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Bond Dissociation Energies = Homolytic Cleavage
Last updated: November 8th, 2024 |
Bond Dissociation Energies Represent Homolytic Bond Cleavage:
Here’s a point which causes a lot of confusion.
Look at these two reactions. Ā What do you think is the stronger bond, O-H or C-H?
According to thisĀ this table (PDF) the bond dissociation energy (BDE) of OH is 460 kJ/mol (110 kcal/mol) and the value for CH is 389 kJ/mol (93 kcal/mol). [For another table, see this page fromĀ Reusch].Ā So why is the stronger bond being broken here?
Another example:
But the bond strengths here are alkyne C-H (523 kJ/mol or 125 kcal/mol) versus the tertiary C-H bond strength in this case (384 kJ/mol or 93 kcal/mol). So Ā why is the C-H bond with the lower bond dissociation energy formed and Ā the higher C-H bond is broken?
Here’s three clues about bond dissociation energies.
- For C-H bonds, bond dissociation energies decrease as you add substitution to the carbon.
- Water can interfere with acid-base reactions, but water tends not to interfere with free radical reactions. If you’ve done a Grignard reaction in the lab, you know how finicky they can be, because you need to remove all traces of water from the solvent in order for it to start. On the other hand, the same restraint doesn’t apply to free radical reactions! It’s possible to run free-radical reactions in the presence of water without any concern that the desired free-radical reaction will be trapped by the H-OH instead.
- Another clue is in that it is much easier to form alkyl radicals than alkenyl and alkynyl radicals.
The answer is that bond dissociation energy = homolytic cleavage
The measured bond dissociation energies (BDE’s) in tables represent the breaking apart ofĀ the bond into two radicals. This is because of the way bond dissociation energies are measured – through calorimetry of radical reactions.
Therefore the bond dissociation energy reflects the stability of the radicals formed!Ā R3Cā¢ is a more stable radical than HOā¢ .Ā R3Cā¢ is also a more stable radical than an alkynyl radical.Ā It also helps to explain why the order of bond strengths goes Ā primary C-H > secondary C-H > tertiary C-H.
Notes
Related Articles
Note 1.Ā Why are homolytic bond strengths measured and not heterolytic? That’s a good question. It’s much easier to break C-H and C-C bonds in alkanes homolytically, for one. Secondly, radicals are neutral and don’t carry around a solvent shell with them, like anions. So they’re less sensitive to solvent effects. For a technical discussion, look here.
Note 2. Why might the OH radical be less stable than R radicals, and stability of alkyl radicals be greater than alkenyl and alkynyl radicals?
(Advanced) References and Further Reading
- Shortcomings of Basing Radical Stabilization Energies on Bond Dissociation Energies of Alkyl Groups to Hydrogen
Andreas A. Zavitsas, Donald W. Rogers, and Nikita Matsunaga
The Journal of Organic Chemistry 2010, 75 (16), 5697-5700
DOI: 1021/jo101127m
Several textbooks, including some advanced ones, provide radical stabilization energies, and this paper discusses why that may not be the best way to quantify the stability of free radicals. - On the Advantages of Hydrocarbon Radical Stabilization Energies Based on RāH Bond Dissociation Energies
Matthew D. Wodrich, W. Chad McKee, and Paul von RaguƩ Schleyer
The Journal of Organic Chemistry 2011, 76 (8), 2439-2447
DOI: 1021/jo101661c
This paper addresses some of the shortcomings with the approach used in Ref #1 above. The late Prof. Schleyer was a very influential figure in organic chemistry, and was a pioneer in using computational methods to address interesting problems in organic chemistry. - The Radical Stabilization Energy of a Substituted Carbon-Centered Free Radical Depends on Both the Functionality of the Substituent and the Ordinality of the Radical
Marvin L. Poutsma
The Journal of Organic Chemistry 2011, 76 (1), 270-276
DOI: 1021/jo102097n - A Single Universal Scale of Radical Stabilization Energies Does Not Exist: Global Bond Dissociation Energies and Radical Thermochemistries Are Described by Combining Two Universal Scales
Andreas A. Zavitsas
The Journal of Organic Chemistry 2008, 73 (22), 9022-9026
DOI: 1021/jo8018768 - Bond Dissociation Energies by Kinetic Methods
A. Kerr
Chemical Reviews 1966, 66 (5), 465-500
DOI: 10.1021/cr60243a001
This paper describes experimental techniques for measuring homolytic BDEs. - III – Bond energies
Sidney W. Benson
Journal of Chemical Education 1965, 42 (9), 502
DOI: 10.1021/ed042p502
This paper describes the empirical measurement of homolytic bond dissociation energies. This paper was written by Prof. Benson while at the Stanford Research Institute (now SRI International), a non-profit research center very close to Stanford University. In 1978, Prof. Benson joined Prof. George Olah at USC and helped established the Loker Hydrocarbon Research Institute there. - From equilibrium acidities to radical stabilization energies
Frederick G. Bordwell and Xian Man Zhang
Accounts of Chemical Research 1993, 26 (9), 510-517
DOI: 10.1021/ar00033a009
This paper attempts to correlate the acidity of a proton with the BDE of the corresponding C-H or X-H bond. - Ab Initio Calculations of the Relative Resonance Stabilization Energies of Allyl and Benzyl Radicals
David A. Hrovat and Weston Thatcher Borden
The Journal of Physical Chemistry 1994, 98 (41), 10460-10464
DOI: 1021/j100092a014
The stabilization energy of a vinyl group (in the allyl radical) and a phenyl group (in the benzyl radical) has been calculated to be 15.7 kcal/mol and 12.5 kcal/mol, respectively. - Effects of adjacent acceptors and donors on the stabilities of carbon-centered radicals
G. Bordwell, Xianman Zhang, and Mikhail S. Alnajjar
Journal of the American Chemical Society 1992, 114 (20), 7623-7629
DOI: 10.1021/ja00046a003
Table I in this paper contains stabilization energies of methyl radicals with various substituents (e.g. Ā·CH2X). - Bond Dissociation Energies of Organic Molecules
Stephen J. Blanksby and G. Barney Ellison
Accounts of Chemical ResearchĀ 2003Ā 36Ā (4), 255-263
DOI: 10.1021/ar020230d
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
- 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
- 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"
- 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
- Learning New Reactions: How Do The Electrons Move?
- 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
- 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
- Learning Organic Chemistry Reactions: A Checklist (PDF)
- 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
- Stereochemistry Practice Problems and Quizzes
08 Substitution Reactions
- Nucleophilic Substitution Reactions - 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
- 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
10 Rearrangements
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 Key Factors For Determining 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
- Alkene Addition Reactions: "Regioselectivity" and "Stereoselectivity" (Syn/Anti)
- Stereoselective and Stereospecific Reactions
- Hydrohalogenation of Alkenes and Markovnikov's Rule
- Hydration of Alkenes With Aqueous Acid
- Rearrangements in Alkene Addition Reactions
- Halogenation of Alkenes and Halohydrin Formation
- Oxymercuration Demercuration of Alkenes
- Hydroboration Oxidation of Alkenes
- m-CPBA (meta-chloroperoxybenzoic acid)
- OsO4 (Osmium Tetroxide) for Dihydroxylation of Alkenes
- Palladium on Carbon (Pd/C) for Catalytic Hydrogenation of Alkenes
- Cyclopropanation of Alkenes
- 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
- Partial Reduction of Alkynes With Na/NH3 To Obtain Trans Alkenes
- Alkyne Hydroboration With "R2BH"
- Hydration and Oxymercuration of Alkynes
- Hydrohalogenation of Alkynes
- 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
15 Organometallics
- 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
16 Spectroscopy
- 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
18 Aromaticity
- 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 (PartĀ 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
- Transesterification
- 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
- Decarboxylation
- The Malonic Ester and Acetoacetic Ester Synthesis
- The Michael Addition Reaction and Conjugate Addition
- The Robinson Annulation
- Haloform Reaction
- The HellāVolhardāZelinsky Reaction
- Enols and Enolates Practice Quizzes
23 Amines
- 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
24 Carbohydrates
- 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
- A Gallery of Some Interesting Molecules From Nature
- 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
- On Cats, Part 4: Enantiocats
- On Cats, Part 6: Stereocenters
- Organic Chemistry Is Shit
- The Organic Chemistry Behind "The Pill"
- Maybe they should call them, "Formal Wins" ?
- Why Do Organic Chemists Use Kilocalories?
- The Principle of Least Effort
- Organic Chemistry GIFS - Resonance Forms
- Reproducibility In Organic Chemistry
- What Holds The Nucleus Together?
- How Reactions Are Like Music
- Organic Chemistry and the New MCAT
26 Organic Chemistry Tips and Tricks
- Common Mistakes: Formal Charges Can Mislead
- Partial Charges Give Clues About Electron Flow
- Draw The Ugly Version First
- Organic Chemistry Study Tips: Learn the Trends
- The 8 Types of Arrows In Organic Chemistry, Explained
- Top 10 Skills To Master Before An Organic Chemistry 2 Final
- Common Mistakes with Carbonyls: Carboxylic Acids... Are Acids!
- Planning Organic Synthesis With "Reaction Maps"
- Alkene Addition Pattern #1: The "Carbocation Pathway"
- Alkene Addition Pattern #2: The "Three-Membered Ring" Pathway
- Alkene Addition Pattern #3: The "Concerted" Pathway
- Number Your Carbons!
- The 4 Major Classes of Reactions in Org 1
- How (and why) electrons flow
- Grossman's Rule
- Three Exam Tips
- A 3-Step Method For Thinking Through Synthesis Problems
- Putting It Together
- Putting Diels-Alder Products in Perspective
- The Ups and Downs of Cyclohexanes
- The Most Annoying Exceptions in Org 1 (Part 1)
- The Most Annoying Exceptions in Org 1 (Part 2)
- The Marriage May Be Bad, But the Divorce Still Costs Money
- 9 Nomenclature Conventions To Know
- Nucleophile attacksĀ Electrophile
27 Case Studies of Successful O-Chem Students
- Success Stories: How Corina Got The The "Hard" Professor - And Got An A+ Anyway
- How Helena Aced Organic Chemistry
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- How to Do Well in Organic Chemistry: One Student's Advice
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- Guest post: "I went from being afraid of tests to actually looking forward to them".
Thanks for your response and input. (Also, MOC is an excellent website!)
Using BDE for C-H activation prediction (or for example to identify the weakest bond likely to be targetted by CYP450-mediated metabolism) makes perfect sense.
My question was already lengthy, but I was asking because in an enzyme-catalysed reaction, I (believe) I was seeing a thermodynamically uphill reaction, ie converting an alkyl ester of the ligand to the weaker phenol ester of a tyrosine residue on the enzyme, which by all intuition (pKa of phenol vs alkyl alcohol, delocalisation of charge by phenol, etc) should not occur.
Thinking along the lines of Hess’s law, I was hoping by using the BDE of all formed/broken bonds to get an idea of how unfavorable the delta enthalpy is (as enthalpy is path invariant), which could provide insights into the catalytic driving force. This is of course, all heterolytic cleavage and in water (easier to separate charges), but the correction factors for the homolytic BDE (Acc Chem Res, 2003) should be roughly the same for each bond-breaking/forming step.
A further wrinkle is that some of the products/reactants are cyclic, which has made predicting BDE’s unusual (usually you calculate the energy of the neutral radical fragments, but homolytic cleavage of a ring gives you one product, not two).
I was hoping to estimate the enthalpy of the reaction in the usual way (bonds formed minus broken) using BDEs, which for the acrylic analogues of the ester to phenyl ester (tyrosine) transesterification is +5.7 kcal/mol. There’s an entropy component (a small group is cleaved, ie 1 reactant -> 2 products), so I’m trying to get a rough idea of whether this transesterification is possible, perhaps a different residue is involved (serine/threonine), or perhaps I’m way off.
If using BDE values to validate/invalidate my hypothesis is a fool’s errand, please let me know! I’m in a synthetic/biology focused lab, not really physical organic, so I can’t quite tell if there is any utility to estimating the thermodynamics of the reaction, especially through BDE estimations.
BDE is the value of the homolytic cleavage, and I get that heterolytic reactivity can be far different than neutral radical mechanism (eg, it’s easier to separate charges in polar solution), but I’m not quite sure if I get how to apply that. Does that mean BDE–when considering heterolytic reactions, acid/base mechanism, etc–is limited, or useless, or outright misleading?
For example, if I was considering a transesterification reaction in water between para-cresyl acetate (CAS 140-39-6) and a benzyl acetate (CAS 140-11-4) and I know the BDE for the phenyl ester and alkyl ester (and the BDE of phenol/akyl deprotonation), would the BDE give me an idea of the favorability of the reaction? Is it possible for the reaction to reverse in this example where I tried to keep all else equal? Can it reverse in general? I get that reactions in solution may be different than breaking the lowest BDE-bond, but if we know the BDE of phenol vs alkyl O-H, can we assume this is the same? I’m also interested to know–in non/polar a/protic solvents, or for example, in the varied nonpolar and polar microenvironments of an enzyme–can we use BDE to compare a transesterification like the above or get any insight from the BDE?
I’m asking many questions ultimately to try to clarify my main question: is BDE comparison to polar/heterolytic reactions acceptable (ceteris paribus), limited, useless, or outright misleading? I did read the article (Acc Chem Res, 2003, p255) and while I get that it’s problematic/more work needs to be done, I don’t think it addresses my main question.
Hi Grant – sorry for late reply.
BDE’s are extremely useful when planning free-radical reactions. One example would be C-H oxidations of alkanes. One time we were planning a late-stage C-H oxidation on a carbon adjacent to an amide and in order to choose a proper oxidant it was helpful to compare its BDE with those of C-H bonds that underwent oxidation with various oxidants.
For a transesterification reaction, the mechanism will be heterolytic. Under basic conditions, your best proxy for deciding which ester is easiest to cleave will be the pKa of the corresponding alcohol. The more acidic the alcohol, the less basic its conjugate base will be, which will give you a fair idea of its ability to stabilize negative charge and thus act as a leaving group.
To give a simple exanple, it is much easier to cleave phenolic esters than it is to cleave the corresponding aliphatic ester. Even more so if the phenolic ester has attached electron-withdrawing groups that can help to stabilize negative charge.
So to answer your question, I would say, no, the BDE of the O-H bond is not going to tell you very much.
Thank you for your reply. The only solvent used is hexane, and the leaving group is supposed to be an “OH” radical that would result from the homolytic cleavage of the hydroperoxide moiety of the oxidized molecule. I am using a wide-range WL LED as a source of photons (I checked the purity of the compound prior to the start of the experiment, and it was above 99%). Under these conditions, is there a possibility that heterolytic cleavage would be more favored? or cleavage of the hydroperoxide moiety other than of the O-O bond (?) … from the analyses, there was no sign of hydroxyl or alkoxy radicals …
Thank you for the useful explanation. I have a question, I have been working on a photoinduced reaction, and during this reaction, I found that Heterolytic cleavage occurs rather than homolytic cleavage, the only energy source is photons, and there are no other reagents or catalysts in the solution. So, when is heterolytic cleavage more favored than homolytic cleavage? (given that the first requires more energy than the latter, I couldn’t find an explanation for this …)
It’s hard to give a good answer without seeing a picture of the reaction. What solvent are you using? Do you have a good leaving group present that might ionize?
I had a friend who was doing a reaction in a photobox with near-UV radiation and the solvent was CH2Cl2. Weird things happened. Turns out the light was generating HCl from CH2Cl2 and it was causing all kinds of polar reactions. Fun times
Wow! Thanks for the explanation. I wish our high school teachers taught this way!
This is soo helpful ššš
The materials have been very useful for me and my students. Congratulations on the incredible job.
When atoms combine to form molecules, energy is released as covalent bonds form. The molecules of the products have lower enthalpy than the separate atoms.
You have a typo in the units of 3/4 of your CāH BDEs. They should all be kJ/mol. :-)
Boo! :-) kcal/mol all the way IMO. A C-H eclipsing interaction is about 0.9 kcal/mol and a C-H bond strength is about 100 kcal/mol. So easy to remember, like the Celsius scale.
Really well presented!! (*Applause!)
Thank you, glad you found it helpful.
Hello,
I just want to make sure I am understanding this article right…So the tertiary bonds of a organic molecule will have the lowest bond dissociation energies because they produce the most stable radicals (tertiary radical)? Thanks!
That is correct!
Thank you! Very helpful!
Glad you found it useful, Sean.
Just found a typo “stabiliity” in the PPS.