Reduction of a nitrile
SyntheticPage 68
DOI:
Submitted: August 16, 2001, published: August 17, 2001
Authors
Stephen Caddick (s.caddick@sussex.ac.uk)
A contribution from
Chemicals
Substrate,
Lithium Aluminium Hydride (LAH),
Ether,
Sodium hydroxide
Lithium Aluminium Hydride (LAH),
Ether,
Sodium hydroxide
Procedure
The nitrile (510 mg, 4.76 mmoles) in ether was added to LAH (1.5 g, 39.5 mmoles) in ether (15 ml) and stirred at room temperature overnight. Sodium hydroxide (2.8 ml, 10% solution) was added at 0 oC and after 30 minutes, water (5 ml) was added to give a granular precipitate. The mixture was filtered and the precipitate washed copiously with ether. The combined, washed and dried organic layers were evaporated "in vacuo" to give the product as an oil (292 mg, 55%). .
Author Comments
Fairly straightforward for a LAH reduction, as always work-up is slightly problematic but this protocol works pretty well. The reaction has only been done a couple of times on this scale and is not optimised. In my experience reductions using LAH can be very dependent on the quality of reagent and sometimes heating is required to force reactions to completion.
Data
5.8, 2H, m, CH; 2.8, 4H, t, CH2NH2; 2.35, 2H, m; 2.0, 1H, m; 1.5, 4H, m;
Lead Reference
For a lead reference see: Rappoport Chemistry of the Cyano Group; Wiley: New York, 1970, pp. 307, 340
Keywords
Comments
My question is is it really necessory to use 10 equivalence of LAH for this reduction. Another suggestion I would like to give is that insted of adding 10% NaOH solution you can add saturated NaSO4 soultion at 0 deg C. This will help you in very easy and clean work up.
By raviraj hande on April 6, 2006
Such type of reduction gives better yield in THF as solvent.
By Gopal Gole on May 7, 2008
My experiences use saturated Potassium Sodium Tartrate (rochelle salts) to quench the solution and result in a granular precipitate,a far more easily filtered and consistent result than the use of Alkali Hydroxides for this step. Give it a try with a small aliquot to be sure. Happy chemistry !
By Mark Bertinetti on November 3, 2008
LAH Workup
Fieser conditions are the best: for n grams of LAH at 0 ºC add n mL of water drop-wise, then n mL of 15% NaOH solution, followed by 3n mL of water. Dilute with ether and stir 10 min, nice white ppt forms that is easily filtered through Celite, conc. and purify.
Fieser, L. F.; Fieser, M. Reagents for Organic Synthesis 1967, 581-595.
By Chris on December 9, 2011