Patent GB-688109-A (GB)
Title: Process for the manufacture of amino diols
IPC: C07C233/00
Filed: 1949-02-15
Abstract: (dl)-Acylamino diols of formula <FORM:0688109/IV (b)/1> are obtained by reducing with an oxidizable aluminium alkoxide in an organic solvent a compound of formula <FORM:0688109/IV (b)/2> where R1 and R2 are the same or different and are hydrogen, halogen, lower alkyl or lower alkoxy radicles, the term acyl including lower aliphatic acyl, halogen-substituted lower aliphatic acyl, benzoyl, substituted benzoyl and araliphatic acyl radicles.  The products may be hydrolysed to the free amino diol or an acid addition salt thereof. Products of reduction and hydrolysis may exist as structural as well as optical isomers and the reduction gives a mixture containing a much larger quantity of the pseudo than the regular isomer of the corresponding amino diol, e.g. 3 to 4 times as much, and the regular isomer may be eliminated during the isolation of the pseudo product or by fractional crystallization or solubilization.  Reduction is effected in an organic solvent usually a lower aliphatic alcohol which preferably corresponds to the alkoxide.  Alkoxides of secondary alcohols, e.g. isopropanol and sec. butanol are preferred although those of tertiary alcohols, e.g. tert. butanol may also be used. Temperatures specified are about 20-125 DEG  C. and one to thirty, e.g. about three, equivalents of alkoxide are used.  Preferably the reaction mixture is refluxed, the aliphatic ketone being distilled off as formed.  Hydrolysis may be effected with either alkaline or acidic hydrolysis catalysts or reagents, dilute mineral acids being preferred when an amine salt results which may be isolated as such or converted to the free base.  Many alkaline and acidic hydrolytic agents are specified, all being of conventional type.  The acylaminodiol mixture may before hydrolysis be separated into the (dl)-q - and (dl)-reg-isomers by recrystallization from water, aqueous alcohol or alcohols and the individual isomers hydrolysed to the amido diols.  Products may be used in the synthesis of, or as, antibiotics.  In examples: (1) p - nitro - a  - acetamido - b -hydroxypropiophenone with aluminium isopropioxide in isopropanol yields mainly (dl)-q  - 1 - p - nitrophenyl - 2 - acetamido - propane-1,3-diol which is optionally purified from a small quantity of the cis isomer by recrystallization from ethanol before hydrolysis with 5 per cent HCl and subsequent pH adjustment to 10-11 leads to the isolation of the free base (dl) - q  - 1 - p - nitrophenyl - 2 - amino - propane-1,3 - diol (the hydrochloride of which may be isolated if the pH adjustment is not made), and the isolation of (dl) pseudo and (dl) reg. isomers of 1 - p - nitrophenyl - 2 - acetamidopropane-1,3-diol by fractional crystallization from water is given; (2) p-nitro-a -benzamido-b -hydroxypropiophenone with aluminium isopropoxide in isopropanol gives (dl)-q -1-p-nitrophenyl - 2 - benzamidopropane - 1,3 - diol and a small quantity of the reg. isomer the pseudo isomer on hydrolysis with 5 per cent HBr and pH adjustment to 10 yields the corresponding 2 - aminopropane - 1,3 - diol; (3) o - methyl - p-nitro - a  - acetamido - b  - hydroxypropiophenone with aluminium sec-butylate in sec. butanol gives mainly (dl)-q - with some (dl)-reg - 1 - (o - methyl - p - nitrophenyl) - 2 - acetamidopropane-1,3-diol which with 5 per cent HCl and adjustment of pH to 10 gives the corresponding diol; (4) m-methoxy-p-nitro-a  - p1 - toluylamido - b  - hydroxypropiophenone with aluminium isopropoxide in isopropanol under nitrogen yields the corresponding 2-p1-toluylamidopropane-1,3-diol (mainly the q -isomer) which with 5 per cent HCl gives the hydrochloride of the corresponding diol which may be isolated as the free base after pH adjustment to 10; (5) 2-nitro-4,5-dimethyl-a -phenacetamido - b  - hydroxypropiophenone with aluminium isopropioxide in isopropanol under nitrogen gives the corresponding (dl)-phenylacetamidopropane-1,3-diol which with 5 per cent HCl and subsequent neutralization gives the free 2-aminopropane-1,3-diol, the diastereo isomers of which may be obtained by recrystallization from water or alcohol; (6) 3 - nitro - 5 - chloro - a  - (a 1 - chloropropionamido) - b  - hydroxypropiophenone is reduced with aluminium isopropoxide in isopropanol under nitrogen and the (dl)-q -product obtained hydrolysed with 5 per cent HI to yield on pH adjustment to 10 (dl)-q -1-(31-nitro - 51 - chlorophenyl) - 2 - aminopropane-1,3-diol and in (7) p-nitro-a -dichloroacetamido-b -hydroxypropiophenone with aluminium isoproxide in isopropanol under nitrogen yields the corresponding (dl)-q -dichloroacetamido-propane-1,3-diol which on hydrolysis with 5 per cent H2SO4 and pH adjustment to 10 yields the corresponding diol. Specification 688,023 is referred to for the preparation of the starting ketones.