Reaction Friday: Friedel Crafts Acylation
Today’s Reaction Friday is about the Friedel Crafts acylation of benzene and other aromatics, an important example of electrophilic aromatic substitution.
One thing I forgot to say at the bottom is that there’s several different ways of showing how the acyl halide is activated by Lewis acid – the convention I drew is common, but your textbook may vary. Also, for the final deprotonation, it’s also possible to show Cl(-) as the base to remove the proton from the carbocation, rather than the Fe-Cl bond.
Chapter 00 A Primer On Organic Reactions
- Leaving Groups Are Nucleophiles Acting In Reverse
- What Makes A Good Nucleophile?
- Nucleophilicity vs. Basicity
- Nucleophiles and Electrophiles
- 7 Factors That Stabilize Positive Charge in Organic Chemistry
- Curved Arrows (2): Initial Tails and Final Heads
- 7 Factors that stabilize negative charge in organic chemistry
- Common Mistakes: Formal Charges Can Mislead
- The Third Most Important Question to Ask When Learning A New Reaction
- Curved Arrows (for reactions)
Chapter 01 Acid Base Reactions
- Putting Acidity In Perspective
- Acid Base Reactions: What's the Point?
- Acid Base Reactions Are Fast
- A Handy Rule of Thumb for Acid-Base Reactions
- Walkthrough of Acid-Base reactions (4) - pKa
- Walkthrough of Acid-Base Reactions (3) - Acidity Trends
- Walkthrough of Acid Base Reactions (2): Basicity
- Walkthrough of Acid Base Reactions (1)
- Introduction to Acid-Base Reactions
- How to Use a pKa Table
Chapter 02 Alcohols, Epoxides and Ethers
Chapter 03 Aldehydes and Ketones
- Weird Nomenclature In Carbonyl Chemistry
- On Acetals and Hemiacetals
- Imines and Enamines
- Acid Catalysis Of Carbonyl Addition Reactions: Too Much Of A Good Thing?
- Breaking Down Carbonyl Reaction Mechanisms: Reactions of Anionic Nucleophiles (Part 2)
- Breaking Down Carbonyl Reaction Mechanisms: Anionic Nucleophiles (Part 1)
- Carbonyls: 10 key concepts (Part 2)
- Carbonyl Chemistry: 10 Key Concepts (Part 1)
Chapter 04 Alkanes and Nomenclature
- Common Mistakes: Drawing Tetrahedral Carbons
- Don't Be Futyl, Learn The Butyls
- Hidden Hydrogens, Hidden Lone Pairs, Hidden Counterions
- Condensed Formulas: Deciphering What the Brackets Mean
- Table of Functional Group Priorities for Nomenclature
- Summary Sheet - Alkane Nomenclature
- The Many, Many Ways of Drawing Butane
- Meet the (Most Important) Functional Groups
- Common Mistakes in Organic Chemistry: Pentavalent Carbon
- Branching, and Its Affect On Melting and Boiling Points
Chapter 05 Alkene Reactions
- Synthesis (4) - Reactions of Alkenes
- Alkyne Addition Reactions - The "Concerted" Pathway
- Alkyne Addition Reactions: The 3-Membered Ring Pathway
- Summary: Alkene Reaction Pathways
- Alkene Reactions: Ozonolysis
- A Fourth Alkene Addition Pattern - Free Radical Addition
- An Arrow-Pushing Dilemma In Concerted Reactions
- Alkene Addition Pattern #3: The "Concerted" Pathway
- Hydroboration of Alkenes: The Mechanism
- Hydroboration of Alkenes
Chapter 06 Amines
Chapter 07 Aromaticity
Chapter 08 Bonding, Structure, and Resonance
- How to apply electronegativity and resonance to understand reactivity
- Drawing Resonance Structures: 3 Common Mistakes To Avoid
- In Summary: Resonance
- Exploring Resonance: Pi-acceptors
- Exploring Resonance: Pi-Donation
- Evaluating Resonance Forms (4): Positive Charges
- Evaluating Resonance Forms: Factors That Stabilize Negative Charges
- Evaluating Resonance Forms (2): Applying Electronegativity
- Evaluating Resonance Forms (1) - The Rule of Least Charges
- How To Use Curved Arrows To Interchange Resonance Forms
Chapter 9 Carbohydrates
Chapter 10 Carboxylic Acid Derivatives
- Simplifying the reactions of carboxylic acid derivatives (part 1)
- Summary Sheet #7 - 21 Carbonyl Mechanisms on 1 page
- Carbonyl Chemistry: Learn Six Mechanisms For the Price Of One
- Carbonyl chemistry: Anionic versus Neutral Nucleophiles
- Summary Sheet #5 - 9 Key Mechanisms in Carbonyl Chemistry
- How Reactions Are Like Music
- Let's Talk About the [1,2] Elimination
- Proton Transfers Can Be Tricky
- Carbonyl Mechanisms: Neutral Nucleophiles, Part 1
- The Magic Wand of Proton Transfer
can we know the catalyst molar ration and the exact electronic enviornment of the benzene ring substrte
This is more of a general introduction: on a practical basis, factors like catalyst ratio are going to be dependent on the exact substrate you’re using. I’d consult the references to Organic Syntheses contained in March’s Advanced Organic Chemistry.
I was reviewing Friedel-Crafts acylation this weekend actually and the book I was reading through made the point that H2O needed to be added afterward because the Lewis acid would wind up accepting electrons from the carbonyl if you didn’t. Is that a common step?
Also, if you do this in water, would the product actually be an enol?
It’s pretty standard procedure in organic chemistry to follow a reaction with an aqueous workup to remove salts, water-soluble byproducts, etc. so it’s kind of a moot point.
You wouldn’t want to do this in water with FeCl3 or AlCl3 because those Lewis acids will hydrolyze in that solvent – as will (importantly) the acid halide. There are ways to do it in water if absolutely desired, but generally it’s performed in organic solvents. Re: enolization, aromatic ketones will favor the enol form more than non-aromatic ketones, but the keto form still outnumbers the enol by at least (I’d guess) about 1000:1 or therabouts. Water would increase the rate of keto-enol interconversion but would not lead to dominance of the enol over the keto form.
Good questions
Is the reaction temperature should be at 0 degree Celsius for both benzene and Acyl chloride + FeCl3?
Just want to add some more info. on Friedel Crafts (F.C.)
To my knowledge:
All Activating groups are Electron Donating Groups (EDG) and are Ortho/Para directors.
Major product is Ortho, unless the Activating group or Electrophile is sterically hindered, then the Para is major product.
All Deactivating groups are Electron Withdrawing Groups (EWG) and are Para directors, except for Halogens. Halogens are Ortho and Para directors too, b/c Halogens can push electron density w/ resonance (lone pairs), making benzene rich in electrons at Ortho and Para positions.
All meta directing groups kill F.C. So N.R. Like an ex. in a video with NO2 group.
Resonance explains why Ortho, Para, or Meta attacks happen.
What are some reasons why acetylferrocene predominated in a Friedel Crafts reaction over ferrocene and diacetylferrocene? Some possible ways are that it was forced to completion (ferrocene) and that the tube wasn’t oven-dried (though I don’t see how the second is applicable).
what happens when you add 3 equivalent of aluminum chloride and 3 equivalent of acyl chloride on a benzene ring? do you pretty much form a benzene ring with three ketones attached two parra to each other and one ortho?
Under the normal conditions for this reaction which don’t involve any heating if you got a tri-substituted (or even a di-substituted) product at all it would be a minor product. If you managed to carry out three acylation reactions in succession though I’m sure they’d most likely be meta to each other.
PS. I love this reaction, even on thiophenes with activating groups on 3 and 4 positions I’ve still not got 2,5-polyacylation carrying out the reaction at ~ 10 degrees C
I am very glad that I came across your website for organic chem. I am studying it after a very long time and your mechanisms help me understand the rxns better.