Aromatic compounds alkyl-substituted

Strategy Problem 1 The wrong substitution pattern . Making aromatic compounds m-substituted with two o -directing groups is always a problem. What strategies can you suggest An example (TM 412) is the alkyl hahde used in the synthesis of some steroids. 

The solubilities of aromatic compounds in the ionic liquid are dramatically higher than those of saturated compounds. Benzene has a solubility of 4.9mol/mol of ionic liquid, and thiophene has a solubility of 6.7mol/mol of ionic liquid. A dramatic steric effect was observed on the solubility of aromatics the alkyl-substituted aromatics showed reduced solubility. Although the solubility of hexene in the ionic liquid is considerably lower than that of the aromatics, it is still measurably higher than that of hexane. Similar structure-solubility relationships characteristic of organic molecules were observed with the ionic liquids [BMIM]BF4, [BMIM]PFg, and [EMIM]BF4 (Fig. 10) (27). 

Substituted aromatic compounds alkylate much more easily, so if you, for... 

From a study of the structure of many substances formed as the result of the introduction of substituents into aromatic compounds, certain general conclusions of great importance can be drawn. It has been pointed out that aromatic compounds yield substitution-products when treated with sulphuric acid, nitric acid, chlorine, and bromine. Under certain conditions iodine can also be introduced directly. Alkyl, acyl, and other radicals can be introduced by means of the Friedel and Crafts synthesis. In all these cases the position in the molecule taken by the entering atom or group is determined by the nature of the atom or group already present. The facts established lead to the following rules —... 

As is broadly true for aromatic compounds, the a- or benzylic position of alkyl substituents exhibits special reactivity. This includes susceptibility to radical reactions, because of the. stabilization provided the radical intermediates. In indole derivatives, the reactivity of a-substituents towards nucleophilic substitution is greatly enhanced by participation of the indole nitrogen. This effect is strongest at C3, but is also present at C2 and to some extent in the carbocyclic ring. The effect is enhanced by N-deprotonation. 

Aryl diazonium ions prepared by nitrous acid diazotization of primary arylamines are substantially more stable than alkyl diazonium ions and are of enormous synthetic value Their use m the synthesis of substituted aromatic compounds is described m the following two sections... 

Friedel-Crafts alkylation (Section 12 6) An electrophilic aro matic substitution in which an aromatic compound reacts with an alkyl halide in the presence of aluminum chloride An alkyl group becomes bonded to the nng... 

The term naphthenic acid, as commonly used in the petroleum industry, refers collectively to all of the carboxyUc acids present in cmde oil. Naphthenic acids [1338-24-5] are classified as monobasic carboxyUc acids of the general formula RCOOH, where R represents the naphthene moiety consisting of cyclopentane and cyclohexane derivatives. Naphthenic acids are composed predorninandy of aLkyl-substituted cycloaUphatic carboxyUc acids, with smaller amounts of acycHc aUphatic (paraffinic or fatty) acids. Aromatic, olefinic, hydroxy, and dibasic acids are considered to be minor components. Commercial naphthenic acids also contain varying amounts of unsaponifiable hydrocarbons, phenoHc compounds, sulfur compounds, and water. The complex mixture of acids is derived from straight-mn distillates of petroleum, mosdy from kerosene and diesel fractions (see Petroleum). 

Olefin Complexes. Silver ion forms complexes with olefins and many aromatic compounds. As a general rule, the stabihty of olefin complexes decreases as alkyl groups are substituted for the hydrogen bonded to the ethylene carbon atoms (19). 

Like other aromatic compounds, aromatic ethers can undergo substitution in the aromatic ring with electrophilic reagents, eg, nitration, halogenation, and sulfonation. They also undergo Eriedel-Crafts (qv) alkylation and acylation. 

Pyridine lies near one extreme in being far less reactive than benzene toward substitution by electrophilic reagents. In this respect it resembles strongly deactivated aromatic compounds such as nitrobenzene. It is incapable of being acylated or alkylated under Friedel-Crafts conditions, but can be sulfonated at high temperature. Electrophilic substitution in pyridine, when it does occur, takes place at C-3. 

Other typical electrophilic aromatic substitution reactions—nitration (second entr-y), sul-fonation (fourth entry), and Friedel-Crafts alkylation and acylation (fifth and sixth entries)—take place readily and are synthetically useful. Phenols also undergo electrophilic substitution reactions that are limited to only the most active aromatic compounds these include nitrosation (third entry) and coupling with diazonium salts (seventh entry). 

The synthesis of an alkylated aromatic compound 3 by reaction of an aromatic substrate 1 with an alkyl halide 2, catalyzed by a Lewis acid, is called the Friedel-Crafts alkylation This method is closely related to the Friedel-Crafts acylation. Instead of the alkyl halide, an alcohol or alkene can be used as reactant for the aromatic substrate under Friedel-Crafts conditions. The general principle is the intermediate formation of a carbenium ion species, which is capable of reacting as the electrophile in an electrophilic aromatic substitution reaction. 

In order to achieve high yields, the reaction usually is conducted by application of high pressure. For laboratory use, the need for high-pressure equipment, together with the toxicity of carbon monoxide, makes that reaction less practicable. The scope of that reaction is limited to benzene, alkyl substituted and certain other electron-rich aromatic compounds. With mono-substituted benzenes, thepara-for-mylated product is formed preferentially. Super-acidic catalysts have been developed, for example generated from trifluoromethanesulfonic acid, hydrogen fluoride and boron trifluoride the application of elevated pressure is then not necessary. 

The reactivity of Ce, C7, Cg aromatics is mainly associated with the benzene ring. Aromatic compounds in general are liable for electrophilic substitution. Most of the chemicals produced directly from benzene are obtained from its reactions with electrophilic reagents. Benzene could be alkylated, nitrated, or chlorinated to important chemicals that are precursors for many commercial products. 

Azonine anions 1 (X = N M + ), the parent compound 1 (X = NH) and, to a lesser extent, alkyl-substituted derivatives (X = NR), however, can be classified as aromatic, as they are flat, display high thermal stability and exhibit diatropic properties. 

The latter reagent also methylates certain heterocyclic compounds (e.g., quinoline) and certain fused aromatic compounds (e.g., anthracene, phenanthrene). The reactions with the sulfur carbanions are especially useful, since none of these substrates can be methylated by the Friedel-Crafts procedure (11-12). It has been reported that aromatic nitro compounds can also be alkylated, not only with methyl but with other alkyl and substituted alkyl groups as well, in ortho and para positions, by treatment with an alkyllithium compound (or, with lower yields, a Grignard reagent), followed by an oxidizing agent such as Bra or DDQ (P- 1511). 

On the other hand, the oxidation of the alkyl substituent in alkyl aromatic compounds can be carried out by various methods efficiently. For example, CAN has been used to oxidize substituted toluene to aryl aldehydes. Selective oxidation at one methyl group can be achieved (Eq. 7.19).44 The reaction is usually carried out in aqueous acetic acid. 

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