Indicate the eletrophile formed by each set of reagents/conditions below.
Note that some textbooks don't draw EAS electrophiles with formal positive charges.
Some textbooks instead draw electrophiles with partial positive charges and a leaving group. It's just a convention, and doesn't affect the product of an EAS reaction. See the problem 595 for an explanation of the difference.
MendelSet practice problem # 596 submitted by Matt on July 9, 2011.
For the anion and cation species, used curved arrows. For the radical species, use hooks.
(This is similar to problem 569, which involved the allylic position.)
Notice that arrows always go from high electron density to low electron density. So for negatively charged species, the arrow starts at the lone pair. For positively charged species, the arrow starts at the double bond and goes towards the positive charge.
(Radical resonance uses hooks instead of arrows and so is a little different.)
MendelSet practice problem # 580 submitted by Matt on July 9, 2011.
Let's draw resonance forms to see why some groups are EDG or EWG. (I've started you off)
Where are the positive or negative charges placed in EDG/EWG? (ortho/meta/para) Why would this affect EAS reactions?
Note: EDG = electron donating group, EWG = electron withdrawing group
The resonance forms for EDG add electron density to the ring (and add a negative charge), while the resonance forms for EWG remove electron density from the ring (and leave a positive charge). This is where the terms electron donating group and electron withdrawing group come from.
EAS reactions require benzene to attack something positive (an electrophile), so the more electron density, the better. This is why EDG tend to speed up EAS reactions, while EWG slow down EAS reactions.
Notice that for EDG, the ortho and para positions are partially negative. In EAS reactions benzene attacks a positively charged electrophile, so its not too surprising that the electrophile will want to add at o/p if a EDG is present.
But for EWG, the o/p positions pick up a partial positive charge. So for EAS reactions with a EWG, it's not surprising that the electrophile will avoid the o/p positions, and add meta instead.
This is one explanation for the general trend:
EDG are ortho/para directors and activating.
EWG are meta directors and deactivating.
MendelSet practice problem # 588 submitted by Matt on July 9, 2011.
Pyrrole undergoes eletrophilic aromatic substitution at C-2. Let's compare the resonance forms of EAS carbocation intermediates to see why this is the case. What do you think? Why C-2 and not C-3?
Electrophilic substitution at C-2 leads to a carbocation intermediate with three resonance forms, while substitution at C-3 leads to a carbocation intermediate with only two resonance forms.
The C-2 intermediate has more resonance forms than the C-3 intermediate, and so is more stable. Therefore, EAS occurs at C-2.
MendelSet practice problem # 591 submitted by Matt on July 9, 2011.
Phenol can be prepared from benzene and hydrogen peroxide in the presence of a really strong acid. Propose a mechanism for this reaction.
The electrophile we need for this EAS reaction is HO+. We can generate it by protonating one of the oxygens in peroxide, which causes it to act as a leaving group.
On the left side of this image I make a note about the structure of the electrophile. Some textbooks use electrophiles with formal positive charges, such as HO+. Other textbooks don't use formal positive charges, and instead use partial positive charges with a leaving group, such as HO-OH2+. Using HO+ as the electrophile is analogous to an SN1 reaction, while using HO-OH2+. is analogous to an SN2 reaction. When you draw mechanisms, you should use whichever convention your textbook uses. Both lead to the same product.
MendelSet practice problem # 595 submitted by Matt on July 9, 2011.
This is a good synthesis to know, because vinyl benzene is a good starting point for many synthesis problems you will encounter down the road.
An ethyl group can be added to benzene via Friedel-Crafts alkylation.
To add that alkene, we you will have to do some sort of elimination reaction. The easiest way to do this is via bromination. Free radical bromination (with NBS or Br2/hν) will add a bromine to the position of the most stable radical, which is the benzylic position (due to resonance).
Then adding a strong base like potassium tert-butoxide will do an E2 reaction to form the alkene.
MendelSet practice problem # 722 submitted by Matt on July 24, 2011.
The allylic alkene gives two products- the 1,2 product, and the 1,4 product.
However, the benzylic alkene only gives the one product (analogous to the 1,2 product), instead of multiple products (like the 1,4 product, 1,6 product, and 1,8 product). Why is this the case?
The allylic carbocation has two resonance forms, and so two positions where a nucleophile can attack, yielding two different products (1,2 and 1,4).
The benzylic carbocation has four resonance forms, and so in theory, four positions where a nucleophile can attack. But all but one of these resonance forms yield a product that is not aromatic, and so do not form.
Aromatic compounds are very stable; aromatic starting materials tend to only form products that are also aromatic.
MendelSet practice problem # 581 submitted by Matt on July 9, 2011.
Allylic and benzylic halides tend to undergo both SN1 and SN2 substitution reactions at a faster rate than their alkyl counterparts.
For example, both allyl chloride and benzyl chloride undergo SN2 reaction at a faster rate than propyl chloride.
The same holds true for SN1 reactions: a 2° allyl or benzyl halide undergoes SN1 reaction faster than a 2° alkyl halide. Explain.
There are separate explanations for SN1 and SN2.
SN1: The SN1 mechanism involves a carbocation intermediate, and both allylic and benzylic carbocations have resonance, which increases the stability of their carbocations, and speeds up the rate of SN1 reaction.
SN2: This explanation is less obvious, and is probably only mentioned in passing in your orgo textbook, if at all.
The pi systems present in allylic and benzylic halides are able to overlap with the pi orbitals of the nucleophile and the leaving group in the 5-coordinate transition state of an SN2 reaction. This orbital overlap lowers the energy of the transition state (which stabilizes it), and so increases the rate of SN2 reaction.
There are other possible explanations as well (Which also vary by textbook). For one, an allylic halide is less sterically hindered than an alkyl halide (less hydrogens sticking out in 3D).
Also, the carbons on the double bond of allyl and benzyl compounds are sp2 hybridized, and so are more electronegative than sp3 carbons. So the sp2 carbons pull alway some electron density from the alpha carbon (the carbon attached to the leaving group), making it more electrophilic, and thus increasing SN2 reactivity.
MendelSet practice problem # 1281 submitted by Matt on October 1, 2011.
-OR is an EDG and an ortho-para director. Let's draw an EAS reaction's cyclohexadienyl cation intermediates to demonstrate why this is true. I've started you off.
What's good about ortho/para? What's bad about meta?
Short answer: -OR is an ortho/para director because the cyclohexadienyl intermediates that result from ortho and para addtitions are more stable than those that result from meta addition.
Long answer: The cyclohexadienyl intermediates from ortho and para addition include a resonance form where the oxygen is adjacent to the carbocation, while the cyclohexadienyl intermediates from a meta addition do not.
When an oxygen (or anything with a lone pair) is adjacent to a carbocation, it can share its lone pair and stabilize the positive charge. This is only possible when the electrophile adds to the ortho or para positions, so those positions are favored with -OR as a substituent. Hence, -OR is an ortho/para director.
Note that this logic holds for any substituent with a lone pair, so -OH, -OR, -NH2, -NR2, -F, -Cl, -Br, and -I are all ortho/para directors.
MendelSet practice problem # 589 submitted by Matt on July 9, 2011.
-NO2 is an EWG and a meta director. Let's draw an EAS reaction's cyclohexadienyl cation intermediates to demonstrate why this is true. I've started you off.
What's good about meta? What's bad about ortho/para?
Short answer: -NO2 is an meta director because the cyclohexadienyl intermediates that result from meta addtition are more stable than those that result from ortho or para addition.
Long answer: Addition at both the ortho or para positions lead to a cyclohexadienyl cation that contains two adjacent positive charges. This is very unstable, and so addition at the ortho or para positions is not favored.
The cyclohexadienyl cations that result from meta addition don't have this problem.
This will be the base for any substituent that has a positive charge (or partial positive charge). So -NO2, -C(O)R, -CF3, -NH3+, -CN, and -SO3R are all meta directors.
MendelSet practice problem # 590 submitted by Matt on July 9, 2011.
Imidazole (shown below) has two nitrogen atoms, N-1 and N-3. Which nitrogen is more basic?
To answer this problem, draw the product after each nitrogen protonates, and compare their stabilities. Explain your reasoning.
Imidazole is aromatic. When N-3 protonates, the product is still aromatic.
But when N-1 protonates, the product is no longer aromatic (and therefore significantly less stable).
Because of this, N-3 is much more basic than N-1. Another way of thinking of this is that the lone pair on N-1 is involved in the aromatic circuit, and so is not available to pick up a proton.
MendelSet practice problem # 584 submitted by Matt on July 9, 2011.
a) Rationalize the relative stabilities of the cation species below.
b) Pyridine undergoes eletrophilic substitution at C-3. Let's compare the resonance forms of EAS carbocation intermediates to see why this is the case. Consider part a) in your explanation.
a) The species on the left are much more stable than the species on the right because they have complete octets.
Nitrogen is less electronegative than oxygen, so a positive nitrogen (with a full octect) is more stable than a positive oxygen; oxygen is electronegative and so doesn't "like" being positive (have low electron density).
The carbocation and the "nitrocation" are both very unstable because they only have 6 valence electrons. Because nitrogen is more electronegative than carbon, the nitrocation is even less stable than the carbocation, because its worse at handling a positive charge.
b) The cation intermediates that result from substitution at C-3 only contain carbocations, while the intermdiates from C-2 or C-4 substitution contain a "nitrocation," which is less stable than a regular carbocation, and so are not favored. So pyridine undergoes EAS reactions at C-3.
One more note: For substitution at C-2 and C-4, it's tempting to draw a resonance form where the positive charge is on the nitrogen, which is flanked by two double bonds. But this cyclic compound is too strained to exist, and so doesn't contribute to this analysis.
MendelSet practice problem # 593 submitted by Matt on July 9, 2011.
A chemist tried to prepare compound A from benzene via Friedel-Crafts alkylation and instead produced compound B.
Why did this happen? How could the chemist prepare compound A?
Friedel-Crafts alkylation is prone to carbocation rearrangement. In this case, alkylation produced a 1º carbocation which rearranged to a 3º carbocation, leading to compound B.
We can avoid this by instead doing Friedel-Crafts acylation. The intermediate in acylation is the acylium ion, which is stabilized by resonance and so won't rearrange.
But after the acylation reaction we have to get rid of the carbonyl (C=O) group, so we do a Wolff-Kishner reduction (N2H4/NaOH, heat).
MendelSet practice problem # 594 submitted by Matt on July 9, 2011.
Naphthalene undergoes eletrophilic substitution at C-1.
Why is this the case, even though substitution at C-2 gives more resonance forms?
Substitution at C-1 and C-2 both lead to many resonance forms. But the resonance forms that arrise from substitution at C-2 are not aromatic, while the resonance forms from substitution at C-1 are aromatic (the benzene ring is maintained).
So the C-1 resonance forms are more stable than the C-2 resonance forms, so substitution occurs at C-1 instead of C-2.
MendelSet practice problem # 592 submitted by Matt on July 9, 2011.