(One Remarkable HyperLab Bee)
11-26-03 08:50
No 473295
(Rated as: excellent)
As requested in Post 472506 (not existing).
Synthetic Communications, 14(3), 215-218 (1984)
James D. Baleja
Department of Chemistry, University of Manitoba
Winnipeg, Manitoba, Canada R3T 2N2
Abstract: Aromatic diazonium salts react readily with methylthiocopper, CuSCH3, to produce arylmethylsulfides in good yield.
The study of high resolution NMR spectra of thioanisoles to indicate the conformational preferences of the methylthio moiety necessitated the preparation of a variety of molecules with appropriate substitutions on the ring. Therefore, a convenient and general method of synthesis was desired from a substrate available with the required substituents.
The methylthio group may be easily introduced onto an aromatic ring via the Sandmeyer reaction, in a method analogous to the widely applicable introduction of the thiocyanato group1. Table 1 lists the substrates used in this study and the yields2 of corresponding arylmethylsulfides. The Gatterman variant for aqueous alkali thiolates3 is inconvenient because methyl mercaptan is gaseous at room temperature.
Arylmethylsulfides have previously been synthesized from aromatic amines only under conditions of elevated temperature and with unstable reagents, or reagents prepared from extremely reactive compounds4. Thus explosions are possible and have been noted in the literature1. In contrast, methylthiocopper reacts with the diazonium salt of the aromatic amine to safely (to date) produce the corresponding arylmethylsulfide at a reduced temperature. The reagent is easily prepared by bubbling methyl mercaptan through an aqueous solution of copper sulfate and filtering the precipitate, washing well with methanol to remove co-produced dimethyl disulfide5.
Synthesis of Arylmethylsulfides from Arylamines
| No. | Substrate | Temperature | Yield(%) |
| 1 | Aniline | 4 | 55 |
| 2 | p-aminobenzonitrile | 4 | 45 |
| 3 | p-methylthioaniline | 4 | 75 |
| 4 | p-ethoxyaniline | 22 | 60 |
| 5 | m-methoxyaniline | 22 | 60 |
| 6 | o-methylthioaniline | 4 | 45 |
| 7 | 2,6-difluoroaniline | 4 | 25 |
| 8 | o-methoxyaniline | 4 | 45 |
| 9 | 2-bromo-4-fluoroaniline | 4 | 37 |
| 10 | 2,6-dibromo-4-fluoroaniline | 4 | 10 |
| 11 | 2-naphthylamine | 4 | 80 |
As indicated by the entries in the table, yields range between 10 and 80%, with low yields associated with electron-withdrawing substituents and with steric hindrance. Conversely, electron-donating substituents improve the yield.
In a typical procedure (entry 3), the aromatic amine is diazotised by the dropwise addition of 0.74 g NaNO2 in 3 mL of water at 4 °C to a chilled suspension of the aromatic amine hydrosulfate (0.01 mole p-methylthioaniline in 10 mL water containing 1.8 mL concentrated H2SO4)6. The diazonium salt solution is added dropwise to an aqueous slurry of CuSCH3 (7.74 g, 0.07 mole), also at 4 °C. Evolution of gas was apparent7. The resultant tan solution is allowed to warm to room temperature with occasional stirring for one-half hour. The reaction mixture is extracted three times with boiling benzene, filtered through sintered glass of medium porosity, and the combined extracts washed with equal volumes of 10% HCl, with 10% NaOH (three times), and with water until neutral. Drying over MgSO4, concentration at the rotary evaporator, and re-crystallization from methanol/water gave 1.28 g (75%) p-bis(methylthio)benzene; lustrous plates, m.p. 84-85 °C, corrected, (literature m.p. 85 °C8), 1H NMR (CCl4, TMS) δ7.10 (s, 4H), δ2.40 (s, 6H), 13C NMR (acetone-d6, proton decoupled) δ135.93 (2C), δ128.05 (4C), δ15.96 (2C), MS, M+=170.
Acknowledgements
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Notes and References
1. Hilgetag, G. and Martini, A., (editors), "Preparative Organic Chemistry", John Wiley & Sons, Inc., New York, 1972, pp. 269, 654.
2. Yields are for isolated, purified products.
3. Adams, R., Reifschneider, W., and Nair, M. D., Croatica Chem. Acta, 1957, 29, 277.
4. Oae, S., Shinhama, K., Kim, Y. H., Bull. Chem. Soc. Jpn., 1980, 53, 2023.
5. Peach, M. E., J. Nucl. Inorg. Chem., 1979, 41, 1390.
6. The use of HCl results in considerable production of the corresponding chloro compound.
7. Higher temperatures result in phenol formation.
8. Zincke, T. and Frohneberg, W., Ber. Deut. Chem. Ges., 1909, 42, 2721.
