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DOI: 10.1055/s-2005-871967
A Facile and Efficient One-Pot Synthesis of Nitriles from Carboxylic Acids
Publication History
Publication Date:
13 July 2005 (online)
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Abstract
Direct transformation of aliphatic carboxylic acids to the corresponding nitriles can be easily performed with acetonitrile in the presence of sulfuric acid.
Key words
carboxylic acids - nitriles - acetonitriles - adamantane derivatives - one-pot procedure
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Similarly, when dicarboxamide 11 was subjected to the same reaction conditions, but the reaction time was reduced to 2 h, the mixture of 11, 12, and 4b was obtained in a 1:3:3 ratio.
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5b: 1H NMR: δ = 1.42-1.61 (12 H, m), 2.10-2.19 (6 H, m, with a distinguishable singlet at 2.11); 13C NMR: δ = 28.17 (d), 31.44 (t), 32.74 (s), 34.78 (t), 40.40 (t), 45.58 (t), 117.09 (s);
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References
General Procedure for the One-Pot Preparation of Nitriles. Concd H2SO4 (10 mmol) was added dropwise at r.t. to a well-stirred suspension of acid (1 mmol) in MeCN (5 mL) and then the mixture was stirred under reflux for the appropriate time (Table [1] ). The excess of acetonitrile was then evaporated and CH2Cl2 (15 mL) and H2O (15 mL) were added. The layers were separated and the water layer was extracted with a fresh portion of CH2Cl2. The combined organic layers were washed with brine, dried over MgSO4, and evaporated under reduced pressure to give the crude product, which was purified by chromatography using EtOAc-hexane as eluent.
111b: IR (KBr): 2919 (s), 2856 (m), 2252 (w), 2226 (w), 1453 (m), 1103 (m) cm-1; 1H NMR: δ = 1.71-1.77 (6 H, m), 2.00-2.08 (9 H, m); 13C NMR: δ = 26.92 (d), 35.56 (t), 39.75 (t), 125.01 (s).
144b: Mp 73-76 °C (lit. [15] 73-74 °C); IR (KBr): 2903 (s), 2850 (m), 2236 (w), 1442 (m), 1347 (m) cm-1; 1H NMR: δ = 1.58-1.77 (12 H, m), 2.00-2.06 (3 H, m), 2.09 (2 H, s, CH2); 13C NMR: δ = 28.14 (d), 31.98 (s), 32.12 (t), 36.14 (t), 41.62 (t), 117.74 (s).
199: Mp 154-156 °C; R f 0.44 (silica gel, EtOAc-hexane, 1:1). IR (KBr): 3273 (m), 2907 (s), 2856 (m), 1727 (s), 1696 (s), 1671 (s), 1470 (m), 1377 (m), 1289 (m), 1207 (m), 1016 (m) cm-1. 1H NMR: δ = 1.68-1.79 (6 H, m), 1.86-1.89 (6 H, m), 2.06-2.12 (3 H, m), 2.48 (3 H, s, CH3), 8.26 (1 H, br s, NH). 13C NMR: δ = 25.45 (q, 1 C), 27.69 (d, 3 C), 36.03 (t, 3 C), 38.48 (t, 3 C), 41.80 (s, 1 C), 173.51 (s, 1 C), 176.55 (s, 1 C). Anal. Calcd for C13H19NO2: C, 70.56; H, 8.65; N, 6.33. Found: C, 70.83; H, 8.63; N, 6.46.
2111: Mp 142-144 °C; R f 0.40 (silica gel, EtOAc-hexane, 1:1); IR (KBr): 3268 (m), 3175 (m), 2902 (s), 2845 (m), 1732 (s), 1531 (m), 1500 (m), 1238 (m), 1135 (m) cm-1; 1H NMR: δ = 1.60-1.75 (12 H, m), 1.98 (3 H, br s), 2.20 (2 H, s, CH2), 2.42 (3 H, s, CH3), 8.78 (1 H, br s, NH); 13C NMR: δ = 25.17 (q, 1 C), 28.43 (d, 3 C), 33.32 (s, 1 C), 36.51 (t, 3 C), 42.27 (t, 3 C), 51.50 (t, 1 C), 171.07 (s, 1 C), 172.67 (s, 1 C); Anal. Calcd for C14H21NO2: C, 71.46; H, 8.99; N, 5.95. Found: C, 71.84; H, 8.88; N, 6.04.