Nitric Acid → 4-Chloro-8-nitroquinoline

HRID 1612039Notes

Reaction equation

HRID 1612039 reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][CH:3]=1.S(=O)(=O)(O)O.[N+:17]([O-])([OH:19])=[O:18].[NH4+].[OH-]>>[Cl:1][C:2]1[C:11]2[C:6](=[C:7]([N+:17]([O-:19])=[O:18])[CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][CH:3]=1

Participants

5

Reactant 4

HCID 944Nitric AcidHCID 1118Sulfuric AcidHCID 14923Ammonium HydroxideHCID 691404-Chloroquinoline

Product 1

HCID 6104404-Chloro-8-nitroquinolineYield 59%

Procedure

4-Chloroquinoline (10.0 g, 61.3 mmol) was added in small portions to sulfuric acid (45 mL) taking care to maintain the temperature at or below 15° C. Then the solution was cooled and maintained at −5° C. during the addition of fuming nitric acid (9 mL). The mixture was allowed to warm to room temperature and stirred for an additional 3 h. The reaction mix was poured on ice and basified (pH 9) with NH4OH. The resulting precipitate was filtered, washed well with water, dried, and recrystallized from methanol to provide 7.5 g (59%) of 6a as golden-brown needles; mp 128-129° C. (lit.32mp 129-130° C.); 1H NMR (CDCl3) δ 7.67 (d, 1H, J=4.5), 7.75 (dd, 1H, J=8.6, J=7.6), 8.10 (dd, 1H, J=7.6, J=1.3), 8.48 (dd, 1H, J=8.6, J=1.3), 8.94 (d, 1H, J=4.5); 13C NMR (CDCl3) δ 123.0, 124.4, 126.5, 127.5, 128.3, 140.6, 143.2, 148.7, 152.1. The mother liquor was evaporated and chromatographed in 19:1 hexanes-ethyl acetate, to provide 2.05 g (16%) of the 5-nitro isomer 6d as a very light yellow solid; mp 144-146° C. (lit.31 mp 150° C.); 1H NMR (CDCl3) δ 7.65 (d, 1H, J=4.7), 7.82 (m, 2H), 8.35 (dd, 1H, J=2.5, J=7.3), 8.90 (d, 1H, J=4.7); 13C NMR (CDCl3) δ 118.2, 123.4, 125.1, 128.8,134.2,135.6, 139.1,149.7,151.2.

Workup

  1. temperatureto maintain the temperature at or below 15° C
  2. temperatureThen the solution was cooled
  3. additionThe reaction mix
  4. filtrationThe resulting precipitate was filtered
  5. washwashed well with water
  6. customdried
  7. customrecrystallized from methanol

Sources & evidence

ORD record
ord-794774febdfa43db95574df37647dbc4
Source dataset
uspto-grants-2006_01
Patent number
US06992089B2

Reaction notes

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