Bromo-4-aminotoluene

Submitted by J. R. Johnson and L. T. Sandbohn. Checked by Feank C. Whitmore and A. M. Griswold. 

The 3-bromo-4-acetaminotoluene separates in crystalline flocks. It is filtered by suction and washed well with water and pressed dry. The wet crude material is dried until its weight does not exceed 500 g. before proceeding with the hydrolysis (Note 3). 

The partially dried 3-bromo-4-acetaminotoluene is refluxed with 500 cc. of 95 per cent ethyl alcohol in a 3-I. round-bottom flask. To the boiling solution is added 500 cc. of concentrated hydrochloric acid and the refluxing is continued for three hours. During this time, crystals of the hydrochloride of 3-bromo-4-aminotoluene separate. The hot mixture is poured into a 2-I. beaker and cooled thoroughly in running water. The hydrochloride is filtered by suction and washed rapidly with two loo-cc. portions of chilled alcohol. The weight of the hydrochloride is 2501-300 g. (Note 4). 

The hydrochloride is suspended in 800 cc. of water in a 2-I. beaker provided with a mechanical stirrer. The base is liberated by the addition of a solution of 140 g. of technical sodium hydroxide in 700 cc. of water, and settles as a heavy brownish oil. After cooling to room temperature, the oil is separated and weighed. The yield of the crude base is 225-250 g. (60-67 per cent of the theoretical amount based on the amount of toluidine used). The crude material may be used directly for the preparation of z-bromotoluene (p. 16). 

The base may be purified by steam distillation but distillation under reduced pressure is more satisfactory. The oil is dried over 5 g. of solid sodium hydroxide and distilled in vacuo. I he first portion of the distillate may contain -toluidine and must be carefully separated, as it causes rapid discoloration. The 3-bromo-4-aminotoluene is obtained as a colorless liquid of b.p. i20-i22°/30 mm. or 92-94 /3 mm. It solidifies on cooling and melts at 16-18°. The loss on purification is about 15 per cent of the weight of the crude base. 

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An example of this is given in Section IV.63—the conversion of 3-bromo-4-aminotoluene into m-bromotoluene. Another application is to the preparation of. iM.-tribromobenzene (Section IV,72) ... 

Bromo-4-aminotoluene hydrochloride. Transfer the partially dried 3-bromo-4-acetaminotoluene to a 1 5-litre round-bottomed flask, add 250 ml. of rectified spirit, and reflux on a water bath until the sohd dissolves completely. Introduce through the condenser 250 ml. of concentrated hydrochloric acid to the boihng solution and continue the refluxing for a further 3 hours. During this time crystals of 3-bromo-4-aminotoluene hydrochloride separate. Pour the hot mixture into a 1-Utre beaker and cool thoroughly. Filter the crystals of the hydrochloride at the pump through a Buchner funnel and wash rapidly with two 50 ml. portions of chilled rectified spirit. The yield of the hydrochloride is 150 g. 

Bromo-4-aminotoluene, Suspend the hydrochloride in 400 ml, of water in a 1-Utre beaker equipped with a mechanical stirrer. Add a solution of 70 g. of sodium hydroxide in 350 ml. of water. The free base separates as a dark heavy oil. After cooUng to 15-20°, transfer the mixture to a separatory funnel and run off the crude 3-bromo-4-amino-toluene. This weighs 125 g. and can be used directly in the next step (3). 

If pure 3-bromo-4-aminotoluene is required, the crude base may be purified either by steam distillation or, more satisfactorily, by distillation under reduced pressure. The oil is dried with 5 g. of sodium hydroxide pellets, and distilled under reduced pressure from a Claisen fiask with a fractionating side arm a little p-tolui-dine may be present in the low boiling point fraction, and the pure substance is collected at 92-94°/3 inin. or at 120-122°/30 mm. The purified amine solidifies on cooling and melts at 17-18°. 

The bromination of />-acetotoluide, followed by hydrolysis of the resulting bromoacetotoluidei is the only practical method which has been used for making 3-bromo-4-aminotoluene, The present process is a modification of the method described by Feitler.2... 

To a cold mixture of 800 cc. of 95 per cent ethyl alcohol and 200 cc. of concentrated sulfuric acid (Note i) in a 5-I. round-bottom flask, provided with an efficient mechanical stirrer, is added 250 g. (1.33 moles) of crude 3-bromo-4-aminotoluene (p. 8). The solution is stirred and cooled to 10° and a solution of 148 g. (2.05 moles) of d.s.p. sodium nitrite in 260 cc. of water is added from a separatory funnel. During this addition, the temperature of the mixture must not be allowed to rise above 10°. After all of the nitrite solution has been added, the mixture is stirred twenty minutes longer to complete the diazotization. 

Bromo-4-acetaminotoluene, 593, 605 p-Bromoacetanilide, 577, 580 p - Bromoace tophenone. 726, 732 m-Bromo-p-acetotoluidido, 593, 605 3-Bromo-4-aminotoluene, 593, 605 hydrochloride, 605 p-Bromoanilides, 361 p-Bromoaniline, 577, 580 o-Bromoanisole, 404 p-Bromobenzaldehyde, 689, 694, 696 diacetate, 696... 

Trinitrobromotoluene, (02N)3(Br).C6H.CH3 mw 306.04, N 13.73% Only one isomer is described in-the literature 2,4,6-Trinitro-3-bromotoluene, col ndls(from ale), mp 143 4°, sol in ale, insol in liqroin was first prepd by nitrating 2,4-dinitro -5 bromotoluene and later by diazotizing 2,6 -dinitro-3-bromo-4 aminotoluene(Ref 1). Qvist et al(Ref 2) prepd this compd by nitrating the 5-bromo deriv of o-cymene(isopropyltoluene) and also by nitrating 2,4 dinitro-5-bromotoluene(Ref 3). The trinitrobromotoluene is definitely an expl compd although no investigator has reported its expl props... 

A number of carefully worked out ethanol procedures are available in Organic Syntheses. Collective Volume I, 2nd ed., 1941, contains directions for the deamination of 3-bromo-4-aminotoluene (p. 133) and 3-nitro-4-aminotoluene (p. 415). The conversion of 2,4,6-tribromoaniline to 1,3,5-tribromobenzene is described in Collective Volume II, p. 592 (1943), and directions for deaminating 2-amino-5-iodobenzoic acid are given on p. 353 of the same volume. 

Bromo-4-aminotoluene m-Bromotoluene (54-69%, pure) Cu powder added. 28... 

Problem 23.21 An azo compound is cleaved at the azo linkage by stannous chloride, SnCl2, to form two amines, (a) What is the structure of the azo compound that is cleaved to 3-bromo-4-aminotoluene and 2-methyI-4-aminophenoI (b) Outline a synthesis of this azo compound, starting with benzene and toluene. 

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