Organic Chemistry Final Exam Review

Table of Contents
Organic Chemsitry 1st Semester
Organic Nomenclature Page 1
Lewis Structures and Bonding Page 5
Resonance Page 7
Intermolecular Forces Page 8
Acids and Bases Page 10
Conformations of Alkanes Page 12
Isomers and Stereochemistry Page 14
SN1, SN2, E1, and E2 Page 17
Alkenes and Alkynes Page 19
Free Radical Reactions Page 25

Organic Chemsitry 2nd Semester

Alcohols, Ethers, and Epoxides Page 26
Conjugated Pi Systems Page 32
Aromatic Compounds Page 36
Aldehydes and Ketones Page 40
Carboxylic Acids and Carboxylic Acid Derivatives Page 42
Substitution Reactions at the Alpha Carbon Page 45
Amines Page 49

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 Alcohols, Ethers, and Epoxides
Acidity of Alcohols

Acidity of Phenols

Deprotonation

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Synthesis of Alcohols
Reduction of Ketones and Aldehydes

Grignard Addition to Ketones and Aldehydes

Protecting Groups of Alcohols

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Substitution Reactions of Alcohols
Reaction with H-X (HI, HBr or HCl/ZnCl2)
-SN1 for 3 and 2 alcohols; SN2 for 1 alcohols

Reaction with PBr3 (for 1 and 2 alcohols)

Reaction with SOCl2 (for 1 and 2 alcohols)

Conversion to Sulfonate Esters

Elimination Reactions (Dehydration) of Alcohols

-E1 for 2 and 3 alcohols; E2 for 1 alcohols

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Oxidation of Alcohols
Chromic Acid
-oxidizes 1 alcohols to carboxylic acids,
2 alcohols to ketones,
and aldehydes to carboxylic acids
PCC (Pyridinium Chlorochromate)
-oxidizes 1 alcohols to aldehydes
and 2 alcohols to ketones

Chromic Acid
Na2Cr2O7 / H2SO4
CrO3 / H2SO4
H2CrO4

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Ethers
Williamson Ether Synthesis (SN2)

Acidic Cleavage -- Reaction with H-X (HCl, HBr, or HI)

-SN1 for 3 and 2 carbons; SN2 for 1 carbons

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Epoxides
Synthesis of Epoxides
SN2

Addition of Peroxyacids to Alkenes

Ring Opening of Epoxides

Strong Nucleophiles (Nucleophile attacks the less substituted side)

Acid-Catalyzed (Nucleophile prefers 3 > 1 > 2)

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 Conjugated Pi Systems
Pi Molecular Orbitals
Ethylene
1,3-Butadiene

1,3,5-hexatriene

Allyl Cation, Radical, and Anion

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Electrophilic Addition to Conjugated Dienes
Thermodynamic Product Kinetic Product
lowest energy product lowest activation energy
most stable product most stable transition state
Major product at higher temperatures and longer major product at lower temperatures and shorter
reaction times reaction times
generally most substituted alkene focus on the most stable resonance contributor for
the carbocation intermediate

PREDICTING THE PRODUCTS FOR ADDITION REACTIONS TO CONJUGATED DIENES

1. Start by identifying the resonance-stabilized carbocation intermediates. Discard/ignore the others.
2. Select the more stable carbocation (shares the positive charge on the more substituted carbon atoms).
3. Draw both possible products when the nucleophile adds to the two carbon that share the positive charge.
4. The product resulting from the nucleophile adding to the more substituted carbon is the kinetic product.
5. The product with the more substituted pi bond is the thermodynamic product.

Predict both the kinetic and thermodynamic products of the following reaction.

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Diels-Alder Reactions
-A 4 + 2 cycloaddition
-concerted mechanism
-syn addition between a conjugated diene and a dienophile

Dienes
The diene must be in the s-cis conformation.

Dienes with electron-donating groups attached are more reactive.

Dienophiles
Dienophiles with electron-withdrawing groups attached are more reactive.

Stereoselectivity in Diels-Alder Reactions

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Regioselectivity in Diels-Alder Reactions
Only 1,2 and 1,4 products are observed with unsymmetrical reagents (relationship of D to W).

Diels-Alder Reactions with Cyclic Dienes

Endo Rule

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 Aromatic Compounds
Aromatic vs Antiaromatic vs Nonaromatic
CRITERIA FOR AROMATIC COMPOUNDS
1 Cyclic and conjugated
2 Each atom in the ring must have an unhybridized p orbital
(No sp3-hybridized atoms in the ring)
3 Planar
4 Delocalization of the pi electrons must lower the electronic energy
-4N+2 π electrons (odd # of pairs)
Antiaromatic compounds satisfy the first 3 rules above but have 4N π electrons.
Nonaromatic compounds don't satisfy one or more of the first 3 rules above.

Classify the following as aromatic, nonaromatic, or antiaromatic.

Carbocations and Lone Pairs

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Electrophilic Aromatic Substitution
EAS Mechanism

EAS Reaction / Reagents Electrophile Name

Bromination

Chlorination

Sulfonation

n/a Desulfonation
Nitration

Friedel-Crafts Alkylation

Friedel-Crafts Acylation

Formylation
(Gattermann-Koch Synthesis)

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Activating and Deactivating Groups | Ortho/Para vs Meta Directors

Ortho/Para Directors
-All are activating groups except for the halogens
-All electron-donating groups are ortho/para directors
-Halogens are deactivating ortho/para directors (pi donating but withdrawing inductively)

Meta Directors
-All are deactivating

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Side-Chain Reactions
Side Chain Oxidation (Permanganate or Chromic Acid Oxidation)
-no reaction for side chains having a quaternary benzylic carbon

Side-Chain Reduction
Clemmensen Reduction / Wolff Kishner Reduction– reduces ketones and aldehydes to alkanes

Nitro Reduction (General and Specific)

Catalytic Hydrogenation
-an elevated pressure is required

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 Aldehydes and Ketones

Nucleophilic Addition of Oxygen Nucleophiles

Hydration of Ketones and Aldehydes
Base-catalyzed Acid-catalyzed

Formation of Hemiacetals and Acetals

Base-catalyzed (Forms hemiacetal) Acid-catalyzed (1eq or 2eq)

Cyclic Acetals as Protecting Groups

Nucleophilic Addition of Nitrogen Nucleophiles

Formation of Imines (Addition of Primary Amines)

Formation of Enamines (Addition of Secondary Amines)

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Nucleophilic Addition of Hydrogen Nucleophiles (Reduction)
NaBH4 reduces ketones, aldehydes, acid halides, and acid anhydrides

LiAlH4 reduces ketones, aldehydes, acid halides, acid anhydrides, esters, carboxylic acids, amides, and nitriles

Catalytic Hydrogenation

Nucleophilic Addition of Carbon Nucleophiles

Acetylide Addition

Grignard Addition

Cyanohydrin Formation

Wittig Reaction

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 Carboxylic Acids and Carboxylic Acid Derivatives

Nucleophilic Acyl Substitution

-More reactive derivatives can generally be converted into less reactive, not the other way around!!

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Reaction with Organometallic Reagents
Reactions with Grignard Reagents

Reactions with Gilman Reagents (Organocuprates)

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20.5 Hydride Reduction Reactions
NaBH4 reduces ketones and aldehydes. It can also be used to reduce acid halides and anhydrides but LiAlH 4 is
more commonly used.

LiAlH4 reduces ketones, aldehydes, acid chlorides, acid anhydrides, esters, carboxylic acids, amides, nitriles
(and others)

Lithium Tri-t-butoxy Aluminum Hydride reduces acid chlorides and acid anhydrides to aldehydes

DIBAH reduces esters to aldehydes

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 Substitution Reactions at the Alpha Carbon

Acidity of the Alpha Hydrogen

LDA (Lithium Diisopropyl Amide)

Alpha Halogenation
Acid-Catalyzed Base-Promoted

-typically occurs just once -all alpha hydrogens can be replaced

Haloform Reaction
-for methyl ketones

HVZ Reaction (Hell-Volhard-Zelinsky)

-alpha halogenation for carboxylic acids

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Alpha Alkylation (including the Stork Reaction)
Alkylation of enolate ions (SN2 reaction with an enolate attacking an alkyl halide)

Stork Reaction
-Alternative method of alpha alkylation
1. ketone is first converted to an enamine
2. alkylation occurs with the enamine followed by
3. hydrolysis back to a ketone

Aldol Reactions
Self-Aldol Reactions

Crossed (Mixed) Aldol Reactions

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Claisen Condensation Reactions
Self-Claisen Condensations

Crossed (Mixed) Claisen Condensations

Must use LDA to form the enolate to get a good yield of a single product.

Malonic Ester Synthesis and Acetoacetic Ester Synthesis

-decarboxylation

Malonic Ester Synthesis

-forms a substituted acetic acid (adds 2 carbons)

Acetoacetic Ester Synthesis

-forms a substituted acetone (methyl ketone)

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Michael Reactions
-a 1,4-addition of a conjugated carbonyl (usually)
-Michael donor is typically a stabilized enolate ion or R2CuLi
-Michael acceptor is a conjugated carbonyl, cyano, or nitro group

Predict the products for the following reaction.

Robinson Annulation
1) Michael Reaction
2) Intramolecular Aldol

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 Amines

Classification of Amines

Basicity of Amines
FACTORS AFFECTING BASICITY OF AMINES
1. Aromaticity decreases basicity
2. Resonance decreases basicity
3. Hybridization affects basicity (sp3 > sp2 > sp)

Synthesis of Amines
Reduction of Nitriles, Azides, and Amides

Hofmann Rearrangement

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Curtius Rearrangement Schmidt Reaction

Gabriel Synthesis
-template synthesis for 1 amines

Reductive Amination

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Reactions of Amines
Hofmann Elimination
-Exhaustive methylation followed by elimination
-major product is the less substituted alkene (Hofmann product)

Cope Elimination
-oxidation of a 3 amine followed by elimination
-major product is the less substituted alkene

Reaction with Nitrous Acid and Reactions of Arenediazonium Salts (Sandmeyer Reactions)-NaNO2/HCl leads
to formation of a nitrosonium ion (NO+)
-1 amines become diazonium salts, 2 amines become nitrosamines

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