Transcript Di- and Polysubstitution
Di- and Polysubstitution
Orientation on nitration benzenes.
of monosubstituted Su bstitu ent OCH 3 CH 3 Cl Br COOH CN NO 2 ortho 44 58 70 37 18 19 6.4
meta 4 1 80 80 93.2
para 55 38 30 62 2 1 0.3
ortho + p ara 99 96 100 99 20 20 6.7
meta trace 4 trace 1 80 80 93.2
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Directivity of substituents
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Directivity of substituents
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Di- and Polysubstitution
Two characteristics of a substituent
•
Orientation:
• Certain substituents direct preferentially to ortho & para positions; others to meta positions.
• Substituents are classified as either ortho-para directing meta directing toward further substitution.
or •
Rate
• Certain substituents cause the be greater than that for benzene itself; others cause the rate to be lower.
rate of a second substitution to • Substituents are classified as activating further substitution.
or deactivating toward 22-4
Di- and Polysubstitution
•
-OCH 3 is ortho-para directing.
OCH 3 + HNO 3 OCH 3 NO 2 + OCH 3 + H 2 O CH 3 COOH
•
An isole
o
-N itroanis ole (44%) -COOH is meta directing.
COOH + HNO 3 H 2 SO 4 100°C COOH NO 2 + Ben zoic acid
o-
N itro ben zoic acid (18%) NO 2
p
-N itroanis ole (55%) COOH NO 2 +
m-
N itro ben zoic acid (80%) COOH NO 2
p-
N itro benzoic acid (2%)
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Di- and Polysubstitution Strongly activating Moderately activating Weakly activating Weakly deactivating Moderately deactivating Strongly deactivating N H 2 O N HCR R F : Cl : N HR O N HCAr N R 2 O OCR OH O OCAr OR Recall the polysubstitution in FC alkylation.
Br : I : O CH O CNH 2 O CR N O 2 O COH SO 3 H N H 3 + O COR C N CF 3 CCl 3
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Di- and Polysubstitution
Generalizations:
•
Directivity : Alkyl, phenyl, and all substituents in which the atom bonded to the ring has an unshared pair of electrons are ortho-para directing. All other substituents are meta directing.
•
Activation : All ortho-para directing groups except the halogens are activating toward further substitution. The halogens are weakly deactivating.
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Di- and Polysubstitution. Example
•
The order of steps is important.
CH 3 o,p o,p CH 3 HNO 3 H 2 SO 4 NO 2 COOH K 2 Cr 2 O 7 H 2 SO 4 NO 2
p
-N itroben zoic acid K 2 Cr 2 O 7 H 2 SO 4 m COOH m COOH HNO 3 H 2 SO 4 NO 2
m
-N itroben zoic acid Note the key point: transformation of
o,p
director into
m
director.
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Theory of Directing Effects
The rate of EAS is limited by the slowest step in the reaction.
For almost every EAS, the rate-determining step is attack of E + on the aromatic ring to give a resonance-stabilized cation intermediate .
The more stable this cation intermediate , the faster the rate-determining step and the faster the overall reaction.
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Theory of Directing Effects
The orientation of the subsitution is controlled by the stability of the carbocation being formed by attack of the electrophile. Different carbocations formed depending on position of substitution.
Products are formed under kinetic control. In some cases, equilibrium can be established leading to different products. (FC alkylation)
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Theory of Directing Effects
•
OCH 3 is directing : assume only para attack is shown.
ortho-para attack . Here OCH 3 OCH 3 + N O 2 + slow : OCH 3 : OCH 3 + + OCH 3 : OCH 3 N O 2 fast - H + H (d) + N O 2 H (e) N O 2 H (f) N O 2 + H (g) N O 2 Very stable resonance structure. Why?
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Theory of Directing Effects
•
OCH 3 is directing ; assume meta attack.
OCH 3 slow + N O 2 + OCH 3 + H (a) N O 2 OCH 3 + H (b) N O 2 OCH 3 H fast - H + + N O 2 (c) OCH 3 N O 2 No corresponding very stable resonance structure. o, p preferred!
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Theory of Directing Effects
•
-CO 2 H is directing ; assume meta attack.
COOH + NO 2 + slow COOH COOH COOH (a) H NO 2 (b) H NO 2 (c) H NO 2 fast -H + COOH NO 2
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Theory of Directing Effects
•
-CO 2 H is directing : assume ortho-para attack.
COOH + NO 2 + slow COOH COOH COOH fast -H + H NO 2 (d) H NO 2 (e) The mos t disfavored contribu ting structu re H NO 2 (f) COOH NO 2
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Activating-Deactivating (Resonance)
Any resonance effect , such as that of -NH 2 , -OH, and -OR, that delocalizes the positive charge on the cation has an EAS.
activating effect toward further
Any resonance effect , such as that of -NO 2 , -CN, C=O, and -SO 3 H, that decreases electron density on the ring deactivates the ring toward further EAS.
Next inductive
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Activating-Deactivating (Inductive Effects)
Any inductive effect , such as that of -CH 3 other alkyl group, that releases or electron density toward the ring EAS.
activates the ring toward further
Any inductive effect , such as that of halogen, -NR 3 + , -CCl 3 , or -CF 3 , that decreases density on the ring deactivates electron the ring toward further EAS.
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Activating-Deactivating (halogens)
• •
For the halogens, the inductive and resonance effects run counter to each other , but the former is somewhat stronger.
The net effect is that halogens are deactivating but ortho-para directing.
: Cl + E + : Cl + H E + : Cl H E
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Nucleophilic Aromatic Substitution
Aryl halides do not undergo nucleophilic substitution by either S N 1 or S N 2 pathways.
They do undergo nucleophilic substitutions, but by two mechanisms quite different from those of nucleophilic aliphatic substitution.
•
Nucleophilic aromatic substitutions are far less common than electrophilic aromatic substitutions.
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Benzyne Intermediates (strong base)
When heated under pressure with aqueous NaOH, chlorobenzene is converted to sodium phenoxide.
•
Neutralization with HCl gives phenol.
Cl O Na + Ch loro benzen e + 2 NaOH H 2 O press ure, 300 o C + Sodium ph enoxide NaCl + H 2 O Halogen reactivity: I > Br > Cl > F
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Benzyne Intermediates (strong base)
• •
The same reaction with 2-chlorotoluene gives ortho and meta-cresol.
CH 3 Cl 1 . NaOH , heat, p res sure CH 3 OH + CH 3 2 . HCl, H 2 O 2-Meth ylp henol (
o-
Cresol) OH 3-Methylphen ol (
m-
Cresol) The same type of reaction can be brought about using sodium amide in liquid ammonia. mixture (!) CH 3 CH 3 CH 3 Cl + NaNH 2 NH 3 (l) (-33 o C) + NH 2 4-Methylaniline (
p
-Toluid ine) NH 2 + NaCl 3-Methylanilin e (
m
-Toluidin e)
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Benzyne Intermediates
•
-elimination of HX gives a benzyne intermediate, that then adds the nucleophile to give products.
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Benzyne Intermediates
•
-elimination of HX gives a benzyne intermediate, that then adds the nucleophile to give products.
CH 3 CH 3 Cl H NaNH 2
-elimin ation A b enzyne intermediate
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Benzyne Intermediates But wait, do we believe this crazy idea? We need some evidence….
A B
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Benzyne Intermediates The deuterated fluoride below exchanges the D with solvent ammonia although the deuterated bromide does not. This indicates a relatively rapid exchange process for the fluoro compound.
C next
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Benzyne Intermediates explanation
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Benzyne Intermediates D Get same product Explation next
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Benzyne Intermediates explanation
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Addition-Elimination (nitro groups)
•
When an aryl halide contains electron-withdrawing NO 2 groups ortho and/or para to X , nucleophilic aromatic substitution takes place readily.
Cl O - Na + NO 2 Na 2 CO 3 , H 2 O NO 2 1 0 0 o C NO 2 1-Ch loro-2,4 dinitrobenzen e NO 2 Sodiu m 2,4-din itro ph enoxide
•
Neutralization with HCl gives the phenol.
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Meisenheimer Complex O + N O
•
Reaction involves formation of reactive intermediate called a Meisenheimer complex.
slow , rate d eterminin g Cl + Nu (1 ) NO 2 O + N O Cl Nu NO 2 A Meisenh eimer complex fast (2 ) O + N O Nu + :Cl NO 2 Similar to nucleophilic subsititution on carboxylic acid derivatives.
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