Hello everyone! My name is Eman, welcome back to my youtube channel!

Today we will cover

chapter 4 for our MCAT Organic Chemistry playlist and this chapter is titled Analyzing Organic
Reactions. In this chapter, we will cover the following objectives:

1. We will begin by discussing acids and bases, focusing on their definitions, how we
classify their strength, and some common functional groups involved in acid-base
chemistry.
2. Then, we will move on to nucleophiles, electrophiles, and leaving groups. We will
define these terms, explore their properties, and examine how they participate in
nucleophilic substitution reactions.
3. After that, we will discuss oxidation-reduction reactions, where we will introduce
oxidizing and reducing agents and analyze how electrons are transferred in these
reactions.
4. We will then move on to chemoselectivity. Here, we will explore how reactive locations
in a molecule influence chemical reactions and how steric protection can affect
selectivity.
5. Finally, we will wrap up with some problem-solving strategies that can help approach
reaction-based questions more systematically.

Let’s begin by discussing acids and bases. There are two main definitions of acids and bases
that are commonly used in organic chemistry: the Brønsted-Lowry definition and the Lewis
definition.

● The Brønsted-Lowry definition describes an acid as a species that donates a proton

(H⁺) and a base as a species that accepts a proton. This definition focuses on proton
transfer and is useful in many acid-base reactions we will encounter.
● For example, when a Brønsted-Lowry acid, such as HA, donates a proton to water, it
forms H₃O⁺ and its conjugate base, A⁻. Similarly, when a Brønsted-Lowry base, B,
accepts a proton, it forms its conjugate acid, HB⁺, along with OH⁻ in solution.
● On the other hand, the Lewis definition describes acids and bases in terms of electron
pairs. A Lewis acid is an electron pair acceptor, while a Lewis base is an electron
pair donor. This definition broadens the scope of acid-base chemistry beyond just
proton transfer.
● For example, when a Lewis acid reacts with a Lewis base, they form a coordinate
covalent bond, where both electrons in the bond originate from the Lewis base. This
type of interaction is especially relevant in many organic reactions, particularly those
involving metal catalysts or electrophilic species.

To quantify acid strength, we use the acid dissociation constant, Ka, which describes the
extent to which an acid donates a proton in solution.

● The equilibrium expression for an acid dissociation reaction is written as:

● A larger Ka value indicates a stronger acid because more of the acid dissociates into
ions, increasing the concentration of H₃O⁺ in solution. To simplify comparisons, we
define the pKa as the negative logarithm of Ka:
● A lower pKa value corresponds to a stronger acid, while a higher pKa value indicates
a weaker acid. This relationship is useful for predicting acid-base behavior in organic
molecules, particularly in reactions where proton transfer plays a key role.
Now that we have established the concepts of acids and bases, let’s take a closer look at how
acidity varies across different functional groups.

● The pKa values of a molecule provide a direct measure of its acidity, with lower pKa
values indicating stronger acids and higher pKa values indicating weaker acids.
● This also means that the conjugate base of a strong acid will be weak, whereas the
conjugate base of a weak acid will be strong. Understanding these trends is essential for
predicting reaction mechanisms and proton transfer events in organic chemistry.
● Let’s start by examining the functional groups with the highest pKa values, which
correspond to the weakest acids and the strongest conjugate bases. Alkanes have
an extremely high pKa of around 50, meaning they are very poor proton donors. Their
conjugate bases, alkyl carbanions, are highly unstable and strong bases.
● Moving slightly down the scale, alkenes have a pKa of about 43, meaning they are still
weak acids, but slightly more acidic than alkanes. Their conjugate bases, alkene anions,
are also highly reactive and strong bases.
● Similarly, molecular hydrogen (H₂) has a pKa of 42, indicating that it is also a very weak
acid.
● Next, we have amines, such as ammonia (NH₃), with a pKa around 35. While still a
weak acid, amines are more acidic than alkanes and alkenes. The conjugate base of an
amine, NH₂⁻ (amide ion), is a strong base that is frequently used in organic synthesis.
● Moving further down, alkynes, which contain a carbon-carbon triple bond, have a pKa of
about 25. This is a significant drop in pKa compared to amines, meaning terminal
alkynes are much stronger acids. Their conjugate bases, alkynyl anions (R-C≡C⁻), are
still strong bases but are more stable than amide ions.
● We then enter the range of functional groups with more moderate acidity. Esters also
have a pKa of around 25, meaning they exhibit similar acidity to alkynes. Their conjugate
bases are resonance-stabilized but still reactive.
● Ketones and aldehydes exhibit slightly greater acidity, with aldehydes having pKa
values ranging from 17-20 and ketones ranging from 20-24. The increased acidity is due
to the resonance stabilization of the enolate conjugate base.
● As we move lower in pKa, we reach alcohols, with a pKa of about 17. Alcohols are
significantly more acidic than amines or alkanes.
● Water, with a pKa of 16, is similar to alcohols in acidity.
● Next, we reach carboxylic acids, which are much stronger acids than alcohols and
ketones, with a pKa around 4. This substantial increase in acidity is due to the
resonance stabilization of the carboxylate ion (R-COO⁻), which makes it far more
stable than an alkoxide ion. This is why carboxylic acids readily donate protons in
aqueous solution.
● Finally, at the lowest end of the pKa scale, we have the hydronium ion (H₃O⁺), with a
pKa of -1.7. This makes it a very strong acid, meaning that its conjugate base, water
(H₂O), is extremely weak.

In summary, we can see that stronger acids have lower pKa values because their conjugate
bases are more stable. Conversely, weaker acids have higher pKa values because their
conjugate bases are highly reactive and unstable.

Now that we have covered acidity and basicity, we can move on to another key concept in
organic chemistry: nucleophiles, electrophiles, and leaving groups. These species play
fundamental roles in reaction mechanisms, particularly in substitution and addition reactions.
 ● Let’s start with nucleophiles, which are defined as "nucleus-loving" species.
Nucleophiles have either lone pairs or π bonds that allow them to donate electron
density and form new bonds with electrophiles. Since they provide electrons in a
reaction, nucleophiles behave as Lewis bases.
● Some common examples of nucleophiles include anions, such as bromide (Br⁻),
hydroxide (OH⁻), and the cyanide ion (C≡N⁻). These species carry a
negative charge, meaning they have excess electron density that makes them highly
reactive toward electrophiles.
● Nucleophiles can also include molecules with π bonds, such as alkenes, alkynes,
and benzene rings, since the delocalized electrons in their π systems can be donated
to an electrophile.
● Finally, neutral molecules with lone pairs, such as water (H₂O), ammonia (NH₃),
and esters (R-COOCH₃), can also act as nucleophiles under the right conditions.

However, not all nucleophiles react with the same efficiency. The ability of a nucleophile to
donate electrons, known as nucleophilicity, depends on four major factors.

1. First, charge plays a critical role. Nucleophilicity increases with increasing electron
density, meaning negatively charged species are stronger nucleophiles than their
neutral counterparts. For example, hydroxide (OH⁻) is a stronger nucleophile than water
(H₂O) because of its negative charge.
2. Second, electronegativity affects nucleophilicity. As electronegativity increases,
nucleophilicity decreasesbecause highly electronegative atoms are less willing to
share their electrons. For instance, oxygen (O) is less nucleophilic than nitrogen (N)
because oxygen holds onto its electrons more tightly.
3. Third, steric hindrance reduces nucleophilicity. Bulkier nucleophiles have more
difficulty accessing the electrophilic center, making them less reactive. For example,
tert-butoxide (a bulky alkoxide, (CH₃)₃CO⁻) is a weaker nucleophile than methoxide
(CH₃O⁻) because its steric bulk prevents efficient attack.
4. Lastly, solvent effects can influence nucleophilicity. Protic solvents, such as water and
alcohols, hinder nucleophilicity because they can hydrogen-bond to and stabilize
nucleophiles, reducing their reactivity. This is particularly relevant for negatively charged
nucleophiles like halide ions.

Now, this point is worth elaborating on, as solvent effects play a crucial role in determining
nucleophilicity. The type of solvent used in a reaction—whether polar protic or polar aprotic—
can significantly influence the strength and reactivity of a nucleophile.

● Polar protic solvents, such as water (H₂O), methanol (CH₃OH), ammonia (NH₃),
and carboxylic acids, have the ability to form hydrogen bonds. These solvents can
interact with negatively charged nucleophiles, surrounding them with a shell of
hydrogen-bonded solvent molecules.
● This solvation stabilizes the nucleophile and effectively reduces its ability to attack an
electrophile. Because of this, nucleophilicity in polar protic solvents increases down
the periodic table, following the trend:
○ I⁻ > Br⁻ > Cl⁻ > F⁻
● This trend occurs because larger anions (like iodide, I⁻) are less affected by solvation
due to their more diffuse electron cloud. In contrast, smaller anions (like fluoride, F⁻)
are strongly solvated, making them less nucleophilic in polar protic environments.
 ● On the other hand, polar aprotic solvents, such as dimethylformamide (DMF),
dimethyl sulfoxide (DMSO), and acetone, lack hydrogen bonding and do not
strongly interact with nucleophiles.
● This allows nucleophiles to remain unsolvated and free to participate in reactions. In
these solvents, nucleophilicity follows the opposite trend, increasing up the periodic
table:
○ F⁻ > Cl⁻ > Br⁻ > I⁻
● Here, fluoride (F⁻) is the strongest nucleophile because it remains free and
unencumbered, whereas iodide (I⁻), being larger and more polarizable, is less effective
as a nucleophile in these conditions.
● Understanding the impact of solvent choice is essential in predicting reaction outcomes.
Many substitution reactions, such as SN1 and SN2 mechanisms, are highly dependent
on whether the reaction is carried out in a protic or aprotic solvent.
● By recognizing how solvent interactions affect nucleophilicity, we can better predict
which nucleophiles will be most reactive under different conditions.

With this in mind, we can now shift our focus to electrophiles.

● Electrophiles are electron-loving species that have either a full positive charge or a
partial positive charge, making them highly reactive toward nucleophiles that donate
electron density.
● The key distinction between electrophilicity and acidity is that electrophilicity is a
kinetic property, meaning it describes how readily an electrophile reacts, rather than
how thermodynamically favorable the reaction is. However, electrophilicity often
correlates with acidity, as molecules that donate protons also tend to be good
electrophiles.
● In practical terms, electrophiles can be categorized based on their degree of positive
charge and polarization. A carbocation (C⁺), which has an empty p orbital, is an
excellent electrophile because it has no electron density to donate and is highly reactive
toward nucleophiles.
● A carbonyl carbon (C=O) is also a strong electrophile, but in this case, the oxygen
withdraws electron density, creating a partial positive charge (δ⁺) on carbon. This
makes carbonyl-containing compounds, such as aldehydes and ketones, prime targets
for nucleophilic attack.
● Another important factor in electrophilicity is the presence of a leaving group. A
molecule with a good leaving group is more likely to undergo a substitution reaction
because the bond can break easily, allowing for nucleophilic attack.
● For example, alkyl halides (R-Br, R-Cl, R-I) are good electrophiles because halides are
stable after leaving. On the other hand, species like alcohols (R-OH) or amines (R-NH₂)
are weaker electrophiles because their leaving groups are less stable, making
substitution reactions less favorable.
● Electrophilicity and acidity are also closely related when ranking carboxylic acid
derivatives. Among these, anhydrides are the most electrophilic because they have
two electron-withdrawing carbonyl groups, followed by carboxylic acids and esters,
and then amides, which are the least electrophilic due to the electron-donating nature of
the nitrogen. This is a concept we will revisit in detail in a later chapter as well.

Now that we’ve established the roles of nucleophiles, electrophiles, and leaving groups, we can
move on to nucleophilic substitution reactions, where these species interact directly.
These reactions serve as key examples of nucleophile-electrophile interactions. In both SN1
and SN2 mechanisms, a nucleophile forms a bond with a substrate carbon, while a
leaving group departs.

● Now we can start our story of SN2 reactions. A strong nucleophile (that also happens
to be a weak base) meets a nice electrophilic carbon that is attached to a halogen,
our leaving group. This is the beginning of a love story. In this fairytale, the strong and
handsome nucleophile makes a bold move, attacking (or as one might say, hitting
on) the electrophilic carbon that is bonded to the halogen.
● After the electrophilic carbon gets hit on by the nucleophile, she dumps the halogen
(our leaving group) and gets with the nucleophile instead. This is a classic case of
substitution, where the nucleophile replaces the halogen in a single step - there are no
intermediates, just one smooth concerted reaction.
● We know this because the reaction energy diagram shows only one transition state,
meaning there are no intermediate steps. The nucleophile enters as the leaving group
exits, forming a new bond in a single step. This is why SN2 is known as a concerted
mechanism, where bond formation and bond breaking occur simultaneously.
● Now, examples of strong nucleophiles that participate in SN2 reactions include halide
ions (Cl⁻, Br⁻, I⁻), alkoxide ions (RO⁻), and thiolates (RS ⁻) . These nucleophiles are
strong enough to attack but weak enough that they do not compete too much with
elimination reactions.
● Another important factor in this love story is the type of carbon that the leaving group
is attached to. Not all carbons are equally available for SN2 reactions. The nucleophile
must approach from the opposite side of the leaving group, which we call a
backside attack. If the carbon is too sterically hindered, meaning it has too many
bulky groups surrounding it, the nucleophile struggles to get close enough to attack.
● This is why SN2 reactions only work well on primary (1°) and secondary (2°)
carbons.
○ A primary carbon (1°) is a carbon bonded to only one other carbon and mostly
hydrogen atoms, making it highly accessible for nucleophilic attack.
○ A secondary carbon (2°) is bonded to two other carbons, making attack
possible but slightly hindered.
○ A tertiary carbon (3°) is bonded to three other carbons, making SN2 practically
impossible due to excessive steric hindrance.
● So, when considering SN2 reactions, primary carbons are ideal, secondary carbons
are possible, and tertiary carbons will not react via SN2 because the nucleophile
simply cannot reach the carbon due to the bulk of surrounding groups.
● Now, you might also be wondering, why is this reaction called SN2? The name
actually gives us key information about the mechanism.
○ S stands for substitution, because one group is replacing another.
○ N stands for nucleophilic, indicating that a nucleophile is responsible for the
substitution.
○ 2 refers to the fact that this reaction is bimolecular, meaning that the rate-
determining step depends on two reactants—the nucleophile and the
electrophilic carbon attached to the leaving [Link] the reaction depends
on both species, the rate law is written as: rate=k[alkyl halide][nucleophile].
○ This tells us that increasing the concentration of either the alkyl halide or the
nucleophile will increase the reaction rate.
● Lastly, SN2 reactions have one defining feature: they result in an inversion of
stereochemistry. Since the nucleophile must attack from the opposite side of the
leaving group, the product will have a flipped configurationat the reaction site. If the
 electrophilic carbon had an R configuration to start, after SN2 reaction, the carbon will
have an S configuration.
● So, to summarize, SN2 is a one-step, concerted reaction where a strong nucleophile
displaces a leaving group through a backside attack, favoring primary and
secondary carbons. The reaction is bimolecular, meaning the rate depends on both
the nucleophile and the electrophilic carbon, and it always results in an inversion of
stereochemistry.

Now that we’ve told the story of SN2, let’s move on to SN1.

● While SN2 was a direct substitution with a backside attack, SN1 takes a more stepwise
approach. Think of it as a love story where the halogen leaves first, and only later does
the nucleophile come in to take its place.
● The process begins when the leaving group departs on its own, breaking its bond with
the carbon and forming a carbocation, a highly reactive positively charged species.
Unlike SN2, where the nucleophile aggressively attacked the electrophilic carbon, SN1
waits for the carbon to become available before the nucleophile steps in.
● Because the leaving group departs first, the nucleophile doesn’t play a role in the rate-
determining step. This is why SN1 is known as a unimolecular substitution reaction,
where the rate of the reaction depends only on the alkyl halide, not the nucleophile.
● The rate law for SN1 is expressed as rate = k[alkyl halide], meaning that increasing the
concentration of the nucleophile does not speed up the reaction. Instead, it is the
formation of the carbocation that determines how quickly the reaction proceeds.
● Since forming a carbocation is required, this reaction is favored by substrates that can
generate a stable carbocation. Tertiary carbons are the most favorable for SN1 because
they are surrounded by three alkyl groups that donate electron density, helping to
stabilize the positive charge.
● Secondary carbons are less stable, but the reaction can still occur under the right
conditions. Primary carbons, however, are highly unstable and do not undergo SN1
because they lack the necessary stabilization for carbocation formation.
● Further, looking at the reaction energy diagram, we can see that SN1 has multiple steps.
The first peak represents the formation of the carbocation, which is the rate-determining
step and the slowest part of the reaction.
● The second peak represents the nucleophilic attack, which happens much more quickly
once the carbocation is available. Because of these distinct steps, the energy diagram
for SN1 features two transition states, unlike the single transition state seen in SN2.
● Once the carbocation is formed, the nucleophile finally makes its move, attacking the
positively charged carbon. This step is much faster than the first because the
nucleophile is simply filling the open spot left by the departing halogen.
● However, there’s one unique consideration with SN1—carbocation rearrangements.
Carbocations are highly unstable, so if there’s a way to become more stable, they will
rearrange before reacting with the nucleophile.
● This often happens through hydride shifts, where a hydrogen moves with its bonding
electrons, or alkyl shifts, where a methyl or larger alkyl group moves to relocate the
carbocation to a more stable position. If a secondary carbocation can shift to a more
stable tertiary position, it will rearrange first before reacting with the nucleophile. This
means the final product of an SN1 reaction may not always form at the original carbon
where the leaving group was attached.
● Finally, just like with SN2, the name SN1 gives insight into its mechanism. The “S”
stands for substitution, meaning one group replaces another. The “N” stands for
nucleophilic, indicating a nucleophile is involved. The “1” stands for unimolecular,
 meaning the rate-determining step depends on only one molecule, the alkyl halide, and
not the nucleophile.

With that, we have completed objective 2 and we can now move into objective 2 which is titled
oxidation-reduction reactions.

● Oxidation-reduction reactions, commonly known as redox reactions, involve the transfer

of electrons between chemical species, leading to changes in their oxidation states.
● Oxidation is defined as the loss of electrons, while reduction is the gain of electrons. A
useful way to remember this is with the mnemonic “LEO the lion says GER”, which
stands for Lose Electrons Oxidation, Gain Electrons Reduction.
● Because oxidation involves the loss of electrons, the species undergoing oxidation
becomes more positively charged. Conversely, reduction, which involves gaining
electrons, results in a more negatively charged species.
● In every redox reaction, there is always an electron donor and an electron acceptor. The
reducing agent is the species that donates electrons, meaning it undergoes oxidation,
while the oxidizing agent is the species that accepts electrons and is therefore reduced
in the process. One example of a redox reaction is the reaction between magnesium and
hydrochloric acid:
○ Mg(s)+2HCl(aq)→MgCl2(aq)+H2(g)
● In this reaction, magnesium is oxidized because it loses electrons to form Mg²⁺, and
hydrogen ions (H⁺) are reduced as they gain electrons to form hydrogen gas (H₂).
Since magnesium donates electrons, it acts as the reducing agent, while the hydrogen
ions, which accept these electrons, function as the oxidizing agent.
● One way to understand redox reactions is by considering how oxidation and reduction
affect the oxidation state of an atom. Oxidation increases an atom's oxidation state,
while reduction decreases it.
● Alternatively, oxidation can be recognized as an increase in the number of bonds to
oxygen or other electronegative atoms, often accompanied by the loss of hydrogen
atoms, while reduction typically involves a decrease in bonds to electronegative
atoms and an increase in hydrogen content.

With that being said, let’s go through some common oxidation reactions that are important to
know for the MCAT.

● Starting with alcohols, the oxidation pathway depends on whether the alcohol is
primary, secondary, or tertiary. Primary alcohols can be oxidized to aldehydes using
pyridinium chlorochromate (PCC, C₅H₅NH⁺CrO₃Cl⁻)or chromium trioxide (CrO₃)
in pyridine, which selectively stops at the aldehyde stage because PCC is a mild
oxidizing agent.
● However, under stronger oxidation conditions, primary alcohols can be oxidized all the
way to carboxylic acidsusing chromic acid (H₂CrO₄), potassium permanganate
(KMnO₄), or hydrogen peroxide (H₂O₂). These strong oxidizing agents allow the
oxidation to proceed fully, ensuring that the carbonyl carbon reaches its highest
oxidation state.
● As for Secondary alcohols, they undergo oxidation to form ketones using PCC or
CrO₃/pyridine. Unlike aldehydes, ketones do not have a hydrogen atom attached to the
carbonyl carbon, preventing further oxidation under normal conditions.
● Aldehydes can be further oxidized to carboxylic acids using chromic acid (H₂CrO₄)
or potassium permanganate (KMnO₄). This oxidation is highly relevant in biological
 systems, particularly in metabolic pathways where aldehydes serve as intermediates
before being converted into carboxylic acids for further processing.
● For aromatic compounds, benzylic alkyl groups, such as those found in toluene
derivatives, can be oxidized to benzoic acid using using potassium permanganate
(KMnO₄). This reaction occurs regardless of the length of the alkyl chain.
● Next, lets talk about alkenes. When oxidizing alkenes, the choice of reagents determines
whether the products are aldehydes and ketones or fully oxidized carboxylic acids.
○ Let’s start with ozonolysis, a key reaction where ozone (O₃) cleaves the carbon-
carbon double bond. The outcome depends on the subsequent workup step.
When the reaction is followed by a reducing agent, such as zinc (Zn) or
dimethyl sulfide (CH₃SCH₃), the alkene is split into ketones and aldehydes.
This is known as a mild ozonolysis reaction, meaning the oxidative conditions
are not strong enough to further oxidize aldehydes into carboxylic acids.
○ On the other hand, when ozonolysis is performed with an oxidizing workup,
such as hydrogen peroxide (H₂O₂), or under strong oxidative conditions
with potassium permanganate (KMnO₄), heat, and acidic conditions
(H₃O⁺), any aldehydes that form will be further oxidized to carboxylic acids.
This is because aldehydes are susceptible to oxidation, whereas ketones remain
unaffected under these conditions.
● Alkenes can also undergo hydroxylation to form vicinal diols, which are compounds
containing two hydroxyl (-OH) groups on adjacent carbon atoms. T
○ his transformation is achieved using osmium tetroxide (OsO₄) or potassium
permanganate (KMnO₄) in basic conditions. Here, the hydroxyl groups
across the double bond in a syn addition.
○ These diols can then be further oxidized into aldehydes or ketones using
sodium periodate (NaIO₄), lead tetraacetate (Pb(OAc)₄), or periodic acid
(HIO₄), which cleave the carbon-carbon bond between the hydroxyl-bearing
carbons.
● Another key oxidation reaction for alkenes is epoxidation, in which a peracid such as
meta-chloroperoxybenzoic acid (mCPBA, C₆H₄ClCO₃H) converts the alkene into an
epoxide. Epoxides are highly reactive due to the ring strain in the three-membered
cyclic ether, making them valuable intermediates in organic synthesis.
● What about alkynes? Alkynes can be cleaved into carboxylic acids under ozone (O₃)
followed by water (H₂O) or potassium permanganate (KMnO₄) under heat in an
acidic medium (H₃O⁺). This reaction efficiently breaks down triple bonds and it leads to
fully oxidized carboxyl groups.
● Finally, oxidation can also modify ketones under specific conditions. Ketones can be
oxidized into esters using meta-chloroperoxybenzoic acid (mCPBA). This reaction
inserts an oxygen atom adjacent to the carbonyl carbon, expanding the functional group
from a ketone to an ester.

Now, let’s do the same for common reduction reactions that are important to know for the
MCAT.

● Aldehydes and ketones are readily reduced to primary and secondary alcohols,
respectively. This reaction can be carried out using lithium aluminum hydride (LiAlH₄)
or the milder reducing agent sodium borohydride (NaBH₄). Because sodium
borohydride is less reactive, it is generally only effective in reducing aldehydes and
ketones, while lithium aluminum hydride is strong enough to reduce a broader range of
functional groups.
 ● Carboxylic acids require a much stronger reducing agent because they are more
oxidized than aldehydes or ketones. Lithium aluminum hydride (LiAlH₄) in ether is
commonly used for this purpose, followed by protonation with water, ultimately yielding
a primary alcohol.
● Esters undergo a similar reduction but produce two products: a primary alcohol and
an additional alcohol fragment that corresponds to the ester’s alkoxy (-OR) group.
● Amides, which contain a carbonyl adjacent to a nitrogen, can be reduced to primary
amines when treated with LiAlH₄ in ether, followed by aqueous workup. Unlike
carboxylic acids and esters, which are reduced to alcohols, the reduction of amides
removes the oxygen entirely, forming an amine rather than an alcohol.

For the reactions that we covered in this objective, I want to note that we will revisit them in the
coming chapters so we will see this content more than once and that will definitely make it
easier for us to learn! Let’s now move into our fourth objective.

● A key aspect of understanding organic reactions is recognizing which sites in a

molecule are most reactive and how different functional groups behave in the
presence of one another.
● This concept is known as chemoselectivity, which refers to the preferential reaction of
one functional group over others when multiple reactive sites are present in a molecule.
Recognizing chemoselectivity is essential for predicting reaction outcomes and
understanding selectivity in chemistry.
● The reactive site of a molecule depends on the type of chemistry that is occurring. On
the MCAT, two key reactive sites to consider are:
1. The carbonyl carbon, which is highly reactive due to the partial positive charge
on carbon from the electronegative oxygen. This makes carbonyl carbons
electrophilic and susceptible to attack by nucleophiles.
2. The substrate carbon in substitution reactions, which is another critical
reactive site. In these cases, nucleophilic substitution can occur when a
nucleophile displaces a leaving group, as we saw with SN1 and SN2
mechanisms.
● In many organic reactions, nucleophilic and redox (oxidation-reduction) reactions
tend to act at the highest-priority functional group. The most oxidized functional group
is often the most reactive site, meaning that oxidation, reduction, or nucleophilic attack
will typically target the functional group with the most bonds to oxygen or other
electronegative atoms.
● However, chemists can manipulate reactivity by taking advantage of steric hindrance.
Steric hindrance refers to the physical crowding of bulky groups around a functional
site, which can either slow down or prevent a reaction from occurring. This property can
be used to selectively target certain functional groups while avoiding reactivity at
others.
● Additionally, steric hindrance is useful for protecting functional groups that might
otherwise react undesirably during a reaction sequence. Protecting groups can be
introduced to temporarily mask a functional group and later removed under specific
conditions to restore its reactivity.
● Do not worry if this seems overwhelming! Again, this is just a preview of what we will see
in later chapters with more details. This is just an introduction to some fundamental
ideas and rules.

Building on our discussion of chemoselectivity, we now turn to how we can systematically

approach reaction problems.
 ● A strong understanding of reactivity and selectivity allows us to predict how different
functional groups will behave in a given reaction. To do this effectively, we need a
structured approach to analyzing reaction mechanisms.
● When solving reaction problems, the first step is to identify all functional groups in
the given molecule. Each functional group has characteristic reactivity, and recognizing
them is essential for determining the type of reaction that might occur.
● Next, we analyze the reagents to understand their function—are they oxidizing agents,
reducing agents, nucleophiles, or electrophiles? By knowing what each reagent does,
we can anticipate how it will interact with the molecule.
● From there, we identify the most reactive functional group in the given conditions. As
we discussed earlier, the most oxidized functional group often serves as the most
reactive site, particularly in oxidation-reduction and nucleophilic reactions.
● Once we establish the site of reactivity, we then determine the first step of the
reaction. Many organic reactions occur in sequential steps, so understanding the initial
transformation is key to predicting the overall outcome.
● Finally, if applicable, we must consider stereospecificity or stereoselectivity—does
the reaction favor one stereoisomer over another? Does it lead to racemization or
retention of configuration? These considerations become especially important in
substitution reactions and certain oxidation or reduction pathways.

Now, let’s apply these principles to a multi-step reaction problem.

● The molecule provided contains an alkane backbone, a ketone, and an ester

functional group. Both the ketone and ester contain carbonyl carbons that are
electrophilic, making them possible targets for nucleophilic attack.
● Additionally, we need to consider the possibility of reduction, as both carbonyl oxygens
are potential sites for transformation.
● The first reagent introduced is ethylene glycol (HOCH₂CH₂OH) in the presence of p-
toluenesulfonic acid (TsOH) and benzene. Ethylene glycol, a diol, is commonly used
as a protecting group for aldehydes and ketones, forming a cyclic acetal. This
protection prevents the ketone functional group from undergoing unintended reactions
in subsequent steps.
● The second step involves lithium aluminum hydride (LiAlH₄) in tetrahydrofuran
(THF). Lithium aluminum hydride is a strong reducing agent, which selectively
reduces the ester functional group into a primary alcoholwhile leaving the protected
ketone intact. This means that only the ester undergoes reduction in this step, while
the ketone remains unaffected due to its temporary protection.
● Finally, the third step involves an acidic workup using hydronium ion (H₃O⁺) and
heat. These acidic conditions hydrolyze the acetal protecting group, regenerating
the original ketone functional group. At the end of the sequence, we are left with a
primary alcohol (from the reduced ester) and a restored ketone (from the deprotected
cyclic acetal).