Orgo II Exam 1 Reactions

Question 1

Alkane Chlorination/Bromonation:
1. Overall Reaction(s)
2. Mechanism
3. Notes

Answer 1

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

Question 2

Radical Halogenation of Alkenes
1. Overall Reaction(s)
2. Notes

Answer 2

1. alkene + HBr —-> monobromonated alkane
   - Markovnikov
2. alkene + HBr –ROOR–> monobromonated alkane
   - Antimarkovnikov

Question 3

Radical Substitution of Benzylic Hydrogens
1. Overall Reaction(s)
2. Mechanism
3. Notes

Answer 3

1. 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
2. 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

Question 4

Radical Substitution of Allylic Hydrogens
1. Overall Reaction(s)
2. Mechanism
3. Notes

Answer 4

Allylic + X2 –∆–> Bromo-allylic substituted
Allylic + NBS –∆,ROOR–>
-must have at least 1 benzylic H
- if resonance is not symmetrical, two products will form

Question 5

General Electrophilic Addition Reaction Mechanism

Question 6

Benzene Halogenation
1. Overall Reaction(s)
2. Mechanism
3. Notes

Answer 6

1. Benzene + Br2 —(FeBr3)–> monobromonated benzene
   - No catalyst needed if the ring already has a strongly activating substituent
2. Benzene + Cl2 —(FeCl3)–> monochloronated benzene
   - No catalyst needed if the ring already has a strongly activating substituent
3. Benzene + I2 –(H2O2, H2SO4)–> monoiodonated benzene

Question 7

Benzene Nitration
1. Overall Reaction(s)
2. Mechanism
3. Notes

Answer 7

1. Benzene + HNO3 –(H2SO4)–> Benzene-NO2 + H2O
   - Can’t nitrate aniline
2. Aniline + CH3C=OCl –(pyr)–> intermediate
   –(HNO3, H2SO4)–> nitrate added
   –1. HCl, H2O, ∆ 2. OH—> acyl substituent released. Nitrated aniline

Question 8

Friedel-Crafts Acylation
1. Overall Reaction(s)
2. Mechanism
3. Notes

Answer 8

1. Benzene + acyl halide
   –1. AlCl3 2. H2O–> carbonyl substituted benzene + HCl
2. 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

Question 9

Benzene Sulfonation and Desulfonation
1. Overall Reaction(s)
2. Mechanism
3. Notes

Answer 9

1. Sulfonation:
   Benzene + H2SO4 <–∆–> SO3H substituted (sulfonated) benzene + H2O
2. Desulfonation
   Sulfonated Benzene + Dilute H3O+ <–> Benzene + SO3H+

Question 10

Friedel-Crafts Alkylation
1. Overall Reaction(s)
2. Mechanism
3. Notes

Answer 10

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

Question 11

Alkylation by Acylation-Reduction
1. Overall Reaction(s)
2. Mechanism
3. Notes

Answer 11

1. 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
2. Wolff-Kishner
   Carbonyl substituted benzene
   –H2NNH2, OH-, ∆–> Benzene-CH2-R
   - Works well in a basic environment
   -reduces all ketones
3. 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

Question 12

Substituent Oxidation
1. Overall Reaction(s)
2. Mechanism
3. Notes

Answer 12

Alkyl substituted benzene
–H2CrO4, ∆–> carboxylic acid substituted benzene

-Oxidizes all alkyl groups as long as they have at least 1 benzylic H

Question 13

Coupling Reactions
1. Overall Reaction(s)
2. Mechanism
3. Notes

Answer 13

1. Gilman Reagent
   Halogenated benzene + (R)2CuLi —> alkyl-substituted benzene + RCu + LiX
2. Suzuki Coupling
   Halogenated benzene + R1-B-(OR)2
   –PdL2, NaOH–> alkyl-substituted benzene

Question 14

Substituent Reduction
1. Overall Reaction(s)
2. Mechanism
3. Notes

Answer 14

1. Alkene substituted benzene + H2
   –Pd/C–> Alkyl substituted benzene
2. Cyano sustituted benzene + H2
   –Raney Ni–> Benzene-CH2-NH2
3. Nitro sustituted benzene + H2
   –Pd/C–> aniline

Question 15

Substituent Reactivity
1. Chart
2. Indicate O/P or Meta
3. Major product

Answer 15

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

Question 16

Arenediazonium Salt Reactions

Answer 16

1. Salt generation
   aniline –NaNO2, HCl, 0°C–>
   Benzene-+N≡N + Cl-
2. 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

3. Iodine
   Benzene-+N≡N –KI–> iodobenzene
4. Schiemann Reaction
   Benzene-+N≡N –HBF4, ∆–> fluorobenzene + N2↑ + BF3
5. 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

6. Hydrogenation
   Benzene-+N≡N –H3PO2–> benzene + N2↑

Question 17

All ways to add an alkyl group and when to use each method

Answer 17

1. Friedel-Crafts Alkylation
   a) Benzene + RCl –AlCl3–> monochlorobenzene (or Br)

-Can’t use with aniline
-Can use with strong deactivating subst.

2. 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

3. 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

Question 18

All the ways to add a halogen and when to use each method

Answer 18

1. Alkane Chlorination/Bromonation
   a) Alkane + X2 –∆–> CH3X + HX
2. Alkene Radicalization
   a) Alkene +HBr –> monobromonated alkane
   b) Alkene + HBr –ROOR–> monobromonated alkane (anti markov)
3. Benzylic position halogenation
   a) Substituted Benzene + X2 –∆–> benzylic halogenation
   b) Substituted Benzene +
   NBS –∆,ROOR-> Benzylic substituted

-must have benzylic H for both

4. Allylic position halogenation
   a) Allylic + X2 –∆–> allylic substituted
   b) Allylic + NBS –∆,ROOR–> allylic subst.

-must be allylic H for both

5. 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.

6. 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

Question 19

Relative reactivities of carbonyls

Answer 19

acyl halide>acid anhydride>aldehyde>ketone>ester=carboxylic acid>amide>carboxylate ion

-consider sterics
-consider inductive effects

Question 20

Aldehyde Synthesis

Answer 20

1. 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
2. Ozonolysis:
   mono/di/tri-substituted alkene
   –1. O3 2.DMS–> Aldehyde(s) + Ketone
3. Hodroboration- Oxidation of Terminal Alkyne:
   Terminal alkyne
   –1. 9BBN/THF 2. H2O2, OH-, H2O–> aldehyde

Question 21

Ketone Synthesis

Answer 21

1. 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
2. Ozonolysis:
   mono/di/tri-substituted alkene
   –1. O3 2.DMS–> Aldehyde(s) + Ketone(s)
3. Hydration by Acid of Terminal Alkyne:
   Terminal alkyne
   –H2SO4, H2O, HgSO4–> ketone
4. Hydration of Internal Alkyne:
   Internal alkyne –H2O, H2SO4–> Ketone

–2 products will form if internal alkyne is asymmetrical

5. Friedel Crafts Acylation
   Benzene + acyl chloride
   –1. AlCl3 2. H2O–> Ketone

Question 22

How Aldehydes and Ketones React

Answer 22

1. Nucleophilic Acyl Substitution (not aldehydes or Ketones. Acyl chlorides)
2. Nucleophilic Addition
3. Nucleophilic Addition-Elimination

Question 23

Preparation of organo-metals

Answer 23

1. Organolithium
   Alkyl halide + 2Li –hexane–> Alkyl-Li + LiX
2. Organomagnesium (Grignard)
   Alkyl bromide + Mg –diethyl ether–> alkyl-Mg-Br
3. Organocuprate (Gilman)
   2 Alkyl-Li + CuI –THF–> (Alkyl)2CuLi + LiI

• React with primary alkyl, methy, aryl, vinylic, or allylic. Replaces halogen with alkyl

Question 24

Grignard Reactions

Answer 24

1. Protonation–> Alkane
2. Ethylene Oxide –> R-CH2CH2O- –H2O–> RCH2CH2OH
3. formaldehyde –> alkoxide ion –H3O+–> primary alc
4. Aldehyde –> Alkoxide ion –H3O+–> secondary alc
5. Ketone–> Alkoxide ion –H3O+–> tertiary alc

–Product is racemic mixture for stereochem

6. CO2 –> Carbonyl ion –H3O+–> Carboxylic Acid

–adds 1 carbon to the Grignard reagent
– MgBr–>COOH

7. Ester–> Ketone + Grignard –> alkoxide ion –H3O+–> teriary alcohol

– alc will have 2 of same alkyl groups bc 2 equiv Grignard

8. Acyl Chloride or Acid anhydride
   –1. 2 Grignard 2. H3O+–> tertiary alc

Question 25

Organolithium Reactions

Answer 25

1. Protonation–> Alkane
2. Acyl chloride –1.R-Li 2. H3O+–> tertiary alc

Question 26

Gilman Reactions

Answer 26

1. Alkyl halide + Gilman –> Alkane + alkyl-Cu + LiX
   2.Ethylene Oxide + Gilman –> R-CH2CH2O-
   –HCl–> CH3CH2R (adds 2 carbons from the epoxide)
2. Acyl Chloride –> Ketone
3. Ketone –> No reaction

–Gilman only reacts with acyl halides

Question 27

Reactions With Acetylide Ions

Answer 27

1. Creation:
   Terminal alkyne–NaNH2–> RC≡C-
2. Aldehyde/Ketone + RC≡C- –> intermediate ion –pyr–> nucleophilic addition

Question 28

Cyanide/Cyanohydrin Reactions

Answer 28

1. Ketone + cyanide ion (XS) –HCl–> cyanohydrin (nucleophilic addition)
2. In a base:
   cyanohydrin <–OH-, H2O–> intermediate ion
   –> ketone + cyanide ion
3. In an acid:
   cyanohydrin –HCl, H2O, ∆–> alpha-hydroxycarboxylic acid

–cyanide ion–> COOH

4. Cyanohydrin +H2 –Raney Ni–> primary amine

Question 29

Hydride Ion Reductions

Answer 29

1. aldehyde –1.NaBH4 2.H3O+–> primary alcohol
2. Ketone –1. NaBH4 2. H3O+–> secondary alcohol
3. Acyl chloride –1. 2NaBH4 2.H3O+–> primary alcohol
4. Acyl chloride –1.LTBA, -78°C 2.H2O–> aldehyde
5. Ester –1. 2 LAH 2.H3O+–> primary alcohol
6. Ester –1. DiBALH 2.H2O–> aldehyde

–esters won’t react with NaBH4 bc it isn’t strong enough

7. Carboxylic Acid –1. LAH 2. H3O+–> primary alc
8. Amide –1. 2LAH 2. H2O–> amine

– C=O –> CH2

Question 30

Reduction by NaBH4

Answer 30

1. Ketone–1.NaBH4 2.H2O–> secondary alc
2. Imine—>secondary amine
3. Nitrile–> primary amine
4. alkene or alkyne –> no rxn

Question 31

Reduction by H2

Answer 31

1. Alkene + H2 –Pd/C–> alkane
2. Alkyne + 2H2 –Pd/C–> alkane
3. Imine + H2 –Pd/C–> Amine
4. Nitrile + 2H2 –Raney Ni–> amine
5. Aldehyde + H2 –Raney Ni–> primary alc
6. Ketone + H2 –Raney Ni–> secondary alc
7. Carboxylic acids, esters, and amides are not reduced with these

–Raney nickel is preferred for reducing aldehydes and ketones

Question 32

Reduction by Na/NH3(l)

Answer 32

Alkyne –> trans alkene

Question 33

Chemoselective Reactions

Answer 33

1. H2 Pd/C only reduce alkenes, alkynes, and imines
2. H2, Raney Ni reduces alkenes, alkynes, ketones, aldehydes, nitriles, and mines
3. 1. NaBH4 2. H2O only reduces aldehydes, ketones, imines, and nitriles

Question 34

Reactions with Primary Amines

Answer 34

1. aldehyde + primary amine <–trace acid–> imine (aka Schiff Base) + H2O
2. Ketone + primary amine <–trace acid–> imine + H2O

–imine formation replaces C=o with C=NR

Question 35

Forming Imine Derivatives

Answer 35

1. Ketone + hydroxylamine (H2NOH)
   <–trace acid–> oxime (C=NOH) + water
2. Ketone + hydrazine (H2NNH2)
   <–trace acid–> hydrazone (C=NNH2) + H2O