Exp093-2.JPG


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Objective

To synthesize a Ugi adduct from Benzophenone, Aniline, tert-butyl isocyanide and Boc-Gly-OH in methanol using Ugi 4CR.

Procedure

Dissolved benzophenone (182 mg, 1 mmol) and aniline(104.6 uL, 1.1 mmol, 10% excess ) in 2 mL methanol-d4 in a 4 mL volumetric flask, immediately transferred the contents to an NMR tube. The reaction was monitored by NMR. The reaction was left overnight to complete forming an imine. The next day a solution of Boc-Gly-OH175 mg,1 mmol), and tert-butylisocyanide (113 uL, 1 mmol) is made up in 4 ml volutmeric flask in methanol. This solution of is added to the preformed Imine. The reaction mix is allowed to sit undisturbed for 6-8, when the Ugi product is obtained. The product is recrystallized from a small amount of methanol analyzed by NMR and saved in a 1 dram vial.

Results

Aniline
H NMR
C NMR(methanol-d4) spectrum does not appear decoupled - peaks showing up as doublets
Benzophenone
H NMR
C NMR
tert-Butyl isocyanide
H NMR
C NMR
Boc-Gly-OH
H NMR
C NMR
93A
t = 04 min
t = 07 min
t = 09 min
t = 34 min
t = 41 min
t = 45 min
t = 55 min IR
t = 02 h 40 min
t = 02 h 45 min
t = 03 h 23 min
t = 03 h 44 min
t = 18 h 11 min
t = 18 h 32 min
93B
H NMR (after 5days of addition of 92A to Boc-Gly and tert-butyl isocyanide)


Discussion

  1. There is no change in the H NMR even 18 h after mixing benzophenone with aniline and thus no evidence of imine formation. Compare this with other reports of imine formation - see refs page for reaction of aniline with ketones. The experiment has reached a dead end.
  2. Although before starting this reaction it was not known that aniline does not react with benzophenone under the conditions applied, however a reference[1] & [2] which indicates the unreactive behavior was found later.

Conclusion

Experiment aborted, (Imine did not form)

Log


2007-04-17

17:56 Made up a solution of solution of benzophenone and aniline in methanol-d4.93A
18:00 Obtained H NMR of 93A t = 04 min
18:03 Obtained H NMR of 93A t= 07 min
18:05 Obtained H NMR of 93A t= 09 min
18:30 Obtained C NMR of 93A t = 34 min
18:37 Obtained H NMR of 93A t = 41 min
18:41 Obtained H NMR of 93A t = 45 min
18:51 Obtained an IR of 93A t = 55 min
20:36 Obtained C NMR of 93A t = 02 h 40 min
20:41 Obtained HNMR of 93A t = 02 h 45 min
21:19 Obtained C NMR of 93A t = 03 h 23 min
21:40 Obtained H NMR of 93A t = 03 h 44 min

2007-04-18

12:07 Obtained H NMR of 93A t = 18 h 11 min
12:28 Obtained C NMR of 93A t = 18 h 32 min
12:40 Made up a solution of Boc Glycine and tert-butylisocyanide in a 2 ml volutmeric flask in methanol (CH3OH).
12:43 Added the aminoacid / isonitrile solution to 93A. This multicomponent reaction mixture is now labelled 93B

2007-04-23

15:19 Obtained H NMR of 93B

Ref

1.Arndtsen, B., A.; Sleiman, H., F.; Chang, A., K.; McElwee-White, L.;J. Am. Chem. Soc., 1991, 113 (13), pp 4871–4876 DOI: 10.1021/ja00013a024
2 Ross, N., A.; MacGregor, R., R.; Bartsch, R., A.; Tetrahedron, 60 (9) 23, pp 2035-2041; DOI: 10.1016/j.tet.2004.01.002

Tags

Tert-butyl isocyanide InChI=1/C5H9N/c1-5(2,3)6-4/h1-3H3
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)