4-Bromoacetophenone, oxidation

The preparation of 2-amino-5-arylselenazoles 99 and 3,5-diaryl-1,2,4-selenadiazoles 101 has been described. Starting from readily available a-arylsulfonyl-a-bromoacetophenones 98 reaction with selenourea gave 2-amino-5-arylselenazoles 99 in good yield. Reaction of 98 with selenobenzamide 100 did not give the expected selenazole the 3,5-diaryl-1,2,4-selenadiazole 101 was obtained in moderate yield. Compound 101 is a known oxidation product of selenobenzamide and a mechanism for its formation is proposed <99JHC901>. 

In this route a dihydroisoquinoline (58) is N alkylated with a highly functionalized o -bromoacetophenone (59) to give a quaternary salt (60), which is treated with base and cyclizes to a pyrroloisoquinoline (60). The pyrrole nucleus is then formylated under Vilsmeier-Haack conditions at position 5 and a proximate mesylated phenolic group is deprotected with base to yield a pen-tasubstituted pyrrole (61). Subsequent oxidative cyclization of this formylpyr-role produces the 5-lactone portion of lamellarin G trimethyl ether (36). This sequence allows for rapid and efficient analog synthesis as well as the synthesis of the natural product. 

The synthesis of rofecoxib can be achieved by several different routes (Drugs Fut., 1998). A highly efficient synthesis for rofecoxib was recently described (Therien et al., 2001). As illustrated in Scheme 79, acetophenon (i) is prepared according to the literature, by Friedel-Crafts acylation with thioanisole. Oxidation with MMPP (magnesium monoperoxyphthalate hexahydrate) affords the sulfone (ii), which is reacted with bromine in chloroform in the presence of a trace amount of AICI3, to give (iii). Bromoketone (iii) is than coupled and cyclized in a second step, one-pot procedure with phenylacetic acid. Firstly, the mixture of bromoacetophenone (iii) and phenylacetic acid in acetonitrile is treated with... 

N-Substituted benzotriazole intermediate (77) is an excellant synthon for the synthesis of 2-ethoxy-2-vinylcyclopropanecarboxylate esters (78) [95JOC6], 1-Propargylbenzotriazole was reacted with bromoacetophenone to provide the novel 2-(benzotriazolomethyl)furan (80) in 60% yield [95JOC638]. Annelated N-aminotriazoles, on oxidation, are a good source of cyclic alkynes as illustrated for the reaction of aminotriazolotropone (80) with 4-phenyloxazole to generate the furyl[3,4-cf]tropone (82) from a Diels-Alder intermediate with facile loss of benzonitrile [94TL8421 ]. 

Aryl-4-formylsydnone 4 -phenylthiosemicarbazones 183 were treated with ethyl 2-chloroacetoacetate and 2-bromoacetophenone in buffer systems of sodium acetate and acetic acid, to produce anti-oxidants 2-[(3-arylsyd-non-4-ylmethylene)-hydrazono]-4-methyl-3-phenyl-2,3-dihydrothiazole-5-carboxylic acid ethyl esters 184 and 3,4-diphenyl-2-[(3-arylsydnon-4-ylmethylene)hydrazono]-2,3-dihydrothiazoles 185 in good yields (Scheme 71) <2004BMC4633>. 

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). 

Methyl-1-phthalazinamine 2-oxide (267) with a-bromoacetophenone gave 6-methyl-2-phenylimidazo[2,l-fl]phthalazin-3(57/)-one (268) (EtOH, reflux, 1 h 49% as hydrobromide). 

Asymmetric synthesis of 8-functionalized optically active secondary alcohols was realized hy TarB-N02-catalyzed enantios-elective reduction of a-halo ketones to an intermediate terminal epoxide and sequential ring opening with various nucleophiles. Optically active st)Tene oxide was prepared from a-bromoacetophenone with NaBH4 and TarB-N02 in high yield and with high enantioselectivity (98% 3ueld and 94% ee). fi-Functionalized secondary alcohols could be obtained from the epoxides by nucleophilic attack under appropriate conditions (eq41). 

It was speculated that the catalyhc achvity was a result of the reduction of one palladium(ll) center under the reaction conditions. This palladium center was stabilized as a mixed-valence complex, and entered the catalytic cycle via oxidative addihon of the aryl halide. It was also shown that heterotrimetallic complexes, bearing additional bridging Zn atoms, gave poor conversions and led to the formation of palladium black. A maximum TON of 490 was observed in the reaction of 4-bromoacetophenone with phenylacetylene at 0.2mol% catalyst loading in NEts at 90 °C. An important observahon here was that the addition of Cul did not improve the catalyhc activity rather, the use of this additive caused an overall decrease in the chemical yield. 

For oxidation of 2-hydroxy -methylacetophenone, 2-hydroxy-4-chloroacetoph-enone, and 4-bromoacetophenone by Mn4(P207)3, in aqueous HCIO4 using substrates in excess, the kinetic dependence is of zero order in oxidant and first order in H+ and substrates. The mechanism (Scheme 1) of similar oxidation of phenothiazine (PTZ) derivatives by Mn4(P207)3 in the presence of excess of Mn +, P04 , and H2SO4 postulated the formation of final product 5-oxide either from the hydrolysis of PTZ " (step 3) formed in step 2 or from the disproportionation (step 4) of PTZ+ formed in step 1. The kinetics of step 2, studied in acidic phosphate medium, indicated that the rate was H+ ion dependent but independent of PTZ. The kinetics of step 4, studied in acidic sulfate medium, suggested an inverse dependence on PTZ+ and direct dependence on H+ ion. ... 

The tetrabutylammonium tribromide (TBATB) oxidation of p-substituted acetophenones to a-bromoacetophenone in ACOH-H2O (50% vol/vol) was first order in TBATB and the rate increased with the substrate concentration. The reactive TBATB species was Br3 ion, and its electrophilic attack on acetophenone gave a transition state which decomposed in the rate-determining step. °... 

Obtained by oxidative rearrangement of 5-chloro-2-hydroxy-a-bromoacetophenone in moist DMSO for 16 h at 20° (56%) [4394]. 

A very different behavior was reported for the release of bromoacetophenone from micelles of poly(styrene)-poly(ethyl-ene oxide). The exit rate constant was directly determined from measurements of luminescence intensity in the presence of increasing amount of quencher. The same method had been used to determine exit rate constants of solubilizates from surfactant micelles. The value of k was very large, 9 x 10 s l, indicating a very fast release of the probe from the micelle. 

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