3. Chemistry...
NUCLEOPHILE ELECTROPHILE
electron rich electron poor
high electron low electron
density density
this slide sums up
the majority of
chemical reactions
(even the funkier ones
follow these
...it’s that simple
principles)
4. Chemistry...
NUCLEOPHILE ELECTROPHILE
electron rich electron poor
high electron low electron
density density
...so that was a
quick lecture...
...it’s that simple
5. lets look at a simple
reaction...
lets just show its
that simple (we do
have 50 minutes to
kill after all)
6. the Lucas test
H3C H3C
ZnCl2 (aq)
H3C OH + HCl H3C Cl + H2O
H3C H3C
the Lucas test is
simple...you’ll do it lab
this week...two water
soluble compounds
react...
water soluble water soluble water insoluble
H-bond ion-dipole two layers
7. the Lucas test
H3C H3C
ZnCl2 (aq)
H3C OH + HCl H3C Cl + H2O
H3C H3C
to give an insoluble
compound. Why
insoluble? (no longer
able to H-bond)
water soluble water soluble water insoluble
H-bond ion-dipole two layers
9. the Lucas test
H3C H3C
ZnCl2 (aq)
H3C OH + HCl H3C Cl + H2O
H3C H3C
ratio of
}
}
compounds in
reaction
reactants products
stoichiometry
1 : 1 : 1 : 1
10. ...simply count atoms (or electrons)...
sorting out the
stoichiometry is
easy...just make sure you
have the same number of
atoms on both sides of
the equation and
remember...
12. unfortunately,
chemists are lazy...
a quick word of
warning...organic chemists
are a little lazy and often
miss side products off their
reaction schemes!
13. depiction of a standard reaction
OMe OMe
H2SO4
HO3S
...so, here is a
standard reaction as
shown in many text
books...
14. depiction of a standard reaction
OMe OMe
H2SO4
HO3S
...problem is, it
doesn’t show
everything...so lets
have a closer look...
16. depiction of a standard reaction
redraw sulfuric acid
and it becomes
clear that we will
loose an OH...
OMe OMe
HO SO3H
HO3S
obviously lost OH
17. depiction of a standard reaction
OMe OMe
HO SO3H
HO3S
...we can’t just add it to
the aryl ring or one C
would have too many
electrons...
obviously lost OH
18. depiction of a standard reaction
OMe OMe
HO SO3H
H HO3S
remember we don’t always draw H
19. depiction of a standard reaction
OMe OMe
HO SO3H O
H H
H HO3S
...overall we have
lost H from
aromatic and OH
from acid...or water
which means we ‘forgot’ to add HOH
20. depiction of a standard reaction
OMe OMe
HO SO3H O
H H
H HO3S
which means we ‘forgot’ to add HOH
21. depiction of a standard reaction
OH
HO Me Br O
O Me
HO
O OMe
O
O OMe
22. depiction of a standard reaction
H
O
HO Me Br O
O Me
HO
O OMe ...break O–H bonds...
O
O OMe
all the bonds broken & formed
23. depiction of a standard reaction
H
O
HO Me Br O
O Me
HO
O OMe
O
O ...break C–Br bond...
OMe
all the bonds broken & formed
24. depiction of a standard reaction
...form C–O bond
AND H–Br
H
O
HO Me Br O
H Br
O Me
HO
O OMe
O
O OMe
...and the ‘mystery’ product
25. depiction of a standard reaction
H
O
HO Me Br O
H Br
O Me
HO
O OMe
O
O OMe
1 3 1 3
don’t forget the stoichiometry
28. Lewis structures
here is the Lucas
reaction again...
H3C H3C
H3C OH + + H3C Cl + O
Cl H H H
H3C H3C
as each bond is two electrons
we have just moved electrons...
29. Lewis structures
H H
H C H H C H
H H H
Cl
H C C O H H C C Cl O H
HH H HH
C H C H
H H
H3C H3C
H3C OH + + H3C Cl + O
Cl H H H
...and here is the
H3C H3C
Lewis structures
as each bond is two electrons
we have just moved electrons...
30. Lewis structures
...we take O with its
complete octet of
electrons and share
H two of them with H H
to...
H C H H C H
H H H
Cl
H C C O H H C C Cl O H
HH H HH
C H C H
H H
H3C H3C
H3C OH + + H3C Cl + O
Cl H H H
H3C H3C
as each bond is two electrons
we have just moved electrons...
31. Lewis structures
H H
...form water...
H C H H C H
H H H
Cl
H C C O H H C C Cl O H
HH H HH
C H C H
H H
H3C H3C
H3C OH + + H3C Cl + O
Cl H H H
H3C H3C
as each bond is two electrons
we have just moved electrons...
32. Lewis structures
...then we share the
electrons of the chloride
octet to make sure the
original C is still an a
happy octet...
H H
H C H H C H
H H H
Cl
H C C O H H C C Cl O H
HH H HH
C H C H
H H
H3C H3C
H3C OH + + H3C Cl + O
Cl H H H
H3C H3C
as each bond is two electrons
we have just moved electrons...
33. Lewis structures
H H
H C H H C H
H H H
Cl
H C C O H H C C Cl O H
HH H HH
C H C H
H H
H3C H3C
H3C OH + + H3C Cl + O
Cl H H H
so just swapped
H3C electronsC
H3 around...
as each bond is two electrons
we have just moved electrons...
36. substitution
reactions
A B + C A C + B
does what it says...the
reagent swaps with a
functional group in our
molecule...
37. substitution
reactions
OH OH
Br CH3NH2 NHCH3 H Br
here’s an example from the
synthesis of prozac® where an
amine substitutes / displaces /
exchanges with a bromide...
38. substitution
reactions
Na O
Cl O
NHCH3 NaCl
NHCH3 F3C
F3C
fluoxetine
here is another example finishing the
Prozac®
synthesis of prozac®; an alkoxide
(alcohol derivative) substitutes a
chloride...
39. A + Y A Y
two molecules add
together or combine...all
atoms in both starting
addition
materials are found in the
product
reactions
40. CH3
CH3
+ H Br Br
H
here hydrogen
bromide adds across
an alkene to give us a
addition
new bromide
reactions
41. at some point you’ll have to
learn why it adds the bromide
to the more hindered end of the CH3
CH3alkene...but that’s someone
+
else’s job! H Br Br
H
addition
reactions
42. O H3C O MgBr
H3C MgBr CH3
CH3
Ph Ph
here a Grignard reagent
is adding to a ketone to
give (eventually) an
addition
alcohol
reactions
43. elimination
reactions
A X A + X
elimination is the opposite
of addition...we rip a bit of
the molecule off.
44. elimination
reactions
OH
CH3 CH3
O
H H
H
this example shows
the elimination of
water (dehydration) to
form an alkene
45. elimination
reactions
CH3 Br
H3C CH3
H3C
H3C H Br
H3C
H
or the elimination of
hydrogen bromide
(hydrobromic acid) to
form an alkene
46. what reagents are
involved in these
reactions?
now we know what reactions
we can perform...what
reagents can we use?
47. nucleophiles
2
electron rich molecules
nucleophiles are electron
rich compounds that
donate two electrons to
form a new bond...
examples include...
donateelectrons
48. anions
H O ≡ H O Br ≡ Br
3 lone pairs 4 lone pairs
H
H3C
≡ Pr C
H
1 lone pair
49. anions
H O ≡ H O Br ≡ Br
negatively charged
compounds that possess a
3 lone pairs
lone pair of electrons that 4 lone pairs
can form a new bond
H
H3C
≡ Pr C
H
1 lone pair
52. anions
nucleophilic reaction
O H O
H H H
note: both sides of
equation have same
charge (both are
neutral overall)
53. anions
nucleophilic reaction
O H O
H H H
note: both sides of
equation have same
charge (both are this is a good sign that you’ve
neutral overall) got the reaction right!
54. lone pairs
lone pairs as
nucleophile
O N S
H H H H H3C CH3
H
water ammonia dimethyl sulfide
(DMS)
lone pairs on neutral
molecules are also good
nucleophiles...
56. lone pairs
nucleophilic reaction
ammonia donates a
pair of electrons to
form a new bond to
hydrogen chloride
H
N H Cl N Cl
H H H H
H H
57. lone pairs
nucleophilic reaction
can’t have two bonds to H
(4 electrons) so break H–
Cl bond with electrons
flowing towards most
electronegative element
H
N H Cl N Cl
H H H H
H H
60. bonds bonds can also be a
source of electrons...and
these cause confussion!
δ– δ+ H
C Y
Y=Li, Mg B
H H
nucleophilic H
site
reactive
σ bond
H H
C C
H H R
high electron density R = electron
nucleophile donating group
61. electrophiles
2
electron poor molecules
the other kind of reagents
are...electrophiles are electron
poor compounds that accept two
electrons to form a new bond...
examples include...
acceptelectrons
62. proton
H ≡ H
empty 1s orbital
no electrons!
simplest electrophile...it
has no electrons and
desperately wants some!
64. proton
electrophilic reagent
H H
H
O H O
H H
nucleophilic water
donates two electrons to
proton, which accepts
them to form new bond
65. Group 13
F
F Cl
F B Cl Al F B
F Cl F
empty 2p empty 3p
orbital orbital have 6 valence
only
electrons...need 8 to obey
octet rule so happily accept a
pair of electrons
66. bonds
δ+ δ– Y = Cl, δ+ δ–
C Y Y = O,
Br, N, O C Y NR
electrophilic electrophilic
site site
bonds can be
electrophiles if they are
polarised and have a δ+
centre
78. H3C O H3C Cl H
H + H Cl + O
H3C H3C
CH3 CH3 H
so here’s the Lucas
test again...overall
it’s a substitution of
hydroxyl for chlorine
what order are the
bonds made and broken?
79. H3C O H3C Cl H
H + H Cl + O
H3C H3C
CH3 CH3 H
what order are the
bonds made and broken?
80. H
H3C O H3C O
H H H
H3C H3C
CH3 CH3
CH3 CH3 H
H3C C O H H H3C C O H
CH3 CH3
addition
step
step
one
81. H
H3C O H3C O
H H H
H3C H3C
CH3 CH3
nucleophilic alcohol
CH3 donates 2 electrons to
CH3 H
a proton from H–Cl in
H3C C O H H anH3C Creaction
addition O H
CH3 CH3
addition
step
step
one
82. H
H3C O H3C O
H H H
H3C H3C
CH3 CH3
note: octet rule is
obeyed and the
charge is the same
CH3 on both sides CH3 H
(positive)
H3C C O H H H3C C O H
CH3 CH3
addition
step
step
one
83. H CH3 H
H3C O
H O
H3C H3C CH3
CH3 H
H H
H C H H C H
H H H H
H C C O H H C C O H
HH HH
C H C H
H H
step
two elimination
84. H CH3 H
H3C O
H O
H3C H3C CH3
CH3 H
H H
elimination of
H C H H water...molecule splits in
C H
H H H two...electrons go with
H
most electronegative
H C C O H H C C atom O H
HH HH
C H C H
H H
step
two elimination
85. H CH3 H
H3C O
H O
H3C H3C CH3
CH3 H
charge is the same
H on both sides (positive)... H
we now have a reactive
H C H intermediate H C H
H H H H
(charged species with 6
H C C O H electrons) H C C O H
HH HH
C H C H
H H
step
two elimination
86. CH3 H3C Cl
Cl H3C
H3C CH3 CH3
H H
H C H H C H
H H
H C C Cl H C C Cl
HH HH
C H C H
H H
addition
step
step
three
87. CH3 H3C Cl
Cl H3C
H3C CH3 CH3
H H
H C H H C
finally, second H
H H
addition step to
H C C Cl H C
complete octet C Cl
HH HH
C H C H
H H
addition
step
step
three
88. CH3 H3C Cl
Cl H3C
H3C CH3 CH3
H H
H C H H C H
H H
H C C Cl H C C Cl
HH HH
C H C H
H H
nucleophile donates two
electrons to electrophile
addition
step
that accepts them to
step form new bond
three
89. CH3 H3C Cl
Cl H3C
H3C CH3 CH3
H H
H C H H C H
H H
H C C Cl H C C Cl
HH note: the charge is HH
C H the same on both C H
sides (neutral)
H H
addition
step
step
three
91. another
representation...
we can follow the change of
energy during a reaction...in a
reaction profile
92. reaction profile
energy
Cl
+
H2O
H
O + Cl
H
OH + HCl
reaction
progress Cl + H2O
93. reaction profile
each hill represents
one step in our
reaction
energy
Cl
+
H2O
H
O + Cl
H
OH + HCl
reaction
progress Cl + H2O
94. reaction profile
each dip
represents an
intermediate we
can see
energy
Cl
+
H2O
H
O + Cl
H
OH + HCl
reaction
progress Cl + H2O
95. reaction profile
higher the hill, the
harder the step
energy
Cl
+
H2O
H
O + Cl
H
OH + HCl
reaction
progress Cl + H2O
96. reaction profile
the lower in energy
any stage the more
stable it is
energy
Cl
+
H2O
H
O + Cl
H
OH + HCl
reaction
progress Cl + H2O
97. just one hill, so
just one step
energy
HO
CH3Br
Br
reaction CH3OH
progress
98. no dip so no
intermediates
energy
HO
CH3Br
Br
reaction CH3OH
progress
99. direct
energy
substitution
would look like
this HO
CH3Br
Br
reaction CH3OH
progress
HO + CH3Br CH3OH + Br
100. once again, you will learn
energy
more about this but not
from me! Why don’t I get
HO
to teach the cool stuff? CH3Br
Br
reaction CH3OH
progress
H 1 H 1 H
SLOW 2 δ– 2 δ–
HO + Br HO Br Nu + Br
H RDS H
H H H H
transition state
104. Br H
H Br
what order are the
bonds made and broken?
105. H Br H
H Br
H
H H
what order are the
bonds made and broken?
First, remember that our
skeletal figures are simplifications...these
are all the atoms around the site of the
reaction
106. H
H Br Br
H3C H H3C H
C C H Br C C H Br
H3C H the alkene is the
H3C
nucleophile. Lots ofH
electrons between two
carbon atoms
step
step
one substitution
107. H
H Br Br
it participates in a
substitution reaction, H
H3C H H3C
replacing the bromide...
C C H Br C C H Br
H3C H H3C H
step
step
one substitution
108. H
H Br Br
the alkene attacks the
proton and not the
H3C H bromide. H do the
H3C Why
electrons go for the less
C C H Br electronegativeH
C C atom? Br
H3C H H3C H
step
step
one substitution
109. H
H Br Br
H3C H H3C H
C C H Br C C H Br
H3C H H3C H
If we attacked the bromide first
then, to obey the octet rule, we
would have to give two electrons to
step
H and it would leave as H–. The
step
substitution
hydride (H–) is not stable as it is not
electronegative
one
110. H
H Br Br
electrons flow towards
H3C H the most electronegative
H3C H
element
C C H Br C C H Br
H3C H H3C H
step
step
one substitution
111. H
H Br Br
reaction is not over as we have
a C with only 6 electrons. It is
not obeying the octet rule so is
very reactive
H3C H H3C H
C C H Br C C H Br
H3C H H3C H
step
step
one substitution
112. H Br H
Br
H3C H Br H
C C H Br H3C C C H
H3C H H3C H
step
two addition
113. H Br H
Br
H3C H Br H
C C H Br H3C C C H
H3C H H3C H
Second step is addition. The
bromide shares 2 electrons
with the carbon so that they
step
addition
both obey the octet rule
two
116. reaction profile
the cation (positive charge) is
the intermediate
energy
Br
H Br
reaction
progress Br
117. HO H
HOH Br
Br
what order are the
bonds made and broken?
118. HO H
HOH Br
Br
H O H H H3C H
H3C C C H H O C C Br
H3C Br H H3C H
step
one elimination
119. HO H
HOH Br
Br
H O H H H3C H
H3C C C H H O C C Br
H3C Br H H3C H
once again the electrons
are flowing towards the
step
elimination
most electronegative
element
one
120. HO H
HOH Br
Br
H O H H H3C H
H3C C C H H O C C Br
H3C Br H H3C H
elimination
all atoms maintain the
step
octet rule
one
