Chapter 17 Flashcards
Electrophilic Aromatic Substitution (_______)
EAS
EAS: substitution of an _______ for a proton on an aromatic ring
electrophile
In EAS what step is the RDS?
step 1
- going from A to NA
EAS require very high Ea which requires _______
harsh conditions
- heat or acid catalyst
What are the 2 steps in all electrophilic aromatic substitution reactions?
1) form E+
2) attack E+
What is the catalyst in the nitration of benzene reaction?
Sulfuric acid (H2SO4)
Reduction of aromatic NO2 = best method for adding an ______ group
amino
- adds nitro and then turns into amino
What are the acceptable reagents for reducing an aromatic NO2
Zn, Sn, or Fe
+ HCl (aq)
- turns nitro into amino
The methyl substituent on an aromatic ring is an _______ group
activator
General rule #1: if the substituent on the benene can stablize the carbocation intermediate (3°>2°>1°) that forms upon electrophilic addition, then it is termed _______-director
o,p
ortho, para
What are the two ways that groups can stabilize intermediates?
1) R-groups can stablize C+ through EDG inductive capabilities (hyperconjugation)
2) groups that contain an atom with a lone pair can stabilize by donating electrons via resonance
Oxygen is a strong electronegative group, but it donates electron density to stabilize the transition state = _______, which makes it an _______
resonance
activator
(resonance EDG characteristic wins over its EDG characteristic)
The nitro substituent is a _______ group
deactivator
General Rule #2: if the substituent on the benzene ring contains an atom that has a + or δ+, it is a _______-director
meta
- avoids + and + next to each other
Halogen substituents are _______ groups and _______- directors
deactivator
o,p
If the substituent on the ring is electron donating, the ortho and para positions will be _______
activated
- EDG activates
If the substituent on the ring is electron withdrawing, the ortho and para positions will be _______
deactivated
- EWG deactivates
If focus atom:
1) is an alkyl group (R-group) = _______-director
2) Has a lone pair = _______-director
3) has a + or δ+ = _______-director
1) o,p
2) o,p
3) m
- 1 and 2 are activating except halogens
- 3 is deactivating
When the directing effects of the 2 or more groups _______ each other, you’ll get 99% of the product
reinforce
Large substituents/electrophiles want to avoid steric interactions leading to the preference of the _______ product
para
If the directors conflict, the _______ activating group determines the final regiochemistry
more
When 2 rings conflict, add new group to the _______ activated ring system
most
What are the reagents for halogenation of benzene (Br)
Br2, FeBr3
What are the reagents for halogenation of benzene (Cl)
Cl2, and AlCl3 or FeCl3
What are the reagents for halogenation of benzene (I)
I2, HNO3
When highly activated aromatic rings (phenol, aniline, etc) are used, _______ substitutions may often result. Must show the # of moles used!
multiple
What is the mild base needed to neutralize acid in halogenation of benzene?
NaHCO3
Halogenation of benzene reactions with multiple moles used are _______ reactions
stepwise
1) para
2) ortho
3) 2nd ortho
What is another name for the reagents that add SO3H to benzene?
fuming sulfuric acid
- SO3, H2SO4
What is another name for the reagents that remove SO3H to benzene?
steam
- H2SO4, H2O, Δ
In Fiedel-crafts alkylation, the limitations are:
1) the product is ________ reactive than the starting material
2) It doesn’t work with compounds possessing moderately or strongly _______ substituents
3) _______ rearrangements can occur
1) more
2) deactivating
- m-directors
3) C+
What are the 2 other ways for the E+ to be formed in Friedel-Craft alkylation?
1) add acid to an alkene (H2SO4 or HF)
2) treat alcohols with lewis base (BF3)
What were 2 ways Suzuki’s graduate work improved Friedel-craft alkylation?
1) solved strong acid problem
2) solved the deactivating substituents problem
Friedel-Crafts acylation is quite sensitive to _______, so will add the “_______” position
sterics
para
Friedel-Crafts acylation, there are no _______ rearrangements
C+
There are no _______ acylations, as the acyl group is deactivating so the product is _______ reactive than the starting material
multiple
less
In Friedel-Crafts acylation, the product complex must be hydrolyzed by _______ to release the free acyl benzene
water
- see 17-11 for ex
If Friedel-Crafts acylation is intramolecular, there is addition at the _______ position
ortho
The Clemmensen reduction allows for _______
reduction of acylbenzene to alkylbenzene
- removes C=O
The Gatterman-Koch synthesis allows ________ to be added to a benzene
aldehyde
What are the reagents for Gatterman-Koch synthesis?
1) CO
2) HCl
3) AlCl3
4) CuCl
What are the two Nucleophilic Aromatic Substitution reactions?
1) Addition-Elimination (EWG)
2) Elimination-Addition (benzyne)
For Addition-Elimination reactions, the original molecule must have an _______ either ortho or para to the halide LG
EWG
In addition-elimination reactions, the leaving group step is not the ______, but the LG does stabilize the intermediate
rds
- rds is addition of nuc to electrophile
The rate of an addition-elimination reaction is based on _______ of LG
EN
Fast: F>Cl>Br>I :Slow
What are the possible nucleophiles for addition-elimination reactions? (3)
1) NH3
2) OH
3) OR
Elimination-Addition requires very strong _______ conditions, or a _______ and high heat
basic
base
What are the possible strong bases used in elimination-addition reactions?
NaNH2
NaNR2
What are the possible bases coupled with heat used in elimination-addition reactions?
NaOH
ROH
needs heat
Elimination-Addition reactions form _______ which is very reactive and usually results in the formation of 2 products
benzyne
- forms 2 products 50:50 ratio
What are the reagents for a birch reduction reaction?
Na or Li
+NH3 (l), ROH
A birch reduction reaction that contains an EDG will result in what?
double bonds on the C with the substituent
A birch reduction reaction that contains an EWG will result in what?
Double bonds that avoid the C with the substituent
Strong oxidation agents such as KMnO4 and Na2Cr2O7 will undergo side-chain _______ when reacted with a substituted benzene
oxidation
- turns any CH connected to or conjugated to a benzene into carboxylic acid
- See 17-15 for explanation
Oxidation of phenols to quinones are done by _______ (reagents)
Na2Cr2O7, H2SO4
