Organic Chemistry

Question 1

Lewis Acids and Bases

Answer 1

• Lewis Acid: Electron pair acceptor. Tend to be Electrophiles. Can be positively polarized or charged.
• Lewis Base: Electron pair donor. Tend to be Nucleophile. Can be negatively charged or polarized.
• Form Coordinate Covalent Bonds, in which both electrons in the bond come from Lewis Base (electron pair donor).
• Acidity increases as pKa and bond strength decrease and as electronegativity increases.
• Alpha-hydrogens (on alpha-carbons of carbonyl compounds) are especially acidic.
• Carboxylic Acids and Derivatives, Alcohols, Aldehydes, and Ketones (at alpha-carbon) act as acids and electrophiles.
• Amines and Amides act as bases and nucleophiles.

Question 2

Nucleophiles and Electrophiles

Answer 2

• Nucleophiles: Species with lone pairs or π bonds that can form new bonds with electrophiles.
• CHON with minus sign or lone pair are good nucleophiles.
• Nucleophilicity increases with increasing electron density (more negative charge).
• Nucleophilicity decreases as electronegativity increases.
• Nucleophilicity decreases in protic solvents, as nucleophile can be protonated or participate in hydrogen bonding.
• Electrophiles: Species with positive charge or positively polarized atom that can accept an electron pair from nucleophile.
• Carbocations and carbonyl carbons are good electrophiles.
• Carboxylic Acid Derivatives: Good electrophiles - Anhydrides, Carboxylic Acids and Esters, Amides - Good nucleophiles.

Question 3

Leaving Group

Answer 3

• In substitution reactions, weaker base (leaving group) is replaced by stronger base (nucleophile).
• Halogens make good leaving groups.

Question 4

Nucleophilic Substitution Reactions (Sɴ1 and Sɴ2)

Answer 4

• In both Nucleophilic Substitution Reactions (Sɴ1 and Sɴ2), nucleophile forms bond with substrate carbon and leaving group leaves.
• Unimolecular Nucleophilic Substitution (Sɴ1): Leaving group leaves to form positively charged Carbocation. Nucleophile attacks carbocation. Tertiary carbocation (with three methyl groups attached) are preferential for Sɴ1 reactions.
• Bimolecular Nucleophilic Substitution (Sɴ2): Concerted (one-step) reaction in which nucleophile attacks electrophile at the same time as leaving group leaves. Less substituted carbons in electrophile are preferential for Sɴ2 reactions. Tertiary substrates will not participate in Sɴ2 reactions.

Question 5

Oxidation and Reaction

Answer 5

• Oxidation: Increasing bonds to oxygen and other heteroatoms and decreasing bonds to hydrogen.
• Primary alcohols oxidized to aldehydes by PCC or to carboxylic acids by CrO3 or Na2Cr2O7/K2Cr2O7.
• Secondary alcohols oxidized to ketones.
• Oxidized groups in a molecule tend to be more reactive.
• Reduction: Increasing bonds to hydrogen and decreasing bonds to oxygen/heteroatoms.
• Carboxylic acids reduced to primary alcohols by LiAlH4 and NaBH4, which also reduces amides to amines.

Question 6

Common Reactive Sites

Answer 6

• Carbon of carbonyl (electrophile).

* Alpha-hydrogens can be deprotonated to form enolate (nucleophile).

Question 7

IR Spectroscopy

Answer 7

• Alcohol O-H: Broad peak at 3300 cm⁻¹.
• Carboxylic Acid O-H: Broad peak at 3000 cm⁻¹.
• N-H: Sharp peak at 3300 cm⁻¹.
• C=O: Sharp peak at 1700 cm⁻¹.

Question 8

Proton NMR Spectroscopy

Answer 8

• Chemical Shift (δ) plotted on x-axis; the left is considered Downfield and Deshielded, and the right is considered Upfield and Shielded.
• Slitting into n+1 peaks will occur due to presence of adjacent hydrogens (excluding hydrogens attached to oxygen or nitrogen).

• In the image, Ha will show up as a Triplet Downfield (to the left) as it is more Deshielded, and Hb will show up as a Doublet Upfield as it is more Shielded.

Question 9

Chromatography

Answer 9

• Mobile Phase is run through Stationary Phase; the more similar compound is to the stationary phase, the slower it will move through.

• Thin-Layer Chromatography: Seperates compounds based on polarity. Stationary phase of silica gel or alumina is placed in Eluent solution, which travels up the stationary phase via capillary action. Polar molecules are attracted to stationary phase and move up very slowly, whereas nonpolar molecules dissolve in the mobile phase and move up quickly and further.
• Paper Chromatography functions via same principle, but stationary phase is cellulose paper.
• Reverse-Phase Chromatography is opposite, with nonpolar stationary phase and polar eluent.
• Column Chromatography: Stationary phase is silica or aluminum beads, and mobile phase is run through via gravity.
• Ion-Exchange Chromatography: Bead are coated with charge substances so that they attract compounds that have an opposite charge; Anion-exchange column binds negatively charged molecules (like DNA or protein) using positively charged resin. After all other compounds have moved through, salt gradient can be used to elute the charged molecules stuck to beads.
• Size-Exclusion: Beads contain tiny pores which allow small compounds to be held longer in the column, while larger compounds move out through the column faster.
• Affinity Chromatography: Beads are coated with a receptor that binds the protein, a specific antibody to the protein, or a substrate of the protein enzyme so that the protein of interest can be retained in the column. Retained proteins can be eluted by washing column with free receptors, antibodies, or substrates, which compete with bead-bound targets for the protein of interest.

Question 10

Isomers

Answer 10

• Structural (Constitutional) Isomers: Same molecular formula but different structures with different physical and chemical properties. Such as five different structural formulas for C6H14.
• Stereoisomers: Share same structure, but spacial arrangements differ. Molecule with n chiral centers has 2ⁿ stereoisomers. Subdivided into Conformational Isomers (which differ in rotation around single sigma bond) and Configurational Isomers (which can only be interconverted by breaking bonds).
• Conformational Isomers: In Newman Projection, butane is in its lowest-energy state with minimal steric repulsion in Anti Staggered Conformation (methyl group on C2 and methyl group on C3 are 180° away). Gauche Staggered Conformation occurs when methyl groups are 60° away from each other. Eclipsed Conformation occurs when the two methyl groups are 120° apart and overlap with the hydrogens on adjacent carbon. When butane is in its energetically unfavorable Totally Eclipsed Conformation, the methyl groups overlap with each other with 0° separation, and the molecule is in its highest-energy state with maximum steric repulsion. Cyclohexane molecules adopt chair conformation with bulky groups (tert-butyl) in equatorial positions to minimize steric strain.
• Configurational Isomers: Enantiomers (nonsuperimposable mirror images) have opposite configurations at each chiral center. Diastereomers (non-mirror-images) differ by at least one, but not all, stereogenic centers and include Cis-Trans Isomers (in which substituents differ in position around immovable bond or ring structure). Both demonstrate Optical Activity. Meso-compounds have chiral centers but also have an internal plane of symmetry, which makes them not optically active.