Exp099

== =Objective= To synthesize a [|Ugi product] from [|benzaldehyde], [|furfurylamine], [|tert-butyl isocyanide] and [|boc-glycine] in methanol using Ugi 4CR. = = =Procedure= A solution of [|benzaldehyde] (212 uL, 2 mmol) and [|furfurylamine] (FFA) (234.8 uL, 2.2 mmol, 10% excess ) was made in methanol in a 4mL volumetric flask. After about two and half hours solution of [|boc-glycine](350 mg, 2 mmol), and [|tert-butyl isocyanide] (226 uL, 2 mmol) made up in 4 ml volutmeric flask in methanol was added the preformed Imine solution. A crystalline [|Ugi product] was obtained which was filtered and washed with methanol. [Assignments for HNMR and CNMR are based on the spectra obtained in Exp206 and reported in Paper03 (see Discussion section)]
 * Charcterization of 099C** :White solid; m.p. 202-204 C;1H NMR  (500MHz,[[image:http://pubs.acs.org/images/gifchars/delta.gif]] ppm, CDCl3) 1.33 (s, 9H), 1.45 (s, 9H), 4.21 (m, 2H), 4.49 (d, J=18Hz, 1H), 4.50 (d, J=18Hz, 1H), 5.47 (s, 1H), 5.60 (s, 1H), 5.62 (s, 1H), 5.89 (s, 1H), 6.10 (s, 1H), 7.19 (s, 1H), phenyl 7.21-7.37 (m, 5H); 13C NMR ; (500MHz, [[image:http://pubs.acs.org/images/gifchars/delta.gif]] ppm, CDCl3) 28.3, 28.6, 42.3, 42.8, 51.7, 62.9, 79.5, 107.7, 110.4, 128.5, 128.7, 129.6, 134.7, 141.9, 149.8, 155.7, 168.4 170.2; IR (//Ʋmax// cm-1 ATR): 1645,1673,1699, 3331; FAB-HRMS -calculated for C24H33N3O5 //m/z// 444.2498 [M+H], obtained 444.2517.

=Results= [|H NMR] [|C NMR] [|HNMR] [|CNMR] [|H NMR] [|C NMR] [|H NMR] [|C NMR]
 * Benzaldehyde**
 * Furfurylamine**
 * tert-butyl isocyanide**
 * Boc-Gly-OH**

__**99A**__ [|t = 33 min] [|t = 48 min] [|t = 40 min] [|t = 46 min] [|t = 51 min] [|t = 57min] __**99C**__ C24H33N3O5 [|HNMR] [|HNMR] (08/18/08) [|Labile H Exchange HNMR] (08/18/08) [dd at 6.1 ppm J= 1.95Hz; 1.22Hz] [|Overlay of HNMR and labile H exchange] [|CNMR] [|DEPT] [|All protonated carbons] [|CNMR Vs DEPT overlay] [|High Res] [|Low Res] [|IR] (08/18/08) M.p -202-204 C =Discussion= [|Tentative assignments-99C] The CNMR Vs DEPT overlay inconjunction with DEPT (image) produces similar results as a DEPTQ experiment where the spectral array includes quaternary carbon also; here in the overlay the CNMR is blue and All protonated carbons are green. All the protonated carbons have a green counterpart beneath blue peaks whereas quat carbons have none. In the Characterization report, NMR data obtained from Exp206 has been used, because the quality of the HNMR from this experiment makes it difficult to identify some peaks...the HNMR from Exp206 shows five peaks in the 5.2-6.2PPM range, this is not very clear from the spectrum in this experiment. The extra peak is assumed to belong to the labile NH protons which are hiding under other peaks; similiniarly the S/N of the CNMR in Exp206 makes the spectrum, more convincing.
 * 99C FAB MS**

=Conclusion= The Ugi product was obtained in 37% yield considering only the first precipitate 99C. Assuming all the crystallization fractions are pure product the yield may be as high as 47%. =Log=

2007-05-15
13:20 Madeup a solution of benzaldehyde and furfurylamine in methanol this is **99A**. 13:53 Obtained HNMR by transferring 800uL of 99A into an NMR tube. The lock on the machine was achieved by immersing a sealed capillary tube filled with acetone-d6. (t = 33min) 13:58 Obtained HNMR of 99A (t = 38min) 14:00 Obtained HNMR of 99A (t = 40min) 14:06 Obtained HNMR of 99A (t = 46min) 14:11 Obtained HNMR of 99A (t = 51min) 14:17 Obtained HNMR of 99A (t = 57min) 15:30 Dissolved Boc-Glycine (350mg) and tert-butylisocyanide (226uL) in methanol (4mL) in a volumetric flask. 15:47 Added the solution of Boc-Glycine and tert-butylisocyanide to 99A, this is **99B-1** 16:30 Left in the sonicator at room temperture 17:30 Removed from the sonicator, an off white precipitate appeared. The precipitate was left in the hood.

2007-05-16
14:00 Transferred 99B-1 from the erlenmeyer into a centrifuge tube, and centrifuged the precipitate out. 14:10 The residue was washed with methanol (3ml x 2), the supernatant was added to the previously collected supernatant, which is the mother liquor **99B-2** 14:30 Scrapped the wet residue from the centrifuge tube and spread it in a watch glass to air dry. 17:50 Obtained a dry **99C** (331mg) 20:38 Obtained HNMR of 99C

2007-05-17
12:00 Obtained CNMR Of 99C.

2007-05-21
17:30 Solid had appeared at the bottom of the erlenmeyer flask containing 99B-2. The solution was poured into a centrifuge tube and the solid was centrifuged out.The supernatant, mother liqour **99B-3** was saved for further crystallization. 18:30 The solid was air dried and an off white powder was scraped out the tube. This is **99C-2** (38mg).

2007-05-24
19:15 Crystals formed in 99B-3 were filered through a sintered glass funnel and the mother liquor was once again saved the mother liquor is **99B-4** and the crystals **99C-3** (49.7mg)- A total of 418.7mg of the ugi product obtained- 47.2% Yield. //**There is no NMR of any fraction except 99C so these additional fractions cannot be counted in the yield until proven to be pure product**//

2008-08-18
14:00 A HNMR of the above ugi product was obtained in CDCl3 (~1.5mL) ; then a exchange of labile protons was performed by adding 90uL CD3OD to the solution. An overlay was created to confirm the presence of labile protons. Each of the two HNMRs were obtained on a 300MHz varian Unity inova instrument. 17:00 Obtained an IR by ATR on a Perkin Elmer- Spectrum one 1000. 19:20 Obtained a melting point of the Ugi product; 202-204C

=Tags= 
 * Compound || [|Inchi Key] |||| [|Inchi] ||
 *  [|Furfurylamine] || [|DDRPCXLAQZKBJP]-[|UHFFFAOYAX] |||| [|InChI=1/C5H7NO/c6-4-5-2-1-3-7-5/h1-3H,4,6H2] ||
 * [|Benzaldehyde] || [|HUMNYLRZRPPJDN]-[|UHFFFAOYAE] |||| [|InChI=1/C7H6O/c8-6-7-4-2-1-3-5-7/h1-6H] ||
 * [|tert-butylisocynide] || [|FAGLEPBREOXSAC]-[|UHFFFAOYAL] |||| [|InChI=1/C5H9N/c1-5(2,3)6-4/h1-3H3] ||
 * [|Boc-Glycine] || [|VRPJIFMKZZEXLR]-[|UHFFFAOYAN] |||| [|InChI=1/C7H13NO4/c1-7(2,3)12-6(11)8-4-5(9)10/h4H2,1-3H3,(H,8,11)(​H,9,10)] ||
 * [|Ugi Product] || [|BXAOUWIVXLQYOZ]-[|UHFFFAOYAZ] |||| [|InChI=1/C24H33N3O5/c1-23(2,3)26-21(29)20(17-11-8-7-9-12-17)27(16- ​18-13-10-14-31-18)19(28)15-25-22(30)32-24(4,5)6/h7-14,20H,15-16H2​ ,1-6H3,(H,25,30)(H,26,29)] ||