Benzaldehyde, electrophilic aromatic substitution

Because the carbon atom attached to the ring is positively polarized a carbonyl group behaves m much the same way as a trifluoromethyl group and destabilizes all the cyclo hexadienyl cation intermediates m electrophilic aromatic substitution reactions Attack at any nng position m benzaldehyde is slower than attack m benzene The intermediates for ortho and para substitution are particularly unstable because each has a resonance structure m which there is a positive charge on the carbon that bears the electron withdrawing substituent The intermediate for meta substitution avoids this unfavorable juxtaposition of positive charges is not as unstable and gives rise to most of the product... 

The mechanism of the reaction has been studied in some detail by Hogberg i2,7i,72) jn contrast to the base-catalyzed oligomerization, the acid catalyzed process involves electrophilic aromatic substitutions by cations, as outlined in Fig. 8. Although formaldehyde does not react with resorcinol to produce cyclic oligomers, other aldehydes such as acetaldehyde and benzaldehyde give excellent yields of... 

Several routes to benz[c]acridines involve electrophilic aromatic substitution to form the heterocyclic ring. Thus, 9-nitrobenz[c]acridine results from the cyclisation of the 2-(l-naphtlylamino)benzaldehyde derived from 1-naphthylamine and 2-fluoro-5-nitrobenzaldehyde (J. Rosevear and J.F.K. Wilshire, Austral. J. Qiem., 1981, 34, 839). The reaction between a ff-aryl-l-naphthylamine and acetic anhydride has been used to synthesise 9- and ll-hydroxy-7-methylbenz[c]acridines and cyclisation of partially reduced 2-(l-naphtltylamino)benzoic acid by phosphorus oxychloride affords the 7-chloro-l,2,3,4-tetralydro derivative (B.V. Lap et ai,y J. heterocyclic Chem., 1983, 20, 281). 

Electrophilic aromatic substitution at the m-position of benzaldehyde with the electrophile gives the product, m-nitrobenzaldehyde. 

The reaction of nitriles with aromatic aldehydes is carried out at heating the reactants to 50-70°C with a 1 -h 10 (v/v) mixture of concentrated sulfuric acid and glacial acetic acid. The cycloaddition reaction is regiospecific. The oxazines 21 (equation 10) are formed as diastereoisomeric pairs which are free from their regioisomeric products in the limit of the NMR analysis. Precursors used were benzonitrile and acetonitrile as well as acetaldehyde, benzaldehyde and its substituted derivatives, and a number of the olefins having various structures. Until now, the reaction of aldehydes with nitriles was interpreted as an extension of the Ritter reaction. The initial O-protonation of aldehyde 22 is postulated to form in the presence of acid the hydroxycarbenium ion 23 which then reacts as a cationoid electrophile with the nitrile (equation 11) giving the nitrilium ion 24. 

A review has covered mainly the preparation of aldehydes from carbon monoxide by electrophilic aromatic substimtions involving superacids. In HF-SbFs, some polynuclear aromatic compounds are diformylated. When pyridine-3-carboxaldehyde is compared with benzaldehyde in acid-catalysed condensation reactions with benzene and substituted benzenes to form diaryl-3-pyridylmethanes, it is found to be... 

Many known color reactions involve electrophilic substitution at an electron-rich aromatic or heteroaromatic (cf. 4-(dimethylamino)-benzaldehyde - acid reagents and vanillin reagents ). Here aliphatic or aromatic aldehydes react in acid medium to yield polymethyne cations which are intensely colored di- or triarylcarbenium ions [4, 10]. 

Other electrophilic substitution reactions on aromatic and heteroaromatic systems are summarized in Scheme 6.143. Friedel-Crafts alkylation of N,N-dimethyl-aniline with squaric acid dichloride was accomplished by heating the two components in dichloromethane at 120 °C in the absence of a Lewis acid catalyst to provide a 23% yield of the 2-aryl-l-chlorocydobut-l-ene-3,4-dione product (Scheme 6.143 a) [281]. Hydrolysis of the monochloride provided a 2-aryl-l-hydroxycyclobut-l-ene-3,4-dione, an inhibitor of protein tyrosine phosphatases [281], Formylation of 4-chloro-3-nitrophenol with hexamethylenetetramine and trifluoroacetic acid (TFA) at 115 °C for 5 h furnished the corresponding benzaldehyde in 43% yield, which was further manipulated into a benzofuran derivative (Scheme 6.143b) [282]. 4-Chloro-5-bromo-pyrazolopyrimidine is an important intermediate in the synthesis of pyrazolopyrimi-dine derivatives showing activity against multiple kinase subfamilies (see also Scheme 6.20) and can be rapidly prepared from 4-chloropyrazolopyrimidine and N-bromosuccinimide (NBS) by microwave irradiation in acetonitrile (Scheme... 

While the so-called halogen dance reaction had been reported for aromatic and heteroaromatic systems, it had never been described for the oxazole ring. This approach was used for an efficient transformation of 5-bromo-2-phenyloxazole, 114, into several 5-substituted 4-bromo-2-phenyloxazoles 115 <05SL1433>. The electrophiles used were water, benzaldehyde, TMSCl, halogens, and CO2 affording the final compounds in good yields (66-78%). 

Dichloroketene acts as a donor toward aromatic aldehyde [165], but chlorocyano-ketene behaves as an acceptor, as shown by the reactivity ofile with a series of substituted benzaldehydes [97]. It must be remembered that chloro and cyano groups belong to different polarity categories, and although the fundamental donor/acceptor characters of the ketene unit do not change, the higher electrophilicity of the cyano-ketene reflects the acceptor influence by the cyano function. 

The reaction mechanism of Lehmstedt-Tanasescu reaction is generally based on an aromatic electrophilic addition of an or/Ao-nitro-substituted benzaldehyde to electron-rich arenes, yielding substituted 3-phenyl 1,2-benzisoxazoles, which are then rearranged to the desired acridones. In the first step of the reaction mechanism the benzaldehyde is protonated by sulfuric acid to form intermediate 5, followed by electrophilic addition to an electron rich arene (benzene in the following scheme), to give compound 6. Intramolecular attack of the formed hydroxyl group to the or/to-positioned... 

A-Methylacridones are synthesized from 2-(A-methyl-A-phenylamino)benzaldehydes in DMF using Sc(OTf)3 as the catalyst and Na2S04 as additive via dehydrogenative cyclization. There are two primary processes in the transformation the aldehyde first coordinates with Sc(OTf)3 and induces the aromatic electrophilic substitution (5eAt) reaction to form the active intermediate Af-methyl-acridin-9-ol, which is then quickly oxidized in situ to afford the acridones. ... 

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