Phenol acylation acetic acid

Aromatic amines 4 are metabolised in vivo by cytochrome P450 mediated oxidation to phenolic and hydroxylamine derivatives 5 and 6. Phase II conjugation of the latter with PAPS or acyl transferase results in formation of the sulfuric or acetic acid esters 7. Nitrogen conjugation to give the A-acetyl analogues is also possible (Scheme l).54 65... 

The alkylation of 5-(4-hydroxyphenoxy)-l/f-l,2,3-triazoles (147) under alkaline conditions exclusively yields the isomeric N(2) and N(3) alkylation products (148) and (149) (Equation (9)). For R = PhCH2, the N(2) and N(3) isomers are obtained in almost equal amounts, but for R = PhjC, only 1% of the N(3) isomer is formed because of steric hindrance. No N(l) alkylation is observed. Acylation and sulfonation of (147) under similar conditions results in attack at the phenolic oxygen <82JHCl 147>. Reaction of benzotriazole with 2-chlorothiophen-3-ones (150) in acetic acid gives 5-(benzotriazol-l-yl)-3-hydroxythiophene-2-carboxylates (151) (Equation (10)) <87JHC1301>. 

Essentially the same route is followed for the synthesis of the triphenylethylene nitromifene (8-5). The sequence starts with Friedel-Crafts acylation of the alkylation product (8-1) from phenol and 1,2-dibromoethane with the acid chloride from anisic acid (8-2). The displacement of bromine in the product (8-3) with pyrrolidine leads to the formation of the basic ether and thus (8-4). Condensation of that product with benzylmagnesium bromide gives the tertiary alcohol (8-5). This product is then treated with a mixture of nitric and acetic acids. The dehydration products from the first step almost certainly consist of a mixture of the E and Z isomers for the same reasons advanced above. The olefin undergoes nitration under reaction conditions to lead to nitromifene (8-6) as a mixture of isomers [8] the separated compounds are reported to show surprisingly equivalent agonist/antagonist activities. 

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. 

The scheme proposed for the reaction over HFAU was that PA dissociates in phenol (P) and ketene and that o-HAP, which was highly favoured over the para isomer, results partly from an intramolecular rearrangement of PA, partly from acyl group transfer from PA to P whereas p-HAP results from this latter reaction only. In these experiments, the zeolite deactivation was very fast, as a result of coke deposition and zeolite dehydroxylation. Catalyst stability can be considerably improved by operating at lower temperatures and especially by substituting equimolar mixtures of PA and water or P and acetic acid for PA. Much higher HAP yields were obtained by using the P - acetic acid mixture as reactants.[68]... 

Figure 3.5 Reaction scheme of the gas phase phenol acylation with acetic acid (AcOH) over HMFI at 553 K. Reprinted with permission from Industrial Engineering Chemistry Research, Vol. 34, Guisnet et al., Kinetic modelling of phenol acylation with acetic acid on HZSM5, pp. 1624-1629, Copyright (1995), American Chemical Society...

Figure 3.6 Yields, X (%) of phenyl acetate, PA ( ), o-hydroxyacetophenone, o-HAP (o) and p-hydroxyacetophenone, p-HAP ( ) as a function of the conversion of phenol, Xp (%), in an equimolar mixture with acetic acid over HMFI at 553 K. Reprinted from Journal of Molecular Catalysis, Vol. 93, Neves et al., Acylation of phenol with acetic acid over a HZSM-5 zeolite, reaction scheme, pp. 169-179, Copyright (1994), with permission from Elsevier...

Phenolic compounds are generally extracted using various mixtures of water and alcohol. Anthocyanins are traditionally extracted in the flavylium cation form, with methanol-containing hydrochloric acid. For the acylated anthocyanins, it is necessary to replace the hydrochloric acid with a weaker acid, either formic or acetic acid. Lipids, carotenoids, and chlorophyll are removed from the water-alcohol extracts with hexane, chloroform, or petroleum ether. The defatted extracts may be analyzed directly or after a partitioning of the phenolics into ethyl acetate. 

Nencki reacUon. The general reaction, zinc chloride-catalyzed acylation of a phenol, is illustrated by the conversion of resorcinol into resacetophenone and of pyrogallol into gallacetophenone. The procedures are similar except that acetic acid is used in the first and acetic anhydride in the second. 

Pyridine-catalyzed acylation of phenols using benzoyl chloride and benzoyl bromide was reported . Acylation of phenols using acetyl chloride or benzoyl chloride can be achieved using triflic acid as the catalyst in nonpolar solvents snch as methylene chloride. The role of pyridine in these reactions seems to be the intermittent formation of the benzoylpyrimidinium ions as the reactive species. The activated phenolic componnds snch as resorcinol, on the other hand, could be acylated in near-supercritical water (250-300 °C) without using any external Lewis acid catalysts (equation 47) . The equilibrium conversions in water, however, are to the extent of about 4%. Running the same reactions in neat acetic acid causes a tenfold increase in yield. 

A kinetic study of the acylation of phenol with phenyl acetate was carried out in liquid phase at 160°C over HBEA zeolite samples, sulfolane or dodecane being used as solvents. The initial rates of hydroxyacetophenone (HAP) production were similar in both solvents. However the catalyst deactivation was faster in dodecane, most likely because of the faster formation of heavy reaction products such as bisphenol A derivatives. Moreover, sulfolane had a very positive effect on p-HAP formation and a negative one on o-HAP formation. To explain these observations as well as the influence of phenol and phenyl acetate concentrations on the rates of 0- and p-HAP formation it is proposed that sulfolane plays two independent roles in phenol acylation solvation of acylium ions intermediates and competition with phenyl acetate and phenol for adsorption on the acid sites. Donor substituents of phenyl acetate have a positive effect on the rate of anisole acylation, provided however there are no diffusion limitations in the zeolite pores. 

Isoflavones (3-aryl-chromones) can also be prepared in this way boron trifluoride-catalysed Friedel-Crafts acylation of a reactive phenol with an aryl acetic acid is followed by reaction with dimethylfor-mamide and phosphorus pentachloride. ... 

Most studies in which acid solids were used concern the synthesis of hydroxyacetophenones either by Fries rearrangement of phenyl acetate [3,5-15] or by acylation of phenol with acetic acid or acetic anhydride [11,16-21]. These reactions were conducted in the gas or liquid phase, zeolites being generally chosen as catalysts (Section 5.3.1). These shape-selective catalysts can also be used... 

Neves, L, Jayat, R, Magnoux, R, Perot, G., Riberito, R R., Guberlmarm, M., and Guisnet, M. 1994. Acylation of phenol with acetic acid over a HZSM5 zeolite, reaction scheme. /. Mol. Catal. 93 169-179. 

Padro, C. L. and Apesteguia, C. R. 2004. Gas-phase synthesis of hydroxyac-etophenones by acylation of phenol with acetic acid.. Catal. 226 308-320. 

The reactivity of aromatic amines towards halogens is reduced by salt formation (mineral acid medium), A-acylation, or JV-alkylation. Aqueous solutions of the amine hydrohalide are treated with the halogen or glacial acetic acid is used as solvent to which sodium acetate is added to bind the halogen acid formed. As with phenols, the formation of mono- and di-bromin-ated amines is of especial interest. 

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