Integrated SequencePhysics Chemistry Organic Biology

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Special points of emphasis

The Chemical Bond

Acids and Bases

Nucleophiles and Electrophiles

Reactions of Alkyl Halides

A nucleophile is characterized by its nonbonded pair of electrons that it can use to form a covalent bond. Nucleophiles are Lewis bases. In SN2 substitution, the entering Lewis base (nucleophile) uses its unshared pair of electrons to displace the leaving group, which is another Lewis base departing with its pair of electrons. The correlation between basicity (Brønsted) and nucleophilicity is complex, depending on the solvent and steric interactions. The facility of leaving groups is also complex, depending on the solvent as well as the nucleophile. In general, though, a good leaving group must be able to take on negative charge. The acidity of the conjugate acid is a reasonable guide for leaving groups. The stronger the conjugate acid, the more stable the anion, so the better the species will serve as a leaving group.

Nucleophiles and Electrophiles

Reactions of Alkyl Halides

A good exercise is to correlate various common nucleophiles in substitution reactions to their substitution products. For several of these nucleophiles, however, substitution could only occur with primary alkyl halides because of their strong Brønsted basicity. Use of alkoxide anion forms ethers; hydrogen sulfide converts alkyl halides into thiols; use of acetylide anion or cyanide anion leads to the formation of new carbon-carbon bonds; use of azide anion leads to carbon-nitrogen bond formation.

Nucleophiles and Electrophiles

Reactions of Aromatic Compounds

Nucleophiles can react with aromatic compounds, although the electrophilic reaction is more prominent. The reaction of a nucleophile with an aromatic compound occurs by nucleophilic aromatic substitution. Don't confuse this reaction on the MCAT with the quintessential aromatic reaction, electrophilic aromatic substititon. On the test you will be expected to know electrophilic aromatic substitution backwards and forwards, but if you were given a passage on nucleophilic aromatic substitution, the passage would probably give you the mechanism.

Nucleophiles and Electrophiles

Reactions of Alcohols and Ethers

Let us continue our survey of nucleophilic mechanisms in organic chemistry with alcohols and ethers. The reason for this kind of survey is to restimulate your familiarity with the organic reactions by approaching them from a different angle. Every time you read through a list of reactions in a different context, you are building structure to your knowledge and encouraging retention. Alcohols and ethers undergo many nucleophilic reactions including the conversion of alcohols to dialkyl ethers, Williamson ether synthesis, acid cleavage of ethers, and epoxide ring opening.

Nucleophiles and Electrophiles

Reactions of Aldehydes and Ketones

One of the major categories of reactions of aldehydes and ketones involves nucleophilic attack on the carbonyl carbon. This critical class of reactions includes the reaction of Grignard reagents with aldehydes and ketones, acetal formation, cyanohydrin formation, reaction of aldehydes and ketones with amines, Wolff-Kishner reduction, the Wittig reaction, Cannizzaro reaction, aldol condensation, and conjugate nucleophilic addition.

Nucleophiles and Electrophiles

Reactions of Carboxylic Acids and Derivatives

Similar in the manner of nucleophilic approach to the reactions of nucleophiles with aldehydes and ketones, reactions involving nucleophilic attack on the carboxyl group of carboxylic acids and their derivatives include Fischer Esterification, Carboxylate Anion in SN2 Ester Formation, Hydrolysis of Acid Halides, Aminolysis of Acid Halides, Esterification of Acid Halides, Esterification of Acid Anhydrides, Saponification of Esters, and Nitrile Hydrolysis.

Nucleophiles and Electrophiles

Bioenergetics and Cellular Respiration

Integration of Metabolism

Organic chemistry takes on a different flavor in the context of the overall learning program for a future doctor compared to a future chemical engineer. The MCAT reflects these broader pedagogical imperatives somewhat, tilting the balance of emphasis in organic chemistry towards the areas of the discipline that will be most pertinent to biochemistry. That being said, we should mention in the context of our position among the subtopics of the Main Cycle, that the amine, hydroxyl, imidazole, and sulfhydryl groups are very important nucleophilic functional groups in biochemistry. The MCAT is fond of presenting a mechanism that is similar to a core organic mechanism, but with a tilt toward biochemistry.

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