Anthony crasto presents Ugi reaction

1. Dr. ANTHONY MELVIN CRASTO
PRINCIPAL SCIENTIST

7. MECHANISM

12. DRUGS

15. VARIATIONS

16. Ugi-Diels-Alder reaction

17. Ugi-Smiles reaction

18. Ugi-Buchwald-Hartwig reaction

19. Ugi-Heck reaction

24. SYNTHESIS

25. Ugi Reaction; N-allyl-N-(2-
(cyclohexylamino)-2-oxo-1-phenylethyl)-
3-nitropropanamide

26. Chemicals Used
Benzaldehyde (Acros Organics)
Allylamine (Merck)
Cyclohexyl isocyanide (Merck)
3-Nitropropionic acid (Sigma)
MeOH
Procedure
A solution of benzaldehyde (1.70 mmol, 0.172 mL), allylamine (1.70 mmol, 0.128
mL), cyclohexyl isocyanide (1.70 mmol, 0.211 mL) and 3-nitropropionic
acid (1.70 mmol, 0.202 g) in 10 mL MeOH was stirred at room temperature under
nitrogen atmosphere. After 28 h, the solution was concentrated under reduced
pressure to leave a pale yellow solid. The residue was washed with cold Et2O (3
x 20 mL) to give pure title compound as a white solid (475 mg, 75% yield, mp
190-192 °C, Rf= 0.44 (ethyl acetate-hexane; 1 : 1). 1H and 13C NMR spectra
showed title compound is a mixture of two rotamers in an approximately 1:4.5
ratio.

27.  Data
 IR-ATR: 3258, 3084, 2926, 2855, 1638, 1629, 1547 cm-1.
1H NMR (400 MHz, DMSO-d ): (both rotamers) ppm = 8.30 (0.18H, d, NH, J=
6
7.71 Hz), 8.21 (0.82H, d, NH, J= 7.71 Hz), 7.40-7.28 (3H, m, aromatic CH), 7.22
(2H, d, aromatic CH, J= 7.08 Hz), 6.12 (0.82H, s, CH-Ar), 5.65 (0.18H, s, CH-
Ar), 5.45-5.37 (1H, m, CH2=CH), 5.02 (1H, appear d, CH2=CH, J=17.39 Hz),
4.95 (1H, dd, CH2=CH, J= 1.12, 10.40 Hz), 4.75-4.72 (2H, m, CH2NO2), 4.04 (2H,
m, CH2=CHCH2), 3.60-3.55 (1H, m, CHNH), 3.05 (2H, t, CH2CH2NO2,
J=5.23Hz), 1.75-1.62 (4H, m, cyclohexyl CH2), 1.55-1.52 (1H, m, cyclohexyl
CH2), 1.30-1.04 (5H, m, cyclohexyl CH2).
13C NMR (100 MHz, DMSO-d ): (both rotamers) ppm = 170.17, 169.24, 167.95,
6
167.34, 136.47, 136.13, 134.83, 134.27, 128.80, 128.47, 128.41, 128.02, 127.84,
115.85, 115.23, 70.53, 62.28, 59.66, 47.75, 47.65, 47.31, 46.87, 32.17, 32.05, 30.03,
25.11, 24.53, 24.43.

 Lead Reference
 1. Ugi, I.; Meyr, R. Angew. Chem., 1958, 70, 702.
2. Ugi, I.; Meyr, R. Fetzer, U. Angew. Chem., 1959, 71, 373.
3. Ugi, I.; Offermann, K. Angew. Chem. Int. Ed. Engl., 1963, 2, 624.
4. Akritopoulou-Zanze, I., Gracias, V., Moore, J. D., Djuric, S. W. Tetrahedron
Lett., 2004, 45, 3421.

29.  1-cyclohexenyl isocyanide (47 mg, 50.2 µL,0.44 mmol) was added
to a solution ofpropionic acid (33 mg, 32.9 µL,0.44
mmol), aniline (41 mg, 40.1 µL, 0.44 mmol), 4-
phenylethylpiperidone (90 mg, 0.44 mmol) in MeOH (2.2 mL) at
room temperature and the solutionwas heated at 55 C and stirred
for 24 h. The solvent was removed underreduced pressure, and
the residue was dissolved in EtOAc (5 mL). The organic solution
was washed with sat aq NaHCO3 (2 2.5 mL) and brine (2.5 mL)
and dried (MgSO4), and the solvent was removed under reduced
pressure. The crude product was purified either via HPLC/MS
preparative with gradient starting from 10% MeOH / 90% H2O /
0.1% ammonia reaching 100% MeOH / 0.1%ammonia. The
product was obtained in 82% yield (165 mg).

 Reference: Tetrahedron Letters Volume 51, Issue 22, 2 June
2010, Pages 2983-2985

34. 
 THANKS AND REGARD'S
DR ANTHONY MELVIN CRASTO Ph.Damcrasto@gmail.com
 MOBILE-+91 9323115463
 GLENMARK SCIENTIST , NAVIMUMBAI, INDIA
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 http://anthonycrasto.jimdo.com/
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