Gattermann—Koch formylation

The Gattermann-Koch formylation was found unsuited to the preparation of aldehydes from phenols and phenol ethers such aldehydes may be obtained by Gattennann s aldehyde reaction. 

A review of formylation reactions involving methyl formate in a hydrogen fluoride-boron trifluoride medium has appeared.60 Regioselectivity and kinetic data have been reported for Gattermann-Koch formylation in superacids and provide evidence for an intra-complex reaction where the formylation electrophile HCO+ is generated by protonation of CO by the arenium ion.61 The observed selectivity results from... 

The mechanisms of the Gattermann and Gattermann-Koch formylation belong to the category of electrophilic aromatic substitution (SEAr) but are not known in detail, since they have a tendency to vary from one substrate to another, and the reaction conditions may also play a role. When carbon monoxide is used, the electrophilic species is believed to be the formyl cation, which is attacked by the aromatic ring to form a -complex. This -complex is then converted to the aromatic aldehyde upon losing a proton. When HCN is used, the initial product after the SEAr reaction is an imine hydrochloride, which is subsequently hydrolyzed to the product aldehyde. 

The mechanism is not fully understood, but it is very similar to the mechanism of the Gattermann-Koch formylation. The first step is the formation of a nitrilium chloride that is subsequently transformed to an imino chloride from which the reactive species, the iminium ion is generated. 

Tanaka, M. A new aspect in electrophilic aromatic substitutions intracomplex and conventional electrophilic aromatic substitutions in Gattermann-Koch formylation. Trends in Organic Chemistry 1998, 7,45-61. 

Tanaka, M., Fujiwara, M., Xu, Q., Ando, H., Raeker, T. J. Influence of Conformation and Proton-Transfer Dynamics in the Dibenzyl s-Complex on Regioselectivity in Gattermann-Koch Formylation via Intracomplex Reaction. J. Org. Chem. 1998, 63,4408-4412. 

Related reactiens Gattermann and Gattermann-Koch formylation, Vilsmeier-Haack formylation ... 

Other references related to the Gattermann-Koch formylation are cited in the literature. 

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. ... 

This reaction is related to the Ciamician-Dennstedt Reaction, Duff Reaction, Gatterman Aldehyde Synthesis, and Gattermann-Koch Formylation. 

ALDEHYDE SYNTHESIS CO + HCI (Gattermann- Koch) Formyl fluoride Acetic-formic anhydride CO HCN (Gattermann) BrCN (Karrer) Formamides (Vilsmeier) Formic acid Ortho- formates... 

In the di-substituted benzene series o- and m-xylene give the expected products. However, p-xylene undergoes isomerisation to furnish 2,4-dimethylbenzaldehyde. The tri-substituted benzene series i.e. mesitylene and pseudo-cumene yield normal formylation products. Tetralin and di-isopropyltetralin in the naphthalene series are reported to undergo Gattermann-Koch formylation whereas naphthalene itself is formylated in the modified reaction using HF and BF3 as catalyst. 

The Friedel-Crafts acylation reaction works for R = alkyl, alkenyl, or aryl, but it is not a useful route to ArCHO because the required acyl halide, HC(=0)C1, is not stable. However, we can use a mixture of HCI and CO, in the presence of AlClj/CuCl—the Gattermann-Koch formylation... 

FIGURE 13.46 Gattermann-Koch formylation of benzene. PROBLEM 13.9... 

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