DAT Organic Chemistry Reaction Summary Sheet Alkene Reactions Hydrohalogenation

Home , Hydrohalogenation, Organic Chemistry

Hydrohalogenation (with Rearrangement)

Halogenation

Hydrobromination with Peroxide

Hydration

Hydration (with Rearrangement)

Bromination in H2O

Oxymercuration- Demurcuration

Hydroboration- Oxidation

Syn-Hydroxylation

Anti-Hydroxylation

Addition of an Alcohol

Bromination in Alcohol

Alkoxymercuration- Demurcuration

Epoxidation

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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

Allylic/Benzylic Bromination NBS Br hv or Δ or ROOR

NBS Br hv or Δ or ROOR Br

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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

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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 2. H O+, Heat Acid R R 3 OH 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

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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

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Alcohol Reactions

Conversion of a 2˚/3˚Alcohol to an alkyl OH HX X halide via SN1

OH X HX

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 CrO O 3 H SO 2 4 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

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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 SN1)

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

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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)

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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

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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:

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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:

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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

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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

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.

In acidic conditions, the H2O attacks the more highly-substituted C:

In basic conditions, H2O attacks the less highly-substituted C:

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Addition of an Alcohol

What’s added: H+ and OR- Regioselectivity: Markovnikov Stereoselectivity: N/A Intermediate: Carbocation Rearrangement: Possible Mechanism:

Bromination in Alcohol

What’s added: Br+ and OR- Regioselectivity: Markovnikov Stereoselectivity: Anti Intermediate: Bromonium ion Rearrangement: Not possible Mechanism:

Alkoxymercuration-Demurcuration

+ - What’s added: H and OCH3 Regioselectivity: Markovnikov Stereoselectivity: Anti Intermediate: Mercurinium ion Rearrangement: Not possible Mechanism: You do not need to know the mechanism for this reaction

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Epoxidation

What’s added: O Regioselectivity: N/A Stereoselectivity: Syn Intermediate: N/A Rearrangement: Not possible Mechanism: You do not need to know the mechanism for this reaction Do know that a commonly-used peroxy acid is m-CPBA:

Catalytic Hydrogenation

What’s added: 2 H atoms Regioselectivity: N/A Stereoselectivity: Syn Intermediate: N/A Rearrangement: Not possible Mechanism: You do not need to know the mechanism for this reaction

Ozonolysis in Reducing Conditions

What’s added: 2 O atoms Regioselectivity: N/A Stereoselectivity: N/A Intermediate: N/A Rearrangement: N/A Mechanism: You do not need to know the mechanism for this reaction Do know that the C=C double bond gets “sawed” in half, and an O atom is placed on the end of each new piece.

Note: (CH3)2S is often abbreviated “DMS” for dimethyl sulfide.

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Ozonolysis in Oxidizing Conditions

What’s added: Multiple O atoms Regioselectivity: N/A Stereoselectivity: N/A Intermediate: N/A Rearrangement: N/A Mechanism: You do not need to know the mechanism for this reaction Do know that the C=C double bond gets “sawed” in half, and an O atom is placed on the end of each new piece. Then, one of the H’s attached to the alkene C’s gets replaced by an –OH group.

Oxidative Cleavage

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Alkynes Reactions Details

Catalytic Hydrogenation

What’s added: 4 H atoms Regioselectivity: N/A Stereoselectivity: Anti Intermediate: N/A Rearrangement: Not possible Mechanism: You do not need to know the mechanism for this reaction

Reduction to Cis-Alkene

What’s added: 2 H atoms Regioselectivity: N/A Stereoselectivity: Syn Intermediate: N/A Rearrangement: Not possible Mechanism: You do not need to know the mechanism for this reaction

Reduction to Trans-Alkene

What’s added: 2 H atoms Regioselectivity: N/A Stereoselectivity: N/A Intermediate: N/A Rearrangement: Not possible Mechanism: You do not need to know the mechanism for this reaction

Hydrohalogenation with HBr (Terminal Alkyne)

What’s added: 1 H atom and 1 halogen atom (can be F, Br, I, or Cl) per equivalent of HX Regioselectivity: Markovnikov Stereoselectivity: N/A Intermediate: Carbocation Rearrangement: Possible Mechanism: The halogen goes to the C with fewer H’s

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Hydrohalogenation with HBr (Internal Alkyne)

What’s added: 1 H atom and 1 halogen atom (can be Cl or Br) per equivalent of HX Regioselectivity: Markovnikov Stereoselectivity: N/A Intermediate: Carbocation Rearrangement: Possible Mechanism: Same as for terminal alkynes, but yields a mixture of two products because both intermediates are equally stable

Halogenation with Br2

What’s added: 2 halogen atoms (can be F, Br, I, or Cl) Regioselectivity: N/A Stereoselectivity: Anti Intermediate: Bromonium ion Rearrangement: Not possible Mechanism:

Hydration of an Internal Alkyne

What’s added: 1 O atoms Regioselectivity: N/A Stereoselectivity: N/A Intermediate: N/A Rearrangement: Not possible Mechanism: You do not need to know the mechanism for this reaction Do know that this reaction produces enols, which then tautomerize to form ketones.

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Hydration of a Terminal Alkyne (Markovnikov)

What’s added: 1 O atom Regioselectivity: Markovnikov Stereoselectivity: N/A Intermediate: N/A Rearrangement: Not possible Mechanism: You do not need to know the mechanism for this reaction Do know that this reaction produces Markovnikov enols, which then tautomerize to form ketones.

Hydration of a Terminal Alkyne (Anti-Markovnikov)

What’s added: 1 O atom Regioselectivity: Anti-Markovnikov Stereoselectivity: N/A Intermediate: N/A Rearrangement: Not possible Mechanism: You do not need to know the mechanism for this reaction Do know that this reaction produces Anti-Markovnikov enols, which then tautomerize to form aldehydes.

SN2 Addition of an Acetylide Ion to an Alkyl Halide

What’s added: additional C atoms (-R of alkyl halide) Regioselectivity: N/A Stereoselectivity: N/A Intermediate: Acetylide Ion Rearrangement: Not possible Mechanism: Deprotonation, then alkylation via SN2 reaction

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SN2 Addition of an Acetylide Ion to a Ketone

What’s added: 2 additional alkyl groups and 1 –OH group Regioselectivity: N/A Stereoselectivity: N/A Intermediate: Acetylide Ion Rearrangement: Not possible Mechanism: Deprotonation, then addition of a ketone via SN2 reaction

SN2 Addition of an Acetylide Ion to an Epoxide

What’s added: 2-hydroxylpropane (from epoxide) Regioselectivity: N/A Stereoselectivity: N/A Intermediate: Acetylide Ion Rearrangement: Not possible Mechanism: Deprotonation, then addition of 2-hydroxyl propane via SN2 reaction

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Free Radical Halogenation Reaction Details

Free Radical Halogenation using Bromine (more selective)

Br Br2

hv or Δ

What’s added: 1 Br atom Regioselectivity: Most Substituted Product Stereoselectivity: N/A Intermediate: Radical Intermediate Rearrangement: Not possible Mechanism: Formation of bromine and carbon radicals and them joining to create an alkyl halide

1. Initiation

hv or Δ Br Br Br Br

2. Propagation

Br HBr

Br Br Br Br

alkyl halide

3. Termination

Br Br Br Br

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Free Radical Halogenation using Chlorine (less selective) Cl Cl Cl2 hv or Δ Cl

Cl What’s added: 1 Cl atom Regioselectivity: N/A Stereoselectivity: N/A Intermediate: Radical Intermediate Rearrangement: Not possible Mechanism: Formation of chlorine and carbon radicals and them joining to create alkyl halides

1. Initiation

hv or Δ Cl Cl Cl Cl

2. Propagation

H H Cl Cl HCl HCl Cl

Cl Cl Cl Cl Cl Cl Cl

alkyl halide alkyl halide

Cl Cl HCl H HCl H

Cl Cl Cl Cl Cl Cl Cl Cl alkyl halide alkyl halide

3. Termination

Cl Cl Cl Cl

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Allylic/Benzylic Bromination

NBS Br hv or Δ or ROOR

NBS Br hv or Δ or ROOR Br

What’s added: 1 Br atom Regioselectivity: N/A Stereoselectivity: N/A Intermediate: Allylic Radical Intermediate Rearrangement: Not possible Mechanism: You do not need to know the mechanism for this reaction

Note: this reaction results in the formation of allylic radical intermediates which resonate and thus allow for the formation of multiple products.

Br Br NBS hv or Δ or ROOR allylic radical intermediates Br Br