Evaluation of L-Proline as a Catalyst for an Asymmetric Aldol Reaction - Lab Report Example

Evaluation of L-Proline as a Catalyst for an Asymmetric Aldol Reaction Learner’s The main purpose of this experimentation was to evaluate the ability of L-proline to function as an asymmetric catalyst in an Aldol reaction. The experimentation also aimed at quantification of the enantiomeric enrichment of the product by use of the Mosher ester approach. To carry out the experimentation, 24mg of L-Proline were dissolved in 5mL of anhydrous DMSO/acetone (4:1), for 15 minutes. 60mg of 4-nitrobenzaldehyde were then added to the solution and thoroughly stirred for further 30 minutes.

After the reaction was complete, 5mL of saturate ammonium chloride were added to the solution, to dilute it. The product was then extracted with 10mL of ethyl acetate. Drying was done over MgSO4 . the separation of the drying agent was done via gravity filtration, whereas that of the solvent was done through rotary evaporation. The product was further taken through purification steps, which involved the use of flash chromatography using 50% petroleum ether/ 50% ethyl acetate as the eluting solvent.

The fractions were then combined and the solvent eliminated via evaporation method. The massed of the obtained products were then recorded, and verification obtained. To conduct the Mosher analysis, 15mg of the Aldol product were dissolved in 0.9mL of anhydrous CH2Cl2 in a flame dried vial. 1.5mg of 4-dimethylaminopyridine (DMAO) followed by 15ᴫL pyridine and MTPA-Cl were added. The solution was then sealed and allowed to react under nitrogen. After the reaction was complete, the isolation process followed.

The crude reacrion was washed with 0.1 N HCL (0.5 mL), saturated bicarbonate solution (0.5 mL) and brine (0.5mL). The ratio of diastereomers by H-NMR was determined and enantiomeric excess of the Aldol reaction computed. From the analysis of the results obtained from the experimentation, it was clear that L-proline functions as a catalyst in a reaction involving Aldol. The product was further quantified by use of the Mosher ester approach. Consequently, a conclusion was drawn that L-proline functions as a catalyst in Aldol reactions.

Introduction One of the powerful methods through which carbon-carbon bonds can be formed is through nucleophilic addition of an enolate to a carbonyl group. An example of the scenarios in which this principle has been applied is in the de novo generation of carbohydrates which results from the development of aldolase enzymes, which catalyze biological Aldol reactions. The ability of aldolases to produce enantiomeric product exclusively is a notable feature, difficult for the modern synthesis chemistry to achieve.

In recent researches, it was found that simple amino acid L-Proline is capable of acting as a catalyst in the asymmetric Aldol reaction of acetone with variety of aldehydes. The product yield from the research was reported as 68% and 76% in excess (% ee), favoring the R enantiomer. This experiment aimed at reproducing the research finding results. Answers to Post-Lab QuestionsQn. 1: The following are the main advantages of organocatalysts over organometallic catalysts:-They are not sensitive to moisture and oxygen (Dalko)Low cost – the organocatalysts are not expensive, unlike the organometallic catalysts.

They are readily available, and hence ease of access (Woods and Smith). They contribute to green chemistry, since no need for metal-based catalysis Low toxicity, when compared with metal catalysts Qn. 2: The main source of rate enhancement in the l-proline reaction is the increase in the amount of catalyst added. In a research be (Zhang et al.) established a positive correlation between the amount of catalyst and the rate of reaction. More yield on the product is realized when the amount of catalyst used is high. Qn. 3: For the Aldol reaction to occur, there must exist carbonyl group in the two molecules.

The carbon-carbon bond is then formed by reduction of one of the molecules. In a nutshell, the molecules lack a reducible hydrogen molecule, which would otherwise detach itself from one molecule, and combine with oxygen on the other molecule to form water, leaving behind two carbons, which can form the carbon-carbon bond. The molecules also contain Oxygen molecules attached to a double bond, and hence making the Oxygen less active in any reaction. Qn. 4: The Mosher method is essential in the determination of enantiomeric excess, since it makes it possible to measure the purity level of a chiral substance (Hoye, Jeffrey and Shao).

It shows the level to which a given substance has a given enantiomer in greater amounts as compared to the other. For instance, when a sample is found to have 60% of one enantiomer, and 40% of the other, its ee value is 30%. ReferencesDalko, Peter I. Enantioselective Organocatalysis. Weinheim: Wiley-VCH, 2007. Print.Hoye, Thomas R, Christopher S Jeffrey, and Feng Shao. Mosher Ester Analysis For The Determination Of Absolute Configuration Of Stereogenic (Chiral) Carbinol Carbons. Nature Protocols 2.10 (2007): 2451-2458. Web.Woods, Philip A, and Andrew D Smith.

 Lewis Base Organocatalysts For Carboxyl And Acyl Transfer Reactions. Print.Zhang, Long et al. Novel Chiral Ionic Liquid (CIL) Assisted Selectivity Enhancement To (L)- Proline Catalyzed Asymmetric Aldol Reactions. J. Braz. Chem. Soc. 22.9 (2011): 1736- 1741. Web. 28 Apr. 2015.