NUCLEOPHILIC ADDITION TO THE

CARBONYL GROUP
A. Synthesis of Aldehyde
1. By Oxidation of 1o Alcohols

C5H5NH+CrO3Cl- (PCC) O
R CH2OH R C H
CH2Cl2
1o alcohol aldehyde

2. By reduction of acyl chlorides, esters and

nitriles
 2. By reduction of acyl chlorides, esters and nitriles

O
(1) LiAlH(O-t-Bu)3, -78oC O
C
R Cl C
(2) H2O R H

O o O
(1) DIBAL-H, hexane, -78 C
C C
R OR' (2) H2O R H

o O
(1) DIBAL-H, hexane, -78 C
R C N C
(2) H2O R H
 CH3
- CH2CHCH3
OC(CH3)3
Li+ H Al OC(CH3)3 Al
H CH2CHCH3
OC(CH3)3 CH3

lithium tri-tert-butoxy-aluminum diisobutylaluminum hydride

hydride (LiAlH(O-t-Bu) (i-Bu2AlH or DIBAL-H)

• Exercise:
Show how you would synthesize propanal
from: (a) 1- propanol; (b) propanoic acid
B. Synthesis of Ketones

1. By ozonolisis of alkenes
R R" (1) O3 R R"
C C C O + O C
R' H (2) Zn, H2O R' H
ketone aldehyde

2. By Friedel-Crafts acylations

O AlCl3 O
ArH + R C Cl R C Ar + HCl
3. By oxidation of alcohol
OH O
H2CrO4
R C R' R C R'
H
4. Ketones from alkynes
HgSO4 H H
C C + H-OH C C C C
H2SO4 OH H O

5. Ketones from nitrile

(1) Et2O
C N + R-MgBr C R'
(2) H3O+ O
Exercise:
• With 1-butanol as your only organic starting
compound, outline a synthesis of 5-nonanone
Nucleophilic Addition
1. Hemiacetal and Acetal Formation
H
R H+ R O R' -H+ R O R'
C O + HO R' C C
-
H O H O H
H
hemiasetal
H+

R O R' R O R' R O R'

C -H+ HO R'' R O R' -H2O
C C+ C
H O R" H O H H O H
H
asetal R" H
 Acetal as protecting groups
O O O O
COC2H5 HA
O COC2H5
HOCH2CH2OH
1. LiAlH4, Et2O
O 2. H2O
+
O H3O , H2O
O CH2OH
CH2OH

2. Addition of Organometallic Compounds

 H3O+
R:MgX + C O R C OMgX R C OH
3. Addition of Hydrida Ion (LiAlH4 or NaBH4)
1. Et2O H
O + LiAlH4
2. H3O+ OH

O MeOH OH
+ Na BH4
OH-

4. Addition of Hydrogen Cyanide

O OH
1. NaC N
CN
2. HA acetone cyanohydrin
5. Addition of Ylides (Wittig Reaction)
+ ..
Ar3P C + C O C C C C + Ar3PO

Ar3P O

6. Addition of Derivatives of Ammonia

.. ..
.. -H2O
N + C O N C OH N C
H
Exercise:

• Write structural formulas for the products

formed when propanal reacts with each of the
following reagents:
a. NaBH4 f. H2 and Pt
b. C6H5MgBr g. HOCH2CH2OH dan HA
c. LiAlH4, then H2O
d. Ag2O, OH-
e.(C6H5)3P=CH2
Oxidation of aldehydes and ketons

O KMnO4 O H3O+ O
R CH R CO- R COH
OH-

O O
Ag(NH3)2+
R CH R CO- + Ag Tollens' Test
H2O (silver mirror)
O
O O
R-COOH
C6H5 C CH3 C6H5 O C CH3
acetophenone phenyl acetate
 Reduction of aldehydes and ketones
OH O O OH
HA, -H2O LiAlH4, H2O
CH3CHCHCH CH3 C CCH CH3 C CCH2
CH3 H CH H CH
3 3
an unsaturated an allylic alcohol
an aldol
aldehyde

H2/Ni H2, Pd-C

high
pressure
H2 OH
H2 O
H3C C CHCH2
H3C C CHCH
CH3
CH3
The acidity of the α hydrogen
O
 
R C C C
H H
hydrogen
are acidic
(pKa=19-20)

:B-
O -
H O .. O
C C C C C C + H-B

keto form enol form

 The aldol reaction
O 10% NaOH, H2O OH O
2 CH3CH CH3CHCH2CH
5oC
3-hydroxybutanal

• The aldol reaction is important in organic synthesis because it

gives us a method for linking two smaller molecules.

Exercise:
One industrial process for the synthesis of 1-butanol begins with
acetaldehyde. Show how this synthesis might be carried out.