Lecture 21 Free-Radical Reactions I: 9.1 Principles
Lecture 21 Free-Radical Reactions I: 9.1 Principles
Lecture 21 Free-Radical Reactions I: 9.1 Principles
R
R
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For example, the synthesis of aldosterone 21-acetate from corticosterone acetate has been
demonstrated.
Me
Me
OAc
O
HO
O
NOCl
light
Me
OAc
O
HO
O
HON
HNO
2
Me
OAc
O
HO
O
O
Me
OAc
O
O
O
OH
Mechanism
Photolysis of organic nitrites gives oxy-radical which abstracts hydrogen from a -CH
bond. The resulting alkyl radical reacts with nitric oxide liberated during the photolysis to
yield a nitroso-derivative which tautomerizes to oxime that can be hydrolyzed to carbonyl
group.
OH
H
NOCl
O
H NO
light
-NO
.
O
H
.
OH
R .
R
R
R
NO
.
OH
R N
O
OH
R N
OH
OH
R N
H
OH
H
OH
R N
OH
H
H
2
O OH
R N
OH
H
H
2
O
OH
R N
OH
H
H-O H
-NH
2
OH
OH
R OH
-H
OH
R O
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9.4.2 Barton Decarboxylation
Thiohydroxamate ester (commonly referred to as a Barton ester) with tributytin hydride
or t-butylmercaptan in the presence of a radical initiator undergoes decarboxylation to
give alkanes. The driving for this reaction is the S-Sn bond formation.
N
O
S
Na
X R
O
+
AIBN, Bu
3
SnH
heat
R-H
Mechanism
Instead of direct reaction of oxygen with the acid chloride, the following occurs:
N
O
S
Na
Cl R
O
..
N
O
S R
X O -X
N
O
S R
O
N
O
S
R
O
N
O
S
R
O
Decarboxylation
N
NC
N
CN
heat or
light
CN
2
.
+ N
2
CN
.
H
CN
+
.
Decarboyxlation Step
N S
O
O
R
.
Sn(n-Bu)
3
N
S
Sn(n-Bu)
3
+
R O
O
.
CO
2
+
R
.
H-Sn(n-Bu)
3
R-H +
.
Sn(n-Bu)
3
H-Sn(n-Bu)
3
Sn(n-Bu)
3
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Examples:
N S
O
NHBoc
O
R
t-BuSH
light
H
N
Boc
R
78%
D. H. R. Barton, Y. Herve, P. Potier, J. Thierry, Tetrahedron 1988, 44, 5479.
Me
EtO
2
C
Cl
O
N S
OH
+
Me
CO
2
Et
S
N
Barton
E. Bacque, F. Pautrat, S. Z. Zand, Org. Lett. 2003, 5, 325.
9.5 Formation of Carbon-Oxygen Bonds
In a wide variety of environments, C-H bond undergoes oxidation on standing in air to
give hydroperoxides. For example, ethers proceed autoxidation to give -hydroperoxide.
O
O
2
O
O
2
H
Since hydroperoxides are known to explode on heating, it is essential to remove them
(e.g. by reduction with aqueous iron(II) sulfate) from ethers before their use as solvents
for the reactions.
Isobutane can be transformed into t-butyl hydroperoxide in the presence of initiator.
Me H
Me
Me
O
2
Me OOH
Me
Me
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Alkenes are more reactive compared to alkanes due to greater stability of allyl radicals
compared to alkyl radicals.
O
2
O
2
H
9.6 Formation of Bonds to Other Elements
Elements such as sulfur, phosphorus and silicon can proceed reactions with alkenes and
alkynes via radical catalyzed process. The characteristics of these reactions are similar to
those described above. For example,
Cl
3
SiH +
SiCl
3
PH
3 + 3
P
3
SH +
S
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Problems:
H
Br
1.
Bu
3
SnH
AIBN
2.
Br
MeO
2
C
Bu
3
SnH
AIBN
5.
O
Br Bu
3
SnH
AIBN
3.
O
SePh
O
Bu
3
SnH
AIBN
4.
O
Br
SnBu
3
AIBN
What would be the products for the following reactions?
6.
O
7.
O
Mg
Ti
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Text Books:
R.O.C. Norman and C. M. Coxon, Principles of Organic Synthesis, CRC Press, New
York, 2009.
J. March, Advanced Organic Chemistry, 4
th
ed, Wiley Interscience, Yew York, 1992.