Heterocycles, acylation electrophilic aromatic

Several aromatic and heterocyclic acyl trimethylsilanes have been used as acyl anion equivalents by treatment with fluoride ion (Scheme 81, path a)23 133 154b160191192. Provided that the acyl substituent is electron-withdrawing, and that there are no aryl substituents on the silicon atom, acyl anions can be trapped by various electrophiles in moderate to good yields indeed, acyl anions and pentacoordinate silicon anionic species have both been detected in gas-phase reactions of acyl silanes with fluoride ion193. 

These solid-acid catalysts are, in principle, applicable to a plethora of acid-catalyzed processes in organic synthesis [18]. These include various electrophilic aromatic substitutions, e.g. nitrations, halogenations, and Fiiedel-Crafts alkylations and acylations, and numerous rearrangement reactions such as the Beckmann and Fries rearrangements. Other examples include a variety of cyclization reactions such as Diels-Alder reactions and the synthesis of pyridines and other heterocycles. 

Electrophilic aromatic substitution reactions of compounds 10 occur in a fashion characteristic for heterocyclic analogues of azulene, and are specific at positions 5 and 7 <1994CB1479>. Thus, 10a (R = H, R = Ph) was successfully brominated, formylated, and acylated, as shown in Scheme 7. 

The Friedel-Crafts reaction involves an electrophilic aromatic substitution that facilitates the alkylation or acylation of arenes (135) and heterocyclic compounds catalyzed by acidic catalysts. Zinc oxide has been found to be an effective catalyst for the Friedel-Crafts acylation of activated and nonactivated aromatic compounds (135) (Hosseini-Sarvari and Sharghi 2004) under solvent-free and room temperature conditions (Scheme 9.44). The catalyst provides a large surface area for the reaction. This Friedel-Crafts reaction is a safe and environmentally benign method which requires simple workup, mild reaction conditions and a short reaction time. 

In the gas phase, alkylation of five-membered heterocycles by alkyl cations usually occurs via the usual addition-elimination mechanism of aromatic electrophilic substitution. The phenyl cation behaves differently, however although its substrate discrimination is limited, in accord with its exceedingly high reactivity, it has marked selectivity for the a position, which does not conform with the hard character of this cation. It has, therefore, been suggested that an electron-transfer mechanism is followed this is thermodynamically allowed for the phenylium, and likewise for the methyl cation, but not for other alkyl cations (Scheme 28). This SET mechanism applies also for acyl cations [87]. 

Instead, these heterocycles and their derivatives most commonly undergo electrophilic substitution nitration, sulfonation, halogenation. Friedel-Crafts acylation, even the Reimer-Tiemann reaction and coupling with diazonium salts. Heats of combustion indicate resonance stabilization to the extent of 22-28 kcal/ mole somewhat less than the resonance energy of benzene (36 kcal/mde), but much greater than that of most conjugateci dienes (about Tlccal/mole). On the basis of these properties, pyrrole, furan, and thiophene must be considered aromatic. Clearly, formulas I, II, and III do not adequately represent the structures of these compounds. 

Azlactone is commonly utilized as a precursor of a-quatemary a-amino acids and various heterocyclic compounds [28-30]. Because the enol form of azlactone has aromatic character, facile deprotonation from the C4-position affords the corresponding enolate under the influence of various bases. Interestingly, the enolate ion shows ambident reactivity and attacks the electrophile at either the C4-position (a-addition) or the C2-position (y-addition), thus acting as an a-amino enolate or an acyl anion equivalent, respectively (Fig. 1). The site-selectivity associated with this enolate seems to be heavily dependent on its stereoelectronic characteristics, and introduction of a bulky substituent into the Cl- or C4-position suppresses the nucleophilicity at the particular position. 

Nevertheless, such reactions catalyzed by zeolites have been discussed in the review of 2001 (1) isomerization (double-bond shift, isomerization of tricyclic molecules, like synthesis of adamantane, isomerization of terpenes, diverse rearrangements, conversion of aldehydes into ketones), (2) electrophilic substitution in arenes (alkylation of aromatics, including the synthesis of linear alkylbenzenes, alkylation and acylation of phenols, heteroarenes and amines, aromatics nitration and halogenation), (3) cyclization, including the formation of heterocycles, Diels-Alder reaction, (4) nucleophilic substitution and addition,... 

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