Chem 150Chem 150Unit 7 - Organic Molecules IIUnit 7 - Organic Molecules II

Carboxylic Acids, Phenols & AminesCarboxylic Acids, Phenols & Amines

In this unit and the next we look at the In this unit and the next we look at the chemical and physical properties of a chemical and physical properties of a

variety of organic families, all of which variety of organic families, all of which play important roles in biochemistry. play important roles in biochemistry. These include the These include the carboxylic acidscarboxylic acids, ,

phenolsphenols, , aminesamines and and amidesamides. We also look . We also look at a new type of stereoisomer that at a new type of stereoisomer that figures predominantly in biological figures predominantly in biological

chemistry; the chemistry; the optical isomeroptical isomer..

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IntroductionIntroduction

TThe organic groups covered in this Unit all have important he organic groups covered in this Unit all have important biological rolesbiological roles• Carboxylic acids Carboxylic acids • Fatty acidsFatty acids• Amino acids and proteinsAmino acids and proteins

• PhenolsPhenols• Colors and flavoringsColors and flavorings• Amino acids and proteinsAmino acids and proteins• Signal moleculesSignal molecules

• AminesAmines• Amino acids and proteinsAmino acids and proteins• Signal moleculesSignal molecules• DrugsDrugs

• AmidesAmides• Amino acids and proteinsAmino acids and proteins

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Carboxylic AcidsCarboxylic Acids

Naming carboxylic acidsNaming carboxylic acids• The IUPAC ending is The IUPAC ending is -oic acid-oic acid..

55

QuestionQuestion

Give the IUPAC names for the following carboxylic acids:Give the IUPAC names for the following carboxylic acids:

A)A)

B)B)

CH3 CH2 CH2 CH2 C

O

OH

HO C

O

CH2 CH CH2 CH

CH3

CH3

CH3

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Carboxylic AcidsCarboxylic Acids

• Carboxylic acid have high melting pointsCarboxylic acid have high melting points• Small carboxylic acids are quite soluble in waterSmall carboxylic acids are quite soluble in water

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Carboxylic AcidsCarboxylic Acids

Small (volatile) carboxylic acids have noticeable odors.Small (volatile) carboxylic acids have noticeable odors.• Ethanoic acid (acetic acid) vinegarEthanoic acid (acetic acid) vinegar

• Butanoic acid (butyric acid) vomit, dirty socksButanoic acid (butyric acid) vomit, dirty socks

• Hexanoic acid (caproic acid) goats, ripe cheeseHexanoic acid (caproic acid) goats, ripe cheese

CH3 C

O

OH

CH3 CH2 CH2 C

O

OH

CH3 CH2 CH2 CH2 CH2 C

O

OH

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PhenolsPhenols

Simplest phenol is Simplest phenol is phenolphenol..• A hydroxyl group attached to a benzene ring.A hydroxyl group attached to a benzene ring.

OH

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PhenolsPhenols

All phenols contain hydroxyl groups attached to aromatic All phenols contain hydroxyl groups attached to aromatic rings.rings.

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PhenolsPhenols

All phenols contain hydroxyl groups attached to aromatic All phenols contain hydroxyl groups attached to aromatic rings.rings.

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These have These have 2 hydroxyl 2 hydroxyl

groups groups attached to a attached to a benzene ringbenzene ring

These have These have 2 hydroxyl 2 hydroxyl

groups groups attached to a attached to a benzene ringbenzene ring

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Carboxylic Acids & Phenols as Weak AcidsCarboxylic Acids & Phenols as Weak Acids

Both carboxylic acids and phenols are weak acidsBoth carboxylic acids and phenols are weak acids

CH3 C

O

OH + H2O CH3 C

O

O + H3O+

acid acidbasebase

OH + H2O O + H3O+

acid acidbasebase

pKpKaa ≈ 5 ≈ 5pKpKaa ≈ 5 ≈ 5

pKpKaa ≈ 10 ≈ 10pKpKaa ≈ 10 ≈ 10

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Questions (Clickers)Questions (Clickers)

Which is the stronger acid?Which is the stronger acid?

A)A) Acetic acidAcetic acid

B)B) PhenolPhenol

CH3 C

O

OH + H2O CH3 C

O

O + H3O+

acid acidbasebase

OH + H2O O + H3O+

acid acidbasebase

pKpKaa ≈ 5 ≈ 5pKpKaa ≈ 5 ≈ 5

pKpKaa ≈ 10 ≈ 10pKpKaa ≈ 10 ≈ 10

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Carboxylic Acids & Phenols as Weak AcidsCarboxylic Acids & Phenols as Weak Acids

The acidity of hydroxyl groups depend on what they are The acidity of hydroxyl groups depend on what they are connected to:connected to:

OC

O

O H H C O H

acidic weakly acidic non-acidic

carboxylicacids

phenols alcohols

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Question (Clickers)Question (Clickers)

At At pHpH 7, which will be the predominant species? 7, which will be the predominant species?

A)A) Carboxylic acidCarboxylic acid

B)B) Carboxylate ionCarboxylate ion

CH3 C

O

OH + H2O CH3 C

O

O + H3O+

acid acidbasebase

pKpKaa ≈ 5 ≈ 5pKpKaa ≈ 5 ≈ 5

carboxylic acidcarboxylic acidcarboxylic acidcarboxylic acid carboxylate ioncarboxylate ioncarboxylate ioncarboxylate ion

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Question (Clickers)Question (Clickers)

At At pHpH 7, which will be the predominant species? 7, which will be the predominant species?

A)A) PhenolPhenol

B)B) Phenoxide ionPhenoxide ion

phenolphenolphenolphenol phenoxide ionphenoxide ionphenoxide ionphenoxide ion

OH + H2O O + H3O+

acid acidbasebase

pKpKaa ≈ 10 ≈ 10pKpKaa ≈ 10 ≈ 10

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Carboxylic Acids & Phenols as Weak AcidsCarboxylic Acids & Phenols as Weak Acids

• At At pHpH 7, the carboxylate ion of carboxylic acids predominate 7, the carboxylate ion of carboxylic acids predominate

• At At pHpH 7, the phenol of phenol predominate 7, the phenol of phenol predominate

CH3 C

O

OH + H2O CH3 C

O

O + H3O+

acid acidbasebase

OH + H2O O + H3O+

acid acidbasebase

pKpKaa ≈ 5 ≈ 5pKpKaa ≈ 5 ≈ 5

pKpKaa ≈ 10 ≈ 10pKpKaa ≈ 10 ≈ 10

pHpH = 7 = 7pHpH = 7 = 7

pHpH = 7 = 7pHpH = 7 = 7

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Carboxylic Acids & Phenols as Weak AcidsCarboxylic Acids & Phenols as Weak Acids

Strong bases can be used to convert carboxylic acids and Strong bases can be used to convert carboxylic acids and phenols to their corresponding carboxylate and phenoxide phenols to their corresponding carboxylate and phenoxide ionsions

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Carboxylic Acids & Phenols as Weak AcidsCarboxylic Acids & Phenols as Weak Acids

Fatty acids are carboxylate ions at Fatty acids are carboxylate ions at pHpH 7 7

• Fatty acids with less that 12 carbons are soluble in waterFatty acids with less that 12 carbons are soluble in water• Fatty acids with greater than 12 carbons are Fatty acids with greater than 12 carbons are amphipathicamphipathic, ,

and form micelles when mixed with water.and form micelles when mixed with water.

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Carboxylic Acids & Phenols as Weak AcidsCarboxylic Acids & Phenols as Weak Acids

IUPAC names for carboxylate ions:IUPAC names for carboxylate ions:• Remove the “-Remove the “-ic acidic acid” from the corresponding conjugate ” from the corresponding conjugate

acids name and replace it with “-acids name and replace it with “-ate ionate ion”.”.

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Carboxylic Acids & Phenols as Weak AcidsCarboxylic Acids & Phenols as Weak Acids

Examples:Examples:

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Carboxylic Acids & Phenols, Other ReactionsCarboxylic Acids & Phenols, Other Reactions

We have already seen how We have already seen how carboxylic acidscarboxylic acids and and carboxylate ionscarboxylate ions can be made from from the hydrolysis of can be made from from the hydrolysis of estersesters..• Base-catalyzed hydrolysis of esters:Base-catalyzed hydrolysis of esters:

• Acid-catalyzed hydrolysis of esters:Acid-catalyzed hydrolysis of esters:

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Carboxylic Acids & Phenols, Other ReactionsCarboxylic Acids & Phenols, Other Reactions

The acid-catalyzed hydrolysis of esters is reversible and can The acid-catalyzed hydrolysis of esters is reversible and can be used to make esters from carboxylic acids and alcohols:be used to make esters from carboxylic acids and alcohols:• Synthesis of Synthesis of estersesters from from carboxylic acidscarboxylic acids and and alcoholsalcohols::

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Carboxylic Acids & Phenols, Other ReactionsCarboxylic Acids & Phenols, Other Reactions

A biologically important reaction involving carboxylic acids is A biologically important reaction involving carboxylic acids is the the decarboxylationdecarboxylation of of αα-keto-keto and and ββ-keto acids-keto acids::

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Carboxylic Acids & Phenols, Other ReactionsCarboxylic Acids & Phenols, Other Reactions

The decarboxylation of The decarboxylation of ββ-keto acids produces -keto acids produces ketonesketones

The decarboxylation of The decarboxylation of αα-keto acids produces -keto acids produces aldehydesaldehydes

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Carboxylic Acids & Phenols, Other ReactionsCarboxylic Acids & Phenols, Other Reactions

The The oxidationoxidation of of hydroquinones is also hydroquinones is also an important biological an important biological reaction.reaction.

• A chemical oxidation A chemical oxidation of hydroquinones of hydroquinones can be carried out can be carried out the oxidizing agent the oxidizing agent KK22CrCr22OO7 7 ((potassium potassium dichromatedichromate))

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Carboxylic Acids & Phenols, Other ReactionsCarboxylic Acids & Phenols, Other Reactions

Example:Example:• Coenzyme Q and the Electron Transport ChainCoenzyme Q and the Electron Transport Chain

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Carboxylic Acids & Phenols, Other ReactionsCarboxylic Acids & Phenols, Other Reactions

Example:Example:• Coenzyme Q and the Electron Transport ChainCoenzyme Q and the Electron Transport Chain

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AminesAmines

Amines are a nitrogen with one or more carbons attached:Amines are a nitrogen with one or more carbons attached:

• Amines are classified based on the number of carbons that Amines are classified based on the number of carbons that are attached to the nitrogen.are attached to the nitrogen.• Primary amine (1°): 1 carbonsPrimary amine (1°): 1 carbons• Secondary amine (2°): 2 carbonsSecondary amine (2°): 2 carbons• Tertiary amine (3°): 3 carbonsTertiary amine (3°): 3 carbons

N

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AminesAmines

It is possible for a fourth carbon to attach to the nitrogenIt is possible for a fourth carbon to attach to the nitrogen• The nitrogen will take on a positive charge to become an The nitrogen will take on a positive charge to become an

ion.ion.

• Quaternary (4°) ammonium ions: 4 carbon atomsQuaternary (4°) ammonium ions: 4 carbon atoms

N

3131

AminesAmines

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AminesAmines

The IUPAC names for 1°, 2°, and 3° amines.The IUPAC names for 1°, 2°, and 3° amines.• Create the parent name by picking the longest chain of Create the parent name by picking the longest chain of

carbons that is attached to the nitrogen.carbons that is attached to the nitrogen.• Replace the “-Replace the “-ee” in the parent with the ending “-” in the parent with the ending “-amineamine”.”.• Number the longest chain from the end that gets you to the Number the longest chain from the end that gets you to the

the carbon to which the nitrogen is attached in the fewest the carbon to which the nitrogen is attached in the fewest number of carbons.number of carbons.

• Use a numbered prefix to indicate which the carbon in the Use a numbered prefix to indicate which the carbon in the longest chain the nitrogen is bonded to.longest chain the nitrogen is bonded to.

• If other substituents are attached to the nitrogen, list them If other substituents are attached to the nitrogen, list them and use the prefix “and use the prefix “N-N-” to indicate that they are attached to ” to indicate that they are attached to the nitrogen. the nitrogen.

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QuestionsQuestions

Give the IUPAC names for the following amines:Give the IUPAC names for the following amines:

A)A) CH3 CH2 CH NH2

CH3

CH3 CH2 CH

CH3

N CH2 CH3

CH2 CH2 CH3

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QuestionsQuestions

Give the IUPAC names for the following amines:Give the IUPAC names for the following amines:

A)A) CH3 CH2 CH NH2

CH3

CH3 CH2 CH

CH3

N CH2 CH3

CH2 CH2 CH3

2-butanamine2-butanamine2-butanamine2-butanamine

2-butanamine2-butanamine2-butanamine2-butanamine

N-ethyl-N-ethyl-N-ethyl-N-ethyl-

N-propylN-propylN-propylN-propyl

N-ethyl-N-propyl-2-butanamineN-ethyl-N-propyl-2-butanamineN-ethyl-N-propyl-2-butanamineN-ethyl-N-propyl-2-butanamine

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AminesAmines

For For heterocyclic aminesheterocyclic amines the nitrogen is part of a ring. the nitrogen is part of a ring.• The ring can be either aromatic or not.The ring can be either aromatic or not.• The nucleic acid nucleotide bases are good examples of The nucleic acid nucleotide bases are good examples of

hetoercyclic amineshetoercyclic amines

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AminesAmines

Hydrogen BondingHydrogen Bonding• 1° and 2° amines can serve as both a hydrogen bond 1° and 2° amines can serve as both a hydrogen bond

donor and acceptor.donor and acceptor.• 3° amines can server as a hydrogen bond acceptors, but 3° amines can server as a hydrogen bond acceptors, but

not donors.not donors.

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AminesAmines

Hydrogen BondingHydrogen Bonding• 4° ammonium ion cannot form hydrogen bonds, but 4° ammonium ion cannot form hydrogen bonds, but

because they are charged, form ionic bonds:because they are charged, form ionic bonds:

CH3 N CH3

CH3

CH3

Cl-

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The ability to hydrogen bond give amines moderately high The ability to hydrogen bond give amines moderately high boiling points and high solubilities in water.boiling points and high solubilities in water.

AminesAmines

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Another notable property of amines is their odor.Another notable property of amines is their odor.• Like carboxylic acids, they can also produce foul odor.Like carboxylic acids, they can also produce foul odor.• The produce a “fishy” smell.The produce a “fishy” smell.

• Examples of amines, whose names imply their odoriferous Examples of amines, whose names imply their odoriferous properties, includeproperties, include

AminesAmines

H2NNH2

putrescine

H2N NH2

cadaverine

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Amines as Weak BasesAmines as Weak Bases

In Unit 6, while discussing the definitions of acids and bases, In Unit 6, while discussing the definitions of acids and bases, we saw that ammonia, NHwe saw that ammonia, NH33, is operationally a base, is operationally a base• That is, when added to water ammonia causes the That is, when added to water ammonia causes the pHpH to to

rise above rise above pHpH 7. 7.

• Ammonia was the example we used to demonstrate the need for the Ammonia was the example we used to demonstrate the need for the Brønsted-Lowry definitionBrønsted-Lowry definition of acids and bases. of acids and bases.

NH3 (aq) + H2O (l) NH4+ (aq) + OH- (aq)

See the Unit 6 Elaboration -See the Unit 6 Elaboration -Definitions of Acids and Bases - Part III:Brønsted-Lowry Definition

See the Unit 6 Elaboration -See the Unit 6 Elaboration -Definitions of Acids and Bases - Part III:Brønsted-Lowry Definition

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Amines as Weak BasesAmines as Weak Bases

Like ammonia, 1°, 2° and 3°, act as Brønsted-Lowry bases.Like ammonia, 1°, 2° and 3°, act as Brønsted-Lowry bases.

+ H2O (l) + OH- (aq)N H (aq)

H

CH3 N H (aq)

H

CH3

H

methanamine(base)

methylammonium ion(acid)

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Amines as Weak BasesAmines as Weak Bases

The conjugate acids are called ammonium ionsThe conjugate acids are called ammonium ions• When placed in water, these ammonium ions will behave When placed in water, these ammonium ions will behave

like acids.like acids.

+ H3O+ (aq)+ H2O (l) N H (aq)

H

CH3N H (aq)

H

CH3

H

methanamine(base)

methylammonium ion(acid)

pKa ≈ 10

4343

Amines as Weak BasesAmines as Weak Bases

Because it is charged, the conjugate acid is even more Because it is charged, the conjugate acid is even more soluble that the amine.soluble that the amine.• Many drugs are amines and are sold the ammonium salts, Many drugs are amines and are sold the ammonium salts,

which are more readily absorbed, due to their increased which are more readily absorbed, due to their increased solubility.solubility.

• Ephedrine is used as a decongestant.Ephedrine is used as a decongestant.

CH

OH

CH

CH3

N

H

CH3

CH

OH

CH

CH3

N

H

CH32

+ HCl

+ H2SO4

CH

OH

CH

CH3

N

H

CH3

H

Cl-

CH

OH

CH

CH3

N

H

CH3

H

SO42-

2

ephedrine ephedrine HCl

ephedrine ephedrine sulfate

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Amines as Weak BasesAmines as Weak Bases

EphedrineEphedrine is an example of an is an example of an alkaloidalkaloid..• Alkaloids are alkaline molecules that are derived from Alkaloids are alkaline molecules that are derived from

plants.plants.• ““alkaline” and another name for basic.alkaline” and another name for basic.

• Ephedrine is isolated from the Chinese Ephedrine is isolated from the Chinese ma huang ma huang plantplant(Ephedra sinica)hyperlink(Ephedra sinica)hyperlink

CH

OH

CH

CH3

N

H

CH3

ephedrine

CH2 CH

CH3

N

H

CH3

methamphetamine

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AmidesAmides

• When a carboxylic acid reacts with an amine it also When a carboxylic acid reacts with an amine it also produces and ammonium saltproduces and ammonium salt

• If the ammonium salt is then heated, an If the ammonium salt is then heated, an amideamide is is produced.produced.

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AmidesAmides

Amides are important in Amides are important in biochemistry.biochemistry.• For example, amino For example, amino

acids are connected acids are connected together to form together to form proteins using amide proteins using amide groups.groups.

amino acidamino acidamino acidamino acid

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AmidesAmides

Amides can be hydrolyzed back to carboxylic acids and Amides can be hydrolyzed back to carboxylic acids and amines by heating them in the presence of an acidamines by heating them in the presence of an acid

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StereoisomersStereoisomers

So far we have encountered two different types of isomers.So far we have encountered two different types of isomers.• Constitutional IsomersConstitutional Isomers• StereoisomersStereoisomers• cis/transcis/trans isomers isomers with alkenes and cycloalkanes, that arise from with alkenes and cycloalkanes, that arise from

restricted rotation about bonds.restricted rotation about bonds.

There is one more type of stereoisomer, which is important in There is one more type of stereoisomer, which is important in biochemistry.biochemistry.• optical isomersoptical isomers

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StereoisomersStereoisomers

Optical isomers arise when a carbon atom has four different Optical isomers arise when a carbon atom has four different things attached to it.things attached to it.• These carbons are called These carbons are called chiral carbonschiral carbons..• The a molecule containing a chiral carbon is non The a molecule containing a chiral carbon is non

superimposable on its mirror image.superimposable on its mirror image.• The molecule and its mirror image are referred to as The molecule and its mirror image are referred to as enantiomersenantiomers

5050

StereoisomersStereoisomers

5151

StereoisomersStereoisomers

5252

StereoisomersStereoisomers

5353

StereoisomersStereoisomers

5454

StereoisomersStereoisomers

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StereoisomersStereoisomers

When developing drugs that are chiral, it is important to look When developing drugs that are chiral, it is important to look at the effects of both the enantiomers.at the effects of both the enantiomers.

RR-thalidomide-thalidomideRR-thalidomide-thalidomide SS-thalidomide-thalidomideSS-thalidomide-thalidomide

is effective in is effective in treating morning treating morning

sickness in sickness in pregnant womenpregnant women

is effective in is effective in treating morning treating morning

sickness in sickness in pregnant womenpregnant women

is a is a teratogen, , causing birth causing birth

defectsdefects

is a is a teratogen, , causing birth causing birth

defectsdefects

N

O

O

NH

O

O

H

N

O

O

NH

O

O

H

RR and and S S are another way of distinguishing enantiomers; are another way of distinguishing enantiomers; RR is is the the rectus rectus (right) isomer, while (right) isomer, while SS is the is the sinistersinister (evil) isomer! (evil) isomer!RR and and S S are another way of distinguishing enantiomers; are another way of distinguishing enantiomers; RR is is the the rectus rectus (right) isomer, while (right) isomer, while SS is the is the sinistersinister (evil) isomer! (evil) isomer!

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StereoisomersStereoisomers

When chiral molecules contain more than one chiral carbon, When chiral molecules contain more than one chiral carbon, it is possible for two molecules to be stereoisomers without it is possible for two molecules to be stereoisomers without being mirror images.being mirror images.• Such molecules are referred to as Such molecules are referred to as diastereomersdiastereomers..

C

OH

CH

CH3

N

HCH3

ephedrine pseudoephedrine

H

C

H

CH

CH3

N

HCH3OH

5757

StereoisomersStereoisomers

Each chiral carbon that a chiral molecule contains doubles Each chiral carbon that a chiral molecule contains doubles the number of stereoisomers for that molecule.the number of stereoisomers for that molecule.• Ephedrine has two chiral carbons, it therefore has 2 x 2 = 4 Ephedrine has two chiral carbons, it therefore has 2 x 2 = 4

stereoisomers.stereoisomers.• pseudoephedrine is one of 4 stereoisomers.pseudoephedrine is one of 4 stereoisomers.

C

OH

CH

CH3

N

HCH3

ephedrine pseudoephedrine

H

C

H

CH

CH3

N

HCH3OH

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Question (Clicker)Question (Clicker)

How many stereoisomers does the sugar glucose have?How many stereoisomers does the sugar glucose have?

A)A) 22

B)B) 44

C)C) 88

D)D) 1616

E)E) 3232

O

C

H

C

C

C

C

C OH

H

H

HO

H OH

H

OH

OH

H

H

The EndThe End