JMGResearch_Discussion

>>>>>>>>>> ==Discussion==

//DOPAL//

 * 1) A plausible assignment of the major peaks for the HMR of 16A: 9.57(CHO),8.96(phenol), 8.9(phenol), 6.5(aromatic), 6.6(aromatic), 6.7(aromatic), 3.5 (CH2). Peaks at 3.4 and 2.5 are attributed to DMSO-d6. Addition of D2O removes the 2 peaks near 9 ppm, supporting the phenolic assignments, although the scale is off and some degradation (perhaps to the carboxylic acid after several days in DMSO).
 * 2) Li et al in 1998 report the HMR for the target aldehyde (in DMSO-d6) as: 9.67(t, 1H, CHO), 7.27 (dd, 1H, aromatic), 7.2 (d, 1H, aromatic), 6.9 (d, 1H, aromatic), 3.5 (d, 2H, CH2). The peaks in the 6.9-7.3 ppm range are inconsistent with HMR spectra of 4-alkylcatechols, such as 4-methylcatechol, with the three aromatic hydrogens generally appearing in the 6.5-6.9 ppm range. Since our spectrum is consistent with the majority of other spectra of similar molecules, we suggest that our assignments are correct and that the peaks reported by Li are erroneous. Our assignment is also consistent with another report from this author. See Exp 016

//Ugi Reaction//

 * 1) The imine reaction reaches completion after 24 hours where all of the amine (peaks 3.65 ppm and 4.05 ppm) is used up but about 3.1% extra aldehyde (peak 9.8 ppm) remains. The disappearing peaks from 1 hour to 24 hours at 1.20 ppm lies with the used up amine as they are present in the raw HMR of aniline. In the HMR of the raw starting aniline the 1.20 ppm peaks seem to be an impurity. The increase in intensity of the 1.20 ppm peaks in the imine HMR after 1 hours (84A) is most likely due to an error of the Sun software or some other NMR glitch. Compared to Exp048 the reaction seems to be 25% fast at the 1 hour mark however the overall rate is still 8.0*10^-3 [1/M*min].
 * 2) The percentage of imine after three days is 96% which is the same percentage of the reacted aldehyde. Virtually all of the amine reacts in the three day period giving an extra 3.1% aldehyde concentration.
 * 3) After two hours, the integration of the imine (8.3 ppm) after the addition of the acid and isocyanide decreases to twice that of the aldehyde peak (9.8 ppm) which did not change at all. This means that the imine is being used up but not reverting back to the aldehyde as the integration of the aldehyde has not changed since the addition of the acid and isocyanide. This is unlike past experiments where the integration went up after the addition of the acid. In this experiment, almost 100mg of 3A molecular sieves and more than 400mg of MgSO4 was used to dry the imine solution. This is sufficient for the size of the solution to absorb water produced from the reaction and any from the CDCl3.
 * 4) There was no initial NMR taken after the addition of the acid and isocyanide and only the one taken after two hours so no kinetics and not relative concentrations can be determined.
 * 5) There are new peaks surrounding the imine peak at 7.85ppm, 8.05ppm, 8.2ppm, and 8.6ppm after the addition of the acid and isocyanide. This means that the imine participated in other reactions besides the Ugi reaction. The crystalline Ugi product did not form possibly because of these side reactions that were for whatever reason more favorable however the peaks around 5.8 and 5.88 and 6.1ppm possibly correspond to one NH group, chiral proton, and furan protons. These results of the enantiomeric proton are consistent with other results from Exp052. See Exp084

//Imine Reversal//

 * 1) The rate constant of the imine reaction is 8.0*10^-3 [1/M*min]. In the same solvent, veratraldehyde and 5-methylfurfurylamine react about 14 times faster at a rate of 1.1*10^-1 [1/M*min].(EXP046) Since veratraldehyde and piperonal are closely related aromatic aldehydes, this difference suggests that t-butylamine's greater steric hindrance may be the cause.
 * 2) Using the peak at 9.75 for the aldehyde and the peak at 8.22 for the imine, there is a 42% conversion of the aldehyde after 94mins. Using the peak at 1.12 for the amine and the peak at 1.29 for the imine, there is a 64% conversion of the amine to imine after the same time.. This means that there was an excess of 20 % of amine/aldehyde. The side bands were used in the calculation of the integrations of the aldehyde, amine and imine though the same result is obtained from just the central bands. The imine formation was not monitored as long as it was in Exp045 or Exp046 and therefore only about 42% conversion was seen and thus the equilibrium composition was not determined. From previous experiments such as Exp046 the imine reaction of an aromatic aldehyde is faster in MeOH so if this reaction were done in CDCl3 it is expected to be even slower.
 * 3) The addition of the carboxylic acid reverses the imine reaction almost completely with only 4% aldehyde left after 20 minutes. This is surprising since in the typical Ugi reaction the four components are simply mixed together without prior isolation of the imine. Steps to remove the water should be taken to see if the addition of the acid still has an effect on the imine.
 * 4) Relative concentrations can not be determined accurately because there appears to be an overwhelming amount of acid compared to the imine. This can be due to a couple factors: 1) the MeOH-d4 slightly evaporated from the acid solution before it was added, 2) the imine decomposes in acid and without anything to react with reverts back to the aldehyde (and there is a slight increase in the aldehyde integration to support this), or 3) the amount of solid acid was weighed incorrectly with an un-calibrated balance.
 * 5) The addition of the isonitrile did not react as thought with the imine and acid. According to Overlay3, the 2-morpholinoethyl isocyanide is destroyed as the triplet of triplets around 3.6 is no longer present. See Exp048

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