Survey of the Natural Sciences Study Guide for the DAT

Organic Chemistry (continued)

Reactions and Compounds

Many of the organic chemistry questions will be based on information in this section. The exam requires you to understand mechanisms and predict products that will result from certain reactions. Many of those are summarized below.

Alkene/Alkyne

Alkenes are synthesized by elimination reactions of alcohols or acyl halides. Alkenes undergo reduction reactions when \(\text{H}_2\) is added in the presence of a catalyst like platinum, palladium, or nickel. In these reactions, the double bond is catalytically hydrogenated.

Another type of reaction is the electrophilic addition, during which the pi (\(\pi\)) bond is broken to add another substituent, while the sigma (\(\sigma\)) bond remains intact. Electrophilic additions include the addition of \(\text{HX}\), \(\text{X}_2\), and \(\text{H}_2\text{O}\).

Free radical addition reactions maximize stability by adding the free radical to the most substituted carbon. Hydroboration utilizes \(\text{B}_2\text{H}_6\) to add a boron to the least sterically hindered carbon, then \(\text{H}_2\text{O}_2/\text{OH}^{-}\) reacts with the molecule to add an \(-\text{OH}\) group in place of the \(\text{BR}_2\) group. \(\text{KMnO}_4\) can also react with an alkene to oxidize it to an alcohol.

Ozonolysis proceeds in two steps, the first being a reaction with \(\text{O}_3\) and \(\text{CH}_2\text{Cl}_2\). Next, the intermediate reacts with \(\text{Zn/H}_2\text{O}\) to form an aldehyde. If, instead, the second reaction is performed with \(\text{NaBH}_4\) and \(\text{CH}_3\text{OH}\), two alcohols will be produced.

Peroxycarboxylic acids can also be used to oxidize alkenes. Polymerization uses radical mechanisms, heat, and high pressure to produce a large polymer chain.

Alkynes can be synthesized by eliminating two molecules of \(\text{HX}\) using heat and a base. Similarly to how alkenes react in the presence of a metal catalyst, alkynes will be reduced in the same manner. Likewise, alkynes behave similarly to alkenes in electrophilic addition reactions, following Markovnikov’s rule of addition.

Free radical additions, by contrast, behave in an anti-Markovnikov manner. Hydroboration reactions allow the triple bond to be broken and the \(\text{BR}_2\) group to be added, which can be further reacted with acetic acid to turn the alkyne into an alkene.

Synthesis of Alkenes: Elimination of Alcohol/Elimination of Acyl Halide

Retrieved from: https://openstax.org/books/organic-chemistry/pages/8-1-preparing-alkenes-a-preview-of-elimination-reactions

Reduction of Alkenes

Retrieved from: https://openstax.org/books/organic-chemistry/pages/8-6-reduction-of-alkenes-hydrogenation

Aromatic

Electrophilic aromatic substitutions, or when an electrophile replaces an atom on the aromatic ring, include halogenation, sulfonation, nitration, and acylation. Halogenation occurs when a halogen element reacts with an aromatic ring along with a Lewis acid.

Sulfonic acids are produced by reacting a benzene ring with sulfuric acid and sulfur trioxide, a process known as sulfonation. Reacting a mixture of nitric acid and sulfuric acid with a benzene ring adds a nitro group to the ring through a process called nitration. Another name for the process of acylation is a Friedel-Crafts reaction, which is a process that adds acyl groups to a benzene ring in the presence of a Lewis acid. Reduction is catalyzed by rhodium or carbon in the presence of \(\text{H}_2\).

Retrieved from: https://openstax.org/books/organic-chemistry/pages/16-2-other-aromatic-substitutions

Reaction Type: Acylation

Retrieved from: https://openstax.org/books/organic-chemistry/pages/16-3-alkylation-and-acylation-of-aromatic-rings-the-friedel-crafts-reaction

Substitution/Elimination

There are two types of nucleophilic substitution reactions: SN1 and SN2. SN1 reactions are unimolecular nucleophilic substitutions involving the formation of a carbocation intermediate when the leaving group breaks off. This type of reaction has a rate-determining step that’s dependent on the concentration of the substrate. SN2 reactions are bimolecular nucleophilic substitutions that occur in one step, which inverts the carbon center’s configuration. The rate of SN2 reactions depends on the concentrations of both the substrate and the nucleophile.

Similarly, there are two kinds of elimination reactions: E1 and E2. E1, or unimolecular elimination reactions, are two-step mechanisms starting with the formation of a carbocation intermediate, just like SN1 reactions. A base takes a proton, forming a double bond. E2, or bimolecular elimination reactions, involve one step, starting with a base taking a proton while the leaving group breaks off, resulting in a double bond.

Aldehyde/Ketone

Aldehydes and ketones are synthesized by oxidizing primary and secondary alcohols, respectively, in the presence of \(\text{PCC}\) or \(\text{Na}_2\text{Cr}_2\text{O}_7/\text{H}_2\text{SO}_4\). Additionally, in the presence of \(\text{O}_3\), \(\text{CH}_3\text{Cl}_2\), and \(\text{Zn/H}_2\text{O}\), an alkene can be used to synthesize an aldehyde or ketone.

Friedel-Crafts acylation, which is mentioned in the section on aromatic reactions, can also be used to produce a ketone when reacting benzene with an acyl halide. Aldehydes can be oxidized to a carboxylic acid by using many reagents, including \(\text{KMnO}_4\), \(\text{K}_2\text{Cr}_2\text{O}_7\), \(\text{Ag}_2\text{O}\), or \(\text{H}_2\text{O}_2\). Aldehydes and ketones can be reduced to alcohols via reagents like \(\text{LAH}\) and \(\text{NaBH}_4\).

Aldehydes and ketones can also be reduced to alkanes via a Wolff-Kishner reduction or a Clemmensen reduction.

• Wolff-Kishner reductions are performed in two steps: (1) \(\text{H}_2\text{NNH}_2\) addition and (2) base and heat addition.

• Clemmensen reductions perform the reduction using amalgamated zinc and hydrochloric acid.

Aldehydes and ketones can undergo enolization via rearrangement. In this type of reaction, aldehydes and ketones can act as nucleophiles. When combined with a base, these molecules can be used to complete Michael addition reactions.

Addition reactions occur when a nucleophile attacks the carbon with a double bond to oxygen and adds itself to the molecule. Similarly, water can act as a nucleophile and hydrate aldehydes and ketones by adding an \(-\text{OH}\) group in a similar fashion to addition reactions.

Reacting one equivalent of alcohol with aldehydes or ketones will result in hemiacetals or hemiketals, respectively, and adding two equivalents of alcohol will form the acetal or ketal products, respectively. When aldehydes or ketones react with hydrogen cyanide (\(\text{HCN}\)), cyanohydrins are produced. In an aldol condensation reaction, the aldehyde is both the nucleophile and the target molecule, forming an aldol molecule from aldehyde and alcohol. The Wittig reaction is used to form a carbon-carbon double bond from the carbon-oxygen double bond.

Aldehyde/Ketone Synthesis via Alcohol Oxidation

Retrieved from: https://openstax.org/books/organic-chemistry/pages/17-7-oxidation-of-alcohols

Friedel-Crafts Acylation

Retrieved from: https://openstax.org/books/organic-chemistry/pages/16-3-alkylation-and-acylation-of-aromatic-rings-the-friedel-crafts-reaction

Wolff-Kishner Reduction

Retrieved from: https://openstax.org/books/organic-chemistry/pages/19-9-nucleophilic-addition-of-hydrazine-the-wolff-kishner-reaction

Carboxylic Acids and Derivatives

Carboxylic acids are synthesized through aldehyde, primary alcohol, and alkylbenzene oxidation reactions using an oxidizing agent such as \(\text{KMnO}_4\), \(\text{K}_2\text{Cr}_2\text{O}_7\), or \(\text{CrO}_3\).

Grignard reagents and carbon dioxide will also react to form carboxylic acids. Additionally, carboxylic acids can be synthesized via hydrolysis of nitriles.

Grignard Reagent Reactions

Retrieved from: https://openstax.org/books/organic-chemistry/pages/20-5-preparing-carboxylic-acids

Nucleophiles can attack the carbon, which is double bonded to oxygen to complete nucleophilic substitution reactions.

Lithium aluminum hydride (\(\text{LAH}\)) can be used to reduce carboxylic acids to the primary alcohol form. Ester formation occurs when carboxylic acids react with alcohols in the presence of acid to form esters and water.

Ester Formation

Retrieved from: https://openstax.org/books/organic-chemistry/pages/21-3-reactions-of-carboxylic-acids

Acyl halide synthesis reactions occur by reacting a carboxylic acid with \(\text{SOCl}_2\).

Decarboxylation reactions can occur spontaneously when carboxylic acids are heated. The elements of a carboxylic acid rearrange into a keto form, releasing carbon dioxide as a product.

Decarboxylation Reactions

Retrieved from: https://openstax.org/books/organic-chemistry/pages/22-7-alkylation-of-enolate-ions

Soap formation reactions occur when long-chain carboxylic acids react with \(\text{NaOH}\) or \(\text{KOH}\).

Derivatives of carboxylic acids include acyl halides, anhydrides, esters, and amides. Acyl halides are synthesized by reacting acid chlorides or acid bromides with a carboxylic acid. Similar to carboxylic acids, acyl halides can undergo nucleophilic acyl substitution reactions in which halides are the leaving group and a carbonyl compound is the product. This includes the hydrolysis reaction, which results in the reformation of the carboxylic acid.

Acyl chlorides react with carboxylate salts to form anhydrides. Acyl halides react with alcohols to form esters via a similar mechanism to that of a nucleophilic attack during hydrolysis. Similarly, acyl halides will react with amines to form amides, with a side product of ammonium halide (\(\text{NH}_4\text{Cl}\)). Acyl halides can undergo Friedel-Crafts acylation reactions as well. They can also be reduced to alcohols with reducing agents like \(\text{LAH}\).

Anhydride Synthesis: Acyl Halide and Carboxylate Salt Reaction/Condensation Reactions

Retrieved from: https://openstax.org/books/organic-chemistry/pages/21-4-chemistry-of-acid-halides AND https://openstax.org/books/organic-chemistry/pages/21-3-reactions-of-carboxylic-acids

Acyl Halide and Amine Reaction (Amide Synthesis)

Retrieved from: https://openstax.org/books/organic-chemistry/pages/21-4-chemistry-of-acid-halides

Anhydrides can undergo cyclic anhydride condensation reactions through heating, which drives the molecule to seek stability by forming a ring. Another way that anhydrides can be synthesized is through condensation reactions of two carboxylic acids with water as a byproduct.

Anhydrides, while less reactive than acyl halides, can also undergo nucleophilic substitution reactions and hydrolysis reactions in a similar fashion. When anhydrides react with ammonia, products of amides and carboxylic acids are produced, and the carboxylic acid continues to react with the ammonia until the ammonium carboxylate is formed. Anhydrides react with alcohols to form esters and carboxylic acids. Additionally, anhydrides can undergo Friedel-Crafts acylation in the presence of Lewis acids like \(\text{AlCl}_3\), resulting in an aryl ketone and carboxylic acid.

Anhydride Hydrolysis, Anhydride and Ammonia Reaction, and Anhydride and Alcohol Reaction (Ester and Carboxylic Acid Synthesis)

Retrieved from: https://openstax.org/books/organic-chemistry/pages/21-5-chemistry-of-acid-anhydrides

Esters can be synthesized via many mechanisms, some aforementioned, but they also can be formed via carboxylic acid and alcohol condensation reactions. Esters are even less reactive than anhydrides, but they will also undergo nucleophilic substitution reactions and hydrolysis. Additionally, with ammonia or another nitrogen base, esters can be converted to amides. Reacting an ester with alcohols can yield another ester and a displaced alkoxy group via transesterification.

Grignard addition reactions can occur through the addition of carbonyl groups and the formation of ketones or by further reacting the ethers to yield tertiary alcohols. Claisen condensation or acetoacetic ester condensation reaction adds an enolate anion to another ester and displaces an ethoxide ion. Reduction for esters alone is accomplished via \(\text{LAH}\).

Ester Synthesis

Retrieved from: https://openstax.org/books/organic-chemistry/pages/21-6-chemistry-of-esters

Claisen Condensation Reaction

Retrieved from: https://openstax.org/books/organic-chemistry/pages/23-7-the-claisen-condensation-reaction

While amides are the least reactive of the carboxylic acid derivatives, they are still able to be used in nucleophilic substitution reactions and hydrolysis. Hofmann rearrangement reactions are used to convert an amide to a primary amine, resulting in the byproducts of carbonyl carbon and carbon dioxide. Amides are reduced to an amine by \(\text{LAH}\).

Amide Hydrolysis

Images retrieved from: https://openstax.org/books/organic-chemistry/pages/21-7-chemistry-of-amides

Acid-Base Chemistry

In organic chemistry, it is important to understand how molecules interact with one another. From the general chemistry section of this study guide, we know that acids are proton donors and bases are proton acceptors. This is foundational in understanding organic chemistry reactions.

Ranking Acidity/Basicity

It is important to understand the impact of the structure of a molecule, as acidity increases with the increasing electronegativity of the bonded elements. As the size of the bonded elements increases, acidity increases. Additionally, the stronger the \(\text{s}\)-character of the molecule, the more acidic. Basicity decreases in the aforementioned situations.

Acidity and basicity can be analyzed via pH and \(pK_a\) data analysis as well. The \(-\log[Ka] = pK_a\), with the \(K_a\) being the dissociation constant. The lower the \(pK_a\), the stronger the acid. Conversely, the greater the \(pK_a\) of the conjugate acid, the stronger the base. When it comes to pH, the lower the value, the more acidic, and the higher the value, the more basic.

Prediction of Products and Equilibria

It is first important to figure out which compound is the acid and which is the base. Reactions tend to favor the formation of weaker acids and weaker bases. The direction of equilibrium follows the weaker acid and the higher pKa. Resonance, inductive effects, and hybridization can stabilize conjugate bases or acids, influencing the equilibrium.

Aromatics and Bonding

In addition to the aromatic reactions that were discussed in the reactions section of the study guide, it is important to understand the structure, resonance, and hybridization of aromatic rings as it relates to their reactivity and interactions with other molecules.

Aromaticity

Huckel’s rule states that aromaticity is indicated by a molecule having \(4n + 2 \pi\) electrons. Aromatic molecules have a planar conformation and are cyclic in structure.

Resonance

Resonance describes the delocalization of the \(\pi\) electrons, which are ultimately shared equally throughout the aromatic ring. The \(\text{p}\) orbitals of these molecules overlap with one another. This quality of the rings allows for very stable bonds of equal length somewhere in between the length of a single and double bond.

Atomic/Molecular Orbitals

Aromatic molecules have a conjugated system of \(\text{p}\) orbitals overlapping above and below the plane of the carbon atoms in the ring. These \(\text{p}\) orbitals combine to form molecular \(\pi\) orbitals. This delocalization creates a lower-energy, more stable structure compared to localized electrons.

Hybridization

Aromatic rings have their carbons in the \(\text{sp}^2\) hybridization. The \(\text{sp}^2\) hybrid orbitals are used to form \(\sigma\)-bonds with two adjacent carbon atoms and one hydrogen atom. The unhybridized \(\text{p}\) orbitals on each carbon atom overlap sideways to form a continuous \(\pi\)-system above and below the plane of the ring. This overlapping of \(\text{p}\) orbitals results in the delocalization of \(\pi\) electrons across the ring.

Bond Angles and Lengths

A bond angle is the angle formed between two adjacent bonds. The hybridization, and therefore the geometry, of the central atom often determines the bond angle value. The measurement of the bond between two atoms is called the bond length. As the amount of bonds increases (e.g., double, triple), the bond length decreases. The stronger the bond due to greater electron overlap, the shorter the bond length.