TBB_termresearchpaper

= = =Abstract= The purpose of the experiments that were performed in this paper were to 1)be introduced to usefulchem.wikispaces.com and open source science, 2)to attempt to synthesize a Ugi Product, and 3)master the applications of usefulchem and chemspider. Since open source science ws being used everything that was performed in lab was updated online while the experiments were being ran. Chemspider was used to create and publish Ugi Products, while the workflow and master tables contained all the procedural data for the lab.

=Introduction= The purpose of this experiment was to synthesize an anti-malarial compound based on the inhibition of falcipain-2, as described in this [|summary post]. Falcipain-2 in an enzyme in malaria that when in the bloodstream breaks down the hemoglobin. As I was introduced into the research a major breakthrough was done in the research, Exp148 and Exp150 precipitated out active UgiProducts. The activity was determined by Jiri Gut from the Rosenthal Research Group at UCSF (Exp165). The research that was conducted combines an amine, an aldehyde, an acid, and an isocyanide all in methanol to form the product known as the Ugi Product. Library 3 is used because all of the compounds that could be made in this library, have all their starting materials in abundance in the Bradley lab. Here is a sample mechanism scheme taken from Exp167: Here the components are [|Phenanthrene 9-carboxaldehyde] ,[|propylamine], [|n-butylisocyanide] and [|3,4-methylenedioxyphenylacetic acid]. Another part of this research is that it was open source science. Through the effectiveness of usefulchem.wikispaces.com I was able to share my information not only with my Drexel colleauges but also anyone else who wanted to take a look at it. Open source science allows anyone to see exactly what you did and when you did it, and most importantly your exact results. Nothing is hidden in open source science but rather everything is shared. Programs like ChemSketch were used to draw mechanism schemes, and [|chemspider] was a very helpful chemical database that allowed me to look up any chemical and it was also used to publish my own chemicals.

=Experimental=

Synthesizing Ugi Products using the Ugi Reaction
A one dram vial was first labeled and 1mL of methanol was added. The amine was then added to the vial. The aldehyde was then added to the solution, followed by the acid, and lastly the isocyanide. 0.5mmol of each substance was used. After each addition to the vial, the vial was capped and vortexed for a specific amount of time, usually 15 seconds but never more then 10 min. A picture of the vial was then taken and stored away for 24 hours. After the 24 hours, a picture of the vial would be taken and be inspected to see if any precipiate formed. In this study no precipitates were formed. The following experiments were completed using the above procedure,Exp161, Exp163, Exp167, Exp168,Exp169, and Exp172.

=Results= The results to each experiment can be found on my opening each link. Overall there was no precipitate formed in any of the experiments.

=Discussion= Despite no precipitate ever being formed in any of the experiments, some interesting observations were able to be made. In Exp163 the Phenanthrene-9-carboxaledhyde which isn't that soluble in some experiments was able to be dissolved completely into the solution after the isocyanide was added. Some experiments that the Phenanthrene-9-carboxaledhyde went into solution were Exp159, Exp160, Exp156, Exp175, andExp176. All of these experiments used either furfuryalmine or benzylamine. The last two experiments actually formed a Ugi Product. It didn't matter what isocyanide was used. N-butyl isocyanide was used in experiments where a solution was and wasn't formed. Also t-butyl isocyanide was used in experiments where a solution was and wasn;t formed. Thus no real hypothesis could be proposed for the effect of the isocyanide with helping Phenanthrene-9-carboxaledhyde go into solution However, in Exp167 the amine used in the experiment was propylamine and no solution was formed from this expeirment. The isocyanide used was n-butyl isocyanide. In Exp160 all the reactants were the same except the amine. The amine was furfurylamine. A clear solution was made but no precipitate formed. Thus it may be possible that the aldehyde is amine specific. The aldehyde may be amine specific to aromatic structures with 5 or 6 carbons. Since both furfurylamine and benzylamine fit this description. Upon further inspection, both Exp148 and Exp150 used Phenanthrene-9-carboxaledhyde, and what is interesting to note is that heptylamine was used in Exp148. Exp148also produced the active UgiProduct. Therefore the amine specific hypothesis can not be substantiated by this observation. Since heptylamine is neither aromatic nor comprised of 5-6 carbons. The acids were then observed to see what pattern they followed when the Phenanthrene-9-carboxaledhyde was used. When crotonic acid or 4-chlorophenylacetic acid were solutions were formed and some using the crotonic acid precipitated active Ugi Products. The 3,4-dihydroxyphenylacetic acid and hydroxyphenylacetic acid didn't form solutions or precipitate. Therefore the makeup of the acid maybe the key to allow the aldehyde go into the solution. The lack of the hydroxy groups on the crotonic acid and 4-chlorophenylacetic acid might help the aldehyde go into solution. The hydroxy groups on the molecules may stearically hinder the combining of the molecules into a solution.

[|Ugi product] for Exp161, Exp163. [|Ugi Product] for Exp167.

[|Ugi product] for Exp168 Exp172. [|Ugi product] for Exp169.

=Conclusion= Working in the lab over the course of ten weeks has expanded my knowledge of organic chemistry. Learning about the Ugi Reaction and its mechanism has taught me how to obtain the starting materials for each expected Ugi Product. I also acquired different lab skills including how to use an HNMR. The research has taught me that using open notebook science is very helpful in achieving goals. By working cooperatively from all around the world, knowledge can be shared and updated every second. I was able to make hypotheses based on the solubility of Phenathrene-9-carboxylaldehyde. I first thought it was amine specific but then by comparing my experiment to others I saw that it wasn't amine specific at all, but rather it may be acid specfic. This dynamic way of working together helped me learn much in the lab over the course of ten weeks and can only help achieve success in the scientific community.