Patent GB-804986-A (GB)
Title: Acylaminopropanediols and the esters, acetals and ketals thereof
Filed: 1956-01-27
Abstract: The invention comprises 1-phenyl- and 1-p-nitrophenyl - 2 - azidoacetylaminopropane - 1 : 3-diols and their esters, acetals and ketals, and the preparation thereof by (a) reacting 1-phenyl- or 1-p-nitrophenyl-2-aminopropane- 1 : 3-diols, or their functional derivatives modified in the hydroxy or amino groups (e.g. acyl derivatives, acetals or Schiff's bases), with azidoacetic acid or its reactive derivatives (e.g. its methyl or ethyl ester, acid chloride, nitrile, amide or imino-methyl ether hydrochloride, or diethyl azidoacetyl phosphite or arsenite); or (b) reacting 1-phenyl- or 1-p-nitrophenyl-2-haloacetylaminopropane - 1 : 3 - diols or their functional derivatives with alkali or alkaline-earth metal azides, followed in either case, if desired, when the product is a free diol, by (c) mono- or di-esterification; (d) esterification of both hydroxy groups with derivatives of dibasic acids to form cyclic esters; or (e) acetalization of both hydroxy groups with aldehydes or ketones to form cyclic acetals or ketals; or (f) (for the p-nitro compounds) by nitrating the 1-phenyl-2-azidoacetylaminopropane-1 : 3-diols or their functional derivatives (e.g. acetals, ketals, esters, or cyclic esters), and, if necessary, subsequently splitting hydrolytically any functionally converted groups present.  In examples, the following compounds are prepared by method (a): D-(-)- and DL-threo - 1 - p - nitrophenyl - 2 - azidoacetylaminopropane-1 : 3-diol, (the former form the free aminodiol or its N-benzal derivative, or from the aminodiol hydrochloride and azidoacetyl chloride via the O1 : O3- and N : O3-diazidoacetyl derivatives), DL-threo-l-phenyl-2-azido-acetylaminopropane - 1 : 3 - diol, DL - threo- 5 - azidoacetylamino - 6 - phenyl - 1 : 3 - dioxan and its 2 : 2-dimethyl and 2 : 2-pentamethylene derivatives, and DL-erythro-1-p-nitrophenyl- and -1-phenyl-2-azidoacetylaminopropane-1 : 3-diol (the former being epimerized to the DL-threo-isomer via the oxazoline derivative); the following by method (b): DL-threo - 1 - p - nitrophenyl - 2 - azidoacetylaminopropane-1 : 3-diol from the corresponding chloracetyl derivative and sodium azide; the following by method (c): D-(+)-threo-1-p-nitrophenyl - 2 - azidoacetylamino - 3 - palmitoyl-oxy-, -lauroyloxy-, -undecylenoyloxy-, -oleoyl-oxy-, -benzoyloxy, -nicotinoyloxy- and -acetoxy - propan - 1 - ol, D - (-) - threo - 1 - p-nitrophenyl - 2 - azidoacetylamino - 1 : 3 - diacetoxy-, -dipropionoxy- and -dipalmitoyloxypropane, and DL-threo-1-phenyl- and 1-p-nitrophenyl - 2 - azidoacetylamino - 1 : 3 - diacetoxypropane; the following by method (d): the cyclic carbonates of D-threo-1-p-nitrophenyl - 2 - azidoacetylaminopropane - 1 : 3 - diol and DL-threo-1-phenyl-2-azidoacetylaminophepane-1 : 3-diol; and the following by method (f): D-(-)- and DL-threo-1-p-nitrophenyl-2-azidoacetylaminopropane-1 : 3 - diol (the hydroxy groups being protected by acetyl groups subsequently removed, or, in the case of the DL-isomer, intermediately converted into nitric ester groups which are likewise subsequently hydrolysed), DL-threo-5-azidoacetylamino - 6 - p - nitrophenyl - 1 : 3 - dioxan, and DL- and D-(-)-threo-2 : 2-pentamethylene- and -2 : 2 - dimethyl - 5 - azidoacetylamino - 6-p - nitrophenyl - 1 : 3 - dioxan (subsequently hydrolysed to DL- and D-(-)-threo-1-p-nitrophenyl - 2 - azidoacetylaminopropane - 1 : 3-diol).  Diethyl azidoacetyl phosphite and arsenite are prepared by refluxing azidoacetic acid in methanol with diethyl chlorophosphite and chlorarsenite respectively.