CHEMOSELECTIVE C-BENZOYLATION OF PHENOLS BY USING ALCl 3 UNDER SOLVENT-FREE CONDITIONS

Substituted phenols were chemo-selectively reacted with benzoylchloride in presence of aluminum chloride under solvent-free condition to afford the corresponding 2'-hydroxy aryl benzophenones in excellent yields (72-96%). Naphthol benzoylation resulted in lower yields as compared to phenols. Both reactions completed in 5-10 min with quantitative yields providing excellent control over regioselectivity of products.

In this work, benzoylation of phenolic compounds was carried out following the two steps of O-benzoylation and then Fries rearrangement of aryl benzoates (Scheme 1).Fries rearrangement employs using anhydrous AlCl 3 [19], CH 3 SO 3 H [20], Bi(OTf) 3 [21], ZrCl 4 [22], Zeolite H-beta [23].Direct Friedel-Crafts acylation of phenols using acetyl chloride (chemoselective reaction) has been done by Bi(OTf) 3 [21] or Hf(OTf) 4 [24] in PhMe-MeNO 2 as solvent at 110 o C for 5-6 h in moderate yield (64-69%) and Sc(OTf) 3 in LiClO 4 -MeNO 2 at 50 o C for 6 h into 62% yield [25a].Furthermore ortho and para propionylation of simple phenols was carried out by propionylchloride in presence of Zeolite H-beta [23] as catalyst under solvent free condition at 140 o C for 6 h in 81% yield, and benzoylation of anisole was achieved by benzoylchloride in presence of B 2 O 3 -ZrO 2 in nitro benzene as solvent at 150 o C for 22 h [25b] or by I 2 -DMF at 140 o C for 12 h in 67% [25c].To the best of our knowledge there is no previous report for direct Cbenzoylation of phenols and naphthol using AlCl 3 under solvent free conditions.The use of aluminum chloride is significant because, it has low cost, commercially available, easy to handle and easy of work-up.On the other hand, avoiding the solvent reduces number of components in reaction, stops any solvent emission problems, and gets around any solvent recycling requirements.Herein we describe a Friedel-Craft benzoylation of substituted phenols, through a modified benzoylation procedure that gives O-substituted benzophenones regioselectively with excellent yields.The objective of the present work is elimination of esterification step (step 1, Scheme 1) in conjunction with absence of solvent, e.g.nitrobenzene, toluene, dichloromethane, nitro methane, etc., and low reaction time.EXPERIMENTAL 1 H-NMR (300 MHz) spectra were recorded on a Varian VXR 300 instrument at 293 o K in CDCl 3 .Chemical shift values were recorded in δ units (ppm) relative to Me 4 Si as internal standard.Melting points were determined by using a Buchi melting point apparatus.Infrared spectra (IR) were recorded using KBr pellets on a Perkin-Elmer 240C analyzer.Thin layer chromatography (TLC) was performed on silica gel 60 PF254 plates or aluminum oxide plates from Merck.

5-Chloro-2-hydroxyphenyl)(phenyl)methanone (
Procedure for benzoylation of 1-naphtol [26 ].To a mixture of 1-naphthol (7 mmol, 1 g) and anhydrous AlCl 3 (10 mmol, 1.38 g) stirred at 50 o C, benzoyl chloride (10 mmol, 1.46 g) was added in several portions, very carefully holding the temperature under 50 °C.After completion, the mixture was poured into ice water and then concentrated HCl (2-4 mL) was added subsequently.The suspension was stirred vigorously for 5-10 min.The crude desired products were obtained as yellow solids after filtration crude product was purified by crystallization in ethanol/methanol and yield of product was recorded as 55%.

RESULT AND DISCUSSION
For comparison of ortho-benzoylation via conventional method and AlCl 3 -solvent free initially, we attempted the C-benzoylation of p-chlorophenol 1, as model reaction, via conventional method (Scheme 1).The p-chlorophenol was treated with benzoyl chloride 2 in dichloromethane at reflux for three hours (Scheme 1, step 1).After extraction (with DCM and dil.NaOH for removing of unreacted phenol), 4-chlorophenyl benzoate 3 was obtained.Fries rearrangement of 3 was accomplished by 2.5 equiv AlCl 3 at 140 o C for one hour (Scheme 1, step 2).After workup the 5-chloro-2-hydroxybenzophenone 4 was isolated.We calculated overall yield of step 1 and step 2, and it was obtained 64%.Step 1 Step 2

Cl
Cl Cl
Direct Friedel-Crafts of p-chlorophenol using benzoyl chloride and aluminum chloride under solvent free condition, was accomplished with different equivalent of AlCl 3 at the 100-110 o C temperature, which summarized in ( In a typical procedure, 1 equivalent of p-chlorophenol and 1.2 equivalent aluminum chloride were mixed at room temperature.The mixture was heated at 110 o C (Scheme 2) followed by addition of 1.2 equivalents of benzoylchloride dropwise with grinding for 10 min.Then ice-water was added slowly to quench the reaction.The solid product was isolated by filtration and recrystallized from methanol.The obtained yield was 93% (Table 2, entry 1).By these results, we found that for C-benzoylation of phenols, neither esterification step nor solvent needed.Furthermore, this method has excellent yield with low reaction time and easy to workup.A number of phenols have been converted to corresponding 2-hydroxy benzophenones (Table 2).The sterically hindered phenols, such as 2,4-dibromophenol 2-bromo-4-chlorophenols have also afforded to the desired benzophenone in excellent yields.As well as p-methoxy benzoylchloride reacted efficiently with 2,4-dichlorophenol and resulted into 81% yield.Interestingly, only 2benzoyl-1-napthol 8 was obtained as a sole product by benzoylation of α-naphthol 7 in 50% yield, and 1-benzoyl-2-naphthol 10 also was formed from β-naphthol 9 at 45 o C in 55% yield (Scheme 3, Table 3 Scheme 2. C-benzoylation of substituted phenols using benzoyl chloride and AlCl 3 under solvent free condition.Benzoylation of arenes by the above procedure such as toluene, benzene, bromobenzene, chlorobenzene anisole has been achieved in quantitative yield (Table 3).It is important that the benzoylation of these substrates was not possible with organo metallic reagents.The benzoylation of nitrobenzene resulted into lower yields of product, naphthalene and anthracene acylated at 30 o C in good yields.The major problem for the use of anhydrous AlCl 3 in F-C benzoylation with electron rich substrate is formation of the strong complexation with Lewis acids, which retard the progress of reaction.While in the presence of activated phenols, the reaction completes smoothly within minutes to give quantitative yields.On the other hand in conventional method, the amount of acid chlorides used are in excess than stoichiometric amount of Lewis acids are required while in the present procedure only stoichiometric amount of aluminum chloride and acid chlorides are used.

CONCLUSION
We have compared C-benzoylation of phenols by conventional method (esterification of phenols and Fries rearrangement of aryl benzoate) and direct C-benzoylation by AlCl 3 under solvent free condition.With this procedure, the benzoylation occurs chemoselectively at benzenoyd ring.Furthermore, the products were obtained with high degree of purity.The reaction completes just within 10 minutes, into excellent yield and avoid from solvent.This renew economical process will be useful for all those laboratories where organo metallic reagents are not accessible.

Table 1 )
which the best condition was obtained by 1.2 equivalents AlCl 3 at 110 o C with 93% yield.OH

Table 1 .
Chemoselective benzoylation of p-chlorophenol in several equivalent of AlCl3 at different temperatures.

Table 3 .
Physico-chemical properties of naphthyl benzophenone and aryl benzophenone by using benzoylchloride and AlCl3 under solvent free condition.