DAT Organic Chemistry Reaction Summary Sheet Alkene Reactions Hydrohalogenation Hydrohalogenation (with Rearrangement) Halogenation Hydrobromination with Peroxide Hydration Hydration (with Rearrangement) Bromination in H2O Oxymercuration- Demurcuration Hydroboration- Oxidation Syn-Hydroxylation Syn-Hydroxylation Anti-Hydroxylation Addition of an Alcohol Bromination in Alcohol Alkoxymercuration- Demurcuration Epoxidation www.datbootcamp.com 1 of 25|Page Catalytic Hydrogenation Ozonolysis (Reducing Conditions) Ozonolysis (Oxidizing Conditions) Oxidative Cleavage Alkyne Reactions Catalytic Hydrogenation (Catalytic Reduction) Reduction to Cis- Alkene Reduction to Trans- Alkene Hydrohalogenation with HBr (Terminal Alkyne) Hydrohalogenation with HBr (Internal Alkyne) Halogenation with Br2 Hydration of an Internal Alkyne Hydration of a Terminal Alkyne (Markovnikov) Hydration of a Terminal Alkyne (Anti-Markovnikov) SN2 Addition of an Acetylide Ion to an Alkyl Halide SN2 Addition of an Acetylide Ion to a Ketone SN2 Addition of an Acetylide Ion to an Epoxide www.datbootcamp.com 2 of 25|Page Free Radical Halogenation Reactions Free Radical Halogenation Br using Bromine (more Br2 selective) hv or Δ Free Radical Halogenation Cl using Chlorine (less selective) Cl Cl 2 hv or Δ Cl Cl Allylic/Benzylic Bromination NBS Br hv or Δ or ROOR NBS Br hv or Δ or ROOR Br www.datbootcamp.com 3 of 25|Page Grignard Reactions Addition of a Grignard O OH 1. MgX , Ether Reagent to an Aldehyde H + 2. H3O 2˚Alcohol Addition of a Grignard O Reagent to a Ketone 1. MgX , Ether HO + 2. H3O 3˚Alcohol Addition of a Grignard O Reagent to an Ester 1. 2 eq. MgX , Ether HO + 3˚Alcohol O 2. H3O Addition of a Grignard O Reagent to an Acyl Chloride 1. 2 eq. MgX , Ether HO Cl 2. H O+ 3 3˚Alcohol Addition of a Grignard O Reagent to CO2 MgX 1. CO2, Ether OH + 2. H3O Carboxylic Acid Addition of a Grignard OH O Reagent to an Epoxide 1. MgX , Ether + (adds to the less subs. side 2. H3O 2˚Alcohol (less subs. alcohol) forming the less subs. alcohol) Addition of a Grignard O O 1. MgX , Ether Reagent to a Carboxylic Acid O OH 2. H O+ MgX 3 Carboxylate Addition of a Grignard O O 1. MgX , Ether Reagent to an Amide NH NH2 2. H O+ MgX 3 Deprotonated Amide Addition of a Grignard O Reagent to a Nitrile 1. MgX , Ether N Ketone 2. H O+ 3 www.datbootcamp.com 4 of 25|Page Electrophilic Aromatic Substitution (EAS) Reactions Friedel-Crafts Alkylation Cl (Rearrangement Possible) AlCl 3 Cl AlCl 3 Friedel-Crafts Acylation O O (No Rearrangement Possible) Cl AlCl3 Bromination Br Br2 FeBr3 Chlorination Cl Cl2 FeCl3 Nitration NO2 HNO3 H2SO4 Sulfonation SO3 SO3H H2SO4 H2SO4/Δ Formylation O CO, HCl H AlCl3 EAS with an ortho/para- O/P O/P O/P directing group on Substituent Substituent Benzene Substituent EAS with a meta-directing M M group on Benzene Substituent Substituent www.datbootcamp.com 5 of 25|Page Friedel-Crafts M O Alkylation/Acylation with a R Cl or Cl R meta-directing group or No Reaction an amine on Benzene AlCl3 NH /NRH/NR O 2 2 R or Cl Cl R No Reaction AlCl3 Benzene Side-Chain Reactions Side-Chain Oxidation of R - 1. KMnO4, OH O Benzene to form Benzoic + R R 2. H3O , Heat OH Acid or or or Na2Cr2O7 H2SO4 - 1. KMnO4, OH 2. H O+, Heat 3 No Reaction Requires free Hydrogen at or Benzylic position Na2Cr2O7 H2SO4 Wolff-Kishner Reduction O - H2NNH2 or N2H4, OH, Heat Clemmensen Reduction O Zn(Hg), HCl, Heat NO2 Zn(Hg), HCl, Heat NH2 www.datbootcamp.com 6 of 25|Page Hydride Reduction Reactions Reduction of an Aldehyde to O OH 1. NaBH4, EtOH a 1˚Alcohol H 2. H O+ H 3 O OH 1. LiAlH4, EtOH H 2. H O+ H 3 Reduction of a Ketone to a O OH 1. NaBH4, EtOH 2˚Alcohol 2. H O+ 3 O OH 1. LiAlH4, EtOH 2. H O+ 3 Reduction of a Carboxylic O OH 1. LiAlH4, EtOH Acid to a 1˚Alcohol + H OH 2. H3O Reduction of an Ester to a O 1. LiAlH , EtOH OH 1˚Alcohol 4 OH + H O 2. H3O Reduction of an Ester to an Aldehyde O 1. DIBAL-H, -78°C O O 2. H2O H Reduction of an Acyl O OH Chloride to a 1˚Alcohol 1. LiAlH4, EtOH + H Cl 2. H3O Reduction of an Acyl O LiAlH[OC(CH ) ] O Chloride to an Aldehyde 3 3 3 Cl H Reduction of an Amide to an O Amine 1. LiAlH4, EtOH + NH NH2 2. H3O 2 Hoffmann Rearrangement O 1. Br2 NH NH2 2. NaOH 2 Reduction of a Nitrile to an 1. LiAlH4, EtOH Amine N NH + 2 2. H3O www.datbootcamp.com 7 of 25|Page Alcohol Reactions Conversion of a 2˚/3˚Alcohol to an alkyl OH HX X halide via SN1 OH HX X Conversion of a 1˚/2˚Alcohol to an alkyl OH Br PBr3 bromide via S 2 N H H OH Br PBr3 Conversion of a 1˚/2˚Alcohol to an alkyl OH Cl SOCl2 chloride via S 2 N H Pyridine H OH Cl SOCl2 Pyridine Conversion of an Alcohol to a Tosylate Ester OH OTs (OTs) TsCl Retention of Stereochemistry Acid-catalyzed Dehydration of an Alcohol OH + H3O Zaitsev’s Rule Chromic Acid Oxidation of a 1o Alcohol to a Na Cr O Carboxylic Acid 2 2 7 or OH O CrO3 H H2SO4 OH Chromic Acid Oxidation of a 2o Alcohol to a Ketone Na2Cr2O7 or OH O CrO3 H2SO4 Chromic Acid Oxidation of an Aldehyde to a Na2Cr2O7 Carboxylic Acid or O O CrO3 H H2SO4 OH PCC or DMP Oxidation of a 1o Alcohol to an OH O Aldehyde PCC or DMP H H o PCC or DMP Oxidation of a 2 Alcohol to a OH O Ketone PCC or DMP www.datbootcamp.com 8 of 25|Page Ether and Epoxide Reactions Williamson Ether Synthesis via SN2 NaH, Na, or K Cl OH O O Acid-catalyzed Cleavage of Ethers when HBr one side is 2˚/3˚ (Nucleophile attacks O Br HO more substituted side via S 1) N HBr O Br HO Acid-catalyzed Cleavage of Ethers when neither side is 2˚/3˚ (Nucleophile O HBr OH attacks less substituted side via SN2) Br Acid-catalyzed Ring Opening of Epoxides Cl (Nucleophile attacks more substituted O HCl side) OH Base-catalyzed Ring Opening of OH O OCH Epoxides (Nucleophile attacks less 3 O substituted side) HOCH3 Aldehyde and Ketone Reactions Nucleophilic Addition to an Aldehyde or O Nucleophile HO Nucleophile Ketone H O+ C or H 3 C or H Addition of water to an Aldehyde or O H O HO OH Ketone forming a Hydrate 2 C or H + - C or H H3O or OH Base-catalyzed addition of an Alcohol O O HO O to an Aldehyde or Ketone forming a C or H C or H Hemi-acetal/Hemi-ketal HO Acid-catalyzed addition of an Alcohol O + H3O O O to an Aldehyde or Ketone forming a C or H C or H Acetal/Ketal (Protecting Group, reversed HO + by H3O ) + H3O Acid-catalyzed addition of Ethylene OH O HO O O Glycol to an Aldehyde or Ketone forming C or H C or H a Acetal/Ketal (Protecting Group, H O+ + 3 reversed by H3O ) H O+ 3 www.datbootcamp.com 9 of 25|Page Addition of a 1˚ Amine to an Aldehyde or O H N N Ketone forming an Imine (Reversed by 2 + C or H H O+ C or H H3O ) 3 + H3O Addition of a 2˚ Amine to an Aldehyde or O N N Ketone forming an Enamine (Reversed H + + by H3O ) C or H H3O C or H + H3O Double bond forms on more substituted end for Ketones Addition of a Wittig Reagent to an O PPh3 Aldehyde or Ketone C or H C or H Michael Addition to an α, β Unsaturated O O Ketone O O - or CN, HNR2, HSR etc. O O Michael Addition to an α, β Unsaturated O O Ketone with a Gilman Reagent (CH3CH2CH2)2CuLi (Organocuprates) www.datbootcamp.com 10 of 25|Page Alpha Addition/Substitution Reactions Self Aldol O -OH, H O O OH H O+, NaOH O Condensation 2 3 2 H and Enone H Δ H Formation O - O + O OH, H2O OH H3O , NaOH 2 Δ Mixed Aldol O O - O OH H O+, NaOH O Condensation OH, H2O 3 H and Enone Δ Formation O O O O - + OH, H2O H3O , NaOH Δ HO Self Claisen O O O Condensation 1. O 2 O + O 2. H3O Mixed Claisen O O O O Condensation 1. O O + 2. H3O Dieckmann O O O O Cyclization 1. O (Intramolecular O O + O Claisen 2. H3O Condensation) Acetoacetic O O O Ester Synthesis 1. O O CO2 HO 2. Cl 3. O 4. Cl + 5. H3O , Δ Malonic Ester O O O 1. Synthesis O O O HO CO2 2 HO 2. Cl 3. O 4. Cl + 5. H3O , Δ www.datbootcamp.com 11 of 25|Page DAT Organic Chemistry Reaction Details Sheet Rearrangements Details When carbocations form, H’s and CH3’s can do a 1,2-shift to generate a more stable carbocation intermediate 1,2-Hydride Shift 1,2-Methyl Shift Alkene Reactions Details Hydrohalogenation What’s added: H+ and Br- Regioselectivity: Markovnikov Stereoselectivity: N/A Intermediate: Carbocation Rearrangement: Possible (methyl and hydride shifts) Mechanism: www.datbootcamp.com 12 of 25|Page Halogenation What’s added: 2 Br atoms Regioselectivity: N/A Stereoselectivity: Anti Intermediate: Bromonium ion Rearrangement: Not possible Mechanism: Hydrobromination with Peroxide What’s added: H× and Br× Regioselectivity: Anti-Markovnikov Stereoselectivity: N/A Intermediate: Radical Rearrangement: Not possible Mechanism: www.datbootcamp.com 13 of 25|Page Hydration What’s added: H+ and OH- Regioselectivity: Markovnikov Stereoselectivity: N/A Intermediate: Carbocation Rearrangement: Possible (methyl and hydride shifts) Mechanism: Bromination in H2O What’s added: Br+ and OH- Regioselectivity: Markovnikov Stereoselectivity: Anti Intermediate: Bromonium ion Rearrangement: Not possible Mechanism: Oxymercuration-Demurcuration What’s added: H+ and OH- Regioselectivity: Markovnikov Stereoselectivity: Anti Intermediate: Mercurinium ion bridge Rearrangement: Not possible Mechanism: You do not need to know the mechanism for this reaction www.datbootcamp.com 14 of 25|Page Hydroboration-Oxidation What’s added: H+ and OH- Regioselectivity: Anti-Markovnikov Stereoselectivity: Syn Intermediate: Hydroxy-boranes Rearrangement: Not possible Mechanism: You do not need to know the mechanism for this reaction Syn-Hydroxylation or What’s added: 2 OH groups Regioselectivity: N/A Stereoselectivity: Syn Intermediate: N/A Rearrangement: Not possible Mechanism: Anti-Hydroxylation What’s added: 2 OH groups Regioselectivity: N/A Stereoselectivity: Anti Intermediate: N/A Rearrangement: Not possible Mechanism: Epoxidation then reaction with aqueous acid or base.