Patent GB-1038332-A (GB)
Title: 1,4-benzodioxan derivatives
Inventor: CHODNEKAR MADHUKAR SUBRAYA
IPC: C07D319/20
Filed: 1963-02-13
Abstract: The invention comprises compounds of the formula <FORM:1038332/C2/1> (wherein R1 is hydrogen or C1- 6 alkyl; R2 is hydrogen or alkyl; R3 is alkyl which may be hydroxy or alkoxy substituted, alkenyl, or aralkyl which may be halogen or alkoxy substituted; and wherein ring A may be substituted by one or more halogen atoms or alkyl radicals or by the group -CH = CH-CH = CH-to form a fused on benzene ring) and the O-esters thereof derived from carboxylic acids, and the acid-addition salts thereof; but excludes the compounds wherein ring A is unsubstituted and either R1 and R2 are both hydrogen and R3 is methyl, ethyl, n-propyl, isopropyl or n-butyl, or R1 is hydrogen and R2 and R3 are both methyl, ethyl, n-propyl, isopropyl, n-butyl or iso-butyl, or R1 is hydrogen, R2 is methyl and R3 is ethyl or n-propyl, or R1 is methyl, R2 is hydrogen and R3 is methyl or ethyl, or R1 is methyl and R2 and R3 are both methyl or ethyl, and the salts thereof.  The invention also comprises the preparation of these benzodioxan derivatives by (1) reaction of the amine NHR2R3 with an appropriate benzodioxan containing in the 2-position the group <FORM:1038332/C2/2> or the group -CHOH.CHR1X (wherein X is a halogen); or (2) the interaction under reducing conditions of an appropriate benzodioxan containing in the 2-position the group -CHOH.CHR1NH2 with a carbonyl compound R5.CO.R6 (wherein R5 is alkyl and R6 is alkyl, hydroxyalkyl, alkoxyalkyl, alkenyl or aryl or aralkyl optionally halo or alkoxy substituted) to give a product wherein R2 is hydrogen and R3 is -CHR5R6 or (3) reduction of the appropriate benzodioxan containing in the 2-position the group -CO.CHR1.NR2R3; or (4) reduction of the appropriate benzodioxan containing in the 2-position the group -CO.R7 (wherein R7 is the group -CO.R1 or the group -CR1(OR8)OR9 wherein R8 and R9 are hydrogen or alkyl) in the presence of the amine NHR2R3; or (5) for the preparation of compounds halogenated in ring A, halogenation of the corresponding unhalogenated benzodioxan; or (6) for the preparation of the O-esters, esterification of the appropriate ol with acid halide or an hydride R10.COY (wherein R10 is alkyl, aryl, aralkyl or alkenyl and Y is halogen or -O.COR10).  In (2) the amino compound may be generated in situ by the reduction of the corresponding diazoacyl derivative, the corresponding azidoacyl derivative, the O-benzyl, N-benzyl or O,N-dibenzyl derivative of the said amino derivatives, or the corresponding 2-nitroalkanol, benzylaminoacyl, nitroacyl or benzyloxycarbonylaminoacyl derivative; or, when R1 is hydrogen, by reduction of the corresponding acyl cyanide, the cyanhydrin derived from the corresponding aldehyde, or the O-benzyl derivative of the said cyanhydrin.  Racemic diastereo isomers of the products of the invention may be separated from each other by, for example, fractional crystallization.  Examples are given.  1 - (1,4 - Benzodioxan - 2 - yl) - 2 - bromoethanol is prepared by reduction of 2-bromoacetyl - 1,4 - benzedioxan.  2 - Chloro - 1-(naphtho[2,3 - b] - 1,4 - dioxan - 2 - yl) - ethanol is prepared by reacting 2,3-dihydroxynaphthalene with ethyl 2,3-dibromopropionate to give 2 - ethoxycarbonyl - (naphtho[2,3 - b] - 1,4-dioxan), saponifying this to naphtho[2,3-b]-1,4-dioxan - 2 - carboxylic acid, converting this to the acid chloride, reacting this with diazomethane to give 2-diazoacetyl-(naphtho[2,3-b]-1,4-dioxan), reacting this with hydrogen chloride to give 2-chloroacetyl-(naphtho[2,3-b]-1,4-dioxan) and reducing this. 2-Chloro-1-[6 or 7-methyl - 1,4 - benzodioxan - 2 - yl] - ethanol is prepared similarly via similar intermediates, the starting materials being 3,4-dihydroxytoluene and ethyl 2,3-dibromopropionate.  2-Amino - 1 - (1,4 - benzodioxan - 2 - yl) - ethanol is prepared by reacting 1-(1,4-benzodioxan-2 - yl) - 2 - chloroethanol with ammonia to give the hydrochloride of the required product, and then liberating the free base from this. 2 - t - Butylaminoacetyl - 1,4 - benzodioxan hydrochloride is prepared similarly.