Reaction #56252

Reaction equation

ammonium hydroxide

crotonaldehyde

hydrogen chloride

5-chlorosalicylhydroxamic acid

→

7-chloro-2-methyl-3,3a-dihydro-2H, 9H-isoxazolo (3,2-b) (1,3) benzoxazin-9-one

Yield 67.0%

Solvents

tetrahydrofuran

water

Conditions

Workup

1. 1
   Otherare passed into the mixture at 20°-30° C
2. 2
   workup.DISSOLUTIONdissolves
3. 3
   TemperatureThe mixture is cooled in a water bath
4. 4
   workup.STIRRINGwith stirring
5. 5
   workup.ADDITIONto rise to about 50° C. during the alkali addition
6. 6
   Otherto remove as much tetrahydrofuarn as possible
7. 7
   OtherA solid precipitates
8. 8
   Temperaturewhile heating
9. 9
   workup.ADDITIONof water are added
10. 10
    Temperaturethe entire mixture is cooled to about 10° C. in an ice bath
11. 11
    FiltrationThe solid is filtered
12. 12
    Washwashed with water
13. 13
    Otherpulled dry
14. 14
    OtherThe cake is recrystallized from 800 ml
15. 15
    Otherboiling isopropanol refrigerated overnight
16. 16
    FiltrationThe crystals are filtered
17. 17
    Washwashed with cold isopropanol
18. 18
    Otherdried at about 100° C

Procedure

360 ml. of tetrahydrofuran is combined with 90 gm. of crotonaldehyde and placed in an ice bath. 100 gm. of hydrogen chloride are passed into the mixture at 20°-30° C. 158 gm. of 5-chlorosalicylhydroxamic acid is added in one portion and the mixture stirred at 25°-30° C. for about two hours until the solid dissolves. The mixture is cooled in a water bath and 400 ml. of concentrated ammonium hydroxide diluted with 400 ml. of water is added with stirring. The temperature of the mixture is allowed to rise to about 50° C. during the alkali addition and the mixture is then heated on a steam bath to about 90° C. and a vacuum applied to remove as much tetrahydrofuarn as possible. A solid precipitates while heating. 400 ml. of water are added and the entire mixture is cooled to about 10° C. in an ice bath. The solid is filtered and washed with water and pulled dry. The cake is recrystallized from 800 ml. boiling isopropanol refrigerated overnight. The crystals are filtered, washed with cold isopropanol and dried at about 100° C. 136 gm. 7-chloro-2-methyl-3,3a-dihydro-2H, 9H-isoxazolo (3,2-b) (1,3) benzoxazin-9-one (m.p. 144°-148° C.) for a yield of 67% is obtained.

Source