Chapter 21 Phenols and Aryl alides Nucleophilic Aromatic Substitution Ch. 21-1
1. Structure and Nomenclature of Phenols Phenol 1-Naphthol (α-naphthol) 9-Phenanthrol Ch. 21-2
1A. Nomenclature of Phenols Cl C 3 N 2 4-Chlorophenol (p-chlorophenol) 2-Nitrophenol (o-nitrophenol) 3-Methylphenol (m-cresol) Ch. 21-3
The benzenediols also have common names 1,2-Benzenediol (catechol) 1,3-Benzenediol (resorcinol) 1,4-Benzenediol (hydroquinone) Ch. 21-4
2. Naturally ccurring Phenols L-Tyrosine + N 3 C 3 C 2 C 3 Methyl salicylate (oil of wintergreen) C 3 Eugenol (oil of cloves) Estradiol Ch. 21-5
3. Physical Properties of Phenols C 3 Phenol Toluene M.W. 94 92 B.P. ( o C) 182 110 Ch. 21-6
4. Synthesis of Phenols 4A. Laboratory Synthesis N 2 N 2 Cu 2, Cu 2+ R N R 2 R e.g. N 2 Cl C 3 1. NaN 2, Cl, 0-5 o C 2. Cu 2, Cu 2+, 2 Cl C 3 Ch. 21-7
4B. Industrial Syntheses ydrolysis of chlorobenzene (Dow Process) Cl 2 Na 350 o C high pressure Na + NaCl + 2 Cl + NaCl Ch. 21-8
From cumene hydroperoxide + 3 P 4 250 o C high pressure (Cumene) 2 95-135 o C + 3 + 50-90 o C (Cumene hydroperoxide) Ch. 21-9
Mechanism Chain initiation Step 1 R + R Ch. 21-10
Step 2 Chain propagation + Step 3 + + Ch. 21-11
Chain propagation + 2-2 2 2 + - 3 + Ch. 21-12
5. Reactions of Phenols as Acids pk a pk a 9.89 2 N 7.15 N 2 3 C 10.17 2 N 3.96 N 2 Cl 9.20 2 N 0.38 N 2 Ch. 21-13
pk a 18 9.89 + 2 + 3 + (N resonance stabilization) Ch. 21-14
+ 3 + + 2 Ch. 21-15
5B. Distinguishing and Separating Question Phenols from Alcohols and Carboxylic Acids If you are given three unknown samples: one is benzoic acid; one is phenol; and one is cyclohexyl alcohol; how would you distinguish them by simple chemical tests? Recall: acidity of > > Ch. 21-16
R + Na R Na (soluble in water) + 2 + Na Na (soluble in water) + Na No Reaction (immiscible with 2 ) Ch. 21-17
+ NaC 3 Na + C 2 (g) + 2 (gas evolved) + NaC3 No Reaction + NaC3 No Reaction Ch. 21-18
6. ther Reactions of the Group of Phenols R R base R R Cl base Ch. 21-19
6A. Phenols in the Williamson Synthesis Na R Na R R R X (X = halides, Ts, Ms) R e.g. 1. Na 2. Br Ch. 21-20
7. Cleavage of Alkyl Aryl Ethers R R conc. X heat R + RX e.g. conc. Cl heat + Cl Ch. 21-21
8. Reactions of the Benzene Ring of Phenols Bromination 3 Br 2 2 Br Br + 3 Br Br (N Lewis acid required for the brominations) Br 2 CS 2, 5 o C + Br Br Ch. 21-22
Nitration 20% N 3 N 2 + 25 o C N 2 (30-40%) (15%) Ch. 21-23
Sulfonation conc. 2 S 4 S 3 25 o C conc. 2 S 4 100 o C conc. 2 S 4 100 o C S 3 Ch. 21-24
Kolbe reaction Na 1. C 2 C 2. 3 + (Salicylic acid) Ch. 21-25
Mechanism Na C C Na tautomerization 3 + Na Salicylic acid Sodium salicylate Ch. 21-26
C R R C 3 C C + (Salicylic acid) Acetylsalicylic acid (Aspirin) Ch. 21-27
9. The Claisen Rearrangement 1. Na 2. Br 200 o C Ch. 21-28
Via a [3,3] sigmatropic rearrangement 2 1 1' 3 2' 3' keto-enol tautomerization Ch. 21-29
10. Quinones - 2 e + 2 e + 2 + ydroquinone p-benzoquinone Ch. 21-30
3 C C 3 + 2 e, + 2 + 3 C C 3 n - 2 e, - 2 + Ubiquinones (n = 6-10) (coenzymes Q) 3 C C 3 3 C C 3 Ubiquinol (hydroquinone form) n Ch. 21-31
1,4-Naphthoquinone C 3 3 Vitamin K 1 Ch. 21-32
11. Aryl alides and Nucleophilic Aromatic Substitution Cl 2 + Na N substitution heat Cl 2 + Na N substitution heat X Nu: X N reaction Ch. 21-33
X X X X X Ch. 21-34
11A. Nucleophilic Aromatic Substitution by Addition Elimination: The S N Ar Mechanism Nucleophilic aromatic substitution can occur when strong electron-withdrawing groups are ortho or para to the halogen atom Cl N 2 + aq. NaC 3 130 o C 3 + N 2 Ch. 21-35
Cl N 2 + aq. NaC 3 130 o C 3 + N 2 N 2 N 2 Cl 2 N N 2 + aq. NaC 3 130 o C N 2 3 + 2 N N 2 N 2 Ch. 21-36
The mechanism that operates in these reactions is an addition elimination mechanism involving the formation of a carbanion with delocalized electrons, called a Meisenheimer intermediate. The process is called nucleophilic aromatic substitution (S N Ar) Ch. 21-37
The S N Ar mechanism Cl Cl N 2 + addition slow N 2 elimination fast + Cl + N 2 N 2 Ch. 21-38
Cl Cl Cl N N N Cl N Ch. 21-39
11B. Nucleophilic Aromatic Substitution through an Elimination Addition Mechanism: Benzyne Cl Na Na 3 + 350 o C Phenol Br N 2 K :N 2 + KBr -33 o C Aniline Ch. 21-40
The benzyne elimination addition mechanism Br Br (-N 3 ) (-Br ) N 2 Benzyne (or dehydrobenzene) N 2 N 2 + N 3 N 2 N 2 Ch. 21-41
* N 2 * Cl K + * N 2 N 2 N 3 50% * elimination addition 50% N 2 Ch. 21-42
CF 3 Cl NaN 2 N 3 (-NaCl) CF 3 N 2 m-(trifluoromethyl)aniline CF 3 Ch. 21-43
X CF 3 > N 2 CF 3 N 2 less stable carbanion CF 3 CF 3 > N 3 more stable carbanion N 2 + N 2 N 2 Ch. 21-44
Benzyne intermediates have been trapped through the use of Diels Alder reactions C C diazotization Anthranilic acid N 3 N N -C 2 -N 2 Benzyne (trapped in situ) Ch. 21-45
11C. Phenylation Et + Br 2 NaN 2 liq. N 3 Et Ch. 21-46
12. Spectroscopic Analysis of Phenols and Aryl alides Infrared spectra (IR) stretching: 3400-3600 cm -1 R X R and R : characteristic absorptions of the benzene rings Ch. 21-47
1 NMR spectra δ (ppm) of pure phenol: 2.55 in CCl 4 (1%) 5.63 δ 0.5 1.0 ppm intramolecular hydrogen bonding Ch. 21-48
Y (Y = or halides) δ 7 9 ppm Ch. 21-49
13 C NMR spectra Y (Y = or halides) δ 135 170 ppm Ch. 21-50
Mass spectra Mass spectra of phenols often display a prominent molecular ion peak, M Phenols that have a benzylic hydrogen produce an M 1 peak that can be larger than the M peak Ch. 21-51
END F CAPTER 21 Ch. 21-52