An Environmentally Benign Procedure for the Synthesis of Aryl and Arylvinyl Nitriles Assisted by Microwave in Ionic Liquid

Abstract

Aryl and arylvinyl nitriles have been prepared in good yields from the corresponding bromides with potassium hexacyanoferrate(II) using palladium-catalyzed reactions in ionic liquid under microwave irradiation.

Key words

palladium - potassium hexacyanoferrate(II) - microwave - ionic liquid

References and Notes

• 1a Larock RC. Comprehensive Organic Transformations   VCH; New York: 1989.  p.819 
• 1b Grundmann C. In Houben-Weyl: Methoden der organischen Chemie   4th ed., Vol. E5:  Falbe J. Thieme; Stuttgart: 1985.  p.1313 
• For the nickel-catalyzed cyanation of aryl halides, see:
• 2a Cassar L. J. Organomet. Chem.  1973,  54:  57 
• 2b Cassar L. Foà M. Montanari F. Marinelli GP. J. Organomet. Chem.  1979,  173:  335 
• 2c Sakakibara Y. Okuda F. Shimoyabashi A. Kirino K. Sakai M. Uchino N. Takagi K. Bull. Chem. Soc. Jpn.  1988,  61:  1985 
• 2d Sakakibara Y. Ido Y. Sasaki K. Sakai M. Uchino N. Bull. Chem. Soc. Jpn.  1993,  66:  2776 
• 2e Rock M.-H, and Merhold A. inventors; WO  98/37058. 
• For the palladium-catalyzed cyanation of aryl halides, see:
• 3a Takagi K. Okamoto T. Sakakibara Y. Oka S. Chem. Lett.  1973,  471 
• 3b Sekiya A. Ishikawa N. Chem. Lett.  1975,  277 
• 3c Takagi K. Okamoto T. Sakakibara Y. Ohno A. Oka S. Hayama N. Bull. Chem. Soc. Jpn.  1975,  48:  3298 
• 3d Takagi K. Okamoto T. Sakakibara Y. Ohno A. Oka S. Hayama N. Bull. Chem. Soc. Jpn.  1976,  49:  3177 
• 3e Dalton JR. Regen SL. J. Org. Chem.  1979,  44:  4443 
• 3f Akita Y. Shimazaki M. Ohta A. Synthesis  1981,  974 
• 3g Chatani N. Hanafusa T. J. Org. Chem.  1986,  51:  4714 
• 3h Takagi K. Sasaki K. Sakakibara Y. Bull. Chem. Soc. Jpn.  1991,  64:  1118 
• 3i Anderson Y. Långström B. J. Chem. Soc., Perkin Trans. 1  1994,  1395 
• 3j Okano T. Kiji J. Toyooka Y. Chem. Lett.  1998,  425 
• 3k Anderson BA. Bell EC. Ginah FO. Harn NK. Pagh LM. Wepsiec JP. J. Org. Chem.  1998,  63:  8224 
• 3l Maligres PE. Waters MS. Fleitz F. Askin D. Tetrahedron Lett.  1999,  40:  8193 
• 3m Jin F. Confalone PN. Tetrahedron Lett.  2000,  41:  3271 
• 4 Sundermeier M. Zapf A. Beller M. Eur. J. Inorg. Chem.  2003,  3513 
• 5a Okano M. Amano M. Takagi K. Tetrahedron Lett.  1998,  39:  3001 
• 5b Ramnauth J. Bhardwaj N. Renton P. Rhakit S. Maddafird S. Synlett  2003,  2237 
• 5c Tschaen DM. Desmond R. King AO. Forin MC. Pipik B. King S. Verhoeven TR. Synth. Commun.  1994,  24:  887 
• 5d Marcantonio KM. Frey LF. Liu Y. Chen Y. Strine J. Phenix B. Wallace DJ. Chen C.-Y. Org. Lett.  2004,  6:  3723 
• 5e Maligres PE. Waters MS. Fleitz F. Askin D. Tetrahedron Lett.  1999,  40:  8193 
• 5f Jiang B. Kan Y. Zhang A. Tetrahedron  2001,  57:  1581 
• 6a Chidambaram R. Tetrahedron Lett.  2004,  45:  1441 
• 6b Jin F. Confalone PN. Tetrahedron Lett.  2000,  41:  3271 
• 6c Okano T. Iwahara M. Kiji J. Synlett  1998,  243 
• 6d Stazi F. Palmisano G. Turconi M. Santagostino M. Tetrahedron Lett.  2005,  46:  1815 
• 6e Hatsuda M. Seki M. Tetrahedron Lett.  2005,  46:  1849 
• 6f Grossman O. Gelman D. Org. Lett.  2006,  8:  1189 
• 7a Okano T. Kiji J. Toyooka Y. Chem. Lett.  1998,  425 
• 7b Cassar L. Foa M. J. Organomet. Chem.  1979,  173:  335 
• 7c Sundermeier M. Zapf A. Beller M. Angew. Chem. Int. Ed.  2003,  42:  1661 
• 7d Sundermeier M. Mutyala S. Zapf A. Spannenberg A. Beller M. J. Organomet. Chem.  2003,  684:  50 
• 7e Yang C. Williams JM. Org. Lett.  2004,  6:  2837 
• 8a First use of potassium ferrocyanide in this capacity (uncatalyzed reaction): Merz V. Weith W. Ber. Dtsch. Chem. Ges.  1877,  10746 
• 8b Schareina T. Zapf A. Beller M. Chem. Commun.  2004,  12:  1388 
• 8c Schareina T. Zapt A. Beller M. J. Organomet. Chem.  2004,  689:  4576 
• 8d Schareina T. Zapf A. Beller M. Tetrahedron Lett.  2005,  46:  2585 
• 8e Weissman SA. Zewge D. Chen C. J. Org. Chem.  2005,  70:  1508 
• 9a Wasserscheid P. Welton T. Ionic Liquids in Synthesis   Wiley-VCH; Weinheim: 2002. 
• 9b Liao MC. Duan XH. Liang YM. Tetrahedron Lett.  2005,  46:  3469 
• 10 Wu JX. Beck B. Ren RX. Tetrahedron Lett.  2002,  43:  387 
• 11a Leadbeater NE. Torenius HM. Tye H. Tetrahedron  2003,  59:  2253 
• 11b Cai L. Liu X. Tao X. Shen D. Synth. Commun.  2004,  34:  1215 
• 11c Srivastava RR. Collibee SE. Tetrahedron Lett.  2004,  45:  8895 
• 11d Arvela RK. Leadbeater NE. J. Org. Chem.  2003,  68:  9122 
• 11e Arvela RK. Leadbeater NE. Torenius HM. Tye H. Org. Biomol. Chem.  2003,  1:  1119 
• 11f Alterman M. Hallberg A. J. Org. Chem.  2000,  65:  7984 
• For recent examples, see:
• 15a Ho T.-L. Su C.-Y. J. Org. Chem.  2000,  65:  3566 
• 15b Williams GM. Roughley SD. Davies JE. Holmes AB. J. Am. Chem. Soc.  1999,  121:  4900 
• 15c Carless HAJ. Dove Y. Tetrahedron: Asymmetry  1996,  7:  649 
• 16a Fleming FF. Pu Y. Tercek F. J. Org. Chem.  1997,  62:  4883 
• 16b Fleming FF. Hussain Z. Weaver D. Norman RE. J. Org. Chem.  1997,  62:  1305 
• 16c Fleming FF. Pak JJ. J. Org. Chem.  1995,  60:  4299 

12

As the ionic liquid, [BMIm]BF₄ was chosen because it was not only most easily manipulated at r.t., but one can be sure to be able to separate the product from the solvent completely via simple extraction with a conventional organic solvent and reused.

13

K₄[Fe(CN)₆]·3H₂O is ground to a fine powder and dried under vacuum (ca. 2 mbar) at 80 °C overnight.

14

Microwave experiments were conducted using a CEM Discover Synthesis Unit (CEM Corp., Matthews, NC). The machine consists of a continuous focused microwave power delivery system with operator selectable power output from 0-300 W.

17

General Procedure for the Cyanation of Aryl and Arylvinyl Bromides under Microwave Promotion.
[BMIm]BF₄ (1.5 mL) was placed into a 10-mL glass microwave tube and to this was added anhyd K₄[Fe(CN)₆] (0.05 mmol), Na₂CO₃ (0.25 mmol), substrate (0.25 mmol), PdCl₂ (2.5 mol%), and DMEDA (10 mol%). After sealing the tube, the mixture was exposed to microwave irradiation (a maximum microwave power of 120 W, a temperature threshold of 200 °C and a pressure threshold of 200 psi) for the requisite time. After the reaction mixture was cooled, the product was extracted from the system by washing the ionic liquid repeatedly with EtOAc-PE = 8:1 (4 × 3 mL). Finally, the product was isolated by flash chromatography on silica gel using EtOAc-PE as mobile phase.

18

Compound 2a: ¹H NMR (300 MHz, CDCl₃): δ = 7.72-7.65 (m, 4 H), 7.60-7.56 (m, 2 H), 7.51-7.41 (m, 3 H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 145.5, 139.0, 132.5, 129.0, 128.6, 127.6, 127.1, 118.9, 110.7 ppm. MS: m/z = 179 [M⁺], 151, 76.
Compound 2c: ¹H NMR (300 MHz, CDCl₃): δ = 7.81-7.78 (m, 4 H), 7.71 (d, J = 8.7 Hz, 4 H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 143.4, 132.8, 127.9, 118.4, 112.3 ppm. MS: m/z = 204 [M⁺], 153, 126, 76.
Compound 4d: ¹H NMR (300 MHz, CDCl₃): δ = 8.22 (d, J = 16.5 Hz, 1 H), 8.03 (d, J = 8.1 Hz, 1 H), 7.95-7.87 (m, 2 H), 7.67-7.46 (m, 4 H), 5.96 (d, J = 16.5 Hz, 1 H) ppm.
¹³C NMR (75 MHz, CDCl₃): δ = 147.8, 133.5, 131.5, 130.8, 130.6, 128.8, 127.3, 126.5, 125.3, 124.6, 122.7, 118.2, 98.7 ppm. MS: m/z = 179 [M⁺], 152, 76.