MCAT Organic Chemistry Review

Analyzing Organic Reactions

Concept Summary

Acids and Bases

·        Lewis acids are electron acceptors; they have vacant orbitals or positively polarized atoms.

·        Lewis bases are electron donors; they have a lone pair of electrons and are often anions.

·        Brønsted–Lowry acids are proton donors; Brønsted–Lowry bases are proton acceptors.

·        Amphoteric molecules can act as either acids or bases, depending on reaction conditions. Water is a common example of an amphoteric molecule.

·        The acid dissociation constantKa, is a measure of acidity. It is the equilibrium constant corresponding to the dissociation of an acid, HA, into a proton (H+) and its conjugate base (A).

o   pKa is the negative logarithm of Ka. A lower (or even negative) pKa indicates a stronger acid.

o   pKa decreases down the Periodic Table and increases with electronegativity.

·        Alcohols, aldehydes, ketones, carboxylic acids, and carboxylic acid derivatives are common acidic functional groups. α-hydrogens (hydrogens connected to an α-carbon, a carbon adjacent to a carbonyl) are acidic.

·        Amines and amides are common basic functional groups.

Nucleophiles, Electrophiles, and Leaving Groups

·        Nucleophiles are “nucleus-loving” and contain lone pairs or π bonds. They have increased electron density and often carry a negative charge.

o   Nucleophilicity is similar to basicity; however, nucleophilicity is a kinetic property, while basicity is thermodynamic.

o   Charge, electronegativity, steric hindrance, and the solvent can all affect nucleophilicity.

o   Amino groups are common organic nucleophiles.

·        Electrophiles are “electron-loving” and contain a positive charge or are positively polarized.

o   More positive compounds are more electrophilic.

o   Alcohols, aldehydes, ketones, carboxylic acids, and their derivatives can act as electrophiles.

·        Leaving groups are the molecular fragments that retain the electrons after heterolysis.

o   The best leaving groups can stabilize additional charge through resonance or induction.

o   Weak bases (the conjugate bases of strong acids) make good leaving groups.

o   Alkanes and hydrogen ions are almost never leaving groups because they form reactive anions.

·        Unimolecular nucleophilic substitution (SN1reactions proceed in two steps.

o   In the first step, the leaving group leaves, forming a carbocation, an ion with a positively charged carbon atom.

o   In the second step, the nucleophile attacks the planar carbocation from either side, leading to a racemic mixture of products.

o   SN1 reactions prefer more-substituted carbons because the alkyl groups can donate electron density and stabilize the positive charge of the carbocation.

o   The rate of an SN1 reaction is dependent only on the concentration of the substrate: rate = k[R–L]

·        Bimolecular nucleophilic substitution (SN2reactions proceed in one concerted step.

o   The nucleophile attacks at the same time as the leaving group leaves.

o   The nucleophile must perform a backside attack, which leads to an inversion of stereochemistry.

o   The absolute configuration is changed—(R) to (S) and vice-versa—if the incoming nucleophile and the leaving group have the same priority in the molecule.

o   SN2 reactions prefer less-substituted carbons because the alkyl groups create steric hindrance and inhibit the nucleophile from accessing the electrophilic substrate carbon.

o   The rate of an SN2 reaction is dependent on the concentrations of both the substrate and the nucleophile: rate = k[Nu:][R–L]

Oxidation–Reduction Reactions

·        The oxidation state of an atom is the charge it would have if all its bonds were completely ionic.

o   CH4 is the lowest oxidation state of carbon (most reduced); CO2 is the highest (most oxidized).

o   Carboxylic acids and carboxylic acid derivatives are the most oxidized functional groups; followed by aldehydes, ketones, and imines; followed by alcohols, alkyl halides, and amines.

·        Oxidation is an increase in oxidation state and is assisted by oxidizing agents.

o   Oxidizing agents accept electrons and are reduced in the process. They have a high affinity for electrons or an unusually high oxidation state. They often contain a metal and a large number of oxygens.

o   Primary alcohols can be oxidized to aldehydes by pyridinium chlorochromate (PCC) or to carboxylic acids by stronger oxidizing agents, like chromium trioxide (CrO3) or sodium or potassium dichromate (Na2Cr2O7 or K2Cr2O7).

o   Secondary alcohols can be oxidized to ketones by most oxidizing agents.

o   Aldehydes can be oxidized to carboxylic acids by most oxidizing agents.

·        Reduction is a decrease in oxidation state and is assisted by reducing agents.

o   Reducing agents donate electrons and are oxidized in the process. They have low electronegativity and ionization energy. They often contain a metal and a large number of hydrides.

o   Aldehydes, ketones, and carboxylic acids can be reduced to alcohols by lithium aluminum hydride (LiAlH4).

o   Amides can be reduced to amines by LiAlH4.

o   Esters can be reduced to a pair of alcohols by LiAlH4.

Chemoselectivity

·        Both nucleophile–electrophile and oxidation–reduction reactions tend to act at the highest-priority (most oxidized) functional group.

·        One can make use of steric hindrance properties to selectively target functional groups that might not primarily react, or to protect leaving groups.

o   Diols are often used as protecting groups for aldehyde or ketone carbonyls.

o   Alcohols may be protected by conversion to tert-butyl ethers.

Steps for Problem-Solving

1.    Know your nomenclature.

2.    Identify the functional groups.

3.    Identify the other reagents.

4.    Identify the most reactive functional group(s).

5.    Identify the first step of the reaction.

6.    Consider stereoselectivity.