Section 2_Functional Groups

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AROMATIC compounds or ARENES include benzene andbenzene derivatives.

Many aromatic compounds were originally isolated

from fragrant oils.

However, many aromatic compounds are odorless.

Aromatic compounds are quite common.

Introduction to Aromatic

Compounds

8 of the 10 best-selling drugs have aromatic moieties.

Introduction to AromaticCompounds


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Coal contains aromatic rings fused together and joinedby nonromantic moieties.

Introduction to Aromatic

Compounds

Benzene is generally the parent name for

monosubstituted derivatives.

Nomenclature of BenzeneDerivatives


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Many benzenederivatives have

common

names.

For some

compounds, the

common name

becomes the

parent name.

Nomenclature of Benzene

Derivatives

If the substituent is larger than the ring, the substituent

becomes the parent chain.

Aromatic rings are often represented with a Ph (for

phenyl) or with a (phi) symbol.



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The common name for dimethyl benzene derivatives isXYLENE.

What do ORTHO, META, and PARA mean?


Derivatives

1. Identify the parent chain (the longest consecutive

chain of carbons).

2. Identify and name the substituents.

3. Number the parent chain and assign a locant (and

prefix if necessary) to each substituent.

Give the first substituent the lowest number possible.

4. List the numbered substituents before the parent

name in alphabetical order.



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Locants are required for rings with more than 2substituents.

1. Identify the parent chain (generally the aromatic ring):

Often a common name can be the parent chain.

2. Identify and name the substituents.


Derivatives

3. Number the parent chain and assign a locant (and

prefix if necessary) to each substituent.

A substituent that is part of the parent

name must be assigned locant NUMBER 1.

4. List the numbered substituents before the parentname in alphabetical order:



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Name the following molecules.


Derivatives

What makes the carbonyl carbon a good electrophile?

1. RESONANCE: There is a minor but significant contributor that

includes a formal 1+ charge on the carbonyl carbon.

What would the resonance hybrid look like for this carbonyl?

Carbonyls as Electrophiles


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What makes the carbonyl carbon a good electrophile?

2. INDUCTION: The carbonyl carbon is directly

attached to a very electronegative oxygen atom.

3. STERICS: How does an sp2 carbon compare to an sp3?


Consider the factors: resonance, induction, and sterics.

Which should be MORE REACTIVE as an electrophile,

aldehydes or ketones? Explain WHY.

Example comparison:



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We want to analyze how nucleophiles attack carbonylsand why some nucleophile react and others dont.

Example attack:

If the nucleophile is weak, or if the attacking nucleophile

is a good leaving group, the reverse reaction will

dominate.

Reverse reaction:

Nucleophilic Attack on a Carbonyl

Show the nucleophilic attack for some other

nucleophiles. Nucleophiles to consider include OH,

CN, H, R, H2O.

When the nucleophile attacks, is the resulting

intermediate relatively stable or unstable? WHY?

If a nucleophile is also a GOOD LEAVING GROUP, is it

likely to react with a carbonyl? Explain WHY.

Compare attack on a carbonyl with attack on an alkyl

halide.



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Show the nucleophilic attack for some other

nucleophiles.

When the nucleophile attacks, is the resulting

intermediate relatively stable or unstable? WHY?

If a nucleophile is also a GOOD LEAVING GROUP, is it

likely to react with a carbonyl? Explain WHY.

Compare attack on a carbonyl with attack on an alkyl

halide.


If the nucleophile is strong enough to attack and NOT a

good leaving group, then the full ADDITION will occur.

The intermediate carries a negative charge, so it will

pick up a proton to become more stable.

Nucleophilic Attack on a CarbonylNucleophilic Addition


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If the nucleophile is weak and reluctant to attack thecarbonyl, HOW could we improve its ability to attack?

We can make the carbonyl more electrophilic:

Adding an acid will help. HOW?

Consider the factors that make it electrophilic in the

first place (resonance, induction, and sterics).


With a weak nucleophile, the presence of an acid will

make the carbonyl more attractive to the nucleophile

so the full ADDITION can occur.

Nucleophilic Attack on a CarbonylNucleophilic Addition


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Is there a reason why acid is not used with strongnucleophiles?


Nucleophilic Addition

Carboxylic acids are abundant in nature and in

pharmaceuticals.

Introduction Carboxylic Acids


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The US produces over 2.5 million tons of acetic acid peryear, which is primarily used to produce vinyl acetate.

Vinyl acetate is used in paints and adhesives.

Carboxylic acid derivatives, such as vinyl acetate, are

very common, and they play a central role in organicchemistry.

Introduction Carboxylic Acids

Monocarboxylic acids are named with the suffix

oic acid.

The carbon of the carboxylic acid moiety is assigned the

locant position 1.

Nomenclature of Carboxylic Acids


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When the carboxylic acid group isattached to a ring, it is named as an

alkane carboxylic acid.

There are also many common names for carboxylic

acids.


Dicarboxylic acids are named with

the suffix dioic acid.

There are also many common names for dicarboxylic

acids:



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The carbon atom of the carboxylic acidhas a trigonal planar geometry. WHY?

The acid moiety is capable of strong hydrogen (H)

bonding including H-bonding between acid pairs.

As a result, carboxylic acids generally have high boiling

points.

Consider the BPs of acetic acid (118 C) and

isopropanol (82 C).

Structure and Properties of

Carboxylic Acids

Carboxylate ions end in the suffix oate.

Compounds that end in the suffix oate are often

found in food ingredient lists as preservatives.

NaOH is a strong base, so it is capable of reacting 100%

with a carboxylic acid.

Structure and Properties ofCarboxylic Acids


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In water, the equilibrium generally favors the acid .

pKa values mostly range between 4 and 5. What is pKa?


Carboxylic Acids

How does the pKa value for a carboxylic acid compare to

a strong acid like HCl, or a very weak acid like ethanol?

HCl

pKa = -7

How can induction and resonance be used to explain

the acidity of a carboxylic acid?



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Lets examine the equilibrium between the carboxylicacid and the carboxylate at physiological pH (7.3).

The acid and the conjugate base make a buffer. HOW?

Recall that the Henderson-Hasselbalch equation can be

used to calculate the pH of a buffer:

Assuming the pKa is 4.3, calculate the ratio ofcarboxylate/acid.


Carboxylic Acids

Many biomolecules exhibit carboxylic acid moieties.

Biomolecules such as pyruvic acid exist primarily as the

carboxylate under physiological conditions.



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Electron withdrawing substituents have a great effecton acidity.

WHY?


Carboxylic Acids

Electron withdrawing substituents affect benzoic acid as

well.



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The reduction of acids with LAH or borane result in adecrease in the oxidation number for carbon. HOW?

There are also many reactions where carboxylic acids

dont change their oxidation state.

What criteria must Z fulfill so that there is no change in

the oxidation state?

Introduction to Carboxylic Acid

Derivatives

When Z is a heteroatom, the compound is called a

carboxylic acid derivative.

Because it has the same oxidation state, a nitrile is also

an acid derivative despite not having a carbonyl group.

Introduction to Carboxylic AcidDerivatives


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Acid halides and anhydrides are relatively unstable, sothey are not common in nature

Some naturally occurring esters are known to have

pleasant odors:


Derivatives

Amides are VERY common

in nature.

What type of molecule in

nature includes amide

linkages?

Many other compoundsfeature amides, including

some natural sedatives

like melatonin.



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To name an acid halide, replace ic acid with ylhalide.


Derivatives

Alternatively, the suffix, carboxylic acid can be

replaced with carbonyl halide.



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Acid anhydrides are named by replacing acid withanhydride.


Derivatives

Asymmetric acid anhydrides are named by listing the

acids alphabetically and adding the word anhydride.



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Esters are named by naming the alkyl group attached tothe oxygen followed by the carboxylic acids name with

the suffix ate.


Derivatives

Amides are named by replacing the suffix ic acid or

oic acid with amide.



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If the nitrogen atom of the amide group bears alkylsubstituents, their names are placed at the beginning of

the name with N as their locant.


Derivatives

Nitriles are named by replacing the suffix ic acid or

oic acid with onitrile.



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Nylon is a polyamide.

Polyester is made similarly.

Preparation and Reactions of Amides

Amides can be hydrolyzed with H3O+, but the process is

slow and requires high temperature.

The mechanism is very similar to that for the hydrolysisof an ester.



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LAH can reduce an amide to an amine.

The mechanism is quite

different from the others

we have seen in this

chapter.

When the H- attacks,which is the best leaving

group?


The iminium is reduced with a second equivalent of

hydride.



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When a 1 or 2 alkyl halide is treated with a cyanideion, the CN acts as a nucleophile in an SN2 reaction.

Nitriles can also be made by dehydrating an amide using

a variety of reagents including SOCl2.

Preparation and Reactions of Nitriles

What base might you use?



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An aqueous strong acid solution can be used tohydrolyze a nitrile.

In the mechanism, the nitrogen is protonated multiple

times and water acts as a nucleophile.

Draw a complete mechanism.


Basic hydrolysis of a nitrile can also be achieved.

Which group in the reaction acts as a nucleophile?

Which group acts to protonate the nitrogen?

Draw a complete mechanism.



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Nitriles can also react with Grignards.

After the nitrile is consumed, H3O+ is added to form an

imine, which can be hydrolyzed with excess H3O+ (aq) to

form a ketone. SHOW a mechanism.




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Similar to how carboxylic acids can be converted toalcohols using LAH (Section 21.5), nitriles can be

converted to amines.

Preparation and Reactions of

Nitriles

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Section 2_Functional Groups