Learn & Review: ACS UH | Organic Chemistry 2 Final Exam

Organic Chemistry II Final Exam Review (2022)

This document summarizes a review session for an Organic Chemistry II final exam. The exam is worth 50% of the final grade, with the remaining 50% coming from an ACS exam that covers both Organic Chemistry I and II material.

Exam Structure and Content

• No "Facts" Section: Unlike the ACS exam, this specific exam does not have a dedicated "facts" section.
• Comprehensive Coverage: The ACS exam, which is multiple-choice, covers material from both Organic Chemistry I and II.
• Key Topics Covered in Review:
  • Nomenclature (IUPAC naming)
  • Reactions (including SN1, SN2, E2, epoxidation, oxidation, Wittig, Diels-Alder, Tollens' reagent, amide formation, Hoffman rearrangement, etc.)
  • Spectroscopy (IR, 1H NMR, 13C NMR)
  • Synthesis problems
  • Mechanisms (Aldol, Claisen, Michael)

Nomenclature Examples

Example 1: Ester with Amine

• Structure: An ester linked to an amine.
• Parent Chain: The ester group.
• Substituent Side: Starts counting from the side without the oxygen bond.
  • "2-phenyl ethyl" is the substituent.
• Parent Side: Starts counting from the carbon attached to the ester.
  • A five-carbon chain (pentane) becomes "pentanoate" due to the ester.
  • A nitrogen group with two ethyl groups attached is named "diethylamino" when it's a substituent.
• Naming Convention:
  • When the nitrogen is part of the parent chain, "N,N-" is used (e.g., N,N-diethyl).
  • When the nitrogen is a substituent, "amino" is used (e.g., diethylamino).
• Final Name: 2-phenylethyl 5-diethylamino pentanoate
  • A space is required between the substituent and parent chain names (e.g., "phenylethyl" and "pentanoate"). Dashes can be used to indicate this space if not explicitly written out.

Example 2: Alkene with Nitrogen Bonding

• Structure: An alkene with a nitrogen atom.
• Parent Chain: The longest chain containing the most double or triple bonds, starting from the nitrogen.
• Numbering: Starts from the nitrogen atom.
• Substituents:
  • Methyl group on carbon 4.
  • Two propyl groups on the nitrogen (N,N-dipropyl).
• Parent Chain Naming:
  • Six-carbon chain: "hexene".
  • Double bond position: "5-hexene".
  • Amine group: "amine" at the end.
• Final Name: 4-methyl-N,N-dipropyl-5-hexen-1-amine (or variations like 5-hexene-1-amine)
  • Alphabetical order is used for substituents (methyl before dipropyl). "Di-" is not considered for alphabetical order.

Example 3: Aldehyde, Ketone, and Ether

• Priorities: Aldehyde > Ketone > Ether. The aldehyde is the parent chain.
• Numbering: Starts from the aldehyde carbon.
• Substituents:
  • "Oxo" group on carbon 6 (from the ketone).
  • "Ethoxy" group on carbon 4 (from the ether).
• Parent Chain Naming:
  • Seven-carbon chain: "heptane".
  • Aldehyde: "heptanal" (dropping the 'e' and adding 'al'). The '1-' is implied.
• Stereochemistry:
  • Identified a chiral carbon.
  • Determined the largest and smallest groups.
  • Traced through carbons to determine relative size of groups.
  • Assigned 'S' configuration based on counter-clockwise rotation (and no need to switch due to wedge/dash placement).
• Final Name: S-4-ethoxy-6-oxoheptanal

Reactions Section

• General Advice: Reactions from both OChem I and OChem II are fair game. Be mindful of reagents and their common reactions (e.g., t-butoxide as a bulky base for SN2/E2).

Reaction Sequence 1

1. Alkene + MCPBA: Forms an epoxide.
2. Epoxide + CH3OH/H+: Acid-catalyzed ring opening via SN2 attack at the most substituted carbon, followed by protonation of the alkoxide. Results in an ether and an alcohol.
3. Secondary Alcohol + Sodium Dichromate: Strong oxidation of the secondary alcohol to a ketone.
4. Wittig Reaction: Replaces the carbonyl oxygen with a carbon group (in this case, a C(CH3)2 group).

Reaction Sequence 2

1. Diene + Aldehyde + Heat (Diels-Alder): Forms a cyclohexene ring with the aldehyde substituent.
2. Cyclohexene Derivative + Tollens' Reagent (Ag2O, NH3, H2O): Oxidizes the aldehyde to a carboxylic acid (forms a "silver mirror").
3. Carboxylic Acid + Amine + Heat: Forms an amide.
4. Amide + Br2, NaOH (Hoffman Rearrangement): Removes the carbonyl group, converting the amide to a primary amine with one less carbon.

Reaction Sequence 3

1. Amide + LiAlH4 / H2O: Reduces the amide to a primary amine, removing the carbonyl.
2. Amine + CH3I (excess) / Ag2O, H2O, Heat: Forms a terminal alkene. The mechanism involves methylation of the nitrogen followed by elimination.
3. Alkene + NBS / Heat: Forms an allylic radical. Resonance stabilization is important. The reaction favors the more substituted alkene product. Bromine is added at the allylic position of the major product.
4. Alkyl Bromide + NaN3: Sodium azide performs an SN2 reaction, replacing bromine with an azide group (N3).
5. Azide + LiAlH4 / H2O: Reduces the azide group to a primary amine.

Reaction Sequence 4 (NAS and Birch Reduction)

1. Nucleophilic Aromatic Substitution (NAS): Occurs when a halide is ortho or para to an electron-withdrawing group (like NO2).
   • Step 1 (2 equivalents NaOH): First equivalent replaces the halide with -OH. Second equivalent deprotonates the -OH to -O-.
   • Step 2 (CH3CH2Br): SN2 reaction where the phenoxide attacks the ethyl bromide, forming an ether.
2. Birch Reduction: Reduces an aromatic ring by removing one double bond and creating two parallel double bonds. These double bonds must not be adjacent to electron-withdrawing groups.

Reaction Sequence 5 (Claisen Condensation)

• Claisen Condensation: Occurs with esters (unlike Aldol which occurs with ketones/aldehydes).
• Reagents: NaOEt / EtOH.
• Mechanism:
  1. Deprotonation of the alpha-hydrogen of one ester molecule to form an enolate.
  2. The enolate attacks the carbonyl carbon of another ester molecule.
  3. A tetrahedral intermediate forms, which then collapses, kicking off the ethoxide group. This results in a beta-keto ester.
  4. A final deprotonation occurs (often by the ethoxide formed), followed by protonation with H3O+ to yield the beta-keto ester.
  5. Acidic workup (H3O+ / heat) cleaves the ester portion, leaving a ketone.

Spectroscopy

• Degree of Unsaturation: Calculated as (2C + 2 - H + N) / 2. A value of 2 indicates two double bonds or one triple bond.
• Proton NMR (1H NMR):
  • Identifies different types of protons and their neighboring protons (splitting patterns).
  • Number of signals indicates the number of chemically distinct proton environments.
  • Integration (number of H's) provides the ratio of protons in each environment.
  • Chemical shift (ppm) indicates the electronic environment (deshielded protons appear further downfield).
• Carbon-13 NMR (13C NMR):
  • Identifies different types of carbon atoms.
  • Number of peaks indicates the number of chemically distinct carbon environments.
  • Chemical shift indicates the electronic environment:
    • ~160-185 ppm: Carboxylic acids, esters.
    • ~182-215 ppm: Aldehydes, ketones.
    • Further downfield carbons are generally more deshielded.
• IR Spectroscopy: Useful for identifying functional groups like O-H (broad peak ~3200-3600 cm-1), C=O (strong peak ~1650-1800 cm-1).
• Interpreting Spectroscopy Data (Example):
  • Formula: C7H12O3
  • Unsaturation: 2
  • 13C NMR: Peaks suggest a ketone (~182 ppm) and an ester (~160-185 ppm). The presence of three oxygens and the chemical shifts strongly indicate a beta-keto ester structure.
  • 1H NMR: Multiple distinct CH3 and CH2 signals, with varying degrees of deshielding, help piece together the arrangement of carbons and their proximity to oxygen or carbonyl groups. A CH2 group between two carbonyls is highly deshielded. A CH3 group adjacent to an oxygen in an ester is also deshielded.

Synthesis

• General Strategy: Work backward from the target molecule, identifying key functional groups and reactions. Consider available starting materials (benzene, aniline, alcohols, 5-carbon chains or less).
• Key Reactions Mentioned:
  • Michael Addition: Addition of a nucleophile (donor, e.g., beta-keto ester enolate) to an alpha, beta-unsaturated carbonyl compound (acceptor).
  • Claisen Condensation: Formation of beta-keto esters from esters.
  • Fischer Esterification: Formation of esters from carboxylic acids and alcohols under acidic conditions.
  • Diazonium Salt Formation: Used to introduce halogens or other groups onto an aromatic ring via aniline.
  • Birch Reduction: Selective reduction of aromatic rings.

Mechanisms

• Aldol Reaction:
  • Involves enolate formation and attack on a carbonyl.
  • Ring formation requires careful selection of the deprotonation site to achieve the desired ring size (5 or 6-membered rings are generally favored).
  • The dehydration step (formation of the double bond) has a specific mechanism that differs slightly from E2, involving enolate formation before elimination.
• Claisen Condensation: (See Reactions Section)
• Michael Reaction: (See Synthesis Section)