Nomenclature & SE Reactions of Benzene derivatives

1. Nomenclature & SE Reactions of Benzene derivatives By: Hamada Abulkhair Ph.D

2. Nomenclature of benzene derivatives Monosubstituted benzenes are named either by prefixing the substituent to benzene as parent name, or by giving the substituent and the benzene ring together a new parent name, e.g.,

3. Disubstituted benzenes are prefixed by ortho-, meta-, and para- (o-, m-, and p-) or by numbers according to the relative positions of the two substituents, e.g., (Dichlorobenzene has 3 isomeric structure)

4. If more than two groups are present on the benzene ring, their relative position must be indicated by the use of numbers. The C6H5- group is prefixed as phenyl, while the C6H5CH2- group as benzyl. By: Hamada Abulkhair Ph. D.

5. Review problems Write structural formulas for each of the following: • 3-Nitrobenzoic acid • p-Bromotoluene • o-Dibromobenzene • m-Dinitrobenzene • 3,5-Dinitrophenol • p-Nitrobenzoic acid • P-toluenesulfonate • Benzyl bromide • p-Nitroaniline • o-Xylene • tert-Butylbenzene • p-Methylphenol • p-Bromoacetophenone • 3-Phenylcyclohexanol • 2-Methyl-3-phenyl-1-butanol • o-Chloroanisole By: Hamada Abulkhair Ph. D

6. Review problems • Tribromobenzenes • Nitroanilines • Isomers of C6H5-C4H9 • Dichlorophenols • Methylbenzenesulfonic acids Write structural formulas and give acceptable names for all representatives of the following By: Hamada Abulkhair Ph. D

7. Electrophilic Aromatic Substitution

8. Background • The characteristic reaction of benzene is electrophilic aromatic substitution—a hydrogen atom is replaced by an electrophile.

9. Benzene does not undergo addition reactions like other unsaturated hydrocarbons, because addition yield a product that is not aromatic. • Substitution of a hydrogen keeps the aromatic ring intact. • There are five main examples of electrophilic aromatic substitution.

10. Electrophilic aromatic substitution reactions allow us to introduce a wide variety of groups into aromatic rings, e.g.: (i) A halo substituent , -X (Hologenation) (ii) A nitro group , -NO2 (Nitration) (iii) A sulphonic acid group , -SO3H (Sulphonation) (iv) An alkyl group , -R (Friedel-Crafts alkylation) (v) An acyl group , -COR (Friedel-Crafts acylation) All of these reactions involve an attack on the benzene ring by an electron-deficient species , i.e. by an electrophile.

12. By: Hamada Abulkhair Ph. D.

13. General mechanism of electrophilic aromatic substitution

14. General mechanism of electrophilic aromatic substitution Step 1: It is important to note that the arenium ion is a resonance hybrid of 3 allylic-type resonance structures each of which has a positive charge on an ortho or para carbon of the ring. Step 2:

15. In halogenation, benzene reacts with Cl2 or Br2 in the presence of a Lewis acid catalyst, such as FeCl3 or FeBr3, to give the aryl halides chlorobenzene or bromobenzene respectively. • Analogous reactions with I2 and F2 are not synthetically useful because I2 is too unreactive and F2react dangerously exothermic and requires special conditions and special types of apparatus.

17. In step1 the Lewis acid forms a complex with bromine in a Lewis acid-base reaction. In step2 this complex acts as an electrophile and transfers a positive bromine ion (Br+) to the benzene ring to form arenium ion and an FeBr4- ion. In step3 the arenium ion transfer a proton to FeBr4-. This results in the formation of bromobenzene and HBr with regeneration of the catalyst, FeBr3.

18. Nitration Benzene reacts slowly with hot concentrated nitric acid to yield nitrobenzene. The reaction is much faster if it is carried out by heating benzene with a mixture of concentrated nitric acid and concentrated sulphuric acid. This mixture is generally called a nitrating mixture.

19. The electrophile in nitration reactions is the nitronium ion , NO2+. Concentrated sulphuric acid increases the rate of the reaction by increasing the concentration of the nitronium ion. By: Hamada Abulkhair Ph. D.

20. Sulphonation The usual sulphonating agents are concentrated sulphuric acid or sluphur trioxide (SO3) in sulphuric acid, i.e. fuming sulphuric acid (or oleum). The electrophile in sulphonation reactions is sulphur trioxide. In concentrated sulphuric acid,

21. By: Hamada Abulkhair Ph. D.

22. Friedel-Crafts Alkylation and Friedel-Crafts Acylation • In Friedel-Crafts alkylation, treatment of benzene with an alkyl halide and a Lewis acid (AlCl3) forms an alkyl benzene.

23. Notes • The ease of formation of the carbocation depends on its relative stability . • The order of reactivity of alkyl halides Allyl or benzyl > tert. > sec. > prim. • The alkylating agents in the Friedel-Crafts reaction are not restricted to alkyl halides, but alkenes and alcohols can also be used. • Aluminium chloride may be the most common catalyst used for Friedel-Crafts reactions • In case of alkylating agent is an alcohol or an alkene • Also proton acid catalysts as HF, H2SO4 , H3PO4, can be used, especially when the alkylating agent is an alcohol or an alkene

24. Another example is the preparation of tert-butylbenzene from benzene and an alkyl halide , an alkene, or an alcohol, All the three reactions proceed through the formation of the electrophile tert-butyl cation.

25. limitation of Friedel-Crafts Alkylation and Friedel-Crafts Acylation Three additional facts about Friedel-Crafts alkylation should be kept in mind. [1] Vinyl halides and aryl halides do not react in Friedel-Crafts alkylation.

26. Friedel-Crafts Alkylation and Friedel-Crafts Acylation ii) Polyalkylations occur, with CH3 and C2H5 group, due to the activation effect that alkyl groups have on an aromatic ring.

27. Friedel-Crafts Alkylation and Friedel-Crafts Acylation [3] Rearrangements can occur. These results can be explained by carbocation rearrangements.

28. Complete the following equation?

30. iv) Friedel-Crafts reactions do not occur when 1) Powerful electron-withdrawing groups are present on the aromatic ring or when the ring bears an -NH2 , -NHR , or NR2 group. Thus nitrobenzene , acetophenone and aniline , as examples, do not undergo the Friedel-Crafts reaction.

31. Friedel-Crafts Acylation • In Friedel-Crafts acylation, a benzene ring is treated with an acid chloride (RCOCl) and AlCl3 to form a ketone.

32. The acylating agents are not restricted to acid chlorides, but acid anhydrides.

33. Some synthetic applications of Friedel-Crafts acylation: 1- synthetic routes to n-alkylbenzenes

34. 1) Polyacylation , in contrast to polyalkylation , is not possible in Friedel-Crafts acylation because the acyl group is an electron-withdrawing group and hence it deactivates the ring towards further substitution

35. Electrophilic Aromatic Substitution and Substituted Benzenes. • A substituent affects two aspects of the electrophilic aromatic substitution reaction: • The rate of the reaction—A substituted benzene reacts faster or slower than benzene itself. • The orientation—The new group is located either ortho, meta, or para to the existing substituent. The identity of the first substituent determines the position of the second incoming substituent.

36. Electrophilic Aromatic Substitution and Substituted Benzenes. All substituents can be divided into three general types:

38. Orientation Effects in Substituted Benzenes • There are two general types of ortho, para directors and one general type of meta director. • All ortho, para directors are R groups or have a nonbonded electron pair on the atom bonded to the benzene ring. • All meta directors have a full or partial positive charge on the atom bonded to the benzene ring.

39. With the NO2 group (and all meta directors) meta attack occurs because attack at the ortho and para position gives a destabilized carbocation intermediate.

40. The reactivity and directing effects of common substituted benzenes

41. The relative rates of these reactions depend on whether S withdraws or releases electrons. If S is an electron-releasing group (relative to H), the reaction occurs faster than the corresponding reaction of benzene. If S is an electron-withdrawing group, the reaction is slower than that of benzene. The electron-withdrawing and electron-releasing properties of groups can be accounted for on the basis of polar factors, either inductive or resonance effects , which also determine orientation in aromatic substitution reactions.

42. On the other hand, when the group present in the ring has a partial or a full positive charge on the atom directly attached to the ring, e.g. NO2, COOH, COR, SO3H, CN,etc., , the product of further substitution is mainly meta. All these groups have at least one strongly electron-attracting atom and a double or triple bond conjugated to the benzene ring, and so cause an electron displacement away from the ring towards the group. This electron withdrawing effect is called -R effect.

45. Limitations in Electrophilic Aromatic Substitutions • A benzene ring deactivated by strong electron-withdrawing groups (i.e., any of the meta directors) is not electron rich enough to undergo Friedel-Crafts reactions.