1939年，H. Hunsdiecker報道了干燥的脂肪羧酸銀和溴反應(yīng)可以得到少一個碳原子的溴代烷烴。脂肪羧酸，α,β-不飽和羧酸和特定的芳基甲酸進(jìn)行脫羧鹵代得到少一個碳原子的鹵代烷烴的反應(yīng)被稱為Hunsdiecker反應(yīng)。

反應(yīng)特點

一、羧酸銀鹽由羧酸和氧化銀反應(yīng)制備；二、羧酸銀鹽在在四氯化碳中劇烈攪拌，加入一倍當(dāng)量的鹵素，加入鹵素的同時放出二氧化碳；三、為了得到較高的產(chǎn)率，銀鹽必須高純度并且嚴(yán)格無水，但由于銀鹽熱不穩(wěn)定，因此得到干燥的銀鹽比較困難；四、脂肪羧酸反應(yīng)最好，帶有吸電子基團(tuán)的芳香羧酸反應(yīng)效果也不錯；五、富電子的芳基羧酸在此反應(yīng)條件下可以發(fā)生芳基親電取代反應(yīng)；六、除了銀鹽，更穩(wěn)定的Tl(I)鹽和Hg(I)鹽也可以用于此反應(yīng)；七、此反應(yīng)條件下可以和鹵素反應(yīng)的基團(tuán)（烯基，炔基）不兼容此反應(yīng)；八、如果使用具有旋光活性的羧酸銀，則產(chǎn)物烷基鹵化物的旋光活性會明顯降低。

反應(yīng)改進(jìn)

由于制備羧酸銀鹽有很高的技術(shù)難度，此反應(yīng)有很多操作簡便的改進(jìn)法：一、如果在回流溫度下將酰氯溶液加入干燥的氧化銀/氯化四氯化碳/溴的懸浮液中，可以避免使用羧酸銀鹽，并且產(chǎn)率較高；二、易結(jié)晶的羧酸鉈(I)鹽用于此反應(yīng)可以提高產(chǎn)率，缺點是鉈鹽毒性較高；三、Cristol-Firth改進(jìn)法【】利用過量的HgO和一個當(dāng)量的鹵素一鍋飯反應(yīng)操作簡便；四、Suárez改進(jìn)法，羧酸和高價碘試劑（乙酸碘苯）在CCl4中反應(yīng)，可以明顯改善官能團(tuán)耐受度【J. Org. Chem.1986, 51, 402-404】；五、Kochi改進(jìn)法【】，四乙酸鉛和碘或鹵化鋰（LiCl或LiBr）可以直接得到鹵代烷烴；六、Barton改進(jìn)法，在鹵素供體試劑(e.g., BrCCl3, CHI3) 存在下加熱或光照分解硫代羥肟酸酯，此方法對大多數(shù)官能團(tuán)耐受；七、如果AIBN用于Barton改進(jìn)法，對于芳基羧酸（活化或非活化的）都可以高產(chǎn)率的脫羧

反應(yīng)機(jī)理

自由基機(jī)理，銀鹽先和鹵素反應(yīng)得到一個不穩(wěn)定的中間體（?；嘻u酸酯），然后脫羰得到鹵代烴。此反應(yīng)碳碳鍵發(fā)生均裂，按自由基機(jī)理進(jìn)行。

反應(yīng)實例

【Org. Synth.1988, Coll. Vol. 6, 179】

【J. Org. Chem.1990, 55, 4333-4337】

1-Bromo-2-(p-methoxyphenyl)ethene (2). To LiOAc (0.2 mmol) in MeCN:H2O (97:3, 4.5 mL) was added p-methoxycinnamic acid 1 (336 mg, 2 mmol). After 5 min stirring at 20 ℃, NBS (365 mg, 2.1 mmol) was added as a solid. The mixture was stirred for 10 min. Workup and chromatography (silica gel, hexane:EA 3:2) afforded 386 mg of 2 (91%).

【J. Org. Chem.1997, 62, 199】

【Tetrahedron Lett.1998, 39, 699-702】

【J. Am. Chem. Soc.2000, 122, 5666-5667】

【Tetrahedron2000, 56, 1369-1377】

【 J. Org. Chem., 2002, 67, 7861-7864】

【J. Org. Chem. 2004, 69, 8561-8563】

【Synthesis, 2005, 1319-1325】

【Tetrahedron Lett.2007, 48, 4347-4351】

【J. Am. Chem. Soc. 2012, 134, 4258-4263】

相關(guān)文獻(xiàn)

1. (a) Borodin, A. Ann. 1861, 119, 121-123. Aleksandr Porfirevi? Borodin (1833-1887) was born in St Petersburg, the illegitimate son of a prince. He prepared methyl bromide from silver acetate in 1861, but another eighty years elapsed before Heinz and Cl?re Hunsdiecker converted Borodin’s synthesis into a general method, the Hunsdiecker or Hunsdiecker-Borodin reaction. Borodin was also an accomplished

composer and is now best known for his musical masterpiece, opera Prince Igor. He kept a piano outside his laboratory. (b) Hunsdiecker, H.; Hunsdiecker, C. Ber. 1942, 75, 291-297. Cl?re Hunsdiecker was born in 1903 and educated in Cologne. She developed the bromination of silver carboxylate alongside her husband, Heinz.

2. Sheldon, R. A.; Kochi, J. K. Org. React. 1972, 19, 326-421. (Review).

3. Barton, D. H. R.; Crich, D.; Motherwell, W. B. Tetrahedron Lett. 1983, 24,4979-4982.

4. Crich, D. In Comprehensive Organic Synthesis; Trost, B. M.; Steven, V. L., Eds.; Pergamon, 1991, Vol. 7, pp 723-734. (Review).

5. Lampman, G. M.; Aumiller, J. C. Org. Synth. 1988, Coll. Vol. 6, 179.

6. Naskar, D.; Chowdhury, S.; Roy, S. Tetrahedron Lett. 1998, 39, 699-702.

7. Das, J. P.; Roy, S. J. Org. Chem. 2002, 67, 7861-7864.

8. Ye, C.; Shreeve, J. M. J. Org. Chem. 2004, 69, 8561-8563.

9. Li, J. J. Hunsdiecker Reaction. In Name Reactions for Functional Group Transformations; Li, J. J., Corey, E. J., Eds., Wiley: Hoboken, NJ, 2007, pp 623-629. (Review).

10. Bazin, M.-A.; El Kihel, L.; Lancelot, J.-C.; Rault, S. Tetrahedron Lett. 2007, 48, 43474351.

11. Wang, Z.; Zhu, L.; Yin, F.; Su, Z.; Li, Z.; Li, C. J. Am. Chem. Soc. 2012, 134, 4258-4263.

參考文獻(xiàn)

一、Strategic Applications of Named Reactions in OrganicSynthesis, László Kürti and Barbara Czakó, Hunsdiecker reaction，page 218-219.

二、Name Reactions （A Collection of Detailed Reaction Mechanisms）, Jie Jack Li, Hunsdiecker-Borodin reaction，page 327-328.

三、organic chemitry portal：Hunsdiecker反應(yīng)

四、Organic Syntheses Based On Name Reactions, 3RdEd, A. Hassner, Page 232.