Chapter 21

Organic Chemistry II
 Types of Isomers

Isomers
same different
connectivity connectivity

Stereoisomers Constitutional Isomers

without with
stereocenters stereocenters

Achiral Chiral
Mirror images Non Mirror images

Cis-Trans Isomers Enantiomers Diastereomers

 Enantiomers
• Non-superposable mirror images.
 Enantiomers
– Enantiomers are isomers that are mirror images of
each other
• Objects that are not superposable on their mirror
images are chiral.
• Carbon with four different groups bonded to it –
most common cause of enantiomerism.
– Chiral center or stereocenter.

• Superposable images – achiral.

 Nomenclature
• R,S system.

– Two enantiomers of ibuprofen.

 How to name R/S enantiomers?

• Arrange groups on the stereocenter in order of

priority (based on the molecular weight of the group).
• To assign an R or S configuration:

1. Assign a priority from 1 (highest) to 4 (lowest) to

each group bonded to the stereocenter.

2. Orient the molecule in space so that the group of

lowest priority (4) is directed away from you; the
three groups of higher priority (1-3) then project
toward you.

3. Read the three groups projecting toward you in order

from highest (1) to lowest (3) priority.

4. If reading the groups 1-2-3 is clockwise, the

configuration is R; if reading them is
counterclockwise, the configuration is S.
 Number of enantiomers
• Maximum number of possible stereoisomers is 2n

• Diastereomers: stereoisomers that are not mirror images.

• A&C and B&D are diastereomers.
Interaction of enantiomers with light
 Chirality in Biomelecules
• Biological molecules are chiral
– Almost only one stereoisomer is found in nature.
– Rarely found more than one stereoisomer in the same biological
system.
• (S)-Naproxen is an active pain reliever.
• (R)-enantiomer is a liver toxin.
• Enantiomers are important in the pharmaceutical industry
• Two enantiomers of a drug may have different effects
• Differing effects of enantiomers demonstrate that organisms are
sensitive to even subtle variations in molecules

L-Dopa D-Dopa
(effective against (biologically
Parkinson’s disease) Inactive)
• how an enzyme distinguishes between a molecule and its
enantiomer.
Alcohols, Ethers, and Thiols
• Alcohol: organic compound containing a hydroxyl group
(OH) bonded to a carbon.
• Nomenclature
– Longest carbon chain contains the –OH group
– Number the chain such that –OH has the lower
number.
– -ol ending.
– Name and number substituents in alphabetical
order
• Diol = two hydroxyl groups
• Triol = three hydroxyl groups
• Glycols = hydroxyl groups on adjacent carbons.
• Alcohols are polar molecules
• The C-O and O-H bonds are both polar
covalent.
bp increases as MW increases.
Solubility in water decreases as MW increases.
Alcohols are weak acid, and do not dissociate in water.
• All simple alcohols are poisonous to some degree:

– LD50 is the amount of a substance lethal to 50% of the

population. Rat data is frequently extrapolated to humans
– LD50 for ethanol is 7.06 g/kg of body mass for rats.

• Ethyl alcohol is potentially toxic -- rapid ingestion of 1 pint will

kill most people. Ethanol kills by depressing the respiratory
control center resulting in failure of the respiratory muscles in
the lungs and suffocation.
– excessive ingestion over time leads to liver deterioration and
memory loss.

• Methanol itself is not terribly toxic (LD50 for rats is high.), but
in humans (and other primates) enzymes in the liver convert
methanol to formaldehyde which is very toxic.
 Uses of Alcohols

• very good solvent

– note: ethanol is often denatured , i.e. something
poisonous is added so ethanol cannot be used as a
beverage.(common denaturants are methanol and
2-propanol).
• Gasohol is a blend of 10% ethanol and 90% gasoline
• Rubbing alcohol is 70% isopropanol and 30% water.
It is used for cooling the skin and reducing fevers
due to its rapid evaporation. It is also used as an
antiseptic because it denatures bacterial enzymes.
• Ethanol is used as a beverage. The proof of an
ethanol sample is equal to 2X the % (90 proof = 45%)
 Types of Alcohols

1. Methanol CH3OH (a primary alcohol)

– We will learn some reactions to help us
differentiate 1o, 2o, and 3o alcohols.
2. Primary alcohols RCH2OH
3. Secondary alcohols R2CHOH
4. Tertiary alcohols R3COH
Dehydration Reactions
• Dehydration: elimination of a molecule of water from adjacent
carbon atoms gives an alkene.
• Dehydration is most often brought about by heating an alcohol
with either 85% H3PO4 or concentrated H2SO4.
• 1° alcohols are the most difficult to dehydrate and require
temperatures as high as 180°C.
• 2° alcohols undergo acid-catalyzed dehydration at somewhat
lower temperatures.
• 3° alcohols generally undergo acid-catalyzed dehydration at
temperatures only slightly above room temperature.
 Dehydration of Alcohols

• Zaitsev’s Rule – more substituted formed

 Dehydration of Alcohols

E and Z produced, major product will have most

bulky groups on opposite sides
When isomeric alkenes are obtained, the alkene having the greater number of
alkyl groups on the double bond generally predominates.
 Oxidation
• 1o alcohol – aldehyde or carboxylic acid.

• 2o alcohol – ketone

• 3o alcohol – No reaction.
 Ethers
• An oxygen bonded to two carbon atoms.
– Simplest – dimethyl ether.
– Most common – diethyl ether.
• IUPAC names
– 2 groups are bonded to O, the larger group is the parent, smaller is
substituent
– alkoxy alkane
• Examples
Crown Ethers
Crown Ethers

• Cyclic compounds with ether linkages

• Bind cations as “host” and “guest”
Crown Ethers
• Naming – [x]-crown-Y
• X = total number of atoms in the ring
• Y = total number of oxygens
 Physiological Properties of Ether
• Ethyl ether acts as a general anesthetic
– a general anesthetic acts on the brain to produce
unconsciousness as well as insensitivity to pain.

• Ethyl ether is relatively safe -- there is a wide gap between the

effective and the lethal dose.

• Ether is very flammable.

– Sometimes used as a starter fluid for very cold engines -
spray on once and it starts.
• Physical Properties of Ethers
– Hygroscopic (absorbs water)
– Volatile and flammable
– More dense than air
– Good organic solvent
• Chemical Properties of Ethers
– Fairly unreactive, like alkanes.
 Thiols
• Sulfhydryl group.

• Nomenclature – similar to alcohol – thiol is added.

• Mercaptan – Alkyl group bonded to –SH and adding
the word “mercaptan”
 Thiols
• Thiols are sulfur analogs of alcohols
• Also called mercaptans (mercury capturing)
• Thiols with a low-molecular weight have an appalling
odor. The skunk scent is caused by the simple thiols
3-methyl-1 butanethiol and butane-1-thiol.

• Thiols have lower boiling points and are less soluble in

water than other alcohols.
 Physical/Physiological Properties of sulfur containing
compounds

• Boiling points and melting points between alkanes and

alcohols.
• Sulfur is intermediate in electronegativity
• H2S (hydrogen sulfide)
• CH3SH, CH3CH2SH (methanethiol, ethanethiol)
– Added to natural gas to provide warning odor.
• CH3CH2CH2SH (propanethiol) fresh onion
• CH2=CHCH2SH garlic
 Reactions of Thiols
• Water-soluble thiolate salts

• Formation of a disulfide bond (-S-S-)

 Chemical Properties
• Sulfides are easily oxidized
Aldehydes and
Ketones
 Structure
• Carbonyl group – C=O
• Aldehyde : -CHO
– carbonyl group bonded to a hydrogen atom.
– Simplest: methanal (or formaldehyde)
• Ketone: R-CO-R
O O O
HCH CH3 CH CH3 CCH3
Methanal Ethanal Propanone
(Formaldehyde) (Acetaldehyde) (Acetone)
 Nomenclature
• IUPAC names for aldehydes:
– change the suffix -e of the parent alkane to -al.
– No need to use a number to locate the aldehyde
group.
• Always in the first position.
– unsaturated aldehydes:
• changing the ending of the parent alkane from -ane to -
enal;
• Start with the aldehyde carbonyl carbon
• Show the location of the carbon-carbon double bond
by the number of its first carbon.
 Nomenclature
O O O
3 1
5 3 1 3 1 2
6 4 2
H
4 2
H H
Hexanal 3-Methylbutanal 2-Propenal
(Acrolein)

CHO
– The IUPAC system
O retains
CHOcommon names
for some aldehydes,
H including these three.
OCH3
OH
t rans-3-Phenyl-2-prop enal Ben zaldehyde Van illin
(Cinn amald ehyd e; in (in almond s) (from van illa
oil of cin namon) bean s)
 Nomenclature
• IUPAC names for ketones:
– Find the longest chain that contains the carbonyl
group.
– Change the -ane of the parent alkane to -one.
– the carbonyl carbon must have the smaller
number.
– 2-propanone’s
O common
O name is O
acetone
1 5 1
3 2
2 4 6

Acetone 5-Meth yl-3-h exanone 2-Methylcycloh exanone

 Nomenclature
• aldehyde or ketone with an -OH (hydroxyl)
or -NH2 (amino) group:
– Give the carbonyl carbon the lower number.
• -OH substituent : hydroxy-,
• -NH2 substituent by amino-.
– Alphabetize substituent.
OH O O
5 4 6 4 3 2 1
3 1 H
NH2
3-Hydroxy-4-meth ylp entanal 3-Amino-4-ethyl-2-h exanone
 Nomenclature
– Common name for an aldehyde :
• the common name of the corresponding carboxylic
acid;
• drop the word "acid" and change the suffix -ic or -oic to
-aldehyde
– Common name for ketone:
• Name each alkyl or aryl group bonded to the carbonyl
O
carbon separately (list in order of increasing M.W.)
O O O
CH3 CH • add
CHthe
3
word "ketone”
COH
Acetaldehyde Acetic acid Methyl ethyl ketone Ethyl isopropyl ketone
 Physical Properties
• A C=O bond is polar
– Therefore, aldehydes and ketones are polar
molecules
 Physical Properties
– In liquid aldehydes and ketones, there are
weak intermolecular attractions
– No hydrogen bonding is possible between
aldehyde or ketone molecules.
– Aldehydes and ketones have lower boiling
points than alcohols and carboxylic acids,
compounds in which there is hydrogen
bonding between molecules.
 Physical Properties
Molecular bp
Name Structural Formu la Weigh t (amu ) (°C )
di ethyl ether CH3 CH2 OCH 2 CH3 74 34
pe ntane CH3 CH2 CH2 CH2 CH 3 72 36
bu tan al CH3 CH2 CH2 CHO 72 76
2-butanon e CH3 CH2 COCH3 72 80
1-butanol CH3 CH2 CH2 CH2 OH 74 117
propanoic aci d CH3 CH2 COOH 74 141

– Formaldehyde, acetaldehyde, and acetone

are infinitely soluble in water.
– Aldehydes and ketones become less soluble
 Oxidation
• Aldehydes are oxidized to carboxylic acids
by a variety of Ooxidizing agents, including
O
K2 Cr2 O 7
potassium dichromate.
H OH
H2 SO 4
Hexanal Hexanoic acid

– Liquid aldehydes
O are so sensitiveOto oxidation
by O2 of the airC that
H + they must be Cprotected
OH
2 O 2 2
from contact with air during storage.
Be nz alde hyde Be nz oic aci d
 Oxidation
• Ketones : no reaction
– Tollens’ reagent is specific for the oxidation of
aldehydes; if done properly, silver deposits on
O the walls of the container as a silver mirror.
+ -
R-C-H + 2 Ag( NH3 ) 2 + 3 OH
A ldehyde Tollens'
reagen t
O
R-C-O- + 2 Ag + 4 NH3 + 2 H2 O
Carboxylic Silver
an ion mirror
 Reduction
• Aldehyde: primary alcohol -CH2OH
• Ketone: Osecondary alcohol R2CHOH.
transition
metal catalyst
H + H2 OH
Pentanal 1-Pentanol
tran sition
metal catalyst
O + H2 OH

Cyclopen tan on e Cyclopen tanol

 Addition of Alcohols
• Hemiacetal: adding an alcohol to the
carbonyl group of an aldehyde or ketone
– The functional group: a carbon bonded to
one -OH group and one -OR group.
– H of the alcohol adds to the carbonyl oxygen
and OROadds H to the carbonyl carbon.
O-H
C + O-CH2 CH3 C OCH2 CH3
H H
Benzald ehyde Eth anol A hemiacetal
 Addition of Alcohols
– Hemiacetals: unstable
• minor components of an equilibrium mixture
– When a hydroxyl group is part of the same
molecule that contains the carbonyl group and
a five- or six-membered ring can form, the
redraw to
compound
O show exists
the -OH almost entirely in a cyclic
3 2
5
4
3
hemiacetal
2
1 an d form.
-CHO clos e 1 H H
H to each oth er 4
C
5 O O-H
O-H O O
4-Hyd roxypentanal H A cyclic hemiacetal
 Addition of Alcohols
• Acetal : A hemiacetal can react further
with an alcohol
– This reaction is acid catalyzed.
– The functionalH group ofH+an acetalOCH
O-H is 2aCHcarbon
3
C OCH2 CH3 + OCH2 CH3 C OCH2 CH3 + H- OH
bonded to two -OR groups.
H H
A hemiacetal Ethanol An acetal
(from benzaldehyde)
 Addition of Alcohols
O-H H
H+ OCH2 CH3
+ OCH2 CH3 + H2 O
OCH2 CH3 OCH2 CH3
A hemiacetal Ethanol An acetal
(from cyclohexan one)

– Reversible steps
– Le Chatelier's principle:
• To drive it to the right, we either use a large excess of
alcohol or remove water from the equilibrium mixture
• To drive it to the left, we use a large excess of water.
 Keto-Enol Tautomerism
• A carbon atom adjacent to a carbonyl
group is called an a-carbon, and a
bonded to it is called an a-
a-hydrogen s
hydrogen atom
O
hydrogen. CH -C- CH -CH
3 2 3
a-carbons
 Keto-Enol Tautomerism
• Enol: a constitutional isomer a ketone.
– “enol”: (-ol). O OH
CH3 -C-CH3 CH3 -C=CH2
Acetone Acetone
(k eto form) (enol form)

– In a keto-enol equilibrium, the keto form generally

predominates.
 Keto-Enol Tautomerism
– example: Draw structural formulas for the two
enol forms for each ketone:
O OH OH
– solution:
(a)

O OH OH
(b )