Part 3iv

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Part 3iv Substitution Reactions Nucleophile
There is some correlation between basicity and
nucleophilicity.
remember both a base (B) and a nucleophile (Nu)
are electronically very similar.
Both have a lone pair of electrons on an atom
within the molecule
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Content of Part 3iv
The Nucleophile and SN1 Reactions The
Nucleophile and SN2 Reactions How to Estimate
the Nucleophilicity of a Nucleophile Some
Guidelines for Estimating Nucleophilicity Caution
on Correlating Basicity with Nucleophilicity! Ha
rd Base/Soft Base
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CHM1C3 Introduction to Chemical Reactivity of
Organic Compounds
Learning Objectives Part 5iv Substitution
Reactions Nucleophile

• After completing PART 4iv of this course you
  should have an understanding of, and be able to
  demonstrate, the following terms, ideas and
  methods.
• Changing the Nu in which the substrate undergoes
  nucleophilic substitution via an SN1 mechanism
  will have no effect on the rate,
• Changing the Nu in which the substrate undergoes
  nucleophilic substitution via an SN2 mechanism
  will have an effect on the rate,
• (iii) The effectiveness of a nucleophile is
  dependent on its ability to donate a lone pair of
  electrons into a s orbital (could also be a p
  orbtial in the case of addition reactions (see a
  later course)),
• (iv) pKa data can be used as a guide to correlate
  basicity with nucleophilicity by considering the
  conjugate base which is equivalent to the
  nucleophile,
• (v) Correlations of basicity and nucleophilicity
  should be done with care as acid/base reactions
  are thermodynamically controlled and are little
  effected by steric influences, whereas
  electrophile/nucleophile reactions are generally
  under kinetic control and are influenced by
  steric factors,
• Correlations of basicity and nucleophilicity
  should only be carried out when considering the
  same heteroatom carrying a lone pair (i.e.
  compare like with like, EtO-, PhO-, CH3C(O)O-).
• The concept of hard and soft bases is useful for
  evaluating the differences in nucleophilicity
  between different heteroatoms carrying lone
  pairs, where the assesment is made on the
  difference in electronegativities of the atoms
  and the degree of polarisability of the lone pair
  of electrons,
• Some nucleophiles carry lone pairs of electrons
  on more than one heteroatom and, therefore, can
  attack electrophilic centres through both
  heteroatoms ambident nucleophiles. The more
  electron rich heteroatom (more lone pairs, higher
  charge) will react with electrophilic centres
  involving SN1 reaction conditions, whilst the
  less electron rich heteroatom will react with the
  electrophilic centre under SN2 conditions, and
• One should not forget the role that solvent can
  have on the nucleophilicity of nucleophiles (see
  part 4ii)

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The Nucleophile and SN1 Reactions
The rate of reaction for an SN1 reaction is
Rate kR-Hal
Thus, simply changing the nucleophile will have
no effect on the rate of reaction as the rate
determining step (the slowest step) only involves
the haloalkane.
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The Nucleophile and SN2 Reactions
Conversely, in a SN2 reaction changing the
nucleophile can have dramatic effects on the rate
of reaction as the rate determining step (the
formation of the transition state) is dependent
on the nucleophile, having a rate equation
described by
Rate kR-HalNu
So if nucleophile A is better than nucleophile
B the reaction rate will be quicker when A is
used!
We refer to the relative degrees of nucleophile
efficiency as NUCLEOPHILICITY
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How to Estimate the Nucleophilicity of a
Nucleophile
The nucleophilicity is all to do with the ease
(or not) of a lone pair of electrons being
donated in to the s orbital of an electrophilic
atom centre
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Some Guidelines for Estimating Nucleophilicity
There is some correlation between basicity and
nucleophilicity.
remember both a base (B) and a nucleophile (Nu)
are electronically very similar.
Both have a lone pair of electrons on an atom
within the molecule
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Elimination Mechanisms
Base, B
The lone pair of electrons on a base attack a
electrophilic hydrogen atom.
Nucleophile, Nu
Substitution Mechanisms
The lone pair of electrons on a nucleophile
attack a electrophilic atom other than hydrogen.
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Thus, by considering pKa values one can estimate
the nucleophilicity. Of course, we will be
considering the conjugate base as the
nucleophile. Thus, the higher the pKa the better
the conjugate base will be as the nucleophile
Nucleophilicity
pKa
conjugate base
Good
15.9
10.00
Intermediate
Bad
4.76
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Caution on Correlating Basicity with
Nucleophilicity!
An base-acid reaction is an equilibrium
process. That is to say that the reaction lies
at its thermodynamically most stable state
A nucleophile-electrophile reaction is not an
equilibrium process. That is to say that the
reaction is kinetically controlled (once the
Nu-carbon bond is formed it is generally not
reversible).
An base-acid reaction is little effected by
steric influences (a proton is small!)
A nucleophile-electrophile reaction is subject to
steric factors.
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Hard Base/Soft Base
Hard Base this is a donor atom of high
electronegativity O and N The lone pair of
electrons are held tightly by the donor
atom Thus, these electrons are not very
polarisable Therefore, more difficult to donate
these electrons to the s orbital
Soft Base this is a donor atom of lower
electronegativity S, I, Br, and Cl The lone
pair of electrons are held loosely by the donor
atom Thus, these electrons are
polarisable Therefore, much easier to donate
these electrons to the s orbital
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Thus, softness promotes nucleophilicity
Harder
Softer
R3N 3.0 RO- 3.5 F- 4.0
R3P 2.1 RS- 2.4 Cl- 3.0
Br- 2.8
I- 2.5
Softer
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Summary Sheet Part 3iv Substitution
Reactions Nucleophile
CHM1C3 Introduction to Chemical Reactivity of
Organic Compounds
It is no surprise that changing the nucleophile
in reactions in which the substrate (the
haloakane) ionises to the carbocation (i.e. SN1
reactions in which the rate is independent of the
Nu) has no effect on the rate of the reaction,
whereas the rate can be dramatically effected in
reactions which follow an SN2 reaction
course. The SN2 substitution reaction is driven
by the ability of a lone pair of electrons to be
donated from a nucleophilic species into the s
orbital associated with an electrophilic atom
(usually carbon). The ability of the the lone
pair to do this donation (the nucleophilicity) is
dependent on several factors which include (i)
the degree of solvation of the nucleophile (high
e or low e solvents (part 4ii)), (ii) the nature
of the solvent (protic or non-protic (part 4ii)),
the electronegativity of the heteroatom carrying
the lone pair of electrons, and (iv) the nature
of the heteroatom (ROH compared to RO-). An
assessment of nucleophilicity between the same
heteroatoms can be carried out utilising pKa
(acid/base) date, bearing in mind that the
analysis is not a direct comparison because (i)
acid/base reactions are thermodynamically
controlled (i.e. reversible equilibria) and are
not influenced by sterics, whilst
electrophile/nucleophile reactions are generally
kinetically controlled (i.e. unreversible
equilibria) and are influenced by steric
factors. For considering the nucleophilicity of
lone pairs of electrons on different heteroatoms
it is useful to use the concept of hard and soft
bases, which is based on the electronegativity of
the heteroatom. The lower the electronegativity,
the smaller the attraction of the nucleus for the
outer valence electrons, and therefore the more
easily the valence lone pairs of electrons will
be polarised by electrophiles. Thus, low
electronegativity atoms soft bases are better
nucleophiles than hard bases. Finally, ambident
nucleophiles (CN-, NO2-) contain more than one
heteroatom carrying a lone pair of electrons.
Thus, they can react with elecrophilic centres in
two fashions. Under SN1 reaction conditions the
more electron rich heteroatom react with the
electrophilic centre, whereas under SN2 reaction
conditions the less electron rich heteroatom
reacts with the electrophilic centre.
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Complete the table and comment on the difference
in rates between the reactions when R H and Ph.
Exercise 1 Substitution Reactions
Comments
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Complete the table and comment on the difference
in rates between the reactions when R H and Ph.
Exercise 1 Substitution Reactions
SN2
1
2
3
4
6
5
kR-BrNu
SN1
rates all the same
kR-Br
1
When R Ph the carbocation can be formed, as
this produces the stablised benzyl cation, thus
reaction goes by SN1 Mechanism. Rate equation for
SN1 process is not dependant on Nu concentration,
as rate determining step is formation of
carbocation. Thus, relative rates are all the
same. When R H the cabocation can not be
formed, as this would produce the highly unstable
primary carbocation, hence reaction proceeds via
SN2 mechanism. SN2 mechanism is dependent on Nu
concentration, hence rates will be dependant on
effectiveness of nucleophiles, which we can
correlate to pKas of the corresponding acids of
the nucleophiles.
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Exercise 1 Substitution Reactions
Identify the products and rationalise the
differences in product outcome.
NaNO2 EtOH Rate kR-BrNaNO2
AgNO2 EtOH
1
2(/-)
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Answer 1 Substitution Reactions
Identify the products and rationalise the
differences in product outcome.
NaNO2 EtOH Rate kR-BrNaNO2
AgNO2 EtOH Rate kR-Br
1
2(/-)
Look up ambident nucleophiles