Benzaldehyde to Benzilic Acid

Starting material

Benzoin: Thaimine hydrochloride (1.52 g, 0.45 mmol), water (2mL) and 95% ethanol (15 mL) were combined in a 50-mL Erlenmeyer flask and swirled until dissolved and homogeneous.  Aqueous sodium hydroxide (4.5 mL) was added and swirled until the solution appeared pale yellow.  Finally, pure benzaldehyde (4.5 mL, 4.41 mmol) was added to the flask and the mixture was stored for two days.  The crystals that formed at room temperature were placed in an ice bath and then filtered under vacuum.  The crystals were washed with 5-mL portions of ice-cold water and left to dry.  To isolate the pure product, the crude material was crystallized with 95% ethanol (24 mL).  The pure product of benzoin showed the following physical characteristics: 2.07 g (44.3 % yield) mp: 129-132°C (lit: 135-135 °C).  ¹H NMR (CDCl₃, 300 MHz) δ: 7.79 (d, J=1.5, 2H) 7.25 (m, 2H), 7.24 (m, 2H), 7.19 (m, 2H), 7.14 (m, 2H), 5.82 (d, J= 1.2, 1H), 3.92 (s, 1H) ppm.  ¹³C NMR (CDCl₃, 75Hz) δ: 199.2, 139.2, 139.1, 134.0, 129.2, 129.1, 128.7, 128.5, 127.8, 76.2 ppm.  IR 3403, 3003, 1761, 1203 cm^-1.

The final product of benzoin contained ¹³C NMR peaks at 199.2 ppm accounting for the carbonyl group and eight peaks in the range of 139.0-127.8 ppm representing the alkene bonds as well as the carbons of the aromatic rings.  Finally, a peak at 76.2 ppm represented the carbon with the alcohol group attached.  Regarding the¹H NMR spectra, four multiplet peaks appeared in the range of 7.79 and 7.14 ppm representing the hydrogens surrounding the aromatic rings.  A peak at 5.82 ppm accounted for the hydrogen attached to the carbon containing the alcohol group.  A peak at 3.92 ppm represented the hydrogen of the alcohol group.  An impurity of ethanol appeared at 4.42 ppm.  Finally, the IR spectra displayed a peak at 3403 cm^-1 representing the C-H stretches, a peak at 3003 cm^-1, accounting for the alcohol group, and a strong peak at 1761 cm^-1representing the carbonyl group.  Overall, the spectra confirmed the condensation of benzoin.

Benzil: Benzoin (2.51g, 1.18 mmol), concentrated nitric acid (12 mL, 28.8 mmol), and a stir bar were placed into a 25-mL round-bottom flask with a water condenser and heated in a hot water bath at 70 °C for one hour.  After heating and magnetically stirring, the mixture was added to 40 mL of cool water and stirred until crystallized into a yellow solid.  Vacuum filtration was used to collect the crude product.  The pure product was collected through recrystallization by using 95% ethanol (20 mL).  The product displayed the following properties: 1.91 g (76.8 % yield) mp: 89-92 °C (lit: 95 °C).  ¹H NMR (CDCl₃, 300 MHz) δ: 7.86 (m, 4H), 7.56 (m, 2H), 7.53 (m, 4H) ppm.  ¹³C NMR (CDCl₃, 75Hz) δ: 192.0, 132.3, 130.4, 127.3, 126.5 ppm.  IR 3010 (w), 1668 (s) cm^-1.

The ¹³C NMR produced a peak at 192.0 ppm representing the two carbonyl groups.  Four peaks appeared between 132.3 and 126.5 ppm accounting for the carbons within the aromatic ring and the alkene bonds.  The ¹H NMR displayed three multiplet peaks at 7.86, 7.56, and 7.53 ppm representing the hydrogens around the aromatic ring that coupled with the surrounding hydrogens.  Finally, the IR spectrum produced a C-H stretch peak at 3010 cm^-1 and a carbonyl peak at 1668    cm^-1.  This data proved the success of the oxidation of benzoin to produce benzil.

¹H-NMR: Benzil300 MHz, CDCl₃delta [ppm]mult.atomsassignment7.50m (d)4 H2-H, 2'-H, 6-H, 6'-H7.64m (dd)2 H4-H, 4'-H7.95m (dd)4 H3-H, 3'-H, 5-H, 5'-H

13C-NMR: Benzil
75.5 MHz, CDCl3
delta [ppm]	assignment
129.0	CH arom.
129.8	CH arom.
133.0	CH arom.
154.8	C quart. arom.
194.5	C=O
76.5-77.5	CDCl3

IR: Benzil[KBr, T%, cm^-1][cm^-1]assignment3064arom. C-H valence1660C=O valence, ketone1594, 1579arom. C=C valence

GC: pure productcolumnDB-1, L=28 m, d=0.32 mm, film=0.25 µminleton column injection, 0.2 µLcarrier gasH2, 40 cm/soven90°C (5 min), 10°C/min --> 240°C (30 min)detectorFID, 270°Cintegrationpercent concentration calculated from relative peak area

Benzilic Acid: Benzil (2.10 g, 1.0 mmol), 95% ethanol (6 mL), and a boiling stone were added to a 25-mL round-bottom flask with a reflux condenser and heated until the solid benzil was dissolved.  Aqueous potassium hydroxide (5 mL, 18.2 mmol) was added dropwise to the flask and the mixture was boiled for 15 minutes.  The mixture was cooled, transferred to a beaker, and placed in an ice-water bath until crystallized.  The crystals were isolated through vacuum filtration and washed with 4-mL portions of cold 95% ethanol.  The solid was transferred to a 100-mL flask of hot water (60 mL) and mixed until completely dissolved.  Concentrated hydrochloric acid (1.3 mL) was added drop-wise until a permanent solid was present and a pH of 2 was maintained.  The solution was cooled in an ice bath and the crystals were filtered through vacuum filtration and washed with 2, 30-mL portions of ice-cold water.  The remaining crystals were identified by the following properties: 0.41 g (17.4% yield) mp: 151-152 °C (lit: 150 °C).  ¹H NMR (CDCl₃, 300 MHz) δ: 7.47 (m, 6H), 7.26 (s, 4H), 2.18 (s, 1H) ppm.  ¹³C NMR (CDCl₃, 75Hz) δ: 175.8, 141.4, 128.3, 128.2, 127.4, 82.0 ppm.  IR 3399 (s), 2889 (s, b), 1718 (s), 1177 (s) cm^-1.

The melting point corresponded to the known melting point of 150 °C. The ¹³C NMR spectra displayed a weak peak at 175.8 ppm, which accounted for the carbonyl group within the carboxylic acid.  Four peaks at 141.4, 128.3, 128.2, and 127.4 ppm represented the carbons within the aromatic rings.  Finally, a peak at 82.0 ppm represented the carbon attached to the alcohol group.  The ¹H NMR spectrum produced a peak at 7.47 and 7.26 ppm representing the two groups of equivalent hydrogens attached to the aromatic rings.  A peak at 2.18 ppm represented the hydrogen of the alcohol group.  A peak did not appear at 12 ppm that would have represented the hydrogen of the carboxylic group, which means the reaction was not carried to completion.  In the IR spectrum, a hydroxyl peak appeared at 3399 cm-1.  A broad peak appeared at 2889 cm^-1 representing the carboxylic acid functional group of compound.  Finally, a peak at 1718 cm^-1 represented the carbonyl group and a peak at 1177 cm^-1 accounted for the carbon-oxygen bond in both alcohol groups.

raman

1 Bruggink, A.; Schoevaart, R.; Kieboom, T. Org. Proc. Res. Dev., 2002, 7,622-640.

2 Pavia, L; Lampman, G; Kriz, G; Engel, R. A Small Scale Approach to Organic Laboratory   Techniques, 2011, 266-269.

3 Lachman, A. J. Am. Chem. Soc., 1922, 44, 330-340.



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 Punjabi sweets on a leaf in Lahore Pakistan, 20 Rupees or about 30 cents. I wasn't sure if one is supposed to eat the leaf too but I ate it anyways. 10/07


 
 

 

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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    

PIPERONYL ALCOHOL AND ESTERS

Synthesis Example 1 Synthesis of piperonyl alcohol  http://www.google.com/patents/WO2004071481A1?cl=en

In a 500-ml autoclave were placed 90 g (0.60 mol) of heliotropin, 270 ml of 1-propanol and 3 g of a Raney nickel catalyst (Raney-Ni) . Hydrogen gas was filled therein up to 4 MPa. The autoclave contents were stirred at 90 °C for about 10 hours. The reaction mixture was filtered and the filtrate was concentrated. The resulting residue was puri¬ fied by silica gel column chromatography (hexane: ethyl ace¬ tate = 20:1) to obtain 27.6 g of piperonyl alcohol as white crystals (yield: 30.3%, G.C. purity: 98.4%) m.p.: 49-51°C ^XH-NMR (CDCI3, δ ppm) 1.86 (s,lH), 4.56 (s,2H), 5.95 (s,2H), 6.77-6.79 (m,2H), 6.85 (s,lH) MS: 152 (M⁺) , 135, 123, 105, 93, 77, 65, 51, 39, 29 IR and NMR spectroscopy was used in order to determine the purity of the intermediate. IR spectroscopy showed a peak at 2986.82 cm-1 which correlated to a C-H bond which should be expected in any organic molecule, but the peaks that were specifically consistent with its structure were at 1490.07 cm-1, 1275.61 cm-1, and 810.03 cm-1. These peaks correlated to a C=C aromatic bond, C-O alcohol bond, and C-H aromatic bond.       NMR Spectroscopic Data-

 

      Synthesis of piperonyl esters  

The piperonyl alcohol produced in Synthesis Example 1 was reacted with a carboxylic acid anhydride or a carbox¬ ylic acid chloride in the presence of a base. The reaction mixture was purified with distilled water or by silica gel column chromatography to produce piperonyl esters having different substituents R₂.

 

   

5-Methylfurfurylamine

5-Methylfurfurylamine
CAS: 14003-16-8

 ((5-Methyl-2-furyl)methylamine)


5-methylfurfurylamine also contains both C=C double bonds and C-O bonds. As in piperonal, the two carbons attached to the oxygen in the 5-methylfurfurylamine molecule could fall in the 145 to 160 ppm range. 
The carbon in the methyl group falls within the alkane chemical shift range of 0 to 35 ppm. A peak at 14 ppm can be seen below. Alkenes have C NMR shifts between 100 and 150 ppm. The two alkene carbons have peaks at about 106 ppm. 
C-N bonds can have a chemical shift between 45 and 55 ppm. This shift is greater in the 5-methylfurfurylamine molecule because the carbon is attached to another carbon with a C=C and a C-O bond. A peak can be seen at 78 ppm.





DEPT



1H nmr





5-methylfurfurylamine could be synthesized by breaking the bond between the amino group and the CH2 attached to carbon number 2 of the 5-membered ring. If using bromine within this SN2 reaction, this break would result in the formation of the electrophile, 5-methylfurfurybromide, and the neutral nucleophile, ammonia. The single lone pair of the nucleophile would then attack the carbon attached directly to the halogen, bromine; and as a result, negatively charged bromine would be released. However, this would not directly result in the formation of the desired reactant, 5-methylfurfurylamine, because of the attachment of positively charged ammonia. Thus, at this point an acid-base reaction would occur with another ammonia molecule, and would result in the formation of the desired neutral reactant, 5-methylfurfurylamine.