Org. Synth. 1925, 5, 17
DOI: 10.15227/orgsyn.005.0017
[Acetophenone, p-bromo-]
Submitted by Roger Adams and C. R. Noller.
Checked by J. B. Conant and C. R. Kinney.
1. Procedure
In a 5-l. round-bottomed, three-necked flask, fitted with a mechanical stirrer, separatory funnel, and reflux condenser connected with a gas absorption trap (Fig. 7 on p. 97) for disposing of the evolved hydrogen chloride, is placed 392 g. (2.5 moles) of bromobenzene in 1-l. of dry carbon disulfide (Note 1). To this is added 750 g. (5.6 moles) (Note 2) of anhydrous aluminum chloride. The mixture is heated on a steam bath until gentle refluxing starts, and then 204 g. (2 moles) of acetic anhydride (Note 3) is added slowly through the dropping funnel. The time of addition is about one hour. Gentle refluxing should be continued throughout the time of addition of the anhydride and for one hour afterward. The reaction is accompanied by a copious evolution of hydrogen chloride which does not entirely cease even after this subsequent heating.
A condenser is attached to one of the side necks, and the carbon disulfide is distilled without removing the flask from the steam bath. After the removal of the solvent (Note 4), the reaction mixture is allowed to cool somewhat (Note 5); but while it is still warm, it is poured slowly with stirring over cracked ice to which hydrochloric acid has been added. In this way only a small amount of the aluminum chloride addition product remains in the flask. This is decomposed with ice and hydrochloric acid and added to the main product. The volume is now about 5 l. Each 2-l. portion is extracted twice with 300-cc. and 200-cc. portions of benzene or ether. The extracts are combined and washed twice with water, once with 10 per cent sodium hydroxide solution, and twice more with water. The final water washings should be practically colorless and the separation sharp, any precipitate being allowed to separate with the water.
The extract is dried for one hour with about 30 g. of calcium chloride and filtered, and the solvent is distilled from a steam bath. The residue is distilled under reduced pressure with a short column (p. 130). Some low-boiling material comes over first, and then the temperature rises rapidly. If care has been taken in the water decomposition to remove all the aluminum salts (Note 6), the product comes over water-white and crystallizes to a white solid melting at 49–50.5°. The yield is 340–395 g. (69–79 per cent of the theoretical amount) of a product boiling over a 3° range (Note 7) and (Note 8). On redistillation the boiling point is 117°/7 mm.; 129–130°/15 mm.; and 255.5°/736 mm.
2. Notes
1. If the carbon disulfide-bromobenzene solution is not clear it should be dried over calcium chloride and filtered before the aluminum chloride is added. In using such large amounts of carbon disulfide, particular precautions must be taken to prevent fires.
2. The aluminum chloride should be added in about this excess. When the excess is larger the yield does not seem to be increased, and when only 2 equivalents are used it is diminished by 10 to 15 per cent.
3. The acetic anhydride should boil at 136–139°. Some commercial grades are satisfactory, whereas others have been found to contain almost 50 per cent of acetic acid.
4. About 600–800 cc. of carbon disulfide is recovered and may be used in the next run.
5. If the product is allowed to come to room temperature before decomposition with water, it becomes semi-solid and is not easily removed from the flask.
6. If the aluminum chloride double compound is not entirely decomposed by water and the aluminum salts thus removed, the distillate comes over slightly red and does not crystallize well on cooling. Redistillation, however, gives a pure product.
7. This method is an improvement over the older methods for the preparation of substituted acetophenone derivatives. The yields obtained by the use of acetyl chloride in place of acetic anhydride in the preparation of p-bromoacetophenone were invariably lower.
The yield is based on the bromobenzene, because a side reaction between the acetic acid, aluminum chloride, and bromobenzene also produces some ketone.
8. Under the same general conditions, satisfactory yields of other acetophenones may be obtained. Thus, from 281 g. of chlorobenzene, 750 g. of aluminum chloride, and 205 g. of acetic anhydride, a consistent yield of 285–300 g. (74–78 per cent of the theoretical amount) of p-chloroacetophenone, boiling at 124–126° /24 mm. and melting at 20–21°, is obtained. Similarly, acetophenone may be obtained in 76–83 per cent yields, p-methylacetophenone in 85–89 per cent yields, and p-methoxyacetophenone in 90–94 per cent yields.
3. Discussion
p-Bromoacetophenone can be prepared by the action of acetyl chloride in carbon disulfide on bromobenzene in the presence of anhydrous aluminum chloride,1 and by the use of acetic anhydride in place of the acetyl chloride.2

References and Notes
  1. Schweitzer, Ber. 24, 550, 3766 (1891); Hale and Thorp, J. Am. Chem. Soc. 35, 266 (1913).
  2. Noller and Adams, ibid. 46, 1892 (1924).

Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)

carbon disulfide-bromobenzene

calcium chloride (10043-52-4)

hydrogen chloride,
hydrochloric acid (7647-01-0)

acetic acid (64-19-7)

Benzene (71-43-2)

ether (60-29-7)

acetic anhydride (108-24-7)

sodium hydroxide (1310-73-2)

acetyl chloride (75-36-5)

aluminum (7429-90-5)

Acetophenone (98-86-2)

chlorobenzene (108-90-7)

aluminum chloride (3495-54-3)

bromobenzene (108-86-1)

carbon disulfide (75-15-0)

Acetophenone, p-bromo- (99-90-1)

p-Chloroacetophenone (99-91-2)

p-Methylacetophenone (122-00-9)

p-Methoxyacetophenone (100-06-1)