Exp105.JPG

Objective

To accomplish a Friedel Crafts tert-butylation of N-(2-furylmethyl)acetamide with tert-butanol.

Procedure

N-(2-furylmethyl)acetamide (309mg, 2.22mmol) was added to t-butanol (148.24mg, 190uL, 2mmol) in glacial acetic acid (1.4 mL) and concentrated sulfuric acid (140 uL). The reaction mixture was sonicated for one hour at room temperature and subsequently left undisturbed overnight. The next morning the reaction mixture was neutralized with 10% NaOH.The product was extracted with dichloromethane and dried over anhydrous MgSO4. The solvent was removed under reduced pressure.

Results

105A
H NMR
105B (after 14 hours and work-up)
H NMR

Discussion

The tert-butyl derivative of the acetamide was only formed in traces (doublets at 5.85 ppm & 6.06 ppm) if at all. The starting material largely remained unreacted. This may call for an optimization of the reaction, a ) increasing the concentration of tert-butanol and b) varying the amount of sulfuric acid catalyst c) longer reaction time. The procedure followed was for anisole, which is much more reactive to Friedel-Crafts alkylation. It would be better to follow a procedure proven to alkylate the 5-position of 2-alkylfurans.

Conclusion

The reaction failed.

Log

2007-05-31

21:00 Made up a solution of tert-butyl alcohol in glacial acetic acid and conc. sulfuric acid.
21:07 Added N-(2-furylmethyl)acetamide to the reaction reaction mixture
21:21 Removed 50uL from the reaction mixture into an NMR tube and obtained an H NMR 800uL of CDCl3 (105A)

2007-06-01

10:45 Added 10% NaOH solution to 105A, until a pH 7-8 was obtained (~3.5mL of 10% NaOH)
11:30 Extracted with dichloromethane (1mL x 4).
12:20 Dried the dichloromethane layer with anhydrous MgSO4, centrifuged the solid off and obtained a clear, dry DCM layer.
16:15 The dry organic layer was set on a vacuum pump to remove the solvent.
18:30 Removed from the vacuum pump and obtained 105B (111.7mg)
19:35 Obtained H NMR of 105B.


Reference
Experimental organic chemistry- A small scale approach Wilcox and Wilcox.2nd Ed.Pg 389 & 390.(Private Access)

Tags

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)