Alumina in Methanesulfonic Acid (AMA) as a New Efficient Reagent for Direct Acylation of Phenol Derivatives and Fries Rearrangement. A Convenient Synthesis of o-Hydroxyarylketones Hashem Sharghi* and Babak Kaboudin Department of Chemistry, Shiraz University, Shiraz 71454, Iran Alumina in methanesulfonic acid is used to prepare o-hydroxyarylketones, by acylation of phenol and naphthol derivatives with carboxylic acids and Fries rearrangement of phenolic esters. The Friedel�}Crafts acylation is one of the most popular reactions for the synthesis of aromatic ketones,8 and direct acylation of phenol derivatives, using AlCl3 or TiCl4 as a promoter, also provides useful synthetic methods for the preparation of o-hydroxyarylketone derivatives.9�}11 However, treatment of the aluminium residue has, some- times, induced environmental problems and the drastic reaction conditions have caused some severe side reactions.On the other hand, acid chlorides or acid anhydrides are commonly used as acylating reagents in these reactions.These reagents are usually prepared from carboxylic acids, and, therefore, it would be useful if the acylations could be carried out by using carboxylic acids as acylating reagents.12�}14 An alternative method is the Fries rearrange- ment of acyloxy benzenes or naphthalenes which provides useful routes to these compounds.15 The acid�}base proper- ties of metal oxide supports have a signiRcant role in the selectivity exhibited by heterogeneous catalysts.19a�}d One of the most common solid supports in heterogeneous catalysis is alumina, which has been used as a dehydrating agent in aromatic cyclodehydration.20a,b We herein present work that describes the direct acylation of phenol derivatives with car- boxylic acids by a mixture of acidic alumina (type 504C) in methanesulfonic acid (AMA).We have also noticed that AMA catalyses the Fries rearrangement of acyloxybenzenes for the preparation of o-hydroxyarylketones (Scheme 2).The reaction of 1d with 2d at 100 8C for 12 h in methane- sulfonic acid a€orded 3d in 15% yield. Unfortunately, the extension of the reaction time, and the increase of the reaction temperature, decomposed the reaction mixture,18 and a darkened solid, which would dissolve in organic solvents, was obtained. Reaction of 1d with m-cresol in the presence of alumina failed in chlorobenzene, toluene and 1,2-dichloroethane when boiled under re�Pux for 24 h.In nitrobenzene, however, compound 5d was obtained in 20% yield. Since attempts to prepare 3d were unsuccessful, atten- tion was turned to methanesulfonic acid/alumina mixtures, which have not yet been used for this purpose. The reaction of 1d (2 mmol) with 2d (2 mmol) in methanesulfonic acid (1 mL) and acidic alumina (0.2�}0.3 g) at 100 8C for 12 h produced 3d in 50% yield. When the reaction was carried out at 140 8C, 3d was produced in 85% yield after 1 h. The extension of this new reagent to the Fries rearrangement of 5d was also successful and 3d was produced in 70% yield after 2 h (Table 2).The reaction of benzoic acid derivatives with m-cresol and Fries rearrangement of m-tolylbenzoate derivatives in the presence of AMA a€ord 2-hydroxyarylketones in high yields (Table 2). The results clearly show that the reactions seem to be faster when the aromatic part of the acid carries electron-donating groups. Acetic acid, cyclo- hexylcarboxylic acid, phenylacetic acid, hexanoic acid and 11-bromoundecanoic acid were also employed as acylating reagents.Fries rearrangement of m-tolylalkanoates also occurs in the presence of AMA and a€ords the desired products in excellent yields. Upon reaction of o-cresol with benzoic acid and Fries rearrangement of corresponding ester, the para isomer was obtained in high yield. With a J. Chem. Research (S), 1998, 628�}629 J. Chem. Research (M), 1998, 2678�}2693 Table 2 Comparison of results obtained from the reaction of phenol derivatives with carboxylic acids and Fries rearrangements of phenolic esters in the presence of AMA Aa Bb Entry Product 3 and ester 5 R1 R2 R3 R4 Time (t/min) Yield (%)c Time (t/min) Yield (%)c 1 a H CH3 H Ph 10 86 120 60 2 b H CH3 H o-ClC6H4 25 82 60 81 3 c H CH3 H m-CH3C6H4 5 90 60 80 4 d H CH3 H m-BrC6H4 60 85 120 70 9 i H CH3 H CH3 5 85d 15 80 13 m H CH3 H Br-(CH2)10 5 80 30 80 14 n H F H CH3 120 63d 180 60 15 o H OH H CH3 30 82d �} �} 18 r OH H H Ph 60 83 �} �} 22 v H H CH3 Ph 20 10(90)e 50 15(85)e 23 w H H Cl Ph 60 13(87)e 90 15(85)e 24 x H OH H Ph 30 85 �} �} 25 y H H CH3 PhCH2 5 12(88)e 10 15(85)e 26 z H H CH3 CH3 5 8(92)e 10 15(85)e 28 b' a-Naphthol CH3(CH2)4 20 91 15 60 29 c' Pyrogallol CH3 20 83d �} �} 30 d' NO2 H H Ph 720f �} 720 �} 31 e' H CH3 H p-NO2-C6H4 720 �} 720 �} aDirect acylation method.bFries rearrangement phenolic esters. cYields refer to isolated yield. dReaction was carried out at 120 8C. eValues in parentheses are referred to the yield of 4-acylated product.fIn this case 15% ester was produced. *To receive any correspondence. 628 J. CHEM. RESEARCH (S), 1998�uorine group at the meta and para positions, acylation and Fries rearrangement give the corresponding 2-hydroxy isomer in good yields. Three mechanistic pathways are proposed in the literature for the Fries rearrangement: (a) intramolecular,23±25 (b) intermolecular26±28 and (c) bimolecular.29±34 Mechanistic studies show that the acylation reaction in AMA occurs through a prior esteri®cation, followed by a Fries rearrange- ment of the phenolic ester by an intermolecular mechanism.In summary, AMA is introduced as an e�cient reagent in the direct acylation reactions of phenol and naphthol derivatives with carboxylic acids, and in Fries rearrange- ments of acyloxy benzene and naphthalene derivatives. The present methods have the following advantages: (a) the reagent is readily available, safe to handle and inexpensive; (b) the procedure is simple; (c) the reaction times are very short, and the reaction can be performed with a wide range of carboxylic acids and phenol derivatives; and (d) workup is easy.Further investigations to develop other synthetic reactions using AMA are now in progress. Techniques used: 1H NMR, IR and mass spectrometry References: 38 Schemes: 4 Table 1: Reaction of m-bromobenzoic acid (1d) with m-cresol (2d) in the presence of some Lewis and some protic acids Table 3: The reaction of o-chlorobenzoic acid (1b) with m-cresol (2b) in AMA Table 4: Progress of the Fries rearrangement of the ester 5b Received, 5th January 1998; Accepted, 16th June 1998 Paper E/8/00158H References cited in this synopsis 8 G.A. Olah, Friedel±Crafts Chemistry, Wiley-Interscience, New York, 1973. 9 (a) B. M. Trost and M. G. Saulnier, Tetrahedron Lett., 1985, 26, 123; (b) L. Crombie, R. 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RESEARCH (S), 1998 629