Photocatalytic Transformation of Organic and Water-Soluble Thiols

Jul 5, 2011 - Department of Chemistry, National University of Singapore, ... route toward the synthesis of disulfides and exhibits 100% atom economy...
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Photocatalytic Transformation of Organic and Water-Soluble Thiols into Disulfides and Hydrogen under Aerobic Conditions Using Mn(CO)5Br Kheng Yee Desmond Tan, Guan Foo Teng, and Wai Yip Fan* Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543 ABSTRACT: The photolysis of Mn(CO)5Br with thiols under aerobic conditions at room temperature produces the corresponding disulfides in high yields, accompanied by the evolution of hydrogen as the only other product. This transformation is a greener route toward the synthesis of disulfides and exhibits 100% atom economy. The catalytic system possesses high chemoselectivity, as evidenced by high disulfide yields even in the presence of numerous functional groups. A mechanism has been proposed to involve free radical species and is based on fac-Mn(CO)3(RSH)2Br being an important catalytic intermediate. Mn(CO)5Br is also able to catalyze the conversion of naturally occurring water-soluble thiols such as cysteine and glutathione. Coupled with suitable enzymes that regenerate thiols from disulfides using proton sources, it is possible to envisage a combined catalytic cycle that is able to reduce protons to hydrogen efficiently.

’ INTRODUCTION Organic compounds containing the element sulfur such as disulfides are extensively utilized in chemistry and biology.1 3 In biological systems, disulfides are known to prevent oxidative damage.4 Disulfides are also useful reagents from the chemical viewpoint, especially for organic syntheses; that is, they are used to sulfenylate various anions.5 In addition, they are often used as a protecting group for thiols.6 In industry, disulfides are used to vulcanize rubber and elastomers.3 Since thiols are readily available, the oxidative coupling of thiols is one of the most common methods for disulfide synthesis. Many reagents have been used to carry out the coupling including permanganates,7 halogens,8 iron(III) chloride,9 peroxides,10 nitrogen monoxide,11 sodium perborate,12 sulfuryl chloride,13 sulfoxides,14 copper(II) nitrate trihydrate,15 manganese compounds,4,16,17 cesium fluoride Celite solid base,18 and rosolic acid.19 Despite the large number of routes available, some appear to be less desirable, which is mainly attributed to a few reasons: (i) the need for expensive and toxic reagents in stoichiometric amounts, (ii) the generation of unwanted sideproducts, (iii) long reaction times, and (iv) the overoxidation of disulfides. Tanaka et al. has previously investigated the usage of transition metal complexes to produce disulfides from thiols,20 and better selectivity was achieved, cf. the usage of oxidants. Karami et al.4 and Montazerozohori et al.21 have also reported on the oxidative coupling of thiols using metals. We have recently reported on the suitability of CpMn(CO)3 as a precursor for a greener catalytic system: the conversion of thiols into disulfides with hydrogen as the only other product.22 Although conditions for the transformation can be considered mild, the catalysis proceeds only in the absence of oxygen. In this paper, we explore the catalytic properties of another group VII metal complex: pentacarbonylmanganese(I) bromide, Mn(CO)5Br (complex 1). For this system, the conversion of r 2011 American Chemical Society

Scheme 1. Transformation of Thiols into Disulfides and Hydrogen Using Complex 1

thiols into disulfides and hydrogen using complex 1 yields comparatively higher TON (turnover number) values and can proceed in the presence of oxygen or air. During the course of our investigation, we have found that water-soluble thiols such as glutathione (GSH) and cysteine could be transformed into their respective disulfides with hydrogen evolution as well. This has initiated keen interest especially since commercially available enzymes such as glutathione reductase and cysteine reductase can easily reduce the respective disulfides into thiols using proton sources.23,24 Hence the combination of the Mn(CO)5Br- and enzyme-catalyzed cycles into one will effectively convert protons into hydrogen without sacrificing any thiols in the process. In this work, we propose a mechanism to account for the experimental observations.

’ RESULTS AND DISCUSSION Broadband irradiation of complex 1 with mono-functional aliphatic thiols in the presence of oxygen affords the corresponding disulfides in high yield, with hydrogen as the only other product (Scheme 1). Although visible light can also effect the same transformation, the time required for full conversion is twice as long compared to UV photolysis. For consistency in the yield studies, we have used a 355 nm UV laser as the source of irradiation. Interestingly, the Received: May 30, 2011 Published: July 05, 2011 4136

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Table 1. Oxidative Coupling of Mono-functional Thiols by Complex 1a

Irradiation (355 nm, ∼20 mJ/pulse) of complex 1 (39.6 μmol, 5.0 mol %) and RSH (0.793 mmol) in 0.5 cm3 cyclohexane for 2 h at room temperature. Irradiation (355 nm, ∼20 mJ/pulse) of complex 1 (19.8 μmol, 0.25 mol %) and RSH (7.93 mmol) for 4 h at room temperature. c Determined via 1H NMR using toluene as internal standard. d Purified and isolated using silica gel column chromatography. e Calculated using the ratio of the number of moles of thiol transformed over complex 1. a b

Table 2a. Oxidative Coupling of 1c by Complex 1 in the Presence of Additivesa

a Irradiation (355 nm, ∼20 mJ/pulse) of complex 1 (39.6 μmol, 5.0 mol %), RSH (0.793 mmol), and additive (0.793 mmol) in 0.5 cm3 cyclohexane for 2 h at room temperature. b Determined via 1H NMR using toluene as internal standard. c Purified and isolated using silica gel column chromatography. d Calculated using the ratio of the number of moles of thiol transformed over complex 1.

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Table 2b. Oxidative Coupling of Bis-functional Thiols by Complex 1a

Irradiation (355 nm, ∼20 mJ/pulse) of complex 1 (39.6 μmol, 5.0 mol %) and RSH (0.793 mmol) in 0.5 cm3 solvent for 2 h at room temperature. Determined via 1H NMR using toluene as internal standard. c Purified and isolated using silica gel column chromatography. d Calculated using the ratio of the number of moles of thiol transformed over complex 1. e In benzene. f In cyclohexane. g In D2O. a b

Figure 1. IR spectra taken over certain time intervals of the reaction mixture containing complex 1 and 1c in cyclohexane initially. The νCO bands of complexes 1, 2, and 3 are shown.

photocatalysis proceeds most efficiently in the presence of oxygen or air; otherwise the disulfide yield is almost negligible under vacuum conditions. In addition, photolysis of aliphatic thiols in air without complex 1 does not give any disulfides. Identities of the organic products have been confirmed using 1 H NMR spectroscopy and EI-MS. The isolated yields of the

purified disulfides are also in good agreement with the values obtained using 1H NMR spectroscopy (Table 1). Using EI-MS, hydrogen has been detected in 75 80% yields relative to the disulfides. The commonly encountered overoxidation products such as sulfoxides and sulfones were not detected, which suggests that the transformation is indeed clean. 4138

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Organometallics We focus on the effect of photolysis on complex 1 with aliphatic thiols in cyclohexane solvent, since the aromatic thiols already spontaneously convert into their corresponding disulfides upon stirring in air even in the absence of manganese. Such transformations of thiols into disulfides and hydrogen are also slightly endergonic (ΔGo values ranging from 20 to 30 kJ mol 1).25 Besides exhibiting 100% atom economy, the transformation can be performed in the absence of a solvent (Table 1, entry 6). This lends further support for the reaction to qualify as a greener approach toward the synthesis of disulfides. Interestingly, comparatively higher TON values were obtained under neat conditions, which suggests the greater degree of stabilization of key catalytic intermediates by coordinating to thiol molecules. As the transformation of mono-functional aliphatic thiols into their respective disulfides produces high yields, we proceeded to explore the photolysis of complex 1 with thiols in the presence of other functional groups. This was achieved via two methods: (i) the usage of thiol 1c in the presence of additives (Table 2a) and (ii) the usage of bis-functionalized thiols (Table 2b). In the presence of numerous functional groups, the system is still catalytic, albeit with reduced disulfide and hydrogen yields. Complex 1 can be considered to be tolerant toward the presence of the aldehyde, ether, phosphine, and silane functional groups, as shown by the high disulfide yields (Table 2a, entries 4, 5, 6, and 9), and comparatively less tolerant toward various other functional groups (Table 2a, entries 2, 3, 7, 8, and 10; Table 2b, entries 1, 2, and 5). Nonetheless, the results suggest the strong preference for complex 1 to coordinate to thiols over other Mn X interactions (e.g., X is an alkene or a phosphine). The only exception is the presence of the carboxyl functional group COOH, which completely quenches the catalytic property of complex 1 (Table 2b, entry 6). However when Na2CO3 was added to deprotonate the substrate, high disulfide yields can be recovered (Table 2b, entry 7). Scheme 2. Structures of Complexes 2, 3, and 4

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We have used thiol 1c as a test case for understanding the reaction pathways toward thiol coupling by complex 1. In order to determine the role of the bromide ligand in the catalytic pathway, tetrabutylammonium bromide has been added to the catalytic mixture. However, no difference in the disulfide yields is detected. Furthermore the reactions involving complex 1 and 1c do not show a precipitate forming upon the addition of AgNO3 to the mixture after catalysis. In addition, Sweany and Watzke have previously reported that the halide does not dissociate upon photolysis of complex 1 with a low-pressure Hg lamp.26 Thus, we propose that the Mn Br dissociation is unlikely to be one of the important steps in the catalytic cycle. IR spectra of the photolytic mixture have been obtained over regular time intervals in an attempt to identify the metal-containing intermediates present during catalysis. The νCO carbonyl stretching frequencies have been assigned to the respective species (Figure 1) based on literature values. Complex 1 (νCO: 2001, 2020, 2051, and 2134 cm 1) appears to undergo sequential substitution of its CO ligands by thiol molecules via a dissociative pathway to form cis-Mn(CO)4(RSH)Br (2)27,28 and subsequently fac-Mn(CO)3(RSH)2Br (3). The structures of complexes 2 (νCO: 1968, 2013, 2027, and 2086 cm 1) and 3 (νCO: 1962, 1994, and 2069 cm 1) are shown in Scheme 2. Hieber and Gscheidmeier have reported the formation of the fac-C2H4(SH)2Mn(CO)3Br species,29 which possesses νCO stretching frequencies similar to those of complex 3. In addition, it was noted that only the cis- and fac-isomers were obtained for the monosubstituted and disubstituted intermediates, respectively. The stronger π-back-bonding of CO compared to Br gives the trans-CO a comparatively stronger metal carbonyl bond. Hence the CO cis to Br is more labile, and that favors the formation of the fac-isomer.27,28 Although Reimann and Singleton previously reported the formation of a trisubstituted complex, Mn(CO)2L3Br, we could not detect such a species in our system.30 However the bromo-bridged manganese carbonyl dimer (4) is observed to form at about t = 20 min into the photolysis,31 but disulfide formation is only seen to be produced much later, at t = 60 min (refer to Figure 2). In addition, a control that involved the irradiation of complex 4, generated independently from heating complex 1 alone in cyclohexane, with thiols shows no disulfide formation.

Figure 2. Plot of νCO intensities for complexes 1, 2, and 3 against time for the oxidative coupling of 1c by complex 1. The relative disulfide concentration as measured using NMR spectroscopy is also shown. 4139

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Scheme 3. One of the Proposed Reaction Pathways for the Oxidative Coupling of Thiols by Complex 1

Scheme 4. Net Conversion of Protons into Hydrogen

To further elucidate the reaction mechanism, a plot of relative intensities against time (the band used for each complex is in parentheses) is obtained for the manganese complexes: 1 (2051 cm 1), 2 (1968 cm 1), and 3 (2069 cm 1). The amount of disulfide formed at each time interval is also included in the same graph. As expected, typical kinetic profiles indicating intermediary behavior of complexes 2 and 3 are observed. These profiles also show that complex 3 is formed from 2, which in turn originated from complex 1. Interestingly, the graph indicates that disulfide formation is detected shortly after the maximum concentration of complex 3 is reached (Figure 2). The rate of disulfide formation also appears to be highest at this point before reaching a plateau at longer time intervals. In contrast, the connection between the disulfide formation and complexes 1 and 2 is not as straightforward. Since complex 3 appears to be closely linked to the formation of disulfides from thiols, we have prepared it separately by reacting Mn(CO)5Br with thiol under vacuum conditions. It was also mentioned earlier that oxygen or air is essential in this catalytic system. To establish the roles of oxygen and light further, complexes 3 and 1c have been reacted under three conditions: (i) UV irradiation in air, (ii) absence of irradiation in air, and (iii) UV irradiation without air. The results show that disulfide formation is observed only for condition (i), hence lending support to the requirement for oxygen, light, and complex 3 to effect the catalysis. In an attempt to better understand the effect of light on the transformation, the catalysis was initiated by the UV irradiation

of complex 3, which was subsequently discontinued. 1H NMR spectroscopy was used to monitor the amount of organic products over time, and the results showed that continuous UV irradiation is required to produce significantly higher disulfide yields. Thus, this could suggest that one of the steps in the catalytic cycle is triggered by light. The requirement for oxygen suggests a catalytic pathway involving free radical species. According to a previous study, the S H bond in thiols can be cleaved homolytically under UV irradiation to give H atom and RS radicals.32 We postulate that oxygen could also have extracted the H atom from the thiol to form a peroxy radical. Since Perkin et al. have previously reported the usage of pyrogallol to scavenge the peroxyl radical,33 we have also adopted the same method to ascertain the possible generation of such a radical in our system. Indeed, addition of pyrogallol (0.1 0.5 equivalent of Mn(CO)5Br) decreases the disulfide yield by approximately 8 times. In addition, results of control experiments show that pyrogallol does not undergo any sidereaction with both complex 1 and the thiol. To further substantiate the presence of radicals in the catalysis, we have used TEMPO, (2,2,6,6-tetramethylpiperidin-1-yl)oxyl, to establish the presence of S-centered radicals. Busfield et al. have previously used the structurally similar aminoxyl radical (1,1,3,3-tetramethyl-2,3-dihydro-1H-isoindol-2-yloxyl) to scavenge for carbon- and sulfur-centered radicals, but not oxygencentered radicals.34 In our experiments, although there is no IR evidence to indicate reactions between TEMPO with either complex 1 or the thiol, the addition of TEMPO (0.1 0.5 equivalents of Mn(CO)5Br) to the catalytic mixture still manages to decrease the disulfide yields by approximately 50%. On the basis of our experiments with the radical scavengers, we conclude that free radicals, possibly both S-centered and O-centered radicals play an important role in the catalytic process. A catalytic cycle for the oxidative coupling of thiols into disulfides by complex 1 is proposed on the basis of the experimental data obtained thus far. The photolysis of complex 1 results in the stepwise dissociation of CO followed by thiol substitution to afford the bis-substituted intermediate complex 3. At this point, the presence of oxygen becomes essential, where it may interact with the metal center of complex 3 or with its thiol ligands instead. In the first case, complex 3 will most likely be oxidized to form a Mn(II) or Mn(III) complex. It is possible that such a complex would then act as the active catalyst. In the second case, a hydrogen atom from one of the coordinated thiol molecules on 3 is abstracted by oxygen to form intermediate I and the peroxy radical as illustrated in Scheme 3. The radical quickly recombines with I to form intermediate II followed by the elimination of hydrogen upon coupling of the H atom of the weak O H bond of the peroxy moiety with the H atom on the adjacent RSH ligand. The resultant intermediate III contains a RSOO fragment, which has been reported to undergo facile dissociation to O2 and the RS radical.32,35 Thus, it is possible for 4140

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Table 3. Oxidative Coupling of Water-Soluble Thiols by Complex 1 under Different Conditionsa

a b

Irradiation (355 nm, ∼20 mJ/pulse) of complex 1 (0.08 mmol, 10 mol %) and RSH (0.793 mmol) in 1.0 cm3 solvent for 5 h at room temperature. 1.0 cm3 D2O. c 0.3 cm3 D2O, 0.7 cm3 tert-butanol.

the oxygen to be eliminated from III, leading to the formation of a S S bond between the two adjacent RS ligands in IV. Finally the dissociation of the disulfide from IV frees up vacant slots for the coordination of the thiol substrates and effectively completes the catalytic cycle. During the course of this work, we went on to explore the conversion of water-soluble thiols into the respective disulfides and hydrogen. This interest was prompted by the well-known fact that a class of enzymes, the disulfide reductases, is able to convert disulfides back into thiols. In an aqueous medium, the hydrogen source is the proton, which usually appears in NADPH form.36 Enzymes such as glutathione and cysteine reductases are also commercially available and relatively easy to use.37,38 Hence it is possible to complete a catalytic cycle by combining the oxidative coupling of thiols into disulfides catalyzed by complex 1 with the enzymes used to reduce the disulfides back into the thiols. The overall reaction would be the conversion of protons into hydrogen (Scheme 4). In this way, the thiols and disulfides act only as mediators or hydrogen atom carriers and will not be consumed in the catalytic cycle. We have used cysteine and glutathione as representatives of water-soluble thiols. Since the carboxyl group inhibits the catalytic property of complex 1, this functional group in cysteine and glutathione has been protected and deprotonated respectively. Two experimental conditions have been used (Table 3), where in the first case the catalysis is allowed to be carried out heterogeneously by dispersing the surface water-insoluble complex 1 in an aqueous solution of the thiol. In the second case, a solvent pair of 70% tert-butanol and 30% D2O is employed to ensure complete miscibility of complex 1 with the thiols. Not surprisingly the disulfide yield for either substrate conducted in the mixed solvent is higher than those in pure water (Table 3). In both cases, the yields for the bulkier glutathione are lower than those for cysteine, hence showing that steric effects play a role in the process. In addition, the mixed-solvent catalysis is less efficient compared to those involving alkanethiols in cyclohexane. It is possible that interactions between complex 1 and the mixed solvent could have slowed the reaction. Nevertheless, the results show that Scheme 4 could be explored further in order to exploit thiols and disulfides as possible hydrogen atom carriers toward the generation of hydrogen gas from proton sources. Current work in our laboratory is now focused on finding the optimum way of coupling the two processes using complex 1 and the enzymes together in an efficient manner.

’ CONCLUSION The photocatalytic conversion of organic thiols into their respective disulfides has been achieved with Mn(CO)5Br in the presence of oxygen. The transformation is tolerant toward many functional groups, proceeds under mild conditions, and produces hydrogen as the only other product. A catalytic mechanism has been proposed on the basis of experimental evidence and may involve fac-Mn(CO)3(RSH)2Br as a key intermediate. Interestingly, water-soluble thiols are also able to undergo the same transformation. By combining complex 1 with suitable enzymes that can regenerate thiols from disulfides using proton sources, it is possible to construct a catalytic cycle that is able to reduce protons to hydrogen efficiently. ’ EXPERIMENTAL SECTION General Considerations. All reactions and manipulations were carried out in the presence of air at room temperature unless otherwise stated. Materials. Ethyl 2-mercaptoacetate (98%), furfuryl mercaptan (98%), pentacarbonyl manganese bromide (98%), 1-butanethiol (98%), 1-dodecanethiol (98%), 1-octanethiol (98%), and 2-mercaptoethanol (98%) were purchased from Alfa Aesar. (2,2,6,6-Tetramethylpiperidin-1-yl)oxy (99%) was purchased from Avocado Research Chemicals. Deuterium oxide (99.9%) was purchased from Cambridge Isotope Laboratories. Pyrogallol (98%) was purchased from Fluka. Acetonitrile (99.8%), ethyl acetate (99.8%), benzaldehyde (99.5%), benzene (99.8%), benzyl mercaptan (99%), chloroform (99%), chloroform-d (CDCl3, 99.8 atom % D, stabilized with 0.5 wt % Ag, contains 0.03% TMS), cyclohexane (99.5%), cyclohexanethiol (97%), diethyl ether (99.9%), L-cysteine ethyl ester hydrochloride (98%), L-glutathione reduced (98%), silver nitrate (99%), sodium carbonate (99%), tertbutanol (99.5%), tetrabutylammonium bromide (99%), toluene (99.8%), triethylsilane (99%), triphenylphosphine (99%), 1-hexene (99%), 1-hexyne (97%), 2-heptanone (99%), 3-mercaptopropionic acid (99%), 4-mercaptophenol (97%), and (3-mercaptopropyl)trimethoxysilane (97%) were purchased from Sigma-Aldrich. All solvents and reagents were used without further purification. Instrumentation. Photolysis experiments were conducted using a Continuum Surelite III-10 Nd:YAG laser (355 nm), a Legrand broadband lamp (300 800 nm), and a Philips broadband lamp (400 800 nm). All IR spectra were obtained using a Shimadazu IR Prestige-21 FTIR spectrophotometer (1000 4000 cm 1, 1 cm 1 resolution, 4 scans co-added for spectral averaging) using a 0.05 nm path 4141

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Organometallics length calcium fluoride cell. 1H NMR spectra were recorded at room temperature in CDCl3 and D2O on a Bruker AV 500 Fourier-transform spectrometer operating at ca. 500 MHz. The chemical shifts were reported relative to TMS for spectra taken in CDCl3 and to the residual solvent peak for spectra taken in D2O. Hydrogen gas was detected using a Balzer Prisma QMS 200 residual mass analyzer. Mass spectra for the organic and water-soluble disulfides were recorded with a Finnigan Mat 95XL-T spectrometer and a Finnigan MAT 731 LCQ spectrometer, respectively. Catalytic Runs Involving Organic Thiols. The metal complex (39.6 μmol, ∼5 mol %) and the respective thiol (0.793 mmol) were added into a round-bottom flask that contained 0.5 cm3 of the solvent. For the functional group tolerance investigations, the respective additive (0.793 mmol, ∼100 mol %) was introduced accordingly into 0.5 cm3 of the solvent. The solutions were laser irradiated (355 nm, ∼20 mJ/ pulse), or broadband irradiated (400 800 nm, 11W), and stirred for 2 h. The amount of disulfide produced was quantified using 1H NMR spectroscopy by calibration with toluene as the internal standard. The products were purified by silica gel chromatography for isolated yield determination. Hydrogen gas was detected by sampling the headspace above the catalytic mixture throughout the reaction, and the calibration was achieved via the introduction of a known amount of pure hydrogen gas. Catalytic Runs Involving Water-Soluble Thiols. One equivalent of glutathione was reacted with 2 equivalents of Na2CO3 to form sodium glutathionate. The metal complex (0.08 mmol) and the respective water-soluble thiol (0.793 mmol) were added into a round-bottom flask that separately contained (i) 1.0 cm3 of D2O and (ii) 0.3 cm3 of D2O, 0.7 cm3 of tert-butanol, and were laser irradiated (355 nm, ∼20 mJ/pulse) for 5 h. Time Scans Using FTIR and 1H NMR Spectroscopy. One equivalent of the metal complex and 10 equivalents of 1-dodecanethiol were dissolved in 0.5 cm3 of cyclohexane. The solution was broadband irradiated in air. Both the IR and 1H NMR spectra were obtained at t = 0, 20, 40, 60, 80, 100, and 120 min. Determination of the Presence of Free Br . One equivalent of the metal complex, 5 equivalents of tetrabutylammonium bromide, and 10 equivalents of 1-dodecanethiol were dissolved in 0.5 cm3 of CHCl3. The solution was laser irradiated for 30 min, and the 1H NMR spectrum was obtained. After the reaction, aqueous AgNO3 was added dropwise to the solution in an attempt to detect AgBr.

Determination of the Presence of Radical Intermediates. One to 5 equivalents of pyrogallol or TEMPO were added separately to 10 equivalents of the metal complex and 100 equivalents of 1-dodecanethiol in 0.5 cm3 of cyclohexane. The solution was laser irradiated for 40 min, and the 1H NMR spectra were obtained. Preparation of fac-Mn(CO)3(RSH)2Br. One equivalent of complex 1 (50 mg, 1.8  10 4 mol) and 10 equivalents of 1-dodecanethiol were dissolved in 0.5 cm3 of cyclohexane and degassed, followed by subsequent broadband irradiation for 1 h. The resultant mixture was subjected to column chromatography to obtain fac-Mn(CO)3(RSH)2Br. Yield: 22%. νCO(cyclohexane): 1962, 1994, and 2069 cm 1. Determination of the Role of O2 and Photolysis. A cyclohexane solution containing fac-Mn(CO)3(RSH)2Br (5 mg, 1.8  10 5 mol) was divided into five portions for subsequent reactions with an additional 0.1 cm3 of 1-dodecanethiol under four sets of conditions: (i) further photolysis in air, (ii) stirring in the absence of light and also in air, and (iii) further photolysis in vacuum, each for 30 min; (iv) continuous irradiation for 30 min; and (v) irradiation for 15 min and stirring in the absence of light for 15 min. 1 H NMR and MS Data for the Disulfides. Dibutyl disulfide, 1H NMR, δ (CDCl3): 2.69 (t, 4H, CH2S). EI-MS, m/z (M+): 178. Dioctyl disulfide, 1H NMR δ (CDCl3): 2.68 (t, 4H, CH2S). EI-MS, m/z (M+): 291. Didodecyl disulfide, 1H NMR δ (CDCl3): 2.68 (t, 4H, CH2S).

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EI-MS, m/z (M+): 403. Bis(2-ethoxy-2-oxoethyl) disulfide, 1H NMR δ (CDCl3): 3.58 (t, 4H, CH2S). EI-MS, m/z (M+): 238. Difurfuryl disulfide, 1H NMR δ (CDCl3): 3.69 (s, 4H, CH2S). EI-MS, m/z (M+): 226. Di(2-hydroxyethyl) disulfide, 1H NMR δ (CDCl3): 2.89 (t, 4H, CH2S). EI-MS, m/z (M+): 154. Bis(4-hydroxyphenyl) disulfide, 1 H NMR δ (CDCl3): 6.76 (d, 4H, ortho to OH). EI-MS, m/z (M+): 250. Bis[3-(trimethoxysilyl)propyl] disulfide, 1H NMR (CDCl3): 2.70 (t, 4H, CH2S). EI-MS, m/z (M+): 391. Dicyclohexyl disulfide, 1H NMR δ (CDCl3): 2.68 (m, 2H, CH2S). EI-MS, m/z (M+): 230. Dibenzyl disulfide, 1H NMR δ (CDCl3): 3.60 (s, 4H, CH2S). EI-MS, m/z (M+): 246. Di(3-propionate) disulfide, 1H NMR δ (D2O): 2.54 (t, 4H, CH2S). ESI-MS ( mode) m/z = 208. Cystine ethyl ester, 1H NMR δ (D2O): 3.27 3.36 (m, 4H, CH2S). ESI-MS (+ mode) m/z = 297.0. Glutathionate disulfide, 1H NMR δ (D2O): 3.24 3.32 (m, 4H, CH2S). ESI-MS ( mode) m/z = 633.1.

’ AUTHOR INFORMATION Corresponding Author

*Fax: (+65) 6779-1691. E-mail: [email protected].

’ ACKNOWLEDGMENT K.Y.D.T. thanked NUS for a studentship. This project was supported by research grants provided by MOE Tier 2 grant nos. T208B1111 and 143-000-430-112. ’ REFERENCES (1) Cremlyn, R. J. In An Introduction to Organosulfur Chemistry; Wiley: New York, 1996. (2) Whitham, G. H. In Organosulfur Chemistry; Oxford University Press: Oxford, 1995. (3) Ghammamy, S.; Tajbakhsh, M. J. Sulfur Chem. 2005, 26, 145. (4) Karami, H.; Montazerozohori, M.; Habibi, M. H. J. Chem. Res. 2006, 8, 490. (5) Bischoff, L.; David, C.; Martin, L.; Meudal, H.; Roques, B.-P.; Fournie-Zaluski, M.-C. J .Org. Chem. 1997, 62, 4848. (6) Hosseinpoor, F.; Golchoubian, H. Catal. Lett. 2006, 111, 165. (7) Noureldin, N. A.; Caldwell, M.; Hendry, J.; Lee, D. G. Synthesis 1998, 1587. (8) Ali, M. H.; McDermott, M. Tetrahedron Lett. 2002, 43, 6271. (9) Ramesha, A. R.; Chandrasekaran, S. J. Org. Chem. 1994, 59, 1354. (10) Hajipour, A. R.; Mallakpour, S. E.; Adibi, H. J. Org. Chem. 2002, 67, 8666. (11) Pyror, W. A.; Church, D. F.; Govindan, C. K.; Crank, G. J. Org. Chem. 1982, 47, 156. (12) McKillop, A.; Koyuncu, D. Tetrahedron Lett. 1990, 31, 5007. (13) Leino, R.; Lonnqvist, J.-E. Tetrahedron Lett. 2004, 45, 8489. (14) Wallace, T. J. J. Am. Chem. Soc. 1964, 86, 2108. (15) Firouzabadi, H.; Iranpoor, N.; Zolfigol, M. A. Synth. Commun. 1998, 28, 1179. (16) Montazerozohori, M.; Fradombe, L. Z. Phosphorus, Sulfur, Silicon 2010, 185, 509. (17) Gondi, S. R.; Son, D. Y.; Biehl, E. R.; Vempati, R. K. Phosphorus, Sulfur, Silicon 2010, 185, 34. (18) Shah, S. T. A.; Khan, K. M.; Fecker, M.; Voelter, W. Tetrahedron Lett. 2003, 44, 6789. (19) Singh, W. M.; Baruah, J. B. Synth. Commun. 2009, 39, 325. (20) Tanaka, K.; Ajiki, K. Tetrahedron Lett. 2004, 45, 25. (21) Montazerozohori, M.; Fradombe, L. Z. Phosphorus, Sulfur, Silicon 2010, 185, 509. (22) Tan, D. K. Y.; Kee, J. W.; Fan, W. Y. Organometallics 2010, 29, 4459. (23) Harvey, R. A.; Ferrier, D. R. In Lippincott’s Illustrated Reviews: Biochemistry; Lippincott Williams and Wilkins, 2010. 4142

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Organometallics

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(24) Romano, A. H.; Nickerson, W. J. J. Biol. Chem. 1954, 208, 409. (25) Lide, D. R. In CRC Handbook of Chemistry and Physics; CRC Press: New York, 2000. (26) Sweany, R. L.; Watzke, D. Organometallics 1997, 16, 1037. (27) Angelic, R. J.; Basolo, F. J. Am. Chem. Soc. 1962, 84, 2495. (28) Atwood, J. D.; Brown, T. L. J. Am. Chem. Soc. 1975, 97, 3380. (29) Hieber, W.; Gscheidmeier, M. Chem. Ber. 1966, 2312. (30) Reimann, R. H.; Singleton, E. J. Organomet. Chem. 1972, 44, C18. (31) Zingales, F.; Graziani, M.; Faraone, F.; Belluco, U. Inorg. Chim. Acta 1967, 1, 172. (32) Razskazovskii, Y.; Colson, A.-O.; Sevilla, M. D. J. Phys. Chem. 1995, 99, 7993. (33) Perkins, M. J. In Radical Chemistry; Ellis Horwood, 1994. (34) Busfield, W. K.; Heiland, K.; Jenkins, I. D. Tetrahedron Lett. 1995, 36, 1109. (35) Zhang, X.; Zhang, N.; Schuchmann, H.-P.; von Sonntag, C. J. Phys. Chem. 1994, 98, 6541. (36) Berkholz, D. S.; Faber, H. R.; Savvides, S. N.; Karplus, P. A. J. Mol. Biol. 2008, 382, 371. (37) Rietveld, P.; Arscott, L. D.; Berry, A.; Scrutton, N. S.; Deonarain, M. P.; Perham, R. N. Biochemistry 1994, 33, 13888. (38) Wong, K. K.; Vanoni, M. A.; Blanchard, J. S. Biochemistry 1988, 27, 7091.

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dx.doi.org/10.1021/om200461j |Organometallics 2011, 30, 4136–4143