Objective

To synthesize a 38 Ugi products suggested in the DoUgi Sheet in methanol
UCExp241-8A:2-[[2-(1,3-benzodioxol-5-yl)ac​etyl]-methyl-amino]-N-cyclohex​yl-2-(3,4-dimethoxyphenyl)acet​amide :C26H32N2O6; White solid; 1H NMR (external image delta.gif ppm, 500MHz, CDCl3) 1.0-1.2 (m, 3H), 1.25-1.4 (m, 2H), 1.5-1.7 (m, 3H), 1.8- 2.0 (m, 2H), 2.86 (s, 3H), 3.69 (s, 2H), 3.75-3.82 (m, 1H), 3.82 (s, 3H), 3.88 (s, 3H), 5.65 -5.75 (m, 1H Labile NH), 5.93 (s, 2H), 6.21 (s, 1H). 6.65-6.72 (m, 1H), 6.72-6.76 (m, 1H), 6.77-6.79 (m, 1H), 6.8-4.85 (m, 2H), 6.87-6.92 (m, 1H);; HRMS (FAB,m-nitrobenzyl alcohol): m/z calcd for C26H32N2O6 (M+Na) 491.215807 Da, found 491.213740 Da; yield 7%

Results

UCExp241- Spreadsheet
Pictures
UCExp241-i [25-48 at the imine stage]
Vials-25-48
UCExp241-1-24-after isonitrile addition
UCExp241-25-48after isonitrile addition
241-8A
HNMR-500MHz
HNMR-300MHz
Labile H Exchange
HNMR-Assignment
CNMR
Nominal mass
HRMS
241-9A
HNMR

UCExp241- Spreadsheet


Discussion

Vials corresponding to 241-8 and 241-9 contain same starting materials run at 0.49M and 0.53M concentration respectively.
From the HNMR of UCExp241-8A, a peak at 9.85ppm corresponding to the unreacted aldehyde suggests that the reaction had not achieved completion. An extra wash with methanol may have rid the product of any unreacted starting material.
HNMR confirms a Ugi product.
Labile H Exchange- It appears like there is some kind of quadrupole coupling of the N with its amide H
[EXP241-36 entry not included in ReactionAttempts because cannot tell if reactants or product is in error JCB]

Conclusion

Only one Ugi product had been isolated from the run.

Log

2009-08-12
14:20 Made-up a 1M solution of 3,4-methylenedixoyphenylacetic acid (5mmol, 900.8mg) in methanol by in a 5mL volumetric flask..did not have too much problem dissolving it. Well, had to place it in a water bath at 25C. Room temp was 24C.
14:45 Made-up a 4M solution of veratraldehyde (4mmol, 668.7mg) in methanol in a 1mL volumetric flask.
15:20 Labeled vials 241-1 to 241-48, however 10 vials which corresponded to solid aldehydes were later discarded for sake of simplicity - [see spreadsheet for details.].
16:20 Pipetted out amines to the vials - first few vial used methylamine (2M, 50uL) and the remaining vials neat amine solutions were used according to the spreadsheet.
16:45 Pipetted out aldehydes in to the vials, first few used veratraldehyde (4M,25uL) and to the remaining vials neat aldehydes were used. .
16:00 Some of the vials between 241-25 to 241-48 appeared to have formed some solid in them...obtained pictures of the vials between 25-48.--[UCExp241-i]
16:15 Pipetted out 3,4-methylenedioxyphenylacetic acid solution (1M, 100uL) to all the vials.
16:25 Pipetted out required amount of 'extra methanol' in to corresponding vials (see spreadsheet).
16:30 Each vial was vortexed for 10s. Soon after vortexing all the solution became clear except 241-32 and 241-35
16:45 Obtained a picture of the vials which crystallized out.
17:20 Completed the addition of isocyanides to the vials following the spreadsheet.
17:30 Obtained a picture of the solutions [UCExp241-1-24 and UCExp241-25-48]...all solution were clear, except for 241-1, 241-2 which kinda appeared cloud.
2009-08-13
12:00 Vials 241-8 and 241-9 have developed solid in them.
20:20 Except 241-8 and 241-9 no other vial has developed any solid in them, although quite a few of them have turned very cloudy.
20:40 To the solid in vials 241-8 and 241-9, methanol (150uL) was pipetted out and vortexed until the solid in it had mixed well the solvent. The mixture was then centrifuged and the supernatant from the vials was transferred out in to another vial.
20:55 The washing step (with 150uL methanol) was repeated twice more, a total of three washes.
21:40 At the end of the washes the vials were placed in a vacuum desiccator and left to dry overnight.
2009-08-14
11:00 After drying obtained 241-8A (15.1mg) from 241-8 and 241-9A (14.8mg) from 241-9.
12:00 Obtained HNMR of 241-8A and 241-9A.
2009-08-15
18:00 Obtained CNMR of 241-8A.
19:00 Submitted for mass analysis of 241-8A.
2009-08-16
15:00 To the NMR tube containing 241-8A, added 250uL D2O
15:30 Obtained a HNMR (done inorder to exchange the labile amide H). After obtaining the HNMR the tube was parafilmed tightly.
2009-08-17
11:00 Left the NMR tube in the sonicator
12:00 Sonicator turned off.
15:30 Obtained another HNMR of the sample.