Orgo II Exam 1 Reactions Flashcards
Alkane Chlorination/Bromonation:
1. Overall Reaction(s)
2. Mechanism
3. Notes
CH4 + X2 –∆–> CH3X + HX
- more substitued radicals are more stable and will be the major product
-if there is stereochem, it will be a racemic mixture bc the halogen can attack from above of below
Radical Halogenation of Alkenes
1. Overall Reaction(s)
2. Notes
- alkene + HBr —-> monobromonated alkane
- Markovnikov - alkene + HBr –ROOR–> monobromonated alkane
- Antimarkovnikov
Radical Substitution of Benzylic Hydrogens
1. Overall Reaction(s)
2. Mechanism
3. Notes
- Substituted Benzene + X2 –∆–> Bromo-benzylic substituted benzene
ie: Ar-CH2CH3 + X2 –∆–> Ar-CH-X-CH3
-must have at least 1 benzylic H
- if resonance is not symmetrical, two products will form - Substituted Benzene + NBS –∆,ROOR–> Bromo-benzylic substituted benzene
- able to react in low conc of HBr and Br2
- must have at least 1 benzylic H
- if resonance is not symmetrical, two products will form
Radical Substitution of Allylic Hydrogens
1. Overall Reaction(s)
2. Mechanism
3. Notes
Allylic + X2 –∆–> Bromo-allylic substituted
Allylic + NBS –∆,ROOR–>
-must have at least 1 benzylic H
- if resonance is not symmetrical, two products will form
General Electrophilic Addition Reaction Mechanism
Benzene Halogenation
1. Overall Reaction(s)
2. Mechanism
3. Notes
- Benzene + Br2 —(FeBr3)–> monobromonated benzene
- No catalyst needed if the ring already has a strongly activating substituent - Benzene + Cl2 —(FeCl3)–> monochloronated benzene
- No catalyst needed if the ring already has a strongly activating substituent - Benzene + I2 –(H2O2, H2SO4)–> monoiodonated benzene
Benzene Nitration
1. Overall Reaction(s)
2. Mechanism
3. Notes
- Benzene + HNO3 –(H2SO4)–> Benzene-NO2 + H2O
- Can’t nitrate aniline - Aniline + CH3C=OCl –(pyr)–> intermediate
–(HNO3, H2SO4)–> nitrate added
–1. HCl, H2O, ∆ 2. OH—> acyl substituent released. Nitrated aniline
Friedel-Crafts Acylation
1. Overall Reaction(s)
2. Mechanism
3. Notes
- Benzene + acyl halide
–1. AlCl3 2. H2O–> carbonyl substituted benzene + HCl - Benzene + acid anhydride
–1. AlCl3 2. H2O–> carbonyl substituted benzene + carboxylic acid
- FC reactions don’t occur when there is already a meta-directing substituent on the ring
- Aniline doesn’t undergo Friedel-Crafts reaction
Benzene Sulfonation and Desulfonation
1. Overall Reaction(s)
2. Mechanism
3. Notes
- Sulfonation:
Benzene + H2SO4 <–∆–> SO3H substituted (sulfonated) benzene + H2O - Desulfonation
Sulfonated Benzene + Dilute H3O+ <–> Benzene + SO3H+
Friedel-Crafts Alkylation
1. Overall Reaction(s)
2. Mechanism
3. Notes
Benzene + RCl –AlCl3–> alkyl substituted benzene + HCl
- Major product is the one with the most stable C+ intermediate. Rearrangements with H-shifts and methyl-shifts will occur
-FC reactions don’t occur when there is already a meta-directing substituent on the ring - Aniline doesn’t undergo Friedel-Crafts reaction
Alkylation by Acylation-Reduction
1. Overall Reaction(s)
2. Mechanism
3. Notes
- Friedel-Crafts
Benzene + acyl halid –1. AlCl3 2.H2O–> carbonyl substituted benzene
–H2, Pd/C–> Benzene-CH2-R
-H2, Pd/C only reduces carbonyls adjacent to the ring - Wolff-Kishner
Carbonyl substituted benzene
–H2NNH2, OH-, ∆–> Benzene-CH2-R
- Works well in a basic environment
-reduces all ketones - Clemmensen
Carbonyl substituted benzene
–Zn(Hg), HCl, ∆–> Benzene-CH2-R
- Works well in acidic environments
-Use then when you don’t want C+ rearrangements
-Carbonyl reduction
Substituent Oxidation
1. Overall Reaction(s)
2. Mechanism
3. Notes
Alkyl substituted benzene
–H2CrO4, ∆–> carboxylic acid substituted benzene
-Oxidizes all alkyl groups as long as they have at least 1 benzylic H
Coupling Reactions
1. Overall Reaction(s)
2. Mechanism
3. Notes
- Gilman Reagent
Halogenated benzene + (R)2CuLi —> alkyl-substituted benzene + RCu + LiX - Suzuki Coupling
Halogenated benzene + R1-B-(OR)2
–PdL2, NaOH–> alkyl-substituted benzene
Substituent Reduction
1. Overall Reaction(s)
2. Mechanism
3. Notes
- Alkene substituted benzene + H2
–Pd/C–> Alkyl substituted benzene - Cyano sustituted benzene + H2
–Raney Ni–> Benzene-CH2-NH2 - Nitro sustituted benzene + H2
–Pd/C–> aniline
Substituent Reactivity
1. Chart
2. Indicate O/P or Meta
3. Major product
Strongly Activating: NH2, NHR, NR2, OH, OR,
Moderately Activating: NHC=O-R (carbonyl), OC=O-R (carbonyl),
Weakly Activating: R, Ph, CH=CHR
N/A: H (regular Benzene)
Weakly Deactivating: F, Cl, Br, I
Moderately Deactivating: HC=O,RC=O, ROC=O, HOC=O, ClC=O
Strongly Deactivating: C≡N, SO3H, +NH3, +NH2R, +NHR2, +NR3, NO2
O/P: Strongly activating-weakly deactivating
Meta: moderately deactivating-strongly deactivating
Para is major if sterics is an issue, otherwise ortho
EWG deactivate by drawing electrons out of the ring and creating positive or partial positive charges
EDG activate by donating electrons to the ring, destabiliting it, and creating negative or partial negative charges
Arenediazonium Salt Reactions
- Salt generation
aniline –NaNO2, HCl, 0°C–>
Benzene-+N≡N + Cl- - Sandmeyer Reactions
a) Benzene-+N≡N –CuBr–> bromobenzene + N2↑
b) Benzene-+N≡N –CuCl–> chlorobenzene + N2↑
c) Benzene-+N≡N –CuC≡N–> cyanobenzene + N2↑
-Sandmeyer Reactions only make the para product
- Iodine
Benzene-+N≡N –KI–> iodobenzene - Schiemann Reaction
Benzene-+N≡N –HBF4, ∆–> fluorobenzene + N2↑ + BF3 - Phenol Synthesis
a) Benzene-+N≡N –H3O+, ∆–> phenol + N2↑ + HCl
b) Benzene-+N≡N –Cu2O, Cu(NO3)2, H2O–> phenol + N2↑
- b allows for higher yield than a
- Hydrogenation
Benzene-+N≡N –H3PO2–> benzene + N2↑
All ways to add an alkyl group and when to use each method
- Friedel-Crafts Alkylation
a) Benzene + RCl –AlCl3–> monochlorobenzene (or Br)
-Can’t use with aniline
-Can use with strong deactivating subst.
- Alkylation by Acylation-Reduction
Friedel-Crafts:
Benzene + carbonyl halide
–1.AlCl3 2.H2O–> carbonyl subst. benzene
a) H2,Pd/C
b) WK: H2NNH2, OH-, ∆
c) Clem: Zn(Hg), HCl, ∆
-carbonyl reductions
-when don’t want C+ rearrangements
-H2, Pd/C only reduces carbonyls adjacent to the ring
-WK works best in basic environments
-Clemmensen works best in acidic environments
- Coupling
a) Gilman:
Bromobenzene + (R)2CuLi –> alkyl substituted benzene, RCu, LiBr
b) Suzuki:
Chlorobenzene + R-B-(OR)2
–Pd(L)2, NaOH–> alkyl substituted benzene
All the ways to add a halogen and when to use each method
- Alkane Chlorination/Bromonation
a) Alkane + X2 –∆–> CH3X + HX - Alkene Radicalization
a) Alkene +HBr –> monobromonated alkane
b) Alkene + HBr –ROOR–> monobromonated alkane (anti markov) - Benzylic position halogenation
a) Substituted Benzene + X2 –∆–> benzylic halogenation
b) Substituted Benzene +
NBS –∆,ROOR-> Benzylic substituted
-must have benzylic H for both
- Allylic position halogenation
a) Allylic + X2 –∆–> allylic substituted
b) Allylic + NBS –∆,ROOR–> allylic subst.
-must be allylic H for both
- Benzene Halogenation
a) Benzene + Br –FeBr3–> monobromobenzene
b) Benzene + Cl –FeCl3–> monochlorobenzene
c) Benzene + I2 –H2SO4,H2O2–> monoiodobenzene
-no catalyst needed when benzene has strong activating subst.
- Arenediazonium Salts
a) Sandmeyer:
1- salt –CuBr–> bromobenzene + N2
2- salt –CuCl–> chlorobenzene + N2
b) Salt –KI–> iodobenzene
c) Shiemann:
Salt –HBF4,∆–> fluorobenzene + N2 + BF3
Relative reactivities of carbonyls
acyl halide>acid anhydride>aldehyde>ketone>ester=carboxylic acid>amide>carboxylate ion
-consider sterics
-consider inductive effects
Aldehyde Synthesis
- Oxidation of primary alcohols
a) Jones: H2CrO4
b) PCC, CH2Cl2
c) NaOCl, CH2COOH, 0°C
d) Swern: 1. DMSO, (COCl)2, -60°C 2. Triethylamine - Ozonolysis:
mono/di/tri-substituted alkene
–1. O3 2.DMS–> Aldehyde(s) + Ketone - Hodroboration- Oxidation of Terminal Alkyne:
Terminal alkyne
–1. 9BBN/THF 2. H2O2, OH-, H2O–> aldehyde
Ketone Synthesis
- Oxidation of secondary alcohols:
a) Jones: H2CrO4
b) PCC, CH2Cl2
c) NaOCl, CH2COOH, 0°C
d) Swern: 1. DMSO, (COCl)2, -60°C 2. Triethylamine - Ozonolysis:
mono/di/tri-substituted alkene
–1. O3 2.DMS–> Aldehyde(s) + Ketone(s) - Hydration by Acid of Terminal Alkyne:
Terminal alkyne
–H2SO4, H2O, HgSO4–> ketone - Hydration of Internal Alkyne:
Internal alkyne –H2O, H2SO4–> Ketone
–2 products will form if internal alkyne is asymmetrical
- Friedel Crafts Acylation
Benzene + acyl chloride
–1. AlCl3 2. H2O–> Ketone
How Aldehydes and Ketones React
- Nucleophilic Acyl Substitution (not aldehydes or Ketones. Acyl chlorides)
- Nucleophilic Addition
- Nucleophilic Addition-Elimination
Preparation of organo-metals
- Organolithium
Alkyl halide + 2Li –hexane–> Alkyl-Li + LiX - Organomagnesium (Grignard)
Alkyl bromide + Mg –diethyl ether–> alkyl-Mg-Br - Organocuprate (Gilman)
2 Alkyl-Li + CuI –THF–> (Alkyl)2CuLi + LiI
- React with primary alkyl, methy, aryl, vinylic, or allylic. Replaces halogen with alkyl
Grignard Reactions
- Protonation–> Alkane
- Ethylene Oxide –> R-CH2CH2O- –H2O–> RCH2CH2OH
- formaldehyde –> alkoxide ion –H3O+–> primary alc
- Aldehyde –> Alkoxide ion –H3O+–> secondary alc
- Ketone–> Alkoxide ion –H3O+–> tertiary alc
–Product is racemic mixture for stereochem
- CO2 –> Carbonyl ion –H3O+–> Carboxylic Acid
–adds 1 carbon to the Grignard reagent
– MgBr–>COOH
- Ester–> Ketone + Grignard –> alkoxide ion –H3O+–> teriary alcohol
– alc will have 2 of same alkyl groups bc 2 equiv Grignard
- Acyl Chloride or Acid anhydride
–1. 2 Grignard 2. H3O+–> tertiary alc
Organolithium Reactions
- Protonation–> Alkane
- Acyl chloride –1.R-Li 2. H3O+–> tertiary alc
Gilman Reactions
- Alkyl halide + Gilman –> Alkane + alkyl-Cu + LiX
2.Ethylene Oxide + Gilman –> R-CH2CH2O-
–HCl–> CH3CH2R (adds 2 carbons from the epoxide) - Acyl Chloride –> Ketone
- Ketone –> No reaction
–Gilman only reacts with acyl halides
Reactions With Acetylide Ions
- Creation:
Terminal alkyne–NaNH2–> RC≡C- - Aldehyde/Ketone + RC≡C- –> intermediate ion –pyr–> nucleophilic addition
Cyanide/Cyanohydrin Reactions
- Ketone + cyanide ion (XS) –HCl–> cyanohydrin (nucleophilic addition)
- In a base:
cyanohydrin <–OH-, H2O–> intermediate ion
–> ketone + cyanide ion - In an acid:
cyanohydrin –HCl, H2O, ∆–> alpha-hydroxycarboxylic acid
–cyanide ion–> COOH
- Cyanohydrin +H2 –Raney Ni–> primary amine
Hydride Ion Reductions
- aldehyde –1.NaBH4 2.H3O+–> primary alcohol
- Ketone –1. NaBH4 2. H3O+–> secondary alcohol
- Acyl chloride –1. 2NaBH4 2.H3O+–> primary alcohol
- Acyl chloride –1.LTBA, -78°C 2.H2O–> aldehyde
- Ester –1. 2 LAH 2.H3O+–> primary alcohol
- Ester –1. DiBALH 2.H2O–> aldehyde
–esters won’t react with NaBH4 bc it isn’t strong enough
- Carboxylic Acid –1. LAH 2. H3O+–> primary alc
- Amide –1. 2LAH 2. H2O–> amine
– C=O –> CH2
Reduction by NaBH4
- Ketone–1.NaBH4 2.H2O–> secondary alc
- Imine—>secondary amine
- Nitrile–> primary amine
- alkene or alkyne –> no rxn
Reduction by H2
- Alkene + H2 –Pd/C–> alkane
- Alkyne + 2H2 –Pd/C–> alkane
- Imine + H2 –Pd/C–> Amine
- Nitrile + 2H2 –Raney Ni–> amine
- Aldehyde + H2 –Raney Ni–> primary alc
- Ketone + H2 –Raney Ni–> secondary alc
- Carboxylic acids, esters, and amides are not reduced with these
–Raney nickel is preferred for reducing aldehydes and ketones
Reduction by Na/NH3(l)
Alkyne –> trans alkene
Chemoselective Reactions
- H2 Pd/C only reduce alkenes, alkynes, and imines
- H2, Raney Ni reduces alkenes, alkynes, ketones, aldehydes, nitriles, and mines
- NaBH4 2. H2O only reduces aldehydes, ketones, imines, and nitriles
Reactions with Primary Amines
- aldehyde + primary amine <–trace acid–> imine (aka Schiff Base) + H2O
- Ketone + primary amine <–trace acid–> imine + H2O
–imine formation replaces C=o with C=NR
Forming Imine Derivatives
- Ketone + hydroxylamine (H2NOH)
<–trace acid–> oxime (C=NOH) + water - Ketone + hydrazine (H2NNH2)
<–trace acid–> hydrazone (C=NNH2) + H2O
