Zeolite 4-hydroxyacetophenone

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. 

If we examine the formation of hydroxyacetophenones more closely, we can see (Fig. 4a) that on HY, at least part of ortho-hydroxyacetophenone could be formed directly from phenylacetate (i.e, intramolecularly) whereas the para-isomer is clearly a secondary product. On HZSM5 both compounds are secondary products (Fig. 4b). Moreover, one can see that the ortho-/para-hydroxyace-tophenone molar ratio changes with conversion especially over HZSM5 where it decreases from 6 to 1 as conversion decreases. Two explanations can be considered i) a consecutive transformation of para-hydroxyacetophenone which would not occur in the case of the ortho-isomer ii) a change in the ortho-/para-selectivity of the zeolite in the course of deactivation. The points at high conversion being obtained on the fresh catalyst, a preferential deactivation of the sites located outside of the particles will decrease the ortho-/para-hydroxyacetophenone molar ratio if one supposes that these sites which are easily accessible favour the formation of the ortho-... 

On HZSM5 both hydroxyacetophenones are formed by trans-acylation. Disproportionation (reaction e) probably does not exist because of steric contraints. Moreover since ortho-hydroxyacetophenone does not react with phenylacetate (probably for the same reason) to give ortho-acetoxyacetophenone, reaction g cannot take place. On the other hand, the formation of products resulting from the oligomerization of ketene (dehydroacetic acid, 6-methyl 4-acetoxy 2-pyrone, reaction h) is favoured presumably because of the confinement effect in the zeolite. These compounds are supposed to be to a large extent responsible for the deactivation of HZSM5. 

The Fries rearrangement of PA over H-BEA zeolites, which is a simple reaction, was chosen to introduce the competition for adsorption on the zeolite catalysts and its role on the reaction rate. Ortho- and para-hydroxyacetophenones (o- and p-HAP), para-acetoxyacetophenone (p-AXAP) and phenol (P) are the main products o-HAP, P and p-AXAP, which are directly formed (primary products),... 

Figure 2.3 Kinetic model for the rearrangement of phenyl acetate (PA) into ortho-hydroxyacetophenone (o-HAP) in presence of a solvent (S). X is the active protonic site of the zeolite...

Fries rearrangement and phenol acetylation The Fries rearrangement is the acid catalysed transformation of aryl esters into hydroxyarylketones. Both this rearrangement and the two-step transformation (esterification, Fries rearrangement) in one-pot operation of phenols with carboxylic acid or anhydrides will be examined hereafter. Most studies in which acid zeolites were used as catalysts (Tables 3.6 and 3.7) deal with the synthesis of o- and p-hydroxyacetophenones (o- and p-HAP) either by the Fries rearrangement of phenyl acetate [Reaction (3.5)] ... 

Reaction scheme The Fries rearrangement of phenyl acetate (PA) was first mentioned as occurring over zeolites in the review paper published in 1968 by Venuto and Landis.[64] This rearrangement was afterwards investigated at 673 K over HFAU and HMFI zeolites.[65] The reaction was not selective the expected o-and p-hydroxyacetophenones (o- and p-HAP) were minor components and phenol the main component. With both zeolites, o-HAP was highly favoured over the para isomer. 

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...

Table 3.8 Influence of the reaction temperature on the gas phase Fries rearrangement of phenyl acetate over a HBEA zeolite. Values of conversion obtained after 1 and 10 h reaction (Xi, Xio) and of selectivity and yield to hydroxyacetophenones after lh reaction...

Figure 3.8 Liquid phase transformation of phenyl acetate (2.2 mol l-1 in sulfolane solvent) at 433 K. (a) Yield in o-hydroxyacetophenone, o-HAP ( ) and p-hydroxyacetophenone, p-HAP (X) versus reaction time, (b) Effect of the addition of phenol (P) on the p-HAP yield. [P] =0 mol l-1 (x) and [P] =0.6 mol l-1 ( ). Reprinted from Catalysis Letters, Vol. 41, Jayat et al., Solvent effects in liquid phase Fries rearrangement of phenyl acetate using a HBEA zeolite, pp. 181-187, copyright (1996), Kluwer Academic Publishers, with kind permission of Springer Science and Business Media...

Gas-phase acetylation of phenol using /3-zeolites gives phenyl acetate rapidly, which rearranges (see Fries rearrangement, vide infra) to orffto-hydroxyacetophenone and para-hydroxyacetophenone. The ojp ratio is high under these conditions. ... 

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. 

Under mild conditions (liquid phase, 160°C) HBEA zeolites can catalyse the acylation of phenol with phenyl acetate. High selectivity to p-hydroxyacetophenone is obtained by using sulfolane as a solvent, which can be explained by a better dissociation of phenyl acetate into acylium ions due to a solvation effect. However a competition between sulfolane and phenyl acetate for adsorption on the active acid sites is also demonstrated. A preliminary investigation of the effect of the acylating agent shows that generally, donor groups in aromatic acetates have a positive effect on the rate of acylation provided they do not block the access of the acetate to the acid sites of the zeolite pores. 

The Fries rearrangement of phenyl acetate to o- and p-hydroxyacetophenone is also a very valuable reaction in the pharmaceutical industry. Nafion-silica composites containing 13 and 40% (w/w) Nafion were also studied in this reaction and compared with pure Nafion and with zeolites such as HBEA, HUSY, HZSM5, and HY. The Nafion-silica composites resulted in better conversion than the pure analog, but in this study the BEA zeolite resulted in the highest conversion and a relatively high selectivity. Unfortunately, no reactions rates were given so no conclusions can be drawn about the intrinsic activity of the different catalysts [17]. 

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... 

A variety of acid solids, particularly zeolites, have been used as catalysts for phenyl acetate (PA) transformation. The reaction is generally performed in a batch reactor. As in the gas phase, o- and p-hydroxyacetophenones (o- and / -HAP), p-acetoxyacetophenone (p-AXAP) and phenol (P) are the main products and deactivation is relatively rapid. Catalyst stability can, however, be significantly improved by continuous extraction of the catalyst with the refluxing reaction mixture... 

Benzoxazoles. Beckmann rearrangement of o-hydroxyacetophenone oximes proceeds on heating with HY zeolite at 160° (8 examples, 84-95%). 

Many products synthesized by Claisen-Schmidt reactions find applications in the pharmaceutical industry. In particular, chalcones and fiavanones are intermediates in the synthesis of flavonoids. The basic structure of fiavonoids, that is, 2 -hydroxychalcone can be obtained by condensation of substituted 2-hydroxyacetophenone and substituted benzaldehyde at 323 K using basic zeolites as catalysts (46) or Mg-Al mixed oxides (47). 

Chung et al reported the liquid phase Beckmann rearrangement of 4-hydroxyacetophenone oxime using zeolite H p catalyst. The reaction was found to be an example of active solvent participation. A solvent having higher dielectric constant or more polar nature is preferred in the rearrangement step. 

U.v. irradiation of formaldehyde on zeolites of types A and X has been shown to produce sugars. A formose reaction carried out in the presence of hydroxyoxo compounds at high pH has been described. Equilibrium constants were evaluated in water and aqueous methanol solution saturated with calcium hydroxide or sodium hydroxide in a unimolecular ratio with formaldehyde and known accelerators, such as 2-hydroxyacetophenone, DL-glyceraldehyde,... 

A new environment-friendly synthesis of hydroxyphenylalkylketones was developed based on the use of a commercial pentasil-type zeolite ensuring both the high conversion of phenylacetate and the high selectivity toward ort/io-hydroxyacetophenone [152],... 

---