Condensation of aminoalcohols with salicylic acids; Salicyloxazolines SyntheticPage 230 (2005)
Submitted 30th Sep 2005, published 30th Sep 2005
Max Hammond
([email protected]),
A contribution from the Scott Group, Warwick
Chemicals Used
3,5-di-tert-butylsalicylic acid (TCI)
2-amino-2-methyl propan-1-ol (Aldrich)
Triphenylphosphine (Aldrich, recrystallized from hot hexane)
CCl4 (Aldrich, distilled from CaH2)
Triethylamine (Aldrich, distilled over CaH2)
Acetonitrile (Aldrich, distilled over CaH2)
Procedure
To 3,5-di-tert-butyl salicylic acid (2.5 g, 10 mmol) in a Schlenk vessel was added PPh3 (10.38 g, 4 eq), and the atmosphere in the vessel replaced with argon. Acetonitrile (25 ml), and then triethylamine (6 ml, 4 eq) were added, with stirring. 2 amino-2-methyl-1-propanol (0.89 g, 1 eq) was injected in a small volume of acetonitrile. CCl4 (10 ml, 10 eq) was added dropwise over 3 hours. The mixture was stirred for 48 hours, after which time the solution was filtered, washed through with Et2O, which caused a further precipitation, this precipitate was also removed by filtration. The solvents were removed in vacuo, and the product extracted with hexane (3 x 100 ml). The combined extracts were dried in vacuo, and the pale yellow powder was purified by flash chromatography on a silica column, eluted with hexane-ethyl acetate (50:1), affording the product as a pale yellow powder (1.4 g, 46%) after removal of solvent.
Author's Comments
We have synthesized a wide range of salicyloxazolines using this procedure, yields are variable between 70% and 10% depending on the species.
It is easier to add the Et2O gradually, with stirring; otherwise the precipitate formed is very sticky and hard to extract from.
Data
1H NMR 400 MHz (CDCl3): ppm 12.60 (s, 1H, OH), 7.54 (d, 4JHH = 2 Hz, 1H, ArH), 7.44 (d, 4JHH = 2 Hz, 1H, ArH), 4.09 (s, 2H, CH2), 1.46 (s, 9H, C(CH3)3), 1.40 (s, 6H, CH3) 1.32 (s, 9H, C(CH3)3)
Lead Reference
H. Vorbrüggen and K. Krolikiewicz, Tetrahedron Lett., 1981, 22, 4471-74.
Other References
H. Vorbrüggen and K. Krolikiewicz, Tetrahedron, 1993, 49, 9353-72.
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User comments on this page |
Max Hammond - 2 Dec 2005 10:19:00
We've been finding recently that if the product is extracted by stirring in hexane overnight, the yield is improved somewhat. |
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