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Enols and Enolates
Kinetic Versus Thermodynamic Enolates
Last updated: May 25th, 2023 |
Kinetic versus Thermodynamic Enolates of Ketones
Enolates have a lot in common with alkenes. They are flat and have a C-C pi bond.
- Zaitsev’s rule reminds us that alkene stability increases with increasing number of carbons directly attached to the alkene (i.e. “more substituted” alkenes are more stable).
- When enolates are formed with strong, non-bulky bases (e.g. NaOH or NaOCH3) the tendency is for the more substituted enolate to form. When the enolate reacts with electrophiles, this means that the electrophile will add to the more substituted alpha carbon.
- We can overcome this tendency of enolates by using a strong, bulky base such as LDA (lithium di-isopropylamide) which reacts with the less sterically hindered proton faster than it does with the more sterically hindered proton.
- This “less substituted” enolate is called the “kinetic enolate“.
Table of Contents
- Thermodynamic Enolate Formation
- Reactions of Thermodynamic Enolates
- Selective Formation of “Kinetic” Enolates
- Reactions of Kinetic Enolates
- The Further Adventures of LDA: Nitrile and Amide Enolates
- Quiz Yourself!
- (Advanced) References and Further Reading
If you aren’t familiar with enolates and need more background, go back and read the previous post on enolates first. [See post: Enolates]
Many ketones are capable of forming two different enolates, depending on which alpha-carbon is deprotonated.
The question is, which one will be favored?
Generally enolates are flat and can be thought of as similar to alkenes, even if they tend to react with electrophiles like they are carbanions.
Going back to Zaitsev’s rule, we’ve seen many examples where alkenes increase in stability as the number of H atoms directly attached to the ring decreases. (or conversely, as the number of attached carbons increases)
In other words, the more substituted the alkene, the more stable it is. [Note 1]
This also applies to enolates. The fewer C-H bonds there are on the alkene, the more thermodynamically stable it is.
Ketones can undergo deprotonation with strong bases like alkoxides RO(-) to give enolates.
Alkoxides are not as basic as ketone enolates, so the acid-base equilibrium tends to favor the starting ketone. However, they are still strong enough bases to set up an equilibrium between the starting ketone and the two different enolates.
The position of that equilibrium will favor the most thermodynamically stable enolate (i.e. the most substituted), even though it is slightly slower to form due to the fact that the C-H bond is more sterically hindered.
For that reason we call the more substituted enolate the thermodynamic enolate because of its greater stability.
We also say that formation of this enolate is under thermodynamic control.
The equilibrium ratio of enolates will depend on the difference in energy between their heats of formation (which is typically 1-2 kcal/mol). As a rough rule of thumb, 4:1 is a good ballpark number but it can vary considerably. [Note 2]
These “thermodynamic” enolates can act as nucleophiles in various reactions.
Any time we form an enolate under thermodynamic control, we should expect that the major product will arise from the reaction of the more substituted enolate with the electrophile, such as in this halogenation reaction. [Note 3]
Similarly, this will also be the case in these examples of the Aldol reaction, enolate alkylation, and conjugate addition. [Note 4]
You may ask, “is that it?”
Are we doomed by this thermodynamic preference of the enolate to never be able to form the other less substituted enolate, just because it screams out, “Thermodynamically, I don’t wanna!“.
No! There’s a workaround!
There are lots of times we might want the less-substituted enolate. So here is a strategy for how to go about making it.
The first thing to note is that the hydrogen on the more-substituted side is slightly more difficult to access due to the presence of the extra alkyl group.
That’s why there is a higher energy barrier for deprotonation in the energy diagram (above).
So what if we were to use a base that is extremely sterically hindered?
In that case the reaction with the more sterically hindered proton should be very slow, and reaction with the less sterically-hindered protons on the other side should be fast.
A good choice for this is the strong bulky base, lithium di-isopropyl amide (LDA).
LDA has two big and bulky isopropyl groups flanking a very basic amide base. The pKa of the conjugate acid is 38, so deprotonating a ketone alpha-carbon (pKa 16-18) is no problem for LDA.
Also, unlike alkoxide bases RO(-), deprotonation goes to completion. So long as an excess of base is used, there is no equilibrium between the different enolates. [Note 5]
LDA is so strong that deprotonation can happen at extremely low temperature. This helps us because we can use low temperatures to slow down that undesirable acid-base reaction even more.
So when our ketone is treated with LDA at low temperature we get preferential formation of the less-substituted enolate. We call this, “kinetic control”.
Note that there is nothing magic about -78°C. That just happens to be the temperature of the convenient (and cheap) dry ice-acetone cooling bath.
We call the less substituted enolate the “kinetic enolate” because we are depending on the difference in reaction rates (“chemical kinetics” remember?) to give us selectivity.
Note that enamines can also be used for performing reactions at the less-substituted alpha carbon. [Note 6]
Kinetic enolates can be used for the same reactions of enolates we’ve seen previously, such as alkylation, the Aldol reaction, and halogenation.
In each case we are forming our new bond at the less substituted alpha carbon of the ketone.
There’s another advantage to using LDA. Since LDA is such a strong base, we can use it form some of the less-accessible enolates of carboxylic acid derivatives such as esters, amides, and nitriles.
These enolates can perform the same types of reactions as those we’ve seen above, such as alkylation and conjugate addition.
In short, LDA is an extremely useful strong base that can form just about any enolate you need, provided that the C-H bond isn’t sterically hindered. [Note 7]
So what have we learned?
- Unsymmetrical ketones are capable of forming two different enolates
- When alkoxide bases are used (RO-/ROH) there is incomplete deprotonation. As a result, an equilibrium exists between the starting ketone and the two possible enolates
- Equilibrium generally favors the more substituted enolate since you can think of it as a more substituted double bond. For this reason the more substituted enolate is called the thermodynamic enolate.
- By using a strong bulky base, the rate of deprotonation at the more substituted enolate can be slowed to the point where only the less-substituted enolate forms. This is referred to as the kinetic enolate.
- LDA (lithium diisopropyl amide) is a strong, bulky base that can be used for deprotonation of ketones, esters, amides, nitriles, and more.
- Enolates – Formation, Stability, and Simple Reactions
- Aldol Addition and Condensation Reactions
- Nucleophilic Addition To Carbonyls
- Reagent Friday: Lithium Di-isopropyl Amide (LDA)
- Base-promoted formation of enolates from ketones (MOC Membership)
- Alkene Stability
- Elimination Reactions (2): The Zaitsev Rule
- Enols and Enolates Practice Quizzes (MOC Membership)
- Reactions of Enols – Acid-Catalyzed Aldol, Halogenation, and Mannich Reactions
- All About Enamines
- The Michael Addition Reaction and Conjugate Addition
Note 1. A rough rule of thumb is that each C-H you replace with a C-C gets you an additional 1 kcal/mol of stability. This might not sound like a lot, but even 1 kcal/mol is enough to give you about 80:20 equilibrium ratio.
Note 2. “it can vary considerably”. A typical ratio of thermodynamic:kinetic enolates under “thermodynamic conditions” (NaOR/ROH) is about 4:1 but it can be significantly larger than that. The identity of the alkali metal counter-ion can have a huge role. Page 2 of this article provides a great overview on forming thermodynamic enolates.
Note 3. .This reaction can be hard to control! One problem with halogenation of ketones under thermodynamic conditions (RO(-) / ROH) is that the halogenation product is more acidic than the starting ketone. This can easily lead to multiple halogenations, as in the Haloform reaction.
Note 4. For more on alkylation of ketones under thermodynamic conditions, see this classic study. It turns out the reaction of the ketone with NaOR/CH3I does indeed put CH3 on the more substituted enolate (in 41% yield), but there are lots of byproducts due to over-alkylation. For the purposes of our course, this is why procedures like the acetoacetic ester synthesis are preferred for enolate alkylation.
Note 7. LDA isn’t particularly useful for the deprotonation of aldehydes. It tends to perform nucleophilic addition to them instead.
- THE FORMATION AND ALKYLATION OF SPECIFIC ENOLATE ANIONS FROM AN UNSYMMETRICAL KETONE: 2-BENZYL-2-METHYLCYCLOHEXANONE AND 2-BENZYL-6-METHYLCYCLOHEXANONE
Martin Gall and Herbert O. House
Org. Synth. 1972, 52, 39
This procedure from Organic Syntheses has detailed experimental conditions for regioselective alkylation of an unsymmetrical ketone through kinetic and thermodynamic enolate formation conditions.
- THE α-ALKYLATION OF ENOLATES FROM THE LITHIUM-AMMONIA REDUCTION OF α,β-UNSATURATED KETONES
Gilbert Stork, Perry Rosen, and Norman L. Goldman
Journal of the American Chemical Society 1961, 83 (13), 2965-2966
This paper has one of the first descriptions of kinetic enolate formation in the literature – “The success of the trapping of the enolate ion IV depends on the alkylation reaction being faster than equilibration of the initially produced enolate IV to the more stable II via proton transfer with some initially formed neutral alkylated ketone.”
- Tetrahedron report number 25: Ketone enolates: regiospecific preparation and synthetic uses
Tetrahedron 1976, 32 (24), 2979-2990
This review covers various methods for enolate formation, and has data on the composition of various ketone-enolate mixtures formed under kinetic and thermodynamic conditions
- Thermodynamic and Kinetic Controlled Enolates: A Project for a Problem-Oriented Laboratory Course
Augustine Silveira Jr., Michael A. Knopp, and Jhong Kim
Journal of Chemical Education 1998, 75 (1), 78
A paper from J. Chem. Ed. that covers how to demonstrate the concepts of kinetic and thermodynamic enolates in an undergraduate laboratory session.
- The Chemistry of Carbanions. V. The Enolates Derived from Unsymmetrical Ketones
Herbert O. House and Vera Kramar
The Journal of Organic Chemistry 1963, 28 (12), 3362-3379
- The Chemistry of Carbanions. IX. The Potassium and Lithium Enolates Derived from Cyclic Ketones
Herbert O. House and Barry M. Trost
The Journal of Organic Chemistry 1965 30 (5), 1341-1348
- Kinetic Enolate Formation by Lithium Arylamide: Effects of Basicity on Selectivity
Linfeng Xie, Keith Vanlandeghem, Kurt M. Isenberger, and Carolyn Bernier
The Journal of Organic Chemistry 2003, 68 (2), 641-643
This paper is on the topic of enolate formation and examines how the stereochemistry of the enolate formed varies depending on the nature of the Li-amide base.
- A stereoselective total synthesis of (±)-gymnomitrol
Steven C. Welch and Suthep Chayabunjonglerd
Journal of the American Chemical Society 1979, 101 (22), 6768-6769
The first step in this total synthesis is the alkylation of the Li enolate of 2-methylcyclohexanone, which is made by deprotonation by LDA at -78 °C, followed by equilibration to the thermodynamically more stable substituted enolate anion at room temperature for 4-5 hours.
- Pseudoephedrine as a Practical Chiral Auxiliary for the Synthesis of Highly Enantiomerically Enriched Carboxylic Acids, Alcohols, Aldehydes, and Ketones
Andrew G. Myers, Bryant H. Yang, Hou Chen, Lydia McKinstry, David J. Kopecky, and James L. Gleason
Journal of the American Chemical Society 1997, 119 (28), 6496-6511
The enolates derived from N-acylation of pseudoephedrine can be selectively facially alkylated. It is easier to induce diastereoselectivity in a reaction than enantioselectivity, and one way to do that is to use a chiral auxiliary – a chiral scaffold that you attach to the substrate and then remove after you’ve alkylated it. This is a paper that demonstrates practical chemistry – at the time, pseudoephedrine was easier to obtain than it is now, and Prof. Myers (now at Harvard) has extensively documented the reaction and the procedures in order to make it reproducible, robust, and reliable.
- Asymmetric alkylation reactions of chiral imide enolates. A practical approach to the enantioselective synthesis of .alpha.-substituted carboxylic acid derivatives
D. A. Evans, M. D. Ennis, and D. J. Mathre
Journal of the American Chemical Society 1982, 104 (6), 1737-1739
This is a landmark paper, in which Prof. Evans pioneered the use of chiral auxiliaries and showed how they could be used for asymmetric aldol reactions. The auxiliary used here is a chiral oxazolidinone, and this chemistry is known as the “Evans Asymmetric Aldol” or the “Evans chiral auxiliary”.
00 General Chemistry Review
01 Bonding, Structure, and Resonance
- How Do We Know Methane (CH4) Is Tetrahedral?
- Hybrid Orbitals and Hybridization
- How To Determine Hybridization: A Shortcut
- Orbital Hybridization And Bond Strengths
- Sigma bonds come in six varieties: Pi bonds come in one
- A Key Skill: How to Calculate Formal Charge
- Partial Charges Give Clues About Electron Flow
- The Four Intermolecular Forces and How They Affect Boiling Points
- 3 Trends That Affect Boiling Points
- How To Use Electronegativity To Determine Electron Density (and why NOT to trust formal charge)
- Introduction to Resonance
- How To Use Curved Arrows To Interchange Resonance Forms
- Evaluating Resonance Forms (1) - The Rule of Least Charges
- How To Find The Best Resonance Structure By Applying Electronegativity
- Evaluating Resonance Structures With Negative Charges
- Evaluating Resonance Structures With Positive Charge
- Exploring Resonance: Pi-Donation
- Exploring Resonance: Pi-acceptors
- In Summary: Evaluating Resonance Structures
- Drawing Resonance Structures: 3 Common Mistakes To Avoid
- How to apply electronegativity and resonance to understand reactivity
- Bond Hybridization Practice
- Structure and Bonding Practice Quizzes
- Resonance Structures Practice
02 Acid Base Reactions
- Introduction to Acid-Base Reactions
- Acid Base Reactions In Organic Chemistry
- The Stronger The Acid, The Weaker The Conjugate Base
- Walkthrough of Acid-Base Reactions (3) - Acidity Trends
- Five Key Factors That Influence Acidity
- Acid-Base Reactions: Introducing Ka and pKa
- How to Use a pKa Table
- The pKa Table Is Your Friend
- A Handy Rule of Thumb for Acid-Base Reactions
- Acid Base Reactions Are Fast
- pKa Values Span 60 Orders Of Magnitude
- How Protonation and Deprotonation Affect Reactivity
- Acid Base Practice Problems
03 Alkanes and Nomenclature
- Meet the (Most Important) Functional Groups
- Condensed Formulas: Deciphering What the Brackets Mean
- Hidden Hydrogens, Hidden Lone Pairs, Hidden Counterions
- Don't Be Futyl, Learn The Butyls
- Primary, Secondary, Tertiary, Quaternary In Organic Chemistry
- Branching, and Its Affect On Melting and Boiling Points
- The Many, Many Ways of Drawing Butane
- Wedge And Dash Convention For Tetrahedral Carbon
- Common Mistakes in Organic Chemistry: Pentavalent Carbon
- Table of Functional Group Priorities for Nomenclature
- Summary Sheet - Alkane Nomenclature
- Organic Chemistry IUPAC Nomenclature Demystified With A Simple Puzzle Piece Approach
- Boiling Point Quizzes
- Organic Chemistry Nomenclature Quizzes
04 Conformations and Cycloalkanes
- Staggered vs Eclipsed Conformations of Ethane
- Conformational Isomers of Propane
- Newman Projection of Butane (and Gauche Conformation)
- Introduction to Cycloalkanes (1)
- Geometric Isomers In Small Rings: Cis And Trans Cycloalkanes
- Calculation of Ring Strain In Cycloalkanes
- Cycloalkanes - Ring Strain In Cyclopropane And Cyclobutane
- Cyclohexane Conformations
- Cyclohexane Chair Conformation: An Aerial Tour
- How To Draw The Cyclohexane Chair Conformation
- The Cyclohexane Chair Flip
- The Cyclohexane Chair Flip - Energy Diagram
- Substituted Cyclohexanes - Axial vs Equatorial
- Ranking The Bulkiness Of Substituents On Cyclohexanes: "A-Values"
- The Ups and Downs of Cyclohexanes
- Cyclohexane Chair Conformation Stability: Which One Is Lower Energy?
- Fused Rings - Cis-Decalin and Trans-Decalin
- Naming Bicyclic Compounds - Fused, Bridged, and Spiro
- Bredt's Rule (And Summary of Cycloalkanes)
- Newman Projection Practice
- Cycloalkanes Practice Problems
05 A Primer On Organic Reactions
- The Most Important Question To Ask When Learning a New Reaction
- The 4 Major Classes of Reactions in Org 1
- Learning New Reactions: How Do The Electrons Move?
- How (and why) electrons flow
- The Third Most Important Question to Ask When Learning A New Reaction
- 7 Factors that stabilize negative charge in organic chemistry
- 7 Factors That Stabilize Positive Charge in Organic Chemistry
- Common Mistakes: Formal Charges Can Mislead
- Nucleophiles and Electrophiles
- Curved Arrows (for reactions)
- Curved Arrows (2): Initial Tails and Final Heads
- Nucleophilicity vs. Basicity
- The Three Classes of Nucleophiles
- What Makes A Good Nucleophile?
- What makes a good leaving group?
- 3 Factors That Stabilize Carbocations
- Equilibrium and Energy Relationships
- What's a Transition State?
- Hammond's Postulate
- Grossman's Rule
- Draw The Ugly Version First
- Learning Organic Chemistry Reactions: A Checklist (PDF)
- Introduction to Addition Reactions
- Introduction to Elimination Reactions
- Introduction to Free Radical Substitution Reactions
- Introduction to Oxidative Cleavage Reactions
06 Free Radical Reactions
- Bond Dissociation Energies = Homolytic Cleavage
- Free Radical Reactions
- 3 Factors That Stabilize Free Radicals
- What Factors Destabilize Free Radicals?
- Bond Strengths And Radical Stability
- Free Radical Initiation: Why Is "Light" Or "Heat" Required?
- Initiation, Propagation, Termination
- Monochlorination Products Of Propane, Pentane, And Other Alkanes
- Selectivity In Free Radical Reactions
- Selectivity in Free Radical Reactions: Bromination vs. Chlorination
- Halogenation At Tiffany's
- Allylic Bromination
- Bonus Topic: Allylic Rearrangements
- In Summary: Free Radicals
- Synthesis (2) - Reactions of Alkanes
- Free Radicals Practice Quizzes
07 Stereochemistry and Chirality
- Types of Isomers: Constitutional Isomers, Stereoisomers, Enantiomers, and Diastereomers
- How To Draw The Enantiomer Of A Chiral Molecule
- How To Draw A Bond Rotation
- Introduction to Assigning (R) and (S): The Cahn-Ingold-Prelog Rules
- Assigning Cahn-Ingold-Prelog (CIP) Priorities (2) - The Method of Dots
- Enantiomers vs Diastereomers vs The Same? Two Methods For Solving Problems
- Assigning R/S To Newman Projections (And Converting Newman To Line Diagrams)
- How To Determine R and S Configurations On A Fischer Projection
- The Meso Trap
- Optical Rotation, Optical Activity, and Specific Rotation
- Optical Purity and Enantiomeric Excess
- What's a Racemic Mixture?
- Chiral Allenes And Chiral Axes
- On Cats, Part 4: Enantiocats
- On Cats, Part 6: Stereocenters
- Stereochemistry Practice Problems and Quizzes
08 Substitution Reactions
- Introduction to Nucleophilic Substitution Reactions
- Walkthrough of Substitution Reactions (1) - Introduction
- Two Types of Nucleophilic Substitution Reactions
- The SN2 Mechanism
- Why the SN2 Reaction Is Powerful
- The SN1 Mechanism
- The Conjugate Acid Is A Better Leaving Group
- Comparing the SN1 and SN2 Reactions
- Polar Protic? Polar Aprotic? Nonpolar? All About Solvents
- Steric Hindrance is Like a Fat Goalie
- Common Blind Spot: Intramolecular Reactions
- The Conjugate Base is Always a Stronger Nucleophile
- Substitution Practice - SN1
- Substitution Practice - SN2
09 Elimination Reactions
- Elimination Reactions (1): Introduction And The Key Pattern
- Elimination Reactions (2): The Zaitsev Rule
- Elimination Reactions Are Favored By Heat
- Two Elimination Reaction Patterns
- The E1 Reaction
- The E2 Mechanism
- E1 vs E2: Comparing the E1 and E2 Reactions
- Antiperiplanar Relationships: The E2 Reaction and Cyclohexane Rings
- Bulky Bases in Elimination Reactions
- Comparing the E1 vs SN1 Reactions
- Elimination (E1) Reactions With Rearrangements
- E1cB - Elimination (Unimolecular) Conjugate Base
- Elimination (E1) Practice Problems And Solutions
- Elimination (E2) Practice Problems and Solutions
11 SN1/SN2/E1/E2 Decision
- Identifying Where Substitution and Elimination Reactions Happen
- Deciding SN1/SN2/E1/E2 (1) - The Substrate
- Deciding SN1/SN2/E1/E2 (2) - The Nucleophile/Base
- Deciding SN1/SN2/E1/E2 (3) - The Solvent
- Deciding SN1/SN2/E1/E2 (4) - The Temperature
- Wrapup: The Quick N' Dirty Guide To SN1/SN2/E1/E2
- Alkyl Halide Reaction Map And Summary
- SN1 SN2 E1 E2 Practice Problems
12 Alkene Reactions
- E and Z Notation For Alkenes (+ Cis/Trans)
- Alkene Stability
- Addition Reactions: Elimination's Opposite
- Selective vs. Specific
- Regioselectivity In Alkene Addition Reactions
- Stereoselectivity In Alkene Addition Reactions: Syn vs Anti Addition
- Hydrohalogenation of Alkenes and Markovnikov's Rule
- Hydration of Alkenes With Aqueous Acid
- Rearrangements in Alkene Addition Reactions
- Addition Pattern #1: The "Carbocation Pathway"
- Halogenation of Alkenes and Halohydrin Formation
- Oxymercuration Demercuration of Alkenes
- Alkene Addition Pattern #2: The "Three-Membered Ring" Pathway
- Hydroboration Oxidation of Alkenes
- m-CPBA (meta-chloroperoxybenzoic acid)
- OsO4 (Osmium Tetroxide) for Dihydroxylation of Alkenes
- Palladium on Carbon (Pd/C) for Catalytic Hydrogenation
- Cyclopropanation of Alkenes
- Alkene Addition Pattern #3: The "Concerted" Pathway
- A Fourth Alkene Addition Pattern - Free Radical Addition
- Alkene Reactions: Ozonolysis
- Summary: Three Key Families Of Alkene Reaction Mechanisms
- Synthesis (4) - Alkene Reaction Map, Including Alkyl Halide Reactions
- Alkene Reactions Practice Problems
13 Alkyne Reactions
- Acetylides from Alkynes, And Substitution Reactions of Acetylides
- Partial Reduction of Alkynes With Lindlar's Catalyst or Na/NH3 To Obtain Cis or Trans Alkenes
- Hydroboration and Oxymercuration of Alkynes
- Alkyne Reaction Patterns - Hydrohalogenation - Carbocation Pathway
- Alkyne Halogenation: Bromination, Chlorination, and Iodination of Alkynes
- Alkyne Reactions - The "Concerted" Pathway
- Alkenes To Alkynes Via Halogenation And Elimination Reactions
- Alkynes Are A Blank Canvas
- Synthesis (5) - Reactions of Alkynes
- Alkyne Reactions Practice Problems With Answers
14 Alcohols, Epoxides and Ethers
- Alcohols - Nomenclature and Properties
- Alcohols Can Act As Acids Or Bases (And Why It Matters)
- Alcohols - Acidity and Basicity
- The Williamson Ether Synthesis
- Ethers From Alkenes, Tertiary Alkyl Halides and Alkoxymercuration
- Alcohols To Ethers via Acid Catalysis
- Cleavage Of Ethers With Acid
- Epoxides - The Outlier Of The Ether Family
- Opening of Epoxides With Acid
- Epoxide Ring Opening With Base
- Making Alkyl Halides From Alcohols
- Tosylates And Mesylates
- PBr3 and SOCl2
- Elimination Reactions of Alcohols
- Elimination of Alcohols To Alkenes With POCl3
- Alcohol Oxidation: "Strong" and "Weak" Oxidants
- Demystifying The Mechanisms of Alcohol Oxidations
- Protecting Groups For Alcohols
- Thiols And Thioethers
- Calculating the oxidation state of a carbon
- Oxidation and Reduction in Organic Chemistry
- Oxidation Ladders
- SOCl2 Mechanism For Alcohols To Alkyl Halides: SN2 versus SNi
- Alcohol Reactions Roadmap (PDF)
- Alcohol Reaction Practice Problems
- Epoxide Reaction Quizzes
- Oxidation and Reduction Practice Quizzes
- What's An Organometallic?
- Formation of Grignard and Organolithium Reagents
- Organometallics Are Strong Bases
- Reactions of Grignard Reagents
- Protecting Groups In Grignard Reactions
- Synthesis Problems Involving Grignard Reagents
- Grignard Reactions And Synthesis (2)
- Organocuprates (Gilman Reagents): How They're Made
- Gilman Reagents (Organocuprates): What They're Used For
- The Heck, Suzuki, and Olefin Metathesis Reactions (And Why They Don't Belong In Most Introductory Organic Chemistry Courses)
- Reaction Map: Reactions of Organometallics
- Grignard Practice Problems
- Degrees of Unsaturation (or IHD, Index of Hydrogen Deficiency)
- Conjugation And Color (+ How Bleach Works)
- Introduction To UV-Vis Spectroscopy
- UV-Vis Spectroscopy: Absorbance of Carbonyls
- UV-Vis Spectroscopy: Practice Questions
- Bond Vibrations, Infrared Spectroscopy, and the "Ball and Spring" Model
- Infrared Spectroscopy: A Quick Primer On Interpreting Spectra
- IR Spectroscopy: 4 Practice Problems
- 1H NMR: How Many Signals?
- Homotopic, Enantiotopic, Diastereotopic
- Diastereotopic Protons in 1H NMR Spectroscopy: Examples
- C13 NMR - How Many Signals
- Liquid Gold: Pheromones In Doe Urine
- Natural Product Isolation (1) - Extraction
- Natural Product Isolation (2) - Purification Techniques, An Overview
- Structure Determination Case Study: Deer Tarsal Gland Pheromone
17 Dienes and MO Theory
- What To Expect In Organic Chemistry 2
- Are these molecules conjugated?
- Conjugation And Resonance In Organic Chemistry
- Bonding And Antibonding Pi Orbitals
- Molecular Orbitals of The Allyl Cation, Allyl Radical, and Allyl Anion
- Pi Molecular Orbitals of Butadiene
- Reactions of Dienes: 1,2 and 1,4 Addition
- Thermodynamic and Kinetic Products
- More On 1,2 and 1,4 Additions To Dienes
- s-cis and s-trans
- The Diels-Alder Reaction
- Cyclic Dienes and Dienophiles in the Diels-Alder Reaction
- Stereochemistry of the Diels-Alder Reaction
- Exo vs Endo Products In The Diels Alder: How To Tell Them Apart
- HOMO and LUMO In the Diels Alder Reaction
- Why Are Endo vs Exo Products Favored in the Diels-Alder Reaction?
- Diels-Alder Reaction: Kinetic and Thermodynamic Control
- The Retro Diels-Alder Reaction
- The Intramolecular Diels Alder Reaction
- Regiochemistry In The Diels-Alder Reaction
- The Cope and Claisen Rearrangements
- Electrocyclic Reactions
- Electrocyclic Ring Opening And Closure (2) - Six (or Eight) Pi Electrons
- Diels Alder Practice Problems
- Molecular Orbital Theory Practice
- Introduction To Aromaticity
- Rules For Aromaticity
- Huckel's Rule: What Does 4n+2 Mean?
- Aromatic, Non-Aromatic, or Antiaromatic? Some Practice Problems
- Antiaromatic Compounds and Antiaromaticity
- The Pi Molecular Orbitals of Benzene
- The Pi Molecular Orbitals of Cyclobutadiene
- Frost Circles
- Aromaticity Practice Quizzes
19 Reactions of Aromatic Molecules
- Electrophilic Aromatic Substitution: Introduction
- Activating and Deactivating Groups In Electrophilic Aromatic Substitution
- Electrophilic Aromatic Substitution - The Mechanism
- Ortho-, Para- and Meta- Directors in Electrophilic Aromatic Substitution
- Understanding Ortho, Para, and Meta Directors
- Why are halogens ortho- para- directors?
- Disubstituted Benzenes: The Strongest Electron-Donor "Wins"
- Electrophilic Aromatic Substitutions (1) - Halogenation of Benzene
- Electrophilic Aromatic Substitutions (2) - Nitration and Sulfonation
- EAS Reactions (3) - Friedel-Crafts Acylation and Friedel-Crafts Alkylation
- Intramolecular Friedel-Crafts Reactions
- Nucleophilic Aromatic Substitution (NAS)
- Nucleophilic Aromatic Substitution (2) - The Benzyne Mechanism
- Reactions on the "Benzylic" Carbon: Bromination And Oxidation
- The Wolff-Kishner, Clemmensen, And Other Carbonyl Reductions
- More Reactions on the Aromatic Sidechain: Reduction of Nitro Groups and the Baeyer Villiger
- Aromatic Synthesis (1) - "Order Of Operations"
- Synthesis of Benzene Derivatives (2) - Polarity Reversal
- Aromatic Synthesis (3) - Sulfonyl Blocking Groups
- Birch Reduction
- Synthesis (7): Reaction Map of Benzene and Related Aromatic Compounds
- Aromatic Reactions and Synthesis Practice
- Electrophilic Aromatic Substitution Practice Problems
20 Aldehydes and Ketones
- What's The Alpha Carbon In Carbonyl Compounds?
- Nucleophilic Addition To Carbonyls
- Aldehydes and Ketones: 14 Reactions With The Same Mechanism
- Sodium Borohydride (NaBH4) Reduction of Aldehydes and Ketones
- Grignard Reagents For Addition To Aldehydes and Ketones
- Wittig Reaction
- Hydrates, Hemiacetals, and Acetals
- Imines - Properties, Formation, Reactions, and Mechanisms
- All About Enamines
- Breaking Down Carbonyl Reaction Mechanisms: Reactions of Anionic Nucleophiles (Part 2)
- Aldehydes Ketones Reaction Practice
21 Carboxylic Acid Derivatives
- Nucleophilic Acyl Substitution (With Negatively Charged Nucleophiles)
- Addition-Elimination Mechanisms With Neutral Nucleophiles (Including Acid Catalysis)
- Basic Hydrolysis of Esters - Saponification
- Proton Transfer
- Fischer Esterification - Carboxylic Acid to Ester Under Acidic Conditions
- Lithium Aluminum Hydride (LiAlH4) For Reduction of Carboxylic Acid Derivatives
- LiAlH[Ot-Bu]3 For The Reduction of Acid Halides To Aldehydes
- Di-isobutyl Aluminum Hydride (DIBAL) For The Partial Reduction of Esters and Nitriles
- Amide Hydrolysis
- Thionyl Chloride (SOCl2)
- Diazomethane (CH2N2)
- Carbonyl Chemistry: Learn Six Mechanisms For the Price Of One
- Making Music With Mechanisms (PADPED)
- Carboxylic Acid Derivatives Practice Questions
22 Enols and Enolates
- Keto-Enol Tautomerism
- Enolates - Formation, Stability, and Simple Reactions
- Kinetic Versus Thermodynamic Enolates
- Aldol Addition and Condensation Reactions
- Reactions of Enols - Acid-Catalyzed Aldol, Halogenation, and Mannich Reactions
- Claisen Condensation and Dieckmann Condensation
- The Malonic Ester and Acetoacetic Ester Synthesis
- The Michael Addition Reaction and Conjugate Addition
- The Robinson Annulation
- Haloform Reaction
- The Hell–Volhard–Zelinsky Reaction
- Enols and Enolates Practice Quizzes
- The Amide Functional Group: Properties, Synthesis, and Nomenclature
- Basicity of Amines And pKaH
- 5 Key Basicity Trends of Amines
- The Mesomeric Effect And Aromatic Amines
- Nucleophilicity of Amines
- Alkylation of Amines (Sucks!)
- Reductive Amination
- The Gabriel Synthesis
- Some Reactions of Azides
- The Hofmann Elimination
- The Hofmann and Curtius Rearrangements
- The Cope Elimination
- Protecting Groups for Amines - Carbamates
- The Strecker Synthesis of Amino Acids
- Introduction to Peptide Synthesis
- Reactions of Diazonium Salts: Sandmeyer and Related Reactions
- Amine Practice Questions
- D and L Notation For Sugars
- Pyranoses and Furanoses: Ring-Chain Tautomerism In Sugars
- What is Mutarotation?
- Reducing Sugars
- The Big Damn Post Of Carbohydrate-Related Chemistry Definitions
- The Haworth Projection
- Converting a Fischer Projection To A Haworth (And Vice Versa)
- Reactions of Sugars: Glycosylation and Protection
- The Ruff Degradation and Kiliani-Fischer Synthesis
- Isoelectric Points of Amino Acids (and How To Calculate Them)
- Carbohydrates Practice
- Amino Acid Quizzes
25 Fun and Miscellaneous
- Organic Chemistry GIFS - Resonance Forms
- Organic Chemistry and the New MCAT
- A Gallery of Some Interesting Molecules From Nature
- The Organic Chemistry Behind "The Pill"
- Maybe they should call them, "Formal Wins" ?
- Intramolecular Reactions of Alcohols and Ethers
- Planning Organic Synthesis With "Reaction Maps"
- Organic Chemistry Is Shit
- The 8 Types of Arrows In Organic Chemistry, Explained
- The Most Annoying Exceptions in Org 1 (Part 1)
- The Most Annoying Exceptions in Org 1 (Part 2)
- Reproducibility In Organic Chemistry
- Screw Organic Chemistry, I'm Just Going To Write About Cats
- On Cats, Part 1: Conformations and Configurations
- On Cats, Part 2: Cat Line Diagrams
- The Marriage May Be Bad, But the Divorce Still Costs Money
- Why Do Organic Chemists Use Kilocalories?
- What Holds The Nucleus Together?
- 9 Nomenclature Conventions To Know
- How Reactions Are Like Music