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Substitution of hydroxy by iodide in phthalic anhydride protected phenylglycinol; (R)-2-(2-iodo-1-phenylethyl)isoindoline-1,3-dione

SyntheticPage 613
DOI: 10.1039/SP613
Submitted Jul 10, 2013, published Jul 12, 2013
Nikola P. Chmel (N.Chmel@warwick.ac.uk), Pratik Gurnani (pratik.gurnani@warwick.ac.uk)
A contribution from Scott group, Warwick University


			Reaction Scheme: <IMG src="/images/empty.gif">Substitution of hydroxy by iodide in phthalic anhydride protected phenylglycinol<IMG src="/images/empty.gif">

Chemicals Used

(R)-2-(2-hydroxy-1-phenylethyl)isoindoline-1,3-dione (Prepared in house, see page 609)
Imidazole (Aldrich)
Triphenylphosphine (Aldrich)
Iodine (Acros)
THF (distilled over potassium)

Procedure

(R)-2-(2-hydroxy-1-phenylethyl)isoindoline-1,3-dione (1.0 g, 3.7 mmol) was dissolved in dry THF (50 ml) under argon and cooled in an ice/water bath. Imidazole (0.97 g, 14.1 mmol), triphenylphosphine (2.62 g, 10.0 mmol) and iodine (2.44 g, 9.6 mmol) were added in that order. The resulting mixure was stirred for 1 h at 0°C and then at ambient temperature for 2 d. The reaction was quenched with a saturated solution of sodium thiosulphate (40 ml) and brine (40 ml). The aqueous layer was extracted with DCM (30 ml) and the combined organic layers were dried over anhydrous magnesium sulphate. The solvents were removed under reduced pressure and the residue was purified on silica using DCM as eluent. Product used as is without further purification. Yield 0.5 g (<37%).

Author's Comments

A second attempt at column purification and various other conditions led to no inprovement in contamination with triphenylphosphine oxide (see 1H NMR) but this was sufficiently good for subsequent reactions. If this is thhe case for you then just run th eone column as above.

Data

1H NMR (400 MHz, 298 K, CDCl3) δH 7.89 – 7.81 (2H, m, Pht), 7.78 – 7.68 (2H+, m, Pht+P(O)Ph3), 7.57 – 7.48 (2H+, m, Ph+ P(O)Ph3), 7.48 – 7.40 (3H, m, Ph), 7.39 – 7.28 (3H, m), 5.56 (1H, dd, 3JHH = 11.5 Hz, 2JHH = 5.3 Hz, CH2), 4.53 (1H, dd, 3JHH = 11.4 Hz, 3JHH = 10.4 Hz, CH), 3.84 (1H, dd, 3JHH = 10.3 Hz, 2JHH = 5.3 Hz, CH2).

MS (ESI+) m/z 250.1 ([M-I]+)

IR (cm-1) ν 3457, 1772, 1700, 1611, 1495, 1467, 1388, 1358, 1266, 1185, 1172, 1120, 1065, 1040, 1013, 999, 877, 838, 793, 765, 719, 698


Lead Reference

D. L. J. Clive, J. Peng, S. P. Fletcher, V. E. Ziffle and D. Wingert, Journal of Organic Chemistry, 2008, 73, 2330-2344. http://dx.doi.org/10.1021/jo7026307

Supplementary Information

1H NMR (1H NMR.jcamp)

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Get structure file (.cdx, .sk2, .mol)

Keywords: alcohols, amines, aromatics/arenes, Iodination, phthalic anhydride, protecting group, substitution

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