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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;
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Publikationsverlauf

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

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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.

Key words

propylphosphonic anhydride - dehydration - nitriles - ­aldoximes - electrophilic activation

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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-¹. 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.