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Hydrohalogenation of Alkenes and Markovnikov’s Rule
Last updated: September 21st, 2023 |
Hydrohalogenation of Alkenes and Markovnikov’s Rule
- When hydrohalic acids (HCl, HBr, HI) are added to alkenes, addition reactions can occur, resulting in formation of a C-H and C-halogen bond and breakage of a C-C pi bond.
- The reaction tends to occur such that the halogen ends up attached to the carbon of the alkene attached to the fewest hydrogen atoms, a phenomenon known as Markovnikov’s Rule.
- Addition of H-X to alkenes occurs through a protonation of the alkene to give a carbocation intermediate, followed by addition of the halide to the carbocation.
- A better reformulation of Markovnikov’s rule is therefore that addition of HX to alkenes will proceed through the most stable carbocation, which is generally the more substituted carbon of the alkene.
- (Note that H-Br with peroxides (RO-OR) operates through a different reaction mechanism – see Free Radical Addition of H-Br to Alkenes).
- Carbocation rearrangements (hydride or alkyl shifts) can occur if they will result in a more stable carbocation intermediate.
- H-X will also add to alkynes (See: Addition of HX to alkynes) and dienes (See: 1,2- and 1,4- Addition of HX To Dienes) but will not add to aromatic rings.
Table of Contents
- Reaction of Alkenes With Hydrohalic Acids (HCl, HBr, HI)
- Markovnikov’s Rule: The Halide Adds To The Most Substituted Carbon
- Stereoselectivity (or Lack Thereof) In Alkene Hydrohalogenation
- Hydrohalogenation of Alkenes: The Mechanism
- The Reaction Energy Diagram
- Carbocation Rearrangements – Hydride and Alkyl Shifts
- Alkynes, Dienes, Aromatic Rings, and the Cationic Cyclization of Alkenes
- Summary: Alkene Hydrohalogenation
- Quiz Yourself!
- (Advanced) References and Further Reading
When alkenes are treated with hydrohalic acids (HCl, HBr, or HI) they form alkyl halides.
These are addition reactions, where
- the C-C pi bond breaks, and;
- a new C-H and C-X bond forms (where X is Cl, Br, or I).
The new C-halogen bond tends to form on the most substituted carbon of the alkene (i.e. the one with the fewest carbons), and the new C-H bond tends to form on the carbon of the alkene containing the most hydrogens.
The reactions of alkenes with HX has been known for over 150 years.
When an alkene is not symmetrical, the reaction has the potential to form two different constitutional isomers (“regioisomers”). However, in many cases, one constitutional isomer is formed in a much higher proportion than the other. In other words, the reaction is regioselective.
In an early study of this reaction, Russian chemist Victor Markovnikov published the observation that the halogen tended to add to the carbon of the alkene which was bonded to the least number of hydrogens.
This has come to be known as “Markovnikov’s Rule“.
Markovnikov’s rule is what we would call an “empirical” rule. It was based purely on observed results, without any underlying understanding of the mechanism of the reaction.
In later years people had a hard time replicating Markovnikov’s results with HBr, often finding that the least substituted regioisomer was formed instead! Later on, in the 1930s the cause of this aberrant regioselectivity was found to be the presence of peroxides in solvent, which led to a free-radical process for addition of H-Br to alkenes, which does not occur with H-I or H-Cl. See article – Free-Radical addition of H-Br to Alkenes.
Subsequently we tend to say, for better or worse, that addition reactions to alkenes that follow this pattern (such as their reaction with H3O+ ) are “Markovnikov-selective“, whereas reactions that follow the opposite pattern are “anti-Markovnikov selective” (such as hydroboration of alkenes).
See if you can apply the pattern in the reaction of the alkene below (1-methylcyclopentene) with H-Cl.
Another example is below. Draw the major product(s) and determine how they will be related:
Can you work backwards to come up with the best starting material for this reaction?
When addition reactions occur across an alkene pi-bond, the (sp2-hybridized) trigonal planar carbons of the alkene are converted into (sp3-hybridized) tetrahedral carbons, and with this comes the potential for formation of stereoisomers. (See article: Types of Isomers)
- When the two new bonds to carbon are formed on the same face of the alkene, the addition is said to be “syn“
- When the two new bonds are formed on opposite faces of the alkene, the addition is said to be “anti“.
Addition reactions that give primarily syn or anti products are said to be stereoselective, and we will meet many examples in subsequent articles in this chapter (e.g. halogenation is stereoselective for anti products, and hydroboration is stereoselective for syn products).
Addition of H-X to alkenes gives a mixture of syn addition products and anti addition products [Note 1].
In other words, the reaction is not particularly stereoselective.
This lack of stereoselectivity leads to mixtures of syn and anti addition products, in some cases each as mixtures of enantiomers. See if you can draw the products of the reaction below:
Markovnikov was one of the more prominent chemists of his era, but back in 1870 he didn’t know why the reaction tended to give the more substituted product. The first to really figure it out was Lucas in 1924 [Ref], based on observations that alkyl groups are more “electron releasing”.
After many decades it was finally proposed that reaction goes through an intermediate carbocation. (The existence of carbocations was a fairly controversial subject until the 1930’s).
In the first step, the alkene (a nucleophile) is protonated by strong acid, resulting in a new carbocation. [Note 2 – pi complex]
Depending on where protonation occurs, two different carbocations may be formed. Being electron-poor species, carbocations are stabilized by adjacent electron-donating groups as well as by delocalization through resonance. (See article – 3 Factors Which Stabilize Carbocations).
The transition state leading to the most stable carbocation will be lower in energy, which tends to be the most substituted carbocation.
The arrow pushing for alkenes reacting with acids like H-X can be a little ambiguous – see Note 3.
So it is ultimately this carbocation intermediate which is the underlying reason for why Markovnikov’s rule is observed.
Carbocations have an empty p-orbital and readily accept a pair of electrons from whatever Lewis bases happen to be present in solution.
In the second step, the best nucleophile present (which tends to be the halide ion) then attacks the carbocation, forming the alkyl halide.
To reiterate: Markovnikov went to his grave not knowing this mechanism. Heck, many chemists of his time didn’t even accept that carbon was tetrahedral! So if you didn’t figure this mechanism out immediately, that’s to be expected and certainly nothing to feel bad about. The body of knowledge that is chemistry is built up of thousands of little experiments that eventually grew into the framework we have today.
Sometimes it can be helpful to trace out the energy profile of a reaction as it progresses from starting material to products.
In these diagrams, peaks (local maxima) are transition states and valleys (local minima) are intermediates.
A simple hydrohalogenation reaction has two steps – each of which has a transition state – and a single carbocation intermediate.
- In the first step, our intrepid alkene is protonated by strong acid, resulting in the high-energy transition state TS 1. This step has the highest activation energy (the barrier between reactants and transition state) making it the rate-determining step for this reaction.
- From the transition state (TS1) energy maximum, the reaction proceeds to the carbocation intermediate.
- The second step involves attack of the halide nucleophile on the carbocation, which proceeds through transition state 2 (TS2). Note that the activation energy for this step is considerably less than for protonation of the alkene – in other words, it will be the fast step.
- The reaction then proceeds through TS2 to give the final product, the alkyl halide.
One key to the proposal of a carbocation intermediate was the observation that some hydrohalogenation reactions give products of carbocation rearrangements in addition to the expected addition product.
For example when 4-methyl-1-butene was treated with HCl and allowed to sit at room temperature for an extended period, the product mixture was found to contain about half the expected Markovnikov addition product in addition to a new tertiary alkyl halide. [Ref]
In this reaction the C-H bond that was originally part of the isopropyl group migrates to the secondary alkyl carbon. (See article – Rearrangements in Alkene Addition Reactions)
See if you can draw a reasonable mechanism!
These rearrangements can occur when a more stable carbocation can result from migration of a hydride or alkyl group. When a quaternary carbon is adjacent to a secondary carbocation, alkyl groups can migrate.
Occasionally migrations between equivalently substituted groups can be favored, as in the example below.
- Alkynes will react with HX to give vinyl halides. A second equivalent of HX will give geminal dihalides. (For more, see Alkyne Hydrohalogenation)
- Dienes such as 1,3-butadiene will react with HX to give various products. See this article in the chapter on conjugated systems for more. (See article: 1,2- and 1,4-Addition of HX To Dienes)
- Aromatic rings such as benzene will not undergo addition reactions with HX. Aromatic rings tend to react through substitution. More in the chapter on aromatic rings. (See article: Introduction to Aromaticity)
Carbocations are reactive intermediates and will readily combine with even poor Lewis bases.
Sometimes those Lewis bases include other alkenes on the same molecule. This can result in cyclic molecules.
For example, consider the reaction below:
There are whole classes of molecules that are synthesized in nature via attack of alkenes on various carbocations. One of the most prominent classes is terpenes. I don’t want to get into it in this article, but if you are looking for a good time, I strongly suggest looking at how the steroid skeleton of lanosterol is built up from the cyclization of squalene. [Note 4]
This isn’t the cyclization of an alkene, but it’s another example of how rearrangements can occur in nature. In this example we start with alpha-pinene, one of the main ingredients in pine oil.
When peroxides are present a very different reaction pathway occurs, where free-radical intermediates are involved. These reactions are anti-Markovnikov selective.
[Q1-D-Cl plus trans alkene]
Ingold’s “Structure and Mechanism in Organic Chemistry” was a valuable guide to the early literature on this topic.
- The Logic Behind Markovnikov’s Rule: Was It an Inspired Guess? …No!
D. E. Lewis, Angew. Chem. Int. Ed. 2021, 60, 4412.
Fun, accessible historical essay examining Markovnikov’s studies in the 1860’s-1870’s.
- I. Ueber die Abhängigkeit der verschiedenen Vertretbarkeit des Radicalwasserstoffs in den isomeren Buttersäuren.
Markownikoff, W. (1870)
Justus Liebigs Ann. Chem., 153: 228-259.
The original Markovnikov paper.
- ELECTRON DISPLACEMENT IN CARBON COMPOUNDS I. ELECTRON DISPLACEMENT VERSUS ALTERNATE POLARITY IN ALIPHATIC COMPOUNDS
Howard J. Lucas and Archibald Y. Jameson
Journal of the American Chemical Society 1924 46 (11), 2475-2482
If not the earliest explanation of Markovnikov’s rule, certainly one of them.
- Secondary Isoamyl Chloride, 3-Chloro-2-methylbutane
Frank C. Whitmore and Franklin Johnston
Journal of the American Chemical Society 1933 55 (12), 5020-5022
One of the first clearly written out explanations of a carbocation rearrangement in addition of HX to alkenes. A subsequent paper ( JACS 1950 1511) goes into more detail.
- The Stereochemistry of the Addition of Hydrogen Bromide to 1,2-Dimethylcyclohexene
George S. Hammond and Thomas D. Nevitt
Journal of the American Chemical Society 1954 76 (16), 4121-4123
OK. When I wrote, above, that the addition of HX to alkenes is not stereoselective, I fibbed. The truth is that it can be stereoselective for anti addition if carried out at low temperatures in non polar solvents such as pentane. The proposed mechanism is not a free carbocation but a termolecular transition state involving two equivalents of H-Br. (Interestingly, though, the reaction of H3O+ with the same compound is not stereoselective).
In the strongly polar solvent acetic acid, the reaction results predominantly (but not exclusively!) through the classic carbocation mechanism.
- Hydrochlorination of cyclohexene in acetic acid. Kinetic and product studies
Robert C. Fahey, Michael W. Monahan, and C. Allen McPherson
Journal of the American Chemical Society 1970 92 (9), 2810-2815
Detailed kinetic studies of the addition of HCl to cyclohexene in acetic acid, discussing a possible third-order mechanism (rate = k[cyclohexene][HX]2).
- SPIROANNELATION OF ENOL SILANES: 2-OXO-5-METHOXYSPlRO[5.4]DECANE
Lee, T. V.; Porter, J. R.
Org. Synth. 1995, 72, 189
The first reaction in the above procedure involves two steps – addition of HBr across the double bond and converting the aldehyde to a dimethyl acetal.
- Markovnikov’s Rule
Robert C. Kerber
Journal of Chemical Education 2007 84 (7), 1109
A 2007 missive urging educators and textbook writers to retire the teaching of Markovnikov’s Rule.
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
- 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
- Acid-Catalyzed Addition of H2O To Alkenes
- 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
- 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