Formamides with aromatic rings

The reaction with disubstituted formamides and phosphorus oxychloride, called the Vilsmeier or the Vilsmeier-Haack reaction,is the most common method for the formylation of aromatic rings. However, it is applicable only to active substrates, such as amines and phenols. An intramolecular version is also known.Aromatic hydrocarbons and heterocycles can also be formylated, but only if they are much more active than benzene (e.g., azulenes, ferrocenes). Though A-phenyl-A-methyl-formamide is a common reagent, other arylalkyl amides and dialkyl amides are also used. Phosgene (COCI2) has been used in place of POCI3. The reaction has also been carried out with other amides to give ketones (actually an example of 11-14),... 

Formylation of aromatic rings with formamides and POCI3... 

Finally, it s worth mentioning the formamide group. Although this looks like a special case of a secondary amide, rotamers of different intensity are often seen. Compounds with a formamide attached to an aromatic ring can give particularly complex spectra. Not only does the NH proton couple to the CHO proton, with a coupling of about 2-3 Hz in the cis isomer, and 8-9 Hz in the trans isomer, but, any aromatic protons ortho to the formamide are also split out in the rotamers ... 

Siddall (48) also reported that the barriers to rotation in N-substituted N-(2-chloro-6-methylphenyl)formamides (11) were high, but not high enough for the isolation of atropisomers. The exact barriers were not reported but, if one compares them with those in compound 9, the barriers to rotation of these compounds are lowered by the substitution of the chloro group for the methyl on the aromatic ring. 

Ohsaka et al. [393] reported on the preparation by electrochemical oxidation and properties of thin films of 1-naphthylamine in acetonitrile solutions. These films had conductivities of 10 to 10" S cm". Aminocoronene, which consists of seven fused aromatic rings and an amino group, has also been polymerized [394]. Eaves et al. [395] polymerized perfluorocyclopentene in dimethyl formamide in the presence of tetrabutlyammonium perchlorate. The fluorocarbon polymers could exhibit enhanced environmental stability in comparison with hydrocarbon polymers. 

The Vilsmeier reaction, whereby amides are converted to highly electrophilic imi-nium ions, which may then react with carbonyl compounds or weakly nucleophilic groups such as aromatic rings, has long been known. Comprehensive reviews on carbonic acid derivatives obtained from formamides are available [1295-1297]. In a wider sense, these derivatives belong to the chemistry of formaldehyde. 

A likely pathway is also that in which the key stage is the addition of the second formamide molecule to the carbonyl group of the intermediate 157 to form the amide 159. The latter, with loss of water, closes the dihydropyrimidine ring 160, which undergoes aromatization to 4-metylpyrimidine via 1,4-hydrogen shift and decarbonylation. 

The spirane ring is formed by treating amides derived from 16 with formamide and reducing the product.(20,56) In the solid state the 4-NPh moiety adopts an equatorial rather than an axial conformation in relation to the piperidine ring,(57) akin to the solid and probable solute state conformation of fentanyl, for which there is X-ray<58) and H-nmr evidence (see 20). The activities of the spiranes 19 also provide evidence that anilido phenyl is a- rather than /3-oriented in active conformations of fentanyl derivatives (21). This aromatic feature is confined to the /3-orientation in the bicyclo analogs 22, neither of... 

Barrett and co-workers adapted ring-opening metathesis polymerization (ROMP) to prepare the ROMPgel TosMlC reagent 1621 (Scheme 1.414, p. 364). Thus copolymerization of the norbornene-derived formamide 1620 with norbor-nene in the presence of Grubbs s catalyst" gave 1621 in quantitative yield after dehydration. Aromatic aldehydes react with 1621 in the presence of a strong... 

Oxazole itself participates as a dienophile in a Diels-Alder reaction with the electron-dehcient 3,6-bis(trifluoromethyl)-l,2,4,5-tetrazine 94 to give A-[3,6-bis-(trifluoromethyl)-pyridazin-4-yl]formamide 96 in 80% yield after 55 h in refluxing toluene (Fig. 3.25). The reaction is postulated to proceed via initial cycloaddition followed by loss of nitrogen to give 95. Ring-opening aromatization of 95 then gave 96. 

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