Gattermann reaction / formylation

The original conditions, called the Gattermann Reaction / Formylation, were to add HCN, HC1 and ZnCh (known as Adam s Catalyst) directly. Use of Adam s catalyst avoids using gaseous HCN. 

Gattermann-Koch reaction Formylation of an aromatic hydrocarbon to yield the corresponding aldehyde by treatment with CO, HCl and AICI3 at atmospheric pressure CuCl is also required. The reaction resembles a Friedel-Crafts acylation since methanoyl chloride, HCOCl, is probably involved. 

Another formylation reaction, which is named after Gattermann, is the Gatter-mann-Koch reaction. This is the reaction of an aromatic substrate with carbon monoxide and hydrogen chloride (gas) in the presence of a Lewis acid catalyst. Similar to the Gattermann reaction, the electrophilic agent 9 is generated, which then reacts with the aromatic substrate in an electrophilic aromatic substitution reaction to yield the formylated aromatic compound 10 ... 

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 reaction of electron-rich aromatic compounds with yV,A -dimethylformamide 2 and phosphorus oxychloride to yield an aromatic aldehyde—e.g. 3 from the substituted benzene 1—is called the Vilsmeier reaction or sometimes the Vilsmeier-Haack reaction. It belongs to a class of formylation reactions that are each of limited scope (see also Gattermann reaction). 

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... 

Aromatic aldehydes. Acetone cyanohydrin can be used in place of hydrogen cyanide in the Gattermann reaction for formylation of arenes.1 Example ... 

From Hydrocarbons.—An interesting method sometimes applicable for the preparation of aromatic aldehydes is from the hydrocarbons by means of the Friedel-Craft reaction, as modified by Gattermann and Koch with carbon monoxide and hydrochloric acid in the presence of CuCl. In this reaction formyl chloride, which is unknown in the free condition, is probably first formed by the union of the carbon monoxide and hydrochloric acid. 

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. 

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. 

Formylation using zinc(ll) cyanide and hydrogen chloride is known as the Gattermann reaction. Whereas the Gattermann-Koch method fails with phenols and aryl ethers, this method does give good... 

Gattermann Aldehyde Synthesis (Gattermann-Adams Formylation) The Reaction ... 

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. 

For preparative purposes the Gattermann reaction is much more useful. It was first usedS5 to prepare ethyl 2-formyl-3,5-dimethyl- and ethyl 3-formyl-2,5-dimethyl-pyrrole-4-carboxylate, by means of hydrogen cyanide and hydrogen chloride in ether. Later applications sometimes involved minor changes such as the use of chloroform as solvent, or of Adams modification of the reaction . Formylation generally occurs at an a-position, but if none is open there is usually no difficulty in jS-substitution. Pyrrole-2-aldehyde cannot be made this way, for it reacts further to form dyestuffs, but several 1-alkylpyrroles have been satisfactorily formylated . The initial... 

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. 

Rahm et al. describes the formylation of anisole (50% isolated yield) and alkylated benzenes in fair yield using acetone cyanohydrin (Eq 1.19). Similar to the Gattermann reaction no formylation is obtained with pyrrole and only traces of aldehydes were observed with phenol and furane as substrates. 

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... 

By passing a mixture of carbon monoxide and hydrogen chloride into the aromatic hydrocarbon in the presence of a mixture of cuprous chloride and aluminium chloride which acts as a catalyst (Gattermann - Koch reaction). The mixture of gases probably reacts as the equivalent of the unisolated acid chloride of formic acid (formyl chloride) ... 

Hydroxy-4-methylthiazole failed to react when submitted to Friedel-Crafts benzoylation conditions (349) on the other hand, it reacted normally in Gattermann and in Reimer-Tiemann formylation reactions, affording the 5-formyl derivative (348). 4-Methylthiazole is insufficiently activated and fails to react under the same conditions. 2,4-Dimethylthiazole undergoes perfluoroalkylation when heated at 200° for 8 hr in a sealed tube with perfluoropropyl iodide and sodium acetate (116) (358). 

In the presence of aluminum chloride and a small amount of cuprous haUde, a mixture of hydrogen chloride and carbon monoxide serves as a formyl a ting agent of aromatics (Gattermann-Koch reaction) (107) ... 

The preparation of a formyl-substituted aromatic derivative 3 from an aromatic substrate 1 by reaction with hydrogen cyanide and gaseous hydrogen chloride in the presence of a catalyst is called the Gattermann synthesis This reaction can be viewed as a special variant of the Friedel-Crafts acylation reaction. 

Formylation may be carried out by use of CO, HC1, and A1C13 (the Gattermann-Koch reaction) it is doubtful whether HCOC1 is... 

The range of the reaction was extended by the elegant aldehyde synthesis of Gattermann and Koch. If a mixture of carbon monoxide and hydrogen chloride is allowed to act in the presence of aluminium chloride (and cuprous chloride) on toluene (benzene is less suitable), the reaction occurs which might he expected with formyl chloride if this substance were capable of existence. 

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