Acylation with

The mechanism of acylation with acyl halides is usually regarded as involving the acyl cation (acyl carbonium or acylium ion) ... 

A ketone having an a-hydrogen atom may be acylated with an eater or an acid anhydride to form a p diketone ... 

Chiral 2-oxazolidones are useful recyclable auxiliaries for carboxylic acids in highly enantioselective aldol type reactions via the boron enolates derived from N-propionyl-2-oxazolidones (D.A. Evans, 1981). Two reagents exhibiting opposite enantioselectivity ate prepared from (S)-valinol and from (lS,2R)-norephedrine by cyclization with COClj or diethyl carbonate and subsequent lithiation and acylation with propionyl chloride at — 78°C. En-olization with dibutylboryl triflate forms the (Z)-enolates (>99% Z) which react with aldehydes at low temperature. The pure (2S,3R) and (2R,3S) acids or methyl esters are isolated in a 70% yield after mild solvolysis. 

Cydopentane reagents used in synthesis are usually derived from cyclopentanone (R.A. Ellison, 1973). Classically they are made by base-catalyzed intramolecular aldol or ester condensations (see also p. 55). An important example is 2-methylcydopentane-l,3-dione. It is synthesized by intramolecular acylation of diethyl propionylsucdnate dianion followed by saponification and decarboxylation. This cyclization only worked with potassium t-butoxide in boiling xylene (R. Bucourt, 1965). Faster routes to this diketone start with succinic acid or its anhydride. A Friedel-Crafts acylation with 2-acetoxy-2-butene in nitrobenzene or with pro-pionyl chloride in nitromethane leads to acylated adducts, which are deacylated in aqueous acids (V.J. Grenda, 1967 L.E. Schick, 1969). A new promising route to substituted cyclopent-2-enones makes use of intermediate 5-nitro-l,3-diones (D. Seebach, 1977). 

Section 20 7 Esters occur naturally or are prepared from alcohols by Fischer estenfi cation or by acylation with acyl chlorides or acid anhydrides (see Table 20 3)... 

Direct nitration of aniline and other arylamines fails because oxidation leads to the formation of dark colored tars As a solution to this problem it is standaid practice to first protect the ammo group by acylation with either acetyl chloride or acetic anhydride... 

Friedel-Crafts acylation of 3,3-dimethyl-2-indolinone by succinic anhydride gives 3,3-dimethyl-5-(3-catboxyptopionyl)-2-indoline, which is used as an intermediate in the preparation of inotropic agents for treatment of heart failure (94). Antibacterial phlotophenone derivatives have been prepared by Friedel-Crafts acylation with ptopanoyl chlotide (95). 

Polystyrene can be cross-linked by its acylation with bifunctional acylating agents such as adipoyl, sebacoyl, or malonyl chlorides ia the presence of AlCl iu CS2 solution at 0°C (106). 

Friedel-Crafts acylation using nittiles (other than HCN) and HCI is an extension of the Gattermann reaction, and is called the Houben-Hoesch reaction (120—122). These reactions give ketones and are usually appHcable to only activated aromatics, such as phenols and phenoHc ethers. The protonated nittile, ie, the nitrilium ion, acts as the electrophilic species in these reactions. Nonactivated ben2ene can also be acylated with the nittiles under superacidic conditions 95% trifluoromethanesulfonic acid containing 5% SbF (Hg > —18) (119). A dicationic diprotonated nittile intermediate was suggested for these reactions, based on the fact that the reactions do not proceed under less acidic conditions. The significance of dicationic superelectrophiles in Friedel-Crafts reactions has been discussed (123,124). 

Sulfonylation. Under Friedel-Crafts reaction conditions, sulfonyl haUdes and sulfonic acid anhydrides sulfonylate aromatics (139), a reaction that can be considered the analogue of the related acylation with acyl haUdes and anhydrides. The products are sulfones. Sulfonyl chlorides are the most frequently used reagents, although the bromides and fluorides also react ... 

Ethynodiol diacetate (53) is prepared by reduction of the 3-oxo group of norethindrone (28) with lithium tributoxyalurninum hydride, followed by acylation with acetic anhydride-pyridine (78,79). It has been reported that higher yields can be obtained in the reduction step by using triethylanainoalurninum hydride (80). 

Liquid crystal polyesters are made by a different route. Because they are phenoHc esters, they cannot be made by direct ester exchange between a diphenol and a lower dialkyl ester due to unfavorable reactivities. The usual method is the so-called reverse ester exchange or acidolysis reaction (96) where the phenoHc hydroxyl groups are acylated with a lower aHphatic acid anhydride, eg, acetic or propionic anhydride, and the acetate or propionate ester is heated with an aromatic dicarboxyHc acid, sometimes in the presence of a catalyst. The phenoHc polyester forms readily as the volatile lower acid distills from the reaction mixture. Many Hquid crystal polymers are derived formally from hydroxyacids (97,98) and thein acetates readily undergo self-condensation in the melt, stoichiometric balance being automatically obtained. 

In the piepaiation of ioveisol (12) (41), the key intermediate (23) is prepared from the diacid (20) by the action of thionyl chloride followed by 3-amino-l,2-propanediol. The alcohol groups of (23) are protected as the acetates (25), which is then N-acylated with acetoxyacetyl chloride and deprotected in aqueous methanol with sodium hydroxide to yield (26). N-alkylation of (26) produces ioversol (12). 

Similar ester carboxylate group containing polymeric titanate esters are obtained by the reaction of titanoxanes with carboxyUc acids (26), by reaction of a tetraalkyl titanate with a carboxyUc acid and 1—2 moles of water (27), or by reacting a polymeric metal acylate with a higher boiling carboxyUc acid and removing the lower boiling carboxyUc acid by distillation (28). 

Mixed-Metal Systems. Mixed-metal systems, where a zirconium alkyl is formed and the alkyl group transferred to another metal, are a new apphcation of the hydrozirconation reaction. These systems offer the advantages of the easy formation of the Zr—alkyl as well as the versatiUty of alkyl—metal reagents. For example, Cp2ZrRCl (R = alkyl or alkenyl) reacts with AICI3 to give an Al—alkyl species which may then be acylated with... 

Resolution of racemic alcohols by acylation (Table 6) is as popular as that by hydrolysis. Because of the simplicity of reactions ia nonaqueous media, acylation routes are often preferred. As ia hydrolytic reactions, selectivity of esterification may depend on the stmcture of the acylatiag agent. Whereas Candida glindracea Upase-catalyzed acylation of racemic-cx-methylhenzyl alcohol [98-85-1] (59) with butyric acid has an enantiomeric value E of 20, acylation with dodecanoic acid increases the E value to 46 (16). Not only acids but also anhydrides are used as acylatiag agents. Pseudomonasfl. Upase (PFL), for example, catalyzed acylation of a-phenethanol [98-85-1] (59) with acetic anhydride ia 42% yield and 92% selectivity (74). 

By taking advantage of the remarkable abihty of subtihsia [9014-01-1] to remain catalyticahy active ia anhydrous dimethylformamide, a number of carbohydrates and other sugar-related compounds have been regioselectively acylated with trichloroethyl butyrate (100). In the case of maltose [69-79-4] (76) and sahcia [138-52-3] (77), for example, acylation occurs exclusively at the C-6 positions. 

Unprotected racemic amines can be resolved by enantioselective acylations with activated esters (110,111). This approach is based on the discovery that enantioselectivity of some enzymes strongly depends on the nature of the reaction medium. For example, the enantioselectivity factor (defined as the ratio of the initial rates for (3)- and (R)-isomers) of subtiHsin in the acylation of CX-methyl-ben zyl amine with tritiuoroethyl butyrate varies from 0.95 in toluene to 7.7 in 3-methyl-3-pentanol (110). The latter solvent has been used for enantioselective resolutions of a number of racemic amines (110). 

Triazoles are acylated with acyl halides, usually initially at the 1-position, but the acyl group may migrate to the 2-position on heating or on treatment with base. Thus acetylation with acetyl chloride often gives 1-acetyl derivatives, which rearrange to the 2-isomers above 120 °C (74AHCil6)33). 

The 17-hydroxy group of 2,3-epithiosteroids and the hydroxy groups of some epi-thiosugars may be acylated with acid anhydrides or chlorides without affecting the episulfide (77CPB1140). 

Ring enlargement of A-acyl compounds, generally observed with oxaziridines, is observed only occasionally with diaziridines. Under more forced conditions of acylation with acetic anhydride, oxadiazolines like (139) were obtained (76MIP50800). A 4-nitrobenzoyl derivative rearranged at room temperature (76JOC3229). 

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