropanol - 1 and dibutylaminoethyl chloride yield l - 1 - phenyl - 2 - (methyl)(dibutylaminoethyl)aminopropanol - 1, the dihydrochloride of which is described; (3) racemic 1 - phenyl - 2 - methylaminopropanol - 1 and diethylaminoethyl p - toluenesulphonate yield racemic 1 - phenyl - 2 - (methyl)(diethylaminoethyl)aminopropanol - 1; (4) p - methoxy - w - chloroacetophenone and 1 - methylamino - 2 - diethylaminoethane yield p - methoxy - w - (methyl)(diethylaminoethyl)aminoacetophenone, which is converted into 1-p-methoxyphenyl-2-(methyl)(diethylaminoethy)aminoethanol-1 by treatment with hydrogen at a slightly raised pressure in the presence of palladium supported on charcoal.  The Specification states also that diaminoalcohols of the formula above (R being defined as an aromatic radicle) are also obtainable (1) by condensing a diketone RCOCOR<1> with a diamine containing a primary and a tertiary amino group (NH2R<11>, where R<11> is a dialkylaminoalkyl group) to yield an azomethine derivative RCOC(R<1>) : NR<11>, which is converted into a diaminoalcohol by simultaneous or subsequent reduction; (2) by condensing a ketoalcohol RCHOHCOR<1> with a diamine NH2R<11> to yield an azomethine derivative RCHOHC(R<1>) : NR<11>, which is similarly converted into a diaminoalcohol by simultaneous or subsequent reduction.  In examples of these methods, (1) 1 - phenylpropane - 1 : 2 - dione and 1 - amino - 2 - diethylaminoethane are condensed in the presence of sulphurous acid and zinc dust to yield directly 1-phenyl-2-diethylaminoethylaminopropanol - 1; (2) 1 - phenyl-1-hydroxypropanone-2 and 1-amino-2-diethylaminoethane yield an azomethine derivative which is reduced, without isolation, by treatment with hydrogen in the presence of a palladium catalyst; 1 - phenyl - 2 - diethylaminoethylaminopropanol-1 is again obtained. This subject-matter does not appear in the Specification as accepted.ALSO:Diaminoalcohols of the formula RCHOHCH(R<1>)NR<11>R<111>, in which R is an aromatic radicle of the benzene series, R<1> is hydrogen or methyl, R<11> is a dialkylaminoalkyl group, and R<111> is hydrogen or a hydrocarbon radicle, are prepared by treating halogenketones of the formula RCOCH(R<1>)X, where X is halogen, with diamines containing a dialkylaminoalkyl group, and subsequently reducing the keto group. An example is given in which a -bromopropiophenone and 1-methylamino-2-diethylaminoethane yield 1-phenyl-2-(methyl) (diethylaminoethyl) aminopropanone-1, which is converted into racemic 1-phenyl-2-(methyl) (diethylaminoethyl)-aminopropanol-1 (the dihydrochloride of which is described) by reduction with hydrogen at atmospheric temperature and slightly raised pressure in the presence of a palladium and barium sulphate catalyst.  The products are of therapeutic value in the treatment of asthma.  The Specification as open to inspection under Sect. 91 states that the reaction of the halogenketones with the diamines and the reduction of the keto group may proceed simultaneously.  Further, it includes an additional example in which (1) p-methoxy-o -chloroacetophenone and 1-methylamino-2-diethylaminoethane yield p-methoxy-o -(methyl) (diethylaminoethyl)-aminoacetophenone, which is converted into 1-p-methoxyphenyl-2-(methyl) (diethylaminoethyl)-aminoethanol-1 by treatment with hydrogen at a slightly raised pressure in the presence of palladium supported on charcoal.  The Specification states also that diaminoalcohols of the formula above (R being defined as an aromatic radicle) are also obtainable (1) by condensing a diketone RCOCOR<1> with a diamine containing a primary and tertiary amino group (NH2R<11>, where R<11> is a dialkylaminoalkyl group) to yield an azomethine derivative RCOC(R<1>): NR<11>, which is converted into a diaminoalcohol by simultaneous or subsequent reduction; (2) by condensing a ketoalcohol RCHOHCOR<1> with a diamine NH2R<11> to yield an azomethine derivative RCHOHR(R<1>) : NR<11>, which is similarly converted into a diaminoalcohol by simultaneous or subsequent reduction.  In an example 1-phenyl-1-hydroxypropanone-2 and 1-amino-2-diethylaminoethane yield an azomethine derivative which is reduced, without isolation, by treatment with hydrogen in the presence of a palladium catalyst; 1-phenyl-2-diethylaminoethylaminopropanol - 1 is obtained.  This subject-matter does not appear in the Specification as accepted.