Hydrochloric Acid → 3-(2-Methyl-4-n-hexyloxybenzoyl)benzonitrile

HRID 1720165Notes

Reaction equation

HRID 1720165 reaction equation
[Cl-].[Al+3].[Cl-].[Cl-].[C:5]([C:7]1[CH:8]=[C:9]([CH:13]=[CH:14][CH:15]=1)[C:10]([OH:12])=O)#[N:6].[CH2:16]([O:22][C:23]1[CH:24]=[C:25]([CH3:29])[CH:26]=[CH:27][CH:28]=1)[CH2:17][CH2:18][CH2:19][CH2:20][CH3:21].Cl>[N+](C1C=CC=CC=1)([O-])=O>[CH3:29][C:25]1[CH:24]=[C:23]([O:22][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])[CH:28]=[CH:27][C:26]=1[C:10]([C:9]1[CH:8]=[C:7]([CH:15]=[CH:14][CH:13]=1)[C:5]#[N:6])=[O:12]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 158753-Cyanobenzoic acidHCID 6451240Aluminum(III) ChlorideHCID 153542531-(Hexyloxy)-3-methylbenzene

Product 1

HCID 224203923-(2-Methyl-4-n-hexyloxybenzoyl)benzonitrileYield 32%

Reagents, catalysts & solvents 1

HCID 7416NitrobenzeneSolvent2×

Procedure

Anhydrous aluminium chloride (38.35 g) is added to a solution of the acid chloride prepared from 3-cyanobenzoic acid (36.3 g) as described in Example 26 and nitrobenzene (200 ml). A solution of 3-n-hexyloxytoluene (39.5 g) in nitrobenzene (50 ml) is added and the resulting mixture heated to 110°-120° C. for 3 hours. The reaction mixture is cooled and poured into a mixture of ice water (1,000 ml) and concentrated hydrochloric acid (100 ml). The mixture is extracted with ether (3×300 ml) and the combined extracts concentrated and the nitrobenzene removed by steam distillation. The resulting residue is dissolved in ether, dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue is chromatographed on silica gel (hexanes:ether; 70:30) to yield 3-(2-methyl-4-n-hexyloxybenzoyl)benzonitrile (21.1 g) as a dark brown oil and 3-(2-hydroxy-4-methylbenzoyl)benzonitrile, which is recrystallized from ethanol to give 5.78 g as a yellow solid (m.p. 126°-128°C.). The 3-(2-methyl-4-n-hexyloxybenzoyl)benzonitrile thereby obtained is heated under reflux in a mixture of acetic acid (160 g) and a solution of 75% sulfuric acid (160 g) for 1 hour. The cooled mixture is then poured into ice water (500 ml) and extracted with ether (3×200 ml). The extract is dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue is chromatographed on silica gel (hexanes:ether:acetic acid; 50:50:1). The main fraction is collected and concentrated in vacuo. The residual yellow solid is crystallized from heptane to yield 3-(4-n-hexyloxy-2-methylbenzoyl)benzoic acid (9.62 g) as yellow needles m.p. 136°-138° C.

Workup

  1. temperaturethe resulting mixture heated to 110°-120° C. for 3 hours
  2. temperatureThe reaction mixture is cooled
  3. extractionThe mixture is extracted with ether (3×300 ml)
  4. concentrationthe combined extracts concentrated
  5. customthe nitrobenzene removed by steam distillation
  6. dissolutionThe resulting residue is dissolved in ether
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue is chromatographed on silica gel (hexanes:ether; 70:30)

Sources & evidence

ORD record
ord-c5977d99a3814d7d9400434d73545673
Source dataset
uspto-grants-1996_04
Patent number
US05504244

Reaction notes

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