Reaction Flashcards (Alkenes and Alkynes)
Alkene Reactions
DAT Organic Chemistry Reaction Summary Sheet
Hydrohalogenation
Hydrohalogenation (with Rearrangement) Halogenation
Hydrobromination with Peroxide Hydration Hydration (with Rearrangement) Bromination in H2O
OxymercurationDemurcuration HydroborationOxidation Syn-Hydroxylation
Syn-Hydroxylation
Anti-Hydroxylation
Addition of an Alcohol Bromination in Alcohol
AlkoxymercurationDemurcuration Epoxidation
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Catalytic Hydrogenation Ozonolysis (Reducing Conditions) Ozonolysis (Oxidizing Conditions) Oxidative Cleavage
Alkyne Reactions Catalytic Hydrogenation (Catalytic Reduction) Reduction to CisAlkene Reduction to TransAlkene 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
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Free Radical Halogenation Reactions Free Radical Halogenation using Bromine (more selective) Free Radical Halogenation using Chlorine (less selective)
Br
Br2 hv or Δ Cl
Cl
Cl2
Cl
hv or Δ
Cl
Allylic/Benzylic Bromination
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NBS hv or Δ or ROOR
Br
NBS hv or Δ or ROOR
Br Br
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Grignard Reactions Addition of a Grignard Reagent to an Aldehyde Addition of a Grignard Reagent to a Ketone
O
1. H
O
OH
MgX , Ether
2. H3O+ 1.
2˚Alcohol
MgX , Ether
HO 3˚Alcohol
2. H3O+ Addition of a Grignard Reagent to an Ester
O
1. 2 eq. O
Addition of a Grignard Reagent to an Acyl Chloride
2. H3
O
MgX, Ether
1. 2 eq. Cl
Addition of a Grignard Reagent to CO2
HO 3˚Alcohol
O+
MgX, Ether
HO
2. H3O+
3˚Alcohol
O MgX
1. CO2, Ether
OH
2. H3O+ Addition of a Grignard Reagent to an Epoxide (adds to the less subs. side forming the less subs. alcohol) Addition of a Grignard Reagent to a Carboxylic Acid
O
1.
MgX , Ether
OH 2˚Alcohol (less subs. alcohol)
2. H3O+
O
1. OH
Carboxylic Acid
MgX , Ether
O O
2. H3O+
MgX
Carboxylate Addition of a Grignard Reagent to an Amide
O
MgX , Ether
1. NH2
O NH MgX
2. H3O+
Deprotonated Amide Addition of a Grignard Reagent to a Nitrile
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N
1.
MgX , Ether
2. H3O+
O Ketone
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Electrophilic Aromatic Substitution (EAS) Reactions Friedel-Crafts Alkylation (Rearrangement Possible)
Cl AlCl3
Cl AlCl3 Friedel-Crafts Acylation (No Rearrangement Possible)
O
O
Cl AlCl3
Bromination
Br2
Br
FeBr3 Chlorination
Cl2
Cl
FeCl3 Nitration
HNO3
NO2
H2SO4 Sulfonation
SO3H
SO3
H2SO4 H2SO4/Δ Formylation
O CO, HCl
H
AlCl3 EAS with an ortho/paradirecting group on Benzene
O/P
EAS with a meta-directing group on Benzene
M
O/P
O/P Substituent
Substituent
Substituent M Substituent Substituent
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Friedel-Crafts Alkylation/Acylation with a meta-directing group or an amine on Benzene
M
O R Cl
or Cl
R
No Reaction
AlCl3 NH2/NRH/NR2
O R Cl
or Cl
R
No Reaction
AlCl3
Benzene Side-Chain Reactions Side-Chain Oxidation of Benzene to form Benzoic Acid
R R
or
R
or
O
1. KMnO4, -OH 2. H3O+, Heat
OH
or Na2Cr2O7 H2SO4
1. KMnO4, -OH 2. H3O+, Heat or
No Reaction
Requires free Hydrogen at Benzylic position
Na2Cr2O7 H2SO4 Wolff-Kishner Reduction
O H2NNH2 or N2H4, -OH, Heat
Clemmensen Reduction
O Zn(Hg), HCl, Heat
NO2
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Zn(Hg), HCl, Heat
NH2
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Hydride Reduction Reactions Reduction of an Aldehyde to a 1˚Alcohol
O
1. NaBH4, EtOH H
2. H3O+
O
1. LiAlH4, EtOH H
Reduction of a Ketone to a 2˚Alcohol
2. H3O+
O
1. NaBH4, EtOH
OH H OH H
OH
2. H3O+
O
1. LiAlH4, EtOH
OH
2. H3O+ Reduction of a Carboxylic Acid to a 1˚Alcohol
O
Reduction of an Ester to a 1˚Alcohol
O
1. LiAlH4, EtOH OH
1. LiAlH4, EtOH O
Reduction of an Ester to an Aldehyde
O
O
O
OH
H
O H
OH
2. H3O+
H
LiAlH[OC(CH3)3]3
O
Cl Reduction of an Amide to an Amine
OH
2. H2O
1. LiAlH4, EtOH Cl
Reduction of an Acyl Chloride to an Aldehyde
2. H3O+
H
1. DIBAL-H, -78°C O
Reduction of an Acyl Chloride to a 1˚Alcohol
2. H3O+
OH
H
O
1. LiAlH4, EtOH NH2
NH2 2. H3O+ Hoffmann Rearrangement
O
1. Br2 NH2
Reduction of a Nitrile to an Amine
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N
2. NaOH
1. LiAlH4, EtOH 2. H3O+
NH2
NH2
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Alcohol Reactions Conversion of a 2˚/3˚Alcohol to an alkyl halide via SN1
Conversion of a 1˚/2˚Alcohol to an alkyl bromide via SN2
OH
HX
X
OH
HX
X
OH
PBr3
H
H
OH Conversion of a 1˚/2˚Alcohol to an alkyl chloride via SN2
SOCl2 H Pyridine
Conversion of an Alcohol to a Tosylate Ester (OTs)
OH
OH
Br
PBr3
OH
OH
Acid-catalyzed Dehydration of an Alcohol
Br
Cl H
Cl
SOCl2 Pyridine
OTs
TsCl
H3O+
Retention of Stereochemistry
Zaitsev’s Rule
o
Chromic Acid Oxidation of a 1 Alcohol to a Carboxylic Acid
OH H
Na2Cr2O7 or CrO3
O
H2SO4
OH
o
Chromic Acid Oxidation of a 2 Alcohol to a Ketone
OH
Na2Cr2O7 or CrO3
O
H2SO4 Chromic Acid Oxidation of an Aldehyde to a Carboxylic Acid
Na2Cr2O7 or CrO3
O H
H2SO4
O OH
o
PCC or DMP Oxidation of a 1 Alcohol to an Aldehyde
OH
PCC or DMP
O
H o
PCC or DMP Oxidation of a 2 Alcohol to a Ketone
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OH
H
PCC or DMP
O
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Ether and Epoxide Reactions Williamson Ether Synthesis via SN2
NaH, Na, or K OH Acid-catalyzed Cleavage of Ethers when one side is 2˚/3˚ (Nucleophile attacks more substituted side via SN1)
O
Cl
O
HBr O
Br
HO
Br
HO
HBr O Acid-catalyzed Cleavage of Ethers when neither side is 2˚/3˚ (Nucleophile attacks less substituted side via SN2)
O
Acid-catalyzed Ring Opening of Epoxides (Nucleophile attacks more substituted side) Base-catalyzed Ring Opening of Epoxides (Nucleophile attacks less substituted side)
OH
HBr
Br
Cl
O
HCl
O
OCH3
OH
OH O
HOCH3
Aldehyde and Ketone Reactions Nucleophilic Addition to an Aldehyde or Ketone
O
Addition of water to an Aldehyde or Ketone forming a Hydrate
O
C or H
C or H
Base-catalyzed addition of an Alcohol to an Aldehyde or Ketone forming a Hemi-acetal/Hemi-ketal
O
Acid-catalyzed addition of an Alcohol to an Aldehyde or Ketone forming a Acetal/Ketal (Protecting Group, reversed + by H3O )
O
Acid-catalyzed addition of Ethylene Glycol to an Aldehyde or Ketone forming a Acetal/Ketal (Protecting Group, + reversed by H3O )
Nucleophile H3O+
OH C or H
H3O+ or -OH HO
O C or H
HO
H3O+ C or H
C or H HO
H 2O
O C or H
Nucleophile
HO
O
O C or H
HO H3O+
O
OH
HO C or H
H3O+
O
O C or H
H3O+
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Addition of a 1˚ Amine to an Aldehyde or Ketone forming an Imine (Reversed by + H 3O )
O
N
H 2N H3O+
C or H
C or H
H3O+ Addition of a 2˚ Amine to an Aldehyde or Ketone forming an Enamine (Reversed + by H3O )
O C or H
N H H3O+
N C or H
H3O+ Double bond forms on more substituted end for Ketones Addition of a Wittig Reagent to an Aldehyde or Ketone
PPh3
O
C or H
C or H Michael Addition to an α, β Unsaturated Ketone
O
O O
O or -CN, HNR2, HSR etc.
Michael Addition to an α, β Unsaturated Ketone with a Gilman Reagent (Organocuprates)
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O O
O
(CH3CH2CH2)2CuLi
O
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Alpha Addition/Substitution Reactions Self Aldol Condensation and Enone Formation
O
-OH,
2
H
OH
O
-OH,
Δ
O
H 2O
O
O
O
H3O+, NaOH
H
2 Mixed Aldol Condensation and Enone Formation
O
H 2O
-OH,
H
H
O
OH H3O+, NaOH Δ OH
O
H 2O
H3O+, NaOH
O
Δ
O
O
O
-OH,
O
H3O+, NaOH
H 2O
Δ HO Self Claisen Condensation
O 2
Mixed Claisen Condensation
O
O
O
Malonic Ester Synthesis
O
O
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O O
O
O
1. O
1. O 2. Cl 3. O 4. Cl 5. H3O+, Δ
O O
2. H3O+
1. O 2. Cl 3. O 4. Cl 5. H3O+, Δ
O
O
O
2. H3O+
O
O
O
O
1. O
O
O
O
2. H3O+
O Dieckmann Cyclization (Intramolecular Claisen Condensation) Acetoacetic Ester Synthesis
O
1. O
O CO2
HO
O HO
CO2
2 HO
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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 BrRegioselectivity: 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
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. 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
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.
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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
Br Br
hv or Δ
Br
Br
2. Propagation
H Br
HBr
Br Br Br
Br alkyl halide
3. Termination
Br
Br
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Br Br
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Free Radical Halogenation using Chlorine (less selective) Cl
Cl
Cl2
Cl
hv or Δ
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
Cl Cl
hv or Δ
Cl
Cl
2. Propagation H H
Cl
Cl
HCl
HCl
Cl Cl
Cl Cl
Cl Cl
Cl
Cl
alkyl halide
Cl
alkyl halide
Cl
H
HCl
HCl H
Cl Cl
Cl Cl
Cl alkyl halide
Cl
Cl Cl alkyl halide
3. Termination
Cl
Cl
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Cl Cl
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Allylic/Benzylic Bromination
NBS hv or Δ or ROOR
Br
NBS hv or Δ or ROOR
Br 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
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DAT Organic Chemistry Reaction Summary Sheet
Hydrohalogenation
Hydrohalogenation (with Rearrangement) Halogenation
Hydrobromination with Peroxide Hydration Hydration (with Rearrangement) Bromination in H2O
OxymercurationDemurcuration HydroborationOxidation Syn-Hydroxylation
Syn-Hydroxylation
Anti-Hydroxylation
Addition of an Alcohol Bromination in Alcohol
AlkoxymercurationDemurcuration Epoxidation
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Catalytic Hydrogenation Ozonolysis (Reducing Conditions) Ozonolysis (Oxidizing Conditions) Oxidative Cleavage
Alkyne Reactions Catalytic Hydrogenation (Catalytic Reduction) Reduction to CisAlkene Reduction to TransAlkene 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
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Free Radical Halogenation Reactions Free Radical Halogenation using Bromine (more selective) Free Radical Halogenation using Chlorine (less selective)
Br
Br2 hv or Δ Cl
Cl
Cl2
Cl
hv or Δ
Cl
Allylic/Benzylic Bromination
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NBS hv or Δ or ROOR
Br
NBS hv or Δ or ROOR
Br Br
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Grignard Reactions Addition of a Grignard Reagent to an Aldehyde Addition of a Grignard Reagent to a Ketone
O
1. H
O
OH
MgX , Ether
2. H3O+ 1.
2˚Alcohol
MgX , Ether
HO 3˚Alcohol
2. H3O+ Addition of a Grignard Reagent to an Ester
O
1. 2 eq. O
Addition of a Grignard Reagent to an Acyl Chloride
2. H3
O
MgX, Ether
1. 2 eq. Cl
Addition of a Grignard Reagent to CO2
HO 3˚Alcohol
O+
MgX, Ether
HO
2. H3O+
3˚Alcohol
O MgX
1. CO2, Ether
OH
2. H3O+ Addition of a Grignard Reagent to an Epoxide (adds to the less subs. side forming the less subs. alcohol) Addition of a Grignard Reagent to a Carboxylic Acid
O
1.
MgX , Ether
OH 2˚Alcohol (less subs. alcohol)
2. H3O+
O
1. OH
Carboxylic Acid
MgX , Ether
O O
2. H3O+
MgX
Carboxylate Addition of a Grignard Reagent to an Amide
O
MgX , Ether
1. NH2
O NH MgX
2. H3O+
Deprotonated Amide Addition of a Grignard Reagent to a Nitrile
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N
1.
MgX , Ether
2. H3O+
O Ketone
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Electrophilic Aromatic Substitution (EAS) Reactions Friedel-Crafts Alkylation (Rearrangement Possible)
Cl AlCl3
Cl AlCl3 Friedel-Crafts Acylation (No Rearrangement Possible)
O
O
Cl AlCl3
Bromination
Br2
Br
FeBr3 Chlorination
Cl2
Cl
FeCl3 Nitration
HNO3
NO2
H2SO4 Sulfonation
SO3H
SO3
H2SO4 H2SO4/Δ Formylation
O CO, HCl
H
AlCl3 EAS with an ortho/paradirecting group on Benzene
O/P
EAS with a meta-directing group on Benzene
M
O/P
O/P Substituent
Substituent
Substituent M Substituent Substituent
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Friedel-Crafts Alkylation/Acylation with a meta-directing group or an amine on Benzene
M
O R Cl
or Cl
R
No Reaction
AlCl3 NH2/NRH/NR2
O R Cl
or Cl
R
No Reaction
AlCl3
Benzene Side-Chain Reactions Side-Chain Oxidation of Benzene to form Benzoic Acid
R R
or
R
or
O
1. KMnO4, -OH 2. H3O+, Heat
OH
or Na2Cr2O7 H2SO4
1. KMnO4, -OH 2. H3O+, Heat or
No Reaction
Requires free Hydrogen at Benzylic position
Na2Cr2O7 H2SO4 Wolff-Kishner Reduction
O H2NNH2 or N2H4, -OH, Heat
Clemmensen Reduction
O Zn(Hg), HCl, Heat
NO2
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Zn(Hg), HCl, Heat
NH2
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Hydride Reduction Reactions Reduction of an Aldehyde to a 1˚Alcohol
O
1. NaBH4, EtOH H
2. H3O+
O
1. LiAlH4, EtOH H
Reduction of a Ketone to a 2˚Alcohol
2. H3O+
O
1. NaBH4, EtOH
OH H OH H
OH
2. H3O+
O
1. LiAlH4, EtOH
OH
2. H3O+ Reduction of a Carboxylic Acid to a 1˚Alcohol
O
Reduction of an Ester to a 1˚Alcohol
O
1. LiAlH4, EtOH OH
1. LiAlH4, EtOH O
Reduction of an Ester to an Aldehyde
O
O
O
OH
H
O H
OH
2. H3O+
H
LiAlH[OC(CH3)3]3
O
Cl Reduction of an Amide to an Amine
OH
2. H2O
1. LiAlH4, EtOH Cl
Reduction of an Acyl Chloride to an Aldehyde
2. H3O+
H
1. DIBAL-H, -78°C O
Reduction of an Acyl Chloride to a 1˚Alcohol
2. H3O+
OH
H
O
1. LiAlH4, EtOH NH2
NH2 2. H3O+ Hoffmann Rearrangement
O
1. Br2 NH2
Reduction of a Nitrile to an Amine
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N
2. NaOH
1. LiAlH4, EtOH 2. H3O+
NH2
NH2
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Alcohol Reactions Conversion of a 2˚/3˚Alcohol to an alkyl halide via SN1
Conversion of a 1˚/2˚Alcohol to an alkyl bromide via SN2
OH
HX
X
OH
HX
X
OH
PBr3
H
H
OH Conversion of a 1˚/2˚Alcohol to an alkyl chloride via SN2
SOCl2 H Pyridine
Conversion of an Alcohol to a Tosylate Ester (OTs)
OH
OH
Br
PBr3
OH
OH
Acid-catalyzed Dehydration of an Alcohol
Br
Cl H
Cl
SOCl2 Pyridine
OTs
TsCl
H3O+
Retention of Stereochemistry
Zaitsev’s Rule
o
Chromic Acid Oxidation of a 1 Alcohol to a Carboxylic Acid
OH H
Na2Cr2O7 or CrO3
O
H2SO4
OH
o
Chromic Acid Oxidation of a 2 Alcohol to a Ketone
OH
Na2Cr2O7 or CrO3
O
H2SO4 Chromic Acid Oxidation of an Aldehyde to a Carboxylic Acid
Na2Cr2O7 or CrO3
O H
H2SO4
O OH
o
PCC or DMP Oxidation of a 1 Alcohol to an Aldehyde
OH
PCC or DMP
O
H o
PCC or DMP Oxidation of a 2 Alcohol to a Ketone
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OH
H
PCC or DMP
O
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Ether and Epoxide Reactions Williamson Ether Synthesis via SN2
NaH, Na, or K OH Acid-catalyzed Cleavage of Ethers when one side is 2˚/3˚ (Nucleophile attacks more substituted side via SN1)
O
Cl
O
HBr O
Br
HO
Br
HO
HBr O Acid-catalyzed Cleavage of Ethers when neither side is 2˚/3˚ (Nucleophile attacks less substituted side via SN2)
O
Acid-catalyzed Ring Opening of Epoxides (Nucleophile attacks more substituted side) Base-catalyzed Ring Opening of Epoxides (Nucleophile attacks less substituted side)
OH
HBr
Br
Cl
O
HCl
O
OCH3
OH
OH O
HOCH3
Aldehyde and Ketone Reactions Nucleophilic Addition to an Aldehyde or Ketone
O
Addition of water to an Aldehyde or Ketone forming a Hydrate
O
C or H
C or H
Base-catalyzed addition of an Alcohol to an Aldehyde or Ketone forming a Hemi-acetal/Hemi-ketal
O
Acid-catalyzed addition of an Alcohol to an Aldehyde or Ketone forming a Acetal/Ketal (Protecting Group, reversed + by H3O )
O
Acid-catalyzed addition of Ethylene Glycol to an Aldehyde or Ketone forming a Acetal/Ketal (Protecting Group, + reversed by H3O )
Nucleophile H3O+
OH C or H
H3O+ or -OH HO
O C or H
HO
H3O+ C or H
C or H HO
H 2O
O C or H
Nucleophile
HO
O
O C or H
HO H3O+
O
OH
HO C or H
H3O+
O
O C or H
H3O+
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Addition of a 1˚ Amine to an Aldehyde or Ketone forming an Imine (Reversed by + H 3O )
O
N
H 2N H3O+
C or H
C or H
H3O+ Addition of a 2˚ Amine to an Aldehyde or Ketone forming an Enamine (Reversed + by H3O )
O C or H
N H H3O+
N C or H
H3O+ Double bond forms on more substituted end for Ketones Addition of a Wittig Reagent to an Aldehyde or Ketone
PPh3
O
C or H
C or H Michael Addition to an α, β Unsaturated Ketone
O
O O
O or -CN, HNR2, HSR etc.
Michael Addition to an α, β Unsaturated Ketone with a Gilman Reagent (Organocuprates)
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O O
O
(CH3CH2CH2)2CuLi
O
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Alpha Addition/Substitution Reactions Self Aldol Condensation and Enone Formation
O
-OH,
2
H
OH
O
-OH,
Δ
O
H 2O
O
O
O
H3O+, NaOH
H
2 Mixed Aldol Condensation and Enone Formation
O
H 2O
-OH,
H
H
O
OH H3O+, NaOH Δ OH
O
H 2O
H3O+, NaOH
O
Δ
O
O
O
-OH,
O
H3O+, NaOH
H 2O
Δ HO Self Claisen Condensation
O 2
Mixed Claisen Condensation
O
O
O
Malonic Ester Synthesis
O
O
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O O
O
O
1. O
1. O 2. Cl 3. O 4. Cl 5. H3O+, Δ
O O
2. H3O+
1. O 2. Cl 3. O 4. Cl 5. H3O+, Δ
O
O
O
2. H3O+
O
O
O
O
1. O
O
O
O
2. H3O+
O Dieckmann Cyclization (Intramolecular Claisen Condensation) Acetoacetic Ester Synthesis
O
1. O
O CO2
HO
O HO
CO2
2 HO
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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 BrRegioselectivity: 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
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. 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
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.
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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
Br Br
hv or Δ
Br
Br
2. Propagation
H Br
HBr
Br Br Br
Br alkyl halide
3. Termination
Br
Br
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Br Br
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Free Radical Halogenation using Chlorine (less selective) Cl
Cl
Cl2
Cl
hv or Δ
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
Cl Cl
hv or Δ
Cl
Cl
2. Propagation H H
Cl
Cl
HCl
HCl
Cl Cl
Cl Cl
Cl Cl
Cl
Cl
alkyl halide
Cl
alkyl halide
Cl
H
HCl
HCl H
Cl Cl
Cl Cl
Cl alkyl halide
Cl
Cl Cl alkyl halide
3. Termination
Cl
Cl
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Cl Cl
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Allylic/Benzylic Bromination
NBS hv or Δ or ROOR
Br
NBS hv or Δ or ROOR
Br 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
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