Friedel-Crafts substitution, 223

Intramolecular Friedel-Crafts substitution has also figured prominently in the synthesis of oxindoles from cx-haloacelanilides. Typical reaction conditions for cyclizalion involve heating with A1CI,[13-17]. 

The most straightforward route toward 15 is likely to be the Friedel-Crafts reaction of 3-benzyloxyphenylacetic acid (19) with iodobenzene (18), as shown in Scheme 5.4. However, preliminary attempts at this type of reaction were met with the very low reactivity of iodobenzene (18) toward Friedel-Crafts substitutions. 

Friedel-Crafts substitution of phenoxazine or V-acetylphenoxazine with acetyl chloride in the presence of aluminum chloride was found to give a C-monoacetylphenoxazine.11,58 This acetylphenoxazine, which was first formulated as 3-acetylphenoxazine,11 was shown later by Vanderhaeghe37 to be 2-acetylphenoxazine (27) this conclusion was supported also by the examination of the infrared and ultraviolet... 

A similar oxidation of 2,8-diethylphenoxazine yields 2,8-diacetyl-phenoxazine,61,82 identical with that obtained by Friedel-Crafts substitution (Section IV, B, 3). 

As might be expected for a polyene metal cation, the arene ligand in complexes (395) is unreactive toward normal Friedel-Crafts substitution. In turn, the FeCp+ adjunct acts as a good electron-withdrawing group and facilitates attack by hydride and carbanion nucleophiles on the benzene ligand to form ( -cyclohexadienyl)FeCp complexes. For LiAlH4 as nucleophile and at low... 

Hydrolysis of the amide forms the Friedel-Crafts substitution products. 

Alcohols, including tertiary alcohols, react readily with the reagent. The reagent adds stereospecifically (Irons) to unhindered olefins, for example, to the 2-butenes tetrasubstituted olefins do not react. The reagent can be used for Friedel-Crafts substitution of aromatic compounds, including azulene. The 2,4-dinitrobenzene-sulfenyl derivatives formed are colored solids readily purified by crystallization or chromatography and hence are useful for purposes of identification. 

These thiadecaboranes have a rich chemistry which includes their conversion to other thiaboranes,2,3 the preparation of metallothiaboranes2,4 and homogeneous catalysis,5 Friedel-Crafts substitution,6,7 hydroboration reactions,8 and acid-base reactions.2,9... 

The iminium salt products from Vilsmeier reactions, before hydrolysis, can be neatly utilised for further Friedel-Crafts substitution. The substituent is strongly meta directing, thus leading to 2,4-diacylated pyrroles, and also serves to protect the potential aldehyde. ... 

It will be noted that Friedel-Crafts substitution on (264a) is successful, but reaction with bromine takes place by addition rather than by electrophilic substitution. It has been suggested that this may be an example of the Mills-Nixon effect , which has received little attention in recent years. Stated simply, the effect is one of reduction in aromatic character due to the strain imposed by annelation. Additional support for the Mills-Nixon effect comes from e.s.r. studies of radical anions of a series of strained compounds, including naphthalenocyclobutene. Large spin-density perturbations were observed which were correlated with calculations supporting the above effect. ... 

Friedel-Crafts substitution using alkyl halides, or nucleophilic substitution by lithium alkyls. The position of substitution reflects the charge distribution within the borane electrophilic substitution for example invariably occurs at the apical (i.e. most negative) positions, nucleophilic substitution at the most positive borons ... 

The development of synthetic methods for solving the problem of the synthesis of substituted arenes by Friedel-Crafts substitution has focused on three-component coupling of acetylenes. However, there are certain restrictions since attempts at trimerizing two or three different alkynes led to complex mixtures (Scheme 2.3) [9]. Synthesis of trisubstituted benzenes is also problematic in terms of the lack of selectivity during the initial formation of metallocycle as well as the reaction with the third alkyne [9]. 

The most widely used reactions are those of electrophilic substitution, and under controlled conditions a maximum of three substituting groups, e.g. -NO2 (in the 1,3,5 positions) can be introduced by a nitric acid/sul-phuric acid mixture. Hot cone, sulphuric acid gives sulphonalion whilst halogens and a Lewis acid catalyst allow, e.g., chlorination or brom-ination. Other methods are required for introducing fluorine and iodine atoms. Benzene undergoes the Friedel-Crafts reaction. ... 

The nitration, sulphonation and Friedel-Crafts acylation of aromatic compounds (e.g. benzene) are typical examples of electrophilic aromatic substitution. 

It is worth noting here that the results of some other studies of aromatie substitutions, sueh as the Friedel-Crafts benzylation and iso-propylation of alkylbenzenes, and the bromination of alkylbenzenes with bromine, eatalysed by ferrie ehloride, are under suspicion as depending upon slow mixing. As regards halogenation eatalysed by Lewis aeids, positive evidenee to support this eritieism has been obtained. ... 

The selectivity of an electrophile, measured by the extent to which it discriminated either between benzene and toluene, or between the meta- and ara-positions in toluene, was considered to be related to its reactivity. Thus, powerful electrophiles, of which the species operating in Friedel-Crafts alkylation reactions were considered to be examples, would be less able to distinguish between compounds and positions than a weakly electrophilic reagent. The ultimate electrophilic species would be entirely insensitive to the differences between compounds and positions, and would bring about reaction in the statistical ratio of the various sites for substitution available to it. The idea has gained wide acceptance that the electrophiles operative in reactions which have low selectivity factors Sf) or reaction constants (p+), are intrinsically more reactive than the effective electrophiles in reactions which have higher values of these parameters. However, there are several aspects of this supposed relationship which merit discussion. 

---