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N-溴代丁二酰亚胺

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N-溴代丁二酰亚胺
Skeletal formula of N-bromosuccinimide
Space-filling model of the N-bromosuccinimide molecule
IUPAC名
1-Bromo-2,5-pyrolidinedione
别名 N-溴琥珀醯亞胺;NBS
缩写 NBS
识别
CAS号 128-08-5
ChemSpider 60528
SMILES
InChI
InChIKey PCLIMKBDDGJMGD-UHFFFAOYAS
ChEBI 53174
性质
化学式 C4H4BrNO2
摩尔质量 177.98 g·mol⁻¹
外观 白色固体
密度 2.098 g/cm3
熔点 175~178 °C
溶解性 1.47 g / 100 mL (25 °C)
溶解性CCl4 不可溶 (25 °C)
蒸氣壓 14.8 hPa (20 °C)
危险性
欧盟危险性符号
有害有害 Xn
警示术语 R:R22-R36/37/38
安全术语 S:S26-S36
若非注明,所有数据均出自一般条件(25 ℃,100 kPa)下。

N-溴代丁二酰亚胺或稱N-溴琥珀醯亞胺[1]英语N-Bromosuccinimide, NBS),是有机合成中的重要试剂。它被广泛应用于自由基取代反应亲电加成反应中。NBS可以當作的替代物。

製備[编辑]

NBS在市面上是可以取得的,但也可以在實驗室中被合成出來。合成方法為將0.16莫耳(約16 g)的丁二醯亞胺英语succinimide溶於至於冰浴中的氫氧化鈉溶液中(6.4 g溶入40 mL水中並加入30 g碎冰),持續攪拌約5分鐘後,過濾並以清水清洗產物,最後將產物以40 °C乾燥。此作法產率約為69.5 %(約20 g)。[2]

除了沃爾–齊格勒溴化反應使用不純的NBS能有比較高的產率,在進行其他反應時通常不會使用不純的NBS(略黃),這可能會產生不可預期的結果。而純化NBS的方法為使用90–95 °C 的水(10 g NBS溶入100 mL水中)進行再結晶[3]

反應[编辑]

烯烴的加成反應[编辑]

NBS能跟烯烴(如下圖 1)在水溶液中反應產生鹵代醇英语halohydrin(如下圖 2)。進行此反應的最佳條件是在0 °C下,將NBS分批加入烯烴的DMSODMETHF叔丁醇其中之一的50 %水溶液中。[4] 溴鎓離子英语Halonium ion的生成和水分子的快速攻擊使這個反應為馬可尼可夫加成反應且為反式加成(立體選擇性)。[5]

NBS Bromohydrin Formation Scheme.png

副產物包括α-溴代酮跟二溴取代化合物,而使用再結晶過的NBS即可以減少這些副產物的產生。

若此反應改使用其他親核基(而非以水當親核基),則可以合成其他各式各樣擁有雙取代基的烷類,下圖即為一例。[6]

環己烯的鹵素加成反應

Allylic and benzylic bromination[编辑]

Standard conditions for using NBS in allylic and/or benzylic bromination involves refluxing a solution of NBS in anhydrous CCl4 with a radical initiator—usually azo-bis-isobutyronitrile (AIBN) or benzoyl peroxide, irradiation, or both to effect radical initiation.[7][8] The allylic and benzylic radical intermediates formed during this reaction are more stable than other carbon radicals and the major products are allylic and benzylic bromides. This is also called the Wohl-Ziegler reaction.[9][10]

Allylic bromination of 2-heptene

The carbon tetrachloride must be maintained anhydrous throughout the reaction, as the presence of water may likely hydrolyze the desired product.[11] Barium carbonate is often added to maintain anhydrous and acid-free conditions.

In the above reaction, while a mixture of isomeric allylic bromide products are possible, only one is created due to the greater stability of the 4-position radical over the methyl-centered radical.

Bromination of carbonyl derivatives[编辑]

NBS can α-brominate carbonyl derivatives via either a radical pathway (as above) or via acid-catalysis. For example, hexanoyl chloride 1 can be brominated in the alpha-position by NBS using acid catalysis.[12]

Alpha-bromination of hexanoyl chloride

The reaction of enolates, enol ethers, or enol acetates with NBS is the preferred method of α-bromination as it is high-yielding with few side-products.[13][14]

Bromination of aromatic derivatives[编辑]

Electron-rich aromatic compounds, such as phenols, anilines, and various aromatic heterocycles,[15] can be brominated using NBS.[16][17] Using DMF as the solvent gives high levels of para-selectivity.[18]

Hofmann rearrangement[编辑]

NBS, in the presence of a strong base, such as DBU, reacts with primary amides to produce a carbamate via the Hofmann rearrangement.[19]

The Hofmann rearrangement using NBS

Selective oxidation of alcohols[编辑]

It is uncommon, but possible for NBS to oxidize alcohols. E. J. Corey et al. found that one can selectively oxidize secondary alcohols in the presence of primary alcohols using NBS in aqueous dimethoxyethane (DME).[20]

The selective oxidation of alcohols using NBS

Oxidative decarboxylation of amino acids[编辑]

NBS electrophilically brominates the amine, which is followed by decarboxylation and release of an imine. Hydrolysis of the imine yields an aldehyde and ammonia. (c.f. with non oxidative PLP dependant decarboxylation)[來源請求]

注意事項[编辑]

相較於溴,NBS是個相對安全的反應試劑,但還是要注意避免吸入體內。純的NBS為白色固體,但會隨時間逐漸分解產生溴,這會使之略帶黃色。NBS應該儲藏在冰箱中

大部分使用NBS試劑的反應都為放熱反應,所以進行大規模反應的時候應特別注意安全。

參見[编辑]

参考文献[编辑]

  1. ^ N-溴琥珀醯亞胺. 國家教育研究院雙語詞彙、學術名詞暨辭書資訊網. [2015-07-04]. 
  2. ^ V K Ahluwalia; Pooja Bhagat, Renu Aggarwal, Ramesh Chandra. 6.A. Intermediates For Organic Synthesis. I K International Publishing House. 2005: 297. ISBN 978-8188237333. 
  3. ^ Dauben Jr., H. J.; McCoy, L. L. N-Bromosuccinimide. I. Allylic Bromination, a General Survey of Reaction Variables. J. Am. Chem. Soc. 1959, 81 (18): 4863–4873. doi:10.1021/ja01527a027. 
  4. ^ Hanzlik, R. P.. "Selective epoxidation of terminal double bonds". Org. Synth.; Coll. Vol. 6: 560. 
  5. ^ Beger, J. Präparative Aspekte elektrophiler Dreikomponentenreaktionen mit Alkenen. J. Prakt. Chem. 1991, 333 (5): 677–698. doi:10.1002/prac.19913330502. 
  6. ^ Haufe, G.; Alvernhe, G.; Laurent, A.; Ernet, T.; Goj, O.; Kröger, S.; Sattler, A. (2004). "Bromofluorination of alkenes". Org. Synth.; Coll. Vol. 10: 128. 
  7. ^ Carl Djerassi. Brominations with N-Bromosuccinimide and Related Compounds. The Wohl-Ziegler Reaction. Chem. Rev. 1948, 43 (2): 271–317. doi:10.1021/cr60135a004. PMID 18887958. 
  8. ^ Greenwood, F. L.; Kellert, M. D. and Sedlak, J. (1963). "4-Bromo-2-heptene". Org. Synth.; Coll. Vol. 4: 108. 
  9. ^ 编辑
  10. ^ 编辑
  11. ^ Binkley, R. W; Goewey, G. S; Johnston, J. Regioselective ring opening of selected benzylidene acetals. A photochemically initiated reaction for partial deprotection of carbohydrates. J. Org. Chem. 1984, 49 (6): 992. doi:10.1021/jo00180a008. 
  12. ^ Harpp, D. N.; Bao, L. Q.; Coyle, C.; Gleason, J. G.; Horovitch, S. (1988). "2-Bromohexanoyl chloride". Org. Synth.; Coll. Vol. 6: 190. 
  13. ^ Stotter, P. L.; Hill, K. A. α-Halocarbonyl compounds. II. Position-specific preparation of α-bromoketones by bromination of lithium enolates. Position-specific introduction of α,β-unsaturation into unsymmetrical ketones. J. Org. Chem. 1973, 38 (14): 2576. doi:10.1021/jo00954a045. 
  14. ^ Lichtenthaler, F. W.; Stewart, JM; O'dea, DJ; Shapiro, GC; Patel, MB; Mcintyre, JT; Gewitz, MH; Hoegler, CT; Shapiro, JT; Zeballos, GA. Various Glycosyl Donors with a Ketone or Oxime Function next to the Anomeric Centre: Facile Preparation and Evaluation of their Selectivities in Glycosidations. Synthesis. 1992, 1992 (9): 784–92. doi:10.1055/s-1992-34167. PMID 1839242. 
  15. ^ Amat, M.; Hadida, S.; Sathyanarayana, S.; Bosch, J. (1998). "Regioselective synthesis of 3-substituted indoles". Org. Synth.; Coll. Vol. 9: 417. 
  16. ^ Gilow, H. W.; Burton, D. E. Bromination and chlorination of pyrrole and some reactive 1-substituted pyrroles. J. Org. Chem. 1981, 46 (11): 2221. doi:10.1021/jo00324a005. 
  17. ^ Brown. W. D.; Gouliaev, A. H. (2005). "Synthesis of 5-bromoisoquinoline and 5-bromo-8-nitroisoquinoline". Org. Synth. 81: 98. 
  18. ^ Mitchell, R. H.; Lai, Y.H.; Williams, R. V. N-Bromosuccinimide-dimethylformamide: a mild, selective nuclear monobromination reagent for reactive aromatic compounds. J. Org. Chem. 1979, 44 (25): 4733. doi:10.1021/jo00393a066. 
  19. ^ Keillor, J. W.; Huang, X. (2004). "Methyl carbamate formation via modified Hofmann rearrangement reactions". Org. Synth.; Coll. Vol. 10: 549. 
  20. ^ Corey, E. J.; Ishiguro, M. Total synthesis of (±)-2-isocyanopupukeanane. Tetrahedron Lett. 1979, 20 (30): 2745–2748. doi:10.1016/S0040-4039(01)86404-2.