Aromatic- Reactivity and Regioselectivity of substituted benzenes in SEAr Flashcards
What does substitution of benzene result in
- Effects both rate and regioselectivity
What is the rate of an SEAr reaction determined by
- Nucleophilicity of the aromatic
What affect
- Electron withdrawing groups reduce the rate of reaction either through inductive effects governed by electronegativity (-F) or mesomeric effects determined by conjugation (-NO2)
- Very electron-poor aromatics require high temperatures and harsher conditions to get them to react
- Electron-donating groups increase the rate of reaction either through inductive effects such as hyperconjugation (alkyl) or mesomeric effects by conjugation (-OME, NMe2)
- Very electron-rich aromatic can be too reactive and difficult to prevent multiple substitutions from occurring
What is Hammett constants
- Shows how electron-donating or electron-withdrawing a specific substituent is
Name some common electron donating groups
- NH2, NHR, NR2- STRONGEST
- OH, OR
- NHOCR, OCOR
- Ph, CH=CH2
- R
Which are have stronger effects- mesomeric or inductive
- Usually mesomeric effects are stronger
2. EDG with strong +M effects stabilise carbocations more effectively than EDG with weaker +M effects
What are some common deactiviting groups
- Cl, Br, I
- CHO, COR
- CO2H, CO2R
- SO3H
- NO2- STONGEST
What direction do EWGs direct substitution to
- The meta position
2. Except halogens- ortho or para
What direction do EDGs direct substitution to
- Ortho or Para position
Why do EWGs direct to the meta position
- The lower energy pathway
- Avoids a disfavoured, high-energy resonance structure where a positive charge is found on the carbon adjacent to the EWG
Why do EDGs direct to the ortho/para position
- Lower energy pathway
- The positive charge can reside on the carbon adjacent to the EDG and can be stabilised either by resonance or hyperconjugation
- Meta has least resonance structures so least favoured pathway
- Wheland intermediates lower in energy for ortho and para
Why do halogens direct ortho and para
- 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
Which aromatic halide is most reactive
- Fluoro>iodo>chloro>bromo
- Fluorobenzene than chlorobenzene as improved orbital overlap 2p vs 3p between the pi-cloud and the halogen
- As the orbitals get more diffuse, bonds get longer and inductive effects weaker
- Iodobenzene has a higher rate of reaction than bromobenzene due to lower electronegativity
Describe ratio of ortho:para for different halogobenzens
- Ortho:para
- Fluoro- 1:9
- Chloro- 4:6
- Bromo- 4:6
- Iodo- 5:5
- Fluorine is so selective for para because of strong inductive effect from the highly electronegative fluorine atom
How can reactivity be adjusted
- Changing the electron density of the aromatic ring
How can regioselectivity be improved
- Effective use of sterics or blocking groups
How can phenols improve their reactivity within SEAr reactions and what is it called
- Phenols can be turned into their corresponding phenoxide anion through treatment with hydroxide
- Allows them to react even with poor electrophiles such as CO2
- Ortho is the major product
- Reaction known as Kolbe-Schmitt process
- Used in industry for synthesis of aspirin
How can anilines reduce their activity
- Temporarily turned into the corresponding acetanilide using a suitable acetylation reagent such as acetyl chloride or acetic anhydride
- 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
- Reduced electron density allows for a single substitution to be performed
- Substitution normally at para due to increased steric hindrance at ortho position
- The acetyl group can then be easily removed through acid or base hydrolysis to return the free aniline
How can you improve the ortho/para selectivity of electron-rich aromatics
- Blocking groups can be used
- Temporarily install functionality at the more reactive position, then remove it after the desired electrophile has been reacted at the less reactive position
What acts as a good blocking group
- Sulfonic acids- reversible nature of the sulfonation SEAr reaction
Describe how sulfonic acid can help to product 2-bromophenol from phenol
- Reacting phenol with bromine would not work as it would lead to 2,4,6-trisubstituted product
- 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
- Heating with dilute sulfuric acid removes the sulfonic acid groups to five the desired ortho-bromophenol product
Give examples of how FGIs can change directing effects
- Meta nitro can be reduced to ortho/para amines
- Meta carbonyls can be reduced to ortho/para alkyls
- Ortho/para methyl can be oxidised to meta carboxylic acids using KMnO4
Describe what happens in poly substituted aromatics
- Different substituents can direct electorphilic aromatic substitution
- Either cooperatively to the same position
- Or competitively to different positions
What happens with cooperative effects
- All work together to stabilise the Wheland intermediate when substitution occurs at the preferred position
- Improves regioselectivity of the reaction
What happens when there are competitive effects
- Likely position of substitution can be difficult to predict
- Both electronic and steric factors need to be considered
- Electronic are considered first
Describe how to determine position from electronic effects of competitive groups
- Activating groups take precedent over deactivating groups
- 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
How can sterics be used to determine position when there are competitive groups
- When electronic factors cannot easily distinguish between positions, steric effects are considered
- Substitution typically occurs at least hindered position
What reactions can electron-rich aromatics undergo
- Iodination
- Formylation
- Azo-coupling
What is a limitation of Friedel-Crafts acylation
- R cannot = H
2. Useful benzaldehyde products cannot be made by this method
How can formylation of electron-rich aromatics occur
- Gatterman reaction
2. Vilsmeier-Haack reaction
Describe the Gatterman reaction
- Either gaseous HCN or easier to handle but just as toxic zin(II) Cyanide with HCl gas combine to give an imine
- In the presence of a Lewis acid catalyst the imine is activated to an iminium cation
- This iminium cation is electrophilic enough to be attacked by an electron-rich aromatic- SEAr
- he imine product from this is hydrolysed in aqueous work-up to obtain formylated product
Describe the Vilsmeier-Haack reaction
- Dimethylformamide (DMF) and phosphorus oxychloride (POCl3) combine to give an iminium directly
- This can be attacked by the aromatic- SEAr
- The imine product from this is hydrolysed in aqueous work-up to obtain formylated product
How can azo dyes be produced
- Aryldiazonium salts can be used as electrophiles with SEAr reactions with electron-rich aromatics
- Electron-rich aromatics react with them at the terminal nitrogen in a standard SEAr manner.
- The products have extended pi-conjugated systems and are therefore highly coloured- dyes and pigments within food and textiles
