aromatic comp. lec.4

Dr.M_T The 3rd Vision Academy 01156281369

I

Aromatic Compound

I. Applications & Retrosynthesis strategy

I. Limitations of FC Rx.

1. Isomerization of the n-alkyl groups before alkylation;

"Rearrangement to gain more stable carbocation therefore more stable

product"

*This point is applied on alkylation and acylation.

- FC Alkylation;

- Rearrangement!

𝑒𝑥1;


II

*Soln. of the problem "Rearrangement";

- FC Acylation; No Rearrangement occur because the acyl carbocation is

stabilized by resonance.

Rx.

The acylium ion is a highly resonance stabilized cation, having both

carbocation and oxonium ion character.

2. FC Rx. do NOT occur if the benzene ring is deactivated;

"if benzene is attached to a deactivating grp. or -𝑁𝐻2,-𝑁𝑅2 and -NHR

grp."

*Halogen -as a substituent for benzene ring- is slashed from this point;

because it's a special weak deactivator (O, 𝜌 director).

*Reasons;

- Deactivator grp.s make the ring less reactive by making it electron

deficient.


III

- The amino groups, -𝑁𝐻𝟐, -NHR, and -𝑁𝑅2, are changed into powerful

electron-withdrawing groups by the Lewis acids used to catalyze Friedel-

Crafts reactions.

*Notice that activator or deactivator rule is to control the orientation

NOT reactivity.

3. Polyalkylation

*How the polyalkylation occurs?!!!

The first substituted alkyl grp. makes the ring and weakly activated to

accept more alkyl grp. in the controlled positions, so polyalkylation

occur.

*What's the problem?!!!

It's NOT accepted in practical synthesis because the hardness of

extraction the main needed compound, the target of the process".

*Soln. of the problem;

- FC Acylation; no polyacylation

*Reasons;

1. The formed ketone is deactivated so no further acylation can occur.

2. The acyl group (RCO–) by itself is an electron-withdrawing group, and


IV

when it forms a complex with Al𝐶𝑙3 in the last step of the reaction, it

made even more electron withdrawing.

4. No Arylation and vinylation by FC Rx.

*Reasons;

- Aryl and vinylic halides cannot be used as the halide component

because they do not form carbocations readily.

II. Application "Clemmensen Reduction"- (acidic conditions)

*Def.

"FC acylation followed by reduction of the carbonyl group to a

𝐶𝐻2 𝑔𝑟𝑝."

*Target;

- give us much better routes to unbranched alkyl benzenes than do FC

alkylation.

*Rx. in steps;

1. Acylation.

2. Clemmensen Reduction.


V

*Note;

- Zn(Hg) in HCl reduced the C=O into -C𝐻2-

- These reduction methods do not reduce C=C or C≡C nor -C𝑂2H

- To reduce the C=O into -𝐶𝐻2-, Wolff-Kishner Reduction method is

applied but in "basic conditions"; 𝑁𝐻2𝑁𝐻2 / KOH / ethylene glycol

(a high boiling solvent).

- The combination of either one of these methods after a FC acylation

gives the equivalent of alkylation but without the problems and

complications associated with carbocation rearrangements.

- The choice of method should be made based on the tolerance of other

functional groups in the system to the acidic or basic reaction conditions.

- Zinc and hydrochloric acid will also reduce nitro groups to amino

groups.


VI

Q; Using FC& its App., outline how you can prepare 𝛼-Tetralone

starting from benzene?

*The soln. is snipped from the principles of Retrosynthesis, so to simplify

that, you should start from the last step of the Rx. actually, it's the target

you need. Then you can imagine how to divide the structure into many

components that you can link them again using the Rx. you studied

before.

III. Protection of activated grp. & Blocking of activated center

1. Protection

*Why?!

- Highly activated ring's exposed to react in electrophilic substitution Rx.,

such as nitric acid, are also strong oxidizing agents.

- 𝑁𝐻2& OH activate the ring toward oxidation.


VII

*Soln. of the problem;

- Protection can hide the group we need to exist even the desired Rx.

occurs.

- Strategy is resided into the concept of activator& deactivator grp.s

to control the orientation of the Rx. to gain the desired product.

- used grp. for protection process, must be;

1. Involved in reversible Rx. to allow reducing it again from the structure.

2. grp. that can invert the nature of the protected grp.


VIII

2. Blocking; used to block an attacked position forcing the grp. to be

substituted in a desired position that was a neglected position for the grp.

at first.

- used grp. for protection process, must be;

1. Involved in reversible Rx. to allow reducing it again from the structure.

2. Reversible in activating effect to the positioned grp.

*Blocking occurs during the Rx.

I. Alkylbenzene & Aryl Halides

- Preparation

*Alkylbenzene; FC Alkylation

*Aryl benzene;

1. Halogenation of arene "Direct"


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2. Sandmeyer Rx. "Indirect Halogenation"

*Schiemann Rx. "Modified Sandmeyer Rx."


X

- Reactions

1. Side Chain Halogenation Rx.

*The benzylic position is the most reactive.

*𝐵𝑟2 reacts ONLY at the benzylic position.

*𝐶𝑙2 is not selective ass bromine so the result is mixture.

*It can be performed under conditions of;

1. Light

2. Heat 3. Peroxide

Rx.

-Mech.

Mech.


XI

2. Side Chain Oxidation Rx.

*Alkylbenzenes are oxidized to benzoic acid by heating in basic medium

using 𝐾𝑀𝑁𝑂4 or heating in 𝑁𝑎2𝐶𝑟2𝑂7/𝐻2𝑆𝑂4

*The benzylic carbon will be oxidized to the carboxylic acid.

-Note;

*Benzylic cation & Benzylic radical are unusual stable! "Give Reason"

1. Benzylic cation

The 𝜋 system of a benzene ring can stabilize an adjacent carbocation by

donating electron density through resonance. Remember that delocalising

charge is a stabilizing effect.

2. Benzylic radical


XII

3. Formation of Aryl Grignard reagent ------- as notes

Used as very useful pre-step in conversions!

f


XIII

Problem Sheet

I. Draw the major product(s) for the following reactions:

1.

2.

3.

4.


XIV

5. Explain the orientation of the substitution

II. One ring of phenyl benzoate undergoes electrophilic aromatic

substitution much more readily than

the other.

(a) Which one is it?

(b) Explain your answer.

III. Many polycyclic aromatic compounds have been synthesized by a

cyclization reaction known as the Bradsher reaction or aromatic

cyclodehydration.

This method can be illustrated by the following synthesis

of 9-methylphenanthrene: ----- solved problem

An arenium ion is an intermediate in this reaction, and the last step

involves the dehydration of an alcohol. Propose a plausible mechanism

for this example of the Bradsher reaction.


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*Soln.---- this problem is applied by the same concept of the equation in

p.VI

III. Provide a detailed mechanism for the following reaction.

1.

2.

3.

IV. Propose structures for compounds G–I:


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V. Both of the following syntheses will fail. Explain what is wrong with

each one.

1.

2.

3. 2-Methylnaphthalene can be synthesized from toluene through the

following sequence of reactions. Write the structure of each

intermediate.

aromatic comp. lec.4

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