Isomerization, under Friedel-Crafts condition

Friedel-Crafts alkylation of 2,5-dimethylthiophene with f-butyl chloride and A1C13 gave only the mono-r-butylated product (49) and none of the expected di-f-butylated thiophene (50). In order to facilitate di-r-butylation at positions 3 and 4, the substituents at 2 and 5 were tied back in the thiophenophane (51). This on alkylation gave, unexpectedly, the rearranged mono-f-butyl derivatives (52 30%) and (53 57%), and the di-f-butyl derivative (54 12%). The structures of the products were proved by NMR, Raney nickel desulfurization and independent synthesis (75T2551). One other such isomerization under Friedel-Crafts conditions had been previously reported (65JOC1058) 2,5-di-f-butylthiophene isomerizing to 2,4-di-f-butylthiophene. 

Phenylalkenes also undergo intramolecular alkylation under Friedel-Crafts conditions to yield five- or six-membered cyclic products (indan or tetralin derivatives, respectively). This cyclialkylation145,146,175 may actually also be considered as an isomerization reaction. 

Stereoselective Friedel-Crafts alkylation. 4 Alkylation of benzene with methyl (S)-2-(mesyloxy)propionate, derived from (S)-lactic acid, under Friedel-Crafts conditions (2 equiv. of A1C13) affords methyl (S)-phenylpropionate in 50-80% chemical yield and as high as 97% optical yield. Unfortunately extension to other aromatics results in mixtures of isomeric products. 

A Wagner-Meerwein rearrangement can be part of the isomerization of an alkyl halide (Figure 14.4). For example, 1 -bromopropane isomerizes quantitatively to 2-bromopropane under Friedel-Crafts conditions. The [l,2]-shift A — B involved in this reaction again is an H atom shift. In contrast to the thermoneutral isomerization between carbenium ions A and B of Figure 14.3, in the present case an energy gain is associated with the formation of a secondary carbenium ion from a primary carbenium ion. Note, however, that the different stabilities of the carbenium ions are not responsible for the complete isomerization of 1-bromopropane into 2-bromopropane. The position of this isomerization equilibrium is determined by thermodynamic control at the level of the alkyl halides. 2-Bromopropane is more stable than 1-bromopropane and therefore formed exclusively. 

Alternatively the alkylated aromatic products may rearrange. -Butylbenzene [104-57-8] is readily isomerized to isobutylbenzene [538-93-2] and j Abutyl-benzene [135-98-8] under the catalytic effect of Friedel-Crafts catalysts. The tendency toward rearrangement depends on the alkylatiag ageat and the reaction conditions (catalyst, solvent, temperature, etc). 

Transalkylation and Dealkylation. In addition to isomerizations (side-chain rearrangement and positional isomerization), transalkylation (disproportionation) [Eq. (5.56)] and dealkylation [Eq. (5.57)] are side reactions during Friedel-Crafts alkylation however, they can be brought about as significant selective hydrocarbon transformations under appropriate conditions. Transalkylation (disproportionation) is of great practical importance in the manufacture of benzene and xylenes (see Section 5.5.4) ... 

Fries rearrangement—that is, the transformation of phenolic esters to isomeric hydroxyphenyl ketones—is related to Friedel-Crafts acylations.392,393 Olah et al.394 have found a convenient way to perform the Fries rearrangement of a variety of substituted phenolic esters in the presence of Nafion-H in nitrobenzene as solvent [Eq. (5.153)]. A catalytic amount of Nafion-H is satisfactory, and the catalyst can be recycled. In contrast, Nafion-silica nanocomposites, in general, exhibit low activities in the Fries rearrangement of phenyl acetate to yield isomeric hydroxyacetophe-nones.239,395 In a recent study, BF3-H20 was found to be highly efficient under mild conditions (80°C, 1 h) to transform phenolic esters of aliphatic and aromatic carboxylic acids to ketones (71-99% yields).396 In most cases the para-hydroxyphenyl isomers are formed with high (up to 94%) selectivity. 

The Friedel-Crafts acylation of alkynes is an extremely rapid reaction, and usually leads to the formation of the r/anj-(3-chlorovinyl ketone (equation 23). Reaction temperatures can be as low as -70 "C. The reaction proceeds via reaction of the acyl halide-Lewis acid complex with the alkyne, and whilst the implied vinyl cation has not been observed directly, the reaction products can be understood in terms of reaction of such an intermediate with nucleophiles, usually halide ion. Whilst the r/ans-chlorovinyl ketone has been described as the sole product of the reaction by some workers, others have reported the formation of mixtures of the cis and trans forms, under conditions that did not appear to lead to isomerization.100... 

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... 

The aliphatic version of the classical aromatic Friedel-Crafts acylation produces, by loss of proton, a non-conjugated enone which can then undergo a second acylation thus generating an unsaturated 1,5-diketone. Clearly, if the alkene is not symmetrical, two isomeric diketones are formed. Under the conditions of these acylations, the unsaturated diketone cyclises, loses water and forms a pyrylium salt. The formation of 2,4,6-trimethylpyrylium, best as its much more stable and non-hygroscopic carboxymethanesulfonate, illustrates the process. 

Friedel-Crafts acylation of aromatic ethers Solvent-free benzoylation of aromatic ethers has been performed under the action of microwave irradiation in the presence of a metallic catalyst, FeCla being one of the most efficient [163], With careful control of the temperature and other conditions, nonthermal microwave effects have not been observed either in terms of yield or isomeric ratios of the obtained products (Eq. 79) ... 

Hydrogen fluoride-boron trifluoride (tetrafluoroboric acid, HF-BF3) is used in numerous Friedel-Crafts reactions, isomerization, rearrangement and car-bonylation, and also has industrial interest (42,54). It has a good solubility in organic solvents and, therefore, acts as a strong acid under nonaqueous conditions. 

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