Anthracene derivatives, Bradsher

As alluded (vide supra), some confusion may arise with respect to this named reaction as there is reference in the literature to an alternative reaction with the same name. The Bradsher reaction forms aromatic rings but via an acid-catalyzed Friedel-Crafts-like process. Thus diaryl-methanes having a carbonyl group in the ortho position can undergo a cyclodehydration reaction to generate the corresponding anthracene derivatives. In this respect, the Bradsher reaction is related to the Elbs reaction, which involves the pyrolytic cyclization of diaryl ketones 6 having an ortho methyl or methylene substituent for the formation of polycyclic aromatics 7. 

Early reports from the Bradsher group highlighted new routes to anthracene derivatives iP In the event, conversion of chloride 49 to ketone 6 was accomplished by treatment with cuprous cyanide followed by 1,2-addition of a Grignard reagent. The cyclized product 7 was obtained by heating with hydrobromic acid. It was reported later that liquid sulfur dioxide as solvent was effective in facilitating the aromatic cyclodehydration. " ... 

The acid-catalyzed cyclization of an acyl substituted diarylalkane 1 into a cyclic carbinol 2, followed by a 1,4-dehydration to produce anthracene derivative 3, is known as the Bradsher Reaction. ... 

Bradsher proposed that the mechanism initially involved reversible addition of the proton to the carbonyl group of 1 to form 7, followed by intramolecular Friedel-Crafls-type electrophilic attack on the aryl ring by the positively charged species in 8.2,5,13-15 Restoration of aromaticity through proton loss from 9 followed by acid-catalyzed 1,4-dehydration of carbinol 2 furnished the anthracene derivative 3. 

Yamato and co-workers introduced dichloromethyl methyl ether in the presence of titanium tetrachloride as a reagent for one-pot formylation followed by in situ Bradsher cyclization. In this way anthracene regioisomers 25 and 26 were obtained from diaryImethane 24 in good yield. The initially formed anthracene derivative presumably reacts with excess dichloromethyl methyl ether to yield 9- or 10-formylanthracene derivative 25 or 26. 

For many years applications of the Bradsher reaction were restricted due to its limited substrate scope and requirement for harsh reaction conditions. However, after the advancement of the arene oxide concept concerning the metabolism of polycyclic aromatic hydrocarbons, synthesis of all the nuclear monohydroxylated derivatives of 7,12-dimethylbenz[a]-anthracene (DMBA), diol epoxide metabolites of DMBA, and fluoro derivatives of DMBA was undertaken for carcinogenicity and mutagenicity determination studies. " Interest in the Bradsher reaction has increased greatly as a consequence of the need to construct these polycyclic aromatic hydrocarbons. Development of fluoroanthracenylmethyl cinchonidine as an efficient phase-transfer catalyst for asymmetric glycine alkylation also expanded the scope of the Bradsher reaction. ... 

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