An Approach to the Synthesis of Thioesters and Selenoesters Promoted by Rongalite ®

Rongalite promove a clivagem de diarildissulfetos gerando os calcogenolatos correspondentes, que reagem facilmente com N-acilbenzotriazóis na presença de K 2 CO 3 , produzindo tioésteres em bons a excelentes rendimentos. As principais características desta metodologia são a não necessidade de catalisdores metálicos ou de reagentes caros e o alto rendimento. É digno de nota que as reações de disseleneto de difenila com N-acilbenzotriazóis são também conduzidas para produzir selenoésteres em bons rendimentos sob condições normais.


Introduction
Thioesters have become increasingly important in the past few years because they have proven to be extremely useful intermediates for the preparation of heterocycles 1 and diverse ketones, 2 acyl radicals, 3 and biologically active compounds. 4The typical procedure for the synthesis of thioesters involves the reaction of acylhalides with thiols, 5 thiol sodium salts 6 or disulfides. 7In addition, carboxylic acids are also transformed into thioesters by treatment with arylthiocyanates and tributyl phosphine in dichloromethane 8 or with thiols by activated using tetramethyl fluoroformamidinium hexafluorophosphate, 9 diphosgene 10 and polyphosphate ester. 11Recently, Katritzky and co-workers 12 introduced a new procedure for preparation of thioesters utilizing N-acylbenzotriazoles. Some other methods include palladium-catalyzed thiocarbonylation of iodoarenes with thiols in ionic liquid, 13 rhodium-catalyzed alkylthio exchange reaction of thioester and disulfide, 14 KF/Al 2 O 3 -catalyzed reaction of N-acylphthalimides with thiols 15 and copper-catalyzed coupling of aryl iodides and thiobenzoic acid. 16However, these methods usually suffer from one or more limitations such as the use of unpleasant odor substrates thiols and expensive, toxic or metallic catalysts, long reaction times, unsatisfactory yields, as well as elevated temperature.Therefore, developing versatile approaches to synthesize thioesters still remains a highly desired goal in organic synthesis.
In continuation of our researches in developing novel synthetic routes for the formations of carbon-sulfur bonds 17 and Rongalite ® -promoted organic reactions, 18 we here demonstrate further extension of this work together with application of Rongalite ® (sodium formaldehyde sulfoxylate, HOCH 2 SO 2 Na) as an inexpensive reagent for the cleavage of diaryl disulfides or diphenyldiselenide and subsequent reaction with N-acylbenzotriazoles (Bt=1Hbenzo[d] [1,2,3]triazol-1-yl) to provide thioesters and selenoesters (Scheme 1).Vol.21, No. 9, 2010

Results and Discussion
At the onset of this work, we have investigated a variety of conditions with the model reaction of (1H-benzo[d] [1,2,3]triazol-1-yl)(phenyl)methanone (1a) and diphenyl disulfide (2a) using Rongalite ® as promoter (Table 1).First, we examined different solvents such as toluene, CH 2 Cl 2 , CH 3 CN, H 2 O, CH 3 CH 2 OH and DMF.Among the solvents screened, it was found that DMF is a much better solvent than all others tested (Table 1, entries 1-6).Next, we evaluated the loading amount of Rongalite ® .No reaction was observed in the absence of Rongalite ® and both starting materials were recovered in quantitative yields (Table 1, entry 7).In order to confirm, the amount of Rongalite ® required for the above transformation, different experiments were carried out by varying the amount of Rongalite ® (Table 1, entries 8-12).These results clearly indicate that, the use of 3 equiv.of Rongalite ® is sufficient to promote the reaction in excellent yield.On the other hand, among the bases such as KF, Et 3 N, K 3 PO 4 , K 2 CO 3 and Cs 2 CO 3 tested, K 2 CO 3 was found to be the best (Table 1, entries 6 and 13-16).We also checked the effect of the amount of K 2 CO 3 , the desired product 3a was afforded in 49% without K 2 CO 3, increasing the amount of K 2 CO 3 to 2 equiv., it was found that 1.5 equiv.resulted in excellent yield ( With the optimal conditions in hand, the scope of both disulfides and N-acylbenzotriazoles were explored and the results are summarized in (Table 2).As expected, this reaction proceeded smoothly and the desired products were afforded in good to excellent yields.A series of N-acylbenzotriazoles with either electron-donating or electron-withdrawing groups attached to aromatic ring were investigated.The substitution groups on the aromatic ring had no obvious effect on the yield.We also examined reaction of aliphatic N-acylbenzotriazole such as 1-(1H-benzo[d][1,2,3]triazol-1-yl)propan-1-one (1d), the desired products of 3j-3l were afforded in good yields (  [1,2,3]triazol-1-yl)(phenyl)methanone (1a) failed to give the expected thioesters.
On the other hand, we extended this method to prepare selenoesters starting from N-acylbenzotriazoles. Selenoesters are important intermediates in several organic Vol.21, No. 9, 2010 transformations.Selenoesters have been used as precursors of acyl radicals 19 and anions, 20 mild acyl transfer reagents, 21 intermediates in the synthesis of ketones, 22 and for asymmetric aldol reactions. 23Under the same conditions, we used diphenyldiselenide as source of selenolate anion, the reaction with N-acylbenzotriazoles afforded the corresponding selenoesters 5a-5d in the presence of Rongalite ® and K 2 CO 3 (Scheme 3).However, acylation of aliphatic diselenide, such as dibenzyl diselenide and dimethyl diselenide, was still unsuccessful under the standard conditions.
In summary, N-acylbenzotriazoles have been introduced as new efficient S-acylating reagents.The reactions have been demonstrated under mild conditions to give diverse thioesters and selenoesters with moderate to good yield.Rongalite ® as an inexpensive promoting reagent for these transformations can be substantiated by short reaction times, which is an additional advantage of this protocol.Efforts to explore the detailed mechanism and further applications of the present system in other transformations using disulfide and diselenide as a reaction partner are ongoing in our group.

Experimental
Chemicals and solvents were either purchased or synthesized by standard techniques.The reagents of N-acylbenzotriazoles were synthesized by reaction of the corresponding carboxylic acids with BtH and SOCl 2 following the reported one-step general procedure. 24elting points were recorded on Digital Melting Point Apparatus WRS-1B and are uncorrected.1 H NMR and 13 C NMR spectra were taken on a Bruker DPX300 spectrometer using CDCl 3 or DMSO-d 6 as the solvent with tetramethylsilane (TMS) as an internal standard at room temperature.Chemical shifts were given in d relative to TMS, the coupling constants J are given in Hz.Mass spectrometric analysis was performed on GC-MS analysis (SHIMADZU GCMS-QP2010). Eemental analysis was determined on a Carlo-Erba 1108 instrument.

General procedure for the preparation of thioesters 3, 4 and selenoesters 5
A mixture of N-acylbenzotriazoles 1 (0.4 mmol), diaryl disulfides 2 or diphenyldiselenide (0.2 mmol), Rongalite ® (3 equiv.), and K 2 CO 3 (1.5 equiv.) in DMF (3 mL) was stirred for the corresponding time at room temperature under air.After the reaction was finished, the reaction mixture was washed with water, extracted with ethyl acetate (3 × 10 mL), the organic phase was separated and dried over anhydrous sodium sulfate, filtered and the solvent was evaporated under vacuum.The residue was purified by flash column chromatography (ethyl acetate or hexane/ethyl acetate) to afford the desired product thioesters 3 or selenoesters 5.If cinnamic N-acylbenzotriazole 1f was used the reaction substrate, the amount of diaryl disulfides 2 is 0.4 mmol.

Table 1 .
Screening conditions for the synthesis of thioesters a

Table 2 .
Synthesis of diverse thiol esters from N-acylbenzotriazoles with disulfides a b Isolated yield.