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CHM 2120 Assignment 4 Reactions of aromatic compounds ANSWERS In this assignment: - Electrophilic aromatic substitution - Manipulation of products of aromatic

ic substitution - Acidity/basicity is affected by aromaticity and substituents on aromatic rings - Synthesis of benzene derivatives 1. Show how you would synthesize each of the following monosubsituted benzenes: a. Nitrobenzene
HNO 3 H 2SO4 NO2

b. Chlorobenzene
Cl2 FeCl3 Cl

c. Methylbenzene (toluene)
MeCl AlCl3 CH 3

d. Isopropylbenzene (2 ways)
n-PrCl OR i-PrCl AlCl3

e. Acetylbenzene (acetophenone)
O Cl AlCl3 O

ANSWERS - Assignment 4 Reactions of aromatic compounds 2. Give the product expected or reagents required for each of the following reactions. Clearly justify the formation of the major product. Note: you could be asked on the test to support your answer with a mechanism and any relevant resonance structures as shown in class.
a) O Br 2 FeBr 3 Br OMe is an o,p-director b) NO 2 Br 2 FeBr3 Br c) Br HNO 3 H2 SO4 O 2N AlCl3 CH 2Cl2 (inert solvent) O i-Pr is an o,p-director but sterics hinder the formation of the o-substituted product H2 Pd/C Br Br NO 2 Br is an o,p-director (even though it's a deactivating group) NO 2 NO2 is a m-director O O Br

d) O

Cl

e)

f)

NBS ROOR heat

Br

just like an allylic bromination, but this is a benzylic bromination instead

ANSWERS - Assignment 4 Reactions of aromatic compounds 3. Give the major product(s) that would be obtained when each of the following compounds is subjected to Br2 and FeBr3:
Br a. Ethylbenzene Br

O b. Anisole Br F c. Fluorobenzene Br CO2 H d. Benzoic acid

O Br

F Br

Br NO2 e. Nitrobenzene Br

ANSWERS - Assignment 4 Reactions of aromatic compounds 4. When benzene is reacted with 1-chloropropane and aluminum trichloride, a mixture of n-propylbenzene and isopropylbenzene is obtained. Explain by drawing the mechanism for the reaction.
Cl AlCl3 major H H Cl AlCl3 H 3C Cl AlCl3 f ast rearrangement slower intermolecular reaction B = ClH :B H H 3C C H2 H + Cl-AlCl3

H B: H CH 3 C H CH 3 H H minor CH 3 C H CH 3 H major

5. Draw a mechanism for the following transformation:


H+ OH CH3 SO3H

O H

H B:

B = - OSO2 CH 3

ANSWERS - Assignment 4 Reactions of aromatic compounds 6. What is the monobromination product expected from the reaction of the following molecules with Br2 and FeBr3?
activates the left-hand phenyl ring a) O O b) deactivates the ring on the right substitution occurs on the more activated ring and bromine adds primarily to the para position (ortho position is hindered by the substituent)

Br O O Br O O

H N O

H N Br O

H N

Br

O deactivated by the activated by the carbonyl lone pair on the group nitrogen

7. Explain the regioselectivity of following transformation by drawing the mechanism for the formation of the indicated product. Note: This question required that the regioselectivity (where the substituent is added) be explained, as well as the formation of the tert-butyl substituent via rearrangement.
sterically hindered o-position MeO Cl strong o, p-director, but the para position is blocked by the alkyl group--reaction occurs at the least sterically hindered ortho position. p-position is blocked Cl H least-hindered o-position AlCl3 AlCl3 MeO

C H2

MeO

MeO

H B:

ANSWERS - Assignment 4 Reactions of aromatic compounds 8. Once substituted benzenes have been synthesized (by electrophilic aromatic substitution reactions or other methods), they can be modified to generate new products. Identify either the required reagents or the expected products in the following examples.
O a) Zn(Hg) HCl b) NO 2 Sn HCl Br c) NBS ROOR d) Br e) identical to allylic bromination CO 2H NH 2

1. KMnO 4, NaOH, heat 2. H 3O+ NaCN (S N2) CN

f)

CH 3

NBS ROOR

H2 C

Br identical to allylic bromination

g)

SO 3H

NaOH heat

OH

9. Which of the following aromatics would react most rapidly and which would react most slowly with Br2/FeBr3? Justify your answer and predict the structure of the major product.
CO2H OMe H 3C 1 SAG 1 SAG + 1 WAG fastest reaction Ranking: 2 (not required in this case) 1 4 3 5 1 WAG + 1 SDG OCH 3 CO 2H Cl 1 SAG + 1 WDG O NO 2 2 SDG's slowest reaction

SAG = strong activating group WAG = weak activating group SDG = strong deactivating group WDG = weak deactivating group

The more activating groups, the faster the reaction. The more deactivating groups, the slower the reaction. "Strong" groups have a greater effect than "weak" groups.

OCH3 H3C Br

Both original substituents are o,p-directors, but the OCH3 has a greater effect than the CH 3, hence the major product shown.

MAJOR product

ANSWERS - Assignment 4 Reactions of aromatic compounds

10. Consider the reaction of nitrobenzene with Br2/FeBr3. Why is the meta product the major product of this reaction?
NO2 Br 2 FeBr3 Br FeBr 3 Br major product Br NO2

NO2 meta H Br vs H H

NO2 H Br ortho (same explanation as with the para product)

NO2 H Br H

NO2 H Br O N H Br

NO2 H

two positive charges side by side = destabilizing (BAD)

Br H positive charge is never directly adjacent to the NO 2 group = better, more stable the transition state of this r.d.s. (leading to the m eta intermediate) is lower in energy than those leading to the o and p-intermediates and therefore this intermediate forms faster. This gives the m eta product as the major one.

11. Aniline is much less basic than dimethylamine. Why?


NH 2 H N

NH2

The lone pairs on the N in the aniline are involved in resonance with the ring. They are less available to react in an acid/base reaction than those on the dimethylamine (no resonance).

ANSWERS - Assignment 4 Reactions of aromatic compounds 12. Which of the following phenols is most acidic? Why?
Both acids are phenols--can't use pKa differences and so a comparison of bases must be made. DRAW both the conjugate bases of the phenols BEFORE doing the explanation. OH OH

O Both conjugate bases are stabilized by resonance with the aromatic ring, however only the phenoxide (c.b. of the phenol) with the acetyl (Ac) group in the para position is additionally stabilized by resonance with the carbonyl group. Stabilization of the negative charge by resonance with the carbonyl group in the meta position is not possible (verify this by drawing resonance structures).

ANSWERS - Assignment 4 Reactions of aromatic compounds 13. Why are two of the following molecules aromatic and one is not?
in a "p" orbital CH 3 - ring is planar - all ring atoms are sp2 - 6 pi electrons = 4n + 2 n=1 the ring is aromatic CH3 H3 C CH3 C sp2 but empty - ring is planar - all ring atoms are sp2 - 6 pi electrons = 4n + 2 n=1 the ring is aromatic

- ring is planar - all ring atoms are sp2 - 4 pi electrons = 4n + 2 n = 0.5 X the ring is not aromatic CH3 p orbital is empty

14. Propose a synthesis of each of the following disubstituted benzenes starting with benzene and any other reagents that are necessary to complete the task. Your proposal should give the desired product as the major product. Note: The order of reactions is important in order to obtain the correct substitution pattern.
a. 1-ethyl-4-nitrobenzene

EtCl AlCl3

HNO3 H2 SO4 NO2

b. 1-amino-3-ethylbenzene (m-ethylaniline) HNO 3 H 2SO 4 NO2 EtCl AlCl3 NO2 Sn HCl NH 2

c. 1-acetyl-4-methoxybenzene (p-acetylanisole) SO3 H SO3 H2 SO4 NaOH heat OH NaOH CH 3 I (deprotonation, then SN 2) OMe AcCl AlCl3 O OMe

ANSWERS - Assignment 4 Reactions of aromatic compounds


d. p-Methylbenzoic acid MeCl AlCl3 Br 2 FeBr3 Br Grignard reaction-to be covered later in the course Note: this reaction was done in the CHM 1321 lab. 1. Mg 2. CO2 3. H3 O+ CO2 H Br

e. 1-(bromomethyl)-4-nitrobenzene (or p-nitrobenzyl bromide) MeCl AlCl3 HNO3 H2 SO4 NO2 f. 1,3-diaminobenzene NO2 HNO 3 H 2SO 4
g. O Cl AlCl3 Note: F-C alkylation can't be used because it would give a rearrangement product O Br2 FeBr 3 Br O

NBS Dibenzoyl peroxide NO2 NH2 Sn HCl NH2

NO 2

Zn(Hg) HCl Br

h. O Cl AlCl3 Note: F-C alkylation can't be used because it would give a rearrangement product H 2N O Sn, HCl HNO3 H2SO4 O2 N Sn, HCl OR H2 , Pd/C

15. Propose a synthesis of each of the following molecules starting with benzene and using any other reagents that are necessary to complete the task. Your proposal should give the desired product as the major product and a retrosynthetic analysis should be included
Retrosynthesis: a) CN SN2 Br allylic bromination Friedel-Craf ts Alkylation

Synthesis (show the actual reagents that you would use) Br EtCl AlCl3 NBS dibenzoyl peroxide (or another radical initiator) NaCN DMSO CN

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ANSWERS - Assignment 4 Reactions of aromatic compounds


Retrosynthesis: b) O epoxidation Br elimination allylic bromination Friedel-Crafts Alkylation

Synthesis: CH3 CH 2Cl AlCl3 NBS dibenzoyl peroxide

Br KOtBu HOt Bu mCPBA

Retrosynthesis: c) elimination Br allylic bromination Clemmensen reduction Friedel-Crafts Acylation O

Note: Two steps are required to install the n-propyl substituent. Friedel-Crafts alkylation would not successf ully give the n-propylbenzene product--why? Synthesis: O Cl AlCl3 O Zn(Hg) HCl NBS dibenzoyl peroxide Br KOtBu HOt Bu

d) Retrosynthesis: Br bromination NO 2 Synthesis: HNO 3 H 2SO4 NO2 Br 2 FeBr3 NO 2 NO2 nitration

Br

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