Appendix C: Reaction Summary Tables
The main chapters deliberately favor patterns and mechanisms over reagent lists — the Common Mistakes sections in Chapters 7–17 repeatedly warn against memorizing tables in place of understanding why a reaction happens. This appendix is the reagent-level reference that goes with that reasoning: once a mechanism is understood, these tables are where to look up which specific reagents accomplish it.
How to use this appendix: each table gives the reaction name, typical reagents/conditions, the product, the key mechanistic pattern (which should already be familiar from the chapter body), and a common pitfall. Use it for exam review, not first-pass learning.
Substitution and Elimination (SN1, SN2, E1, E2)
| Reaction | Typical Reagents/Conditions | Substrate | Mechanism | Product / Stereochemistry | Common Pitfall |
|---|---|---|---|---|---|
| SN2 | Strong nucleophile (e.g., NaOH, NaOR, NaCN, NaN₃, thiolate); polar aprotic solvent (DMSO, DMF, acetone) | Methyl, primary (secondary possible) | One step, concerted, backside attack | Inversion of configuration at the reactive carbon | Attempting SN2 on a tertiary substrate — sterics make backside attack impossible |
| SN1 | Weak nucleophile, often the solvent itself (H₂O, ROH); polar protic solvent | Tertiary (secondary possible) | Two steps via carbocation intermediate | Racemization (attack from either face of the planar carbocation) | Forgetting that carbocation rearrangements (hydride/alkyl shifts) can change the constitution of the product |
| E2 | Strong, often bulky base (e.g., NaOEt, KOtBu, DBU) + heat | Primary, secondary, tertiary | One step, concerted; requires anti-periplanar H and leaving group | Alkene; Zaitsev (more substituted) product usually favored unless the base is bulky | Ignoring the conformational requirement — if no anti-periplanar H is accessible, E2 cannot proceed from that conformation |
| E1 | Weak base, polar protic solvent, heat | Tertiary (secondary possible) | Two steps via carbocation intermediate | Alkene; Zaitsev product favored; rearrangements possible | Assuming E1 and SN1 don’t compete — they arise from the same carbocation and typically occur together |
Decision Framework
Reasoning through these four questions, in order, resolves most substitution/elimination problems:
- Is the substrate methyl or primary? → SN2 is likely (unless the base/nucleophile is bulky, which favors E2 even on primary substrates).
- Is the substrate tertiary? → SN1/E1 are likely if the nucleophile/base is weak; E2 is likely if the base is strong.
- Is the nucleophile/base strong and unhindered? → Favors the concerted pathways (SN2 on unhindered carbons, E2 otherwise).
- Is the solvent polar protic? → Favors the stepwise, carbocation pathways (SN1/E1).
See Chapter 10 for the underlying reasoning; this table is the condensed version for quick lookup.
Addition to Alkenes and Alkynes
| Reaction | Typical Reagents/Conditions | Mechanism | Product / Regiochemistry | Common Pitfall |
|---|---|---|---|---|
| Hydrogenation | H₂, Pd or Pt catalyst | Syn addition across a metal surface | Alkane; both H atoms add to the same face | Forgetting that a catalyst is required — H₂ does not add to alkenes uncatalyzed |
| Hydrohalogenation | HX (HCl, HBr, HI) | Carbocation intermediate | Markovnikov addition — H adds to the less substituted carbon, X to the more substituted (more stable carbocation) carbon | Placing the halogen on the wrong carbon by not identifying the more stable carbocation first |
| Acid-catalyzed hydration | H₃O⁺ / H₂O | Carbocation intermediate | Markovnikov addition — OH ends up on the more substituted carbon; rearrangements possible | Forgetting that this pathway can rearrange, unlike the anti-Markovnikov alternative below |
| Hydroboration–oxidation | BH₃ (or BH₃·THF), then H₂O₂/NaOH | Concerted, single-step addition (no carbocation) | Anti-Markovnikov addition — OH ends up on the less substituted carbon; syn addition; no rearrangement | Confusing this with acid-catalyzed hydration — same overall transformation (alkene → alcohol), opposite regiochemistry |
| Halogenation | X₂ (Cl₂, Br₂) | Bridged halonium ion intermediate | Vicinal dihalide; anti addition | Predicting syn addition — the bridged intermediate forces the second halogen to attack from the opposite face |
Regiochemistry note: the Markovnikov vs. anti-Markovnikov contrast above is the classic example of the regiochemistry reasoning introduced in Chapter 9 — identifying which pathway proceeds through the more stable intermediate (a carbocation, for Markovnikov addition) versus which pathway avoids a carbocation altogether (hydroboration).
Aromatic rings do not undergo these reactions — see Electrophilic Aromatic Substitution, below, and the Chapter 9 Common Mistake on this point.
Nucleophilic Addition to Aldehydes and Ketones
| Reaction | Typical Reagents/Conditions | Product | Common Pitfall |
|---|---|---|---|
| Hydration | H₂O | Geminal diol (hydrate) | Assuming this equilibrium always favors the hydrate — for most ketones, the carbonyl form is favored |
| Reduction | NaBH₄ or LiAlH₄, then aqueous workup | Alcohol | Using the same reagent for reducing a carboxylic acid derivative — NaBH₄ is generally too weak for esters/amides, while LiAlH₄ is strong enough to reduce those as well |
| Organometallic addition | Grignard reagent (RMgX) or organolithium (RLi), then aqueous workup | New C–C bond; alcohol | Forgetting that these are strong bases as well as strong nucleophiles — they are incompatible with acidic protons (O–H, N–H) elsewhere in the molecule |
| Hemiacetal/acetal formation | Alcohol (ROH), acid catalyst | Hemiacetal (1 equiv. ROH) or acetal (2 equiv. ROH, water removed) | Forgetting that this is reversible — acetals hydrolyze back to the carbonyl under aqueous acid, which is exactly why they are useful as protecting groups |
Every reaction in this table follows the same general pattern introduced in Chapter 12: a nucleophile attacks the electrophilic carbonyl carbon, electron density shifts onto oxygen, and (where applicable) a proton transfer restores neutrality.
Nucleophilic Acyl Substitution (Carboxylic Acid Derivatives)
Unlike aldehydes and ketones, carboxylic acid derivatives have a leaving group attached to the carbonyl carbon. The tetrahedral intermediate formed by nucleophilic attack collapses by ejecting that leaving group and reforming the C=O — substitution, not addition. This is the central distinction developed in Chapter 13.
Relative reactivity: Acid chlorides → Anhydrides → Esters → Amides (most to least reactive), tracking how good a leaving group each derivative provides.
| Starting Material | Typical Reagents/Conditions | Product | Common Pitfall |
|---|---|---|---|
| Carboxylic acid | SOCl₂ | Acid chloride | Forgetting this is usually the first step needed before making an anhydride, ester, or amide from a carboxylic acid directly |
| Carboxylic acid | Alcohol (ROH), acid catalyst (Fischer esterification) | Ester | Assuming this reaction goes to completion — Fischer esterification is an equilibrium and usually needs excess alcohol or water removal to favor the ester |
| Acid chloride or anhydride | H₂O | Carboxylic acid | — |
| Acid chloride or anhydride | Alcohol (ROH) | Ester | — |
| Acid chloride or anhydride | Amine (R₂NH) | Amide | — |
| Ester | H₃O⁺ or NaOH (saponification), H₂O | Carboxylic acid (or carboxylate, if base) | Confusing acid- and base-mediated hydrolysis — base-mediated hydrolysis (saponification) is irreversible because the carboxylate product is unreactive toward further attack |
| Ester | Amine (R₂NH) | Amide | Requires more forcing conditions than starting from an acid chloride, since alkoxide is a worse leaving group than chloride |
Reading this table as a cascade: acid chlorides and anhydrides are reactive enough to be converted directly into acids, esters, or amides by choosing the nucleophile (water, alcohol, or amine, respectively) — the same substitution mechanism, three different nucleophiles.
Enols, Enolates, and Carbon–Carbon Bond Formation
| Reaction | Typical Reagents/Conditions | Product | Mechanistic Note | Common Pitfall |
|---|---|---|---|---|
| Enolate alkylation | Strong, non-nucleophilic base (e.g., LDA) to form the enolate, then an alkyl halide | New C–C bond at the α-carbon | Enolate acts as a nucleophile toward the alkyl halide’s electrophilic carbon (an SN2-like step) | Using a nucleophilic base (e.g., NaOH) instead of LDA — a nucleophilic base can attack the alkyl halide itself instead of just deprotonating |
| Aldol reaction | Base (e.g., NaOH) or acid catalyst | β-hydroxy carbonyl compound | Enolate (or enol) attacks the carbonyl carbon of a second molecule | Forgetting to identify the α-carbon correctly before drawing the enolate nucleophile |
| Aldol condensation | Aldol product, heat (or the same conditions, driven further) | α,β-unsaturated carbonyl compound | Dehydration of the β-hydroxy group, favored by conjugation with the carbonyl | Stopping analysis at the aldol product when the question asks for the condensation (dehydrated) product |
| Claisen condensation | Alkoxide base (e.g., NaOEt) | β-keto ester | Ester enolate attacks the carbonyl carbon of a second ester molecule, expelling alkoxide (acyl substitution, not simple addition) | Confusing this with the aldol reaction — Claisen requires an ester (a leaving group is needed for the substitution step that follows addition) |
See Chapter 14 for the acidity argument (enolate resonance stabilization) and Appendix B’s section on carbonyl α-carbons for representative pKa values.
Electrophilic Aromatic Substitution
| Reaction | Typical Reagents/Conditions | Electrophile Generated | Product |
|---|---|---|---|
| Halogenation | X₂, FeX₃ (Lewis acid catalyst) | X⁺ (halogenium, activated by the Lewis acid) | Aryl halide |
| Nitration | HNO₃, H₂SO₄ | NO₂⁺ (nitronium ion) | Nitrobenzene derivative |
| Sulfonation | SO₃, H₂SO₄ (fuming sulfuric acid) | SO₃ (electrophilic sulfur) | Benzenesulfonic acid (reversible — can be removed later by treatment with dilute aqueous acid) |
| Friedel-Crafts alkylation | R–X, AlCl₃ | R⁺ (carbocation, or a polarized complex) | Alkylbenzene; carbocation rearrangements possible; over-alkylation possible since the product is more electron-rich than the starting arene |
| Friedel-Crafts acylation | R–COCl, AlCl₃ | Acylium ion (R–C≡O⁺) | Aryl ketone; no rearrangement (acylium is resonance-stabilized); no over-acylation (the ketone product deactivates the ring) |
Directing and Activating Effects (Chapter 17)
| Substituent Type | Examples | Effect on Reactivity | Directs To |
|---|---|---|---|
| Strong activators | –OH, –NH₂, –OR | Strongly activating (lone pair donates into the ring by resonance) | Ortho/para |
| Weak activators | Alkyl groups (–CH₃, etc.) | Mildly activating (inductive electron donation, hyperconjugation) | Ortho/para |
| Deactivating, o/p-directing | Halogens (–F, –Cl, –Br, –I) | Deactivating overall (inductively electron-withdrawing) but still ortho/para-directing (lone pairs can still donate by resonance) | Ortho/para |
| Deactivating, meta-directing | –NO₂, –C≡N, –COOH, –CHO, –C(=O)R, –SO₃H | Strongly deactivating (withdraw electron density by resonance and induction, with no lone pair to donate back) | Meta |
Why halogens are the exception to the activating/directing correlation: halogens withdraw electron density inductively (deactivating the ring overall) but still possess lone pairs that can donate into the ring by resonance at the ortho/para positions specifically — enough to direct substitution there, even though the net effect on the ring is deactivating. See Chapter 17 for the full resonance argument.
Addition vs. Substitution at Carbonyls — A Direct Comparison
This is one of the most frequently confused pairs in Organic Chemistry II. Both reactions begin identically — a nucleophile attacks the electrophilic carbonyl carbon, forming a tetrahedral intermediate — but what happens next depends entirely on what else is attached to that carbon.
| Aldehydes/Ketones (Chapter 12) | Carboxylic Acid Derivatives (Chapter 13) | |
|---|---|---|
| Leaving group on carbonyl carbon? | No (only H or R groups) | Yes (Cl, OR, OCOR, NR₂) |
| Fate of the tetrahedral intermediate | Protonated to give a stable alcohol (or hemiacetal) | Collapses, ejecting the leaving group and reforming C=O |
| Net transformation | Addition (C=O becomes C–OH, no atoms lost) | Substitution (one heteroatom group replaces another) |
Reasoning through this table only requires one question: is there a leaving group already attached to the carbonyl carbon? If not, addition is the outcome; if so, substitution is.
Cross-References
- Chapters 7–10 (Substitution, Elimination, Addition, Comparing Reactions) — the mechanistic reasoning behind the first two tables.
- Chapters 12–14 (Carbonyl Chemistry) — the mechanistic reasoning behind the carbonyl, acyl substitution, and enolate tables.
- Chapters 16–17 (Aromaticity) — the mechanistic reasoning behind electrophilic aromatic substitution and directing effects.
- Appendix A (Functional Group Atlas) — the interconversion map that this appendix supplies specific reagents for.
- Appendix B (pKa Tables) — acidity values referenced in the enolate and acyl substitution discussions above.
- Chapter 21 (Retrosynthesis) — using these tables in reverse to plan a synthetic route.