Patent GB-669574-A (GB)
Title: A process for the production of 1(p-hydroxyphenyl)-1-hydroxy-2-(aralkyl-amino)-propanes
Filed: 1949-04-04
Abstract: Aminopropanols of the formula <FORM:0669574/IV (b)/1> (where R is an aliphatic hydrocarbon residue of 2-5 carbon atoms) are prepared by the following methods: (1) hydrogenating the ketone <FORM:0669574/IV (b)/2> or a salt thereof (R1=H or group split off during hydrogenation, e.g. benzyl) with a noble metal or nickel catalyst; in the latter case, when using a salt, 1 mol. of alkali is added either initially or after 1 mol. of hydrogen has been taken up (by elimination of R1); (2) decomposing the derivative <FORM:0669574/IV (b)/3> by hydrogenation with palladium or heating with mineral acid (when R2=benzyl) or saponification (when R2=residue of a carboxylic or sulphonic acid); (3) reacting an aralkylamine with HO-C6H4-CO.CO.CH3 (or a benzyl ether or carboxylic or sulphonic ester thereof) to give a Schiff's base or aldehyde ammonia; the product is then hydrogenated with a noble metal or nickel catalyst whereby C=N and C=O bonds are reduced and the benzyloxy group if present is converted to a hydroxy group; where an ester was used as starting material, final hydrolysis gives the free p-hydroxy group; (4) an aralkyl or aralkenyl aldehyde or ketone is condensed with <FORM:0669574/IV (b)/4> (or the corresponding R2O- compound) with simultaneous or subsequent reduction; the residue R2 if present is then eliminated as in (2); (5) suspending <FORM:0669574/IV (b)/5> in an organic solvent in which it is sparingly soluble and hydrogenating it together with an aldehyde or ketone R5-CO-R4-C6H5, where R4 and R5 are aliphatic hydrocarbon residues or R5 may be hydrogen, and the sum of the carbon atoms in R4 and R5 is 1-4.  In method (1) the reduction and splitting off of R1 may occur simultaneously or successively in either order, depending on the reaction conditions.  Suitable solvents for method (5) are methanol, ethanol and isopropanol, with or without water.  The products may be obtained as mixtures of stereoisomers which may be separated; hydrochlorides and hydrobromides are described.  Examples are given of all 5 methods, the group R in the products being -CHMe-, -CH2-CH2-, -CHMe-CH2-, -CH2-CH2-CH2-, -CHMe-CH2-CH2-, -CH2-CH2-CH2-CH2- and -CHMe-CH2-CH2-CH2-.  The acyl group R2 is preferably toluene p-sulphonyl.  The starting materials for method (2) are obtained by method (1), or else by the Meerwein-Ponndorf reduction with aluminium isopropylate, e.g. the following (a) R2=benzyl, R=-CHMe-CH2-CH2-, (b) R2=toluene p-sulphonyl, R=-CHMe-CH2-CH2, and (c) R2=toluene p-sulphonyl, R= -CH2-CH2-CH2-.  Aralkylaminopropanones (p) R2O-C6H4-CO-CHMe-NH-R-C6H5, where R and R2 are as above, are made by reacting NH2-R-C6H5 with R2O-C6H4-CO-CHMe-Hal (especially Br), e.g. the compounds (1) R2= benzyl, R=-CH2-CH2-CH2-, the benzyl group being subsequently split off with hydrogen, (2) R2=H, R=-CH2-CH2-CH2-, (3) R2=benzyl, R=-CHMe-CH2-CH2-, the benzyl group being subsequently split off with hydrogen, (4) R2=H, R=-CHMe-CH2-CH2-, (5) R2=toluene p-sulphonyl, R= -CHMe-CH2-CH2-, the tosyl group being subsequently split off with alcohol, and (5) R2=toluene p - sulphonyl, R=-CH2-CH2-CH2-.  p-Hydroxypropiophenone derivatives are made as follows: (1) the ketone is converted into its acetate, toluene p-sulphonate and benzyl ether, all three being then brominated.  The acetyl-bromo-compound is treated with strong ammonia to give p-hydroxy-a -aminopropiophenone which is catalytically reduced to the corresponding carbinol; (2) the ketone or its benzyl ether or esters as in (1) is treated with nitrous acid or a nitrous ester to form the isonitroso derivative.  This is then catalytically reduced to 1-(p-hydroxyphenyl)-2-amino-1-propanol or the corresponding ether or ester.ALSO:A hydrogenation catalyst comprises freshly prepared palladium chloride solution to which charcoal has been added.