Essential Organic Chemistry Principles and Reactions

Organic Synthesis and Reaction Mechanisms

Malonic Ester Synthesis and Carbonyl Reactivity

Electrophiles (e+) for Malonic Ester Synthesis include epoxides, primary haloalkanes, and conjugated ketones. Esters react with 2 equivalents of irreversible nucleophiles, such as LiAlH4 and RMgBr, to yield an alcohol product. Acyl halides undergo fast hydrolysis and do not require a catalyst because the acyl halide is a better electrophile compared to carboxylic acids, and Cl- is a better leaving group than OH-.

Carbohydrate Chemistry

• Reducing sugars contain hemiacetals at the anomeric carbon.
• Alpha 1,4-linked polyglucans are known as amylose, used for energy storage in plants (digestible by humans).
• Oligosaccharides consist of 3-10 units.
• Reduction of monosaccharides yields alditols, occurring with both aldoses and ketoses.
• Monosaccharides react as carbonyls, enols, and alcohols.
• General carbohydrate formula: Cx(H2O)y; monosaccharides: Cx(H2O)x.

Enolates and Acidity

The pKa of an ester enolate is approximately 25, while the pKa of a beta-ketoester enolate is approximately 11. The pKa alpha to a ketone is 19-21, and alpha to an aldehyde is 16-18; this difference is due to electron donation, induction, and hyperconjugation by alkyl groups on the ketone. To achieve 100% enolate ion formation, LDA is used (NaOH creates an equilibrium enolate, and RMgBr acts as a nucleophile).

Carbocations and Rearrangements

Carbocation rearrangements can shift either H or alkyl groups and typically form lower energy carbocation intermediates. Rearrangements shift a cation by 1 central atom. HBr and HCl are two nucleophilic acids that facilitate substitution reactions with alcohols.

Ethers and Epoxides

Ethers do not react with redox reagents or bases, but do react with strong acids. Most do not react with nucleophiles, with the exception of epoxides. Epoxides form by reacting alkenes with mcpba. Reaction of epoxides in both acidic and basic conditions follows an SN2 mechanism and inverts stereochemistry at the reacting carbon. In acid, epoxides react at the more substituted side; in base, they react at the less substituted side.

Aromaticity and Functional Groups

Aromatic molecules must be cyclic, conjugated, planar, and possess 4N+2 Pi electrons. Aromatic molecules have lower internal energy. Friedel-Crafts Alkylation problems include carbocation rearrangement and polyalkylation. Common names include benzoic acid for benzene with a -COOH group, and benzyl for the C6H5CH2– substituent. Conjugated molecules with 8 Pi electrons tend to twist out of plane.

Redox and Addition Reactions

Reduction of carbon is the loss of bonds to electronegative atoms or the gain of bonds to hydrogen. Alkanes are the most reduced organic functional group. It is hard to selectively oxidize alkanes to alcohols, but easy to selectively oxidize secondary alcohols to ketones using H2CrO4/PCC. Weakly basic nucleophiles tend to add via 1,4-addition to conjugated carbonyls because the reaction at the carbonyl is reversible.