Hydrochloric Acid → 3-Chloro-5-(methylthio)benzonitrile

HRID 447820

Reaction equation

HRID 447820 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([Cl:10])[CH:9]=1)[C:5]#[N:6].[CH3:11][S-:12].[Na+].C(N(CC)C(C)C)(C)C.Cl>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[Cl:10][C:8]1[CH:7]=[C:4]([CH:3]=[C:2]([S:12][CH3:11])[CH:9]=1)[C:5]#[N:6]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 4378561Sodium methanethiolateHCID 159658933-Bromo-5-chlorobenzonitrile

Product 1

HCID 668786863-Chloro-5-(methylthio)benzonitrileYield 76.6%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

(Step 1) A mixture of 3-bromo-5-chlorobenzonitrile (4.0 g), sodium methanethiolate (1.42 g), Pd2(dba)3 (84 mg), Xantphos (106 mg) and N,N-diisopropylethylamine (4.78 g) was stirred in toluene (100 ml) at 90° C. for 9 hr. The reaction mixture was treated with 1N hydrochloric acid, and extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:20) to give 3-chloro-5-(methylsulfanyl)benzonitrile (2.6 g) as a solid.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:20)

Sources & evidence

ORD record
ord-ce758c7710584c07936b1fa8bf5ecaec
Source dataset
uspto-grants-2013_07
Patent number
US08481569B2

Linked notes

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