Patent GB-553270-A (GB)
Title: Manufacture of 1-arylhydroxy-3-alkylamino-2-propanols or-2-propanones
IPC: D01F2/06
Filed: 1941-09-25
Abstract: 553,270. Arylhydroxyalkylamino - pro - panols. GEIGY AKT.-GES., J. R. Sept. 25, 1941, No. 12432. Convention date, Sept. 25, 1940. [Class 2 (iii)] 1-Arylhydroxy-3-alkylamino-2-propanols and the corresponding propanones are prepared by reacting an epihalogen hydrin with a monovalent phenol or with a substituted polyvalent phenol with only one free hydroxyl group, and then treating this reaction product with a monovalent or polyvalent amine which contains at least one replaceable hydrogen atom in the molecule, and finally oxidizing if the propanone is desired. The propanols are compounds of the general formula where A is an aryl or a substituted aryl group, R 1  is hydrogen or alkyl, R 2  is alkyl or substituted alkyl or R 1  and R 2  may together constitute a bivalent radical. The oxidizing agent used to convert the propanols to the corresponding propanones may be any oxidizing agent known to be suitable for converting a secondary alcohol to a ketone. The oxidation may be carried out if desired before the reaction with the amine. Also if desired, hydrochloric acid may be reacted with the initial reaction product to open the oxide ring before the subsequent step. In examples (1) Glycerine chlorohydrin phenyl ether prepared from epichlorhydrin and phenol is treated with morpholine in xylene solution to give N (3-phenoxy- 2 - hydroxypropyl) morpholine; (2) 1 - Chloro - 3 - (2<SP>1</SP> - methoxy - phenoxy - 11) - propanol - 2 obtained from guaiacol and epichlorhydrin is reacted with morpholin as in example (1) to give 1-(2<SP>1</SP>-methoxyphenoxy)-3- morpholinyl - propanol - 2. (3) Epihydrin - xylenyl ether obtained by the reaction of 1:2:4- xylenol with epichlorhydrin in the presence of potassium hydroxide is treated with morpholine to give 1-(3<SP>1</SP>:4<SP>1</SP>-dimethylphenoxy-1<SP>1</SP>)-3-morpholinyl - propanol - 2. In place of morpholine there may be used piperidine in which case there is obtained 1-(3<SP>1</SP>:4<SP>1</SP>-dimethylphenoxy-1<SP>1</SP>)- 3-piperidyl-propanol-2. This may be oxidized to the corresponding ketone by treatment with chromium trioxide in glacial acetic acid solution. (4) α-Naphthyl epihydrin ether prepared by the reaction of α-naphthol with epichlorhydrin in the presence of potassium hydroxide is reacted with morpholine to give 1-(α-naphthyloxy)-3-morpholinyl-propanol-2. The corresponding #-naphthyloxy-compound may be similarly obtained. (5) α-naphthyl epihydrin ether prepared as above is reacted with piperidine to give the corresponding piperidyl compound. (6) o-Epicresylene prepared by the reaction of epichlorhydrine with o-cresol is reacted with excess of diethylethylene diamine to give 1-(2<SP>1</SP>-methylphenoxy - 1<SP>1</SP>) - 3- diethylaminoethyl) - amino - propanol - 2. (7) Epiguaiacolene is reacted with diethylethylene diamine to give 1-(2<SP>1</SP>-methoxy-phenoxy)-3- (diethylaminoethyl) amino - propanol - 2. (8) o - Benzyloxy - epiphenylene prepared as described in Specification 553,202 is reacted with piperidine to give 1-(-2<SP>1</SP> benzyloxyphenoxy)- 3-piperidyl propanol -2. The benzyl residue may be split off with hydrochloric acid to give 1-(2<SP>1</SP>-hydroxyphenoxy) 3-piperidyl-propanol-2. (9) o-Benzyloxy-epiphenylene is reacted with morpholine to give 1-(2<SP>1</SP>-benzyloxyphenoxy-1<SP>1</SP>)- 3 morpholinyl-propanol-2 which on acidolysis is split to form 1-(2<SP>1</SP>-hydroxyphenoxy)-3-morpholinyl - propanol - 2. The intermediate compound obtained above may be oxidized as in example (3) to form 1-(2<SP>1</SP>-benzyloxyphenoxy-1<SP>1</SP>) - 3 morpholinyl propanone-2. (10) o-Benzyloxyepiphenylene is treated with diethylamine in an autoclave to give 1-(2<SP>1</SP>-benzyloxyphenoxy-1<SP>1</SP>) - 3-diethylamino - propanol - 2 which on acidolytic cleavage gives the corresponding hydroxyphenoxy compound which may be oxidized as above to the propanone. (11) o-Benzyloxy - epiphenylene is reacted with diethylethylene diamine as above and the product subjected to acid hydrolysis to give 1-(2<SP>1</SP>-hydroxyphenoxy)-3- (diethylaminoethyl) - aminopropanol - 2. (12) Glycerine chlorhydrin-phenyl ether is oxidized with sodium bichromate to 1-phenoxy- 3-chloro-propanone-2 which is then reacted with morpholine to give 1-phenoxy-3-morpholinyl-propanone-2. This same ketone is formed by the oxidation with chromic acid in glacial acetic acid of the phenoxymorpholinylpropanol prepared according to example (1).