Quiz 4 Flashcards
Do Friedel-Crafts rxns occur with meta directors?
F-C rxns are the slowest electrophilic aromatic substitution rxns and do not occur if the ring has a meta director (if the ring is moderately or strongly deactivated)
what are meta directors
a substituent that favors electrophilic attack meta to the substituent. Most meta directors are also deactivators
Electron withdrawing groups are deactivators and therefore act as meta directors
explain why F-C rxns can’t have certain substituents
the lone pair on the lewis basic group (-NH2, -NHR, or -NR2) forms a complex with a Lewis acid catalyst, which converts the substituent to a meta director and thus deactivates the ring.
how do you install a straight chain alkyl group on a benzene ring
reactants: benzene + R with carbonyl group (c double bonded to O and a halogen like Cl)
1. reacts with AlCl3 which removes Cl and attaches R and carbonyl group to benzene ring (carbonyl is in between R and benzene – very important)
2. that reacts with H2 and Pd/C to produce just the benzene ring with the R group attached.
what are the effects of the substituents on the reactivity of a benzene ring
LEAST REACTIVE: benzene with an electron withdrawing group: substituents decrease benzene’s nucleophilicity and destabilizes the carbocation intermediate
benzene with a hydrogen:
MOST REACTIVE: benzene with an electron donating group: substituents increase benzene’s nucleophilicity and stabilizes the carbocation intermediate.
electron withdrawing group
typically electronegative atoms or groups that pull electron density away from a molecule, making it more positive and less reactive. Examples include halogens (such as fluorine, chlorine, and bromine), nitro groups, and carbonyl groups.
electron donating group
usually electron-rich and can donate electron density to a molecule, making it more negative and more reactive. Examples include alkyl groups, phenyl groups, and amino groups.
what is inductive electron withdrawal
When an electronegative atom is present in a molecular structure, it can pull electron density towards itself, creating a dipole moment and withdrawing electrons from neighboring atoms. This leads to a partial positive charge on the atom where the electrons are being withdrawn. This effect can propagate through a chain of atoms in a molecule.
what is inductive electron donation
If there’s an atom with a lower electronegativity, it may donate electron density to its neighboring atoms. This results in a partial negative charge on the atom donating electrons. Again, this effect can extend through a chain of atoms.
explain resonance electron donation and withdrawal
- a lone pair on an atom directly attached to the ring DONATES electrons by resonance. This applies to all atoms with an available lone pair.
- an atom directly attached to the ring that is doubly or triply bonded to an electronegative atom withdraws electrons by resonance
for resonance electron donation, where does the charge occur
usually three structures move the negative charge around the ring (the charge is only on the ortho and para positions)
for resonance electron withdrawal, where does the charge occur
usually three structures move the positive charge around the ring (the charge is only on the ortho and para positions)
what are strongly activating substituents
- N or O with a lone pair
- all substituents donate electrons by resonance and withdraw electrons inductively
- because substituents are activating, electron donation by resonance is more significant than inductive electron withdrawal
what is the rule about activating vs. deactivating substances
activating substances always beat deactivating substances no matter how weak / strong either of them are
explain moderately activating substituents
- donate electrons by resonance and withdraw electrons inductively
- the lone pair is in competition for where it wants to delocalize, since it is in between an R group (usually with a carbonyl) and the benzene ring. So the two groups end up playing a tug of war with the lone pair.
- the amount donated to the ring is less with the carbonyl present.
which are more effective, strongly or moderately activating substances?
moderately activating substituents are less effective than strongly activating substituents because they donate electrons in two competing directions
explain weakly activating substituents (alkyl vs. halogen)
- alkyl substituents donate electrons inductively. weakly activating substituents (ex. aryl and CH=CHR) donate and withdraw electrons by resonance.
- all the weakly deactivating substituents (halogens) donate electrons by resonance and withdraw electrons inductively
in the competition between inductive withdrawal and resonance electron donation, what wins?
inductive withdrawal wins but both donation and withdrawal still happen
explain strongly deactivating substituents
- all the strongly deactivating substituents (except ammonium ions) withdraw electrons inductively and by resonance
- ammonium ions strongly withdraw electrons inductively
list strongly activating groups
- NH2
-NHR
-NR2
-OH
-OR
list moderately activating groups
-NHC(double bonded to O)R
-OC(double bonded to O)R
list weakly activating groups
-R
-Ar
-CH=CHR
list weakly deactivating groups
-F
-Cl
-Br
-I
list moderately deactivating groups
-C(double bonded to O)H
-C(double bonded to O)R
-C(double bonded to O)OR
-C(double bonded to O)OH
-C(double bonded to O)Cl
list strongly deactivating groups
-C triple bonded to N
-SO3H
-N+H2R
-N+R3
-NO2
which substituents direct where
- strongly activating, moderately activating, weakly activating, and weakly deactivating –> ortho / para directing
- moderately deactivating and strongly deactivating –> meta directing
what is the substituent orientation effect
EAS rxns always produce a mixture of all three products BUT, for simplicity:
- meta directors give only meta-substituted products
- ortho / para directors give only ortho / para-substituted products
what is a general rule about meta directors
all moderately and strongly deactivating substituents are meta director
what is a general rule about ortho / para directors
- any substituent with a lone pair is an ortho / para director
- all activating substituents are ortho / para directors
- weakly deactivating substituents (halogens) are ortho / para directors
describe the sterics on the ortho / para ratio
- in EAS, you always get a mixture of ortho and para products that you must separate
- BIGGER GROUPS inhibit ortho and favor para (sterics)
what is an alternative way to predict whether a substituent directs ortho / para versus meta (based on the donation of electrons by resonance into a benzene ring)
resonance structures show that the ortho and para positions have more electron density than a normal benzene. Because of this increased electron density, an electrophile preferentially reacts at the ortho / para positions
- there is more electron density where the electrophile wants
to add
what is an alternative way to predict whether a substituent directs ortho / para versus meta (based on the withdrawal of electrons by resonance into a benzene ring)
resonance structures show that the ortho and para positions have less electron density than a normal benzene. because of this decreased electron density, an electrophile preferentially reacts at the meta position
what needs to be considered for the synthesis of trisubstituted benzenes
the directing effects of both substituents on a disubstituted benzene must be considered in deciding where the third group will add. the best situation is when both substituents direct to the same positions (ex. para so on either side of the molecule)
what beats what for trisubstituted benzens
- the strong activator wins out over the weak activator
- both substituents direct to different positions
describe halogenation of benzene with a strongly activating group present
- halogenation of a ring with a strongly activating -OH and -OR substituent does not require a catalyst to add one halogen (ex. Br adds on easily)
- once you stuck on the first bromine, you have to use the
catalyst because you deactivated it enough - if a catalyst is used, substitution occurs at all ortho and para positions (ex. Br goes on three different places - almost looks like staggard conformation)
explain halogenation with the strongest activating group present
- aniline (for ex.) is so strongly activated that even triple halogenation does not require a catalyst.
- to only halogenate the ring once: use acetylation (introduction of an acetyl functional group into a chemical compound), which reduces the -NH2 group slightly to activate it, so that the ring can be halogenated. the acetyl group can then be removed via base-promoted amide hydrolysis (NaOH + water)
reactants used to put on an acetyl group for halogenation
acetyl group (ex. (CH3CO)2O) and pyridine
reactants used to take off on an acetyl group for halogenation
NaOH and water
why do we have to remove the acetyl group via base promoted amide hydrolysis
aniline cannot be nitrated directly because nitric acid will oxidize (be chemically combined with) an NH2 group. but, if the ring is protected by acetylation (acetyl group added) the ring can be nitrated.
reactants used to help alkyl substituents to be oxidized to carbonyl groups
KMnO4
H2O
**key here is there are many oxygens
can alkyl substituents be oxidized even if they aren’t attached to a benzene?
no
reactants for free radical benzylic bromination
NBS and peroxide
alkyl substituents oxidized to be carbonyl groups
benzene ring with an alkyl group becomes benzene ring with a -COOH group
free radical benzylic bromination product
benzene-C(two hydrogens bonded)-CH2CH3 goes to benzene-C(one hydrogen and one bromine bonded)-CH2CH3 + NBS (that has an H instead of a Br)
NBS
5 membered ring with N and two oxygen double bonds in the ortho position closest to N. The N is bonded to a Br
does a bulky base encourage elimination or substitution
the use of a bulky base encourages elimination over substitution
how do you reduce unsaturated substances
unsaturated substances –> have a double bond
reducing the double bond = making it a single bond
use: Pd/C
what conditions is a benzene ring reduced at
high temps and high pressures
what reactants remove all double bonds from benzene ring
H2, Pt, 130 atm, 25 degrees C
what is an arenediazonium salt
benzene ring with an N triple bonded to N substituent and a Cl floating outside
how do you synthesize NH2 to produce an arenediazonium salt
NaNO2, HCl at 0 degrees C
what are arenediazonium salts used to generate
HONO (nitrous acid) in situ
for the synthesis of a disubstituted benzene, how does reaction order matter
if the substituent is a meta director, the Br adds in the meta position. vs. if it was an ortho para director, which would add in the ortho / para position
note: if the substituent adds FIRST to the meta position, a Friedel-Crafts acylation will not occur (because it deactivates the ring).
how can you use retrosynthetic analysis to determine what kind of substituent was used
see if the disubstituted benzene is in the meta or ortho / para position
rule to remember about what carbons can perform what reactions
SN1 and SN2 reactions cannot perform a reaction on an sp2 carbon
what reaction do aryl halides not react with
they don’t react with nucleophiles via an SN1 reaction because an aryl halide cation is too unstable toform
they don’t react with nucleophiles via SN2 because a nucleophile is repelled by the pi electron cloud and backside displacement is sterically impossible
where can electrons be delocalized
electrons can be delocalized onto ortho and para substituents but cannot be delocalized onto a meta substituent
How to add I on a benzene ring
I2 and H2O2
how to add ONE Br to a benzene
FeBr3 and Br2
how to add ONE Cl to a benzene
FeCl3 and Cl2
how to add NO2 to a benzene
HNO3 and H2SO4
how to add SO3H to a benzene
fuming H2SO4
how to reduce an SO3H benzene to just a benzene
H3O+ and heat
how to add CH2CH3 to a benzene
Cl-R (R=CH2CH3) and AlCl3
how to add C(double bonded to O)-CH3 to a benzene
CH3C(double bonded O)Cl and AlCl3
from a benzene with NO2, how do you change that substituent to NH2
H2 and Pd/C
from a benzene with NH2, how do you change that substituent to N triple bonded to N+
NaNO2 and HCl
from a benzene with NH2, how do you change that substituent to H-N-C(double bonded to O)CH3
CH3C(double bonded to O)Cl and pyridine
from a benzene with H-N-C(double bonded to O)CH3, how do you change that substituent to a benzene with N-C(double bonded to O)CCH3 WITH an NO2 para
NHO3 and H2SO4
from a benzene with N-C(double bonded to O)CCH3 WITH an NO2 para, how do you change that substituent to a benzene with NH2 WITH NO2 para
NaOH and H2O
from a benzene with CH2CH3, how do you change that substituent to BrCHCH3
NBS and peroxide
from a benzene with CH2CH3, how do you change that substituent to COOH
KMnO4
from a benzene with BrCHCH3, how do you change that substituent to HOCHCH3
OH-
from a benzene with BrCHCH3, how do you change that substituent to CH=CH2
OTS
from a benzene with CH=CH2, how do you change that substituent to BrCHCH3
HBr
from a benzene with CH=CH2, how do you change that substituent to HOCHCH3
H3O+
from a benzene with CH=CH2, how do you change that substituent to CH2CH2Br
HBr and peroxide
from a benzene with CH=CH2, how do you change that substituent to CH2CH2OH
BH3 and H2O2 and HO-
from a benzene with N triple bonded to N+, how do you change that substituent to an F
HBF4 and heat
from a benzene with N triple bonded to N+, how do you change that substituent to a Cl
CuCl
from a benzene with N triple bonded to N+, how do you change that substituent to a Br
CuBr
from a benzene with N triple bonded to N+, how do you change that substituent to an I
KI
from a benzene with N triple bonded to N+, how do you change that substituent to an H
H3PO2
from a benzene with N triple bonded to N+, how do you change that substituent to an OH
Cu2O and Cu(NO3)2 and H2O
from a benzene with N triple bonded to N+, how do you change that substituent to a benzene connected to a C which is triple bonded to an N
CuCN
