Aldehydes and Ketones

OCOC-II : Properties-I

Class 2
 Reactions of Aldehydes & Ketones

(I) Typical (Direct) Nucleophilic Addition :

1. Of Hydride ion (H ) : LiAlH 4 /ether or NaBH 4 /H O
2

2. Of Alkynide ion (R-C C-Na)

+

3. Of H 2 O/H (Hydration)
4. (a) Of ROH/H (b) Of Glycols (c) Of 1,3 Diols
+

5. Of HCN/KOH
6. Of NaHSO3 (Bisulphate addition)
7. Of Grignard Reagent
8. Of Ylides (Wittig Reaction)
9. Of Ammonia & it’s derivatives 10 20

(a) of ammonia (b) of Amines (RNH 2 & RNHR)

(c) of special derivatives (NH 2-Y) (d) Reductive amination
 Nucleophilic Addition Reactions :

O
OH
8-1 8-
I. Nu
-

2 .
H+
C 1 C C

Nu
RDS sp3 Nu
sp2 ( Nu addn
Tetrahedral intermidalé
-

product )

* * * *

( H ) SPZ : Planar (4) * chiral Centre) ( H) (4)

1
,

• R , ≠ Rz Racemisation
◦ R ,
or
Rz = H

Note : if Hcno is taken or if R

,
=Rz e.
g
Me co
- -
Me
; in
that chiral Centre is observed ( only
No .

product
1

is formed] - -
- .
 MCHO t.NU
Hye
-

•
04
chiral Centre
-

(formaldehyde)
: No
2 . ut u
,
-
Nu

I Nt
Mezco
'

Me OH NO chiral centre
}
•

- , .

2 +
.

H '
Nu
Me

1. Nu Phi # - OH
-

Ph o_0 Racemisation
nF
-
•
:
-
in
2 -1
.

H
Nu
or Et

OH
1. Nui
~ : NO chiral centre
•

me
2. Ht

(cydoalkanone)
 Reactivity Order : Easeof Nu -
addn

(a) Electronic factor (b) steric factors

ERG/ EWG
usually due to
Ft 5-
\
, sp3 (alkyl) hybrid
-

ya
C = 0 / ← Focus
/
(only int ketones
\ '
RDS Nu

of electrophile city of carbonyl

'

Rxn
• ease
depends upon
✗ polarity of >c=o group . carbon atom

1+18-1 8- R
R\É=o
. c=o > =o >
It
/I=o H
+I of R R
/
+ I
effect of É
'
R

(formaldehyde) decreases polarity

or decreases
reactivity
Observe ERG decrease
reactivity
^

:
+ I
.

EWG : increase
reactivity
Me
✗ \"
• Cltz -
CHO > HCHO > ÉHzCHO > Cltzcitzclto ) Ch
/
-
Cho
I
+I
N°2 : EWG I : ER
effect Me

M
+ I : ERG
0 1- o
11
•
R→ 'd # it >
Ac
s
-

8-1
H

C- I : ER ) I
Very weak) < + M
(Benzophenone)
-

effect

&
11
H
Ac
%
-42 >
A. §
•
-

>
8-1 8-1 8-1
+ I
+ in +1-9 I
[Benzaldehyde ) (aromatic ketone) •
(very weakly polar)
• least reactive
towards Nw
-

a
 Eito
+ H -
I > + "^
+ I + my -
I -

/
I -
M -

Il -
M

: G : H
, Cltz Cl OCH
}
-
CN Noz
, , , ,

I 4
1 2 3 5 6
G
.

CHO CHO CHO CHO CHO

CHO

< < < < <

"
I 1 " I 1
CN N°2
◦ Me
@ M) Me
@ 4) M
(NO effect
Cl GI) Gta) GM)
Para Position II effect
: is NOT observed except Halogens
± in
effect is observed ( Farci)
± H effect is observed .

Note : In
halogens ; -
I > + M : × : are
deactivating
are EWG .
2 .

Caz -
come > cuz -
co -

cuz > the -

co -

cuz cuz >

+ I ← c- + I
-
I :
strong EWG
Me
"R
> Meco -

qn cuz
-

me
d- Me 3%

§
- -

cuz 1 + I
→
Me
+ I
/ steric steric
crowding
crowding ↓ is too much
3- Is I < II < III. < Iv ( least reactive
ketone

Cry yourself )
 (I) Typical (Direct) Nucleophilic Addition :
1. Of Hydride ion (H ) : LiAlH4 /ether or NaBH4 /H O
-

H H
HT
H
-

C C
C

④ ) u o
-

(Hz0) OH
• an alcohol

liAlH%tner H NABHA
-
•

= a- •
Reduction
Uzo = H+ c- Hzo ( Nu -
addn)

NABHA
= ± }¥µ☐
☐ 20 ☐+
Nw -
addn

NaBDq =
D- { ¥50M products

Credos
☐
R CHO- It -1
1+20
products)

H W
-
-
NaBD4
Dzo
=
÷ P¥°☐ "
D

* Phcno ; Mccone
ₕydᵣₒcₐᵣbₒₙₛ
; Try Yourself C̲ i ̲r ̲c̲l ̲e̲
 2. Of Alkynide ion (R-C C-Na)
Rc -=C -119+-1 NÉÑHz →
R - C=EÑa +
Ny
Terminal alkyne) base sod .

alkynide
> .
a nucleophile
£' nice
-

C
8-
+ R-c=EÑa C

C -=c-R
H+ ( NHS)

OH
-

NHI
⇐Lkynylol) c
⇐ c- R
St +
-=EN+a
St

HCICH
Nantz NAE 2. RCHO
•
→
2.
Oeg

[ ""
37,0 °

R - C
,
+ c- = c- + É -
R

]
' '
n n 12=4
Ht
•

OH
•
R = Ph
OH
R -
du -
C _=C -
du -
R •
Melone

(Alkynyldiol)
ₕydᵣₒcₐᵣbₒₙₛ C̲ i ̲r ̲c̲l ̲e̲
 +

3. Of H O/H (Hydration)
2 Note : If attacking NI is weaker

(neutral) ,
then reaction
⇐ em -

Dihydrate)
needs to be Acid Catalysed .

??
= 0 : + 420 : →

] neutral/ weaker
4-1
= 0+4 d- OH 1- Nu

(weaker)
•
protonated carbonyl group is
strongly electrophilic
OH
C : + Ht c. = 0+4
°
: Hz : Neutral £ -
y
nucleophile
Eh
• A
gem dihydrate is
- Unstable 04

e
In H+ ; it n -1
presence of gives
-

OH
back
ₕydᵣₒcₐᵣbₒₙₛ
carbonyl group quickly • A
gem dihydrate C̲ i ̲r ̲c̲l ̲e̲
 Stability of Dihydrate : HCHO > CH3CH0 > CH3C0CH3
↑
( Gen )
(most ↑
Stabilised Gem diols :
stable) ketones
: steric
form unstable
zero

+
+11+20 OH
crowding @ ) dihydrate
em

OH
↑ ↑
&
sp2( unstable ) sp3 : strain decreases stability
increases
too much strained
Hp Chloral dihydrate
- -

gem
-

C1
- -
•

is stable
"

C / 3C CHO
1++11+20
Cl
I -
CH
due to

bonding
-

Intramolecular H
-

1
Chloral) % . . _ . .
11-0

0
0 H
stable due
- - -

to
-

µ
-1
to intramolecular
0
H2O 4-
bonding
Q
O
O - - - -
H
Indane -1,33 -
tri one
Ninhydrin
Gem dihydrate s are unstable & in
presence of Ht ions ( acids ,

they give back carbonyl compounds .

EH h+
C Hz A
C n
OH
C= c=o
-

OH -420
Dihydrate
•
.
-4-1 1,
Carbonyl
Note isotope following
•

Observe the in
:
exchange .

group

16 H -1/42018 18
a c = 0
,

-
42016
I
 +
Acetal Formation
4. (a) Of ROH/H (b) Of Glycols (c) Of 1,3 Diols
( Au'd catalysed
" °" ROH

≠
OH
-
=o OR
Ht /
-
◦ R
1+-1
_
/ OR
@ cohotshemi -
acetals
Acetals/ ketals
( ketals)
( gem hydroxy ethers) : unstable ( stable
¢11201T)z 0 -

CHZ

H -1 ¥0 -
1
CHZ
cyclic Acetals
( Di oxalans)
1,2 Diol :(Glycols)
-

◦
,CHzOH
C

CHZOH
H+
cyclic Acetals
(1) 3- Diols)
• Visualisation of Reaction :

H+ OH
204
0+4
. .

c. C =
C

7
as Nu

& -
r -
Ht
45 "

(1^910-1)
+ 04
◦
Nz Ht a

C 0+-12 a
OR
-420 QR
(Hemi acetal)
•
-

12-0 :
, +
a Elimn .

OR
°
OR

of
-
Ctu
°
r Acetal)
n -1
-
-

OR
ng
• Observe that : Nu -
addn : ROH
Nu -
Elimn :
H2O
• Remove 420
&
keep excess
of Ron for FORWARD
Rxn .
Try Yourself : ◦ R
H -1
a ? visualise the
013 yo
Path of Rxn .
 H+ stable

4 4
£ g
3
3

G
1- ~
6 1- \ /
µ
4 ? -

h -1
z
@ (
,
H
2-
Hydroxy Pyran)
4
3
"+ 1
40 : +
HO 5 µ
2

-
n +

② -

Hydroxy furan)
5. Of HCN/KOH
HCN + KOH Hzo + K -
C- =N :

-
strongly nucleophilic
CN HCN
C
-

or

( RCN) KOH C
8-1
CN HoH
Note :
1. let
'
c- CL of
◦ 4
/
-

\o/
a
2. IN /
1 I CN
CN
on
Cyanohydrin) Gem :
430-1
④ canal)

430-1
04
113
c-
✗

d- /
{
cook
% 1004
✗
Hydroxy Acid
-
•

acids
•
13 -

hydroxy
 HCN
* 104 " PM
CH3CH0
•

CU -
CH CH -
CH COOH
]
-

KOH }
↳ : lactic Acid
C- hydroxy acid)
•
(±) : Racemic
mixture
Na/Eton P"
cyanohydrin CM] CN CnzNHz
•
-
-
_

✗ 13
↳
RA
. ← amina ,oa•,
•
H CHO A B
KOH
Na
C
Eto #

HCN
µ,
•
CH3=O A
/
KOH
Ph Na
C
Eto #

HCN 1+30-1
•
D E
→
KOH
Na
F
ETOH
6. Of NaHSO3 (Bisulphite addition) 0
11
Not 11-503 → Nat + H -

O -
S -
E
God bisulphite)
.

↑
i Nucleophilic site
C. + :S -
OH ( strong Nu]
,
0
valonia
-

( Nu -

addn C
◦
OH

product) g
C
O

O H S
0T¥
-

O
While
•

crystalline solid
:( Bi suephiteaddn
-
0
( insoluble in 420)
product) sod .
Salt of
• used in Purification of carbonyl compound sulphuric acid
Ca hydroxy)
& ( ?)
-

separation of carbonyl , ,

Protection
•

of carbonyl compounds as these compounds

are stable except when heated in HCl ( ?) !!!
 Inta Nacl +
NaCl
c y + song +
,
°

s
-
n -1

0
0-4
a
•
Regeneration of
carbonyl compounds

IMP : St is observed that all

aldehydes give this reaction
but
only few ketones give this reaction .

CH3COCH3 ; coats ; 5
Acetone
Acetophenone cyclohexaneone &
penta none

why ?
higher ketones do not
give above reaction due

to steric in
crowding 1.1.1 .
resulting poor
stability of the
product .
7. Of Grignard Reagent

RM9Br 1+30-1
OH

¥
/
=o
-
R
Etzo
alcohols
HCHO
(a) RMGBV
H3°+
RCHO + 10/20/30
Rzco (b) PhMgBr alcohols .

\
8. Of Ylides (Wittig Reaction) ✗ F-

Ylide : A Nucleophile : Phzp Cltz Phzp -

CHZ

,
_
-
- - -
,
,
( RzP=cHz)
"

¥
,

+ Phzp i CHZ Ph]P=0

-40 c
cuz +

( ylide) "
'

- -
-
-
(
an alkene)

Preparation of Ylidecs)
-

•
: Nu

Phz # + CH3I -

Ph3Ñ - C- Hz I
Ph3Ñ - ÉH
≥

( C- HI)
Triphenylphosphine ) (Basey
PhzP=CHz

2
Visualisation ?

°
-

Phz O P -

Phz

C
CHP C C
Hz

@ P
)
Phs + c
cuz

(
an alkene)

t.

Terminal alkenes
C O + PhzP= CH -

R
} -_ Ch -
R
@ on -
Terminal
(
another ylide) alkene)

R R
\g=c
/
( Dialkylated
/
C O -1
Phz -p=c -

R
-

R
alkenes)

PhzP=CHz Cexocydic)
cuz
Terminal
-

PhzP=CHCH3
ch -93 Non Terminal
-

cyclohexane
-

PhzP=c(CH③z
-

c3 •
Non Terminal
-

Dialkylated
cuz
◦
 Phzp -_CHz
-
cn=

PhzP= CHCH }
C=0

4
-

cu=

@ enzaldehyde) PhzP=c(CH③z
-
C4=

Note : Intramolecular
Wittig Reaction :

ii.
"
- i
3 2

#
- -
-
_
, ,

,
,

° 4 2 ,
4 I
Phz
' >
Me ,

, 3 1 '
'
_
_
.
5 6

- -
- OR the
y ,

'
'
-
= . - -
_ ,

;
Me
6
5
4
3
2

f- Phz
,
I"
1 -
- - -
9. Of Ammonia & it’s derivatives 1° 20
(a) of ammonia (b) of Amines (RNH 2 & RNHR)
(c) Reductive Amination (d) of special derivatives (NH Y) 2

(a) With ammonia ( addn + Elimn = condensation )

( Nhs) ( -

Hao)

iii. N
'
'

i
-
n
c.
-
. .
.
: C N -4 Imines
H+ + Hz 04
a u C

(Protonated) ¥e
'
- set

carbonyl compd
+
04
+ 042 Ht
C
C H C N -
U C

H+
'
NUZ NHZ
h
-420 & hydroxy
-

amines )
*
usually Imines are NOT much stable
! ,,
,
 H+
• HCHO : HCUO + NU Hzc =
NH
}

( formaldehyde) ( formaldimine)

Aprotic Urotropinei@42J.g Not >

olymerises
Solvent
(Hexamethylenetetramine)
kidney Ailment
↓
Drug structure :
Cage like

¥:

[
@ n%N , + KNO
} ¢42 -
N -

N°2
≥
•

cyclonite "
N°2
•
RDX µ -1
• An explosive

N
Moz
 "+
1-
CUZCUO :
CNZCUO NU CUzCn=NH
•

(Acetaldimine)
rimerises
3¢43 Ch =
)
NH
Me me

N
N
N N
( Trimer
me 7- acetaldimine
)
N
"

€]
" "

H.W. N

Ht H+
? H+ H+
V43
' C-yo] ?
""
3
C-go,
(b) With Primary Amines RNHZ : 1° amine

H -1
-

I
-

C
! - - -
reign
-
-

R C N -
R
(stable
H+ Imines)
RCHO + nzN -
R Rcn -_ N -
R ( Aldimines
n
,
-

Ht
RzC=0 -1 Han R
Rzc -_ N R
( ketimines
- -

up

42N
Schiff 's
cn=0 + -

µ -1
Bases

Cn=N -

: Benzol aniline

Try yourself its Visualisation .

Riina H+
N -
R

C- ketimine)
• With Secondary Amines :
RZNH : 2° Amine

•
Carbonyl compounds having 2-4 give the 's reaction

(HCHO & Phcno will not give this

reaction
n -
it -
R-
-1µF -
R
N
IR
-
R
✗
↳

O OH
-

H 1
✗
Ha Ha
R
/
R -
R 4-1
ñi
+ "
R 1 ↳Hz
-

H+ Ha Ha
(d)

413 Unsatd 3° amine

R
-
•

✗
-
N
'
•
Ene + amine = Eneamine
R
13
 Try Yourself
he
-4in Ht
•
MezNH Product
-
Ha

+
"
•
CHZCHO MezNH Product

+
"
Ph
cuz -9, MezNH Product
-

+
"
cyg-q-cnz.cn} MezNH Product
•

0
(c) Reductive Amination
2° amines
1 .

NHS 2 - RA
a a NH c- NHZ
Ht ; Do
tf
unstable twine

•
RA :
Na/Eto4 ; Hz / Nior Pt j NaBHzCN
⇐

(sod Cyano borohydride

.

A-
I. NM } / Ht 1° ,

MHz Cyclohexane mine

^

⇐ .

2.
Na☐HzCN/D
1. RNHZ / Ht 2°
N Alkyl
-

A NHR :

NABH
cyclohexamine
2.
>
CN
/0
1. RZNH / Ht 3°
R
µ, : N, N -

Dialky /
2.
NaBH3CN/W R
cyclohexanamine
(d) With special derivatives (NH 2 Y)

See Tomorrow at 3.00 PM

•

You
.
Please revise
Today 's class in 90 MIN ( Max]
• Do attempt Homework Sheet

Thanked
BE
-