Aroylation of aromatics with arylcarboxylic acids over Nafion-H (polymeric perfluoroalkanesulfonic acid), an environmentally friendly solid acid catalyst

Aromatic hydrocarbons undergo direct aroylation with arylcarboxylic acids over Nafion-H, an environmentally friendly, perfluorinated resinsulfonic acid catalyst to give benzophenones and their derivatives. Furthermore, one of the bistrifluoromethylated benzophenone derivative was trifluoromethylated to a new DDT analog


Introduction
2][3] Lewis acids of variable strengths were used. 3,4Mechanistic aspects of different Lewis acid catalysed alkylation and acylation have been well studied. 5,6Generally, Friedel-Crafts acylation requires molar amounts of the catalyst, which forms complexes with both the acylating agents and the product, carbonyl compounds. 7Aqueous workup has been generally used to decompose the carbonyl-Lewis acid complexes, which renders the catalyst in most cases non recoverable.Only extremely reactive aromatics such as thiophenes and substituted thiophenes have been successfully acylated using solid catalysts such as sulfonated polystyrene resins. 8Recent advances towards environmentally friendly processes which are economically feasible have shown that ionic liquid systems have great potential for various reactions. 91][12] A suitable environmentally benign solid catalyst, which can be easily separated and recycled would be highly beneficial.In our recent study, acylation of aromatics has been efficiently achieved using gallium triflate, which is stable to aqueous treatment. 13afion-H, a perfluoroalkanesulfonic acid resin, has been found to be a suitable solid acid catalyst with high selectivity, and catalytic activity giving good yields of products. 14The reaction with Nafion-H conveniently eliminates the use of volatile or noxious reagents.After the reactions with Nafion-H, the catalyst can be easily recovered and regenerated.This solid perfluoroalkanesulfonic acid resin catalyst is more convenient and environmentally friendly in comparison with corrosive acid catalysts (liquid acids) generally used in reactions involving strong acids.Unlike conventional resinsulfonic acids (polystyrenesulfonic acids) such as Dowex-50, Amberlyst IR-112 and Permutit-Q, Nafion-H and related perfluroalkanesulfonic acids are not only much stronger acids but are also stable at temperatures up to 200°C.These unique properties have led to the application of Nafion-H to wide variety of organic reactions such as Friedel-Crafts type electrophilic reactions, synthesis of esters and ethers, various rearrangements etc. 14 Herein, we report our studies for the convenient intermolecular aroylation of aromatic hydrocarbons using benzoic acids as acylating agents in the presence of Nafion-H as a catalyst.

Results and Discussion
ω-Arylalkanoic acids (1) and their derivatives (2) undergo intramolecular Friedel-Crafts cycliacylation in the presence of Nafion-H, a perfluorinated resinsulfonic acid catalyst.Synthesis of anthraquinone, anthrone, fluorenone and heterocycles such as acridone, xanthone etc. has been achieved in good yields (>80%) by this method under the conditions of azeotropic removal of water (Scheme 1). 15

ISSN 1424-6376
Page 105 © ARKAT USA, Inc Recent studies on direct Friedel-Crafts sulfonylation of aromatics with arene/alkanesulfonic acids (5) showed that Nafion-H acts as a very convenient and efficient catalyst for the preparation of symmetric and unsymmetric diaryl/aryl alkyl sulfones (6). 16Nafion-H catalysed acylation of benzene and substituted benzene with aroyl chlorides and anhydrides was described earlier. 2 However, direct acylation with carboxylic acids have not been explored under these conditions.This prompted us to study direct intermolecular aroylation of aromatics with benzoic acids (7), with azeotropic water removal.
Aroylation of activated aromatics afforded the corresponding benzophenones (8) in moderate to good yields (Table 1).However, toluene on benzoylation with benzoic acid gave mixture of benzophenones in only low yield (<5 %).When the reaction was performed with more reactive thiobenzoic acid, the major product was a mixture of triphenylmethane derivatives (~ 15 %).In all these reactions, the aromatics play the dual role as the substrate as well as the solvent.Reactions were carried out with the corresponding carboxylic acid in excess of the arene under reflux (175-180 °C) using a Dean-Stark apparatus for efficient water removal.In the case of toluene the reaction was carried out in a pressure tube at 150 °C.Though benzoylation proceeded faster with thiobenzoic acid, formation of a mixture of ketones and thioketones was observed (GCMS).In the case of anisole, cleavage at the ether linkage followed by benzoylation leads to the formation of phenyl benzoate (24 %) as a secondary product.In the case of xylenes and mesitylene, side products due to alkylation and dealkylation were also observed.Amount of catalyst varied from 50-100 wt % with respect to the amount of carboxylic acid used.
Our work was also extended for the preparation of perfluoro derivatives of DDT, which might be more lipophilic and biodegradable.Many studies have been conducted on the structureactivity correlation in DDT analogs. 17It has been found that changing substituents at the α position of the ethane bridge greatly affects the activity of the analogs. 18Studies of the carbinol analogues on house flies (Musca Domestica L.) show different mode of action.Among the carbinol derivatives studied FDMC (9k) and Dicofol (10) were found to have strong insecticidal activity.The symptoms reported showed increased activity.These carbinols were found to be potent inhibitors of DDT dehydrochlorinase and this explains the minimal resistance of the DDT resistant strains to these carbinols. 19At the same time as biodegradability increases, these molecules may tend to build up to a lesser degree than DDT in the environment.

ISSN 1424-6376
Page 107 © ARKAT USA, Inc  The important role of fluorine in drug molecules in increasing the biological potency of the molecule by better cell penetration, better binding at lipophilic pocket on the receptor and better enzyme activation led us to explore the preparation of fluorinated moieties.We have prepared a number of fluorinated benzophenones (see Table 1).In addition, their direct trifluoromethylation using CF 3 transfer methodology 20 with TMS-CF 3 has been adopted to synthesize the perfluoro hydroxy derivative of DDT.For example 3,5-bis(trifluoromethyl)-2',5'-dimethylbenzophenone (8j) gave the corresponding trifluoromethylated alcohol (9j) in 92 % yield (Scheme 4).
The presently developed intermolecular acylation method is a convenient addition to the presently available methods for the synthesis of benzophenones from the corresponding benzoic acids.