slide1 n.
Download
Skip this Video
Loading SlideShow in 5 Seconds..
NUCLEOPHILICITY PowerPoint Presentation
Download Presentation
NUCLEOPHILICITY

Loading in 2 Seconds...

play fullscreen
1 / 38

NUCLEOPHILICITY - PowerPoint PPT Presentation


  • 144 Views
  • Uploaded on

NUCLEOPHILICITY. WHAT IS A NUCLEOPHILE ? A BASE ?. WHAT MAKES A GOOD NUCLEOPHILE?. NUCLEOPHILES AND BASES. THE FUNDAMENTAL DISTINCTION. kinetic (or rate) parameter. Nucleophilicity. Basicity. thermodynamic (or equilibrium) parameter. All nucleophiles are bases …...

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'NUCLEOPHILICITY' - yoshi-walls


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
slide1

NUCLEOPHILICITY

WHAT IS A NUCLEOPHILE ? A BASE ?

WHAT MAKES A GOOD NUCLEOPHILE?

slide2

NUCLEOPHILES AND BASES

THE FUNDAMENTAL DISTINCTION

kinetic (or rate) parameter

Nucleophilicity

Basicity

thermodynamic (or equilibrium)

parameter.

All nucleophiles are bases …...

and all bases are nucleophiles.

A good base is not necessarily

a good nucleophile, and vice versa.

HOWEVER :

slide3

NUCLEOPHILE VERSUS BASE

Nu1

Nu2 is a better

nucleophile

Nucleophilicity = Kinetic

( FASTER RATE )

Rate = k2[RX][Nu]

Nu2

good nucleophile

increases k2

(I.e., the rate)

Nu1 is a

better base

Basicity = Thermodynamic

( STRONGER BOND )

B:- + H+

B-H

strong base

shifts equilib.

slide4

DIFFERENT PLACES ON THE ENERGY PROFILE

DETERMINE NUCLEOPHILICITY AND BASICITY

NUCLEOPHILES

Nucleophilicity is

determined here

activation energy

and rate (kinetics)

faster is better

BASES

Basicity is

determined here

strength of bonds

and position of

equilibrium

lower energy is better

slide5

IS THE NUCLEOPHILE IMPORTANT

IN BOTH SN1 AND SN2 REACTIONS ?

slide6

NUCLEOPHILES

IMPORTANCE IN SN1 AND SN2 REACTIONS

Nucleophiles are unimportant in an SN1 reaction;

they are not involved in the rate-determining step.

SN1 rate = K1 [RX]

The nature of a nucleophile is only important to

an SN2 reaction.

SN2 rate = K2 [RX][Nu]

slide7

WHAT IS A

GOOD NUCLEOPHILE ?

SN2 REACTIONS

slide8

..

:

:

Y

..

..

-

:

:

X

..

WHAT IS THE IDEAL NUCLEOPHILE ?

SN2 REACTIONS

LARGE

STERIC PROBLEMS

no way ! bad

R

SMALL

:

C

Br

good

R

R

Smaller

is better !

For an SN2 reaction the nucleophile must find

the back lobe of the sp3 hybrid orbital that the

leaving group is bonded to.

slide9

..

..

:F:

:Cl:

..

..

EXPECTED “IDEAL” NUCLEOPHILES

cyanide

-

ROD OR SPEAR

SHAPED

:C N:

-

-

+

:N N N:

azide

SMALL

SPHERES

These types

should be

able to find

the target !

-

-

etc.

Generally this idea is correct.

slide10

OUR NAÏVE EXPECTATION

We would expect the halides to be good nucleophiles:

ionic radii:

1.36 A 1.81 A 1.95 A 2.16 A

smallest

ion

-

-

-

-

F

Br

I

Cl

and we would expect the smallest one (fluoride)

to be the best nucleophile,

….. however, that is not usually the case.

slide11

EXPERIMENTAL RESULTS

RELATIVE RATES OF REACTION FOR THE HALIDES

MeOH

CH3-I + NaX

CH3-X + NaI

Rate = k [CH3I] [X-]

SN2

k

slowest

F-

5 x 102

Cl-

2.3 x 104

Br-

6 x 105

fastest

I-

2 x 107

* MeOH solvates like water but dissolves everything better.

slide12

SOLVATION

Solvation reverses our ideas of size.

slide13

HEAT OF SOLVATION

ENERGY IS RELEASED WHEN AN ION IS PLACED IN WATER

-

F

gas phase

- 120 Kcal / mole

HEAT OF SOLVATION

F- (g)

F- (aq)

O

H

H

O

The interaction between

the ion and the solvent

is a type of weak bond.

Energy is released when

it occurs.

Solvation lowers the

potential energy of the

nucleophile making it

less reactive.

-

SOLVATED

ION

H

H

F

H

H

O

H

H

O

water solution

slide14

-

X(H2O)n

HALIDE IONS

IONIC

RADIUS

1.36 A 1.81 A 1.95 A 2.16 A

smallest

ion

-

-

-

-

F

Br

I

Cl

Heats of

solvation

in H2O

- 120

- 90

- 75

- 65

Kcal / mole

increasing solvation

larger n

smaller n

SMALL IONS SOLVATE MORE THAN LARGE IONS

slide15

WATER AS A SOLVENT

polar OH bonds

Water is a polar molecule.

Negative on the oxygen end, and positive on the hydrogen end.

It can solvate both cations and anions.

slide16

SMALL IONS SOLVATE MORE HEAVILY THAN LARGE ONES

strong interaction

with the solvent

-

-

F

I

BETTER

NUCLEOPHILE

O

H

H

H

O

H

O

H

...smaller

solvent shell

...escapes

easily

…more

potential

energy

H

-

O

H

H

H

-

O

H

O

H

H

H

H

H

H

H

O

O

H

O

O

solvent

shell

H

H

“Effective size” is larger.

Heavy solvation lowers the

potential energy of the nucleophile.

weak interaction

with the solvent

It is difficult for the solvated nucleophile

to escape the solvent shell.

This ion is less reactive.

slide17

PROTIC SOLVENTS

water methanol ethanol amines

Water is an example of a “protic” solvent.

Protic solvents are those that have

O-H, N-HorS-H bonds.

Protic solvents can form hydrogen bonds and can

solvate both cations and anions.

slide18

LARGER IONS ARE BETTER NUCLEOPHILES

IN PROTIC SOLVENTS

THREE FACTORS ARE INVOLVED :

In protic solvents the larger ions are solvated less

(smaller solvent shell) and they are, therefore,

effectively smaller in size and have more potential

energy.

1

Since the solvent shell is smaller in a larger ion

it can more easily “escape” from the surrounding

solvent molecules during reaction. There is more

potential energy.

2

3

The larger ions are thought (by some) to be

more “polarizable”.

see the next slide …..

slide19

POLARIZABILITY

Polarizability assumes larger ions are able to easily

distort the electons in their valence shell, and that

smaller ions cannot.

C

Br

VERY

HYPOTHETICAL

The distortion of large ions is easier because the

orbital clouds are more diffuse.

The nucleophile “flows” into the reactive site.

slide20

BASICITY

If everything else is equal, the stronger base is

the better nucleophile.

This principle shows up in a period, where

atoms do not vary appreciably in size, and

solvate to similar extents.

OH- is a better nucleophile than F-

slide21

NUCLEOPHILICITY TRENDS

IN PROTIC SOLVENTS

slide22

OBSERVED NUCLEOPHILICITY TRENDS

H2O OR OTHER “PROTIC” SOLVENTS

GROUP

IV V VI VII

increasing nucleophilicity (ROWS)

basicity

CH3-NH2-OH- F-

increasing

nucleophilicity

PH2-SH- Cl-

(COLUMNS)

Br-

I-

basicity

more solvation,

larger effective size,

lower potential energy

slide23

RELATIVE RATES OF SOME NUCLEOPHILES

MeOH

CH3-I + Nu:

CH3-Nu + I-

SN2

Rate = k [CH3I] [X-]

CH3OH 1.0

NH3 3.2 x 105

(CH3)2S 3.5 x 105

C6H5NH2 5 x 105

C6H5SH 5 x 105

(solvolysis is faster)

F- 5 x 102

CH3COO- 2 x 104

Cl- 2.3 x 102

C6H5O- 5.6 x 105

N3- 6 x 105

Br- 6 x 105

CH3O- 2 x 106

CN- 5 x 106

I- 2 x 107

C6H5S- 8 x 109

these are the good

nucleophiles, but

watch out, some

are strong bases

CHARGED

NEUTRAL

slide25

APROTIC SOLVENTS

-

-

+

+

dimethylsulfoxide

“DMSO”

dimethylformamide

“DMF”

hexamethylphosphoramide

“HMPA”

acetone

acetonitrile

APROTIC SOLVENTS

DO NOT HAVE

OH, NH, OR SH BONDS

if scrupulously

free of water

They do not form

hydrogen bonds.

slide26

APROTIC SOLVENTS SOLVATE CATIONS,

BUT NOT ANIONS (NUCLEOPHILES)

+

crowded

-

-

+

The nucleophile is

“free” (unsolvated),

and therefore is small

and not hindered by

a solvent shell.

slide27

DIMETHYLSUFOXIDE

space-filling

O

S

H

H

density - electrostatic potential plot

slide28

DIMETHYLFORMAMIDE

X-

nucleophile is “free”

(unsolvated)

slide29

OBSERVED NUCLEOPHILICITY

APROTIC SOLVENTS

GROUP

IV V VI VII

increasing nucleophilicity (ROWS)

CH3-NH2-OH-F-

increasing

nucleophilicity

PH2-SH-Cl-

(COLUMNS)

Br-

I-

decreasing

ionic size

basicity

The direction of the red arrow (COLUMNS) represents a

different order than in protic solvents.

slide30

WHY NOT ALWAYS USE

APROTIC SOLVENTS FOR SN2 ?

Mostly, it is a matter of expense.

Water, ethanol, methanol and acetone are much

cheaper, especially water.

Water “free”

Methanol $14.70 / L

Ethanol $15.35 / L

Acetone $16.60 / L

DMSO $47.50 / L

DMF $33.75 / L

HMPA $163.40 / L

Cheapest grades available, Aldrich Chemical Co., 2000.

slide31

SOLVENTS

WHAT ARE GOOD SOLVENTS FOR SN1 AND SN2 ?

slide32

SN1 SOLVENTS = POLAR

SN1 reactions prefer polar-protic solvents that

can solvate the anion and cation formed in the

rate-determining step.

ions

R-X

R+ + X-

rate-determining

step

solvation of both ions

speeds the ionization

Carbocation

slide33

SN2 SOLVENTS = NONPOLAR

OR POLAR-APROTIC

SN2 reactions prefer “non-polar” solvents, or

polar-aprotic solvents that do not solvate the

nucleophile.

..

R

:

:

X

..

:

C

Br

SMALL,

UNSOLVATED

R

R

smaller is better !

slide34

SN1

POLAR

APROTIC

SOLVENTS

POLAR

overall

polarity

SN2

POLAR

PROTIC

SOLVENTS

NONPOLAR

SOLVENTS

NONPOLAR

slide36

SOLVENT MIXTURES ARE VERY COMMON

RX

Alkyl halides don’t dissolve in water,

but dissolve in most organic solvents.

NaX

Nucleophile salts don’t dissolve in most

organic solvents, but dissolve in water.

Both dissolve in a mixed solvent.

miscible solvents

soluble in EtOH

soluble in H2O

slide37

EXCEPTIONS

NaX

Dissolve in polar-aprotic organic solvents:

DMF, DMSO, HMPA.

NaI and NaCN dissolve in acetone,

but NaCl and NaBr do not

slide38

THE BOTTOM LINE

SN1

CARBOCATIONS REACT WITH ALL NUCLEOPHILES EQUALLY

The nucleophile is not involved in the rate-determining step.

SN2

BETTER NUCLEOPHILES REACT FASTER GIVING MORE PRODUCT

The nucleophile is involved in the rate-determining step.