Eosin Y Catalyzed Visible-Light-Promoted Aerobic Oxidative Cyclization of 2-Aminobenzothiazole

A mild and efficient one-pot visible light irradiated synthesis of 2-aminobenzothiazole 4(a–l) from arylisothiocyanate 1(a–l) and secondary amines 2 have been reported in presence of eosin Y as an organophotoredox catalyst at room temperature under aerobic condition. This synthesis includes application of air and visible light as inexpensive, readily available, high atom economy, non-toxic and sustainable regents.


INTRODUCTION
HE potential of developing new synthetic methodologies using visible light has recently received much attention from a number of research groups. [1]This is because solar energy (visible light) is clean, easy to handle and an unlimited energy source having great prospects for the development of sustainable and eco-friendly protocols for organic synthesis. [2][5] Therefore, some pioneering researchers have dedicated to converting solar energy into chemical energy for chemical transformations [6,7] which includes a promising strategy for the application of photoredox catalysts to initiate single electron transfer processes have been developed. [8,9]A surge of interest from the synthetic community has brought photoredox manifolds to the forefront of catalysis.[12][13][14][15] In their revolutionary work in this area, MacMillan, [16] Yoon [17] and Stephenson [18][19] have used Ruthenium and Iridium complexes as the photoredox catalyst, which has inspired the development of several powerful methods for various chemical transformations useful in organic synthesis.
However, these transition metal based photocatalysts disadvantageously exhibit high cost, low sustainability and potential toxicity.Recently, a superior alternative to transition metal photoredox catalysts, especially metal-free organic dyes such as eosin Y, fluorescein, Rose Bengal, Nile Red, Perylene and Rhodamine B have been used as economically and ecologically superior surrogates for Ru(II) and Ir(II) complexes in visible-light promoted organic transformations involving SET [20][21][22][23] (single electron transfer).These organic dyes have got much more attention with the last few years also due to easy handling, eco-friendly and have great potential for applications in visible-light-mediated organic synthesis [24][25][26][27] which fulfils the basic principle of green chemistry.
Heterocycles bearing thiazole, sulphur and nitrogen moieties constitute the core structure of a number of pharmacologically and biologically active interesting compounds.Benzothiazole derivatives possess a wide spectrum of biological applications such as antitumor, T schictosomicidal, anti-inflammatory, anticonvulsant, antidiabetic, antipsychotic, diuretic, and antimicrobial activities. [28]he synthesis of 2-aminobenzothiazole have not been reported by photooxidation reaction so far.[33] Encouraged by organocatalytic visiblelight-mediated aerobic oxidative transformations [34,35] and in continuation of our work on development of novel environmentally benign synthesis [36][37][38][39] herein we report a simple, visible light irradiated, efficient and green protocol for the synthesis of 2-aminobenzothiazole, using eosin Y as photocatalyst with excellent yield as depicted in Scheme 1.

EXPERIMENTAL
Melting points were determined by open glass capillary method and are uncorrected.All chemicals used were reagent grade and were used as received. 1H NMR and 13 C NMR spectra were recorded on a Bruker AVANCE DPX (400 MHz and 75 MHz) FT spectrometer in DMSO using TMS as an internal reference (chemical shift in δ, ppm).Mass spectra were recorded on JEOL SX-303 (FAB) mass spectrophotometer.Elemental analyses were carried out using a Coleman automatic C, H, N analyser.

General Procedure for the Synthesis of 2-Aminobenzothiazoles 4(a-l)
A solution of an arylisothiocyanate 1(a-l) (1.0 mmol) and an secondary amine 2 (1.0 mmol) in DMF (3 mL) was heated at 65 °C for 2-5 h to form the corresponding N-arylthioureas (as monitored by TLC).Then, eosin Y (2.0 mol %) and i Pr2NEt (2.0 equiv.)were added and the mixture was irradiated with green LEDs (2.4 W, 120 lm) with stirring under an air atmosphere at rt for 10-18 h.After completion of the reaction (monitored by TLC), water (5 mL) was added and the mixture was extracted with EtOAc (3 × 5 mL).The combined organic phase was dried over MgSO4, filtered and evaporated under reduced pressure.The resulting product was purified by silica gel column chromatography using a gradient mixture of hexane / ethyl acetate as eluent to afford an analytically pure 4(a-l).All the products are known compounds and were characterized by the comparison of their spectral data with those reported in the literature.  h) The reaction was carried out with 1.0 mol % of eosin Y. (a) Reaction conditions: arylthiourea (1.0 mmol), eosin Y (2.0 mol %), Base (2.0 equiv.),b) Isolated yield of the product (4a-l).

RESULTS AND DISCUSSION
In order to work out the envisaged protocol, a key reaction was conducted with arylthiourea 3(a-l) in DMF containing 2 mol % of eosin Y under an air atmosphere (without air bubbling) by irradiation with visible light (green light-emitting diodes (LEDs), λmax = 535 nm) at rt.The reaction delivered the desired 2-aminobenzothiazole 4(a-l) in 12 % isolated yield after 24 h (Table 1, entry 1).Following this experiment, a series of control experiments were performed, which indicates that an organic base is essential to give the desired product with high yield (97 %) (Table 1, entry 2) and i Pr2NEt was found to be the best base (Table 2, entry 2 versus 6, 7, 9).There was no product formation or it was formed in traces in the absence (-) of any one of the reagents / catalyst (Table 1, entries 3-5).The reaction did not proceed satisfactorily when a household 20 W fluorescent lamp was used instead of green LEDs (Table 1, entries 6 versus 2).Notably, the same result was obtained on using O2 (balloon) instead of an air atmosphere (Table 1, entry 8 versus 2), where as in the absence of any gas or under a nitrogen atmosphere no product formation was detected (Table 1, entry 5, 7).These results establish that visible light, base, photocatalyst and air all are essential (+) for the reaction and support the photocatalytic model of the reaction.
Next, the reaction conditions were optimized with respect to solvents and the catalyst used in the reaction.In all the tested solvents (DMF, DMSO, MeOH and EtOH) the yield of 4(a-l) was > 55 % (Table 2), which indicates that the reaction is not very sensitive to reaction media.DMF was the best solvent in terms of the reaction time and yield (Table 2, entry 1), hence it was used throughout the synthesis.When the amount of the catalyst was decreased from 2 mol % to 1 mol %, the yield of 4(a-l) considerably reduced (Table 2, entry 3), but the use of 3 mol % of the catalyst did not affect the yield (Table 2, entry 1).
Under the established reaction conditions in hand, the reaction was tried in a one-pot procedure starting directly from an arylisothiocyanate 1(a-l) and a secondary amine (2) to give the desired product 4(a-l) as depicted in Scheme 2.
To our delight, it worked well and a number of symmetrical and unsymmetrical 2-aminobenzothiazoles were successfully synthesized starting directly from various arylisothiocyanate 1(a-l) and secondary amines (2) (Table 3).This clearly shows that the reaction is very mild and applicable to aryl and alkyl, tolerates considerable functional group variations like, MeO, Me, Cl and NO2 in the substrate 1(a-l), which results the desired product 4(a-l) in good to excellent yields (78-97 %).However, arylisothiocyanate (1) and a secondary amine (2) with an electron-donating group on the aromatic ring appear to react faster and afford marginally higher yields in comparison to those bearing an electron withdrawing group.On the basis of the above observations and the literature precedents, a plausible mechanism involving photoredox catalysis for the oxidative cyclization of N-arylthioureas is depicted in Scheme 3. On absorption of visible light, the organophotoredox catalyst eosin Y (EY) is excited to its singlet state 1 EY* which through inter system crossing (ISC) comes to its more stable triplet state 3 EY* and undergoes a single electron transfer (SET). 3[42][43][44] A SET from A to 3 EY* generates thioacyl radical B, which undergoes intramolecular cyclization (5-endo-trig) to form C followed by attack of ( 2O   ) to give the product 4, successively.The formation of superoxide radical anion ( 2O   ) during the reaction was confirmed by the detection of the resulting H2O2 using KI / starch indicator. [45]The redox potential of eosin Y has also been incorporated in Scheme 4 for catalytic activity.

CONCLUSION
In conclusion, we have developed a novel organocatalysed method for the synthesis of 2-aminobenzothiazole directly from arylisothiocyanate and secondary amine in a one-pot procedure by using inexpensive eosin Y as a powerful organophotoredox catalyst at rt.The reaction involves visible light, a base and O2 (air) as a valuable reagents.This synthetic pathway includes a superior visible light promoted and Eosin Y organophotoredox catalysed methodology, which is superior in comparison to all other alternative synthetic methods for 2-aminobenzothiazole.This synthesis widens the scope of substrates for visible light photoredox reactions.The present methodology also offers many advantages of green chemistry such as high atom economy, reduced reaction time, one-pot consolidated procedure and high efficiency.

Table 1 .
Screening and control experiments.(a)

Table 2 .
Optimization of reaction conditions.(a)