7 8

V
32
11 Br * Br

Br
& +
-3 111
ba 30

I 4
Br 2
21
2 & Br Br-

T
3 NV
major
·

30 radical
Br product

CHAPTER 9 :

nucleophilic subsitution is a rxn in which one nucleophile replaces one leaving group .

SN2 ·
subsitution nucleophile Dimolecular : Bromine , Iodine

NaNH2s

:
B-
S
SPA

-
<
W

↓
~ Br

-
&
- H
o
-

RXN [00 RD "

.

backside attack"

&1 ·
subsitution nucleophile unimolecular :

CH30H3
Br +
8 CH3
·
why is Br a good electrophile for SNI ?

RDS
be it forms a 30 carbocation

&

↑ HOCH3 8 CH3

I CHNOTRD CH3C
↑

g
8-

T
&

W "carbocation-like "
< -

Br

↓
CH30H CH30

RXN [00 RD .
S2 : attack will see inversion of configuration
backside
-

· SR
1 : F
: 3
Me CH3Br
SN]
X
SN2
~

10 Br
X* ~
SN7 : results in vacemic mixture
20 sometimes sometimes

& OCH3 Bu
S Et DCH3
Me R
↓ racemic mixture 30 ~ X

SP2 Tequal mix of both enantiomers) Br

carbocation
stability

* SN1-10 alkyl halides :

exception be
Pr & 29
stabilized by resonance
L +

I
+

SN1 SN2

I
-
"Me NO

↓
Br &
- CH3-Br

EXAM REVIEW : allyl OR

10 benzul

Br
-

what orbitals can participate in a bond ? halides Br

solvent- solvent :

Synthesis a 1 31 . in textbook review Br protic polar aprotic

20 o r non-polar

9 , Br
S

ethylene 1 butene solvent :

Brotic

Br
30 V

SN2 :

- Leaving Groups :
NU S - Nu single step ·
weak bases : I , Br , Cl , He-good L6
BV
:
:
strong bases : OH - CH30 ;, NH2-DOOr LG
·

Strong acids : HI
·

, HBr , HCl-good L

weak acids : + 20 CH3OH-poor LG

&
·

Nu

ABIRDS
,

SN1 :
+ Nv T
+

H I
H SHE
 PROTIC : POLAR APROTIC : NONPOLAR :
>

·
H2W ·
DMSO : : 0 :
S

·
CH30H
S
. toulene :
1
·

*
s
S

·
acetone : : 0:
OH ·

diethyl ether :

.
·

BMF : 0 :

N H

·
acetonitrile : CH3C = Y

protic solvents have OH or NH bonds , and can participate in H bonding

a protic solvents lack OH or NH bonds

SN1 : ↑
Br
:
-
t :
Br&
:j H H H
-j
= -

#
.

protic solvent

D OH bond

NV
+:r
=

SN2 : Nu &

Br
-

H
H-j H-j-H
- :

Nucleophilicity now good : of a nucleophile something is

GREAT : VERY GOOD : WEAK :

I I
CR- =
-

L
-i

N =
[CH3]zN
-

-i
- ·

--

CH3NH2
·

NB :N [CH3]zNH
·

- -

NH3
 I I
*
g
:
-

:
V
8H *

CH30-
·
CH3CH20- ·
CH3CHzOH
*
M

:
-

I
-

Br
-

V ·
Cl
-

F
-

·
[CH3]z

CH3S- CH3SH
S
· ·

·
CH3CH2S- ·
CH3CHzSH

)
-
↑2
Brotic Solvent So SNI
+ CH30H &
! -
H

S ,
/g
2

↓
SN1-carbocation intermediate

- CH3
↓

[1 [2

-
H1 : NV
CH3-Br
NV : BX
Nu
S >

& base] Br :
<NU] Br

Br
BETA ELIMINATION : SUBSITUTION :

[2 SNI Br
El SN2
 E2 :
AH
1
-

·
CH3 - - CH3H :
Br
:

H: CHzp5 *
·
single Step
·

........... ·

double bond formed

&
·
- H
1
·
*

&

Br :

·
I forms double bond , Br leaves

ET :

A :
&
Bu :
-v
RDS +: Br
electrophile Step 1 :
leaving group leaves
. form carbocation
2
It

I
↓

-
CH3WH

REGIUSELECTIVITY :
-trisubsituted

disubsituted /
In
stable
E2 : 30 .
* more
⑧
.2
· Or · more
8 subsituted
*

Z aitser rule" always formed

~
01 -
more sub be more stable

x
E1 :

&Br
09
+

E2 : Br Y

&

3 or more stable
B

BI Be

30 alkul nalide [Cis]

E

#rans]

( base)

Bil
H 9

301
Bu
 E2 b strong
g bast
1111IIL
-inn
BI
CH38 >
X
CH30H H
12 * Cl
a

↓It Fros
2 alkul halide

2 bound to X is bonded .

to 2 other carbons] a

H
DCH3

if & more stable be both

groups are both +quitorial]

Bu

B
Br

CH30-
CH30H
on
B HB HA

deprotonate HB deprotonate Ha
for "Z" for "f"

:
SNT/ET SN2 E2 .

- =

Me CHzBr * *
primary alkyl halides always favor SN2 unless

Sterically hindered

* * * = sterically hindered

it :
Br
·
·
protic solvent ·

polar aprotic or
·

polar abrotic or
good Da

Br ·
weak Nul nonpolar solvent nonpolar solvent .

H
strongly basic nucleophiles :

Br
·

↑ OH

-
SN2 product
1

base Sie : H20

.

, ·
"great" and "very good" .
2
any aloxides [deprotonated alcohol] :

CH30H] nucleophiles
CHOCH3
.
6 acetylide : R- :" * A ↑
·
protic solvent

weak Nul
E2
30 base Sie : H20 ,

Br
CH30H]
can use acttylide or deprotonated terminal alkynes
to form new carbon-carbon bonds but only w/

methul and 7o alkyll nalides be if you use

a 20 alkull halide or 30 alkyll halide you will get

the E2 pathway instead .
 CHAPTER 10 : ALCOHOLS
Sp3
q
CH3H-alcohols are sp3 bound to hydroxyl group
in
hydroxyl

:H
.8
1 20 30
H
H

nomenclature :

HO
I

23 6

& S

nexant H
b

CE]2-nexthe -1 -

81 3 [R]-heptanol

physical properties: molecular weight bp[02] Solubility in128

C gIMOl]
bp
78 ·
CH3CH20H 46 78 infinite
OH
[ ethanol]
-
12
·
CH3CH2[H3 64 -

12 IMSOUble
BH
97 [propane]

* ·

CHzCHzCHzBH 68 97 infinite
& propanol]
117
OH
[H3CH2CH2CHs 58 * Insoluble
·

30 [ butane]

CH3CHzCHzCHzOH 14 117 8 g/100g

[butanol]

H
-0-H H ·

CH3CHeCHzCHzCH3 12 36 Insoluble
H0 H -

H H30
+ T pentane]
+

CHICH
I
CH3CHH H -

0 -

D
H
2
~

acconot-bases it
= 16 DK9 = 16
pka

GH ↓

-
-H -
Poor leaving group

8H H t
&
+ -
H30+ 2 H20 S H20
··
CH30H [methanol] CH3 : - favor E2 for 2and 30
alky/ halides

SN1/E] SN2
CH3UH + Nat - E2

·
aloxide
rule out 1 polar aprotic
·

path
·
NH2
I
you have neg NU

2 CH30H +
2 Nao > 2 CHz : Nat strong NV ! OH
·

be that is a

Ko sodium methoxide alkyne anious

Liv * neat prefers Elimination

·1 =
weak base

CONVERTING ALTOHOL INTO A BROMINE : ·

E2 =
strong base
·

SN1 :
weak NV

·
SN2 =
Strong Nu

> RCH2OH RCHzBr

-
-
>
-

.
1

OH + H()- Cl + H20
only 10 and 30
not best
way if other
.
2
Br
functional groups present
8H +
1+ Br + H20
&

·
MECHANISMS :

-
-A
OH + HC) S -
-
: S +
+ H20 & CSN1
base acid

Protonate Of
·

-x
↑ -H
--

H + HBr Br

+
9 &
SN2
H28
·

can't form 1" carbocation

MORE PRACTICAL WAY WITH NEW REAGENT :

Br-i-Br :
·

PBVz : :
v -

: Bri

bPBr3
H

↑
&
: 2
HEpBra
SN2
↑
- -

Br
:
Br :
Br
-

: : 9lkul bromide
:

: W :
It

: + He SN2

Stack Si
A LCOHOL INTO GOOD LEAVING GROUP [SULFONYLESTHER/SULFONATE] : *
II
8
&
D
S
: :

:l 0 - -
CH3 BMS OH &CH3
11
ester
* CHz-S-El > * =

: OMs =
methyl sulfonate

- *
! & is -
para-toluene sulfonate

:H
①
: NV
#
NV :
SOCI2s &
SN2 Inversion of
config

OMS Nu
MSE or -
3
TSCI NU &

no inversion of config

CONVERTING ALCOHOL TO ALKENE :

le : dehudration : need acid +heat

:H
H2SO +
El
H20

:H
3
. HS8gH Z
Hi
& 2
t

+
H2O 3 + H2S0y
T
1585031

SYNTHETIC TOOLBOY :
& 10 and 20 alcohols] :
*
II

Jones -
⑧
It
H +, A
2
8H
PBV3S
Br
1 e
OH
5Ones
-
H

H+ , H2
B 8
SOC12
HO

D
B4L

-
y

C TSCI
Ms[I

& OMS O TS
OHH H
↑
11
or
 : Al
H2SOy Or
H3POY
heat
2aitsev rule

more sub major product

trans more stable than

CSOr"Z"

it+
ET :
-"TH20
protonated

20
: H
SHA20 -
+H30t

protic
I
i
solvent Nu-base - -
H

E acid
-

H2SDy
& ----
8 10-170 %
12 %
minor 56 . 32 %

#2 BC To
- 12 %

D &
+ H T +
H38
+

L &
t
1, 2 shift
Intermediate can # t

form other prod.

1. 2 shift happen & same time LG leaves :

* &

u +
H
--

OH OH 8
HaSONs PINNACLE REARRANGEMENT:

↑ innacle rearrangement

OSOVg
of
· I
&
# :

H -
Yy
*
-
H
&
H:

-
↑

I
Nu 3) SO H28
E leaves and forms 1. 2 alkul shift
carbocation

-t
H
S28 :
y
#

% k Y = >
-
+
more stable

resonance stabilized
 Oxidation =
-H + bond to so-TH 10 bond
8
+
,

&
# :0 :
Il
[O] 2 O]
H
OH T E ~
&
--

aldenude Carboxylic
acid
84 903i
Ketone

OH
4&
no Its to oxidize

CrOs , H20 , HeSOy

& carbonyl , carbon electrophilic
2/
KrzCr201 H2D , H2SOy
,
: 8.
It
# 2CrDy

-nudroxul
3

8H "5ONESI H
*
OH : GrO3H : 0:
*
·
-

i wo,o
It
5 ONES &
Havor & OH
OH
oa
H2 :

aldenude
form
reagent to Stop & aldenude PCC =

pyridinium Chloro chromate

-
* CICrOs *

i PCS
Il

8H H

&3

Y
* H

H 2
10

a
I

OSOrs
[ &
1 6 =0
- S
i
did periodic ↑
a sid

N9IOy
b
Il

sodium
periodate

O -
-
I ⑧H

-
OH

H ↑

To
10 8
II
: I -
OH
=> 8 !
is
*

O Il
&