aromatic chemistry - reactivity

Question 1

how do alkenes and aromatics react similarly?

Answer 1

both functional groups react with electrophiles

Question 2

how do alkenes and aromatic react differently?

Answer 2

aromatics are much less reactive
alkenes react via electrophilic addition, whereas aromatics react via electrophilic aromatic substitution (SeAr)

Question 3

why are aromatics less reactive than alkenes?

Answer 3

aromatics are much more stable meaning reactions have greater activation energies
- to overcome this, the activation energy either needs to be lowered or the electrophile needs to be improved

Question 4

outline the process of the SeAr mechanism

Answer 4

1- in situ generation of the electrophile e.g. by reaction with a catalyst
2- aromatic attacks electrophile from a double bond
3- stabilisation of +ve wheland intermediate through resonance, essentially the hydrogen returning to complete the ring
4- proton loss and rearomatisation to form final product

Question 5

what are the rough kinetics for SeAr reactions + why is this the case?

Answer 5

the electrophilic attack step is slow, then stabilisation of the wheland intermediate is fast
this is because the breaking of the C-H bond in the last part is quick, but the initial breaking of the aromaticity is slow, therefore rate determining

Question 6

outline how halogenation follows the SeAr mechanism

Answer 6

1- X2 halogen reacts with lewis acid catalyst to generate electrophile
2- aromatic attacks the electrophile
3- wheland intermediate is formed + stabilised via resonance, proton completes the ring
4- proton is lost to reform catalyst and product is made

Question 7

give 2 examples of a lewis acid catalyst used in halogenation of benzene

Answer 7

AlCl3, FeBr3

Question 8

what is the trend of electrophilicity of halogens going down the group + why?

Answer 8

going down the group, electrophilicity decreases:
F2 is very reactive and doesn’t need a catalyst, but is too reactive (explosive)
Cl2/Br2 both react well but require lewis acid catalysts
I2 does not react

this is because electronegativity decreases down the group, causing reactivity to decrease down the group

Question 9

outline how nitration of benzene follows the SeAr mechanism

Answer 9

1- electrophile is generated via reaction of nitric acid (pKa = -1) and sulphuric acid (pKa = -3), sulfuric acid protonates nitric acid
electrophile = NO2+ nitronium ion, formed by loss of water after protonation
2- aromatic attacks nitronium ion
3- wheland intermediate forms and stabilises itself
4- proton loss and product forms
- this process is irreversible

Question 10

how can nitrogenated benzene react further?

Answer 10

the NO2 nitro group can be reduced to NH2 amine group - 2 mechanisms:
- Bechamp reduction, Sn + HCl
- H2 + Pb/C catalyst

Question 11

outline how sulfonation of benzene follows SeAr mechanism

Answer 11

1- electrophile is generated in situ, high concentration of sulfuric acid, it protonates itself + loses water
electrophile = SO3H+ (only a small ammount is made at a time but as it is so reactive equilibrium stays on the RHS)
2- aromatic attacks electrophile
3- wheland intermediate is formed and stabilised and hydrogen completes the ring
4- proton is lost and product is formed

Question 12

how can sulfonated benzene react further?

Answer 12

traditional sulfonated benzene can react with a salt e.g. NaCl to form another salt which is very water soluble

chlorosulfonated benzene formed from chlorosulfonic acid can react with an amine to form a sulfonamide

Question 13

give 3 functional groups that can alkylate aromatic compounds

Answer 13

alkyl halides, alcohols, alkenes

Question 14

outline the process of friedel-crafts alkylation

Answer 14

via alkyl halides:
1- alkyl halide reacts with lewis acid catalyst to generate electrophile, a carbocation
2- aromatic attacks carbocation
3- wheland intermediate is formed + stabilised
4- proton loss to reform catalyst and halogen acid, and product is formed

via alcohols/alkenes:
1- alcohol/alkene reacts with acid, forming carbocation intermediate (in alcohols case water leaves)
2- aromatic attacks electrophile
3- wheland intermediate is formed and stabilised and hydrogen completes the ring
4- proton loss and product is formed

the exact same products can be made from both reaction mechanisms

Question 15

outline the trend in reactivity in alkyl electrophiles

Answer 15

tertiary reactivity > secondary > primary
this is due to stability of carbocation decreasing by this same trend

Question 16

give 2 limitations of friedel-crafts alkylation

Answer 16

• overalkylation is very common, it is challenging to generate specific products and requires specific conditions to separate the desired product
• carbon rearrangements occur if a cationic carbon is adjacent to a methyl group, an alkyl group can migrate generating a more stable carbocation, known as wagner-meerwein rearrangement

Question 17

order the reactivities of common substituted benzenes + explain this trend

Answer 17

nitrobenzene < halogenated benzene < benzene < methylbenzene < benzene methyl ether < dimethylbenzylamine

where the substituent is an EWG the reactivity decreases, because of inductive effects of EWGs which pull electron density away from the ring and towards themselves, making the ring less polarising therefore a worse nucleophile
where the substituent is an EDG the reactivity increases by enabling hyperconjugation with alkyl groups or conjugation with lone pairs of heteroatoms, which are both stabilising effects and increase the polarising ability of benzene

Question 18

how are substituent groups named based on reactivity?

Answer 18

substituents that increase reactivity are activating, whereas substituents that decrease reactivity are deactivating

Question 19

with what kind of substituted benzenes is multiple substitutions most likely?

Answer 19

the most reactive benzene derivatives, with EDG substituents

Question 20

how does the benzene substituent affect regioselectivity?

Answer 20

EWGs are meta directing, they will direct new substituents to 3- positions
EDGs are ortho/para directing, and will direct new substituents to 2,4- positions

this is because these substitutions offer the least destabilised pathways based on resonance of lone pairs

Question 21

how are halogens different to most EWGs?

Answer 21

although halogens are EWGs due to their high electronegativity, they also direct substitution to ortho/para positions
this is because of orbital overlap between halogen p-orbitals and π cloud
halogens also have a selectivity for para over ortho substitution which decreases down the group along with electronegativity

Question 22

how does rate of reaction of aromatics change with different halogen substituents ?

Answer 22

rate F > Cl due to improved orbital overlap of 2p vs 3p
rate I > Br due to electronegativity decreasing
rate of Br and Cl is similar, and rate of F and I is similar

Question 23

how can phenols be activated ?

Answer 23

reacting a phenol with NaOH will activate it, as the phenol group is deprotonated to form a phenolate
phenolates are more reactive as its -ve charge is easily donating into the π-ring

Question 24

how can aromatic amines be deactivated?

Answer 24

reacting an aromatic amine with an acyl chloride, to form an aromatic secondary amide, will deactivate it through resonance, as amides are less reactive and improve regioselectivity through steric hinderance,
this is useful for preventing multiple substitutions

Question 25

how is the addition of blocking groups useful in aromatic chemistry + how is it done?

Answer 25

blocking groups such as sulfonic acid can be added to the aromatic ring to decrease reactivity or physically prevent multiple substitution by taking up spots where the substitutions would normally occur sulfonic acid can be added via reaction with concentration H2SO4 at high heat, followed by reaction with a salt, this will substitute a sulfonate salt group which decreases reactivity

Question 26

how can directing effects of particular substituents be worked around?

Answer 26

the substituent can be masked via a simple conversion to another group with an opposite directing affect, then easily converted back after the reaction has taken place

Question 27

what are cooperative substituent effects?

Answer 27

when 2 substituents on an aromatic ring enhance the reactivity at the same position, and would direct a third substituent to the same position

Question 28

what are competitive substituent effects?

Answer 28

when 2 substituents on an aromatic ring do not enhance reactivity at the same position, and therefore have competing directing effects

Question 29

what 4 rules can be used to determine where a third substituent would go under competitive substituent effects?

Answer 29

1- electronic effects override steric effects e.g. resonance/donation of a lone pair is a stronger effect than hyperconjugation and so influences the incoming substitution more 2- activating groups override deactivating groups 3- mesomeric activating groups override inductive/hyperconjugation activating groups e.g. a heteroatom which donates a lone pair has a stronger effect 4- when substitutions cannot be determined by electronics, sterics are used e.g. whichever group sterically hinders the others directing effects more, will have its own directing effects be relatively stronger

Question 30

how does activation enhance reactions of an aromatic group?

Answer 30

electron rich/activated aromatics can react with poorer electrophiles than unsubstituted benzene

Question 31

give 3 reactions only possible with activated aromatics

Answer 31

iodination formylation azo-coupling

Question 32

what is iodination?

Answer 32

the substitution of iodine onto aromatic ring, occurs with an activated aromatic and in excess I2

Question 33

what is formylation

Answer 33

the substitution of an aldehyde group onto an aromatic ring, occurs as a result of the reaction between an activated aromatic and formyl chloride (HCOCl), which is unstable due to the loss of HCl

Question 34

what are the 2 mechanisms by which formylation can occur?

Answer 34

gatterman reaction vilsmeier-haack reaction

Question 35

outline the mechanism of formylation via the gatterman reaction

Answer 35

starts with HCN or Zn(CN)2 this reacts with HCl to form a halogen-imine compound (X-C=N) this compound reacts with a lewis acid catalyst, becoming +vely charged at N, allowing the aromatic to attack it the halogen leaves to form the wheland intermediate which stabilises itself a proton is lost and the product is a benzene-imine, which reacts with water to form benzaldehyde

Question 36

outline the mechanism of formylation via the vilsmeier-haack reaction

Answer 36

starts with POCl3 and and amide, which react, losing HPO2Cl2 to form a halogen-imine compound, which is +vely charged at N the aromatic ring attacks this compound and the halogen leaves the wheland intermediate is formed and stabilises itself a proton is lost and the product forms a benzene-imine, +vely charged at the N, which reacts with water to form benzaldehyde

Question 37

what is azo-coupling?

Answer 37

the addition of a N≡N+ group onto an aromatic form an amine, formed from the reaction of the aromatic amine with salt NaNO2 and a halogenic acid HX, and low temperatures

Question 38

why must low temperatures be used for azo-coupling?

Answer 38

high heat will give off N(g), regenerating benzene, this is also explosive

Question 39

outline the mechanism of azo-coupling

Answer 39

NaNO2 reacts with HX to form nitrous acid, and reacts further with HX to protonate this acid to H2NO2 the water leaving group leaves forming a nitrosonium ion, N≡O+, which is attacked by the amine on the aromatic ring a proton is lost and the molecule resonates between -NH-N=O and -N=N-OH from its N=N form, a N≡N triple bond is formed between the two atoms, releasing water as a leaving group the product formed is a diazonium +ve ion

Question 40

radical reactions definition

Answer 40

reactions involving the movement of a single electron

Question 41

what is the sandmeyer reaction?

Answer 41

the reaction by which diazonium salts/ions are converted into other functional groups e.g. converted to halobenzene if reacted with CuX or converted to benzylnitrile if reacted with CuCN

Question 42

what is the balz-schiemann reaction?

Answer 42

a derivative of the sandmeyer reaction diazonium ion is formed from the reaction of benzylamine and NaNO2 + HBF4 at low heats then at high heat the diazonium reacts with BF4 -ve charged in situ to form fluorobenzene - this is a good way to fluorinate benzene in pharmaceuticals

Question 43

give 3 other possible reactions of diazonium salts

Answer 43

iodination - via reaction with KI hydration to alcohol - via reaction with water under heat hydrogenation to generate pure benzene - via reaction with HSO4- and H3PO2, this is a good way to remove a nitro group

Question 44

what is the birch reduction?

Answer 44

the mechanism by which benzene can be reduced, removing a double bond leaving just 2 - this occurs when benzene is reacted with Na or Li and NH3(l) in alcohol solvent

Question 45

how does the birch reduction work?

Answer 45

metal loses electrons in liquid ammonia, generating metal 1+ ions, this can be seen as the solution turns blue this initiates a radical mechanism and leads selectively to the E-alkene

Question 46

what is benzyne?

Answer 46

a benzene molecule where one of the double bonds is a C≡C triple bond instead

Question 47

what mechanism is also known as the benzyne mechanism + why?

Answer 47

SnAr (nucleophilic aromatic substitution) named as it occurs via a benzyne intermediate

Question 48

how is the benzyne mechanism reminiscent of other mechanisms?

Answer 48

the formation or benzyne occurs in a similar manner to an E1cB reaction: deprotonation followed by elimination this is then followed by an addition to the benzyne

Question 49

give 1 piece of evidence for the benzyne intermediate

Answer 49

the reaction has been done with 1 carbon atom on the benzene replaced with 14C, and a 50/50 mixture of benzylamine was produced (the amine was found in 2 different places relative to the substituted 14C carbon) for a 50/50 mixture to be produced the mechanism must go through a symmetrical intermediate, which was determined to be benzyne, despite instability

Question 50

give 1 other milder method of producing benzyne

Answer 50

reaction of benzene (disubstituted, 1-COOH, 2-N≡N+) with heat, this releases CO2 and N2 to form benzyne

Question 51

what is the role of benzyne in a reaction?

Answer 51

electrophilic, it reacts with nucleophiles

Question 52

give 4 examples of further reactions of benzyne

Answer 52

formation of tertiary aromatic amine via reaction with R2NH formation of ether via reaction with alcohol formation of ester via reaction with carboxylic acid formation of alkylbenzene via reaction with RMgBr (a grignard reagent)

Question 53

how does the stability of benzyne impact its potential for reactions?

Answer 53

benzyne is not very stable, making it very reactive this means it is less useful for synthesising more complicated molecules

Question 54

how does benzyne make SnAr possible + under what other condition can it be done?

Answer 54

benzyne decreases the electron density of the aromatic ring allowing it to interact with nucleophiles this can sometimes also be done with aromatic rings substituted with an EWG

Question 55

what are the rough kinetics for SnAr reactions + why is this the case?

Answer 55

the first step = nucleophilic attack, this is slow - rate determining the second step = loss of the LG, this is fast

Question 56

how do EWGs affect the speed of SnAr reactions?

Answer 56

more stabilising groups make the -ve charge more stable so rate determining step 1 is faster

Question 57

how does different halogen LGs affect the speed of SnAr reactions?

Answer 57

it shouldn't affect speed as much as it is not dependent on bond strength F >> Cl > Br > I despite C-F being the strongest carbon-halogen bond, F reacts the fastest - this is because F is very small, sterics are favourable to allow nucleophile to easily enter π* orbital - also because F is so electronegative, it is even more stabilising/electron withdrawing

Question 58

how does substitution position affect speed?

Answer 58

if LG is ortho/para to EWG, the -ve charge can be delocalised to the EWG sometimes, which is stabilising and speeds up reaction if LG is meta to EWG, this isn't possible so the reaction is slower