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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
23
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
24
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
25
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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
27
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
28
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
29
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)
30
Substituent Effects on Acidity
Electronegative substituents promote formation of the carboxylate ion
31
Inductive Effects on Acidity Fluoroacetic, chloroacetic, bromoacetic, and
iodoacetic acids are stronger acids than acetic acid
Multiple electronegative substituents have synergistic effects on acidity
32
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
33
34
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
35
5.17 Substituent Effects on
Acidity
36
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
37
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
38
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
39
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)
40
Preparation of carboxylic acid
from alcohols
Oxidation of a primary alcohol or an aldehyde with
CrO3 in aqueous acid
41
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
42
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
43
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
44
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
45
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)
46
Mechanism of Dehydration of Amides
Nucleophilic amide oxygen atom attacks SOCl2 followed by deprotonation and elimination
47
Reactions of Nitriles RCN is strongly polarized and with an
electrophilic carbon atom
Attacked by nucleophiles to yield sp2-
hybridized imine anions
48
Hydrolysis: Conversion of Nitriles into
Carboxylic Acids
Hydrolyzed in with acid or base catalysis to a
carboxylic acid and ammonia or an amine
49
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
50
51
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
52
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
53
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