Persulfate-activated charcoal mixture: an efficient oxidant for the synthesis of sulfonated benzo[d][1,3]oxazines from N-(2-vinylphenyl)amides and thiols in aqueous solution

A series of 2,4-aryl-4-((arylsulfonyl)methyl)-4H-benzo[d][1,3]oxazines in good to excellent yields have directly been obtained from N-(2-vinylphenyl)amides and thiols by employing a mixture of K2S2O8-activated charcoal in aqueous acetonitrile solution at 50 °C. A plausible mechanism for the reaction is reported. It reveals that the reaction follows a radical pathway and the persulfate has been the oxygen source for formation of the sulfone group in the products. It is worth mentioning that this protocol utilizes an easily accessible K2S2O8-activated charcoal mixture and thiols, respectively, as an oxidant and sulfonylating precursors for the first time.


Results and discussion
We chose N-(2-(1-phenylvinyl)phenyl)benzamide (1a, 1.0 mmol) and benzenethiol (2a, 2.0 mmol) as model substrates to optimize conditions for this reaction, and the obtained results are summarized in Table 1 , v/v mL) could also afforded the desired product 3aa, but in poor yield (Table 1, entries 6-10). To improve the product yield, we then investigated the stoichiometry of K 2 S 2 O 8 to substrate N-(2-(1-phenylvinyl)phenyl)benzamide (1a). A slightly improved yield (43%) of 3aa was noticed by increasing the amount of K 2 S 2 O 8 to 4.0 equiv. (Table 1, entries 11-13); however further raising the amount of K 2 S 2 O 8 did not improve the reaction efficiency drastically ( Table 1, entries 14-15). Under similar conditions, the reaction gave 54% of product (3aa) with higher quantity of benzenethiol (3.0 equiv., Table 1, entry 16). Additional optimizations revealed that the reaction atmosphere was crucial for outcome of the reaction. The reaction proceeded efficiently under nitrogen gas atmosphere while the involvement of air or molecular oxygen brings down yield of 3aa, cf. entries 18 and 19 in Table 1. To further improve the product yield, we decided to activate the persulfate by a mild protocol. As the productivity of sulfate radicals from persulfate can be inuenced by the activation types.
Recently, granulated activated carbon has been reported to successfully activate persulfate under a mild condition. 13 It has a certain advantage in being non-metallic species free from metal leaching problems. Also, the activation of persulfate by granulated activated carbon proceeds on the surface of activated carbon during the radical propagation mechanism. 14 Thus, the inuence of activated charcoal was studied for the formation of 3aa from 1a and 2a under the reaction conditions mentioned in entry 16 of Table 1. By addition of 40 mg of activated charcoal to the mixture of 1a, 2a and K 2 S 2 O 8 in CH 3 CN/H 2 O (6 : 4, v/v mL) at room temperature, expected product 3aa was obtained in 64% yield (Table 1, entry 20). However, rate of the reaction was too low (52 h). More examinations revealed that the complete conversion of mixture of 1a (1.0 equiv.) and 2a (3.0 equiv.) to 3aa in 93% yield required K 2 S 2 O 8 (4.0 equiv.) and activated charcoal (0.03 g mmol À1 of 1a) in CH 3 CN/H 2 O (6 : 4, v/v mL) at 50 C for 6 h ( Table 1, entry 24). Control experiments revealed that K 2 S 2 O 8 ( Table 1, entry 26) was essential, and no desired product was detected in its absence. From these experiments, we determined the optimized conditions as: N-(2-vinylphenyl)amide (1.0 equiv.), thiol (3.0 equiv.), K 2 S 2 O 8 (4.0 equiv.), and activated charcoal (0.03 g mmol À1 of N-(2-vinylphenyl)amide) in CH 3 CN/H 2 O (6 : 4, v/v mL) under nitrogen gas atmosphere at 50 C for 6 h ( Table 1, entry 24).
To further explore the substrate scope, we then studied the scope of thiols (Table 3). Thiols with methyl-, methoxy-and chloro-group at the para-position of the arene ring produced the Table 3 Substrate scope for the synthesis of 2,4-aryl-4-((arylsulfonyl)methyl)-4H-benzo[d] [1,3]oxazines from N-(2-(1-phenylvinyl)phenyl) benzamide and various thiols a a Unless stated otherwise, all reactions were performed in a Schlenk tube with N-(2-(1-phenylvinyl)phenyl)benzamide (1a, 1.0 mmol), thiols (2b-2i, 3.0 mmol), K 2 S 2 O 8 (4.0 mmol) and activated charcoal (0.03 g) in CH 3 CN/H 2 O (6 : 4, v/v mL) under nitrogen gas atmosphere at 50 C for 6 h. desired products in excellent yields (3ab-3ad). However, 4nitrobenzenethiol leads to a dramatic decrease of the reaction efficiency and afforded product 3ae in 10% yield. To our delight, this protocol is also applicable to cyclohexanethiol and thiophene-2-thiol and was converted to the corresponding products (3af and 3ag) in signicant yield. Unfortunately, thiols with a hydroxy or an amino group on the arene ring could not afford the desired product (3ah and 3ai).
To understand the mechanism of this transformation, some control experiments were carried out as described in Scheme 4. On addition of 2 equiv. of radical scavenger 2,2,6,6tetramethylpiperidine-1-oxyl (TEMPO) under the standard conditions, no desired product (3aa) was observed (instead thiol$TEMPO adduct detected by GCMS analysis). In other words, TEMPO completely inhibited this reaction indicating that the reaction follows a radical pathway. 7,8 In addition, the sulfurcontaining benzo[d] [1,3]oxazine (VI) could also be converted to the sulfone-containing benzo[d] [1,3]oxazine (3aa) in good yield under similar reaction conditions in the absence of thiol. Thus, it would be reasonable to deduce that sulfur-containing benzo[d] [1,3] oxazine (VI) was the plausible intermediate in this reaction. 6 On the basis of the results described above and previous reports, a plausible mechanism is outlined in Scheme 5. Initially, the activated charcoal-assisted heterolytic cleavage of S 2 O 8 2À affords sulfate radical anions (SO 4 c À ), which then abstract the hydrogen atoms from the thiol (2) to afford a sulfur-centered sulfonyl radical (II). 13,14 The addition of radical II to C]C bond of N-(2-vinylphenyl)amide (1) would lead to the formation of alkyl radical III. Later, III undergoes an intramolecular radical cyclization to provide a new radical intermediate IV. Subsequently, the radical IV was further oxidized to the corresponding carbocation (V) by oxidant followed by deprotonation to afford the sulfur-containing benzo[d] [1,3]oxazine (VI). 5 However, a cationic cyclization cannot be excluded completely, in which the alkyl radical intermediate III is further oxidized to carbocation and subsequently trapped by the carbonyl group of amide. 6 The resulting VI would be rapidly oxidized to desired sulfone-containing benzo[d] [1,3]oxazine (3) by K 2 S 2 O 8 . 7,13 The inuence of activated charcoal on reactivity of K 2 S 2 O 8 is not clear, however, we believe that the high surface area and micro porosity of activated charcoal may play role through widespread interactions and scission of S 2 O 8 2À to more powerful sulfate radical anions (SO 4 c À ) that accelerates the reaction under mild conditions. 14 In summary, a mild and cost-efficient protocol was developed for the synthesis of 2,4-aryl-4-((arylsulfonyl)methyl)-4H-benzo[d] [1,3]oxazines from N-(2-vinylphenyl)amides and thiols by employing mixture of K 2 S 2 O 8 -activated charcoal in aqueous acetonitrile solution at 50 C. The facile formation of new C-S, C-O and S-O bonds take place in a one-pot procedure. Versatility of this synthetic method for a broad range of N-(2-vinylphenyl)amides and thiols as well as the benets of use of easily accessible K 2 S 2 O 8activated charcoal mixture and thiols, respectively, as an oxidant and sulfonylating precursors. Further studies on the mechanism and applications are ongoing in our laboratory.

Experimental section
General procedure for the synthesis of 2,4-aryl-4-((arylsulfonyl)methyl)-4H-benzo[d] [1,3]oxazines An oven-dried Schlenk-tube equipped with a magnetic stir bar was charged with N-(2-vinylphenyl)amides (1.0 mmol, 1.0 equiv.), thiol (3.0 mmol, 3.0 equiv.), K 2 S 2 O 8 (4.0 mmol, 4.0 equiv.) and activated charcoal (0.03 g). To this mixture, CH 3 CN/ H 2 O (6 : 4, v/v mL, 10 mL) was added. Then, the tube was sealed and inlet/outlet for N 2 gas was provided by a side-neck. Resultant mixture was vigorously stirred under nitrogen gas atmosphere at 50 C for 6 h. Aer the completion (as indicated by TLC, z6 h) volatiles were evaporated under reduced pressure and then admixed with aqueous K 2 CO 3 solution (20 mL). The organic matters are extracted with ethyl acetate, dried over Na 2 SO 4 and evaporated under reduced pressure to yield a paleyellow gummy-solid, which was puried by a column chromatography using a mixture of ethyl acetate and hexane. The identity and purity of the product was conrmed by spectroscopic analysis as well as by a comparison with authentic samples spectra, vide infra.

Conflicts of interest
There are no conicts to declare.