Trichloroisocyanuric Acid , a New and E ffi cient Catalyst for the Synthesis of 2 '-Aminobenzothiazolo-arylmethyl-2-naphthols

An efficient one-pot synthesis of 2'-aminobenzothiazolo-arylmethyl2-naphthols is described. This involves the three-component reaction of β-naphthol, aromatic aldehydes and 2-aminobenzothiazole in the presence of a catalytic amount of trichloroisocyanuric acid under solvent-free conditions.


Introduction
Benzothiazoles are an important group of heterocyclic compounds.Several derivatives have been found to possess useful biological activities such as anti-inflammatory 1 , anti-tumour 2 , anticonvulsant 3 , antibacterial 4 , antifungal 5 and topoisomerase II inhibitory activities 6 .In addition, benzothiazoles are also useful synthetic intermediates that are prone to various transformations and transition-metal-catalyzed cross-coupling reactions, such as Heck 7 , Negishi 8 , Stille 9 and Sonogashira couplings 10 .
As a result of their importance as substructures in a broad range of natural and designed products, significant effort continues to be directed toward the development of new benzothiazole-based structures and new methods for their construction.Recently, synthesis of 2'-aminobenzothiazolo-arylmethyl-2-naphthols have been reported using LiCl 11 and [Hnmp] HSO 4 12 as catalysts.However, many of these methodologies suffer from one or more disadvantages such as requirement of excess or expensive catalysts, prolonged reaction time.Therefore, the development of mild, efficient, inexpensive and facile methods for the synthesis of 2'-aminobenzothiazolo-arylmethyl-2-naphthols is necessary part of organic synthesis.
Trichloroisocyanuric acid (TCCA), an inexpensive, easily available reagent, low toxicity and less corrosive, has been widely used in organic reactions 13 , but it has not been carefully studied as a catalyst in the synthesis of 2'-aminobenzo-thiazolo-arylmethyl-2naphthols until now.In continuation of our efforts to explore newer reactions for the synthesis of heterocyclic compounds 14 , we decided to explore the possibility of synthesizing 2'-aminobenzo-thiazolo-arylmethyl-2-naphthols by one-pot, three-component condensation of β-naphthol, aromatic aldehydes and 2-aminobenzothiazole in the presence of a catalytic amount ofTCCA under solvent-free conditions (Scheme 1).

Experimental
IR spectra were determined on FTS-40 infrared spectrometer; NMR spectra were recorded on Bruker AV-400 spectrometer at room temperature using TMS as an internal standard, coupling constants (J) were measured in Hz; Elemental analysis were performed by a Vario-III elemental analyzer; Melting points were determined on a XT-4 binocular microscope and were uncorrected; Commercially available reagents were used throughout without further purification unless otherwise stated.

General procedure for the preparation of 4
A mixture of the β-naphthol (1 mmol), aldehydes (1 mmol), 2-aminobenzothiazole (1 mmol), and TCCA (0.1 mmol) was stirred at 80 ºC for the appropriate time according to Table 2. Completion of the reaction was indicated by TLC.The reaction was cooled to room temperature, washed with water, extracted with ethyl acetate (3×10 mL).The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure to afford a white powder.The pure solid products were obtained by recrystallization from ethanol.

Results and Discussion
The model reaction of β-naphthol, benzaldehyde and 2-aminobenzothiazole was conducted to screen the optimal reaction conditions and the results were listed in Table I.First, the effect of temperature was tested.At 80 °C, the reaction proceeded smoothly and gave short reaction time and high yield.Therefore, we kept the reaction temperature at 80 °C.Moreover, we also studied influence of the amount of TCCA on the reaction yields.One 10 mol% of TCCA was sufficient, excessive amount of catalyst did not increase the yield remarkably (Table 1, Entries 11-14).In light of these results, subsequent studies were carried out under the following optimized conditions, that is, with 10 mol% TCCA at 80 °C under solvent-free conditions.Next stage, we studied the scope of reaction for the synthes of 2'-aminobenzothiazoloarylmethyl-2-naphthols from various aldehydes under optimized conditions (Table 2).A series of substituted aromatic aldehydes with electron-donating or electron-withdrawing groups attaching aromatic ring were investigated.Aromatic aldehydes with both the electron-withdrawing groups and the electron-releasing groups gave high yields of the desired products.The substituents on the ortho or opposite position have no obvious difference.Unfortunately, with aliphatic aldehydes, a mixture of products was obtained and the desired product could not been isolated.

Conclusion
In conclusion, we developed a new application for TCCA.By using this catalyst, a series of 2'-aminobenzothiazolo-arylmethyl-2-naphthols were obtained in high yields via threecomponent reaction of β-naphthol, aromatic aldehydes and 2-aminobenzothiazole under solvent-free conditions.Further applications of TCCA in organic transformation are currently in progress in our laboratories.