Dimethyl Sulfate → 2-(Methoxy(3-nitrophenyl)methylene)malononitrile

HRID 530968Notes

Reaction equation

HRID 530968 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]([CH:10]=[CH:11][CH:12]=1)[C:7](Cl)=[O:8])([O-:3])=[O:2].[C:13](#[N:17])[CH2:14][C:15]#[N:16].[CH3:18]CN(C(C)C)C(C)C.COS(OC)(=O)=O>[Cl-].[Na+].O.CCOC(C)=O.C1COCC1>[CH3:18][O:8][C:7]([C:6]1[CH:10]=[CH:11][CH:12]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=1)=[C:14]([C:13]#[N:17])[C:15]#[N:16]

Participants

8

Reactant 4

HCID 6497Dimethyl SulfateHCID 8010MalononitrileHCID 8495Benzoyl chloride, 3-nitro-HCID 81531Diisopropylethylamine

Product 1

HCID 895868902-(Methoxy(3-nitrophenyl)methylene)malononitrileYield 37%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A solution of 3-nitrobenzoylchloride (25 g, 134 mmol), malononitrile (9.74 g, 147 mmol) and THF (140 mL) was cooled to 0° C. DIPEA (59 mL, 335 mmol) was added dropwise and the reaction was allowed to warm to room temperature and proceed for 2 hours. Afterwards, dimethylsulfate (38 mL, 399 mmol) was added and the temperature was raised to 70° C. for 4 hours. Next, the reaction mixture was brought to room temperature and allowed to proceed for an additional 12 hours. EtOAc (200 mL) was added to the reaction mixture in addition to brine (200 mL). The organic and aqueous layers were separated and the aqueous layer was extracted with EtOAc (4×25 mL). The combined organic layers were dried with MgSO4 and concentrated in vacuo. The material was purified over a silica column using chloroform:hexane (90:10) initially and eluted with pure chloroform. After concentrating the fractions containing the product, a yellow oil was triturated with diethyl ether to yield a solid (11.3 g, 37% yield): 1H NMR (400 MHz, DMSO) δ 8.63 (s, 1H), 8.51 (d, J=7.7, 1H), 8.16 (d, J=7.7, 1H), 7.94 (t, J=7.8, 1H), 3.93 (s, 3H); 13C NMR (100 MHz, DMSO) δ 183.66, 147.82, 135.23, 131.00, 129.55, 127.15, 124.08, 113.31, 111.87, 66.71, 61.87; [M+H]− calculated for C11H7N3O3 228.0, found 214.10 (product appears to hydrolyze during LC/MS analysis).

Workup

  1. temperaturethe temperature was raised to 70° C. for 4 hours
  2. customwas brought to room temperature
  3. waitto proceed for an additional 12 hours
  4. customThe organic and aqueous layers were separated
  5. extractionthe aqueous layer was extracted with EtOAc (4×25 mL)
  6. dry with materialThe combined organic layers were dried with MgSO4
  7. concentrationconcentrated in vacuo
  8. customThe material was purified over a silica column
  9. washeluted with pure chloroform
  10. concentrationAfter concentrating the fractions
  11. additioncontaining the product
  12. customa yellow oil was triturated with diethyl ether

Sources & evidence

ORD record
ord-3c10a814dbe846758b471b2d10688c92
Source dataset
uspto-grants-2016_05
Patent number
US09353116B2

Reaction notes

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