Ortho-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 HY, phenylacetate dissociates into phenol and ketene (reaction a). Ortho-hydroxyacetophenone is produced partly by the Fries rearrangement of phenylacetate (intramolecular reaction, reaction b) and by trans-acylation (reaction c) while para-hydroxyacetophenone is exclusively the result of trans-acylation (reaction d). Phenylacetate can also disproportionate into phenol and acetoxyacetophenones (reaction e). Para-acetoxyacetophenone can also be formed through transesterification between para-hydroxyacetophenone and phenylacetate (reaction f).The formation of secondary products like 2-methylchromone and 4-methylcoumarine is consecutive to the formation of... 

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 mechanism of phenylacetate transformation can be described as shown in scheme 3. Phenylacetate adsorbs on a protonic center and then can either rearrange into ortho-hydroxyacetophenone (Fries rearrangement) or desorb phenol. The adsorbed acylium ion can then react with phenol (if the conversion is high enough) to give ortho- and para-hydroxyacetophenone which will then appear as secondary products. It can also react with phenylacetate to give ortho- and para-acetoxyacetophenones or react with ketene to give the condensation 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...

The variants on this route are many for example condensation of ortho-hydroxyacetophenone with the Vilsmeier reagent produces 3-formylchromone, and combination with dimethylformamide dimethyl acetal, then an electrophile, bromine in the example below, gives 3-substituted chromones. ... 

Garda, H., Primo, J., and Miranda, M. A., The photo-Fries rearrangement in the presence of potassium carbonate a convenient synthesis of ortho-hydroxyacetophenones. Synthesis, 901,1985. 

The ester and catalj st are usually employed in equimoleciilar amounts. With R =CjHs (phenyl propionate), the products are o- and p-propiophenol with R = CH3 (phenyl acetate), o- and p-hydroxyacetophenone are formed. The nature of the product is influenced by the structure of the ester, by the temperature, the solvent and the amount of aluminium chloride used generally, low reaction temperatures favour the formation of p-hydroxy ketones. It is usually possible to separate the two hydroxy ketones by fractional distillation under diminished pressure through an efficient fractionating column or by steam distillation the ortho compounds, being chelated, are more volatile in steam It may be mentioned that Clemmensen reduction (compare Section IV,6) of the hj droxy ketones affords an excellent route to the substituted phenols. 

On the other hand, 1,1,1-trisubstituted alkanes behave similarly to aldehydes, yielding pyrjdium salts (128) with identical substituents in positions 2 and 6. Thus, Dorofeenko and co-workers condensed 2 moles of acetophenone with 1 mole of benzotrichloride in the presence of perchloric acid obtaining 2,4,6-triphenjdpjTylium perchlorate with 1 mole of ethyl orthoformate, they obtained 2,6-diphenyl-pyrylium perchlorate (57) from o-hydroxyacetophenone, ortho-formic ester and perchloric acid, 4-ethoxybenzopyrylium perchlorate was formed. 

Next, ask yourself what an immediate precursor of the target might be. Since an acetyl group is a meta director while a hydroxyl group is an ortho and para director, acetophenone might be a precursor of m-hydroxyacetophenone. Benzene, in turn, is a precursor of acetophenone. 

Figure 1 Normalized 2 -hydroxyacetophenone concentration versus time data obtained during the reaction of 2-hydroxyacetophenone with different chlorobenzaldehydes over MgO para-chlorobenzaldehyde, meta-chlorobenzaldehyde, ortho-chlorobenzaldehydes and 2,3-...

Upon oxidation with IBD, a series of o-hydroxyacetophenones and related compounds 57 give the corresponding 2-methoxycoumaran-3-ones 59 [84JCS(CC)1342] (Scheme 19). These reactions probably occur via intramolecular participation of the ortho hydroxy group, which attacks the a-carbon of the intermediate 58 to yield the intermediate product 58a. A similar reaction occurs when /3-diketones 60 are oxidized with IBD-KOH/MeOH,... 

The above process is applicable to almost all hydroxyalde-hydes in which the hydroxyl and carbonyl groups occupy ortho or para positions relatively to each other 1 in the latter case derivatives of hydroquinone are produced. When the hydroxyl and carbonyl groups occupy the meta position with respect to each other, no reaction takes place, as is also the case with certain ortho and para compounds containing nitro groups and iodine atoms. o-Hydroxyacetophenone and />-hydroxyaceto-phenone are also capable of yielding catechol and hydroquinone respectively under the above conditions. 

Problem 19.16 Phenyl acetate undergoes the Fries rearrangement with AlCl, to form ortho- and para-hydroxyacetophenone. The ortho isomer is separated from the mixture by its volatility with steam. 

The transformations of hydroxyacetophenones and of ortho-acetoxyaceto-phenone were studied in solution in phenylacetate (10 mol %) under the same conditions as the transformation of phenylacetate. The effect of water on the transformation of phenylacetate was also studied. 

Scheme 8). The system is applicable to a wide variety of aldehydes, and a series of syn-a,P-dihydroxyketones (syn-11) can be synthesized in excellent yield. Moreover, the diastereo- and enantioselectivity are almost perfect in some cases using as little as 1 mol % of the catalyst. The introduction of a meth-oxy group at the ortho position of 2-hydroxyacetophenone has crucial effects on the reactivity and selectivity. The structure of the real catalytic species is of great interest and is currently under investigation [16]. 

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),... 

Preparation of the ortho-qamont 162 from p-hydroxyacetophenone (160). This involved silylation of acetophenone, ketal protection, desilylation, and regiose-lective oxidation of phenol to o-quinone 162 using o-iodoxybenzoic acid (IBX) (Scheme 10a). 

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