.

CO -

Chem Recipes
Acids 4 Bases
•
Branstad acid proton donor

•
Bronstead base proton acceptor

ka [Ht][ AT 1 acid ( strong conjugate

bafogergns
acid
=
→ =
strong meat

CHAT weak acid

L 1 =

Large acid 4
'
tea
strong weak base
=

1 Label
conjugate acid 4
.

conjugate base

2 Which ?
.
is a
stronger conjugate base

4
HF ka = 6.3 X Io
-
.

HF ka > HUO Ka
8
HC IO 4. o acid
stronger weaker
conjugate
-

ka X Io
.
=
=

base

H CIO will base

have
stronger conjugate
'

Lewis acid accepts e-

"
Lewis base donates e-

Ex .
It
F
\ H F

µ Bt
I
N
•

F B SH F
.
-
- -

H e- rich e- -
poo
H F
F
H
 Nucleophile and Electrophile
Nucleophile : e- rich ( donates a pair of e- )
Electrophile : e-
poor (accepts pair of e)

Ex .

nucleophiles ?
3 .
Which of the
following are electrophiles and which are

H
nucleophile
→

CHSO → nucleophile
CHzC=CHz →
nucleophile
CHSCHTCHZ →
electrophile
NHS →
electrophile

Bi -

Molecular Substitution SNZ

I .
K=[substrate][nucleophile] ( involves both .
'

.
bimolecular)
2 .
I step mechanism ( back -
side attack
) r transition
state
3 . If LG is bonded to stereo
genic
centre t

inversion of
configuration
-

energy
Ex .

An
progress
 Sferics

SNZ due to
steric hindrance reduces reactivity for reactions
-

bulkiness of substituents

H H
CHS H

Hsc C Br
tfzc
C B -
H
& B- H C
-
Br
l
l
CHS
Chez CHS H

5 2 to methyl
tertiary secondary primary
>
reaction rate in S Nz reactions

Methyl 4 I
always react by sN2 SN
•

,
never
by ,

Nucleophile
K = [substrate][nucleophile]
•
Needs a GOOD nucleophile

Leaving Group
•
Needs a
good LG

Solvent
have dipole and therefore
Polar aprotic solvent i a
electronegative
.
an

atom but not acidic Ht

↳
an
,

stabilizes cations but not anions

ex . DMF , DMSO

4 . Determine the product that would be formed from the SNZ

reaction of S - 3 -
chloro hexane and the hydroxide
ion
; draw the mechanism and explain stereochemistry

X : H →
N
Mbf
"
Hot
N
Cl R - 3 -
hexanol

( inversion of
config)
Uni molecular Substitution SNI
1. kcsubstrate]
-

l molecule involved in the RDS

2. carbocation intermediate formation

-

front or back -
side attack

3.
2 -

step mechanism
before
LG
departs nucleophile approaches
•

If LG bonded to stereo center → racemic mixture

genic
'

Example : H
H
i. O '

front

[CHzdHzCH3
back
.
.
+
-

CH3CHzCHz side attack H H

-
?? .

T CHSCHZCHZ fat
+y§NtB¥
Br
a
- .

"④f*
Br
'
Hsc
HgH¥C
-

s
it
CHzCH2 cHzCH3 CHgCHz
-
carbocation
intermediate t
H CHzCHzCH3
H
'
T Tf
c
:
o :O ""
CHSCHZCHZ Sh R enantiomer H
'
It E. CHS
\ n
"
.
H
CHzCHz
c -

Oj g
CHI l H
-
racemic
l

CHzCH3 mixture

Carbocation Stability

R R
H H
✓
R C
) ) )
t
R ( t R C t
H C t

l
R H H H

5 > I > to > methyl

 Hype conjugation
- : delocalization of e-
by overlap of carbon -

hydrogen
or carbon carbon Sigma bond with an
empty p orbital
- -

( e- donating)

Example
5
Why does 3 bromo l butene solvolysis in methanol
undergo
-
-
-
.

much more rapidly than 2 -

bromobutane ?

~
~ l
l Br
Br

im
3- bromo -
I -
butene 2 -

bromobutane

too
i ⑤

← If
⑤
↳ more stable carbocation = faster reaction

Nucleophile
f- =[substrate]
'

Poor nucleophile is
preferred ( prevent S
Nz route )

Leaving group
•

Needs an excellent LG
 Solvent

-
polar protic solvent i can donate at least I Ht

↳ stabilizes cations and anions

ex . ethanol and water

Practice Problems

for
I .
Draw the products the
following reactions :

CHzCH€
A '

cH2CH3

d → '

NAI
.
.

H I t NaOH → HO H t
7 *

(
.
.

CH ,
[excellent LG
CHS

active
I *
optically

7.73k¥
b.

E÷*÷:ia. i
pm
.

.
'
on
G
PH
CHIEH I

ftp.aa.r.EE#
(¥1/ I 1µm t

THEM
outs

¥ocHz
RS RR
C .
-2 -

bromo hexane with Na HS in DMSO

s #

jpg
sN2Ehy
rs aphotic

Na HS
# t DMSO
g
inversion of
config
-

good
-

HS is
active
nucleophile optically
-

(s) -

Z -

hexanethiol

d. iodo cyclohexane methanol

methy in
cH3 CHS
IF
)#
CI tha
,

I leaves ←
#
t Ee x
f f deprotonate
-

CHIEH 7
-

+
+ I s

X methanol
X X
•
achiral
poor Nii

Ju
-

- otic solvent SN
p ,
-

OCHS
{✓

-
not optically active
e . Draw the reaction mechanism b/w chloro ethane and

methane ate and name the compound that forms

O
P 11
Nat Ht -
o: .
- Ii → or
"

H H
o
(Cl is )LG ( Nucleophile) ethyl methanoate

10 =) SN
z

f 3- 40
.

Classify the carbon atoms as methyl ,

lo, 2; or in

1 .
2 -

methyl butane

2 .

2,2 -

dimethyl propane
On LG
which carbon would you put a in order to ensure sive

(
O
10

# ✓
10 10

\ - o

or to
go
2 .
X LG on
any 10 carbon

40N
30

§ /
.
to
to zo z

O yo
/
best for SNZ
g.

)
-
-

(b/w CI and OH
,
Cl is a better LG
CHS
\ A
CHS

CHZCHZ -

q
-
CHS t H -
Cl
→ cHzcHz -
d -

CHS
:
? It
+
fl O
↳H l l
H H

-
good LG

L
CHS CHS
l l
H2O t CHSCHZ - C
-

CHS ← CHzCHz -
C -
CHZ
I
Cl
⑦
f -

Cl

Planning Reactions
I LG reactant Is lo, I Carbon ?
.

Identify the on the .

it on a ,
or 30

-
where the LG is ( identify new bond ,
how can you form
it ? )
2 .
Based on the product ,
what nucleophile is needed ?
°
Nii are e- rich

3 .
Consider the reactant and product together and decide
what want
type of mechanism
you
to occur .
Choose

the solvent
appropriate .

SN , tic solvent
polar
•

pro
-

(form H -
bonds with anions and cations )
•
SN z -

polar aprotic
( stabilizes cations , but not anions
)

✓
Cnext page)
 solvents
considering
:
example

a .

O
r

s
.
If
t
Hi H
t
/( s
tf s ft -
H

LG Hsc cuz '

:O -
H 21
/ H
H

5
f
→ SN
, pola p otic
- -
Explain j:
solvent
H1 htt
807 . water 120T .
acetone

SN ,
= KC / KD is more p
- otic
,
therefore
L
T
electrophile facilitating the formation

of a carbocation b/c Hzo

OH
is able to stabilize the

intermediate .

b. Determine what
reagents to use in order to reach specific
product :

Na CN
"
it

(
O
2¥ *
Hbr Ican
LG on to C SNZ - ,

SNz= pola -
aphotic ( DMSO ) *
adding acid will help protonated
into H2O which will mate
group ,

Mechanism it into a better LG

+
H
→ It
-
s

N
N
.

l
#
.

r
H H -
Br → Oto DMI
✓
t
µ
-

in
Naan C
B - leaves
g M
-0
a. NIC:
•
Na CN =
nucleophile

polar aphotic solvent

•

DMSO =

HBr= acid to
promote protonation
°
C .

smooYEutessoanf.o.it fronton
→ fans HOH,

µ
around backside
*zomove '
¥
""

Nt Rall
I-11111
l
"
Naor ?
*
loses
↳ stereochemistry
will provide (Planar)
c, leaves racemic mixtures
-

excess OH
which
3°=SN can act
, as Nii
0

More practice problems

I .
Consider the solvolysis reaction of tert-butyl iodide in ethanol

a .
Draw the
complete mechanism
HOW
b. Draw and label the reaction coordinate
* Ethanol polar paretic

a . A f
h
polar photic = SN
,
Ethanol
✓
I
S ⑤ →
HOW
*

H
-

better LG
-

* I

than
)
OH H
.

b -

Nf RDS -_ bond
break
&

§→eep→na*o
→ N attack

Energy ,
+ OV
F protonated -

ether
1-I p

1-
of
reaction
progress

2.) next
page
 Br O

I :O
01h
X
.

I
X
.

W n
'
s
T
-

electrophile node 'Ifif ✓

Br is LG product

3 solvents and for

.
Show the
reagents ,
conditions
necessary each

of substitution
following
the reactions .

'

OH
a-
SNZ
Me g No ,
DMF

bond
b
→ being formed
The on
.

n
H s
l→l

~f¥* .fr s~l.no snz

c-

O -
inversion of
configuration
product enantiomer ,
Cally
-

pure
4 Draw SNz
.
the product for the
following reaction

a . (s) -

2 -
chloro pentane and Na HS

ef.ge
't
¥
t Na HS J
# x
\ H
-
inversion of
configuration
5 . For each determine if the species are identical enantiomers
, ,

or another type of isomer

a b

.IE#aFiQqLHand!$oaiooii
.
.

Fight and

F
'

identical enantiomers
6 In nucleophile
.
the
following reaction ,
which molecule is the

NOH t aim →
NON
Nucleophile Electrophile

7 reactive
Which of
following be most
.
the molecules will

towards ethanol solvolysis ? Briefly explain .

ethanol solvolysis : ethanol is nucleophile and solvent

F- TOH is photic SN
polar ,

YI
a Br b I c d
.
.
. .

✓
Ans '

. B will be most reactive since the LG is on a

tertiary carbon →
forming
a stable 3 carbocation .

Also ,
-

I is a better LG than Br .

8. Predict the reaction

following
of :
product the

# Cl

H
t 5-
& - H

l H
H
-

c
5-
f '
it

ix. a s
rats -
9. What best definition of
is the hyperconjugation
of of
Delocalization electrons
by overlap carbon -

hydrogen
carbon bond
or -
carbon
pi -
with an
empty
p
-
orbital