Lecture Alkene Benzen 2

8/10/2019 Lecture Alkene Benzen 2

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Organic ChemistryFor USTH Students

Lecture 2: Electrophilic additionto C=C

Dr. Doan Duy Tien


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Electrophilic addition to C=C

+ General mechanism+ Electrophilic Addition to CarbonCarbon Multiple Bonds

+ Addition of HX

+ Addition of HOH and addition of YX

+ Addition to allene and alkyne+ Substitution at -carbon

+ Reactions via organoborane intermediates

Nucleophilic addition to C=C+ Electron withdrawing group stabilze negative charge

+ Michael reaction with carbon nulceophiles

-1,2 addition favored for more reactive group without steric hindrance

-1,4 addition favored for strerically unhindered 4 position if 2 position is blocked

Contents


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Alkenes are also called olefins.

Alkenes contain a carboncarbon double bond. Terminal alkenes have the double bond at the end of the carbon chain.

Internal alkenes have at least one carbon atom bonded to each end of thedouble bond.

Cycloalkenes contain a double bond in a ring.

Structure and Bonding of C=C


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Structure and Bonding of C=C

Recall that the double bond consists of a bond and a

bond. The

bond is stronger than the bond.

The carbon atom is sp2 hybridized to obtain trigonal planar geometry,with bond angles of approximately 120.


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s + 2 p

=

3 sp2 orbitals

sp2 Hybridization

There is one p orbital left over,and it would be along the z axis.


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H s

Orbital Picture of Ethylene

C

C

H s1

sp2

sp2

sp2

sp2

sp2

sp2

H s

H s

p

x

px

CH

H

CH

H


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Interesting AlkenesEthylene, an industrial starting material for many useful products


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Interesting Alkenes


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The characteristic reaction of alkenes is addition: the bond is broken

and two new bonds are formed.

Addition Reactions

Alkenes have exposed electrons, with the electron density of the bondabove and below the plane of the molecule.

Because alkenes are electron rich, simple alkenes do not react withnucleophiles or bases, reagents that are themselves electron rich. Alkenesreact with electrophiles.

No pi bond


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Because the carbon atoms of a double bond are both trigonalplanar, the elements of X and Y can be added to them from the

same side or from opposite sides.

Addition Reactions


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Five addition reactions of cyclohexene

No pi bond

in products

Addition Reactions


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Two bonds are broken in this reaction: the weak bond of the

alkene and the HX bond, and two new

bonds are formed: one

to H and one to X.

Recall that the HX bond is polarized, with a partial positive

charge on H. Because the electrophilic H end of HX is attracted

to the electron-rich double bond, these reactions are called

electrophilic additions.

Electrophilic Addition ofHydrohalogenation(HX) to C=C


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To draw the products of an addition reaction:

Electrophilic Addition of Hydrohalogenation(HX) to C=C


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The mechanism of electrophilic addition consists of two successive Lewis acid-base reactions. In step 1, the alkene is the Lewis base that donates an electronpair to HBr, the Lewis acid, while in step 2, Br is the Lewis base that donatesan electron pair to the carbocation, the Lewis acid.

Electrophilic Addition of Hydrohalogenation(HX) to C=C: The mechanism


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In the representative energy diagram below, each step has its own energy

barrier with a transition state energy maximum. Since step 1 has a higherenergy transition state, it is rate-determining. H for step 1 is positivebecause more bonds are broken than formed, whereas H for step 2 isnegative because only bond making occurs.

Energy diagram for electrophilic addition:

CH3CH2=CH2 + HBr CH3CH2CH(Br)CH3

Electrophilic Addition of Hydrohalogenation(HX) to C=C: Energy diagram


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With an unsymmetrical alkene, HX can add to the double bond to givetwo constitutional isomers, but only one is actually formed:

This is a specific example of a general trend called Markovnikovs rule.

Markovnikovs rule states that in the addition of HX to an unsymmetricalalkene, the H atom adds to the less substituted carbon atom, that is, thecarbon that has the greater number of H atoms to begin with.

Electrophilic Addition of Hydrohalogenation

(HX) to C=C: Markovnikovs Rule


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The basis of Markovnikovs rule is the formation of a carbocation in therate-determining step of the mechanism.

In the addition of HX to an unsymmetrical alkene, the H atom is added tothe less substituted carbon to form the more stable, more substituted

carbocation.

Electrophilic Addition of Hydrohalogenation

(HX) to C=C: Markovnikovs Rule


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Recall that trigonal planar atoms react with reagents from twodirections with equal probability.

Achiral starting materials yield achiral products.

Sometimes new stereogenic centers are formed fromhydrohalogenation:

A racemic mixture

Electrophilic Addition of Hydrohalogenation(HX) to C=C: Stereochemistry


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The mechanism of hydrohalogenation illustrates why two enantiomers areformed. Initial addition of H+ occurs from either side of the planar doublebond.

Both modes of addition generate the same achiral carbocation. Eitherrepresentation of this carbocation can be used to draw the second step of

the mechanism.



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Hydrohalogenation occurs with syn and anti addition of HX. The terms cis and trans refer to the arrangement of groups in a particular

compound, usually an alkene or disubstituted cycloalkene.

The terms syn and anti describe stereochemistry of a process, for example,how two groups are added to a double bond.

Addition of HX to 1,2-dimethylcyclohexene forms two new stereogeniccenters, resulting in the formation of four stereoisomers (2 pairs ofenantiomers).



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22Reaction of 1,2-dimethyl cyclohexene with HCl



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Electrophilic Addition of Hydrohalogenation(HX) to C=C: Summary


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Electrophilic Addition of Water to C=C


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Electrophilic Addition of Water to C=C


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Alcohols add to alkenes, forming ethers by the same mechanism. For

example, addition of CH3OH to 2-methylpropene, forms tert-butyl methylether (MTBE), a high octane fuel additive.

Note that there are three consequences to the formation of carbocationintermediates:

1. Markovnikovs rule holds.

2. Addition of H and OH occurs in both syn and anti fashion.

3. Carbocation rearrangements can occur.

Electrophilic Addition of Alcohols to C=C


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Halogenation is the addition of X2 (X = Cl or Br) to an alkene to form avicinal dihalide.

Electrophilic Addition of Halogen to C=C


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Carbocations are unstable because theyhave only six electrons around carbon.Halonium ions are unstable because of

ring strain.

Electrophilic Addition of Halogen to C=C


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Consider the chlorination of cyclopentene to afford both enantiomers oftrans-1,2-dichlorocyclopentane, with no cis products.

Initial addition of the electrophile Cl+ from (Cl2) occurs from either sideof the planar double bond to form a bridged chloronium ion.

Electrophilic Addition of Halogen toC=C: Stereochemistry


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In the second step, nucleophilic attack of Cl must occur from the backside.

Since the nucleophile attacks from below and the leaving group departs fromabove, the two Cl atoms in the product are oriented trans to each other.

Backside attack occurs with equal probability at either carbon of the three-membered ring to yield a racemic mixture.



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cis-2-Butene yields two enantiomers, whereas trans-2-butene yields a single

achiral meso compound.

Halogenation of c is- and trans-2-butene


Electrophilic Addition of Halogen in


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Treatment of an alkene with a halogen X2 and H2O forms a halohydrin byaddition of the elements of X and OH to the double bond.

Electrophilic Addition of Halogen inWater to C=C: Halohydrin Formation:


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Even though X is formed in step [1] of the mechanism, its concentration issmall compared to H2O (often the solvent), so H2O and not X is thenucleophile.


i i A i i f i


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El hili Addi i C C


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Hydroborationoxidation is a two-step reaction sequence that

converts an alkene into an alcohol.

Electrophilic Addition to C=C:Hydroboration - Oxidation

El hili Addi i C C


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With unsymmetrical alkenes, the boron atom bonds to the less substituted

carbon atom.

Electrophilic Addition to C=C:Hydroboration - Oxidation


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Bi t f ti f C C


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Biotransformation of C=C:


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Biotransformation of C=C:


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KEY CONCEPTS


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KEY CONCEPTS


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KEY CONCEPTS

El t hili Additi t C C


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Electrophilic Addition to C

C


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Electrophilic Addition to CC

El t hili Additi t C C


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Electrophilic Addition to C

C


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Problems


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Problems


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Organic Chemistry

For USTH Students

Lecture 3:

Electrophilic substitution inAromatic systems

Dr. Doan Duy Tien

El hili b i i i A i


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Electrophilic substitution in Aromatic systems

Contents:

+ The General Mechanism

+ Halogenation

+ Nitration and Sulfonation

+ Nitration and Sulfonation

+ Substituted Benzenes: Inductive Effects, Resonance Effects

+ Electrophilic Aromatic Substitution of Substituted Benzenes

+ Application : Synthesis of the hallucinogenic effects of LSD

I t ti b i


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Interesting benzene rings

St t f b


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Structure of benzene

Aromaticity-Hckels Rule:

+ A molecule must be cyclic

+ A molecule must be planar+ A molecule must be completely conjugated+ A molecule must satisfy Hckels rule, and contain a particular numberof electrons. An aromatic compound must contain 4n + 2 electrons (n= 0, 1, 2, and so forth).


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Antimalarial drugthat reduces feverDrug for the treatment of type2 diabetes; that increases the

bodys ability to lower blood

sugar levels,

Aromaticity-Hckels Rule ?

A ti it H k l R l ?


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Aromaticity-Hckels Rule ?

Buckminsterfullerene, C60

Mg

NN

NN

OMeOOCO

O phytyl

phytyl =

chlorophyll a

E

1

R R

1

2

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5

6

7

8

9

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11

12

13141516

17

18

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Molecule of life

Electrophilic Aromatic Substitution


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The characteristic reaction of benzene is electrophilic aromaticsubstitution: a hydrogen atom is replaced by an electrophile.

Background:



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Benzene does not undergo addition reactions likeother unsaturated hydrocarbons, because addition

would yield a product that is not aromatic.

Substitution of a hydrogen keeps the aromatic ring

intact. There are five common examples of electrophilic

aromatic substitution.


Background:



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Mechanism:



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The energy changes in electrophilic aromatic

substitution are shown below:Figure 18.2 Energy diagram for electrophilic aromatic substitution:

PhH + E+ PhE + H+


Background:


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Figure 18.1Five examples

of electrophilic

aromaticsubstitution



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Nitration and sulfonation introduce two differentfunctional groups into the aromatic ring.

Nitration is especially useful because the nitro group

can be reduced to an NH2 group.

Nitration and Sulfonation:




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Generation of the electrophile in nitration requires

strong acid.


Nitration and Sulfonation:

Generation of the electrophile in sulfonation requires

strong acid.



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In Friedel-Crafts alkylation, treatment of benzene withan alkyl halide and a Lewis acid (AlCl3) forms an alkyl

benzene.

Friedel-Crafts Alkylation and Friedel-Crafts Acylation:




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In Friedel-Crafts acylation, a benzene ring is treatedwith acid chloride (RCOCl) and AlCl3 to form a ketone.

Because the new group bonded to the benzene ring is

called an acyl group, the transfer of an acyl group from

one atom to another is an acylation.





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Friedel-Crafts Alkylation:



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Four additional facts about Friedel-Crafts alkylationshould be kept in mind:

[1] Vinyl halides and aryl halides are less reactive than

alkyl halides so do not react in Friedel-Crafts alkylation.



[2] Alkyl groups activate the benene ring toward further

EAS so polyalkylation can occur.


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Each carbocation can then go on to react with benzene

to form a product of electrophilic aromatic substitution.

For example:

p

Starting materials that contain both a benzene ring and

an electrophile are capable of intramolecular Friedel-

Crafts reactions.




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Considering the inductive effect, the NH2 group

withdraws electron density. The CH3 donates electron

density through hyperconjugation.


Substituted Benzenes:



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Resonance effects are only observed with substituents

containing lone pairs or bonds.

An electron-donating resonance effect is observed

whenever an atom Z having a lone pair of electrons is

directly bonded to a benzene ring.





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An electron-withdrawing resonance effect is observed

in substituted benzenes having the general structure

C6H5-Y=Z, where Z is more electronegative than Y.

Seven resonance structures can be drawn for

benzaldehyde (C6H

5CHO). Because three of them place

a positive charge on a carbon atom of the benzene ring,

the CHO group withdraws electrons from the benzene

ring by a resonance effect.





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The inductive and resonance effects in compoundshaving the general structure C6H5-Y=Z (with Z more

electronegative than Y) are both electron withdrawing.




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These compounds represent examples of the generalstructural features in electron-donating and electron

withdrawing substituents.





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First, consider tolueneToluene reacts faster thanbenzene in all substitution reactions.

The electron-donating CH3 group activates the

benzene ring to electrophilic attack.

Ortho and para products predominate.

The CH3 group is called an ortho, para director.


EAS and Substituted Benzenes:



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Now consider nitrobenzeneIt reacts more slowlythan benzene in all substitution reactions.

The electron-withdrawing NO2 group deactivates the

benzene ring to electrophilic attack.

The meta product predominates.

The NO2 group is called a meta director.





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All substituents can be divided into three general types:





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p




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To understand how substituents activate or deactivate

the ring, we must consider the first step inelectrophilic aromatic substitution.

The first step involves addition of the electrophile (E+)

to form a resonance stabilized carbocation.

The Hammond postulate makes it possible to predictthe relative rate of the reaction by looking at the

stability of the carbocation intermediate.




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p




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Orientation Effects in Substituted Benzenes:

There are two general types of ortho, para directors

and one general type of meta director.

All ortho, para directors are R groups or have a

nonbonded electron pair on the atom bonded to the

benzene ring.

All meta directors have a full or partial positive charge

on the atom bonded to the benzene ring.

p



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Figure 18.7 The reactivity anddirecting effects of common

substituted benzenes

p

Orientation Effects in Substituted Benzenes:



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Limitations in Electrophilic Aromatic Substitutions:

Benzene rings activated by the strong electron-

donating groups, OH, NH2, and their derivatives (OR,NHR, and NR2), undergo polyhalogenation when

treated with X2 and FeX3.



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A benzene ring deactivated by strong electron-

withdrawing groups (i.e., any of the meta directors)is not electron rich enough to undergo Friedel-Crafts

reactions.

Friedel-Crafts reactions also do not occur with NH2groups because the complex that forms between the

NH2 group and the AlCl3 catalyst deactivates the ring

towards Friedel-Crafts reactions.

Limitations in Electrophilic Aromatic Substitutions:


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2. If the directing effects of two groups oppose eachother, the more powerful activator controls the

reaction.

Disubstituted Benzenes:


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Planning Synthesis of Benzene Derivatives:

In a disubstituted benzene, the directing effects indicatewhich substituent must be added to the ring first.

Let us consider the consequences of bromination firstfollowed by nitration, and nitration first, followed by

bromination.



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Pathway I, in which bromination precedes nitration,

yields the desired product. Pathway II yields the

undesired meta isomer.



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Halogenation of Alkyl Benzenes:

Electrophilic Aromatic SubstitutionHalogenation of Alkyl Benzenes:


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Note that alkyl benzenes undergo two different

reactions depending on the reaction conditions:

With Br2 and FeBr3 (ionic conditions), electrophilic

aromatic substitution occurs, resulting in replacementof H by Br on the aromatic ring to form o and p isomers.

With Br2 and light or heat (radical conditions),

substitution of H by Br occurs at the benzylic carbon of

the alkyl group.

Halogenation of Alkyl Benzenes:



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Oxidation and Reduction of Substituted Benzenes:

Arenes containing at least one benzylic CH bond are

oxidized with KMnO4 to benzoic acid.

Substrates with more than one alkyl group are

oxidized to dicarboxylic acids. Compounds without

a benzylic hydrogenare inert to oxidation.



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We now know two different ways to introduce an alkyl

group on a benzene ring:

1. A one-step method using Friedel-Crafts alkylation.

2. A two-step method using Friedel-Crafts acylation to

form a ketone, followed by reduction.

Figure 18.8 Twomethods to prepare

an alkyl benzene




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Although the two-step method is longer, it must be

used to synthesize certain alkyl benzenes thatcannot be prepared by the one-step Friedel-Crafts

alkylation because of possible rearrangements.




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A nitro group (NO2) that has been introduced on abenzene ring by nitration with strong acid can

readily be reduced to an amino group (NH2) under a

variety of conditions.




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+ Application : Synthesis of the hallucinogenic effects of LSD

El t hili b tit ti i A ti t


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Application: Swimming pool test kit forchlorine

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NH2

Cl2(aq.)

NH2

CH3

Cl

ClCH3

o-toluidine

bright yellow!




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Naproxen production: Albemarle Company

Anti-inflammatory drugHeck Coupling: Nobel prize 2010:

KEY CONCEPTS
http://en.wikipedia.org/wiki/Nonsteroidal_anti-inflammatory_drughttp://en.wikipedia.org/wiki/Nonsteroidal_anti-inflammatory_drug


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KEY CONCEPTS

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KEY CONCEPTS


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KEY CONCEPTS

KEY CONCEPTS


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KEY CONCEPTS


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Problems


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Problems


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Problems


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Reaction of Carbocation

Key intermediate for biosynthesis

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