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

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.

propylphosphonic anhydride - dehydration - nitriles - ­aldoximes - electrophilic activation

References and Notes

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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.