Ferric Hydrogensulfate Catalyzed Synthesis of Aryl 14 H-Dibenzo [ a , j ] xanthene Derivatives under Thermal and Solvent-Free Conditions

O hidrogenossulfato férrico tem sido utilizado como catalisador para a preparação em um único pote dos derivados de aril 14H-dibenzo[a,j]xantenos por ciclocondensação de -naftol e benzaldeídos substituídos, em condições livres de solvente e aquecimento. Este método tem a vantagem de fornecer rendimentos elevados, reações mais limpas, metodologia simples, menor tempo de reação, fácil tratamento e condições experimentais menos poluentes.


Introduction
Organic syntheses involving greener process and under solvent-free conditions have been investigated world wide due to stringent environment and economic regulations. 1oxic, homogeneous, corrosive liquid acid catalysts, such as H 2 SO 4 , HF, HBr, HCl, CF 3 COOH and complexes of BF 3 are frequently used in organic synthesis. 2However, processes involving conventional acids are inherently associated with problems such as polluting reagents, catalyst waste, difficulty in separation and recovery. 3Replacement of these conventional acids by solid heterogeneous catalyst is desirable to achieve effective catalyst handling, product purification and to decrease waste production. 4Considering the facts that most of the organic reagents involved in fine chemical synthesis are sensitive to harsh conditions, it is desirable to choose catalysts which can catalyze organic transformations under mild conditions. 3,4In this research, ferric hydrogensulfate as the solid heterogeneous acid catalyst deserves special mention.The catalyst has shown strong surface acidic sites, easily recoverable and reusable properties with low toxicity.Also, this catalyst is safe, easy to handle, environmentally benign, presents fewer disposal problems and is stable in reaction media.Ferric hydrogensulfate has been demonstrated to be efficient catalyst for several industrially important reactions such as Schmidt reaction of ketones to amides 5 and gained much interest in the Friedel-Crafts acylation of alkoxy benzenes by aliphatic anhydrides. 6anthenes synthesis, especially benzoxanthenes, has attracted the attention of organic chemists due to their wide range of biological and therapeutic properties such as antibacterial, 7 antiviral activities, 8 and also they are candidates in photodynamic therapy (PDT). 9,10Furthermore, benzoxanthenes are used as dyes, 11 in laser technologies, 12 and in fluorescent materials. 13he synthesis of 14H-dibenzo[a,j]xanthene is generally achieved by a) dehydration of bis(2-hydroxy-1-naphthyl) methane using POCl 3 14 or by boiling acetic acid diester of bis(2-hydroxy-1-naphthyl) methane, 15 b) condensation of -naphthol with aliphatic and aromatic aldehydes in the presence of hydrochloric acid or phosphoric acid 16 and also sulfuric acid 17 in acetic acid as solvent.All these methods suffer from harsh reaction conditions, long reaction times, unsatisfactory yields and tedious experimental procedures.Recently, the synthesis of 14H-dibenzo[a,j]xanthene has been reported by condensation of -naphthol and aldehydes in the presence of p-toluenesulfonic acid, 18,19 Amberlyst-15, 20 molecular iodine, 21,22,23 sulfamic acid, 24 silica sulfuric acid, 25,26 Al(HSO 4 ) 3 , 27 heteropolyacid, 28,29 LiBr, 30 selectfluor TM , 31 cation-exchange resins, 32 wet cyanuric chloride, 33 HClO 4 -SiO 2 , 34 K 5 CoW 12 O 40 •3H 2 O, 35 methanesulfonic acid, 36 , 37 and dowex-50w 38 as catalyst.Now, we have developed new one-pot methodologies to perform synthesis of aryl 14H-dibenzo[a,j]xanthene derivatives by the condensation reaction of various aromatic aldehydes with -naphthol in solvent-free condition in the presence of ferric hydrogensulfate under thermal conditions.

Results and Discussion
Ferric hydrogensulfate as a recyclable solid Brønsted acid catalyst is safe, easy to handle, environmentally benign and presents fewer disposal problems.This catalyst was prepared from the reaction of anhydrous ferric chloride (1 mmol) with concentrated sulfuric acid (3 mmol).This salt is a stable and non-hygroscopic solid material, insoluble in most organic solvents.
In the present research, we wish to describe a new protocol for the rapid preparation of 14H-dibenzo[a,j] xanthene derivatives using a catalytic amount of Fe(HSO 4 ) 3 as a solid acid catalyst (Scheme 1).
As summarized in Table 1, several different aromatic aldehydes and -naphthol were reacted in the presence of ferric hydrogensulfate as catalyst under thermal and solvent-free conditions resulting into the corresponding aryl 14H-dibenzo[a,j]xanthenes in good to high yields (Scheme 1 and Table 1).
The reaction was performed with benzaldehyde containing withdrawing as well as electron donating groups, but benzaldehydes with electron donating groups are generally more reactive than their corresponding ones with electron withdrawing groups and give the desired product at short reaction time with excellent yield (Table 1).This observation shows clearly that the preparation of benzoxanthenes is more strongly affected by the electronic factors.
The suggested mechanism of the ferric hydrogensulfate catalyzed transformation is shown in Scheme 2.
In a typical experiment, after the necessary time for the reaction to be complete, chloroform was poured in cooled reaction mixtures until solid crude product was dissolved.Then, the ferric hydrogensulfate as catalyst was isolated from the reaction mixture by simple filtration and could be reused again after washing by chloroform.In continuation of work up, the chloroform was evaporated and the aqueous ethanol 15% was added to the crude product, the precipitate was separated and then recrystallized using aqueous ethanol 15% for two times.The catalytic activity of the recovered catalyst, ferric hydrogensulfate, was examined again, and it showed almost the same catalytic activity as fresh ferric hydrogensulfate.
To show the merit of the present work in comparison with reported results in the literature, we compared results of ferric hydrogensulfate with p-toluenesulfonic acid, 19 iodine 21 and sulfamic acid 22 in the synthesis of aryl 14H-dibenzo[a,j]xanthene derivatives.As shown in Table 2, ferric hydrogensulfate can act as effective catalyst with respect to reaction times, yields and the obtained products (Table 2).

Conclusions
In conclusion, we have demonstrated that ferric hydrogensulfate is a new, efficient and heterogeneous catalyst for synthesis of a variety of aryl 14H-dibenzo[a,j] xanthene derivatives using aryl aldehydes and -naphthol under solvent-free conditions.The reactions were carried out at oil bath with short reaction time and produce the corresponding product in good to high yields.This method is important from an environmental point of view and economic considerations, because it produces little waste.Greener conditions and simple work-up procedure, including filtering and recrystallization are another advantage of this method.

Experimental
All reagents were purchased from Merck and Aldrich and used without further purification.Ferric hydrogensulfate was prepared according to the reported procedure. 5,6ll yields refer to isolated products after purification.Products were characterized by comparison with authentic samples and by spectroscopic data (IR, 1 H NMR spectra) and melting point.The NMR spectra were recorded on a Bruker Avance DEX 500 and 300 MHz instrument.The spectra were measured in CDCl 3 relative to TMS (0.00 ppm).IR spectra were recorded on a Perkin-Elmer 781 spectrophotometer.All of the compounds were solid and solid state IR spectra were recorded using the KBr disk technique.Melting points were determined in open capillaries with a BUCHI 510 melting point apparatus and are uncorrected.TLC was performed on Silica-gel polygram SIL G/UV 254 plates.

Preparation of 14H-dibenzo[a,j]xanthene derivatives using ferric hydrogensulfate as catalyst
To a mixture of aldehyde (1 mmol) and -naphthol (2 mmol), ferric hydrogensulfate (0. 15 mmol, 0.05 g) was added and the mixture was inserted in an oil bath and heated at 125 o C for the appropriate time (Table 1).Completion of the reaction was indicated by TLC.After completion, the reaction mass was cooled to 25 o C, then warm aqueous EtOH (15%) was added and the mixture stirred for 5 min.The solid residue was isolated and dissolved in CHCl 3 .The ferric hydrogensulfate was filtered; chloroform was evaporated from the reaction mixture.The solid product was purified by recrystallization procedure in aqueous EtOH (15%).The desired pure products were characterized by comparison of their physical data with those of known benzoxanthenes [17][18][19][20][21][22][23][24] The spectral data of some representative aryl 14H-dibenzo[a,j]xanthenes are given below: