GB743446A - Improvements in or relating to aromatic 2-aminoalkanediols-(1.3) - Google Patents

Abstract

Propanediols of the formula R1-CHOH-CH(NHR2)-CH2OH where R1 is phenyl or substituted phenyl and R2 is hydrogen or a carboxylic acyl residue are nitrated and the resulting nitric ester hydrolysed to give a product where R1 contains a nitro group; the hydroxyl groups in the starting material may be present as a cyclic acetal or ketal which is hydrolysed by the nitric acid; similarly when R2 is not acyl the amino group may be protected as a Schiff's base (which may contain some of the corresponding oxazolidine). No stereo-inversion or optical racemization occurs during the reaction. The nitration is preferably carried out at -45 DEG to +25 DEG C., and particularly below 0 DEG C. The hydrolysis of the nitric ester groups is desirably effected in the presence of an agent which destroys nitrite (e.g. sulphamic acid or urea) and/or a reducing agent (e.g. a ferrous salt). The products are preferably isolated as their derivatives with aldehydes, and such derivatives may then be acylated to introduce the group R2. Valuable products are obtained by acylation with an ester of a halo-fatty acid (e.g. dichloracetic) in the presence of an alkaline salt such as an alkali metal carbonate or salt of a fatty acid or halofatty acid. The aldehyde group is then hydrolysed off by treatment with water, preferably in the presence of an immiscible solvent. In the examples: (1) the nitrate salt of dl-threo-1-phenyl - 2 - aminopropane - 1 : 3 - diol (from 2 : 2 - dimethyl - 5 - amino - 6 - phenyl - 1 : 3 - dioxane and nitric acid) is treated with fuming nitric acid and sulphuric acid to give the nitrate salt of the di-nitric ester of dl-threo-1-(p-nitrophenyl) - 2 - aminopropane - 1 : 3 - diol, hydrolysed to the free diol; (2) the product of (1) is condensed with benzaldehyde, acylated with methyl dichloracetate and hydrolysed to dl-chloramphenicol; (3) as in (2) using methyl bromacetate for the acylation; (4) as in (1) starting from dl-threo-2 : 2-pentamethylene-5-amino-6-phenyl-1 : 3-dioxane; (5) the process of (1) and (2) is carried out with the l-threo isomer giving chloramphenicol; (6) threo-1-phenyl-2-aminopropane-1 : 3-diol is condensed with benzaldehyde to give a mixture of the Schiff's base and the oxazolidine; the mixed product is nitrated and treated as in (1) and (2) to yield dl-chloramphenicol; (7) as in (6) condensing with benzaldehyde after the nitration; (8) as in (7) using the optically active form to give d-( - )-chloramphenicol; (9) dl-threo-2 : 6-di-phenyl-5-amino-1 : 3-dioxane (see Specification 735,454) is nitrated, the nitric ester groups hydrolysed and the product isolated as its n-butyraldehyde derivative; (10) dl-threo-1-phenyl - 2 - dichloracetylaminopropane - 1 : 3 - diol is nitrated and the nitric ester hydrolysed to give dl-chloramphenicol; the l-threo form may be treated similarly.