2,6-DIETHYLPHENOL

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2,6-diethylphenol (3.80 g, 25.3 mmol) in acetic acid (30 mL) hexamethylenetetraamine (5.3 g, 37.9 mmol) is added and the mixture is heated to 120° C. A first fraction of the solvent is distilled off (Dean-Stark), then the mixture is refluxed for 3 h. The mixture is cooled to rt, diluted with water (100 mL) and extracted twice with EA (2×200 mL). The organic extracts are washed with sat. aq. NaHCO3, dried and the solvent is removed in vacuo. The crude product is purified by column chromatography eluting with DCM containing 2% of methanol to give 3,5-diethyl-4-hydroxybenzaldehyde (1.8 g) as colourless solid; 1H NMR (CDCl3): δ 9.85 (s, 1H), 7.57 (s, 2H), 5.32 (s, 1H), 2.69 (q, J=7.6 Hz, 2H), 1.30 (t, J=7.6 Hz, 3H). A first fraction of the solvent is distilled off (Dean-Stark) the mixture is refluxed for 3 h The mixture is cooled to rt diluted with water (100 mL) extracted twice with EA (2×200 mL) The organic extracts are washed with sat. aq. NaHCO3 dried the solvent is removed in vacuo The crude product is purified by column chromatography eluting with DCM containing 2% of methanol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2,4-diamino-5-bromomethylpyrimidine was reacted with 2,6-diethylphenol using the experimental conditions described in Example 1. 2,4-diamino-5-(3,5-diethyl-4-hydroxybenzyl)pyrimidine was obtained in a yield of approximately 65%.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2,4-Diamino-5-hydroxymethylpyrimidine (1.4 g.), prepared as in Example 1, and 2,6-diethylphenol (1.6 g.) in toluene-4-sulphonic acid (10 g.) containing conc. hydrochloric acid (3 ml.) were heated on the steam-bath for 6 hours. The solution was cooled, diluted with ether and the ether decanted. The residue was treated with a soln. of sodium hydrogen carbonate and the solid filtered off. Recrystallisation from aqueous ethanol gave colourless needles of 2,4-diamino-5-(3,5-diethyl-4-hydroxybenzyl)pyrimidine, m.p. 200°-202° C. were heated on the steam-bath for 6 hours The solution was cooled the ether decanted The residue was treated with a soln of sodium hydrogen carbonate and the solid filtered off Recrystallisation from aqueous ethanol