Direct Oxidative Conversion of Alkyl Halides into Nitriles with Molecular Iodine in Aqueous Ammonia

Abstract

The direct oxidative conversion of various benzylic alkyl halides and primary alkyl halides into corresponding nitriles was efficiently and simply carried out using molecular iodine in aqueous ammonia. This novel reaction converts alkyl halides into corresponding nitriles without changing the number of carbon atoms.

Key words

iodine - ammonia - nitrile - halide

References and Notes

• 1 Review: Togo H. Iida S. Synlett  2006,  2159 
• 2a Friedrick K. Wallensfels K. The Chemistry of the Cyano Group   Rappoport Z. Wiley-Interscience; New York: 1970. 
• 2b North M. Comprehensive Organic Functional Group Transformation   Katritzky AR. Meth-Cohn O. Rees CW. Pergamon; Oxford: 1995. 
• 2c Murahashi S.-I. Synthesis from Nitriles with Retention of the Cyano Group, In Science of Synthesis   Vol. 19:  Thieme; Stuttgart: 2004.  p.345-402  
• 2d Collier SJ. Langer P. Application of Nitriles as Reagents for Organic Synthesis with Loss of the Nitrile Functionality, In Science of Synthesis   Vol. 19:  Thieme; Stuttgart: 2004.  p.403-425  
• 3 Fabiani ME. Drug News Perspect.  1999,  12:  207 
• 4 Comprehensive Organic Transformation   Larock RC. VCH Publishers, Inc.; New York: 1989.  p.976-993  
• 5a Clarke TG. Hampson NA. Lee JB. Morley JR. Scanlon B. Tetrahedron Lett.  1968,  5685 
• 5b Vargha L. Remenyi M. J. Chem. Soc.  1951,  1068 
• 5c Cason J. Org. Synth., Coll. Vol. III   Wiley; New York: 1955.  p.3 
• 5d Mihailovic ML. Stojiljkovic A. Andrejevic V. Tetrahedron Lett.  1965,  461 
• 5e Stojiljkovic A. Andrejevic V. Mihailovi ML. Tetrahedron  1967,  23:  721 
• 5f Below JS. Garza C. Mathieson JW. J. Chem. Soc., Chem. Commun.  1970,  634 
• 5g Troyanskii EI. Svitanko IV. Ioffe VA. Nikishin GI. Izv. Akad. Nauk. SSSR, Ser. Khim.  1982,  2180 
• 5h Yamazaki S. Yamazaki Y. Bull. Chem. Soc. Jpn.  1990,  63:  301 
• 5i Biondini D. Brinchi L. Germani R. Goracci L. Savelli G. Eur. J. Org. Chem.  2005,  3060 
• 5j Chen E. Peng Z. Fu H. Liu J. Shao L. J. Chem. Res., Synop.  1999,  726 
• 5k Lee GA. Freedman HH. Tetrahedron Lett.  1976,  1641 
• 5l Yamazaki S. Synth. Commun.  1997,  27:  3559 
• 5m Jursic B. J. Chem. Res., Synop.  1988,  168 
• 5n Nikishin GI. Troyanskii EI. Joffe VA. Izv. Akad. Nauk. SSSR, Ser. Khim.  1982,  2758 
• 5o Kametani T. Takahashi K. Ohsawa T. Ihara M. Synthesis  1977,  245 
• 5p Capdevielle P. Lavigne A. Maumy M. Synthesis  1989,  453 
• 5q Capdevielle P. Lavigne A. Sparfel D. Baranne-Lafont J. Nguyen KC. Maumy M. Tetrahedron Lett.  1990,  31:  3305 
• 5r Maeda Y. Nishimura T. Uemura S. Bull. Chem. Soc. Jpn.  2003,  76:  2399 
• 5s Tang R. Diamond SE. Neary N. Mares F. J. Chem. Soc., Chem. Commun.  1978,  562 
• 5t Schroder M. Griffith WP. J. Chem. Soc., Chem. Commun.  1979,  58 
• 5u Bailey AJ. James BR. Chem. Commun.  1996,  2343 
• 5v Mori K. Yamaguchi K. Mizugaki T. Ebitani K. Kaneda K. Chem. Commun.  2001,  461 
• 5w Yamaguchi K. Mizuno N. Angew. Chem. Int. Ed.  2003,  42:  1480 
• 5x Moriarty RM. Vaid RK. Duncan MP. Ochiai M. Inenaga M. Nagao Y. Tetrahedron Lett.  1988,  29:  6913 
• 5y Chen F. Kuang Y. Dai H. Lu L. Huo M. Synthesis  2003,  2629 
• 6a Mori N. Togo H. Synlett  2004,  880 
• 6b Mori N. Togo H. Tetrahedron  2005,  61:  5915 
• 6c Ishihara M. Togo H. Synlett  2006,  227 
• 6d Ishihara M. Togo H. Tetrahedron  2007,  63:  1474 
• 7a Mori N. Togo H. Synlett  2005,  1456 
• 7b Iida S. Togo H. Synlett  2006,  2633 
• 7c Iida S. Togo H. Tetrahedron  2007,  63:  8274 

8

Typical Procedure for Oxidative Conversion of Benzyl Halides into Nitriles with I ₂
To a mixture of 4-methylbenzyl chloride (140.6 mg, 1 mmol) and aq NH₃ (3.0 mL, 45 mmol) was added I₂ (533.0 mg, 2.1 mmol) at r.t. under an empty balloon. The obtained mixture was stirred at 60 °C. After 4 h at the same temperature, the reaction mixture was quenched with H₂O (10 mL) and sat. aq Na₂SO₃ (2 mL) at 0 °C and was extracted with Et₂O (3 × 15 mL). The organic layer was washed with brine and dried over Na₂SO₄ to provide p-tolunitrile in 82% yield in an almost pure state. If necessary, the product was purified by a column chromatography (SiO₂; hexane-EtOAc, 4:1) to give pure p-tolunitrile as a colorless solid; mp 25 °C. IR (NaCl): 2230 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 7.55 (2 H, d, J = 7.9 Hz), 7.27 (2 H, d, J = 7.9 Hz), 2.42 (3 H, s).

9

Typical Procedure for Oxidative Conversion of Alkyl Halides into Nitriles with I ₂
A mixture of 3-phenylpropyl bromide (199.1 mg, 1 mmol) and aq NH₃ (5.0 mL, 75 mmol) in a screw-capped glass vial (10 mL) was stirred at 60 °C for 24 h. Then, aq NH₃ (3.0 mL, 45 mmol) and I₂ (761.4 mg, 3.0 mmol) were added. After 4 h at the same temperature, the reaction mixture was quenched with H₂O (10 mL) and sat. aq Na₂SO₃ (2 mL) at 0 °C and was extracted with Et₂O (3 × 15 mL). The organic layer was washed with brine and dried over Na₂SO₄ to provide 3-phenylpropionitrile in 73% yield in an almost pure state. If necessary, the product was purified by column chromatography (SiO₂; hexane-EtOAc, 4:1) to give pure 3-phenylpropionitrile as a colorless oil. IR (NaCl): 2250 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 7.34 (2 H, t, J = 8.2 Hz), 7.28 (1 H, t, J = 8.2 Hz), 7.23 (2 H, d, J = 8.2 Hz), 2.96 (2 H, d, J = 7.9 Hz), 2.62 (2 H, d, J = 7.9 Hz).
All nitrile products mentioned in this work, except 10-cyanodecanoic acid, were identified with commercially available authentic samples.
10-Cyanodecanoic Acid
Mp 42-44 °C. IR (neat): 2243, 1690 cm^-1. ¹H NMR (400 MHz, CDCl₃): d = 2.35 (t, J = 7.4 Hz, 2 H), 7.34 (t, J = 7.2 Hz, 1 H), 1.64 (m, 4 H), 1.44 (br, 2 H) 1.32 (br, 9 H). ¹³C NMR (100 MHz, CDCl₃): d = 179.7, 119.9, 34.0, 29.1, 29.0, 28.72, 28.66, 25.4, 24.7, 17.2. HRMS: m/z calcd for C₁₁H₁₉O₂N: 198.1494; found: 198.1484.