Versatile and Fluoride-Free Cyanation of Alkyl Halides and Sulfonates with Trimethylsilyl Cyanide

Abstract

Cyanation of biphenyl-4-ylmethyl methanesulfonate with trimethylsilyl cyanide using fluoride-free inorganic salts, such as Cs₂CO₃, K₂CO₃, and LiOH˙H₂O, as additives in MeCN quantitatively gave biphenyl-4-ylacetonitrile. This methodology was applied to various alkyl halides to give the corresponding nitrile compounds in good to excellent yields. Of note, 4-(hydroxymethyl)benzyliodide O-protected by the silyl group was converted into phenylacetonitrile derivative in 99% yield without desilylation.

Key words

cyanation - trimethylsilyl cyanide - fluoride-free inorganic salt

References and Notes

• 1a Prasad ASB. Kanth JVB. Periasamy M. Tetrahedron  1992,  48:  4623 
• 1b Cha JS. Brown HC.
  J. Org. Chem.  1993,  58:  3974 
• 1c Gowda S. Gowda DC. Tetrahedron  2002,  58:  2211 
• 1d Khurana JM. Kukreja G. Synth. Commun.  2002,  32:  1265 
• 2a Mukherjee C. Zhu D. Biehl ER. Hua L. Eur. J. Org. Chem.  2006,  5238 
• 2b Mills FD. Brown RT. Synth. Commun.  1990,  20:  3131 
• 2c Naota T. Shichijo Y. Murahashi S. J. Chem. Soc., Chem. Commun.  1994,  11:  1359 
• 2d Luo F.-T. Jeevanandam A. Tetrahedron Lett.  1998,  39:  9455 
• 3 Amantini D. Beleggia R. Fringuelli F. Pizzo F. Vaccaro L. J. Org. Chem.  2004,  69:  2896 
• 4 Caron M. Sharpless KB. J. Org. Chem.  1985,  50:  1557 
• 5 Gassman PG. Haberman LM. J. Org. Chem.  1986,  51:  5010 
• 6 Imi K. Yanagihara N. Utimoto K. J. Org. Chem.  1987,  52:  1013 
• 7 Reetz MT. Drewes MW. Harms K. Reif W. Tetrahedron Lett.  1988,  29:  3295 
• 8 Deng H. Isler MP. Snapper ML. Hoveyda AH. Angew. Chem. Int. Ed.  2002,  41:  1009 
• 9 Zieger HE. Wo S. J. Org. Chem.  1994,  59:  3838 
• 10 Reetz MT. Chatziiosifidis I. Künzer H. Müller-Starke H. Tetrahedron  1983,  39:  961 
• 11a Sugita K. Ohta A. Onaka M. Izumi Y. Chem. Lett.  1990,  481 
• 11b Onaka M. Higuchi K. Sugita K. Izumi Y. Chem. Lett.  1989,  1393 
• 11c Higuchi K. Onaka M. Izumi Y. Bull. Chem. Soc. Jpn.  1993,  66:  2016 
• 12 Soli ED. Manoso AS. Patterson MC. DeShong P. Favor DA. Hirschmann R. Smith AB. J. Org. Chem.  1999,  64:  3171 
• 13 Otera J. Nakazawa K. Sekoguchi K. Orita A. Tetrahedron  1997,  53:  13633 
• 14 Sassaman MB. Prakash GKS. Olah GA. J. Org. Chem.  1990,  55:  2016 
• 15 Schaus SE. Jacobsen EN. Org. Lett.  2000,  2:  1001 
• 16a Liu X. Qin B. Zhou X. He B. Feng X. J. Am. Chem. Soc.  2005,  127:  12224 
• 16b Chen FX. Feng X. Synlett  2005,  892 
• 16c He B. Li Y. Feng X. Zhang G. Synlett  2004,  1776 
• 17 Hatano M. Ikeno T. Miyamoto T. Ishihara K. J. Am. Chem. Soc.  2005,  127:  10776 
• 18 Kitani Y. Kumamoto T. Isobe T. Fukuda K. Ishikawa T. Adv. Synth. Catal.  2005,  347:  1653 
• 19 Kitano Y. Manoda T. Miura T. Chiba K. Tada M. Synthesis  2006,  405 
• 20 Lamont RB. Allen DG. Clemens IR. Newall CE. Ramsay MVJ. Rose M. Fortt S. Gallagher T. J. Chem. Soc., Chem. Commun.  1992,  1693 
• 22 Kikugawa Y. Synthesis  1981,  460 
• 23 Zhang P. Lui R. Cook JM. Tetrahedron Lett.  1995,  36:  3103 
• 24 Pettit GR. Grealish MP. Jung MK. Hamel E. Pettit RK. Chapuis J.-C. Schmidt JM. J. Med. Chem.  2002,  45:  2534 
• 25 Zacharie B. Connolly TP. Rej R. Attardo G. Penney CL. Tetrahedron  1996,  52:  2271 
• 27 Zimmerman HE. Heydinger JA. J. Org. Chem.  1991,  56:  1747 

21

For cyanosilylation, the addition of a carbonyl compound with TMSCN using a catalytic amount of K₂CO₃ was already reported. [¹6]

26

General Procedure To a mixture of alkyl halide or methanesulfonate (5.40 mmol) and K₂CO₃ (6.49 mmol) in MeCN (10 mL) was added TMSCN (6.49 mmol). The reaction mixture was stirred at the required temperature until the reaction was completed. At the end of the reaction, 1 N NaOH (25 mL) was added to the reaction mixture, which was extracted with toluene (30 mL). The organic layer was washed with 1 N NaOH (25 mL) and then brine (25 mL), dried over MgSO₄, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel to give pure nitrile compounds.
Biphenyl-4-ylacetonitrile (2) [²7]
White solid; mp 94-96 ˚C. IR (ATR): ν = 3033, 2360, 2249, 1485, 1406, 1005, 907, 812, 750, 684, 461 cm^-¹. ^¹H NMR (300 MHz, CDCl₃, TMS): δ = 3.78 (2 H, s), 7.33-7.47 (5 H, m), 7.56-7.61 (4 H, m). MS: m/z = 193 [M⁺]. Anal. Calcd for C₁₄H₁₁N: C, 87.01; H, 5.74; N, 7.25. Found: C, 86.80; H, 5.70; N, 7.05.
{1-[(4-Methylphenyl)sulfonyl]-1 H -indole-3-yl}aceto-nitrile (4g) White solid; mp 161-163 ˚C. IR (KBr): ν = 3117, 2929, 2258, 1595, 1450, 1364, 1175, 1135, 1095, 979, 814, 670, 532 cm^-¹. ^¹H NMR (300 MHz, CDCl₃, TMS): δ = 2.34 (3 H, s), 3.74 (2 H, s), 7.23 (2 H, d, J = 8.2 Hz), 7.25-7.31 (1 H, m), 7.35-7.40 (1 H, m), 7.49 (1 H, d, J = 7.8 Hz), 7.60 (1 H, s), 7.77 (2 H, d, J = 8.4 Hz), 8.01 (1 H, d, J = 8.3 Hz). MS: m/z = 310 [M⁺]. Anal. Calcd for C₁₇H₁₄N₂O₂S: C, 65.79; H, 4.55; N, 9.03; S, 10.33. Found: C, 65.69; H, 4.58; N, 8.94; S, 10.37.
(4-{[ tert -Butyl(diphenyl)silyl]oxy}phenyl)acetonitrile (4h) Colorless oil. IR (neat): ν = 3071, 2930, 2891, 2857, 2250, 1736, 1609, 1509, 1427, 1256, 1113, 914, 821, 699, 611 cm^-¹. ^¹H NMR (300 MHz, CDCl₃, TMS): δ = 1.10 (9 H, s), 3.57 (2 H, s), 6.74 (2 H, d, J = 8.6 Hz), 7.02 (2 H, d, J = 8.7 Hz), 7.34-7.43 (6 H, m), 7.68-7.71 (4 H, m). MS: m/z = 371 [M⁺]. Anal. Calcd for C₂₄H₂₅NOSi: C, 77.58; H, 6.78; N, 3.77. Found: C, 77.70; H, 6.94; N, 3.72.
[4-({[ tert -Butyl(diphenyl)silyl]oxy}methyl)phenyl]aceto-nitrile (4i) White solid; mp 88-90 ˚C. IR (ATR): ν = 2930, 2857, 2245, 1588, 1514, 1427, 1112, 1083, 817, 704, 504, 490, 468 cm^-¹. ^¹H NMR (300 MHz, CDCl₃, TMS): δ = 1.10 (9 H, s), 3.73 (2 H, s), 4.76 (2 H, s), 7.11-7.46 (10 H, m), 7.67-7.70 (4 H, m). MS: m/z = 386 [M + H⁺]. Anal. Calcd for C₂₅H₂₇NOSi: C, 77.88; H, 7.06; N, 3.63. Found: C, 77.74; H, 7.04; N, 3.70.