Objective

To study the interaction between N-(tert-butoxycarbonyl) glycine and 2-Moprholinoethyl isocyanide in Methanol-D4 by NMR spectroscopy.

Procedure

One molar methanol-D4 solutions of 2-morpholinoethyl isocyanide (105uL, 1mmol) 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

Boc-Gly-OH
1H NMR
13C NMR
2-Morpholinoethyl isocyanide (MEIC)
1H NMRCH2 - 3.68 ppm (t) 4H, J=4.74Hz; CH2 - 3.60 ppm(tt) 2H, J big=6.35Hz, J small=1.95Hz; CH2 - 2.65 ppm (tt) 2H,J big=6.35Hz, J small=2.2Hz; CH2 - 2.51ppm (distorted t) 4H,J=4.64Hz with peak integrations of 2:1:1:2; Solvent peaks at 4.78 ppm (s) and 3.30 ppm (quintet).

13C NMR [triplet peaks:156.6 ppm J=24Hz and another triplet peak at 40.0 ppm J=26Hz]

49A (Boc-Gly-OH + MEIC)
t = 02min
t = 04min
t = 08min
t = 20min
t = 24min
t = 28min
t = 33min
t = 65min [13CNMR]
t = 76min
t = 79min
t = 119min
t = 138min
t = 168min [13CNMR]
t = 190min
t = 223min [13CNMR]
t = 240min
t = 274min
t = 286min
t = 19h 53min [13CNMR]
t = 23h 14min

Overlay1: Includes an overlay of the 1H NMRs of Boc-Gly-OH, 2-Morpholinoethyl isocyanide and few selected 49A 1H NMRs.
Overlay2: Includes an overlay of 13C NMRs of Boc-Gly-OH , 2- Morpholinoethyl isocyanide and the 65min, and 23h 14min 13C NMRs of 49A.

Discussion

  1. The 65 minute C NMR shows that the isonitrile triplet near 157 ppm is gone, indicating that the isonitrile is consumed by this time. Overlays 1 and 2 show the formation of intractable multiple products over the 23 hour period. This is unexpected since 2-morpholinoethyl isonitrile has been used successfully in at least one Ugi reaction. (Harriman 1997)
  2. One possible explanation for the special reactivity of this particular isonitrile is the reported cyclization to a spiro type quaternary ammonium compound upon reaction with p-toluenesulfonic or hydrochloric acid (Polyakov 1983). Benzyl isonitrile does not react in this way (EXP050)

Conclusion

It does not appear that 2-morpholinoethyl isonitrile is compatible with the reaction conditions for our Ugi reactions.

Log

2007-01-13

17:00 - Obtained a 1H NMR and a 13C NMR of 2-morpholinoethyl isocyanide and Boc-Gly-OH in methanol-d4.
18:14 - Added Boc-Gly-OH solution to 2-morpholinoethyl isocyanide solution and obtained an HMR.
18:16 - Obtained 1H NMR (t = 02min)
18:18 - Obtained 1H NMR (t = 04min)
18:22 - Obtained 1H NMR (t = 08min)
18:34 - Obtained 1H NMR (t = 20min)
18:38 - Obtained 1H NMR (t = 24min)
18:42 - Obtained 1H NMR (t = 28min)
18:47 - Obtained 1H NMR (t = 33min)
19:19 - Obtained 13C NMR (t = 65min)
19:30 - Obtained 1H NMR (t = 76min)
19:33 - Obtained 1H NMR (t = 79min)
20:13 - Obtained 1H NMR (t = 119min)
20:32 - Obtained 1H NMR (t = 138min)
21:02 - Obtained 13C NMR (t = 168min)
21:24 - Obtained 1H NMR (t = 190min)
21:57 - Obtained 13C NMR (t = 223min)
22:14 - Obtained 1H NMR (t = 240min)
22:48 - Obtained 1H NMR (t = 274min)
22:56 - Obtained 1H NMR (t = 286min)

2007-01-14

14:07 - Obtained 13C NMR (t = 19h 53min)
17:28 - Obtained 1H NMR (t = 23h 14min)

Tags

2-morpholin ethyl isocyanideInChI=1/C7H12N2O/c1-8-2-3-9-4-6-10-7-5-9/h2-7H2
Boc-Gly-OH InChI=1/C7H13NO4/c1-7(2,3)12-6(11)8-4-5(9)10/h4H2,1-3H3,(H,8,11)(H,9,10)