Formylation of amines

Por the formylation of amines with the mixed anhydride of formic and trimethylacetic acid, see Vlietstra, E.J. Zwikker, J.W. Nolte, R.J.M. Drenth, W. Reel. Trav. Chim. Pays-Bas, 1982, 101, 460. 

Other metal carbonyls also catalyze the formylation of amines (90). 

Isocyanides can be reduced to the corresponding hydrocarbon by (TMS SiH. The reaction can be considered as the deamination of primary amines since isocyanides are obtained via formylation of amines and dehydration. The efficiency of the reduction is independent of the nature of the alkyl substituent. That is, primary, secondary and tertiary isocyanides at 80 °C gave the corresponding hydrocarbon in good yields21. An example is given in equation 184. 

Formylation of amines is performed with formic acid/acetic acid anhydride. The application of other mixed anhydrides with acetic acid as well as benzoic acid is less fovorable, because both possible amides will form in varying amounts. 

Formylation of amines and alcohols. Behai,8 discoverer of the reagent, found that it reacts unidirectionally with simple alcohols to produce alkyl formates free from acetates. Hurd et al. J found that acetic-formic anhydride (prepared from formic acid and ketene) reacts quantitatively with aniline to give formanilide. Another study10 established that acetic-formic anhydride mixes endothermally with 2-nitro-2-methyl-l-propanol, exothermally with 2-nitro-2-methyl-l,3-propanediol, and displays no appreciable temperature effect with either 2-nitro-l-butanol or tris-(hydroxymethyl)-nitromethane. Formic esters are favored by avoiding a high reaction temperature and by not using sulfuric acid as catalyst. The mixed anhydride has been used for the preparation of formyl fluoride.11... 

Formylation of amines with ethyl formate is of general preparative value. Largo quantities can be formylated quickly in a steel pressure vessel.—E / -Naphthylamine heated 1 hr. with 10 moles of ethyl formate at 100-110° —> formyl-jd-naphthylamine. Y nearly 100%. (I. P. E. Human and J. A. Mills, Soc. 1948, 1457.)... 

In enzymes, folic acid catalyzes the iV-formylation of amines and the 5-hy-droxymethylation of uracil. None of these reactions has been performed in enzyme-free systems. 

Formamides An improved procedure for the formylation of amines involves... 

Another method for formylation of amines is withp-nitrophenyl formate, which usually gives products in high yield. However, removing the last traces of the p-nitrophenol is difficult. Treating carbon dioxide and amines with EDC gives symmetrical ureas (eq 4). DCC with CO2 at ambient pressure works equally well. 

A green synthetic protocol under solvent-free conditions for the synthesis of phos-phono malonates (162) from alkenes (160) and phosphorous nucleophiles (161) using nanoflake ZnO at 50°C has been documented (Scheme 9.52) (Hosseini-Sarvari and Etmad 2008). The reaction is an example of one of the most powerful and important C-P bond-forming reactions, which is the phospha-Michael addition. The advantages of this method include mild reaction conditions, a simple set up, high yields, and so on. The formylation of amines (163) with formic add (70) under solvent-free... 

Hosseini-Sarvari, M. and Sharghi, H. 2006. ZnO as a new catalyst for N-formylation of amines under solvent-free conditions. J. Org. Chem. 71 6652-6654. 

Formylation of amines, to give formamides, is a special case of acylation and warrants separate comment. Most studies of this reaction have been preparative rather than mechanistic, and although many procedures have been described, the range of applicability seems to be limited. 

V-Formylation. Formylation reactions employing formyl halides or anhydrides are difficult to carry out due to the instability of these reagents. A(-Formyl derivatives have also been used for the formylation of amines, amides, imines, and alcohols, but... 

Nitromethane s. under H(PO H)JOH Acetic formic anhydride Formylation of amines s. 13, 442... 

Ortega N, Richter C, Glorius F (2013) V-formylation of amines by methanol activation. Org... 

Sulphimides have uses in synthesis in addition to the selective or/Ao-formylation of amines and phenols discussed earlier in this chapter (p. Aryl and... 

Scheme 17.2 Zinc catalysed formylation of amines with formic acid.

Several p-block compounds have been employed in this acid-amine coupling reaction these include bismuth, indium and antimony. Indium metal has been found useful for the N-formylation of amines. This reaction requires only 10 mol% indium catalyst and can be used for formic acid reactions with amino alcohols resulting in no side reaction on the alcohol terminus. Electron-rich triarylbismuthanes have been reported to couple carbo>ylic acids to amines within reaction times of 12 hours. In numerous cases, high yields were obtained although little amine scope is explored and in some cases where hindered carbojq lic acids were used, only starting materials were recovered. ... 

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