Activated aromatic substrates

Vilsmeier reagent The reagent obtained from POCI3 mixed with either N,N-dimethyl-formamide or N-methylformanilide. Used for introducing the methanoyl (formyl) (-CHO) group into activated aromatic substrates. 

RELATIVE REACTIVITIES OF SOME HALO-AZA-ACTIVATED AROMATIC SUBSTRATES WITH NUCLEOPHILES ... 

An expeditious microwave assisted SNAr reaction with cyclic amines has been reported for activated aromatic substrates [83] (Eq. 29). 

Fluorine has been used for the generation of extremely strong electrophilic halogenating agents in electrophilic iodination and bromination of deactivated aromatic substrates in highly acidic reacton media. Polyhalogenation of more activated aromatic substrates is also possible (Fig. 90) [231-233]. 

The Sn(AE) mechanism consists of the initial addition (A) of the nucleophile (attachment) to the carbon atom bearing the potential leaving group, followed by the elimination (E) of the latter.85 It is analogous to the one usually occurring in the nucleophilic substitution of nitro-activated aromatic substrates. 

The same authors have also investigated the stereoselective synthesis of unsym-metrically disubstituted azetidin-2-ones (V, Fig. 21) by using Lewis acid mediated functionalization of (3-lactams with various active aromatic substrates [298],... 

In order to gain insight into how peroxynitrite attacks activated aromatic substrates, Nonoyama and co-authors (1999) examined the kinetic features of the reaction of peroxynitrite with para-substituted phenols. The authors used ONOONa as a reagent. The latter was prepared by ozonolysis of sodium azide in aqueous solution at pH 12. The reactions... 

On heating the sulfonium ylide 464 (R = H) the isomeric bis(methoxycarbonyl)methyl-thiophene 465 is formed. Thermolysis of the ylide 464 (R = Cl) yields the thienofuran 466. When heated in the presence of copper or rhodium catalysts, 464 (R = Cl) undergoes cleavage of the carbonsulfur bond resulting in the formation of carbenoid intermediates which can trapped with activated aromatic substrates or alkenes to yield the corresponding arylmalonates or cyclopropanes, respectively. 

In the past 15 years, a number of research groups have investigated, often in batch reactors, the use of zeolites to catalyse liquid phase aromatic acylation. Good activities and selectivities have been achieved with activated aromatic substrates. Experiments in flow reactors show that deactivation is the main problem to be solved, which can be made by an adequate adjustment of the zeolite characteristics and especially of the operating conditions. 

The aminoalkylation reactions applied to the synthesis of alkaloids arc mostly cycliyui-tions of the type described in Chap, I, C.4, usually involving CH substrates such as alkyl ketones. The analogous reactions on alkcncs arc frequently accompanied by more or less relevant modiheations of the substrate molecule (Chap. I, C.5). Activated aromatic substrates, particularly phenols and their alkylether derivatives, arc also subjected to Mannich reaction. 

More powerful nitrite scavengers than phthaloyl chloride can improve the yield of the fluoroaro-matic compound. In this regard, phthaloyl fluoride (2) or tetrafluorophthaloyl fluoride, which are easy to prepare from inexpensive sources, are very reactive nitrite anion trapping agents, even for more activated aromatic substrates, suppressing the side reactions initiated by the nitrite ion. " ... 

Xenon difluoride has also been used for the fluorination of enol derivatives [5] and 1,3-dicarbonyl compounds [140], and fluorination of activated aromatic substrates is possible in the presence of a Lewis acid [141]. 

Bis(methoxycarbonyl)carbene generated in this way is a highly electrophilic species and readily reacts with mesomerically activated aromatic substrates to give the corresponding aryl malonates in fair to excellent yields. 

Smiles rearrangement Intramolecular nucleophilic aromatic rearrangement of activated aromatic substrates. 416... 

Scheme 2.141 Electrophilic trifluoromethylation of activated aromatic substrates by an HF/ CCf/SbF system and subsequent treatment with 70%...

The incursion of a redox chain characterized by the Eq. (7) into the propagation steps of Scheme 2 has been suggested in the case of activated aromatic substrates (phenol, phenol ethers, anilides)... 

To overcome tbe problem of tbe bigb amount of graphite utilized and mainly to avoid tbe use of tbe expensive and pollutant acyl balides and benzene, graphite can be coupled with para-toluenesulfonic acid and utilized to activate the more ecocompatible carboxylic acids toward electrophilic acylation. i With this catalyst, not only a solvent-free process can be developed but also high yields with not activated aromatic substrates and with unactivated carboxylic acids (i.e., para-nitrobenzoic acid) can be obtained (Table 4.25). 

In basic solutions, of an activated aromatic substrate, diazonium salts decompose and eouple to give biaryls (Ar-Ar).2 9 Reaction of benzenediazonium ion (398) and toluene gave a 67% yield of 411, along with 19% of 412 and 14% of 413. This result suggests the coupling is rather unselective. Selectivity is observed only when the substituent is part of the aryl diazonium ion, as in the eonversion of 414 to 415. ... 

On the reaction path of aromatic nitration the initial interaction of the reactive nitrating agent (NOg" ") with activated aromatic substrates leading to tr-complex (benzonium ion) formation can involve a low energy barrier (2-3 kcal/mol) as the highly energetic NO2 provides the excess energy. 

Besides that, electrochemical methods can be used to activate aromatic substrates by means of redox-umpolung procedure, which makes possible to cOTivert imreactive arenes, azoles, phenols, and other aromatic compounds, bearing electron-donating groups, into the intermediate radical cation species, which are able to react with nucleophiles (Scheme 61) [47, 187]. 

A novel intramolecular alkylation using a spiroketal (14) with BFj.OEt, in THF at reflux forms the benzene-fused 8-oxabicyclo[3.2.1]octane ring system (15) in satisfactory yield. IV-Tosylpipecolinic acid (16) in the presence of sulfuric acid in benzene forms the unexpected aromatized derivative (17) in 18% yield and the mechanism is suggested to involve the reaction of intermediate (18) with benzene to form (19). Cumyl and r-butyl hydroperoxides have been used for the electrophilic alkylation of activated aromatic substrates, mainly phenols and phenol ethers.The hydroperoxides behave differently as far as catalysis and regioselectivity are concerned. The latter is believed to be explicable by steric and reactivity/selectivity considerations. Electrophilic r-butylation may be followed by radical reactions due to the r-butyl... 

From zwitterionic intermediate complexes (e.g., that formed from an amine and an activated aromatic substrate), proton removal by excess nucleophile or an added base sometimes facilitates nucleophilic substitution. In such cases, the measured rate... 

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