Researcher- Alicia Holsey, Khalid Mirza

Supervisor - Prof. Jean-Claude Bradley

Furufyl Cleavage (2007-03-08)



Fufurylcleavage-UCExp065.png


Objective

To cyclize a Ugi product to form a diketopiperazine via a boc-deprotected intermediate. This Ugi product was synthesized here.

Procedure:

Prepared 10% TFA solution by adding 100uL TFA to 1mL volumetric flask. Diluted to mark with deuterated chloroform. Took NMR spectra. Added 50mg Ugi Product (62E) to NMR tube and monitored reaction via NMR spectra at specific intervals.

Results:

Starting Materials

10% TFA Solution
HNMR

62E Ugi Adduct
HNMR

10% TFA Solution with 0.95 mmol t-butyl amine
HNMR

65A (After Adding Crystals to TFA solution)

exp065A jdx files
T=10min
HNMR

T=20min
HNMR

T=40min
HNMR

T=80min
HNMR

T=160min
HNMR

T=320 min
HNMR

T=24hrs
HNMR

T=50hrs 30mins
HNMR

T=1wk
HNMR

65B (After Reflux)

exp065B jdx files
TAR(time after reflux)=30mins
HNMR

TAR=75mins
HNMR

TAR= 140 mins
HNMR

TAR= 195 mins
HNMR

Second Reflux (65C)

TA2R= 265mins
HNMR

After water wash (65D)

HNMR

Discussion:

1. Over time the furan protons are disappearing.
2. After the water wash, the NMR of the organic layer shows no evidence that the Ugi Product cyclized.
3. The doublets at 8.39 ppm and 5.41 (T=1wk HNMR) point towards a clear 'Furfuryl cleavage'. This is the first time this type of cleavage has ever been observed in 10% TFA in CDCl3. This is clearly seen in the HNMR of the sample in TFA at room temperature after one week- Khalid


Conclusion:


Fufuryl cleavage observed for the first time. The Ugi Product did not cyclize .


Log:

2007-03-07

11:10 Prepared 10% TFA solution. Took NMR spectra.
12:06 Weighed out 50 mg of 62E.
12:14 Added TFA solution. Solution turned pale yellow orange.
12:24 Took NMR spectra. Solution turned orange-brown.
12:34 Took NMR spectra.
12:54 Took NMR spectra. Solution turned dark red.
13:34 Took NMR spectra.
14:55 Took NMR spectra.
17:32 Took NMR spectra.Solution brown-red.

2007-03-08

12:20 Took NMR spectra. Solution turned brown-red.

2007-03-09

14:30 Turned on temperature bath and set to 60C in order to reflux reaction in NMR tube. Took NMR Spectra of sample.
15:00 Water bath at 65C. Placed NMR in water bath.
15:05 Noticed condensation inside of NMR tube.
15:29 Removed NMR tube from water bath. Bath temperature 65C. Took NMR spectra (some problems with shimming)
15:53 Placed NMR tube in water bath. Bath temperature 65C.
16:15 Removed NMR tube from water bath. Bath temperature 65C. Took NMR spectra.
16:26 Placed NMR tube in water bath. Bath temperature 65C.
17:03 RemovedNMR tube in water bath. Bath temperature 65C. Took NMR spectra. Unable to get a spectra until 17:27
17:34 Placed NMR tube in water bath. Bath temperature 65C.
17:59 Removed NMR tube from water bath. Bath temperature 65C. Took NMR spectra at 18:12
18:20 Left sample at room temperature.

2007-03-14

11:37 Set water bath to 60C. Added 70uL (0.95mmol) t-butylamine and 100uL TFA to tube. Diluted to 1mL mark with CDCl3. Noticed vapors emerge from the tube. Some precipitae formed.
12:05 Took NMR spectra of reaction tube and t-butylamine solution.
12:43 Temperature bath at 67C. Set bath to approximately 57C. Placed NMR tube of reaction in bath.
12:49 Noticed condensation on the inside of the tube. Temperature 65C
17:08 Removed tube from water bath. Temperature 65C

2007-03-20

12:13 Added contents of NMR tube to 5 dram vial. Rinsed NMR tube twice with 2mL chloroform. Added 5mL of distilled water to vial. Shook vigorously and allowed organic and water layer to separate. Removed water layer. Washed twice more.
13:25 Added 0.5g magnesium sulfate to organic layer.
13:34 Placed cotton inside a 9" Pasteur pipet. Added organic layer to round bottom flask. Evaporated off solvent.
14:51 Added 1mL deuterated chloroform and placed solution in an NMR tube. Took NMR 65D.

Tags

UgiproductInChI=1/C26H35N3O7/c1-16-8-10-18(35-16)14-29(21(30)13-27-24(32)36-26(5,6)7)22(23(31)28-25(2,3)4)17-9-11-19-20(12-17)34-15-33-19/h8-12,22H,13-15H2,1-7H3,(H,27,32)(H,28,31)
DKP065 InChI=1/C17H16N2O5/c1-10-2-4-12(24-10)8-19-15(20)7-18-17(21)16(19)11-3-5-13-14(6-11)23-9-22-13/h2-6,16H,7-9H2,1H3,(H,18,21)