Ochem 2 PDF

Preview

Summary

Organic Chemistry Notes
Dr. Allen...

Description

Chapter 14: Aromaticity Benzene (C6H6) is a hydrocarbon that belongs to a class of compounds called aromatics – a family of conjugated ring systems with similar chemical properties Recall from Chem 341: Conjugation –

benzene

Benzene has a planar cyclically conjugated structure with 6 p-electrons – all C–C bond lengths are identical at 139.5 pm

Resonance delocalization of electrons creates a circle of electron density

The Stability of Benzene Benzene behaves very differently than isolated alkenes Compare: Br HBr

HBr

H2

H2

Pd/C

Pd/C

cyclohexene

benzene Δ

Δ

Benzene (and other aromatic compounds) show unusual and remarkable stability

The Stability of Benzene How much energy is electron delocalization worth? H 2, Pd/C

–120 kJ/mol

If benzene were 3 isolated alkenes, we would expect: However, experimentally we measure:

energy (kJ/mol)

–120

The Criteria for Aromaticity: Hückel’s Rule For a molecule to be aromatic, it must: – be cyclic – have a p-orbital on every atom in the ring (fully conjugated) – be planar (so p-orbitals are aligned) – have 4n+2 p electrons (where n is an integer, i.e. 0, 1, 2, 3,...) These conditions make up Hückel’s Rule for aromaticity Example: Benzene

Which of the following molecules are considered aromatic? OCH3

Cl

CH3

The Basis of Hückel’s Rule Why is 4n+2 p-electrons important? – The answer lies in molecular orbital theory

Review of p-bonding in ethylene:

Extend to p-bonding an allyl system:

The Basis of Hückel’s Rule p-molecular orbitals in benzene:

Aromatic Molecular Orbitals: We can predict molecular orbitals for monocylic aromatic molecules using the inscribed polygon method. – Draw a circle (centered on non-bonding level) – Draw the molecule inside the circle with a vertex pointed down – Where the ring meets the circle there is an orbital – Fill electrons from the bottom up Example: Benzene

Aromaticity and Atoms with Lone Pairs When cyclic molecules carbanions), we contain the lone pairs

(i.e. heteroatoms or and what orbitals

Consider the following molecules:

N H

–

N

Remember: s -bonds use hybridized orbitals and p-bonds use unhybridized p-orbitals lone pairs can be in either hybridized orbitals or unhybridized p-orbitals

Aromaticity and Polycyclic Molecules When considering molecules with more than one ring, we need to consider a closed loop of p-electrons. Generally this is the largest closed loop in the molecule and may or may not include all of the p-electrons in the molecule. Consider each example below:

The Basis of Hückel’s Rule: Molecules that have are considered antiaromatic

, but fit all the other criteria (cyclic, conjugated)

Example: Cyclobutadiene Consider the following data H 2, Pd/C

DHº = –130 kcal/mol

H 2, Pd/C

D Hº = –380 kcal/mol

Cyclobutadiene is destabilized by conjugation! Why is this? Consider the molecular orbitals…

Aromaticity and Antiaromaticity: Practice

O

+

N N

B CH3

Implications of Aromaticity: Reactivity Aromaticity and antiaromaticity can have large impacts on reactivity when they are created or destroyed. Consider the examples below. Acidity and Basicity: – H+

– H+

N

– H

H

N

H

H

H

pKa ~50

H

pKa 11 + H+

– H+

H

+

N

–

H

H

H

+

N

H

H

H

pKa 15

pKa –3.8

Substitution Reactions:

R

Br

F 3C

OH F 3C

O

Br

R

krel:

1014

Br

160

Br

1.0

Substituted Benzenes: Positions of the Benzene Ring When a benzene ring is substituted, this creates three different positions among the remaining unsubstituted carbons. These positions are referred to by prefixes that are relative to the original substituent Positions of a benzene ring

X

Substituted Benzenes Substituents on a benzene will affect the electron density of the aromatic ring making them more or less electron rich than benzene Electron density can be donated or withdrawn from the ring by substituents via two mechanisms: 1. Inductive effects 2. Resonance effects Inductive Effects: Need to consider electronegativity, polarizability, and charges – Atoms (and groups) more electronegative than carbon n – e.g. F, O, N – Polarizable alkyl groups d donating inductive effect – e.g. CH3

y and have an electron–

– Atoms with a positive charge (full or partial) are F

CH3

Substituted Benzenes Resonance Effects: Need to consider lone pairs and p-bonds conjugated to the aromatic ring – A resonance effect is electron-donating when electrons are donated towards the aromatic ring – places a negative charge on the ring *generally from a lone pair on an atom directly bonded to the aromatic ring* – A resonance effect is electron-withdrawing when electrons are withdrawn from the aromatic ring – places a positive charge on the ring *generally from a conjugated p -bond involving an electronegative atom* O

Examples:

NH2

Substituted Benzenes Some groups and atoms (O, N, halogens) effects and the identity of the element 1.

When a neutral O or N atom is bonded directly to benzene, r and the group is electron-donating NH2

2.

When a

OH

is bonded directly to a benzene ring, the and the group is electron withdrawing F

.

Br

t r.

Substituted Benzenes: Practice Are the following aromatic rings more or less electron rich than benzene? NO2

SH

CN

Substituted Benzenes: Benzylic Oxidation benzylic carbon

The benzylic position is the atom directly attached to the benzene ring

The benzylic carbon is more reactive than other carbons in an alkyl chain due to stabilization by the neighboring aromatic ring

The benzylic carbon can be oxidized to a carboxylic acid with KMnO4 O CH3 KMnO 4

Any alkyl group that contains

OH

can be oxidized

Birch Reduction of Aromatic Compounds The Birch Reduction is a reaction that breaks aromaticity and reduces a benzene ring to a 1,4-cyclohexadiene using sodium, ammonia and an alcohol. H

H

H

H

Na, NH 3 CH3CH2OH

Mechanism:

Birch Reduction: Regioselectivity The Birch reduction can also be done on substituted benzene rings with predictable regioselectivity based on the substituents present. Benzene rings with electron donating groups: OCH3 H

OCH3

H

Na, NH 3 CH3CH2OH

H H

Benzene rings with electron withdrawing groups: O

O

H OCH3

OCH3 Na, NH 3 CH3CH2OH

H H

Chapter 15: Reactions of Aromatic Compounds Recall from Chem 341: Halogens (X2) add to p bonds to create vicinal dihalides Br 2

Br Br

Benzene does not undergo addition reactions, despite having three p bonds Br 2

Br H

X No Reaction

H Br

not aromatic! Benzene undergoes that keep the aromatic ring intact This type of reaction is called electrophilic aromatic substitution

E+

Electrophilic Aromatic Substitution: General Mechanism Electrophilic aromatic substitution is a two-step substitution mechanism on aromatic molecules Step 1: Addition of the electrophile to benzene H E+

E

+

Step 2: Deprotonation to regain aromaticity H E

B

E

+

Since benzene is very stable, the electrophile must be very reactive

Electrophilic Aromatic Substitution: Halogenation Bromine and chlorine are not reactive enough to react with benzene alone, however, in the presence of a Lewis acid (AlCl3 or FeBr3) a substitution occurs H

Cl

H

Br

Cl2

Br 2

AlCl3

FeBr 3

Mechanism Step 1: Electrophile generation

Step 2: Electrophilic aromatic substitution

Electrophilic Aromatic Substitution: Nitration Nitration introduces a nitro group (–NO2) onto the benzene ring H

HNO 3

NO2

H 2SO4

The electrophile is the nitronium ion (NO2) formed by reacting nitric acid with sulfuric acid Mechanism Step 1: Formation of the nitronium ion

Step 2: Electrophilic aromatic substitution

+ O

N

O

nitronium ion

Electrophilic Aromatic Substitution: Sulfonation Sulfonation uses sulfuric acid to introduce a sulfonic acid functional group (–SO3H) onto benzene to produce benzenesulfonic acid H

H 2SO4 (99%) or SO3, H 2SO4

SO3H

The electrophile is a protonated sulfur trioxide cation, SO3H+

O S

Mechanism

O

+

O

H

Step 1: Formation of the electrophile

Step 2: Electrophilic aromatic substitution

Friedel–Crafts Acylation Friedel–Crafts acylation forms a new carbon-carbon bond using an acid chloride with a Lewis acid via electrophilic aromatic substitution to create a benzylic ketone O

O H Cl

R

R

AlCl3

The electrophile is an acylium ion, formed via AlCl3-mediated ionization of the C–Cl bond of the acid chloride. Mechanism Step 1: Electrophile generation

Step 2: Electrophilic aromatic substitution

+

O

R

acylium ion

Friedel–Crafts Alkylation Friedel–Crafts alkylation introduces an alkyl group onto the benzene ring via treatment with an alkyl halide (usually an alkyl chloride) and a Lewis acid H

R RCl AlCl3

R = alkyl

The identity of the electrophile depends on the alkyl halide Methyl and ethyl halides: the electrophile is a Lewis acid-base complex

+ CH3CH2 Cl

+

CH3CH2 Cl

AlCl3

– AlCl3

Friedel–Crafts Alkylation With all other alkyl halides the electrophile is a carbocation: Cl

+

AlCl3

+

–

Cl

AlCl3

+

Carbocations, as always, can undergo rearrangements to form a more stable carbocation before reacting with benzene Cl

+

AlCl3

Friedel–Crafts Alkylation: 1º Alkyl Halides Why do primary alkyl halides larger than ethyl form carbocation electrophiles in Friedel–Crafts alkylations? Answer: concerted loss of AlCl4 and rearrangement Cl

+

AlCl3

Remember: primary (1º) halides larger than ethyl always provide branched products AlCl3 Cl

+

X

does not form! Example: Cl AlCl3

Reactions of Substituted Benzenes: Carbonyl Reduction Aldehydes and ketones can be reduced to alkyl group though the two methods below. Note: the carbonyl does not need to be at the benzyllic position. Clemmensen Reduction (acidic conditions) O Zn(Hg), HCl Δ

Wolff–Kishner Reduction (basic conditions) O NH2NH2, NaOH Δ

These reactions lead to a two-step method to install an alkyl group on a benzene without the possibility of rearrangements. How would you make propyl benzene?

Summary of Electrophilic Aromatic Substitution Reaction Type

Reagents

Bromination

Br2, FeBr3

Cl2, AlCl3

Chlorination

Nitration

HNO3, H2SO4

Sulfonation

H2SO4 (99%) or SO3, H2SO4

Electrophile

Br

+ Br

– FeBr 3

Cl

+ Cl

– AlCl3

Product Br

Cl

NO2

+ O N O

SO3H

O S O

+ O H O

Friedel–Crafts Acylation

Friedel–Crafts Alkylation

O Cl

R, AlCl3

R–Cl, AlCl3

+ O

R

R

+ – R Cl AlCl3 (R = methyl or ethyl)

or

+ R

R

Electrophilic Aromatic Substitution of Substituted Benzenes Electrophilic aromatic substitution can occur on all aromatic compounds Substituents on a benzene ring will affect the reactivity in two ways 1.

substitution pattern – three possible sites of reactivity X

2.

reaction rate – either faster or slower than benzene

Electrophilic Aromatic Substitution of Substituted Benzenes When performing an electrophilic aromatic substitution on a substituted benzene, the location of the new group depends on the identity of the first group Consider the following reactions: CH3

CH3

CH3

CH3

Br Br 2

+

+

FeBr 3

Br Br

trace

NO2

NO2

NO 2

NO 2

Br Br 2

+

FeBr 3

+ Br Br

7%

trace

Electrophilic Aromatic Substitution of Substituted Benzenes Why are electrophilic aromatic substitutions selective for either ortho/para or meta? We need to examine the rate limiting step of the mechanism: X

ortho:

E+ X

para:

E+ X

meta:

E+

If X is an electron-donating group and/or has lone pairs:

If X is an electron-withdrawing group without lone pairs:

Electrophilic Aromatic Substitution of Substituted Benzenes Let’s also consider the energy diagram and the rates of each reaction Ortho/Para Substitution

Meta Substitution

+ X=H

H

X

X E

E

X

+ H X=H

X

Electron-donating groups:

Electron-withdrawing groups:

Summary of Directing Substitutions Ortho/Para Directors

Meta Directors

Strongly Activating

Strongly Deactivating

NH 2

NHR

NR 2

OH

+ NR 3

NO 2

CCl3

CF 3

Moderately Activating

O OR R

N H

Weakly Activating

Moderately Deactivating

R (alkyl)

SO 3H

Weakly Deactivating

X (X = F, Cl, Br, I)

O

O OH

CN O

O OR

R

H

Substituted Benzenes: Practice Predict the products and decide whether the reaction will occur faster or slower than the analogous reaction with benzene. O CH3

CH3CH2Cl AlCl3

OCH3

HNO 3, H 2SO4

O Cl Cl AlCl3

Br 2, FeBr 3

Reactivity of Disubstituted Benzenes For electrophilic aromatic substitution of disubstituted benzenes, we need to consider the directing effects of both substituents and use the following guidelines: 1. When the directing effects reinforce, the new substituent is located on the position directed by both groups O2N

OCH3

Br 2, FeBr 3

1. When the directing effects oppose, the new substituent is directed by the stronger activating group H 3C

OCH3

Br 2, FeBr 3

1. No substitution occurs between two meta substituents because of crowding H 3C

CH3

Br 2, FeBr 3

Ranking of Activating and Deactivating groups

Disubstituted Benzenes: Practice Predict the products of the following reactions. CH3

O CH3

HNO 3, H 2SO4

O NC

H N

CH3 O

H 3CO

CH3

Cl

CH3 AlCl3

Cl2, AlCl3

Synthesis of Substituted Benzenes When designing a synthesis of a substituted benzene compound, we need to consider the directing effects of each substituent to decide which to install first. Consider how to make the following compounds from benzene:

Cl

NO2

Br

O

Sulfonation: A Synthetically Useful Reaction The sulfonation of benzene is a reversible reaction, so the sulfonic acid group can be removed after it has been installed SO3H

H

H 2O, H 3O+, Δ

Sulfonation removal mechanism:

This creates a useful strategy for synthesis. The sulfonic acid group is very large and adds predominately para, so it can be used to block the para position. OCH3

OCH3 Br

?

Nucleophilic Aromatic Substitution While benzene itself is a weak nucleophile, aryl halides bearing strong electronwithdrawing groups can also react with nucleophiles and undergo a substitution – we call this Nucleophilic Aromatic Substitution (SNAr)

–OH

O2N

Cl

O2N

OH

Proceeds via a two-step addition–elimination mechanism:

Nucleophilic Aromatic Substitution: Aryl Halide Reactivity The position of the electron withdrawing group is important in SNAr reactions – the electron withdrawing group must be either ortho or para to halide – an aryl halide with a Why? Consider the mechanism:

Cl

O2N

O2N

Cl

Reactions of Substituted Benzenes: Nitro Reduction A nitro group in the benzylic position can be reduced to an amino group using H2, Pd/C

This reduction creates a useful two-step process for preparing aniline (a benzene with an amino group)

NH2

NO2 HNO 3 H 2SO4

H 2, Pd/C

Formation of Aryl Diazonium Salts from Aniline Anilines will react with nitrous acid to result in an aryl diazonium salt Cl – NH2

Mechanism:

NaNO2 HCl

N

N

Reactions of Aryl Diazonium Salts Aryl diazonium salts are useful intermediates to produce a variety of substituted benzenes NH2

+ N2

NaNO2

X

reagent

+

HCl

Halogenation:

Cyanation:

+ N2

N2

+ N2

Cl CuCl

+ N2

CN CuCN

Br

Hydrolysis:

CuBr

+ N2

OH H 2O D

Reduction: +

N2

HBF 4

+ N2

F

H H 3PO 2

D

Reactions of Aryl Diazonium Salts: General Mechanisms The reactions of aryl diazonium salts are generally thought to proceed through an aryl cation or an aryl radical. H

Aryl cation mechanism:

O

OH H

N

H 2O

N

BF4–

F

Aryl radical mechanism: Cl – N

N CuCl

N

Cl N

CuCl2