"Master Organic Chemistry" Note - this sheet is not meant to be comprehensive.

Your course
Key Reactions of Aldehydes and Ketones masterorganicchemistry.com may provide additional material, or may not cover some of the
reactions shown here. Your course instructor is the final authority.

A Simple "Formula" for Seven Key Reactions of Aldehydes & Ketones What factors affect the reactivity of Synthesis of Aldehydes and Ketones (continued)
aldehydes and ketones?
Bonds Bonds 1. Electronic effects
O OH Formed Broken Oxymercuration of alkynes
1. "Nucleophile" In aldehydes and ketones, the C=O bond is polarized; due to the greater
C–Nu C–O ( π ) electronegativity of oxygen relative to carbon [3.4 vs. 2.5]; the carbon bears a
R H 2. Protonation R H partial positive charge and the oxygen bears a partial negative charge O This adds water to the more substituted
Nu Hg(OAc) 2 end of the alkyne, forming an enol, which
Aldehyde ( but O–H R H then tautomerizes to the ketone.
δ– H 2O, H 2SO4 R
also applies to ketones) The oxygen is electron-rich (nucleophilic)

↑
O
Reaction Nucleophile Product δ+
OH Ozonolysis of alkenes

↑
R H The carbon is electron-poor (electrophilic)
Grignard Reaction R MgX
R H O O Ozonolysis cleaves C–C π bonds.
R 1) O 3
Most of the reactions of aldehydes and ketones involve an electron-rich H If a "reductive workup" is used,
nucleophile forming a bond with the electron-poor electrophile that is the 1
2
3 2) Zn 2 H 3 C–H bonds attached to the alkene
OH carbonyl carbon of the aldehyde or ketone. 1 4
are preserved, leading to aldehydes.
Addition of Organolithiums R Li 4
or CH 3SCH 3
R H The more electron-poor the aldehyde or ketone, the more reactive it will be
R with nucleophiles this is "reductive workup"
OH Oδ
– Oδ
–
Reduction by sodium
Na H–BH3 R H δ+ δ+ Other Key Reactions of Aldehydes and Ketones
borohydride (NaBH4) H F 3C H H 3C H
more electrophilic less electrophilic
Hydration Water will add to aldehydes and
OH this aldehyde is more electron-poor than the aldehyde on the right due to the
Reduction by lithium electron-withdrawing fluorines ketones to give hydrates.
O H 2O Equilibrium favors the starting
aluminum hydride (LiAlH4) Li H–AlH3 R H HO OH
H aldehyde/ketone
2. Steric effects R H R H The reaction is made faster by acid.
Addition of cyanide ion to OH The larger the group adjacent to the carbonyl carbon, the more difficult
form cyanohydrins CN Hydrate
R it will be for nucleophiles to attack. This is referred to as steric hindrance.
H
NC O O O O Hemiacetal
formation Alcohols will add to aldehydes/ketones
< < <
OH to give hemiacetals.
H H H 3C H H 3C CH3 H 3C O ROH
Addition of hydroxide ion RO OH Equilibrium usually favors the starting
to form hydrates OH R aldehyde/ketone, except in cases where
H Most reactive
HO Least reactive R H R H a ring is formed.
Aldehydes are more reactive than ketones largely for this reason. Hemiacetal The reaction is made faster by acid.
OH
Electron withdrawing groups on the
Addition of alkoxide ions OR R 3. Acid catalysis Acetal formation aldehyde favor hemiacetal formation
to form hemiacetals H
RO
When acid ("HX" is added to an aldehyde or ketone it can make the carbonyl carbon O Treatment of an aldehyde or ketone
R–OH RO OR
more electrophilic (and thus more reactive) with an alcohol in acid leads to an
Each of these reactions follows a "two-step" pattern: 1) addition 2) protonation
R H R H acetal. The acetal can be removed
Protonation of oxygen makes H X
How to draw the mechanism for this pattern: H H this resonance form more Acetal by heating with aqueous acid.
Step 1 is donation of a lone pair of electrons from the nucleophile to the carbonyl O H–X O O
significant than it normally would
carbon, which bears a partial positive charge [oxygen is more electronegative than be, and therefore there is a
R H R H R H Acetals as protecting groups
carbon]. A bond forms between the nucleophile and carbon, and the carbon-oxygen greater positive charge on
double bond [π bond] breaks. The oxygen then bears a negative charge. carbon in the resonance hybrid RMgBr, RLi, RO, OH,
RO OR NaBH 4, LiAlH 4, PCC, etc.
bottom line: carbon is more electrophilic no reaction
Step 1: Addition of nucleophile A R H
δ– The only "catch" with using acid to accelerate a reaction is that it can't be used with Acetals only react with aqueous
Bonds formed Bonds broken acid. So forming an acetal is a method
O O strongly basic nucleophiles, because it will protonate them irreversibly. For instance using
of "masking" a carbonyl group.
δ+ C–Nu C–O (π) strong acid to accelerate a Grignard reaction would not work because Grignard reagents
R H R H are strong bases; once protonated, they can't be regenerated.
Nu Imine formation
Nu Acid catalysis works well with neutral nucleophiles like H 2O, ROH, and amines, and also R Aldehydes/ketones treated with
with weakly basic nucleophiles like CN O R–NH 2 N
a primary amine will give imines.
Step 2: Protonation of oxygen P
R H R H Mild acid can be used to promote
In the second step of this reaction, acid is added the oxygen is protonated Synthesis of aldehydes and ketones this reaction
to give a neutral hydroxyl [O-H] group: + H 2O
Through oxidation of alcohols
O H OH Enamine formation
OH O Secondary alcohols can also be oxidized Aldehydes/ketones treated with
R H R H PCC O
Nu Nu to ketones with oxidizing agents such as H 2CrO 4 R 2NH NR 2 a secondary amine give enamines.
and others. R CH3 Acid catalyzes their formation.
PCC = pyridinium chlorochromate H X CH2
Specific example: Grignard addition + H 2O
Step 1: Addition of nucleophile Step 2: Protonation O PCC is a mild oxidant that does not oxidize Wittig Reaction
OH PCC R
R the aldehyde further to the carboxylic acid O Ph 3P=CH 2 CH2 Treatment of an aldehyde/ketone
MgBr H with a phosphorus ylide leads to
O O H OH R H R H formation of an alkene. This is
X
MgBrX the Wittig Reaction.
R R Hydroboration of alkynes + Ph 3P=O
R H H H
BrMg CH3 H 3C H 3C
This first forms the enol, which then tautomerizes
1) R 2BH O to the aldehyde.
R H R Omissions, Mistakes, Suggestions? This sheet copyright 2019
draw the arrow as coming 2) H 2O 2
from the Mg–C bond H James A. Ashenhurst
james@masterorganicchemistry.com masterorganicchemistry.com