Aromatic- Reactivity and Regioselectivity of substituted benzenes in SEAr

Question 1

What does substitution of benzene result in

Answer 1

1. Effects both rate and regioselectivity

Question 2

What is the rate of an SEAr reaction determined by

Answer 2

1. Nucleophilicity of the aromatic

Question 3

What affect

Answer 3

1. Electron withdrawing groups reduce the rate of reaction either through inductive effects governed by electronegativity (-F) or mesomeric effects determined by conjugation (-NO2)
2. Very electron-poor aromatics require high temperatures and harsher conditions to get them to react
3. Electron-donating groups increase the rate of reaction either through inductive effects such as hyperconjugation (alkyl) or mesomeric effects by conjugation (-OME, NMe2)
4. Very electron-rich aromatic can be too reactive and difficult to prevent multiple substitutions from occurring

Question 4

What is Hammett constants

Answer 4

1. Shows how electron-donating or electron-withdrawing a specific substituent is

Question 5

Name some common electron donating groups

Answer 5

1. NH2, NHR, NR2- STRONGEST
2. OH, OR
3. NHOCR, OCOR
4. Ph, CH=CH2
5. R

Question 6

Which are have stronger effects- mesomeric or inductive

Answer 6

1. Usually mesomeric effects are stronger

2. EDG with strong +M effects stabilise carbocations more effectively than EDG with weaker +M effects

Question 7

What are some common deactiviting groups

Answer 7

1. Cl, Br, I
2. CHO, COR
3. CO2H, CO2R
4. SO3H
5. NO2- STONGEST

Question 8

What direction do EWGs direct substitution to

Answer 8

1. The meta position

2. Except halogens- ortho or para

Question 9

What direction do EDGs direct substitution to

Answer 9

1. Ortho or Para position

Question 10

Why do EWGs direct to the meta position

Answer 10

1. The lower energy pathway
2. Avoids a disfavoured, high-energy resonance structure where a positive charge is found on the carbon adjacent to the EWG

Question 11

Why do EDGs direct to the ortho/para position

Answer 11

1. Lower energy pathway
2. The positive charge can reside on the carbon adjacent to the EDG and can be stabilised either by resonance or hyperconjugation
3. Meta has least resonance structures so least favoured pathway
4. Wheland intermediates lower in energy for ortho and para

Question 12

Why do halogens direct ortho and para

Answer 12

1. Effective orbital overlap of a lone pair of halogen with the Wheland intermediate which helps to stabilise it in a similar manner as a conjugated EDG

Question 13

Which aromatic halide is most reactive

Answer 13

1. Fluoro>iodo>chloro>bromo
2. Fluorobenzene than chlorobenzene as improved orbital overlap 2p vs 3p between the pi-cloud and the halogen
3. As the orbitals get more diffuse, bonds get longer and inductive effects weaker
4. Iodobenzene has a higher rate of reaction than bromobenzene due to lower electronegativity

Question 14

Describe ratio of ortho:para for different halogobenzens

Answer 14

1. Ortho:para
2. Fluoro- 1:9
3. Chloro- 4:6
4. Bromo- 4:6
5. Iodo- 5:5
6. Fluorine is so selective for para because of strong inductive effect from the highly electronegative fluorine atom

Question 15

How can reactivity be adjusted

Answer 15

1. Changing the electron density of the aromatic ring

Question 16

How can regioselectivity be improved

Answer 16

1. Effective use of sterics or blocking groups

Question 17

How can phenols improve their reactivity within SEAr reactions and what is it called

Answer 17

1. Phenols can be turned into their corresponding phenoxide anion through treatment with hydroxide
2. Allows them to react even with poor electrophiles such as CO2
3. Ortho is the major product
4. Reaction known as Kolbe-Schmitt process
5. Used in industry for synthesis of aspirin

Question 18

How can anilines reduce their activity

Answer 18

1. Temporarily turned into the corresponding acetanilide using a suitable acetylation reagent such as acetyl chloride or acetic anhydride
2. Prevents lone pair of electrons on the nitrogen atom from being donated into the aromatic ring as much, since it is now in conjugation with the amide
3. Reduced electron density allows for a single substitution to be performed
4. Substitution normally at para due to increased steric hindrance at ortho position
5. The acetyl group can then be easily removed through acid or base hydrolysis to return the free aniline

Question 19

How can you improve the ortho/para selectivity of electron-rich aromatics

Answer 19

1. Blocking groups can be used
2. Temporarily install functionality at the more reactive position, then remove it after the desired electrophile has been reacted at the less reactive position

Question 20

What acts as a good blocking group

Answer 20

1. Sulfonic acids- reversible nature of the sulfonation SEAr reaction

Question 21

Describe how sulfonic acid can help to product 2-bromophenol from phenol

Answer 21

1. Reacting phenol with bromine would not work as it would lead to 2,4,6-trisubstituted product
2. Heat phenol with concentrated sulfuric acid - first blocks the para and one of the ortho positions so in subsequent bromination reaction, SEAr only occurs at the remaining ortho position
3. Heating with dilute sulfuric acid removes the sulfonic acid groups to five the desired ortho-bromophenol product

Question 22

Give examples of how FGIs can change directing effects

Answer 22

1. Meta nitro can be reduced to ortho/para amines
2. Meta carbonyls can be reduced to ortho/para alkyls
3. Ortho/para methyl can be oxidised to meta carboxylic acids using KMnO4

Question 23

Describe what happens in poly substituted aromatics

Answer 23

1. Different substituents can direct electorphilic aromatic substitution
2. Either cooperatively to the same position
3. Or competitively to different positions

Question 24

What happens with cooperative effects

Answer 24

1. All work together to stabilise the Wheland intermediate when substitution occurs at the preferred position
2. Improves regioselectivity of the reaction

Question 25

What happens when there are competitive effects

Answer 25

1. Likely position of substitution can be difficult to predict 2. Both electronic and steric factors need to be considered 3. Electronic are considered first

Question 26

Describe how to determine position from electronic effects of competitive groups

Answer 26

1. Activating groups take precedent over deactivating groups 2. When more than one activating group- those directed by conjugation have a much stronger effect and take precedent over those directed by hyperconjugation or inductive effects

Question 27

How can sterics be used to determine position when there are competitive groups

Answer 27

1. When electronic factors cannot easily distinguish between positions, steric effects are considered 2. Substitution typically occurs at least hindered position

Question 28

What reactions can electron-rich aromatics undergo

Answer 28

1. Iodination 2. Formylation 3. Azo-coupling

Question 29

What is a limitation of Friedel-Crafts acylation

Answer 29

1. R cannot = H | 2. Useful benzaldehyde products cannot be made by this method

Question 30

How can formylation of electron-rich aromatics occur

Answer 30

1. Gatterman reaction | 2. Vilsmeier-Haack reaction

Question 31

Describe the Gatterman reaction

Answer 31

1. Either gaseous HCN or easier to handle but just as toxic zin(II) Cyanide with HCl gas combine to give an imine 2. In the presence of a Lewis acid catalyst the imine is activated to an iminium cation 3. This iminium cation is electrophilic enough to be attacked by an electron-rich aromatic- SEAr 4. he imine product from this is hydrolysed in aqueous work-up to obtain formylated product

Question 32

Describe the Vilsmeier-Haack reaction

Answer 32

1. Dimethylformamide (DMF) and phosphorus oxychloride (POCl3) combine to give an iminium directly 2. This can be attacked by the aromatic- SEAr 3. The imine product from this is hydrolysed in aqueous work-up to obtain formylated product

Question 33

How can azo dyes be produced

Answer 33

1. Aryldiazonium salts can be used as electrophiles with SEAr reactions with electron-rich aromatics 2. Electron-rich aromatics react with them at the terminal nitrogen in a standard SEAr manner. 3. The products have extended pi-conjugated systems and are therefore highly coloured- dyes and pigments within food and textiles