Phenols, acyl => carboxylic acids

The O acylation of phenols with carboxylic acid anhydrides can be conveniently catalyzed m either of two ways One method involves converting the acid anhydride to a more powerful acylatmg agent by protonation of one of its carbonyl oxygens Addi tion of a few drops of sulfuric acid is usually sufficient... 

The Hf(OTf)4, is also effective in the ortho-acylation of phenols using carboxylic acids instead of the acid chlorides, although somewhat lower yields are obtained and larger amounts of the catalyst are required (equations 42 and 43). ... 

A chlorocyclopropane species is the preferential starting material if Af,0-acetals or )V,0-acylals possessing an AT-amido moiety are to be prepared. Thus heating 1-amido-l-chlorocyclopropanes with a mixture of triethylamine and alcohol, phenol or carboxylic acid in tetrahydrofuran... 

The Fries rearrangement is the acid-catalyzed transformation of aryl esters into hydroxy ary Iketones [1] and often plays an important role in the production of hydro-xyarylketones by acylation of phenols with carboxylic acids, anhydrides, or acyl chlorides. 

Table 5.4 Promotion of acylation of phenols with carboxylic acids by graphite-methanesulfonic acid...

O-Acylation. Trimethylsilyl acetate added dropwise to P2O5 under N2 with stirring and ice-cooling, the mixture heated at 50° for 1 h, cooled to 20-5", / -chlorobenzyl alcohol added dropwise (or in portions), the mixture heated at 80 for 4 h, cooled to 15°, and neutralized with cold satd. aq. NaHCOj - p-chlorobenzyl acetate. Y 70%. F.e., also O-acylation of phenols and carboxylic acids, N-acylation of amines, and S-acylation of thiophenols, s. C.S. Rao et al., Indian J. Chem. 26B, 407-11 (1987). 

When acyl chlorides react with alcohols and phenol, we get esters (and HCl) formed. The reactions happen more quickly than the reactions of alcohols or phenol with carboxylic acids. The acyl chloride reactions also go to completion and do not form an equilibrium mixture. Therefore they are useful in the synthesis of esters in the chemical industry. 

With phenol, the reaction with an acyl chloride proceeds if warmed. There is no reaction between phenol and carboxylic acids, so acyl chlorides must be used if you want to make phenyl esters. The reaction takes place in the presence of a base. The initial reaction between phenol and the base creates the phenoxide ion, CgH O", which acts as the nucleophile to attack the acyl 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)... 

Carboxylic acids react with trifluoroacetic anhydride to give mixed anhydrides that are especially useful for the acylation of hindered alcohols and phenols ... 

Since the imidazolide method proceeds almost quantitatively, it has been used for the synthesis of isotopically labeled esters (see also Section 3.2), and it is always useful for the esterification of sensitive carboxylic acids, alcohols, and phenols under mild conditions. This advantage has been utilized in biochemistry for the study of transacylating enzymes. A number of enzymatic transacylations (e.g., those catalyzed by oc-chymo-trypsin) have been shown to proceed in two steps an acyl group is first transferred from the substrate to the enzyme to form an acyl enzyme, which is then deacylated in a second step. In this context it has been shown[21] that oc-chymotrypsin is rapidly and quantitatively acylated by Af-fraw.s-cinnamoylimidazole to give /ra/w-cinnamoyl-a-chymotrypsin, which can be isolated in preparative quantities and retains its enzymatic activity (see also Chapter 6). 

The chemical diversity of carboxylic acid esters (R-CO-O-R ) originates in both moieties, i.e., the acyl group (R-CO-) and the alkoxy or aryloxy group (-OR7). Thus, the acyl group can be made up of aliphatic or aromatic carboxylic acids, carbamic acids, or carbonic acids, and the -OR7 moiety may be derived from an alcohol, an enol, or a phenol. When a thiol is involved, a thioester R-CO-S-R7 is formed. The model substrates to be discussed in Sect. 7.3 will, thus, be classified according to the chemical nature of the -OR7 (or -SR7) moiety, i.e., the alcohol, phenol, or thiol that is the first product to be released during the hydrolase-catalyzed reaction (see Chapt. 3). Diesters represent substrates of special interest and will be presented separately. 

Hill, C.A.S. and Papadopoulos, A.N. (2002). The pyridine-catalysed acylation of pine sapwood and phenolic model compounds with carboxylic acid anhydrides. Determination of activation energies and entropy of activation. Holzforschung, 56(2), 150-156. 

Phenol esters of a,(3-unsaturated carboxylic acids have an interesting reactivity due to the synthetic utility of the resulting hydroxychalcones (Scheme 19). This aspect will be illustrated in Section IV. However, from the basic point of view, it is worth mentioning that the cis or trans configuration of the olefinic part of the acyl moiety can have a marked influence on the photochemical reactivity of the ester. When para-methoxyphenyl fumarates are irradiated, the normal ortho-rearranged products are obtained. By contrast, irradiation of para-me-thoxyphenyl maleates does not lead to rearrangement. Instead, cyclization products are obtained (Scheme 20). 

Support-bound phenols, oximes, and related compounds yield, upon acylation, esters that are highly susceptible to nucleophilic cleavage. These esters are often used as insoluble acylating agents for the preparation of amides or esters, but only occasionally as linkers for carboxylic acids [113]. These linkers are considered in Sections 3.3.3 and 3.5.1. 

Both aliphatic alcohols and phenols have been immobilized as esters of support-bound carboxylic acids. The esterification can be achieved by treatment of resin-bound acids with alcohols and a carbodiimide, under Mitsunobu conditions, or by acylation of alcohols with support-bound acyl halides (see Section 13.4). 

As reported in the literature, the acylation of aromatic hydrocarbons can be carried out by using zeolites as catalysts and carboxylic acids or acyl chlorides as acylating agents. Thus toluene can be acylated by carboxylic acids in the liquid phase in the presence of cation exchanged Y-zeolites (ref. 1). The acylation of phenol or phenol derivatives is also reported. The acylation of anisole by carboxylic acids and acyl chlorides was obtained in the presence of various zeolites in the liquid phase (ref. 2). The acylation of phenol by acetic acid was also carried out with silicalite (ref. 3) or HZSM5 (ref. 4). The para isomer has been generally favoured except in the latter case in which ortho-hydroxyacetophenone was obtained preferentially. One possible explanation for the high ortho-selectivity in the case of the acylation of phenol by acetic acid is that phenylacetate could be an intermediate from which ortho-hydroxyacetophenone would be formed intramolecularly. 

Fries rearrangement—that is, the transformation of phenolic esters to isomeric hydroxyphenyl ketones—is related to Friedel-Crafts acylations.392,393 Olah et al.394 have found a convenient way to perform the Fries rearrangement of a variety of substituted phenolic esters in the presence of Nafion-H in nitrobenzene as solvent [Eq. (5.153)]. A catalytic amount of Nafion-H is satisfactory, and the catalyst can be recycled. In contrast, Nafion-silica nanocomposites, in general, exhibit low activities in the Fries rearrangement of phenyl acetate to yield isomeric hydroxyacetophe-nones.239,395 In a recent study, BF3-H20 was found to be highly efficient under mild conditions (80°C, 1 h) to transform phenolic esters of aliphatic and aromatic carboxylic acids to ketones (71-99% yields).396 In most cases the para-hydroxyphenyl isomers are formed with high (up to 94%) selectivity. 

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