メンシュトキン反応

メンシュトキン反応
名前の由来	ニコライ・メンシュトキン
反応タイプ	カップリング反応
識別子
RSCオントロジーID	RXNO:0000223

有機化学において、メンシュトキン反応は、第三級アミンをアルキルハライドと反応させて第四級アンモニウム塩に 変換する反応です。第三級ホスフィンをアルキルハライドで処理した場合にも同様の反応が起こります。

メンシュトキン反応

The reaction is the method of choice for the preparation of quaternary ammonium salts.^[1] Some phase transfer catalysts (PTC) can be prepared according to the Menshutkin reaction, for instance the synthesis of triethyl benzyl ammonium chloride (TEBA) from triethylamine and benzyl chloride:

Menshutkin reaction

Scope

Reactions are typically conducted in polar solvents such as alcohols.^[1] Alkyl iodides are superior alkylating agents relative to the bromides, which in turn are superior to chlorides. As is typical for an S_N2 process, benzylic, allylic, and α-carbonylated alkyl halides are excellent reactants. Even though alkyl chlorides are poor alkylating agents (gem-dichlorides especially so), amines should not be handled in chlorinated solvents such as dichloromethane and dichloroethane, especially at high temperatures, due to the possibility of a Menshutkin reaction. (Sometimes, kinetically facile reactions like acylations are sometimes conducted in chlorinated solvents nonetheless.) Highly nucleophilic tertiary amines like DABCO will react with dichloromethane at room temperature overnight and at reflux (39-40 °C) over several hours to give the quaternized product (see the article on Selectfluor). Due to steric hindrance and unfavorable electronic properties, chloroform reacts very slowly with tertiary amines over a period of several weeks to months.^[2] Even pyridines, which are considerably less nucleophilic than typical tertiary amines, react with dichloromethane at room temperature over a period of several days to weeks to give bis(pyridinium)methane salts.^[3]

In addition to solvent and alkylating agent, other factors strongly influence the reaction. In one particular macrocycle system the reaction rate is not only accelerated (150000 fold compared to quinuclidine) but the halide order is also changed

Accelerated reaction.^[4]

History

The reaction is named after its discoverer, Nikolai Menshutkin, who described the procedure in 1890.^[5][6][7][8] Depending on the source, his name (and the reaction named after him) is spelled as Menšutkin, Menshutkin, or Menschutkin.

References

1. W. R. Brasen; C. R. Hauser (1954). "o-Methylethylbenzyl Alcohol". Org. Synth. 34: 58. doi:10.15227/orgsyn.034.0058.
2. Hansen, Steen Honoré; Nordholm, Lars (1981年1月16日). 「クロロホルム、ジクロロメタン、および1,2-ジクロロエタンによる第三級脂肪族アミンのN-アルキル化」. Journal of Chromatography A. 204 : 97–101 . doi : 10.1016/S0021-9673(00)81643-X.
3. 常温下におけるジクロロメタンとピリジン誘導体の反応Alexander B. Rudine, Michael G. Walter, Carl C. Wamser J. Org. Chem. 2010 , 75, 4292–95 doi :10.1021/jo100276m
4. メンシュトキン反応の劇的な加速とハロゲン化物脱離基秩序の歪みKeith J. Stanger, Jung-Jae Lee, Bradley D. Smith J. Org. Chem. 2007 , 72, 9663–68 doi :10.1021/jo702090p
5. N.メンシュトキン。 Beiträgen zur Kenntnis der Affinitätskoeffizienten der Alkylhaloide und derorganischen Amine Z. Physik.化学。 5 ( 1890 ) 589。
6. N メンシュトキン。アルキルハロゲン化物とアミンZ. Physik を使用してください。化学。 6 ( 1890 ) 41.
7. MB Smith, J March. March's Advanced Organic Chemistry (Wiley, 2001) ( ISBN 0-471-58589-0）
8. Lexikon bedeutender Chemiker (VEB Bibliographisches Institut Leipzig、1989) ( ISBN 3817110553