Alkylation aromatic rings

There are a few exceptions. Certain alkyl and vinylic Inflates alkylate aromatic rings without a catalyst see Gramstad Haszeldinei. Chem. Soc. 1957,4069 Olah Nishimura J. Am. Chem. Soc. 1974,96,2214 Slang Anderson Tetrahedron Lett. 1977, 1485, J. Am. Chem. Soc. 1978,100, 1520. 

Examples of benzylic alkylation, aromatic ring deprotonation, and nucleophilic addition to a -position were used in a synthesis of (+)-20-methoxy-serrulat-14-en-7,8-diol. Deprotonation of the optically active complex (54) followed by reaction with chloromethyl methyl ether affords (55)... 

In each of the cases you have met so far, we have used a functional group present in the molecule to help us to disconnect the C-C bond using a 1,2 C-C disconnection. You can look for 1,2 C-C disconnections in alkynes, carbonyl compounds, and alkylated aromatic rings. And, if the target isn t a carbonyl compound, consider what would be possible if functional groups such as hydroxyl groups were converted to carbonyl groups (just as we did with belfosdil). 

In a Friedel-Crafts alkylation, aromatic rings react with alkyl halides in the presence of a Lewis add such as AICI3 to produce alkylbenzenes. Rearrangements and overaUgrlation can be a problem. 

At high temperatures, alkyllithiums have been observed to alkylate aromatic rings by addition to the r-system and subsequent loss of LiH. Of the butyllithiums, r-BuLi has been found to be more reactive than either of its isomers in the alkylation of naphthalene and other condensed aromatics. Addition of r-BuLi, as well as other organolithiums, across the azomethine linkage of pyridine and similar nitrogen heterocycles is a facile process. ... 

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 ... 

Alkyl groups attached to aromatic rings are oxidized more readily than the ring in alkaline media. Complete oxidation to benzoic acids usually occurs with nonspecific oxidants such as KMnO, but activated tertiary carbon atoms can be oxidized to the corresponding alcohols (R. Stewart, 1965 D. Arndt, 1975). With mercury(ll) acetate, allyiic and benzylic oxidations are aJso possible. It is most widely used in the mild dehydrogenation of tertiary amines to give, enamines or heteroarenes (M. Shamma, 1970 H. Arzoumanian. 1971 A. Friedrich, 1975). 

The transmetallation of various organometallic compounds (Hg, Tl, Sn, B, Si, etc.) with Pd(II) generates the reactive cr-aryl, alkenyl, and alkyl Pd compounds. These carbopalladation products can be used without isolation for further reactions. Pd(II) and Hg(II) salts have similar reactivity toward alkenes and aromatic compounds, but Hg(II) salts form stable mercuration products with alkenes and aromatic rings. The mercuration products are isolated and handled easily. On the other hand, the corresponding palladation products are too reactive to be isolated. The stable mercuration products can be used for various reactions based on facile transmetallation with Pd(II) salts to generate the very reactive palladation products 399 and 400 in rim[364,365]. 

Substituents other than alkyl groups may also be present on the aromatic ring but their reduction is beyond the scope of the present discussion... 

Alkyl halides by themselves are insufficiently electrophilic to react with benzene Aluminum chloride serves as a Lewis acid catalyst to enhance the electrophihcity of the alkylating agent With tertiary and secondary alkyl halides the addition of aluminum chlonde leads to the formation of carbocations which then attack the aromatic ring... 

Because acylation of an aromatic ring can be accomplished without rearrangement it is frequently used as the first step m a procedure for the alkylation of aromatic compounds by acylation-reduction As we saw m Section 12 6 Friedel-Crafts alkylation of ben zene with primary alkyl halides normally yields products having rearranged alkyl groups as substituents When a compound of the type ArCH2R is desired a two step sequence IS used m which the first step is a Friedel-Crafts acylation... 

Neither Friedel-Crafts acylation nor alkylation reactions can be earned out on mtroben zene The presence of a strongly deactivating substituent such as a nitro group on an aromatic ring so depresses its reactivity that Friedel-Crafts reactions do not take place Nitrobenzene is so unreactive that it is sometimes used as a solvent m Friedel-Crafts reactions The practical limit for Friedel-Crafts alkylation and acylation reactions is effectively a monohalobenzene An aromatic ring more deactivated than a mono halobenzene cannot be alkylated or acylated under Friedel-Crafts conditions... 

Friedel-Crafts acylation followed by Clemmensen or Wolff-Kishner reduction is a standard sequence used to introduce a primary alkyl group onto an aromatic ring... 

Carbocations usually generated from an alkyl halide and aluminum chloride attack the aromatic ring to yield alkylbenzenes The arene must be at least as reactive as a halobenzene Carbocation rearrangements can occur especially with primary alkyl hal ides... 

A primary or secondary alkyl side chain on an aromatic ring is converted to a carboxyl group by reaction with a strong oxidizing agent such as potassium permanga nate or chromic acid... 

An additional curious feature of alkylaromatic oxidation is that, under conditions where the initial attack involves electron transfer, the relative rate of attack on different alkyl groups attached to the same aromatic ring is quite different from that observed in alkane oxidation. For example, the oxidation of -cymene can lead to high yields of -isopropylbenzoic acid (2,205,297,298). 

The alpha-olefin sulfonates (AOS) have been found to possess good salt tolerance and chemical stabiUty at elevated temperatures. AOS surfactants exhibit good oil solubilization and low iaterfacial tension over a wide range of temperatures (219,231), whereas less salt tolerant alkylaromatic sulfonates exhibit excellent chemical stabiUty. The nature of the alkyl group, the aryl group, and the aromatic ring isomer distribution can be adjusted to improve surfactant performance under a given set of reservoir conditions (232,233). 

Poly(phenylene oxide)s undergo many substitution reactions (25). Reactions involving the aromatic rings and the methyl groups of DMPPO include bromination (26), displacement of the resultant bromine with phosphoms or amines (27), lithiation (28), and maleic anhydride grafting (29). Additional reactions at the open 3-position on the ring include nitration, alkylation (30), and amidation with isocyanates (31). 

The alkylation desctibed in this article is the substitution of a hydrogen atom bonded to the carbon atom of a paraffin or aromatic ring by an alkyl group. The alkylations of nitrogen, oxygen, and sulfur are described in separate articles (see Amines Ethers). 

The first step in the catalytic alkylation of aromatics is the conversion of an olefin or olefin-producing reagent into a carbonium ion or polari2ed complex. Then, this carbonium ion or complex, which is a powerful electrophile, attacks the aromatic ring (32). 

The aromatic ring of alkylphenols imparts an acidic character to the hydroxyl group the piC of unhindered alkylphenols is 10—11 (2). Alkylphenols unsubstituted in the ortho position dissolve in aqueous caustic. As the carbon number of the alkyl chain increases, the solubihty of the alkah phenolate salt in water decreases, but aqueous caustic extractions of alkylphenols from an organic solution can be accomphshed at elevated temperatures. Bulky ortho substituents reduce the solubihty of the alkah phenolate in water. The term cryptophenol has been used to describe this phenomenon. A 35% solution of potassium hydroxide in methanol (Qaisen s alkah) dissolves such hindered phenols (3). 

Methylphenol. This phenol, commonly known as o-cresol, is produced synthetically by the gas phase alkylation of phenol with methanol using modified alumina catalysis or it may be recovered from naturally occurring petroleum streams and coal tars. Most is produced synthetically. Reaction of phenol with methanol using modified zeoHte catalysts is a concerted dehydration of the methanol and alkylation of the aromatic ring. 2-Methylphenol [95-48-7] is available in 55-gal dmms (208-L) and in bulk quantities in tank wagons and railcars. 

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