4-(Nitrooxy)butan-1-ol synthesis

Yield: 72.5%

Reaction Conditions:

with methanol;sodium hydroxide;water at 20; for 1.75 h;

Steps:

3; 5
Example 3; Preparation of 4-Nitrooxybutan-l-ol (compound Ia); 4-Nitrooxybutan-l-ol butyrate (1350 g, 95 % w/w, 6.25 mol) was added at room temperature to a mixture of methanol (1930 ml) and water (515 ml). Sodium hydroxide (30 %, 911 g, 6.83 mol)0 was added with stirring over 45 min and the resulting reaction mixture was allowed to stir at room temperature for 1 hour. Sulphuric acid (5 %, 300 ml) was added which gave a pH of 7 - 8. Methanol was removed completely by vacuum distillation (80 - 110 mbar, inner temperature: 40 - 43 °C, jacket temperature: 60- 65 °C) . The methanol amount in the reaction mixture was checked by GC (result: 0.04 % related to 4-Nitrooxybutan-l-ol) .Water (10300 ml) was added to the aqueous residue and the resulting reaction mixture was extracted 3 times with hexane(1800 ml, 650 ml, 650 ml) to remove 4-nitrooxybutan-l-ol butyrate and 1, 4-dinitrooxybutane . The washed water layer was extracted 3 times with dichloromethane (3 x 5150 ml) . The combined organic layers were washed once with saturated sodium bicarbonate solution (1280 ml) and two times with water (1280 ml, 640 ml) . The resulting organic layer was concentrated to 4000 g (72.5 % of theory related to 4-nitrooxybutan-l-ol butyrate) of a 15.3 % w/w solution of the title compound. The purity according to GC was 99.7 %.; Example 5; Preparation of 4-Nitrooxybutan-l-ol by a continuous process; 1, 4-butandiol monobutyrate (1350 g, 95 % w/w, 6.25 mol) was added at room temperature to a mixture of methanol (1930 ml) and water (515 ml) . Sodium hydroxide (30 %, 911 g, 6.83 mol) was added with stirring over 45 min and the resulting reaction mixture was allowed to stir at room temperature for 1 hour. Sulphuric acid (5 %, 300 ml) was added which gave a pH of 7 -8. Methanol was removed completely by vacuum distillation (80 -110 mbar, inner temperature: 40 - 43 ⁰C, jacket temperature: 6065 ⁰C) . The methanol amount in the reaction mixture was checked by GC (result: 0.04 % related to 4-Nitrooxybutan-l-ol). Water (10300 ml) was added to the aqueous residue and the resulting reaction mixture was extracted 3 times with hexane(1800 ml, 650 ml, 650 ml) to remove 4-nitrooxybutan-l-ol butyrate and 1, 4-dinitrooxybutane . The washed water layer was extracted 3 times with dichloromethane (3 x 5150 ml) . The combined organic layers were washed once with saturated sodium bicarbonate solution (1280 ml) and two times with water (1280 ml, 640 ml) . The resulting organic layer was concentrated to 4000 g (72.5 % of theory related to 4-nitrooxybutyl butyrate) of a 15.3 % w/w solution of the title compound. The purity according to GC was 99.7 %.

References:

NICOX S.A. WO2009/723, 2008, A1 Location in patent:Page/Page column 23-24; 25