Pyridine → Benzo[b]thiophene-6-carbonitrile

HRID 883603Notes

Reaction equation

HRID 883603 reaction equation
Br[C:2]1[S:6][C:5]2[CH:7]=[CH:8][CH:9]=[CH:10][C:4]=2[CH:3]=1.[N:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[Cu]C#N.C(N)CN>CN(C)C=O.O>[C:12]([C:10]1[C:4]2[CH:3]=[CH:2][S:6][C:5]=2[CH:7]=[CH:8][CH:9]=1)#[N:11].[C:16]([C:15]1[CH:14]=[CH:13][C:12]2[CH:3]=[CH:2][S:6][C:5]=2[CH:4]=1)#[N:11]

Participants

8

Reactant 4

HCID 1049PyridineHCID 3301EthylenediamineHCID 947862-Bromobenzo(b)thiopheneHCID 178418546HCID 178418546, compound

Product 2

HCID 21816574Benzo[b]thiophene-6-carbonitrileYield 41%HCID 218165751-Benzothiophene-4-carbonitrileYield 39%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of the isomeric bromobenzo[b]thiophene (14.2 g, 66.5 mmol) from Step B above in N,N-dimethylformamide (130 mL) were added pyridine (7.5 mL) and copper(I) cyanide (7.75 g). The reaction mixture was heated under reflux for 20 hours. The reaction solution was then cooled to 60° C. and poured into a solution of ethylene diamine in water. The resultant mixture was stirred for 30 minutes and extracted with diethyl ether and ethyl acetate. The combined organic extract was washed with 1:1 brine/water, dried over sodium sulfate and concentrated under reduced pressure. The crude product obtained was purified by flash column chromatography (95:5 to 91:9 hexanes/ethyl acetate) to give 4-cyanobenzo[b]thiophene (4.15 g, 39%) as a light yellow solid, and 6-cyanobenzo[b]thiophene (4.34 g, 41%) as a reddish oil: 1H NMR for 4-cyanobenzo[b]thiophene (CDCl3, 500 MHz) δ 8.10 (d, J=8.2 Hz, 1H), 7.74-7.70 (m, 2H), 7.62 (dd, J=5.5, 0.6 Hz, 1H), 7.43 (d, J=7.8 Hz, 1H); 1H NMR for 6-cyanobenzo[b]thiophene (CDCl3, 500 MHz) δ8.22 (app s, 1H), 7.90 (d, J=8.3 Hz, 1H), 7.72 (d, J=5.4 Hz, 1H), 7.59 (d, J=8.3 Hz, 1H), 7.42 (dd, J=5.4, 0.5 Hz, 1H).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureunder reflux for 20 hours
  3. extractionextracted with diethyl ether and ethyl acetate
  4. extractionThe combined organic extract
  5. washwas washed with 1:1 brine/water
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product obtained
  9. customwas purified by flash column chromatography (95:5 to 91:9 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-8ccd0542e12142f595cebddcb6c6b152
Source dataset
uspto-grants-2012_08
Patent number
US08236796B2

Reaction notes

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