Cyanoethylation
Cyanoethylation is a process for the attachment of CH2CH2CN group to another organic substrate. The method is used in the synthesis of organic compounds.[1]
Cyanoethylation entails addition of protic nucleophiles to acrylonitrile. Typical protic nucleophiles are alcohols, thiols, and amines. Two new bonds form: C-H and C-X (X = carbon, nitrogen, sulfur, phosphorus, etc):
The β-carbon atom that is furthest from the nitrile group is positively polarized and therefore binds the heteroatom on the nucleophile. Acrylonitrile is a Michael acceptor.[2] The reaction is normally catalyzed by a base.[3]
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Cyanethylation is used to prepared numerous commercial chemicals. Detailed laboratory procedures are available for several variants of this reaction.
- Cyanoethylation of amines.[5][6]
- Cyanoethylation of phosphines.[7]
- Cyanoethylation of carbon nucleophiles.[8] In one commercial example, acetone is cyanoethylated to give the keto hexanenitrile, a precursor to 2-methylpyridine.[9]
An alternative method for cyanoethylation entails alkylation of the substrate with 3-chloropropionitrile.
De-cyanoethylation
[edit]Cyanoethyl is a protecting group. It is removed by treatment with base:
- RNuCH2CH2CN + OH− → RNu− + CH2=CHCN + H2O
This methodology is popular in the synthesis of oligonucleotides.[10]
References
[edit]- ^ Eller, Karsten; Henkes, Erhard; Rossbacher, Roland; Höke, Hartmut (2000). "Amines, Aliphatic". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a02_001. ISBN 3527306730.
- ^ Smith, Michael B.; March, Jerry (2007), Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (6th ed.), New York: Wiley-Interscience, ISBN 978-0-471-72091-1
- ^ Hajime Kabashima, Hideshi Hattori (1998). "Cyanoethylation of Alcohols Over Solid Base Catalysts". Catalysis Today. 44 (1–4): 277–283. doi:10.1016/S0920-5861(98)00200-4..
- ^ Trofimov, Boris A.; Arbuzova, Svetlana N.; Gusarova, Nina K. (1999). "Phosphine in the synthesis of organophosphorus compounds". Russian Chemical Reviews. 68 (3): 215–227. doi:10.1070/RC1999v068n03ABEH000464. S2CID 250775640.
- ^ J. Cymerman-Craig, M. Moyle (1956). "N-2-Cyanoethylaniline". Organic Syntheses. 36: 6. doi:10.15227/orgsyn.036.0006.
- ^ S. A. Heininger (1958). "3-(o-Chloroanilino)propionitrile". Organic Syntheses. 38: 14. doi:10.15227/orgsyn.038.0014.
- ^ Theodore E. Snider, Don L. Morris, K. C. Srivastava, K. D. Berlin (1973). "1-Phenyl-4-Phosphorinanone". Organic Syntheses. 53: 98. doi:10.15227/orgsyn.053.0098.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ E. C. Horning A. F. Finelli (1950). "α-Phenyl-α-Carboethoxyglutaronitrile". Organic Syntheses. 30: 80. doi:10.15227/orgsyn.030.0080.
- ^ Shimizu, S.; Watanabe, N.; Kataoka, T.; Shoji, T.; Abe, N.; Morishita, S.; Ichimura, H. "Pyridine and Pyridine Derivatives". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a22_399. ISBN 978-3527306732.
- ^ Liu, Qiang; Van Der Marel, Gijsbert A.; Filippov, Dmitri V. (2019). "Chemical ADP-ribosylation: Mono-ADPr-peptides and oligo-ADP-ribose". Organic & Biomolecular Chemistry. 17 (22): 5460–5474. doi:10.1039/c9ob00501c. hdl:1887/85621. PMID 31112180. S2CID 160014127.