Sixth International Electronic Conference on Synthetic Organic Chemistry (ECSOC-6), http://www.mdpi.org/ecsoc-6, 1-30 September 2002

[A003]
Charles University, Faculty of Pharmacy

Comparison of Influence of Conductor, Semiconductor and Insulator Copper Heterogeneous Catalysts on Bis(4-methoxyphenyl)disulphide Formation



Josef Jampilek1*, Martin Dolezal1, Bohumir Dvorak2

1Department of Pharmaceutical Chemistry and Drug Control, Charles University in Prague, Faculty of Pharmacy in Hradec Kralove, 500 05 Hradec Kralove, Czech Republic
tel.: +420-49-5067375, (272), fax: +420-49-5512423, e-mail: jamp@faf.cuni.cz, dolezalm@faf.cuni.cz

2Department of Organic Technology, Faculty of Chemical Technology, Institute of Chemical Technology, Prague, 166 28 Prague 6, Czech Republic
tel.: +420-2-24354216, fax: +420-2-24311968, e-mail: bohumir.dvorak@vscht.cz

* Author to whom correspondence should be addressed.



Abstract: Disulfides rise very easily by oxidation from their thiols. Using thiols for the synthesis is often a great problem, because disulfides may be significant by-products. A lot of various methods of formation of bis(4-methoxyphenyl)disulfide from 4-methoxybenzenethiol (as the main product or as a by-product) have been described. This article deals with the formation of this disulfide as a by-product formed on copper heterogeneous catalysts — conductor, semiconductors and insulators; respectively it deals with the conditions of eliminating this unwanted product. A lot of various methods and conditions have been tried and at some reaction also various types of copper heterogeneous catalysts (metal, copper(I), copper(II)) were used.

Keywords: Heterogeneous catalysis; Copper; Conductor; Semiconductor; Insulator; Dimerization




Introduction

Some problem arose at the alkylation of aromatic thiols substituted by substituent with positive mesomeric effect in the benzene ring and various copper heterogeneous catalysts at the same time. These compounds were oxidized respectively dehydrogenised to their disulfides. The reaction of thiols and thiolates with transition metals and their ions in higher oxidation groups are very quick reactions [1]. The reaction involves the intermediary of thiyl (RS·) radicals formed by one-electron oxidation of the thiolate anion. The autooxidation of thiol is catalysed by typical one-electron oxidants, e.g. Cu conductor and semiconductors [2]. These catalysts are usually employed to enhance the rate of oxidation. A number of studies of the interactions of metal compounds with thiols have been carried out [3—7]. In comparison to this effect of copper insulator catalysts is not only in generating thiyl radicals, but in generating cations too. Thiyl radical or cations react then with thiols or thiolates to their disulphides.

Most catalytic reactions belong to either of the two classes of reactions [8]. Oxidation—reduction (redox) reactions include hydrogenation, dehydrogenation, selective or complete oxidation. These reactions involve neutral radical-type intermediates bonded by homopolar bonds to the catalyst. They are catalyzed by metals, semiconductors. The solids among these catalysts represent redox systems and have common characteristics explainable by the presence of highly mobile electrons.

Acid—base reactions comprise various substitution, addition, elimination, and molecular rearrangement reactions exemplified by alkylation, isomerization. These reactions involve charged ionic intermediates and are catalyzed by acidic or basic solids as well as by soluble Broensted or Lewis acids and bases. Insulator catalysts have needed polar solvents or trace amount of water [9].

The metal copper (conductor) and its copper semiconductors (oxides, halides, sulphides) show high oxidative respectively dehydrogenative activity and their mechanism of effect is radical. The metallic character of the elements is closely connected with electronegativity. The catalytic activity of metals for redox-type reactions is a function of their chemisorption properties. The catalytic activity of certain metal oxides depends on their chemisorption capability, semiconductivity, and on the variable valence of their metal ions. Thus, semiconductive Cu catalysts show oxidation and hydrogenation—dehydrogenation activities. Especially copper semiconductors with copper(II) have been used in organic technology for oxidation, oxychloration and as mild dehydrogenative agents. They have been used e.g. for the production of methanol, butadiene, acrolein, methacrolein, acetic anhydride, vinyl acetate, dichloroethane, vinyl chloride [10].

Metal sulfides have semiconducting and acidic properties. Therefore, they have applications in both redox and acid-catalyzed reactions [11].

Cu(I),(II) halides have semiconducting properties too. Copper chlorides are the most utilization especially for oxychloration and for deacon reaction. The addition of chlorides of the rare-earth and alkaline-earth metals (potassium chloride) to the CuCl2 catalyst reduces volatility of CuCl2 and prevents formation of inactive polymeric CuCl2 chains [12].

The sulfates of copper act as unprotonated acids and cause double-bond isomerization [13] and alkylation. The applications of phosphates catalysts are in typical acid-catalyzed reactions and also in oxidation, aromatization, and dehydrogenation [14].

All these compounds are used for synthesis of unsymmetrical sulphides (Williamson synthesis); formed by the alkylation of metal salt of an aryl thiol with nonreactive aryl halides (without a substituent with negative mesomeric effect in the aromatical ring). 4-Methoxybenzenethiol was chosen as a model substance for easy oxidability resp. for its easy dehydrogenation. On this substrate the margin of ability of copper heterogeneous catalysts is tested to oxidate resp. dehydrogenate aromatic thiols with the substituent in position 4 of the aromatic core showing positive mesomeric effect on respective disulfides and thus to eliminate them from the main reaction.

In the below mentioned works besides disulfide different quantities of the other oxidation products appeared (sulfonic acids, sulfone). On the other hand the reactions carried out on copper heterogeneous catalysts always lead to disulfide as the only product of oxidation respectively dehydrogenation.

4-Methoxybenzenethiol (1) was oxidated to its bis(4-methoxyphenyl)disulfide (2) see Scheme 1. This product formed as many as 70 % of the yield by means of some methods.

Scheme 1: Bis(4-methoxyphenyl)disulfide (2) formation through copper heterogeneous catalysts.


Various conditions of generating its bis(4-methoxyphenyl)disulfide (2) using copper heterogeneous catalysts are described in this paper, but this could be prepared in various synthetic pathways with various yielding; bis(4-methoxyphenyl)disulfide could be generated as the main product by e.g. hydrogen peroxide [15] (98 %), sodium hypochlorite [16] (92 %), sodium iodate [17] (98 %), DMSO [18,19] (98 %), sodium iodide [20] (97 %), copper(II) nitrate [21] (99 %), aq. potassium hydroxide, potassium ferricyanide [22] (93 %), sodium perborate tetrahydrate [23,24] (78 %), chromium trioxide [25] (76 %), and as a by-product using e.g.: chlorotrimethylsilane [26] (80 %), 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2,2,2] octane bis(tetrafluoroborate) [27] (58 %), toluene-4-sulphonyl iodide [28] (37 %), meso-tetraphenylporphyrin [29] (13 %).


Results and Discussion

Our experiment was realized in different solvents with atmospheric oxygen, under the atmosphere of nitrogen or argon. Different types of copper heterogeneous catalysts with the copper component in different oxidizing state were tested. The catalysts were applied in powder form, the smooth dispersion of the effective component was prepared by means of coagulative or impregnating procedures.

In fact metal wire copper Cua and powder Cub were used and metal copper Cuc (on inert support), which is the actived catalyst CHEROX 46-11. Then powder copper(I)oxide Cu2Od, powder copper(II)oxide CuOe and CuOf (CHEROX 46-00 oxide on inert support) were used. All the remaining copper heterogeneous catalysts are powders: Cu2Sg, CuSh, CuCli, CuCl2j, CuIk, CuOCll (according to IUPAC or GMELIN Cu(II)trihyroxichloride is CuCl2 · 3Cu(OH)2), CuSO4m, Cu(PO4)2 · 2H2On and CuCO3 · Cu(OH)2o.

All the reactions are showed in four tables. Catalysts in tables are divided according to copper oxidizing state of the copper component (Table 1, 2, 3) and insulator catalysts are present in the Table 4.

Altogether 39 reactions were carried out on copper heterogeneous catalysts with the copper component in different oxidation state with different electronic parameters and various types of ligands.

On the basis of the experiments carried out it is evident that the activity of copper in the form of metal even in by relatively low temperatures (ethanol 78 °C). Cu(II) in accordance with all assumptions has not appeared to be the most efficient dehydrogenative catalyst, but Cu(0) is the most effective catalyst. Various types of ligands have great influence on oxidative respectively dehydrogenative properties of the catalysts. The most efficient dehydrogenative catalysts were halides, then oxides and the least activity have sulphides. Great disappointment was a proportionally high oxidizing respectively dehydrogenative activity of insulator catalysts, although these catalysts are used due to their properties for alkylation reactions mainly. Cu(PO4)2 · 2H2O has the least oxidizing activity from the used insulator copper heterogeneous catalysts. Cu(I) has the least dehydrogenative activity. Using the same type of catalyst the yield of disulfide is higher in polar solvents and in the presence of water, which is important for insulator catalysts function. If the precursor is used in the form of salt (sodium or potassium) the yields of disulfide are higher. The reaction process is facilitated by atmospheric oxygen (parallel oxidation reaction).


Table 1. Conditions and yields of performed reactions with metal copper Cu(0).
Method Conditions Atmosphere Yields %
1a Na, ethanol, Cua oxygen 51
1b Na, ethanol, Cua nitrogen 43
2a KOH(aq), Cua oxygen 69
2b KOH(aq), Cua nitrogen 63
3a K2CO3, Et-Me ketone, Cub oxygen 56
3b K2CO3, Et-Me ketone, Cub nitrogen 49
3c K2CO3, Bu-Me ketone, Cub oxygen 72
3d K2CO3, Bu-Me ketone, Cub nitrogen 65
4a Bu-Me ketone, Cub nitrogen 49
3e K2CO3, Bu-Me ketone, Cuc argon 50
4b Bu-Me ketone, Cuc nitrogen 32
4c Bu-Me ketone, Cuc argon 23
[a] is wire, [b] is powder 97% purity, [c] metal on "silicate" support


Table 2. Conditions and yields of performed reactions with Cu(I) semiconductors.
Method Conditions Atmosphere Yields %
3f K2CO3, Bu-Me ketone, Cu2Od argon 15
4d Bu-Me ketone, Cu2Od argon 9
5a K2CO3, DMF, Cu2Od argon 5
6a NaH, DMF, Cu2Od argon 3
7a xylene, Cu2Od argon 1
6b NaH, DMF, Cu2Sg argon 2
7b xylene, Cu2Sg argon 0.5
6c NaH, DMF, KCl, CuCli argon 23
7c xylene, KCl, CuCli argon 19
6d NaH, DMF, CuIk argon 12
7d xylene, CuIk argon 7
[d, g, i, k] catalysts are powder 99 % purity


Table 3. Conditions and yields of performed reactions with Cu(II) semiconductors.
Method Conditions Atmosphere Yields %
3g K2CO3, Bu-Me ketone, CuOe argon 32
4e Bu-Me ketone, CuOe argon 27
5b K2CO3, DMF, CuOe argon 25
7e xylene, CuOe argon 22
6e NaH, DMF, CuOf argon 31
7f xylene, CuOf argon 28
6f NaH, DMF, CuSh argon 23
7g xylene, CuSh argon 19
6g NaH, DMF, CuOCll argon 34
7h xylene, CuOCll argon 30
6h NaH, DMF, KCl, CuCl2j argon 43
7i xylene, KCl, CuCl2j argon 39
[e, h, j] catalysts are powder 97% purity, [f] is on "silicate" support and [l] is powder 50 % purity


Table 4. Conditions and yields of performed reactions with Cu(II) insulators.
Method Conditions Atmosphere Yields %
5c K2CO3, DMF, CuSO4m argon 41
6i NaH, DMF, CuSO4m argon 36
5d K2CO3, DMF, Cu(PO4)2 · 2H2On argon 27
5e K2CO3, DMF, CuCO3 · Cu(OH)2o argon 42
[m] is powder 99 % purity, [n] is powder 97 % purity, [o] is not mentioned


Conclusions

The carried out experiments proved that the lowest percentage of the formation of disulfide from thiophenols with the substituent in position 4 of the aromatic ring is achieved when using copper(I)sulphide, oxide and iodide as heterogeneous catalysts. Inert atmosphere and using anhydrous dipolar aprotic solvents (DMF) or nonpolar solvents (xylene) help the reduction the yield of the disulphide.


Experimetal

All organic solvents used for the synthesis were of analytical grade. The solvents were dried and freshly distilled under argon atmosphere. Flash chromatography was realized on Silica gel Kieselgel 60 by Merck. TLC was performed on Silufol UV 254 plates (Kavalier, Votice). Silica gel plates, besides detection under UV 254, were visualized in addition to the solution of bromothymol blue in NAOH (proof of thiol, sulphide, disulphide). Melting points were measured on Kofler block BOËTIUS PHMK 05 (VEB KOMBINAT NAGEMA, VEB Wagetechnik RAPIDO, Radebeul, Germany). Elementary analysis was carried out on Automatic Microanalysers EA1110CE (Fisons Instruments S.p.A., Milano). Infrared spectra were measured in KBr pellets on IR-Spectrometer Nicolet Impact 400. 1H and 13C NMR Spectra were recorded on Varian Mercury — Vx BB 300 (299.95 MHz - 1H and 75.43 MHz - 13C) Bruker Comp. (Karlsruhe, Germany). Chemical shifts reported are given relative to internal Si(CH3)4.

Copper catalyst Cua — wire copper (ThermoQuest Italia S.p.A., cod 338 35310) and Cub — powder 99% purity (Sigma-Aldrich, cod 29,258-3) were used and metal copper Cuc is an activated catalyst CHEROX 46-11, the precursor of this catalyst is a product of CHEMOPETROL a. s. Litvínov. Suspension activated powder catalyst in an organic solvent was prepared. The catalyst is formed, metallic copper being finely dispersed on silicate support. CHEROX 46-11 was activated in organic solvent in autoclave under hydrogen atmosphere under the temperature of 180 °C and pressure 5 MPa. Cu2Od — powder 97% purity (Sigma-Aldrich, cod 20,882-5) and CuOe 98% purity (Sigma-Aldrich, cod 20,884-1) were used. CuOf is the product of CHEMOPETROL a. s. Litvínov CHEROX 46-00 (catalyst contents 40 % CuO on "silicate" support: SiO2, MgO, CaCO3). CuOCll (CuCl2 · 3Cu(OH)2) powder 50% purity is the product of SPOLANA a. s. Neratovice KUPRIKOL 50. Cu(PO4)2 · 2H2On powder 97 % purity is the product of Riedel-deHaën, cod 04252. The mixture of CuCO3 · Cu(OH)2o is the product of Sigma-Aldrich, cod 20,789-6. Purity is not mentioned. All the rest copper heterogeneous catalysts are powder 99% purity from Sigma-Aldrich: Cu2Sg (cod 51,065-3), CuSh (cod 34,246-7), Cu2Cl2i (cod 22,433-2), CuCl2j (cod 45,166-5), Cu2I2k (cod 21,555-4), anhydrous CuSO4m (cod 45,167-7).


Bis(4-methoxyphenyl)disulfide (2)

Method 1: Sodium (0.23 g, 10.0 mmol) was dissolved in dry ethanol (20 mL) then 4-methoxybenzenethiol (1.0 g, 8.0 mmol) was dissolved there and Cua (3.0 g) was added and the reaction mixture was stirred and refluxed for 3 h according to the open air (1a) method or under nitrogen (1b). Then the reaction mixture was filtered while hot and the filtrate evaporated in vacuo.
Method 2: Potassium hydroxide (1.4 g, 25 mmol) was dissolved in H2O (12 mL), 4-methoxybenzenethiol (1.0 g, 8.0 mmol) and Cua (3.0 g) were added and the reaction mixture was stirred and refluxed for 3 h according to the open air (2a) method or under nitrogen (2b). Then the reaction mixture was extracted with EtOEt and the combined extracts were dried over MgSO4 and evaporated in vacuo.
Method 3: K2CO3 (0.7 g, 5.0 mmol) was suspended in freshly distilled Et-Me ketone, respectively in Bu-Me ketone (20 mL) and 4-methoxybenzenethiol (1.0 g, 8.0 mmol) and Cub (1.0 g) for 3a-d; Cuc (0.2 g) for 3e; Cu2Od (1.0 g) for 3f; CuOe (1.0 g) for 3g were added. The reaction mixture was stirred and refluxed for 1 h according to the open air (3a, 3c) method or under nitrogen (3b, 3d) or under argon (3e, 3f, 3g). Then the reaction mixture was filtered while hot and the filtrate evaporated in vacuo.
Method 4: 4-Methoxybenzenethiol (1.0 g, 8.0 mmol) was dissolved in freshly distilled dry Bu-Me ketone (20 mL) and copper catalyst was added; method 4a: Cub (1.0 g); method 4b, 4c: Cuc (0.2 g); method 4d Cu2Od (1.0 g); method 4e CuOe (1.0 g) were added. The reaction mixture was stirred and refluxed for 1 h under nitrogen (4a,b) or argon (4c-e). Then the reaction mixture was filtered while hot and the filtrate evaporated in vacuo.
Method 5: K2CO3 (0.7 g, 5.0 mmol) was suspended in freshly distilled DMF (20 mL), 4-methoxybenzenethiol (1.0 g, 8.0 mmol) was dissolved there and Cu2Od (1.0 g) for 5a; CuOe (1.0 g) for 5b; CuSO4m (2.5 g) for 5c; Cu(PO4)2 · 2H2On (3.0 g) for 5d; CuCO3 · Cu(OH)2o (2.5 g) for 5e was added. The reaction mixture was stirred and refluxed for 1 h under argon. Then the reaction mixture was filtered while hot and the filtrate evaporated in vacuo.
Method 6: NaH 60% suspension in paraffin oil (0.2 g, 9.0 mmol) was suspended in freshly distilled dry DMF (20 mL), 4-methoxybenzenethiol (1.0 g, 8.0 mmol) was dissolved there and Cu2Od (1.0 g) for 6a; Cu2Sg (1.0 g) for 6b; CuCli (1.0 g) and KCl (0.1 g) for 6c; CuIk (1.0 g) for 6d; CuOf (0.2 g) for 6e; CuSh (1.0 g) for 6f; CuOCll (2.5 g) for 6g; CuCl2j (1.0 g) and KCl (0.1 g) for 6h; CuSO4m (2.5 g) for 6i was added. The reaction mixture was stirred and refluxed for 1 h under argon. Then the reaction mixture was filtered while hot and the filtrate evaporated in vacuo.
Method 7: 4-Methoxybenzenethiol (1.0 g, 8.0 mmol) was dissolved in freshly distilled dry xylene (20 mL) and Cu2Od (1.0 g) for 7a; Cu2Sg (1.0 g) for 7b; CuCli (1.0 g) and KCl (0.1 g) for 7c; CuIk (1.0 g) for 7d; CuOe (1.0 g) for 7e; CuOf (0.2 g) for 7f; CuSh (1.0 g) for 7g; CuOCll (2.5 g) for 7h; CuCl2j (1.0 g) and KCl (0.1 g) for 7i was added. The reaction mixture was stirred and refluxed for 1 h under argon. Then the reaction mixture was filtered while hot and the filtrate evaporated in vacuo.

Flash chromatography on silica gel provided bis(4-methoxyphenyl)disulfide as lightly yellow solid compound. Yields are described in Tables 1—4, m. p. = 39.0—39.5 °C, petroleum ether-diethylether (φr = 3 : 1), Rf = 0.49 (disulphide), 0.88 (thiol). For C14H14S2O2 (Mr = 278.22) wi (calc.): 60.40 % C, 5.07 % H, 23.03 % S; wi (found): 60.46 % C, 5.09 % H, 22.93 % S. IR spectrum (KBr), /cm: 1249 (C-O), 1590 (Ph), 2835 (O-CH3), 2956 (CH3). 1H NMR (300 MHz, DMSO), δ: 7.42-7.38 (m AA'BB', 4H CHarom.), 6.96-6.94 (m AA'BB', 4H CHarom.), 3.76 (s, 3H CH3). 13C NMR (75 MHz, DMSO), δ: 159.92, 132.31, 127.14, 115.23, 55.53.


Acknowledgements. This work was supported by the Research project LN00B125 of the Czech Ministry of Education. We thank Mrs. D. Karlickova for elementary analysis, Mrs. J. Zizkova for IR spectrum, Mr. T. Vojtisek for his skillful technical assistance and Doc. PharmDr. J. Kunes, CSc. for the service of NMR spectrometer.


References

  1. R. Sheldon, K. Kochi, Metal Catalyzed Oxidations of Organic Compounds, Academic Press, New York, 1981, p. 392—397.
  2. G. Capozzi, G. Modena, in The Chemistry of the Thiol Group, Part 2 (Eds.: S. Patai), Wiley, New York, 1978, p. 785.
  3. T. Nakaya, H. Arabori, M. Imobo, Bul. Chem. Soc. Japan 1970, 43, 1888.
  4. T. J. Wallace, J. Org. Chem. 1966, 31, 3071.
  5. C. F. Cullis, D. L. Trimm, Discuss. Faraday Soc. 1968, 46, 144.
  6. C. J. Swan, D. L. Trimm, Adv. Chem. Series 1968, 76, 182.
  7. J. D. Hopton, C. J. Swan, D. L. Trimm, Adv. Chem. Series 1968, 75, 216.
  8. J. E. Germain, Catalytic Conversion of Hydrocarbons, Academic Press, New York, 1969, pp. 81, 187, 191.
  9. In Kirk-Othmer encyclopedia of chemical technology, 3th edition, Vol. 5, Wiley, New York, 1984, pp. 16—61.
10. R. S. Mann, D. J. Rouleau, Selective Oxidation Processes, Proceedings of the 148th Meeting of the American Chemical Society, Chicago, Sept. 3—4, 1964, p. 40. American Chemical Society, Washington, D.C. 1965.
11. O. Weisser, S. Landa, Sulfide Catalysts, Their Properties and Applications, Pergamon Press, Oxford-New York, Vieweg, Braunschweig, 1973.
12. R. L. Dotson, J. Catal. 1974, 33, 210.
13. D. A. Dowden, C. R. Schnell, G. T. Walker, Proc. Int. Congr. Catal., 4th edition, Vol. 1, Dept. Chemical Engineering, Rice Univ., Houston, Tex., 1968, p. 1120.
14. J. B. Moffat, Catal. Rev. Sci. Eng. 1978, 18, 199.
15. V. Kesavan, D. Bonnet-Delpon, J. P. Begue, Synthesis 2000, 2, 223.
16. M. Khurana-Jitender, S. Singh, A. Sehgal, A., Indian J. Chem. Sect. B 1997, 36, 819.
17. M. Hirano, S. Yakatabe, K. Ando, T. Morimoto, J. Chem. Res. Synop. 1998,12, 816.
18. M. Hirano, S. Yakatabe, H. Monobe, T. Morimoto, J. Chem. Res. Synop. 1998, 8, 472.
19. S. Krihnamurthy, D. Aimino, J. Org. Chem. 1989, 54, 4458.
20. N. Iranpoor, B. Zeynizadeh, Synthesis 1999, 1, 49.
21. H. Firouzabadi, N. Iranpoor, M. A. Zolfigol, Synth. Commun. 1998, 28, 1179.
22. R. C. Hartley, I. C. Richards, S. Warren, J. Chem. Soc. Perkin Trans. 1 1996, 4, 359.
23. P. W. N. Christian, S. E. Gibson, R. Gil, P. C. V. Jones, C. F. Marcos, Recl. Trav. Chim. Pays-Bas 1995, 114, 4.
24. A. McKillop, D. Koyuncu, A. Krief, W. Dumont, P. Renier, M. Trabelsi, Tetrahedron Lett. 1990, 31, 35.
25. M. Juaristi, J. M. Aizpurua, B. Lecea, C. Palomo, Can. J. Chem. 1984, 62, 2941.
26. S. Oae, H. Togo, T. Numata, K. Fujimori, Chem. Lett. 1980, 1193.
27. M. Zupan, J. Iskra, S. Stavber, Bull. Chem. Soc. Jpn. 1995, 68, 1655.
28. S. Jongsma, J. Simon, J. Cornelisse, Tetrahedron Lett. 1981, 22, 2919.
29. G. Palumbo, R. Caputo, Synthesis 1981, 11, 888.