Non-conjugated (beta-gamma unsaturated) alkenones by addition of organozinc intermediates (derived from allyl bromides) to nitriles; Pent-4-en-2-one and hept-1-en-4-oneSyntheticPage 165 (2001)
Submitted 25th Sep 2001, published 25th Sep 2001
A contribution from the Walton Group, St Andrews
Alkanenitrile (as received),
Zinc filings (or powder),
Silver acetate (as received),
glacial acetic acid (as received)
THF (distilled from Na/benzophenone),
ether (distilled from Na/benzophenone),
Allyl bromide (as received)
A zinc-silver couple was prepared: Zinc filings (83 g) were added to a refluxing solution of silver acetate (0.1 g) in acetic acid (200 cm3). The mixture was washed for a further 30 seconds, then cooled in an ice bath. The mixture was decanted, and the zinc-silver couple washed repeatedly with ether until no acetic acid was present (judged by smell). A zinc-silver dust was also prepared using this method.
To a mixture of acetonitrile (8.2 g; 10.4 cm3; 0.2 mol) and zinc-silver couple (filings; 18 g) in THF (5 cm3) and ether (45 cm3) was added, over a period of 2.5 hours, allyl bromide (32.4 g, 23.2 cm3; 0.27 mol). The mixture was then stirred overnight, then poured onto a mixture of ether (100 cm3), saturated aqueous ammonium chloride solution (200 cm3), and ice water (100 g). The mixture was stirred for 10 minutes, then the aqueous layer was separated and extracted with ether (3 x 75 cm3). The combined organic layers were dried, and the solvents removed under reduced pressure at room temperature. Careful bulb-to-bulb distillation (105 oC @ 760 mmHg) yielded pure pent-4-en-2-one as a colourless oil (6.59 g; 39%).
Hept-1-en-4-one was prepared (0.108 mole scale) in a similar manner. The solvent was ether (rather than ether/THF), zinc silver dust rather than filings was used, and purification was achieved using column chromatography (PE/DCM, as quickly as possible).
The addition of allyl bromide was at a rate sufficient to maintain slight reflux of the ether, although this was sometimes easier said than done, and this was just used as a rough guide to rate of addition.
The main problem with this reaction was the rapid isomerisation of the product to the conjugated ketone. The lead reference (Conia) reported both products to be stable, but we found them to be anything but; pent-1-en-4-one isomerised in less than a day. Distillation was also problematic, as the boiling point of the product and unreacted starting material were very similar, especially under reduced pressure, and best results were obtained by distilling carefully under atmospheric pressure.
Distillation of hept-1-en-4-one also provided problems due to the similar boiling points of butyronitrile and the product. Surprisingly, we were able to obtain pure product using column chromatography on silica. With PE/DCM, the product was fast running, and not isomerised.
The lead reference provided several examples of the reaction, in various solvents. Pentenone was the only example in which a solvent mix was used. It was reportedly necessary to use this mix to prevent the formation of oily salts on the surface of the zinc.
The reaction is quite a messy one, with a gloop forming after stirring, so it was sometimes easier to start pouring the aqueous mixture onto the reaction mixture, rather than the other way round.
The lead reference used 'coarse zinc powder'. We only had filings or fine powder available. Both worked reasonably, but care had to be taken with the powder to prevent too vigorous a reaction.
The preparations were repeated on the same scales, and with the same moderate yields.
Pent-4-en-2-one. 1H nmr, CDCl3: 2.17 (3H, s), 3.29 (2H, d, J = 6.6 Hz), 5.07-5.23 (2H, m), 5.80-6.08 (1H, m)
Hept-1-en-4-one. 0.92 (3H, t, J = 7.4 Hz), 1.60 (2H, m), 2.42 (2H, t, J = 7.4 Hz), 3.16 (2H, d, J = 6.9 Hz), 5.11-5.20 (2H, m), 5.86-5.98 (1H, m).
G. Rousseau and J. M. Conia, Tetrahedron Lett., 1981, 22, 653.
A. J. McCarroll, PhD Thesis, University of St. Andrews, 2000.
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