Reaction #312601

Reaction equation

potassium hydroxide

5-benzylthio-1-methylpyrazole-4-carboxylic acid

thionyl chloride

hydrochloric acid

hydroxyamine hydrochloride

→

aimed product

Yield 61.1%

5-benzylthio-1-methylpyrazole-4-carbohydroxamic acid

Yield 61.1%

Solvents

tetrahydrofuran

water

toluene

tetrahydrofuran

water

Conditions

Workup

1. 1
   workup.ADDITIONwere added
2. 2
   Temperaturerefluxed for 4 hours
3. 3
   OtherThe residue obtained
4. 4
   workup.DISTILLATIONby distilling off the solvent
5. 5
   workup.STIRRINGAfter further stirring at 3° C. for 1.5 hour
6. 6
   Extractionextracted with ethyl acetate
7. 7
   WashThe resulting ethyl acetate solution was washed with water
8. 8
   Dryingdried over anhydrous sodium suite
9. 9
   workup.DISTILLATIONthe solvent was distilled off
10. 10
    OtherThe resulting residue was purified with silica gel column chromatography (developing solution: n-hexane/ethyl acetate=1/1)

Procedure

In a suspension of 5-benzylthio-1-methylpyrazole-4-carboxylic acid (15.9 g, 64.0 mmol) in toluene (100 ml), thionyl chloride (11.4 g, 95.8 mmol) and N,N-dimethylformamide (0.1 g) were added, and refluxed for 4 hours. The residue obtained by distilling off the solvent was dissolved in tetrahydrofuran (40 ml), On the other hand, in a solution of hydroxyamine hydrochloride (13.3 g, 191 mmol) in water (40 ml), a solution of 85% potassium hydroxide (12.6 g, 191 mmol) in water (40 ml) was added at 5-15° C., and stirred at room temperature for 15 minutes. Then, the above-mentioned tetrahydrofuran solution was added dropwise at 3-15° C. After further stirring at 3° C. for 1.5 hour, the mixture was adjusted to pH 3-4 by adding 35% hydrochloric acid (20 ml) and extracted with ethyl acetate. The resulting ethyl acetate solution was washed with water, dried over anhydrous sodium suite, and the solvent was distilled off. The resulting residue was purified with silica gel column chromatography (developing solution: n-hexane/ethyl acetate=1/1) to obtain the aimed product (10.3 g). Resinous substance. Proton nuclear magnetic resonance chemical shift values δ (ppm) (in CDCl3) 3.42 (s, 3H), 3.95 (s, 2H), 6.93-7.01 (m, 2H), 7.20-7.28 (m, 3H), 8.04 (s, 1H), 9.76 (brs 1H).

Source