Nitric Acid → 4-Chloro-5-nitro-2-(pyridin-3-yl)thiazole

HRID 2199222Notes

Reaction equation

[Cl:1][C:2]1[N:3]=[C:4]([C:7]2[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=2)[S:5][CH:6]=1.OS(O)(=O)=O.[N+:18]([O-])([OH:20])=[O:19].C([O-])(O)=O.[Na+]>>[Cl:1][C:2]1[N:3]=[C:4]([C:7]2[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=2)[S:5][C:6]=1[N+:18]([O-:20])=[O:19]

Participants

Reactant 4

HCID 944Nitric Acid

HCID 1118Sulfuric Acid

HCID 516892Sodium Bicarbonate

HCID 595806044-Chloro-2-(pyridin-3-yl)thiazole

Product 1

HCID 666452254-Chloro-5-nitro-2-(pyridin-3-yl)thiazoleYield 80.1%

Conditions

Temperature: 0 °C

Procedure

4-Chloro-2-(pyridin-3-yl)thiazole (1.00 g, 5.09 mmol) was placed in a dry flask and concentrated H2SO4 (2.50 g, 25.4 mmol) was added. The contents were cooled to 0° C., and fuming HNO3 (641 mg, 10.17 mmol) was slowly added. The mixture was stirred at 40° C. for 3 h and cooled to room temperature. The contents were slowly added to an ice-cold saturated aqueous solution of NaHCO3. The mixture was extracted with ethyl acetate (2×50 mL) and the extracts were combined, rinsed with brine and concentrated in vacuo to give 4-chloro-5-nitro-2-(pyridin-3-yl)thiazole as a peach-colored solid (985 mg, 80% yield): mp 110-112° C.; 1H NMR (300 MHz, CDCl3) 9.18 (d, J=2.1 Hz, 1H), 8.81 (dd, J=5.1, 1.8 Hz, 1H)), 8.27 (ddd, J=7.3, 4.2, 2.4 Hz, 1H), 7.49 (dd, J=7.8, 5.1 Hz, 1H); EIMS m/z 241 ([M+H])+.

Workup

temperaturecooled to room temperature
extractionThe mixture was extracted with ethyl acetate (2×50 mL)
washrinsed with brine
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-258cb6bd364a4e0b998901b96a240589
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09357780B2

Reaction notes

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