strong bases via an E2 process.

When a tertiary alkyl halide is dissolved in a polar solvent that is

hess. When
a weak a tertiary
base and alkyl halide
a weak nucleophile is dissolved
(such as ethanol, EtOH), in a polar
we expect an Ssolvent that
N2 process to be
IX. Unimolecular
cleophile
avored, because(such
the substrate isReactions(S
as ethanol, EtOH),
tertiary and because N1
we
the and E1) an
expect
nucleophile SN2Weprocess
is weak. also expectto
an b
process to be disfavored because the base is weak. However, substitution and elimination products
eboth Consider  and
•is observed
tertiary the  following  
because reaction,   where  a  substitution  
is weak.aWe nd  elimination  
to form over time, as the
seen innucleophile
the following example: also expect a
products  are  formed  when  dissolving:  
use the base is weak. However, substitution and elimination produc
Br OEt
ime, as seen in the following EtOH
(Solvent)
example:+
Substitution Elimination
product product
OEt
• EtOH
The   substrate  is  3˚,  Hello
so  S 2  substitution  is  not  possible.  
+ N
erimental observations for this reaction (and others like it) are not consistent with SN2 and E2 processes.
(Solvent)
• theMethyl  
example, groups  of
rate of formation physically  
each productprevent  
is foundatonything  
have thefrom   attacking  
following at  the  
rate expression:
back-­‐side.   Substitution Elimination
product Rate = k product
[substrate]
• The  reagent  is  EtOH  is  not  a  strong  base,  so  E2  elimination  is  also  
unlikely.  
rate equation is said to be first order, because the rate is linearly dependent on the concentra-
reaction
of only (and
• oneProtic  
compound sothers (the like
olvents   also  it) are
are  
substrate). not
no  
This consistent
gobservation
ood   with Sthat
for  SNdemonstrates
2  reactions   N2theand E2 processe
products must be
nmed
•ofvia
each product
It  processes
turns   oother isformation  
than
ut  the   found
SN2 andto of  have
E2 reactions,thewhich
following
the  substitution   would and  beerate expression:
expected to exhibit
limination   second-
products  
r rate follow  
equations. In this section,
first-­‐order   we w
kinetics,   will explore
hich   new mechanisms,
confirms   neither  SN2  called
nor  ES2  
N1is  and E1, that
occurring.  
unt for these and other observations. Both mechanisms begin with the same first step—loss of a
ng group to give
Rate = k [substrate]
a carbocation intermediate:
What  is  this  rate  law  telling  us??
⊝
Substitution
on is said to be first order, because the rate is linearly dependent on th
IX. Unimolecular
compound (the substrate). Reactions(S N1 anddemonstrates
This observation E1) that the prod
esses other than SN2 and E2 reactions, which would be expected to exh
tions. In this
• The   section, owe
mechanisms   will explore
f  substitution   new
and   mechanisms,
elimination   in  this  ccalled SN1 a
ase  both  
e and start  
otherwobservations.
ith  the  same  sBoth mechanisms
tep:  ionization   begin
of  the   with the same first st
substrate  
give •a carbocation intermediate:
Tertiary  carbocation   is  stabilized  by  hyperconjugation  

Hello
⊝
Substitution (SN1)&
Br – Br

⊕
Elimination (E1)%
The$leaving$group$leaves$to$form$
$a$carboca5on$intermediate$
l halide is said to undergo ionization, because it dissociates into a pair o
• After  the  carbocation  is  formed,  it  will  either  undergo  substitution  
bromide ion). The fate of the carbocation intermediate then determines
or  elimination,  depending  on  how  it  reacts  with  the  solvent  
are two possibilities, depending on the role played by the solvent in th
(EtOH).
nt can function as a nucleophile, giving a substitution reaction, or the
ase, giving an elimination reaction. Let’s first explore the substitution
lore the elimination process.
 7.9 Loss of a leaving group
Unimolecular Reactions (SN1 and E1) 35
Nucleophilic attac

IX. Unimolecular Reactions(SN1 and E1) ⊝

Br – Br EtOH
echanism ⊕
• The   s ubstitution   reaction   o f   a   3˚   s ubstrate,  
y alkyl halide undergoes ionization in a polar solvent, such as EtOH, the i n   a n   alcohol   solvent  
solvent can
like  
ucleophile and EtOH,  
attackpthe
roceeds  
Since a tsolvent
hrough  
intermediate a  two-­‐step  
molecule
carbocation, resulting(stepwise)  
functions as athe
in attacking
two-step msubstitu-
echanism  
nucleophile, the p
Notice that the result of this two-step substitution process is an oxonium
positive charge on an oxygen atom). This oxonium ion can then lose its p
Loss  of   Nucleophilic
Loss of a leaving group
leaving  group giving the observed substitution
Nucleophilic
attack attack product:

⊝
Hello HH ⊕
⊕
Br – Br EtOH O Et
O Et EtOH OEt
⊕

Substitution
t molecule functions as the attacking nucleophile, the process is called a solvolysis. product
• ofThe  
result this e ntire  m
two-step echanism  
Figure 7.16 ishows
substitution s  actually  
process 3  sdiagram
is an oxonium
an energy teps,  
ion (anbthat
ut   tdepicts
he  last  
intermediate
allssteps
tep  aiin
with s  jthis
ust  solvoly
a  
on an oxygen atom).
proton   This oxonium
transfer   (this  sion can
tep   is  then loseleft  
often   its proton to assolvent
out  for   molecule,
implicity)  
rved substitution product: Substitution

H
• This  is  called  
O Et “solvolysis”  
⊕
EtOH because  
OEtthe  nucleophile  
Loss of a is  also  the  
solvent. leaving
group
Substitution Nucleophilic
product Proto
attack
transfe
IX. Unimolecular Reactions(SN1 and E1)

• The  highest  energy  transition  state,  in  SN1,  is  for  the  formation  of  
the  carbocation  intermediate.    So,  formation  of  the  carbocation  
is  the  rate  determining  step  (the  slowest,  highest  energy  step).  

Hello

Intermediate  I
Intermediate  II
 Substitution Elimination
IX. product
Unimolecular product
Reactions(S N1 and E1)

• Since  the  formation  of  the  carbocation  requires  only  ionization  

action (and others like it) are not consistent with SN2 and E2 processes.
of  the  substrate,  the  rate  of  it’s  formation  depends  only  on  the  
of each productso  
substrate,   is tfound to have
he  reaction   the following
follows   first-­‐order  rate expression:
kinetics  

The$rate$of$SN1$subs0tu0on$
Rate = k [substrate]
Hello depends$only$on$the$substrate$

• Now  ibecause
st order, t  is  clear  tthe
hat  rate
when  issubstitution  
linearly dependent
occurs  via  aon the concentra-
 carbocation  
ubstrate). This observation
intermediate,   it  is  called  “demonstrates
SN1” that the products must be
N2 and E2 reactions, which would be expected to exhibit second-
ion, we will explore new mechanisms, called SN1 and E1, that
vations. Both mechanisms begin with the same first step—loss of a
n intermediate:

⊝
Substitution
IX. Unimolecular Reactions(SN1 and E1)
Recap:
• A  substitution  reaction  that  occurs  stepwise,  where  the  leaving  
group  first  leaves  to  form  a  carbocation  intermediate,  followed  
by  nucleophilic  attack  is  called  SN1  substitution.  

Hello

• Remember  that  when  the  nucleophile  is  a  neutral  species,  such  

as  an  alcohol,  there  will  be  a  proton  transfer  after  nucleophilic  
attack
E2 process. When a tertiary alkyl halide is dissolved in a polar solv
weak nucleophile (such
IX. Unimolecular as ethanol,N1EtOH),
Reactions(S and E1) we expect an SN2 pro
substrate is tertiary and because the nucleophile is weak. We also
The  elimination  
ed• because the base risxn  weak.
of  a  3˚  However,
substrate,  substitution
in  an  alcohol  sand
olvent   like  
elimination
EtOH,  proceeds  through  a  two-­‐step  (stepwise)  mechanism  
m over time, as seen in the following example:

Br OEt
EtOH Hello +
(Solvent) Loss  of   β-­‐hydrogen
leaving  group elimination
Substitution Elimination
product product
• Here,  EtOH  is  serving  as  a  base  (not  as  a  nucleophile)  to  
deprotonate  the  carbocation  and  form  an  alkene  
s for this reaction (and others like it) are not consistent with SN2 and E2
ormation of each product is found to have the following rate expressio
• Like  SN1,  the  E1  mechanism  is  unimolecular,  and  follows  the  same  
kinetics.    
Rate = k [substrate]
 are both observed to form over time, as seen in the following examp
IX. Unimolecular Reactions(SN1 and E1)
Br OEt
EtOH
+
• The  rate  of  E1  is  the  same  as  for  SN1:  in  (Solvent)
both  cases,  the  rate  
determining  step  is  the  formation  of  the  carbocation   intermediate
Substitution Elim
product pr
Both  E1  and  SN1  share
The  same  rate  determining  step
Experimental observations for this reaction (and others like it) are not con
Hello
For example, the rate of formation of each product is found to have the

Rate = k [substrate]

The rate equation is said to be first order, because the rate is linea
tion of only one compound (the substrate). This observation demon
formed via processes other than SN2 and E2 reactions, which woul
order rate equations. In this section, we will explore new mecha
account for these and other observations. Both mechanisms begin w
leaving group to give a carbocation intermediate:
In  this  case  SN1  is  both  the  
kineGc  and  thermodynamic  product
IX. Unimolecular Reactions(SN1 and E1)
Draw  the  carbocation  intermediate  that  is  expected  when  the  
following  alkyl  chloride  undergoes  ionization.    If  the  carbocation  
is  resonance  stabilized,  draw  the  resonance  structures.

Hello
Cl
IX. Unimolecular Reactions(SN1 and E1)
Answer:

Cl
Hello

major  resonance  
structure  
terGary  carbocaGon
IX. Unimolecular Reactions(SN1 and E1)
Draw  the  carbocation  intermediate  that  is  expected  when  the  
following  alkyl  chloride  undergoes  ionization.    If  the  carbocation  
is  resonance  stabilized,  draw  the  resonance  structures.
Br

a.                                                              Hello
     d.                                                        g.  
Br

Br

Cl
Br Cl

b.                                                                    e.                                                        h.  

c.                                                                    f. I
IX. Unimolecular Reactions(SN1 and E1)
Answers:

a.   Br

Hello
Cl

b.  

c.
 IX. Unimolecular Reactions(SN1 and E1)
Answers:
d.  

Br
Hello

e.   Br

f. I
 IX. Unimolecular Reactions(SN1 and E1)
Answers:

g.  
Br

Hello

h.
Cl
 7.9 Unimolecular Reactions (SN1 and E1)

IX. Rearrangements in Unimolecular Processes

rangements in Unimolecular Processes
s additional evidence
• Predict   that solvolysis
the  products   and  dprocesses
raw  the  involve carbocation intermediates. For ex
mechanism:
er the following solvolysis reaction, in which two substitution products are obtained:

H2O
+ + Elimination products
Br heat OH
OH
Hello
Substitution products

case, the solvent is water, and the substitution products are both alcohols (ROH). The re
ords elimination products, but let’s focus our attention on the substitution products. Forma
t product could certainly be rationalized by an SN2 process, but formation of the second p
s a rearrangement, which is inconsistent with an SN2 process. The observed rearrangement is
ce that the reaction proceeds via a carbocation intermediate, which is consistent with an SN1 p
lowing SN1 mechanism, involving a hydride shift, justifies the formation of the rearranged pr

⊝ Hydride O O
– Br H H H H H
⊕ shift
Br ⊕ H
H ⊕O H
 s a rearrangement, which is inconsistent with an SN2 process. The observed rearrangemen
ce that the reaction proceeds via
7.9a carbocation intermediate,
Unimolecular Reactions which
(SN1isand
consistent
E1) with an SN
IX. Rearrangements
lowing SN1 mechanism, involving ina hydride
Unimolecular
shift, justifiesProcesses
the formation of the rearranged
O O
rrangements
• Because  
– Br
⊝ in Unimolecular
SN1  and   Hydride
⊕ E1  rshift
Processes
eactions  proceed  through  
H H H a  carbocation   H H
intermediate,  
isBradditional evidencetthathe  csolvolysis
arbocation   may  
H rinvolve
processes
⊕
earrange   through  
carbocation 1,2-­‐hydride,  
intermediates. For e
H ⊕O H
der themethyl,  
following solvolysis reaction, in
or  other  alkyl  shifts. which two substitution products are obtained:
H

f the leaving group generates

H2O a secondary carbocation,
+ which
+ rearranges
Elimination via a hyd
products
Br
a more stable, tertiaryheat Hello
carbocation. OH
The solvent (water) OH then functions as a nucleo
the carbocation. The resulting oxonium ion is then deprotonated by the solvent to
SN1  product
nged substitution product. SN1  product after  1,2-­‐hydride
Substitution productsshift
Methyl shifts are also observed, as seen in the following example:
s case, the solvent is water, and the substitution products are both alcohols (ROH). The
ffords elimination products,
H2O but let’s focus our attention on the substitution products. Form
+ + Elimination products
st product couldBr certainly
heat be rationalized OHby an SN 2 process, but formation of the second
OH
es a rearrangement, which is inconsistent with an SN2 process. The observed rearrangement i
nce that the reaction proceeds viaSNa1  carbocation
product intermediate,
SN1  product which is consistent with an SN1
llowing SN1 mechanism, involving a Substitution
hydride shift, justifies
after  
products the formation of the rearranged p
1,2-­‐methyl
shift
again, formation
⊝
of the second
Hydride
product requires a rearrangement,
O which is Oinconsis
H H H H H
2 process.– Br
The observed⊕ rearrangement
shift is strong evidence that the reaction proceeds
 ⊕O H
CH3 CH3 ⊕O H OH ⊕
H H H
IX. Rearrangements in Unimolecular Processes
he previous
s very similar
This reaction,
to although
the previous
reaction a methyl
is very reaction,
similar shift occurs
toalthough instead
a methyl
the previous of aalthough
shift
reaction, occurs instead
a metho
hydride
• When   a  1˚  shift.
substrate  is  reacted  under  solvolysis  conditions,  only  
undergoesbromide
neopentyl solvolysis
Curiously, in water
undergoes tosolvolysis
neopentyl give onlyinone substitution
water product:
to giveis  solvolysis
only one substitution produ
the  product   resulting   from  bromide undergoes
rearrangement   in water to give
observed   on
Br OH Br OH OH
H2O H2O H2O
+ + +
heat heat heat
Hello OH OH O
NOT OnlyNOT This  product  
Only NOT is On
Neopentyl bromide
observed Neopentyl
SN1  bromide
substitution product substitution
product not  product
observed
observed observed substitut

observed
drawn at all,
• Remember  
above
The because
isfirst
notalcohol it cannot
1observed bebecause
at all,
drawn formed
˚  carbocations  
aboveare  
is not itvia
too   ueither
cannot
observed pathway
nstable  
be tall,
atformed (SN2
o  fbecause
orm.  
via  either
So,   in  pathway
it cannot this  be form
(S
SNbe
ot 2 pathway
case  
formed because
or tShe  
via
N1). ran of steric
earrangement  
ItScannot
N2 pathway befactors (as
viawe
occurs  
because
formed ofan saw inlfactors
as  steric
Sthe   Section(asgbecause
eaving  
N2 pathway
7.3), and
roup  
we saw leaves.
ofinsteric
Section 7.3),(aa
factors
hway, because
med via that would
anitScannot
N1 pathway, be formed require
viaformation
because that
an Swould ofrequire
N1 pathway,
a primary carbocation:
formation
because that of a primary
would require carbocatio
formati
Br Br
⊕ ⊝ ⊕ ⊝ ⊕
+ Br + Br + B
1,2-­‐methyl  shift  and
ionization  NOT
is  concerted,
formed NOT formed NOT formed
3˚  carbocation  is  formed
(primary carbocation)(primary carbocation) (primary carbocation)
IX. Effect of Solvent on Reaction Rates

• Experimental  data  indicates  SN1  and  E1  reactions  are  faster  in  a  
polar  protic  solvent

Hello

most  polar

least  polar
 IX. Effect of Solvent on Reaction Rates
• Overall:    For  SN2  reactions,  a  polar  aprotic  solvent  is  best  
• You  do  NOT  want  stabilization  of  the  nucleophile,  you  want  it  to  be  
higher  in  energy  and  reactive  
• For  SN1  reactions,  a  polar  protic  solvent  is  best  
• You  want  to  stabilize  the  carbocation  and  the  anionic  leaving  
group.    Protic  Hello
solvents  are  the  best  at  this!
Nucleophile  NOT  
stabilized   Carbocation  NOT  
(easier  for  it  to  react) stabilized  
(difficult  for  it  to  form)

Stabilized  carbocation  
(easier  for  it  to  form)

Nucleophile    
stabilized  
(harder  for  it  to  react)
IX. Effect of the Substrate on the Ionization Rates

The  better  the  leaving  group,  the  faster  the  SN1  or  E1  reaction  

Hello

• Remember  the  rate-­‐determining  step  for  SN1  and  E1  of  alkyl  
halides  is  the  ionization  step:  the  formation  of  a  carbocation  and  a  
halide  ion  

• So,  the  more  stable  the  halide  ion,  the  faster  the  ionization  
✴ Larger,  more  polarizable  ions,  are  better  at  stabilizing  a  
negative  charge.    That  means  these  anions  are  the  best  
leaving  group.
IX. Effect of the Substrate on the Ionization Rates

The  more  stable  the  carbocation  intermediate,  the  faster  the  SN1  
and  E1  reactions  will  be.    
• Solvolysis  reactions  of  1˚  and  2˚  alkyl  halides  are  often  too  slow  to  
observe  the  formation  of  SN1  and  E1  products    
Hello
• 1°  and  2°  carbocations  are  too  high  in  energy  (not  enough  
hyperconjugation  to  stabilize  them.  
• However,  3˚  alkyl  halides,  as  well  as  benzylic  and  allylic  halides  will  
undergo  solvolysis  at  a  practical  rate  thanks  to  the  stability  of  the  
carbocation  intermediates:

Recall  that  benzylic  and  allylic  carbocations

are  resonance  stabilized
IX. Effect of the Substrate on the Ionization Rates

• Be  able  to  judge  whether  or  not  a  given  alkyl  halide  will  undergo  a  
solvolysis  (SN1  and/or  E1)  reaction.      
• In  general,  a  1˚  or  2˚  alkyl  halide  will  only  undergo  solvolysis  if  
rearrangement  to  a  more  stable  carbocation  is  possible.  
Hello
• Loss  of  leaving  group  with  a  1,2-­‐migration  (concerted  mechanism)  
• 2˚,  allylic  and  benzylic  alkyl  halides  will  undergo  solvolysis  to  give  
a  mixture  of  SN1  and  E1  products  

benzylic  substrate Mixture  of  SN1  and  E1  products

is  observed
IX. Effect of the Substrate on the Ionization Rates
For  each  pair  of  compounds,  identify  which  is  expected  to  
undergo  solvolysis(nucleophile  is  your  solvent)  more  rapidly  in  
water,  and  explain  your  choice  in  each  case.
Br Br

a.  
Hello

b.   Br Br

Cl Br
c.
IX. Effect of the Substrate on the Ionization Rates
Answers:    The  leaving  group  will  leave  the  fastest  for  the  
compound  with  the  most  stabilized  carbocation.
Br Br A  tertiary  allylic  carbocation  is  more  
a.   stabilized  than  just  a  tertiary  
carbocation.    That  means  the  Br-­‐C  bond  
in  the  first  compound  is  the  weakest  so  
Hello its  easier  for  the  Br−  to  leave  (that  is  it  is  
leaving  group   easier  to  pull  off  that  Br−)
leaves  the  fastest
A  secondary  allylic  carbocation  is  more  
stabilized  (by  resonance)  than  simply  a  
b.   secondary  carbocation.    Therefor  the  Br−  
Br Br leaves  more  quickly  in  the  second  
molecule  (aka  the  Br-­‐C  bond  is  the  
leaving  group  
weakest  in  the  second  molecule)
leaves  the  fastest
A  Br−  is  more  stable  in  solution  (aka  a  
better  leaving  group)  than  a  Cl−  since  a  
Br−  is  much  larger  in  size  and  better  able  
c. Cl Br
to  accommodate  the  negative  charge.    
leaving  group   Therefore  the  Br  will  leave  more  
−

leaves  the  fastest quickly.  (A  C-­‐Br  bond  is  weaker  than  a  
C-­‐Cl  bond)
IX. Effect of the Substrate on the Ionization Rates
Draw  the  expected  products  of  the  following  solvolysis  process.    
Draw  in  all  the  curved  arrows  and  each  intermediate  that  is  
formed  in  the  processes

Hello Br

MeOH
heat
 IX. Effect of the Substrate on the Ionization Rates

Answer
H
O
H
O H
Br O

MeOH
Hello
heat
H
H

E1 product SN1 product

IX. Regioselectivity

• Like  we  saw  with  E2  eliminations,  it  is  possible  for  E1  elimination  
to  yield  more  than  one  regioisomer,  as  in  the  following  example:  
Major  product
of  E1  elimination
Hello

• Predict  the  products  formed  in  the  reaction  above.

IX. Regioselectivity

• Like  we  saw  with  E2  eliminations,  it  is  possible  for  E1  elimination  to  
yield  more  than  one  regioisomer,  as  in  the  following  example:  

Major  product
of  E1  elimination
Hello

• E1  reactions  will  always  give  the  most  stable  alkene  as  the  major  
product,  which  will  be  the  most  substituted  alkene  

• So  E1  reactions  are  regioselective  (preference  of  a  specific  bond  

being  formed),  but  we  cannot  control  the  regioselectivity  like  we  can  
with  E2  reactions  (E1  gives  more  products;  it  is  a  messier  reaction.).
IX. Regioselectivity

• It  is  further  possible  to  obtain  several  alkene  stereoisomers  in  an  
E1  reaction,  as  in  the  following  example:  

Hello

• Predict  the  products  formed  in  the  reaction  above

IX. Regioselectivity

• It  is  further  possible  to  obtain  several  alkene  stereoisomers  in  an  
E1  reaction,  as  in  the  following  example:  
Major  product
of  E1  elimination

Hello

• It  still  holds  true  that  the  E1  reaction  will  give  the  most  stable  
alkene  as  the  major  product.    When  two  stereoisomers  are  
obtained,  the  least  sterically  hindered  isomer  will  be  more  stable.  
• So  E1  reactions  are  stereoselective.    But  realize  a  mixture  of  all  
possible  products  is  still  obtained.
IX. Regioselectivity

• When  the  α-­‐carbon  in  an  SN1  reaction  is  chiral,  we  obtain  two  
substitution  products  that  have  opposite  configurations  at  the  
reactive  carbon:  

Hello

The  nucleophile  can  attack  

the  carbocation  from
either  side

• Recall  that  in  an  SN2  reaction,  the  nucleophile  does  a  backside  
attack,  and  only  the  inversion  of  configuration  product  is  
obtained.
IX. Regioselectivity

• Even  though  a  mixture  of  configurations  is  obtained  in  SN1  

substitution,  typically  more  of  the  inversion  product  is  observed

Hello
The  leaving  group
will  form  an  ion-­‐pair
with  the  carbocation,
making  it  more  difficult
for  the  nucleophile
to  attack  from  the
same  side
 IX. Regioselectivity
Draw  all  of  the  expected  products  for  each  of  the  following  
solvolysis  reactions.
Br
a.   MeOH
heat

Br Hello
MeOH
b.   heat

H 2O

c.   Cl heat

Cl

MeOH
heat
d.
 IX. Regioselectivity

Answers:  Remember  for  solvolysis,  both  SN1  and  E1  mechanisms  

are  possible!    Also  don't  forget  to  pay  attention  to  
stereochemistry!

Br
Hello OMe
a.  
MeOH
+ +
heat

SN1 E1   E1  
Br OMe

MeOH
+
b.   heat
E1  
SN1

c.
H 2O
+ +
Cl heat OMe

SN1 E1   E1  
 IX. Regioselectivity

Answers:  Remember  for  solvolysis,  both  SN1  and  E1  mechanisms  

are  possible!    Also  don't  forget  to  pay  attention  to  
stereochemistry!

d. Hello
Cl MeO

MeOH
+ +
heat

SN1 E1   E1  
OMe

SN1 E1  
IX. Regioselectivity
The  following  tertiary  alkyl  halide  was  heated  in  ethanol  for  
several  days,  and  the  resulting  mixture  of  products  contained  
five  different  elimination  products  and  two  substitution  
products. Br

Hello
a. Draw  all  the  substitution  products  and  identify  the  
relationship  between  them.  
b. Identify  which  substitution  product  is  expected  to  be  
favored,  and  explain  your  choice  
c. Draw  all  of  the  elimination  products,  and  identify  which  
products  are  stereoisomers  
d. For  each  pair  of  stereoisomeric  alkenes,  identify  which  
stereoisomer  is  expected  to  be  favored.
IX. Regioselectivity
Br
Answers:

a. Draw  at  the  substitution  products  and  identify  the  

relationship  between  them.
EtO Hello OEt

1 2
Attack  from  either  side  of  the  carbocation  will  give  a  mixture  of  enantiomers

b. Identify  which  substitution  product  is  expected  to  be  favored,  

and  explain  your  choice compound  1  is  favored

In  theory  one  would  expect  an  equal  mixture  of  enantiomers,  however  product  1  
forms  more  quickly  since  the  Br−  will  still  temporarily  block  the  back  side  of  the  
molecule
 IX. Regioselectivity
Br
Answers:

c. Draw  all  of  the  elimination  products,  and  identify  which  

products  are  stereoisomers  
d. For  each  pair  of  sHello
tereoisomeric  alkenes,  identify  which  
stereoisomer  is  expected  to  be  favored.

(E)
(Z)
Preferred

Stereoisomers
(most  stable)

(E)
(E)
Preferred

Stereoisomers
(most  stable)
X. Kinetic Isotope Effects in Elimination Reactions

• As  you  learn  all  these  mechanisms  of  substitution  and  elimination,  

you  should  appreciate  how  we  have  come  to  know  how  the  
mechanisms  occur.  

• One  way  we  to  study  

Hello a  mechanism  is  to  see  how  replacing  a  
hydrogen  atom  with  it’s  isotope,  deuterium,  affects  the  rate  of  a  
reaction.    If  the  rate  is  affected,  it  is  likely  that  particular  H  atom  is  
involved  in  the  rate  determining  step  (primary  isotope  effect).      

1H    is  called  hydrogen,  abbreviated  as  “H”,  and  2H  is  called  
•
deuterium,  abbreviated  as  “D”  

• Deuterium  (D)  has  the  same  chemical  reactivity  as  hydrogen  (H)
X. Kinetic Isotope Effects in Elimination Reactions

• Consider  the  following  reaction,  where  an  alkyl  halide  undergoes  

elimination  with  a  strong  base  (which  you  already  know  is  called  
an  E2  reaction).  

Hello
• When  we  replace  the  β-­‐hydrogens  with  deuteriums,  the  reaction  
occurs  at  a  slower  rate.    This  is  called  the  kinetic  isotope  effect

Rate  =  kH[CH3CH2CH2Br][Base]
kH/kD  =  6.7
Rate  =  kD[CH3CH2CH2Br][Base]
X. Kinetic Isotope Effects in E2 Reactions

• C  –  D  bonds  are  stronger  than  C  –  H  bonds.    So,  if  replacing  the  b-­‐
hydrogens  with  deuteriums  results  in  a  slower  rate,  a  KH/KD  ratio  
of  3-­‐8,  then  we  can  conclude  the  breaking  of  the  C  –  H  bond  
occurs  during  the  rate  determining  step.  Primary  isotope  effect  
• If  the  KH/KD    ratioHello
 is  1-­‐2  then  the  C-­‐H  bond  is  broken  during  a  step  
that  is  NOT  rate  limiting.    This  is  called  the  secondary  isotope  
effect.  

Rate  =  kH[CH3CH2CH2Br][Base]  
Rate  =  kD[CH3CD2CH2Br][Base]
• The  reaction  above  is  6.7  times  slower  with  β-­‐deuteriums  instead  
of  β-­‐hydrogens.    This  is  one  of  the  reasons  why  we  believe  that  
the  E2  elimination  is  a  concerted  elimination
 X. Kinetic Isotope Effects in E1 Elimination Reactions
Kinetic  Isotope  Effects  in  E1  Processes
H 3C Cl
H 2O
Rate = kH[C4H9Cl]
heat
H 3C CH3

Hello CD3
D 3C Cl
H 2O D Rate = kD[C4D9Cl]
heat D 3C
D 3C CD3
D

• If  the  KH/KD    ratio  is  1.1  so  the  C-­‐H  bond  is  broken  during  a  step  that  
is  NOT  rate  limiting.  (secondary  isotope  effect)  
• A  separate  step  must  be  occurring  that  is  rate  limiting  
(dissociation  of  the  leaving  group).  
• Excellent  evidence  for  the  E1  mechanism
IX. Regioselectivity

For  each  pair  of  compounds  below,  identify  which  one  is  
expected  to  undergo  elimination  more  rapidly  when  treated  with  
a  strong  base

a.   Br CD3 Br
Hello
D 3C CD3

Br H Br D

b.   D 3C CD3

D D D
Cl
c. D D Cl
 IX. Regioselectivity
Answers:  The  rate  will  only  decrease  if  the  rate  determining  step  is  
breaking  the  C-­‐D  bond.    A  C-­‐D  bond  is  stronger  than  a  C-­‐H  bond  so  a  
C-­‐H  bond  breaks  more  quickly  (faster  rate)  and  a  C-­‐D  bond  breaks  
more  slowly  (slower  rate)
a.   Br CD3 Br

D 3C CD3 Hello
Slower  elimination,  breaking  a  C-­‐D  bond Faster  elimination,  breaking  a  C-­‐H  bond

Br H Br D

b.   D 3C CD3
Slower  elimination,  breaking  a  C-­‐D  bond.   Faster  elimination,  breaking  a  C-­‐H  bond.  
The  H  is  in  the  alpha  position  so  it  is  not   The  D  is  in  the  alpha  position  so  it  is  not  
eliminated.    Elimination  occurs  at  the  β   eliminated.  Elimination  occurs  at  the  β  position
position D D D
Cl
c. D D Cl

Slower  elimination,  breaking  a  C-­‐D  bond.   Faster  elimination,  breaking  a  C-­‐H  bond.  
(see  explanation  for  part  b) (see  explanation  for  part  b)
 IX. Regioselectivity
Identify  whether  each  of  the  following  reactions  is  expected  to  
exhibit  a  primary  isotope  effect  if  (CD3)3CBr  is  used  instead  of  
(CH3)3CBr.    Explain  your  reasoning  in  each  case.

Br
a.   HelloNaOEt

Br
EtOH
b.
 IX. Regioselectivity
Answers:    Think  about  the  mechanism,  then  determine  when  a  C-­‐D  
bond  will  break  when  using  (CD3)3CBr.    If  a  C-­‐D  bond  breaks  during  
the  slow  (rate  determine  step),  then  it  will  exhibit  a  primary  isotope  
effect.

Br
a.   HelloNaOEt

Primary  isotope  effect  observed,  breaking  a  C-­‐D  bond  and  the  C-­‐Br  bond  occur  at  the  same  
time  since  this  mechanism  is  concerted.    This  is  also  the  slow,  rate  determining  step.

Br
EtOH
b.
Primary  isotope  effect  NOT  observed.  The  slow  step  of  this  reaction  is  the  dissociation  of  
the  bromide  ion.    Once  that  occurs,  a  faster  elimination  step  will  occur.    This  elimination  
step  (breaking  the  C-­‐D  bond  vs  the  C-­‐H  bond)  is  not  rate  determining.    
XI. Predicting Products: Substitution vs. Elimination

• By  now,  it  should  be  clear  that  a  number  of  factors  affect  the  
product(s)  formed  when  reacting  an  alkyl  halide  with  a  
nucleophile  and/or  base  (the  substrate,  the  reagent,  and  the  
solvent).  
Hello
• It  should  also  be  clear  that  in  many  cases,  a  mixture  of  
substitution  and/or  elimination  products  will  be  obtained
XI. Predicting Products: Substitution vs. Elimination

• It  is  also  possible,  for  a  given  substrate,  that  only  one  mechanism  
will  occur  

Hello

• In  order  to  understand  how  to  use  these  reactions,  to  transform  
alkyl  halides  into  a  desired  compound,  one  must  be  able  to  
predict  ALL  the  products  that  will  form  in  a  given  reaction,  as  well  
as  the  major  and  minor  product(s)
XI. Predicting Products: Substitution vs. Elimination

To  successfully  predict  the  product(s)  formed  in  a  given  reactions,  we  

can  follow  a  three-­‐step  analysis:  

1. DETERMINE  THE  FUNCTION  OF  THE  REAGENT  

2. ANALYZE  THE  SUBSTRATE(and  

Hello solvent)  AND  DETERMINE  THE  
EXPECTED  MECHANISM(S)  

3. CONSIDER  ANY  RELEVANT  REGIOCHEMICAL  AND  

STEREOCHEMICAL  REQUIREMENTS
For  this  section,  avoid  rote  memorization,  make  sure  you  
understand  everything!  (They  WHY  is  more  important  than  
the  what)  
There  will  be  too  much  to  memorize  for  this  class,  but  the  
underlying  principles  will  remain  constant  for  12A  and  12B
 XI. Predicting Products: Substitution vs. Elimination

Review  your  Bases:

• Quantitative  approach  allows  you  to  determine  base  strength  by  
using  pKa’s  of  the  conjugate  acid.  

★ Qualitative  approach:    Chemistry  Logic.    Get  good  at  this!!!  

Hello
• When  looking  left  to  right  across  the  periodic  table,  size  doesn’t  
change  all  that  much,  the  most  electronegative  atom  is  the  
strongest  base.  
• When  going  up  and  down  on  the  periodic  table,  the  larger  atoms  
are  much  better  at  stabilizing  the  negative  charge  (it  is  more  
dispersed).    Larger  anions  are  weaker  bases  than  smaller  anions.  
• F−  is  a  stronger  base  than  Cl−  (Cl−  is  basically  a  non  base)
 XI. Predicting Products: Substitution vs. Elimination

Review  your  Nucleophiles:

★ Qualitative  approach:    Chemistry  Logic.    Get  good  at  this!!!  

• Polarizable  atoms  are  better  nucleophiles  in  protic  solvents.  They  

aren’t  as  easily  deactivated  and  concentrated  negative  charges.  
Hello
• I−  is  an  excellent  nucleophile  in  protic  solvent  since  it  is  not  
easily  deactivated.    Typically,  for  most  strong  nucelophiles,  an  
aprotic  solvent  is  required.
 XI. Predicting Products: Substitution vs. Elimination
Review  your  Nucleophiles:

• H−  (obtained  from  NaH)  is  a  horrible  nucleophile.      

• NOT  soluble  in  aprotic  solvents  so  it  cant  act  as  a  
nucleophile.  (exists  as  large  aggregates)  
Hello
• It  will  function  as  a  strong  base  since  β  hydrogens  are  
more  accessible  then  the  nucleophilic  site.  
• FYI  each  H  atoms  has  a  1s  orbital.    These  orbitals  
overlap  very  well  with  other  1s  orbitals  since  they  are  
the  same  size  and  energy  level.    Easier  to  form  bonds  
this  way.  (BDE  =  436  kcal/mol).    For  C-­‐H  overlap  isn't  
as  efficient  (BDE  =    410  kcal/mol)  
• β  elemination  is  both  the  thermodynamic  and  kinetic  
product  with  H−.    
Bases  vs.  Nucleophiles.
★ Qualitative  approach:    Chemistry  Logic.    Get  good  at  this!!!  
• Strong  bases,  typically  are  smaller  in  size  with  concentrated  
negative  charge.      
• Better  overlap  with  the  1s  orbital  of  hydrogen!    
• Better  overlap  =  lower  energy  =  more  stable.  
• Weak  bases,  larger  
Helloin  size  with  a  dispersed  negative  charge  or  
they  can  be  smaller  but  without  a  negative  charge  
• Conjugate  bases  of  strong  acids.  
• Large  size  =  poor  overlap  with  the  1s  orbital  of  hydrogen  
• Poor  overlap  =  higher  potential  energy  =  less  stable.  
• Strong  nucleophiles:    Larger  in  size  and  more  polarizable  in  protic  
solvents  or  oxygen  and  carbon  atoms  with  a  negative  charge  in  
aprotic  solvents.  
• Weak  nucleophiles:    H−,  neutral  compounds,  or  large  amine  
bases,  DBU,  or  DBN
Dealing  with  the  Oxygen  Atom!

★ Qualitative  approach:    Chemistry  Logic.    Get  good  at  this!!!  

• Strong  base  when  it  has  a  negative  charge  (especially  in  protic  
solvents)  
• Weak  base  when  it  does  NOT  have  a  negative  charge.  
• Strong  nucleophile  
Hellowhen  it  has  a  negative  charge.  (especially  in  
aprotic  solvents)  
• Weak  nucleophile  when  it  does  NOT  have  a  negative  charge.
Oxygen  is  kinda  in  the  middle.    Its  orbitals  can  overlap  well  with  both  
carbon  and  hydrogen.    Therefore  it  can  be  both  a  nucleophile  or  a  base.    
It  is  not  really  all  that  polarizable  so  the  neutral  species  is  a  poor  
nucleophile  and  its  electron  density  is  not  concentrated  enough  to  be  a  
good  base,  however,  the  charged  species  has  enough  free  electrons  
that  it  will  react  with  an  electrophile  and  the  electron  density  is  
concentrated  enough  that  it  will  act  as  a  good  base.
 XI. Predicting Products: Substitution vs. Elimination
Step  1:    Determine  the  function  of  the  reagent.

• Remember  what  kind  of  reagents  promote  SN1,  SN2,  E1  and  E2  
    SN2  =  strong  nucleophile      E2  =  strong  base  
    SN1  =  weak  nucleophile          E1  =  weak  base  
• The  following  table  
Hello is  a  good  resource  for  categorizing  reagents  and  
the  mechanisms  they  will  promote

E2 SN2  and  E2 SN1  and  SN2   SN1  and  E1

The  are  many  (future)  in-­‐between  examples  that  don't  fit  well  on  this  
chart,  so  understanding  is  best!
XI. Predicting Products: Substitution vs. Elimination

E2
Hello
S 2  and  E2 SN1  and  SN2   SN1  and  E1
N

N N

N N

1,2-Diazabicyclo[4.3.0]non-5-ene 1,8-Biazabicyclo[5.4.0]undec-7-ene
(DBN) (DBU)

H H
H A

N N N
+ A

N N N

Resonance  Stabilized
DBN, DBU: Weak nucelophiles do to their large size (steric hindrance), but grabbing an
H for elimination is much easier.

NaH: Strong base! Insoluble so it exists as an aggregate (non nucleophilic, very large in size)
Hello
HO−,MeO−, EtO−: Strong enough to do anything, but not as reactive as H−. Their reactivity
will strongly depend upon the solvent and substrate.
SN2: Need aprotic solvent so they are not deactivated. Need to have access to
nucleophilic site (fastest with primary haloalkane, secondary will give mixtures of
elimination products).
E2: Protic solvent is often used to discourage SN2. They have no access to the
nucleophilic center so they will act as a base instead forming the kinetic product.
I− and other polarizable ions: These are conjugate bases of strong acids. There is no way
they can grab onto a hydrogen and act as a base. They will only act as nucleophiles. Like all
nucleophiles, they work better in aprotic solvents, but unlike less polarizable ions, they will also
work in protic solvents. Since these tolerate protic solvents, they can also work with E1 and SN1
reactions (E1 if basic, SN1 if non basic like I−).
Water, MeOH, EtOH: Weak base, weak nucleophile. These function well with E1 and SN1
reactions since they help to stabilize the carbocation. These will work in protic solvents since they
ARE the protic solvent. In this case the base/nucleophile is the solvent (solvolysis).
XI. Predicting Products: Substitution vs. Elimination

Step  2:    Analyze  the  Substrate.    What  is  it  physically  possible??
• Once  you  determine  what  mechanism(s)  will  be  favored  by  the  
reagent,  analyze  the  substrate  (to  see  which  mechanism(s)  will  
dominate…  is  the  substrate  1˚,  2˚,  or  3˚?
Hello

This  chart  should  be  a  crude  guide,  it  isn’t  always  accurate,  and  changing  
small  things  like  the  solvent  can  have  a  large  effect  on  the  mechanism.
 XI. Predicting Products: Substitution vs. Elimination

Step  2:    Analyze  the  Substrate.    What  is  physically  possible??

• Primary  Haloalkane:  

• Can  NOT  form  carbocations,  not  enough  stabilization  

(hyperconjugation)  
Hello
• No  SN1  or  E1  mechanisms  possible  unless  you  
somehow  get  a  concerted  1,2-­‐hydride  or  methyl  
shift.  A  protic  solvent  or  a  weak  nucleophile  may  be  a  
sign  that  rearrangement  will  occur  in  tandem  with  
the  formation  of  a  stable  tertiary  carbocation.  
• Look  for  SN2  reactions  (strong  nucleophiles  with  aprotic  
solvents)  or  E2  reactions  (strong  base  in  protic  solvents)  
• SN2  often  product  is  major,  E2  product  is  minor
XI. Predicting Products: Substitution vs. Elimination

• Secondary  Haloalkane:  
• SN1  or  E1  are  not  possible  (unlikely),  but  mix  of  SN2  and  E2  
products  are  typically  formed  
• Protic  solvents:  SN2  is  mostly  deactivated,  E2  preferred  
• Polarizable  
Hello Nucleophiles   l ike   ( like   I-­‐):  S 2  
N

• Strong  base/weak  base:  E2,  minor  SN2  

• Aprotic  solvents:  mix  of  products  
• Strong  nucleophile,  strong  base:  primarily  E2  
(kinetic  product)  but  some  SN2.  
• Strong  nucleophiles,  but  weak  bases:  SN2    
• example:  NaI  +  acetone  
• Strong  base,  weak  nucleophiles:  E2  
• example:  NaH,  DBU,  DBN
 XI. Predicting Products: Substitution vs. Elimination
Step  2:    Analyze  the  Substrate.    What  is  physically  possible??
• Tertiary  Haloalkane:  

• Too  Bulky  for  SN2  

• E2  will  be  the  primary  mechanism  here  if  aprotic  
solvents  Hello
are  used  or  strong  bases.  
• With  protic  solvents  SN1,  E1,  and  E2  are  possible.  
• SN1:  strong  nucleophile,  weak  base  like  I-­‐(HI  in  water)  
• E1:  weak  nucleophile,  weak  base,  EtOH,  MeOH,  etc.  
• E2:  strong  base  
• Carbocations  will  rarely  rearrange  here,  but  may  
rearrange  if  a  tertiary  benzylic  or  allylic  carbocation  is  
possible.  
• Usually  gives  a  mixture  of  both  SN1  and  E1  products.  
 XI. Predicting Products: Substitution vs. Elimination
Step  3:    Draw  the  products
★ Qualitative  approach:    Chemistry  Logic.    Get  good  at  this!!!

The  following  steps  for  me  are  hard  to  follow,  I  prefer  using  logic  
to  determine  which  Hello
products  are  formed.  I  have  included  them  
for  your  convenience.
XI. Predicting Products: Substitution vs. Elimination

• After  analyzing  the  reagent  and  the  substrate,  you  can  say  which  
mechanism(s)  will  occur.    Draw  all  the  possible  regio-­‐  and  
stereoisomers,  then  choose  the  major,  using  the  guidelines  you  
have  learned.  
Hello
• For  SN2,  you  will  observe  a  single  product,  which  is  inversion  of  
configuration  at  the  α-­‐carbon
XI. Predicting Products: Substitution vs. Elimination

For  E2,  draw  all  the  possible  alkene  isomers.    Only  alkenes  which  
result  from  a  β-­‐hydrogen  anti-­‐periplanar  to  the  leaving  group  can  
form  

  -­‐  if  a  bulky  base  is  Hello

used,  the  Hofmann  product  is  the  major  
  -­‐  if  a  non-­‐bulky  base  is  used,  the  most  stable  alkene  is  the  major  
Remember  your  Newman  Projections  
 
XI. Predicting Products: Substitution vs. Elimination

For  SN1,  draw  the  carbocation  intermediate,  consider  if  it  will  
rearrange.    If  not,  then  attach  nucleophile  to  the  carbocation.    If  it  
rearranges,  draw  the  resulting  carbocation,  then  attach  the  
nucleophile  to  it.      
Hello
  -­‐  if  a  chiral  carbon  is  formed  by  attack  of  the  nucleophile,  then  
     two  products  are  formed  (“R”  and  “S”).    Draw  them  both.  
 
XI. Predicting Products: Substitution vs. Elimination

For  E1,  draw  the  carbocation  formed  from  loss  of  the  leaving  group.    If  
it  will  rearrange,  draw  the  rearranged  carbocation.    Then,  draw  all  
possible  alkene  isomers  resulting  from  elimination  of  a  β-­‐hydrogen.    
All  possible  alkene  stereoisomers  will  form  (E1  is  not  stereospecific).  
Hello
  -­‐  the  major  product  will  always  be  the  most  stable  alkene.  
? NaSH
XI. Predicting Products: Substitution
(f)

?
vs. Elimination

Example:  Predict  the  product(s)  of  the  following  reaction,  and  label  
?
the  major  product.
(h)

?
Br NaOEt

Br

(j)
Hello
NaOH
water ?
Br

?
• STEP  1:  ANALYZE  THE  REAGENT(S).  NaOMe
strong  nucleophile,  
?
 NaOH  is  a  strong  base,  and  a  
(l)
so  SN2  and  E2  will  be  favored

?
Br
NaOEt
• STEP  2:  LOOK  AT  THE  SUBSTRATE.    It  is  a  2˚  halide,  so  SN2  and  E2  will  
(n)

occur,  but  E2  will  dominate  (because  2˚  substrates  are  somewhat  
hindered,  and  backside  attack  is  more  difficult)
NQPVOE
B
BSF
DPOTUJUVUJPOBM
JTPNFST
XJUI
UIF
NPMFDVMBS
GPSNVMB

JT
USFBUFE
XJUI
TPEJVN
NFUIPYJEF
B
TVCTUJUVUJPO
SFBDUJPO
QSF
E
B
JT
USFBUFE
XJUI
TPEJVN
NFUIPYJEF
BO
FMJNJOBUJPO
SFBDUJPO

? NaSH
XI. Predicting Products: Substitution
(f)

?
vs. Elimination

Example:  Predict  the  product(s)  of  the  following  reaction,  and  label  
?
the  major  product.
(h)

Br
?NaOEt

Br

(j)
Hello
NaOH
water ?
• STEP  3:  consider  the  regio-­‐  and  
Br stereochemical  requirements.      

? NaOMe
?
For  the  SN2  product,  backside  attack  gives  inversion  of  configuration
(l)

?
Br
NaOEt

(n)

SN2  product
NQPVOE
B
BSF
DPOTUJUVUJPOBM
JTPNFST
XJUI
UIF
NPMFDVMBS
GPSNVMB

JT
USFBUFE
XJUI
TPEJVN
NFUIPYJEF
B
TVCTUJUVUJPO
SFBDUJPO
QSF
E
B
JT
USFBUFE
XJUI
TPEJVN
NFUIPYJEF
BO
FMJNJOBUJPO
SFBDUJPO

 ? (f)

?
XI. Predicting Products: Substitution vs. Elimination
H
? Br
?
NaOEt

Example:  Predict  the  product(s)  of  the  following  reaction,  and  label  
(h)

the  major  product. Br

? (j)

NaOH
water ?
• STEP  3:  consider  tHello
he  regiochemical  
Br
and  stereochemical  
?
Me requirements.    E2  reaction?

(l)

NaOMe
?
For  the  E2  product(s),  draw  all  the  β-­‐hydrogens  that  can  be  anti-­‐
periplanar  to  the  leaving  group,  then  draw  the  resulting  alkenes  (use  
?Newman  projections  if  necessary) ?
Br
NaOEt

(n)

water
DPNQPVOE
B
BSF
DPOTUJUVUJPOBM
JTPNFST
XJUI
UIF
NPMFDVMBS
GPSNVMB


A
JT
USFBUFE
XJUI
TPEJVN
NFUIPYJEF
B
TVCTUJUVUJPO
SFBDUJPO
QSF
elimination elimination elimination
VOE
B
JT
USFBUFE
XJUI
TPEJVN
NFUIPYJEF
BO
FMJNJOBUJPO
SFBDUJPO

of  Ha   of  Hb   of  Hc  
SVDUVSFT
GPS
DPNQPVOET
A
BOE
B
 ? (f)

?
XI. Predicting Products: Substitution vs. Elimination
H
? Br
? NaOEt

Example:  Predict  the  product(s)  of  the  following  reaction,  and  label  
(h)

the  major  product. Br

? (j)

NaOH
water ?
Now  we  have  all  the  products  
Hello resulting   Br from  SN2  and  E2.    Now  label  the  
Me
?
major  product.    E2  is  major  pathway,  and  NaOMe
Zaitsev  product(the  m(l)

?
the  base  is  not  hindered,  so  the  
ost  stable  product)  is  the  major.  
most  stable
?
Br

? (n)

alkene  
NaOEt

Br
DPNQPVOE
B
BSF
DPOTUJUVUJPOBM
JTPNFST
XJUI
UIF
NPMFDVMBS
GPSNVMB

NaOH
MAJOR

A
JT
USFBUFE
XJUI
TPEJVN
NFUIPYJEF
B
TVCTUJUVUJPO
SFBDUJPO
QSF
Br
VOE
B
JT
USFBUFE
XJUI
TPEJVN
NFUIPYJEF
BO
FMJNJOBUJPO
SFBDUJPO

SVDUVSFT
GPS
DPNQPVOET
A
BOE
B
IX. Regioselectivity

Predict  the  product(s)  of  the  following  reaction,  and  identify  the  
major  and  minor  products
Everything  we  have  been  learning  has  been  leading  up  to  this  point!

Hello
Cl
NaOEt
EtOH
 IX. Regioselectivity
Answers:
1. Determine  the  function  of  the  reagent(solvent)  
Protic  solvent  +  strong  base  =  E2  mechanism  (major)  
NaOEt  =  SN2  or  E2  mechanisms trace  SN2  mechanism  possible.
2. Analyze  the  substrate  and  determine  the  expected  mechanism(s)  
Secondary  haloalkane  =  SN  or  elimination

3. Consider  any  relevant  

Helloregiochemical  and  stereochemical  
requirements.
small  base:  thermodynamic  product  is  favored  for  E2
chiral  center:  inversion  of  stereochemistry  for  SN2
Cl OEt
NaOEt
EtOH
Minor:  E2  product  
Minor:  SN2  product (kinetic,  less  stable  alkene)

Minor:  Cis  alkene  experiences   Major:  E2  product  

more  steric  interactions (thermodynamic,  most  stable  alkene)
 IX. Regioselectivity
Predict  the  product(s)  of  the  following  reaction,  and  identify  the  
major  and  minor  products

Br
NaCl b.   Br
NaOH
a.   DMSO
Hello
I Br

t-BuOK d.   DBN
c.  

t-BuOK
f. NaHS
e. I I
 IX. Regioselectivity

Answers
Br Cl
a.   NaCl
DMSO

DMSO  =  aprotoic  solvent  =  SN2  if  haloalkane  is  1°  or  2°  
Hello
No  base:  Cl−    is  more  of  a  non  base,  elimination  is  not  likely  
NaCl  =  Cl−  is  a  strong  nucleophile

Br
b. NaOH

Minor
Major:  E2  product  
3°  haloalkane:  No  SN2.     (thermodynamic,  most  stable  alkene)
Strong  base:  NO  E1  or  SN1,  must  be  E2  
Small  base:  Thermodynamic  product  is  favored
 IX. Regioselectivity

Answers
I

t-BuOK
c.  
3°  haloalkane:  No  SN2.     Hello Major   Minor    
Strong  base:  NO  E1  or  SN1,  must  be  E2   (kinetic  product) (thermodynamic  product)
bulky  base:  kinetic  product  is  favored  (most  accessible  hydrogen  is  removed)
Br

DBN

d.
Only  Product    
(both,  thermodynamic  and  kinetic  product)

DBN:    Strong  base,  NOT  a  nucleophile  (No  SN  processes  available)  

Only  one  location  that  an  H  can  be  pulled  off.
 IX. Regioselectivity

Answers

e.   t-BuOK
I Ot-Bu
Major   Minor    
Hello (E1  product) (SN2  product)
1°  haloalkane:  SN2  or  E2  however  SN2  has  a  faster  rate  for  strong  bases  
Strong  base  bulky:  SN2  hindered  by  the  size  of  the  base,  E2  more  likely  
Only  one  place  to  pull  off  a  hydrogen
NaHS
f. I SH

Likely  not  formed Major/only  product  

(SN2  product)
1°  haloalkane:  SN2  or  E2  however  SN2  has  a  faster  rate  for  strong  bases  
Excellent  Nucleophile:  SN2  likely  
Weak  base:  E2  unlikely,  too  hard  to  pull  of  a  hydrogen  
Only  one  place  to  pull  off  a  hydrogen
 IX. Regioselectivity
Predict  the  product(s)  of  the  following  reaction,  and  identify  the  
major  and  minor  products

g.   Br
NaOH h.   Br NaOEt

Hello
Br
I
i.   j.  
EtOH NaOH
Heat

Br
NaOMe Br NaOMe
k.   l.  

Br Br
NaOH NaOEt
m. n.
IX. Regioselectivity

Answers

g.   Br OH
NaOH

Hello
Major  product   Minor  product  
(SN2  product) (E2  product)

Br NaOEt OEt

h. Major  product   Minor  product  

(SN2  product) (E2  product)
same  explanation  for  g.  and  h.
1°  haloalkane:  SN2  or  E2  however  SN2  has  a  faster  rate  for  strong  base/strong  nucleophiles  
Excellent  Nucleophile:  SN2  likely  
Strong  base:  E2  slower  SN2  faster  
Only  one  place  to  pull  off  a  hydrogen
 IX. Regioselectivity

Answers

OEt
i.   I
EtOH
Heat

3°  haloalkane:  SN1  or  E1  or  E2   Minor  product Major  product Minor  product
Weak  nucleophile,  weak  bHello ase:  E1  preferred  if  a  tertiary  or  quaternary  alkene  is  formed,  if  a  
secondary  alkene  then  SN1  is  preferred.  Both  SN1  and  E1  products  expected  
Two  places  to  pull  off  a  hydrogen:    Thermodynamic  product  is  always  favored  for  E1  
With  solvolysis,  a  mixture  of  products  is  unavoidable
Br OH
NaOH

j. Minor  product Minor  product Minor  product

2°  haloalkane:  SN2  or  E2,  Likely  not  SN1  or  E1  since  the  base  is  strong   Major  product
Small  strong  base:    Since  it  is  2°,  E2  will  be  faster,  and  the  
thermodynamic  product  will  be  favored
 IX. Regioselectivity
Answers
OMe
Br

k.   NaOMe

Minor  product Minor  product Minor  product

Exact  same  logic  as  example  

Hello j.    Just  a  new  small  strong  base/good  
nucleophile
Major  product

OMe
Br NaOMe

l.
Minor  product Minor  product Major  product

2°  haloalkane:  SN2  or  E2,  Likely  not  SN1  or  E1  since  the  
Br
Me H Rotatate
base  is  strong   Me H
C-C bond Br
Me
Small  strong  base:    Since  it  is  2°,  E2  will  be  faster,  and  the  
Me H
thermodynamic  product  will  be  favored   H

Only  one  β  hydrogen  at  a  chiral  center  so  make  sure  you  
find  a  way  to  determine  the  stereoselectivity.    I  used  
Newman  projections
 IX. Regioselectivity
Answers
Br
m.   Br
NaOH
OH

H
Major  product Minor  product
2°  haloalkane:  SN2  or  E2,  Likely  not  SN1  or  E1  since  the  base  is  strong.  
Hello
Small  strong  base:    Since  it  is  2°,  E2  will  be  faster,  and  there  is  only  one  anti  β  hydrogen  so  there  
is  only  one  elimination  product  possible.  
Br
Br OEt
NaOEt
n. H
H
Minor  product Major  product Minor  product

2°  haloalkane:  SN2  or  E2,  Likely  not  SN1  or  E1  since  the  base  is  strong  
Small  strong  base:    Since  it  is  2°,  E2  will  be  faster,  and  the  thermodynamic  product  will  be  
favored  
Two  β  hydrogen’s  are  available  so  make  sure  you  draw  the  product  of  each  one
IX. Regioselectivity

I  love  logic  problems!    Here  are  couple  for  you  to  think  about  at  
home
1.  Compound  A  and  compound  B  are  constitutional  isomers  with  
the  molecular  formula  C3H7Cl.    When  compound  A  is  treated  with  
sodium  methoxide,   a  substitution  reaction  predominates.    When  
Hello
compound  B  is  treated  with  sodium  methoxide,  an  elimination  
reaction  predominates.    Prepose  a  structure  for  A  and  B.

2.  Compound  A  and  compound  B  are  constitutional  isomers  with  

the  molecular  formula  C4H9Cl.    Treatment  of  compound  A  with  
sodium  methoxide  gives  trans-­‐2-­‐butene  as  the  major  product,  
while  treatment  of  compound  B  with  sodium  methoxide  gives  
a  disubstituted  alkene  as  the  major  product.    Draw  the  
structures  for  compound  A  and  B.  
IX. Regioselectivity
Answer  for  1:    Try  to  draw  out  as  many  constitutional  isomers  as  
you  can  with  the  structural  formula  C3H7Cl.    Once  you  do  that,  using  
your  chemistry  knowldege,  determine  which  ones  will  do  
substitution  reactions  and  which  ones  will  do  elimination  reactions.
Hello
Cl NaOMe OMe

A Major
Minor

Cl OMe
NaOMe

B Minor Major
IX. Regioselectivity
Answer  for  2:    Once  again,  draw  out  as  many  constitutional  
isomers  as  you  can  with  the  structural  formula  C4H9Cl.    Once  you  
do  that,  using  your  chemistry  knowldege,  determine  which  one  will  
make  trans-­‐2-­‐butene,  and  which  one  will  give  you  a  different
disubstituted  alkene  as  a   Cl NaOMe OMe
Hello
major  product  (so  an  
elimination  product  major  
product,  NOT  a  
NaOMe

substitution  product)
Cl
A trans-2-butene

Cl NaOMe OMe
I  only  drew  the  major  
products  since  the  
minor  products  are   Cl
NaOMe

irrelevant. B
 O

XII. SubstitutionAn alkyl halide and Elimination Reactions with Other

An alkyl sulfonate

With anSubstrates
alkyl sulfonate, the leaving group is a sulfonate ion, which is highly stabilized by resonance:

Sulfuric  Acid  is  a  known  

O
strong   acid  
O
since  
⊝ the   HSO
O 4
−  anion  is  so  

stable  (it  is  a  non  

O b
⊝
Sase).
R O S R O S R
O O O
⊝

• Therefore  RSO4−Sulfonate  groups   (alkyl  

leaving groupss areulfonates)   will  make  excellent  
resonance-stabilized

leaving  groups!  
Since sulfonate ions are such good leaving groups, alkyl sulfonates undergo substitution and elimina-
• Just  
tion reactions, muchlike   ow  Hello
likehalkyl l−,  Br−Many
Chalides. ,  and   I−  are  eare
sulfonates xcellent  
commonly leaving   groups  
used, including since  
mesylates,
tosylates, andthey  
triflates:
too  are  conjugate  bases  of  strong  acids.
mesylate tosylate triflate
group group group
O O O
O S CH3 O S CH3 O S CF3
O O O

An alkyl mesylate (ROMs) An alkyl tosylate (ROTs) An alkyl triflate (ROTf)

Tosylates are the most commonly used, although triflates have the best leaving group. Recall that the
Mesylates,  
• leaving
best groups are tosylates,  
the weakest bases.and  tThe
riflates  
triflate ionare  
is excellent  
one leaving  
of the weakest known groups.    
bases, because
They  
it is the are  abase
conjugate lso  ofqan
uite   large,  
especially strongand  acid.
so  we  usually  
Compare the pKuase  
valuesabbreviations  
of the following sulfonic
acidswhen  
(RSO3H): drawing  their  structures  (OMs,  OTs,  and  OTf)
O O O
es, and triflates:
X (X = , Br, or Cl) O S R
XII. Substitution and Elimination Reactions with Other
O
Substrates
mesylate tosylate trifla
alkyl halide
group group An alkyl sulfonate gro

• Sulfonates  
O are  such  good  leaving  
O groups  because  they  are  very   O
ate, the
O leaving
S CH3 group is a sulfonate
stable   Sion, whichCH
(like  halides,  they  are  Othe   conjugate  is highly
b3ases   of  sstabilized by reson
trong  acids)   O S
O O O
⊝
lkyl mesylate
O (ROMs) An
O alkyl tosylate (ROTs) O An alkyl triflate (
⊝
O S R O S R O S R
tes are the most commonlyHello used, although triflates have the best leaving group. Recall
O
aving groups are the weakest bases.OThe triflate ion is one of the O weakest known bases,
⊝
Sulfonate  
e conjugateSulfonate
base of an ions  arestrong
especially Resonance  
acid. sCompare
tabilized! the pK values of the following s
leaving groups are resonance-stabilized a
RSO• 3Based  
H): on  pKa  values,  which  sulfonate  is  the  best  leaving  group?
are such good leaving groups, alkyl sulfonates undergo substitution and elim
O O O
h like alkyl halides. ManyH sulfonates
H O S CH3 O S
are commonly
CH3
used, including mesy
H O S CF3
es: O O O
Methanesulfonic acid p-Toluenesulfonic acid Trifluoromethanesulfonic acid
(MsOH) tosylate
(TsOH) (TfOH) triflate
pKa = –1.9 group
pKa = –2.8 pKa = –14 group
O O
H O S CH O S C
XII. Substitution and Elimination Reactions with Other
Substrates

• Sulfonates  are  made  from  the  corresponding  alcohol  

Hello
Similar  to  an  SN2  reaction

• Realize  we  are  just  strapping  the  “ Ts”  group  to  the  oxygen  of  the  
alcohol…  no  change  in  the  carbon  atom  bearing  the  OH  group  
occurs
Now  we  have  a  good
leaving  group!  
Alcohols  are  not
good  leaving  groups The  stereochemistry  is  
left  unchanged.

Pyridine  is  often  shortened  to  pyr.  or  py

XII. Substitution and Elimination Reactions with Other
Substrates

• To  envision  the  compounds  that  can  be  synthesized  from  an  alkyl  
tosylate,  treat  them  EXACTLY  the  same  as  you  would  an  alkyl  
halide. With  a  strong  Nu/strong  base,  a  1˚  substrate
gives  mostly  SN2,  with  a  little  E2

Hello

With  a  strong  Nu/strong  base,  a  2˚  substrate

gives  mostly  E2,  with  a  little  SN2
XII. Substitution and Elimination Reactions with Other
Substrates
Predict  the  major  and  minor  products  for  each  of  the  following  
reactions:    (At  Home  Practice  Problems)
OTs
NaOEt OTs
a.   b.   NaOH

Hello

OTs OTs
c.   NaSH
d.   NaH

HO
e. 1) TsCl, pyr.
2) t-BuOK
f. OH
1) TsCl, pyr.
2) NaOEt
XII. Substitution and Elimination Reactions with Other
Substrates
Answers:    With  sulfonates,  treat  them  EXACTLY  like  you  would  
with  a  haloalkane  since  they  are  excellent  leaving  groups.    You  
wont  go  wrong!

OTs OEt
a.   NaOEt
Hello
Major  product Minor  product

OTs OH
NaOH

b. Major  product
Minor  product Minor  product

Minor  product
XII. Substitution and Elimination Reactions with Other
Substrates
Answers:    With  sulfonates,  treat  them  EXACTLY  like  you  would  
with  a  haloalkane  since  they  are  excellent  leaving  groups.    You  
wont  go  wrong!
OTs SH
NaSH
c.   Hello

NaSH  is  a  good  nucleophile  but  a  weak  base.    It  can  readily  do  substitution  but  it  is  not  
strong  enough  to  pull  off  a  hydrogen,  so  no  eliminations.

OTs

d.
NaH

NaH  is  a  very  strong  base  but  a  very  poor  nucleophile.    Elimination  only,  and  in  this  
case  there  is  only  one  beta  hydrogen  that  is  antiperiplanar  to  the  OTs  group.
 XII. Substitution and Elimination Reactions with Other
Substrates
Answers:    First  step,  form  the  tosylate.    The  second  step  is  the  
same  as  all  other  haloalkanes.

e.  
HO TsO
Hello
1) TsCl, pyr. 2) t-BuOK

A  bulky  base  will  give  the  kinetic  product.     Major   Minor  

It  is  too  hindered  so  it  can’t  easily  grab  the   product product
hydrogen  that  gives  the  kinetic  product
f.
1) TsCl, pyr. 2) NaOEt
OH OTs OEt
Major  product

1°  tosylate,  strong  base/nucleophile  

so  SN2  is  major  and  E2  is  minor
Minor  product
XII. Substitution and Elimination Reactions with Other
Substrates
• Alcohols  can  also  be  used  in  substitution  and  elimination  reactions,  
and  used  as  starting  materials  to  make  alkyl  halides  and  alkenes.    

• Since  an  -­‐OH  is  NOT  a  good  leaving  group,  we  first  have  to  
make  it  a  good  leaving  group  by  adding  a  strong  acid  
Hello
•        -­‐OH  ⟶  -­‐OH2+        

• -­‐OH2+  is  an  excellent  leaving  group!

1˚  alcohol 1˚  bromide
XII. Substitution and Elimination Reactions with Other
Substrates
Mechanism,  alcohols  to  a  haloalkanes:

Hello
XII. Substitution and Elimination Reactions with Other
Substrates

• The  mechanism  will  be  either  SN1  or  SN2,  depending  on  the  
substrate.    1˚  alcohols  react  via  SN2,  but  2˚  and  3˚  alcohols  react  via  
SN1  

Hello

3˚  alcohol 3˚  bromide

• Strongly  acidic  conditions  are  protic  conditions,  which  would  favor  

SN1.    But,  since  1˚  carbocations  are  too  unstable  to  form,  1˚  
alcohols  react  via  SN2  mechanism
XII. Substitution and Elimination Reactions with Other
Substrates
• Alcohols  will  undergo  E1  elimination  when  reacted  with  H2SO4  

3˚  alcohol alkene
• Again,  the  strongly  Hello
acidic  conditions  are  protic  conditions,  which  
favors  E1  for  2˚  and  3˚  substrates

3˚  alcohol
E1  mechanism
• Water  is  the  only  base  possible  (unless  say  ethanol  is  used  as  a  
solvent),  any  added  base  would  react  with  the  starting  acid  (H2SO4  in  
this  case)  and  neutralize  it.
XII. Substitution and Elimination Reactions with Other
Substrates
Predict  the  major  product  for  each  of  the  following  reactions.

OH

a.   Hello HBr

OH

conc. H2SO4

b.
XII. Substitution and Elimination Reactions with Other
Substrates
Answers:

H
Br
OH O H Br

a.   HBr -H2O

Hello
First  the  OH  gets  protonated  by  a  strong  acid,  then  it  leaves.    There  are  no  strong  bases  
present  but  there  is  an  excellent  nucleophile  
H
so  the  reaction  proceeds  predominantly  
through  OH
an  SN1  mechasim. O H
H
O
H
conc. H2SO4 -H2O H
b.

+ H 2O
-H
This  is  very  similar  to  example  a.,  however  there  are  no  good  nucleophiles.    I  am  sure  water  
adds  back  in,  but  then  you  are  left  with  the  starting  material  again  which  further  reacts  
with  H2SO4.    However,  water  can  also  act  as  a  base  and  form  the  elimination  product.
XII. Substitution and Elimination Reactions with Other
Substrates
Draw  a  plausible  mechanism  for  each  of  the  following  
transformations
OH
HBr
a.  
Hello
conc. H2SO4
b.   OH heat

HBr
c.   OH

OH

d.
conc. H2SO4
heat
XII. Substitution and Elimination Reactions with Other
Substrates
Answers:

a.   O H H Br O H
Br

Hello Br

Br−  is  an  excellent  nucleophile  so  is  rate  of  addiuon  is  faster  than  the  eliminauon  
step  since  water  is  not  a  very  good  base  (remember  water  is  a  stronger  base  than  
Br− O H

b.
H
H O S O O
O
H O H
H
H
O

H
HSO4  is  NOT  a  good  nucleophile  so  instead  water  (in  being  a  weak  base)  will  grab  
the  hydrogen  and  form  the  thermodynamic  product.  The  kineuc  product  is  rarely  
formed  in  E1  reacuons.    Remember  HSO4  is  NOT  a  base  since  H2SO2  is  a  strong  
acid.
XII. Substitution and Elimination Reactions with Other
Substrates
Answers:
Br

H
c.   O H Br O Br

H H

Br−  is  an  excellent  nucleophile  so  is  rate  of  addiuon  is  faster  than  the  eliminauon  
step  since  water  is  not  Hello
a  very  good  base
H H
H O O H
O
d. O S O

O H

Since  the  leaving  group  is  on  a  secondary  

carbon,  the  leaving  group  will  leave  before  
the  1,2-­‐methyl  shiv  (2-­‐steps).    If  the  leaving  
H
group  were  instead  on  a  primary  carbon,  the   H
loss  of  the  leaving  group  and  the  1,2-­‐ No  good  leaving  groups,  so  water  
O

migrauon  would  have  happened  in  one  step   acts  as  a  base  and  forms  the  E1   H
(concerted  mechanism) product.
XIII. Synthesis Strategies
• The  whole  point  to  organic  synthesis  is  to  make  valuable,  complex  
compounds  from  cheap  and  readily  available  starting  materials  
• You  now  know  how  to  make  a  variety  of  compounds  starting  with  
an  alkyl  halide!!!
1˚  halide
Hello
XIII. Synthesis Strategies

• In  order  to  envision  how  a  desired  compound  can  be  made,  you  
need  to  be  able  to  recall  the  reactions  you  can  use  (meaning  you  
have  to  remember  these  reactions!!!)

3˚  halide
Hello
XIII. Synthesis Strategies

• When  thinking  about  how  to  make  something,  we  FIRST  think  
about  what  the  finished  product  will  look.    

• If  we  were  building  a  brick  house,  we  would  first  imagine  what  the  
Hello
house  will  look  like.    THEN  we  would  decide  what  bricks  would  be  
used  to  make  it.  

• Organic  synthesis  is  the  same  way:    we  first  look  at  the  desired  
product,  and  from  there  we  decide  what  substrates  and  reactants  
we  would  need  to  use  to  make  it  

★ This  approach  is  called  retrosynthetic  analysis

XIII. Synthesis Strategies
• Suppose  we  need  to  synthesize  the  following  ether:  

STEP  1:  identify  a  bond  in  the  target  molecule  that  can  be  made  using  
a  reaction  that  you  know.  
Hello  
STEP  2:  draw  the  substrate  and  the  nucleophile  necessary  to  for  the  
reaction.  

We  can  make  this  bond  by The  retrosynthetic  arrow  is  used  to  show
SN2  reaction  between  an we  are  “thinking  backwards”  with  regards
alkyl  halide  and  an  alkoxide to  the  reaction  we  could  do
 XIII. Synthesis Strategies

• There  are  two  C  –  O  bonds  in  an  ether,  so  we  could  also  envision  an  
alternative  SN2  reaction  to  make  it:  

Hello
Alternatively,  we  could These  are  the  reactants  we
make  this  bond  via  SN2 would  need

• You  will  find  that  when  “thinking  backwards”  this  way,  more  than  
one  reaction  will  often  come  to  mind  to  make  a  target  compound
XIII. Synthesis Strategies

STEP  3:  verify  that  the  reaction  you  have  proposed  is  reasonable  

YES!  We  expect

1˚  halide this  reaction  to  work
Strong,  unhindered  Nu
(good  substrate  for  SN2) Hello (good  for  SN2)

STEP  4:  draw  the  reaction  in  the  forward  direction

We  are  trying  to  do  an  SN2  reaction,  

So  we  better  use  an  aprotic  solvent!!!!
 IX. Regioselectivity

What  reactants  would  you  need  in  order  to  make  the  following  
compound  as  the  product  of  a  substitution  reaction?  

Hello
IX. Regioselectivity
Answers:  Think  about  the  bonds  that  we  know  how  to  form.    We  
know  how  to  form  carbon-­‐oxygen  bonds  either  through  an  SN2  
mechanism  or  through  an  SN1  mechanism

O O
Hello
(can be made from)
+
LG

O O

Since  it  is  a  primary  LG  (leaving  group),  it  can  NOT  be  an  SN1  mechanism  must  be  
SN2.    Also,  our  use  of  a  nucleophile  would  work  best  with  a  non-­‐prouc  solvent  
(less  stabilizauon  between  the  solvent  and  the  nucleophile).    All  we  have  lev  to  
do  is  choose  a  good  leaving  group  like  an  iodide  or  a  bromide.
O
O
ONa
Br O
DMSO
 IX. Regioselectivity

Which  one  is  the  better  retrosythesis  for  the  given  target  
molecule,  a  or  b?.    Explain.

Br
Hello a.

b.

Br
IX. Regioselectivity
Answer:    b.  would  be  the  superior  retrosynthesis.    With  a.,  you  
could  actually  make  the  desired  product  plus  an  undesired  
product.    With  pathway  b.,  elimination  from  any  of  the  beta  
hydrogens  will  give  you  the  same  product,  the  desired  product.
Elimination of Ha
Ha Br

Hello wrong product

Hb
Elimi
na tion o
f Ha

desired product

Ha
Elimination of Ha

Br

Elimination of Hb
Hb

These are the same compound.

Both are the desired product.
 Build your toolbox of reactions staring now!!!!

Step  1:  Buy  a  new  notebook!  

Step  2:    Title  your  fist  page  SN2  reaction.  
Step  3:    Show  an  example  reaction  complete  with  a  detailed  mechanism  
-­‐ reaction  first      A  ⟶  B,  don't  leave  out  the  conditions  
-­‐ detailed  mechanism   Hello below  
Step  4:    List  all  important  considerations,  need  to  know  facts,  useful  tips,  
etc.  
-­‐  Solvent  choices  (protic  vs  aprotic),  substrats  1°,  2°,  3°,  any  
exceptions,  etc.  
Step  5:  Repeat  for  your  next  reaction  (E2)  in  this  case.  
Step  6:    Each  day  you  leave  class,  add  all  new  reactions  to  your  notebook.
Build your toolbox of reactions staring now!!!!

This  strategy  saved  me  in  orgo!!!  I  spent  more  time  looking  at  
my  reaction  notebook  than  my  original  notes!      
You  will  never  be  able  to  forget  these  reactions  (for  12A  and  
12B)  and  you  will  regularly  need  to  decide  what  reactions  to  
use!   Hello

Each  chapter  will  add  more  reactions  to  your  toolbox,  and  
when  you  are  trying  to  synthesis  a  compound,  you  may  need  to  
use  5+  reactions  at  a  time  or  avoid  pesky  side  reactions.  
• Having  all  your  reactions  clearly  organized  in  your  words  
will  be  invaluable  to  your  success  in  organic  chemistry!

Show  me  your  updated  “toolbox  of  reactions”  next  week  in  lab  
for  5  extra  credit  points!