To synthesize a Ugi adduct from 3,4-dimethoxybenzaldehyde, 5-methylfurfurylamine, Benzylisocyanide and Boc-Gly-OH in methanol using Ugi 4CR.


Dissolved 3,4-dimethoxybenzaldehyde (Veratradlehyde) (332mg, 2mmol) and 5-methylfurfurylamine(5-MFA) (244uL, 2.2mmol, 10% excess ) in 4mL methanol-d4 in a 4mL volumetric flask, immediately transferred the contents to a 25mL Erlenmeyer flask, The reaction is allowed to sit for about 6 hours without stirring to form the imine.
A solution of Boc-Gly-OH(350mg, 2mmol), and Benzylisocyanide(240uL, 2mmol) is made up in 4ml volutmeric flask in methanol-d4. This solution of Boc-Gly-OH and benzylisocyanide is added to the preformed Imine. The reaction mix is allowed to sit undisturbed overnight, when the Ugi product is obtained. The product is recrystallized from a small amount of methanol and saved in a 1 dram vial.
UCExp64C-C30H37N3O7; White solid; tert-butyl (2-{[2-(benzylamino)-1-(3,4-dimethoxyphenyl)-2-oxoethy​ l][(5-methylfuran-2-yl)methyl]amino}-2-oxoethyl)carbamate : M.Pt- 176-177C; 1H NMR (external image delta.gif ppm, 500MHz, CDCl3) 1.44 (s, 9H), 2.1 (s, 3H), 3.72 (s, 3H), 3.86 (s, 3H), 4.196 (s, 2H), 4.32-4.64 (m, 4H), 5.64-5.46, (s, 2H), 6.70-6.82 (m, 2H), 6.83-6.93 0(m, 1H), 7.15-7.40 (m, 8); 13C NMR (external image delta.gif ppm, CDCl3) 13.3, 28.2, 42.5, 42.8, 43.5, 55.67, 55.8, 63.1, 79.5, 106.2, 108.8, 110.7, 112.7, 122.3, 126.4, 127.4, 127.6, 128.5, 137.9, 147.7, 148.9, 149.2, 151.7, 155.7, 169.28, 170.150; IR (cm-1) 3250.01, 1692.10, 1665.94, 1644.09, 1516.65, 1147.11; HRMS (CI-methane): m/z calcd for C30H37N3O7 (M+H) 552.270976 Da, found 552.270854 Da.:


(Reactant NMRs from Exp054)
5-Methyl furfurylamine
Homodecoupled HNMR spectrum [One of the furan protons is irradiated to decouple from the methyl group conifrming its position]
Tentative assignments
Benzyl isocyanide
H NMR Signature triplet at 4.68ppm. J = 2.2Hz

64A (Veratraldehyde + 5-Methyl furfurylamine)
HNMR -13min
H NMR - 5h 15min
C NMR - 6h 15min
C NMR- 7h 06min
H NMR- 7h 10min
H NMR- 24h 00min

Benzylisocyanide + Boc-Gly-OH in CD3OD

64B (Boc-Gly-OH + Benzyl Isonitrile + 64A) [H NMR analysis]
t = 03min
t = 09min
t = 12min
t = 15min
t = 24min
t = 31min
t = 37min
t = 46min
t = 59min
t = 1h 06min
t= 1h 52min [solid in the NMR tube]

64C [C30 H37 N3 O7]
First batch of crystals -179 mg
H NMR in CDCl3
H NMR in CDCl3 / CD3OD
64C Overlay
64C 13C-NMR
CNMR from Exp060C

should get one HMR in pure methanol -d4 to see the shifts in the monitoring NMRs
Melting Point : 176-177C
64C -DEPT spectrum (beautiful! - looks like you figured this out)
64C [DEPT] all protonated carbon along a single scale
Ugi Product 64C-2

Mass analysis - Ionization Source- CI (methane)
Nominal mass
High Res
Elemental analysis
High Res
MS- pdf

64C -2
Second batch of crystals -304 mg
Melting point :176-178C
43%, 478.7mg (179.5+304.2; 64C and 64C-2)


  1. Imine Assignments and her is mechanism of imine formation (general) (animation from MSU Chemistry)
  2. Proton NMR of 64C in CD3Cl3 accounts for all 37 attached protons. After the addition of CD3OD the integration of the peaks account for only 35 protons, suggesting 2 labile protons (amide N-H) as expected. There are a few problems with that - first the reaction was done in methanol-d4 so there should be no N-H's to exchange. Adding the methanol-d4 would not change the total number of H's because any exchanged ones would show up as CD3OH. Now adding a bit of methanol-d4 does shift a few peaks, for example in the furan region removing the overlap between the furan H and the chiral benzylic H. It is worth taking the spectrum in pure methanol-d4 to get some reproducible values that can be compared with the reaction monitoring samples.
  3. 13CNMR of 64C shows exactly 26 signals which are as expected for the ugi product 64C. Good - now list them and identify which are what from the DEPT
  4. Proton NMR assignments for 64C. There are 3 diastereotopic CH2's between 4.0-4.8ppm range, the protons on these carbons (d,e,f in the image) are diastereotopic coupling with each other. [coupling would not happen with the N-H's but with each other. 2 singlets don't couple differently with a next door H; then you have a set of doublets that do - this should be the benzylic CH2 since Alicia's 2 CH2s were just singlets]. There is an enantiomeric proton at 5.6 ppm ( i in the image) overlapping with one of the furan protons, however after adding deuterated methanol (CD3OD) to the sample it becomes visible.


  • A pure product was prepared via a 4 component Ugi reaction. The experiment was successful.



12:41 : Dissolved 332mg (2mmol) of veratraldehyde in CD3OD in a clean 4ml volumetric flask added 244uL (2.2mmol) 5-methyl frufurylamine to it and immediately made it up to the 4ml mark with CD3OD. This is 64A.
12:54 : Obtained H NMR of 64A t = 13min
17:56 : Obtained H NMR of 64A t = 5h 15min
18:56 : Obtained C NMR of 64A t = 6h 15min
19:47 : Obtained C NMR of 64A t = 7h 06min
19:51 : Obtained H NMR of 64A t = 7h 10min


12:41 : Obtained H NMR of 64A t = 24h 00min
13:30 : Made up a solution of 350mg (2mmol) Boc-Gly-OH and 240uL (2mmol) Benzylisocyanide in CD3OD in a 4ml volumetric flask.
14:00 : Obtained a H NMR of the solution of Boc-Gly-OH and Benzylisocyanide
14:35 : Added the solution of Benzylisocyanide and Boc-Gly-OH to 64A (preformed imine solution), this is 64B
14:38 : Obtained H NMR of 64B [t = 03min]
14:44 : Obtained H NMR of 64B [t = 09min]
14:47 : Obtained H NMR of 64B [t = 12min]
14:50 : Obtained H NMR of 64B [t = 15min]
14:59 : Obtained H NMR of 64B [t = 24min]
15:06 : Obtained H NMR of 64B [t = 31min]
15:12 : Obtained H NMR of 64B [t = 37min]
15:21 : Obtained H NMR of 64B [t = 46min]
15:34 : Obtained H NMR of 64B [t = 59min]
15:41 : Obtained H NMR of 64B [t = 01h 06min]
16:17 : Obtained H NMR of 64B [t = 1h 52min]
16:27 : A solid mass has appeared in the erlenmyer flask containing the reaction mixture 64B.
17:38 : The solid was filtered through a buchner funnel and washed with methanol. This is 64C (179.5mg). The mother liquor (64D) is set on a steam bath to concentrate it for further crystallization.
18:35 : Obtained H NMR of 64C (~30mg) in CDCl3 (800uL, 0.03% V/V TMS).
18:50 : Added CD3OD (200uL, 0.053% V/V TMS) in the same NMR tube containing 64C in CDCl3, and obtained H NMR.


13:00 : The filterate 64D (mother liquor) was concentrated on a steam bath when it became thick and cloudy, this was filtered through a buchner funnel, washed with ice cold methanol and dried (by letting the product sit in an oven maintained at 80C for 7min. (- these harsh conditions should be avoided - always just dry on the high vac pump).A filterate was again collected (64E)
17:00 : Obtained a second batch of white solid...Ugi product, 64C-2 (304mg)- Yield : 43.8%


12:00 : Concentrated the mother liquor 64E on a steam bath - again should use a rotovap then high vac to avoid decomposing the product - give weight and appearance of 64E when dry


15:50 : 64E (mother liquor) has started to develop solid again.


Benzylisocyanide InChI=1/C8H7N/c1-9-7-8-5-3-2-4-6-8/h2-6H,7H2