Anhydrides cyclic, acylation

Figure 6.2 Separation of products by (a) cyclic anhydrides as acyl donors and (b) fluorous phase technique.

The scope of this reaction is similar to that of 10-21. Though anhydrides are somewhat less reactive than acyl halides, they are often used to prepare carboxylic esters. Acids, Lewis acids, and bases are often used as catalysts—most often, pyridine. Catalysis by pyridine is of the nucleophilic type (see 10-9). 4-(A,A-Dimethylamino)pyridine is a better catalyst than pyridine and can be used in cases where pyridine fails. " Nonbasic catalysts are cobalt(II) chloride " and TaCls—Si02. " Formic anhydride is not a stable compound but esters of formic acid can be prepared by treating alcohols " or phenols " with acetic-formic anhydride. Cyclic anhydrides give monoesterified dicarboxylic acids, for example,... 

Rate constants and Arrhenius parameters for the reaction of Et3Si radicals with various carbonyl compounds are available. Some data are collected in Table 5.2 [49]. The ease of addition of EtsSi radicals was found to decrease in the order 1,4-benzoquinone > cyclic diaryl ketones, benzaldehyde, benzil, perfluoro propionic anhydride > benzophenone alkyl aryl ketone, alkyl aldehyde > oxalate > benzoate, trifluoroacetate, anhydride > cyclic dialkyl ketone > acyclic dialkyl ketone > formate > acetate [49,50]. This order of reactivity was rationalized in terms of bond energy differences, stabilization of the radical formed, polar effects, and steric factors. Thus, a phenyl or acyl group adjacent to the carbonyl will stabilize the radical adduct whereas a perfluoroalkyl or acyloxy group next to the carbonyl moiety will enhance the contribution given by the canonical structure with a charge separation to the transition state (Equation 5.24). 

Like other anhydrides, cyclic anhydrides react wfth ammonia to yield amides in this case the product contains both --CONH2 and —COOH groups. If this acid-amide is heated, a molecule of water is lost, a ring forms, and a product is obtained in which two acyl groups have become attached to nitrogen compounds of this sort are called imides. Phthalic anhydride gives phthalamic acid and phthalimide ... 

Another example by Gotor and coworkers is kinetic resolution by acylation of a primary alcohol [52]. With cyclic anhydrides as acyl donors the reaction product (now bearing a carboxylic acid) could easily be separated from the mixture by alkaline extraction. The non-reacting enantiomer is an intermediate in the synthesis of (-)-paroxetine, a selective inhibitor of 5-hydroxytryptamine reuptake (Scheme 13.4). 

In this paper, we give some examples of ethylaluminum dichloride (EtAlCl2)-induced acylations with different acylating agents such as saturated acyl chlorides, dicarboxylic acid dichlorides, cyclic anhydrides, unsaturated acyl chlorides, and aromatic and heteroaromatic acyl chlorides. 

Dicarboxylic acid anhydrides from o-quinones via cyclic acyl peroxides s. 16,198... 

Fragmentation In the case of linear anhydrides abundant acyl ions due to cleavage next to carbonyl group. For cyclic anhydrides maxima due to decarboxylation (Am 44), followed by decarbonylation. 

T riphenylphosphine Dicarboxylic acid anhydrides from cyclic acyl peroxides... 

In Summary The hydroxy group in COOH can be replaced by halogen by using the same reagents used to convert alcohols into haloalkanes—SOCI2 and PBrs. The resulting acyl halides are sufficiently reactive to be attacked by carboxylic acids to generate carboxyUc anhydrides. Cyclic anhydrides may be made from dicarboxylic acids by thermal dehydration. 

After acyl halides acid anhydrides are the most reactive carboxylic acid derivatives Three of them acetic anhydride phthahc anhydride and maleic anhydride are mdus trial chemicals and are encountered far more often than others Phthahc anhydride and maleic anhydride have their anhydride function incorporated into a nng and are referred to as cyclic anhydrides... 

During electrochemical fluorination retention of important functional groups or atoms in molecules is essential. Acyl fluorides and chlorides, but not carboxylic acids and anhydrides (which decarboxylate), survive perfluorination to the perfluorinated acid fluorides, albeit with some cyclization in longer chain (>C4) species [73]. Electrochemical fluorination of acetyl fluoride produces perfluoro-acetyl fluoride in 36-45% yields [85]. Electrochemical fluorination of octanoyl chloride results in perfluorinated cyclic ethers as well as perfluorinated octanoyl fluonde. Cyclization decreases as initial substrate concentration increases and has been linked to hydrogen-bonded onium polycations [73]. Cyclization is a common phenomenon involving longer (>C4) and branched chains. a-Alkyl-substituted carboxylic acid chlorides, fluorides, and methyl esters produce both the perfluorinated cyclic five- and six-membered ring ethers as well as the perfluorinated acid... 

The acylation of enamines derived from cyclic ketones, which can lead to the acyl ketone or ring expansion (692-694), was studied by NMR and mass spectroscopic analysis of the products (695,696). In a comparative study of the rates of diphenylketene addition to olefins, a pronounced activation was observed in enamines (697). Enamine N- and C-acylation products were obtained from reactions of Schiff s bases (698), vinylogous urethanes (699), cyanamides (699), amides (670,700), and 2-benzylidene-3-methylbenzothiazoline (672) with acid chlorides, anhydrides, and dithio-esters (699). 

Despite its widespread application [31,32], the kinetic resolution has two major drawbacks (i) the maximum theoretical yield is 50% owing to the consumption of only one enantiomer, (ii) the separation of the product and the remaining starting material may be laborious. The separation is usually carried out by chromatography, which is inefficient on a large scale, and several alternative methods have been developed (Figure 6.2). For example, when a cyclic anhydride is the acyl donor in an esterification reaction, the water-soluble monoester monoacid is separable by extraction with an aqueous alkaline solution [33,34]. Also, fiuorous phase separation techniques have been combined with enzymatic kinetic resolutions [35]. To overcome the 50% yield limitation, one of the enantiomers may, in some cases, be racemized and resubmitted to the resolution procedure. 

Friedel-Crafts acylation can be carried out with cyclic anhydrides, in which case the product contains a carboxyl group in the side chain. When succinic... 

Reactions with Acylium Ions. Alkenes react with acyl halides or acid anhydrides in the presence of a Lewis acid catalyst to give (3,y-unsaturated ketones. The reactions generally work better with cyclic than acyclic alkenes. 

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