Exp097new.JPG

Objective:

To isolate the product after a prolonged treatment of 86B with 50% trifluoroacetic acid in CDCl3 inorder to answer the Disappearing Methyls puzzle.

Procedure:

rewrite to standard of experimental format - all full sentences and actual times and amounts from log
Dissolved 47.5 mg (0.1 mmol) of the Ugi product 86B from Exp086 in 500 uL CDCl3. Then 500 uL of trifluoroacetic acid was added to the above solution in the NMR tube (50% solution in CDCl3) The reaction was monitored by NMR. After a complete conversion the solution was poured into a centrifuge tube and neutralized using 10% NaOH solution. The organic component was extracted from the solution using dichloromethane and dried with anhy. MgSO4. The product was subjected to NMR and MS analyses.
Characterization of 97B 2-[(aminoacetyl)amino]-N-tert-butyl-2-phenylacetamide: Brown oil; 1H NMR (external image delta.gif ppm, CDCl3) 1.28 (s, 9H), 1.85 (sb, 2H), 3.35 (sb, 2H, 5.45 (d, 1H, J 6.8 Hz), 5.84 (s, 1H), 7.26-7.42 (m, 5H), 8.27 (d, 1H J 6.8 Hz); 13C NMR (external image delta.gif ppm, CDCl3) (put numbers in sequence and double check them - some are obviously wrong) 28.5, 44.7, 51.7, 56.7,1 27.2, 128.1, 12.9, 138.5, 169, 172.2; FAB MS 264.78 (nominal), 267.1703 (exact mass). Yield- 100%? Quantitative conversion.


Results

86B (C25H35N3O5, Mol. Wt.: 457.56)
H NMR -500 MHz
H NMR 300 MHz
H NMR(on 05/04/07-1849)
C NMR
DEPT
All protonated carbons
Overlay of C NMR and All protonated carbons
FAB
97A
t = 05min
t = 09min
t = 13min
t = 33min
t = 43min
t = 50min
t = 01h 00min
t = 01h 02min
t = 02h 05min
t = 02h 07min
t = 18h 01min
t = 45h 29min
t = 66h 01min
t = 6 days
097B (Extract of the basified 097A in CDCl3)
H NMR(300MHz)
H NMR-500MHz
C NMR(300MHz)
C NMR (500MHz)
DEPT
FAB MS
High Res
Low Res

Kinetcs spreadsheet- UCExp097-1

Discussion

Tentative H NMR assignments of 97B
UCExp-097-Kineticsof1,6-Elimination.PNG
Fig - UCExp09-i : Kinetics of 1,6-methylfurfuryl elimination

Kinetics of the 1,6-methyl furfuryl elimination from the Ugi product 086B in 50% TFA in CDCl3, was determined to be first order with a rate constant k= 0.9x10-3 min-1
This is similar to the kinetics of 1,6-elimination observed previously;
Exp097, k= 0.9x10-3 min-1 50% TFA/ CDCl3
Exp091, k = 1.2x10-3 min-1 50% TFA/ CDCl3
Exp070, k = 0.9x10-3 min-1 10% TFA/CDCl3

Conclusion

From the NMRs it can be conclusively said that, after an initial boc deprotection, the ugi product undergoes a loss of methyl furfuryl group which has been recorded several time in analogous ugi products (with methyl furfuryl group) under similar conditions as in Exp098, Exp091, Exp070, EXP065, EXP067. This has also been reported in the UsefulChem blog.

Log

2007-05-04

18:00 Weighed the ugi product (86B) (47.5 mg, 0.1 mmol) in an NMR tube and dissolved it in CDCl3 (500 uL)
18:49 Obtained H NMR of the ugi product 86B in CDCl.
19:02 Added TFA (500 uL) to the NMR tube, this is 97A
19:07 Obtained H NMR of 97A. (t = 05min)
19:11 Obtained H NMR of 97A (t = 09min)
19:15 Obtained H NMR of 97A (t = 13min)
19:35 Obtained H NMR of 97A (t = 33min)
19:45 Obtained H NMR of 97A (t = 43min)
19:52 Obtained H NMR of 97A (t = 50min)
20:02 Obtained H NMR of 97A (t = 1h 00min)
20:04 Obtained H NMR of 97A (t = 1h 02min)
21:07 Obtained H NMR of 97A (t = 2h 05min)
21:09 Obtained H NMR of 97A (t = 2h 07min)

2007-05-05

13:03 Obtained H NMR of 97A (t = 18h 01min)

2007-05-06

16:31 Obtained H NMR of 97A (t = 45h 29min)

2007-05-07

13:03 Obtained H NMR of 97A (t = 66h 01min)

2007-05-10

17:41 Obtained H NMR Of 97A (t = 6days)
18:00 Poured the contents (97A) of the NMR tube into a centrifuge tube and basified the acidic (pH ~1) solution with 10% NaOH (2 mL) until the pH reached ~10. As the base was added to 97A, the centrifuge tube warmed up, and the deep brown color of the solution lost its intensity.
18:15 Added dichloromethane (3 mL) to the centrifuge tube, mixed the contents well by squirting with a pasteur pippet. The deep brown bottom layer settled, on top of which a clear aqueous layer incorporating a yellow precipitate (almost at interface of the organic and aqueous layers) appeared.
18:30 The bottom organic layer was pipetted out and the top aqueous layer was extracted once agian with methylene chloride (2 mL).
18:45 The organic layers were combined together and washed with distilled water (2 mL). The accumulated brown organic layer was dried with anhydrous MgSO4.
21:00 After letting sit in for about half an hour in MgSO4, dichloromethane containing brown liquid was set on a vacuum pump for evaporation.
21:35 After evaporating the solvent 97B (29mg) was obtained. [ Problem with the yield- because a 100% recovery cannot be more than 26.3mg, weight likely swollen by some solvent or other impurities]

2007-05-11

19:06 Obtained H NMR of 97B by dissolving it in CDCl3 (1ml)

2007-05-12

09:49 Obtained C NMR of 97B

2007-05-17

16:30 Obtained mass spectra (both low resolution and the exact mass)

Tags

86B InChI=1/C25H35N3O5/c1-17-13-14-19(32-17)16-28(20(29)15-26-23(31)33-25(5,6)7)21(18-11-9-8-10-12-18)22(30)27-24(2,3)4/h8-14,21H,15-16H2,1-7H3,(H,26,31)(H,27,30)
097product InChI=1/C14H21N3O2/c1-14(2,3)17-13(19)12(16-11(18)9-15)10-7-5-4-6-8-10/h4-8,12H,9,15H2,1-3H3,(H,16,18)(H,17,19)