To synthesize the acetamide of 5-methylfurfurylamine to use as a model compound for the loss of the furan ring and methyl group in the attempted cyclization of Ugi products with TFA.


5-methyl furfurylamine (2.786 mL, 0.025mol) was cooled in dryice for 5mins when acetylchloride ( 1.777mL, 0.025mol) precooled in dryice-acetone bath was added to it. The reaction mixture was cooled for 10min when a brown solid was obtained.The solid was dissolved in dichloromethane, washed with water and 10%NaOH and dried with anhydrous MgSO4. The solvent was rotovaped and the product was vacuum dried. However the product was washed with 10% HCl, dried with anhydrous MgSO4, filtered, rotovaped and vacuum dried further to remove the suspect unreacted amine. The compound was characterized by NMR spectroscopy.


IR of 5MFA
IR of 78A
IR Overlay of 5MFA & 78A
HMR of 5-MFA
HNMR of 78B
CNMR of 78B
All protonated carbons of 78B
DEPT of 78B -Image

Characterization of 78C (after base and acid wash)

HNMR of 78C
HOMODEC of 78C-Image [Amide proton at 7.43 ppm irradiated]
Mass Spectrum of 78B
FAB of 78B [matrix - Glycerol, solvent -methylene chloride]


  1. Although the CH2 peak (4.28 ppm) is a doublet, the NH amide (7.43 ppm) does not appear tobe a triplet, which is what one would expect.To prove that the amide proton is coupling to the CH2 a selective homonuclear decoupling experiment was performed by irradiating the amide proton (7.43 ppm) which resulted in knocking off its coupling to the CH2 peak (4.28 ppm) in 78C; The CH2 ended up being a singlet.
  2. Assigning a structure from the spectra : CNMR- There are 8 Carbons, four of which are aromatic, one amide (170 ppm), and three aliphatic carbons (below 40 ppm). HNMR - There are 2methyls, one methylene, and the two aromatic methynes, and one amide NH. The methyls are isolated, of which one is attached to the carbonyl of the amide making it acetamide, HOMODEC experiment indicates that CH2 is attached to NH. Off the 4 aromatic carbons, two exist as methynes (CH).The remaining two are tertiary carbons, one attached to NH and the other attached to the CH3 group. The only thing that cannot be said with certainity is the point of attachement to the aromatic ring... which is only possible if there was a heteroatom in it....
  3. Fast atom bombardment of 78B using Glycerol as a matrix confirmed that the main product was the acetamide of 5MFA (peak at 154.18), although te peak at 110.1 corresponds to the amine, also under FAB conditions there seems to be a dimer of the primary compond plus H. The results were also confirmed using a different matrix - 3-Nitrobenzylalchohol. (parent peak at 154.18)
  4. However to assign a correct structure to 78C, in the absence of elemental analysis and a HETCOR, chemical reactivity of the starting materials, there identity and conditions applied can used. To that affect it can be safely confirmed that 78C is the acetamide represented in the reaction scheme above.


The experiment accomplished the synthesis of the acetamide of 5-methyl furfurylamine as desired in x% isolated yield.



20:10 Measured out 5-methyl furfurylamine (2.786 mL) in a 25mL erlenmeyer flask and cooled it in a dry ice bath. (this was open to air?)
20:25 Cooled down a small amount of acetylchloride in a dryice bath. Transferred 1.777mL acetylchloride in to a dropping funnel.
20:35 Started adding acetylchloride, dropwise to the erlenmyer (in the dryice bath) containing 5-methylfurfurylamine.
20:45 Completed adding the acid chloride to the amine.
20:57 Swirled the reaction mixture in the erlenmeyer flask. (always stir reaction with a stirring bar)
21:00 A brown solid was obtained.
21:05 Removed the erlenmeyer flask from the dryice bath and let it sit in the hood at room temperature for 15min.
21:20 Added dichloromethane (10mL) to the erlenmeyer, dissolved some of the solid in it, transferred to a separatory funnel, added another 10mL dichloromethane, and dissolved the remaining solid, transferred the solution to the separatory funnel. Then added distilled water (10mL) to the separatoy funnel, after shaking the funnel, separated the bottom organic layer from the aqueous layer. Then washed the organic layer with 10% NaOH (10mL), separated the organic layer, washed it again with distilled water (10mL). Then to the combined aqueous layers dichloromethane (10mL) was added and the organic layer was separted by a separatory funnel and added to the earlier obtained organic layer.
21:45 The organic layer was dried with anhydrous MgSO4. The solid was fileterd by a buchner funnel.
21:50 The dichloromethane was evaporated using a rotovap set at 80C.The product is called 78A.
22:00 Obatained IR of 78A and 5-methylfurfurylamine to see if a carbonyl stretching has evolved.
22:30 The brown liquid was left in a stoppered round bottom flask for further analysis.


11:30 After evaporating the solvent under a high vac for 1hr, 78B (2.0805g), a brown oil was obtained.
12:15 Obtained HNMR
13:45 Obtained CNMR
18:10 Obtained DEPT


14:30 Poured out 78B from the NMR tube into a separatory funnel, and rinsed the tube out with dichloromethane.
14:45 Added dichloromethane to the separatory funnel, added 10% HCl (10 mL) to it, then, shook the separatory funnel, separated the organic layer.
15:20 wased the organic layer with distilled water (20 mL), separated the organic layer, dried it with anhydrous MgSO4 and set it on a rotovap.
18:30 The product was set on a high vac.
19:30 Removed from the high vac and obtained 78C (1.1907g)
20:30 Obtained HNMR and a selective proton decoupled spectrum (HOMODEC) by irradiating the amide peak at 7.43 ppm.
21:20 Started running a C13NMR with relaxation time of 15 sec and 2400 transients.


10:00 Obtained CNMR of 78C.


Acetylchloride InChI=1/C2H3ClO/c1-2(3)4/h1H3
Acetamide InChI=1/C8H11NO2/c1-6-3-4-8(11-6)5-9-7(2)10/h3-4H,5H2,1-2H3,(H,9,10)