Nitric Acid → Methyl 5-chloro-2-ethyl-3-nitrobenzoate

HRID 1959289Notes

Reaction equation

HRID 1959289 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:12][CH3:13])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].OS(O)(=O)=O.[N+:19]([O-])([OH:21])=[O:20].O=S(Cl)Cl>CO>[Cl:1][C:2]1[CH:3]=[C:4]([N+:19]([O-:21])=[O:20])[C:5]([CH2:12][CH3:13])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8]

Participants

6

Reactant 4

HCID 944Nitric AcidHCID 1118Sulfuric Acid2×HCID 24386Thionyl ChlorideHCID 59382453Methyl 5-chloro-2-ethylbenzoate

Product 1

HCID 70872923Methyl 5-chloro-2-ethyl-3-nitrobenzoateYield 98.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
-2.5 °C

Procedure

A solution of methyl 5-chloro-2-ethylbenzoate (5.12 g, 25.77 mmol) in concentrated H2SO4 (31 ml, 587 mmol) was cooled to −5° C. in an acetone/ice bath in air. A mixture of concentrated nitric acid (2.15 ml, 33.51 mmol) and concentrated H2SO4 (2 ml, 37.52 mmol) was added dropwise to the reaction mixture at −5 to 0° C. over 15 minutes. The pale yellow reaction mixture was stirred at −5 to 0° C. for 1 hour before being poured onto ice (500 ml) and this was extracted with EtOAc (3×100 ml). The combined organic phases was washed with deionized water (100 ml) and then brine (100 ml). The organic phase was dried over MgSO4, filtered and concentrated under reduced pressure. LCMS and NMR showed ˜30% hydrolysis of the ester. The crude material was dissolved in Methanol (30 ml) and cooled to 0° C. under nitrogen where SOCl2 (2.25 ml, 30.93 mmol) was added slowly. The reaction mixture was then heated to reflux for 6 hours before being concentrated under reduced pressure to give 6.18 g (98.4%) of methyl 5-chloro-2-ethyl-3-nitrobenzoate as an orange oil. Product contained 1:1 mixture of 3-nitro:6-nitro isomers along with some ethyl ester which was suitable for use without any further purification.

Workup

  1. additionwas added dropwise to the reaction mixture at −5 to 0° C. over 15 minutes
  2. additionbefore being poured onto ice (500 ml)
  3. extractionthis was extracted with EtOAc (3×100 ml)
  4. washThe combined organic phases was washed with deionized water (100 ml)
  5. dry with materialThe organic phase was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. custom˜30% hydrolysis of the ester
  9. additionwas added slowly
  10. temperatureThe reaction mixture was then heated
  11. temperatureto reflux for 6 hours
  12. concentrationbefore being concentrated under reduced pressure

Sources & evidence

ORD record
ord-adfc66519db641b6bfe01bce5ca0de40
Source dataset
uspto-grants-2013_04
Patent number
US08410088B2

Reaction notes

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