上海
在强酸环境下醇和腈反应制备酰胺的反应。叔碳或苄位的碳正离子比较稳定，如果体系中有合适的亲核试剂，碳正离子可以与这些亲核试剂反应。利用这一点，如果在体系中加入腈，酰胺，叠氮等亲核试剂做胺源，可以制备各种胺或胺的衍生物。腈类化合物与碳正离子反应生成N-烷基酰胺的反应统称为Ritter type反应，实际上使用最多的碳正离子前体依然是烯烃和醇，常用的酸包括质子酸H2SO4、HClO4、RSO3H、PPA等和Lewis酸如AlCl3、BF3OEt2、SbCl5等。
含有氰基的底物在进行脱Boc时，脱掉的叔丁基正离子会和氰基进行Ritter反应得到N-叔丁基酰胺副产物。
反应机理
Ritter反应的机理并不复杂，与类似，现以底物醇为例对反应机理进行简要介绍。首先醇羟基被质子化后以水的形式离去得到碳正离子，腈类化合物的氰基N原子亲核进攻碳正离子得到腈正离子（nitrilium ion），进一步共振将正电荷分布在电负性更小的碳原子上，反应体系中的水分子捕获碳正离子并互变异构得到稳定的酰胺产物。
反应实例
【 J. Org. Chem. 1981 , 46, 78-82】
【 J. Org. Chem. 1989 , 54, 2242-2244】
【 Synthesis, 1997,9, 1034-1040 】
A solution of 1-adamantanol (0.304 g, 2 mmol)and urea (0.24 g, 4 mmol) in TFA (1.54 mL, 20 mmol) was heated at 115-120oCfor 7 hr. After the reaction was complete, the mixture was kept at r.t.overnight. Then acetone (2 mL) was added to and precipitate was formed. Thecrude product was filtratrated after cooling, washed with pentane and dried togive 0.43 g target compound (83%).
【 Tetrahedron Lett. 2001 , 42, 5175-5176】
【 J. Org. Chem. 2004 , 69, 5906-5925】
【 Org. Lett. 2013 , 15, 546-549】
/Ritter串联反应
相关文献
1. (a) Ritter, J. J.; Minieri, P. P. J. Am. Chem. Soc. 1948, 70, 4045-4048. (b) Ritter, J. J.; Kalish, J. J. Am. Chem. Soc. 1948, 70, 4048-4050.
2. Krimen, L. I.; Cota, D. J. Org. React. 1969, 17, 213–329. (Review).
3. Top, S.; Jaouen, G. J. Org. Chem. 1981, 46, 78-82.
4. Schumacher, D. P.; Murphy, B. L.; Clark, J. E.; Tahbaz, P.; Mann, T. A. J. Org. Chem.1989, 54, 2242-2244.
5. Le Goanvic, D; Lallemond, M.-C.; Tillequin, F.; Martens, T. Tetrahedron Lett. 2001,42, 5175-5176.
6. Tanaka, K.; Kobayashi, T.; Mori, H.; Katsumura, S. J. Org. Chem. 2004, 69,5906-5925.
7. Nair, V.; Rajan, R.; Rath, N. P. Org. Lett. 2002, 4, 1575-1577.
8. Concellón, J. M.; Riego, E.; Suárez, J. R.; García-Granda, S.; Díaz, M. R. Org. Lett. 2004, 6, 4499-4501.
9. Brewer, A. R. E. Ritter reaction. In Name Reactions for Functional Group Transformations; Li, J. J., Ed.; Wiley: Hoboken, NJ, 2007, pp 471-476. (Review).
10. Baum, J. C.; Milne, J. E.; Murry, J. A.; Thiel, O. R. J. Org. Chem. 2009, 74,2207-2209.
11. Yadav, J. S.; Reddy, Y. J.; Reddy, P. A. N.; Reddy, B. V. S. Org. Lett. 2013, 15, 546-549.
编译自：J.J. Li, Name Reactions: A Collection of Detailed Mechanisms and Synthetic Applications, Ritter reaction ，page 517-518.
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