Home / Reactions of Grignard Reagents
Reactions of Grignard Reagents
Last updated: February 28th, 2023 |
All About The Reactions of Grignard Reagents
- Grignard reagents are excellent carbon-based nucleophiles as well as strong bases.
- They will add to aldehydes and ketones to form alcohols (after a protonation step)
- They will add twice to esters to give tertiary alcohols.
- They will add to the less-substituted side of epoxides
- Grignard reagents will also react with carbon dioxide (CO2) to give carboxylic acids (after acid workup).
- Grignard reagents will not perform SN2 reactions with alkyl halides. They are also not compatible with carboxylic acids or alcohols.
Table of Contents
- Reminder: Grignard Reagents Are Nucleophiles
- Addition of Grignard Reagents To Epoxides
- Reaction of Grignard Reagents With Aldehydes And Ketones
- Reaction of Grignard Reagents With Esters
- Why Do Grignards Add Twice To Esters? The Mechanism
- Summary: Reactions of Grignard Reagents
- (Advanced) References and Further Reading
So far in this series we’ve introduced organometallic compounds and said that their carbons tend to be nucleophilic. We’ve learned how to make them from alkyl, alkenyl or aryl halides (along with some ways not to make them!) and saw that they are very strong bases.
Most interesting about Grignards is that they are carbon-based nucleophiles and we can thus combine Grignard reagents with various electrophilic carbon species to form new carbon-carbon bonds.
And since carbon-carbon bonds constitute the “backbone” of molecules in organic chemistry, it turns out that this class of reactions is very useful. As a matter of fact, it won its discoverer, Victor Grignard, the Nobel Prize for Chemistry back in 1912.
For our purposes, the key carbon-based electrophiles that Grignard reagents react with are epoxides, aldehydes, ketones, and esters. Let’s go through them in turn.
Epoxides (“oxiranes” if you are an IUPAC stickler) are 3-membered cyclic ethers which possess considerable ring strain. As we’ve seen, this ring strain makes them somewhat “spring loaded” toward attack by nucleophiles, which will result in formation of a new bond to carbon and opening of the ring.
Negatively charged nucleophiles (such as Grignards) tend to react with epoxides in a manner similar to the SN2 reaction: attack occurs at the least substituted carbon of the epoxide. Here’s an example:
Note the bonds that formed and broke here: we formed a new C-C bond (between carbons A and B), and broke a C-O bond (between carbon A and the oxygen). This resulted in a negatively charged oxygen (alkoxide): to produce final alcohol product, we typically quench the reaction with a source of acid, forming O–H.
Here’s how the reaction works. The hard thing is to recognize that the nucleophile is the pair of electrons in the C-Mg bond: remember from previous posts that carbon is strongly δ- (nucleophilic) because of its greater electronegativity as compared to magnesium.
It might be helpful to imagine the Grignard reagent below as CH3CH2– . Other than that the reaction is fairly straightforward if you’ve seen an SN2 reaction before: we simultaneously form C-C and break C-O.
Note that this reaction also forms an “alkoxide”. In order to obtain our neutral alcohol product at the end, we must perform second step: a “workup” (“quench”) with a source of acid. This is written a variety of ways – H+, H3O+, H2O, or just “acid workup”. This step occurs after our key Grignard reaction, for what should be obvious reasons – being strong bases, Grignard reagents are destroyed by acid.
Another thing to keep in mind is stereochemistry of the epoxide.Consistent with an SN2 reaction, if the reaction occurs at a secondary carbon, we will observe inversion of configuration:
A second class of important electrophiles that react with Grignards (and arguably THE most important class of electrophiles) is aldehydes and ketones. If you haven’t covered the reactions of these functional groups yet, a short summary would be this: the carbonyl carbon is an electrophile, and when nucleophiles react at this carbon, it’s accompanied by cleavage of the C-O pi bond (π bond). (For more on the addition mechanism to carbonyls, see post: Nucleophilic Addition)
Here are some examples of reactions of Grignards with aldehydes and ketones. Note that in each case we are forming a new bond between the carbonyl carbon (labelled A) and the carbon bound to magnesium (labelled B), and we are breaking the C-O pi bond in the process.
So how does this reaction work?
Let’s get familiar with a VERY important mechanism called “addition” (sometimes called, “1,2-addition”). This is by far the most important reaction of the carbonyl group, and if you give yourself a chicken for every time you will see variations of it in Org 2, you will have a lot of eggs in your room by the end of the semester.
Note that this reaction also forms an “alkoxide”. In order to obtain our neutral alcohol product at the end, we must perform a “workup” (“quench”) with a source of acid, forming O-H.
Esters are close relatives of aldehydes and ketones: they consist of a carbonyl group directly attached to an OR group. As you might expect, they react with Grignards in a similar fashion to aldehydes and ketones: with formation of a new C-C bond and breakage of a C-O (pi bond).
However, there’s a twist with the reaction of esters that isn’t present with aldehydes and ketones. Look carefully: what’s different?
Note that in both cases we added two equivalents of our Grignard reagent to the ester, forming a tertiary alcohol.
Wait a minute – how did this happen?!
This reaction incorporates the second most important mechanism of carbonyls (next to “addition”), namely, “elimination“. In fact “elimination” is the exact reverse of “addition” ! Let’s walk through it. There are 4 steps
- In the first step, the Grignard performs an addition reaction on the ester, forming C-C and breaking C-O (pi), giving us an intermediate with a negatively charged oxygen. We’ve seen this type of reaction before in the addition of Grignards to aldehydes and ketones.
- Now comes the new step: elimination (sometimes, “1,2 elimination”). This intermediate has a reasonably good leaving group (OCH2CH3 in the case below). What happens next is reformation of the C-O pi bond with expulsion of the leaving group (CH3CH2O– in the case below). In other words, we form C–O π and break a C–O single bond. The new product is a ketone.
Together, these two steps are often referred to as Nucleophilic Acyl Substitution (See post: Nucleophilic Acyl Substitution)
Elimination does not occur in addition to aldehydes and ketones because the leaving group would have to be the extremely strong bases H(-) or R(-). It is reasonably favorable for esters because the leaving group RO(-) is of comparable basicity to the negatively charged oxygen of the tetrahedral intermediate. [Note 1]
- But wait! There’s more! After Step 2, we have a new ketone. As we’ve seen before, Grignards will react quickly with ketones in yet another addition reaction [Step 3]. Here, as in Step 1, we form C–C and break C–O (pi). The result is a tertiary alkoxide (the conjugate base of a tertiary alcohol).
[Wait, you might ask. If we just use one equivalent of Grignard reagent, is it possible to get the reaction to stop at the ketone stage? The short answer is “no”. [See Note 3 for the long answer]]
- Finally, protonation of this tertiary alkoxide yields the tertiary alcohol (Step 4).
Here’s the graphical walkthrough:
That does it for the key reactions of Grignard reagents you’ll see in most Org 1 and Org 2 courses.
In the next post we’ll talk about yet another way to screw up formation of Grignard reagents, and it involves the reactions in this post.
Next Post: Protecting Groups In Grignard Reactions
- Nucleophilic Addition To Carbonyls
- Nucleophilic Acyl Substitution (With Negatively Charged Nucleophiles)
- Protecting Groups In Grignard Reactions
- Grignard Practice Problems: Synthesis (1)
- Grignard Reactions And Synthesis (2)
- Gilman Reagents (Organocuprates): What They’re Used For
- Reaction Map: Reactions of Organometallics
Note 1: Although alkoxides (RO–, the conjugate base of alcohols, pKa 16-18) are not on anyone’s list of Great Leaving Groups, they are some 25 orders of magnitude better leaving groups than hydrides (H–, the conjugate base of hydrogen, pKa 40) and more than 30 orders of magnitude better than alkyl groups (R- , the conjugate base of alkanes, pKa 50). Thus, when the alkoxide intermediate is formed in Step 1, there is not any deep energetic penalty for the C-O pi bond to reform and for RO- to be expelled: after all, we are simply replacing a strong base (the O- ) with one of comparable basicity.
Note 2. Why are ketones more reactive towards Grignard reagents than esters? This requires understanding the phenomenon of pi donation. The lone pair on oxygen donates electron density into the carbonyl carbon. This is worthy of a separate post, but here’s the bottom line:
Note 3. Alas, no. Using 1 equivalent of Grignard will result in 0.5 equivalents of a tertiary alcohol and 0.5 equivalents of the starting ester. The reason why is that Step 2 [elimination] is quite fast!
Once elimination occurs, we will have ketone in the presence of an ester. For interesting reasons [see Note 2] ketones are more reactive than esters toward Grignard reagents, which means they will be consumed more quickly.
- The Grignard Reagents
Organometallics 2009 28 (6), 1598-1605
A historical overview on Grignard reagents by the late Prof. Dietmar Seyferth (MIT), founding editor of the journal Organometallics.
- Secondary and Tertiary Alkyllithium Compounds and Some Interconversion Reactions with Them
Henry Gilman, Fred W. Moore, and Ogden Baine
Journal of the American Chemical Society 1941, 63 (9), 2479-2482
Prof. Henry Gilman (Iowa State) was a pioneer in organometallic chemistry in the first half of the 20th century. In this paper he describes the synthesis and reactivity of various alkyllithiums (n-butyllithium, s-butyllithium, isopropyllithium, and t-butyllithium). The synthesis is from the alkyl halide and lithium metal, as can be seen in the experimental section.
Paul D. Bartlett, C. Gardner Swain, and Robert B. Woodward
Journal of the American Chemical Society 1941, 63 (11), 3229-3230
This communication is from some legendary figures in organic chemistry and describes the preparation of t-butyllithium.
C. W. Evans and C. F. H. Allen
Org. Synth. 1938, 18, 70
The first step in this procedure is a preparation of phenyllithium from bromobenzene and lithium metal. Organic Syntheses is a reputable source of reproducible and independently tested synthetic organic procedures.
- The mechanism of the lithium – halogen Interchange reaction : a review of the literature
Bailey, W. F.; Patricia, J. J.
Organomet. Chem. 1988, 352 (1-2), 1-46
In modern organic chemistry, organolithium reagents are rarely prepared from scratch (i.e. using Li metal), due to the ready availability of alkyllithium reagents from vendors (e.g. MeLi, the BuLi reagents, PhLi, etc.). Instead, these reagents can be used to form other organolithium species through a process known as lithium-halogen exchange.
- What’s Going on with These Lithium Reagents?
Hans J. Reich
The Journal of Organic Chemistry 2012, 77 (13), 5471-5491
Prof. Hans Reich (U. Wisconsin-Madison) has spent his career studying the behavior of organolithium species, and this is an account of his research and the surprising findings he made. This is classic Physical Organic chemistry.
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
- SN1 vs E1 and SN2 vs E2 : The Temperature
- Deciding SN1/SN2/E1/E2 - The Solvent
- 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