Learn key MCAT concepts about the fundamentals of organic chemistry, plus practice questions and answers

Fundamentals of Organic Chemistry for the MCAT banner

(Note: This guide is part of our MCAT Organic Chemistry series.)

Part 1: Introduction to the fundamentals of organic chemistry

At first blush, organic chemistry can be quite frightening. The topic covers many concepts: from electron movement to functional groups and organic structures. To top it off, many college-level organic chemistry courses require the memorization of complicated, multi-step reactions.

Here is some good news: the organic chemistry content tested on the MCAT may be much less extensive than what you have learned in a college class. In this guide, we will introduce the fundamental concepts of organic chemistry you must be familiar with to succeed on the MCAT. By the end of this guide, you will be well-prepared to tackle more complex organic chemistry topics in our other guides.

Throughout this guide, there are several high-yield terms listed in bold. These terms will also be listed at the end of the guide. Additionally, there are several MCAT-style practice questions for you to test your knowledge of these fundamental principles.

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Part 2: Arrow-pushing mechanisms

a) Double-headed arrows

Take a look at the organic reaction above. A quick glance shows that a reaction occurs to produce a new product. A molecule with an aldehyde functional group reacts with a hydrogen ion and alcohol to produce a hemiacetal. (For more information on this topic, be sure to refer to our organic chemistry guide on functional groups.)

All of these molecules are connected by two types of arrows. There are the two half-arrows pointing to the left and to the right in between each step of the reaction. These arrows, known as equilibrium arrows, signify that a reaction is reversible. Thus, each step of the reaction can proceed to the next or previous step with equal probability. Equilibrium arrows are not necessarily always the same length. A reaction can be reversible and have equilibrium arrows of different lengths. The length of the half-arrow corresponds to the likelihood that the organic reaction will travel in that direction.

Mechanisms are illustrated depictions of chemical reactions. Mechanisms are used to illustrate the formation and breaking of various bonds between atoms. In general, mechanisms typically use arrows to depict the movement of electrons. Arrows are generally drawn with an origin at a specific electron pair and point to the bond or atom they attack. Double-headed arrows indicate the movement of an electron pair, or two electrons at once.

Take another look at the illustrated mechanism, and track the movement of electrons between each step.

In the first step, valence electrons from the oxygen atom attack the hydrogen ion to initiate this reaction.
In the second step, there are two double arrows. The first double arrow originates from the valence electrons on the oxygen in the alcohol group and attacks the carbon atom. The second double arrow shows the movement of electrons from the carbon-oxygen double bond to the oxygen atom.
In the third step, electrons from the oxygen-hydrogen bond move to the oxygen, releasing a hydrogen ion.

It’s important to remember that drawing double arrows in a reverse fashion (from a source without electrons) is incorrect and can result in a costly mistake when interpreting a reaction on the MCAT! The arrows extend to the target from the source of electrons.

b) Single-headed arrows

Arrows can be double- or single-headed, with either type having a different meaning.

In the organic reaction shown above, a single bromine molecule (Br2) splits into two bromine ions (Br-). The catalyst for this reaction is light; in chemical reactions, the letters hv are used to represent high-energy light that breaks bonds. In contrast to the first mechanism, this mechanism uses single-headed arrows.

Single-headed arrows are similar to double arrows in that they show the movement of electrons. Like double-headed arrows, single-headed arrows extend from the source of electrons to the target. In this example, electrons originate in a single bond and are sent to each bromine atom.

Unlike double-headed arrows, single-headed arrows, also referred to as fish hooks, show the movement of only one electron. Thus, as the original bond in the bromine molecule is broken, each resulting ion receives only one electron (instead of a pair of electrons).

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Part 3: Nucleophiles and electrophiles

a) Overview of functional groups

In organic chemistry, the origin of electrons in a reaction is very important. The sources and targets of electron transfer can usually be classified into nucleophiles and electrophiles.

Nucleophiles are atoms on a molecule that donate electrons (usually two at a time) to a target molecule to form a bond. Generally, atoms are nucleophiles, or nucleophilic, if they have a large electron density that results from full or partial negative charge. This means that atoms such as oxygen, fluorine, and chlorine are excellent nucleophiles. They have lone pairs of electrons that “seek out” regions of electron density on other atoms, and usually form covalent bonds.

Electrophiles play the opposite role. These are atoms that accept electrons (usually two at a time) from a source to form a bond. Similarly, atoms with very limited electron density tend to be electrophilic. These atoms generally have full or partial positive charge, or share electrons with multiple atoms. Hydronium ions and boron trifluoride are great examples of electrophiles since the electron density is diffused around the molecule.

**Figure 3** The oxygen atom in hydronium and the boron atom in boron trifluoride are considered to be good electrophiles.

When studying reactions for the MCAT, it is important to refer to reactants in the context of nucleophiles and electrophiles. Although there are a limitless amount of reactants that could be used in organic reactions, these reactions can only behave as a nucleophile (electron donor) or electrophile (electron acceptor)!

To begin, let’s discuss the properties of various functional groups. There are several key functional groups to be familiar with, including hydroxyl, carbonyl (aldehydes and ketones), carboxyl (carboxylic acid and its derivatives), and amines.

Hydroxyl functional groups are common in alcohol molecules. Hydroxyl functional groups are characterized by the formula R-OH, where the letter “R” signifies the rest of the molecule and -OH is the chemical formula of the hydroxyl functional group. Hydroxyl groups have the ability to act as a nucleophile or electrophile, depending on their local environment. If a hydroxyl group is neutral or has a negative charge, the group (specifically the oxygen atom) will act as a nucleophile. If a hydroxyl group has a positive charge, the group (specifically the oxygen atom) will act as an electrophile.

**Figure 4** An -OH group can appear in many different forms

Take a closer look at the hydroxyl groups shown above. When the hydroxyl group is neutral or negatively charged, there is a higher electron density around the oxygen atom, enabling it to act as a nucleophile. When the oxygen is positively charged due to the presence of extra bonds, there is a lower electron density around the oxygen atom. Thus, the ability to donate electrons is reduced and the oxygen atom becomes an electrophile.

Carbonyls are a type of functional group that includes both aldehydes and ketones. The characteristic structure of a carbonyl functional group is its inclusion of a carbon atom double-bonded to an oxygen atom. Because oxygen is more electronegative, the oxygen atom attracts electron density away from the carbon atom. As a result, the carbon atom in the carbonyl group has a partial positive charge.

As a result, the carbonyl carbon atom often acts as an electrophile. Other nucleophiles commonly attack carbonyl carbons to create new bonds, resulting in a disruption to the double-bond formed with oxygen.

**Figure 5** Ketone and aldehyde functional groups

The presence of additional substituents that are bonded to the carbon atom of the carbonyl group can affect the reactivity. Electron-poor electron withdrawing groups (EWGs) serve to draw electron density away, creating a partially positive charge on the carbon atom itself. In contrast, electron-rich electron donating groups (EDGs) serve to donate electron density, creating a partially negative charge on the carbon atom. These partial charges can change the behavior of the carbonyl carbon as an electrophile or nucleophile.

Carboxylic acids are functional groups that contain both a carbonyl group and a hydroxyl group. The structure of a carboxylic acid is R-COOH. As we’d expect, carboxylic acids can act as both nucleophiles and electrophiles. The carbon center of a carboxylic acid is a strong electrophile since the two bonded oxygen atoms remove electron density. With this extra electron density, both oxygen atoms have the potential to act as nucleophiles.

Carboxylic acids also have special derivatives with similar electrophilic and nucleophilic properties. Some of the most common derivatives you’ll see on the MCAT are anhydrides, esters, and amides.

**Figure 6** Commonly found carboxylic acid derivatives

Amines are one type of nitrogen-based functional group. Amines are generally represented by the formula NR_x. The nitrogen atom in amines has a greater electron density; as a result, amines generally act as nucleophiles.

b) Nucleophilic substitution reactions

Once functional groups are classified as electrophilic or nucleophilic, the overall reactions between molecules can be classified as nucleophilic or electrophilic. Some of the most common reactions encountered on the MCAT are nucleophilic substitution reactions.

Nucleophilic reactions occur through two “flavors:” Sn1 or Sn2. In these reaction names, the letter “S” indicates a substitution reaction, the lowercase “n” indicates a nucleophilic attack, and the number 1 or 2 indicates the number of molecules involved in the rate-determining step.

Sn2 reactions occur in one step. As all of the required steps occur at once, this type of reaction is known as a concerted mechanism. Sn2 reactions involve the addition of a nucleophile and the departure of a leaving group in the same step. Both actions are part of the rate-limiting step of Sn2 reactions.

**Figure 8** Example of an Sn2 reaction; note the inversion of stereochemistry

The biggest obstacle to a nucleophile during Sn2 attack is steric hindrance. The nucleophile must be able to have the physical space to attack the carbon center of the target molecule and carry out the reaction. This occurs in a step referred to as backside attack.

A characteristic result of Sn2 reactions is the inversion of stereochemistry. If a molecule has an S-configuration before the attack, it has an R-configuration after the Sn2 reaction. Inversion of stereochemistry is expected since the new nucleophilic group attacks the carbon center from the opposite side of the leaving groups. For this reason, the Sn2 attack is also referred to as umbrella inversion, as the rearrangement of bonds resembles the turning-out of an umbrella on a windy day.

Sn1 reactions occur in two steps. The first step is the departure of the leaving group. Once the leaving group is gone, a positively charged carbon known as a carbocation is formed. The formation of a carbocation is the rate-limiting step of an Sn1 reaction.

**Figure 9** Example of an Sn1reaction, which forms a racemic mixture of products

Recall that carbon atoms have relatively low electronegativity and thus are highly unstable when charged. As a result, carbocation intermediates are more likely to form on a molecule with additional functional groups that can delocalize the charge, such as the presence of additional alkyl groups, or resonance structures.

If a carbocation is stable enough to exist, then a nucleophile can successfully attack and carry out a reaction from anywhere. Note that the carbocation intermediate is bonded to three other atoms, thus creating a planar molecule. As steric hindrance is no longer a concern for Sn1 reactions, the nucleophile is free to attack from either side of the planar molecule. As a result, the products are found in a mixture of R- and S-products, with equal abundances of each. This is known as a racemic mixture.

To review R and S configuration, be sure to consult our guide on isomers.

c) Elimination reactions

Just as there are mechanisms describing the addition of a nucleophile to a molecule, there are reactions to remove groups and create double bonds. These are known as elimination reactions. There are two elimination reactions you may see on the MCAT: E1 and E2 reactions.

As with Sn1 and Sn2 reactions, E1 and E2 reactions differ in the number of species involved at the limiting step. E1 reactions take place in two distinct steps. The first step involves the loss of a leaving group to create a carbocation. This is the rate-limiting step. Next, a hydrogen ion is lost from an adjacent carbon, allowing the electrons to create a double bond with the carbocation center. As a result, the product contains a double bond and has “lost” two groups from the original molecule.

E2 reactions follow similar principles but occur in one step. In an E2 reaction, a nucleophile attracts a hydrogen ion, leaving the electrons. (Typically, this hydrogen atom is located “anti” to the leaving group. This means that the hydrogen must be on the other side of the double bond.) The electrons create a double bond with an adjacent carbon, “kicking off” a leaving group. The rate of this reaction depends on both the leaving group as well as the nucleophile concentration.

We’ve discussed carbocations in the context of substitution and elimination reactions. Carbon atoms can also adopt a negative charge after dissociating from another moiety, such as a hydrogen atom. These negatively charged carbon atoms are called carbanions and are also extremely reactive.

Note that the content outlined here is simply an introduction to organic chemistry. Although the MCAT does not necessarily require the memorization of specific mechanisms, you should be able to recognize when functional groups act as nucleophiles or electrophiles. Further, you should be able to understand factors that affect the rate of a reaction of stability of an intermediate compound, such as carbocation stability or steric hindrance.

Familiarity with these components of an organic chemistry reaction is much higher-yield than memorizing specific mechanisms. By recognizing electrophiles and nucleophiles, you will be able to understand any unfamiliar mechanisms that may come up on test day!

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Part 4: High-yield terms

Equilibrium arrows: two half-arrows pointing to the left and to the right between each step of the reaction; signify that a reaction is reversible

Mechanism: illustrated depiction of a chemical reaction

Double-headed arrows: curved arrows that indicate the movement of two electrons at once

Single-headed arrows: curved arrows that indicate the movement of one electron at once; also referred to as fish hooks

Nucleophiles: atoms on a molecule that donate electrons to a target molecule to form a bond

Electrophiles: atoms that accept electrons from a source to form a bond

Hydroxyl: characterized by R-OH chemical formula

Carbonyls: characterized by C=O double bond

Carboxylic acid: functional group that contains both carbonyl and hydroxyl group; chemical formula R-COOH

Amine: nitrogen-based functional group represented by formula NRx

Sn2: concerted mechanism that is second-order nucleophilic substitution reaction; also referred to as umbrella inversion

Sn1: first-order nucleophilic substitution reaction; results in the production of racemic mixture; proceeds through carbocation intermediate

Carbocation: positively charged carbon atom on a molecule; very unstable intermediate

Racemic mixture: mixture of R- and S-products with equal abundances of each

E1: first-order elimination reaction that proceeds through carbocation intermediate and produces a double bond in the product

E2: second-order elimination reaction and produces a double bond in the product

Leaving group: any functional group or species that leaves a reactant during a reaction

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Part 5: Passage-based questions and answers

Palladium complexes and palladium catalysis reactions are important tools in the synthesis of other organic molecules. The importance of these reactions is highlighted by the citation for the Nobel Prize in Chemistry 2010, which was awarded "for palladium-catalyzed cross couplings in organic synthesis."

Palladium catalysis continues to be studied to further the current understanding of the mechanism and seek new applications for its usage. Beta-hydrogen elimination appears to play a key role in reactions of palladium catalysis. The eliminated hydrogen atom usually falls into one of two categories, depending on the molecular hybridization of the carbon atom it is attached to.

The most common carbon hybridization of such an atom is sp³. Both alkyl and alkenyl palladium complexes in this pathway undergo a mechanism to create olefins and allenes. Of lesser abundance in this context is sp²-hybridized carbon atoms. The products resulting from this scheme are poorly investigated. These two modes of elimination are shown in Figure 1.

**Figure 1** Alkene synthesis based on beta-hydrogen elimination from sp3- and sp2-hybridized carbons.

Researchers seek to generate allenes from the second mode of palladium catalysis, involving sp²-hybridized carbon atoms. To do so, a pathway in which a desired δ-allylic palladium intermediate is generated from oxidative addition/isomerization of classic allylic alcohol derivatives of palladium. The proposed reaction is shown in Figure 2.

**Figure 2** A proposed palladium-catalyzed synthesis of allene

_{CREATOR AND ATTRIBUTION PARTY: ZHANG, G., SONG, YK., ZHANG, F. ET AL. PALLADIUM-CATALYZED ALLENE SYNTHESIS ENABLED BY Β-HYDROGEN ELIMINATION FROM SP2-CARBON. NAT COMMUN 12, 728 (2021). THE ARTICLE’S FULL TEXT IS AVAILABLE HERE: HTTPS://WWW.NATURE.COM/ARTICLES/S41467-020-20740-W. THE ARTICLE IS NOT COPYRIGHTED BY SHEMMASSIAN ACADEMIC CONSULTING. DISCLAIMER: SHEMMASSIAN ACADEMIC CONSULTING DOES NOT OWN THE PASSAGE PRESENTED HERE. CREATIVE COMMON LICENSE: HTTP://CREATIVECOMMONS.ORG/LICENSES/BY/4.0/. CHANGES WERE MADE TO ORIGINAL ARTICLE TO CREATE AN MCAT-STYLE PASSAGE.}

Question 1: Which of the following types of reactions is investigated in the experiment?

A) Sn1 and E1

B) Sn1 and Sn2

C) E1 and E2

D) E1 and Sn2

Question 2: According to the information presented in Figure 2, which of the following molecules has a good leaving group?

A) Molecule 1

B) Molecule 3a

C) Molecule 4a

D) Molecule 5a

Question 3: Which of the following is required for an E2 reaction?

A) A good leaving group

B) An anti-hydrogen

C) A carbonyl that’s a good target for attack

D) A suitable leaving group and an anti-hydrogen

Question 4: Which of the following functional groups listed below are considered to be good electrophiles?

A) Aldehyde, ketone, carboxylic acid, amines

B) Aldehyde, ketone, carboxylic acid

C) Aldehyde, alcohols

D) Hydroxyl, carboxylic acid, ketone

Answer key for passage-based questions

1. Answer choice C is correct. The passage discusses elimination reactions. Elimination reactions include E1 and E2 reactions. Sn1 and Sn2 reactions are examples of nucleophilic attack mechanisms (choice B is incorrect). There is insufficient evidence to deduce which form of elimination reaction occurs (choice C is correct).

2. Answer choice B is correct. A good leaving group is a functional group that can dissociate from a molecule and acts as an ion. These species usually have high electronegativity. Bromine is a leaving group, as it is a halogen with relatively high electronegativity (choice B is correct). None of the other molecules contain leaving groups that would be particularly stable.

3. Answer choice D is correct. An E2 reaction occurs in a one-step mechanism. For the one-step mechanism to occur, there must be a hydrogen anti, or opposite to, the leaving group. Otherwise, the reaction is unable to proceed (choice D is correct).

4. Answer choice B is correct. In general, carbonyl functional groups are electrophilic. Of the answer choices listed, ketones, aldehydes, and carboxylic acids all have carbon atoms within carbonyls that can serve as electrophiles (choice B is correct). Amines and hydroxyl groups generally serve as nucleophiles (choice D is incorrect). Alcohols may exhibit either nucleophilic or electrophilic behavior (choice C is incorrect).

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Part 6: Standalone questions and answers

Question 1: Which of the following statements best describes the primary difference between a nucleophile and an electrophile?

A) A nucleophile has a higher electron density, attracting more electrons; an electrophile has a lower electron density, donating electrons to create a bond

B) A nucleophile has a lower electron density, attracting more electrons; an electrophile has a higher electron density, donating electrons to create a bond

C) An electrophile has a higher electron density, attracting more electrons; a nucleophile has a lower electron density, donating electrons to create a bond

D) An electrophile has a lower electron density, attracting more electrons; a nucleophile has a higher electron density, donating electrons to create a bond

Question 2: Which of the following molecules is most likely to serve as either an electrophile or a nucleophile?

A)

B)

C)

D)

Question 3: What is the most likely stereochemical configuration of products resulting from the following reaction?

A) Racemic mixture

B) S-configuration

C) R-configuration

D) Not enough information provided

Question 4: Without considering any bond rotation, which of the following molecules could successfully undergo an elimination reaction?

A)

B)

C)

D)

Question 5: Which of the following statements most accurately compares single- and double-headed curved arrow mechanisms?

A) Both mechanisms show the movement of electrons but differ in the speed of reaction

B) Both mechanisms show the movement of energy

C) A single arrow signifies two electrons moving together, while a double arrow indicates two electrons moving separately

D) A single arrow mechanism involves the movement of one electron, while a double arrow mechanism involves the movement of a pair of electrons

Answer key for standalone questions

1. Answer choice D is correct. A nucleophile is an atom or molecule that has a high electron density with the potential to attack an electrophile to create a bond. An electrophile is an atom or molecule that has low electron density and readily accepts electrons to create a bond (choice D is correct).

2. Answer choice C is correct. Recall that an electrophile is a functional group with low electron density, and a nucleophile is a functional group with high electron density. Thus, the molecule of interest must contain both an electron-rich atom and an electron-poor atom. While alcohol functional groups can serve as either electrophiles or nucleophiles, their exact role is highly dependent on the pH of the environment (choice A is incorrect). Carbonyls are generally electrophilic (choices B and D are incorrect). In the case of a molecule containing a carboxylic acid, the hydroxyl oxygen can be nucleophilic while the carbonyl carbon is electrophilic (choice C is correct).

3. Answer choice A is correct. This mechanism depicts a nucleophilic addition reaction; thus, it is either an Sn1 or Sn2 reaction. The presence of a carbocation intermediate tips us off that the reaction is Sn1. Sn1 reactions create racemic products, or a mixture of both R- and S-molecules (choice A is correct).

4. Answer choice B is correct. Elimination reactions require two items: a good leaving group and hydrogen located anti to the leaving group. All of the molecules have bromine as a leaving group, which is a good leaving group. Thus, a decision must be made based on the location of the hydrogen atom. The only viable option must have a hydrogen atom located on the opposite side of the double bond to the bromine atom (choice B is correct).

5. Answer choice D is correct. Curved arrows indicate the movement of electrons; straight arrows indicate the progression of a reaction (choice A is incorrect). Recall that a single arrow mechanism involves the movement of one electron (choice C is incorrect). A double-headed arrow mechanism indicates the movement of a pair of electrons (choice D is correct).

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Fundamentals of Organic Chemistry for the MCAT: Everything You Need to Know

Learn key MCAT concepts about the fundamentals of organic chemistry, plus practice questions and answers

Table of Contents

Part 1: Introduction to the Fundamentals of Organic Chemistry