Formylation process

In 1927 Putochin studied the effect of temperature on the nature of the products formed when the formylation reaction was carried out in benzene and observed that 1-formyl derivatives were the major products obtained at low temperatures, whereas the 3-formyl derivatives predominated at higher temperatures. Britton et al. in 1947 claimed that the formation of the 3 -formylindole derivative is probably favored, relative to the alternate 1-formylation process, by elevated temperatures and pressures.However, it was apparently not possible to suppress completely the formation of the 1-formyl derivatives and yields of the order of 40% of both products were usually obtained. 

The actual formylation process is preceded by the formation of dichlorocarbene 3 as the reactive species. In strongly alkaline solution, the chloroform is deproto-nated the resulting trichloromethide anion decomposes into dichlorocarbene and a chloride anion ... 

The process of Shell starts from ethylene oxide, which is prepared by oxidation of ethylene. Ethylene oxide is transformed with synthesis gas in a hydro-formylation process to 3-hydroxypropanal as well, but for this reaction very high pressure (150 bar) is required [27]. The aldehyde is extracted from the organic phase with water and subjected to hydrogenation using nickel as a catalyst, again under high pressure. 

Water-soluble phosphine ligands and metal complexes1 have elicited considerable interest since the commercialization of a two-phase hydro-formylation process by Ruhrchemie in 1984.2 A water-soluble rhodium... 

Formylation of the less reactive phenol and anisole with CO in HF-BF3 was found to require at least stoichiometric amount of the acid for effective transformation (50 equiv. of HF, 2 equiv. of BF3, 50 bar CO, 45°C).445 Conversion increases with increasing reaction time but results in decreasing paralortho ratios suggesting a change from kinetic control to thermodynamic control and the reversibility of formylation. Furthermore, the amount of byproducts (mainly diphenylmethane derivatives) originating from reactions between substrates and products also increases. Additional studies in ionic liquids showed that imidazolium cations with increased chain lengths—for example, l-octyl-3-methylimidazolium salts—are effective in the formylation process. This was attributed to the enhanced solubility of CO in the ionic liquid medium. Tris(dichloromethyl)amine, triformamide, and tris (diformylamino)methane have recently been applied in the formylation of activated aromatic compounds in the presence of triflic acid at low temperature (— 10 to 20°C) albeit yields are moderate.446... 

Finally, it should be noted that a specific ortho formylation process which uses 1,3-dithiane as a formaldehyde equivalent has been described.48 The reaction process appears to be of wide applicability and is similar to the ortho formylation of primary aromatic amines which has been described by the same authors (see p. 909). 

The combination of tertiary amides, such as dimethylformamide, and phosphoryl chloride generates reactive electrophiles capable of being attacked by electron-rich nucleophiles and is widely used as the Vilsmeier formylation process. The Vilsmeier process has become more general, with the use of more varied amides, and has been particularly successful for the functionalization of pyrroles and indoles. Greater flexibility has been achieved with the replacement of phosphoryl chloride by trifluoromethanesulfonic anhydride. 

After polymerization processes, one of the most important aqueous phase reactions to be performed on an industrial scale is the Rhone-Poulenc hydro-formylation process that utilizes a water soluble rhodium phosphine catalyst. This process will be discussed in more detail in Chapter 10. The success of this process has led to many exciting results in metal catalysed aqueous phase chemistry. Additionally, amazing advances have been made where reactions that are typically considered unsuited to the presence of moisture, e.g. Grignard-type chemistry, can be performed in water. 

A variation that is more of an acyl addition (16-25) involves the reaction of an allylic alcohol with benzaldehyde. With a ruthenium catalyst and in an ionic liquid, the C=C unit reacts with the aldehyde, with concomitant oxidation of the allylic alcohol unit, to give a p-hydroxy ketone, PhCHO - -C=C—CH(OH)R PhCH(OH) CH(Me)COR. In another variation, formate esters add to alkenes using a ruthenium catalyst to give an alkyl ester via a formylation process. 

Scientifically, another major challenge is the development of a biphasic hydro-formylation process for internal alkenes combining isomerization and hydroformy-lation of linear internal alkenes and affording predominantly terminal hydro-formylation products. Such a technology would be of primary interest for the fine chemical and the detergent alcohol markets. 

The total alcohols are determined by acetylation in the usual manner, and the citronellol by formylation. The formylation process is carriedi out as follows —... 

The relative proportions of the two alcohols, geraniol and dtronellol, in oil of geranium oil is a matter of considerable interest, and the determination is frequently of importance. The only method available in practice for this purpose is the combination of the acetylation process, which gives the measure of the total alcohols and the formylation process, by which the geraniol is decomposed, and the citronellol estimated. 

This method has been referred to under Otto of Bose, but has been more critically studied by Simmons in reference to geranium oil. Simmons has shown that the determination of citronellol in the presence of geraniol by the formylation process is not strictly accurate, but tbe results are exceedingly useful for comparative purposes. 

The formylation process, as recommended by MM. Jeancard and Satie, consists in heating 10 c.c. of oil with 20 c.c. of 98 to 100 per cent, formic acid, in a flask attached to a reflux condenser for one hour on a sand-bath. It may be mentioned that the addition of 2 grams anhydrous sodium formate per 10 c.c. oil, while it enables the mixture to be boiled steadily on a sand-bath, does nbt affect the result. 

Furthermore, carbon monoxide is produced in abundance as side-product in Sasol s Fischer-Tropsch water-gas shift reaction, making it a cheap and subsequently attractive formylating agent. Thus, using CO as reagent in the formylation process will result in further reduced production costs. 

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