Pyridine → 7-Methoxynaphthalene-1-carbonitrile

HRID 1035588Notes

Reaction equation

HRID 1035588 reaction equation
[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([CH2:7][CH2:8][CH2:9][C:10]2=O)=[CH:5][CH:4]=1.C[Si]([C:18]#[N:19])(C)C.N1C=CC=CC=1.O=P(Cl)(Cl)Cl.[OH-].[Na+].ClC1C(=O)C(C#N)=C(C#N)C(=O)C=1Cl>C1(C)C=CC=CC=1.[Zn+2].[I-].[I-]>[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([CH:7]=[CH:8][CH:9]=[C:10]2[C:18]#[N:19])=[CH:5][CH:4]=1

Participants

9

Reactant 6

HCID 1049PyridineHCID 67752,3-Dichloro-5,6-dicyano-1,4-benzoquinoneHCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 812767-Methoxy-1,2,3,4-tetrahydronaphthalen-1-oneHCID 82115Trimethylsilyl cyanide

Product 1

HCID 113443927-Methoxynaphthalene-1-carbonitrileYield 78%

Reagents, catalysts & solvents 2

HCID 9883512zinc(II)iodideCatalystHCID 1140TolueneSolvent

Conditions

Temperature
45 °C

Procedure

7-Methoxy-1-tetralone (8.16 g, 46 mmol, 1 eq) and ZnI2 (0.365 g, 1 mmol, 0.025 eq) were dissolved in 25 ml of toluene and heated at 45° C. Trimethylsilylcyanide (TMSCN) (5.0 g, 50 mmol, 1.1 eq) is added over a period of 20 min, and all is refluxed for 3 h. After cooling the mixture at about 35° C., pyridine (5.5 ml, 69 mmol, 1.5 eq) and POCl3 (6.4 ml, 69 mmol, 1.5 eq) are added, and the mixture is boiled under reflux for another 6 h. Thereafter, 80 ml of a 3 N NaOH cooled at 3° C. is added over a period of 15 min. The aqueous phase is extracted with 48 ml of toluene, and the organic phase is washed twice with 40 ml of 1 N NaOH, once with 40 ml of water, three times with 40 ml of 3 N HCl, once with 40 ml of water, once with 40 ml of a saturated NaHCO3 solution and once with a saturated sodium chloride solution. After the addition of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) (8.41 g, 37 mmol, 0.8 eq) over 20 min, the organic phase is boiled under reflux for 2 h. After cooling, the precipitate was filtered off and washed twice with 32 ml of 1 N NaOH and once with 32 ml of a saturated sodium chloride solution. Drying of the precipitate yielded the desired product in a yield of 78%, 6.6 g.

Workup

  1. temperatureall is refluxed for 3 h
  2. temperatureAfter cooling the mixture at about 35° C.
  3. temperatureunder reflux for another 6 h
  4. additionis added over a period of 15 min
  5. extractionThe aqueous phase is extracted with 48 ml of toluene
  6. washthe organic phase is washed twice with 40 ml of 1 N NaOH, once with 40 ml of water, three times with 40 ml of 3 N HCl, once with 40 ml of water, once with 40 ml of a saturated NaHCO3 solution and once with a saturated sodium chloride solution
  7. temperatureunder reflux for 2 h
  8. temperatureAfter cooling
  9. filtrationthe precipitate was filtered off
  10. washwashed twice with 32 ml of 1 N NaOH and once with 32 ml of a saturated sodium chloride solution
  11. customDrying of the precipitate

Sources & evidence

ORD record
ord-ae86271b573f434c93060e5d4b338287
Source dataset
uspto-grants-2013_10
Patent number
US08546392B2

Reaction notes

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