Leuckart苯硫酚合成反应

苯胺或相应的芳基重氮盐与烷基黄原酸钾反应得到芳基黄原酸酯和二芳基硫代碳酸酯，接着碱性条件下水解得到苯硫酚的反应被称为Leuckart苯硫酚合成反应。此反应由Leuckart在1890年首先报道。

反应机理

反应实例

m-Bromoaniline ( 43 g, 0.25 mol) was diazotized at 5◦C with 49 mL conc. HCl and 17.2 g NaNO2 (0.25 mol) in 110 mL water. The solution of the diazonium salt was added over a1.5-h period to a solution of 40 g potassium ethyl xanthate (0.25 mol) and 33.0 g Na2CO3(0.3 mol) in 250 mL water at 70◦C. The mixture was maintained at this temperature for anadditional hour, the resulting oil was separated, the aqueous phase was extracted twice withether, and the ether layers were combined with the oil. The ether was removed on a steambath in a stream of nitrogen, and the residual oil was added to a solution of 40 g NaOH in250 mL MeOH and 40 mL water. The mixture was refluxed for 2 h under nitrogen, dilutedwith 4 L water, and acidifified with hydrochloric acid. The resulting oil was separated, theaqueous phase was washed with methylene chloride, and the latter was combined withthe oil and dried over anhydrous Na2SO4. Distillation at 100–104◦C (10 mmHg) yielded 19.1 g m-bromothiophenol, in a yield of 40%. The m-bromothiophenol was redistilled at123–124◦C (40 mmHg) for further purifification.

【 J. Am. Chem. Soc., 1953, 75, 6019】

p-Aminophenol (110 g, 1.0 mol) was mixed with excess of 10% HCl (2.25 mol). Thesolution was cooled <15◦C and diazotized by the gradual addition of 70 g NaNO2 (1.0 mol)while the temperature was maintained between 1.5◦ and 20◦C by means of ice. The diazosolution was then run slowly beneath the surface of a hot solution of 224 g potassium ethylxanthate (1.4 mol) in 650 g water, and the reaction mixture was stirred vigorously andkept at 70 –75◦C to ensure complete decomposition of the intermediate diazo combination.When all the diazo solution was in, the temperature was raised to 90◦C and maintained for30 min. The xanthate ester was then decomposed by adding 160 g solid NaOH (4 mol) andreflfluxing for several hours, the mixture was then strongly acidifified with an excess of 50%H2SO4 and further reflfluxed in the presence of zinc and benzene to reduce any disulfifide thatmay have been formed. The crude thiohydroquinone was separated as an oil, washed withdilute hydrochloric acid and water, and distilled in vacuo to afford 61.0 g thiohydroquinoneas a clear colorless liquid, in a yield of 48.4%, b.p. 133–137◦C at 11.0 mmHg.

【J. Am. Chem. Soc., 1933, 55, 1224】

In a 1-l. flask, equipped with a mechanical stirrer and thermometer for reading low temperatures, and immersed in an ice bath, are placed 150 ml. of concentrated hydrochloric acid (sp. gr. 1.18) and 150 g. of crushed ice. The stirrer is started, and 80 g. (0.75 mole) of m-toluidine (b.p. 92–93°/15 mm.) is slowly added. The mixture is cooled to 0°, and a cold solution of 55 g. (0.8 mole) of sodium nitrite in 125 ml. of water is slowly added, the temperature being kept below 4°.

In a 2-l. flask equipped with a thermometer, dropping funnel, and stirrer is placed a solution of 140 g. of potassium ethyl xanthate (Note 1) in 180 ml. of water. This mixture is warmed to 40–45° and kept in that range during the slow addition of the cold diazonium solution (Note 2); about 2 hours is required (Note 3). After an additional 30 minutes at this temperature to ensure complete decomposition of the intermediate compound, the red, oily m-tolyl ethyl xanthateis separated and the aqueous layer is extracted twice, using 100-ml. portions of ether. The combined oil and extracts are washed once with 100 ml. of 10% sodium hydroxide solution (Note 4) and then with several portions of water until the washings are neutral to litmus. The ether solution is dried over 25 g. of anhydrous calcium chloride, and the etheris removed by distillation. The crude residual m-tolyl ethyl xanthate is dissolved in 500 ml. of 95% ethanol, the solution brought to boiling, and the source of heat removed. To this hot solution is added slowly 175 g. of potassium hydroxidepellets so that the solution keeps boiling, and the mixture is refluxed until a sample is completely soluble in water (about 8 hours). Approximately 400 ml. of ethanol is then removed by distillation on a steam bath, and the residue is taken up in the minimum of water (about 500 ml.). The aqueous solution is extracted with three 100-ml. portions of ether, the extract being discarded. The aqueous solution is now made strongly acid to Congo red paper, using 6 Nsulfuric acid (Note 5) (625–650 ml.). The acidified solution is placed in a 3-l. flask, 2 g. of zinc dust is added, and the m-thiocresol is distilled with steam. The lower layer of the m-thiocresol is separated; the aqueous layer is extracted with three 100-ml. portions of ether, the extracts being added to the oil. After drying with 50 g. of Drierite, the ether is removed by distillation, and the oily residue is distilled under reduced pressure. The yield of colorless m-thiocresol, b.p. 90–93°/25 mm., is 59–69 g. (63–75%) (Note 6) and (Note 7). It is best preserved in sealed glass bottles because of its disagreeable odor.

【Org. Synth. 1947, 27, 81；DOI: 10.15227/orgsyn.027.0081】

相关文献

1. Leuckart, R., J. Prakt. Chem., 1890, 41, 179.

2. Cox, J. R.; Gladys, C. L.; Field, L. and Pearson, D. E., J. Org. Chem., 1960, 25, 1083.

3. Biamonte, M. A.; Shi, J. D.; Hurst, D.; Hong, K.; Boehm, M. F. and Kasibhatla, S. R., J. Org.Chem., 2005, 70, 717.

4. Holzle, K., ¨ Helv. Chim. Acta, 1946, 29, 1883.

5. Bordwell, F. G. and Andersen, H. M., J. Am. Chem. Soc., 1953, 75, 6019.

6. Miller, E. and Read, R. R., J. Am. Chem. Soc., 1933, 55, 1224.

7. Fukushima DK., Org Synth., 1947, 27, 81

8. Tarbel DS., J Am Chem Soc., 1952, 74, 48

9. Zard SZ., Tet Lett., 2005, 46, 971

参考资料
一、Comprehensive Organic Name Reactions and Reagents, by Zerong Wang，P1743-1745.

二、Organic Syntheses Based On Name Reactions, 3RdEd, A. Hassner, Page 287-288.