Exp108

== =Objective= To synthesize a [|Ugi adduct] from [|benzaldehyde], [|furfurylamine], [|benzylisocyanide] and [|Boc-Gly-OH] in methanol using Ugi 4CR. =Procedure= A solution of [|benzaldehyde] (212 uL, 2.09 mmol) and [|furfurylamine] (FFA) (235uL, 2.66 mmol )was prepared in methanol-d4 in a 4mL volumetric flask to form an imine overnight. The next day a solution of [|Boc-Gly-OH](350 mg, 1.99 mmol), and[| benzylisocyanide] (240uL, 1.97 mmol) made up in a 4ml volumetric flask in methanol was added to the preformed imine. The product was filtered and washed with ice cold methanol (5mL).
 * Characterization of 108C**:**//tert//-butyl 5-(benzylamino)-3-(furan-2-ylmethyl)-2,5-dioxo-4-phenylpentylcarbamate:** Colorless Crystals; M.pt 146-148C; HNMR ([[image:http://pubs.acs.org/images/gifchars/delta.gif]] ppm, CDCl3) 1.43 (s, 9H), 4.18 (m, 2H), 4.43 (m, 2H), 4.48 (s, 2H), 5.46 (s, 1H), 5.68 (s, 1H), 5.94 (s, 1H), 6.09 (m, 1H), 6.30 (s, 1H), 7.10-7.50 (m 11H) 13C NMR ([[image:http://pubs.acs.org/images/gifchars/delta.gif]] ppm, CDCl3) 28.3, 42.5, 42.8, 43.6, 63.0, 79.5, 107.9, 110.3, 110.8, 127.4, 127.6, 128.6, 128.7, 129.6, 134.2, 137.7, 142.0, 149.5, 155.7, 169.0, 170.3; FAB HRMS: //m/z// 478.2366; calcd for C27H31N3O5 (M+H).

=Results=

[|H NMR (CDCl3)] - **//you also need spectrum in undeuterated methanol if you choose to monitor this way//** [|C NMR] [|H NMR] [|C NMR] [|H NMR] [|C NMR] [|H NMR] [CH2- 4.6 ppm (t) J=2.2Hz, aromatics- 7.3 - 7.4 ppm (broad multiplet)] [|C NMR] [CH2 (t)-46 ppm(J=28Hz), aromatics 127.9-134.5, Isonitrile Carbon (t)-157 ppm(J=22Hz)]
 * Benzaldehyde**
 * Furfurylamine**
 * Boc-Gly-OH**
 * Benzyl isocyanide**

[|t = 25min] No deuterated solvent added. [|t = 17h 18min] (**//spectrum way off scale - set methanol CH3 peak//**) [|t = 20h 34min] [|t = 5 days] [|t = 1week] [|HNMR] (53mg / 800uL CDCl3) [|image] [|CNMR] [|Image] [|High Res] [|Low Res]
 * 108A**
 * 108B**
 * 108C**-1 (192mg)
 * FAB MS**

= = =Discussion=

A four component ugi reaction involving the imine of benzaldehyde and furfurylamine, and boc-glycine and benzyl isocyanide is only ~70% complete after one week, assuming the peak at 1.4 ppm (108B spectra) is the tert-butyl group. =Conclusion=

The ugi product was successfully synthesized

=Log=

2007-06-14
19:35 Made up a solution of benzaldehyde and furfurylamine in methanol, in a 4 mL volumetric flask.This is **108A** 2005 Obtained an H NMR of 108A by removing 800uL of 108A in an NMR tube....spectrum obtained without an addition of any deuterated solvent.

2007-06-15
12:53 Obtained H NMR of 108A (800uL) t = 17h18min 13:15 Made up a solution of benzyl isocyanide and Boc-glycine in a 4mL volumetric flask and added it to 108A, the preformed imine, this is **108B**

2007-06-16
21:49 Obtained an H NMR of 108B (200uL in 600uL CD3OD)

2007-06-18
14:00 Left the reaction mixture in a refrigerator.

2007-06-19
15:00 Removed from the refrigerator.

2007-06-20
13:18 Obtained an H NMR of 108B (200uL/600uL CD3OD) (t = 5days)

2007-06-23
15:42 Obtained an H NMR of 108B (200uL/600uL CD3OD) (t = 1 week)

2007-06-24
14:20 The reaction mixture did not develop any solid (usually seen with similar reactants). The erlenmeyer flask containing 108B was placed in a dry ice-acetone bath for one hour. 15:30 No solid had appeared even after placing the reaction mixture in dry ice acetone bath (-70C). 16:00 This is when some of the solvent was evaporated off with a gentle stream of N2. 16:20 Solid had appeared in the erlenmeyer flask containing 108B.

2007-06-25
10:30 The solid was recrystallized from cold methanol (2ml). The product was dried under vacuum. The recovered mother liquor was saved for further crystallization (**108D**) 16:20 A dry **108C**-1 was obtained (192 mg)- [20.4% Yield] 20:23 Obtained HNMR of 108C by dissolving 53mg in CDCl3 (800uL).[| HNMR]

=Tags= [|Benzaldehyde] [|InChI=1/C7H6O/c8-6-7-4-2-1-3-5-7/h1-6H] [|Furfurylamine] [|InChI=1/C5H7NO/c6-4-5-2-1-3-7-5/h1-3H,4,6H2] [|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)] [|Ugiproduct108] [|InChI=1/C27H31N3O5/c1-27(2,3)35-26(33)29-18-23(31)30(19-22-15-10-16-34-22)24(21-13-8-5-9-14-21)25(32)28-] [|17-20-11-6-4-7-12-20/h4-16,24H,17-19H2,1-3H3,(H,28,32)(H,29,33)/i1-12,2-12,3-12,4-12,5-12,6-12,7-12,8-12,9-12,10-12,11-12,] [|12-12,13-12,14-12,15-12,16-12,17-12,18-12,19-12,20-12,21-12,22-12,23-12,24-12,25-12,26-12,27-12,28-14,29-14,30-14,31-16,32-16,33-16,34-16,35-16]

media type="custom" key="85179"