Objective

To study the chemical interaction between N-(tert-butoxycarbonyl) glycine and Benzyl isocyanide in Methanol-D4 by NMR spectroscopy.

Procedure

One molar methanol-D4 solutions of Benzylisocyanide (120uL, 0.99mmol) and Boc-Gly-OH(175mg, 1mmol) in CD3OD are prepared in separate 1 dram vials. 800uL of the solutions are used to obtain initial NMR spectra. Then 400uL of each solution is transfered to a clean nmr tube and shaken vigorously for a few seconds, the reaction is monitored by NMR spectra.

Results

Benzyl isocyanide
1H NMR [CH2- 4.6 ppm (t) J=2.2Hz, aromatics- 7.3 - 7.4 ppm (broad multiplet)]
13C NMR [CH2 (t)-46 ppm(J=28Hz), aromatics 127.9-134.5, Isonitrile Carbon (t)-157 ppm(J=22Hz)]
Boc-Gly-OH
H NMR
13C NMR
50A (Boc-Gly-OH + Benzyl isocyanide)
t = 02min
t = 06min
t = 8min
t = 15min
t =19min
t = 31min [C-13 NMR]
t = 34min
t = 37min
t = 87min [C-13 NMR]
t = 92min
t = 94min
t = 158min
t = 175min [C-13 NMR]
t = 211min
t = 215min
t = 24h 27min [C-13 NMR]
t = 25h 59min
t = 26h 47min [C-13 NMR]
t = 27h 05min

Spectral Overlays

Overlay1 (Includes 1H NMR of Boc-Gly-OH, Benzylisocyanide, and spectra after 2min, 415min, 34min, 92min, 215min and 27h 5min after mixting them.)
Overlay2 (Includes 13C NMR of Boc-Gly-OH, Benzylisocyanide, and spectra after 31min, 87min, 175min, 24h 27min and 26h 47min).

Discussion

  1. Overlays 1 and 2 show little change over a 27 hour period, indicating that benzyl isonitrile does not react with Boc-glycine to any significant extent during this time period. This contrasts sharply with the reactivity of 2-morpholinoethyl isonitrile under the same conditions. (EXP049)
  2. The triplet peaks at about 46 ppm (J=28 Hz) and 157 ppm (J=22 Hz) in the C13 NMR spectra correspond to the carbons directly linked to and coupling with the isonitrile nitrogen, consistent with prior reports of isonitrile NMR spectra.[1]
  3. The proton nmr of Benzyl isocyanide shows a triplet for the CH2 group at 4.6ppm, this peak has moved to 4.7ppm in the 27h 05min spectrum. In general there is a drift of about 0.1 ppm in the chemical shifts after the acid addition in the HNMR.
  4. Overlay 2 shows extraneous C NMR peaks at 203.8 ppm and 176.3ppm ppm appearing in some spectra, including the initial Boc-Gly spectrum. These appear to be related to our Varian 300 instrument and highlights the importance of using multiple spectra in an NMR monitoring run.

Conclusion

The isonitrile group by itself is not sufficient to explain the reactivity of 2-morpholinoethyl isonitrile with Boc-Gly in methanol. In the future, benzyl isonitrile will be used in our Ugi reactions involving Boc-Gly-OH.

Log

2007-01-15

18:00 - Obtained a 1H NMR and a 13C NMR of Benzylisocyanide and Boc-Gly-OH in methanol-d4.
19:49 - Added Boc-Gly-OH solution to Benzylisocyanide solution and obtained an HMR.
19:51 - Obtained H NMR (t = 02min)
19:55 - Obtained H NMR (t = 06min)
19:57 - Obtained H NMR (t = 08min)
20:05 - Obtained H NMR (t = 15min)
20:08 - Obtained H NMR (t = 19min)
20:20 - Obtained C13 NMR (t = 31min)
20:23 - Obtained H NMR (t = 34min)
20:26 - Obtained H NMR (t = 37min)
21:16 - Obtained C13 NMR (t = 87min)
21:21 - Obtained H NMR (t = 92min)
21:23 - Obtained H NMR (t = 94min)
22:27 - Obtained H NMR (t = 158min)
23:14 - Obtained C13 NMR (t = 175min)
23:20 - Obtained H NMR (t = 211min)
23:24 - Obtained H NMR (t = 215min)

2007-01-16

08:16 - Obtained C13 NMR (t = 24h 27min)
09:48 - Obtained H NMR (t = 25h 59min)
10:36 - Obtained C13 NMR (t = 26h 47min)
10:54 - Obtained H NMR (t = 27h 05min)
References
1. Ernö Pretsch, Renato Zenobi; Anal Bioanal Chem (2004) 378 : 15–16

Tags

Benzylisocyanide InChI=1/C8H7N/c1-9-7-8-5-3-2-4-6-8/h2-6H,7H2
Boc-Gly-OHInChI=1/C7H13NO4/c1-7(2,3)12-6(11)8-4-5(9)10/h4H2,1-3H3,(H,8,11)(H,9,10)