Formylation of aromatic hydrocarbons

Formylation of aromatic hydrocarbons to aldehydes with dichloromethyl ether 47, 2... 

Other methods which are variously suitable for the formylation of aromatic hydrocarbons, phenols, phenolic ethers and heterocyclic systems, employ a range of alternative formaldehyde equivalents. These latter include the species 0... 

Graph 2.1 Aromatic p-aldehyde product and substrate distributions over time during the CO formylation of aromatic hydrocarbons in HF/BF3 at 45°C... 

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),... 

The only formic acid derivative that allows the direct formylation of aromatics is formyl fluoride1617 since others (halides and the anhydride) that could be used in Friedel-Crafts-type acylations are quite unstable. Other related methods, however, are available to transform aromatic hydrocarbons to the corresponding aldehydes. The most frequently used such formylations are the Gattermann-Koch reaction16 17 and the Gattermann synthesis.10 16 17... 

Oxidations with chromic oxide encompass hydroxylation of methylene [544] and methine [544, 545, 546] groups conversion of methyl groups into formyl groups [539, 547, 548, 549] or carboxylic groups [550, 55i] and of methylene groups into carbonyls [275, 552, 553, 554, 555] oxidation of aromatic hydrocarbons [556, 557, 555] and phenols [559] to quinones, of primary halides to aldehydes [540], and of secondary halides to ketones [560, 561] epoxidation of alkenes [562, 563,564, and oxidation of alkenes to ketones [565, 566] and to carboxylic acids [567, 565, 569]. 

Vilsmeier reaction. A British group2 has reported several cases in which the combination of N,N-dimethylthioformamide with acetic anhydride gave definitely better yields of formyl derivatives of aromatic hydrocarbons than the usual Vilsmeier reagent (DMF-POCl3). 

The presence of Cu(I) chloride and HCl as cocatalysts is desirable. When the reaction is carried out at atmospheric pressure of CO and at 25-60 C, 1 mol of AlBrj/mol of aromatic hydrocarbon is used. At 20°C, under atmospheric pressure CO, toluene is converted to the AlBrj-p-tolualdehyde complex . A formyl cation is formed in the presence of HCl and the aluminum halide, which then attacks the aromatic hydrocarbon ... 

The superacidity of chloro-aluminate melts, cf paragraph 4.4) allows them to be ideal candidates for CO formylations. In order to compare the formylation of phenolics to that of aromatic hydrocarbons in ionic liquids, a study of formylation using CO in an ionic liquid was started with toluene as substrate and acidic chloro-aluminate melts (Table 2.15). A 1 1 mol ratio of toluene to ionic liquid with mol fraction AlCb = 0.67 gave moderate yields of the aldehyde derivative at mild temperature (Runs 1 and 2). When the ethyl-derivative of the melt was used, a slight increase in the conversion was observed which may be attributed to the higher solubility of CO in this specific melt. 

Formylation of Aromatic Rings. The Vilsmeier reagent attacks electron-rich aromatic systems to form aryl-methyleneiminium ions which liberate a formylated aromatic compound upon hydrolysis (eq 2). Thio- and selenoaldehydes can be prepared by hydrolysis in the presence of Sodium Hydrogen Sulfide or Sodium Hydrogen Selenide. A wide range of aromatic systems can be formylated in this fashion, including benzene derivatives, polyaromatic hydrocarbons (eq 3), and azulene. Substitution occurs at relatively electron-rich positions. 

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. 

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) ... 

MORPHYLEX A liquid-liquid extraction process for removing aromatic hydrocarbons from hydrocarbon mixtures. The solvent is N-formyl morpholine, the operating temperature is 180 to 200°C. The process was developed by Krupp Koppers in the 1960s and first commercialized in 1972. Only one plant had been built as of 1994. See also MORPHYLANE, OCTENAR. 

Certain reactive aromatic hydrocarbons are formylated by dimethylforma-mide in the presence of phosphorus oxychloride (the Vilsmeier reaction, e.g. 9-formylanthracene, Expt 6.114). This method can also be used with advantage for the formylation of re-excessive heteroaromatic systems (e.g. 2-formylthiophene, cognate preparation in Expt 6.114). 

A generally applicable method of formylation involves the reaction of an aromatic hydrocarbon and dichloromethyl methyl ether under Friedel-Crafts conditions (cf. Section 6.11.1, p. 1006). The intermediate chloroacetal (1) thus formed is readily hydrolysed to the corresponding aldehyde (e.g. p-t-butylbenzaldehyde, Expt 6.115). 

The formyl cation HCO+ (vco at 2110 cm ) is generated from CO under pressure in the presence of HF/SbFs. Concentrated sulfuric acid or the HCl/CuCl system, activates carbon monoxide toward the electrophilic attack on aromatic hydrocarbons to form aromatic aldehydes (Gatterman-Koch reaction). Branched carboxylic acids are obtained from alkenes and CO in the presence of concentrated sulfuric acid (Koch process) (equation 3). ... 

Duff reaction (1, 430). Review. In the clastical procedure highly activated aromatic compounds are converted into their formyl derivatives by treatment with hexamethylenetetramine and glyceroboric acid yields are generally low. Smith finds that a variety of aromatic compounds, including simple hydrocarbons, when treated with hexamethylenetetramine in conjunction with trifluoroacetic acid al reflux temperature (82- 90") arc converted into i mine products which yield aldehydes on hydrolysis ... 

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. 

More recently, Olah and Kuhn588 have performed such formylations by the relatively stable formyl fluoride at 0-10° in carbon disulfide with boron trifluoride as catalyst yields of 56-78% were obtained from various aromatic hydrocarbons. 

Gatterman-Koch reaction A reaction for substituting a formyl (methanoyl) group (HCO-) onto a benzene ring of an aromatic hydrocarbon. It is used in the industrial production of benzaldehyde from benzene ... 

Therefore, reaction of iminium chlorides, or their complexes with phosphorus oxychloride, thionyl chloride, carbonyl chloride, etc., with suitable substrates, such as aromatic hydrocarbons, activated methylene compounds and nucleophilic olefins, occurs quite readily. The overall reaction generally results in the formylation of the corresponding substrate. 

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