Synlett 2009(20): 3378-3382  
DOI: 10.1055/s-0029-1218388
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Propylphosphonic Anhydride (T3P®): A Remarkably Efficient Reagent for the One-Pot Transformation of Aromatic, Heteroaromatic, and Aliphatic Aldehydes to Nitriles

John Kallikat Augustine*, Rajendra Nath Atta, Balakrishna Kolathur Ramappa, Chandrakantha Boodappa
Syngene International Ltd., Biocon Park, Plot Nos. 2 & 3, Bommasandra IV Phase, Jigani Link Road, Bangalore 560 099, India
Fax: +91(80)28083150; e-Mail: john.kallikat@syngeneintl.com;
Weitere Informationen

Publikationsverlauf

Received 8 September 2009
Publikationsdatum:
27. November 2009 (online)

Abstract

Propylphosphonic anhydride has been demonstrated to be an efficient reagent for the transformation of aromatic, heteroaromatic, and aliphatic aldehydes to respective nitriles in excellent yields. This procedure offers simple and one-pot access to nitriles and highlights the synthetic utility of T3P® as a versatile reagent in organic chemistry.

    References and Notes

  • 1 Sandier SR. Karo W. In Organic Functional Group Preparations   Vol. 12-I:  Academic Press; San Diego: 1983.  p.Chap. 17 
  • 2a Mowry DT. Chem. Rev.  1948,  42:  250 
  • 2b Friedrich K. Wallensfels K. In The Chemistry of the Cyano Group   Rappoport Z. Wiley-Interscience; New York: 1970. 
  • 2c North M. In Comprehensive Organic Functional Group Transformations   Katrizky AR. Meth-Cohn O. Rees CW. Pergamon; Oxford: 1995.  p.617 
  • 3a Katritzky AR. Zhang GF. Fan WQ. Org. Prep. Proced. Int.  1993,  25:  315 
  • 3b Forey HG. Datlon DR. J. Chem. Soc., Chem. Commun.  1973,  628 
  • 3c Kukhar VP. Pasternak VI. Synthesis  1974,  563 
  • 3d Shinozaki H. Imaizumi M. Tajima M. Chem. Lett.  1983,  929 
  • 3e Meshram HM. Synthesis  1992,  943 
  • 3f Findlay JA. Tang CS. Can. J. Chem.  1967,  45:  1014 
  • 4a Brackman W. Smit P. J. Recl. Trav. Chim.  1963,  82:  757 
  • 4b Sato R. Itoh Y. Itep K. Nihina H. Goto T. Saito M. Chem. Lett.  1984,  1913 
  • 4c Erman MB. Snow JW. Williams MJ. Tetrahedron Lett.  2000,  41:  6749 
  • 4d Talukdar S. Hsu JL. Chou TC. Fang JM. Tetrahedron Lett.  2001,  42:  1103 
  • 4e Bandgar BP. Makone SS. Synth. Commun.  2006,  36:  1347 
  • 5a Karmarkar SN. Kelkar SL. Wadia MS. Synthesis  1985,  510 
  • 5b Blatter HM. Lukaszewski H. de Stevens G. J. Am. Chem. Soc.  1961,  83:  2203 
  • 5c Olah GA. Keumi T. Synthesis  1979,  112 ; and references cited therein
  • 5d Dauzonne D. Demerseman P. Royer R. Synthesis  1981,  739 
  • 5e Saednya A. Synthesis  1982,  190 
  • 5f Ganboa I. Palomo C. Synth. Commun.  1983,  13:  219 
  • 5g Capdevielle P. Lavigne A. Maumy M. Synthesis  1989,  451 
  • 5h Bose DS. Narsaiah AV. Tetrahedron Lett.  1998,  39:  6533 
  • 5i Kumar HMS. Reddy BVS. Reddy PT. Yadav JS. Synthesis  1999,  586 
  • 6a Wissmann H. Kleiner H.-J. Angew. Chem., Int. Ed. Engl.  1980,  19:  133 
  • 6b Escher R. Bünning P. Angew. Chem., Int. Ed. Engl.  1986,  25:  277 
  • For a brief review of the reagent, see:
  • 7a Llanes García AL. Synlett  2007,  1328 
  • 7b Schwarz M. Synlett  2000,  1369 
  • 8 Meudt A, Scherer S, and Nerdinger S. inventors; WO  2005070879.  ; Chem. Abstr. 2005, 143, 172649
  • 9 Holla W, Napierski B, and Rebenstock H.-P. inventors; DE  19802969.  ; Chem. Abstr. 1999, 131, 131507
  • 10 Meudt A, Scherer S, and Böhm C. inventors; WO  2005123632.  ; Chem. Abstr. 2005, 144, 69544
  • 11 Olah GA. Narang SC. Fung AP. Gupta B. Balaram G. Synthesis  1980,  657 
  • 12 Wilson BD. Burness DM. J. Org. Chem.  1966,  31:  1565 
  • 13 Adler M, Baeurle S, Bryant J, Chen M, Chou Y.-L, Hrvatin P, Khim S.-K, Kochanny M, Lee W, Mamounas M, Meurer Odgen J, Phillips GB, Selchau V, West C, Ye B, Yuan S, and Krueger M. inventors; WO 2008/071451  A1. 
14

General Procedure for the Synthesis of Nitriles from Aldehydes
To a mixture of aldehyde (0.01 mol), hydroxylamine hydrochloride (0.011 mol), and Et3N (0.011 mol) in DMF (10 mL) was added T3P (0.011 mol, 50% soln in EtOAc), and the mixture was stirred at 100 ˚C for 1-3 h. The completion of reaction was monitored by TLC (5% EtOAc in hexane). The mixture was cooled and carefully poured onto sat. aq NaHCO3 solution (40 mL) and extracted with EtOAc (2 × 25 mL). The combined organic phase was washed with H2O (1 × 25 mL), brine (1 × 25 mL), and dried over Na2SO4. On evaporating the solvent under vacuum, the nitrile was obtained in good yield and purity (Note: Aliphatic nitriles were extracted with Et2O or pentane).
Characterization Data for Compound 18
Off-white solid; mp 194.2-195.9 ˚C. ¹H NMR (400 MHz, DMSO-d 6): δ = 14.65 (br s, 1 H), 8.37 (s, 1 H), 8.01 (dd, 1 H, J = 8.8, 1.2 Hz), 7.81 (d, 1 H, J = 8.8 Hz), 3.88 (s, 3 H). ¹³C NMR (100 MHz, DMSO-d 6): δ = 165.7, 141.5, 127.7, 125.0, 123.2, 121.1, 119.0, 113.4, 112.1, 52.3. IR (KBr): 3286, 2242 (CN), 1721, 1433, 1240, 738. ESI-MS (APCI, negative mode) for C10H7N3O2: m/z = 200 [M - H]+. Anal. Calcd (%) for C10H7N3O2: C, 59.70; H, 3.51; N, 20.89. Found: C, 59.76; H, 3.55; N, 20.82.
Characterization Data for Compound 27
Pale yellow liquid. ¹H NMR (400 MHz, DMSO-d 6): δ = 3.17 (s, 2 H), 1.94 (t, 2 H), 1.64 (s, 3 H), 1.55-1.49 (m, 2 H), 1.43-1.40 (m, 2 H), 0.98 (s, 6 H). ¹³C NMR (100 MHz, DMSO-d 6): δ = 132.2, 127.7, 119.6, 38.6, 34.5, 32.1, 27.2, 19.5, 18.6, 15.3. IR (liquid film): 2930, 2243 (CN), 1463, 1382 cm. MS (GC) for C11H17N: m/z = 163 [M - H]+. Anal. Calcd (%) for C11H17N: C, 80.93; H, 10.50; N, 8.58. Found: C, 80.99; H, 10.57; N, 8.52.