chapter 14
TRANSCRIPT
Chapter 14: Benzene ChemistryTable of Contents
Chapter 14: Benzene Chemistry....................................................................................5914.1 Naming Substituted Benzene................................................................................5914.2 Electrophilic Addition: It Can Happen to Benzene!............................................6214.3 Electrophilic Aromatic Substitution.....................................................................6314.3.1 General Reaction and Mechanism....................................................................6314.3.2 Halogenation.....................................................................................................6514.3.3 Nitration............................................................................................................6614.3.4 Sulfonation........................................................................................................6814.4 Directing Effects of Monosubstituted Benzene....................................................7014.4.1 Ortho/Para Directing Effect of the R Group.....................................................7014.4.2 Ortho/Para Directing Effect of the X Group.....................................................7314.4.3 Meta Directing Effect of the Z Group..............................................................7614.5 Directing Effect Rules in Disubstituted Benzene.................................................7814.6 Friedel-Crafts Alkylation......................................................................................8014.7 Friedel Crafts Acylation.......................................................................................8614.7.1 Synthesis of Linear Alkylbenzenes..................................................................8714.7.2 Carboxylation of Phenols.................................................................................8814.8 Electrophilic Aromatic Substitution of Polycyclic and Heterocyclic Aromatics. 8914.9 Reactions of the Alkyl Group in Alkylbenzenes..................................................9014.9.1 Radical Bromination.........................................................................................9114.9.2 Side Chain Oxidation........................................................................................9314.10 Diazonium Salts: Synthesis and Chemistry.......................................................9414.10.1 Synthesis of Diazonium Salts.........................................................................9414.10.2 Azo Dye Synthesis..........................................................................................9414.10.3 Sandmeyer Reaction.......................................................................................9614.10.4 Other Nucleophilic Substitution Reactions....................................................9614.11 Nucleophilic Aromatic Substitution...................................................................9714.12 Benzynes: Synthesis and Chemistry..................................................................98Chapter 14 Exercises..................................................................................................100Answers to Chapter 14 Exercises...............................................................................106
Chapter 14: Benzene Chemistry
14.1 Naming Substituted Benzene If a benzene ring has only one substituent (monosubstituted), the compound may be named as the substituent prefix followed by benzene:
However, common names are often used for the following monosubstituted benzenes (Fig. 14.1). The functional group basis for the name is automatically position #1.
Figure 14.1 Common Names for Monosubstituted Benzenes.
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On disubstituted benzene, the groups can be named with either position number + prefix name in alphabetical order or with o (ortho) designation for 1,2-disubstituted, m (meta) for 1,3-disubstituted, and p (para) for 1,4-disubstituted:
Examples
There are even a few important common names for disubstituted benzenes (Fig. 14.2). The functional group basis for the name is automatically the lowest numbered positions.
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Figure 14.2 Common Names for Some Disubstituted Benzenes.
For tri- and tetrasubstituted benzenes, only numbers give the positions of the groups, which are placed in alphabetical order:
Finally, for substituted biphenyl, each ring is numbered differently. One ring has numbers 1-6 and the other has numbers 1'-6' (read as "one prime to six prime").Only use 1'-6' when necessary:
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14.2 Electrophilic Addition: It Can Happen to Benzene! As you read in Chapter 13, even though they contain C=C bonds, benzene and other aromatic compounds do not easily perform the addition reactions of typical alkenes. However, this does not mean addition to benzene is impossible! For example, in the presence of air and nutrient broth, a strain of the bacterium Pseudomonas putida adds two adjacent OH groups onto benzene in a syn (same side) orientation (Scheme 14.1):
Scheme 14.1 Syn-1,2-dihydroxylation of benzene catalyzed by P. putida
OH
OH
P. putida
O2, broth
(You'll read more about electrophilic addition to benzene to make single enantiomers of 1,2-diols later.) Thus, benzene's stability doesn't make electrophilic addition impossible. But with the exception of adding O or H atoms under special conditions, addition to aromatic compounds does not occur. For example, Br2 will react with benzene in the presence of the catalyst FeBr3, but you get substitution of one hydrogen by one Br atom instead of addition of both Br atoms (Scheme 14.2):
Scheme 14.2
Br2, FeBr3 (cat.)
H
H
H
H
H
H
Br
H
H
H
H
H
H
H
H
H
H
H
Br
Br
+ HBr
If you calculate the free energy of bromine addition to benzene, Go is positive, so addition of Br2 to benzene will not happen. But for bromine substitution, Go is negative, so this reaction will occur.
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14.3 Electrophilic Aromatic Substitution
14.3.1 General Reaction and Mechanism
When benzene and other aromatic compounds react with an electrophile (E+), the electrophile substitutes for a proton (H+) attached to the aromatic ring (Scheme 14.3). This reaction is called electrophilic aromatic substitution.
Scheme 14.3 General Reaction of Electrophilic Aromatic Substitution
The accepted mechanism of the reaction is shown below (Scheme 14.4):
Scheme 14.4 General Mechanism of Electrophilic Aromatic Substitution
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For clarity, the benzene picture in Scheme 14.4 has individual double bonds, even though we know better. In the first step, the electrophile, looking for a source of electrons, attacks the electrons in benzene. Destruction of the aromaticity costs about 36 kcal/mol, which is why this step is slow and why the electrophile has to be more reactive than the ones that attack simple alkenes. The intermediate is called an arenium ion, which is a resonance-stabilized carbocation. Since the first step of the reaction is rate-determining, the rate expression for electrophilic aromatic substitution is:
Rate = k [ArH] [E+]
[ArH] is the concentration of the aromatic compound and [E+] is the concentration of the electrophile. In the second step, Y-, the conjugate base of the electrophile, always removes the proton from the same carbon that E+ is attached to, reforming the benzene ring. Since benzene is so stable and easy to make, the second step is the fast step of the mechanism. The concentration of Y- has no effect on the overall rate of the reaction because is involved in the fast step. Scheme 14.5 depicts the reaction energy diagram of electrophilic aromatic substitution.
Scheme 14.5 Reaction Energy Diagram of Electrophilic Aromatic Substitution
Now we will examine several important examples of electrophilic aromatic substitution. ALL of these reactions use the same mechanism shown in Scheme 14.4. The only difference is how we make the electrophile itself, which will involve the catalyst for the reaction.
Progress of reaction
Energy H
H
H
H
H
HE Y
H
H
H
H
H
H
E
E
H
H
H
H
H
+ HY
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14.3.2 Halogenation
Halogenation of benzene is defined as the substitution of H on a benzene ring (or other aromatic ring) by Cl, Br, or I. Direct reaction of benzene with F2 is useless because fluorine is too reactive. The overall reactions of chlorination and bromination are shown in Scheme 14.6:
Scheme 14.6
In halogenation, the electrophile E+ = Cl+, Br+, or I+. For chlorination (E+ = Cl+) and bromination (E+ = Br+), the catalyst that forms the electrophile is either FeCl3 or just Fe, since Fe will spontaneously react with Cl2 (eq. 1) and Br2 (eq. 2) to make the catalysts FeCl3 and FeBr3, respectively:
(1) 2Fe + 3Cl2 → 2FeCl3 (2) 2Fe + 3Br2 → 2FeBr3
The mechanism of chlorination and bromination requires formation of Cl+ or Br+ by the catalyst, then reaction of the electrophile with the aromatic ring. Since both chlorination and bromination work exactly the same way, only the mechanism of chlorination will be illustrated (Scheme 14.7):
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Scheme 14.7
Cl
H
H
H
H
H
+ HCl
H
H
H
H
H
H
Cl
H
H
H
H
H
H
Cl
arenium ion
slow fast
Cl FeCl3 Cl FeCl3
Cl Cl FeCl3Cl Cl FeCl3 Cl Cl FeCl3
+ FeCl3
MAKING Cl :
SUBSTITUTION STEPS:
For iodination (E+ = I+), the catalyst is HNO3, nitric acid. It is suspected that I+ is formed by oxidation of I2 by nitric acid.Because the true nature of the electrophile in iodination is unknown, only the overall reaction is shown below (Scheme 14.8):
Scheme 14.8
H
H
H
H
H
I
H
H
H
H
H
+ HIHNO3 (cat.)
I I
IODINATION:
14.3.3 Nitration
Nitration is defined as the substitution of H on a benzene ring (or other aromatic ring) by NO2 (nitro) (Scheme 14.9):
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Scheme 14.9
H
H
H
H
H
H
NO2
H
H
H
H
HH2SO4
NITRATION:
N
O
O
OH
In nitration, the electrophile E+ = NO2
+. NO2+ comes from the reaction of nitric acid
(HNO3) with the catalyst sulfuric aid (H2SO4). NO2+ then reacts with benzene in the
standard two-step substitution mechanism (Scheme 14.10).
Scheme 14.10
H
H
H
H
H
+
H
H
H
H
H
H
H
H
H
H
H
H
arenium ion
slow fast
MAKING NO2 :
SUBSTITUTION STEPS:
N
O
O
OH S
O
O
O
H N
O
O
OH2 N
O
O
H2O
S
O
O
OS
O
O
O +
N
O
O
S
O
O
O N
O
O
S
O
O
O NOO
S
O
O
O
H
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14.3.4 Sulfonation
Sulfonation is defined as the substitution of H on a benzene ring (or other aromatic ring) by SO3H (sulfonic acid) (Scheme 14.11):
Scheme 14.11
In sulfonation, the electrophile E+ = +SO3H. +SO3H comes from the reaction of sulfur trioxide (SO3) with the catalyst sulfuric acid (H2SO4). This mixture is called fuming sulfuric acid. +SO3H then reacts with benzene in the standard two-step substitution mechanism (Scheme 14.12).
Scheme 14.12
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Sulfonation is reversible. This means that reacting benzenesulfonic acid with steam will form benzene and sulfuric acid in a process called desulfonation (Scheme 14.13):
Scheme 14.13
The mechanism of desulfonation is the reverse of sulfonation: first you attach H+, then you knock off SO3H (Scheme 14.14):
Scheme 14.14
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14.4 Directing Effects of Monosubstituted Benzene When benzene has one substituent attached to the ring, it is called monosubstituted benzene. This substituent will direct where an incoming electrophile will preferentially attack the benzene ring. There are three kinds of substituents:
1. R (C with single bonds, C=C, C≡C)2. X (an atom with one or more lone pairs, e.g., N, O, F, Cl, Br, and I)3. Z (an atom with full positive charge or large partial positive charge, e.g., C in
CCl3, N in NO2, S in SO3H, C in C=O, and C in C≡N) To understand this directing effect, you must always heed this rule:
The electrophile will most quickly make the most stable arenium ion.
14.4.1 Ortho/Para Directing Effect of the R Group
When monosubstituted benzene has an R group, the electrophile is directed mostly ortho and para to the R group (Scheme 14.15):
Scheme 14.15
The arenium ion that you get when E+ attaches to the ortho or para position is more stable than when E+ attaches to the meta position. The Reason: When E+ attaches ortho or para to an R group, the positive charge can resonate to a 3o
position (Scheme 14.16):
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Scheme 14.16
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However, when E+ attaches meta to an R group, the positive charge can only resonate to the less stable 2o positions (Scheme 14.17):
Scheme 14.17
Example
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14.4.2 Ortho/Para Directing Effect of the X Group
When monosubstituted benzene has an X group, the electrophile is directed mostly ortho and para to the X group (Scheme 14.18). Except for the halogens (F, Cl, Br, I), the X group is electron-releasing, making the benzene ring more reactive to electrophiles than benzene itself. The halogens make the benzene ring less reactive to electrophiles than benzene by itself. OH and NH2 make the ring so reactive that halogenation occurs without any catalyst and at EVERY available ortho and para position:
Scheme 14.18
The arenium ion that you get when E+ attaches to the ortho or para position is more stable than when E+ attaches to the meta position. The Reason: When E+ attaches ortho or para to an X group, the arenium ion will be stabilized by four resonance structures (Scheme 14.19).
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Scheme 14.19
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However, when E+ attaches meta to an X group, the arenium ion will be stabilized by only three resonance structures (Scheme 14.20):
Scheme 14.20
Example
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14.4.3 Meta Directing Effect of the Z Group
When monosubstituted benzene has a Z group, the electrophile is directed almost exclusively meta to the Z group (Scheme 14.21). The Z group is an electron-withdrawing group. The Z group makes the benzene ring react more slowly to electrophiles than benzene would react by itself.
Scheme 14.21
The arenium ion that you get when E+ attaches to the meta position is more stable than when E+ attaches to the ortho or para position. The Reason: When E+ attaches meta to the Z group, the positive charge never resonates next to the already positive Z group. This makes the arenium ion more stable (Scheme 14.22):
Scheme 14.22
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However, when E+ attaches ortho or para to the Z group, the positive charge resonates to the already positive Z group. This makes the arenium ion less stable (Scheme 14.23):
Scheme 14.23
Example
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14.5 Directing Effect Rules in Disubstituted Benzene If there are two substituents on a benzene ring, follow these three rules to predict the major position of attack by an electrophile: Rule 1: When ortho/para-directing groups (X, R) compete, because of resonance, X directs more strongly than R, except for the halogens. R is a stronger director than any halogen. Both X and R groups are stronger directors than meta-directing (Z) groups:
Order of Influence:
A mnemonic: X-Ray Zach's Right Hand
for X beats R, which beats Z, and R beats Halogens.
Examples
Examples (cont.)
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Rule 2: When two groups are meta to each other, because of the tight fit (steric effect), an electrophile is less likely to come between these groups than to attach to another directed site.
Example
Under Rule 1, see Example (c). Rule 3: When Z groups are meta to X or R groups, the incoming electrophile will attack mostly ortho to the Z group rather than para. This is known as the ortho effect.
Example
Under Rule 1, see Example (c).
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14.6 Friedel-Crafts Alkylation Friedel-Crafts alkylation is defined as the substitution of H on a benzene ring (or other aromatic ring) by an alkyl group (Scheme 14.24). In Friedel-Crafts alkylation, the electrophile E+ = +CR3 (carbocation), where R can be H or C (Scheme 14.24):
Scheme 14.24
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The carbocation is usually made in one of three ways:
1. Reaction of an alkyl halide with a Lewis acid catalyst, typically AlCl3. In terms of reactivity, F > Cl > Br > I (Scheme 14.25).
Scheme 14.25
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2. Reaction of an alkene with strong acid, e.g., H2SO4 (Scheme 14.26):
Scheme 14.26
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3. Reaction of an alcohol with a strong acid, e.g., H2SO4 (Scheme 14.27):
Scheme 14.27
As with ALL electrophiles, the reaction of the carbocation with the benzene ring follows the same two-step mechanism (see substitution steps in Scheme 14.27).
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Once the carbocation is made, it is very picky about the kind of benzene it likes. Only plain benzene or benzene "flavored" with X or R groups are acceptable. Carbocations dislike the "taste" of benzenes with Z groups. Why? As electrophiles go, carbocations are somewhat wimpy, so they only react with reasonably reactive benzenes. In addition, NH2 and NR2 (where R is an alkyl group) don't work for Friedel-Crafts alkylation because the catalyst turns them into Z groups (Scheme 14.28):
Scheme 14.28
N attached to C=O (amide) is an excellent group for Friedel-Crafts reactions, because resonance of the lone pair of N into C=O keeps N from binding to the catalyst and turning into a Z group (Scheme 14.29):
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Scheme 14.29
Another important note about the carbocations for Friedel-Crafts reactions: DO NOT pick ones that undergo rearrangement (hydride or carbon shifts). For example, if you try to make n-propylbenzene with 1-chloropropane, AlCl3, and benzene, you'll mostly get isopropylbenzene because the propyl cation will rearrange to the more stable isopropyl cation (Scheme 14.30):
Scheme 14.30
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We can't make n-propylbenzene directly by Friedel-Crafts alkylation, but n-propylbenzene and longer, linear alkylbenzenes can be made in a two-step process described in the next section.
14.7 Friedel Crafts AcylationFriedel-Crafts Acylation is defined as the substitution of H on a benzene ring (or other aromatic ring) by an acyl or RC=O group (Scheme 14.31). In Friedel-Crafts acylation, the electrophile E+ = [RC=O]+ (acylium ion), where R = alkyl, C=C, or C≡C. AlCl3 is a typical catalyst, and leaving groups include Cl (from acid chlorides) and O(C=O)R (from acid anhydrides). Scheme 14.31
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Friedel-Crafts acylations have two of the same restrictions as Friedel-Crafts alkylations:1. The benzene ring cannot have a Z group.2. The benzene ring cannot have an NH2 or NR2 group.
However, in contrast to Friedel-Crafts alkylations, the R in RC=O can be a long alkyl chain because acylium ions do NOT rearrange; they are too stable for that.
14.7.1 Synthesis of Linear Alkylbenzenes
As previously stated, acylium ions do not rearrange like their alkyl cousins. Thus, linear alkyl benzenes can be made by Friedel-Crafts acylation followed by reduction of C=O in the ketone to CH2 (Scheme 14.32): Scheme 14.32
There are various ways to reduce C=O in a ketone to CH2 (Table 14.1): Table 14.1. Reduction Methods (C=O in Ketones to CH2)Name of Reaction ReagentsWollf-Kishner* N2H4 (hydrazine), KOH, heatClemmensen* Zn-Hg, HCl*Both reactions also reduce C=O in aldehydes, but not in carboxylic acids or amides.
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14.7.2 Carboxylation of Phenols
There are two ways to put CO2H directly onto a phenol. The most important method is the Kolbe-Schmitt reaction, in which CO2 in the presence of sodium or potassium phenoxide selectively carboxylates the ortho position, producing the salt of salicylic acid, the precursor to aspirin (acetylsalicylic acid):
To selectively carboxylate the para position of sodium or potassium phenoxide, use potassium carbonate and CO:
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14.8 Electrophilic Aromatic Substitution of Polycyclic and Heterocyclic Aromatics Two principles govern electrophilic aromatic substitution on polycyclic and heterocyclic aromatics:
1. Attach the electrophile where you get the most resonance stabilization of positive charge.
2. Resonance stabilization of positive charge should not have to sacrifice aromaticity in another ring.
Example: Bromination of Naphthalene
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Example: Bromination of Furan
14.9 Reactions of the Alkyl Group in Alkylbenzenes In an alkylbenzene, the position on the alkyl chain next to the benzene ring is called benzylic (Fig. 14.3). The benzylic position is also the position (alpha) to the benzene ring.
Figure 14.3 Benzylic Position in Alkyl Benzene.
This is the only reactive position on the alkyl chain. There are two common reactions performed at the benzylic position:
1. Radical bromination2. Side chain oxidation.
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14.9.1 Radical Bromination
Radical bromination at the benzylic position involves substitution of an H by Br (Scheme 14.33): Scheme 14.33
A tiny amount of bromine is originally generated by the reaction of N-bromosuccinimide (NBS) with a trace amount of HBr. A radical initiator (ROOR) stimulates bromine radical formation. In the mechanism (Scheme 14.34), benzoyl peroxide (a source of ROOR) decomposes with heat to form carbon dioxide and a phenyl radical. The phenyl radical breaks the weak Br-Br bond, initiating bromine radical formation. The bromine radical next abstracts a benzylic hydrogen atom, producing a benzylic radical and HBr. The benzylic radical makes the final product by breaking another Br-Br bond and regenerating a bromine radical. The HBr formed is used to generate Br2 from NBS.
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Scheme 14.34
Bromination only occurs at the benzylic position. The reason for this extreme selectivity is that a resonance-stabilized radical is formed when the benzylic C-H bond is broken (Fig.14.4): Figure 14.4 Resonance stabilization of the benzylic radical.
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14.9.2 Side Chain Oxidation
In the presence of potassium permanganate (KMnO4) in aqueous acid, the alkyl side chain is oxidatively cleaved to a carboxylic acid group (CO2H) (Scheme 14.35):
Scheme 14.35
There must be at least one hydrogen at the position for the reaction to work (Scheme 14.36):
Scheme 14.36
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14.10 Diazonium Salts: Synthesis and Chemistry
14.10.1 Synthesis of Diazonium Salts
Diazonium salts are very valuable, particularly for the manufacture of dyes. The preparation of diazonium salts is a two-step process (Scheme 14.37): Scheme 14.37
The first step is the reduction of a nitrobenzene to aniline. The second step is the oxidation of the NH2 to the diazonium salt using nitrous acid (HNO2). An ice-cold solution of sodium nitrite (NaNO2) dissolved in dilute HCl or H2SO4 is a typical source of nitrous acid. Note: The solution must be kept cold, between 0-5 oC, to prevent the decomposition of the diazonium salt.
14.10.2 Azo Dye Synthesis
Once you have a diazonium salt solution, you can convert it into an azo dye. Azo dyes contain the N=N (azo) group. Azo dyes are made by an electrophilic aromatic substitution reaction between aniline or phenol and the diazonium salt as the electrophile (Scheme 14.38):
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Scheme 14.38
(As an electrophile, diazonium salts are incredibly weak; they only react with anilines and phenols.) Below are some examples of azo dyes used as biological stains:
Amido black 10B Orange G(used to stain the proteins collagen and reticulin)
(used to stain cells in the pancreas and pituitary gland)
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14.10.3 Sandmeyer Reaction
Diazonium salts can also perform nucleophilic substitution reactions in which N2 gas is the leaving group. When the nucleophiles are Cl, Br, or CN, a copper (I) salt is employed. These substitutions are called Sandmeyer reactions (Scheme 14.39):
Scheme 14.39
14.10.4 Other Nucleophilic Substitution Reactions
In addition to Sandmeyer reactions, nucleophilic displacement of N2 gas from diazonium salts can occur under a variety of other conditions to yield fluorobenzene, iodobenzene, and phenol (Scheme 14.40):
Scheme 14.40
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14.11 Nucleophilic Aromatic SubstitutionNucleophilic aromatic substitution is defined as the displacement of a leaving group (a departing nucleophile) from an aromatic ring by a nucleophile. Previously, we noted that diazonium salts will perform this reaction under various conditions. Benzene compounds containing NO2 ortho or para to a leaving group (F, Cl, Br, or I) will also undergo substitution. An example is the synthesis of p-nitroaniline from p-chloronitrobenzene (Scheme 14.41):
Scheme 14.41
If you take away the nitro group, there will be no reaction. You need the nitro group to stabilize the negative charge in the intermediate, which quickly decomposes to product (Scheme 14.42):
Scheme 14.42
For nucleophilic aromatic substitution, the typical leaving group order (best to worst, left to right) is F, Cl, Br, and I. The reason for this order is that the first step in the mechanism is rate-determining. This means that the more partial positive the attacked carbon is, the more likely the nucleophile will "stick," and the faster the reaction will be.
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14.12 Benzynes: Synthesis and ChemistryBenzyne is a strange creature. The reaction of fluoro-, chloro-, bromo-, or iodobenzene with sodium amide (NaNH2) produces benzyne (Scheme 14.43):
Scheme 14.43
Is that really a C≡C in the ring? No. The so-called "triple" bond acts like +C=C-. Benzyne reacts as a powerful dienophile in Diels-Alder reactions and also combines with nucleophiles (Scheme 14.44): Scheme 14.44
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For substituted benzenes, the preferred resonance character of benzyne will put the negative charge closest to a highly electronegative groups (F, Cl, Br, OR, NO2, etc.) and
the negative charge furthest away from electron-rich groups (C, CO2-, O
-) (Scheme
14.45):
Scheme 14.45
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Thus, we can predict the major products of nucleophilic addition to benzynes (Scheme 14.46):
Scheme 14.46
Chapter 14 Exercises
1. Name each of the following compounds:
2. Draw each of the following compounds:
a. m-nitrophenolb. 4-methylresorcinolc. o-cyanobenzoic acidd. 2,4,6-trichloroanilinee. p-isopropylbenzenesulfonic acidf. 2,3,5,6-tetrachlorohydroquinoneg. 2,6-diethyl-4'-nitro-1,1'-biphenyl
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3. Predict the major product(s) of each of the following reactions. Part 1:
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Part 2:
102
4. Starting with benzene, propose a reasonable synthetic route to each of the following compounds:
5. a) Starting with acetanilide, propose a reasonable synthetic route to the analgesic
(painkiller) and anti-inflammatory agent, Tylenol®. b) What is the chemical name of Tylenol®?
6. Ibuprofen (found in Advil®, Nuprin®, Motrin®) is an analgesic (painkiller) sold as a racemate (50:50 mixture of R and S enantiomers). However, only (S)-ibuprofen
actually blocks pain. Starting with (S)-2-phenylpropionic acid, propose a plausible synthetic route to (S)-ibuprofen:
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7. Write a plausible mechanism for each of the following transformations:
8. Why is compound A formed, but NOT compound B?
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9. Why is compound C formed, but not compound D?
10. Why is compound E the major product?
11. Predict the major product of the reaction of indole with N-methyl-N-methylenemethanaminium chloride (1), and EXPLAIN your prediction based on the stability of the reaction intermediate.
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Answers to Chapter 14 Exercises
1.a. 2-bromo-4-methylanisole or 3-bromo-4-methoxytolueneb. 3-nitrobenzenesulfonic acid or m-nitrobenzenesulfonic acidc. 1,3-dimethyl-5-tert-butylbenzene or 5-tert-butyl-m-xylened. 2-fluoro-4-iodo-1-nitrobenzenee. 2,4,6-trichloro-4'-cyclopentyl-1,1'-biphenyl 2.
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3. Part 1:
107
Part 2:
108
4.
109
5. a.
b. p-hydroxyacetanilide or 4-hydroxyacetanilide 6.
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7.
111
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8. Compound A is formed because the C-F bond is broken much more rapidly by AlCl3
than the C-Cl bond. 9. The leaving group must be ortho or para to NO2 for nucleophilic aromatic substitution to occur. The Cl which is not displaced is inert to this reaction because it is meta to NO2. 10. When benzyne is formed in the first step, the major resonance form places negative charge as far away as possible from the phenyl group, because phenyl is electron-rich. Thus, the - charge is para and the + charge is meta, so H+ attaches para and Br- attaches meta. 11.
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