Process for mono N-alkylation of aminophenol

Abstract

The invention relates to a process for the preparation of a compound represented by formula (I) wherein X is selected from the group consisting of —H, -halogen, linear or branched C1-C7 alkyl group, linear or branched C1-C5 alkoxy group, —NO.sub.2 and —CN and Y is a linear or branched C1-C7 alkyl group, comprising the steps of: 10 a) reacting a compound represented by formula (II) with a compound represented by (III) to obtain an intermediate product, wherein X is as defined with respect to formula (I), wherein Z is H, CH.sub.3 or C.sub.2H.sub.5, b) reacting the intermediate product of step a) with a compound represented by Y.sub.2SO.sub.4 (IV) wherein Y is as defined with respect to formula (I) to obtain a salt and c) hydrolyzing the salt of step b) to obtain the compound of formula (I). ##STR00001##

Claims

1. A process for the preparation of a compound represented by formula (I) ##STR00011## wherein X is selected from the group consisting of —H, a halogen, linear or branched C1-C7 alkyl group, linear or branched C1-C5 alkoxy group, —NO.sub.2 and —CN and Y is a linear or branched C1-C7 alkyl group, comprising the steps of: a) reacting a compound represented by formula (II) with a compound represented by (III) to obtain an intermediate product, ##STR00012## wherein X is as defined with respect to formula (I), ##STR00013## wherein Z is H, —CH.sub.3 or —C.sub.2H.sub.5, b) reacting the intermediate product of step a) with a compound represented by Y.sub.2SO.sub.4 (IV) wherein Y is as defined with respect to formula (I) to obtain a salt and c) hydrolyzing the salt of step b) to obtain the compound of formula (I).

2. The process according to claim 1, wherein the —OH group is ortho with respect to the carbon atom to which the —NH.sub.2 group is attached in compound (II).

3. The process according to claim 1, wherein X is —H or a linear or branched C1-C7 alkyl group in compound (II).

4. The process according to claim 1, wherein Z is —H in compound (III).

5. The process according to claim 1, wherein step a) is performed in the presence of a reagent for nitration of an aromatic compound.

6. The process according to claim 1, wherein Y is —CH.sub.3 or —C.sub.2H.sub.5 in compound (IV).

7. The process according to claim 1, wherein step b) is performed in the presence of an organic solvent.

8. The process according to claim 1, wherein step c) is performed by the addition of HCI solution to the salt of step b).

9. The process according to claim 5, wherein the aromatic compound is copper (II) nitrate.

10. The process according to claim 6, wherein Y is —CH.sub.3 in compound (IV).

11. The process of claim 7, wherein the organic solvent is toluene.

Description

EXAMPLES

Example 1

2-(Benzylideneamino)phenol

(1) ##STR00007##

(2) To a stirred solution of 2-aminophenol (10.91 gm; 0.1 mol) in 60 ml ethanol was added benzaldehyde (10.6 gm; 0.1 mol) and Cu(NO.sub.3).sub.2.6H.sub.2O (1 mol %) and the resulting solution was stirred at room temperature for 1-2 hours. After completion of reaction water 100 ml was added to give brown solid, m.p.: 112-116° C. as 2-(benzylideneamino)phenol 18.1 gm (91%), (TLC single spot).

2-(methylamino)phenol

(3) ##STR00008##

(4) A solution of 2-(benzylideneamino)phenol (10 gm, 0.05 mol), dimethyl sulfate (6.3 gm, 0.05 mol) and 70 ml toluene were mixed and heated to 70-75° C. for 1-2 hours to form complex. The reaction mixture was cooled to 40-50° C. and 50 ml dilute HCl solution was gradually added. The mixture was warmed to 60-65° C. for 30 min to complete hydrolysis and then cooled to room temperature. The bottom aqueous layer was separated from upper toluene layer, which contains benzaldehyde. The aqueous acidic solution was basified with dilute sodium carbonate solution to give 2-methylaminophenol 5.2 gm (85%), m.p. 89-93° C. (TLC single spot)

Example 2

2-(Benzylideneamino)-4-(tertbutyl)phenol

(5) ##STR00009##

(6) To a stirred solution of 2-amino-4-tert-butylphenol (16.5 gm; 0.1 mol) in 90 ml ethanol was added benzaldehyde (10.6 gm; 0.1 mol) and Cu(NO.sub.3).sub.2.6H.sub.2O (1 mol %) at room temperature. The resulting solution was stirred under nitrogen at room temperature for 2-4 hours. After completion of reaction (checked by TLC), water 125 ml was added to give solid, as 2-(benzylideneamino)-4-(tertbutyl)phenol 22.7 gm (89%), (TLC single spot).

2-(methylamino)-4-(tertbutyl)phenol

(7) ##STR00010##

(8) A solution of 2-(benzylideneamino)-4-(tertbutyl)phenol (10 gm, 0.04 mol), dimethyl sulfate (6.3 gm, 0.05 mol) and 70 ml toluene were mixed and heated to 70-75° C. for 1-2 hours to form complex. The reaction mixture was cooled to 30° C. and 50 ml dilute HCl solution was gradually added. The mixture was warmed to 70-75° C. for 30 min to complete hydrolysis and then cool to room temperature. The bottom aqueous layer was separated from upper toluene layer, which contains benzaldehyde which was recovered by distillation (85%). The aqueous acidic solution was basified with dilute sodium carbonate solution to give 2-methylamino-4-tertbutyl-phenol 6.44 gm (92%), m.p. 140-45° C. (TLC single spot)