Exp050

=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= [|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)] [|H NMR] [|13C NMR] [|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]
 * Benzyl isocyanide**
 * Boc-Gly-OH**
 * 50A (Boc-Gly-OH + Benzyl isocyanide)**

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) 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-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="15991"
 * References**