Download Notes 10

TOPIC 10. REVIEW
MOLECULAR STRUCTURE
CONCEPTS, MODELS, RULES AND THEORIES
Concept
Prediction
Octet rule
Valency, presence of lone pairs
Lewis Dot Structures
Formal charges electronegativity
Electronegativity
Polar bonds, molecular dipoles
Bonding
Covalent bonds between atoms of
similar electronegativity
Ionic bonds between atoms of
different electronegativity
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VSEPR
Molecular geometry
Hybridization
Molecular geometry
Resonance
Electron distribution, hybrid structures
Hyperconjugation
σ-bonds as electron donors
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RESONANCE THEORY
X
Y
Z
Resonance theory helps to explain:
Structure
i.e.,
O
C
R
Reactivity
i.e.,
NH2
O
C
R
D.M. Collard 2007
O
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HYPERCONJUGATION
Hyperconjugation accounts for the enhanced stability of cations, radicals
and alkenes with high degrees of substitution.
H
C
C
H
H
H
C
H
C
H
C
H
C
C
H
H
SYSTEMATIC IUPAC NOMENCLATURE
Linear (Unbranched) Alkanes
CH4
CH3CH3
CH3CH2CH3
CH3(CH2)2CH3
CH3(CH2)3CH3
CH3(CH2)4CH3
CH3(CH2)5CH3
.
.
C1
2
3
4
5
6
7
8
9
10
methane
ethane
propane
butane
pentane
C11
12
13
14
15
16
17
18
19
20
Substituents
-CH3 methyl
-CH(CH3)CH2CH3 sec-butyl
-C6H5 phenyl
-CH2CH3 ethyl
-CH2CH(CH3)2 isobutyl
-CH2C6H5 benzyl
-CH(CH3)3 isopropyl
-C(CH3)3 tert-butyl
Branched Alkanes
Longest chain numbered from the end that has the substituents at the lowest
possible number. Substituents listed alphabetically (ignoring di, tri, sec, tert)
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Alkyl Halides
R
Hal
Classes of alkyl halides
Alcohols
Classes of alcohols
88 kcal/mol
110 kcal/mol
R
O
0.97 Å
1.43 Å
Ethers
R
H
O
H
R
R'
N
H
H
Amines
Ri
Classes of Amines
N
Rii
Riii
Ri
177 kcal/mol
1.22 Å
Ri
C
R
N
H
O
ketone
C
R
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Rii
O
Aldehydes and Ketones
aldehyde
N
Ri
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Carboxylic acids
Carboxylic esters
O
O
C
C
R(H)
OH
Amides
Ri
R(H)
O
Nitriles
O
Ri(H)
C
R(H)
R
C
N
N
Rii(H)
Functional Molecules
Alcohols, R-OH:
OH at lowest possible position
Alkyl halides, R-Hal:
named as halo-substituted alkane
Alkenes (and alkynes):
Longest chain containing C=C (C≡C),
numbered to keep C=C (C≡C) as low as possible
D.M. Collard 2007
Aldehydes:
Numbered from CHO (C1)
Ketones:
Numbered to keep C=O as low as
possible
Ene-Ols
#-alken-#-ol (OH at lower position)
Ene- Ynes
#-alken-#-yne (C=C at lower
position)
Alkenes:
(E) or (Z)
Compounds with Stereocenters:
(R) or (S)
© D.M. Collard, 2005
CHIRALITY: ENANTIOMERS
An object which has a non-superimposable mirror image is chiral (the opposite
of chiral is “achiral”).
Another test for chirality is to assess whether the object itself has a mirror plane
of symmetry or point of symmetry (point of inversion).
Enantiomers
Molecules can be chiral. Pairs of molecules which are non-superimposable
mirror images of one another are called enantiomers. Enantiomers are
examples of stereoisomers: molecules which differ only in the spatial
arrangement of atoms.
Molecules with a single carbon atom bearing four different substituents can
exist as a pair of enantiomers which differ in the arrangement
(“configuration”) of these substituents.
The carbon is stereogenic
A
A
The carbon is a stereocenter
B
C
D
D
C
B
You must be able to recognize when pairs of molecules are identical
(superimposable) or entiomers (non-superimposable mirror images)
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Designating Configuration
Stereocenters are designated as having either R- or S-configurations….
- Assign priorities to the substituents using the Cahn-Ingold-Prelog
system (briefly, atoms are ranked in order of atomic weight; if two
atoms are identical, the next set of attached atoms is considered).
- View the molecule with the lowest priority (4) substituent pointing away
from you.
- Trace from highest priority (1) to second priority (2), to third (3)….
Clockwise = R
Counterclockwise = S
e.g.,
H
Cl
F
Br
Optical Rotation
The observed rotation is
α
The observed specific rotation is [α] = a / c·l
where c = concentration in g/mL and l = pathlength in dm (10-1 m)
The observed rotation, α or [α ] depends on solvent, temperature and
wavelength of the polarized light. Generally the sodium D line is used for
the light source and the experiment is done at room temperture, 25 °C.
The specific rotation is then noted as
25
[α] D (conc./solvent)
The specific rotation of an optical pure chiral compound is a “property” like
melting point or boiling point
The specific rotation of a given sample depends on it “optical purity”
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STEREOISOMERS WITH MORE THAN
ONE STEREOCENTER
Diastereomers
A
X
B
Y
C
Z
Problem: Draw all the stereoisomers of the molecule below.
OH OH
CO2H
H3C CH CH CO2H
CO2H
CO2H
CO2H
For a molecule with n stereocenters, there are a maximum of 2n
stereoisomers.
Meso Compounds
If the sets of substituents on stereogenic centers are identical there will be
fewer than 2n stereoisomers.
A
A
B
B
C
C
B
C
A
A
C
B
B
C
A
A
B
C
Compounds with stereogenic centers which are not chiral are called meso
compounds.
Meso compounds possess a point or plane of symmetry
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CLASSIFYING REACTIONS
Reactions are conveniently classified as substitutions, additions,
eliminations and rearrangements. These terms describe the overall
process, simply comparing the structure of starting materials and products.
They do not indicate anything about the pathway (“mechanism”) by which
the reaction proceeds.
Substitutions
Additions
Eliminations
Rearrangements
(often in combination
with another type of reaction)
TWO CLASSES OF NUCLEOPHILIC
SUBSTITUTIONS
C L
Nu
C Nu
L
• Substitution reactions can be performed under different conditions which
give rise to dramatically different outcomes. Nucleophilic substitution
reactions can be classified as one of two types, based on these
experimental observations.
• Characteristics which allow this classification are listed on the next slide, and
will be studied in greater detail in the next two sections.
• In order to develop predictive tools, we need to understand reasons why
these observations are important. That is, we need to develop proposals for
two different mechanisms which are consistent with the two sets of data and
which we can use to predict the outcome of other reactions.
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Substitution At 1° Substrates: Bimolecular Nucleophilic
Substitutions
Rate = k[R-L][Nu]
Chirality
Chiral R-L forms R-Nu with opposite stereochemistry
(inversion of stereochemistry, “Walden Inversion”)
Effect of Nucleophile
Rate: I– > OH– > Br– > Cl– > F– > H2O
Effect of Leaving Group
Rate: -I > -Br > -Cl >> -F
Effect of substrate
Rate: methyl > 1° > 2° ( 3° unreactive)
Adjacent groups slow the reaction
Nu
HH
L
H
Nu
MeMe
L
Me
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Substitution at 3° Substrates: Unimolecular Nucleophilic
Substitutions
Rate = k[R-L] {independent of concentration of Nu}
Chirality
Optically active R-L forms racemic R-Nu
Effect of substrate
Rate: 3° > 2° (1°, methyl not reactive)
Effect of Nucleophile
Concentration
Identity
Effect of Leaving Group
Rate: -I > -Br > -Cl (F: unreactive)
Summary of Factors Effecting SN1 and SN2 Reactions
SN1
Substrate: 3°>2°>>1°,methyl
- Stability of carbocation
intermediate
Nu: No effect
- Nu not involved in RDS
Rate increases by use of polar
solvents
Enhanced rate of ionization
Generally only useful for solvolyses
(reactions with H2O, ROH,
RCO2H)
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SN2
Substrate: Methyl>1°>2°>>3°
- Steric bulk hinders attack of Nu
Rate a [nucleophile]
Rate depends on type of Nu
- Nu involved in RDS
Often performed in polar aprotic
solvents, e.g., DMF (Me2NCHO),
DMSO (Me2SO) to dissolve
substrate and ionic reagent, and
increase reaction rate
© D.M. Collard, 2005
Nucleophilic Substitution Reactions
Learn the Reagents!!
CN
Br
SH
OMe
OTs
OH
Test yourself: Solomons 6.21
Use Mechanism to Rationalize Outcomes of Reactions
HBr
O
O
Δ
CH3
Br
OH
HBr
Δ
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2
Br
CH3
© D.M. Collard, 2005
Radical bromination of alkanes is only useful when replacing a
hydrogen on a 3o carbon, e.g.,
Br2
hν
or when there is only one possible monobrominated product
Br2
hν
TWO CLASSES OF ELIMINATION REACTIONS
E2 Reaction
B
H
L
E1 Reaction
H
L
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Regiochemistry of Eliminations
EtOK
EtOH
Br
Zaitsev’s Rule: _______ substituted (stable) alkene is formed
Use of bulky bases can lead to formation of “anti-Zaitsev”
products
t-BuOK
t-BuOH
Br
Stereochemistry: Anti Elimination
Cl
H
Cl
t-Bu
H
t-Bu
H
H
trans - slow elimination
cis - fast elimination
Observations
CH3
H3C C Br
CH3
CH3CH2 Br
H3C
CH Br
or KCN
CH3ONa
CH3ONa
H3C
H3C
CH Br
H3C
CH2
CH3ONa
KCN
H3C
C
CH3
CH3CH2 OCH3
CH3CH CH2
H3C
CH CN
H3C
CH3
H3C C OK
CH3CH2 Br
D.M. Collard 2007
CH3
heat
H2C CH2
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Competition between SN1, SN2, E1 and E2 Reactions
3° substrates only undergo substitution with weakly basic nucleophiles
(ROH, H2O, RCO2H). Stronger bases promote elimination. 1° substrates
generally undergo substitution unless the base itself is sterically crowded
(e.g., t-BuO-).
substrate
nucleophile/base
Mechanism
3°
ROH, H2O, RCO2H
Anionic bases, NH3
SN1 (some E1 on heating)
E2
2°
Less basic than HO –
SN2
1°
(e.g.., HS –, RS –, NH3, CN, RCO2–)
More basic than HO –
ROH, H2O
E2
SN1 (some E1 on heating)
All except t-BuO–
t-Bu-O–
SN2
E2
Me all
SN2
Rearrangement During Elimination
OH
H3PO4
Δ
not:
B:
H
2°
D.M. Collard 2007
3°
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ADDITIONS TO ALKENES
Alkenes and Alkynes are Basic and Nucleophilic
H
Br
C C
E
Regiochemistry
H3C
C CH2
H
H3C Br
C CH3
H3C
Br
H3C
Markovnikov’s Rule
In the addition of HX to an unsymmetrical alkene, the hydrogen adds to the
_____________ substituted carbon and the X groups adds to the
_____________ substituted carbon.
Mechanistic Markovnikov’s Rule
In the ionic addition of HX to an unsymmetrical alkene, protonation gives the
more stable carbocation as an intermediate.
Anti-Markovnikov Addition
The addition of HBr (only), in the presence of peroxides, to unsymmetrical
alkene gives the more stable free radical intermediate. Therefore H adds to the
more substituted carbon and Br to the less substituted carbon.
H3C
C CH2
H3C
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H
Br
peroxide
H3C
CH CH2Br
H3C
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Addition and Elimination Reactions of Alkenes
Learn the Reagents!!
Understanding of mechanism tells you something about regiochemistry (R)
and stereochemistry (S).
S(syn)
S(syn)
R(anti-Markov.)
Br
R(Markov.)
OH
Br
Br
OH
R(anti-Markov.)
S(anti)
R(Markov.)
e
Br
S(syn)
O
OH
+ CO2
OH
O
Br
O
+
H
H
H
S(anti)
R
O
OH
OH
S(syn)
S(syn)
Test yourself: Solomons 8.21, 8.22
Addition and Elimination Reactions of Alkynes
Learn the Reagents!!
O
2
O
Br
OH
Br
Test yourself: Solomons 8.23, 8.24
D.M. Collard 2007
Br
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SYNTHETIC STRATEGIES
C C
H
H
C C
H
Br
C C
C C
H
OH
C C
Work Synthesis Problems!
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Work More Synthetic Problems!!
O
OH
Keep Going!!!
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O
Here are some more…..
Solomons problems:
6.17 (one step substitutions)
7.22, 7.23, 7.32 (one step eliminations, additions)
7.24 (multistep synthesis)
8.25, 8.26 (multistep synthesis)
11.35, 11.42 (one-step and multistep)
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© D.M. Collard, 2005