O-chloroacetophenones

To a solution of 279 g of o-chloroacetophenone in 2 liters of anhydrous diethyl ether were added about 3 g of dibenzoyl peroxide. 5 g of bromine were added to the resulting solution, and after 3 minutes, the color of bromine had been discharged, indicating that the formation of oj-bromo-o-chloroacetophenone had been initiated. A further amount of 288 g of bromine was added dropwise to the reaction mixture over a VA hour interval. After the addition of the bromine had been completed, the reaction mixture was stirred for one-half hour and poured over about 1 kg of crushed ice. 

A solution of 400 g of oj-bromo-o-chloroacetophenone in one liter of methanol was cooled to about 25 C. A cold solution of 92.5 g of sodium borohydride in one liter of methanol was added as rapidly as possible to this cooled solution while maintaining the temperature... 

As described in U.S. Patent 2,308,232, 100 g 3,4-dihydroxy-o -chloroacetophenone, 200 cc ethyl alcohol and 200 cc of about 50% aqueous isopropylamlne solution are boiled during 3 hours on the water bath with the use of a reflux condenser, whereupon neutralizing with diluted sulfuric acid is carried out and the sulfate, obtained upon cooling, from alcohol of 50% is recrystallized its MP is 245°C. 

A solution of 400 g of co-bromo-o-chloroacetophenone in one liter of methanol was cooled to about 25°C. A cold solution of 92.5 g of sodium borohydride in one liter of methanol was added as rapidly as possible to this cooled solution while maintaining the temperature below about 25°C. After the addition had been completed, the reaction mixture was allowed to stand for 4 hours at ambient room temperature, to complete the reduction of the keto group of the (o-bromo-o-chloroacetophenone. The reaction mixture containing a mixture of o-chlorophenyl ethylene-p-bromohydrin and o-chlorophenyl ethylene oxide was then evaporated in vacuo at room temperature to a syrup which was poured into about one liter of 5% hydrochloric acid to decompose any borate-alcohol complexes. 

The method is especially valuable for the preparation of certain substituted acetophenones, namely, o- and p-nitroacetophenone and o-chloro-acetophenone. Methods involving Grignard, Friedel-Crafts, or nitration reactions are apparently not applicable for the preparation of these nitro compounds, and the Friedel-Crafts reaction is not applicable to the preparation of o-chloroacetophenone. Although the acetoacetic ester synthesis has been used for the preparation of these and other substituted acetophenones, it may be complicated by O-acylation and also by cleavage at either acyl group (cf. method 212). 

The oven-all yields are stated to be 13-20% from the acid chloride however, the directions are not clear. If the chloride of a dibasic acid is used, a diketone results. Thus, terephthalic acid chloride gives p-diacetylbenzene (15% over-all). o-Chloroacetophenone, a halo ketone, has been prepared from ethyl acetoacetate and o-chlorobenzoyl chloride... 

A special case, leading directly to 3-hydroxy-2-aroylbenzofurans or 3-hydroxy-2-acylbenzofurans (238), is the ring closure (NaH) of 2-aroyloxy-o)-chloroacetophenones or 2-acyloxy-co-chloroacetophen-... 

Husain, K., Kumar, R, and Malhotra, R.C., A comparative study of biochemical changes induced by inhalation of aerosols of o-chloroacetophenone and dibenz (b,f)-... 

Lithium selenide reacts with o-chloroacetophenone in aprotic medium to give unexpectedly a significant amount (25%) of selenoindoxyl <88TL6ll9>. Reaction of HjSe with ketoepoxide (61) gives 12% of the selenolane derivative besides a tetrahydroselenopyran derivative (Equation (17)) <91ZOR942>. 

Scheme 8.11 Pd-catalyzed a-arylation of o-chloroacetophenones with o-dibromobenzenes [33].

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