Lecture i and ii alcohols and phenols

Acidity electron
withdrawing groups make alcohol be
-

stab
1) Electronegativity stronger acid by tiring the
conjugate base
_
.

more
electronegative ← alkoxide ion →
,
g- ( RO ) g-
acidic
¥
more -
c
B-
HI.tk#g-cH3 ( pka
c-
CES
"=3
2) Bonding ( pka 5,4 ) -18)
-
=

alkoxide ion
< <
,
→ e
withdrawing grs stab bize

more acidic → lower plea

RE solvation
by Hao energetically favored
→
-

stability goes uf -

Resonance stabilization
of Phenoxide ion

reactivity
→
Phenols are more acidic than alkohols .

"
? Phenols w/
withdrawing substituent > donating
-

" e e

NaOH
Hyo
→
+
( more acidic

( Resonance
of phenoxide
ion
)

EI : CF CH OH
, ,
→ RÑH" -

give
1 e
for 0 → It is
partial A) charge
↓ -

o has
high EN → 0 is
strong e
withdrawing molecule
F is the withdraw
CF2 +
4-12-40 -4 H
highest ENI atoms →
stronger than 0
-
e
✗

F ↓ flow of
withdrawing e

EI :

b)
,I°<
"
in "
,
+0¥ ,

OH

to
steric less stable H+
a) are more →

EN than C
0 is
higher
→ 0TH
 Alkoxide
synthesis
2K →
120-14++11-2

Nat
-

Natl →
120 +
Ha
ROH +

Nat
-

Nana
,
-
RO +
NHS

MgBr++CH4
-

RO
CHgMgBr
→

Alcohols preparation
Reduction
of
C=0 (
carbonyl compound ) > alcohol
-

reagent
( sodium
:
NaBHy
borohydride
aldehydes
/ £ µ ) → 1° alcohol

not sensitive to moisture

11° 1. Nabha , ethanol
>
↑"
RCH RCH
2.
Hgot
it
-

ketones

0
% , )
,
→ 2° alcohol

¥01T
12111,21 1.

2.
NABHY , ethanol
Hgot
, RIRI

electrophilic positively nucleophilic

Caton polarized
hydride
MECHANISM :
[ ↓

↳ alkoxide protonated
 -

Reduction
of carboxylic acids s 1° alcohol

ether
110 1. LIAIHY ,
,
reagent :tiA1Hy RCOH 2.
Ago
-1
RCHz0H
( since NaBHy isnt
effective
esters > 1° alcohol

ether
12%0121
1. LIAIHY ,
,
2.
Ago
-1

RCHLOH
+ R' OH

E- ✗ 117155)
i
"
20 ,LiA1Hy ,
ether
OH '
"
OR
-1
Hyo , or

( them R )
Grignard Reagent CRNg✗)
-

2° 3°
g- g+
R: 1° / /
alkyl aryl vinylic
, ,

R R
✗
Ng Mg✗ U.br ,
+ '
✗ I
- -
=

carbonyl compound alcohols

>
RMGX +

° OH
1. RMGX ether

Ed
,
, +
HOMGX
'
2.
Hgo -
-
k

MECHANISM : nucleophilic
bon anions

[
 +
Aldehydes ran

(Hatorah) " "

0
a. Mix in ether
CAN "
¥
9 ,

H0MgBr
+
+
-
2.
1+30-1
*

( aldehydes rxn
)

,9Br + fits
cHgCHCH2ÑH
0
1. mix

2 .
in ether

Hgot
,
ftb
cHgCHCHgdH-{
OH

H0MgBr
+ Ketones ran
OH
°
+
← 1- Mix in
either / CHIH,
CHgCH2MgBr 2. Hgot
HOMGBR
+

+
Esters rxn > 3° alcohol
°
1. 2CHgMgBr PH
CHzCH2CH2É -

0Ut2CHg 2.
+130-1
>
CHgCH2CH2 4-4-13 +
cHgCH20H
CHG

+
Carboxylic acids >
not give addition prods
( and
yeildscxtly Rmg )

1-imitation presence of
reactive Fct prevents GR
being formed
from organo halide (12-11)
Br -
Molecule -
FG

FG -
OH ,
-
NH ,
-
SH ,
COOH : GR is protonated by these gr
i i o

FA
-

CH
,
TR ,
-

c"NR2 ,
: Ctr adds to these
gr
-

CIN -11102 , -50012

,

-
 Alcohols reactions
1) Substitution
halides
( is conversion of alcohols into alkyl
3° alcohols + HU carbocation intermediate
by Snit through
-

HBR

1° and 2° alcohols
Solly through SNL mechanism
-

PBrz

( Ii ) Conversion of alcohols into Tosylates

◦
°
t.gs Pyridine
T
R
ROH
Pyridine
+
£ >
+ -

HA
a
-
ca ,
,

p
-
Toluen
sulfonyl chloride Tosylate ( ROTO )
 -

Stereochemical uses Tosylate

of

R' 0
'

"
ᵗ%qBr R' 0 Nat
' -

PB.rs
, , i.ca
ether ' 5m£
2,1 µ R
/
1,21
HO H
, g. (s) ( R)
← CIR
'

.gr#R'
'

p-tosUTOSQ.q.HR"0Na+
' ,
Ha
.
0

ether
¥1,21 5M£
pf\R '
( R) (S)

2) Elimination :
dehydration ( major prod)
-

3° alcohols use acid catalyzed rxn ( follow Zaitsev's rule > more stable alkene)
R, R,
Hit THF 1,2 ,

d- R2
i 1. ,

R2 4=12
+
R
G
-
°
-

} 2 .
25°C ,
1

OH
R B
,

f major prod) ( minor prod )

MECHANISM :

¥ :O
" H "
ÉÉÉ ¥
É¥÷
-

> >
# .

,
Hao :
 Lecture iii ethers and epoxies
Thiols and sulfides

1)
'
Ethers ( R O R) derivatives water
organic
-

of
-

organic gr bonded to same 0 atom

0
cHzCH2\o/CH2CHg
same
geometry as water CO spˢ)
C diethyl ether) (
tetrahydrofuran)
useful as solvent in lab

Relative
\cHg
stable

)
" "
in
many aspects
( methyl phenyl ether -
anisole inactive

R' ✗ '
Nat
-

>
ROH + NAH RO s 12012 + Max

d) Synthesis of ethers
1° alcohols SNL
sulfuric acid
catalyzed rxn by
-
+

" "

ii:^* ,;
' ÷
"
% H

"
city CH
}
¥ ,c-¥iI sit _i-%ii
ÉH
CHG CHG } CHG

+ H2O
+ Hgot
"

ii.
It CH
}
 ( best method ) -

Williamson ether synthesis

THF R' I '
R Nat
_

ROH + NAH s : > 12012 +

NAI

(
strong base) ( metal alkoxide)

Silver oxide
catalyzed ether formation
-

1-1-1920 '
ROH > 12012 ( in 1 step )
2. R'✗

Pentaether 856
Aggro
→
811-1206 + excess CH
}
I +

Ciodo methane

E± :
prepared ethers
by using William
synthesis
a) Methyl propyl ether b) Anisole (
methyl phenyl ether)
Br
CHgCHaCH0- CHgBr r
cHgCH2Clt20CHg
+
+
"
cHsBr
cHgCH2CH2Br +
CHGO
, %,

Alkoxymer curation alkenes

-

of
1210
1.61=302721+9
,
121,0 ,Hg02CCFg NABHY 1
It
I
c. = c c -
c , c -
c
2. R' OH

Overall Markovnikov addition of alcohol to alkene

-
0 is nucleophile since it withdraws

CH
e
from }

Ea , Ez :O added to 2°C
since it's more stable
EX :( 11142) rank halides in order in SNL
of reactivity
b) CHSCHLBR > CHICHI U > CHIH -
CHI

a) cHgCH2Br > cHg%HcHg > ⇐¥

" ( not reactive
better poorer
↓
( bromo ethane) ( 2- bromo ethane Caryl halide ) leaving gr
( not reactive
→ SNL prefer less steric → more
effective

( Ii ) Reactions ether
of
-

cleavage by strong acids ( HI ,

HBR )

O
R
- - RI H Br , +120
s R-

OH +
'
R Br
Reflux
( bromo alkane )

more hindered less hindered

\ . % ✗ SNL
HCCH O
H§qH cH2CHg I
> OH
tgcc
+
CHACH} > H
CHzCH2
- - -
- - -

[ :÷
I 1 ,

↳
H
"
+3 CH
, CHG
:

> halide binds to less hindered component →

alkyl halide
'

R go R
HBR
E± (14/42) ,
+ Br +

CHGOH
Snl , Ey

piita.io
◦
Iain
tdu.org ? nhanh voi 3° 3 halide 1°
'

9×1 ,
E, cho Br cu
→
ra , ,
ROH

(3°C forms
CarboCanion
very fast )
 Claisen
rearrangement
-

+
specific to allyl aryl and
allyl vinyl ethers

%H2cH=CH2
" Nat
i f-
ctta-CHCH2.BR
y
THE
+ NAH Solum + NaBr

heat -250°C
allyl phenol
+
200 > o -

PFA OH

(allyl phenyl ether

)~ daisenrearr
250°C
,
[cH2cH=cH2 Co -

allyl phenol)
(has to put in a
ring og
6- C → stable
configuration

( isomeration) It
.
iɥ
rearrangement fore called mechanism
>
pericyclic