Trichloroisocyanuric Acid → 2-Chloro-3-(chloromethyl)pyrazine

HRID 2427264Notes

Reaction equation

HRID 2427264 reaction equation
[CH3:1][C:2]1[C:7]([Cl:8])=[N:6][CH:5]=[CH:4][N:3]=1.[Cl:9]N1C(=O)N(Cl)C(=O)N(Cl)C1=O>C(Cl)(Cl)Cl.C(N)(=O)C1C=CC=CC=1>[Cl:9][CH2:1][C:2]1[C:7]([Cl:8])=[N:6][CH:5]=[CH:4][N:3]=1

Participants

5

Reactant 2

HCID 6909Trichloroisocyanuric AcidHCID 66769Pyrazine, 2-chloro-3-methyl-

Product 1

HCID 217924052-Chloro-3-(chloromethyl)pyrazineYield 43.7%

Reagents, catalysts & solvents 2

HCID 2331BenzamideCatalystHCID 6212ChloroformSolvent

Procedure

Prepare the title compound using the chlorination procedure as essentially described by Jeromin, G. E.; et al., DE3519364, 1986, and Russell, M. G. N.; et al. J. Med. Chem. 2005, 48, 1367-1383. Dissolve 2-methyl-3-chloropyrazine (24.3 g, 189 mmol) in CHCl3 (100 mL). Add benzamide (100 mg, 0.8 mmol) and heat to reflux. At reflux, add solid trichloroisocyanuric acid (17.6 g, 75.6 mmol) and continue to reflux for 96 h. Cool and filter through 200 g silica gel, eluting with methylene chloride. Purify by silica gel chromatography using a gradient of 35% chloroform/hexane to 60% chloroform/hexane over one hour. Obtain the title compound as a colorless oil, 5.39 g pure title compound and 9.4 g that is >70% desired product. 1H-NMR (CDCl3) δ 8.50 (d, 1H, J=2.2 Hz), 8.37 (d, 1H, J=2.6 Hz), 4.80 (s, 2H), 2.50 (s, 3H); GC/MS M=162+164.

Workup

  1. temperatureAt reflux
  2. temperatureto reflux for 96 h
  3. temperatureCool
  4. filtrationfilter through 200 g silica gel
  5. washeluting with methylene chloride
  6. customPurify by silica gel chromatography
  7. customover one hour

Sources & evidence

ORD record
ord-435025b1e82846269b550efaea99d20b
Source dataset
uspto-grants-2011_06
Patent number
US07968587B2

Reaction notes

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