Exp103-4.JPG

Objective

To synthesize the N-(2-furylmethyl)acetamide (acetamide of furfurylamine) to use as a model compound to help explain the loss of the methyl furfuryl group upon treating the ugi products containing the group with 50% TFA in CDCl3 for 2 days or longer, as experienced in Exp098, Exp091, Exp070, EXP067, EXP065., also summarized in the UsefulChem blog.

Procedure

A solution of Furfurylamine(1.767 mL, 1.94g, 20 mmol) and triethylamine (8.539mL, 6.2 g, 60.0 mmol) was stirred in CH2Cl2 (30 mL) at room temperature for 10 min. A solution of acetyl chloride (1.621mL, 1.8 g, 23 mmol) in CH2Cl2 (20 mL) was added slowly into the above solution at 0 ÂșC for 15 min. The mixture was stirred at room temperature for 1 h. The reaction mixture was extracted with CH2Cl2. The combined organic layers were dried by anhydrous MgSO4. The solvent was removed under vacuum to give N-(2-furylmethyl)acetamide as a colorless oil (1.5551g 55.8%) 1H NMR (note the J constants) (external image delta.gif ppm, CDCl3) 1.97 (s, 3H), 4.37 (d, 2H J 5.6 Hz), 6.19 (dd, 1H J Hz, Hz), 6.29 (dd, 1H J Hz, Hz), 6.77(sb, H), 7.32 (dd, 1H J Hz, Hz) 13C NMR (external image delta.gif ppm, CDCl3) 22.7, 36.2, 107.1, 110.2, 141.8, 151.2, 170.1

Results

Furfurylamine
H NMR
C NMR
103A
H NMR
H NMR image
C NMR
C NMR image
DEPT
All CH's
103B
H NMR

Discussion

The product appears to be relatively pure for with a small of impurities ( ~ 5%). The product will be used as a starting material for the next step (Exp105) for Friedel Crafts tert-butylation.

Conclusion

An acetamide of furfurylamine was successfully synthesized.

Log

2007-05-28

15:30 Made up a solution of furfurylamine and triethylamine in methylene chloride in a 250mL round bottom flask on a stir plate.The solution was stirred.
15:42: Made up a solution of acetylchloride in dichloromethane in an erlenmeyer flask placed in an ice bath. The temperature reached 0C.
15:52 Started adding the cold (0C) acetylchloride solution to the amine solution slowly with a pasteur pipette over 15mins.
16:07 Completed adding the acetylchloride solution in the amine solution. The reaction mixture became thick and started to form a precipitate. The reaction mixture was stirred for the next hour at room temperature. A picture.
17:07 Stopped stirring the reaction mixture and poured it out in a clean separatory funnel.
17:15 washed it with distilled water (3 x 50 mL). As soon as water was added to the thick solution, the precipitate disappeared and two distinct appeared. Soon after the layers settled, they were separated. The bottom organic layer was set aside.
17:40 To the combined aqueous layers, added dichloromethane (10 mL) and extracted the remaining (if any) product with it.
18:00 Dried the dichloromethane layer with anhydrous MgSO4 (5g), filtered it through a sintered galss funnel.
18:25 The organic layer was transferred into a preweighed round bottom flask and set on a high vac.
19:20 Removed from the high vac and obtained 103A (1.5551g 55.8%) [crude product]
19:25 Transferred 100uL of 103A into an nmr tube for analysis.

2007-05-29

11:00 Added 1N HCl (10mL) to 103A extracted it with dichloromethane (2x 20mL).
11:20 Dried the dichloromethane layer with anhydrous MgSO4 (7g), filtered it off through a sintered glass funnel.
11:35 The dry DCM layer was set on a high vac for solvent evaporation.
12:40 Removed from the high vac and obtained 103B (1.3876 g)


Reference
1.Hao Song et.al. Org Lett.; 2006; 8(26) pp 6011 - 6014 Exp & Supproting info.

Tags

Furfurylamine: InChI=1/C5H7NO/c6-4-5-2-1-3-7-5/h1-3H,4,6H2
N-(2-furylmethyl)acetamide: InChI=1/C7H9NO2/c1-6(9)8-5-7-3-2-4-10-7/h2-4H,5H2,1H3,(H,8,9)