JMGExpSummary

Here are the experiments I have done starting with the most recent. Procedures and specific results/conclusions are given but for more detail please follow the link to the experiment. //**Add a brief conclusion for each experiment - every experiment needs to have one. We can discuss any that you have trouble coming up with one. No need to put the discussion here - we can just click over to the experiments to see that. You may also want to think about what you can conclude from the experiments, now that we know what a successful Ugi looks like.**//

Exp085

 * Procedure**: Prepared solutions of Crotonaldehyde (83uL, 1mmol, 2mL CDCl3, 0.5M) and methylfurfurylamine (110uL, 1mmol, 2mL CDCl3, 0.5M). These separate solutions were not treated with sieves or MgSO4. Mixed solutions together in the presence of 3A molecular sieves. Allowed the imine reaction to continue over 3 days.

Exp084

 * Procedure**: Prepared solutions of piperonal(150.3mg, 1mmol, 2mL CDCl3, 0.5M) and aniline(91uL, 1mmol, 2mL CDCl3, 0.5M). Solutions separately were not treated with sieves or MgSO4. Mixed aldehyde and amine solutions together in a 13mL vial in the presence of 97(Xmg) 3A molecular sieves. Added 415mg of MgSO4 to imine solution to remove water generated from reaction then filtered. Prepared a solution of Boc-Gly-OH(188.0mg, 1.07mmol, 2mL CDCl3, 0.536M) and tert-butylisocyanide(113uL, 1mmol, 2mL CDCl3, 0.5M) in 2mL volumetric flasks. Added the two solutions in a 5mL volumetric flask shook well and then added to imine solution.

Exp083

 * Procedure**: Prepared solutions of crotonaldehyde(83uL, 1mmol, 2mL CDCl3, 0.5M) and tertbutylamine(105uL, 1mmol, 2mL CDCl3, 0.5M). Mixed aldehyde and amine solutions together in the presence of 68(Xmg) 3A molecular sieves. Allowed imine to form over 3 days. Added 425.7mg of MgSO4 to imine solution to remove water produced from the reaction then filtered. Prepared a solution of Boc-Gly-OH(182.2mg, 1.04mmol, 2mL CDCl3, 0.52M) and tert-butylisocyanide(113uL, 1mmol, 2mL CDCl3, 0.5M) in 2mL volumetric flasks. Added the two solutions in a 5mL volumetric flask shook well and then added to imine solution.

Exp080

 * Procedure**: Prepared solutions of piperonal(155.2mg, 1.03mmol, 2mL CDCl3, 0.516M) and tertbutylamine(105uL, 1mmol, 2mL CDCl3, 0.5M) in 2mL volumetric flasks. Mixed solutions in the presence of 83(Xmg) 3A molecular sieves. Let imine form over 3 days. Added 446.8mg of MgSO4 to imine solution to remove water produced from reaction then filtered. repared a solution of Boc-Gly-OH(175.0mg, 1mmol, 2mL CDCl3, 0.5M) and tert-butylisocyanide(113uL, 1mmol, 2mL CDCl3, 0.5M) in 2mL volumetric flasks. Added the two solutions in a 5mL volumetric flask shook well and then added to imine solution.

Exp077

 * Procedure**: To remove water from starting solvent, added 3A molecular sieves to 10mL of CDCl3, stirring and then adding approx. 180mg of MgSO4. Made a solution of piperonal(159.1mg, 2mL, 1.06mmol, 0.53M, CDCl3) and a solution of tertbutylamine(105uL, 1mmol in 2 ml CDCl3, 0.5M) using the newly dired CDCl3 after filtering through cotton in a glass pipette. Combined the two solutions in the presence of X x 3A molecular sieves(Ymg) with stirring overnight. Took an NMR of the resulting solution. . Made a solution of Boc-Gly-OH(178.8mg, 2mL, 1.02mmol, 0.51M, CDCl3) and resulting imine solution. After about 4 hours took HMR.

Exp076

 * Procedure**: To remove water from starting solvents, added 3A molecular sieves and MgSO4 to about 10mL of Methanol to use for making solutions. Made a solution of piperonal(148.1mg, 2mL, 0.986mmol, 0.49M, MeOH) and a solution of tertbutylamine(105uL, 1mmol in 2 ml MeOH, 0.5M). Combined the two solutions in the presence of X x 3A molecular sieves(Ymg) with stirring letting reaction go over weekend. Took an NMR of the resulting solution. Prepared a solution of Boc-Gly-OH(176.1mg, 2mL, 1mmol, 0.502M, MeOH) and added to the resulting imine solution. After about 4 hours took and HMR.

Exp069

 * Procedure**: Made a solution of piperonal(148.1mg, 0.986mmol in 2 ml MeOH, 0.49M) and a solution of tertbutylamine(105uL, 1mmol in 2 ml MeOH, 0.5M). Combined the two solutions in the presence of 66 x 3A molecular sieves(~453mg) with stirring overnight. Took an NMR of the resulting solution. Filtered off crushed molecular sieves to obtain an NMR. Made a solution of Boc-Gly-OH(186.7mg, 1.066mmol in 2 ml MeOH, 0.53M) and added 1mL to the resulting imine solution.

Exp066

 * Procedure**: Made solutions of piperonal(75mg, 0.5mmol in 1 ml MeOH-d4, 0.5M) and tertbutylamine(57.8uL, 0.55 mmol in 1 ml MeOH-d4, 0.55M ) for HMR identification. Next, made up piperonal(301.9mg, 2mmol in 2 ml MeOH, 1M-) and tertbutylamine(231uL, 2.2mmol in 2 ml MeOH, 1.099M-) solutions using 10% extra amine for imine formation. Aldehyde and amine solutions were mixed in the presence of 65 activated 3A sieves (452mg). The solution was stirred by hand for two minutes and left over night. Stirring by stir bar not yet used in this step.

Exp058

 * Procedure**: Solutions of [|piperonal] (603mg, 4.0 mmol in 2 ml MeOH-d4, 2 M) and [|tert-butylamine](420uL, 4.0 mmol in 2 ml MeOH, 2 M) were mixed in presence of 28x 3A sieves(~174mg). H NMR was taken at the start of the reaction and after 14.5hrs. [|Boc-Gly-OH](352mg, 2mmol) was added without the presence of sieves and changes were monitored by H NMR. 800uL of the same acid solution was added with 800uL of the imine solution in the presence of 16x 3A sieves(~100mg) for a little over an hour. 800uL of this solution was added to 800uL of [|tert-butyl isocyanide](226uL, 2mmol). Changes were monitored by HMR.

Exp051

 * Procedure**: Measured out [|piperonal] (301mg, 2mmol), [|Boc-Gly-OH] (351mg, 2mmol) and separately diluted with 1mL MeOH-d4 then brought up to 2mL mark in a 2mL volumetric flasks. Also measured out [|tert-butylamine] (210uL, 2mmol) diluted in 1mL MeOH-d4 then brought up to 2mL in 2mL volumetric flask. Proton and Carbon NMR were taken of a mixture of the aldehyde and amine. The imine solution is then exposed to some drying agent, in this case 3A sieves and a little MgSO4. The acid is then added and more HMR are taken to monitor the concentration of the aldehyde and imine.

Exp048

 * Procedure**: Made 2M solutions of [|piperonal] (240mg, 1.6mmol), and [|Boc-Gly-OH] (280mg, 1.6mmol), while [|2-morpholinoethyl isocyanide] (220uL, 1.6mmol) was made at a 1.56M concentration and [|tert-butylamine] (168uL, 1.6mmol), was made at a 1.65M concentration. All solutions were made with 800uL of MeOH-d4. A volume of 400uL of each starting material was taken and diluted with another 400uL of MeOH-d4 making each 1M. HMRs were taken of each starting material. The remaining 400uL 2M of piperonal and tert-butylamine were added together giving each a concentration of 1M. HMRs were taken over a period 94mins. The remaining 400uL 2M of Boc-Gly-OH was added to the solution of aldehyde and amine giving a concentration of 0.75M for each component. HMRs were taken over the next 20mins. Because the volume of soultion was becoming too much for the NMR tube, the solution in the NMR tube was transfered to a 5 dram vial and the remaining 400uL of isocyanide was added to the solution and 800uL was pipetted into the same NMR tube. HMRs were taken over 77 mins. All HMRs were done on a Varian 300MHz NMR.

Exp031

 * Procedure**: Ugi reaction will be made as proposed in [|1996 Armstrong J. Am. Chem. Soc.]with a 1M concentration for each component. TLCs of each starting material will be compared to a t=0 Ugi reaction and further subsequent times. If a decent C13 can be obtained, the time frame of each observation will be double the last observation (eg 15min, 30min, 1hr, 2hr, 4 hr, 8hr, etc). Kept all components at a 1:1:1:1 ratio. Under nitrogen in a round bottom flask (50mL) added methanol (2mL) and then [|phenylacetaldehyde] by syringe(350µL, 3mmol), [|5-methylfurfurylamine] by syringe (330µL, 3mmol), and let that stir for 12 minutes. Next added [|Boc-Gly-OH] (525mg, 3mmol) and [|benzylisocyanide] (365µL, 3mmol). Continue to stir under nitrogen for over 24 hours. [|Video]

Exp021

 * Procedure**: To a 50ml Erlenmeyer flask added methanol (25ml), [|3,4-dihydroxybenzaldehyde] (80.23mg, 0.58mmol), [|5-methylfurfurylamine] (65µl, 0.58mmol) by micropipette, [|benzylisocyanide] (70µl, 0.58mmol) by 500µl GE syringe, and [|Boc-Gly-OH] (101.41mg, 0.58mmol). Vacuumed of solvent and performed chromatotron chromatography.

Exp020
At quick analysis, the NMR of Fraction2 seems reasonable in that the peaks that we expect for the methylfurfurylamine are there. There are some peaks that I can't identify just yet but there is also some aldehyde present which is expected by the ghost-like second spot on the TLCs which will be uploaded. Also it is disturbing that the D2O does not exchange with most of the peaks present. It is difficult to make a conclusion for this experiment at this time because the peak splitting we see in the HMR of Frac1 in the 5.8 region is not consistant with previous NMR of methylfurfurylamine. There seems to be coupling with some thing but we can not determine what without clear C13 or COSY.
 * Procedure**: To a 50ml Erlenmeyer flask added methanol (25 mL), [|3,4-dihydroxybenzaldehyde] (80.38mg, 0.58mmol), [|5-methylfurfurylamine] (65µl, 0.58mmol) by micro pipette, [|benzylisocyanide] (70µl, 0.58mmol) by 500 µl GC syringe and [|Boc-Gly-OH] (101.98mg, 0.58mmol). After stirring at room temperature for 20 hours, the solvent was evaporated. A 10% solution of TFA in THF (30 mL) was added and stirred under nitrogen for 20 hours. Performed Flash column chromatography.
 * Conclusion**: Based on the HMR of 20B, there is a small peak at 9.7 suggesting there is still some aldehyde present, a cluster of peaks in the 4.4-4.6 region may suggest some benzylisocyanide is still present as well. The sharp peak at 3.8 may suggest that there is also some acid but it may be misleading as the CH2 group between the N and carboxyl group may lead that peak anywhere. The NH on the amine can be anywhere on the spectrum so it can not be determined readily.

Exp 018
Looking at this [|review article], the cyclization step can be done at room temperature which could reduce the number of side reactions. Experiment was inconclusive.
 * Procedure**: To a 50ml Erlenmeyer flask added methanol (20ml), [|3,4-dihydroxybenzaldehyde] (67.65mg, 0.49mmol), [|5-methylfurfurylamine] (50µl, 0.44mmol) by GC syringe, [|benzylisocyanide] (50µl, 0.41mmol) by GC syringe, and [|Boc-Gly-OH] (87.84mg, 0.50mmol). After vacuuming off methanol, 10%TFA in THF was added and refluxed under nitrogen for 30minutes. An extraction with methylene chloride and water is performed. Vacuum off excess solvent after drying. Perform chromatography for purification if NMR and TLCs warrant.
 * Conclusion**: The HMR of 18D has many broad peaks and there is a problem with phasing however the amine 5.8-6 region, 2.3-2.5 region and benzene ring 7-8 region are there so continuing to the chromatography step is warranted. Unfortunately due to the chromatotron plate breaking apart during the addition of the solvent the experiment was aborted.

Exp 016
A solution of [|adrenaline] (227.74 mg, 1.243mmol) in 85% phosphoric acid (6 mL) was heated in a 12mL vial to 120C for 15 min in a glycerol bath then removed from heat and allowed to cool for 30 seconds. The solution was added to distilled water (36 mL) and then saturated with NaCl. Ether extracts (15 mL, 15 mL, 10mL), were combined and dried over MgSO4 then evaporated to yield 16A (15.6 mg, 1.24 mmol, 6.84 %yield).
 * Procedure**: Taken from [|Robbins (1965)].
 * Conclusion**:DOPAL can be made and isolated in 5-10% yield as a major product after a brief (15 min) decomposition of adrenaline in 85% phosphoric acid at 100-120 C. This material is not quite pure enough to be used without chromatography.