Condensation of cyclohexylamine and acetophenone; N-(1-Phenylethylidene)cyclohexanamine
SyntheticPage 752
DOI:
10.1039/SP752
Submitted Jul 10, 2014, published Aug 11, 2014
Christopher Kelly (
christopher.b.kelly@uconn.edu), Michael Mercadante (
michael.mercadante@uconn.edu), Nicholas Leadbeater (
nicholas.leadbeater@uconn.edu), Leon Tilley (
ltilley@stonehill.edu)
A contribution from
Tilley Group
Chemicals Used
Cyclohexylamine (ReagentPlus®, 99% Sigma Aldrich)
Acetophenone (ReagentPlus®, 99% Sigma Aldrich)
p-Toluenesulfonic Acid (ACS reagent, ≥98.5% Sigma Aldrich)
Benzene (ACS reagent, ≥99.0% Sigma Aldrich)
Procedure
To a 100 mL one-neck round bottom flask equipped with stirbar, was added benzene (50 mL), cyclohexylamine (5.21g, 0.0525 mol, 1.05 equiv), acetophenone (6.01 g, 0.050 mol, 1 equiv, 1 M) and p-toluenesulfonic acid monohydrate (0.0951 g 0.00050 mol, 0.01 equiv). The flask was equipped with a graduated Dean-Stark trap along with a reflux condenser.1 The reaction mixture was heated to reflux in a 120 oC oil bath and stirred via a magnetic stir plate. The reaction mixture was allowed to reflux until 1 equivalent of water was observed in the trap (≈ 0.9 mL). Upon completion the reaction mixture was cooled to room temperature and the benzene was removed in vacuo by rotary evaporation. p-Toluenesulfonic acid was precipitated out by diluting the mixture with pentane. The fine precipitate was filtered, followed by removal of the solvent in vacuo by rotary evaporation. The crude imine was then purified via vacuum distillation2,3 (b.p. 96-99 oC @ 0.1 mmHg) giving the pure N-(1-phenylethylidene)cyclohexanamine as a clear, colorless oil.4.
Author's Comments
1. To ensure that the vapor made it to the condenser, the Dean-Stark trap was insulated with a layer of glass wool.
2. Residual cyclohexamine would often distill at lower temperatures (20-30 oC)
3. Use of SiO2 or similar purification procedures is not advisable as the imines are unstable in the presence of acidic media (will revert to the ketone and the amine
4. Long term storage (> 2 weeks) of the imines requires either storage in a dry non-polar solution (e.g. pentane and MgSO4) or storage in a moisture free environment such as a glovebox or desiccator. Exposure to atmospheric conditions will result in slow be steady hydrolysis back to the ketone and amine.
Data
1H NMR (400 MHz, CDCl3) d ppm 1.26 - 1.45 (m, 3 H) 1.56 (qd, J = 12.00, 3.00 Hz, 2 H) 1.65 - 1.74 (m, 3 H) 1.80 - 1.88 (m, 2 H) 2.25 (s, 3 H) 3.49 (spt, J = 4.80 Hz, 1 H) 7.33 - 7.39 (m, 3 H) 7.75 (dd, J = 6.83, 2.73 Hz, 2 H) 13C NMR (125 MHz, CDCl3) d ppm 15.31 (CH3) 25.05 (CH2) 26.01 (CH2) 33.77 (CH2) 60.02 (CH) 126.82 (CH) 128.27 (CH) 129.22 (CH) 142.06 (C) 162.39 (C) GC-MS (EI) 201 ([M]+, 20%), 200 ([M-1]+, 51%), 186 (100%), 172 (19%), 158 (47%), 146 (27%), 144 (26%), 130 (29%), 120 (68%), 117 (17%), 104 (94%), 91 (16%), 77 (37%), 55 (24%), 41 (19%).
Lead Reference
Mercadante, M.; Kelly, C. B.; Hamlin, T.A., Delle Chiaie, K.; Drago, M.; Duffy, K.; Dumas, M.; Fager, D.; Glod, B.; Hansen, K.; Hill, C.; Leising, R.; Lynes, C.; MacInnis, A.; McGohey, M.; Murray, S.; Piquette, M.; Roy, S.; Smith, R.; Sullivan, K.; Truong, B.; Gorbatyuk, V.; Vailonis, K.; Leadbeater N. E.; Tilley L. J. Chem. Sci. 2014 DOI: 10.1039/C4SC01732C
Other References
Watson, J. M.; Irvine, J. L.; Roberts, R. M. J. Am. Chem. Soc., 1973, 95, 3348.
Supplementary Information
H NMR (cyclohexyliminehnmr.jpg)
C13 NMR (cyclohexyliminec13.jpg)
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Keywords: amines, condensation, imines, ketones
