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Nitrile reduction using Pd/C; primary amine

SyntheticPage 262
DOI: 10.1039/SP262
Submitted Apr 13, 2007, published Apr 16, 2007
Tim Snape (t_snape@hotmail.com)
A contribution from Snape Group, Manchester


			Reaction Scheme: Nitrile reduction using Pd/C

Chemicals Used

3,4-Dimethoxyphenylacetonitrile (Aldrich, 98%)
10% Palladium on carbon (Aldrich)
Solvents and conc. HCl (Analytical Reagent Grade)

Procedure

3,4-Dimethoxyphenylacetonitrile (2 g, 11.3 mmol) was placed in a 1L single-neck round-bottomed flask containing a magnetic stirrer bar and was dissolved in MeOH (225 mL). Concentrated HCl (9.4 mL) and 10% Pd/C (1 g) were added and the flask was sealed with a new septum. The air was evacuated with a diaphragm pump through the septum using a needle. A balloon of hydrogen replaced the diaphragm pump and the evacuation process was repeated once more. The reaction was left to stir at room temperature for 2 hours. The reaction mixture was filtered through a pad of celiteĀ® in a sintered funnel under a blanket of nitrogen; CARE! DO NOT ALLOW Pd TO DRY OUT IN AIR. The celite was washed with MeOH (100 mL) and the solvents were removed under reduced pressure. The resulting pale brown oil was suspended in DCM (50 mL) and 2M NaOH (20 mL) added. The layers were separated and the organic layer washed washed with 2M NaOH (20 mL). The combined aqueous layers were extracted with DCM (20 mL), dried (MgSO4) and the solvent was removed under reduced pressure to yield the desired amine as an off-white solid (1.98 g, 97%) which was very pure by NMR.

Author's Comments

The difficulty in sourcing the product 2-(3,4-dimethoxyphenyl)ethylamine from commercial suppliers led to the procedure being developed. Current literature methods are plagued with contamination by dimer and trimer formation, including those that claim not to produce these products (see lead ref.). Higher dilution and catalyst loading, along with the use of HCl to protonate the amine as it forms helps to prevent these by-products. CARE! must be taken when filtering off the palladium, especially on larger scale.

Data

1H NMR (300 MHz, CDCl3) 1.68 (2H, br. s), 2.70 (2H, t, J=6.8), 2.95 (2H, t, J=6.8), 3.85 (3H, s), 3.87 (3H, s), 6.72 (1H, s), 6.73 (1H, d, J=7.7), 6.80 (1H, d, J=7.7)

Lead Reference

K. Diker, M. Doe de Maindreville and J. Levy, Tetrahedron Lett, 1995, 2497-2500.

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Keywords: nitrile reduction, Pd catalysed hydrogenation, amines

Post new comment
  • Registered user Veeresha Sharma P MMar 20 2008 11:03AM

    Is there any effect of methoxy groups on yeild? if any effect of electoron withdrawing groups

  • Registered user Colin SwinburneJun 30 2008 4:04PM

    The difficulty in sourcing this material is because it comes under the UK Home Office Misuse of Drugs Act 1971 Schedule 1 paragraph 1 (d) as a controlled substance. Be aware that you should have a licence. www.drugs.gov.uk/drugs-laws/licensing

  • Registered user Mark BertinettiNov 4 2008 7:03PM

    In the USA, this compound is not regulated because even though it has positional isomer similarities to compounds convertable to abusable substances, the Federal Laws do not interfere with its sourcing...presently.

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