Substitution, electrophilic benzoylation

Not all radical aromatic substitutions are as immune to polar effects as is attack by phenyl. Some radicals reveal marked electrophilic or nucleophilic character. Oxygen-centered radicals, for example, are electrophilic, as would be expected if there is substantial polar contribution to the transition state. Table 9.13 lists partial rate factors for substitution by benzoyl radicals note that the orientation and activation trends found in typical electrophilic substitutions have begun to appear, but are still modest compared with the dramatic effects shown in Table 9.12 for a true heterolytic substitution.179... 

One mode of substitution occurring when the nitrating system consists of dinitrogen pentoxide in organic solvents involves molecular dinitrogen pentoxide as the effective electrophile ( 4.2.3). Evidence that the same electrophile operates when the nitrating system consists of a solution of benzoyl nitrate in carbon tetrachloride has also been given ( 5-2)-... 

Acetanilides, benzoyl-colour couplers in colour photography, 1, 372 Acetanilides, pivaloyl-colour couplers in colour photography, 1, 372 Acetazolamide — see l,3,4-Thiadiazole-2-sulfonamide, 5-acetamido-Acetic acid, acetamidocyano-ethyl ester, 1, 307 Acetic acid, 2-acylphenyl-isochroman-3-one synthesis from, 3, 858 Acetic acid, 3-benzo[6]thiophenyl-biological activity, 4, 912 Acetic acid, l,2-benzoxazol-3-yl-electrophilic substitution, 6, 48... 

An 5-(l-m-nitrophenyl-2-benzoyl)ethyl thioether was used to protect thio-phenols during electrophilic substitution reactions of the benzene ring. ... 

The reaction is less selective than the related benzoylation reaction (/pMe = 30.2, cf. 626), thereby indicating a greater charge on the electrophile this is in complete agreement with the greater ease of nuclophilic substitution of sulphonic acids and derivatives compared to carboxylic acids and derivatives and may be rationalized from a consideration of resonance structures. The effect of substituents on the reactivity of the sulphonyl chloride follows from the effect of stabilizing the aryl-sulphonium ion formed in the ionisation step (81) or from the effect on the preequilibrium step (79). 

The scope of the acid-catalyzed formation of C-glycosyl compounds has been greatly expanded with the finding that enol ethers and ketene acetals can be used as the carbon source in electrophilic substitution reactions at the anomeric center.126 Treatment of 198 with the trimethylsilyl enol ether derived from cyclohexanone, in the presence of stannic chloride, led to 2-(2,3,5-tri-0-benzoyl-/J-D-ribofuranosyl)cyelohexanone (206), presumably by way of the inter-... 

As substrates, pyrrolotetrazoles 12 and 13 have been used in a variety of electrophilic substitutions. It has been observed that with the exception of bromination, monosubstitution (acetylation, benzoylation, carbamoylation, formylation, azo coupling, nitrosation, and reaction with dimethyl acetylenedicarboxylate (DMAD)) occurs preferentially at C-5, if the 5- and 7-positions are both available. Upon bromination, double substitution occurs at C-5 and C-7 with the same substrates. It has further been observed that substitution at C-7 occurs only if C-5 is occupied <2001J(P1)729>. 

The benzanthrone system is susceptible to both electrophilic and nucleophilic attack. The most reactive sites towards electrophiles are the 3- and 9-positions, which can be compared with the 4,4 -positions in biphenyl. The 9-position is somewhat deactivated by the carbonyl group, however. Thus, for example, monobromination takes place at the 3-position and further substitution gives 3,9-dibromobenzanthrone. Nitration and benzoylation similarly give rise to the 3-substituted product. The 3-position is in fact peri-hindered (compare naphthalene) so that sulphonation yields the 9-sulphonic acid. Electron withdrawal by the carbonyl group activates the 4- and 6-positions towards nucleophilic attack for example, hydroxylation occurs at these sites. 

Among dichloro bis-electrophiles, malonyl chloride with enamine 183b affords pyridone 189, probably resulting from C-alkylation and cyclocondensation followed by aromatization (02T2821). Finally, o-chloro-benzoylchloride leads to C-benzoylation and subsequent intramolecular substitution of the isolable intermediate to yield quinoline 190 (03ARK (is.2)146). 

The 2-position of dibenzofuran represents an average of 88% of the total reactivity of dibenzofuran for protodetritiation, protodetrimethylsilylation, and benzoylation, which accords well with the results recorded for other electrophilic substitution reactions of dibenzofuran. Mercuration and lithia-... 

With this purpose, several different types of solid acid catalysts have been investigated for the acylation of aromatics, but the best performances have been obtained with medium-pore and large-pore zeolites (3-9). In general, however, the use of acylating agents other then halides, e.g., anhydrides or acids, is limited to the transformation of aromatic substrates highly activated towards electrophilic substitution. In a previous work (10), we investigated the benzoylation of resorcinol (1,3-dihydroxybenzene), catalyzed by acid clays. It was found that the reaction mechanism consists of the direct 0-benzoylation with formation of resorcinol monobenzoate, while no primary formation of the product of C-benzoylation (2,4-dihydroxybenzophenone) occurred. The latter product formed exclusively by... 

This does not occur in the case of catalyst and reactants here described. With Bronsted-type catalysis, the reaction between the benzoyl cation, Ph-C" =0, and the hydroxy group in phenol is quicker than the electrophilic substitution in the ring. This hypothesis has been also confirmed by running the reaction between anisole and benzoic acid in this case the prevailing products were (4-methoxy)phenylmethanone (the product of para-C-benzoylation) and methylbenzoate (obtained by esterification between anisole and benzoic acid, with the co-production of phenol), with minor amounts of phenylbenzoate, phenol, 2-methylphenol and 4-methylphenol. Therefore, when the 0 atom is not available for the esterification due to the presence of the substituent, the direct C-acylation becomes the more favored reaction. 

Electrophilic substitution and metallation reactions of [l]benzothieno[3,2-3][l]benzofuran 63 were studied <2000CCC58>. Bromination, acetylation, benzoylation, formylation, and nitration usually afforded inseparable mixtures of 2- and 7-substituted derivatives as the main products. Disubstitution reactions preferably led to 2,7-disubstituted derivatives. [l]Benzothieno[3,2-3][l]benzofuran-10,10-dioxide 64 and [l]benzothieno[3,2-3][l]ben-zofuran-lO-oxide 65 can be selectively obtained by oxidation of 63. Mononitration of 64 and 65 led selectively to corresponding 7-nitro derivatives, respectively. Only sulfoxide 65 was successfully reduced. 

In general, reactive carbon electrophiles have been shown to react preferentially at the nitrogen atoms of the purine bicycle (see Section 10.11.5.2.1). However, 9-(2,3,5-tris-0-/r /T-butyldimethylsilyl)-a-D-ribofuranosyl-6-chloro-2-(tri-butylstannyOpurine reacted with benzoyl chloride to substitute the 2-tributylstannyl group (PhCOCl, pyridine, toluene, 60% yield) <1997JOC6833>. Indirect C-alkylations have been achieved through deprotonation and alkylation see Section 10.11.5.3.4. The major routes to (7-alkyl and (7-aryl substitution are through nucleophilic displacement or transition metal-catalyzed reactions of halopurines see Sections 10.11.7.4.1 and 10.11.7.4.2. 

The monomers described so far have all been prepared by starting with 4-bromobenzocyclobutene, 2. A different approach to the preparation of monomers begins with the parent hydrocarbon benzocyclobutene 1 by carrying out electrophilic aromatic substitution reactions [36]. Benzocyclobutene readily undergoes a Friedel-Crafts benzoylation reaction with a variety of substituted acid chlorides (Fig. 7). 

A poly(arylene ether phenylquinoxaline) of structure 14 was prepared by the aluminum chloride catalyzed reaction of 6,6 -bis[2-(4-phenoxyphenyl)-3-phenylquinoxaline] and isophthaloyl chloride in 1,2-dichloroethane [51]. The polymer had an inherent viscosity of 1.29 dL/g and a Tg of 224 °C. A polymer of the same chemical structure was prepared from the reaction of 3,3, 4,4 -tetraaminobiphenyl with l,3-bis(phenylglyoxalyl-4-phenoxy-4 -benzoyl)-benzene that gave a Tg of 239 °C [16], significantly higher than that prepared by the electrophilic route. In addition, a polymer of the same chemical structure (third polymer in Table 3) prepared via nucleophilic substitution exhibited a Tg of 240 °C. 

The 3-pyridyl O-carbamate affords, under the sec-BuLi/TMEDA conditions, only 4-substituted products. A reinvestigation of LDA metalation (85JOC5436) has shown that high-yield conversion of 320 into the 4-TMS (319) and 2,4-bis-TMS (321) derivatives can be effected (Scheme 97) [90UP1]. Furthermore, LiTMP metalation of 319 followed by electrophile quench leads to derivatives 322, thus demonstrating the TMS protection route to 2-substituted 3-oxygenated pyridines. Another, potentially useful result is the 2-position selective ipso carbodesilylation of 321 with benzoyl chloride, yielding 323. 

This mechanism explains much of the experimental evidence obtainedhfrom studies of the solvolysis of acyl chlorides, but it may not be in agreement (as was pointed out to Minato by a referee) with the linear relationship between electrophilic catalysis observed in the solvolysis of certain acid chlorides would possibly be explained by a simpler mechanism such as the SN1 or hydration-ionisation mechanism. However, it is of interest to see how the mechanism applies to acetyl, benzoyl and mesitoyl chlorides. For acetyl chloride, kY and k-Y would be very large and the rate would approximate to... 

Binuclear complexes have also been obtained by the electrophilic substitution reaction of [Ni(Me2[Z]dienatoN4)]+ (Z = 13,14) with -substituted benzoyl chlorides (Scheme 53), 2791 A series of dimeric nickel(II) complexes of type (385) has been synthesized as outlined in Scheme 54.2792 In the complex with m-xylene bridges the two nickel(II) atoms are 1360 pm apart, separated by the cavity of the pair of 16-membered macrocyclic ligands. 

In a mechanistically similar process, the neutral palladium(II) dipyridylamine complex (24), obtained by deprotonation of complex (23), underwent reaction with benzoyl chloride to give the substituted complex (25) together with some free ligand (Scheme 8).33 This particular reaction sequence could not be generalized because of the relative instability of other metal complexes related to compound (24). However, a more extensive series of electrophilic substitutions could be carried out on the neutral complex (26), which displayed ambident nucleophilic behaviour by reaction with benzyl chloride and benzoyl chloride at nitrogen and reaction with benzenediazonium fluoroborate at carbon (Scheme 9). 

An attempt has been made to analyse whether the electrophilicity index is a reliable descriptor of the kinetic behaviour. Relative experimental rates of Friedel-Crafts benzylation, acetylation, and benzoylation reactions were found to correlate well with the corresponding calculated electrophilicity values. In the case of chlorination of various substituted ethylenes and nitration of toluene and chlorobenzene, the correlation was generally poor but somewhat better in the case of the experimental and the calculated activation energies for selected Markovnikov and anti-Markovnikov addition reactions. Reaction electrophilicity, local electrophilicity, and activation hardness were used together to provide a transparent picture of reaction rates and also the orientation of aromatic electrophilic substitution reactions. Ambiguity in the definition of the electrophilicity was highlighted.15... 

Figure 5.33 presents Friedel-Crafts acylations, taking benzoylations of toluene (top line) and para-tert-butyl toluene (Figure 5.33, bottom) as an example. The methyl group of toluene preferentially directs the benzoyl residue into the para-position. The ortho-benzoylated toluene occurs only as a by-product. In para-tert-butyl toluene both the methyl- and the tert-butyl substituent direct the electrophile towards the ortho-position, since both para-positions are occupied and could at best react with de-ferf-butylation, i.e., in a—sterically hindered — ipso-substitution (cf. Figure 5.5). Indeed, we see reaction ortho to the methyl group and not ortho to the ferf-butyl group. This selectivity can be ascribed to minimized steric interactions in the preferred sigma complex intermediate.

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