Abstract
A new application of carbon disulfide in the presence of KF/Al2O3 is reported for the synthesis of organic symmetrical diaryl disulfides. These products were synthesized by one-pot reaction of aryl halides with the in situ generated trithiocarbonate ion in the presence of copper under air atmosphere.
1. Introduction
Carbon disulfide is a very important reagent for which many and varied uses have been reported in chemistry and also serves as an industrial and chemical nonpolar solvent [1–3]. The compound is frequently used as a building block in synthetic chemistry for the preparation of trithiocarbonates [4–9], dithio- and monothio-carbamates and carbonates [10, 11], thiourea [12, 13], and other organic compounds containing sulfur or thiocarbonyl (C=S) moiety [14–16]. Interestingly, carbon disulfide is also used for the synthesis of diaryl disulfides from diazonium salts under conditions of radicalic pathway [17, 18].
In continuation of our efforts to synthesize organic compounds containing sulfur and to use carbon disulfide in organic reactions [4–6, 19, 20], we report a method for the direct synthesis of symmetrical diaryl disulfides via domino coupling reactions of aryl halides with the trithiocarbonate anion. However, recently symmetrical diaryl trithiocarbonates are synthesized from the reaction of Na2S and CS2 with Ar-X in the presence of CuI [21]. In our process, KF/Al2O3 was used as a strong, recyclable, and heterogeneous base, which has a history of use in both synthetic methodology reactions [22–27] and the in situ production of the trithiocarbonate ion from carbon disulfide [4].
Organic disulfides are also valuable compounds in synthetic chemistry, industry, and biochemistry [28, 29]. They are typically prepared by oxidation of the corresponding thiols [30–36]. There are a limited number of methods for the direct synthesis of disulfides from aryl halides [20, 37].
2. Results and Discussion
To find the optimal reaction conditions in terms of temperature and type of copper source, the coupling reaction of the carbon disulfide with iodobenzene was examined in the presence of KF/Al2O3 under air (Scheme 1).
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The trithiocarbonate anion was prepared by the in situ reaction of three equivalents of carbon disulfide in the presence of 1.0 gram of KF (40% by weight)/Al2O3 in DMF. First, the effect of different copper salts was examined. As is shown in Table 1, copper iodide can catalyze the synthesis of diphenyl disulfide from phenyl iodide better than that from the other salts tested (Table 1, entry 4). As strong bases are commonly used for preparation [10, 11], Cs2CO3 and KOH were also tested to evaluate the efficiency of KF/Al2O3. They catalyze the reaction under optimized reaction conditions, but not as well as KF/Al2O3 as the reaction yields were 65% and 35%, respectively.
It can be deduced from the previous literature reports that the temperature and the nature of an added ligand significantly affect the progress of coupling reactions of sulfur-containing compounds because some of them have not been carried out at room temperature and/or in the absence of a ligand [38, 39]. In our studies on the reaction, the best result was obtained at 110°C. However, significant progress of the reaction was also observed at lower temperatures (Table 1, entries 6 and 7). In addition, the reaction also proceeded well in the absence of a ligand. It seems that acts as both a ligand and a sulfur source.
It was expected that some symmetrical diaryl trithiocarbonate and thiol would be generated as by-products with the desired diaryl disulfide. However, no traces of these compounds were found at the end of the reaction. Thus, a large number of derivatives of symmetrical diaryl disulfides were synthesized in good to excellent yields under optimal conditions (Scheme 2, Table 2). Aryl bromides also reacted under these conditions, but not as well as aryl iodides.
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A wide range of diaryl disulfides was synthesized according to the nature and position of the attachment of the substituents on the aryl groups. Thus, the products bearing different substituents, both electron-withdrawing and electron-donating, were obtained at the ortho-, para-, and metapositions.
Symmetrical diheteroaryl disulfides were readily synthesized from the corresponding heteroaryl halides (Table 2, entries 7 and 8). The optimal reaction conditions were also tested for the synthesis of symmetrical dialkyl disulfides (Table 2, entry 13) but were proved to be ineffective in yielding the dibenzyl disulfide and dibenzyl trithiocarbonate (as the major product); dibenzyl sulfide was obtained in 76% and 16% yields, respectively. Interestingly, a high chemoselectivity is observed in the coupling reactions (Table 2, entries 11 and 5). It is the case of 1-bromo-2,4-difluorobenzene to bis-(2,4-diflouro phenyl) disulfide (Table 2, entry 11) and 1-bromo-4-iodobenzene to bis-(4-bromo phenyl) disulfide (Table 2, entry 5) yielded as the main products. The reactivity of carbon–halide (C–X) bonds in aryl halides (Ar–X) probably depends on the nature of the halides. As was seen, the reactivity of carbon–X bonds is in the order of C–I > C–Br > C–F (Table 2, entries 4 and 10, 7 and 8, 5, 11).
Although we cannot yet clearly delineate the catalytic reaction pathway for the synthesis of diaryl disulfides from aryl halides and , it is possible that this reaction proceeds through an addition/oxidation Cu(I)-catalyst reaction of trithiocarbonate anion to aryl halides to generate an aryl trithiocarbonate ion via Ullman-type mechanism and then the fragmentation of formed aryl trithiocarbonate anion into carbon disulfide and aryl thiolate [40], which is followed by thiolate oxidation to corresponding disulfides in the presence of KF/Al2O3 [41, 42]. Aryl (alkyl) halides are activated via a Cu(I)/Cu(II) redox couple single electron transfer (SET) [43].
3. Conclusion
In summary, in this study, carbon disulfide was used as an inexpensive and readily available source of sulfur in the presence of KF/Al2O3. The reaction proceeds well under air. This strategy provides a new method for the direct synthesis of symmetrical diaryl disulfides from aryl halides and . Other advantages of this process are the ability to reuse the recyclable base KF/Al2O3, ease of performing and controlling the reaction as well as purification of the product, and the avoidance of expensive and/or dangerous reagents.
4. Experimental
4.1. Direct Synthesis of Diaryl Disulfides from Aryl Halides and Trithiocarbonate Ion: General Procedure
6 mmol of carbon disulfide and 2 mmol of aryl halide were added to a two-neck flask containing 4 mL of DMF and 1.0 gram of KF (40% by weight)/Al2O3 [4, 44]. The mixture was vigorously stirred for 15 minutes at room temperature on a hot-plate magnetic stirrer, so that it was blood red in color. Then 0.32 mmol (60 mg) of CuI was added, and the reaction continued at 110°C under air atmosphere and in a condenser until the reaction was completed (5 h). The reaction progress was controlled by TLC. The reaction mixture was then filtered, the filtrate was evaporated under vacuum, CH2Cl2 (20 mL) was added, and the mixture washed with H2O ( mL). The organic layer was dried over anhydrous Na2SO4. The solvent was evaporated to give the crude diaryl disulfide, which was purified by plate chromatography (silica gel, n-hexane: ethyl acetate 20 : 1). All the products are known compounds and were characterized by comparison of NMR spectral data and melting points with those reported in the literature.
4.2. Selected Spectral Data for Representative Disulfides
Diphenyl Disulfide (Table 2, entry 1). mp = 59-60°C (59–61°C lit. [31]). 1H NMR (CDCl3, 400 MHz): δ = 7.24–7.36 (m, 6H), 7.54 (m, 4H). NMR (CDCl3, 100 MHz): .
Bis(4-mathoxyphenyl) Disulfide (Table 2, entry 2). mp = 42-43°C (42-43°C lit. [34, 35]). 1H NMR (CDCl3, 400 MHz): δ = 3.82 (s, 6H), 6.87 (d, Hz, 4H), 7.32 (d, Hz, 4H). NMR (CDCl3, 100 MHz): .
Bis(thiophen-2-yl) Disulfide (Table 2, entry 7). mp = 54-55°C (54–56°C lit. [36]). 1H NMR (CDCl3, 400 MHz): δ = 1H NMR (CDCl3, 400 MHz): δ 6.97–7.00 (m, 2H), 7.22–7.25 (m, 2H), 7.36–7.38 (m, 2H). NMR (CDCl3, 100 MHz): .