DAT OChem Reactions

HBr

Hydrohalogenation

• markovnikov addition (Br attaches to the less substituted side of alkene)

HBr

Hydrohalogenation (with Rearrangement)

2° Carbocation near 3° Carbon → Hydride Shift

• HBr indicates Markovnikov addition (the intermediate that’s going to form is going to be the most stable, most substituted intermediate possible)

• initial intermediate would be a 2° carbocation right next to a 3° carbon

• intermediate undergoes a hydride shift so the carbocation can then be more highly substituted as a 3° carbocation

Br₂

CCl₄

Halogenation

• anti addition

• products are enantiomers

• ignore CCl₄ it’s just a solvent

HBr

ROOR

Hydrobromination with Peroxide

• anti-mark addition (Br goes on less substituted side of alkene)

• ROOR (peroxide) causes it to be anti-mark

H₃O⁺ *

*any acid catalyst (H₂SO₄, H₃PO₄, etc.) and water

Hydration

H₃O⁺

Hydration (with Rearrangement)

• markovnikov addition (add to more substituted)

• intermediate creates 2° carbocation right next to 3° carbon → hydride shift for carbocation to be in 3° position (more stable)

• 3° carbocation formed and 3° alcohol is product

Br₂

H₂O

Bromination in H₂O

• OH and Br added anti to each other

• when we have a protonated epoxide looking intermediate, H₂O will always attack the more substituted side and result in anti addition

1. Hg(OAc)₂, H₂O

2. NaBH₄

Oxymercuration-Demurcuration

• produces the more highly substituted alcohol

• NO rearrangements possible (no carbocations)

1. BH₃, THF

2. H₂O₂, OH^-, H₂O

Hydroboration-Oxidation

• anti-markov product (add to less substituted side of alkene)

• H is added to more substituted side of alkene

• OH is added to less substituted side of alkene

• since both groups are added at the same time, it is SYN addition

• OH and H are both placed on a wedge and the methyl is pushed back on a dash (or vice versa)

1. OsO₄

2. H₂O₂

Syn-Dihydroxilation of Alkenes

• OsO₄ adds 2 hydroxy groups onto alkene in SYN addition

• meso compound = no enantiomer it would just be the same compound

KMnO₄ (cold, dilute)

OH^-

Syn-Dihydroxilation of Alkenes

• KMnO₄ is cold and dilute so it won’t be doing ozonolysis (cleaving/splitting through alkene bond) unlike if it were hot and acidic

• KMnO₄ adds 2 hydroxy groups onto alkene in SYN addition

• meso compound = no enantiomer it would just be the same compound

1. mCPBA

2. H₃O⁺

Anti-Dihydroxylation

• hydroxyl groups added anti to each other

• step 1: mCPBA → forms epoxide intermediates

• step 2: aqueous acid H₃O⁺ (or aqueous base OH^-)

  • protonates the epoxide O

  • rule: whenever epoxide has + charge, you are going to attack the more substituted side (none here)

  • second OH is added anti to first

    

CH₃OH

H⁺

Addition of an Alcohol to Produce an Ether

• markovnikov addition

• ether is produced

Br₂

CH₃OH

Bromination in Alcohol

• “epoxide” with Br formed with + charge → means that next thing added goes to more substituted side

• anti addition (Br and OCH₃ are opposite)

• ether formed

1. Hg(OAc)₂, CH₃OH

2. NaBH₄

Alkoxymercuration-Demercuration

• NO rearrangements possible (no carbocation formed)

• be careful: reagents look very similar to oxymercuration-demercuration conditions. if it were oxymercuration-demercuration, it would use water instead (resulting in OH added)

• this however has methanol (CH₃OH) which ends up being added as an alkoxy group (R-O-R), forming an ester

mCPBA (or RCO₃H)

Epoxidation

• mCPBA is a peroxy acid that converts alkene → epoxide

• need to form both enantiomers

  • mirror image but NOT superimposable (if they were: identical and can be placed directly on top of one another so that all parts align perfectly)

H₂, Pd-C ^{_{(or Pt)}}

Catalytic Hydrogenation (alkene → alkane)

• Pd-C is a palladium catalyst that helps the H’s reduce the alkenes

• Need either Pd-C as catalyst or Pt (platinum) catalyst

1. O₃

2. (CH₃)₂S _{(aka DMS)} or Zn/H₂O

Ozonolysis (Reducing Conditions)

• cleave double bond and form 2 carbonyl products

• the carbonyl on the right side keeps its H, making it an aldehyde

• O₃ + DMS → ketone + aldehyde

1. O₃

2. H₂O₂

or

1. KMnO₄/heat (acidic or basic doesn’t matter)

2. H₃O⁺

Ozonolysis (Oxidizing Conditions)/Oxidative Cleavage

• HOT KMnO₄ → double bond is cleaved and forms two carbonyls

• carbonyl on the right is originally bonded to an H. it is then replaced by an OH, so either H₂O₂ or H₃O⁺

• cold, dilute KMnO₄ → would NOT cleave double bond. would instead just add an OH on either side of where the alkene was originally

H₂, Pd-C

Catalytic Hydrogenation (Catalytic Reduction)

• alkyne → alkane

• H₂ alone will not react, need Pd-C catalyst

• H₂ + Pd-C = Lebron, can’t stop it, takes it all the way to alkane

• Pd-C: P Diddy doesn’t stop he goes all the way

H₂, Lindlar's catalyst

Reduction to Cis-Alkene (alkyne → cis alkene)

Lindlar’s Catalyst:

• H₂/Lindlar’s: alkyne → cis alkene “linda says sisss but only gets halfway into story”

• poisoned (ineffective) metal catalyst. ineffective and slow so only reduces down to alkene

• we know product is cis because metal tends to grab the pi bond from one face

Na or Li, NH_{3 (liquid)}

Reduction (alkyne → trans alkene)

• Na or Li/NH₃: alkyne → trans alkene (Naaa u Lied ur trans - NoHate(NH₃)

• Na / Li are neutral, meaning they are radicals → electrons in intermediate want to be as far apart as possible → H’s go as far apart as possible → TRANS configuration

1 eq HBr

Hydrohalogenation with HBr (Terminal Alkyne)

1 eq HBr → 2nd eq HBr

Hydrohalogenation with HBr (Internal Alkyne)

1 eq Br₂

Halogenation with Br₂

HgSO₄, H₂SO₄

Hydration of an Internal Alkyne

HgSO₄, H₂SO₄

Hydration of a Terminal Alkyne (Markovnikov)

• Oxygen is added Markovnikov

• HgSO₄ is the catalyst because the reaction is so slow

1. Sia₂BH, THF

2. H₂O₂, OH^-, H₂O

Hydration of a Terminal Alkyne (Anti-Markovnikov)

NaNH₂

S_N2 Addition of an Acetylide Ion to an Alkyl Halide

NaNH₂

S_N2 Addition of an Acetylide Ion to a Ketone

NaNH₂

S_N2 Addition of an Acetylide Ion to an Epoxide

1. O₃

2. H₂O₂

or

1. KMnO₄/heat

2. H₃O⁺

Ozonolysis/Oxidative Cleavage on an Internal Alkyne

1. O₃

2. H₂O₂

or

1. KMnO₄/heat

2. H₃O⁺

Ozonolysis/Oxidative Cleavage on a Terminal Alkyne

• Terminal carbon becomes CO₂

Br₂, hv (light) or Δ (heat)

Free Radical Halogenation using Bromine (more selective)

• Markovnikov

Cl₂, hv (light) or Δ (heat)

Free Radical Halogenation using Chlorine (less selective)

NBS, hv or Δ (heat) or ROOR

Benzylic Bromination

NBS, hv or Δ (heat) or ROOR

Allylic Bromination

hv or Δ (heat)

Diene Addition to a Dienophile (Alkene)

hv or Δ (heat)

Diene Addition to a Dienophile (Alkyne)

hv or Δ (heat)

Diene Addition to a cis Dienophile

hv or Δ (heat)

Diene Addition to a trans Dienophile

hv or Δ (heat)

Diene Addition to a substituted Dienophile

1. CH₃CH₂MgX, Ether

2. H₃O⁺

Addition of a Grignard Reagent to an Aldehyde

• produces 2° alcohol

1. CH₃CH₂MgX, Ether

2. H₃O⁺

Addition of a Grignard Reagent to a Ketone

• produces 3° alcohol

1. 2 eq. CH₃CH₂MgX, Ether

1. H₃O⁺

Addition of a Grignard Reagent to an Ester

• produces 3° alcohol

1. 2 eq. CH₃CH₂MgX, Ether

2. H₃O⁺

Addition of a Grignard Reagent to an Acyl Chloride

• produces 3° alcohol

1. CO₂, Ether

2. H₃O⁺

Addition of a Grignard Reagent to CO₂

• produces carboxylic acid

1. CH₃CH₂MgX, Ether

2. H₃O⁺

Addition of a Grignard Reagent to an Epoxide

• adds to the less substituted side

1. CH₃CH₂MgX, Ether

2. H₃O⁺

Addition of a Grignard Reagent to a Carboxylic Acid

• produces carboxylate

1. CH₃CH₂MgX, Ether

2. H₃O⁺

Addition of a Grignard Reagent to an Amide

• produces deprotonated amide

1. CH₃CH₂MgX, Ether

2. H₃O⁺

Addition of a Grignard Reagent to a Nitrile

• produces ketone

CH₃CH₂Cl, AlCl₃

Friedel-Crafts Alkylation (Rearrangement Possible)

_{(Electrophilic Aromatic Substitution (EAS) Reaction)}

CH₃CH₂Cl, AlCl₃

Friedel-Crafts Alkylation (Rearrangement Possible)

_{(Electrophilic Aromatic Substitution (EAS) Reaction)}

Friedel-Crafts Acylation (No Rearrangement Possible)

_{(Electrophilic Aromatic Substitution (EAS) Reaction)}

Br₂, FeBr₃

Bromination

_{(Electrophilic Aromatic Substitution (EAS) Reaction)}

Cl_2, FeCl₃

Chlorination

_{(Electrophilic Aromatic Substitution (EAS) Reaction)}

HNO₃, H₂SO₄

Nitration

_{(Electrophilic Aromatic Substitution (EAS) Reaction)}

→ SO₃, H₂SO₄

← H₂SO₄/heat

Sulfonation

_{(Electrophilic Aromatic Substitution (EAS) Reaction)}

CO, HCl

AlCl₃

Formylation

_{(Electrophilic Aromatic Substitution (EAS) Reaction)}

substituent

EAS with an ortho/para-directing group on Benzene

• ortho/para director = electron donating group

_{(Electrophilic Aromatic Substitution (EAS) Reaction)}

substituent

EAS with a meta-directing group on Benzene

• M = electron-withdrawing group (because those code for meta)

_{(Electrophilic Aromatic Substitution (EAS) Reaction)}

Friedel-Crafts Alkylation/Acylation with a meta-directing group or an amine on Benzene

• no reaction

_{(Electrophilic Aromatic Substitution (EAS) Reaction)}

Friedel-Crafts Alkylation/Acylation with a meta-directing group or an amine on Benzene

• no reaction

_{(Electrophilic Aromatic Substitution (EAS) Reaction)}

1. KMnO₄, ^-OH

2. H₃O⁺, heat

or

Na₂Cr₂O₇, H₂SO₄

Side-Chain Oxidation of Benzene to form Benzoic Acid

_{(Benzene Side-Chain Reactions)}

1. KMnO₄, ^-OH

2. H₃O⁺, heat

or

Na₂Cr₂O₇, H₂SO₄

Side-Chain Oxidation of Benzene to form Benzoic Acid

• no reaction (requires free hydrogen at benzylic position)

_{(Benzene Side-Chain Reactions)}

H₂NNH₂ or N₂H₄, ^-OH, heat

Wolff-Kishner Reduction

_{(Benzene Side-Chain Reactions)}

Zn(Hg), HCl, Heat

or

H₂, Pd/C

Clemmensen Reduction

_{(Benzene Side-Chain Reactions)}

Zn(Hg), HCl, Heat

or

H₂, Pd/C

or

Sn, HCl

Clemmensen Reduction

_{(Benzene Side-Chain Reactions)}

pyridine

Acetylation of Aniline using Acetic Anhydride

_{(Benzene Side-Chain Reactions)}

1. NaBH₄

2. H₃O⁺

Reduction of an Aldehyde to a 1° Alcohol

1. LiAlH₄

2. H₃O⁺

Reduction of an Aldehyde to a 1° Alcohol

1. NaBH₄

2. H₃O⁺

Reduction of a Ketone to a 2° Alcohol

1. LiAlH₄

2. H₃O⁺

Reduction of a Ketone to a 2° Alcohol

1. LiAlH₄

2. H₃O⁺

Reduction of a Carboxylic Acid to a 1° Alcohol

1. LiAlH₄

2. H₃O⁺

Reduction of an Ester to a 1° Alcohol

1. DIBAL-H, -78°C

2. H₂O

Reduction of an Ester to an Aldehyde

1. LiAlH₄

2. H₃O⁺

or

1. NaBH₄, EtOH

2. H₃O⁺

Reduction of an Ester to a 1° Alcohol

Reduction of an Acyl Chloride to a 1° Alcohol

LiAlH[OC(CH₃)₃]₃

Reduction of an Acyl Chloride to an Aldehyde

1. LiAlH₄

2. H₃O⁺

Reduction of an Amide to an Amine

1. Br₂

2. NaOH

Hofmann Rearrangement

• takes out the carbon with a double-bonded O on it

1. LiAlH₄

2. H₃O⁺

Reduction of a Nitrile to an Amine

HX

Conversion of a 2°/3° Alcohol to an alkyl halide via S_N1

HX

Conversion of a 2°/3° Alcohol to an alkyl halide via S_N1

PBr₃

Conversion of a 1°/2° Alcohol to an alkyl bromide via S_N2

PBr₃

Conversion of a 1°/2° Alcohol to an alkyl bromide via S_N2

SOCl₂, pyridine (or PCl₃ or PCl₅)

Conversion of a 1°/2° Alcohol to an alkyl chloride via S_N2

SOCl₂, pyridine

Conversion of a 1°/2° Alcohol to an alkyl chloride via S_N2

TsCl

Conversion of an Alcohol to a Tosylate Ester

• retention of stereochemistry

H₃O⁺

Acid-catalyzed Dehydration of an Alcohol

• Zaitsev’s Rule: the major product is the most substituted alkene

Na₂Cr₂O₇ or CrO₃, H₂SO₄

Chromic Acid Oxidation of a 1° Alcohol to a Carboxylic Acid

Na₂Cr₂O₇ or CrO₃, H₂SO₄

Chromic Acid Oxidation of a 2° Alcohol to a Ketone

Na₂Cr₂O₇ or CrO₃, H₂SO₄

Chromic Acid Oxidation of an Aldehyde to a Carboxylic Acid

PCC or DMP

PCC or DMP Oxidation of a 1° Alcohol to an Aldehyde

PCC or DMP

PCC or DMP Oxidation of a 2° Alcohol to an Aldehyde

HIO₄

Oxidative Cleavage of a 1,2 Diol

HIO₄

Oxidative Cleavage of a 1,2 Diol

NaH, Na, or K

Williamson Ether Synthesis via S_N2

HBr

Acid-catalyzed Cleavage of Ethers when one side is 2°/3°

• nucleophile attacks MORE substituted side via S_N1

HBr

Acid-catalyzed Cleavage of Ethers when one side is 2°/3°

• nucleophile attacks MORE substituted side via S_N1

HBr

Acid-catalyzed Cleavage of Ethers when neither side is 2°/3°

• nucleophile attacks LESS substituted side via S_N2