Compound Structure
Carbonyl Fundamentals
Aldehyde
(All information and examples borrowed from Chem. 14D Thinkbook for Fall
2006, Dr. Hardinger’s Lecture Recordings and Paula Yurkanis Bruce’s
Organic Chemistry 4th edition, unless otherwise indicated)
 Carbonyl- the functional group is comprised of a carbon atom
double-bonded to an oxygen atom (C=O). The various types of
carbonyl containing functional groups are listed in the table on the
right.
 Carbonyls can function as both a nucleophile and an electrophile.
 The polarity of the carbon-oxygen bond causes there to be a
partial positive charge on the carbon atom and a partial
negative charge on the oxygen atom. This electron-deficient
carbon atom acts as an electrophile.
 The carbonyl group can also act as a nucleophile. The oxygen
of this functional group is electron rich because of its lone
pairs and the pi bond. Nucleophilic attack on another
molecule by the lone pairs on oxygen or by the pi bond give
the same result because the products are resonance structures
and thus identical.
 Three C=O Fates
 Accept nucleophile at carbon



Occurs in ALL Carbonyl addition mechanisms
Produces tetrahedral adduct which occurs when the
carbonyl carbon goes from sp2 to sp3 hybridization.
Depending on if there is a leaving group attached to
the carbonyl carbon there are two possibilities for the
product of a nucleophilic attack on the carbonyl
carbon.
Ketone
Carboxylic
Acid
Ester
Amide
Primary,
Secondary,
Tertiary
(shown)
Enone
Acetyl
Chloride
Acetic
Anhydride
Table Note: Imines are not included in this table
however they have similar chemistry to aldehydes
because the functional groups share many
similarities. Both contain a pi bond between a
carbon and heteroatom. In addition both can
undergo the three fates: nucelophilic attach,
electrophilic attach, and enolate formation.
Table Diagrams: www.wikipedia.org
o Addition: no leaving group (LG) present.
Occurs with aldehydes and ketones since alkenes and hydrogen are not LGs.
• The first step involves nucleophilic attack on the partially positive carbon
atom to create the tetrahedral adduct resulting in an oxygen with a formal
positive charge. The oxygen is then protonated to create an alcohol.
Diagram Taken From: http://www.chemhelper.com/nucadd.html
o Nucleophilic Carbonyl Substitution: LG is present. Occurs with ester, amide,
anhydride, and acid chloride functional groups.
Diagram Taken From: http://chemistry2.csudh.edu/rpendarvis/carboxder.html
 Accept electrophile (usually H+) at oxygen
 There are two possible sites for nucleophilic attack of the carbonyl on an electrophile:
the lone pairs and the pi bond.
 Is there a preference for the electrophile (usually H+) to be accepted by the lone pair or
the pi bond? No. Both sites are nucleophilic and both lead to the same product through
resonance.
 Form Enolate
 Assisted by resonance stabilization of conjugate base
 Initiated by a base deprotonating the carbon adjacent to the C=O carbon.
Diagram From: http://www.chem.leeds.ac.uk/People/CMR/labstuff/litreviews/carbonylchemistry.doc
 How do we determine the rate of a C=O reaction?
o The rate determining step (rds) is the slowest step of the reaction, the step with the
highest energy of activation. This is the step that controls the rate of the reaction.
o In order to determine the rate determining step of the C=O, we must use its
mechanism.
o Proton transfers are usually not the rate-determining step so we can ignore them for
our analysis.
o Nucleophilic attack on the C=O is usually the RDS.
 What factors control the rate of nucleophilic attack on C=O? (in order of importance)
1) Magnitude of δ+ on the carbonyl carbon: A larger δ+ makes the carbonyl group
more electrophilic, nucelophilic attack will occur faster as a result.
2) Resonance: Resonance can increase or decrease the δ+ on the carbonyl carbon.
Resonance may also be lost when the tetrahedral adduct is formed. Resonance adds
extra stability to the molecule. As Dr. H put it, “Resonance is like money. Molecules
that have it want to keep it and molecules that don’t have it want to get it.”
Therefore, if resonance is lost the energy of the transition state is higher since the
molecule is less stable. This will make the molecule more resistant to nucleophilic
attack. As a general rule, resonance between atoms in the same row of the periodic
table is stronger than resonance between atoms that are in different rows.
3) Leaving group: The presence of a good leaving group controls whether addition or
substitution occurs. (Study the mechanisms for addition and substitution to better
visualize this concept).
4) Steric effects: If there are large groups attached to the carbonyl carbon the
nucleophile may be sterically hindered from attacking the carbonyl carbon and thus
nucleophilic attack will be slowed because the carbon is blocked.
 What to think about when asked to identify the fastest reaction relative to other
reactions:
o Look for differences between the reactions, considering similarities will not help in
your analysis.
o Analyze each of the four factors

Examining nucleophilic addition and nucleophilic substitution in the various carbonyl
containing functional groups
•
As mentioned before, the presence of a good leaving group determines if
nucleophilic addition or nucleophilic substitution will occur. With that in mind, when
observing the various carbonyl containing functional groups, aldehydes and ketones
will undergo nucleophilic addition since alkenes and hydrogen are not good leaving
groups. By the same logic, thiolester (R-C-O-S-R), ester, amides, and carboxylate
ion (R-C-O-O-) can undergo nucleophilic substitution since they contain good
leaving groups.
•
Nucelophilic addition reactivity for aldehydes vs. ketones

Considering the four factors mentioned in the previous section:
o
We will consider the differences between aldehydes and ketones. Note that
neither have a leaving group and that resonance is the same. Therefore, these
two factors do not affect the relative reactivity of the functional group in this
case.
o
δ+ C=O: The δ+ on the aldehyde carbonyl carbon is greater than that of the
ketone carbonyl carbon because the ketone contains two alkyl groups that
donate electron density to the carbonyl carbon whereas the aldehyde only has
one alkyl group. The more the magnitude of the δ+ is reduced the more
resistant the carbonyl carbon is to nucleophilic attack. If the δ+ is reduced, the
molecule will be more stable initially and there will be less of a need to get rid
of the partial positive charge.
ROHROR
Diagram From:
http://www.chem.leeds
.ac.uk/People/CMR/la
bstuff/litreviews/carbo
nylchemistry.doc
o
Sterics: The ketone has two large alkyl groups attached to the carbonyl carbon,
whereas the aldehyde only has one large alkyl group attached. Therefere, the
ketone has more steric hinderance which inhibits the nucleophile from
attacking the carbonyl carbon more than in the aldehyde case. As a result,
ketones are less reactive than aldehydes.
 Conclusion: The rate of addition of aldehydes is faster than that of
ketones.
•
Nucleophilic substitution in thiolesters, esters, amides, and carboxylate ion. (Adapted
from Chem 14D Thinkbook CFQ #9, Carbonyl Chemistry-Fundamentals)

Considering the four factors that affect reaction rate:
o
Carbonyl carbon δ+ and Resonance: controlled by the magnitude of
resonance between the carbonyl carbon and its attachments. We must
consider the resonance lost as a result of substitution in addition to the
affects of resonance on the magnitude of the δ + on the carbonyl carbon
(described above). The magnitude of resonance lost will affect the rate
nucleophilic attack on the carbonyl carbon. Let’s consider the resonance of
each function group in question individually.
• Thiolester: Resonance is between carbon and sulfur. Resonance is
best between atoms in the same row of the periodic table. This is not
the case here as carbon is in the second row and sulfur is in the third
row.
• Ester: Resonance between carbon and oxygen. Stronger resonance
because carbon and oxygen are within the same row of the periodic
table.
• Amide: Better resonance than ester case because C and N are on the
same row of the periodic table and N is less electronegative than O,
meaning it is more willing to share its lone pair electrons.
• Carboxylate ion: Resonance with a negative oxygen in the
carboxylate case results in much more significant resonance
contributors than with neutral nitrogen in the amide case.
• Thus we conclude based on carbonyl carbon δ+ and resonance that
the order of increasing resonance stabilization is thiolester < ester <
amide < carboxylate ion.
o
Steric effects: Difficult to determine. SR, OR, and NR2 are larger than O-,
however it is difficult to distinguish between the others. Overall, resonance
plays a more crucial role in determining the rate of nucleophilic attack. In this
analysis, steric effects can be ignored because its effect on the reaction rate is
minimal.
Leaving group:
• Thiolester: –SR is a good leaving group because of its high polarizability
• Ester: -OR is a poorer leaving group than –SR because it is less
polarizable than S, however, its higher electronegativity makes it a better
leaving group than –NH2.
• Amide: -NH2 a poorer leaving group than –OR because N is less
electronegative and less willing to accept electrons.
• Carboylate: -O2 is a horrible leaving group. It has a formal charge of 2and low polarizability.
o
 Conclusion: In order of nucelophilic carbonyl substitution reactivity:
thiolester > ester > amide > carboxylate ion.

Recognizing Mechanism Patterns
The flowchart below can help you recognize the mechanistic patterns present in carbonyl chemistry
and help you logically reason out what comes next when thinking about mechanisms.
1. C=O
2. Nucleophilic
attack at carbonyl
carbon
3. Protonate carbonyl
oxygen
5. Tetrahedral
Intermediate
6. Form Enol
8. Eject a Leaving
Group
4. Enolate formation
7. _-carbon acts as
nucleophile
9. O— acts as a
nucleophile
(This flowchart was derived from OWLS-Survey of Carbonyl Reactions and Mechanisms Problem #1)
*Note: At every tetrahedral intermediate step (5), you should ask yourself “Is there a leaving
group?” in order to know if nucleophilic carbonyl substitution or nucleophilic carbonyl addition will
occur.

Examples of the Various Mechanism Steps
The numbers at the various mechanism steps correspond to the numbers in the flowchart. Look at
the flowchart while following the mechanisms to reinforce the concepts learned and help guide you
through the possibilities of what can come next.
Mechanism #1
1) Start with C=O
2) Nucleophilic attack
3)Tetrahedral
intermediate (no
LG present)
Deprotonate H2O+
9) O— acts as a
nucleophile
Product
Mechanism #2
1) Start with C=O
2) Nucleophilic attack
Mechanism #3
1) Start with C=O
4) Enolate Formation
3)Tetrahedral
intermediate (LG
present)
Deprotonate
H2O+
8) Eject a Leaving
Group
1) Re-form C=O
Draw Resonance
structure
7) _-carbon acts
as nucleophile
Product
Product
Mechanism #4
1) Start with C=O
4) Enolate Formation
6) Form Enol
Product
Mechanism #5- Fischer Esterification
Even though we have not explicitly learned this mechanism yet, using the flowchart of possible
mechanism steps as well as our knowledge of carbonyl chemistry, we can predict the mechanism.
We will learn the intricacies of this reaction in our Carbonyl Survey of Reactions in the next topic
we will cover. But for now, let’s analyze the mechanism steps with respect to our flowchart.
Some Notes about Fischer Esterification:
o In Fischer Esterification we begin with a carboxylic acid in the presence of strong acid and a
large excess of alcohol. The reaction results in the formation of an ester.
o The carboxylic acid carbonyl must be protonated first because the carbonyl carbon is a poor
electrophile due to significant resonance with the hydroxyl group. Also, methanol is a poor
nucleophile due to the high electronegativity of oxygen. Putting a formal negative charge on
the methanol by deprotonating it in the presence of strong acid makes the methanol a better
nucleophile.
With this information, we can now analyze the mechanism (see next page).
(A) 3. Protonation of the Carbonyl Oxygen
(B) 2. Nucleophilic attack at carbonyl carbon
(C) Deprotonation
(D) Protonation to create a leaving group
(E) 8. Eject a Leaving group
(F) More significant resonance structure
(G) Deprotonation