Reaction #75432

Reaction equation

ammonium chloride

water

cyclooctanone

Hydroxylamine-O-sulfonic acid

→

2-Azacyclononanone

Yield 65.0%

Solvents

—

silicon oil

formic acid

formic acid

Conditions

Workup

1. 1
   OtherA 5 L three-neck round bottom flask was fitted with a heating mantle, an overhead mechanical stirrer, an addition funnel
2. 2
   Otherto form a white slurry
3. 3
   workup.ADDITIONAfter the addition
4. 4
   Otherthe addition funnel was replaced by a reflux condenser
5. 5
   Temperaturethe reaction was heated
6. 6
   Otherto give a brown solution
7. 7
   TemperatureAfter the solution was cooled to room temperature
8. 8
   ExtractionThe aqueous mixture was extracted with chloroform (3×1200 mL)
9. 9
   workup.ADDITIONwas added slowly
10. 10
    OtherThe chloroform layer was then separated
11. 11
    Dryingdried over anhydrous sodium sulfate
12. 12
    Otherevaporated under reduced pressure
13. 13
    Otherto afford a brown oil
14. 14
    OtherThe oil was placed in a 500 mL round bottom flask with a magnetic stirrer
15. 15
    Otherwas fitted with a short path vacuum distillation head
16. 16
    Otherequipped with a thermometer

Procedure

A 5 L three-neck round bottom flask was fitted with a heating mantle, an overhead mechanical stirrer, an addition funnel, and a thermometer. The reaction was performed under an argon atmosphere. Hydroxylamine-O-sulfonic acid (196.7 g, 1.74 moles, 1.10 equiv.) and formic acid (1 L) were charged into the round bottom flask and stirred to form a white slurry. A solution of cyclooctanone (200.0 g 1.58 moles, 1.0 equiv.) in formic acid (600 mL) was added dropwise to the white slurry via the addition funnel. After the addition, the addition funnel was replaced by a reflux condenser, and the reaction was heated to reflux (internal temperature about 105° C.) for 1 hour to give a brown solution. After the solution was cooled to room temperature, it was poured into a mixture of saturated aqueous ammonium chloride (1.5 L) and water (1.5 L). The aqueous mixture was extracted with chloroform (3×1200 mL). The combined chloroform layers were transferred into a beaker, and saturated sodium bicarbonate (2 L) was added slowly. The chloroform layer was then separated, dried over anhydrous sodium sulfate, and evaporated under reduced pressure to afford a brown oil. The oil was placed in a 500 mL round bottom flask with a magnetic stirrer. The round bottom flask was placed in silicon oil bath and was fitted with a short path vacuum distillation head equipped with a thermometer. A Cow-type receiver was connected to three 250 mL flasks. 2-Azacyclononanone (145 g, 65%, mp 64-69° C.) was obtained by vacuum distillation (fraction with head temperature range from 80 to 120° C. at pressures between 3.0 and 3.4 mmHg).

Source