2-Bromo-4 -bromoacetophenone

Photolysis of 3-phenyl-2,l-benzisoxazole in 48% HBr produced reduction and substitution products via a proposed triplet state nitrenium ion intermediate (71HCA2111). Photolytic decomposition of 5-bromo-3-phenyl-2,l-benzisoxazole in 48% HBr gave 2-amino-5-bromoacetophenone and 2-amino-3,5-dibromoacetophenone (Scheme 18). A nitrenium ion intermediate was also proposed for the photolytic decomposition of 3-phenyl-2,l-benzisoxazole in concentrated HCl (Scheme 19) (7IHCA2111). 

Nuclear halogenation of acetophenone depends on formation of the aluminum chloride complex. If less than one equivalent of aluminum chloride is used, side-chain halogenation occurs. 3-Bromoacetophenone has been prepared from 3-aminoaceto-phenone by the Sandmeyer reaction. The synthesis described here has been taken from work of the submitters, who have used it to prepare many 3-bromo- and 3-chloroacetophenones and benzaldehydes, as well as more highly halogenated ones (Notes 7 and 8). 

Theophylline is reacted first with 1 -bromo-3-chloropropanetogivechloropropyl theophylline, then with benzylamine to give benzylaminopropyltheophylline. That is reacted with 3,5-di-hydroxy-CJ-bromoacetophenone to give the starting material. 

The SET mechanism is chiefly found where X = I or NO2 (see 10-104). A closely related mechanism, the SrnE takes place with aromatic substrates (Chapter 13). In that mechanism the initial attack is by an electron donor, rather than a nucleophile. The Srn 1 mechanism has also been invoked for reactions of enolate anions with 2-iodobicyclo[4.1.0]heptane. An example is the reaction of l-iodobicyclo[2.2.1]-heptane (15) with NaSnMe3 or LiPPh2, and some other nucleophiles, to give the substitution product. Another is the reaction of bromo 4-bromoacetophenone (16) with Bu4NBr in cumene. " The two mechanisms, Sn2 versus SET have been compared and contrasted. There are also reactions where it is reported that radical, carbanion, and carbene pathways occur simultaneously. ... 

Jegou and Jenekhe [63] have developed a different approach toward di-ethynylated quinoline monomers, as shown in Scheme 10. Reaction of 2-amino-5-bromobenzophenone with 4-bromoacetophenone gave 6-bromo-2-(4 -bro-mophenyl)-4-phenylquinoline, which was alkynylated and deprotected ac-... 

Similar decomposition is observed in p-bromoacetophenone, o-bromo-, p-bromo, and p,p -dibromobenzophenone, and p-iodobenzophenone44 but not in the fluoro- and chloro-substituted compounds. This order of reactivity follows the bond dissociation energies for aromatic halides which are about 90 kcal/mole for chlorobenzene, 70 kcal/mole for bromobenzene, and 60 kcal/ mole for iodobenzene. The lowest-lying triplet of p-bromoacetophenone is 71.2 kcal45 while that of the substituted benzophenones is slightly lower since benzophenone itself has a lower triplet energy than acetophenone. p,p Dibromobenzophenone was the least reactive of the compounds that photoeliminated halogen atoms. 

Reduction of oj.-bromoacetophenone gave the corresponding bromo-hydrin in 85% yield.6 Smooth reduction, also occurred with chloral2-16 and bromal.6 However, a-bromopropiophenone 44 gave only 35 to 42% yields of the bromohydrin the remainder of the product was halogen-free, consisting of a mixture of benzylmethylcarbinol and some ethers. 

The photostimulated carbonylation of aryl and vinyl halides by Co(CO)4" ions under phase-transfer catalysis conditions [Co2(CO)8, C6H6/NaOHaq, CO, Bu4N+Br", 65 °C] has been reported211,212. Thus PhBr, o- and /7-bromo toluenes, /7-bromoanisole, p-bromofluorobenzene, 4-bromoacetophenone and 1- and 2-bromonaphthalenes gave ArC02Na in 90-98% yields. Under the conditions used, carbonylation did not occur with unsubstituted PhCl, but when it was substituted, as in / -chlorobenzoic acid, or p-chlorophenylacetic acid, carbonylation was quantitative (98% yield). 

Mixed Aliphatic-aromatic Ketone Arsinic Acids. —These compounds are formed by the interaction of bromine-substituted mixed aliphatic-aromatic ketones, such as 4-bromoacetophenone or. S-amino-4-bromo-acetophenone, with arsenites in hot solution. 

The oxidants dimethyl sulfoxide and nitroso compounds react easily with oL-bromo ketones and convert them into a-dicarbonyl compounds. The reaction with nitroso compounds is usually carried out in the presence of pyridine and proceeds through a nitrone stage. Phenacyl bromide (a-bromoacetophenone) is thus transformed first into phenacylpyridinium bromide and further, with nitrosobenzene, into a-ketoaldonitrone, which is subsequently treated with hydroxylamine to give phenylglyoxal monoxime or with phenylhydrazine to give phenylglyoxal osazone [985] (equation 411). 

A direct and simpler conversion of w-bromoacetophenone into phenylglyoxal is achieved by treatment with dimethyl sulfoxide at room temperature [1003], The reaction of a-bromo ketones with dimethyl sulfoxide can be carried out in anhydrous medium [1003], as well as in the presence of water [1001], The mechanism of the reaction in aqueous medium is more... 

---