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Nucleophilicity vs. Basicity
Last updated: December 8th, 2022 |
Understanding The Differences Between Nucleophilicity vs Basicity
Following up on Nucleophiles and Electrophiles, here’s a common question students have about nucleophilicity:
1. What’s the difference between nucleophilicity and basicity?
Great, great question.
First of all, remember that basicity is a subset of nucleophilicity. All nucleophiles are Lewis bases; they donate a lone pair of electrons. A “base” (or, “Brønsted base”) is just the name we give to a nucleophile when it’s forming a bond to a proton (H+). To summarize, when we’re talking about basicity and nucleophilicity, we’re talking about these two types of events.
- Basicity: nucleophile attacks hydrogen
- Nucleophilicity: nucleophile attacks any atom other than hydrogen. Because we’re talking about organic chemistry here, for our purposes, this is going to mean “carbon” most of the time.
2. Nucleophilicity vs Basicity: What Is A Base?
So how do reactions of nucleophiles at hydrogen differ from reactions of nucleophiles at carbon? Well, they’re more easily reversible, for one thing. We can measure acidity (and, by extension, basicity) through the measure known as pKa, which is a reflection of the position of the equilibrium between an acid and its conjugate base.
Let’s put it up in a graphic:
Because we can measure the equilibrium constants for reversible acid-base reactions, we can get a fairly good idea of the relative strengths of acids and bases. There’s some complications; solvent effects can play a role in stabilities, for instance* but overall, the pKa table is our friend. It’s a great “reactivity ladder” to hang our hats on.
We talked about what made species strong bases a few posts ago – it’s here. The bottom line is that the more unstable a lone pair of electrons is, the more basic it will be (and vice versa).
3. Nucleophilicity vs Basicity: What Is A Nucleophile?
And then there’s nucleophilicity. How is nucleophilicity different from basicity? Well, since it’s not limited to simply forming a bond to hydrogen anymore, this leads to some extra complications. Let’s just talk about the measurement problem first.
Many reactions of nucleophiles are not reversible. A bond forms, a bond breaks, and that’s the end of the reaction. The problem with this from a measurement standpoint is that we often can’t determine an equilibrium constant for a reaction. And if we can’t do that, then we can’t develop a reactivity scale based on equilibria.
If we can’t measure equilibria, then what do we do? Well, we use the next best measurement available: to measure reaction rates.
There’s one important thing to remember with reaction rates. They don’t always reflect overall stability. There are a few more variables at play here.
- Factor #1: Steric hindrance. Reactions where nucleophiles attack carbon-based electrophiles are significantly more sensitive to steric effects, because empty orbitals on carbon are not as accessible. Steric hindrance is like a fat goalie.
- Factor #2: Solvents. The medium (solvent) in which a reaction takes place can greatly affect the rate of a reaction. Specifically, the solvent can greatly attenuate (reduce) the nucleophilicity of some Lewis bases through hydrogen bonding.
Again, let’s go to the graphic:
Here’s another question that comes up. How do you know when something is going to act as a base, and when it’s going to act as a nucleophile? Another great question!
Like the prototypical three-handed economist, I’ll tell you that it depends upon what type of reaction you’re talking about. Acid-base reactions tend to be fast, relatively speaking. But it will greatly depend on the situation. More soon, I assure you.
Next: So what, specifically, makes something a good nucleophile?
Next post: What Makes A Good Nucleophile?
Notes
Related Articles
Note 1. (for more advanced readers) For instance, alcohols are dramatically less acidic in dimethyl sulfoxide [DMSO] than they are in water, and since many pKa values for less acidic species are given in DMSO, it’s easy to misjudge the acidity of alcohols relative to other species.
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 (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
- 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 Hell–Volhard–Zelinsky 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 attacks 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
- From a "Drop" To B+ in Org 2 – How A Hard Working Student Turned It Around
- How Serge Aced Organic Chemistry
- Success Stories: How Zach Aced Organic Chemistry 1
- Success Stories: How Kari Went From C– to B+
- How Esther Bounced Back From a "C" To Get A's In Organic Chemistry 1 And 2
- How Tyrell Got The Highest Grade In Her Organic Chemistry Course
- This Is Why Students Use Flashcards
- Success Stories: How Stu Aced Organic Chemistry
- How John Pulled Up His Organic Chemistry Exam Grades
- Success Stories: How Nathan Aced Organic Chemistry (Without It Taking Over His Life)
- How Chris Aced Org 1 and Org 2
- Interview: How Jay Got an A+ In Organic Chemistry
- How to Do Well in Organic Chemistry: One Student's Advice
- "America's Top TA" Shares His Secrets For Teaching O-Chem
- "Organic Chemistry Is Like..." - A Few Metaphors
- How To Do Well In Organic Chemistry: Advice From A Tutor
- Guest post: "I went from being afraid of tests to actually looking forward to them".
Great work Mr. James. But I still have a question, can you please explain how to check nucleophilicity and basicity simultaneously? Like i was studying substitution and elimination reaction and came through that I- is a very good nucleophile but a weak base, similarly RO- and HO- are good nucleophiles and strong bases as well, or Cl- is a fair nucleophile but a weak base. LIKE HOW? I AM CONFUSED AND CONFUSED FOR ALMOST A MONTH. Can you please explain in detail? It will be of great help. Thank You!
Basicity, for our purposes, involves the reaction of a lone pair with H (proton).
Nucleophilicity, for our purposes, involves the reaction of a lone pair with *any atom other than H*, by which we usually mean *carbon*.
The biggest difference is that when a lone pair is attacking any atom other than H, it generally has to be to an empty orbital, which is most often an antibonding orbital (e.g. sigma star) like it is with the SN2 reaction.
And that means approaching the backside of the C-X bond (where X is a good leaving group) which means that it can be *much* more subject to steric interactions (i.e. bulkiness).
Anything which affects steric bulk around the base is going to affect its nucleophilicity. Solvent is a perfect example – you’ve probably learned the difference between polar protic and polar aprotic solvents. The more hydrogen bonding there is around a base, the less nucleophilic it will be.
Thank you sir🙏 for genuine and easy explanation of concept .
Can you please tell me the directive infulence in trisubsituted aromatic system?
Hard to generalize too much, but generally speaking the most activating substituent will “win”. Also, putting a substituent on a C-H ortho to two substituents tends to be disfavored. Can’t be more specific other than to say the old, “it will be mixture of steric and electronic facgtors”.
What if the two groups, -OH alcohol (tert position) and -COOH (primary position), present on the same molecule, then which one would be better nucleophile?
I think, in aprotic solvents, -OH group would be good nucleophile than -COOH.
If we are comparing neutral OH with neutral COOH, with equal steric hindrance, then the stronger nucleophile would be the group that is the most basic.
It is easier to protonate R-OH to R-OH2 (+) than it is to protonate R-CO2H to R-CO2H2 (+). We know this because the pKa of protonated R-OH is about -2.2 (CH3-OH2+) and the pKa of protonated R-CO2H is about -7.7 (Ph-CO2H2 + ) Source: http://evans.rc.fas.harvard.edu/pdf/evans_pKa_table.pdf
If there is significant difference in steric hindrance then this would affect the relative nucleophilicity to some extent. You are correct that protic solvent would retard the nucleophilicity of both these species, and polar aprotic solvent would augment it.
Indicate which reagents in the pair is expected to be more nucleophilic towards ch3br in ethanol and why ?
1) ch3oh or ch3sh
What are the key nucleophilicity trends as one descends the periodic table?
In very first line , you start with saying ‘Basicity is subset of Nucleophilicity’…And in the next line you wrote ‘All Nucleophiles are Lewis base’…..Your both statements produce contradiction against each other.
Should be interpreted as “bronsted basicity is a subset of nucleophilicity”.
Hi there. Can you please help me in my confusion? In a case, where I am given a tertiary alkyl and H2O. How do I know if the H2O will be acting as a base and undergo elimination or, acting as a nucleophile and undergo substitution? Thanks!
I assume you mean that you have a tertiary alkyl halide, in the presence of H2O. The first step will be loss of halide ion to give a carbocation. What happens next could either be attack of the carbocation by water (SN1) or deprotonation adjacent to the carbocation to give an alkene (elimination – E1). Both pathways will occur. However in my experience the elimination pathway is generally only going to be the major product if the reaction also mentions “Heat”.
Does basicity of a compound has anything to do with its size or steric factor? Because anything it has to do is just to take out a proton from a molecule.?
The pKa of t-BuOH is about 18 versus 16 for methanol, so for a first-order analysis, no. However, as always, “it depends”. There are certain reactions (e.g. elimination) requiring base that can undergo different pathways with bulky bases than with non sterically hindered bases. See: https://www.masterorganicchemistry.com/2012/10/24/bulky-bases-in-elimination-reactions/
Great help .. I have a question that in secondary alkyl cyanide can substitution or elimination can occur in the presence of CH3COONa+CH3COOH? Plz give me good explanation for it. I m counting on you. Plzzzzzzz
Hi, im wondering how to order these nucleophiles here: NEt3, PEt3 and pyridine. As you already told, PEt3 is surely more nucleophile than NEt3. But what about pyridine? Is it more nucleophile than PEt3 due to steric hindrance?
the nitrogen in pyridine is sp2 hybridized, which means it has a higher effective electronegativity and thus should be less nucleophilic than NEt3. The order is PEt3 > NEt3 > pyridine
Hi ! In your first example why is N in NH3 donating its lone pair to water? Why can’t water donates its lone pair to bond with H in NH3 ?
Very conceptual question… Hopefully this will clear it up!
O being more electronegative than N, makes the lone pair in water less available for donation as compared to the lone pair in NH3. This makes NH3 a better base than H2O. Conversely, H2O is a stronger acid than NH3, because O is more electronegative than N, thereby making the O-H bond easier to break as compared to the N-H bond. The two facts combined make sure that NH3 de-protonates H2O and not the other way around.
You’ve thought through this correctly. Good job.
In some reactions a good nucleophile is desired while in other a good base….
Give me the reason Also tell why is hydroxyl ion a good base but not a good nucleophile?????
Short and precise explanation about the difference !!Thank you
Pls tell the order of nucleophilicity of the anions and mention the reason : PhO-, PhS- , o-,p- dinitroPhO-, p-nitroPhO-
You can describe basicity as a thermodynamic process (acid-base equilibrium exists and an equilibrium constant can be measured) while nucleophilicity is considered a kinetic process where rate of reaction can be evaluated.
Trying to make my daughter to understand organic chemistry (being a student in pharmacy) it was a great help.Thank you.
Dennis
Hey! but here I don’t find about flipping!!! I have heard that flipping affects the basicity
Flipping??
Which is a stronger nucleophille R3P or R3N?
In general how do i find out which is a stronger nucleophille?
Going down the periodic table, the electrons will be held more loosely, phosphorus should be more nucleophilic than nitrogen just like sulfur is more nucleophilic than oxygen.
Hi! What about the basicity of R3P and R3N? Also can you please provide examples of species which are good nucleophiles but bad bases and vice versa.
To James:
I think you mean “nucleophillicity is a subset of bases”, since all nucleophiles are bases;
like {1,2} is a subset of {1,2,3}, since all of {1,2} is a part of {1,2,3}.
Please check and revert.
(Apologies if this sounds like nitpicking)
Parakh
What I meant was that Bronsted basicity is a subset of nucleophilicity, if we consider “nucleophilicity” to be synonymous with Lewis basicity.
so nucleophilicity is the same as lewis basicity?
please say yes, that clears up a lot of stuff!! :P
I don’t feel comfortable saying there is 100% overlap.
Nucleophilicity is measured by rate, Lewis basicity can be measured by equilibria given the right conditions.
hi, WHEN comparing the basicities of OH- and CN-, Which is more basic?
as for my argument the negative charge on oxygen is well stabilised compared to the negative charge on nitrogen as O is more electronegative so it better stabilises the negative charge so CN- is a stonger base?? is this a possible explanation??
The best guide to basicity is by looking at a pKa table. The pka of water is 15.5, the pka of HCN is about 9. The stronger the acid the weaker the conjugate base, and since HCN is a stronger acid, its conjugate base (CN-) will be a weaker base than the conjugate base of H2O (HO-).
it is better to understand why something is a stronger acid/base than to refer to a table of pka. when a student is first learning the subject, if they continuously refer to the table the will never learn that it has to do with electron density, location, and movement. telling them to refer to a table only stunts their growth of knowledge.
This was not a clear cut example where one could point to periodic trends. If the student was asking about -CH3 vs -OH, then that’s clearly a situation where one can mention a factor like increasing electronegativity across the periodic table leads to a decrease in basicity.
However with nitrogen being coordinated to C in -CN using that principle, they would draw the wrong conclusion.
Because multiple variables are in play [we are changing the basic atom as well as the substituents connected to that atom] the only recourse is to check a pKa table because the effect of changing two variables at once is not easily predictable.
This site is not deficient in describing why certain species are stronger acids and bases according to a set of principles.
I have a whole series of articles where I discuss acidity trends and refer to electronegativity, polarizability, resonance, adjacent electron withdrawing groups, and even aromaticity.
The point of the current article is to mention that basicity is measured by pKa – it is an equilibrium – whereas nucleophilicity is measured by rate. So only a brief treatment of basicity was given here, with reference to the series on acid-base reactions.
I like your explanation. If pKa is an equilibrium description that makes it thermodynamic in nature; nucleophilicity is a description of a rate, which makes it kinetic behavior. Kinetic and thermodynamic properties tend to push in similar directions- except in those cases where they don’t!
True enough!
But cn- is a good nucleophile than oh-
On basis of electonegativity
Is this correct??
There’s a lot of factors that go into the nucleophilicity of a species, not just electronegativity.
You are correct in all of your assumptions. O being more electronegative would make it the weaker base IF the N was holding the negative charge however, the base you listed actually has the negative charge on the carbon molecule, so in this case your comparison is not applicable. if you change your comparison to NH2- and OH- your logic applies.
hi. regarding nucleophilic attack by hydride on aldehydes and ketones, why can’t reaction happen with NaH just because NaH is too basic? What is the link between being too basic and the hydride in NaH not being able to carry out the nucleophilic attack?
Thank you.
That’s a great question. NaH is generally not observed to add to aldehydes and ketones, although it will add to Lewis acids such as borane (BH3). You can think about the rates of competing reactions – 1) addition of hydride to aldehyde (slow) versus 2) deprotonation of the alpha-carbon by hydride (fast) and the latter reaction prevails.
NaH acts as a non nucleophilic base so basically involves in deprotonation rather in addition of the hydride to the carbonyl.In general all non nucleophilic base acts by the same mechanism.
Hi. I am wondering about the difference between nucleophicity and basicity,
but here on your resources i don’t seen such type wondering difference between electrophilicity and acidity, so, give a difference about that….
Thank you for all great resources.
Greetings.
Good question. Lewis acidity is essentially electrophilicity. Acidity (Bronsted acidity) is what we call it when the electrophile is a proton.