Other Formylations

Other Formylations. Formyl fluoride, the only known stable formic acid derivative, can be used to perform Friedel-Crafts-type acylation to form aromatic aldehydes. The method was developed by Olah and Kuhn.105 Although a number of Lewis acids may be used, BF3 is the best catalyst. It is dissolved in the aromatic compound to be formylated then formyl fluoride is introduced at low temperature and the reaction mixture is allowed to warm up to room temperature. The aldehydes of benzene, methylbenzenes, and naphthalene were isolated in 56-78% yields. Selectivities are similar to those in the Gattermann synthesis ( toiuene benzene = 34.6, 53.2% para isomer). The reacting electrophile was suggested to be the activated HCOF BF3 complex and not the free formyl cation. Clearly there is close relationship with the discussed CO—HF—BF3 system. 

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The formylation of a phenol 1 with chloroform in alkaline solution is called the Reimer-Tiemann reaction. It leads preferentially to formation of an ortho-formylated phenol—e.g. salicylic aldehyde 2 —while with other formylation reactions, e.g. the Gattermann reaction, the corresponding /jara-formyl derivative is obtained as a major product. The Reimer-Tiemann reaction is mainly used for the synthesis of o-hydroxy aromatic aldehydes. 

The applicability of the Reimer-Tiemann reaction is limited to the formylation of phenols and certain reactive heterocycles like pyrroles and indoles. Yields are usually below 50%. In contrast to other formylation procedures, the Reimer-Tiemann reaction is ort/zo-selective it is therefore related to the Kolb e-Schmitt reaction. 

Besides 11-15-11-17, several other formylation methods are known. In one of these, dichloromethyl methyl ether formylates aromatic rings with Friedel-Crafts catalysts.The Compound ArCHClOMe is probably an intermediate. Orthoformates have also been used. In another method, aromatic rings are formylated with... 

At high pressures the presence of the H02 radical also contributes via HCO + H02 — H202 + CO, but H02 is the least effective of OH, O, and H, as the rate constants in Appendix C will confirm. The formyl radical reacts very rapidly with the OH, O, and H radicals. However, radical concentrations are much lower than those of stable reactants and intermediates, and thus formyl reactions with these radicals are considered insignificant relative to the other formyl reactions. As will be seen when the oxidation of large hydrocarbon molecules is discussed (Section H), R is most likely a methyl radical, and the highest-order aldehydes to arise in high-temperature combustion are acetaldehyde and propionaldehyde. The acetaldehyde is the dominant form. Essentially, then, the sequence above was developed with the consideration that R was a methyl group. 

Besides 1-15 to 1-17, several other formylation methods are known.302 In one of these, dichloromethyl methyl ether formylates aromatic rings with Friedel-Crafts catalysts.303 ArCHClOMe is probably an intermediate. Orthoformates have also been used.304 In another method, aromatic rings are formylated with formyl fluoride HCOF and BF3.305 Unlike formyl chloride, formyl fluoride is stable enough for this purpose. This reaction was successful for benzene, alkylbenzenes, PhCl, PhBr, and naphthalene. Phenols can be regioselectively formylated in the ortho position in high yields by treatment with two equivalents of paraformaldehyde in aprotic solvents in the presence of SnCL and a tertiary amine.306 Phenols... 

TIPSOCHjSEt, CuBrj, BU4NBL 4-A molecular sieves, CH2CI2,89-98% yield. This method can also be used to prepare a variety of other formyl acetals and esters. 

The reaction of 0-Li—C6H4CH2NMe2 with DMF in Et20 has to be carried out at temperatures in the range of —10 to + 30°, which is considerably higher than that in most of the other formylation reactions. In this case, the slight solubility of the lithium compound might be responsible for the decreased reactivity. 

Nevertheless, compared to other formylation reactions, such as the Duff Formylation, Gattermann Aldehyde Synthesis, and Gattermann-Koch Formylation, the Reimer-Tiemann reaetion is the only one that occurs under basic conditions, and in certain cases, it is the only feasible method for the direct formylation, e.g., the formylation of oestrogens. ... 

Again, the formyl chloride was detected only by its conversion into methyl formate while the other formyl halides were converted into formanilide. 

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