This isThis is Doug Henning! Doug Henning!

He performed his first show at the age He performed his first show at the age of 14 at the birthday party of a friend of 14 at the birthday party of a friend and was inspired by his audience's and was inspired by his audience's

spellbound reaction spellbound reaction

He won The Tony AwardHe won The Tony Award

Debuting in December 1975, Debuting in December 1975, Doug Doug Henning's World of MagicHenning's World of Magic captured captured the attention of more than 50 million the attention of more than 50 million viewers!viewers!

Hughes and and Sir Christopher Ingold

In In 1935, , Edward D. Hughes and and Sir Christopher Ingold studied studied nucleophilic substitution reactions of nucleophilic substitution reactions of alkyl halides and related compounds. and related compounds.

They proposed that there were two They proposed that there were two main mechanisms at work, both of main mechanisms at work, both of them competing with each other. them competing with each other.

Are just as spectacular!!!!!Are just as spectacular!!!!!

The two main mechanisms are the The two main mechanisms are the SN

1 reaction and the and the SN2 reaction. .

The “S” stands for chemical The “S” stands for chemical substitution, substitution,

And the “N” stands for nucleophilic, And the “N” stands for nucleophilic, and the number represents the and the number represents the kinetic order of the reaction. of the reaction.

Sir Christopher Ingold

Known for Organic reaction Known for Organic reaction mechanismsmechanisms

“ “Cahn-Ingold-Prelog” rules !Cahn-Ingold-Prelog” rules !

He received the He received the Longstaff Medal of the of the Royal Society of Chemistry in 1951, in 1951, the the Royal Medal of the of the Royal Society in 1952, and was in 1952, and was knighted in 1958 in 1958

Just like Paul Macartney!!!Just like Paul Macartney!!!

Sir Christopher IngoldIs one bad dude!!!!!Is one bad dude!!!!!

This is how he got down!!!This is how he got down!!!

A graph showing the relative reactivities of the different A graph showing the relative reactivities of the different alkyl halides towards Salkyl halides towards SNN1 and S1 and SNN2 reactions2 reactions

the the SN1 reaction

the the SN2 reaction

Effect of the NucleophileEffect of the Nucleophile

   The nucleophile takes part in the The nucleophile takes part in the

slow step (the only step) of the Sslow step (the only step) of the SNN2 2 reaction but not in the slow step of reaction but not in the slow step of the Sthe SNN1. Therefore, a strong 1. Therefore, a strong nucleophile promotes the Snucleophile promotes the SNN2 but not 2 but not the Sthe SNN1. 1.

Effect of the NucleophileEffect of the Nucleophile

Weak nucleophiles fail to promote Weak nucleophiles fail to promote the Sthe SNN2 reaction; therefore, reactions 2 reaction; therefore, reactions with weak nucleophiles often go by with weak nucleophiles often go by the Sthe SNN1 mechanism if the substrate is 1 mechanism if the substrate is secondary or tertiarysecondary or tertiary

Effect of the NucleophileEffect of the Nucleophile

SSNN1:     Nucleophile strength is 1:     Nucleophile strength is unimportant (usually weak).unimportant (usually weak).

Effect of the NucleophileEffect of the Nucleophile

SSNN2:     Strong nucleophiles are 2:     Strong nucleophiles are required.required.

Effect of the SubstrateEffect of the Substrate

The structure of the substrate (the The structure of the substrate (the alkyl halide) is an important factor in alkyl halide) is an important factor in determining which of these determining which of these substitution mechanisms might substitution mechanisms might operate. operate.

Effect of the SubstrateEffect of the Substrate

Methyl halides and primary halides Methyl halides and primary halides cannot easily ionize and undergo Scannot easily ionize and undergo SNN1 1 substitution because methyl and substitution because methyl and primary carbocations are high in primary carbocations are high in energy. They are relatively energy. They are relatively unhindered, however, so they make unhindered, however, so they make good Sgood SNN2 substrates.2 substrates.

Tert-butyl-chloride-3DTert-butyl-chloride-3D

Tertiary halides are too hindered to Tertiary halides are too hindered to undergo Sundergo SNN2 displacement, but they 2 displacement, but they can ionize to form tertiary can ionize to form tertiary carbocations. Tertiary halides carbocations. Tertiary halides undergo substitution exclusively undergo substitution exclusively through the Sthrough the SNN1 mechanism. 1 mechanism. Secondary halides can undergo Secondary halides can undergo substitution by either mechanism, substitution by either mechanism, depending on the conditionsdepending on the conditions

Tert-butyl-chloride-3DTert-butyl-chloride-3Dwill exhibit Steric hinderancewill exhibit Steric hinderance

SSNN2 substrates 2 substrates

SSNN2 substrates:2 substrates:CHCH33X > 1° > 2°X > 1° > 2°

(3° is not suitable(3° is not suitable

SSNN1 substrates1 substrates

SSNN1 substrates: 3° > 2°1 substrates: 3° > 2°

(1° and CH(1° and CH33X are unlikely)X are unlikely)

silver nitrate (AgNOsilver nitrate (AgNO33))

If silver nitrate (AgNOIf silver nitrate (AgNO33) is added to ) is added to an alkyl halide in a good ionizing an alkyl halide in a good ionizing solvent, it removes the halide ion to solvent, it removes the halide ion to give a carbocation. This technique give a carbocation. This technique can force some unlikely ionizations, can force some unlikely ionizations, often giving interesting often giving interesting rearrangements (see Problem 6-29.)rearrangements (see Problem 6-29.)

Effect of the SolventEffect of the Solvent

The slow step of the SThe slow step of the SNN1 reaction 1 reaction involves formation of two ions. Solvation involves formation of two ions. Solvation of these ions is crucial to stabilizing of these ions is crucial to stabilizing them and lowering the activation energy them and lowering the activation energy for their formation. Very polar ionizing for their formation. Very polar ionizing solvents such as water and alcohols are solvents such as water and alcohols are needed for the Sneeded for the SNN1. The solvent may be 1. The solvent may be heated to reflux (boiling) to provide the heated to reflux (boiling) to provide the energy needed for ionizationenergy needed for ionization

Effect of the SolventEffect of the Solvent

Less charge separation is generated Less charge separation is generated in the transition state of the Sin the transition state of the SNN2 2 reaction. reaction.

Strong solvation may weaken the Strong solvation may weaken the strength of the nucleophile because strength of the nucleophile because of the energy needed to strip off the of the energy needed to strip off the solvent molecules. solvent molecules.

Effect of the SolventEffect of the Solvent

Thus, the SThus, the SNN2 reaction often goes 2 reaction often goes faster in less polar solvents if the faster in less polar solvents if the nucleophile will dissolve. Polar nucleophile will dissolve. Polar aprotic solvents may enhance the aprotic solvents may enhance the strength of weak nucleophilesstrength of weak nucleophiles

Effect of the SolventEffect of the Solvent

  

The slow step of the SThe slow step of the SNN1 reaction 1 reaction involves formation of two ions. involves formation of two ions. Solvation of these ions is crucial to Solvation of these ions is crucial to stabilizing them and lowering the stabilizing them and lowering the activation energy for their formation. activation energy for their formation. Very polar ionizing solvents such as Very polar ionizing solvents such as water and alcohols are needed for water and alcohols are needed for the Sthe SNN1. 1.

Effect of the SolventEffect of the Solvent

The solvent may be heated to reflux The solvent may be heated to reflux (boiling) to provide the energy (boiling) to provide the energy needed for ionizationneeded for ionization

This is . . . This is . . .

..

The same as this . . . The same as this . . .

the transition statethe transition state Less charge separation is generated in the Less charge separation is generated in the

transition state of the Stransition state of the SNN2 reaction. Strong 2 reaction. Strong solvation may weaken the strength of the solvation may weaken the strength of the nucleophile because of the energy needed nucleophile because of the energy needed to strip off the solvent molecules. Thus, to strip off the solvent molecules. Thus, the Sthe SNN2 reaction often goes faster in less 2 reaction often goes faster in less polar solvents if the nucleophile will polar solvents if the nucleophile will dissolve. dissolve.

Polar aprotic solvents may enhance the Polar aprotic solvents may enhance the strength of weak nucleophilesstrength of weak nucleophiles

the transition statethe transition state

the transition statethe transition state

..

aprotic solvents:aprotic solvents:

Common characteristics of aprotic Common characteristics of aprotic solvents:solvents:

Examples are Examples are dimethyl sulfoxide, , dimethylformamide, , dioxane and and hexamethylphosphorotriamide, , tetrahydrofuran

dimethyl sulfoxideYou might see this laterYou might see this later

dimethyl sulfoxide

..

tetrahydrofuran

..

tetrahydrofuranYou will definitely need this later. You will definitely need this later.

..

Effect of the SolventEffect of the Solvent

Polar Protic SolventsPolar Protic Solvents

Let's start with the meaning of the adjective Let's start with the meaning of the adjective protic. In the context used here, protic refers to a protic. In the context used here, protic refers to a hydrogen atom attached to an electronegative hydrogen atom attached to an electronegative atom. For our purposes that electronegative atom atom. For our purposes that electronegative atom is almost exclusively oxygen. is almost exclusively oxygen.

In other words, polar protic solvents are In other words, polar protic solvents are compounds that can be represented by the compounds that can be represented by the general formula ROH. The polarity of the polar general formula ROH. The polarity of the polar protic solvents stems from the bond dipole of the protic solvents stems from the bond dipole of the O-H bond. O-H bond.

Effect of the SolventEffect of the Solvent

The large difference in electronegativities of the The large difference in electronegativities of the oxygen and the hydrogen atom, combined with oxygen and the hydrogen atom, combined with the small size of the hydrogen atom, warrant the small size of the hydrogen atom, warrant separating molecules that contain an OH group separating molecules that contain an OH group from those polar compounds that do not. from those polar compounds that do not.

Examples of polar protic solvents are water (HExamples of polar protic solvents are water (H22O), O), methanol (CHmethanol (CH33OH), and acetic acid (CHOH), and acetic acid (CH33COCO22H).H).

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The slow stepThe slow step

The slow step of the SN1 reaction The slow step of the SN1 reaction involves formation of two ions. involves formation of two ions. Solvation of these ions is crucial to Solvation of these ions is crucial to stabilizing them and lowering the stabilizing them and lowering the activation energy for their formation. activation energy for their formation. Very polar ionizing solvents such as Very polar ionizing solvents such as water and alcohols are needed for water and alcohols are needed for the SN1. the SN1.

The slow stepThe slow step

The solvent may be heated to reflux The solvent may be heated to reflux (boiling) to provide the energy (boiling) to provide the energy needed for ionization.needed for ionization.

The slow stepThe slow step

Less charge separation is generated in the Less charge separation is generated in the transition state of the SN2 reaction. Strong transition state of the SN2 reaction. Strong solvation may weaken the strength of the solvation may weaken the strength of the nucleophile because of the energy needed nucleophile because of the energy needed to strip off the solvent molecules. to strip off the solvent molecules.

less polar solventsless polar solvents

Thus, the SN2 reaction often goes Thus, the SN2 reaction often goes faster in less polar solvents if the faster in less polar solvents if the nucleophile will dissolve. Polar nucleophile will dissolve. Polar aprotic solvents may enhance the aprotic solvents may enhance the strength of weak nucleophiles.strength of weak nucleophiles.

SN1SN1

SN1: Good ionizing solvent required. SN1: Good ionizing solvent required.

SN2SN2

SN2: May go faster in a less polar SN2: May go faster in a less polar solventsolvent

KineticsKinetics

The rate of the SN1 reaction is The rate of the SN1 reaction is proportional to the concentration of proportional to the concentration of the alkyl halide but not the the alkyl halide but not the concentration of the nucleophile. It concentration of the nucleophile. It follows a first-order rate equation.follows a first-order rate equation.

KineticsKinetics

The rate of the SN2 reaction is The rate of the SN2 reaction is proportional to the concentrations of proportional to the concentrations of both the alkyl halide [R—X] and the both the alkyl halide [R—X] and the nucleophile [Nuc: −]. It follows a nucleophile [Nuc: −]. It follows a second-order rate equation.second-order rate equation.

KineticsKinetics

SN1 rate  =  kr[R—X]SN1 rate  =  kr[R—X]

SN2 rate  =  kr[R—X][Nuc: −]SN2 rate  =  kr[R—X][Nuc: −]

StereochemistryStereochemistry

The SN1 reaction involves a flat The SN1 reaction involves a flat carbocation intermediate that can be carbocation intermediate that can be attacked from either face. Therefore, attacked from either face. Therefore, the SN1 usually gives a mixture of the SN1 usually gives a mixture of inversion and retention of inversion and retention of configurationconfiguration

StereochemistryStereochemistry

The SN2 reaction takes place The SN2 reaction takes place through a back-side attack, which through a back-side attack, which inverts the stereochemistry of the inverts the stereochemistry of the carbon atom. Complete inversion of carbon atom. Complete inversion of configuration is the result.configuration is the result.

StereochemistryStereochemistry

SN1 stereochemistry:SN1 stereochemistry: Mixture of retention and inversion; Mixture of retention and inversion;

racemization. racemization.

StereochemistryStereochemistry

SN2 stereochemistry SN2 stereochemistry

Complete inversion Complete inversion

RearrangementsRearrangements

The SN1 reaction involves a The SN1 reaction involves a carbocation intermediate. This carbocation intermediate. This intermediate can rearrange, usually intermediate can rearrange, usually by a hydride shift or an alkyl shift, to by a hydride shift or an alkyl shift, to give a more stable carbocation.give a more stable carbocation.

RearrangementsRearrangements

The SN2 reaction takes place in one The SN2 reaction takes place in one step with no intermediates. step with no intermediates.

No rearrangement is No rearrangement is possible in the SN2 possible in the SN2 reaction.reaction.

rearrangement reactionrearrangement reaction

An example of a reaction taking place with An example of a reaction taking place with an SN1 reaction mechanism is the an SN1 reaction mechanism is the

hydrolysis of tert-butyl bromide with water hydrolysis of tert-butyl bromide with water

forming tert-butyl alcoholforming tert-butyl alcohol

a tert-butyl carbocationa tert-butyl carbocation

Formation of a tert-butyl carbocation Formation of a tert-butyl carbocation by separation of a leaving group (a by separation of a leaving group (a bromide anion) from the carbon bromide anion) from the carbon atom: this step is slow and atom: this step is slow and reversible! reversible!

http://en.wikipedia.org/http://en.wikipedia.org/wiki/SN1_reactionwiki/SN1_reaction

The hydride shift The hydride shift

The mechanism for hydride shift The mechanism for hydride shift occurs in occurs in multiple stepsmultiple steps that includes that includes various intermediates and transition various intermediates and transition states. Below is the mechanism for states. Below is the mechanism for the given reaction above:the given reaction above:

The hydride shiftThe hydride shift

The hydride shiftThe hydride shift

rearrangement reactionrearrangement reaction

A A rearrangement reactionrearrangement reaction is a broad is a broad class of organic reactions where the class of organic reactions where the carbon skeleton of a molecule is carbon skeleton of a molecule is rearranged to give a structural isomer of rearranged to give a structural isomer of the original molecule [1] . Often a the original molecule [1] . Often a substituent moves from one atom to substituent moves from one atom to another atom in the same molecule. In the another atom in the same molecule. In the example below the substituent R moves example below the substituent R moves from carbon atom 1 to carbon atom 2 from carbon atom 1 to carbon atom 2

RearrangementsRearrangements

SN1: Rearrangements are common. SN1: Rearrangements are common.

RearrangementsRearrangements

SN2: Rearrangements are impossible SN2: Rearrangements are impossible

Nucleophillic substitutionsNucleophillic substitutions

SN1: SN1: SN2: SN2:

Promoting factorsPromoting factors weak nucleophiles are weak nucleophiles are

OKOK strong nucleophile strong nucleophile needed needed

NucleophileNucleophile3° > 2°3° > 2° CHCH33X > 1° >3° >2°X > 1° >3° >2°

substrate (RX)substrate (RX) good ionizing solvent good ionizing solvent

neededneeded wide variety of wide variety of

solventssolvents SolventSolvent good ionizing solvent good ionizing solvent

needed needed wide variety of wide variety of

solventssolvents leaving groupleaving group

good one requiredgood one required good one requiredgood one required

OtherOther

You will use this!You will use this!***AgNO***AgNO33 force force

ionization!ionization!

the nucleophile competes . . . the nucleophile competes . . . In both reactions, the nucleophile competes with In both reactions, the nucleophile competes with

the leaving group. Because of this, one must the leaving group. Because of this, one must realize what properties a leaving group should realize what properties a leaving group should have, and what constitutes a good nucleophile. have, and what constitutes a good nucleophile. For this reason, it is worthwhile to know which For this reason, it is worthwhile to know which factors will determine whether a reaction follows factors will determine whether a reaction follows an SN1 or SN2 pathway.an SN1 or SN2 pathway.

good leaving groupsgood leaving groups

Very good leaving groups, such as Very good leaving groups, such as triflate, tosylate and mesylate, triflate, tosylate and mesylate, stabilize an incipient negative stabilize an incipient negative charge. The delocalization of this charge. The delocalization of this charge is reflected in the fact that charge is reflected in the fact that these ions are not considered to be these ions are not considered to be nucleophilicnucleophilic

good leaving groupsgood leaving groups

Very good leaving groups, such as Very good leaving groups, such as triflate, tosylate and mesylate, triflate, tosylate and mesylate, stabilize an incipient negative stabilize an incipient negative charge. The delocalization of this charge. The delocalization of this charge is reflected in the fact that charge is reflected in the fact that these ions are not considered to be these ions are not considered to be nucleophilicnucleophilic

good leaving groupsgood leaving groups

good leaving groupsgood leaving groups

Hydroxide and alkoxide ions are not Hydroxide and alkoxide ions are not good leaving groups; however, they good leaving groups; however, they can be activated by means of Lewis can be activated by means of Lewis or Brønsted acidsor Brønsted acids