Blanc chloromethylation

The Blanc chloromethylation (also called the Blanc reaction) is the chemical reaction of aromatic rings with formaldehyde and hydrogen chloride catalyzed by zinc chloride or other Lewis acid to form chloromethyl arenes. The reaction was discovered by Gustave Louis Blanc (1872-1927) in 1923. The reaction is performed with care as, like most chloromethylation reactions, it produces highly carcinogenic bis(chloromethyl) ether as a by-product. The Blanc chloromethylation (also called the Blanc reaction) is the chemical reaction of aromatic rings with formaldehyde and hydrogen chloride catalyzed by zinc chloride or other Lewis acid to form chloromethyl arenes. The reaction was discovered by Gustave Louis Blanc (1872-1927) in 1923. The reaction is performed with care as, like most chloromethylation reactions, it produces highly carcinogenic bis(chloromethyl) ether as a by-product. The reaction is carried out under acidic conditions and with a ZnCl2 catalyst. These conditions protonate the formaldehyde carbonyl making the carbon much more electrophilic. The aldehyde is then attacked by the aromatic pi-electrons, followed by rearomatization of the aromatic ring. The benzyl alcohol thus formed is quickly converted to the chloride under the reaction conditions. Other possibilities for the electrophile include (chloromethyl)oxonium cation (ClH2C–OH2+) or chlorocarbenium cation (ClCH2+), which may be formed in the presence of zinc chloride. These species may account for the fact that moderately and strongly deactivated substrates that are inert to Friedel-Crafts reactions like acetophenone, nitrobenzene and p-chloronitrobenzene do show marginal reactivity of limited synthetic utility under chloromethylation conditions. Deactivated substrates give better results under modified chloromethylation conditions using chloromethyl methyl ether (MOMCl) in the presence of 60% H2SO4. Highly activated arenes like phenols and anilines are not suitable substrates, since they undergo further electrophilic attack by Friedel-Crafts alkylation with the formed benzylic alcohol/chloride in an uncontrolled manner. In general, the formation of diarylmethane side product is a common outcome.