Blanc chloromethylation

Lewis acid-promoted chloromethyl group installation onto the aromatics rings with 1,3,5-trioxane and HCl. 

Gustave Louis Blanc (1872—1927), bom in Paris, France, studied under Charles Friedel in Paris. He developed the chloromethylation of aromatic hydrocarbons while he was a director at the Intendance mih-taire aux Invalides. 

Tolgyesi, W. S. In Friedel—Crafts and Related Reactions vol. 11, Part 2, Olah, G., Ed. Interscience New York, 1963, pp 659-784. (Review). 

Franke, A. Mattern, G. Traber, W. Helv. Chim. Acta 1975, 58. 283. 

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Benzilic acid rearrangement Benzoin reaction (condensation) Blanc chloromethylation reaction Bouveault-Blanc reduction Bucherer hydantoin synthesis Bucherer reaction Cannizzaro reaction Claisen aldoi condensation Claisen condensation Claisen-Schmidt reaction. Clemmensen reduction Darzens glycidic ester condensation Diazoamino-aminoazo rearrangement Dieckmann reaction Diels-Alder reaction Doebner reaction Erlenmeyer azlactone synthesis Fischer indole synthesis Fischer-Speior esterification Friedel-Crafts reaction... 

Diphenyltellurophene treated with formaldehyde and hydrogen chloride in glacial acetic acid yielded 3,4-bis[chloromethyl]-2,5-diphenyltellurophene (Blanc chloromethylation)6. 

Blanc (chloromethylation) reaction. Introduction of the CLLjCl group into aromatic rings on treatment with formaldehyde and hydrochloric acid in the presence of zinc chloride. 

Benzilic acid rearrangement Benzoin reaction (condensation) Blanc chloromethylation reaction Bouveault-Blanc reduction Bucherer hydantoin synthesis. Bucherer reaction. . ... 

Other references related to the Blanc chloromethylation are cited in the literature. ... 

This reaction is closely related to the Blanc Chloromethylation. 

In 1932, Quelet used the Blanc procedure, replacing formaldehyde with aliphatic aldehydes in the reaction with phenolic ethers. The resulting reaction mixtures were found to contain a-chloroalkyl derivatives. Although the conditions are virtually identical and the reaction proceeds via the same basic mechanism, the Blanc chloromethylation is often referred to as the Quelet reaction. 

For a more thorough discussion of the history of the Blanc chloromethylation, its scope and limitations as well as its use in synthesis prior to 1963, the reader is directed to excellent reviews by Fuson and McKeever and Olah and Tolgyesi. ... 

Issues of regioselectivity in the Blanc chloromethylation and related Friedel-Crafts reactions have been studied extensively. As is common with a majority of electrophilic aromatic substitution reactions, substitution typically occurs ortho or para to electron-donating substituents, with issues of steric strain playing a role in the relative ratio of ortho and para products. The Blanc reaction is t3q)ically somewhat regioselective, favoring the para-isomer but accompanied by lesser amounts of the ortho product. ... 

Owing to their high electron density, furans have been especially useful in the Blanc chloromethylation. In particular, Pevzner and coworkers have recently published numerous papers using this combination of reactants. Directed toward the synthesis of dialkoxyphosphorylmethyl derivatives of furans, introduction of a chloromethyl side chain was envisioned to proceed through the Blanc reaction. Thus treatment of 22... 

Benzothiophenes have also found utility in the Blanc chloromethylation, especially in the area of medicinal chemistry. " As demonstrated by Cross and co-workers during their efforts toward the synthesis of selective thromboxane synthetase inhibitors, treatment of 33 under the standard conditions resulted in 34. While benzothiophene typically substitute preferentially at C-3, in this case the methyl at C-3 forces substitution to occur at C-2. 

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