Chapter 1. Carbon Compounds & Chemical Bonds Ch1.3:
Valence, C–C Bonds (single, double, triple), Isomer (constitutional), Molecular/Structural formula, Connectivity
Ch1.4-8: Ionic/covalent bonds, Octet rule, Ions, Electronegativity Lewis structure, Formal charges, Resonance structures, Resonance stabilization Ch1.9-15: Atomic/molecular orbitals Orbital hybridization (sp3, sp2, sp) Sigma(σ)/Pi (π)bonds (structure of ethane/ethene/ethyne) Stereoisomer Ch1.16:
Molecular geometry (tetrahedral, trigonal planar, linear, trigonal pyramid, bent)
Ch1.17:
Representation of structural formulas (dash, condensed, bond line, three-dimensional)
The Structural Theory of Organic Chemistry Valence: the measure of ability that atoms in organic compounds can form fixed number of bonds.
Isomer: different compounds that have the same molecular formula (Constitutional Isomer)
Electronegativity and Ionic Bonds Octet rule: the tendency for an atom to achieve a configuration where its valence shell contains eight electrons. Electronegativity: a measure of the ability of an atom to attract electrons.
Ionic bonds: an attractive force between oppositely charged ions.
Covalent Bonds and Lewis Structures Covalent bond: electron sharing between atoms with same or similar electronegativity to achieve noble gas configuration.
Covalent Bonds and Lewis Structures Lewis structure (electron dot formula): a structure of molecules or ions showing the constituent atoms and the valence electrons.
HNO3,
H3PO4,
CH2N2,
O3
Formal Charges Indicator of how many electrons are gained/lost by an atom
Formal Charges Indicator of how many electrons are gained/lost by an atom
Resonance Structures Resonance structures: a tool we use for understanding structure and reactivity (not structures for the actual molecule or ion).
SP3–Hybrid Atomic Orbital Hybridization: A mathematical process combining individual wave functions
The shape of an sp3 orbital
The Structure of Methane
σ (sigma) bond
SP2–Hybrid Atomic Orbitals
π (pi) bond An sp2-hybridized carbon
SP–Hybrid Atomic Orbitals
An sp-hybridized carbon
Bond Lengths and Angles of Ethyne, Ethene, and Ethane
sp-hybridized C
sp2-hybridized C
sp3-hybridized C
s-character
50%
33.3%
25%
p-character
50%
66.6%
75%
***The higher s-character of a carbon atom, the higher its electronegativity.
Rule of Thumb using hybridized molecular orbitals SP3 hybridization: Any atom in a molecule that is not a part of a double or triple bond – Tetrahedral 109.5°
109.5°
H O H H
N H H H
C H H H
109.5° 109.5°
SP2 hybridization: Any atom in a molecule that is a part of a double bond – Trigonal planar H
H
H N C
C C H
H
H
H
H H B
O C H
H
H
H H C+ H
SP hybridization: Any atom in a molecule that is a part of a triple bond – Linear N N
N C CH3
Rule of Thumb using hybridized molecular orbitals What is the hybridization of the indicated atom(s) in each molecule? CH3 C C
(a)
Me (b)
Me C
(c)
+
Me
O O
(d)
(e)
(f) O
(h)
(g)
(i)
N
O (j)
Me
Me Al Me
(k)
O H
(l)
N
Chapter 2: Functional Groups Ch 2.1–2.4: Hydrocarbons (Alkane, Alkene, Alkyne, Saturated & unsaturated compounds, Aromatic compounds) Dipole moment, Polar & nonpolar covalent bonds Ch 2.5–2.13: Functional groups (name and structure–connectivity) General formula of compounds with specific f.g. (Table 2.3) Alkane, Alkene, Alkyne, Benzene (aromatic), Haloalkane Alcohol, Ether, Amine, Carbonyl compounds Aldehyde, Ketone, Carboxylic acid, Ester, Amide Nitrile Ch 2.14
: Hydrogen bond, Polarizability
Functional Group Certain arrangement of atoms with covalent bonds that has a unique structure and reactivity (function) O O OH O
Aspirin
Polar Covalent Bonds The nature of chemical bond in a molecule dictates the chemical and physical properties of the molecule.
Cl Cl
C Cl Cl
Functional Group
Functional Group
Chapter 3: An Introduction to Organic Reactions – Acids and Bases Ch 3.1:
Substitution, Addition, Elimination, Rearrangement Reaction mechanism, Hetrolytic/homolytic bond cleavage
Ch 3.2:
Brønsted-Lowry and Lewis definition of acid/base Conjugate acid/base
Ch 3.3-4: Carbocation and carbobanion, the use of curved arrows Ch 3.5-11: Strength of acid/base (Ka and pKa) and its prediction Effect of hybridization on acidity, Inductive/Resonance effect Equilibrium constant (Keq), Standard free-energy change (ΔG°) Ch 3.12-14: Protonation on lone pair electrons (alcohols, amines, ethers, carbonyl compounds), Mechanism for organic reactions Acid/base reaction in nonaqueous solution, leveling effect
Categories of Organic Reactions Substitutions: one group replaces another
Additions: two molecules becomes one
Eliminations: one molecule loses the elements of another
Rearrangement: Reorganization of a molecule’s constituent parts
What’s common in these reactions?
Covalent bond cleavage:
Heterolytic bond cleavage requires polarized bond
Heterolytic bond cleavage often requires external assistance
Acid–Base Reaction Why acid–base?
Many reactions in organic chemistry are: either acid–base reaction themselves or involves acid–base reaction at some stage
Brønsted-Lowry definition: Acid – a substance that can donate (or lose) a proton Base – a substance that can accept (or remove) a proton
Acid–base reaction of other strong acids
Acid–Base Reaction Lewis definition:
Acid – an electron pair acceptor Base – a an electron pair donor
Other examples of Lewis acid–base reaction
Carbocations and Carbanions Carbocation: Ionic species with positively charged carbon atom Carbanion: Ionic species with negatively charged carbon atom
Carbocations are strong Lewis acids while carbanions are strong bases (both Lewis and Brønsted)
The Strength of Acid / Base: Ka and pKa
Predicting the Strength of Acid / Base The stronger the acid, the weaker will be its conjugate base. (The larger the pKa of the conjugate acid, the stronger the base)
Can we predict the relative basicity of two bases ?
Predicting the Strength of Acid / Base The relationship between structure (size) and acidity FHO-
Cl-
s e s a re c In y it il b ta S
Br-
B a
HS-
I-
HSe-
The extent of electron delocalization (overall size) of the corresponding conjugate bases may correlate with the acidity.
Predicting the Strength of Acid / Base The relationship between electronegativity and acidity
Predicting the Strength of Acid / Base The relationship between structure / electronegativity and acidity
Predicting the Strength of Acid / Base The relationship between structure / hybridization and acidity
*The higher the s-character, the higher is the carbon’s electronegativity. H
H C C
H C C H H
H
H
H H
H
C C H
H
H
H
Acidity Increases H H C C
C C H
H
H
Basicity Increases
C C H
H
The Strength of Acid / Base: Inductive Effect
Inductive Effect: propagation of bond polarity through σ-bond network (decrease with the distance)
The Strength of Acid / Base: Resonance Effect Resonance Effect: stabilization of the system by having resonance structures (increase with the # of equivalent resonance structures)
requires energy for the change endothermic
Mechanism for Organic Reactions Reaction Mechanism: a step by step description of the events occurring from the starting materials to the products. Step 1
Step 2
Step 3
Chapter 4: Alkanes – Conformational Analysis & an Introduction to Synthesis Ch 4.1–4.7:
Branched/unbranched alkanes, Constitutional isomers, Cycloalkanes, IUPAC system
Ch 4.8–4.11: Conformation (σ-bond rotation, staggered, eclipsed, gauche, anti), Conformational analysis, Newman projection Torsional strain, Steric hindrance Ring strain (torsional/angle strain), Hyperconjugation Ch 4.12–4.15: Conformation of cyclohexane (chair/boat, equatorial/axial) Ring flip (upper/lower bond), Cis/trans isomers Ch 4.16–4.19: Hydrogenation, Reduction of alkyl halide, Alkylation Alkynide anion, Nucleophile/electrophile Retrosynthetic analysis
Sigma (σ) Bond Rotation: Conformation Conformation: temporary molecular shapes resulting from σ-bond rotation
Staggered Conformation
Eclipsed Conformation
Conformational Analysis of Butane Torsional barrier = Steric hindrance + Orbital interactions
Chair vs. Boat Conformation of Cyclohexane H H
CH3
H
gauche conformation of butane
.
.
CH3
. .
Chair conformation
H
. .
.
.
. .
.
.
.
.
HH
HH
Boat conformation eclipsed conformation of butane CH3 CH 3
.
.
.
.
.
. .
.
Substituted Cyclohexane: Axial vs. Equatorial . .
H
H
H
CH3
H2C
H
H
CH3 H gauche conformation of butane
H
.
.
H
.
H
.
H
H
H
.
H H
H
H
.
3.8 kj/mol .
.
.
.
.
H H
H
H
H
.
H H
anti conformation of butane
H
H
C H2
H H
H
CH3
H
CH3
H
. .
H H
Disubstituted Cyclohexanes: Cis–Trans Isomers . .
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. .
lower bond
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Chemistry of Alkanes .
Alkanes: inert to many chemical reagent (originally called paraffins–little affinity) .
Synthesis of alkanes and cycloalkanes Natural source: petroleum (as a mixture) Chemical synthesis: particular alkane (in pure form)
Hydrogenation: addition of hydrogen(s) to π-bond(s)
.
.
Alkylation of Terminal Alkynes . .
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.
Planning an Organic Synthesis: Retrosynthetic Analysis . .
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Chapter 5: Stereochemistry – Chiral Molecules Ch 5.1–5.6:
Stereochemistry, Chirality, Stereoisomers, Enantiomers Diastereomers, Mirror image, Chiral/Achiral molecules Stereogenic carbon (center), Plane of symmetry
Ch 5.7–5.9:
Configuration, R/S-system, Group priority, Optical activity Dextrorotatory/Levorotatory, Specific rotation Racemic forms (Racemate), Enantiomeric excess
Ch 5.10–5.13: Stereoselective synthesis (dia-/enatiostereoselective) Kinetic resolution, Chiral drug, Meso compound Fisher projection formula Ch 5.14–5.18: Stereoisomerism of cyclic molecules, Retention/Inversion Relative/Absolute configurations, Resolution
Isomerism: Constitutional and Stereoisomers
C4H10O OH
O
.
.
.
.
Test of Chirality: Plane of Symmetry A molecule will be judged to be chiral (or achiral) by; **the presence (or absence) of a single tetrahedral stereogenic carbon. **the absence (or presence) of certain symmetry elements– a plane of symmetry (also called a mirror plane is defined as an imaginary plane that bisects a molecule. .
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Naming Enantiomers: The R,S -System 1. Assign a priority (or preference): based on atomic number (the higher atomic number, the higher priority) .
3
.
CH3
.
.
.
1
H
Br .
4
.
.
2
.
.
.
.
Cl
2. Assign a priority at the first point of difference (following 1.) .
.
H
3
.
.
CH2
1
H
HO
2
4
H2C CH3 . .
. .
Naming Enantiomers: The R,S -System 3. Look through the bond between stereogenic atom and the lowest priority group. .
.
3
H
.
.
CH2
1
H3C
H
HO
4
OH C
.
.
.
2
H2C
CH2CH3
.
CH3
.
4. Trace a path in sequence of the priority from 1 to 3. .
.
.
.
H3C
OH C
.
.
CH2CH3
. .
.
.
.
.
.
Naming Enantiomers: The R,S -System 6. Groups containing double or triple bonds are assigned priorities as if both atoms were duplicated or triplicated, that is; .
.
.
.
.
O
enantiomers
O
.
.
H
H .
(S)- (+)-Carvone (Caraway seed oil)
(R)- (-)-Carvone (Spearmint oil) .
.
Racemic Forms (Racemate) Racemate
.
.
. .
. .
O
CH2CH3
H3CH2C
CH3
H3C
.
.
O
Naming Molecules with Multi-Stereogenic Centers .
enantiomers
S
R
R
S
.
.
. .
diastereomers
.
diastereomers
diastereomers .
R
S R
S
enantiomers (2R,3R)-2,3-dibromobutane
.
.
.
.
.
. .
Diastereomers have different physical properties: different m.p. and b.p., different solubilities, and so forth. Total number of stereoisomers will not exceed 2n, where n is equal to the number of tetrahedral stereogenic centers.
Molecules with Multi-Stereogenic Centers Meso Compounds . .
.
S
Meso Compound
R
.
.
.
. . .
diastereomers .
.
R
S R
S
enantiomers
.
.
.
.
.
Total number of stereoisomers will not exceed 2n, where n is equal to the number of tetrahedral stereogenic centers.
Molecules with Multi-Stereogenic Centers Fisher Projection Formula . .
CH3 .
H
S
Br
H
R
Br
.
CH3 .
.
. . .
.
.
CH3
CH3 Br
H
R R
H
H
S S
Br
Br
Br H CH3
CH3 .
.
.
.
.
Vertical lines represent bonds that project behind the plane of the paper (or that lie in it). Horizontal lines represent bonds that project out of the plane of the paper.
1,2-Dimethylcyclohexane trans-1,2-dimethylcyclohexane
Me
H
Me
Me
Me
Me
Me
H
Enantiomers
Me
H
H
Me
diastereomers cis-1,2-dimethylcyclohexane
.
.
Me
Enantiomers
H
Me
H
H
.
Me
H
.
Me
Me
Me
Me 1,2-dimethylcyclohexane
Identical Me H
H
H
H Me
Me
Enantiomers
Me
Me
Chapter 6: Ionic Reactions – Nucleophilic Substitution and Elimination Reactions Ch 6.1–6.8:
Alkyl halide (polar bond, bond strength), Nucleophile Nucleophilic substitution, Leaving group, SN2 reaction Bimolecular, Transition state, Free energy of activation Retention and inversion of configuration, Concerted reaction
Ch 6.9–6.13: SN1 reaction, Unimolecular, Multistep reaction Rate-limiting step, Intermediates, Carbocation stability Hyperconjugation, Racemization, Solvolysis Ch 6.13–6.14: Factors affecting rates of SN1 and SN2 reactions Steric effect, Hammond–Leffler postulate Nucleophilicity vs. basicity, Protic/aprotic solvent Polar/nonpolar solvent, Polarizability, Nature of leaving group Ch 6.15–6.18: Elimination reactions, Dehydrohalogenation β-Elimination, E1 and E2 reactions Competing reactions (SN2 vs. E2, SN1 vs. E1)
Mechanism for the SN2 Reaction .
.
HOMO
LUMO
The Stereochemistry of SN2 Reactions
SN2 reactions always occur with inversion of configuration.
The Reaction of t-BuCl with HO- : SN1 Reaction
In the transition state that controls the rate of the reaction, hydroxide ions do not participate but only t-butyl chloride. This reaction is said to be unimolecular (first order) in the rate-determining step. an SN1 reaction (substitution, nucleophilic, unimolecular).
Step 1
The Reaction of t-BuCl with HO- : SN1 Reaction .
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Step 1
.
.
Step 2 .
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Step 3 .
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The Stereochemistry of SN1 Reactions
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. .
. . .
Rates of SN1 and SN2 Reactions The most important factors that affect the relative rates of SN1 and SN2 reactions are: .
.
1. 2. 3. 4.
the structure of the substrate the concentration and reactivity of the nucleophile (for SN2 only) the effect of the solvent the nature of the leaving group
General order of SN2 reaction:
.
.
.
. .
. . .
Rates of SN1 and SN2 Reactions The most important factors that affect the relative rates of SN1 and SN2 reactions are: .
.
1. 2. 3. 4.
the structure of the substrate the concentration and reactivity of the nucleophile (for SN2 only) the effect of the solvent the nature of the leaving group
SN1 Reactions: The primary factor is the relative stability of the carbocation that is formed. The rate of SN1 reaction correlates with that of carbocation stability. .
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.
. .
. . .
The E2 Reaction (Dehydrohalogenation) .
.
.
.
The E1 Reaction .
.
.
.
Step 1
.
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Step 2
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.
.
Substitution (SN2, SN1) vs. Elimination (E2, E1)
.
.
Substitution
H R
Nu
Nu +
R
R
δ R
R
Xδ
R
H
R
δ X
R SN2
δ
H R
Elimination
B
Nu R R X
R SN1
R
H R
R
δ X
R E2
δ
B H R
R R X
R E1
