Exp049

=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= [|1H NMR] [|13C NMR] [|1H NMR]CH2 - 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).
 * Boc-Gly-OH**
 * 2-Morpholinoethyl isocyanide (MEIC)**

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

[|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]
 * 49A (Boc-Gly-OH + MEIC)**

[|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= =Conclusion= It does not appear that 2-morpholinoethyl isonitrile is compatible with the reaction conditions for our Ugi reactions. =Log=
 * 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)

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 isocyanide][|InChI=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)] media type="custom" key="15689"