Patent GB-994918-A (GB)
Title: Naphthoxy-substituted alkanolamines
Inventor: CROWTHER ALBERT FREDERICK
IPC: C07D295/092
Filed: 1962-11-23
Abstract: The invention comprises compounds of the formula <FORM:0994918/C2/1> wherein R1 represents a hydrogen atom or an alkyl, hydroxyalkyl, cycloalkyl, alkenyl, aralkyl or alkanoyl radical, R2 represents a hydrogen atom or an alkyl, cycloalkyl, alkenyl, alkynyl or aralkyl radical, any of which may be substituted by one or more hydroxy, alkylamino, dialkylamino, N-containing heterocyclic, alkoxy, alkoxyalkoxy, aryloxy or halogenoaryloxy groups, or R1 and R2 together complete a 5- or 6-membered N-containing heterocyclic ring which may be substituted by one or more alkyl groups and wherein R3, R4 and R5 each represent a hydrogen atom or an alkyl group containing no more than 5 carbon atoms and may be the same or different and the naphthalene nucleus may be substituted by one or more halogen atoms, alkyl, hydroxy alkyl and acyl radicals, and the esters thereof and the acid addition salts thereof, but excluding 1 - amino-, 1 - n - propylamino, 1 - n - butylamino-, 1 - diethylamino-, 1 - di - n - propylamino-, 1 - di - isopropylamino, 1 - di - n-butylamino-, 1 - morpholino-, and 1 - piperidino - 3 - (2 - naphthoxy) - 2 - propanol, and 1 - ethylamino-, 1 - dimethylamino-, 1 - diethylamino-, 1 - morpholino- and 1 - piperidino - 3 - (2 - naphthoxy) - 2 - propanol, and 1 - (1 - chloro - 2 - naphthoxy) - 3 - piperidino - 2 - propanol, and the esters and acid addition salts thereof.  A preferred group of compounds is that in which R1, R3, R4 and R5 are hydrogen atoms and R2 is defined as above. Numerous values of R1-R5, both substituted and unsubstituted, and of substituent groups in the naphthalene nucleus are specified.  Esters of the naphthalene compounds may be derived from acids of the formula R6.COOH wherein R6 represents an alkyl, alkenyl or aryl radical. Suitable acid addition salts are those derived from the usual inorganic acids and organic acids including o-acetoxybenzoic and 1,11-methylene - bis - 2 - hydroxy - 3 - naphthoic acids and sulphonated polystyrene reins.  The compounds of the invention may be prepared by a variety of methods, (a) the condensation of a halogeno compound of the formula <FORM:0994918/C2/2> where X is halogen, with an anine NHR1R2, (b) the reaction of an epoxide of the formula <FORM:0994918/C2/3> with an anine NHR1R2, (c) the reaction of a naphthol derivative <FORM:0994918/C2/4> with an anine X.CR3R4.CHOH.CHR5.NR1R2 or an epoxide <FORM:0994918/C2/5> (d) the reaction, under reducing conditions, of an amine <FORM:0994918/C2/6> with a carbonyl compound R7.CO.R8 to give a compound wherein R1 is hydrogen and R2 is -CHR7R8 and R7 and R8 are such that -CHR7R8 falls within the definition of R2, (e) the hydrogenolysis of a compound <FORM:0994918/C2/7> wherein R9 is a hydrogenolysable radical and in the resulting naphthalene compound, R1 is hydrogen, (f) the reduction of compounds in which the naphthalene nucleus bears an oxoalkyl to give compounds in which the naphthalene nucleus substituent is a hydroxyalkyl group, (g) the acylation of the naphthalene derivatives with acyl halides or acid anhydrides to give the corresponding esters, and (h) the isomerization of the esters of the formula <FORM:0994918/C2/8> wherein R10 represents an alkyl group, to give the naphthalene derivatives containing a free hydroxy group in which R1 is an alkanoyl group-COR10.  The invention is illustrated by numerous examples.  The intermediates of the formula <FORM:0994918/C2/90> may be obtained by the reduction of the corresponding a -diazoketone, a -azido-ketone and -alcohol, a  - hydroxyiminoketone, a  - nitroketone and -alcohol, cyanhydrin oracyl cyanide.ALSO:Example 22 relates to a complex salt of 1-isopropyl - amino - 3 - (1 - naphthoxy( - 2 - propanol and a sulphonated polystyrene resin obtained by treating an aqueous suspension of the sodium form of a sulphonated polystyrene resin with an aqueous solution of 1-isopropylamino-3-(naphthoxy(-2-propanol hydrochloride.