Nitric Acid → 1,1,1-Trichloroethane

HRID 374253Notes

Reaction equation

HRID 374253 reaction equation
[C:1](N[C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=[O:10])=[C:7](C)[CH:6]=1)(=O)C.[N+]([O-])(O)=[O:16].BrBr.BrN1[C:26](=[O:27])[CH2:25][CH2:24][C:23]1=O.BrN1[C:36](C)([CH3:37])[C:34](=O)N(Br)C1=O.[C:40]([Cl:44])(Cl)([Cl:42])[Cl:41]>C(Cl)(Cl)Cl.C(#N)C>[Cl:41][C:40]([Cl:44])([Cl:42])[CH3:1].[C:26]([O:27][O:11][C:9](=[O:10])[C:8]1[CH:7]=[CH:6][CH:5]=[CH:13][CH:12]=1)(=[O:16])[C:25]1[CH:37]=[CH:36][CH:34]=[CH:23][CH:24]=1

Participants

10

Reactant 6

HCID 944Nitric AcidHCID 5943Carbon TetrachlorideHCID 64791,3-Dibromo-5,5-dimethylhydantoinHCID 24408BromineHCID 67184N-bromobutanimideHCID 27352244-Acetamido-2-methylbenzoic acid

Product 2

HCID 62781,1,1-TrichloroethaneHCID 7187Benzoyl Peroxide

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6342AcetonitrileSolvent

Procedure

4-Acetylamino-2-methylbenzoic acid (Peltier) is converted into the 5-nitro compound by treatment with cold fuming nitric acid. The reaction mix was poured into crushed ice and the solid product collected by filtration and purified by recrystallization from DMF/water or by silica chromatography. The acetamide is removed by alkaline hydrolysis with 1-10% NaOH solution in 90% ethanol. The reaction mixture was added to excess dilute HCl and the solvent evaporated. The crude acid is esterified with satd. methanolic HCl at room temperature for several days. After removal of solvent the product is partitioned between ethyl acetate and satd. sodium bicarbonate. After washing with water the organic phase is evaporated and the residue purified by silica chromatography. The nitro group is reduced to the amino using hydrogen and palladium on carbon in ethanol or DMF. After filtration through celite and evaporation, the crude diamine is converted to the methyl 2-amino-6-methylbenzimidazole-5-carboxylate using cyanogen bromide in methanol at reflux. The mixture is cooled and poured into satd. aq. sodium bicarbonate and the solid product filtered and purified by recrystallization. The exocyclic amino group is acylated by refluxing with phthaloyl dichloride in pyridine followed by reaction of the diazepine with pyrazole in refluxing acetonitrile according to the method of Katritzky. The compound is reacted with either bromine or N-bromosuccinimide or 1,3-dibromo-5,5-dimethylhydantoin either neat or in carbon tetrachloride or chloroform or 1,1,1-trichloroethane with the aid of a high intensity sun lamp and/or benzoyl peroxide, to provide the benzylic bromide. It is possible to acylate the diazepine further with isobutryl chloride in pyridine to produce a triply acylated benzimidazole species. This is normally done prior to the bromination.

Workup

  1. additionThe reaction mix
  2. additionwas poured
  3. custominto crushed ice
  4. filtrationthe solid product collected by filtration
  5. custompurified by recrystallization from DMF/water or by silica chromatography
  6. customThe acetamide is removed by alkaline hydrolysis with 1-10% NaOH solution in 90% ethanol
  7. additionThe reaction mixture was added to excess dilute HCl
  8. customthe solvent evaporated
  9. waitmethanolic HCl at room temperature for several days
  10. customAfter removal of solvent the product
  11. customis partitioned between ethyl acetate
  12. washAfter washing with water the organic phase
  13. customis evaporated
  14. customthe residue purified by silica chromatography
  15. filtrationAfter filtration
  16. customthrough celite and evaporation
  17. temperatureat reflux
  18. temperatureThe mixture is cooled
  19. additionpoured into satd
  20. filtrationaq. sodium bicarbonate and the solid product filtered
  21. custompurified by recrystallization
  22. temperatureby refluxing with phthaloyl dichloride in pyridine
  23. customfollowed by reaction of the diazepine with pyrazole

Sources & evidence

ORD record
ord-78d2db6b065b4f25b8deb8a98034ad55
Source dataset
uspto-grants-1992_11
Patent number
US05166315

Reaction notes

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