Free Radicals
Definition: Any chemical species with
one or more unpaired electrons
Examples of radical species
O O
Na NO & NO2 O2 R Ar RO ArO R C R C O ROO
(Ar) (Ar) (Ar)
any atom with odd elec tron diradic al
unpaired elec trons molecules molecule
Nature of Free Radicals
Geometry
Example I:
H Br CH3
Br 2 Br 2
C2 H5 C CH2 Cl C2 H5 C CH2 Cl C2 H5 C CH2 Cl + C2 H5 C CH2 Cl
h
CH3 CH3 CH3 Br
(S )-enantiomer racemic mixture
Example II: CH3
CH3 O CH3 CH3 n- C3 H7 C H
RO CO
n-C3 H7 C C n-C3 H7 C C O n- C3 H7 C C2 H5
RCHO +
C2 H5 H C2 H5 C2 H5
CH3
(S )-enantiomer
H C n-C3 H7
C2 H5
racemic mixture
Rationalization to account for
racemization in radical reactions
Explanation I :
Participation by a planar radical s pecies capable of undergoing "top" or "bottom" attac k
w ith equal likelihood
Z C X
Y
Explanation I I:
Participation by a rapidly equilibrating pair of enantiomeric pyramidal radical s pecies
that w ould lead to racemic products
X X
C C Z
Z
Y Y
Evidence in favor of the “pyramidal” radical
Cons ider the follow ing reaction:
CCl4
-CO R R Cl
RO
R C H R C
O O
CCl4
R C Cl
O
Object: Change R- from a group that can easily adopt a planar geometry to one
that cannot. If planar geometry is favored for free radicals, that fact s hould
RCOCl ratio.
be reflected in a low RCl:
Observations: R-group RCl:RCOCl ratio Stability of R
(CH 3 )3 C 12.3:1.0 1.0 (ref.)
15.2:1.0 1.2
30.5:1.0 2.5
is
Conc lus ion: The formation of pyramidal radicals not accompanied by adverse
energy considerations. In fact, the oppos ite is true.
More evidence in favor of the “pyramidal” radical?
Cons ider the following obs ervation:
CH3 O CH3
R *CH C O _ R *CH O
CO2
Both stereogenic centers remain intact
R *CH C O R *CH C
CH3 O CH3 O
Plaus ible explanation
Los s of carbon dioxide leads to a pyramidal alkyl radical that rapidly recombines
w ith incipient oxyradical before invers ion of c onfiguration c an occur (an example
of the "cage effec t").
CH3 CH3 CH3
*C *C *C
H O H H
C R O
R R
O _ CO2 O H C
H R
O C C O
H R *
C C* O
R CH3
C* O
CH3
CH3
Alternate explanation
CH3
*C O CH3
H C *C
R H
O
O _ CO2 R a conc erted non-radical proc ess
O H
O R C
H C O
R C*
C* CH3
CH3
Stability of Free Radicals
Observation: Measurement of Bond Dis sociation Energies
R = CH3 CH H
3 RCH2 H R2 CH H R3 C H
435 kj/mole 406 kj/mole 395 kj/mole 380 kj/mole
Conclusion: The orde r of radical stability is tertiary>secondary>primary>meth yl
Observation:
CH3 CH2
_H
H = 355 kj/mole
_H
CH2 CH CH3 CH2 CH CH2 H = 355 kj/mole
ion
Rationale: Abstract of either benzylic or allylic hydrogen atoms to produce benzyl or allylic
radicals is a low er energy proces s than that for corresponding saturated s ystems due
to the pos sibility of-delocalization of the odd electron in the former sys tems .
Observation: CH3
C6 H5 CH2 Increasing stability, decreasing reactivity,
(C6 H5 )2 CH greater selectivity
(C6 H5 )3 C
-delocalization, the greater the s tability of the
Rationale: The greater the poss ibility for
radic al species.
Stabilities of Substituted Benzyl Radicals
Observation:
CH 3 CH 2
+ RO + ROH = -0.38
Z Z
Relative stabilitie s:
Z= CH3 OCH
3 H Br CN 2NO
1.9 1.2 1.0 1.8 3.7 4.0
Conclusions :
1. Based on the measured rho value for benzyl radical formation, the reaction is
relatively insensitive to substituent electronic effec ts.
2. Both electron donating and electron w ithdraw ing s ubstituents stabilize the
benzyl radical produced.
Rationale:
H C H H H H C H H H H C H H H
C C C
OCH3 OCH3 CH 3 H CH2 N N
O O O O
Substituted Benzyl radicals
Steric effects
Cons ider the following dissociation reaction:
R R R
CH2 CH2 2 CH2
R R R
Observations : As the s ize of R increas es (methyl, ethyl, isopropyl, t-butyl),
a) the magnitude of the equilibrium constant increases
b) the reactivity of the resulting benzyl radical dec reases
c) the benzyl radical w ith the largest ortho-substituents forms fas tes t (at a fixed temp.)
d) the benzyl radical w ith the largest ortho-substituents is formed under the mildes t
reaction conditions (under variable temp. conditions)
Rationale:
As R increas es in s ize, the reactant is destabilized.Production of the substituted benzyl
radical s erves to relieve s teric s train.
Once formed, the benzyl radical w ith the largest ortho-s ubstituents w ill experience the
greatest s teric hindrance to recombination or to other reactions at the radical site.
Generation of Free Radicals
Thermolysis
Photolysis
a) C6 H 5 C O O C C6 H 5 o 2 C6 H 5 C O 2 C6 H 5 + 2 CO2
80o - 100 C
O O O
b) (CH 3 )2 C N N C(CH 3 )2 o 2 (CH 3 )2 C + N 2
80o - 100 C
CN CN CN
c) (CH 3 )3 C O O C(CH 3 )3 2 (CH 3 )3 C O
140o- 150oC
d) (R C O )4 Pb o o
(R C O )2 Pb + 2 R C O
140 - 150 C
O O O
e) RONO2 o RO + NO2
200 C
f) 2 RMgX + CoCl2 R2 Co o 2 R + Co
35 C
a) CH 3 C C CH 3 2 CH 3 C
h
O O O
b) CH 3 C CH 2 Cl CH 3 C CH 2 + Cl
h
O O
Generation of Free Radicals
Redox reactions
-
a) RCOO
- -e RCOO R + CO2 (Kolbe electrolysis)
anode
+3 -
b) Ti+2 + H 2 O2 Ti + OH + OH
c) C6 H 5 CH 2 Cl C6 H 5 CH2 + NaCl
Na vapor
+ +3
d) (C6 H 5 )3 COH +
(C6 H 5 )3 C +2
(C6 H 5 )3 C + V
H V
- o
e) (C6 H 5 )3 CH (C6 H5 )3 C (C6 H 5 )3 C + Ag
- +
NH 2 Ag
o
Na
f) R C OEt RCH2 OH
o EtOH H
Na O
EtOH R C H
R C OEt
O
O
EtOH o
Na
H H
R C OEt R C H
o
O Na H O
o
EtOH
R C OEt R C H Na R C H
O O O
Characteristics of Radical
Reactions
Most radical reactions occur readily in the gas phase
Radical reactions generally are not influenced by solvent
polarity
Radical reactions generally are not influenced by acid or
base catalysis
Unlike cations or anions, radicals generally are not
influenced by electron-donating or electron-withdrawing
substituents
Radical reactions are often preceded by an induction
period during which time they are subject to inhibition
Radical reactions are frequently chain reactions
Radical reactions generally are not accompanied by
skeletal rearrangements
A Typical Radical Reaction
Overall reaction
H3 C CH3
C
O
h low temp.
CH4 + CO+ CH6 + CH C O + CH3 C C CH3 + CH3 C H +
2 2
O O O
CH3 C CH2 C CH3 + CH3 C CH2 CH2 C CH3 + CH3 C CH2 CH3
O O O O O
A Typical Radical Reaction: Mechanism
H3 C C CH3 CH3 + H3 C C (homolytic decomposition)
h
O O
CH3 + H3 C C H3 C C CH3 (recombination)
O O
CH3 + CH3 C2 H 6 (dimerization)
H3 C C + H3 C C H 3 C C C CH3 (dimerization)
O O O O
CH3 + H3 C C CH4 + H2 C C O (abstraction/trans fer)
O
CH3 + H 3 C C CH3 CH4 + H3 C C CH2 (abstraction/trans fer)
O O
H3 C C CH2 + H3 C C CH2 H3 C C CH2 CH2 C CH3 (dimerization)
O O O O
H3 C C CH2 + CH3 H3 C C CH2 CH3 (recombination)
O O
H3 C C + H3 C C H3 C C H + H2 C C O (dis proportionation)
O O O
H3 C C CH2 + H3 C C H3 C C CH2 C CH3 (recombination)
O O O O
H3 C C CH2 + H 3 C C H3 C C CH3 + H2 C C O (abstraction)
O O O
H3 C C CH3 + CO (decomposition)
O