© 2013 Pearson Education, Inc. Outline 17.1Carboxylic Acids and Their Derivatives: Properties and Names 17.2Some Common Carboxylic Acids 17.3Acidity of

© 2013 Pearson Education, Inc.

Outline

17.1 Carboxylic Acids and Their Derivatives: Properties and Names

17.2 Some Common Carboxylic Acids

17.3 Acidity of Carboxylic Acids

17.4 Reactions of Carboxylic Acids: Ester and Amide Formation

17.5 Aspirin and Other Over-the-Counter Carboxylic Acid Derivatives

17.6 Hydrolysis of Esters and Amides

17.7 Polyamides and Polyesters

17.8 Phosphoric Acid Derivatives


Goals1. What are the general structures and properties of carboxylic acids and

their derivatives? Be able to describe and compare the structures, reactions, hydrogen bonding, water solubility, boiling points, and acidity or basicity of carboxylic acids, esters, and amides.

2. How are carboxylic acids, esters, and amides named? Be able to name the simple members of these families and write their structures, given the names.

3. What are some occurrences and applications of significant carboxylic acids, esters, and amides? Be able to identify the general occurrence and some important members of each family.

4. How are esters and amides synthesized from carboxylic acids and converted back to carboxylic acids?

Be able to describe and predict the products of the ester- and amide-forming reactions of carboxylic acids and the hydrolysis of esters and amides.

5. What are the organic phosphoric acid derivatives? Be able to recognize and write the structures of phosphate esters and their ionized forms.



• Carboxylic acids have an —OH group bonded to the carbonyl carbon atom. In their derivatives, the —OH group is replaced by other groups.

• Esters have an —OR’ group bonded to the carbonyl carbon atom.

• Amides have an —NH2, —NHR’ or —NR’2 group bonded to the carbonyl carbon atom.

• Acid anhydrides are formed when two carboxylic acids join together by eliminating a molecule of water.



• The polarity and structural similarity of carboxylic acids, esters, and amides account for similarities in the properties of these compounds: all boil at a higher temperature than comparable alkanes, and carboxylic acids and amides that have a H on the nitrogen can hydrogen bond.



• Carboxylic acids and their derivatives commonly undergo carbonyl-group substitution reactions, in which a group we represent as —Z replaces (substitutes for) the group bonded to the carbonyl carbon atom.



• The portion of the carboxylic acid that does not change during a carbonyl-group substitution reaction is known as an acyl group.

• In biochemistry, carbonyl-group substitution reactions are quite often called acyl transfer reactions. They play an important role in the metabolism of biomolecules.



Carboxylic Acids:

• Carboxylic acids surrender the hydrogen of the carboxyl group, —-COOH, to bases and establish acid–base equilibria in aqueous solution.

• Like alcohols, carboxylic acids form hydrogen bonds with each other.

• Acids with saturated, straight-chain R groups of up to nine carbon atoms are volatile liquids with strong, pungent, and usually unpleasant odors; those with up to four carbons are water-soluble.

• Acids with larger saturated R groups are waxy, odorless solids.



Carboxylic Acids:

• Carboxylic acids are named in the IUPAC system by replacing the final -e of the corresponding alkane name with -oic acid.



Carboxylic Acids:

• The common names of many carboxylic acids are used far more often than their IUPAC names.

• In the common system, the carbon atoms attached to the —COOH group are identified by Greek letters and so on, rather than numbers.





Carboxylic Acids:• The acyl group that remains when a carboxylic acid

loses its —OH is named by replacing the -ic at the end of the acid name with -oyl.

• One very important exception is the acyl group from acetic acid, which is traditionally called an acetyl group.



Carboxylic Acids:

• Dicarboxylic acids, which contain two —COOH groups, are named systematically by adding the ending -dioic acid to the alkane name (the -e is retained).

• Simple dicarboxylic acids are usually referred to by their common names.

• Unsaturated acids are named systematically in the IUPAC system with the ending -enoic.



Esters:

• When the —OH of the carboxyl group is converted to the —OR of an ester group, the ability of the molecules to hydrogen-bond with each other is lost.

• Simple esters are lower boiling than the acids from which they are derived.

• Simple esters are colorless, volatile liquids with pleasant odors, and many of them contribute to the natural fragrance of flowers and ripe fruits.



Esters:• Ester names consist of two words. The first is the name

of the alkyl group R' in the ester group. The second is the name of the parent acid, with the family-name ending -ic acid replaced by -ate.



Amides:• Compounds with a nitrogen directly attached to the

carbonyl carbon atom are amides.

• The nitrogen of an amide may be an —NH2 group or may have one or two R’ groups bonded to it.

• Unsubstituted amides (RCONH2) can form multiple hydrogen bonds to other amide molecules.



Amides:• Low-molecular-weight unsubstituted amides are solids

(except formamide (HCONH2), which is a liquid).

• That are soluble in both water (with which they form hydrogen bonds) and organic solvents.

• Monosubstituted amides (RCONHR’) can also form hydrogen bonds to each other, but disubstituted amides (RCONR2’) cannot do so and are therefore lower boiling.



Amides:• It is important to note the distinction between amines and

amides. The nitrogen atom is bonded to a carbonyl-group carbon in an amide, but not in an amine.

• Amides are NOT basic like amines.

• Amides with an unsubstituted —NH2 group are named by replacing the -ic acid or -oic acid of the corresponding carboxylic acid name with -amide.

• If the nitrogen atom has alkyl substituents on it, the compound is named by specifying the alkyl group and then identifying the amide name. The alkyl substituents are preceded by the letter N to identify them as being attached directly to nitrogen.



Amides:



Properties of Carboxylic Acids, Esters, and Amides:• All undergo carbonyl-group substitution reactions.• Esters and amides are made from carboxylic acids.• Esters and amides can be converted back to carboxylic acids.• Carboxylic acids and unsubstituted or monosubstituted amides

exhibit strong hydrogen bonding to one another; disubstituted amides and esters do not hydrogen bond to one another.

• Simple acids and esters are liquids; all unsubstituted amides (except formamide) are solids.

• Carboxylic acids give acidic aqueous solutions. Esters and amides are neither acids nor bases (pH neutral).

• Small (low-molecular-weight) amides are water-soluble, while small esters are somewhat water-soluble.

• Volatile acids have strong, sharp odors; volatile esters have pleasant, fruity odors. Amides generally are odorless.



• Acetic acid is the primary organic component of vinegar.

• Vinegar is a solution of 4–8% acetic acid in water.• In concentrations over 50%, acetic acid is

corrosive and can damage the skin, eyes, nose, and mouth.

• Pure acetic acid is known as glacial acetic acid because, with just a slight amount of cooling below room temperature (to 17 ºC), the liquid forms icy-looking crystals that resemble glaciers.



• Citric acid is produced by almost all plants and animals during metabolism, and its normal concentration in human blood is about 2 mg/100 mL.

• Lemon juice contains 4–8% and orange juice about 1% citric acid.

• Pure citric acid is a white, crystalline solid (mp 153 ºC) that is very soluble in water.

• Citrates (a term used to describe mixtures of citric acid and its salts) are commonly used to buffer pH.



• Carboxylic acids are weak acids that establish equilibria in aqueous solution with carboxylate anions.

• Carboxylate anions are named by replacing the -ic ending in the carboxylic acid name with -ate.



• The comparative strength of an acid is measured by its acid dissociation constant (Ka); the smaller the value of Ka, the weaker the acid.

• Many carboxylic acids have about the same acid strength as acetic acid.

• Carboxylic acids undergo neutralization reactions to give water and a carboxylic acid salt.



Acids for the Skin• Weakly acidic solutions used in skin treatments fall at the

borderline of the distinction between prescription drugs and cosmetics.

• Trichloroacetic acid, a strong acid is used for chemical peeling of the skin in what is the equivalent of a first- or second-degree burn.

• As the result of healing, old skin is replaced by a new, smoother skin surface.

• Naturally occurring -hydroxy acids provide less aggressive skin treatments.

• Alpha-hydroxys increase the sensitivity of the skin to ultraviolet radiation from the sun.


17.4 Reactions of Carboxylic Acids

Ester and Amide Formation

• The reactions of alcohols and amines result in substitution of other groups for the —OH of the acid and formation of water.

• With alcohols, the —OH of the acid is replaced by the —OR of the alcohol.

• With amines, the —OH of the acid is replaced by the —NH2, —NHR’ or —NR’2 of the amine.





• Esterification is carried out by warming a carboxylic acid with an alcohol in the presence of a strong-acid catalyst such as sulfuric acid.

• These reactions are reversible and often reach equilibrium with approximately equal amounts of both reactants and products present.



Amide Formation• Unsubstituted amides are formed by the reaction

of carboxylic acids with ammonia.



Amide Formation• Substituted amides are produced in reactions

between primary or secondary amines and carboxylic acids:



Amide Formation• The first step of the reaction is formation of the

ammonium salt; amide formation reactions must be heated to proceed.

• The overall reaction is formation of an amide accompanied by formation of water.

• Tertiary amines do not have a hydrogen on the amine nitrogen and, therefore, do not form amides, generating only the ammonium salt.



Aspirin and Other Salicylic Acid Derivatives• Aspirin is a white, crystalline solid (mp 135 °C).

Chemically, aspirin is acetylsalicylic acid, an ester formed between acetic acid and the —OH group of salicylic acid.



Aspirin and Other Salicylic Acid Derivatives• As early as the fifth century B.C., Hippocrates

knew that chewing the bark of a willow tree relieved pain.

• By the 1800s, salicylic acid had been identified as the active ingredient but was insoluble in water and too irritating to the stomach to be of widespread use.

• Chemical modifications of salicylic acid were investigated and led to the ultimate discovery of aspirin.



Aspirin and Other Salicylic Acid Derivatives• Aspirin is a prodrug: it is administered inactive and

metabolized in vivo into the active form.

• Aspirin is best known for providing pain relief (analgesic), reducing fever (antipyretic), and reducing inflammation (anti-inflammatory).

• The principal undesirable side effects of aspirin are gastric bleeding and gastrointestinal distress.

• Efforts have been made to produce a modification that retains the beneficial effects while eliminating the negative ones, but none has yet proved as effective.

• Methyl salicylate, or oil of wintergreen, is poisonous, but has value as a counterirritant. It is one of the active ingredients in liniments.



• Acetaminophen (best known by the trade name Tylenol), is an amide that also contains a hydroxyl group.



Acetaminophen• Acetaminophen reduces fever, but it is not an

anti-inflammatory agent. • The major advantage of acetaminophen is that it

does not induce internal bleeding. • For this reason, it is the pain reliever of choice

for individuals prone to bleeding or recovering from surgery or wounds.

• Overdoses of acetaminophen can cause kidney and liver damage.


17.5 Aspirin and Other Over-the-Counter Carboxylic Acid Derivatives• Ibuprofen is a nonsteroidal anti-inflammatory drug

(NSAID) used for relief of symptoms of arthritis, abdominal cramps, and fever and as an analgesic. Ibuprofen is also known to have a mild, short-lived effect on blood-clotting times.

• At low doses, ibuprofen has the lowest incidence of adverse gastrointestinal side effects of all general NSAIDs.



Benzocaine and Lidocaine

• Benzocaine is a local anesthetic used in many topical preparations. It works by blocking the transmission of impulses by sensory nerves.

• Lidocaine (Xylocaine) is most commonly administered by injection to prevent pain during dental work; it is more soluble than benzocaine.



Ester Hydrolysis

• An ester is treated with water in the presence of a strong acid catalyst, and hydrolysis takes place.



Amide Hydrolysis• Amides are stable in water, but hydrolyze with

heating in the presence of acids or bases. • Under acidic conditions, the carboxylic acid and

amine salt are obtained. • Using base produces the neutral amine and

carboxylate anion.



• Nylons are polyamides produced by reaction of diamines with diacids.

• Nylon 6,6 is made by heating adipic acid (hexanedioic acid, a six-carbon dicarboxylic acid) with hexamethylenediamine (1,6-hexanediamine, a six-carbon diamine) at 280 ºC:



• The polymer molecules are composed of thousands of the repeating unit.

• High impact strength, abrasion resistance, and a naturally slippery surface make nylon an excellent material for bearings and gears.

• It can be formed into very strong fibers, making it valuable for a range of applications from nylon stockings, to clothing, to mountaineering ropes and carpets.

• Sutures and replacement arteries are also fabricated from nylon.



• Diacids and dialcohols react to yield polyesters.

• The most widely used polyester is made by the reaction of terephthalic acid (1,4-benzenedicarboxylic acid) with ethylene glycol.

• In clothing, it has the trade name Dacron.

• As mylar, it is used in plastic film.

• Poly(ethylene terephthalate) or PET, is used when it is used in clear, flexible bottles.



Kevlar: A Life-Saving Polymer • Kevlar is a polyamide created in 1965 at DuPont by chemist

Stephanie L. Kwolek who, in anticipation of gasoline shortages, was searching for a new fiber to use in making light but strong tires.

• It is five times stronger than steel, almost half as dense as fiberglass, highly resistant to damage by chemicals, dimensionally stable, very difficult to cut or break, a poor electrical conductor, and flame-resistant (if ignited, it self-extinguishes).

• Kevlar is produced by the reaction of a dicarboxylic acid with a diamine. Because it contains aromatic rings, it is classified as a polyaramide. Uniformly arranged hydrogen bonding holds the polymer chains together.

• Kevlar is used in bulletproof vests, heat-protective apparel, helmets for firefighters and bicycle riders, automotive and industrial hoses, structural composites for boats and aircraft, emergency tow lines for boats, brake linings, and other friction-resistant applications.


17.8 Phosphoric Acids Derivatives

• Just like a carboxylic acid, phosphoric acid reacts with alcohols to form phosphate esters. It may be esterified at one, two, or all three of its —OH groups by reaction with an alcohol.



• Phosphate monoesters and diesters are acidic because they contain acidic hydrogen atoms. In neutral or alkaline solutions, they are ions.

• The PO32− group as part of a larger molecule is

known as a phosphoryl group.• Two or three molecules of phosphoric acid can

combine to lose water, forming diphosphoric and triphosphoric acid.



• Transfer of a phosphoryl group from one molecule to another is known as phosphorylation.

• In biochemical reactions, phosphoryl groups are often provided by a triphosphate (adenosine triphosphate, ATP), which is converted to a diphosphate (adenosine diphosphate, ADP) in a reaction accompanied by the release of energy.

• The addition and removal of phosphoryl groups is a common mechanism for regulating the activity of biomolecules.



Organic Phosphates

• Organic phosphates contain C-O-P linkages.

• Organic phosphates with one or two R groups (monoesters or diesters) are acids and exist in ionized form in body fluids.

• The diphosphate and triphosphate groups, which are important in biomolecules, contain one or two phosphoanhydride linkages, respectively.

• Phosphorylation is the transfer of a phosphoryl group from one molecule to another.


Chapter Summary

1. What are the general structures and properties of carboxylic acids and their derivatives?

• Carboxylic acids, amides, and esters have the general structures:

• They undergo carbonyl-group substitution reactions. Most carboxylic acids are weak acids (a few are strong acids), but esters and amides are neither acids nor bases. Acids and unsubstituted or monosubstituted amides hydrogen-bond with each other, but ester and disubstituted amide molecules do not do so. Simple acids and esters are liquids; all amides (except formamide) are solids. The simpler compounds of all three classes are water- soluble or partially water-soluble.


Chapter Summary, Continued

2. How are carboxylic acids, esters, and amides named?

• Many carboxylic acids are best known by their common names, and these names are the basis for the common names of esters and amides.

• Esters are named with two words. The first is the name of the alkyl group that has replaced the —H in —COOH, and the second is the name of the parent acid with -ic acid replaced by -ate (for example, methyl acetate).

• For amides, the ending -amide is used, and where there are organic groups on the N, these are named first, preceded by N (as in N-methylacetamide).



3. What are some occurrences and applications of significant carboxylic acids, esters, and amides?

• Natural carboxylic acids and esters are common; the acids have bad odors, whereas esters contribute to the pleasant odors of fruits and flowers.

• Acetic acid and citric acid occur in vinegar and citrus fruits, respectively.

• Aspirin and other salicylates are esters; acetaminophen (Tylenol) is an amide; ibuprofen (Advil, Motrin) is a carboxylic acid; benzocaine is representative of a family of amides that are local anesthetics.

• Proteins and nylon are polymers containing amide bonds. Fats and oils are esters, as are polyesters, such as Dacron.



4. How are esters and amides synthesized from carboxylic acids and converted back to carboxylic acids?

• In ester formation, the —OH of a carboxylic acid group is replaced by the —OR group of an alcohol.

• In amide formation, the —OH group of a carboxylic acid is replaced by —NH2 from ammonia, or by —NHR’ or —NR’2 from an amine.

• Hydrolysis with acids or bases adds —H and —OH to the atoms from the broken bond to restore the carboxylic acid and the alcohol, ammonia, or amine.



5. What are the organic phosphoric acid derivatives? • Phosphoric acid forms mono-, di-, and triesters:

ROPO3H2, (RO)2PO2H and (RO)3PO.

• There are also esters that contain the diphosphate and triphosphate groups from pyrophosphoric acid and triphosphoric acid.

• Esters that retain hydrogen atoms are ionized in body fluids—for example, ROPO3

2−, (RO)2PO2−.

• Phosphorylation is the transfer of a phosphoryl group, PO3

2− from one molecule to another.

• In biochemical reactions, the phosphoryl group is often donated by a triphosphate (such as ATP) with release of energy.



Summary of Reactions

1. Reactions of carboxylic acids:

a) Acid–base reaction with water:

b) Acid–base reaction with a strong base to yield a carboxylic acid salt:




1. Reactions of carboxylic acids:

c) Substitution with an alcohol to yield an ester:

d) Substitution with an amine to yield an amide:




2. Reactions of esters:

a) Hydrolysis to yield an acid and an alcohol:

b) Hydrolysis with a strong base to yield a carboxylate anion and an alcohol (saponification):




3. Reactions of amides:

a) Hydrolysis to yield an acid and an amine:




4. Phosphate reactions:

a) Phosphate ester formation:

b) Phosphorylation:

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© 2013 Pearson Education, Inc. Outline 17.1Carboxylic Acids and Their Derivatives: Properties and Names 17.2Some Common Carboxylic Acids 17.3Acidity of