Benzene derivatives Friedel-Crafts alkylation

All attempts to prepare selenazole derivatives by the Gatterman (for-mylation) or Friedel-Crafts (alkylation) methods failed (19, 26). indicating that the electrophilic reactivity of the 5-position is less than that of benzene or toluene. 

Vinylchlorosilanes react with aromatic compounds in the presence of Lewis acid to give the alkylation products 2-(chlorosilyl)ethylarenes. In the Friedel-Crafts alkylation of aromatic compounds, the reactivity of vinylchlorosilanes is slightly lower than that of allylchlorosilanes.Friedel-Crafts alkylation of benzene derivatives with vinylsilanes to give 2-(chlorosilyl)ethylarenes was first reported by the Andrianov group (Eq. (5))." The reactivity of vinylsilanes in the... 

Bismuth tra-tri lluoromcthancsulfonate, Bi(OTf)3, and BiCh were found to be effective catalysts for the Friedel-Crafts acylation of both activated and deactivated benzene derivatives such as fluorobenzene.19 Ga(III) triflate is also effective for Friedel-Crafts alkylation and acylation in alcohols and can tolerate water.20 This catalyst is water-stable... 

Allylchlorosilanes undergo Friedel-Crafts alkylation with aromatic compounds such as benzene derivatives and ferrocene to give [p-(chlorosilyl)alkyl]arene compounds in the presence of Lewis acid catalyst. Allylsilanes containing two or more chlorine atoms on silicon react smoothly with benzene under mild conditions to give alkylation products in good yields [Eq. (15)]. In alkylations of benzene, the reactivity of the allylsilanes increases as the number of chlorine atoms on the silicon increases, but decreases as the number of methyl groups increases. Because the reactivity of allylsilanes is sensitive to the electronic nature of the substituents on the silicon atom, allylsilane selection is an important factor for alkylation reactions. 

The range of preparatively useful electrophilic substitution reactions is often limited by the acid sensitivity of the substrates. Whereas thiophene can be successfully sulfonated in 95% sulfuric acid at room temperature, such strongly acidic conditions cannot be used for the sulfonation of furan or pyrrole. Attempts to nitrate thiophene, furan or pyrrole under conditions used to nitrate benzene and its derivatives invariably result in failure. In the case of sulfonation and nitration milder reagents can be employed, i.e. the pyridine-sulfur trioxide complex and acetyl nitrate, respectively. Attempts to carry out the Friedel-Crafts alkylation of furan are often unsuccessful because the catalysts required cause polymerization. 

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. 

Substrates of Friedel-Crafts acylations are benzene and naphthalene, as well as their halogen, alkyl, aryl, alkoxy, or acylamino derivatives. Acceptor-substituted aromatic compounds are inert. Because Friedel-Crafts acylations introduce an acceptor into the aromatic substrate, no multiple substitutions take place. This distinguishes them from Friedel-Crafts alkylations. Free OH and NH2 groups in the aromatic compound prevent Friedel-Crafts acylations because they themselves are acylated. However, the O-acylphenols available in this way can later be rearranged with A1C1, into orf/zo-acylated isomers (Fries rearrangement). 

Alcohols are another source of carbocations for Friedel-Crafts alkylations. Alcohols commonly form carbocations when treated with Lewis acids such as boron trifluoride (BF3). If benzene (or an activated benzene derivative) is present, substitution may occur. 

In the presence of aluminum chloride, an acyl chloride reacts with benzene (or an activated benzene derivative) to give a phenyl ketone an acylbenzene. The Friedel-Crafts acylation is analogous to the Friedel-Crafts alkylation, except that the reagent is an acyl chloride instead of an alkyl halide and the product is an acylbenzene (a phenone ) instead of an alkylbenzene. 

Ferrocene reacts with acetyl chloride and aluminum chloride to afford the acylated product (287) (Scheme 84). The Friedel-Crafts acylation of (284) is about 3.3 x 10 times faster than that of benzene. Use of these conditions it is difficult to avoid the formation of a disubstituted product unless only a stoichiometric amount of AlCft is used. Thus, while the acyl substituent present in (287) is somewhat deactivating, the relative rate of acylation of (287) is still rapid (1.9 x 10 faster than benzene). Formation of the diacylated product may be avoided by use of acetic anhydride and BF3-Et20. Electrophilic substitution of (284) under Vilsmeyer formylation, Maimich aminomethylation, or acetoxymercuration conditions gives (288), (289), and (290/291), respectively, in good yields. Racemic amine (289) (also available in two steps from (287)) is readily resolved, providing the classic entry to enantiomerically pure ferrocene derivatives that possess central chirality and/or planar chirality. Friedel Crafts alkylation of (284) proceeds with the formation of a mixture of mono- and polyalkyl-substituted ferrocenes. The reaction of (284) with other... 

Friedel-Crafts Alkylation Reactions. The activation of glyoxylate esters,trifluoromethyl pyruvate esters, and unsaturated a-ketoesters by catalyst 2 converts these materials into effective electrophiles for asymmetric Friedel-Crafts alkylation reactions with activated arenes (eqs 16 and 17). In fact, bis(triflate) (2) is far superior to tbe bis(hexafluoroantimonate) complex at catalyzing the enantioselective alkylation of benzene derivatives. Aniline and anisole derivatives both give the reaction, as do heterocyclic aromatic compounds such as indole and furan. 

When the Hammett plot bends the other way, so that the rate of the reaction decreases as it passes the discontinuity, we have a single mechanism with a change in rate-determining step. A reaction goes by the fastest possible mechanism but its rate is limited by the slowest of the steps in that mechanism. An example is the intramolecular Friedel-Crafts alkylation of a diphenyl derivative where the alkylating agent is a diaryhnethanol attached to one of the benzene rings in the ortho position. 

The f-butylated naphthalene derivative (18 equation 49) is of interest as an intermediate for the synthesis of fungicides. Tetrahydronaphthalene derivatives, such as (20), have been evaluated as antifertility agents. Sugita et al. have studied the AlCb-catalyzed Friedel-Crafts alkylation of benzene with l-phenyl-2-propanol and 2-phenyl-1-propanol in the presence of additives, such as CuCb, CU2CI2 and decalin. Highly regioselective formation of 1,1-diphenylpropane was observed with Cu or Cu chloride as the additive. Some pertinent results of synthetic value are shown in Scheme 5. The addition of decalin diminished the alkylation reaction to give Ae reduction product 1-phenylpropane. 

The characteristic reaction of benzene and its derivatives is electrophilic aromatic substitution. In these reactions, a hydrogen on the benzene ring is replaced by a chlorine (chlorination), a bromine (bromination), an alkyl or acyl group (Friedel-Crafts alkylation or acylation), a nitro group (nitration), or a sulfonic acid group (sulfonation). 

In Friedel-Crafts alkylation, benzene is reacted with alkyl chlorides in the presence of metal halides (AICI3, AlBrj) as catalysts. The catalyst serves as Lewis acid and increases the electrophilicity of the alkyl halide. Alkylation is important for the synthesis of alkyl substituted derivatives of benzene. But there is a possibility of rearrangement of the intermediates resulting in undesired products. For example, if primary halides are used in alkylation, they can rearrange to form secondary or tertiary carbocations which are more stable intermediates. This can result in multiple products. 

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