1. PARVATHY’S ARTS & SCIENCE COLLEGE
DINDIGUL.
Prepared
J. Balamurugan
Assistant professor
DEPARTMENT OF CHEMISTRY
Subject: Organic chemistry-I Class: I B.Sc Chemistry
Year: 2018-2019 Semester: I
2. ORGANIC CHEMISTRY-I
UNIT-I
ALKENES AND ALKYNES
Preparation of alkanes dehydration of alcohols, dehydrohalogenation of alkyl halides. Sayzeff rules, partial
dehydrogenation of alkynes. Conjugated isolated and cumulative dienes with examples Alkynes preparation acetylene
from CaC2, dehydrogenation of tetra halides and halogenations of vicinal dihalides.
UNIT-II
AROMATIC HYDROCARBONS
Aromaticity, Huckel’s rule, structure of benzene. Preparation of benzene from phenol acetylene and by decarboxylation.
Electrophilic substitution reaction mechanism of nitration sulphonation halogenations. Preparation of toluerne, xylene
and mesitylene.
UNIT-III
POLYNUCLEAR HYDROCARBONS, CYCLOALKANES AND CONFORMATION
Preparations and reactions of biphenyl, napthalence,anthracence phenanthrene cyclo alkanes preparation using
dickmann ‘s method, freund ‘smethod and reduction Of hydrocarbons Bayer ‘s straintheory and thery of strain less rings
Conformational analysis of ethane, n butane,1,2 dichloroethane,cyclohexane.
UNIT-IV
ALKYL AND ARYL HALIDES
Aryl halides preparation from phenol Sandmeyer ‘s reaction substitution by oh group (nucleophilic bimoleculer
mechanism) and by NH2 group(benzyne mechanism) Poly halogen derivatives preparation
Applications of westron and Freon.
UNIT-V
STEREO CHEMISTRY
Geometrical isomerism maleic acid and fumaric acids, Aldoximes and ketoximes, determination of configuration of
geometrical isomers, e z notation. Asymmetry sysnthesis,specification of R S rotations optically activity of compounds
without Asymmetric carbon atoms allenes, spirenes spirenes and biphenyl compounds.
3. Preparations of alkenes
1. Dehydrohalogenation of alkyl halides
C C
XH
+ KOH
alcohol
C C + KX + H2O
Ease of dehydrohalogenation of alkyl halides
3° > 2° > 1°
Example:
CH3CH2CH2CH2Cl
KOH
CH3 CH2 HC CH2
n-butyl chloride 1-butene
KOH is an OH
-
donor use to abstract H
+
CH3CH2CHClCH3
KOH
CH3 HC CHCH3 + CH3CH2HC CH2
sec - butyl chloride 2 - butene (80%) 1 - butene (20%)
4. 2. Dehydration of alcohol
C C
H OH
acid
C C + H2O
alkene
Ease of dehydration of alcohols
3° > 2° > 1°
ex.
CH C
H
H
H
H
OH
H2SO4
CH
H
C H
H
+ H2O
ethylene
ethyl alcohol
acid serves as H
+
donor
5. CH3CH2CH2CH2OH
H2SO4
CH3CH2HC CH2 CH3 HC CHCH3
n-butyl alcohol 1-butene 2-butene
(chief product)
CH3CH2 HC CH3
OH
H2SO4
Al2O2 in
heated tube
CH3 HC CHCH3 + CH3CH2HC CH2
sec-butyl alcohol 2-butene 1-butene
(chief product)
6. 3. Dehalogenation of vicinal dihalides
(same side)
C C
X X
+ Zn C C + ZnX2
dihalides
Example:
CH3 HC CH CH3
Br Br
Zn
CH3 HC CHCH3 + ZnX2
2,3- Dibromobutane 2- butene
7. C C + X2 C C
X X
X2 = CL2, Br2
I2 - unreactive with alkane
Reactions of Alkenes
1. Addition of Halogens (X2)
Example.
HCH3C CH2
Br2
CH3CHBrCH2Br
propene(propylene) 1,2 dibromopropane (propylene bromide)
CCl4
8. C C + HX C C
H X
HX = HCL, HBr, HI
3. Addition of hydrogen halides
9. C C + H2SO4 C C
H OSO3H
alkyl hydrogen sulfates
4. Addition of sulfuric acid
Ex.
HCH3C CH2
propene
80% H2SO4
H2O, heat
CHCH3
OSO3H
CH3
CHCH3
OH
CH3
Isopropyl alcohol
10. 8. Alkylation
C C + R H
acid
C C
RH
ex.
H3C C CH2
CH3
isobutylene
+ H3C C H
CH3
CH3
H2SO4
H3C C CH2 C CH3
CH3 CH3
CH3
H
isobutane 2, 2, 4 - trimethyl pentane
11. mechanism:
H3C C CH2
CH3
+ H3C C
CH3
CH3
+ H3C C CH2 C CH3
CH3 CH3
CH3
+
H3C C CH2 C CH3
CH3
CH3
CH3
+
+ H C CH3
CH3
CH3
H3C C CH2 C CH3
CH3 CH3
CH3H
+
C CH3
CH3
CH3
+
Addition of a hydrogen
ion to form carbocation
Addition of a
tert-butyl
carbocation to
isobutylene
Carbocation
abstracts a
hydrogen atom with
its pair of electrons
from a molecule of
alkane. This
abstraction of
hydride ion yields
an alkane of 8
carbons and a new
carbocation to
continue the chain.
H3C C CH2
CH3
+ H:B H3C C CH3
CH3
+ :B
+
12. 11. Addition of free radicals
C C + Y Z C C
Y Z
peroxides
or light
n - C6H13CH CH2 + BrCCl3 n - C6H13CH
Br
CH2 CCl3
peroxide
1 - octane bromotrichloromethane
3 - bromo - 1,1,1 - trichlorononane
stability of radical: 3º > 2º > 1º CH3
RCH CH2+ CCl4 RCH CH2 CCl3
Cl
peroxides
14. Free – radical polymerization
nCH2 CH
Cl
peroxide
H2C CH CH2 CH CH2 CH CH2
Cl Cl Cl
or
H2C CH2
Cl n
poly (vinyl chloride)
Polyvinyl chloride - use to make phonograph, records, plastic pipes,
when plasticized with high boiling esters – raincoats, shower
curtains and coatings for metal and upholstery fabrics.
Peroxide – initiator, required in small amount in polymerization
-Free radical initiator
15. CH C C + X2
heat
CX C C X2 = Cl2, Br2
low conc.
HCH3C CH2
propylene
Cl2, 600º
Cl - CH2CH CH2
allyl chloride
+ NBS
Br
cychlohexene
N - bromosuccinimide
3 - bromocyclohexene
15. Halogenation. Allylic substitution ( same mechanism with substitution in
alkenes)
Ex.
16. 16. Ozonolysis (Cleavege rxn)
C C + O3 O
O
O
O
O
H2O, Zn
C O + O C
ozone
ozonide
aldehyde ketone
Cleavage – a rxn in which the double bond is completely broken and the alkene
molecules converted into 2 smaller molecule.
Reducing agent (Zn) – prevent formation of hydrogen peroxide
will not react with aldehyde and ketone (aldehyde are often
converted to acid, RCOOH for ease of isolation.)
17. CH3CH2CH=CH2
O3 H2O, Zn
CH3CH2CHO + CH2=O
C=CH2
CH3
CH3
O3 H2O, Zn
C=O
CH3
CH3 + CH
H
O
CH3CH2CH2CHO + CH3CHO
H2O, Zn O3
CH3CH2CH2CH=CHCH3
CH2CH3C
H
O + O C
H
CH2CH3
H2O / Zn O3
CH2CH3C
H
C CH2CH3
H
aldehydes 3 - hexene
18. 18
Aromatic Compounds
• Aromatic was used to described some fragrant
compounds in early 19th
century
– Not correct: later they are grouped by chemical behavior
(unsaturated compounds that undergo substitution rather
than addition)
• Current: distinguished from aliphatic compounds by
electronic configuration
19. 19
15.1 Sources and Names of
Aromatic Hydrocarbons
• From high temperature distillation of coal tar
• Heating petroleum at high temperature and pressure over
a catalyst
20. 20
Naming Aromatic Compounds
• Many common names (toluene = methylbenzene; aniline
= aminobenzene)
• Monosubstituted benzenes systematic names as
hydrocarbons with –benzene
– C6H5Br = bromobenzene
– C6H5NO2= nitrobenzene, and C6H5CH2CH2CH3 is propylbenzene
22. 22
The Phenyl Group
• When a benzene ring is a substituent, the term phenyl is
used (for C6H5
)
– You may also see “Ph” or “φ” in place of “C6H5”
• “Benzyl” refers to “C6H5CH2
”
23. 23
Disubstituted Benzenes
• Relative positions on a benzene ring
– ortho- (o) on adjacent carbons (1,2)
– meta- (m) separated by one carbon (1,3)
– para- (p) separated by two carbons (1,4)
• Describes reaction patterns (“occurs at the para position”)
24. 24
Naming Benzenes With More Than
Two Substituents
• Choose numbers to get lowest possible values
• List substituents alphabetically with hyphenated numbers
• Common names, such as “toluene” can serve as root
name (as in TNT)
25. 25
15.2 Structure and Stability of
Benzene: Molecular Orbital Theory
• Benzene reacts slowly with Br2 to give bromobenzene
(where Br replaces H)
• This is substitution rather than the rapid addition reaction
common to compounds with C=C, suggesting that in
benzene there is a higher barrier
26. 26
Benzene’s Unusual Structure
• All its C-C bonds are the same length: 139 pm — between
single (154 pm) and double (134 pm) bonds
• Electron density in all six C-C bonds is identical
• Structure is planar, hexagonal
• C–C–C bond angles 120°
• Each C is sp2
and has a p orbital perpendicular to the
plane of the six-membered ring
27. 27
Molecular Orbital Description of Benzene
• The 6 p-orbitals combine to give
– Three bonding orbitals with 6 π electrons,
– Three antibonding with no electrons
• Orbitals with the same energy are degenerate
28. 28
15.3 Aromaticity and the Hückel 4n+2 Rule
• Unusually stable - heat of hydrogenation 150 kJ/mol less negative
than a cyclic triene
• Planar hexagon: bond angles are 120°, carbon–carbon bond lengths
139 pm
• Undergoes substitution rather than electrophilic addition
• Resonance hybrid with structure between two line-bond structures
• Huckel’s rule, based on calculations – a planar cyclic molecule with
alternating double and single bonds has aromatic stability if it has
4n+ 2 π electrons (n is 0,1,2,3,4)
• For n=1: 4n+2 = 6; benzene is stable and the electrons are
delocalized
29. 29
Compounds With 4n π Electrons Are Not
Aromatic (May be Antiaromatic)
• Planar, cyclic molecules with 4 n π electrons are much less stable than
expected (antiaromatic)
• They will distort out of plane and behave like ordinary alkenes
• 4- and 8-electron compounds are not delocalized (single and double
bonds)
• Cyclobutadiene is so unstable that it dimerizes by a self-Diels-Alder
reaction at low temperature
• Cyclooctatetraene has four double bonds, reacting with Br2, KMnO4, and
HCl as if it were four alkenes
46. 46
Cycloalkanes
Cycloalkanes have molecular formula CnH2n and contain carbon atoms arranged in
a ring. Simple cycloalkanes are named by adding the prefix cyclo- to the name of
the acyclic alkane having the same number of carbons.
47. 47
Cycloalkanes are named by using similar rules of naming alkane,
but the prefix cyclo- immediately precedes the name of the parent.
1. Find the parent cycloalkane.
48. 48
2. Name and number the substituents. No number is needed to
indicate the location of a single substituent.
For rings with more than one substituent, begin numbering at one
substituent and proceed around the ring to give the second
substituent the lowest number.
49. 49
With two different substituents, number the ring to assign the lower
number to the substituents alphabetically.
Note the special case of an alkane composed of both a ring and a
long chain. If the number of carbons in the ring is greater than or
equal to the number of carbons in the longest chain, the compound
is named as a cycloalkane.
50. 50
Introduction to Cycloalkanes
• Besides torsional strain and steric strain, the conformations of cycloalkanes are
also affected by angle strain.
• Angle strain is an increase in energy when bond angles deviate from the
optimum tetrahedral angle of 109.5°.
• The Baeyer strain theory was formulated when it was thought that rings were flat.
It states that larger rings would be very highly strained, as their bond angles
would be very different from the optimum 109.5°.
• It turns out that cycloalkanes with more than three C atoms in the ring are not flat
molecules. They are puckered to reduce strain.
52. 52
Cyclohexane
In reality, cyclohexane adopts a puckered “chair” conformation, which is
more stable than any possible other conformation.
The chair conformation is so stable because it eliminates angle strain (all C
—C—C angles are 109.5°), and torsional strain (all hydrogens on adjacent C
atoms are staggered).
53. 53
• An important conformational change in cyclohexane involves “ring-
flipping.” Ring-flipping is a two-step process.
• As a result of a ring flip, the up carbons become down carbons, and
the down carbons become up carbons.
• Axial and equatorial H atoms are also interconverted during a ring-
flip. Axial H atoms become equatorial H atoms, and equatorial H
atoms become axial H atoms.
54. 54
• The chair forms of cyclohexane are 7 kcal/mol more stable than the
boat forms.
• The boat conformation is destabilized by torsional strain because
the hydrogens on the four carbon atoms in the plane are eclipsed.
• Additionally, there is steric strain because two hydrogens at either
end of the boat, the “flag pole” hydrogens, are forced close to each
other.
Figure 4.14
Two views of the boat
conformation of cyclohexane
55. 55
How to draw the two conformations of a substituted cyclohexane:
56. 56
How to draw the two conformations of a substituted cyclohexane:
57. 57
• Note that the two conformations of cyclohexane are different, so
they are not equally stable.
• Larger axial substituents create destabilizing (and thus unfavorable)
1,3-diaxial interactions.
• In methylcyclohexane, each unfavorable H,CH3 interaction
destabilizes the conformation by 0.9 kcal/mol, so Conformation 2 is
1.8 kcal/mol less stable than Conformation 1.
59. 59
Substituted Cyclohexane
• Note that the larger the substituent on the six-membered ring, the
higher the percentage of the conformation containing the equatorial
substituent at equilibrium.
• With a very large substituent like tert-butyl [(CH3)3C-], essentially
none of the conformation containing an axial tert-butyl group is
present at room temperature, so the ring is essentially anchored in a
single conformation having an equatorial tert-butyl group.
Figure 4.16
The two conformations of
tert-butylcyclohexane
60. 60
Disubstituted Cycloalkanes
• There are two different 1,2-dimethylcyclopentanes—one having two
CH3 groups on the same side of the ring and one having them on
opposite sides of the ring.
• A and B are isomers. Specifically, they are stereoisomers.
61. 61
• Stereoisomers are isomers that differ only in the way the atoms are oriented in
space.
• The prefixes cis and trans are used to distinguish these isomers.
• The cis isomer has two groups on the same side of the ring.
• The trans isomer has two groups on opposite sides of the ring.
62. 62
• A disubstituted cyclohexane, such as 1,4-dimethylcyclo-
hexane, also has cis and trans stereoisomers. In addition, each
of these stereoisomers has two possible chair conformations.
• Cis and trans isomers are named by adding the prefixes cis and
trans to the name of the cycloalkane. Thus, the cis isomer would be
named cis-1,4-dimethylcyclohexane, and the trans isomer would be
named trans-1,4-dimethylcyclohexane.
• All disubstituted cycloalkanes with two groups bonded to different
atoms have cis and trans isomers.
63. 63
Ch. 3: Alkanes and Cycloalkanes: Conformations and
cis-trans Stereoisomers
Stereochemistry: three-dimensional aspects of molecules
Conformation: different spatial arrangements of atoms that
result from rotations about single (σ) bonds
Conformer: a specific conformation of a molecule
3.1: Conformational Analysis of Ethane
Sawhorse
C C
H
H
H
H
H
H
HH
H
H H
H
64. 64
Staggered EclipsedNewman projection
There are two conformations of ethane:
Dihedral (torsion) angle: angle between an atom (group) on the
front atom of a Newman Projection and an atom (group)
on the back atom
Dihedral angles of ethanes:
Staggered conformation: 60° (gauche), 180° (anti),
and 300° (-60°, gauche)
Eclipsed conformation: 0°, 120°, and 240° (-120°)
H
H
H
H
H
H
Front
carbon
Back
carbon
65. 65
The barrier to C-C rotation for
propane is 13 KJ/mol = 1 (CH3-H)
+ 2 (H-H) eclipsing Interactions.
A CH3-H eclipsing interaction
is 5 KJ/mol
eclipsed
staggered
Conformations of Propane
C C
CH3
H
H
H
H
H
HH
H
H H
H3C
5.0 KJ/mol
66. 66
3.2: Conformational Analysis of Butane
Two different staggered and eclipsed conformations
C C
CH3
H3C
H
H
H
H
HH
CH3
H H
H3C
Staggered: anti
C C
CH3
H
H3C
H
H
H
CH3H
H
H H
H3C
Staggered: gauche
3 KJ/mol
67. 67
Steric Strain: repulsive interaction that occurs when two groups
are closer than their atomic radii allow
3 KJ/mol
Eclipsed conformations of butane: rotational barrier of butane is
25 KJ/mol. A CH3-CH3 eclipsing interaction is 17 KJ/mol.
CH3 - H CH3 - CH3
68. 68
3.3: Conformations of Higher Alkanes - The most stable
conformation of unbranched alkanes has anti relationships
between carbons (extended carbon chain).
3.4 The Shapes of Cycloalkanes: Planar or Nonplanar?
Angle Strain: strain due to deforming a bond angle from its ideal
value (Baeyer Strain Theory)
60° 90° 108° 120° 128° 135°
Internal angles of polygons
69. 69
CH2
H
H
H
H
CH2
Cyclobutane - reduced angle and torsional strain relative to
cyclopropane
Puckering partially
relieves torsional strain
3.6: Cyclopentane: planar conformation is strain free according
to Baeyer; however, there is considerable torsional strain (10
H-H eclipsing interactions)
Envelope and half-chair conformations relieve much of the
torsional strain
70. 70
axial
equatorial
a
e
a
e
a
a
e
e
a
e
a
e
top face bottom face
3.7: Conformations of Cyclohexane - ΔHcomb suggests that
cyclohexane is strain-free; favored conformation is a chair.
3.8: Axial and Equatorial Bonds in Cyclohexane
Chair cyclohexane has two types of hydrogens:
axial: C-H axis is “perpendicular” to the “plane of the ring”
equatorial: C-H axis is “parallel” to the “plane of the ring”
Chair cyclohexane has two faces; each face has alternating axial
and equatorial -H’s
71. 71
All H-H interactions are staggered - no torsional strain; minimal
angle strain (~111°)
Other conformations of cyclohexane:
half chair; twist boat, and boat
3.9: Conformational Inversion (Ring-Flipping) in Cyclohexane
Ring flip interchanges the axial and equatorial positions. The
barrier to a chair-chair interconversion is 45 KJ/mol.
45 KJ/mol
73. 73
3.10: Conformational Analysis of Monosubstituted Cyclohexanes
most stable chair conformation has the substituent in the equatorial
position R
H
H
R
Keq
R= -CH3 5 : 95
1,3-diaxial
interactions
75. 75
3.11: Disubstituted Cycloalkanes: Stereoisomers
Stereochemistry: three-dimensional arrangement of atoms
(groups) in space
Isomers: different chemical compounds with the same formula
Constitutional isomers: same formula, but different
connectivity of atoms (or groups)
Stereoisomers: same connectivity, but different spatial
arrangement of atoms or groups
ethylcyclopropane 1,2-dimethylcyclopropane
C5H10
CH3
HH
H3C H
CH3H
H3C
trans: on opposite sides of the ring
cis: on the same side of the ring
cis-1,2-dimethylcyclopropane trans-1,2-dimethylcyclopropane
ΔHcomb is ~ 5KJ/mol higher for the cis isomer
76. 76
H
CH3
H
CH3
cis
(two equatorial)
H
CH3
trans
(one equatorial, one axial)
H
CH3
trans
(one equatorial, one axial)
cis
(two axial)
H
H3C
CH3
H
H3C
H
H
H3C
1,3-dimethylcyclohexane 1,4-dimethylcyclohexane
H
CH3
H
CH3
trans
(two equatorial)
H
CH3
cis
(one equatorial, one axial)
H
CH3cis
(one equatorial, one axial)
trans
(two axial)
CH3
H
H
H3C
H
H3C
CH3
H
3.13: Medium and Large Rings (please read)
77. 77
3.14: Polycyclic Ring Systems - contains more than one ring
fused - two rings share a pair of bonded atoms
spirocyclic - one atom common to two rings
bridged bicyclic - nonadjacent atoms common to two rings
fused spiro bridged
cis- and trans-decalin are stereoisomers, they do not interconvert
into each other
H
H
H
H
H
H
H
H
trans-decalin cis-decalin
79. 79
Drawing Structures
CYCLIC ALKANES: Substituents on a cycloalkane can be cis or trans to
each other. You should draw the ring in the plane of the paper (solid lines)
and use dashes and wedges to show whether substitutents are above or
below the plane of the ring.
correct incorrect
On occasion you may wish to distinguish the faces of a cycloalkane.
••
• •
cis trans
top face
bottom face
a
b
a
b
b b
b
a a
a
80. 80
CYCLOHEXANE: For cyclohexanes you may be asked to draw a chair, in
which case all substituents must be either axial or equatorial. The following
is the correct way to draw chair cyclohexane. Note how the axial and
equatorial substituents are represented off each carbon.
Disubstituted chair cyclohexanes:
correct
incorrect
••
• •
a
a
e
e
a
a
e
e
a
e
a
e
trans trans cis
trans cis cis
trans trans cis
82. 82
Reactions of Alkyl Halides (R-X): [SN
1, SN
2, E1, & E2 reactions]
When a nucleophile (electron donor, e.g., OH-
)
reacts with an alkyl halide, the halogen leaves
as a halide
There are two competing reactions of alkyl halides with nucleophiles….
1) substitution
2) elimination
C C
H
X
Nu:-
+
C C
H
Nu
+ X-
+ C C
H
X
Nu:
- C C + X- + Nu H
The Nu:-
replaces the halogen on the α-carbon.
The Nu:-
removes an H+
from a β-carbon & the
halogen leaves forming an alkene.
BrR
..
.. :
..
.. ::BrNu:
α
α
β
83. 83
• There are two kinds of substitution
reactions, called SN
1 and SN
2.
• As well as two kinds of elimination
reactions, called E1 and E2.
• Let’s study SN
2 reactions first. SN
2 stands
for Substitution, Nucleophilic,
bimolecular. Another word for
bimolecular is ‘2nd
order’.
Bimolecular (or 2nd
order) means that the
rate of an SN
2 reaction is directly
proportional to the molar concentration
of two reacting molecules, the alkyl halide
2nd Order Nucleophilic Substitution Reactions, i.e., SN2 reactions
C C
H
X
Nu:-
+
C C
H
Nu
+ X-
α
Note that the nucleophile must hit the back side of the α-carbon.
The nucleophile to C bond forms as the C to X bond breaks.
No C+
intermediate forms. An example is shown on the next slide.
84. 84
2nd Order Nucleophilic Substitution Reactions, i.e., SN2 reactions
The rate of an SN2 reaction depends upon 4 factors:
1. The nature of the substrate (the alkyl halide)
2. The power of the nucleophile
3. The ability of the leaving group to leave
4. The nature of the solvent
1. Consider the nature of the substrate:
Unhindered alkyl halides, those in which the back side of the α-carbon is not blocked,
will react fastest in SN2 reactions, that is:
Me° >> 1° >> 2° >> 3°
While a methyl halides reacts quickly in SN2 reactions, a 3° does not react. The back
side of an α-carbon in a 3° alkyl halide is completely blocked.
O H
..
..
: C Br
..
.. :
H
H
H
+
transition state
C Br
..
.. :
H H
H
OH
..
..
+
..
.. :Br:C
H
H
H
OH
..
..
85. 85
• The mechanism of an S
N1 reaction occurs in 2 steps:
• Reaction Steps …
1. the slower, rate-limiting dissociation of the alkyl halide forming a C+
intermediate
2. a rapid nucleophilic attack on the C+
Mechanism of SN1 reactions
C
CH3
H3C
CH3
3°
Br..
..
: + Na+
Br-
C
CH3
H3C
CH3
I
..
..
:
1.
Br --
C
CH3
H3C
CH3
+
3° C+
rapid
Na+
I -
..
..: :
2.
Note that the nucleophile is not involved in the slower, rate-limiting step.
86. 86
• The rate of an S
N1 reaction depends upon 3 factors:
1. The nature of the substrate (the alkyl halide)
2. The ability of the leaving group to leave
3. The nature of the solvent
• The rate is independent of the power of the nucleophile.
•1. Consider the nature of the substrate:
Highly substituted alkyl halides (substrates) form a more stable C+.
The Rate of SN1 reactions
C
H
H
H +C
CH3
H
H +C
CH3
H
H3C +C
CH3
CH3
H3C +
tertiary
3º
secondary
2º
primary
1º
methyl
more
stable
less
stable
> > >
increasing rate of SN1 reactions
87. 87
• Alkyl groups are weak electron donors.
They stabilize carbocations by donating electron density by induction (through σ
bonds)
They stabilize carbocations by hyperconjugation (by partial overlap of the alkyl C-to-
H bonds with the empty p-orbital of the carbocation).
Stability of Carbocations
C
CH3
CH3
H3C +
Inductive effects:
Alkyl groups donate (shift) electron
density through sigma bonds to
electron deficient atoms.
This stabilizes the carbocation.
vacant p orbital
of a carbocation
sp2
hybridized
carbocation
Csp3-Hs
sigma bond
orbital
overlap (hyperconjugation)
HYPERCONJUGATION
+
C C
..
H
H
H
88. 88
Allyl and benzyl halides also react quickly
by SN1 reactions because their carbocations
are unusually stable due to their resonance
forms which delocalize charge over an
extended π system
Stability of Carbocations
H2C CH +
CH2
CH2HCH2C
+
1º allyl carbocation
H2C CH +
CHR CHRHCH2C
+
2º allyl carbocation
2º benzylic
1º benzylic
C
H
R
+C
H
H
+
C
H
H
C
H
H
C
H
H
+ +
+
89. 89
Relative Stability of All Types of Carbocations
2º allylic
> >
3º allylic
> >
>
3º C+
CCH3
CH3
CH3
+
CH2 CH CHR
+
CH2 CH CR2
+
C R2
+
3º benzylic
C HR
+
2º benzylic
1º allylic
CCH3
CH3
H
+
2º C+
CH2 CH CH2
+
C H2
+
1º benzylic
1º C+
CCH3
H
H
+
+
+
CH
H
H
methyl C
+
phenyl
> CH2 CH
+
+
vinyl C
Increasing C+ stability and rate of SN1
reaction
Note that 1° allylic and 1° benzylic C+’s are about as stable as 2°alkyl C+’s.
Note that 2° allylic and 2° benzylic C+’s are about as stable as 3° alkyl C+’s.
Note that 3° allylic and 3° benzlic C+’s are more stable than 3° alkyl C+’s
Note that phenyl and vinyl C+’s are unstable. Phenyl and vinyl halides do
not usually react by SN1 or SN2 reactions
90. 90
• Consider the nature of the Nucleophile:
Recall again that the nature of the nucleophile has no effect on the rate of SN1
reactions because the slowest (rate-determining) step of an SN1 reaction is the
dissociation of the leaving group and formation of the carbocation.
All carbocations are very good electrophiles (electron acceptors) and even weak
nucleophiles, like H2O and methanol, will react quickly with them.
The two SN1 reactions will proceed at essentially the same rate since the only
difference is the nucleophile.
Effect of the nucleophile on rate of SN1 reactions:
C
CH3
H3C
CH3
Br + Na+
I- C
CH3
H3C
CH3
I + Na+
Br-3°
C
CH3
H3C
CH3
Br + C
CH3
H3C
CH3
F + K+
Br-3° K+ F-
91. 91
•We have seen that alkyl halides may react with basic nucleophiles such as NaOH via
substitution reactions.
•Also recall our study of the preparation of alkenes. When a 2° or 3° alkyl halide is treated
with a strong base such as NaOH, dehydrohalogenation occurs producing an alkene – an
elimination (E2) reaction.
• bromocyclohexane + KOH → cyclohexene (80 % yield)
•Substitution and elimination reactions are often in competition. We shall consider the
determining factors after studying the mechanisms of elimination.
Elimination Reactions, E1 and E2:
Br
KOH in ethanol + KBr + H2O
-HBr
O H
..
..
: C Br
..
.. :
H
H
H
+
transition state
C Br
..
.. :
H H
H
OH
..
..
+
..
.. :Br:C
H
H
H
OH
..
..
92. 92
+ C C
H
Br
OH- C C + Br- + HO H
• There are 2 kinds of elimination reactions, E1 and E2.
• E2 = Elimination, Bimolecular (2nd order). Rate = k [RX] [Nu:-
]
E2 reactions occur when a 2° or 3° alkyl halide is treated with a strong base such as
OH-
, OR-
, NH2
-
, H-
, etc.
E2 Reaction Mechanism
The Nu:-
removes an H+
from a β-carbon & the
halogen leaves forming an alkene.
α
β
All strong bases, like OH-
, are good nucleophiles. In 2° and 3° alkyl
halides the α-carbon in the alkyl halide is hindered. In such cases, a
strong base will ‘abstract’ (remove) a hydrogen ion (H+) from a β-carbon,
before it hits the α-carbon. Thus strong bases cause elimination (E2) in
2° and 3° alkyl halides and cause substitution (SN2) in unhindered
methyl° and 1° alkyl halides.
93. 93
•In E2 reactions, the Base to H σ bond formation, the C to H σ bond breaking, the C to C π
bond formation, and the C to Br σ bond breaking all occur simultaneously. No
carbocation intermediate forms.
•Reactions in which several steps occur simultaneously are called ‘concerted’ reactions.
•Zaitsev’s Rule:
•Recall that in elimination of HX from alkenes, the more highly substituted (more stable)
alkene product predominates.
E2 Reaction Mechanism
B:
-
C
H
C
R
R
X
B
R
R
H
C CR
R
R
R X
δ
+
-
δ
C C
R R
R
R
+ B H + X
-
CH3CH2CHCH3
Br CH3CH2O
-
Na
+
EtOH
CH3CH CHCH3 + CH3CH2CH CH2
2-butene 1-butene
major product
( > 80%)
minor product
( < 20%)
94. 94
Just as SN
2 reactions are analogous to E2
reactions, so SN
1 reactions have an analog, E1
reaction.
E1 = Elimination, unimolecular (1st order); Rate = k × [RX]
E1 eliminations, like SN
1 substitutions, begin with unimolecular dissociation, but the
dissociation is followed by loss of a proton from the β-carbon (attached to the C+
)
rather than by substitution.
E1 Reactions
CCH3
CH3
CH3
Br
slow
B:-
CCH3
CH3
C H
H
H
+ rapid
C C
CH3 H
CH3
H
+ B H + Br-
Br--
95. 95
As with E2 reactions, E1 reactions also produce the more highly substituted alkene
(Zaitsev’s rule). However, unlike E2 reactions where no C+
is produced, C+
rearrangements can occur in E1 reactions.
e.g., t-butyl chloride + H2
O (in EtOH) at 65 °C → t-butanol + 2-methylpropene
In most unimolecular reactions, SN
1 is favored over E1, especially at low temperature.
Such reactions with mixed products are not often used in synthetic chemistry.
If the E1 product is desired, it is better to use a strong base and force the E2 reaction.
Note that increasing the strength of the nucleophile favors SN
1 over E1. Can you
postulate an explanation?
E1 Reactions
CCH3
CH3
CH3
Cl +
H2O, EtOH
65ºC
CCH3
CH3
CH3
OH C C
CH3
H
CH3
H
64%
36%
SN1
product
E1
product
96. Aryl Halides Ar-X
Organic compounds with a halogen atom attached to an aromatic
carbon are very different from those compounds where the halogen is
attached to an aliphatic compound. While the aliphatic compounds
readily undergo nucleophilic substitution and elimination reactions,
the aromatic compounds resist nucleophilic substitution, only reacting
under severe conditions or when strongly electron withdrawing groups
are present ortho/para to the halogen.
98. reactions of alkyl halides Ar-X
1. SN2 NR
2. E2 NR
33 organo metallic compounds similar
4. reduction similar
99. C C X
X
aryl halide
vinyl halide
Ag+
-
OH
-OR
NH3
-CN
ArH
AlCl3
NO REACTION
100. Aryl halides, reactions:
1. Formation of Grignard reagent
2. EAS
3. Nucleophilic aromatic substitution (bimolecular displacement)
(Ar must contain strongly electron withdrawing groups ortho and/or para to X)
4. Nucleophilic aromatic substitution (elimination-addition)
(Ring not activated to bimolecular displacement)
102. 2) EAS The –X group is electron-withdrawing and deactivating
in EAS, but is an ortho/para director.
Br
HNO3, H2SO4
H2SO4,SO3
Br2,Fe
CH3CH2-Br, AlCl3
+
+
+
+
Br Br
Br
Br Br
Br
NO2
SO3H
Br
CH2CH3
Br
NO2
Br SO3H
Br CH2CH3
103. 3) Nucleophilic aromatic substitution (bimolecular displacement)
Ar must contain strongly electron withdrawing groups ortho and/or para
to the X.
Cl
NO2
NO2
+ NH3
NH2
NO2
NO2
Br
NO2
NO2
+ NaOCH3
OCH3
NO2
NO2
O2N O2N
105. 4) Elimination-Addition, nucleophilic aromatic substitution.
When the ring is not activated to the bimolecular displacement and the
nucleophile is an extremely good one.
Br
+ NaNH2, NH3
NH2
F
+
Li
Li
H2O
106. Stereochemistry
Stereochemistry refers to the
3-dimensional properties and
reactions of molecules. It has its
own language and terms that need
to be learned in order to fully
communicate and understand the
concepts.
107. Definitions
• Stereoisomers – compounds with the same
connectivity, different arrangement in space
• Enantiomers – stereoisomers that are non-
superimposible mirror images; only properties
that differ are direction (+ or -) of optical
rotation
• Diastereomers – stereoisomers that are not
mirror images; different compounds with
different physical properties
108. More Definitions
• Asymmetric center – sp3
carbon with 4 different
groups attached
• Optical activity – the ability to rotate the plane of
plane –polarized light
• Chiral compound – a compound that is optically
active (achiral compound will not rotate light)
• Polarimeter – device that measures the optical
rotation of the chiral compound
109. Chirality
• “Handedness”: Right-hand glove does not
fit the left hand.
• An object is chiral if its mirror image is
different from the original object.
Chapter 5 111
112. Chiral Carbon Atom
• Also called asymmetric carbon atom.
• Carbon atom that is bonded to four different groups
is chiral.
• Its mirror image will be a different compound
(enantiomer).
Chapter 5 114
113. Stereocenters
• An asymmetric carbon atom is the most common
example of a chirality center.
• Chirality centers belong to an even broader group
called stereocenters. A stereocenter (or
stereogenic atom) is any atom at which the
interchange of two groups gives a stereoisomer.
• Asymmetric carbons and the double-bonded
carbon atoms in cis-trans isomers are the most
common types of stereocenters.
Chapter 5 115
114. Examples of Chirality Centers
Asymmetric carbon atoms are examples of chirality centers, which are
examples of stereocenters.
Chapter 5 116
115.
116. Achiral Compounds
Take this mirror image and try to
superimpose it on the one to the
left matching all the atoms.
Everything will match.
When the images can be superposed, the
compound is achiral.
Chapter 5 118
117. Planes of Symmetry
• A molecule that has a plane of symmetry is
achiral.
Chapter 5 119
118. Cis Cyclic Compounds
• Cis-1,2-dichlorocyclohexane is achiral because the
molecule has an internal plane of symmetry. Both
structures above can be superimposed (they are
identical to their mirror images).
Chapter 5 120
119. Trans Cyclic Compounds
• Trans-1,2-dichlorocyclohexane does not have a
plane of symmetry so the images are
nonsuperimposable and the molecule will have
two enantiomers.
Chapter 5 121
120. (R) and (S) Configuration
• Both enantiomers of alanine receive the same name in the
IUPAC system: 2-aminopropanoic acid.
• Only one enantiomer is biologically active. In alanine only
the enantiomer on the left can be metabolized by the
enzyme.
• A way to distinguish between them is to use
stereochemical modifiers (R) and (S).
Chapter 5 122
121. Cahn–Ingold–Prelog
Priority System
• Enantiomers have different spatial arrangements of the
four groups attached to the asymmetric carbon.
• The two possible spatial arrangements are called
configurations.
• Each asymmetric carbon atom is assigned a letter (R) or
(S) based on its three-dimensional configuration.
• Cahn–Ingold–Prelog convention is the most widely
accepted system for naming the configurations of chirality
centers.
Chapter 5 123
122. (R) and (S) Configuration: Step 1 Assign
Priority
• Assign a relative “priority” to each group
bonded to the asymmetric carbon. Group 1
would have the highest priority, group 2
second, etc.
• Atoms with higher atomic numbers receive
higher priorities.
I > Br > Cl > S > F > O > N > 13
C > 12
C > 2
H > 1
H
Chapter 5 124
124. (R) and (S) Configuration: Breaking
Ties
In case of ties, use the next atoms along the
chain of each group as tiebreakers.
Chapter 5 126
125. (R) and (S) Configuration: Multiple
Bonds
Treat double and triple
bonds as if each were
a bond to a separate
atom.
Chapter 5 127
126. (R) and (S) Configuration: Step 2
• Working in 3-D, rotate the
molecule so that the lowest
priority group is in back.
• Draw an arrow from highest
(1) to second highest (2) to
lowest (3) priority group.
• Clockwise = (R),
Counterclockwise = (S)
Chapter 5 128
127. Assign Priorities
Draw an arrow from Group 1 to Group 2 to Group 3 and back to Group 1.
Ignore Group 4.
Clockwise = (R) and Counterclockwise = (S)
CounterclockwiseCounterclockwise
((SS))
Chapter 5 129
131. Properties of Enantiomers
• Same boiling point, melting point, and density.
• Same refractive index.
• Rotate the plane of polarized light in the same
magnitude, but in opposite directions.
• Different interaction with other chiral molecules:
– Active site of enzymes is selective for a specific enantiomer.
– Taste buds and scent receptors are also chiral. Enantiomers
may have different smells.
Chapter 5 133
135. Specific Rotation
Observed rotation depends on the length of
the cell and concentration, as well as the
strength of optical activity, temperature, and
wavelength of light.
[α] = α (observed)
c • l
Where α (observed) is the rotation observed in the polarimeter, c is
concentration in g/mL, and l is length of sample cell in decimeters.
Chapter 5 137
136. When one of the enantiomers of 2-butanol is placed in a polarimeter, the observed rotation is 4.05°
counterclockwise. The solution was made by diluting 6 g of 2-butanol to a total of 40 mL, and the
solution was placed into a 200-mm polarimeter tube for the measurement. Determine the specific
rotation for this enantiomer of 2-butanol.
Since it is levorotatory, this must be (–)-2-butanol The concentration is 6 g per 40 mL = 0.15 g/mL, and
the path length is 200 mm = 2 dm. The specific rotation is
[α]D
25 =
– 4.05°
(0.15)(2)
= –13.5°
Solved Problem 2
Solution
Chapter 5 138
140. Racemic Mixtures
• Equal quantities of d- and l-enantiomers.
• Notation: (d,l) or (±)
• No optical activity.
• The mixture may have different boiling point (b. p.) and
melting point (m. p.) from the enantiomers!
Chapter 5 142
141. Racemic Products
If optically inactive reagents combine to form
a chiral molecule, a racemic mixture is
formed.
Chapter 5 143
142. Chirality of Conformational Isomers
The two chair conformations of cis-1,2-dibromocyclohexane are
nonsuperimposable, but the interconversion is fast and the molecules are in
equilibrium. Any sample would be racemic and, as such, optically inactive.
Chapter 5 144
143. Nonmobile Conformers
• The planar conformation of the biphenyl derivative is too
sterically crowded. The compound has no rotation around the
central C—C bond and thus it is conformationally locked.
• The staggered conformations are chiral: They are
nonsuperimposable mirror images.
Chapter 5 145
144. Allenes can be Chiral
C C C
H
CH3
C C
Cl
H
C
CH3
H
Cl
H
146. Fischer Projections
• Flat representation of a 3-D molecule.
• A chiral carbon is at the intersection of horizontal
and vertical lines.
• Horizontal lines are forward, out of plane.
• Vertical lines are behind the plane.
Chapter 5 148
148. Fischer Rules
• Carbon chain is on the vertical line.
• Highest oxidized carbon is at top.
• Rotation of 180° in plane doesn’t change
molecule.
• Rotation of 90° is NOT allowed.
Chapter 5 150
149. 180° Rotation
• A rotation of 180° is allowed because it will not
change the configuration.
Chapter 5 151
150. 90° Rotation
• A 90° rotation will change the orientation of the
horizontal and vertical groups.
• Do not rotate a Fischer projection 90°.
Chapter 5 152
151. Glyceraldehyde
• The arrow from group 1 to group 2 to group 3
appears counterclockwise in the Fischer
projection. If the molecule is turned over so the
hydrogen is in back, the arrow is clockwise, so this
is the (R) enantiomer of glyceraldehyde.
Chapter 5 153
152. When naming (R) and (S) from
Fischer projections with the
hydrogen on a horizontal bond
(toward you instead of away
from you), just apply the normal
rules backward.
Chapter 5 154
153. Fischer Mirror Images
• Fisher projections are easy to draw and make it
easier to find enantiomers and internal mirror
planes when the molecule has two or more chiral
centers.
CH3
H Cl
Cl H
CH3
Chapter 5 155
154. Fischer (R) and (S)
• Lowest priority (usually H) comes forward, so
assignment rules are backward!
• Clockwise 1-2-3 is (S) and counterclockwise 1-2-3
is (R).
• Example:
(S)
(S)
CH3
H Cl
Cl H
CH3
Chapter 5 156
155. Racemic Mixture
o
ρ (g/mL) 1.7598 1.7598 1.7723
m.p. C 168-170 168-170 210-212
[α] (degrees) - 12 + 12 0
(R,R) Tartaric acid (S,S) Tartaric Acid (+/-) Tartaric acid
Racemic Mixture (Racemate): 50/50 mixture of enantiomers
CO2H
CO2H
H OH
HO H H OH
HO H
CO2H
CO2H
R,R S,S
156. Meso Compound
Internal Plane of Symmetry
Optically Inactive
o
rotate 180
superimposible
CO2H
CO2H
H OH
H OH HO H
HO H
CO2H
CO2H
R,S S,R
mirror
plane
157. Diastereomers: Cis-trans
Isomerism on Double Bonds
• These stereoisomers are not mirror images of
each other, so they are not enantiomers. They
are diastereomers.
Chapter 5 159
160. Two or More Chiral Carbons
• When compounds have two or more chiral
centers they have enantiomers, diastereomers, or
meso isomers.
• Enantiomers have opposite configurations at each
corresponding chiral carbon.
• Diastereomers have some matching, some
opposite configurations.
• Meso compounds have internal mirror planes.
• Maximum number of isomers is 2n
, where n = the
number of chiral carbons.
Chapter 5 162
162. n = 3; 2n
= 8
CH3
CH2CH3
H Cl
Cl H
H Cl Cl H
H Cl
Cl H
CH3
CH2CH3
CH3
CH2CH3
Cl H
H Cl
H Cl Cl H
Cl H
H Cl
CH3
CH2CH3
H Cl
H Cl
H Cl
CH3
CH2CH3
Cl H
Cl H
Cl H
CH3
CH2CH3
Cl H
H Cl
H Cl
CH3
CH2CH3
H Cl
Cl H
Cl H
CH3
CH2CH3
S
S
R
R
R
S
164. • Meso compounds have a plane of symmetry.
• If one image was rotated 180°, then it could be
superimposed on the other image.
• Meso compounds are achiral even though they have chiral
centers.
Meso Compounds
Chapter 5 166
165. Number of Stereoisomers
The 2n
rule will not apply to compounds that may have a plane of symmetry.
2,3-dibromobutane has only three stereoisomers: (±) diastereomer and the meso
diastereomer.
Chapter 5 167
166. Properties of Diastereomers
• Diastereomers have different physical properties,
so they can be easily separated.
• Enantiomers differ only in reaction with other
chiral molecules and the direction in which
polarized light is rotated.
• Enantiomers are difficult to separate.
• Convert enantiomers into diastereomers to be
able to separate them.
Chapter 5 168
167. Chemical Resolution of
Enantiomers
React the racemic mixture with a pure chiral
compound, such as tartaric acid, to form
diastereomers, then separate them.
Chapter 5 169
