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Chapter 21 Phenols and Aryl Halides: Nucleophilic Aromatic Substitution.

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Presentation on theme: "Chapter 21 Phenols and Aryl Halides: Nucleophilic Aromatic Substitution."— Presentation transcript:

1 Chapter 21 Phenols and Aryl Halides: Nucleophilic Aromatic Substitution

2 Chapter 212  Structure and Nomenclature of Phenols  Phenols have hydroxyl groups bonded directly to a benzene ring  Naphthols and phenanthrols have a hydroxyl group bonded to a polycyclic benzenoid ring

3 Chapter 213 Nomenclature of Phenols  Phenol is the parent name for the family of hydroxybenzenes  Methylphenols are called cresols

4 Chapter 214  Synthesis of Phenols Laboratory Synthesis  Phenols can be made by hydrolysis of arenediazonium salts

5 Chapter 215 Industrial Syntheses  1. Hydrolysis of Chlorobenzene (Dow Process)  Chlorobenzene is heated with sodium hydroxide under high pressure  The reaction probably proceeds through a benzyne intermediate (Section 21.11B)  2. Alkali Fusion of Sodium Benzenesulfonate  Sodium benzenesulfonate is melted with sodium hydroxide

6 Chapter 216  3. From Cumene Hydroperoxide  Benzene and propene are the starting materials for a three-step sequence that produces phenol and acetone  Most industrially synthesized phenol is made by this method  The first reaction is a Friedel-Crafts alkylation

7 Chapter 217  The second reaction is a radical chain reaction with a 3 o benzylic radical as the chain carrier

8 Chapter 218  The third reaction is a hydrolytic rearrangement (similar to a carbocation rearrangement) that produces acetone and phenol  A phenyl group migrates to a cationic oxygen group

9 Chapter 219  Reactions of Phenols as Acids Strength of Phenols as Acids  Phenols are much stronger acids than alcohols

10 Chapter 2110  Phenol is much more acidic than cyclohexanol  Experimental results show that the oxygen of a phenol is more positive and this makes the attached hydrogen more acidic  The oxygen of phenol is more positive because it is attached to an electronegative sp 2 carbon of the benzene ring  Resonance contributors to the phenol molecule also make the oxygen more positive

11 Chapter 2111 Distinguishing and Separating Phenols from Alcohols and Carboxylic Acids  Phenols are soluble in aqueous sodium hydroxide because of their relatively high acidity  Most alcohols are not soluble in aqueous sodium hydroxide  A water-insoluble alcohol can be separated from a phenol by extracting the phenol into aqueous sodium hydroxide  Phenols are not acidic enough to be soluble in aqueous sodium bicarbonate (NaHCO 3 )  Carboxylic acids are soluble in aqueous sodium bicarbonate  Carboxylic acids can be separated from phenols by extracting the carboxylic acid into aqueous sodium bicarbonate

12 Chapter 2112  Other Reactions of the O-H Group of Phenols  Phenols can be acylated with acid chlorides and anhydrides

13 Chapter 2113 Phenols in the Williamson Ether Synthesis  Phenoxides (phenol anions) react with primary alkyl halides to form ethers by an S N 2 mechanism

14 Chapter 2114  Cleavage of Alkyl Aryl Ethers  Reaction of alkyl aryl ethers with HI or HBr leads to an alkyl halide and a phenol  Recall that when a dialkyl ether is reacted, two alkyl halides are produced

15 Chapter 2115  Reaction of the Benzene Ring of Phenols Bromination  The hydroxyl group is a powerful ortho, meta director and usually the tribromide is obtained  Monobromination can be achieved in the presence of carbon disulfide at low temperature Nitration  Nitration produces o- and p-nitrophenol  Low yields occur because of competing oxidation of the ring

16 Chapter 2116 Sulfonation  Sulfonation gives mainly the the ortho (kinetic) product at low temperature and the para (thermodynamic) product at high temperature

17 Chapter 2117 The Kolbe Reaction  Carbon dioxide is the electrophile for an electrophilic aromatic substitution with phenoxide anion  The phenoxide anion reacts as an enolate  The initial keto intermediate undergoes tautomerization to the phenol product  Kolbe reaction of sodium phenoxide results in salicyclic acid, a synthetic precursor to acetylsalicylic acid (aspirin)

18 Chapter 2118  The Claisen Rearrangement  Allyl phenyl ethers undergo a rearrangement upon heating that yields an allyl phenol  The process is intramolecular; the allyl group migrates to the aromatic ring as the ether functional group becomes a ketone  The unstable keto intermediate undergoes keto-enol tautomerization to give the phenol group  The reaction is concerted, i.e., bond making and bonding breaking occur at the same time

19 Chapter 2119  Allyl vinyl ethers also undergo Claisen rearrangement when heated  The product is a  -unsaturated carbonyl compound  The Cope rearrangement is a similar reaction  Both the Claisen and Cope rearrangements involve reactants that have two double bonds separated by three single bonds

20 Chapter 2120  The transition state for the Claisen and Cope rearrangements involves a cycle of six orbitals and six electrons, suggesting aromatic character  This type of reaction is called pericyclic  The Diels-Alder reaction is another example of a pericyclic reaction

21 Chapter 2121  Quinones  Hydroquinone is oxidized to p-benzoquinone by mild oxidizing agents  Formally this results in removal of a pair of electrons and two protons from hydroquinone  This reaction is reversible  Every living cell has ubiquinones (Coenzymes Q) in the inner mitochondrial membrane  These compounds serve to transport electrons between substrates in enzyme- catalyzed oxidation-reduction reactions

22 Chapter 2122  Aryl Halides and Nucleophilic Aromatic Substitution  Simple aryl and vinyl halides do not undergo nucleophilic substitution  Back-side attack required for S N 2 reaction is blocked in aryl halides

23 Chapter 2123  S N 2 reaction also doesn’t occur in aryl (and vinyl halides) because the carbon-halide bond is shorter and stronger than in alkyl halides  Bonds to sp 2 -hybridized carbons are shorter, and therefore stronger, than to sp 3 -hybridized carbons  Resonance gives the carbon-halogen bond some double bond character

24 Chapter 2124 Nucleophilic Aromatic Substitution by Addition- Elimination: The S N Ar Mechanism  Nucleophilic substitution can occur on benzene rings when strong electron-withdrawing groups are ortho or para to the halogen atom  The more electron-withdrawing groups on the ring, the lower the temperature required for the reaction to proceed

25 Chapter 2125  The reaction occurs through an addition-elimination mechanism  A Meisenheimer complex, which is a delocalized carbanion, is an intermediate  The mechanism is called nucleophilic aromatic substitution (S N Ar)  The carbanion is stabilized by electron-withdrawing groups in the ortho and para positions

26 Chapter 2126 Nucleophilic Aromatic Substitution through an Elimination-Addition Mechanism: Benzyne  Under forcing conditions, chlorobenzene can undergo an apparent nucleophilic substitution with hydroxide  Bromobenzene can react with the powerful base amide

27 Chapter 2127  The reaction proceeds by an elimination-addition mechanism through the intermediacy of a benzyne (benzene containing a triple bond)

28 Chapter 2128  A calculated electrostatic potential map of benzyne shows added electron density at the site of the benzyne  bond  The additional  bond of benzyne is in the same plane as the ring  When chlorobenzene labeled at the carbon bearing chlorine reacts with potassium amide, the label is divided equally between the C-1 and C-2 positions of the product  This is strong evidence for an elimination-addition mechanism and against a straightforward S N 2 mechanism

29 Chapter 2129  Benzyne can be generated from anthranilic acid by diazotization  The resulting compound spontaneously loses CO 2 and N 2 to yield benzyne  The benzyne can then be trapped in situ using a Diels-Alder reaction Phenylation  Acetoacetic esters and malonic esters can be phenylated by benzyne generated in situ from bromobenzene

30 Chapter 2130  Spectroscopic Analysis of Phenols and Aryl Halides Infrared Spectra  Phenols show O-H stretching in the cm -1 region 1 H NMR  The position of the hydroxyl proton of phenols depends on concentration  In phenol itself the O-H proton is at  2.55 for pure phenol and at  5.63 for a 1% solution  Phenol protons disappear from the spectrum when D 2 O is added  The aromatic protons of phenols and aryl halides occur in the  7- 9 region 13 C NMR  The carbon atoms of phenols and aryl halides appear in the region 

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