Acylation aromatic rings

Friedel-Crafts acylation of aromatic compounds (Section 12 7) Acyl chlorides and carboxylic acid anhydrides acylate aromatic rings in the presence of alumi num chloride The reaction is electrophil ic aromatic substitution in which acylium ions are generated and attack the ring... 

Heating dicarboxylic acids, HOOC(CH,) COOH n = 2 or 3), forms cyclic anhydrides by intramolecular dehydration [Problem 16.22(a), (6)]. Anhydrides resemble acid halides in their reactions. Because acetic anhydride reacts less violently, it is often used in place of acetyl chloride. Acid anhydrides can also be used to acylate aromatic rings in electrophilic substitutions. 

Similarly, a series of m- and -substituted anilides 68 of thienoic acid were prepared and their H NMR spectroscopic characteristics were examined. In general, good correlations were observed between the chemical shifts of proton signals of the acyl aromatic rings and the Hammett . 

Friedel-Crafts acylation (Section 12.7) Acyl cations (acylium ions) generated by treating an acyl chloride or acid anhydride with aluminum chloride acylate aromatic rings to yield ketones. The arene must be at least as reactive as a halobenzene. Acyl cations are relatively stable, and do not rearrange. 

Examples of these various alternative methods for acylating aromatic rings are given in Scheme 7.5. 

In a Friedel-Crafts acylation, aromatic rings react with acid chlorides in the presence of a Lewis add such as AICI3 to produce acylbenzenes. 

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... 

One of the most useful reac tions of acyl chlorides was presented in Section 12 7 Friedel-Crafts acylation of aromatic rings takes place when arenes are treated with acyl chlorides in the presence of aluminum chloride... 

Fnedel-Crafts acylation In the presence of alumi num chloride acyl chlorides and carboxylic acid an hydrides acylate the aromatic ring of phenols... 

Acylatmg agents such as acyl chlorides and carboxylic acid anhydrides can react with phenols either at the aromatic ring (C acylation) or at the hydroxyl oxygen (O acylation)... 

PoIysuIfonyIa.tlon, The polysulfonylation route to aromatic sulfone polymers was developed independendy by Minnesota Mining and Manufacturing (3M) and by Imperial Chemical Industries (ICI) at about the same time (81). In the polymerisation step, sulfone links are formed by reaction of an aromatic sulfonyl chloride with a second aromatic ring. The reaction is similar to the Friedel-Crafts acylation reaction. The key to development of sulfonylation as a polymerisation process was the discovery that, unlike the acylation reaction which requires equimolar amounts of aluminum chloride or other strong Lewis acids, sulfonylation can be accompHshed with only catalytic amounts of certain haUdes, eg, FeCl, SbCl, and InCl. The reaction is a typical electrophilic substitution by an arylsulfonium cation (eq. 13). 

The steric bulk of the three iodine atoms in the 2,4,6-triiodoben2ene system and the amide nature of the 1,3,5-substituents yield rotational isomers of the 5-A/-acyl-substituted 2,4,6-triiodoisophthalamides. Rotational motion in the bonds connecting the side chains and the aromatic ring is restricted. These compounds also exhibit stereoisomerism when chiral carbon atoms are present on side chains. (R,5)-3-Amino-l,2-propanediol is incorporated in the synthesis of iohexol (11) and ioversol (12) and an (3)-2-hydroxypropanoyl group is used in the synthesis of iopamidol (10). Consequendy, the resulting products contain a mixture of stereoisomers, ie, meso-isomers, or an optical isomer. 

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. 

With a substituted aromatic ring compound 2, mixtures of isomeric coupling products may be formed the ort/zo-product usually predominates. The rules for regiochemical preferences as known from electrophilic aromatic substitution reactions (see for example Friedel-Crafts acylation), do not apply here. 

Cefotiam (67) has an acyl aromatic C-7 side chain bioisosteric with an anilino ring. It can be prepared by... 

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