Patent GB-732309-A (GB)
Title: Improvements in or relating to propanediols and their preparation
Filed: 1953-07-02
Abstract: The invention comprises compounds of the formula <FORM:0732309/IV (b)/1> where R1 and R2 are hydrogen, alkyl (C1-C6) or hydroxyethyl, R3 is hydrogen, halogen, alkyl or alkoxy (C1-C6), and the acyl radical is acetyl, chloracetyl, dichloracetyl, bromacetyl or dibromacetyl; they may exist in d-, l- and dl-threo and -erythro forms.  In their preparation a sulphonyl fluoride of the formula <FORM:0732309/IV (b)/2> (obtained from the corresponding sulphonyl chloride and aqueous potassium fluoride or from the p-ethylbenzenesulphonyl fluoride by oxidation with potassium permanganate and magnesium nitrate) is halogenated in the o -position, condensed with hexamethylenetramine to give a quaternary salt and the latter treated with sulphurous acid to form a sulphite of the type R-CO-CH2-NH-CH2-OSO2H, from which the o -amino-acetophenone is obtained by hydrolysis; the appropriate acyl radical is introduced on to the nitrogen atom, the product condensed with formaldehyde to yield a 1-aryl-2-acylamino-3-hydroxypropanone-(1) and the latter reduced to the propanediol; finally reaction with R1-NH-R2 gives the desired sulphonamide.  Alternatively, a similar series of operations can be carried out on a p-ethylbenzenesulphonamide. The reduction step can be carried out with an aluminium alkoxide or sodium borohydride, whereby mainly the threo isomer is formed. The latter may be resolved into its optically active forms by hydrolysis to the aminodiol, salt-formation with an optically active acid and re-acylation.  In the examples: (1) p-ethylbenzenesulphonyl chloride is converted successively into p-ethylbenzenesulphondimethylamide, p - dimethylsulphamylacetophenone, p - dimethylsulphamyl - phenacyl bromide, p - dimethyl - sulphamyl - o -(hydroxymethylamino) - acetophenone sulphite ester, p - dimethylsulphamyl - o  - aminoacetophenone, p - dimethylsulphamyl - o  - dichloracetamido - acetophenone, 1 - (p - dimethylsulphamyl - phenyl) - 2 - dichloracetamido - 3 - hydroxy - propanone - (1) and 1-(p - dimethylsulphamyl - phenyl) - 2 - dichloracetamido - 1 : 3 - propanediol; (2) 1 - (p-diethylsulphamyl - phenyl) - 2 - dichloracetamido - 1 : 3 - propanediol is obtained from the sulphonyl fluoride and diethylamine; (3) the product of (1) is made from the sulphonyl fluoride and dimethylamine dimethylcarbamate; (4) 1 - (p - sulphamyl - phenyl) - 2 - dichloracetamide - 1 : 3 - propanediol and 1-(p - methylsulphamyl - phenyl) - 2 - dichloracetamido - 1 : 3 - propanediol are prepared from the sulphonyl fluoride and ammonia and methylamine respectively; the products of (1)-(4) are the dl-threo forms; (5) dl-threo-1-(p - dimethylsulphamyl - phenyl) - 2 - amino-1 : 3-propanediol (from hydrolysis of (1)) is crystallized with d-camphorsulphonic acid, fractionated to give the d- and l-salts and the corresponding free bases obtained by ion-exchange; they are each re-acylated with methyl dichloracetate; (6) the d- and l-threo-1-(p - sulphamyl - phenyl) - 2 - dichloracetamido-1 : 3-propanediols are each obtained by treating the corresponding optically-active sulphonyl fluorides with ammonia.  In other products mentioned R1 and R2 can be ethyl, hydroxyethyl, bis-hydroxyethyl or dipropyl, R3 can be hydrogen, methyl, chloro, bromo, fluoro, ethyl or methoxy, and the other acyl groups specified above may be present.ALSO:Compounds of the formula <FORM:0732309/I/1> which are effective in the control of bacterial and rickettsial infections are useful as nutritional supplements for livestock such as chickens, sheep, hogs and cattle; R1 and R2 are hydrogen, alkyl (C1-C6) or hydroxyethl, R3 is hydrogen, halogen, alkyl or alkoxy (C1-C6), and the acyl radical is acetyl, chloracetyl, dichloracetyl, bromacetyl or dibromacetyl.