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Protection of an alcohol as a p-toluenesulfonate; tosylate (1,2:3,4-di-O-isopropylidene-6-O-p-toluenesulfonyl-alpha-D-galactose)

SyntheticPage 80
DOI: 10.1039/SP80
Submitted Aug 17, 2001, published Aug 17, 2001
Melanie Reich (m.t.reich@sussex.ac.uk)
A contribution from Caddick, Sussex


			Reaction Scheme: Protection of an alcohol as a p-toluenesulfonate

Chemicals Used

alcohol (1,2:3,4-di-O-isopropylidene-alpha-D-galactose) (prepared, 1 equiv.),
p-toluenesulfonyl chloride (Aldrich, 1.5 equiv./hydroxyl group),
pyridine (Avocado, 500 mL/mmol),
ice-water (18 mL/mol, then 730 mL/mol)

Procedure

The alcohol (1,2:3,4-di-O-isopropylidene-6-O-p-toluenesulfonyl-alpha-D-galactose) (143.6 g, 0.55 mol) was dissolved in pyridine (288 mL) and p-toluenesulfonyl chloride (145.4 g, 0.84 mol, 1.5 equiv.) was added in portions allowing the internal temperature to reach 60 ºC (on a large scale cooling in a cold water bath may be necessary). The reaction mixture was allowed to stir for 4 hours while slowly cooling to room temperature resulting in an orange suspension. A small amount of ice-water (10 mL) was added slowly (carefully on large scale) while cooling the mixture to 0 °C in an ice bath. This resulted in crystallisation of the desired product (after solvation of the pyridinium salt). Additional cold water (400 mL) was added slowly in portions until crystallisation no longer took place. The mixture was allowed to stir for 15 minutes after which the product, a pale orange solid, was collected by filtration and washed with a little petroleum ether. Purification was achieved by recrystallisation from methanol to yield the desired product as a white crystalline solid (183.1 g, 87 %). (Caution: large quantities of pyridine are employed. Dispose of all pyridine waste (including aqueous fraction) in an appropriate manner.)

Author's Comments

This procedure is very valuable for the preparation of 6-tosyl diisopropylidene protected D-galactose and other related carbohydrate derivatives, but is less useful for the formation of most other tosylates, as pyridine is used in vast excess. This is of an advantage in this case because the product can be forced to crystallise resulting in an easy work-up. In most other cases the product will not easily crystallise and removal of the excess pyridine will be extremely tedious if not impossible. In those cases standard conditions utilising catalytic pyridine and employing e.g. dichloromethane as the solvent is advised. Depending on the alcohol to be protected, the reaction may proceed best at low temperature, room temperature or elevated temperature. This procedure has been carried out on 5 to 100 g of starting material without experiencing any difficulties. It should however be noted that the smaller the scale (<5 g), the more difficult it is to force the product to crystallise upon quenching the reaction.

Data

1H NMR(300 MHz; CDCl3) 5.51 (1 H, d, J 5.0, H-1), 4.57 (1 H, dd, J 8.0 and 2.5, H-3), 4.25 (1 H, dd, J 5.0 and 2.5, H-2), 4.21 (1 H, dd, J 8.0 and 2.0, H-4), 3.82-3.77 (2 H, m, CH2), 3.63-3.61 (1 H, m, H-5), 2.38 (1 H, s, OH), 1.48 (3 H, s, CH3), 1.40 (3 H, s, CH3),1.26 (6 H, s, 2 x CH3)

Lead Reference

R. L. Whistler, M. L. Wolfrom, (T. Schmidt); Methods in Carbohydrate Chemistry I; Academic Press; New York; 1962; 190

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Keywords: carbohydrate, sugar, saccharide, tosyl, alcohol, p-toluenesulfonyl, tosylate, p-toluenesulfonate, 80

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  • Registered user Oct 22 2006 1:36PM

    pyridine will be protecting the acetonide functions from the tosylchloride.

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