EH 243 1C

1. CARBONYL GROUP C=O

Carbonyl compounds are everywhere.

majority of biological molecules contain

carbonyl groups

many different kinds of carbonyl

compounds depending on which other

groups are bonded to the C=O unit

TYPES OF CARBONYL COMPOUNDS

ALDEHYDE NOMENCLATURE

Aldehydes are named by replacing the terminal -e

of the corresponding parent alkane name with the

suffix –al

carbonyl or the aldehyde is always assumed to be

the #1 carbon of the alkane chain when

numbering.

When the -CHO group is attached to a ring, the

suffix -carbaldehyde is attached to the cycloalkane

name.

ALDEHYDE NOMENCLATURE

Ketones are named by replacing the -e of the

alkane containing the carbonyl group with the suffix

-one (pronounced own)

The chain is numbered so as to give the C=O unit

of the ketone the lowest possible number.

ALDEHYDE NOMENCLATURE

ALDEHYDE NOMENCLATURE

Aldehyde

Ketone

NATURE OF CARBONYL GROUP

carbonyl carbon is sp2 hybridized

forms three sigma bonds.

4th valence electron remains in a p-orbital

and forms a π-bond to oxygen by overlap

with an oxygen p orbital.

SYNTHESIS OF CARBONYL

SYNTHESIS OF CARBONYL

REACTION OF CARBONYL This reaction makes use of the slight positive charge on

the carbonyl carbon.

Carbon is susceptible to nucleophilic attack.

nucleophile attacks the electrophilic carbon of the polar

carbonyl group from a direction approximately

perpendicular to the plane of the group.

Aldehydes are more reactive for both steric and

electronic reasons.

REACTIONS OF CARBONYL

Ketones:Inductive stabilization

of electron deficient

carbonyl carbon

by two adjacent

carbon groups.

Aldehydes: Stabilization of the

carbonyl group is only by one carbon

group...less stable than ketone, thus

more reactive than ketone.

REACTIONS OF CARBONYL

A. Addition of water; formation of gem-diols

A. The mechanism of gem diols formation

i.Acid catalyzed hydration of carbonyl

ii. Base catalyzed hydration of carbonyl

REACTIONS OF CARBONYL

B. i. Reduction-Addition of a Hydride

C. Nucleophilic Addition of Carbon Nucleophiles

- Grignard reagent addition

-Nucleophillic addition of HCN

Cyanohydrin Formation

D. Nucleophilic Addition of Amines

E. Wolff-Kishner Deoxygenation of Carbonyl

F. The Wittig Reaction

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5.14 Naming Carboxylic Acids

and Nitriles Carboxylic Acids, RCO2H

If derived from open-chain alkanes, replace the terminal -e of the alkane name with -oic acid

The carboxyl carbon atom is C1

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Alternative Names

Compounds with CO2H bonded to a ring are named using the suffix -carboxylic acid

The CO2H carbon is not itself numbered in this system

Use common names for formic acid (HCOOH) and acetic acid (CH3COOH) – see Table 20.1

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Nitriles, RCN

Closely related to carboxylic acids named by adding -nitrile as a suffix to the alkane name, with the nitrile carbon numbered C1

Complex nitriles are named as derivatives of carboxylic acids.

Replace -ic acid or -oic acid ending with -onitrile

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5.15 Structure and Properties of

Carboxylic Acids

Carboxyl carbon sp2 hybridized: carboxylic acid

groups are planar with C–C=O and O=C–O

bond angles of approximately 120°

Carboxylic acids form hydrogen bonds,

existing as cyclic dimers held together by two

hydrogen bonds

Strong hydrogen bonding causes much

higher boiling points than the corresponding

alcohols

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Dissociation of Carboxylic Acids

Carboxylic acids are proton donors toward weak and strong bases, producing metal carboxylate salts, RCO2

+M

Carboxylic acids with more than six carbons are only slightly soluble in water, but their conjugate base salts are water-soluble

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Acidity Constant and pKa

Carboxylic acids transfer a proton to water to give H3O

+ and carboxylate anions, RCO2,

but H3O+ is a much stronger acid

The acidity constant, Ka,, is about 10-5 for a typical carboxylic acid (pKa ~ 5)

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Substituent Effects on Acidity

Electronegative substituents promote formation of the carboxylate ion

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Inductive Effects on Acidity Fluoroacetic, chloroacetic, bromoacetic, and

iodoacetic acids are stronger acids than acetic acid

Multiple electronegative substituents have synergistic effects on acidity

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Although carboxylic acids much weaker than mineral acids, it is much stronger than alcohol and phenol

Why it more acidic than alcohol even though both contain –OH group?

Alcohol dissociates to give alkoxide ion in which the negative charge is localized on single electronegative atom

Carboxylic acid dissociate to give a carboxylate ion in which the negative charge is delocalized over two equivalent oxygen atom

Carboxylate ion is a stabilized resonance hybrid of two equivalent structures

Since a carboxylate ion is more stable than alkoxide ion-it is lower in energy thus favored in dissociation equilibrium

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5.16 Biological Acids and the

Henderson-Hasselbalch Equation

• If pKa of given acid and the pH of the medium are known, % of dissociated and undissociated forms can be calculated using the Henderson-Hasselbalch eqn

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5.17 Substituent Effects on

Acidity

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Aromatic Substituent Effects An electron-withdrawing group (-NO2)

increases acidity by stabilizing the carboxylate anion, and an electron-donating (activating) group (OCH3) decreases acidity by destabilizing the carboxylate anion

We can use relative pKa’s as a calibration for effects on relative free energies of reactions with the same substituents

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Because the dissociation of carboxylic acid is an equilibrium

process, any factor that stablizes the carboxylate anion

relative to dissociated carboxylic acid will drive the

eqiulibrium toward increased dissociation and result in

increased acidity

Because inductive effects operate through σ bonds and

are depent on distance, the effect of halogen substitution

decreases as the substituent move farther from the carbonyl

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5.18 Preparation of Carboxylic Acids

Oxidation of a substituted alkylbenzene with KMnO4 or Na2Cr2O7 gives a substituted benzoic acid (see Section 16.9)

1° and 2° alkyl groups can be oxidized, but tertiary groups are not

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Preparation of carboxylic acid

from alkenes

Oxidative cleavage of an alkene with KMnO4

gives a carboxylic acid if the alkene has at least

one vinylic hydrogen (see Section 7.9)

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Preparation of carboxylic acid

from alcohols

Oxidation of a primary alcohol or an aldehyde with

CrO3 in aqueous acid

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Preparation of carboxylic acid from

hydrolysis of nitriles Hot acid or base yields carboxylic acids Conversion of an alkyl halide to a nitrile (with cyanide

ion) followed by hydrolysis produces a carboxylic acid with one more carbon (RBr RCN RCO2H)

Best with primary halides because elimination reactions occur with secondary or tertiary alkyl halides

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Carboxylation of Grignard

Reagents• Grignard reagents react with dry CO2 to yield

a metal carboxylate

• Limited to alkyl halides that can form Grignard reagents

• The organomagnesium halide adds to C=O of carbon dioxide

• Protonation by addition of aqueous HCl in a separate step gives the free carboxylic acid

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5.19 Reactions of Carboxylic Acids: An

Overview Carboxylic acids transfer a proton to a base to give

anions, which are good nucleophiles in SN2 reactions

Like ketones, carboxylic acids undergo addition of nucleophiles to the carbonyl group

In addition, carboxylic acids undergo other reactions characteristic of neither alcohols nor ketones

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5.20 Chemistry of Nitriles

• Nitriles and carboxylic acids both have a

carbon atom with three bonds to an

electronegative atom, and contain a bond

• Both both are electrophiles

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Preparation of Nitriles by Dehydration

Reaction of primary amides RCONH2 with SOCl2or POCl3 (or other dehydrating agents)

Not limited by steric hindrance or side reactions

(as is the reaction of alkyl halides with NaCN)

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Mechanism of Dehydration of Amides

Nucleophilic amide oxygen atom attacks SOCl2 followed by deprotonation and elimination

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Reactions of Nitriles RCN is strongly polarized and with an

electrophilic carbon atom

Attacked by nucleophiles to yield sp2-

hybridized imine anions

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Hydrolysis: Conversion of Nitriles into

Carboxylic Acids

Hydrolyzed in with acid or base catalysis to a

carboxylic acid and ammonia or an amine

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Mechanism of Hydrolysis of Nitriles

Base-catalyzed nitrile hydrolysis involves nucleophilic addition of hydroxide to CN bond

Protonation gives a hydroxy imine, which tautomerizes to an amide

A second hydroxide adds to the amide carbonyl group and loss of a proton gives a dianion

Expulsion of NH2 gives the carboxylate

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Reduction: Conversion of Nitriles into

Amines Reduction of a nitrile with LiAlH4 gives a primary amine

Nucleophilic addition of hydride ion to the polar CN bond, yield an imine anion The C=N bond undergoes a second nucleophilic addition of hydride to give a

dianion, which is protonated by water

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Reaction of Nitriles with Organometallic

Reagents

Grignard reagents add to give an

intermediate imine anion that is hydrolyzed

by addition of water to yield a ketone

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ETHERS

&

EPOXIDES

ETHERS (R-O-R‘)

a substance that has two carbon groups (alkyl, aryl

or vinyl) connected to an oxygen atom

example of an ether is diethyl ether (CH3CH2-O-

CH2CH3) a substance that has been used

medicinally as an anesthetic or as a solvent in

laboratory

Thiols (R-S-H) and sulfides (R- S-R’) are sulfur

analogs of alcohols andethers, respectively.

Ethers can be thought of as organic derivatives of water in which both hydrogenshave been replaced by carbon groups.

The oxygen atom is sp3 hybridized and the C-O-C bond angle is close to the tetrahedral angle of 109°(actually 112°).

The presence of the electronegative atom sets up a slight dipole along the C-O bonds of alcohols, thus ethers have a slightly higher boiling point than hydrocarbons of similar size.

Nomenclature of ethers

1. Identifying the two carbon groups and

adding the words ether

Eg :

Eg :

Nomenclature of ethers

2. If other functional groups are present, the

ether part is considered an alkoxy substituent.

For example:

Properties of Ethers The electronegative oxygen atom gives ethers a

slight dipole moment, and the boiling points of

ethers are often slightly higher than the boiling

points of comparable alkanes.

Synthesis of Ethers

1. Sulfuric acid–catalyzed reaction of alcohols.

* Only applicable to primary alcohol

Synthesis of Ethers2. Williamson Ether Synthesis

Alkoxide ion reacts with a primary alkyl halide or

tosylatein an SN2 reaction

Synthesis of Ethers

3. Alkoxymercuration of Alkenes

Reactions of Ethers1. Acidic cleavage

Ethers undergo only one truly general reaction,they

are cleaved by strong acids. Aqueous HBr and HI

both work well, but HCl does not cleave ethers.

nucleophilic substitution reactions

Reactions of Ethers

2. Claisen Rearrangement

* Specific to specific to allyl aryl ethers

(H2C=CHCH2–O–Ar ) or allyl vinyl

ethers (H2C=CHCH2–O–CH=CH2)

EPOXIDES

Three member ring compounds that contain

an oxygen atom are called epoxides

(oxiranes).

These three-membered cyclic ethers resemble

cyclopropane where one of the carbons has

been replaced by an oxygen atom.

Sythesis of Epoxides

1. treatment of an alkene with a peroxyacid

(RCO3H)

Synthesis of Epoxides

2. Electrophilic addition of HO-X to alkenes

Reactions of Epoxides

1. Acid-Catalyzed Epoxide Opening

* dilute aqueous acid at room temperature is sufficient

to cause the hydrolysis of epoxides to give 1,2-diols,

also called vicinal glycols.

* If anhydrous HX is used, for instance, an

epoxide is converted into a trans halohydrin.

Reactions of Epoxides

2. Base-Catalyzed Epoxide Opening