Patent GB-782448-A (GB)
Title: N-aralkyl-n-(acyloxyalkyl)-halogenated-alkanoamides
IPC: C07C233/16
Filed: 1955-02-16
Abstract: The invention comprises compounds of the formula <FORM:0782448/IV (a)/1> where Ar is a phenyl, naphthyl, biphenylyl, furyl, pyridyl or thienyl radical (which may have from one to three halo, lower alkoxy, methylenedioxy, ethylenedioxy, lower alkyl, lower alkylmercapto, lower alkylsulphonyl, nitro- or di-(lower alkyl)amino substituents, X is an alkylene radical having one to four carbon atoms, Y is an alkylene radical having two to six carbon atoms and having its two free valence bonds on different carbon atoms, Ac1 is a carboxylic acyl group having from one to eight carbon atoms and Ac is a lower halogenated-alkanoyl radical having one to four carbon atoms.  Such compounds are obtained by reacting a compound having the formula <FORM:0782448/IV (a)/2> with an acylating agent having the formula Ac1-halogen or (Ac1)2O or, in the case where Ac1 is formyl, with formic acid.  When Ac and Ac1 are alike, the products can be obtained without isolation of the intermediate N-aralkyl - N - (hydroxyalkyl) - halogenated alkanoamide by reacting an aralkylaminoalkanol (Ar-X-NH-Y-OH) with at least two molar equivalents of a halogenated alkanoyl halide.  Radicals listed for Ac1 are formyl, haloformyl, alkanoyl, mono-, di- and trihaloalkanoyl, carboxyalkanoyl, di-(lower alkyl)aminoalkanoyl, benzoyl, alkoxybenzoyl, mono-, di- and trihalobenzoyl, including acetyl, butanoyl, 3-methylbutanoyl, hexanoyl, chloracetyl, bromoacetyl, 3 - iodopropanoyl, 2 fluorobutanoyl, dichloracetyl, 2,2 - bromopropanoyl, 2 - chloro - 3 - bromobutanoyl, tribromoacetyl, 2,2,3 - trichloropropanoyl, 2,3,4 - trichlorobutanoyl, 2,2 - dibromo - 6 - chlorohexanoyl, carboxyethanoyl, 2- or 3-carboxypropanoyl, 6 - carboxyhexanoyl, diethylaminoacetyl, 2-dimethylaminopropanoyl and 4-di-n-propylaminobutanoyl.  Radicals listed for Ac are chloroformyl, chloroacetyl, iodoacetyl, fluoroacetyl, dichloroacetyl, dibromoacetyl, trichloroacetyl, 2-chloropropanoyl, 3-bromopropanoyl, 2,2 - diiodopropanoyl, 2 - bromo - 3 - chloropropanoyl, 2,2 - dichloropropanoyl, 2,2 - difluoropropanoyl, 2,2,3 - trichloropropanoyl, 2-chlorobutanoyl, 3 - bromobutanoyl, 2,2 - dichlorobutanoyl, 3,4 - dibromobutanoyl and 2,2,3- and 2,3,4-trichlorobutanoyl.  The intermediate N-aralkyl-N-(hydroxy-alkyl)-halogenated alkanoamides are obtained by reacting the appropriate halogenated - alkanoylating agent with a compound of the formula Ar-X-NH-Y-OH.  Such aralkylaminoalkanols are obtained by (a) reaction of an aralkyl halide Ar-X-halogen with an alkanolamine H2N-Y-OH; (b) for compounds where X is CH2, reaction of an aldehyde Ar-CHO with an alkanolamine H2N-Y-OH and catalytic hydrogenation of the resulting anil Ar-CH = N-Y-OH; (c) reaction of an aralkylamine Ar-X-NH2 with a haloalkanol, halogen-Y-OH.  In Example (1A) 2-(4-isopropylbenzylamino)ethanol is prepared by reacting 4-isopropylbenzaldehyde and ethanolamine and hydrogenating the product.  By the alternative method 2-(2,4-dichlorobenzylamino)ethanol is prepared by reacting 2,4-dichlorobenzyl chloride with ethanolamine; (1B) N - (3,4 - dichlorobenzyl) - N - (2 - hydroxyethyl)dichloracetamide is prepared by reacting N - (3,4 - dichlorobenzylamino)ethanol with dichloroacetyl chloride; (1C) N-(2,4-dichlorobenzyl) - N - (2 - chloracetoxyethyl)dichloracetamide is prepared by reacting N-(2,4-dichlorobenzyl) - N - (2 - hydroxyethyl)dichloracetamide with chloracetyl chloride; (2) N - (4 - isopropylbenzyl) - N - (2 - n - butanoyloxyethyl)dichloracetamide is prepared by reacting butanoic anhydride with N-(4-isopropylbenzyl) - N - (2 - hydroxyethyl)dichloracetamide; (3) N-(2,4-dichlorobenzyl)-N-[2 (3-carboxypropanoyl)ethyl] dichloracetamide is prepared by reacting N-(2,4-dichlorobenzyl)-N - (2 - hydroxyethyl)dichloracetamide with succinic anhydride; (4) N-(2,4-dichlorobenzyl)-N - [2 - (2,4 - dichlorobenzoxy)ethyl] dichloracetamide is obtained by reacting N-(2,4-dichlorobenzyl) - N - (2 - hydroxyethyl) dichloroacetamide with 2,4-dichlorobenzoyl chloride; (5) N - benzyl - N - (2 - formyloxyethyl) dichloracetamide is prepared by reacting N-benzyl - N - (2 - hydroxyethyl) dichloroacetamide with formic acid; (6) N-(2,4-dichlorobenzyl) - N - (2 - trichloroacetoxyethyl) - trichloroacetamide is prepared by reacting 2-(2,4 - dichlorobenzylamino)ethanol with trichloroacetyl chloride; (7) N-(2,4-dichlorobenzyl) - N - (2 - diethylamino - acetoxyethyl)dichloracetamide is prepared by reacting N-(2,4 - dichlorobenzyl) - N - (2 - chloroacetoxyethyl)dichloracetamide with diethylamine; (8A) 2 - (2,4 - dichlorobenzylamino)ethanol and chloracetyl chloride are reacted to give N-(2,4 - dichlorobenzyl) - N - (2 - hydroxyethyl)chloracetamide which (8B) is reacted with dichloroacetyl chloride to give N-(2,4-dichlorobenzyl) - N - (2 - dichloroacetoxyethyl) - chloracetamide; (9A) N-(2,4-dichlorobenzyl)-N-(2-hydroxyethyl)dichloroacetamide is treated in dioxane with anhydrous hydrogen chloride to give N - (2 - dichloroacetoxyethyl) - 2,4 - dichlorobenzylamine and this is reacted (9B) with trichloroacetyl chloride to give N-(2,4-dichlorobenzyl) - N - (2 - dichloroacetoxyethyl)-trichloracetamide.  A large number of additional compounds (final products and intermediates) is described or listed.  These illustrate various further combinations of the possible radicals which Ar, X, Y, Ac and Ac1 may represent. Specifications 747,592 and 767,246 are referred to.