Conjugated dienes, aromaticity. Allylic and benzylic reactivity. Phenols.

1. Conjugated dienes, aromaticity. Allylic and benzylic reactivity. Phenols.

2. Required background: Alkenes Electrophilic addition to alkenes Molecular shapes Stability of intermediates Resonance structures Acidity of alcohols Essential for: 1. Chemistry of the carbonyl group 2. Understanding of antioxidants 3. Enols and enolates

3. Outline 1. Conjugated and non-conjugated dienes. Chemistry of vision 2. Conjugated addition to 1,3-dienes 3. Aromaticity 4. Derivatives of benzene 5. Aromatic electrophilic substitution 6. Allylic and benzylic oxidation 7. Phenols

4. Heats of combustion: CH2=C=CH-CH2-CH3 CH2=CH-CH2-CH=CH2 CH2=CH-CH=CH-CH3 3251 kJ/mol 3217 kJ/mol 3186 kJ/mol Least stable Most stable Weak s-p* conjugation Better s-p* conjugation Both s-p* and p-p* conjugations =C= is a new example of sp-hybridized carbon Lowest p-orbitals for 1,4- and 1,3-dienes

5. Each additional double bond in conjugation increases the wavelength of absorption Consequence: 1. Absorption at some point crosses from the UV into the visible area of light

6. Ability of polyenes to absorb visible light enables retinol to change shape upon illumination by light and send a signal to the brain Consequences: 1. Our eyes are able to sense light 2. Absorption shifts toward longer wavelength and at some point crosses from the UV into the visible area In the cone cell there are three different types of Opsins: Red Opsin, Blue Opsin and Green Opsin. The wavelength where Retinal absorbs light is different for each. The Blue Rhodopsin absorbs at 420 nanometers; Green Rhodopsin absorbs at 530 nanometers and Red Rhodopsin absorbs at 570 nanometers. There may be only one chromophore (Retinal), but because the proteins are a little different, the way the Retinal is attached to a protein has a great deal of affect on its wavelength of absorption.

7. The aldehyde group of retinal enables its attachment to opsins to form rhodopsins

8. Outline 1. Conjugated and non-conjugated dienes. Chemistry of vision 2. Conjugated addition to 1,3-dienes 3. Aromaticity 4. Derivatives of benzene 5. Aromatic electrophilic substitution 6. Allylic and benzylic oxidation 7. Phenols

10. Polymerization of 1,3-dienes n CH2=CH-CH=CH2 => -(-CH2-CH=CH-CH2-)n-

11. Outline 1. Conjugated and non-conjugated dienes. Chemistry of vision 2. Conjugated addition to 1,3-dienes 3. Aromaticity 4. Derivatives of benzene 5. Aromatic electrophilic substitution 6. Allylic and benzylic oxidation 7. Phenols

12. An aromatic system is formed from a polyene p-system with an odd number of occupied orbitals (2n+1), bearing 4n+2 electrons (Huckel’s rule of aromaticity) An anti-aromatic system is formed from a polyene p-system with an even number of occupied orbitals (2n), bearing 4n electrons (Huckel’s rule of anti-aromaticity) The Huckel’s rule is valid for planar monocyclic systems.

14. Reactions that demonstrate the concept of aromaticity

15. Outline 1. Conjugated and non-conjugated dienes. Chemistry of vision 2. Conjugated addition to 1,3-dienes 3. Aromaticity 4. Derivatives of benzene 5. Aromatic electrophilic substitution 6. Allylic and benzylic oxidation 7. Phenols

16. Nomenclature and physical properties of substituted benzenes Substituents in the benzene ring are ranked and numbered in the following order: -COOH > -CHO > -OH > -Alkyl > others Examples: Note: Hydroxy-derivatives of benzene are called phenols, not alcohols. Some derivatives also have common names:

17. Boiling and points of substituted benzenes and cyclohexenes are very close. Benzene: m.p. 5.5 oC, b.p. 80.1 oC Cyclohexene: m.p. 6.6 oC, b.p. 80.7 oC Melting points of para-derivatives usually much higher, than of meta- and ortho-derivatives, because the molecules of para-derivatives are packed easier in the crystal lattice. 2. Reactivity of benzene versus alkenes

18. Outline 1. Conjugated and non-conjugated dienes. Chemistry of vision 2. Conjugated addition to 1,3-dienes 3. Aromaticity 4. Derivatives of benzene 5. Aromatic electrophilic substitution 6. Allylic and benzylic oxidation 7. Phenols

19. Electrophilic substitution (SEAr). a. Bromination

20. b. Chlorination (same mechanism as for bromination) Iodination does not occur this way. Fluorination proceeds through a different mechanism. Nitration

21. Alkylation and acylation

22. Alkylation, catalyzed by aluminium chloride, can be complicated by carbocation rearrangements

24. Electronic effect of substituents at the benzene ring a. Inductive acceptor. The atom of the substituent, connected to the benzene ring, has higher electronegativity, than H. Examples: -OCH3, -NH2, -Cl, -NO2 b. Resonance acceptor. Conjugation between p-orbitals is depicted by resonance structures with the positive charge in the benzene ring. Examples: -COR, -NO2, -SO3H c. Resonance donor. Conjugation between p-orbitals is depicted by resonance structures with the negative charge in the benzene ring. Examples: -OCH3, -NH2, -Cl, -phenyl

25. d. Hyperconjugative donor. Conjugation, involving s-orbitals, is depicted by non-classical resonance structures (allowing breaking s-bonds) with the negative charge in the benzene ring. Examples: -CH3, -Alkyl e. Hyperconjugative acceptor. Conjugation, involving s-orbitals, is depicted by non-classical resonance structures (allowing breaking s-bonds) with the positive charge in the benzene ring. Examples: -CF3

26. Substituent effect on reactivity of substituted benzenes Electron donors increase reactivity in SEAr Examples: -CH3, -NR2, -OR, -CH=CH2 Electron acceptors decrease reactivity in SEAr Examples: -NO2, -NH3+, -COR, -Cl For substituents with opposite effects, the resonance effect overrides all other effects, except for chlorine and bromine, where the inductive effect is the strongest. Example of activation

27. Directing effect of substituents (already present at the benzene ring before substitution) on substitution (Note: the signs of resonance refers to the structures before the substituent is added) All electron donors direct the incoming substituent to the ortho- and para-positions (regardless of any accepting effects) Examples: -CH3, -NR2, -OR, -Cl, -Br, -CH=CH2

29. (Note: the signs of resonance refers to the structures before the substituent is added) Pure electron acceptors direct the incoming substituent to the meta-position Examples: -NO2, -NH3+, -COR, -CF3

31. Outline 1. Conjugated and non-conjugated dienes. Chemistry of vision 2. Conjugated addition to 1,3-dienes 3. Aromaticity 4. Derivatives of benzene 5. Aromatic electrophilic substitution 6. Allylic and benzylic oxidation 7. Phenols

32. Allylic (benzylic) oxidation

33. Outline 1. Conjugated and non-conjugated dienes. Chemistry of vision 2. Conjugated addition to 1,3-dienes 3. Aromaticity 4. Derivatives of benzene 5. Aromatic electrophilic substitution 6. Allylic and benzylic oxidation 7. Phenols

34. Acidity of phenols Phenols are much more acidic, than alcohols because of stabilization of the conjugate base (phenoxide) due to conjugation with the aromatic ring. Substituents at the ortho- and para-positions further increase acidity of phenols.

35. As opposed to NaOH, NaHCO3 is a too weak base to bring phenol in aqueous solution. 6. Oxidation of phenols

36. Phenols are able to intercept free radicals and inhibit free-radical reactions