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CuO hollow nanosphere-catalyzed cross-coupling of aryl iodides with thiols
Nanoscale Research Letters volume 8, Article number: 390 (2013)
New functionalized CuO hollow nanospheres on acetylene black (CuO/AB) and on charcoal (CuO/C) have been found to be effective catalysts for C-S bond formation under microwave irradiation. CuO catalysts showed high catalytic activity with a wide variety of substituents which include electron-rich and electron-poor aryl iodides with thiophenols by the addition of two equivalents of K2CO3 as base in the absence of ligands.
Sulfur-containing aromatic compounds, notably aryl sulfides and their derivatives, are prominent in fields such as biological, pharmaceutical, and materials fields. In particular, their use in synthesizing biologically and pharmaceutically important organosulfur compounds such as HIV protease inhibitors  (Viracept, Nelfinavir Mesylate, AG 1343), LFA-1/ICAM-1 antagonists , and arylthioindoles  (potent inhibitors of tubulin assembly) is still not fully understood by synthetic chemists. In general, molecules containing one or more carbon-sulfur bonds can be used as molecular precursors for the synthesis of new materials . However, compared to C-N and C-O bonds, the transition metal-catalyzed C(aryl)-S bond formation has not been well studied. This bond formation is thought to be partial because of the formation of an S-S coupled product and a concurrent deactivation of the metal catalyst due to the strong coordinative and adsorptive properties of sulfur, which can decrease catalytic activity . General methods for C-S cross-coupling involve the condensation of aryl halides with thiols and, usually, require temperatures greater than 200°C. These methods also require strongly basic, toxic, high-boiling, polar solvents, namely HMPA, quinolone, or N,N-dimethylacetamide. In order to circumvent these complications, a meticulous effort has been focused on the development of transition metal-catalyzed coupling of thiophenols with aryl halides. Previously, iron , nickel [7, 8], palladium [9, 10], cobalt , and copper-based [12–16] catalytic systems have been reported for this purpose. Even though significant improvements have been made, appropriate techniques are still needed for the synthesis of diaryl thioethers. To date, metal and metal oxide nanoparticles have often been used as metal catalysts because of their physical and chemical stability. In addition, the advantage of nanoparticles including large surface area and heterogeneous nature make them applicable to a broad range of scientific fields and functions such as the immobilization of biomolecules , catalysis of organic [18–23] and electrochemical reactions , use in electrochemical sensors and biosensors , enhancement of electron transfer , labeling of biomolecules , and synthesis of nanofluids , antibacterial materials , photocatalysts [25, 26], solar cells , and so on. Among the various available metal oxide nanoparticles, two copper oxides (Cu2O, CuO) have been studied for use in p-type semiconductor materials with narrow band gaps. This is because copper oxides are less expensive, recyclable, and non-toxic and have suitable optical and electronic properties [28–32]. Thus, as part of the effort to find new catalytic systems and better understand the role of transition metal nanoparticles in organic transformations, we report herein the use of CuO hollow nanoparticles as catalysts for efficient syntheses of diaryl thioethers. These CuO hollow nanoparticles have advantages in terms of large-scale synthesis and uniform shape compared to previous reported CuO nanoparticles [33, 34]. In recent times, microwave-irradiated organic reactions have become increasingly popular as valuable alternatives to the use of conductive heating for promoting chemical reactions. Besides, improved yields within short reaction time were observed. Microwave activation, as a non-conventional energy source, is becoming a very popular and valuable technique in organic synthesis, as evidenced by the increasing number of annual publications on this topic. In continuation of our previous reports , we discovered that microwave irradiation can even accelerate the Ullmann coupling of activated aryl iodides and thiophenols.
Reagents were purchased from Aldrich Chemical Co. (St. Louis, MO, USA) and Strem Chemical Co. (Bischheim, France) and used as received. Reaction products were analyzed by the literature values of known compounds. CuO, CuO/AB, and CuO/C were characterized by transmission electron microscopy (TEM) (Philips F20 Tecnai operated at 200 kV, KAIST, Amsterdam, the Netherlands). Samples were prepared by placing a few drops of the corresponding colloidal solution on carbon-coated copper grids (Ted Pellar, Inc., Redding, CA, USA). The X-ray diffractometer (XRD) patterns were recorded on a Rigaku D/MAX-RB (12 kW; Shibuya-ku, Japan) diffractometer. The copper loading amounts were measured by inductively coupled plasma atomic emission spectroscopy (ICP-AES). Elemental compositions of CuO/AB were obtained using energy-dispersive X-ray spectroscopy (EDS) (550i, IXRF Systems, Inc., Austin, TX, USA).
Preparation of Cu2O nanocubes
Poly(vinylpyrrolidone) (PVP, Aldrich, Mw 55,000; 5.3 g), dissolved in 45 mL of 1,5-pentanediol (PD, Aldrich, 96%), was heated to 240°C under inert conditions. Then, 4.0 mmol of Cu(acac)2 (Strem, 98%), dissolved in 15 mL of PD, was injected into the hot PVP solution at 240°C, and the mixture was stirred for 15 min at the same temperature. The resulting colloidal dispersion was cooled to room temperature, and the product was separated by adding 150 mL of acetone, with centrifugation at 8,000 rpm for 20 min. The precipitates were washed with ethanol several times and re-dispersed in 50 mL of ethanol.
Synthesis of CuO hollow nanostructures
An appropriate concentration of aqueous ammonia solution was added to 25 mL of the Cu2O cube dispersion in ethanol (16 mM with respect to the precursor concentration). The mixture was subjected to stirring at room temperature for 2 h. The volume and concentration of the aqueous ammonia solution used for each structure were 1.0 mL and 14.7 M, respectively, for hollow cubes; 2.0 mL and 7.36 M, respectively, for hollow spheres; and 6.0 mL and 2.45 M for urchin-like particles, respectively. For shape optimization of the hollow spheres, a 3.68-M aqueous ammonia solution was used. After the reaction, the products were collected by centrifugation at 6,000 rpm for 20 min.
Synthesis procedures of CuO/AB and CuO/C
The acetylene carbon black (STREM, 99.99%, 1.2 g) was mixed with 100 mL of the CuO hollow nanosphere dispersion in ethanol (17.0 mM), and the reaction mixture was sonicated for 1 h at room temperature. After 1 h, the product CuO/AB was washed with ethanol several times and vacuum dried at room temperature. For the synthesis of CuO/C, the mixture solution of charcoal (0.8 g) and 50.0 mL of CuO hollow nanosphere dispersion in ethanol (50.0 mM) was refluxed for 4 h. After 4 h, the black suspension was cooled to room temperature and precipitated by centrifugation. The product CuO/C was washed with ethanol thoroughly and dried in a vacuum oven at room temperature.
General procedure for cross-coupling of aryl halides with thiophenol
Into a 10-mL glass vial, 4.0 mg of CuO/AB and CuO/C, iodobenzene (0.11 mL, 1.0 mmol), thiophenol (0.11 mL, 1.1 mmol), and solvent (5.0 ml) were placed. The reaction mixture was irradiated with a microwave stove (MAS II, Sineo Microwave Chemistry Technology Co., Ltd., Shanghai, China) for 10 to 30 min. After reaction, the vial was cooled to RT. The solution was then filtered, concentrated under reduced pressure, and characterized by Gas chromatography–mass spectrometry (GC-MS) spectra. Yields were based on the amount of iodobenzene used in each reaction.
Results and discussion
The CuO hollow nanostructures were prepared by a controlled oxidation of Cu2O nanocubes using an aqueous ammonia solution according to a method in the literature . The Cu2O nanocubes (average edge size of 50 nm) were converted to CuO hollow nanospheres by addition of ammonia solution (2.0 mL, 3.7 M) into Cu2O colloidal solution by a dissolution-precipitation process. The TEM images in Figure 1a,b show monodisperse CuO hollow nanospheres that are composed of needle-like branches. The average size of these CuO hollow nanospheres was measured to be 103 ± 8 nm (Figure 1d). The CuO hollow nanospheres were analyzed using XRD analysis (Figure 1c). Two main peaks were present in the XRD patterns of the CuO hollow nanospheres that could be assigned to the reflections of the (002)/(11–1) and (111)/(200) planes in the CuO phase (JCPDS no. 48–1548).
Immobilization of CuO hollow nanospheres on acetylene black (CuO/AB) was performed by sonication for 1 h at room temperature. The TEM images in Figure 2a,c show well-dispersed CuO/AB and CuO/C, maintaining their original size and structure. ICP-AES confirmed the content of copper metal on the acetylene black. EDS spectrum in Figure 2d showed that hollow CuO nanoparticles were immobilized on acetylene black. The X-ray photoelectron spectroscopy data at the energy regions of the Cu bands confirm that the elements of the three different shapes are only Cu(II). The peaks at 933.8 and 953.7 eV correspond to Cu 2p3/2 and Cu 2p1/2 bands, and the other two signals, at 943.8 and 962.4 eV, are the shakeup satellites, which are characteristic of d9 Cu(II) compounds .
Ullmann reaction of aryl halides with thiols catalyzed by CuO hollow nanoparticles
Initially, the reaction of iodobenzene with thiophenol was chosen as a model reaction. Reaction mechanism about Ullmann coupling is already reported . Scheme 1 shows a proposed mechanism for synthesis of aryl thioethers. To optimize the reaction, several experiments were performed by varying solvent, reaction time, and reaction temperature and using either hollow nanospherical CuO, CuO/C, or CuO/AB as the catalyst. First, 5.0 mol% of hollow nanospherical CuO/C in DMF were used at a temperature of 120°C, and diphenyl thioether was obtained with 49% conversion (entry 1, Figure 3). CuO hollow nanoparticles were used as a catalyst to compare the catalytic activity with supported CuO catalysts and showed 75% conversion (entry 2, Figure 3). Quantity of catalyst was also checked to observe the catalytic activity of CuO/C catalyst. There was no difference in conversion between 2.5 and 5 mol% of the catalyst (entries 3 to 5, Figure 3). When the reaction time was increased to 20 min, 81% conversion was achieved under the same conditions but with slight deviation in selectivity (entry 5, Figure 3). Only charcoal catalyst showed less catalytic activity and selectivity (entry 6, Figure 3). We tried one reaction using commercially available CuO nanopowder as catalyst. CuO nanopowder exhibited less catalytic activity than CuO/C catalyst although there is no surfactant in CuO nanopowder (entries 5 and 7, Figure 3). Our CuO hollow nanostructure showed better catalytic activity because of a high surface area. Conversion of 66% was achieved with the use of two equivalent thiophenols (2.2 mmol), and the amount of diphenyl disulfide increased due to homocoupling reaction as expected (entry 8, Figure 3). Next, the catalytic activity of the hollow nanospherical CuO/AB was compared with that of the hollow nanospherical CuO/C catalyst at the same condition. The catalytic activities of both catalysts were almost equivalent, and 61% conversion was obtained (entry 9, Figure 3). Interestingly, when the solvent was changed to dimethyl sulfoxide (DMSO), diphenyl thioether was dominant under the same conditions (entry 10, Figure 3). At a temperature of 80°C and a reaction time of 10 min, >% conversion of diphenyl disulfide was achieved in the presence of MeCN (entry 11, Figure 3). There was no difference in the conversion between reaction temperatures of 180°C and 60°C (entries 12 and 13, Figure 3). When the reaction time was increased to 30 min, the conversion was slightly increased and the selectivity of diphenyl thioether was decreased (entry 14, Figure 3). We found that selectivity was dependent on several factors such as solvent used (entries 9 to 11, Figure 3), quantity of thiophenol (entries 8 and 9, Figure 3), reaction temperature (entries 12 to 14, Figure 3), and reaction time (entries 10 and 14, Figure 3).
The versatilities of our nanocatalyst were investigated by performing Ullmann coupling reactions of various substrates under optimized reaction conditions. The reactions of substrates with electron-rich and electron-poor groups on the iodobenzene resulted in different yields and selectivities of the cross-coupling products (Figure 4). When the electron-rich substrates were used, more than 95% selectivity for diphenyl disulfide was obtained due to a homocoupling reaction of thiophenol although only a low yield of product was obtained in this case (entries 1, 2, 4, and 5, Figure 4). On the contrary, only 79% conversion was obtained in the case of electron-poor substituents such as 1-iodo-4-nitro-benzene, and the selectivity for product (A) was increased to 66% (entry 3, Figure 4). Interestingly, the reaction of substrates with -NO2 group was found to have high selectivity on product (A) although it had a low conversion (entry 6, Figure 4). A regioselectivity test was performed using thiophenol and 1-bromo-4-benzene. 4-Bromo diphenyl sulfide (selectivity of 100%) was formed with 46% conversion.
In conclusion, CuO hollow nanospheres were synthesized by controlled oxidation of Cu2O nanocubes using aqueous ammonia solutions. Ullmann coupling reactions of aryl iodide with thiols were conducted to check the respective catalytic activities of CuO, CuO/AB, and CuO/C hollow nanosphere catalysts under microwave irradiation. Various diaryl thioethers were obtained from electron-deficient aryl iodides, while diaryl disulfide was produced from electron-rich aryl iodides. Transition metals loaded on acetylene black or charcoal have significant importance in the field of organic synthesis. Furthermore, it is noteworthy that these heterogeneous systems are characterized by high chemical atomic efficiency, which is advantageous in industrial catalysts.
CuO hollow nanospheres on acetylene black
CuO hollow nanospheres on charcoal
Energy-dispersive X-ray spectroscopy
Inductively coupled plasma atomic emission spectroscopy
Transmission electron microscopy
Kaldor SW, Kalish VJ, Davies JFII, Shetty BV, Fritz JE, Appelt K, Burgess JA, Campanale M, Chirgadze NY, Clawson DK, Dressman BA, Hatch SD, Khalil DA, Kosa MB, Lubbehusen PP, Muesing MA, Patick AK, Reich SH, Su KS, Tatlock JH: Viracept (nelfinavir mesylate, AG1343): a potent, orally bioavailable inhibitor of HIV-1 protease. J Med Chem 1997, 40: 3979–3985. 10.1021/jm9704098
Liu G, Huth JR, Olejniczak ET, Mendoza R, DeVries P, Leitza S, Reilly EB, Okasinski GF, Fesik SW, von Geldern TW: Novel p-arylthio cinnamides as antagonists of leukocyte function-associated antigen-1/intracellular adhesion molecule-1 interaction. 2. mechanism of inhibition and structure-based improvement of pharmaceutical properties. J Med Chem 2001, 44: 1202–1210. 10.1021/jm000503f
Martino GD, Edler MC, Regina GL, Coluccia A, Barbera MC, Barrow D, Nicholson RI, Chiosis G, Brancale A, Hamel E, Artico M, Silvestri R: New arylthioindoles: potent nhibitors of tubulin polymerization. 2. structure − activity relationships and molecular modeling studies. J Med Chem 2006, 49: 947–954. 10.1021/jm050809s
Wang Y, Chackalamannil S, Hu Z, Clader JW, Greenlee W, Billard W, Binch H, Crosby G, Ruperto V, Duffy RA, McQuade R, Lachowicz JE: Design and synthesis of piperidinyl piperidine analogues as potent and selective M2 muscarinic receptor antagonists. Bioorg Med Chem Lett 2000, 10: 2247–2250. 10.1016/S0960-894X(00)00457-1
Kondo T, Mitsudo TA: Metal-catalyzed carbon-sulfur bond formation. Chem Rev 2000, 100: 3205–3220. 10.1021/cr9902749
Correa A, Carril M, Bolm C: Iron-catalyzed S-arylation of thiols with aryl iodides. Angew Chem Int Ed 2008, 47: 2880–2883. 10.1002/anie.200705668
Zhang Y, Ngeow KN, Ying JY: The first N-heterocyclic carbene-based nickel catalyst for C-S coupling. Org Lett 2007, 9: 3495–3499. 10.1021/ol071248x
Jammi S, Barua P, Rout L, Saha P, Punniyamurthy T: Efficient ligand-free nickel-catalyzed C–S cross-coupling of thiols with aryl iodides. Tetrahedron Lett 2008, 49: 1484–1487. 10.1016/j.tetlet.2007.12.118
Fernandez-Rodriguez MA, Shen Q, Hartwig JF: Highly efficient and functional-group-tolerant catalysts for the falladium-catalyzed coupling of aryl chlorides with thiols. Chem Eur J 2006, 12: 7782–7796. 10.1002/chem.200600949
Fernandez-Rodriguez MA, Shen Q, Hartwig JF: A general and long-lived catalyst for the palladium-catalyzed coupling of aryl halides with thiols. J Am Chem Soc 2006, 128: 2180–2181. 10.1021/ja0580340
Wong YC, Jayanth TT, Cheng CH: Cobalt-catalyzed aryl-sulfur bond formation. Org Lett 2006, 8: 5613–5616. 10.1021/ol062344l
Lv X, Bao WA: β-keto ester as a novel, efficient, and versatile ligand for copper(I)-catalyzed C-N, C-O, and C-S coupling reactions. J Org Chem 2007, 72: 3863–3867. 10.1021/jo070443m
Carril M, SanMartin R, Dominguez E, Tellitu I: Simple and efficient recyclable catalytic system for performing copper-catalysed S-arylation reactions in the presence of water. Chem Eur J 2007, 13: 5100–5105. 10.1002/chem.200601737
Verma AK, Singh J, Chaudhary R: A general and efficient CuI/BtH catalyzed coupling of aryl halides with thiols. Tetrahedron Lett 2007, 48: 7199–7202. 10.1016/j.tetlet.2007.07.205
Rout L, Saha P, Jammi S, Punniyamurthy T: Efficient copper(I)-catalyzed C–S cross coupling of thiols with aryl halides in water. Eur J Org Chem 2008, 4: 640–643.
Sperotto E, van Klink GPM, de Vries JG, van Koten G: Ligand-free copper-catalyzed C-S coupling of aryl iodides and thiols. J Org Chem 2008, 73: 5625–5628. 10.1021/jo800491k
Luo X, Morrin A, Killard AJ, Smyth MR: Application of nanoparticles in electrochemical sensors and biosensors. Electroanalysis 2006, 18: 319–326. 10.1002/elan.200503415
Harsha Vardhan Reddy K, Prakash Reddy V, Shankar J, Madhav B, Anil Kumar BSP, Nageswar YVD: Copper oxide nanoparticles catalyzed synthesis of aryl sulfides via cascade reaction of aryl halides with thiourea. Tetrahedron Lett 2011, 52: 2679–2682. 10.1016/j.tetlet.2011.03.070
Satish G, Harsha Vardhan Reddy K, Ramesh K, Karnakar K, Nageswar YVD: Synthesis of 2-N-substituted benzothiazoles via domino condensation-hetero cyclization process, mediated by copper oxide nanoparticles under ligand-free conditions. Tetrahedron Lett 2012, 53: 2518–2521. 10.1016/j.tetlet.2012.03.012
Prakash Reddy V, Vijay Kumar A, Rama Rao K: Copper oxide nanoparticles catalyzed vinylation of imidazoles with vinyl halides under ligand-free conditions. Tetrahedron Lett 2010, 51: 3181–3185. 10.1016/j.tetlet.2010.04.022
Lin K-S, Pan C-Y, Chowdhury S, Tu M-T, Hong W-T, Yeh C-T: Hydrogen generation using a CuO/ZnO-ZrO2 nanocatalyst for autothermal reforming of methanol in a microchannel reactor. Molecules 2011, 16: 348–366. 10.3390/molecules16010348
Monopoli A, Nacci A, Calò V, Ciminale F, Cotugno P, Mangone A, Giannossa LC, Azzone P, Cioffi N: Palladium/zirconium oxide nanocomposite as a highly recyclable catalyst for c-c coupling reactions in water. Molecules 2010, 15: 4511–4525. 10.3390/molecules15074511
Woo H, Kang H, Kim A, Jang S, Park JC, Park S, Kim B-S, Song H, Park KH: Azide-alkyne huisgen [3 + 2] cycloaddition using CuO nanoparticles. Molecules 2012, 17: 13235–13252. 10.3390/molecules171113235
Chang M-H, Liu H-S, Tai CY: Preparation of copper oxide nanoparticles and its application in nanofluid. Powder Technol 2011, 207: 378–386. 10.1016/j.powtec.2010.11.022
Akhavan O, Ghaderi E: Cu and CuO nanoparticles immobilized by silica thin films as antibacterial materials and photocatalysts. Surf Coat Technol 2010, 205: 219–223. 10.1016/j.surfcoat.2010.06.036
Meng Z-D, Zhu L, Ye S, Sun Q, Ullah K, Cho K-Y, Oh W-C: Fullerene modification CdSe/TiO2 and modification of photocatalytic activity under visible light. Nanoscale Res Lett 2013, 8: 189–199. 10.1186/1556-276X-8-189
Yeo CI, Kim JB, Song YM, Lee YT: Antireflective silicon nanostructures with hydrophobicity by metal-assisted chemical etching for solar cell applications. Nanoscale Res Lett 2013, 8: 159–166. 10.1186/1556-276X-8-159
Ma D, Cai Q: N, N-dimethyl glycine-promoted Ullmann coupling reaction of phenols and aryl halides. Org Lett 2003, 5: 3799–3802. 10.1021/ol0350947
Altman RA, Shafir A, Choi A, Lichtor PA, Buchwald SL: An improved Cu-based catalyst system for the reactions of alcohols with aryl halides. J Org Chem 2008, 73: 284–286. 10.1021/jo702024p
Huang F, Quach TD, Batey RA: Copper-catalyzed nondecarboxylative cross coupling of alkenyltrifluoroborate salts with carboxylic acids or carboxylates: synthesis of enol esters. Org Lett 2013, 15: 3150–3153. 10.1021/ol4013712
Zhang Y, Yang X, Yao Q, Ma D: CuI/DMPAO-catalyzed N-arylation of acyclic secondary amines. Org Lett 2012, 14: 3056–3059. 10.1021/ol301135c
Kumar RV, Elgamiel R, Diamant Y, Gedanken A, Norwig J: Sonochemical preparation and characterization of nanocrystalline copper oxide embedded in poly(vinyl alcohol) and its effect on crystal growth of copper oxide. Langmuir 2001, 17: 1406–1410. 10.1021/la001331s
Gou L, Murphy CJ: Solution-phase synthesis of Cu2O nanocubes. Nano Lett 2003, 3: 231–234. 10.1021/nl0258776
Chang Y, Teo JJ, Zeng HC: Formation of colloidal CuO nanocrystallites and their spherical aggregation and reductive transformation to hollow Cu2O nanospheres. Langmuir 2005, 21: 1074–1079. 10.1021/la047671l
Kang H, Lee HJ, Park JC, Song H, Park KH: Solvent-free microwave promoted [3 + 2] cycloaddition of alkyne-azide in uniform CuO hollow nanospheres. Top Catal 2010, 53: 523–528. 10.1007/s11244-010-9481-0
Park JC, Kim J, Kwon H, Song H: Gram-scale synthesis of Cu2O nanocubes and subsequent oxidation to CuO hollow nanostructures for lithium-ion battery anode materials. Adv Mater 2009, 21: 803–807. 10.1002/adma.200800596
Wu CK, Yin M, O’Brien S, Koberstein JT: Quantitative analysis of copper oxide nanoparticle composition and structure by X-ray photoelectron spectroscopy. Chem Mater 2006, 18: 6054–6058. 10.1021/cm061596d
Sperotto E, van Klink GPM, van Koten G, de Vries JG: The mechanism of the modified Ullmann reaction. Dalton Trans 2010, 39: 10338–10351. 10.1039/c0dt00674b
This work was supported by a 2-year Research Grant of Pusan National University and National Research Foundation of Korea (NRF) through the Human Resource Training Project for Regional Innovation.
The authors declare that they have no competing interests.
The manuscript was written through the contributions of all authors (HW, MB, EH, JCP, HS, and KHP). All authors read and approved the final manuscript.
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Woo, H., Mohan, B., Heo, E. et al. CuO hollow nanosphere-catalyzed cross-coupling of aryl iodides with thiols. Nanoscale Res Lett 8, 390 (2013). https://doi.org/10.1186/1556-276X-8-390
- Copper oxide
- Acetylene black