LITTLE SISTER WILL TEACH YOU NMR.....6,7-methylenedioxy-4-phenylcoumarin

LITTLE SISTER WILL TEACH YOU NMR

6,7-methylenedioxy-4-phenylcoumarin
8-Phenyl-6H-[1,3]dioxolo[4,5-g]chromen-6-one

6H-1,3-Dioxolo[4,5-g][1]benzopyran-6-one, 8-phenyl-

Molecular Formula: C₁₆H₁₀O₄

Molecular Weight: 266.2482

Coumarins are naturally occurring molecules that are found in plants that have numerous uses in the medical field because of its biological activity.  The wide varieties of its uses include antibiotics, anticoagulants, and sometimes even used in the perfume industry.   

SYNTHESIS

Synthesis of 6,7-methylenedioxy-4-phenylcoumarin from sesamol and ethyl phenylpropiolate using a Pd(OAc)2 catalyst to illustrate coumarin synthesis. This procedure is simple and easy and can be applied to the synthesis of other coumarins that have electron-rich phenol groups. The reaction is conducted by stirring a solution of Pd(OAc)2, sesamol and ethyl phenylpropiolate in trifluoroacetic acid at room temperature (15-20 degrees C) under atmospheric conditions.

STEP 1

phenyl acetylene is the starting material

Ethyl Phenylpropiolate: 

Phenylacetylene (500 mg, 4.896 mmol, 1 equivalent) was added to a round bottom flask and flushed with nitrogen.  A septum and balloon of nitrogen was then attached and 3-4mL of THF was added by syringe.  The flask was cool to -78^oC in a dry ice and acetone bath.  Next, n-butyllithium (2.36 mL, 1.2 equivalent) was added to the solution and allowed to warm to 0^oC for 1 hour.  The solution was cooled to -78^oC again for 15 minutes, and then ethyl chloroformate (0.702 mL, 7.344 mmol, 1.5 equivalent) was added dropwise by syringe and allowed to warm again to 0^oC.  The reaction mixture was then quenched by adding 10mL of saturated aqueous NaHCO₃ and allowed to stir for 15 minutes. The resulting substance Ethyl Phenylpropiolate was a yellowish-orange liquid.  

¹H NMR (200 MHz, CDCl₃) δ 7.60-7.26 (m, 5H),

4.38 (m, 2H),      -O CH2 CH3

1.44 (m, 3H);   -O CH2 CH3

IR (neat, NaCl)

3551.4, 3399.9, 3958.2, 2934.4, 2872.2, 2236.4, 2211.6, 1744.0, 1709.5 cm^-1

The conversion of phenylacetylene to ethyl phenylpropiolate was made apparent by the comparison of IR spectras.  The phenylacetylene reference IR spectra found on the Spectral Database of Organic Compounds shows a strong peak at about 3300 that the IR of the intermediate lacks.  Also the intermediate’s IR contains strong peaks at 3000 and 2230 which are both absent from the starting material’s IR spectrum.  Both of these changes indicate a successful conversion of phenylacetylene to the intermediate ethyl phenylpropiolate. 

STEP 2

This specific reaction will result in a ring closure and addition of the ethyl phenylpropiolate aided by the palladium acetate catalyst.  The palladium catalyst allows for the addition of an ester to a phenol resulting in a ring closure and product coumarin derivative.

6,7-methylenedioxy-4-phenylcoumarin:  

Sesamol (0.075g, 0.5167mmol, 0.9 equivalent) and ethyl phenylpropiolate (102mg, 0.57405 mmol,1 equivalent) and Palladium acetate (Pd(OAc)₂)(0.00394g, 3mol%) were added to a 1 dram vial and cooled to 0^oC in an ice water bath.  Trifluoroacetic acid (0.5mL) was added to the vial, then the vial was capped and the reaction allowed to proceed overnight. The resulting solid was a brown, sticky, crystalline (0.387 mmol, 67 %yield). 

 ¹H NMR (300 MHz, CDCl₃)

δ 7.55-7.38 (m, 5H),

6.90 (s, 1H),

6.83 (s, 1H),

6.24 (s, 1H),

6.05 (s, 2H);  CH2 SANDWICHED BETWEEN 2 OXYGEN ATOMS

IR (DCM, NaCl)

3553.8, 3401.9, 2958.2, 2872.2, 2236.3, 2211.4, 1744.4, 1717.4 cm^-1

References

Kotani, M., Yamamoto, K., Oyamada, J., Fujiwara, Y., Kitamura, T.,Synthesis, 2004, 9, 1466-1470.

Oyamada, J., Jia, C., Fujiwara, Y., Kitamura, T., 2002, Chemistry Letters,2002, 3, 380-381.

Kitamura, T., Yamamoto, K., Kotani, M., Oyamada, J., Jia, C., Fujiwara, Y.,Bulletin of the Chemical Society of Japan, 2003, 76, 1889-1895 http://www.ncbi.nlm.nih.gov/pubmed/17446885 http://wenku.baidu.com/view/ce68818683d049649b665879.html Mech   The insertion of the ethyl phenylpropiolate to the sesamol-palladium intermediate is initially achieved in a cis confirmation.  There is then an internal rearrangement of the palladium and CO₂Et ligands to the trans confirmation which then allows for an electrophilic aromatic substitution to close the ring.

 ETHYL PHENYL PROPIOLATE





Ethyl phenylacetylenecarboxylate~Phenylpropiolic acid ethyl ester

  1H NMR 13 C NMR


    MASS
      IR


    RAMAN



  UNDERSTAND SPECTRA WITH METHYLENE DIOXY GROUP USING  A DIFFERENT EXAMPLE


4-Bromo-1,2-(methylenedioxy)benzene 1H NMR


  13 C NMR   IR   MASS     RAMAN  


  PRESENTING TO YOU COUMARIN TO UNDERSTAND SPECTRA COUMARIN






  1H NMR   13 C NMR IR   MASS   RAMAN  



  NOW PHENYL ACETYLENE






  1H NMR         13 C NMR   MASS   IR AND