Kevin L. Evans Ph.D.
Associate Professor of Chemistry
Office: Science Hall 404
Telephone: 304-462-7361 ext. 231
Kevin.Evans@glenville.edu

Research

Developing Undergraduate Laboratory Experiments

The goal of these research projects is to develop laboratory exercises that emphasize organic chemistry concepts that are discussed in a typical sophomore organic chemistry course. In addition to the reactions yielding the expected products, it is also imperative that sophomore organic chemistry students have the manipulative skills to safely perform the experiment within three to four hours. If a successful experiment is created, the results will be published in the Journal of Chemical Education or another appropriate scientific journal. Current projects include the following.

Investigations into Selective Reductions of Methyl trans-Cinnamate

Research Students: Ryan Moss (Fall 2001) and Jason Fincham (Spring 2002)

Methyl trans-cinnamate has three reducible functional groups, an alkene, an aromatic ring, and an ester. Two main categories of reducing reagents are catalytic hydrogenation and hydride donors. Catalytic hydrogenation (Pd/C with H₂) reduces alkenes to alkanes but does not readily reduce carboxyl groups. Reductions of aromatic rings by catalytic hydrogenation occur only if extremely high temperatures and high pressures are used. Therefore, it should be possible to selectively reduce the alkene without affecting the other two functional groups.

The reactivity and selectivity of three hydride donors can also be illustrated with methyl trans-cinnamate. In general, hydride donors do not reduce alkenes, alkynes or aromatic rings. Sodium borohydride (NaBH₄) is a mild hydride donor and does not readily reduce esters. Therefore, mild conditions with sodium borohydride should result in no reaction. If only one equivalent of diisobutylaluminum hydride (DIBAL) is used and temperature is kept low, then an ester is reduced to the aldehyde in good yields. Lithium aluminum hydride (LiAlH₄) is a strong reducing reagent and reduces esters to the primary alcohol. When harsh conditions are used in the LiAlH₄ reduction with an a,ß-unsaturated carboxylate, the alcohol initially produced is subsequently lost with the formation of a cyclopropyl ring.

Diimide (HN=NH) is unique from the above reagents in that it is the only nonmetallic, organic compound. Diimide, generated in situ from acid treatment of potassium azodicarboxylate, reduces alkenes to alkanes but is typically unreactive towards carboxyl and aromatic substituents. Therefore, diimide should yield the same product as catalytic hydrogenation using Pd/C with H2.

Grignard Reactions of Carbonyl and Carboxyl Compounds

Research Student: Lisa Siegrist (Summer 2002)

Aldehydes, ketones, and esters react with Grignard reagents to yield alcohols. As illustrated below, aldehydes and ketones react with one equivalent of the Grignard reagent to yield secondary and tertiary alcohols, respectively. Esters react with two equivalents of Grignard reagent to yield tertiary alcohols. The reaction of p-anisaldehyde, 1, should yield a racemic mixture of (R) and (S)-1-(4-methoxyphenyl)ethanol, 4.

The reaction of 4'-methoxyacetophenone, 2, and methyl 4-methoxybenzoate, 3, should both yield 2-(4-methoxyphenyl)propan-2-ol, 5.

Carboxylic acids and N-methoxy-N-methylbenzamides react with Grignard reagents to yield ketones. The reaction of p-anisic acid, 6, with two equivalents of methyl magnesium bromide should yield 4'-methoxyacetophenone, 2, a reactant in the above reaction. The reaction of 4',N-dimethoxy-N-methylbenzamide, 7, should also yield 4'-methoxyacetophenone, 2.

If time permits, additional Grignard reactions may be attempted. Other carboxyl reagents that could provide interesting results include 4-methoxy-N-methylbenzamide (secondary amide), 4-methoxy-N,N-dimethylbenz-amide (tertiary amide) or 4-methoxybenzonitrile (nitrile). The reaction of 4-methoxybenzonitrile with methyl magnesium bromide should yield ketone 2. The outcome of the reaction of the secondary and tertiary amide with methyl magnesium bromide is less clear as amides are typically not used in Grignard reactions. The reactions may produce no result (i.e., starting material will be recovered) or ketone 2 or tertiary alcohol 5.

Nucleophilic Addition Reactions of Cinnamic Acid and Derivatives

Research Student: Zeke Price (Summer 2002)

Nucleophilic addition of α,ß-unsaturated carbonyl compounds can occur either at the carbonyl carbon or at the α-carbon. The site of nucleophilic attacks depends on the type of nucleophile. In general, strong nucleophiles, such as hydride and Grignard reagents, preferentially attack at the carbonyl carbon. Weak nucleophiles, such as amines and organocuprates, preferentially attack at the α-carbon.

Common hydride reagents are lithium aluminum hydride (LiAlH₄), sodium borohydride (NaBH₄), and diisobutylaluminum hydride (DIBAL, (i-Bu)₂AlH). Cinnamaldehyde, 1, cinnamic acid, 2, and methyl cinnamate, 3, should be reduced to cinnamyl alcohol, 4, by LiAlH₄. The milder reducing reagent NaBH₄ should reduce only aldehyde 1 to the alcohol 4. Two equivalent of DIBAL should reduce the ester 3 to the alcohol 4, whereas, one equivalent of DIBAL at low temperatures should stop at aldehyde 1.

These three cinnamic acid derivates should also react with Grignard reagents. Cinnamaldehyde, 1, requires only one equivalent and yields a secondary alcohol. Cinnamic acid, 2, and methyl cinnamate, 3, both require two equivalent of Grignard reagent and should yield a ketone and tertiary alcohol, respectively.

Weak nucleophiles are predicted to perform nucleophilic attack predominately at the ß carbon on cinnamaldehyde, 1, and methyl cinnamate, 2. Possible weak nucleophiles include amines, thiols, organocuprates and enolate anions (Michael reaction). The product from the Michael reaction could undergo a subsequent decarboxylation.