Hydrochloric Acid → HCID 66743782, compound

HRID 2199532Notes

Reaction equation

HRID 2199532 reaction equation
[CH3:1][O:2][C:3]1[C:10]([O:11][CH3:12])=[CH:9][CH:8]=[CH:7][C:4]=1[CH:5]=[O:6].[C:13]1(=[O:19])[O:18][C:16](=[O:17])[CH2:15][CH2:14]1.C(N(CC)CC)C.Cl>[Cl-].[Cl-].[Zn+2].C(Cl)Cl>[CH3:1][O:2][C:3]1[C:10]([O:11][CH3:12])=[CH:9][CH:8]=[CH:7][C:4]=1[CH:5]1[CH:15]([C:16]([OH:18])=[O:17])[CH2:14][C:13](=[O:19])[O:6]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 7922Succinic anhydrideHCID 8471TriethylamineHCID 665812,3-Dimethoxybenzaldehyde

Product 1

HCID 66743782HCID 66743782, compoundYield 73.9%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 6344DichloromethaneSolvent

Procedure

Into a flame-dried 3-neck flask, fitted with a condenser and addition funnel were placed 25.0 g (0.184 mol) of anhydrous, powdered ZnCl2. Then 100 mL of CH2Cl2 were added, followed by 15.3 g (0.092 mol) of 2,3-dimethoxybenzaldehyde and 13.8 g (0.138 mol) succinic anhydride. Triethylamine (25.6 mL, 0.184 mol) was added dropwise to the flask with rapid stirring and the reaction was heated at reflux for 4 days. The reaction was cooled to room temperature and poured over a mixture of ice and conc HCl. The mixture was extracted with EtOAc (3×250 mL), then washed with 2 N HCl (1×250 mL), and brine (1×250 mL). The product was extracted with saturated NaHCO3 (4×200 mL) until TLC indicated no product remaining in the organic layer. The aqueous layer was washed with CH2Cl2 (1×200 mL) and acidified with conc HCl. The white, milky solution was extracted with CH2Cl2 (3×250 mL), the organic extracts were dried over Na2SO4, and evaporated under vacuum to produce 18.0 g (0.068 mol, 73.6%) of pale yellow solid that was recrystallized from EtOAc/hexanes; mp 129-130° C. (lit.34 mp 132° C.). 1H NMR: (300 MHz, CDCl3): δ 7.01 (t, 1H, J=7.5 Hz, ArH); 6.89 (dd, 1H, J=8.1 Hz, J=2.5 Hz, ArH); 6.82 (dd, 1H, J=8.1 Hz, J=2.5 Hz, ArH); 5.73 (d, 1H, J=6.6 Hz, ArCH); 3.81 (s, 3H, ArOCH3); 3.80 (s, 3H, ArOCH3); 3.44 (dt, 1H, J=8.5 Hz, J=6.6 Hz, CHCOOH); 2.90 (d, 2H, J=8.5 Hz, COCH2). EIMS (M+)=266. Additional details are described in Stevens et al., “A New Synthetic Route to Furofuranoid Lignans Via the Intramolecular Mukaiyama Reaction,” J. Chem. Soc., Perkin Trans. 1, 185-190 (1992), the disclosure of which is incorporated herein by reference.

Workup

  1. customInto a flame-dried 3-neck flask, fitted with a condenser and addition funnel
  2. temperaturethe reaction was heated
  3. temperatureat reflux for 4 days
  4. extractionThe mixture was extracted with EtOAc (3×250 mL)
  5. washwashed with 2 N HCl (1×250 mL), and brine (1×250 mL)
  6. extractionThe product was extracted with saturated NaHCO3 (4×200 mL) until TLC
  7. washThe aqueous layer was washed with CH2Cl2 (1×200 mL)
  8. extractionThe white, milky solution was extracted with CH2Cl2 (3×250 mL)
  9. dry with materialthe organic extracts were dried over Na2SO4
  10. customevaporated under vacuum

Sources & evidence

ORD record
ord-2dd09f44da424163adac0906b9ca505a
Source dataset
uspto-grants-2016_06
Patent number
US09359303B2

Reaction notes

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