Objective

To synthesize two different Ugi adducts following the EXPLAN005 . The compounds will contribute toward a library for enoyl reductase inhibitors.

Procedure

Two ugi reactions were carried out in 1.5 ml eppendorf tubes labeled EP1 and EP2. The EP1 labeled tube contained methanol (500uL), furfurlyamine (0.5mmol, 44.2uL), 2-naphthaldehyde (0.5mmol, 78.09mg), formic acid (0.53mmol, 20uL), and benzyl isocyanide, added in that order. In EP2 tube, methanol (500uL), methylamine (2.0M solution in methanol, 0.5mmol, 250uL), o-tolualdehyde (0.5mmol, 57.8uL), acetic acid (0.5mmol, 28.62uL), and p-toluenesulforylmethyl isocyanide (0.5mmol, 97.6mg) were added in that order.
After each addition the solution was vortexed for 15s and made sure a homogeneous solution was obtained. The eppendorf tubes were left at room temperature.

Results

119A
11.7mg, white powder

Exp119A-i.JPG

HNMR

Discussion

A ugi product with methylamine , o-tolualdehyde, acetic acid and p-toluenesulforylmethyl isocyanide did not crystallize.
That may be because the product a) has high solubility in methanol b) was never formed or c) may only have been formed in traces which are not isolable.
The solid which came from EP1 was formed using Benzyl isocyanide and other components.
Peaks in the HNMR of the solid 119A does not show it to be a clean Ugi product. Apart from regions which could possibly be assigned to the Ugi product, there are peaks in the spectrum which should not have been in the spectrum for the compound (singlet 1.2-2 ppm, a large peak at in the cluster between 4.45-4.5ppm).

Conclusion

Only one of the reactions yielded a solid product.

Log

2007-08-09

13:30 Weighed Eppendorf tubes (EP1 - 0.8263g, EP2 - 0.8370g)
13:40 Added methanol (500uL) to both Eppendorf tubes
13:47 Weighed out 2-naphthaldehyde (78.09mg)
13:55 Weighed out p-toluenesulfonylmethyl isocyanide (97.6mg)
14:10 Added the amines into each of the Eppendorf tubes (EP1-furfurlyamine, EP2-methylamine)
14:20 Added the aldehydes into the tubes (EP1-2-naphthaldehyde, EP2- o-tolualdehyde), vortexed each for 15s after the additions - Solution in EP2 precipitated out
14:30 Added the acids to each tube (EP1-formic acid, EP2- acetic acid), vortexed for 15s.
14:40 Added the isocyanides to each tube ((EP1-benzyl isocyanide, EP2-p-toluenesulforylmethyl isocyanide), vortexed for 15-30s. p-toluenesulfonylmethyl isocyanide had limited solubility in methanol, even after vortexing multiple times, some of it still remained undissolved.
16:00 Let tubes sit undisturbed in fume hood

2007-08-10

11:00 Observed brown solid formed partially on the bottom on EP1 tube, white precipitate in EP2 tube, vortexed each for 15s. let sit in fume hood
13:00 Brown solid formed throughout all of EP1 tube, small amount of white precipitate (probably remaining p-toluenesulforylmethyl isocyanide) in EP2 dissolved into liquid solution
15:00 Centrifuged EP1 tube at 14000 RPM for 60 seconds, then discarded supernatant
15:05 Added methanol (500uL), mechanically mixed on vortex for 15 seconds
15:10 Centrifuged at 14000 RPM for 60 seconds, then discarded supernatant
15:15 Added methanol (500uL), mechanically mixed on vortex for 15 seconds
15:20 Centrifuged at 14000 RPM for 60 seconds, then discarded supernatant
15:25 Added methanol (500uL), mechanically mixed on vortex for 15 seconds
15:30 Centrifuged at 14000 RPM for 60 seconds, then discarded supernatant
17:45 Put tube under high vac (pressure - 7.4mm)
20:00 Removed from vacuum

2007-08-14

12:40 Weighed EP1 tube with solid - 0.8380g (0.0117g of solid precipitate obtained)
14:00 Obtained HNMR of 119A inCDCl3 (800uL)

2007-08-17

15:00 Poured solution 119A from NMR tube into a 10mL round-bottomed flask, let sit out to dry

2007-08-20

12:00 Placed 10mL flask on high vacuum (pressure: )


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