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Delépine胺合成反应，烷基卤代物和六亚甲基四胺反应得到铵盐，接着用HCl乙醇溶液酸解得到伯胺的反应。此反应以法国化学家 Stéphane Marcel Delépine (1871－1965) 的名字命名。反应机理和Gabriel反应（产物为胺），Sommelet反应（产物为醛）类似。对于Delépine反应， 活性卤代物（如苄基卤代物，烯丙基卤代物和α-卤代酮）的反应效果都很好。碘代烷烃反应速度最快，氯代与溴代底物反应比较缓慢。在氯仿中原料是可溶的，反应后产物可以结晶出来，通常不需要继续纯化。优点为底物易得，副反应少，反应步骤简单，条件温和。六亚甲四胺已为叔胺，第一步只能在氮上引入一个烷基，因此水解后生成比较纯净的伯胺。二杂原子取代亚甲基一般很活泼，但乌洛托品通常很稳定。在中性条件下，在水溶液中乌洛托品在沸腾条件下都很稳定，在酸性醇溶液中会分解，得到的乌洛托品季铵盐，也可以分解得到氯化铵盐和甲醛（二乙缩甲醛）。![]()
此反应和Sommelet反应非常类似，但是Sommelet反应反应，底物通常为苄基卤代物，HMTA通常是过量的，而且是在弱酸性条件下进行，和Duff反应类似。Delépine反应，一般卤代物和HMTA基本上等当量反应得到季铵盐，然后在强酸的醇溶液中水解得到伯胺。两个反应没有完全的界限，比如Delépine反应生成的伯胺, 如果体系中还有过量的HMTA, 酸性条件下加热也有可能生成Sommelet反应的产物醛。反应机理
烷基卤代物和六亚甲基四胺经过 SN2 反应得到六亚甲基四铵盐，在酸性水解或醇解过程中，首先生成半胺醛，继续分解得到甲醛，铵盐和氯化铵：
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反应实例
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【 J. Am. Chem. Soc. 1949, 71, 375-384】
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【Synthesis, 1988, 347-348】
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【Synthesis 2002, 1101-1109】
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【J. Med.Chem. 2004, 47, 756-760】
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【Synthesis 2006,1975-1980】
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Hexamethylene tetramine (49.2 g, 0.350 mol) was dissolved in 750 mL chloroform, then
97.4 g 2,4-dibromo-acetophenone (7.4 g, 0.350 mol) was added all at once; the suspension
was stirred overnight and the quaternary salt was collected, washed with 750 mL chloroform,
and dried at 60◦C under reduced pressure (20 mmHg) for 4 h. The product was treated
with 900 mL methanol and 120 mL 48% hydrobromic acid at 20◦C for 2 days. Solid was
always present, so 600 mL methanol was added, and the suspension was heated at 50◦C
overnight and then at reflux for 1.5 h, cooled to 20◦C, and evaporated at a bath temperature
of 50◦C to obtain a mushy solid, which was recrystallized from 700 mL water to give 84.4 g
4-bromobenzoylmethylammonium bromide dihydrate, in a yield of 73%, m.p. 273–277◦C
(dec.)
【J. Org. Chem., 2003, 68, 839】
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【 Russ. J. Gen. Chem., 2006, 1304-1309】
相关文献
1. (a) Delépine, M. Bull. Soc. Chim. Paris 1895, 13, 352-355; (b) Delépine, M. Bull.Soc. Chim. Paris 1897, 17, 292-295. Stephe Marcel Delépine (1871-1965) was born in St. Martin le Gaillard, France. He was a professor at the Collège de France after working for M. Bertholet at that institute. Delépine’s long and fruitful career in science encompassed organic chemistry, inorganic chemistry, and pharmacy.2. Galat, A.; Elion, G. J. Am. Chem. Soc. 1939, 61, 3585-3586.3. Wendler, N. L. J. Am. Chem. Soc. 1949, 71, 375-384.4. Quessy, S. N.; Williams, L. R.; Baddeley, V. G. J. Chem. Soc., Perkin Trans. 1 1979, 512-516.5. Blažzević, N.; Kolnah, D.; Belin, B.; Šunjić, V.; Kafjež, F. Synthesis 1979, 161-176.(Review).6. Henry, R. A.; Hollins, R. A.; Lowe-Ma, C.; Moore, D. W.; Nissan, R. A. J. Org.Chem. 1990, 55, 1796-1801.7. Charbonnière, L. J.; Weibel, N.; Ziessel, R. Synthesis 2002, 1101-1109.8. Xie, L.; Yu, D.; Wild, C.; Allaway, G.; Turpin, J.; Smith, P. C.; Lee, K.-H. J. Med.Chem. 2004, 47, 756-760.9. Loughlin, W. A.; Henderson, L. C.; Elson, K. E.; Murphy, M. E. Synthesis 2006,1975-1980.一、Name Reactions （A Collection of Detailed Reaction Mechanisms）, Jie Jack Li, Delépine amine synthesis，page 198-199.二、有机化学门户：https://www.organic-chemistry.org/namedreactions/delepine-reaction.shtm
相关反应
Duff反应
Sommelet反应
