Friedel-Crafts alkylation reversal

The topics analysed here include reversible termination and the formation of p-tolyl end-groups on polystyrenes made in toluene. For unknown reasons, most authors have very largely ignored this Friedel-Crafts alkylation, which in a polymer context is a transfer reaction. It was unfortunately termed molecular termination by Overberger and was explored by his and Smets groups. 

Reversal of Friedel—Crafts Alkylation Hydro-de-alkylation or Dealkylation... 

The dicyclopentadienyl metal compounds undergo Friedel-Crafts alkylation and acylation, sulfonation, metalation, arylation, and formyla-tion in the case of ferrocene, dicyclopentadienyl ruthenium, and dicyclopentadienyl osmium, whereas the others are unstable to such reactions ( ). Competition experiments (128) gave the order of electrophilic reactivity as ferrocene > ruthenocene > osmocene and the reverse for nucleophilic substitution of the first two by n-butyl lithium. A similar rate sequence applies to the acid-catalysed cleavage of the cyclopentadienyl silicon bonds in trimethylsilylferrocene and related compounds (129), a process known to occur by electrophilic substitution for aryl-silicon bonds (130). 

It has been demonstrated9 that photo-protonation of 2-diphenylmethyl-l,3-dimethoxy-benzene (4) to the cyclohexadienyl cation (5) not only results in dissociative cleavage of the diphenylmethyl cation (the reverse of the step in a Friedel-Crafts alkylation that produces the cyclohexadienyl cation), but is accompanied by a surprising rearrangement to the isomeric 2,4-dimethoxybenzenium ion (6). This (see Scheme 3) represents the first example of a system where rearrangement involving two isomeric... 

Rates for the key step of Friedel-Crafts alkylations, i.e., the attack of carbocations on arenes have only recently been reported [214,215]. Problems arising from the reversibility of the CC-bond-forming step have been overcome by performing experiments in presence of R4N + MC1,7+i salts, where MCl,r+1 acts as a base for the rapid deprotonation of the intermediate benzenium ions (Scheme 52). 

True reversibility of the Friedel-Crafts alkylation—which implies dissociation of an alkylbenzene into benzene and olefin—does not occur... 

Any time an alkyl halide or alcohol is a precursor to a Friedel-Crafts alkylation reaction, rearrangement of the initially formed cation can occur prior to attachment to the aromatic nucleus. Rearrangement can be accompanied by isomerization of the initially formed product, due to the action of the Lewis acid (such as AICI3), required for the reaction. OO Isomerization of groups can occur via 1,2-shifts or via dissociation to a cation and readdition.idl 1,1-Dimethylpropylbenzene (167) dissociates in the presence of aluminum chloride to give 168, for example. The reaction can be reversible under these conditions. When the cation adds to the aromatic ring two products are possible, 169 or 171. Addition to give intermediate cation 169 leads to product... 

Bexarotene is an RXR-selective retinoid marketed by Ligand Pharmaceuticals Inc., for treatment of refractory advanced-stage cutaneous T-cell lynq>homa. Bexarotene is orally administered, safe and side effects are reversible.(Jtl) The synthesis of Bexarotene starts with tetrahydronaphthalene 11, prepared in 91% yield by Friedel-Crafts alkylation of toluene with 2,5-dichloro-2,S-dime1hylhexane 10 (Scheme 5).(31-33) Friedel-Crafts acylation of 11 with chloromethylterphthalate 12 afforded ester 13 in 72% yield. 

Working with the Concepts Reversible Friedel-Crafts Alkylations... 

Reversible nature of Friedel-Crafts alkylation of benzene derivatives has been applied to remove ortho-tert-huty group, which is an essential substituent to isolate an atropisomeric anilide derivative as a stable compound at an ambient temperature. Simpkins and coworkers reported that during the AICI3 catalyzed trans-tert-butylation reaction of the particular enamide compound (12) in benzene, enamide function undergoes Friedel-Crafts alkylation to give phenylated product (13) in good yield (Scheme 6.12) [14]. Thus, in this case, Friedel-Crafts alkylation and dealkylation occur at the same time. 

Sogah (24) and McGrath (25) have reported tert-butyl and phenyl-substituted poly(aryl ether ketones) respectively, which are prepared by nucleophilic substitution reaction of the corresponding substituted hydroquinones and 4,4 -difluorobenzophenone. The resulting polymers were amorphous and highly soluble in common organic solvents as a result of the bulky substituents which suppressed crystallization. The bulky substituents were cleaved with acid in a reverse Friedel-Crafts alkylation reaction to produce the semi-crystalline PEEK (24). 

Review Problem 6 Some chemists who were investigating the possibility of reversible Friedel-Crafts reactions, wanted an activated aromatic ring cormected to a branched alkyl chain and chose to make TM 82. How would you do it ... 

Rearrangement can also occur after the initial alkylation. The reaction of 2-chloro-2-methylbutane with benzene is an example of this behavior.35 With relatively mild Friedel-Crafts catalysts such as BF3 or FeCl3, the main product is 1. With A1C13, equilibration of 1 and 2 occurs and the equilibrium favors 2. The rearrangement is the result of product equilibration via reversibly formed carbocations. 

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