Connie He

Results Sheet G: Question #5

Due: 4/21/17

Chiral resolution:

The first method of isolating enantiomerically pure compounds that we used was through

generating a diastereomeric mixture of salts. The desired material could then be selectively

crystallized, since one diastereomer was significantly more soluble in the ethanol solution than the

other. A drawback of this method is that the process was time-consuming and highly involved.

Furthermore, the theoretical yield of each enantiomer of mandelic acid should be 50% of the total

theoretical amount, with the optical purity of each at 100%. However, polarimetry revealed an

enantiomeric excess of 68.3% of (R)-mandelic acid, and a corresponding yield of 44.8%, while (S)-

mandelic acid had an ee of 42.5% and a yield of approximately 80%. With this method, one must

consider the trade-off between purity and yield. However, an advantage of this method is that it

allows you to form both enantiomers and effectively separate them with a variable margin of error.

Racemic reduction:

Theoretically, if you wanted to produce a racemic mixture of methyl mandelate, this would

be the most effective method because it is not enantioselective. The reaction converts an sp2 center to

a sp3 center while undergoing a tetrahedral intermediate, so there is no inherent preference for one

enantiomer over the other. From GC results, we can conclude that there is almost a perfect 1:1 ratio

of enantiomers present, suggesting an almost completely racemic mixture. A disadvantage of this

method is the inability to separate the two enantiomers of mandelic acid after formation. In addition,

the side reaction between MeOH as the solvent and NaBH4 as the reducing agent forms hydrogen

gas. The presence of side reactions deactivates some of the NaBH4 in the primary reaction, leading to

a reduced yield.
Enzymatic reduction:

Enzymes employ the use of NADH to reduce compounds. This reducing agent has been

evolutionarily fine-tuned to be selective and efficient in forming the pure, desired product while

eliminating the possibility of unwanted side reactions. It is the most precise method of isolating a

single enantiomer, with almost 100% purity. However, it is time consuming, and the yeast must

remain alive for about a week. On the flip side, the percentage yield of this reaction is relatively high,

although this can be attributed to residual ethyl acetate present in the product after rotovap. The

reagents necessary for the reaction (i.e. yeast and sucrose) are relatively inexpensive to purchase and

benign.

Enantioselective reduction:

The formation of a tartaric acid-NaBH4 complex favors formation of one enantiomer over

the other, but is not as selective as enzymatic reduction. An advantage of asymmetric reduction is the

ability to favor one enantiomer over the other. Enantiomers have the same physical properties and

interact with other achiral molecules in the same manner. However, they associate differently with

other chiral molecules, such as biologically active enzymes. Furthermore, this reaction uses THF as

the solvent, which is aprotic and will not react with the NaBH4 like it did in the previous reaction. A

disadvantage of enantioselective reduction is that it requires anhydrous conditions to operate, and

NaBH4 is a highly reactive, dangerous reagent. It can be difficult to control and is sensitive to

environmental conditions. In addition, the percent yield of this reaction could potentially be much

greater than 100%. This happens because when you add HCL, some remaining tartaric acid-NaBH4

complex in the sample will be protonated forming an undesired white solid which decreases the

purity of the product. Tartaric acid and NaBH4 are also expensive in comparison with yeast and

sucrose.