Visible-light-promoted Wohl-Ziegler functionalization of organic molecules with N-bromosuccinimide under solvent-free reaction conditions

Article abstract of DOI:10.1002/hlca.200800308

The visible-light-induced transformation of toluenes with N-bromosuccinimide (NBS) under solvent-free reaction conditions (SFRC) was studied. The reaction took place in spite of the very restricted molecular motion; toluenes could be regioselectively converted to benzyl bromides. Selective radical-chain reactions with NBS were carried out in liquid/liquid and in solid/solid systems; furthermore, reactions could be performed in the presence of air. The radical scavenger TEMPO (=2,2,6,6-tetramethylpiperidin-1- yloxy) completely suppressed the side-chain bromination of toluenes with NBS under SFRC. Electron-withdrawing groups decreased the reactivity of the toluenes, and the Hammett reaction constant ρ⁺ = -1.7 indicated involvement of polar radical intermediates with electrophilic character.

Full text of DOI:10.1002/hlca.200800308

Helvetica Chimica Acta – Vol. 92 (2009)
555
Visible-Light-Promoted Wohl – Ziegler Functionalization of Organic
Molecules with N-Bromosuccinimide under Solvent-Free Reaction Conditions
by Marjan Jereb*a), Marko Zupana)b), and Stojan Stavberb)
a
ˇ
ˇ
) Faculty of Chemistry and Chemical Technology, University of Ljubljana, Askerceva 5, P.O. Box 537,
1001 Ljubljana, Slovenia
(phone: þ 386-1-2419248; fax: þ 386-1-2419220; e-mail: marjan.jereb@fkkt.uni-lj.si)
b
ˇ
) Jozef Stefan Institute, Jamova 39, 1000 Ljubljana, Slovenia
The visible-light-induced transformation of toluenes with N-bromosuccinimide (NBS) under
solvent-free reaction conditions (SFRC) was studied. The reaction took place in spite of the very
restricted molecular motion; toluenes could be regioselectively converted to benzyl bromides. Selective
radical-chain reactions with NBS were carried out in liquid/liquid and in solid/solid systems; furthermore,
reactions could be performed in the presence of air. The radical scavenger TEMPO (¼2,2,6,6-
tetramethylpiperidin-1-yloxy) completely suppressed the side-chain bromination of toluenes with NBS
under SFRC. Electron-withdrawing groups decreased the reactivity of the toluenes, and the Hammett
reaction constant 1þ ¼ ꢀ1.7 indicated involvement of polar radical intermediates with electrophilic
character.
Introduction. – In the context of promoting a sustainable development, the concept
and principles of green chemistry, which emerged a decade ago [1], have had a
considerable effect on modern research and scientific trends in chemistry, especially in
organic chemistry. To diminish the pollution of the environment, the development of
alternative methodologies and protocols for the transformation of organic compounds
is becoming one of the major challenges for organic chemists, while improvement of
atom economy, reduction of health and safety risks, waste minimization, and cost
efficiency of chemical processes are their principal components. Reusable reaction
media, such as ionic liquids or a fluorous phase, is an often used alternative, but in the
scope of green chemistry ꢀthe best solvent is no solventꢁ [2]. Examples of solvent-free
fluorination [3], chlorination [4], iodination [5], and bromination [6 – 8] are presented
in both old and recent reports.
Achieving selectivity of radical-chain reactions in dilute solution is often not a
trivial task, while an even more delicate situation in photoinduced reactions under
solvent-free reaction conditions (SFRC) could be anticipated. Many UV- or X-ray-
induced [2 þ 2] cycloadditions and other photoinitiated transformations are known
under SFRC [2b], but reactions frequently involve one solid reactant and take place in
a single crystal (photodimerization for example), whereas reports on the reactivity of
two discrete solids in a visible-light-induced transformation appear to be rare. A few
examples of thermal and microwave-initiated Wohl – Ziegler brominations under
SFRC have been published [9], with the main focus on the synthetic method. However,
photoinduced radical reactions with NBS under SFRC still remain unexplored.
ꢂ 2009 Verlag Helvetica Chimica Acta AG, Zꢃrich

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N-Bromosuccinimide (NBS) is one of the basic reagents in organic chemistry, and
the Wohl – Ziegler bromination [10] has been one of the most extensively studied
reactions [11]. Transformation of organic molecules with NBS was studied under
thermal [12], photochemical [13], sonochemical [14], and microwave reaction
conditions [15], as well as in H2O [16], in ionic liquids [17], and in supercritical CO2
[18]. Chain-carrying radicals (succinimidyl or bromine) were a matter of controversy
for years [19]. We were interested in the question about the occurrence of selective
reactions under SFRC. Another issue is how product formation influences the
conversion of the remaining reactant since the product could cover or coat the surface
of the starting material. Mercury or strong tungsten lamps, hazardous solvents like
CCl4, and a dry, inert atmosphere with air carefully removed are often regarded as
ꢀnormalꢁ conditions for radical-chain reactions (see, e.g., an exception in [20]). The
question arises whether it is possible to perform radical reactions with a 40 W tungsten
lamp in the presence of air without an inert-gas atmosphere. Is it necessary to employ a
radical initiator? What types of intermediates are likely to be involved in such a
transformation? These were the issues investigated in this study.
Results and Discussion. – NBS is known to be a light-sensitive molecule, and the
commercial reagent is always slightly yellow due to the presence of traces of Br2, and
this could influence the stability of NBS, but it is unclear how the system behaves under
SFRC. Therefore, we initially tested the stability of crystallized NBS under illumination
with a 40 W bulb as detailed in Table 1. Irradiation in an open flask for 16 h resulted in
only 2% conversion to succinimide; this rose to 6 – 11% in a stoppered flask or with
small amounts of solvent, to 14 – 21% in solution, and to 100% with added MeOH or in
MeOH solution. Clearly, NBS is most stable under solvent-free open-flask conditions,
Br2 not being generated, and another reaction partner is needed to induce electron
flow.
Table 1. Stability of NBS under Various Conditions under Illumination with a 40 W Tungsten Lamp
Reaction conditionsa)
Conversion [%]b)
SFRC, open flaskc)
added H2O (1 equiv.)
SFRC, stoppered flaskc)
SFRC, Br2 (vap.)c)
added CCl4 (1 equiv.)
0.1m NBS in H2O
0.1m NBS in CCl4
added MeOH (1 equiv.)
0.1m NBS in MeOH
2
6
8
9
11
14
21
100
100
a) 0.2 mmol of NBS irradiated for 16 h at 368. b) Determined by 1H-NMR. c) SFRC ¼ solvent-free
reaction conditions.
First, we studied the effect of the aggregate state of the following substituted
toluenes on bromination under SFRC: 4-(tert-butyl)toluene (1a; liquid), 2,3,4,5,6-
pentafluorotoluene (3; liquid), and 4-nitrotoluene (1b; solid). It was not clear whether

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557
a photoinitiated radical-chain reaction in liquid/solid and solid/solid systems under
SFRC could take place, but [9c] provides an indication for this. The reactions were first
tested in the dark and, as anticipated, none of them took place, not even in the presence
of dibenzoyl peroxide at 608. In the photoinitiated reactions, stirring obviously
facilitated the transformation to 2a in the liquid/solid system 1a/NBS (Table 2, Entries 1
and 2); on the other hand, the reaction could take place without stirring but required a
longer reaction time t (Entry 3). In a solid/solid system, stirring is of much greater
relevance than in a liquid/solid system due to the great difference in molecular motion
(Entries 6 and 7). A remarkable effect of the substituent R or the F-atoms was noted in
the case of no stirring (Entries 3, 6, and 10), in contrast to an only moderate effect in the
case of stirring (Entries 4, 7, and 11). An electron-releasing group favored the reaction
much more than an electron-withdrawing group, since 2,3,4,5,6-pentafluorotoluene (3)
was the least reactive among these substrates (!4).
Table 2. Effect of Substituent, Aggregate State, and Reaction Conditions on Photoinduced Benzylic
Bromination of Toluenes with NBS under SFRC
Entry
Substrate
t [min]a)
Reaction conditionsb)
Conversion [%]
1
2
3
4
5
6
7
8
9
1a
160
160
480
480
600
480
480
960
960
480
480
1080
B
A
B
A
A
B
A
B
A
B
A
A
0
36
85c)
92c)
100c)
5
1b
3
60c)
83c)
96c)
4
10
11
12
40
100c)
a) t, Reaction time. b) A, under stirring; B, no stirring. c) Accompanied by the CHBr2 derivative: Entry 3,
9%; Entry 4, 8%; Entry 5, 10%; Entry 7, 4%; Entry 8, 4%; Entry 9, 4%; and Entry 12, 6%.
Next, beside toluene (1c), we chose anisole (5) and acetophenone (7) as substrates
(Table 3). Anisole is sensitive to ring substitution, also under radical or cation-radical
conditions [21], while acetophenone could be halogenated via the enol form. In the
light-induced bromination, 1c could readily be converted to benzyl bromide (2c; 87%),
5 exclusively furnished 4-bromoanisole (6), while 7 was a-brominated (! 8a); these

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transformations did not take place in the absence of light (Entries 1, 4, and 7). The
transformation of toluene (1c) in the presence of the radical scavenger TEMPO
(¼2,2,6,6-tetramethylpiperidin-1-yloxy) was completely suppressed (Entry 3); thus
benzyl bromide (2c) was formed in a radical process. A significantly lower effect was
noted for 5 and 7 (Entries 6 and 9).
Table 3. Effect of the Substituent (Me, MeO, or MeCO) on the Type of Reaction with NBS under SFRC
Entry
Substrate
t [h]a)
Reaction conditions
Conversion [%]
Selectivityb)
87: 13
1
2
3
4
5
6
7
8
9
1c
1c
1c
5
5
5
7
7
7
9.5
9.5
9.5
18
18
18
16
16
16
dark
0
94
0
hn
hn, TEMPOc)
dark
hn
hn, TEMPOc)
dark
0
100
74
2
73
62
hn
68 : 32
88 : 12
hn, TEMPOc)
a) t, Reaction time. b) For 1c, 2c/2cc; for 7, 8a/8aa. c) TEMPO (0.25 equiv.) was added.
Next, we examined the progress of bromination of 1c, 5, and 7, and various
induction periods were observed (Fig. 1). Further, we investigated the role of the
substituent on the benzylic C-atom, i.e., the behavior of 1c vs. 11a vs. 11b, and the role
of the structure of the dimethylbenzenes 11c – 11e on the functionalization with NBS;
the results are shown in Table 4. A crucial influence on the reaction rate was found; the
nitrile group in 11a (Entry 3; ! 12a) contributed significantly to retardation, while the
H-atom or the Me group in 1c and 11b (Entries 1 and 5) had a beneficial effect on the
rate of conversion (!2c and 12b, resp.). This indicates that the benzyl radical has
principally an electrophilic character. In contrast, illumination of benzyl ethyl ether
(PhCH2OEt) under SFRC led to fragmentation, and a complex mixture was isolated.
However, benzaldehyde (PhCHO) was the main product, and a similar observation
was noted for the reaction of the related benzyl methyl ether (PhCH2OMe) in CCl4
[22]. Further, we established that the only reactive sites in the dimethylbenzenes 11c –
11e are the Me groups (!12c – 12e), and no ring functionalization occurred. In
contrast to toluene (1c), no (dibromomethyl)-substituted products were obtained. The
relative ratio of the CH2Br vs. the bis(CH2Br) derivative was practically independent of
the structure of the molecule (Table 4, Entries 8 – 12). Transformation of dimethyl-
benzenes with NBS under photoinduced SFRC obviously takes place with a higher

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559
Fig. 1. The course of photoinduced bromination with NBS under SFRC: ring- vs. ꢀbenzylicꢀ- vs. a-
carbonyl-substitution
Table 4. Effect of Substituents on Reactivity and Selectivity in the Photoinduced Bromination of Toluenes
and Xylenes with NBS under SFRC
Entry
Substrate
Reaction time [h]
Conversion [%]
Selectivitya)
1
2
3
4
5
6
7
8
9
1c
1c
3
6
3
21
3
5
3
6
3
6
90
94
23
> 99
91
> 99
70
89
79
87
84
85 : 15
87: 13
> 99
11a
11a
11b
11b
11c
11c
11d
11d
11e
11e
> 99
> 99
95 : 5b)
> 99
87: 13
85 : 15
82 : 18
87: 13
86 : 14
10
11
12
3
6
86
a) For 1c, 11a, and 11b mono- vs. dibromination (2c/2cc, 12a/12aa, and 12b/12bb); for 11c – 11e CH2Br vs.
bis(CH2Br) (12c – 12e/12cc – 12ee). b) 5% of 2-bromo-1-phenylethanone was formed.

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selectivity in comparison with microwave-induced bromination [9b], bromination in
H2O with Br2 [23], or bromination in the H2O2/HBr system [24], while no
dibromination was noted in the microwave-assisted reaction under SFRC [25].
Functionalization of substrates possessing secondary and primary, or tertiary and
primary H-atoms like in 4-ethyltoluene and 4-isopropyltoluene resulted in complex
reaction mixtures.
To further establish the role of the reaction conditions, 4-(tert-butyl)toluene (1a)
and 4-nitrotoluene (1b) were targeted (Table 5). Recently, a remarkable rate
acceleration of organic reactions was demonstrated after preorganization of the
reactants in a solvent, which was then immediately evaporated [26]. Similarly 1a and 1b
were separately preorganized with NBS, either in petroleum ether/CH2Cl2 or in MeOH.
Preorganization of 1a in petroleum ether/CH2Cl2 had a very beneficial effect on the
reaction rate (Table 5, Entries 1 and 3), while it had a completely opposite effect on the
transformation of 1b (Table 5, Entries 1 and 3). Obviously, this preorganization
enhanced the intermolecular contact in the case of 1a, whereas it contributed to the
separation of the reactants in the case of 1b. In the latter case, during evaporation of
petroleum ether/CH2Cl2, the more volatile CH2Cl2 evaporated before the petroleum
ether, which induced selective crystallization of NBS, while 1b was still in solution and
crystallized last. The difference in reactivity in the solid/solid system could thus be
attributed to consecutive crystallization of the reactants. Preorganization of 1a and
NBS in MeOH also had an advantageous effect, but an even more dramatic
enhancement was noted in the case of 1b (Entry 4). Both reactants started to
crystallize from the solution during the evaporation of MeOH at about the same time,
which brought the molecules into much more intimate contact, thus enhancing the
reactivity. Recently, an exceptional rate enhancement in solid/solid systems was
established when a small amount of solvent vapor was present [27]. As evident from
Table 5, the addition of a small quantity of MeOH was exceedingly beneficial for both
1a and 1b (Entry 5). On the other hand, the effect of deionized H2O was not uniform,
Table 5. Effect of Reaction Conditions, Substituent, and Aggregate State of 4-(tert-Butyl)toluene (1a) and
4-Nitrotoluene (1b) on Photoinduced Benzylic Bromination with NBS under SFRC at 368
Entry
Reaction conditionsa)
t [min]; conversion [%]b)
1a (R ¼ t-Bu)
1b (R ¼ NO2)
1
2
3
4
5
6
7
8
9
SFRC
SFRC
160; 36
360; 90
160; 86
160; 66
160; 90
160; 50
160; 30
160; traces
160; 0
300; 15
960; 96
300; 0
300; 82
300; 42
300; 8
300; traces
300; traces
300; 0
PO (petroleum ether/CH2Cl2), SFRCc)
PO (MeOH), SFRCc)
added MeOH (1 equiv.)
added H2O (1 equiv.)
0.1m 1 in MeOH
0.1m 1 in Et2O
SFRC, TEMPOd)
c
a) SFRC ¼ solvent-free reaction conditions. b) t ¼ reaction time. ) PO ¼ preorganization, i.e., 1 and NBS
were dissolved in solvent (MeOH or petroleum ether/CH2Cl2), and the solvent was evaporated.
d) TEMPO (0.25 equiv.) was added.

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561
and its role was much more limited. Photoinduced reactions in solution are clearly less
effective in comparison with reactions under SFRC (Entries 7 and 8). TEMPO,
regardless of the aggregate state, completely supressed the benzylic bromination,
suggesting that radicals are the intermediates (Entry 9). From Table 5, it can be
summarized that photoinitiated reactions with NBS under SFRC are very sensitive to
reaction conditions. From Tables 2 and 5, the rather diverse reactivity of 1a and 1b is
evident, but their inherent reactivity is yet to be estimated. Reaction profiles of 1a – 1c
and 3 in the reaction with NBS were determined (Fig. 2). Induction periods differed
considerably and rose with decreasing reactivity of the substrates. Toluene (1c) was
more reactive than 4-(tert-butyl)toluene (1a), reflecting the fact that the motion of
reactants is a more crucial parameter than electronic effects under SFRC. The 2,3,4,5,6-
pentafluorotoluene (3) had an induction period which was one hour longer than that of
4-nitrotoluene (1b) and exhibited a strong electronic effect on the radical-chain
reaction. Such an interference of effects prevents the definite prediction of reactivity,
but in general, solid substrates with electron-withdrawing groups are less reactive than
liquid substrates possessing electron-releasing groups.
Fig. 2. The effect of aggregate state and substituents on the course of the photobromination of toluenes
with NBS under SFRC
In addition, we examined the role of the brominating agent (NBS vs. Br2) and of the
structure of the deactivated toluenes on benzylic bromination (Table 6). The 4-
nitrotoluene (1b) gave the highest conversion in reaction with NBS; the liquid
nitrotoluenes 13a and 13b exhibited rather diverse results (Entries 1, 5, and 9). These
substantial differences indicate that a nitro group in close proximity (ortho position) to
the reaction center acts as an inhibitor. A similar reactivity in liquid/liquid (13a or 13b)
and in solid/liquid systems (1b) was established in the bromination with Br2 under
SFRC, furnishing the related benzyl bromides 14a, 14b, and 2b. Bromination with NBS
of the deactivated toluenes, regardless of their aggregate state and reactivity, took place
via radical intermediates (Entries 2, 6, 12, and 16). Reaction intermediates in the case
of bromination with Br2 did not appear to be so invariable (Entries 8, 14, and 18).
The Hammett correlation analysis is a very convenient mechanistic tool for the
evaluation of the transition state, character, and polarity of intermediates, but kinetic

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Table 6. Effect of Structure and Aggregate State of Deactivated Toluenes and of the Reagent on
Photoinduced Bromination under SFRC
Substrate
R
Reagent
Additive
Reaction time [h]
Conversion [%]
1
2
3
1b (s)
4-NO2
NBS
NBS
Br2
–
16
16
16
16
96
0
75
0
TEMPO
–
4
Br2
TEMPO
5
6
7
8
13a (l)
3-NO2
NBS
NBS
Br2
–
16
16
16
16
83a)
0
33
0
TEMPO
–
Br2
TEMPO
9
13b (l)
2-NO2
H
NBS
Br2
NBS
NBS
Br2
–
16
16
16
8
97
0
69b)
22b)
100
0
10
11
12
13
14
15
16
17
18
–
1c
–
0.83
0.83
0.83
0.83
18
18
18
18
TEMPO
–
Br2
TEMPO
–
TEMPO
3
2,3,4,5,6-F5
NBS
NBS
Br2
100
100
–
Br2
TEMPO
a) 17% of CHBr2 derivative was formed. b) Refers only to benzylic bromination, ring bromination takes
place as well.
studies under SFRC are very scarce. Benzylic bromination of toluene derivatives
conducted in benzene [19c][19e] exhibited 1 ¼ ꢀ1.46, in CCl4 1 ¼ ꢀ1.38 [19d], and in
CH2Cl2 1 ¼ ꢀ1.41 [28]. We examined the photoinduced benzylic bromination of the 3-
and 4-substituted toluenes 1b, 13a, and 15 under SFRC with NBS. In our case, despite
the heterogeneous reaction mixture, and even though only neat reactants were mixed
and the resulting mixture was illuminated with a 40 W tungsten lamp, a surprisingly
good agreement (r¼ 0.95) was obtained (Fig. 3 and Table 7). The best correlation was
obtained with sþ parameters (1 ¼ ꢀ1.73, T 368) which indicates that the transition state
is similarly polar as that in solution, suggesting the involvement of electron-deficient,
electrophilic radical intermediates in the charge-separated dipolar transition state.
Conclusions. – In this report, we showed that in visible-light-induced (40 W
tungsten lamp) radical-chain bromination of toluenes with NBS under SFRC, reaction

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563
Table 7. Hammett-Correlation Analysis of the Benzylic Bromination with NBS of Toluene Derivatives
under SFRCa)
b
Entry
Substrate
R
sþ
kR/kH
)
log kR/kH
1
2
3
4
5
6
7
8
9
1c
15a
15b
15c
15d
15e
15f
15g
13a
1b
4-H
4-F
4-Cl
4-Br
3-F
0
1
0
ꢀ 0.073
0.781
0.812
0.698
0.273
0.219
0.233
0.086
0.037
0.069
ꢀ 0.11
ꢀ 0.09
ꢀ 0.16
ꢀ 0.56
ꢀ 0.66
ꢀ 0.63
ꢀ 1.07
ꢀ 1.44
ꢀ 1.16
0.11
0.15
0.352
0.399
0.405
0.52
0.674
0.79
3-Cl
3-Br
3-CF3
3-NO2
4-NO2
10
a) 0.3 mmol of NBS and 0.3 mmol of toluene (1c) (Entries 2 – 7) or 0.3 mmol of 3-bromotoluene (15f)
(Entries 8 – 10) as references and 0.3 – 0.6 mmol of another substrate, stirring and illumination with a
40 W lamp at 368 to full consumption of NBS. b) The relative reactivity of the substituted toluenes was
determined vs. toluene (as a reference). 1 Equiv. of toluene and 1 equiv. of substituted toluene and 1
equiv. of NBS were mixed and stirred, the reaction mixture was analyzed by NMR, and krel was obtained.
In the case of toluenes possessing substantially different reactivity, 2 equiv. of less reactive substrate was
taken. The difference in reactivity of 4-nitrotoluene and toluene, for example, was too high to obtain
reliable krel in this way. For this reason, 3-bromotoluene (significantly less reactive than toluene) was
taken as a second reference molecule for 3-nitrotoluene, 4-nitrotoluene, and 3-trifluoromethyltoluene.
Relative reactivity of these three molecules vs. toluene was therefore determined indirectly, for example
k(4-NO2)/k(4-H) was obtained from: k(3-Br)/k(4-H) and k(3-Br)/k(4-NO2).
Fig. 3. Hammett linear free-energy relationship for photoinduced benzylic bromination of toluenes with
NBS under SFRC

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takes place in the presence of air, so no inert atmosphere is needed. Molecular
migration is dramatically reduced; the aggregate state of the substrates plays an
important role, but both liquid and solid toluenes could selectively be converted to the
corresponding benzyl bromides. Ring bromination of anisole (5) and side-chain
bromination of acetophenone (7) were observed under SFRC. The reactivity of
toluenes depends on the substituents; electron-releasing groups facilitate, whereas
electron-withdrawing groups decrease the reactivity. The inherent reactivity of
substrates differs as well; the induction period is longer in the case of solids and
electron-poorer substrates. The radical scavenger TEMPO completely suppresses side-
chain bromination with NBS. Despite being a heterogeneous reaction system, a good
Hammett free-energy relationship (r¼ 0.95, 1 ¼ ꢀ1.73 sþ) was obtained. It is suggested
that substantial charge separation in the dipolar transition state is involved in the
radical reaction under SFRC; reactions in solution exhibit a similar reaction course.
The authors are grateful to the Ministry of Higher Education, Science, and Technology of the
Republic of Slovenia for financial support.
Experimental Part
General. Reactions were performed under air in ordinary flasks. Heterogeneous reaction mixtures
(solid/liquid or solid/solid) under solvent-free-reaction conditions (SFRC) were stirred with a small
stirring bar, and despite the fact that only a part of the reaction mixture was stirred (120 – 160 rpm), no
problems were observed in the progress of the reaction. The experimental procedure for solid/liquid,
solid/solid, and liquids was the same; NBS or Br2 was added to the substrate. Chemicals were obtained
from commercial sources and distilled or crystallized if necessary. NBS was crystallized, solvents were
used as received. An ordinary 40 W tungsten lamp was used throughout all the experiments, and the
average reaction temp. was 368. Blank experiments were performed in the dark at 368. Crude reaction
mixtures were directly subjected to column chromatography (CC). Conversions were determined by
1H-NMR, and yields of isolated product refer to pure products. All the products are known compounds,
and their properties were in agreement with published data. Flash column chromatography (FC): silica
gel 60 (63 – 200 mm, 70 – 230 mesh ASTM; Fluka). TLC: Merck-60-F254 plates: mixtures of light
petroleum ether (b.p. 40 – 608) and CH2Cl2. NMR Spectra: Bruker-Avance-300-DPX instrument.
Photoinduced Reactions with NBS or Br2 under SFRC. General Procedure. To toluene (47 mg,
0.5 mmol; 1c), NBS (98 mg, 0.55 mmol) was added, and the resulting mixture was subjected to stirring
and illumination with a 40 W tungsten lamp until practically full conversion was achieved (4 h). After
CC, benzyl bromide was obtained. The procedure is the same for other solid substrates.
General Preorganization Procedure. Substrate and NBS were dissolved in MeOH or in a petroleum
ether/CH2Cl2, and the solvent was immediately evaporated at 238 under reduced pressure. The resulting
mixture was exposed to illumination with a 40 W tungsten lamp.
Measurement of Relative Rates in the Hammett Correlation Analysis: General Procedure. The
relative reactivities of substituted toluenes (Fig. 3) were determined by competitive reactions as follows:
To a mixture of two substrates (reference and the examined substituted toluene, rel. ratio 1:1 or 1:2,
depending on reactivity), NBS (1 equiv.) was added, and the mixture was stirred. The crude reaction
mixture was analyzed by NMR. Relative reactivities expressed by relative rate factors kR were calculated
from the equation [19e] kR ¼ kA/kB ¼ log ((A – X)/A)/log ((B – Y)/B), derived from the Ingold – Shaw
relation [29], where A and B are the amounts of starting material and X and Y the amounts of products
derived from them. The relative rate factors thus obtained, collected in Fig. 3 and Table 7, are the
averages of at least three measurements; the average deviation of measurements was as follows: 4-F
(10%), 4-Cl (2%), 4-Br (4%), 3-F (5%), 3-Cl (3%), 3-Br (5%), 3-CF3 (3%), 3-NO2 (10%), and 4-NO2
(6%).

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Received August 6, 2008