Burgess 試劑，即N-(三乙基銨磺酰)氨基甲酸甲酯，是一個(gè)氨基甲酸酯類的內(nèi)鹽，用作有機(jī)化學(xué)中的脫水劑。它可溶于大多數(shù)有機(jī)溶劑中，CAS號(hào)為29684-56-8。黃白色晶體，Burgess試劑很容易氧化，同時(shí)對(duì)濕氣也非常敏感，新鮮制備后應(yīng)立即使用。上世紀(jì)70年代，E.M. Burgess等人發(fā)現(xiàn)利用此內(nèi)鹽可以將仲醇和叔醇脫水得到相應(yīng)的烯烴，此內(nèi)鹽被稱為Burgess試劑。是一個(gè)高效的脫水試劑，能夠用于從甲酰胺、硝基烷烴化合物到異腈[J. Chem.Soc., Perkin Trans. 1,1998, 1015]、腈[Tetrahedron Lett.,1988, 29,21552]和氧化腈化合物[Tetrahedron Lett.,1997, 38, 1547]的制備反應(yīng)。

Burgess脫水試劑是非常有效的由仲醇和叔醇脫水制備烯烴的試劑，相對(duì)于其他脫水反應(yīng)，此反應(yīng)溫和，有選擇性，反應(yīng)在中性條件下進(jìn)行，兼容性高。但一級(jí)醇反應(yīng)效果不佳，會(huì)生成氨基甲酸甲酯。β位消除，遵循熱消除Ei機(jī)理（消除過(guò)程中，兩種離去基團(tuán)同時(shí)離去，互相之間又迅速成鍵）。消除具有順式選擇性，仲醇順式選擇性更高；叔醇脫水反應(yīng)更快，條件更加溫和，但是如果可以形成穩(wěn)定的碳正離子，可以觀察到E1消除產(chǎn)物。如果產(chǎn)物含有C=C或C=O鍵，更容易消除生成共軛烯烴產(chǎn)物。

近年來(lái)，Burgess試劑的最大用途是實(shí)現(xiàn)羥基酰胺和硫酰胺的環(huán)化脫氫反應(yīng)，得到相應(yīng)的雜環(huán)化合物。

試劑的制備：

(a) Burgess, E. M.; Penton, H. R., Jr.; Taylor, E. A.; Williams, W. M. Org. Synth. Coll. Edn.1987, 6, 788–791. (b) Duncan, J. A.; Hendricks, R. T.; Kwong, K. S. J. Am.Chem. Soc.1990, 112, 8433–8442.

Preparation of Bugess reagent:

將無(wú)水甲醇19.2g (0.6 mol) 和無(wú)水苯40mL的混合物在30-40分鐘內(nèi)，滴入ClSO2NCO85g (52.3 mL, 0.6 mol)和無(wú)水苯200mL的混合物中，控溫10-15℃。加畢，室溫?cái)嚢?小時(shí)。然后加入1000mL無(wú)水苯稀釋后，小心滴入190mL無(wú)水三乙胺和250mL無(wú)水苯的混合物中，控溫10-15℃，約40分鐘左右加完。加畢，室溫?cái)嚢?小時(shí)，析出大量固體。反應(yīng)畢，過(guò)濾，固體用無(wú)水苯200mL、無(wú)水THF200mL洗后，濾液濃縮后，（控溫<30℃），加入無(wú)水THF溶解后，重結(jié)晶得123g, 收率86%。注：整個(gè)操作溫度要低于30℃。

反應(yīng)機(jī)理

先和醇反應(yīng)生成磺酸酯，接著β位消除，遵循熱消除Ei機(jī)理。

Khapli, S.; Dey, S.; Mal, D. J. Indian Inst. Sci.2001, 81, 461–476. (Review).

反應(yīng)實(shí)例

在噻唑啉中與氨基酸2-C相連的手性中心很容易發(fā)生差向異構(gòu)化，以至于大多數(shù)羥基硫酰胺的環(huán)化脫水反應(yīng)都會(huì)生成非對(duì)映異構(gòu)體混合物。然而在Burgess 試劑1 的誘導(dǎo)下，羥基硫酰胺會(huì)高立體選擇性地得到96%產(chǎn)率和大于94%對(duì)映選擇性的手性單體。

【Tetrahedron Lett.,1994, 35, 5397】

將 Burgess 試劑與多聚乙二醇連接后得到的試劑2 相比于Burgess 試劑1 本身，能夠更高產(chǎn)率地誘導(dǎo)實(shí)現(xiàn)唑啉和噻唑啉化合物的制備。

【Tetrahedron Lett.,1996, 37, 4659】

在脫水試劑2的誘導(dǎo)下，羥基硫酰胺能夠高產(chǎn)率地轉(zhuǎn)化為噻嗪 ，這一方法比Mitusnobu反應(yīng)能獲得更高的產(chǎn)率。

【Tetrahedron,1998, 54, 6987】

對(duì)于伯醇一般是更容易發(fā)生取代反應(yīng)，而不是消除脫水。

【W(wǎng)ipf, P.; Xu, W. J. Org. Chem.1996, 61, 6556–6562.】

該試劑不僅能用于烯的合成，也能用于腈，異腈以及氧化腈的合成。此外它還被用于合成雜環(huán)惡唑啉和噻唑啉。

【W(wǎng)ipf, P.; Fritch, P. C. Tetrahedron Lett.1994, 35, 5397】

To a flamedried reaction vessel equipped witha stir bar and septum was added 4-(4-nitrophenyl)butan-1-ol (0.21 mL, 1.25mmol) followed by a benzene solution of1(5.0 mL, 1.25 mmol, 0.25 M).The septum was then removed and quickly replaced with a Teflon cap prior to thereaction being placed into a 50°C bath. After 1 h, the bath temperature wasincreased to 85°C and a small aliquot of the reaction mixture was removed tocheck for the formation of the initial adduct2(LC/MSgenerally shows M++18(H2O): 426). The reaction was stirred for 12–16 h and thenperiodically monitored, by LC/MS, for the disappearance of2.(CAUTION: Remove the reaction vessel from the heating bath and allow itstemperature to drop below the boiling point of the solvent prior to removing ananalytical sample.) Frequently, LC/MS spectra obtained prior towork-up show numerous side products that disappear after work-up. Aftercomplete disappearance of2, the reaction was cooled to ambienttemperature, benzene was removed in vacuo, and the residue was partitionedbetween EtOAc and 0.5 M HCl. The organic layer was washed with 5% sodiumbicarbonate and brine, then dried over sodium sulfate. Filtration, solventremoval and silica gel chromatography (10–60% EtOAc in hexanes, lineargradient) provided the target compound (318 mg, 77%) as a white solid.

【Tetrahedron Letters2002, 3887–3890】

Fredericamycin的合成【Kita, Y. et al. J. Am. Chem. Soc.2001,123, 3214.】

Taxol的合成【Holton, R. A. et al. J. Am. Chem. Soc.1994, 116, 1597. 】

【J. Am. Chem. Soc.1996, 118, 3303-3304】

【J. Am. Chem. Soc.1999, 121, 10270-10280】

Penitrem D的合成【Smith, A. B., III et al. J. Am. Chem. Soc.2003, 125, 8228.】

【Miller, C. P.; Kaufman, D. H. Synlett2000, 8, 1169–1171.】

Keller, L.; Dumas, F.; D’Angelo, J. Eur. J. Org. Chem.2003, 2488–2497.

【Nicolaou, K. C.; Snyder, S. A.; Longbottom, D. A.; Nalbandian, A. Z.; Huang, X. Chem. Eur. J.2004, 10, 5581–5606.】

Preparation of 5：Reagent 3 (0.35 g, 1.5 mmol) was added in one portion to a solution of 4 (0.18 g, 1 mmol) in dry dichloromethane (25 ml). The solution was heated at reflux, under a nitrogen atmosphere, until TLC analysis indicated that the formamide had been consumed (80 min), then cooled, diluted with dichloromethane (20 ml), washed with water (2 × 20 ml) and dried (MgSO4). Evaporation of the organic solution under vacuum and dry flash chromatography of the residue on silica gel 60, using 5% dichloromethane in hexanes as eluent, gave 5 (0.14 g, 88%) as a clear oil which darkened rapidly on standing。

【 J. Chem. Soc., Perkin Trans. 11998, 1015-1018 】

相關(guān)文獻(xiàn)

1. Burgess, E. M.; Penton, H.R.; Taylor, E. A. J. Org. Chem.,1973, 38, 26.

2. Creedon, S. M.; Crowley, H. K.; McCarthy, D. G. J. Chem.Soc., Perkin Trans. 1, 1998, 1015.

3. Claremon, D. A.; Phillips, B.T. Tetrahedron Lett., 1988, 29,21552.

4. Maugein, N.; Wagner, A.; Mioskowski, C., Tetrahedron Lett.,1997, 38, 1547.

5. Wipf, P.; Fritch, P. C. Tetrahedron Lett., 1994, 35, 5397.

6. Wipf, P.; Venkatraman, S. Tetrahedron Lett., 1996, 37, 4659.

7. Wipf, P.; Hayes, G. B. Tetrahedron, 1998, 54, 6987.

參考資料

一、Name Reactions （A Collection of Detailed Reaction Mechanisms）, Jie Jack Li, Burgess dehydrating reagent，page 95-96.

二、Strategic Applications of Named Reactions in Organic Synthesis, LászlóKürti and Barbara Czakó,Burgess Dehydration Reaction, page 72-73.

三、化學(xué)空間：http://www.chem-station.com/cn/reactions/%e6%b6%88%e9%99%a4%e5%8f%8d%e5%ba%94/2014/08/post-2566.html

四、《現(xiàn)代有機(jī)合成試劑——性質(zhì)、制備和反應(yīng)》，胡躍飛等編著