Sommelet reaction mechanism

It is interesting that the alternative allowed five-center Sommelet reaction often dominates, when it can compete with the Stevens rearrangement. Since systems such as these often become much more complex than we have shown (Lepley and Giumanini, 1967), these mechanisms should be reappraised in each new application. 

Note 6. The ice must be made from metal-free water see Note 4. The washing is to remove the concentrated acid mother liquor. If the pH is too low during the next step, the hexamine will merely hydrolize more rapidly than it will be quatemized by the chloromethyl compound. The mechanism of the Sommelet reaction has been... 

In 1913, Marcel Sommelet (1877-1952) of the Faculty de Pharmacie of Paris University published his seminal article in Comptes Rendus with the title Decomposition of Alkyl Halide Addition Products of Hexamethylenetetramine, where he delineated the formation of aldehydes by treatment of benzyl halides followed by hydrolysis.4,5 In 1954, S. J. Angyal published a review in Organic Reactions, where he summarized the mechanism, scope, and limitations of the Sommelet reaction.1 Angyal s review ignited a flurry of research and the Sommelet reaction became a well-known standard for the transformation of benzyl halides to the corresponding benzaldehydes. 

The hasubanan skeleton (243) has been prepared in 90% yield by the alkylation of the amine (242) with formaldehyde and formic acid the synthesis resembles the Sommelet reaction and the authors offer the plausible mechanism shown. 

A modern adaptation uses trifluoroacetic acid as catalyst. That allows for formylation of aromatics such as toluene and xylene and even electron deficient phenols such as 2,4-difluorophenol under mild conditions in good yields.A high order of para regioselectivity is exhibited even for phenols.The mechanism involves fast aminomethylation followed by a rate-determining dehydrogenation step to the imine similar to that observed in the Sommelet reaction hydrolysis then gives the aldehyde (Eq 1.42). ... 

Otter et al. (89JHC1851) obtained the thienopyrimidine 253 in 50% yield by heating 5-(2-propynylthio)pyrimidine 248 in DMSO at 145°C. The reaction proceeds via a Claisen rearrangement of 248 in the allene 249, which then cyclizes to the product 253. An 18% yield of the thiomethyl compound 252 was also isolated. This was explained by a mechanism involving solvent incorporation into allene 249 to give intermediate 250 this intermediate then undergoes a Sommelet-Hauser type of rearrangement to afford 251, which cyclizes to the product 252. 

However, he did not understand the nature of the third stage. He tentatively suggested that the reaction occurred by shift of the double bond in ArCH2NH=CH2 (5) to give ArCH2=NHCH3 (6), which in turn was hydrolyzed to benzaldehyde and methylamine. Quickly, Sommelet realized that the mechanism was not tenable and recognized the... 

The mechanism of the Gassman indole synthesis bears some resemblance to that of the Fischer indole reaction. An Sn2 displacement of the TV-chlorinated aniline with the a-keto sulfide gives rise to a sulfonium ion. After deprotonation, a [2,3]-sigmatropic rearrangement (Sommelet-Hauser rearrangement) takes place where the weak N-S bond is broken and a strong C-C bond is formed. Similar to the Fischer indole reaction, the resulting imine was transformed into indole after re-aromatization and cyclization. 

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