Formylation, para-selective

Orientation of the incoming acyl group with an electron-releasing monosubstituted benzene, however, is predominantly para over ortho but selectivity can depend also on reaction conditions. For acylation or benzoylation of simple benzene monoalkylbenzene derivatives, the para-selectivity can approach 20 1 or greater. The reason for this was initially attributed to steric factors but a systematic analysis has shown that the relative reactivity of the electrophilic acylating agents can also affect the selectivity. For example, acylation of more reactive less stable acylium ion derivatives such as formyl and dinitrobenzoyl ion, the ortho para selectivity can diminish greatly ( 1 1). ... 

Using this method for substituting aluminum trichloride with hydrofluoric acid, trifluoromethoxy benzene (CeHsOCFs) is formylated in excellent yield and para-selectivity... 

With toluene as substrate formylation proceeded in a high yield (99%) with respect to aldehyde formation and with good para-selectivity (90%) in a reaction time of only 1 hour. The reaction was carried out on phenol under the same reaction conditions. Surprisingly, the reactivity of phenol proved to be much lower than that of toluene and a reaction time of more than 4 hours was required to obtain acceptable yields, albeit with reduced para-selectivity. When the reaction was extended to anisole, only small differences compared to phenol were observed within the first hour of the reaction, but at extended reaction times phenol proved to give better conversions. The results indicate that the reaction is sustained for a longer time with phenol than with anisole. 

Chloro-aluminate ionic liquids promote the carbonylation of alkylated aromatic compounds, but fails in the case of oxygenated aromatics. Aldehyde yields of formylation in the acidified neutral ionic liquids were generally similar compared to reactions conducted in HF as solvent/catalyst (cf Table 2.2). The increase in aldehyde yields with the use of extended alkyl chain lengths of the cationic part of the melt, may be due to improved CO solubility. HF/BFs-acidified neutral ionic liquids showed both increases in para-selectivity compared to HF as solvent and catalyst. Formylation of anisole and toluene, but not of phenol in the neutral ionic liquids resulted in increased secondary product formation in comparison with hydrogen fluoride used as solvent/catalyst. This difference in behaviour is not understood at present, but suggests that phenol is a good substrate for formylation in this medium, particularly with the development of a system catalytic with respect to HF/BF3 in mind. 

By contrast with the reconcilable data observed with para-substituted substrates, a range of ortho substituents (entries h-j, Table 2.1) all resulted in significant weakening of the C7-C8 anti selectivity. We take these data to suggest that ortho substitution results in some steric inhibition of the rotamer in which the faces of the aromatic ring and formyl group are parallel (see structure III). 

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. 

Among the most frequently used formylation methods, the Gattermann-Koch reaction shows the highest selectivity reflected both in the observed high toluene- benzene rate ratios as well as a high degree of para substitution (Table 5.30). 

The formylation of phenols with the electron-rich olefin to give imidazolidin-2-yl-phenols is very selective and avoids mixtures of o- and p-isomers which are frequently obtained by methods commonly employed for the synthesis of phenolaldehydes. Para substitution of the cyclic aminal group in the phenol is preferred. If the p-position is blocked or sterically hindered, the reaction proceeds via the ortho- aminals to salicylaldehydes. Incorporation of more than one aldehyde group in the benzene nucleus is often achieved with hydroxy- and aminophenols. 

S R ratio = 5 1) [22]. Yanada and Yoneda constructed the deazaflavinophane 26, which exhibits complete facial selectivity in its oxidation and reduction reactions, e.g. the reduction with NaBD to afford 27 [23], Belokon and Rozen-berg used scalemic 4-formyl-5-hydroxy[2.2]para-cyclophane (FHPC) 28 in the synthesis of a-ami-no acids (ee 45-98 %) [24], An alternative approach to FHPC was more recently reported by Hopf [25]. Other interesting advances in the area of chiral cyclophanes include the homochir-al [2.2]paracyclophane-derived amino acids 29 and 30 [26], as well as (5)-PHANEPHOS (31) [27], which has been shown to be an effective ligand for highly enantioselective Ru-catalyzed asymmetric hydrogenations of -ketoesters and... 

Benzene can be formylated very easily. Fluorobenzene gives fluorobenzaldehyde with a total selectivity in para isomer. On the contrary chloro and bromobenzene are transformed in poor yield, and chloro and bromo toluenes 17 are obtained next to halobenzaldehydes 16, showing that methyl formate can act as an alkylating agent. 

Increased selectivity has also been obtained using polyethylene glycol as complexing agent.Using toluene as solvent, the authors report a 1 10 para. ortho ratio in the formylation of phenol. 

Selective dealkylation of alkyl phenyl ethers (cf Sodium tUoethoxide, 4, 465). This reagent in combination with HMPT cleaves alkyl phenyl ethers under mild conditions. Methoxy groups ortho or para to a formyl group are cleaved selectively. ... 

ABSTRACT. Selective formylation of phenol at the 4-position is achieved by using 3-cyclodextrin as catalyst in the reaction of phenol with chloroform in aqueous alkali. The reactions of 1,3-dihydroxybenzene and indol, respectively, in the place of phenol give 2,4-dihydroxybenz-aldehyde and indole-3-aldehyde in virtually 100% selectivies and high yields. The reactions of para-substituted phenols, 4-methylphenol and 5,6,7,8-tetrahydro-2-naphthol, instead of phenol, effect the selective dichloromethylation at the para-positions. Selective carboxylation of phenol at the 4-position is achieved in the reaction of phenol with carbon tetrachloride in aqueous alkali by using 3-cyclodextrin and copper powder as catalyst. 

The present authors [4] have found the control of the rate of addition of chloroform is very important for the selectivity of para-formylation. The conventional method referrs to "all at once method" and the new method to "dropwise method". The molar ratio of CyD to the total charged chloroform is usually small, e.g. 0.06 - 0.17. Consequently, the molar ratio of CyD to the chloroform present in the reaction mixture is also small for "all at once method", i.e. 0.06 at the initial stage of the reaction. However, the molar ratio is... 

The dependence of the selectivity for para-dichloromethylation on the initial molar ratio of 3-CyD to phenol was similar to that for para-formylation of phenol as shown in Fig. 1. The dropwise method required only a small amount of 3 CyD, i.e., 10 mol % to 4-methylphenol for 96 % selectivity [5]. 

Orientation of the incoming acyl group in Friedel-Crafts acylations can be quite sensitive to the reaction solvent and other procedural variables. In general, however, para attack predominates for alkylbenzenes. The percentage of ortho attack increases with the electrophilicity of the acylium ion and approaches 1 1 with such less selective species as formyl and 2,4-dinitrobenzoyl ions. For simple alkanoyl and benzoyl halides, the o p ratio is usually 1 20 or higher. ... 

Table 1.4 shows that benzene is formylated rather easily while fluorobenzene yields the corresponding aldehyde with total selectivity for the para isomer. Chlorobenzenes show poor reactivity while the formation of chloro-toluene, in a competing reaction, indicates the alkylation potential of methyl formate under the reaction conditions. 

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