3R3‘3\333 A 3:33333
`
`33333 3333 33333333 :33:3333333333
`
`ORGANIC
`
`CHEMISTR
`
`ADVANCED
`
`
`
`THIRD [50131033
`
`Part A: Structure and Mechanisms
`
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`Library of Congress Cataloging in Publication Data
`
`(Revised for 3rd ed.)
`Carey, Francis A., 1937-
`Advanced organic chemistry.
`Includes bibliographical references.
`Contents: pt. A. Structure and mechanisms-pt. B. Reactions and synthesis.
`. I. Title.
`1. Chemistry, Organic. I. Sundberg, Richard J., 1938-
`QD251.2.C36 1990
`547
`ISBN 0-306-43440-7 (Part A)
`ISBN 0-306-43447-4 (pbk.: Part A)
`ISBN 0-306-43456-3 (Part B)
`ISBN 0-306-43457-1 (pbk.: Part B)
`
`90-6851
`
`10 9 8
`
`© 1990, 1983, 1977 Plenum Press, New York
`A Division of Plenum Publishing Corporation
`233 Spring Street, New York, N.Y. 10013
`
`All rights reserved
`
`No part of this book may be reproduced, stored in a retrieval system, or transmitted
`in any form or by any means, electronic, mechanical, photocopying, microfilming,
`recording, or otherwise, without written permission from the Publisher
`
`Printed in the United States of America
`
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`

`

`r I
`
`I
`
`12
`
`Free-Radical Reactions
`
`12.1. Generation and Characterization of Free Radicals
`
`12.1.1. Background
`
`A free-radical reaction is a chemical process in which molecules having unpaired
`electrons are involved. The radical species could be a starting compound or a
`product, but in organic chemistry the most common cases are reactions that involve
`radicals as intermediates. Most of the reactions discussed to this point have been
`heterolytic processes involving polar intermediates and/ or transition states in which
`all electrons remained paired throughout the course of the reaction. In radical
`reactions, homolytic bond cleavages occur. The generalized reactions shown below
`illustrate the formation of alkyl, vinyl, and aryl free radicals by hypothetical
`homolytic processes.
`
`Ox-v+z --+ Ox-v· + z. --+ 0· + X=Y
`
`The idea that substituted carbon atoms with seven valence electrons could be
`involved in organic reactions took firm hold in the 1930s. Two experimental studies
`have special historical significance in the development of the concept of free-radical
`reactions. The work of Gomberg around 1900 provided evidence that when triphenyl-
`
`651
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`652
`
`CHAPTER 12
`FREE-RADICAL
`REACTIONS
`
`methyl chloride was treated with silver metal, the resulting solution contained Ph3C·
`in equilibrium with a less reactive molecule. It was originally thought that the more
`stable molecule was hexaphenylethane, but eventually this was shown not to be so.
`The dimeric product is actually a cyclohexadiene derivative. 1
`
`The dissociation constant is smalJ, only about 2 x 1 o-4 M at room temperature. The
`presence of the small amount of the radical at equilibrium was deduced from
`observation of reactions that could not be reasonably attributed to a normal hydro(cid:173)
`carbon.
`The second set of experiments was carried out in 1929 by Paneth. The decompo(cid:173)
`sition of tetramethyllead was carried out in such a way that the decomposition
`products were carried by a flow of inert gas over a film of lead metal. The lead was
`observed to disappear, with re-formation of tetramethyllead. The conclusion was
`reached that methyl radicals must exist long enough in the gas phase to be transported
`from the point of decomposition to the lead film.
`
`Since these early experiments, a great deal of additional information about the
`existence and properties of free-radical intermediates has been developed. In this
`chapter, we will discuss the structure of free radicals and some of the special
`properties associated with free radicals. We will also discuss some of the key chemical
`reactions in which free-radical intermediates are involved.
`
`12.1.2. Stable and Persistent Free Radicals
`
`Most organic free radicals have very short lifetimes, but various structural
`features enhance stability. Radicals without special stabilization rapidly dimerize
`or disproportionate. The usual disproportionation process involves transfer of a
`hydrogen from the carbon f3 to the radical site, leading to formation of an alkane
`and an alkene.
`
`Dimerization
`
`Disproportionation
`
`I
`I
`I
`2 -C-+ -C-C-
`I
`I
`I
`I
`I
`I
`I
`2 -C-C -+ -C-C-
`I
`I
`I
`I
`H
`H H
`
`"'
`
`/
`+ C=C
`/
`
`"'
`
`1. H. Lankamp, W. Th. Nauta, and C. MacLean, Tetrahedron Lett., 249 (1968); J. M. McBride,
`Tetrahedron 30, 2009 (1974); K. J. Skinner, H. S. Hochester, and J. M. McBride, J. Am. Chern. Soc.
`96, 4301 (1974).
`
`I I
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`

`

`653
`
`SECTION 12.1.
`GENERATION AND
`CHARACTERIZATION
`OF FREE RADICALS
`
`Radicals also rapidly abstract hydrogen or other atoms from many types of solvents,
`and most radicals are highly reactive toward oxygen.
`
`Hydrogen atom abstraction
`
`I
`I
`-C + H-Y- -C-H + Y·
`I
`I
`
`Addition to oxygen
`
`I
`-C-0-0·
`I
`
`A few free radicals are indefinitely stable. Entries 1, 4, and 6 in Scheme 12.1
`are examples. These molecules are just as stable under ordinary conditions of
`temperature and atmosphere as typical closed-shell molecules. Entry 2 is somewhat
`less stable to oxygen, although it can exist indefinitely in the absenc~ of oxygen.
`The structures shown in entries 1, 2, and 4 all permit extensive delocalizaticm {lf
`the unpaired electron into aromatic rings. These highly delocalized radicals show
`no tendency toward dimerization or disproportionation. Radicals that have long
`lifetimes and are resistant to dimerization or other routes for bimolecular self(cid:173)
`annihilation are called stable free radicals. The term inert free radical has been
`suggested for species such as entry 4, which is unreactive under ordinary conditions
`and is thermally stable even at 300°C. 2
`Entry 3 in Scheme 12.1 has only alkyl substituents and yet has a significant
`lifetimes in the absence of oxygen. The tris( t- butyl )methyl radical has an even longer
`lifetime, with a half-life of about 20 min at 25°C. 3 The steric hindrance provided by
`the t-butyl substituents greatly retards the rates of dimerization and disproportion(cid:173)
`ation of these radicals. They remain highly reactive toward oxygen, however. The
`term persistent radicals is used to describe these species, since their extended lifetimes
`have more to do with kinetic factors than with inherent stability. 4 Entry 5 is a
`sterically hindered perfluorinated radical, which is even more stable than similar
`alkyl radicals.
`There are only a few functional groups that contain an unpaired electron and
`yet are stable in a wide variety of structural environments. The best example is the
`nitroxide group, and there are numerous specific nitroxide radicals which have been
`prepared and characterized.
`
`R
`.. -
`'\...
`N-0:+--+
`/+ ..
`R
`
`R
`'\.. ....
`..
`N-0·
`/
`R
`
`Many of these compounds are very stable under normal conditions, and heterolytic
`reactions can be carried out on other functional groups in the molecule without
`destroying the nitroxide group. 5
`
`2. M. Ballester, Ace. Chern. Res. 18, 380 (1985).
`3. G. D. Mendenhall, D. Griller, D. Lindsay, T. T. Tidwell, and K. U. Ingold, J. Am. Chern. Soc. 96,
`2441 (1974).
`4. For a review of various types of persistent radicals, see D. Griller and K. U. Ingold, Ace. Chern.
`Res. 9, 13 (1976).
`5. For reviews of the preparation, reactions, and uses of nitroxide radicals, see J. F. W. Keana, Chern.
`Rev. 78, 37 (1978); L. J. Berliner (ed.), Spin-Labelling, Vol. 2, Academic Press, New York, 1979.
`
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`

`654
`
`CHAPTER 12
`FREE-RADICAL
`REACTIONS
`
`Scheme 12.1. Stability of Some Free Radicals
`
`Structure
`
`Conditions for stability
`
`Indefinitely stable as a solid, even in the presence of
`air.
`
`PHPh
`
`PhyPh
`Ph
`
`Crystalline substance is not rapidly attacked by
`oxygen, although solutions are air sensitive; the
`compound is stable to high temperature in the
`absence of oxygen.
`
`I
`
`Stable in dilute solution ( < 1 o-s M) below - 30°C in
`the absence of oxygen, t112 of 50 sec at 25°C.
`
`Cl
`
`Stable in solution for days, even in the presence of
`air. Indefinitely stable in solid state. Thermally
`stable up to 300°C.
`
`Cl
`
`Cl
`
`Cl
`
`Cl
`
`Cl
`
`Cl
`
`Stable to oxygen; thermally stable to 70°C.
`
`Stable to oxygen; stable to extended storage as a
`solid. Slowly decomposes in solution.
`
`Stable to oxygen even above 1 00°C.
`
`a. C. F. Koelsch, f. Am. Chern. Soc. 79, 4439 (1957).
`b. K. Ziegler and B. Schnell, Justus Liebigs Ann. Chern. 445, 266 ( 1925).
`c. G. D. Mendenhall, D. Griller, D. Lindsay, T. T. Tidwell, and K. U. Ingold, f. Am. Chern. Soc. 96, 2441 (1974).
`d. M. Ballester, J. Riera, J. Castaner, C. Badia, and J. M. Monso, f. Am. Chern. Soc. 93, 2215 (1971).
`e. K. V. Scherer, Jr., T. Ono, K. Yamanouchi, R. Fernandez, and P. Henderson, f. Am. Chern. Soc. 107, 718 (1985).
`f. G. M. Coppinger, f. Am. Chern. Soc. 79, 501 ( 1957); P. D. Bartlett and T. Funahashi, f. Am. Chern. Soc. 84, 2596 ( 1962).
`g. A. K. Hoffmann and A. T. Henderson, J. Am. Chern. Soc. 83, 4671 (1961).
`
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`

`

`Although the existence of the stable and persistent free radicals we have
`discussed is of significance in establishing that free radicals can have extended
`lifetimes, most free-radical reactions involve highly reactive intermediates that have
`relatively fleeting lifetimes and can only be studied at very low concentrations. The
`techniques for study of radicals under these conditions are the subject of the next
`section.
`
`655
`
`SECTION 12.1.
`GENERATION AND
`CHARACTERIZATION
`OF FREE RADICALS
`
`12.1.3. Direct Detection of Radical Intermediates
`
`The distinguishing characteristic of free radicals is the presence of an unpaired
`electron. Species with an unpaired electron are said to be paramagnetic. The most
`useful method for detecting and characterizing unstable radical intermediates is
`electron paramagnetic resonance (EPR) spectroscopy. Electron spin resonance (ESR)
`spectroscopy is synonymous. This method of spectroscopy detects the transition of
`an electron between the energy levels associated with the two possible orientations
`of electron spin in a magnetic field. An EPR spectrometer records the absorption
`of energy when an electron is excited from the lower to the higher state. The energy
`separation is very small on an absolute scale and corresponds to the energy of
`microwaves. EPR spectroscopy is a highly specific tool for detecting radical species·
`since only molecules with unpaired electrons give rise to EPR spectra. As with other
`spectroscopic methods, detailed analysis of the absorption spectrum can give rise
`to structural information. One feature that is determined is the g value, which
`specifies the separation of the two spin states as a function of the magnetic field
`strength of the spectrometer.
`
`where Jl-B is a constant, the Bohr magneton ( =9.274 x 10-21 erg/G), and H is the
`magnetic field in gauss. The measured value of g is a characteristic of the particular
`type of radical, just as the line positions in IR and NMR spectra are characteristic
`of the absorbing species.
`A second type of structural information can be deduced from the hyperfine
`splitting in EPR spectra. The origin of this line splitting is closely related to the
`factors that cause spin-spin splitting in proton NMR spectra. Certain nuclei have
`a magnetic moment. Those which are of particular interest in organic chemistry
`include 1H, 13C, 14N, 19F, and 31 P. Interaction of the unpaired electron with one or
`more of these nuclei splits the signal arising from the electron. The number of lines
`is given by the equation
`
`number of lines= 2ni + 1
`
`where I is the nuclear spin quantum number, and n is the number of equivalent
`interacting nuclei. For 1H, 13C, 19F and 31 P, I=~- Thus, a single hydrogen splits a
`signal into a doublet. Interaction with three equivalent hydrogens, as in a methyl
`group, gives rise to splitting that produces four lines. This splitting is illustrated in
`Fig. 12.1. Nitrogen e4N), with I = 1, splits each energy level into three lines. Neither
`
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`
`

`

`r .. I,
`
`t
`~
`
`I '
`.I
`
`l
`
`I
`
`:I
`
`' I
`I I
`
`. I
`
`I
`
`''
`I
`
`' i
`
`656
`
`CHAPTER 12
`FREE-RADICAL
`REACTIONS
`
`No interacting
`hydrogen nucleus(cid:173)
`one absorption
`line
`
`One interacting
`hydrogen nucleus(cid:173)
`two absorption
`lines
`
`Two equivalent
`interacting
`hydrogen nuclei(cid:173)
`three absorption
`lines
`
`Fig. 12.1. Hyperfine splitting in EPR spectra.
`
`12C nor 160 has a nuclear magnetic moment, and just as they cause no splitting in
`NMR spectra, they have no effect on the multiplicity in EPR spectra.
`A great deal of structural information can be obtained by analysis of the
`hyperfine splitting pattern of a free radical. If we limit our discussion for the moment
`to radicals without heteroatoms, the number of lines indicates t.re number of
`interacting hydrogens, and the magnitude of the splitting, given by the hyperfine
`splitting constant a, is a measure of the unpaired electron density in the hydrogen
`1 s orbital. For planar systems in which the unpaired electron resides in a 7T-orbital
`system, the relationship between electron spin density and the splitting constant is
`given by the McConnell equation6
`
`:
`
`a= pQ
`
`where a is the hyperfine coupling constant for a proton, Q is a proportionality
`constant (about 23 G), and pis the spin density on the carbon to which the hydrogen
`is attached. For example, taking Q = 23.0 G, the hyperfine splitting in the benzene
`radical anion may be readily calculated by taking p = ~' since the one unpaired
`electron must be distributed equally among the six carbon atoms. The calculated
`value of a = 3.83 is in good agreement with the observed value. The spectrum (Fig.
`12.2a) consists of seven lines separated by a coupling constant of 3.75 G.
`The EPR spectrum of the ethyl radical presented in Fig. 12.2b is readily
`interpreted, and the results are of interest with respect to the distribution of unpaired
`electron density in the molecule. The 12-line spectrum is a triplet of quartets resulting
`from unequal coupling of the electron spin to the a and {3 protons. The two coupling
`constants are aa = 22.38 G and a13 = 26.87 G and imply extensive delocalization of
`spin density through the a bonds.
`EPR spectra have been widely used in the study of reactions to detect free-radical
`intermediates. An interesting example involves the cyclopropylmethyl radical. Much
`
`6. H. M. McConnell, 1. Chern. Phys. 24, 764 (1956).
`
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`
`

`

`(a)
`
`(b)
`
`657
`
`SECTION 12.1.
`GENERATION AND
`CHARACTERIZATION
`OF FREE RADICALS
`
`5 Gauss
`
`26.9G
`
`22.4G
`
`I
`
`I
`
`I
`
`I
`
`I
`
`Fig. 12.2. Some EPR spectra of small organic free radicals: (a) Spectrum of the benzene radical anion.
`[From J. R. Bolton, Mol. Phys. 6, 219 (1963). Reproduced by permission of Taylor and Francis, Ltd.]
`(b) Spectrum of the ethyl radical. [From R. W. Fessenden and R. H. Schuler, J. Chern. Phys. 33, 935
`(1960); 39, 2147 (1963); Reproduced by permission of the American Institute of Physics.]
`
`chemical experience has indicated that this radical is unstable, giving rise to 3-butenyl
`radical rapidly after being generated.
`
`The radical was generated by photolytic decomposition of di-t-butyl peroxide in
`methylcyclopropane, a process that leads to selective abstraction of a methyl hydro(cid:173)
`gen from methylcyclopropane.
`
`hv
`(CH 3hCOOC(CH 3h ----+ 2 (CHJhC-0·
`(CH 3hC-O· + [>--- CH 3 --+ [>--- CH 2• + (CH 3 ) 3COH
`
`Below -140°C, the EPR spectrum observed was that of the cyclopropylmethyl
`radical. If the photolysis was done above -140°C, however, the spectrum of a second
`species was seen, and above -100°C, this was the only spectrum observed. This
`spectrum could be shown to be that of the 3-butenyl radical. 7 This study also
`established that the 3-butenyl radical did not revert to the cyclopropylmethyl radical
`on being cooled back to -140°C. The conclusion is that the ring opening of the
`
`7. J. K. Kochi, P. J. Krustic, and D. R. Eaton, J. Am. Chern. Soc. 91, 1877 (1969).
`
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`

`

`658
`
`CHAPTER 12
`FREE-RADICAL
`REACTIONS
`
`cyclopropyl radical is a very facile process, so that the lifetime of the cyclopropyl
`radical above -1 oooc is very short. The reversal of. the ring opening can be detected
`by isotopic labeling experiments, which reveal the occurrence of deuterium
`migration:
`
`' I·
`
`! •
`•'
`
`The rates of both the ring opening (k = 2 x 108 s- 1 at 25°C) and the ring closure
`(k = 3 x 103 s- 1
`) have been measured andshow that only a very small amount of
`the cyclopropylmethyl radical is present at equilibrium, in agreement with the EPR
`results. 8
`It is important to emphasize that direct studies such as those carried out on
`the cyclopropylmethyl radical can be done with low steady-state concentrations of
`the radical. In the case of the study of the cyclopropylmethyl radical, removal of
`the source of irradiation would lead to rapid disappearance of the EPR spectrum,
`because the radicals would react rapidly and not be replaced by continuing radical
`formation. Under many conditions, the steady-state concentration of a radical
`intermediate may be too low to permit direct detection. Failure to observe an EPR
`signal therefore cannot be taken as conclusive evidence against a radical inter(cid:173)
`mediate.
`A technique called spin trapping can sometimes be used to study radicals in
`this circumstance. A diamagnetic molecule that has the property of reacting rapidly
`with radicals to give a stable paramagnetic species is introduced into the reaction
`system being studied. As radical intermediates are generated, they are trapped by
`the reactive ·molecule to give more stable, detectable radicals. The most useful spin
`traps are nitroso compounds. They rapidly react with radicals to give stable nitro xi de
`radicals. 9 Analysis of the EPR spectrum of the nitroxide radical product can often
`provide information about the structure of the original radical.
`
`R· + R'N=O---. N-0
`R'/
`
`R " .
`
`Another technique that is highly specific for radical processes is known as
`CIDNP, an abbreviation for chemically induced dynamic nuclear polarization. 10 The
`instrumentation required for such studied is a normal NMR spectrometer. CIDNP
`is observed as a strong perturbation of the intensity of NMR signals for products
`formed in certain types of free-radical reactions. The variation in intensity results
`
`8. A. Eiffio, D. Griller, K. U. Ingold, A. L. J. Beckwith, and A. K. Serelis, 1. Am. Chern. Soc. 102, 1734
`(1980); L. Mathew and J. Warkentin, 1. Am. Chern. Soc. 108, 7981 (1986).
`9. E. G. Janzen, Ace. Chern. Res. 4, 31 (1971); E. G. Janzen, in Free Radicals in Biology, W. A. Pryor
`(ed.), Vol. 4, Academic Press, New York, 1980, pp. 115-154.
`10. H. R. Ward, Ace. Chern. Res. 5, 18 (1972); R. G. Lawler, Ace. Chern. Res. 5, 25 (1972).
`
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`

`

`BPO 0.05 Min cyclohexanone
`100 MHz ll0°C
`
`659
`
`SECTION 12.1.
`GENERATION AND
`CHARACTERIZATION
`OF FREE RADICALS
`
`1=12min
`
`1 = 8 min
`
`1 =4 min
`
`1=0
`
`Fig. 12.3. NMR spectra recorded during thermal decompo(cid:173)
`sition of dibenzoyl peroxide. Singlet at high field is due to
`benzene; other signals are due to dibenzoyl peroxide. [From
`H. Fischer and J. Bargon, Ace. Chern. Res. 2, 110 (1969).
`Reproduced by permission of the American Chemical
`Society.]
`
`when the normal population of nuclear spin states dictated by the Boltzmann
`distribution is disturbed by the presence of an unpaired electron. The magnetic
`moment associated with an electron causes a redistribution of the nuclear spin states.
`Individual nuclei can become overpopulated in either the lower or upper spin state.
`If the lower state is overpopulated, an enhanced absorption signal is observed. If
`the upper state is overpopulated, an emission signal is observed. The CIDNP method
`is not as general as EPR spectroscopy because not all free-radical reactions can be
`expected to exhibit the phenomenon. II
`Figure 12.3 shows the observation of CIDNP during the decomposition of
`dibenzoyl peroxide in cyclohexanone:
`
`0
`0
`II
`II
`PhCOOCPh ~ 2 Ph· + 2 C02
`
`The emtsswn signal corresponding to benzene confirms that it is formed by a
`free-radical process. As in steady-state EPR experiments, the enhanced emission
`and absorption are observed only as long as the reaction is proceeding. When the
`
`11. For a discussion of the theory of CIDNP and the conditions under which spin polarization occurs,
`see G. L. Closs, Adv. Magn. Reson. 1, 157 (1974); R. Kaptein, Adv. Free Radical Chern. 5, 318 (1975);
`G. L. Closs, R. J. Miller, and 0. D. Redwine, Ace. Chern. Res. 18, 196 (1985).
`
`I
`
`L
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`660
`
`CHAPTER 12
`FREE-RADICAL
`REACTIONS
`
`reaction is complete or is stopped in some way, the signals rapidly return to their
`normal intensity, because the equilibrium population of the two spin states is rapidly
`reached.
`One aspect of both EPR and CIDNP studies that should be kept in mind is
`that either technique is capable of detecting very small amounts of radical intermedi(cid:173)
`ates. This aspect makes both techniques quite sensitive but can also present a pitfall.
`The most prominant features of either EPR or CIDNP spectra may actually be due
`to radicals that account for only minor products of the total reaction process. An
`example of this was found in a CIDNP study of the decomposition oftrichloroacetyl
`peroxide in alkenes:
`
`In addition to the emission signals of CHCh and Cl3CCH2C(CH3)=CH2, which
`are the major products, a strong emission signal for Cl3CCHCh was identified.
`However, this compound is a very minor product of the reaction, and when the
`signals have returned to their normal intensity, Cl3CCHC12 is present in such a
`small amount that it cannot be detected.12
`
`12.1.4. Sources of Free Radicals
`
`There are several reactions that are quite commonly used as sources of free
`radicals, both for the study of radical structure and reactivity and also in synthetic
`processes. Some of the most general methods are outlined here. Examples of many
`of these will be encountered again when specific reactions are discussed. For the
`most part, we will defer discussion of the reactions of the radicals until then.
`Peroxides are a common source of radical intermediates. An advantage of the
`generation of radicals from peroxides is that reaction generally occurs at relatively
`low temperature. The oxygen-oxygen bond in peroxides is weak ( -30 kcal/mol),
`and activation energies for radical formation are low. Diacyl peroxides are sources
`of alkyl radicals because the carboxyl radicals that are initially formed lose C02
`very rapidly. 13 In the case of aroyl peroxides, products may be derived from the
`carboxyl radical or the radical formed by decarboxylation. 14
`
`12. H. Y. Loken, R. G. Lawler, and H. R. Ward, J. Org. Chern. 38, 106 (1973).
`13. J. C. Martin, J. W. Taylor, and E. H. Drew, J. Am. Chern. Soc. 89, 129 (1967); F. D. Greene, H. P.
`Stein, C.-C. Chu, and F. M. Vane, J. Am. Chern. Soc. 86, 2080 (1964).
`14. D. F. DeTar, R. A. J. Long, J. Rendleman, J. Bradley, and P. Duncan,]. Am. Chern. Soc. 89,4051 (1967).
`
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`
`

`

`661
`
`SECTION 12.1.
`GENERATION AND
`CHARACTERIZATION
`OF FREE RADICALS
`
`0
`0
`0
`II
`II
`II
`PhCOOCPh SO--IO<fC 2 PhCO· ------. 2 Ph· + 2 C02
`
`Alkyl hydroperoxides give alkoxy radicals and the hydroxyl radical. t- Butyl hydro(cid:173)
`peroxide is often used as a radical source. Detailed studies have been reported on
`the mechanism of the decomposition, which is a somewhat more complicated process
`than simple unimolecular decomposition. ~ 5 Dialkyl peroxides decompose to give
`two alkoxy radicals. 16
`
`Peroxyesters are also sources of radicals. The acyloxy portion normally loses carbon
`dioxide, so peroxyesters yield an alkyl (or aryl) and an alkoxy radical. 17
`
`The decomposition of peroxides, which occurs thermally in the examples cited
`above, can also be readily accomplished by photochemical excitation. The alkyl
`hydroperoxides are also sometimes used in conjunction with a transition metal ion.
`Under these conditions, an alkoxy radical is produced, but the hydroxyl portion
`appears as hydroxide ion as a result of one-electron reduction by the metal ion. 18
`
`The thermal decompositions described above are unimolecular reactions that
`should exhibit first-order kinetics. Under many conditions, peroxides decompose
`at rates faster than expected for unimolecular thermal decomposition, and with
`more complicated kinetics. This behavior is known as induced decomposition and
`occurs when part of the peroxide decomposition is the result of bimolecular reactions
`with radicals present in solution, as illustrated specifically for diethyl peroxide:
`
`X· + CH3CH 200CH 2CH3 --+ CH3(::HOOCH 2CH3 + H-X
`CH3(::HOOCH 2CH 3 --+ CH3CH=O + ·OCH2CH3
`
`The amount of induced decomposition that occurs depends on the concentration
`and reactivity of the radical intermediates and the susceptibility of the substrate to
`radical attack. The racial X· may be formed from the peroxide, but it can also be
`derived from subsequent reactions with the solvent. For this reason, both the structure
`
`15. R. Hiatt, T. Mill, and F. R. Mayo, J. Org. Chern. 33, 1416 (1968), and accompanying papers.
`16. W. A. Pryor, D. M. Huston, T. R. Fiske, T. L. Pickering, and E. Ciuffarin, J. Am. Chern. Soc. 86,
`4237 (1964).
`17. P. D. Bartlett and R. R. Hiatt, J. Am. Chern. Soc. 80, 1398 (1958).
`18. W. H. Richardson, J. Am. Chern. Soc. 87, 247 (1965).
`
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`

`

`662
`
`CHAPTER 12
`FREE-RADICAL
`REACTIONS
`
`of the peroxide and the nature of the reaction medium are important in determining
`the extent of induced decomposition relative to unimolecular homolysis.
`Another quite general source of free radicals is the decomposition of azo
`compounds. The products are molecular nitrogen and the radicals derived from the
`substituent groups.
`
`R-N=N-R' -
`
`~or
`
`hv
`
`R· + N=N + ·R'
`
`Both symmetrical and unsymmetrical azo compounds can be made so a single radical
`or two different ones may be generated. The energy for the decomposition can be
`either thermal or photochemical. 19 In the thermal decomposition, it has been estab(cid:173)
`lished that the temperature at which decomposition occurs depends on the nature
`of the substituent groups. Azomethane does not decompose to methyl radicals and
`nitrogen until temperatures above 400°C are reached. Azo compounds that generate
`relatively stable radicals decompose at much lower temperatures. Azo compounds
`derived from allyl groups decompose somewhat above 100°C, for example:
`
`Unsymmetrical azo compounds must be used to generate phenyl radicals because
`azobenzene is very stable thermally. Phenylazotriphenylmethane decomposes readily
`because of the stability of the triphenylmethyl radical.
`
`PhN=NC(Phh -
`
`6o·c
`
`Ph· + Ph3C· + N2
`
`Ref. 21
`
`Many azo compounds also generate radicals when photolyzed. This can occur
`by a thermal decomposition of the cis azo compounds that are formed in the
`photochemical step. 22 The cis isomers are thermally much more labile than the trans
`isomers.
`
`/
`N=N
`
`R
`
`-
`
`/
`R
`
`/
`R
`
`N=N
`
`"'
`
`R
`
`- R· N 2 ·R
`
`N-Nitrosoanilides are an alternative source of aryl radicals. There is a close
`mechanistic relationship between this route and the decomposition of azo com(cid:173)
`pounds. TheN -nitrosoanilides rearrange to an intermediate with a nitrogen-nitrogen
`double bond. This intermediate then decomposes to generate aryl radicals. 23
`
`19. P. S. Engel, Chern. Rev. 80, 99 (1980).
`20. K. Takagi and R. J. Crawford, J. Am. Chern. Soc. 93, 5910 (1971).
`21. R. F. Bridger and G. A. Russell, 1. Am. Chern. Soc. 85, 3754 (1963).
`22. M. Schmittel and C. Riichardt, 1. Am. Chern. Soc. 109, 2750 (1987).
`23. C. Riichardt and B. Freudenberg, Tetrahedron Lett., 3623 (1964); J. I. G. Cadogan, Ace. Chern. Res.
`4, 186 (1971).
`
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`
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`

`r I
`
`A technique that is a convenient source of radicals for study by EPR involves
`photolysis of a mixture of di-t-butyl peroxide, triethylsilane, and the alkyl bromide
`corresponding to the radical to be studied. 24 Photolysis of the peroxide gives t-butoxy
`radicals, which selectively abstract hydrogen from the silane. This reactive silicon
`radical in turn abstracts bromine, generating the alkyl radical at a steady-state
`concentration suitable for EPR study.
`
`663
`
`SECTION 12.1.
`GENERATION AND
`CHARACTERIZATION
`OF FREE RADICALS
`
`(CH3hCOOC(CH3h ~ 2 (CH3hCO·
`(CH3hCO· + (C2HshSiH ---+ (CH3hCOH + (C2H5hSi·
`(C2HshSi• + RBr ---+ (C2H5hSiBr + R·
`
`The acyl derivatives of N-hyroxypyridine-2-thione are a synthetically versatile
`source of free radicals. 25 These compounds are readily prepared from reactive
`acylating agents, such as acid chlorides, and a salt of the N -hydroxypyridine-2-
`thione.
`
`~
`
`RCCI + -0-N
`
`/;
`
`p
`
`~ p
`
`---+ RC-0-N
`
`/;
`
`s
`
`s
`
`Radicals react at the sulfur, and decomposition generating an acyloxy radical ensues.
`The acyloxy radical undergoes decarboxylation. Usually, the radical then gives
`product and another radical, which can continue a chain reaction. The process can
`be illustrated by the reactions with tri-n-butylstannane and bromotrichloromethane.
`
`(a) Reductive decarboxylation by reaction with tri-n-butylstannane
`
`~p RC-0-N
`s
`
`/;
`
`0
`/,-'
`R-C :·
`
`"'-0
`
`-+ R· + C02
`
`0
`j/
`R-c:· +
`\'-.
`0
`
`Ref. 26
`
`(b) Conversion of aromatic carboxylic acid to aryl bromide by reaction with bromotrichloromethane
`
`;,--
`
`~p
`
`ArC-O-N
`
`/;
`
`s
`
`0
`;,-·
`ArC:·
`\-,
`0
`
`0
`+ ·CCI3 ---+ArC:· +
`\-,
`0
`
`No~
`
`Cl3CS
`
`Ref. 27
`
`Ar· + BrCCl3 -+ Ar- Br + ·CCI3
`
`24. A. Hudson and R. A. Jackson, J. Chern. Soc., Chern. Commun., 1323 (1969); D. J. Edge and J. K.
`Kochi, J. Am. Chern. Soc. 94, 7695 (1972).
`25. D. H. R. Barton, D. Crich, and W. B. Motherwell, Tetrahedron 41, 3901 (1985).
`26. D. H. R. Barton, D. Crich, and W. B. Motherwell, J. Chern. Soc., Chern. Commun., 939 (1983).
`27. D. H. R. Barton, B. Lacher, and S. Z. Zard, Tetrahedron Lett. 26, 5939 (1985).
`
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`

`664
`
`CHAPTER 12
`FREE-RADICAL
`REACTIONS
`
`12.1.5. Structural and Stereochemical Properties of Radical Intermediates
`
`EPR studies and other physical methods have provided the basis for some
`insight into the detailed geometry of radical species. 28 Deductions about structure
`can also be drawn from the study of the stereochemistry of reactions involving
`radical intermediates. Several structural possibilities must be considered. If dis(cid:173)
`cussion is limited to alkyl radicals, the possibilities include a rigid pyramidal
`structure, rapidly inverting pyramidal structures, or a planar structure.
`
`rigid pyramidal
`
`flexible pyramidal
`
`planar
`
`Precise description of the pyramidal structures would also require that the bond
`angles be specified. The EPR spectrum of the methyl radical leads to the conclusion
`that its structure could be either planar or a very shallow pyramid. 29 TheIR spectrum
`of methyl radical has been recorded at very low temperatures in frozen argon.30
`The IR spectrum puts a maximum of -5° on the deviation from planarity.
`The t-butyl radical has been studied extensively. While experimental results
`have been interpreted in terms of both planar and slightly pyramidal structures,
`theoretical calculations favor a pyramidal structure. 31 It appears that simple alkyl
`radicals are generally pyramidal, although the barrier to inversion is very small. Ab
`initio molecular orbital calculations suggest that two factors are of principal import(cid:173)
`ance in favoring a pyramidal structure. One is a torsional effect in which the radical
`center tends to adopt a staggered conformation of the radical substituents. There
`is also a hyperconjugative interaction between the half-filled orbital and the hydrogen
`that is aligned with it. This hyperconjugation is stronger in the conformation in
`which the pyramidalization is such as to minimize eclipsing. 32 The theoretical results
`also indicate that the barrier to inversion is no more than 1-2 kcal/mol, so rapid
`inversion will occur.
`
`planar
`
`preferred
`pyramidalization
`
`C2
`H
`H
`\
`HII\11\IC - - c \\IIIII
`(J 'H
`I
`H
`
`less stable
`pyramidalization
`
`28. For a review, see J. K. Kochi, Adv. Free Radicals Chern. 5, 189 (1975).
`29. M. Karplus and G. K. Fraenkel, J. Chern. Phys. 35, 1312 (1961).
`30. L. Andrews and G. C. Pimentel, J. Chern. Phys. 47, 3637 (1967).
`31. L. Bonazolla, N. Leroy, and