Synthesis of Isopentyl Acetate

A wide range of commercial products, including perfume, deodorant, toothpaste, or most packaged foods, owe their odor, and much of their taste, to one or more synthetic chemical additives. Many of these “synthetic” compounds are identical to naturally occurring ones (and they do not have to be listed on a product label when this is the case), but we call them “synthetic” because they are manufactured, rather than grown.

All fragrances and flavorings, natural and synthetic, are volatile compounds that selectively bind to and activate olfactory nerves in the nose. Binding requires a good match between the three-dimensional geometry of the fragrance molecule and the receptor. Binding also requires reasonably strong nonbonding interactions between the fragrance molecule and receptor. Despite this knowledge, we still know very little about why certain compounds smell the way they do.

Some odors are clearly associated with particular functional groups. Volatile compounds that contain thiol (or sulfide) groups (-SH), amine groups (-NH-), or pyridine rings (C₅H₅N), often have horrible odors. Special precautions must be taken when working with these chemicals.

Carboxylic acid esters (RCO₂R), on the other hand, tend to smell light and fruity. In fact, many fruits owe their pleasant aromas to naturally occurring esters:

Some of these compounds serve several purposes in nature [W. F. Wood, J. Chem. Ed., 1983, 60, 531, DOI 10.1021/ed060p531]. Honey bees (Apis mellifera), for example, store isopentyl acetate in their sting gland and emit this compound to signal other members of the hive to sting an enemy [R. Boch, D. A. Shearer, and B.C. Stone, Nature, 1962, 195, 1018 DOI 10.1038/1951018b0].

This experiment attempts to prepare isopentyl acetate from acetic acid and isopentyl alcohol (a.k.a. 3-methyl-1-butanol). The reaction is catalyzed by sulfuric acid, but the catalyst affects only the rate of reaction, not the extent of reaction. The desired product accumulates only if the equilibrium constant is favorable.

As it happens, the equilibrium constant for this reaction is favorable, but small (~4) (comparing bond energies in the reactants and products will tip you off as to why the equilibrium constant is so small). Therefore, simply mixing equal amounts of the starting materials will convert only about 67% of the starting material into product.

If you recall Le Chatelier’s principle, you may remember that there are two ways to adjust reagent concentrations to force isopentyl alcohol to become isopentyl acetate. One way is to remove product as it forms. The other way is to use a large excess of acetic acid. This experiment is based on the latter approach, but it raises two issues. We can use excess acetic acid only if 1) acetic acid is cheap, and 2) unreacted acetic acid can be removed easily from the product mixture.

The previous section explains why this experiment uses unequal amounts of acetic acid and isopentyl alcohol. This procedure, however, creates a new problem: there will be a large quantity of unreacted acetic acid at the end of the experiment and this material must be separated from the desired product.

None of the separation techniques that you have learned so far can separate large quantities of acetic acid from isopentyl acetate, but a new technique, acid-base extraction, can get the job done (see Padias p. 130-142).

Extractions work as follows. First, you combine your product mixture with two other solvents. The solvents must be immiscible and they must have different densities so that they can be easily separated. A frequently used solvent pair is water and diethyl ether, CH₃CH₂OCH₂CH₃.

Second, you mix all of these materials thoroughly so that mutually soluble materials combine, and immiscible materials separate. All kinds of organic compounds dissolve in diethyl ether, but few dissolve in water. Ionic compounds, on the other hand, often dissolve readily in water, but not in diethyl ether.

Third, you separate the two solvents (and the things that are dissolved in them) using a special mixing/drainage apparatus called a separatory funnel. Obviously. if acetic acid and isopentyl acetate combine selectively with different solvents, the job is done.

The following table shows the solubility properties of isopentyl acetate and acetic acid in water and diethyl ether. As you can see, isopentyl acetate is only soluble in diethyl ether, but acetic acid is soluble in both solvents. Therefore, an extraction procedure like the one described above would remove some acetic acid from isopentyl acetate, but it would not separate the two compounds completely.

Compound	H2O solubility	CH3CH2OCH2CH3 solubility
	very low	very high
	very high	very high
	very high	very low

An acid-base extraction improves on the simple two-solvent extraction scheme outlined above by using acid-base reactions to change acetic acid into another compound with different solubility behavior. For example, the table shows us that if we can convert acetic acid into its conjugate base, sodium acetate, we will obtain a compound that is soluble in water, but not in diethyl ether.

Acid-base extraction procedures are practically identical to solvent extractions. The only difference is that, instead of using water and diethyl ether, we use saturated aqueous sodium bicarbonate (NaHCO₃) and diethyl ether. Sodium bicarbonate reacts with acetic acid to make sodium acetate and carbonic acid, H₂CO₃, but it does not react with isopentyl acetate. Therefore, if we use the proper amount of sodium bicarbonate solution, we can convert all of the acetic acid into water-soluble sodium acetate and no acetic acid will remain in the diethyl ether solution.