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PETER F. NELSON
Royal Melbourne Technical College,
Victoria, Australia
ALTHOUGA electrophilic and nucleophilic aromatic the reaction would not be susceptible to directive in-
substitution have been treated extensively in recent fluences due t o substituents. If this were so, the ratios
texts and review articles ( I ) , homolytic substitution has of isomers produced would he 40 per cent ortho, 40
received relatively little attention. An attempt is made per cent meta, and 20 per cent para. Since substitu-
here to summarize recent investigations upon orienta- tion is found to be predominantly para-ortho (i. e.,
tion and reaction rates. meta < 40 per cent), substituents evidently do exert
EARLY WORK
a directive effect.
As in many cases of activation toward electro-
The various early reports of aromatic radical sub- philic reagents, activating groups usually activate all
stitution must be treated with caution, since quantita- positions, but the predominance of para and ortho
tive data is usually lacking. Solubility differences substituted products may be understood from a con-
made strict comparison of yields difficult, and in many sideration of the transition states for substitution of
cases only the principal products were isolated. Al- Ph-Y by radical R (5).
though the Gomberg reaction had been established as a
method of arylation since about 1924, the first recorded
example of the isolation of all three isomers in a homo-
lytic arylation process (2) did not appear until ten years
later. (1) (11) (111)
Nevertheless, in the period from 1930 to 1950 it be- Evidently the energy of structures (I) and (IS) should
came clear that in radical reactions the usual rules of be lower than that of (III), since the conjugation is lees
orientation were not observed, and that substitution complete in the latter case.
frequently took place para and ortho to the original The transition state in radical substitution of ben-
substituent, irrespective of whether i t was normally zene presumably involves the formation of a pentadienyl
classified as para-ortho or meta directing. radical, which, since i t may be considered as derived
I n 1938-39, Hey (3) obtained approximate figures from either a pentadienyl cation or anion, ought to be
for the isomer distributions observed when chloro- stabilized by substituents which will stabilize either
benzene, bromobenzene, and toluene were substituted the ration or the anion (6). Thus, formation of the
by the diphenyl radical, which pointed definitely to
para-ortho orientation. Some ten years later a some-
what similar picture emerged from the work of Loebl,
Stein, and Weiss on the hydroxylation of nitrobenzene transition state should be facilitated by both elec-
(4). tron-yielding and electron-withdrawing snbstituents.
Much of the earlier work involved the separation of Quantum-mechanical studies by Wheland and Coulson
reaction products and the value of the results was there- lead to similar conclusions (7,s).
fore markedly dependent on the separation techniques. The fate of the H atom ~vhichis lost from the tran-
It is not surprising that the less soluble para compounds sition state, presumably a t the position of substitution,
were often isolated in higher yield than the generally is uncertain. It may produce new radicals, or it may
more soluble ortho isomers, a fact which led to under- reduce either reactants or products.
estimation of the extent of ortho substitution. The It must be remembered that substitution is not the
last few years have seen the application of more rigor- only possible mode of attack by radicals on aromatic
ous analytical methods which do not require separation
-
systems. Abstraction of hydrogen may also take place
of the products a t all, particularly infrared spectros- with the production of aromatic radicals:
copy. Although earlier semiquantitative reports are
discussed, i t is chiefly with the more recent accurate re- A-H + R. Ar. + RH
sults that this paper is concerned. and these would be expected to yield diaryls by dimer-
THEORY OF AROMATIC HOMOLYTIC SUBSTITUTION ization.
Since in homolytic substitutions the attacking entity
usually carries zero charge, it might be expected that Although abstraction of hydrogen has been found to
606
DECEMBER, 1955
occur in some reactions, disubstituted derivatives of droxyl radicals produced by X-rays has been shown to
diphenyl are not found as products of the phenylation yield less than 40 per cent of the meta isomer, though
of monosnbstituted benzenes (9). the figures cited are approximate (14). The isomer
The reactivity of organic radicals varies consider- distrihution was found to vary with changing pH of
ably; in general, alkyl radicals do not react with ben- the reaction medium, the percentage of meta isomer
zene derivatives unless the latter are highly activated. being higher a t pH 2 than a t pH 6 or 12. Similar re-
In most investigations the organic radicals have been sults attended the use of Fenton's reagent.
aromatic. The authors formulated the hydroxylation reaction
as follows:
ORIENTATION BY SUBSTITUENTS
HIO M . + H. + .OH
Nitro Group. Substitution of nitrobenzene has been
extensively studied (6, 10, l l ) , especially by Hey and
co-workers. Attack by phenyl and substituted phenyl
radicals is effective a t all positions in the nucleus, and
para-ortho orientation is the rule; phenyl radicals from
five different sources yield snbstantially the same isomer Phenyl radicals attack the halobenzenes in all three
distribution. Quantitative data for this and other re- positions, the isomer distribution being similar for all
actions are given in Table 1. Analyses were carried four compounds (16, 16). The percentage of ortho
out both by bromometric titration of the bases obtained isomer is roughly the same as in the phenylation of
on reduction of the nitrodiphenyls, and by infrared nitrobenzene, but the figures for meta and para isomers
spectroscopy. are quite dissimilar. In the case of the halogen com-
All three mononitrophenols are produced by attack pounds the percentage of meta isomer is approxi-
of hydroxyl radicals on nitrobenzene, but the proportion mately three to four times as great as that found for
of meta isomer is substantially less than the "statisti- nitrobenzene, while the percentage of para isomer is
cal" 40 per cent. Loehl, Stein, and Weiss have used about half as great. The ratio of meta to para halo-
Fenton's reagent (4) and the action of X-rays on diphenyls is roughly 2: 1, i. e., the "statistical" ratio.
aqueous solutions (13) as radical sources. Although When attached to a naphthalene nucleus, chlorine
the two methods appear to yield similar results, side- and bromine direct benzoyloxy radicals mainly into
reactions made i t difficult to obtain any but approxi- the 4- and 5-positions, but some 2- isomer is also formed
mate figures with Fenton's reagent, and only the results (IS). The mole ratios of the various isomers are as
with X-rays are included in Table 1. Isomer propor- indicated.
tions were found to vary somewhat with changing pH. C1 Br
The reactions proceeded readily in the cold, and were
formulated :
latter reactions has been estimated from paper chro- and meta-directing suhstituents is much less definite
matograms as approximately three or four to one. for homolytic substitution than for many heterolytic
The formation of salicyclic acid also was ohsenred. reactions, and this blurring of familiar distinctions ap-
The most reactive positions for attack by benzoyloxy plies equally well to the rates of homolytic substitution
radicals in solvent chlorobenzene a t 80°C. have been reactions. The enormous changes in rate which fre-
studied for a number of polycyclic aromatic hydro- quently accompany change of substitnent in hetero-
carbons (19). These positions are indicated by arrows lytic substitutions have not been observed in corre-
in the formulas below. Phenanthrene and chrysene sponding homolytic reactions.
Two main approaches are available for the study of
the effect of substituents on reaction rates. The first
is the direct measurement of rate constants with and
without the substituent. This method involves the
difficulty that in many cases there is no certainty that
the rate-determining stage is the substitution itself..
The second method, that of competitive reaction, con-
sists in allowing an equimolar mixture of two compounds
are inert under these conditions. There is a low yield under comparison to compete for a limited quantity of
of dibenzanthraquinones when 1,2-5,6-dibenzanthra- reactant. The latter approach has proved the more
cene reacts in the presence of air. useful in the study of both heterolytic and homolytic
Diphenyl is substituted by phenyl radicals in all substitution. An extension of the method allows in-
three positions, the ortho isomer comprising about 50 direct comparison of rates for two compounds which
per cent of the total (20). The percentage of para iso- cannot be compared directly (85).
mer is slightly greater than that of meta. One of the first experiments of the competition type
Two examples of the orientating effect of an aliphatic to yield useful information was that of Grieve and Hey
side chain recently have been studied by Hey and co- ($61, who observed that the yield of nitrodiphenyls
workers. The compounds chosen, toluene and tert- was four times as great as the yield of methyl dipbenyls
bntyl benzene, present a striking contrast. Phenyl- when toluene and nitrobenzene were allowed to com-
ation of toluene' results in a yield of o-methyl diphenyl pete for phenyl radicals. Eighteen years later, Hey
of approximately 71 per cent, with the yield of meta and co-workers obtained a quantitative comparison of
compound somewhat greater than that of the para (21). the rates of substitution of benzene, nitrobenzene,
Tert-hutyl benzene, on the other hand, yields only 24 chlorobenzene, and pyridine by phenyl radicals (9).
per cent of o-lert-butyldiphenyl, with the meta and para The relative rates are as shown in parentheses:
isomers in approximately statistical ratio (22). As can PhH (1); PyH ( I ) ; PhC1 (1.44); PhN02 (4)
be seen from Table 1, the ortbo isomer invariably
accounts for a t least half the total product in other Since the isomer proportions are known for the
aromatic phenylations, and the low yield of o-tert- phenylation of nitrobenzene, partial rate factors2 can
butyldiphenyl is ascribed to steric hindrance. It is be calculated, and the effect of the nitro group com-
interesting that the other examples of homolytir suh- pletely specified. Partial rate factors for this and for
stitutions in which the yield of ortho isomer is well other phenylations are set out in Table 2. Evidently
below 50 per cent are the hydroxylation of nitrobenzene the nitro group weakly activates all positions, but
and chlorobenzene. chiefly the ortho and para. These results agree qualita-
Heterocycles. Little quantitative information is tively with theoretical predictions (7).
available concerning radical substitutions in hetero- A similar investigation has been carried out with
cycles. It recently has been shown that pyridine is chlorobenzene (15), and the partial rate factors (Table
phenylated a t all positions, but more than 50 per cent 2) show that the ortho position is activated to the great-
of the product is 2-phenyl pyridine (25). The ratio of est extent, the para position only slightly, while the
meta to para isomer is statistical, i. e., 2: 1. meta position is scarely more reactive than henzene it-
Recent work has shown that auinoline is nitrated bv self. The over-all rate of substitution is 1.44 (ben-
pernitrous in the 6- and 7:positions, i. e,, in t& zene = I), so that the nitro group activates about three
henaenoid ring ($4). This reaction is believed to times more powerfully than does the chlorine atom.
involve both hydroxyl and nitrogen dioxide radicals, %Thepartial rate factor for a given position in a given reaction
and is of interest since the reactivity of benzene and is the numerical value of the reactivity of that position com-
pyridine toward phenyl radicals is about ~h~~~ pared to the reactivity of a position in benzene in the same reac-
tion, the latter having the value unity. The partisl rate faotor
is formation of 5- and 8-nitroquino1ines' incorporates the statistical fact that there are six equivalent posi-
REACTION RATES tions in benzene, and two equivalent ortho and two equivalent
met8 pos~tionsin a monosubstituted benzene. A partial rate
The wroblem of reaction rate is closelv connected factor greater than unity means activation, a ~artialrate factor
with of orientation, The division i n t i para-ortho- l e s s t h i n unity means- deactivation. he o\er-dl rate of a
- .
reaction relative to benzene is obtained bv addine the ~aItia1rate
Substitution in the side chain m a y a180 occur, but can be factors for the five positions in s monosubstituted compound and
eliminated by using a low concentration of benzoyl peroxide. dividing by six.
DECEMBER, 1955 609