Exp099.JPG

Objective

To synthesize a Ugi product from benzaldehyde, furfurylamine , tert-butyl isocyanide and boc-glycine in methanol using Ugi 4CR.

Procedure

A solution of benzaldehyde (212 uL, 2 mmol) and furfurylamine (FFA) (234.8 uL, 2.2 mmol, 10% excess ) was made in methanol in a 4mL volumetric flask. After about two and half hours solution of boc-glycine(350 mg, 2 mmol), and tert-butyl isocyanide (226 uL, 2 mmol) made up in 4 ml volutmeric flask in methanol was added the preformed Imine solution. A crystalline Ugi product was obtained which was filtered and washed with methanol.
Charcterization of 099C :White solid; m.p. 202-204 C;1H NMR (500MHz,external image delta.gif ppm, CDCl3) 1.33 (s, 9H), 1.45 (s, 9H), 4.21 (m, 2H), 4.49 (d, J=18Hz, 1H), 4.50 (d, J=18Hz, 1H), 5.47 (s, 1H), 5.60 (s, 1H), 5.62 (s, 1H), 5.89 (s, 1H), 6.10 (s, 1H), 7.19 (s, 1H), phenyl 7.21-7.37 (m, 5H); 13C NMR ; (500MHz, external image delta.gif ppm, CDCl3) 28.3, 28.6, 42.3, 42.8, 51.7, 62.9, 79.5, 107.7, 110.4, 128.5, 128.7, 129.6, 134.7, 141.9, 149.8, 155.7, 168.4 170.2; IR (Ʋmax cm-1 ATR): 1645,1673,1699, 3331; FAB-HRMS -calculated for C24H33N3O5 m/z 444.2498 [M+H], obtained 444.2517.
[Assignments for HNMR and CNMR are based on the spectra obtained in Exp206 and reported in Paper03 (see Discussion section)]

Results

Benzaldehyde
H NMR
C NMR
Furfurylamine
HNMR
CNMR
tert-butyl isocyanide
H NMR
C NMR
Boc-Gly-OH
H NMR
C NMR

99A
t = 33 min
t = 48 min
t = 40 min
t = 46 min
t = 51 min
t = 57min
99C C24H33N3O5
HNMR
HNMR (08/18/08)
Labile H Exchange HNMR (08/18/08) [dd at 6.1 ppm J= 1.95Hz; 1.22Hz]
Overlay of HNMR and labile H exchange
CNMR
DEPT
All protonated carbons
CNMR Vs DEPT overlay
99C FAB MS
High Res
Low Res
IR (08/18/08)
M.p -202-204 C

Discussion

Tentative assignments-99C
The CNMR Vs DEPT overlay inconjunction with DEPT (image) produces similar results as a DEPTQ experiment where the spectral array includes quaternary carbon also; here in the overlay the CNMR is blue and All protonated carbons are green. All the protonated carbons have a green counterpart beneath blue peaks whereas quat carbons have none.
In the Characterization report, NMR data obtained from Exp206 has been used, because the quality of the HNMR from this experiment makes it difficult to identify some peaks...the HNMR from Exp206 shows five peaks in the 5.2-6.2PPM range, this is not very clear from the spectrum in this experiment. The extra peak is assumed to belong to the labile NH protons which are hiding under other peaks; similiniarly the S/N of the CNMR in Exp206 makes the spectrum, more convincing.

Conclusion

The Ugi product was obtained in 37% yield considering only the first precipitate 99C. Assuming all the crystallization fractions are pure product the yield may be as high as 47%.

Log

2007-05-15

13:20 Madeup a solution of benzaldehyde and furfurylamine in methanol this is 99A.
13:53 Obtained HNMR by transferring 800uL of 99A into an NMR tube. The lock on the machine was achieved by immersing a sealed capillary tube filled with acetone-d6. (t = 33min)
13:58 Obtained HNMR of 99A (t = 38min)
14:00 Obtained HNMR of 99A (t = 40min)
14:06 Obtained HNMR of 99A (t = 46min)
14:11 Obtained HNMR of 99A (t = 51min)
14:17 Obtained HNMR of 99A (t = 57min)
15:30 Dissolved Boc-Glycine (350mg) and tert-butylisocyanide (226uL) in methanol (4mL) in a volumetric flask.
15:47 Added the solution of Boc-Glycine and tert-butylisocyanide to 99A, this is 99B-1
16:30 Left in the sonicator at room temperture
17:30 Removed from the sonicator, an off white precipitate appeared. The precipitate was left in the hood.

2007-05-16

14:00 Transferred 99B-1 from the erlenmeyer into a centrifuge tube, and centrifuged the precipitate out.
14:10 The residue was washed with methanol (3ml x 2), the supernatant was added to the previously collected supernatant, which is the mother liquor 99B-2
14:30 Scrapped the wet residue from the centrifuge tube and spread it in a watch glass to air dry.
17:50 Obtained a dry 99C (331mg)
20:38 Obtained HNMR of 99C

2007-05-17

12:00 Obtained CNMR Of 99C.

2007-05-21

17:30 Solid had appeared at the bottom of the erlenmeyer flask containing 99B-2. The solution was poured into a centrifuge tube and the solid was centrifuged out.The supernatant, mother liqour 99B-3 was saved for further crystallization.
18:30 The solid was air dried and an off white powder was scraped out the tube. This is 99C-2 (38mg).

2007-05-24

19:15 Crystals formed in 99B-3 were filered through a sintered glass funnel and the mother liquor was once again saved the mother liquor is 99B-4 and the crystals 99C-3 (49.7mg)- A total of 418.7mg of the ugi product obtained- 47.2% Yield. There is no NMR of any fraction except 99C so these additional fractions cannot be counted in the yield until proven to be pure product

2008-08-18

14:00 A HNMR of the above ugi product was obtained in CDCl3 (~1.5mL) ; then a exchange of labile protons was performed by adding 90uL CD3OD to the solution. An overlay was created to confirm the presence of labile protons. Each of the two HNMRs were obtained on a 300MHz varian Unity inova instrument.
17:00 Obtained an IR by ATR on a Perkin Elmer- Spectrum one 1000.
19:20 Obtained a melting point of the Ugi product; 202-204C



Tags


Compound
Inchi Key
Inchi
Furfurylamine
DDRPCXLAQZKBJP-UHFFFAOYAX
InChI=1/C5H7NO/c6-4-5-2-1-3-7-5/h1-3H,4,6H2
Benzaldehyde
HUMNYLRZRPPJDN-UHFFFAOYAE
InChI=1/C7H6O/c8-6-7-4-2-1-3-5-7/h1-6H
tert-butylisocynide
FAGLEPBREOXSAC-UHFFFAOYAL
InChI=1/C5H9N/c1-5(2,3)6-4/h1-3H3
Boc-Glycine
VRPJIFMKZZEXLR-UHFFFAOYAN
InChI=1/C7H13NO4/c1-7(2,3)12-6(11)8-4-5(9)10/h4H2,1-3H3,(H,8,11)(​H,9,10)
Ugi Product
BXAOUWIVXLQYOZ-UHFFFAOYAZ
InChI=1/C24H33N3O5/c1-23(2,3)26-21(29)20(17-11-8-7-9-12-17)27(16- ​18-13-10-14-31-18)19(28)15-25-22(30)32-24(4,5)6/h7-14,20H,15-16H2​ ,1-6H3,(H,25,30)(H,26,29)