Acetophenone chlorination

A three-step process involving the oxidation of acetophenone, hydrogenation of the ketone to a-phenylethanol, and dehydration of the alcohol to styrene was practiced commercially by Union Carbide (59) until the early 1960s. Other technologies considered during the infancy of the styrene industry include side-chain chlorination of ethylbenzene followed by dehydrochlotination or followed by hydrolysis and dehydration. 

Thus, reduction of the Mannich reaction product (65) from acetophenone leads to alcohol 66. Replacement of the hydroxyl group by chlorine (67) followed by displacement of halogen with the anion from o-cresol affords the ether 68. Removal of one of the methyl groups on nitrogen by means of the von Braun reaction or its modem equivalent (reaction with alkyl chloroformate followed by saponification) leads to racemic 69 which is then resolved with L-(+)-mandelic acid to give the levorotary antidepressant tomoxetine (69) [16]. 

Acetophenone bromination to 3 bromo acetophenone, 40,9 chlorination to 3 chloroacetophenone 40,9... 

Havel J, W Reineke (1993) Microbial degradation of chlorinated acetophenones. Appl Environ Microbiol 59 2706-2712. 

Higson FK, DD Focht (1990) Bacterial degradation of ring-chlorinated acetophenones. Appl Environ Microbiol 56 3678-3685. 

The above procedure2 is modeled after that described for the nitrosation of arylethyl ketones.4-5 w-Chloroisonitroso-acetophenone has been prepared by the chlorination of isonitro-... 

In the flask are placed 240 g. (2 moles) of acetophenone and 1 1. of glacial acetic acid. The thermometer is adjusted so that it extends considerably below the surface of the solution, and chlorine is admitted at such a rate that the temperature does not exceed 60° (Note 1). Chlorination is continued until an excess of the halogen has been absorbed. This requires about five hours completion of the reaction is indicated by the development of a yellow color. The reaction mixture is poured over 6 1. of crushed ice in a 2-gal. jar. The mixture is stirred several times (Note 2) and allowed to stand until the ice has melted. The dichloroacetophenone, which separates as a heavy lachrymatory oil, is removed. The yield is 340-370 g. (90-97 per cent of the theoretical amount). This product, containing only a few per cent of water and acetic acid, is pure enough for the preparation of mandelic acid. It may be purified by adding about 100 cc. of benzene, removing the... 

According to Beilstein (VII, 283) trichloroacetophenone is obtained by chlorination of acetophenone at elevated temperatures.1 However, at 60° less than 1 per cent of trichloroacetophenone is formed. 

Dichloroacetophenone has been prepared by chlorination of acetophenone with and without aluminum chloride 1 by action of dichloroacetyl chloride upon benzene and aluminum chloride 1 by action of hypochlorous acid upon phenylacetylene 2 by heating trichloromethylphenylcarbinol 3 and by chlorination of phenylacetylene in alcohol.4... 

In 1978, Bergmark determined that photorelease can also take place when the a-position of an o-methyl acetophenone has a good leaving group, such as a chlorine atom. ° He showed that photolysis of 33 in benzene resulted in the formation of 36, whereas in methanol, both 36 and 37 were formed (Scheme 24). In 1985, Bergmark followed up his earlier work with a more detailed study and showed that the elimination of a chorine atom from 33 took place in high quantum yields, especially in methanol. Thus, Bergmark concluded that both E-34 and Z-34 released their chlorine atoms. Additionally, he theorized that the release from Z-34 took place via solvolysis to from carbocation 35. 

The quantitative solid-state reaction of Viehe salt (100) with acetophenone (328b) by stoichiometric comilling at 0 °C leads to the highly labile iminium salt 435 and the couple product 436 [9]. A 4-cascade is assumed consisting of substitution (Cl by enol-C of328b), reaction of the oxygen with a second molecule of 100, chlorine migration, and elimination of 436. 

Although 2,4-dichloro-6-ethyl-5-fluoropyrimidine (13) contained the correct carbon skeleton for condensation with the acetophenone, only self-condensation products were obtained following metallation with LDA. A reduction in electrophilicity was achieved by removal of the 2-chloro substituent via a three-step sequence involving hydrolysis of the more reactive 4-chloro substituent, followed by hydrogenation of the 2-chlorine and rechlorination with phosphorous oxychloride. The overall yield for the three steps resulting in 4-chloro-6-ethyl-5-fluoropyrimidine (14) was 72%. 

Most of the phenol used in the United States is made by the oxidation of cumene, yielding acetone as a byproduct. The first stqn in the reaction yields cumene hydroperoxide, which decomposes with dilute sulfuric acid to the primary products, plus acetophenone and phenyl dimethyl carbinol. Other processes include sulfonation, chlorination of benzene, and oxidation of benzene. The compound is purified by rectification. 

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