Toluene → 3,4-Dimethoxybenzonitrile

HRID 2253546Notes

Reaction equation

HRID 2253546 reaction equation
[C-]#N.[Na+].C1(C)C=CC=CC=1.C[NH:12][CH2:13][CH2:14]NC.Br[C:18]1[CH:19]=[C:20]([O:26][CH3:27])[C:21]([O:24][CH3:25])=[CH:22]C=1>N.[Cu]I>[CH3:25][O:24][C:21]1[CH:22]=[C:14]([CH:18]=[CH:19][C:20]=1[O:26][CH3:27])[C:13]#[N:12]

Participants

7

Reactant 4

HCID 1140TolueneHCID 8070N,N'-DimethylethylenediamineHCID 8929Sodium CyanideHCID 76114Benzene, 4-bromo-1,2-dimethoxy-

Product 1

HCID 748423,4-DimethoxybenzonitrileYield 91%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 222AmmoniaSolvent

Conditions

Temperature
110 °C

Procedure

A Schlenk tube was charged with NaCN (204 mg, 4.16 mmol), CuI (66 mg, 0.35 mmol, 10 mol %/D), and KI (114 mg, 0.687 mmol, 20 mol %), briefly evacuated and backfilled with argon three times. Anhydrous toluene (2.4 mL), N,N′-dimethylethylenediamine (370 μL, 3.48 mmol), and 4-bromoveratrole (500 μL, 3.46 mmol) were added under argon. The Schlenk tube was sealed with a Teflon valve and the reaction mixture was stirred at 110° C. for 24 h. The resulting suspension was allowed to reach room temperature, diluted with 30% aq ammonia (2 mL), and extracted with ethyl acetate (4×4 mL). The combined organic phases were dried over MgSO4, concentrated, and the residue was purified by distillation at reduced pressure (bp 160° C. @1 Torr) to provide the desired product as pale yellow solid (500 mg, 91% yield). Mp 60-62° C. (lit. 63.0-63.5° C., See Murahashi, S.-I.; Naota, T.; Nakajima, N. J. Org. Chem. 1986, 51, 898). 1H NMR (400 MHz, CDCl3, J values are reported in Hz, lit. See Murahashi, S.-I.; Naota, T.; Nakajima, N. J. Org. Chem. 1986, 51, 898): δ 7.29 (dd, J=8.3, J=2.0, 1H), 7.08 (d, J=2.0, 1H), 6.91 (d, J=8.3, 1H), 3.94 (s, 3H), 3.91 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 153.2, 149.6, 126.9, 119.7, 114.3, 111.6, 104.3, 56.54, 56.51; IR (neat, cm−1): 2225, 1598, 1583, 1519, 1245, 1158, 1139, 1018, 876, 811, 617. Anal. Calcd. for C9H9NO2: C, 66.25; H, 5.56; N, 8.58. Found: C, 66.02; H, 5.72; N, 8.69.

Workup

  1. custombriefly evacuated
  2. customThe Schlenk tube was sealed with a Teflon valve
  3. customto reach room temperature
  4. extractionextracted with ethyl acetate (4×4 mL)
  5. dry with materialThe combined organic phases were dried over MgSO4
  6. concentrationconcentrated
  7. distillationthe residue was purified by distillation at reduced pressure (bp 160° C. @1 Torr)

Sources & evidence

ORD record
ord-9411738e46a543e2a581512f2e92278a
Source dataset
uspto-grants-2008_01
Patent number
US07323608B2

Reaction notes

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