Patent GB-687284-A (GB)
Title: Mono and di-acylated amino diols
Filed: 1950-02-15
Abstract: The invention comprises mono- and diacylated 1 - biphenylyl - 2 - aminopropane - 1 : 3 - diols of the general formula <FORM:0687284/IV (b)/1> (wherein n is 1 or 2, R represents hydrogen, halogen, a nitro group or an alkyl or alkoxy group of not more than 4 carbon atoms, the two R's being the same or different when n is 2, and R3 represents hydrogen or an acyl radical), and the manufacture thereof by the following processes: (a) reducing a ketonic compound of the formula <FORM:0687284/IV (b)/2> (b) (when R3=H) reacting a compound of the formula <FORM:0687284/IV (b)/3> (wherein R1 represents hydrogen or an acyl radical) with a strongly alkaline material in an aqueous solution containing a water-miscible organic solvent; (c) (when R3=acyl) heating a compound of the formula <FORM:0687284/IV (b)/4> (wherein R2 represents hydrogen or an acyl radical) with an acid anhydride or halide (preferably at 60-135 DEG  C.); (d) (when R3=H) acylating an aminodiol of the general formula in (c) but wherein R2=H, under such mild conditions as will result in the acylation of the amino group only.  The reduction in (a) may be effected with hydrogen in the presence of a metal hydrogenation catalyst, nascent hydrogen generated in the reaction mixture by interaction of a metal with an acid, lower aliphatic alcohol, water or mixtures thereof, or especially an oxidizable aluminium alkoxide in the presence of a lower aliphatic alcohol, the last method being particularly desirable when the starting material contains a halogen or nitro substituent in the phenyl ring.  The hydrolysis in (b) is advantageously effected with an alkali or alkaline-earth metal hydroxide or alkali metal carbonate in an aqueous lower aliphatic alcohol or ketone at about -20 DEG  to +50 DEG  C.  The monoacylation in (d) may be effected with an ester-type acylating agent under substantially anhydrous conditions or with an acid anhydride or halide either under substantially anhydrous conditions at a low temperature (below 15 DEG  C.) or in a mildly alkaline aqueous reaction medium.  The products have antibiotic activity or are useful as intermediates for compounds having this property.  Examples describe the preparation of: (1) dl-q -1-(41-biphenyl) - 2 - acetamidopropane - 1 : 3 - diol; (2) l- and dl-q -1-(41-biphenylyl)-2-dichloracetamidopropane - 1 : 3 - diol, l - q  - 1 - (41 - biphenylyl) - 2 - benzamidopropane - 1 : 3 - diol, dl - q - 1 - (41 - biphenylyl) - 2 - acetamido - 3 - acetoxypropane - 1 - ol, and dl - q  - 1 - (41 - biphenylyl) - 2 - p - nitrobenzamido -, - 2 - furamido -, - 2 - b  : b  - dimethylacrylamido - and 2 - b  - carboxypropionamido - propane - 1 : 3 - diol; (3) unresolved 1-(31-biphenylyl)-2-benzamidopropane - 1 : 3 - diol; (4) dl - q  - 1 - (31 - and 21 - biphenylyl) - 2 - dibromacetamido-propane - 1 : 3 - diol; (5) unresolved and dl - q  - 1 - (31 - biphenylyl) - 2 - benzamido - 3 - acetoxypropane - 1 - ol; (6) unresolved and dl - q  - 1 - (411 - methoxy - 41 - biphenylyl) - 2 - phenylacetamidopropane - 1 : 3 - diol; (7) dl-q -1 - (411 - methoxy - 41 - biphenylyl) - 2 - methoxyacetamido-, -2-cyanoacetamido- and -2-lactamido - propane - 1 : 3 - diol; (8) dl - q  - 1 - (411 - nitro - 41 - biphenylyl) - 2 - acetamido-propane - 1 : 3 - diol; (9) dl - and l - q  - 1 - (411 - nitro - 41 - biphenylyl) - 2 - dichloracetamidopropane - 1 : 3 - diol; (10) unresolved 1 - (411 - iodo - 41 - biphenylyl) - 2 - benzamidopropane - 1 : 3-diol; (11) dl-q - and -reg.-1-(211-methyl-41-biphenylyl) - 2 - p - toluylamidopropane - 1 : 3 - diol; (12) dl - q  - 1 - (411 - nitro - 61 - methyl - 31 - biphenylyl) - 2 - acetamidopropane - 1 : 3 - diol.  Additional acyl groups specified include mono-, di- and tri-fluoroacetyl.  Ketones of the second general formula above are obtainable by the process of Specification 687,336.  The preparation of the starting materials for this process is described somewhat more fully than in the said Specification, though without examples.