GB698765A - Haloacetamido diols and methods for obtaining the same - Google Patents

Abstract

The invention comprises the N-forms of haloacetylaminodiols of the general formula <FORM:0698765/IV (b)/1> and the manufacture thereof by one- or two-step di-haloacetylation of a q -1-p-aminophenyl-2-aminopropane-1 : 3-diol. The one-step process may consist in the simultaneous introduction of two identical haloacetyl groups by reacting the aminodiol with a haloacetic anhydride at a temperature below about 60 DEG C. (e.g. by heating to 40-50 DEG C. under anhydrous or aqueous conditions, in the latter case preferably in the presence of an alkaline catalyst such as an alkali metal salt of an organic acid or an alkali or alkaline-earth metal bicarbonate or carbonate). The two-step process (which is essential when the two haloacetyl groups are different and also applicable when they are identical) is preferably effected by first haloacetylating the aromatic amino group by the action of a haloacetic anhydride or halide under aqueous conditions in the presence of at least one equivalent of a mineral acid (e.g. hydrochloric, hydrobromic or sulphuric acid), preferably at a temperature below about 35 DEG C. neutralizing the resulting salt of q -1-p-haloacetylaminophenyl-2-amino-propane-1 : 3-diol and reacting the free base with a lower (1-4 C) alkyl ester, halide or anhydride of a haloacetic acid under anhydrous conditions (e.g. at a temperature up to about 100 DEG C. but preferably below about 35 DEG C. in an organic solvent such as methanol, ethanol or isopropanol). Alternatively the aliphatic amino group may first be acylated by reaction with a lower alkyl ester of a haloacetic acid under anhydrous conditions and then the aromatic amino group by the action of a haloacetic anhydride under the same conditions as for the one-step process. The products are useful as antibiotics suitable for oral administration. Examples describe the preparation of l- and dl - q - 1 - p - dichloracetylaminophenyl - 2 - di - chloracetylaminopropane - 1 : 3 - diol and of l - q - 1 - p - dichloracetylaminophenyl - 2 - di - bromoacetylamino - and 1 - p - difluoroacetyl - aminophenyl - 2 - iodoacetylamino - propane - 1 : 3-diol. q - 1 - p - Aminophenyl - 2 - aminopropane - 1 : 3 - diols are obtainable by reduction of the corresponding p-nitro compounds; e.g. l-q -1-p-nitrophenyl - 2 - aminopropane - 1 : 3 - diol is reduced with hydrogen in methanol in the presence of palladium on charcoal.