Aldehydes and Ketones
Aldehydes and Ketones: 14 Reactions With The Same Mechanism
Last updated: September 25th, 2022 |
The Simple Two-Step Pattern For Seven Key Reactions Of Aldehydes And Ketones
“There are just so many reactions! I can’t remember all the mechanisms!!” – distressed organic chemistry student
Yes, yes there are a lot of reactions, particularly in second semester organic chemistry. But there is good news on this front: there is a tremendous amount of repetition in these reactions.
For instance, what if I told you that there was a simple, two-step pattern behind seven different reactions that each work for aldehydes and ketones? By learning this key pattern, you’d therefore know the mechanism for 7 × 2 = 14 different reactions.
That would be useful, right? Read on!
Table of Contents
- The “Two Step” Pattern For Addition Reactions To Aldehydes and Ketones
- The Generic Mechanism Behind This “Two Step” Pattern For Addition Reactions Of Aldehydes And Ketones
- A Table Showing How The “Two Step” Mechanism Is Applied In Reactions Of Aldehydes With Grignards, Organolithiums, NaBH4, LiAlH4, Cyanide Ion, Hydroxide Ion, And Alkoxide Ions
- So You Want The Mechanisms Of These Seven Reactions Drawn Out In Detail? OK
- The Grignard Reaction With Aldehydes And Ketones: Mechanism
- Addition of Organolithium Reagents To Aldehydes: Mechanism
- Reduction of Aldehydes and Ketones with Sodium Borohydride: Mechanism
- Reduction of Aldehydes and Ketones With LiAlH4 : Mechanism
- Addition of Cyanide Ion To Aldehydes And Ketones: Mechanism
- Addition Of Hydroxide Ion To Aldehydes To Form Hydrates (“geminal diols”): Mechanism
- Addition of Alkoxides To Aldehydes And Ketones To Form Hemiacetals: Mechanism
- Summary: The Simple Two-Step Pattern For Addition Reactions To Aldehydes And Ketones
- Quiz Yourself!
1. The “Two-Step” Pattern For Addition Reactions To Aldehydes and Ketones
The two steps are the following:
- Addition of a nucleophile to an aldehyde or ketone
- Protonation of the negatively charged oxygen with acid (often called “acidic workup”)
Here’s the general case for the reaction. I’ve drawn an aldehyde here, but everything I will say here also applies to ketones.
Pay attention. What bonds form, and what bonds break?
Hopefully you can see that a C–O (π) bond is being broken, a C–Nu bond is being formed, and an O–H bond is formed also.
Any mechanism we draw has to account for these bond-forming and bond-breaking events.
- Step 1 is addition of a nucleophile to the electrophilic carbonyl carbon. This forms C–Nu and breaks C–O (π), resulting in a negatively charged oxygen.
- Step 2 is addition of an acid (“protonation”), which results in formation of the O–H bond. This is generally done after the reaction with the nucleophile is complete – otherwise the acid would destroy the nucleophile, sometimes in violent fashion (e.g. LiAlH4 is not something you’d want to bring in close proximity to acid).
2. The Generic Mechanism Behind This “Two Step” Pattern For Addition Reactions Of Aldehydes And Ketones
Here’s the general mechanism. First comes addition of the nucleophile, and second comes protonation of the resulting alkoxide.
That’s it for the general example. Now let’s get to specifics.
3. A Table Showing How The “Two Step” Mechanism Is Applied In Reactions Of Aldehydes With Grignards, Organolithiums, NaBH4, LiAlH4, Cyanide Ion, Hydroxide Ion, And Alkoxide Ions
This two-step pattern is behind the following seven reactions:
Again, although aldehydes are pictured here, the reaction applies equally well to ketones. So this represents fourteen reactions that proceed through this two step mechanism.
These types of mechanistic patterns are a little bit like Hollywood movies: there’s only so many different kinds of plot elements, and they repeat. If you’re familiar with the Hero’s Journey, you’ll recognize a lot of similarities between Star Wars: A New Hope and Happy Gilmore, even though the latter film is ostensibly about a hockey goon turned professional golfer. Likewise, the number of discrete mechanistic steps you will learn in organic chemistry could be counted on your fingers and toes.
Hope you find this useful.
4. So You Want The Mechanisms Of These Seven Reactions Drawn Out In Detail? OK
Wait. You want specifics? Like, each reaction written out individually, with a general example, a specific example, and then a mechanism?
That sounds like overkill. But this is MOC. Overkill is what we do here.
Here’s each of those seven reactions treated individually.
5. The Grignard Reaction With Aldehydes And Ketones: Mechanism
The Grignard reaction is the addition of an organomagnesium compound to a carbonyl species. Recall that carbon is significantly more electronegative (2.5) than magnesium, so the partial negative charge is on carbon. In this example I used R-MgBr, although other halides (Cl, I) also work. Also, in the acid workup step I showed the spectator anion for H3O+ which is generally not necessary, but I like to balance the charges so you can see all the byproducts.
6. Addition of Organolithium Reagents To Aldehydes: Mechanism
For our purposes, essentially the same as the Grignard reaction for aldehydes and ketones.
7. Reduction of Aldehydes and Ketones with Sodium Borohydride: Mechanism
In the borohydride anion (BH4–) it’s important to remember that hydrogen has a higher electronegativity (2.2) than boron (2.0). This means that although boron has the negative “formal” charge, the partial charges are on hydrogen. Hence, it’s the hydrogen that acts as a nucleophile [technically, “hydride” (H–) ].
The mechanistic pattern is the same – addition to carbonyl carbon, followed by protonation of oxygen.
In practice, reduction with NaBH4 is often run at low temperature with methanol as a solvent, with the subsequent workup step being addition of a mild acid such as NH4Cl to ensure full protonation of the alkoxide.
8. Reduction of Aldehydes and Ketones With LiAlH4 : Mechanism
Everything I said above with respect to NaBH4 applies to LiAlH4 which is also a source of nucleophilic hydride. On paper, NaBH4 and LiAlH4 are equally effective in performing the reduction of an aldehyde or ketone to an alcohol. In practice, LiAlH4 is a much stronger reductant that will also reduce esters and carboxylic acids to alcohols. NaBH4 will not. Using LiAlH4 to reduce an aldehyde or ketone is like using a sledgehammer to kill a fly.
9. Addition of Cyanide Ion To Aldehydes And Ketones: Mechanism
Addition of cyanide ion (CN –) to aldehydes and ketones will result in a cyanohydrin. On paper, this also follows the two-step sequence of addition-protonation, although in practice the reaction can be run in the presence of a proton source such as H2O; unlike Grignards and some hydrides, cyanide ion is only weakly basic and will not be irreversibly destroyed by protonation. [In practice, however, care must be taken not to lower the pH too much; that may result in the formation of deadly HCN gas. ]
A related process, the Strecker synthesis of amino acids, begins with the addition of cyanide ion to an imine.
10. Addition Of Hydroxide Ion To Aldehydes To Form Hydrates (“geminal diols”): Mechanism
Hydroxide ion will add to aldehydes or ketones to form hydrates, the mechanism of which also follows the two-step pattern. In practice, this doesn’t involve a separate workup step; hydroxide ion would be administered with at least some water as a co-solvent.
One thing to know about hydrates, however; they aren’t easily isolated, except for cases where the carbonyl is adjacent to an electron withdrawing group, such as in the case of chloral hydrate (a solid)
11. Addition of Alkoxides To Aldehydes And Ketones To Form Hemiacetals: Mechanism
Last example. Addition of alkoxides to aldehydes and ketones will result in the formation of a hemiacetal.
12. Summary: The Simple Two-Step Pattern For Addition Reactions To Aldehydes And Ketones
There’s probably nobody reading by this point, but I would just remind those who are left of the tremendous importance of breaking down reactions into key steps of bonds formed/bonds broken and paying attention to how they build up into patterns. They save you a lot of work!
22 thoughts on “Aldehydes and Ketones: 14 Reactions With The Same Mechanism”
Excellent post, as usual, but there is a little devil in several details:
– in the second scheme, the generic Nu suddenly turns into a methyl; please keep the reaction general;
– in the Appendix section, in some general reactions, the nucleophile is not depicted in blue, and there is one case (reaction 1) when you have two R’s (which can depict two different moieties) in the product; see reactions 1, 3, 4, 5 (in the last case also in the specific example).
Thank you so much. I wish I could pay you.
Excellent post, as usual, but there is a little devil in several details
Thanks. Could you be more specific?
I was really confused as to how to form the products of aldehyde and ketone reactions. This article helped me a lot. Thank you so much!
I’m really glad this helps Sanskriti.
Why can’t also condensation occur with hydroxide ion?
This specific post is about a simple reaction pattern.
Excellent post. I will share this with my student who is relearning organic after a 50 year break! He memorized his way 50 yrs ago and this time we are going after understanding. I really like what you’re doing
Thanks Tulip! I appreciate it!
I just want to say, thank you so much for building this website. A real godsend.
This thing really helped a lot in my studies. Your works are smart and simple. Keep on going.
Glad you find it helpful Vidhu.
This website is very helpful 😊. Thanks a lot. Expecially for Organic Chemistry
How would it be able to site this if it is used for laboratory work (only the mechanism)
Thise staff has really helped me to realize my potentiality in chemistry of aldehydes and ketones,,I wish I could pay you.thanks alot,be blessed.
In the case of alkoxides, wouldn’t the reaction continue to form acetals and ketals? Good post, anyway; MOC’s been such a great help.
To form acetals and ketals you need acid catalysis. The problem with base is that your leaving group would have to be O(2-) which is a terrible leaving group.
Okay, so we need an acid to catalyse the reaction so that it’s an OH, and it further gets protonated and gets off of the molecule. This wouldn’t happen with a base, I get that. But your mechanism specifies an acid work-up, so wouldn’t an acetal form?
Good question! A “workup” is usually a brief, room temperature treatment with acid that is sufficient to neutralize any strong bases present. In order to fully form the acetal, however, you have to heat with acid in the presence of an excess of alcohol, and also sequester the H2O that forms en route to the acetal. So the reaction conditions are significantly different.
Thnx a lot mate , just revised my rexns quickly here . Cheers !
This helped me remember most of the reactions quickly, Amazing website