Duff reaction

The Duff reaction is a formylation method normally used for electron-rich aromatics such as phenols and aromatic amines with the formylating agent being hexamethylenetetramine in the presence of glycerol or acetic acid. Conditions are rigorous and the yields are generally low, but the main value is the occurrence of mainly 

Kreutzberger et used the HCI/AICI3 system to produce aldehydes in good yield 

Using this method for substituting aluminum trichloride with hydrofluoric acid, trifluoromethoxy benzene (CeHsOCFs) is formylated in excellent yield and para-selectivity 

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).  

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Hydroxy benzo[6]thiophene-4-carboxaldehyde, which is prepared from 5-hydroxybenzo[6]thiophene by the Duff reaction 338 or, better, by a modified Gattermann reaction,340 reacts with diethyl bromo-malonate to give the thienobenzofuran (282), and undergoes the Perkin reaction to give the thienobenzo-a-pyrone (283).338... 

Duff reaction (1, 430). Review. In the clastical procedure highly activated aromatic compounds are converted into their formyl derivatives by treatment with hexamethylenetetramine and glyceroboric acid yields are generally low. Smith finds that a variety of aromatic compounds, including simple hydrocarbons, when treated with hexamethylenetetramine in conjunction with trifluoroacetic acid al reflux temperature (82- 90") arc converted into i mine products which yield aldehydes on hydrolysis ... 

Duff reaction. A new application is the mono- and diformylation of 4-substituted... 

Duff reaction. Hexamine condenses with a phenol in the ortho position to give a Schiff base which on hydrolysis yields the o-hydroxy aldehyde ... 

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