Test Topics

Unit 1 Test

• General – Review the Orgo 1 and Orgo 2 reactions summaries here

• Elimination Reactions of Alkyl Halides – E2 mechanism, E2 regioselectivity and Zaitsev’s rule, exceptions to Zaitsev’s rule (bulky bases, fluoride leaving group), E1 mechanism, E1 regioselectivity, carbocation rearrangements, how to predict major product stereoisomer(s) in E2 and E1 reactions (see Bruice 9.5-9.6 and weekly meeting slides)

• Substitution vs. Elimination – Reaction conditions favoring E2/SN2 (high concentration of good nucleophile/strong base), reaction conditions favoring E2 over SN2 (stronger and bulkier base, heat), why heat favors E2 over SN2 (see weekly meeting slides), reaction conditions favoring E1/SN1 (poor nucleophile/weak base), major product prediction (see Bruice Table 9.6)

• Substitution Reactions of Alcohols – Mechanisms for SN1 and SN2 using binary acids (HBr, HI, HCl + ZnCl2), substitutions using phosphorus trihalides (PCl3, PBr3, PI3), thionyl chloride (SOCl2), and sulfonate esters (e.g. tosyl chloride), important stereochemical effects (see Bruice 10.3, Problem 6 and weekly meeting slides)

• Elimination Reactions of Alcohols – E1 and E2 mechanisms for elimination using acid catalyst and heat, E2 elimination under milder conditions with phosphorus oxychloride (POCl3) and pyridine

• Epoxide Preparation – Mechanism for preparation of epoxides from alkenes using peroxyacid (see Bruice 4.9 and weekly meeting slides), preparation of epoxides using nucleophilic substitution (see Bruice p. 480, Problem 73 and weekly meeting slides)

• Substitution Reactions of Ethers and Epoxides – Mechanism for ether cleavage using binary acid, substitution reactions of epoxides under acidic vs. basic conditions, stereochemistry of epoxide substitutions 

• Multistep Synthesis – Williamson ether synthesis, consecutive E2 eliminations to synthesize alkynes, preparation of cyclic ethers (see Bruice 9.11, Example 4), examples from problem sets and weekly meeting slides

• Amine Nomenclature – See Traynham Ch. 12 or these videos

Unit 2 Test -- Test will be cumulative, though the focus will be on the below topics

• General – Review reactions summary here

• Radical Substitutions of Alkanes – Mechanisms for radical chlorination and radical bromination of alkanes, homolytic bond cleavage, initiation vs. propagation vs. termination steps, rate-determining step (first propagation step), relative stabilities of methyl vs. primary vs. secondary vs. tertiary radicals (and why), general factors influencing radical substitution product distribution (probability and reactivity), reactivity-selectivity principle (bromine radicals are less reactive and more regioselective than chlorine radicals; see Bruice Figure 11.2 and weekly meeting slides), why radical fluorination and iodination do not work

• Radical Substitutions of Benzylic and Allylic Hydrogens – Definitions of allylic and benzylic radicals, stabilities of allylic and benzylic radicals (both more stable than tertiary radicals), drawing resonance contributors for radical species, why N-bromosuccinimide (NBS) works to brominate allylic and benzylic carbons (see Bruice 11.8 and weekly meeting slides), product prediction given resonating allylic radical (see Bruice 11.8, Problem 16), kinetic vs. thermodynamic products and reaction control (see weekly meeting slides)    

• Radical Additions of Alkenes – Mechanism for the addition of HBr to an alkene in the presence of a peroxide, rationale for why the bromine ends up on the less substituted carbon

• Stereochemistry of Radical Additions and Substitutions – sp2 hybridization of carbon in radical intermediate, trigonal planar geometry (120° bond angle), unpaired electron housed in p orbital, determination of when stereochemistry matters (when new asymmetric center created), stereochemical product prediction

• Multistep Synthesis – Use of radical substitutions and additions (see Bruice 11.9, Examples 2-4), examples from problem sets and weekly meeting slides

• Biochemical and Environmental Examples – Examples of radicals in biological systems, examples of radical inhibitors in biological systems, chlorofluorocarbons (CFCs) and stratospheric ozone depletion

Unit 3 Test -- Test will be cumulative, though the focus will be on the below topics

• General – Review reactions summary here

• Aromaticity and Antiaromaticity – Criteria for aromaticity and antiaromaticity, defining compounds as aromatic, antiaromatic, or nonaromatic, Hückel’s rule, effects of aromaticity/antiaromaticity on compound acidity and polarity, molecular orbital descriptions of aromaticity/antiaromaticity and Frost circles (see Bruice 14.7, supplemental reading, and weekly meeting slides)

• Electrophilic Aromatic Substitutions – Mechanisms for the five most common electrophilic aromatic substitutions (halogenation, nitration, sulfonation/desulfonation, Friedel-Crafts acylation, Friedel-Crafts alkylation), definition of a Lewis acid, use of Lewis acids (e.g. FeBr3, FeCl3, AlCl3) in electrophilic aromatic substitutions, Gatterman-Koch formylation (see Bruice 14.14 and weekly meeting slides), incipient carbocations (see Bruice p. 663 and weekly meeting slides)

• Reactions of Benzene Substituents – Methods of reducing benzylic ketones and aldehydes (H2 + Pd/C, Clemmensen, Wolff-Kishner), diverse reactions presented in Bruice 14.19      

• Multistep Synthesis – Importance of acylation-reduction (see Bruice 14.16), examples from problems sets and weekly meeting slides

• Aromatic Nomenclature, Part 1 – See Traynham Ch. 5 or this video

Fall Final Exam -- Test will be cumulative, and it will include the below additional topics

• General – Review reactions summary here

• Effects of Benzene Substituents on Electrophilic Aromatic Subsitutions – Methods by which benzene substituents can donate or withdraw electrons (inductive effect, hyperconjugation, resonance), activating vs. deactivating substituents (see Bruice Table 15.1), ortho-para vs. meta direction (how transition state leading to carbocation intermediate is stabilized or destabilized by substituents), factors affecting ortho-para product ratio, substituent effects on Friedel-Crafts reactions (see Bruice p. 695 and weekly meeting slides)

• Effects of Benzene Substituents on Compound pKa – See Bruice 15.4  

• Preparation and Use of Arenediazonium Salts – Mechanism for formation of arenediazonium ion from aniline (using sodium nitrite and acid), mechanism for electrophilic aromatic substitution using an arenediazonium ion electrophile (to form azo linkage), preparation of various substituted benzenes using arenediazonium salts (see Bruice 15.9), replacement of diazonium group with hydrogen using hypophosphorous acid (H3PO2) 

• Nucleophilic Aromatic Substitutions of Aryl Halides – Addition-elimination mechanism (SNAr), specific requirements for SNAr (electron-withdrawing group[s] ortho and/or para to halogen), elimination-addition mechanism (via benzyne intermediate, using -NH2/NH3), orbital geometry of benzyne, direct vs. cine substitution products

• Multistep Synthesis – Factors affecting synthesis of disubstituted and trisubstituted benzenes (See Bruice 15.7-15.8), examples from problems sets and weekly meeting slides

• Aromatic Nomenclature, Part 2 – See Traynham Ch. 8 or this video

Unit 5 Test -- Test will be cumulative, though the focus will be on the below topics

• General – Review reactions summary here, hybridization and geometry of carbonyl carbon, Class I vs. Class II carbonyl compounds

• Nucleophilic Acyl Substitutions – General reaction mechanisms (base-promoted vs. acid-catalyzed vs. neutral), role of tetrahedral intermediate, molecular orbital description (see Bruice Figures 1.8 and 16.3), relative reactivities of carboxylic acid derivatives (understand reasons for reactivity order, how it can be used to predict possible reactions), definitions of hydrolysis, alcoholysis, and aminolysis, study specific reactions (see below) and how to apply the general reaction mechanisms to these examples

  1. Reactions of Acyl Halides – Reactions with carboxylate ions, alcohols, water, and amines

  2. Reactions of Acid Anhydrides – Reactions with alcohols, water, and amines

  3. Reactions of Esters – Reactions with alcohols (transesterifications), water, and amines, unique mechanism for hydrolysis of esters with tertiary alkyl groups

  4. Reactions of Carboxylic Acids – Reactions with alcohols (Fisher esterifications), why carboxylic acids do not undergo nucleophylic acyl substitutions with amines, activation of carboxylic acids by heating with SOCl2, PCl3 or PBr3, dehydration of carboxylic acids into anhydrides using P2O5, preparation of cyclic anhydrides from dicarboxylic acids

  5. Reactions of Amides – Reactions with water and alcohols (using acid and heat), dehydration of primary amides to a nitriles using P2O5 and heat

  6. Other Reactions – Gabriel synthesis of primary amines (and why it's useful – see Bruice 16.18, Problem 38), hydrolysis of nitriles (see weekly meeting slides), reduction of nitriles to primary amines using H2 (with Pd/C)

• Multistep Synthesis – Examples from problems sets and weekly meeting slides, use of nucleophilic acyl substitution in preparing cyclic compounds (see Bruice 16.20 and 16.23)

• Soaps, Detergents, and Micelles – Chemical definition of a soap, how fats/oils are converted into soaps via base-promoted nucleophilic acyl substitution (saponification), formation of miscelles in aqueous soap solution, rationale for development of detergents (synthetic soaps)

• Biochemical Examples – General examples of nucleophylic acyl substitutions in biosynthesis (see Bruice 16.22)

• Nomenclature

  1. Carboxylic Acids – See Traynham Ch. 9 or this video

  2. Carboxylic Acid Derivatives – See Traynham Ch. 10 or this video

Unit 6 Test -- Test will be cumulative, though the focus will be on the below topics

• General – Review reactions summary here, relative reactivities of carbonyl compounds (understand reasons for reactivity order, how it can be used to predict possible reactions)

• Organometallic Compounds – Preparation and use of organolithium compounds, Grignard reagents, and Gilman reagents, destruction of organometallic compounds in the presents of water and/or acidic groups

• Nucleophilic Addition

  1. General reaction mechanism (see Bruice 17.3)

  2. Application of this general reaction mechanism to reactions of ketones/aldehydes with Grignard reagents, acetylide ions, hydride ions (sodium borohydride, NaBH4), hydrogen cyanide, water, alcohols, and thiols

  3. Relevant Definitions – Hydrate, hemiacetal, acetal, hemiketal, ketal, thioacetal, thioketal, Re vs. Si face

  4. Reactions of α,β-Unsaturated Aldehydes/Ketones – direct vs. conjugate addition, kinetic control by use of strong base (e.g. Grignard reagent, hydride ion) to favor direct addition product, thermodynamic control by use of weak base (e.g. halide, cyanide, thiol, alcohol, amine, Gilman reagent) to favor conjugate addition product

• Nucleophilic Acyl Substitution + Nucleophilic Addition

  1. Reactions of Acyl Halides and Esters with Grignard Reagents

  2. Reactions of Acyl Halides with Hydride Ions (sodium borohydride, NaBH4)

  3. Reactions of Esters, Carboxylic Acids, and Amides with Hydride Ions

     • Use of lithium aluminum hydride (LiAlH­4)

     • Use of diisobutylaluminum hydride (DIBAL-H)

• Nucleophilic Addition-Elimination

  1. General reaction mechanism (see Bruice 17.3)

  2. Application of this general reaction mechanism to reactions of ketones/aldehydes with primary amines, secondary amines, and amine derivatives (e.g. hydroxylamine)

  3. Relevant Definitions – Imine, enamine

• Other Reactions

  1. Reductive Amination – Preparation of primary, secondary, and tertiary amines by reducing imines and enamines

  2. Wolff-Kishner Reductions of Ketones/Aldehydes

  3. Formation, Use, and Removal of Protecting Groups – How to protect aldehydes, ketones, alcohols, carboxylic acids, and amino groups

  4. Wittig Reaction – Definition of an ylide, preparation of phosphonium ylides, use of phosphonium ylides in Wittig reactions

  5. Reactions of α,β-Unsaturated Carboxylic Acid Derivatives – Nucleophilic acyl substitution vs. conjugate addition

• Multistep Synthesis – Examples from problems sets and weekly meeting slides, use of disconnections, synthons, and synthetic equivalents (see Bruice 17.15)

• Aldehyde and Ketone Nomenclature – See Traynham Ch. 11 or these videos