Researcher

David Bulger


Since Google Wave is "Sunsetting" in 2012, here's a zip file with all the files and discussion from the wave: Ugi Characterization Wave.zip

Objective

To synthesize a Ugi product from different combinations of 3,5-Dimethoxybenzaldehyde, 1-Amino-1-Cyclohexanecarboxylic acid, Phenylpropionic acid, Boc-L-Proline, Benzylamine, t-butylisocyanide, and cyclohexyl isocyanide in methanol as a U4CR.
[Your selection of Ugi reactants should not have competing groups in general - for example an amine on the carboxylic acid component JCB]
[The selection was based on the top 20 results from the Hex docking software results. Would this affect the reaction rate and/or the actual product of the reaction? DB]
[It would lead to multiple products with 2 reagents competing as amine groups - it should not have been added to the virtual library in the first place. But you were not able to make a solution in methanol anyway. JCB]

Procedure

Previous Experiment

Experiment can be found at Ugi Reaction Blog#001.

NMR Spectra: Sample 4, Sample 10. Note: Samples analyzed in deuterated chloroform and original solvent was methanol.
[You will have to thoroughly dry this sample under a vacuum to get rid of methanol and get a yield and get spectra to properly characterize. Ugi products with propynoic acid are tricky because they show up as rotamers: see the **isolated compounds list** to compare NMRs JCB][A large residual CHCl3 peak just means that you have very little compound JCB]
[Also your spectra are badly shifted (looks like more than 1 ppm) - you will need to resolve this to properly characterize JCB] I am redoing the NMR spectra for this Ugi Product characterization similar to that found in Exp234. This should give a higher concentration, purity, and detail than before. Also, many more types of NMR will be run, such as NOESY, which might be able to show which rotamers are present. [It will be interesting to see if NOESY can identify the rotamers - but it might not be easy JCB]

Characterization by NMR


A concentrated sample of Ugi Product labeled "Ugi1.4" was prepared in CDCl3. Various 1H and 13C NMR runs will be performed on this sample, including some two-dimensional analyses. These will be used with NMR prediction software (HyperChem release 7.5 and HyperNMR) to confirm the identity. Comparing with 173G19-4 in Exp193 should especially aid the characterization of the groups from the phenylpropionic acid, benzylamine, and dimethoxybenzaldehyde as well as the rotamers. Infrared Spectroscopy will also be used to identify key functional groups and to compare with 173G19-4 in Exp193.

Results

Ugi 233 Spreadsheet
BenzoicAcid_CDCl3.jdx
Raw JCAMP-DX for BenzoicAcid_CDCl3

ACD/NMR Processor 12.1 Corrected Spectra with XY conversion via JSpecView
Ugi233H1.jdx
Ugi233C13.jdx
Raw JCAMP-DX for Ugi233H1
Raw JCAMP-DX for Ugi233C13
Ugi233NOESY.pdf
Ugi233COSY.pdf
Ugi233CHSHF.pdf
Note: Peaks will be added to 2D .pdf spectra at a later date.

FT-IR Pressed Disk Method: FTIRUgi1.10close, FTIRUgi1.10cor

IR (KBr, thin film) (cm-1): 3300 (s, NH), 3150-3000 (m, aromatic), 3000-2850 (s, aliphatic), 2222 (s, C≡C), 1950 (w), 1680 (s, 1,3,5-trisubstituted benzene ring aromatic), 1640 (s, C=O, amide II), 1600 (s, m-trisubstituted symmetric aromatic ring stretch), 1540 (s, Amide II NH bend), 1490 (s, m-trisubstituted symmetric aromatic ring stretch), 1150 and 1050 (s, m-trisubstituted symmetric aromatic in-plane CH bend), 800-666 (br, m, out-of-plane NH wagging), 680 and 775 and 820 (s, m-trisubstituted symmetric aromatic out-of-plane CH bend).
References: (Brain C. Smith “Infrared spectral Interpretation: a systematic approach” (GoogleBooks), 78)(Silverstein 82,86,87,101)(Shriner 200,202).

H NMR with TMS converted by Dr. Antony Williams: 233hnmrtmsjdx
1H NMR: uc233final
1H NMR with TMS: 233hnmrtms[This is really strange - with the TMS at zero, the high field section seems reasonable but your methoxys and phenyl are definitely higher field than they should be - I can't even find the residual CHCl3 at 7.27 - it seems like the spectrum is compressed JCB] I am almost certain that the issue resides in the exporting of the NMR spectrum. On the spectra I printed out, TMS is at zero and chloroform is at about 7.26 with the aromatic groups downfield past 7.0 ppm. Furthermore, a close-up of the peaks on the print-out shows much better resolution than on the exported spectra. For now, I will continue to upload both the interactive and paper copies of the NMR spectra.
Photos of 1H NMR with TMS print-out: Ugi1.4tms.pdf, Ugi1.4tmsdoublet.pdf, Ugi1.4tmsclose.pdf, Ugi1.4jspectmsclose.pdf
Note: These two close-ups seem to show the compression distorting the resolution. The peaks look the same, except they are closer together and the bottoms are distorted in the JspecViewer. And if one looks close enough, one can even see where the spectrum was shifted together causing the compression and distortion.
FT-IR Pressed Disk Method: FTIRUgi1.10close, FTIRUgi1.10cor
IR (KBr, thin film) (cm-1): 3300 (s, NH), 3150-3000 (m, aromatic), 3000-2850 (s, aliphatic), 2222 (s, C≡C), 1950 (w), 1680 (s, 1,3,5-trisubstituted benzene ring aromatic), 1640 (s, C=O, amide II), 1600 (s, m-trisubstituted symmetric aromatic ring stretch), 1540 (s, Amide II NH bend), 1490 (s, m-trisubstituted symmetric aromatic ring stretch), 1150 and 1050 (s, m-trisubstituted symmetric aromatic in-plane CH bend), 800-666 (br, m, out-of-plane NH wagging), 680 and 775 and 820 (s, m-trisubstituted symmetric aromatic out-of-plane CH bend). (Brain C. Smith “Infrared spectral Interpretation: a systematic approach” (GoogleBooks), 78)(Silverstein 82,86,87,101)(Shriner 200,202)
13C NMR: ugi1.4c13, ugi1.4c13close1, ugi1.4c13close2
Distortionless Enhancement by Polarization Transfer (DEPT) (135 deg) decoupled:ugi1.4dept135, ugi1.4dept135close1, ugi1.4dept135close2
DEPT (90 deg) decoupled:ugi1.4dept90
Double Quantum Filtered Correlation Spectroscopy (DFQ COSY):ugi1.4cosy, ugi1.4cosyclose1, ugi1.4cosyclose2
Heteronuclear shift correlation (chshf):ugi1.4chshf, ugi1.4chshfclose1, ugi1.4chshfclose2
Nuclear Overhauser Effect Spectroscopy (NOESY):ugi1.4noesy, ugi1.4noesyclose1, ugi1.4noesyclose1, ugi1.4noesyclose3
HyperChem screen capture of Ugi 233 Closed: 233closed1, 233closed2
HyperNMR Computed Coupling and Shielding Constants for all atoms with the propionic keto group in the closed position relative to the rest of the molecule: (C)
HyperNMR Computed Coupling and Shielding Constants for all atoms with the propionic keto group in the closed position after molecular dynamics (300K for 1ps in vacuum): (CMD)
HyperChem screen capture of Ugi 233 Open: 233open1, 233open2
HyperNMR Computed Coupling and Shielding Constants for all atoms with the propionic keto group in the open position: (O)
HyperNMR Computed Coupling and Shielding Constants for all atoms with the propionic keto group in the open position after molecular dynamics (300K for 0.1-0.2 ps in vacuum): (OMD)
Index (C)
Shift (C)
Index (CMD) 0.1 ps
Shift (CMD) 0.1 ps
Index (O)
Shift (O)
Index (OMD) 0.2 ps
Shift (OMD) 0.2 ps
19H
0.693
15H
0.693
19H
0.896
14H
-0.606
20H
1.044
20H
0.85
20H
0.904
13H
0.22
16H
1.188
18H
0.983
11H
1.051
11H
1.06
18H
1.244
19H
1.027
16H
1.107
16H
1.256
17H
1.339
16H
1.119
18H
1.286
19H
1.259
15H
1.373
17H
1.511
15H
1.338
20H
1.329
12H
1.531
10H
1.52
12H
1.347
15H
1.472
14H
1.617
11H
1.53
14H
1.352
18H
1.579
11H
1.65
14H
1.64
10H
1.379
17H
1.61
10H
1.69
12H
1.719
17H
1.452
10H
1.687
13H
2
13H
2.635
13H
1.637
12H
1.854
46H
3.21
46H
3.196
38H
3.404
31H
2.804
52H
3.449
45H
3.545
32H
3.43
32H
3.973
45H
4.308
52H
3.571
31H
3.986
38H
4.606
61H
5.46
59H
5.359
45H
6.192
65H
6.559
59H
6.121
59H
5.982
47H
6.469
47H
6.656
34H
6.558
37H
6.33
66H
6.74
45H
6.661
37H
6.753
9H
6.675
64H
6.787
36H
6.664
49H
6.763
34H
6.769
65H
6.844
63H
6.671
33H
6.851
51H
6.852
35H
6.801
50H
6.695
51H
6.86
47H
6.894
63H
6.928
64H
6.791
36H
6.9
65H
6.945
36H
6.97
35H
6.812
50H
6.944
36H
6.968
37H
6.999
66H
6.983
35H
6.956
35H
7.002
62H
7.052
37H
7.004
47H
6.994
48H
7.037
34H
7.079
62H
7.141
48H
7.006
49H
7.076
33H
7.116
33H
7.158
9H
7.285
33H
7.089
50H
7.435
34H
7.612
65H
7.568
50H
7.113
51H
7.906
9H
7.839
66H
7.687
66H
7.578
46H
7.945
46H
8.142
60H
7.972
60H
8.155
9H
8.087
51H
8.186


Discussion


The DEPT90 has been having problems and will not be used in the interpretation.

Conclusion

Ugi 233 was successfully synthesized.

Log

11.16.09
18.40 - Added Ugi 1.4 to clean NMR tube
18.42 - Auto-gradient shim and lock (Z1:-1214;Z2:-1009;Z3:-108;Z4:594)
18.45 - Setup NMR to run overnight as follows: 1H NMR (64 scans), 13C NMR, DEPT130, DEPT90, DQF (Double Quantum Filter) COSY, Heteronuclear Shift Correlation (chshf), NOESY

11.23.09
15.35 - Vaccum-desiccated with heat the equipment following washing with Methylene Chloride
15.45 - Weighed out 0.114 2 g KBr
15.55 - Lightly pressed large chunks of KBr into sand-size particles in a mortar using a pestle
15.56 - Vaccum-desiccated with heat the KBr in the mortar
16.08 - Removed KBr from dessicator (National Appliance Company Model 5831) and added ~1 mL of Methylene Chloride to Ugi 1.10 solid (dissolved readily)
16.10 - Poured solution on KBr and let evaporate
16.10 - Vaccum-desiccated with heat the Ugi 1.10/KBr sample in mortar
16.22 - Removed from dessicator
16.24 - Transferred sample from the mortar to barrel with one bolt
16.26 - Vaccum-desiccated with heat the barrel with sample
16.30 - Removed from dessicator
16.34 - Pressed other bolt into barrel using bench-press
16.35 - Vaccum-desiccated with heat the barrel
16.38 - Removed from dessicator
16.40 - Removed bolts revealing opaque disk
16.42 - Collected background and spectrum of Ugi 1.10
16.47 - Removed disk, saving in original glass vial

12.06.10
18.00 - Weighed NMR Tube (2.6846 g)
18.03 - Added Benzoic Acid and weighed NMR Tube (2.7163 g)
18.05 - Added Chloroform-d (99.8%) and weighed NMR Tube (3.7952 g)
18.20 - 1H NMR Spectrum (Gain value: 16) (BenzoicAcid_CDCl3.jdx)
18.30 - Reweighed NMR tube (3.7953 g)

Acknowledgements

The author thanks Dr. William Collier (Instructor for CI) for his help with the characterization of these Ugi Products, and the Chemical Instrumentation (CI) Lab partners Chelsea Kimbrough, Jessica Jowers, Dustin Sprouse, and Gloria Jordan for helping with the project (use of camera) as part of the CI Lab Group Project for a few weeks during the Fall 2009 semester.

References


Silverstein R. and Webster F. Spectrometric Identification of Organic Compounds, Sixth Edition. John Wiley & Sons: New York, 1998.
Shriner R., Hermann C., Morrill T., Curtin D., Fuson R. The Systematic Identification of Organic Compounds, 8th Edition. John Wiley & Sons: New York, 2004.
Spectra of Starting Materials

3,5-Dimethoxybenzaldehyde
http://www.sigmaaldrich.com/spectra/ftir/FTIR000627.PDF (FTIR)
http://www.nmrdb.org/predictor?smiles=C%3D1%28C%28%3DCC%28C%3DO%29%3DCC%3D1OC%29OC%29 (Predicted FTNMR)

Phenylpropionic acid
http://webbook.nist.gov/cgi/cbook.cgi?ID=C501520&Units=SI&Type=IR-SPEC#IR-SPEC (FTIR)
http://www.sigmaaldrich.com/spectra/fnmr/FNMR000998.PDF (FTNMR)

Benzylamine
http://webbook.nist.gov/cgi/cbook.cgi?ID=C100469&Type=IR-SPEC&Index=1#IR-SPEC (FTIR)
http://www.sigmaaldrich.com/spectra/fnmr/FNMR002357.PDF (FTNMR)

Cyclohexylisocyanide
http://www.sigmaaldrich.com/spectra/ftir/FTIR000824.PDF (FTIR)
http://www.sigmaaldrich.com/spectra/fnmr/FNMR000952.PDF (FTNMR)

Methanol
http://www.astrochem.org/compare.html (FTIR Low-Quality)
http://www.hull.ac.uk/chemistry/spectroscopy/infrared_spectrum.php?res=high&molecule=methanol (FTIR High-Quality)
http://www.muhlenberg.edu/depts/chemistry/chem201woh/1Hmethanol.html (FTNMR)
http://www.chem.purdue.edu/gchelp/nmr/meoh4.html (FTNMR)