Reaction #640544

Reaction equation

sodium nitrite

3-amino-2-methylbenzoic acid

urea

sulfuric acid

nitrite

→

yellow solid

Yield 36.0%

3-Hydroxy-2-methylbenzoic Acid

Yield 36.0%

Solvents

—

ice water

water

water

Conditions

Workup

1. 1
   workup.ADDITIONwas added to the flask
2. 2
   Temperaturethe resulting slurry was cooled below 15° C. in an ice bath
3. 3
   workup.STIRRINGAfter stirring at 0-5° C. for 30 min.
4. 4
   OtherReaction
5. 5
   workup.WAITwas left
6. 6
   workup.STIRRINGstirring for 30 min
7. 7
   ExtractionThe reaction mixture was extracted with diethyl ether (3×)
8. 8
   ConcentrationThe organic extracts were concentrated to approximately one-fourth the original volume
9. 9
   Extractionextracted with 25 mL 1N sodium hydroxide solution
10. 10
    OtherThe layers were separated
11. 11
    ExtractionThe acidified aqueous layer was then extracted with diethyl ether (3×)
12. 12
    Dryingdried (MgSO4)
13. 13
    Concentrationconcentrated
14. 14
    Otherto yield a reddish-colored oil
15. 15
    OtherPurification by flash chromatography on silica gel using a gradient of 0-7% methanol/methylene chloride

Procedure

A one-necked 100 mL round-bottomed flask (magnetic stirring) was charged with 1.0 gram (6.6 mM) 3-amino-2-methylbenzoic acid. A warm mixture of 2.3 mL conc. sulfuric acid in 4.3 mL water was added to the flask, the resulting slurry was cooled below 15° C. in an ice bath, and 6.6 grams of ice was added. The reaction mixture was treated via subsurface addition with a solution of 0.6 gram (8.6 mM) sodium nitrite in 6.6 mL ice water with the reaction temperature maintained at 0-5° C. during the addition. After stirring at 0-5° C. for 30 min., a few crystals of urea were added to decompose the excess nitrite. The reaction mixture was then poured into a room temperature solution of 23.8 grams (102.3 mM) copper (II) nitrate hemipentahydrate in 200 mL water. With vigorous stirring, the reaction mixture was treated with 0.9 gram (6.0 mM) copper (I) oxide. The reaction mixture foamed and changed from turquoise blue to dark green in color. Reaction was left stirring for 30 min. The reaction mixture was extracted with diethyl ether (3×), and the organic extracts were combined. The organic extracts were concentrated to approximately one-fourth the original volume, then extracted with 25 mL 1N sodium hydroxide solution. The layers were separated, and the dark-red aqueous layer was acidified to pH=2 using 1N hydrochloric acid solution. The acidified aqueous layer was then extracted with diethyl ether (3×), and the ether extracts were combined, dried (MgSO4), and concentrated to yield a reddish-colored oil. Purification by flash chromatography on silica gel using a gradient of 0-7% methanol/methylene chloride afforded 0.39 grams (36%) of a yellow solid.

Source