WWU-Chemistry The Esters

WWU-Chemistry Fischer Esterification This is not necessarily the best method of preparing esters, but it does serve to illustrate that esters are essentially the products of a reaction between a carboxylic acid and an alcohol.

WWU-Chemistry Lactones Lactones are cyclic esters formed by the intramolecular interaction of an alcohol functional group with a carboxylic acid functional group: a lactone

WWU-Chemistry The Triacylglycerols A very important class of esters, from a biological point of view, is in the triacylglycerols -- the common simple fats. “Triacylglycerol” is a relatively modern term; you may also hear of these substances as “simple lipids” or as “triglycerides.” The triacylglycerols are esters of long-chain carboxylic acids combined with glycerol.

WWU-Chemistry The Triacylglycerols The nature of the R groups can vary.

WWU-Chemistry Glycerol Since glycerol has three -OH groups, it can react with three molecules of carboxylic acid to form a triester.

WWU-Chemistry The Fatty Acids The carboxylic acid components of triacylglycerols are known as fatty acids. Fatty acids are simple, long-chain carboxylic acids -- their name comes from the simple fact that they occur in fats! Naturally-occurring fatty acids always have: –an unbranched carbon chain –an even number of carbon atoms

WWU-Chemistry The Fatty Acids

WWU-Chemistry Saturated versus Unsaturated Fatty Acids When the carbon chain (excluding the C=O bond) contains single bonds only, the fatty acid is known as a saturated fatty acid, and the triacylglycerol thus becomes a saturated fat. When the carbon chain contains one or more C=C double bonds, the fatty acid becomes an unsaturated fatty acid, and the triacylglycerol thus becomes an unsaturated fat.

WWU-Chemistry Unsaturated Fatty Acids Naturally-occurring unsaturated fatty acids have the following characteristics: –The first double bond appears at carbon #9 –If there are two or more double bonds, they are separated by a -CH 2 - group -- the double bonds are never conjugated. –Double bonds always have the cis geometry. The so-called trans fatty acids are not naturally- occurring.

WWU-Chemistry Hydrogenation of Fats

WWU-Chemistry Hydrogenation of Fats The hydrogenation of an unsaturated fat converts it into a saturated fat. This is an important process in the food industry, where unsaturated (liquid) fats are converted into saturated (solid) fats. Often, in an effort to retain some of the nutritional benefits of an unsaturated fat, food manufacturers will only partially hydrogenate a liquid fat -- just sufficiently for the material to turn semi-solid. This would be a partially hydrogenated fat.

WWU-Chemistry Isomerization of Fatty Acids

WWU-Chemistry Olestra (“Olean”)

WWU-Chemistry Molecular Model of Triolein

WWU-Chemistry Molecular Model of Olestra

WWU-Chemistry Fischer Esterification This is the most direct way of preparing esters.

WWU-Chemistry Fischer Esterification This is a reversible reaction; the equilibrium constant is only slightly greater than unity (between 1 and 10). To be successful, this reaction requires that one be able to shift the equilibrium to the right This is accomplished by: removing water by azeotropic distillation using an excess of whichever reagent is inexpensive.

WWU-Chemistry Fischer Esterification 84% yield

WWU-Chemistry Preparation of Esters (Best Method)

WWU-Chemistry Also Good: You would use this alternative when the acid anhydride is cheaper than the corresponding acid chloride. There are relatively few commercially-available acid anhydrides, however.

WWU-Chemistry Methyl Ester Formation Carboxylic acids can be converted to methyl esters by the action of diazomethane. CH 2 N 2

WWU-Chemistry Methyl Ester Formation Notice that the CH 2 of diazomethane appears to insert itself between the O and the H of the O-H bond!

WWU-Chemistry Diazomethane Diazomethane is a highly toxic and dangerously explosive gas. In spite of its hazardous nature, it can be handled relatively safely in dilute ether solutions (and in small quantities)

WWU-Chemistry Diazomethane (continued) In dilute solution it is a very useful reagent for the preparation of methyl esters, particularly in cases where only small quantities of carboxylic acid are available. This reaction proceeds in nearly quantitative (100%) yields!

WWU-Chemistry Structure of Diazomethane

WWU-Chemistry Reactivity of Diazomethane The high reactivity of diazomethane arises from the fact that it possesses an exceedingly reactive leaving group, the nitrogen molecule (which is exceptionally stable). As the following mechanism shows, a nucleophilic substitution reaction on the protonated diazomethane molecule transfers a methyl group to the oxygen atom of the carboxylic acid, while liberating nitrogen gas (a very stable product).

WWU-Chemistry Mechanism of Methyl Ester Formation This process is very favorable energetically, owing to the great stability of N 2.

WWU-Chemistry Reactions of Esters

WWU-Chemistry By far the most important reaction of the esters is hydrolysis. Hydrolysis can take place in either acidic or basic solution.

WWU-Chemistry Hydrolysis of Esters

WWU-Chemistry Example Can anyone suggest why an ester might not make a suitable perfume?

WWU-Chemistry Another Example Notice that, in a basic medium, the product of the hydrolysis is a carboxylate ion. The basic hydrolysis of an ester is often known as a saponification.

WWU-Chemistry Hydrolysis of an Ester in Base

WWU-Chemistry Hydrolysis of an Ester in Acid

WWU-Chemistry Saponification – The World’s Second- Oldest Known Organic Reaction Recall that the triacylglycerols (simple lipids or fats) are esters.

WWU-Chemistry If we hydrolyze a fat in aqueous base: The products are three equivalents of carboxylate ion.

WWU-Chemistry If our starting fat were something like tristearin, which would be representative of an animal fat:

WWU-Chemistry Then basic hydrolysis would give us three equivalents of the corresponding sodium carboxylate. This is the structural formula for ordinary soap! (“Grandma’s lye soap”) “Saponification” (from Latin: sapo = soap). Saponification is a soap-making reaction.

WWU-Chemistry Transesterification Sometimes, it is more convenient to convert the alkyl group of an ester to another alkyl group. This process is known as transesterification. Transesterification can take place under either acidic or basic conditions, although most commonly it is done under acidic conditions.

WWU-Chemistry Transesterification

Transesterification (in base)

WWU-Chemistry Example Thus, we’ve converted a methyl ester to a benzyl ester.

WWU-Chemistry A Problem: Suppose we have a sample of a fat.

WWU-Chemistry What are R 1, R 2, and R 3 ? With what frequency do they appear in a sample of the fat? What is their relative distribution in the sample? We can’t analyze the fat sample directly, because it isn’t very soluble and it isn’t volatile. We need to convert it from a glycerol ester to some more convenient form of ester.

WWU-Chemistry Transesterification

The methyl esters are much more volatile. The transesterified fat sample can now be analyzed by gas chromatography.

WWU-Chemistry Reaction of Esters with Organometallic Reagents

WWU-Chemistry We can outline (crudely) the mechanism as follows:

WWU-Chemistry BUT: The ketone can also react with the organometallic reagent! So, addition of organometallic reagent happens a second time. So, the product is a tertiary alcohol.

WWU-Chemistry Example

Reduction of Esters Lithium aluminum hydride (LiAlH 4 ) reduces esters through two 2-electron reduction steps, all the way to the primary alcohol.

WWU-Chemistry Crude Outline of the Mechanism BUT: The aldehyde can also be reduced by LiAlH 4 !

WWU-Chemistry And so…. Sodium borohydride (NaBH 4 ) will not attack esters.

WWU-Chemistry Example 99 % yield

WWU-Chemistry Reduction of Esters to Aldehydes

WWU-Chemistry Example