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 and supplemental reading)

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

• 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 (see supplemental reading), 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 – Use of disconnections, synthons, and synthetic equivalents (see Bruice 17.15), examples from problems sets and weekly meeting slides

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

Unit 7 Test -- Test will be cumulative, though the focus will be on the below topics

• General – Review reactions summary here, definition of organic oxidation vs. organic reduction

• Reduction Reactions

  1. Catalytic Hydrogenation – Hydrogenation with Pt, Pd, or Ni to reduce alkenes, alkynes, imines, and nitriles, hydrogenation with Lindlar catalyst to reduce alkynes, hydrogenation with Raney nickel to reduce aldehydes and ketones, hydrogenation with partially deactivated Pd to reduce acyl chlorides (Rosenmund reduction)

  2. Dissolving-Metal Reduction – Reduction of alkynes with Na or Li in liquid ammonia

  3. Reduction of Carbonyl Compounds – Use of sodium borohydride (NaBH4) to reduce aldehydes, ketones, and acyl halides, use of lithium aluminum hydride (LiAlH4) to reduce carboxylic acids, esters, and amides, use of diisobutylaluminum hydride (DIBAL-H) to reduce esters, use of lithium tri-tert­-butoxyaluminum hydride to reduce acyl halides

• Oxidation Reactions

  1. Oxidation of Alcohols – Use of chromic acid (CrO3 + acid; Na2Cr2O7 + acid) to oxidize primary and secondary alcohols, mechanism of alcohol oxidation by chromic acid, use of pyridinium chlorochromate (PCC) to oxidize primary alcohols, mechanistic rationale for the difference in outcome between chromic acid and PCC for primary alcohol oxidations (see weekly meeting slides and blue box on Bruice p. 918), Swern oxidation of primary and secondary alcohols and its mechanism

  2. Oxidation of 1,2-Diols – Oxidative cleavage of 1,2-diols using periodic acid (HIO4), mechanism of this reaction

  3. Oxidation of Aldehydes and Ketones – Oxidation of aldehydes using chromic acid, use of silver oxide (Tollens reagent) to oxidize aldehydes under basic conditions, Tollens test for aldehydes (silver mirror), oxidation of aldehydes and ketones using peroxyacid (Baeyer-Villiger oxidation), mechanism of Baeyer-Villiger oxidation, relative migration tendencies in Baeyer-Villiger oxidation

  4. Oxidation of Alkenes – Use of either potassium permanganate (KMNO4) or osmium tetroxide (OsO4) to oxidize alkenes, mechanism and stereospecificity of cis glycol formation using either KmnO4 or OsO4, oxidative cleavage of alkenes using ozone (ozonolysis), mechanism of ozonolysis (see weekly meeting slides), options for ozonide workup (differences in outcome between reducing and oxidizing conditions), oxidative cleavage of alkenes using potassium permanganate (permanganate cleavage)   

  5. Oxidation of Alkynes – Ozonolysis and permanganate cleavage of alkynes

• Multistep Synthesis – Functional group interconversion (see Bruice 19.9), examples from problems sets and weekly meeting slides

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

Option 1 – Reactions at Carbonyl α-Carbon

• General – Review reactions summary here, definition of α-carbon and α-hydrogen, relative acidities of different carbon acids and reasons for these differences

• Keto-Enol Tautomerization – General mechanisms for base-catalyzed and acid-catalyzed keto-enol interconversion

• α-Substitutions – General mechanisms for base-catalyzed vs. acid-catalyzed α-substitution, study specific reactions (see below) and how to apply the general reaction mechanisms to these examples

1. Halogenation of α-Carbon – Acid-catalyzed and base-promoted α-carbon halogenation of of ketones and aldehydes, conversion of methyl ketones to carboxylate ions (haloform reaction), why carboxylic acids cannot undergo substitution reactions at the α-carbon, alternate pathway for halogenation of α-carbon of carboxylic acids (Hell-Volhard-Zelenski reaction)

2. Alkylation and Acylation of α-Carbon of Carbonyl Compounds – Use of LDA to form enolate ion, kinetic vs. thermodynamic enolate ions, direct alkylation of enolate α-carbon via SN2, alkylation and acylation of α-carbon using enamine intermediate, advantages of using enamine intermediate over direct alkylation of enolate (see top of p.868)  

3. Alkylation of β-Carbon (Michael Reaction) – Reactions of enolate ions with α,β-unsaturated aldehydes and ketones, use of enamines instead of enolate ions (Stork enamine reaction)

4. Aldol Addition and Condensation – Definition of aldol, preparation of β-hydroxyaldehydes and β-hydroxylketones (aldol addition), definition of condensation reaction, preparation of α,β-unsaturated aldehydes and ketones via aldol addition followed by dehydration (aldol condensation), mixed aldol addition, use of reaction conditions to reduce number of possible mixed aldol additions products (see p. 875), intramolecular aldol additions, Robinson annulation (Michael reaction + intramolecular aldol condensation)

5. Claisen Condensation – Condensation reactions of esters, why you need to use esters with at least 2 α-hydrogens and an equivalent amount of base, difference between Claisen condensation and aldol addition (and reason for this difference – see p. 877), mixed Claisen condensation, intramolecular Claisen condensation (Dieckmann condensation) 

6. Other Reactions - Decarboxylation of 3-oxocarboxylic acids, preparation of carboxylic acids via malonic ester synthesis, preparation of methyl ketones via acetoacetic ester synthesis

• Multistep Synthesis – Preparation of nucleophilic vs. electrophilic α-carbon (see Bruice 18.7), strategies for syntheses involving carbon-carbon bond formation (see Bruice 18.21), examples from problems sets

Option 2 – Bioorganic Chemistry

• General – Review reactions summary here, drawing and interpretation of Fisher projections, determining R,S configuration of compounds drawn as Fisher projections

• Carbohydrates – Definition of carbohydrate, methods of carbohydrate classification, D and L notation, epimers, configurations of aldoses vs. ketoses (no need to memorize names/structures of simple sugars – e.g. erythrose, ribulose, etc.), reduction of aldoses and ketoses, mechanism for formation of cyclic hemiacetal from monosaccharide, conversion of acylic monosaccharide Fisher projection to cyclic Haworth projection, anomers and anomeric carbon, mutarotation, pyranose vs. furanose, conversion between Haworth projection and chair conformation for given pyranose, glycosides and glycosidic bonds, mechanism for glycoside formation, anomeric effect, types of glycosidic linkages, examples of disaccharides and polysaccharides

• Proteins – General structure of amino acid, D and L notation, amino acid synthesis via reductive amination, peptide bonds, regional planarity in polypeptide chains (and why this occurs), disulfide bonds, disulfide bridges between cysteine residues in polypeptides

• Metabolism – Structure of adenosine triphosphate (ATP), mechanism for phosphorylation of glucose via ATP (phosphoryl transfer reaction), mechanistic options for phosphoryl transfer (nucleophilic attack on α vs. β vs. γ phosphorus)

• Lipids – Definition of lipid, general structure of fatty acid (no need to memorize names/structures of common fatty acids), saturated vs. unsaturated fatty acids and related physical properties, general structure of waxes, general structure of triacylglycerols, formation of triacylglycerols from glycerol and fatty acids, fats vs. oils, radical oxidation of polyunsaturation fats and oils, structure of isoprene (head vs. tail), linkage of isoprene units to form terpenes, general concepts involved in biochemistry of vision (vitamin A oxidation and isomerization), general structure of steroids (tetracyclic ring system), examples of natural and synthetic steroids

• Nucleic Acids – General structure of nucleic acid (no need to memorize names/structures of nitrogenous bases), nucleoside vs. nucleotide, mechanism of phosphodiester bond formation in nucleic acid biosynthesis, role of hydrogen bonding in DNA/RNA base pairing, mechanistic explanation for why RNA is more easily cleaved than DNA, attachment of amino acids to tRNA via ATP, formation of peptide bonds via nucleophilic acyl substitution (See Bruice Figure 27.13)  

• Drugs – Lead compounds and molecular modification, famous examples of molecular modification, famous examples of serendipity in drug development, definition of receptor, examples of drugs than bind receptors (e.g. antihistimines), antiviral drugs and their general mechanism of action