MCAT Organic Chemistry Review

Alcohols

Conclusion

Alcohols are a particular favorite of the MCAT testmakers. We got our first look at the unique properties that stem from hydrogen bonding, an important ability of alcohols. Alcohols can be oxidized to aldehydes, ketones, or carboxylic acids depending on the substitution of the alcohol and the strength of the oxidizing agent. From this point forward, oxidation and reduction will be important reactions with all functional groups. Alcohols can also participate in nucleophilic substitution reactions, which may be facilitated by converting the alcohol into a mesylate or tosylate. Finally, phenols (and their oxidized counterparts, quinones and hydroxyquinones) are involved in a number of biochemical pathways. In particular, their utility is seen in processes that require rapid oxidation and reduction, such as photosynthesis and the electron transport chain.

Over the next four chapters, we’ll explore other oxygen-containing compounds. Recognize that these chapters are put in a specific order: as you move further along in MCAT Organic Chemistry Review, the functional groups will become more reactive. First, we’ll look at aldehydes and ketones (and their deprotonated forms, enols and enolates). Then, we’ll explore carboxylic acids and their derivatives: amides, esters, and anhydrides.

Concept Summary

Description and Properties

·        Alcohols have the general form ROH and are named with the suffix – ol. If they are not the highest priority, they are given the prefix hydroxy–.

·        Phenols are benzene rings with hydroxyl groups. They are named for the relative positions of the hydroxyl groups: ortho– (adjacent carbons), meta– (separated by one carbon), or para– (on opposite sides of the ring).

·        Alcohols can hydrogen bond, raising their boiling and melting points relative to corresponding alkanes. Hydrogen bonding also increases the solubility of alcohols.

·        Phenols are more acidic than other alcohols because the aromatic ring can delocalize the charge of the conjugate base.

·        Electron-donating groups like alkyl groups decrease acidity because they destabilize negative charges. Electron-withdrawing groups, such as electronegative atoms and aromatic rings, increase acidity because they stabilize negative charges.

Reactions of Alcohols

·        Primary alcohols can be oxidized to aldehydes only by pyridinium chlorochromate (PCC); they will be oxidized all the way to carboxylic acids by any stronger oxidizing agents.

·        Secondary alcohols can be oxidized to ketones by any common oxidizing agent.

·        Alcohols can be converted to mesylates or tosylates to make them better leaving groups for nucleophilic substitution reactions.

o   Mesylates contain the functional group –SO3CH3, which is derived from methanesulfonic acid.

o   Tosylates contain the functional group –SO3C6H4CH3, which is derived from toluenesulfonic acid.

·        Aldehydes or ketones can be protected by converting them into acetals or ketals.

o   Two equivalents of alcohol or a dialcohol are reacted with the carbonyl to form the acetal (a primary carbon with two –OR groups and a hydrogen atom) or ketal (a secondary carbon with two –OR groups).

o   Other functional groups in the compound can be reacted (especially by reduction) without effects on the newly formed acetal or ketal.

o   The acetal or ketal can then be converted back to a carbonyl by catalytic acid, which is called deprotection.

Reactions of Phenols

·        Quinones are synthesized through oxidation of phenols.

o   Quinones are resonance-stabilized electrophiles.

o   Vitamin K1 (phylloquinone) and Vitamin K2 (the menaquinones) are examples of biochemically relevant quinones.

·        Hydroxyquinones are produced by oxidation of quinones, adding a variable number of hydroxyl groups.

·        Ubiquinone (coenzyme Q) is another biologically active quinone that acts as an electron acceptor in Complexes I, II, and III of the electron transport chain. It is reduced to ubiquinol.

Answers to Concept Checks

·        5.1

1.    Phenols like p-ethylphenol have increased acidity due to resonance and the electron-withdrawing character of the phenol aromatic ring. If p-ethylphenol is a stronger acid than ethanol, it will have a lower pKa.

2.    1,6-Hexanediol will have the highest boiling point; a molecule with two hydroxyl moieties can have more hydrogen bonding. The 1-hexanol boiling point will be next, with 1-pentanol having the lowest boiling point. 1-Hexanol has a higher boiling point than 1-pentanol because the longer hydrocarbon chain has increased van der Waals forces.

·        5.2

1.    In the presence of strong oxidizing agents, primary alcohols are completely oxidized to carboxylic acids. Secondary alcohols can only be oxidized to ketones.

2.    Primary alcohols can only be oxidized to aldehydes using pyridinium chlorochromate (PCC).

3.    Mesylates and tosylates are used to convert an alcohol into a better leaving group. This is particularly useful for nucleophilic substitution reactions because it increases the stability of the product. They can also be used as protecting groups because many reagents (especially oxidizing agents) that would react with an alcohol cannot react with these compounds.

4.    Aldehydes or ketones can be reacted with two equivalents of alcohol or a diol to form an acetal or ketal. Acetals and ketals are less reactive than aldehydes and ketones (especially to reducing agents), and can thus protect the functional group from reacting. The acetal or ketal can then be reverted back to the carbonyl by catalytic acid.

·        5.3

1.    Quinones are produced by oxidation of phenols.

2.    Hydroxyquinones are produced by the oxidation of quinones, adding a variable number of additional hydroxyl groups.

3.    Ubiquinone has conjugated rings, which stabilize the molecule when accepting electrons. Additionally, the long alkyl chain in the molecule allows for lipid solubility, which allows the molecule to function in the phospholipid bilayer.

Shared Concepts

·        Biochemistry Chapter 5

o   Lipid Structure and Function

·        General Chemistry Chapter 8

o   The Gas Phase

·        Organic Chemistry Chapter 1

o   Nomenclature

·        Organic Chemistry Chapter 4

o   Analyzing Organic Reactions

·        Organic Chemistry Chapter 6

o   Aldehydes and Ketones I

·        Organic Chemistry Chapter 8

o   Carboxylic Acids