Take Home Lessons from Lecture 4

MECHANISMS (CONT.)

1. Carbonyl compounds initially react as an electrophile at the C atom, or are protonated at the O atom, depending on whether the reaction is run in acid or not. In either case, a nucleophile will generally react at the C atom to give a tetrahedral addition intermediate that is either protonated to give an alchohol product, or loses a leaving group to give a new carbonyl species.

KEY EXAMPLES: Acetal formation, Grignard reaction with an aldehyde/ketone and base promoted ester hydrolysis

2. Enolates are important nucleophiles because they make new C-C bonds with carbonyl groups.

KEY EXAMPLE: Aldol reaction

3. Alpha, beta unsaturated carbonyls can add nucleophiles at the C=C bond.

KEY EXAMPLE: Michael Reaction

4. Electrophilic aromatic substution occurs when the weakly nucleophilic aromatic pi system reacts with a wicked strong electrophile to create an arenium ion intermediate. Charge distribution within the arenium ion determines whether groups already on the ring are activating, deactivating, ortho-para directing or meta directing.

A. GOOD groups (alkyl or have a lone pair on the atom attached to the ring) are electron donating and therefore activating, ortho-para directing.

B. BAD groups (have a pi bond on atom attached to ring) are electron withdrawing and therefore deactivating, meta directing.

C. UGLY groups (the halogens) are a bit Good and a bit Bad, they are the halogens, and they are deactivating but ortho-para directing.

KEY EXAMPLE: Electrophilic aromatic substitution: nitration, sulfation, halogenation

REACTIONS

5. The best way to study reactions is to make roadmaps. This is explained fully in the Roadmaps section of this website.

A. An organic chemistry roadmap is a graphical representation of the different reactions that can be used to interconvert functional groups in molecules. Comparing the organic chemistry roadmap to a real roadmap, the functional groups are analogous to cities, and the reactions are the roads between them.

B. A roadmap is a large piece of paper, usually the size of a poster, in which the important functional groups are listed. The essential information (i.e. reagents used, stereochemistry, regiochemistry, key mechanistic steps) about each reaction we study is recorded.

Roadmap 1: First semester reactions. Use this template to make your own roadmap of first semester reactions (through the ethers/epoxides.) Note how these are almost entirely interconversions of functional groups with onlya couple carbon-carbon bond forming reactions and only one carbon-carbon bond breaking reaction. Use this summary of first semester reactions as a guide to place reactions on your roadmap.

SUMMARY OF SKILLS YOU MUST MASTER FOR THE MCAT:

1) Be familiar with the many reactions involving carbonyl compounds, including reactions with enolates.

2) Be familiar with electrophilic aromatic subsitution reactions including cases in which a group is already on the aromatic ring.

3) Be familiar with a large number of different reactions, and the best way to study these is to use a roadmap.