Azoles. Part 43:1 reactions of N-(phenylsulphonylmethyl)- and N-(phenylsulphinylmethyl)azoles with some nitroarenes

Article abstract of DOI:10.1016/S0040-4020(00)00624-4

Treatment of nitroarenes with 1-(phenylsulphonylmethyl)azoles in the KOH/DMSO system at room temperature resulted usually in the cleavage of the phenylsulphonyl group, whereas the t-BuOK/DMF system at low temperature promotes to a greater extent oxidation of the σ-adducts. When 1-(phenylsulphinylmethyl)azoles were used for the reaction only elimination of the phenylsulphinyl group was observed. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(00)00624-4

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 7273–7284
Azoles. Part 43:1 Reactions of N-(Phenylsulphonylmethyl)- and
N-(Phenylsulphinylmethyl)azoles with some Nitroarenes
*
Marek K. Bernard
´
Department of Organic Chemistry, University of Medical Sciences, ul. Grunwaldzka 6, 60-780 Poznan, Poland
Received 4 February 2000; revised 16 June 2000; accepted 6 July 2000
Abstract—Treatment of nitroarenes with 1-(phenylsulphonylmethyl)azoles in the KOH/DMSO system at room temperature resulted usually
in the cleavage of the phenylsulphonyl group, whereas the t-BuOK/DMF system at low temperature promotes to a greater extent oxidation of
the s-adducts. When 1-(phenylsulphinylmethyl)azoles were used for the reaction only elimination of the phenylsulphinyl group was
observed. ᭧ 2000 Elsevier Science Ltd. All rights reserved.
Scheme 1.
Scheme 2.
Keywords: azoles; sulfones; sulfoxides; vicarious nucleophilic substitution.
* Tel./fax: ϩ48-061-8659624; e-mail: akgzella@eucalyptus.usoms.poznan.pl
0040–4020/00/$ - see front matter ᭧ 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00624-4

7274
M. K. Bernard / Tetrahedron 56 (2000) 7273–7284
Scheme 3.
The vicarious nucleophilic substitution (VNS) of hydrogen,
also called the Ma˛kosza reaction, is a versatile method for
the introduction of a variety of substituents into electro-
philic arenes.2,3 The reaction is also a useful tool for
building heterocyclic rings.4 The VNS of hydrogen is a
two-step reaction proceeding via fast and reversible
formation of the s-adducts, followed by slower, base-
induced b-elimination (Scheme 1, only the ortho isomer is
shown).2
8 were obtained according to known procedures.7,8
However, oxidation of 1-(phenylthiomethyl)benzimidazole
(6) with m-chloroperoxybenzoic acid (m-CPBA) at 0ЊC
gave both 1-(phenylsulphonylmethyl)- and 1-(phenyl-
sulphinylmethyl)benzimidazole 7 and 8 that required
separation by chromatography.
The pyrazole and triazole derivatives 4, 5 and 10, 11 were
obtained in a two-step synthesis (Scheme 2). Sodium salts of
3,5-dimethylpyrazole or 1,2,4-triazole were treated with
chloromethyl phenyl sulphide to give phenylthiomethyl
derivatives 3 or 9. Oxidation of compound 3 with
m-CPBA led to both sulphone 4 and sulphoxide 5, whereas
oxidation of compound 9 with the same reagent provided
only the sulphone 10. On the other hand, the sulphoxides 5
and 11 could be obtained by oxidation of the sulphides 3 and
9 with NaIO4.
In continuation of my studies on nucleophilic substitution in
azoles5 I investigated the VNS of hydrogen using
carbanions of some 1-(phenylsulphonylmethyl)- and
1-(phenylsulphinylmethyl)azoles 1, 4, 7, 10 and 2, 5, 8,
11, respectively.6
The benzotriazole and benzimidazole derivatives 1, 2 and 7,

M. K. Bernard / Tetrahedron 56 (2000) 7273–7284
7275
substitution of hydrogen (ONSH).12–15 Although the VNS
products usually prevailed, the ratio of both products
depends on the nature of the starting nitroarene and the
reaction conditions. The ONSH products were obtained in
higher yields, and even in some cases were the major
products, when the reactions were performed in the
t-BuOK/dimethylformamide (DMF) system at Ϫ30ЊC
(abbreviated further in the text to ‘t-BuOK/DMF system’).
The final outcome of the reaction was controlled to a
large extent by electrophilic strength of the nitroarene.
The reaction gave reasonable to good yields when strong
electrophiles, like 1-chloro-4-nitrobenzene (15), 1,3-
dinitrobenzene (16) and its chloro derivative 17, or such
nitroheteroaromatics like derivatives of pyrazole 19 and
benzotriazole 22, were used as starting materials (Schemes
3 and 4, Table 1). In all these cases but 19 the reaction
pattern was as follows: the VNS products 15a–17a and
22a were the sole or predominant compounds in the
KOH/DMSO system, and the ONSH products 15b–17b
and 22b prevailed in the t-BuOK/DMF one. A different
kind of compound, namely 17c, resulted from the aromatic
nucleophilic substitution (SNAr) of the chlorine atom by the
phenylsulphinate ion, was isolated in 6–8% yield from the
reaction of 1 and 17 in both systems. Compound 17c was
also obtained in 67% yield by treatment of the benzotriazole
derivative 17a with sodium benzenesulphinate in DMSO.
This way of preparation of compound 17c constitutes an
additional proof for both its structure and possibility of its
formation under the VNS conditions. Furthermore, another
product of the substitution of the chlorine atom, namely
compound 16b, was detected in the same reaction mixture
but its attempted isolation was unsuccessful.
Table 1. Products of the reaction of nitroarenes 12–23 with compounds 1
or 2
Nitroarene Products
Yields (%)
Starting material: 1
Starting material: 2
Method Aa Method B Method A Method B
12
12a
12b
12c
13a
13b
14a
14b
12c
15a
15b
12c
16a
16b
17a
17b
17c
18a
18b
19a
19b
20a
21a
21b
22a
22b
23a
23b
0
0
4
2
25
4
7 (30)b
–
–
33 (30)
3
44
–
–
10
–
–
65 (10)
–
38 (5)
–
20
–
–
50
3
63
–
–
47
–
–
38 (5)
–
22 (5)
–
Tracesc
Traces
39
2
0
0
52
49
Traces
6
71
0
49
2
6
13
14
31
8
14
11
41
11
4
45
4
37
8
15
16
17
–
–
20
–
31
18
19
0
3
0
0
68 (50)
–
82
–
61
54 (60)
–
64
–
46
–
Traces
41
0
48
0
72
0
48
2
Traces
45
0
–
20
21
20 (35)
26
–
63
–
37
–
5
Traces
6
15
20
9
22
23
a Method A: KOH/DMSO/23ЊC; method B: t-BuOK/DMF/Ϫ30ЊC.
b The reaction time (min), if different from the values in the Experimental
part, is given in brackets.
c Traces means yields less than 2%, usually of not isolated compounds.
Only the ONSH product 19b was isolated from the reaction
mixture of 19 and 1 in both systems (Scheme 4, Table 1).
1
Particularly interesting is 1-(phenylsulphonylmethyl)benzo-
triazole (1) for the benzotriazolate anion is regarded as a
good leaving group that can be used in place of halogen in
many reactions.9 Hence, one could expect the benzo-
triazolate anion to leave in the course of the VNS. This
assumption was confirmed by a recent work of Katritzky
and Xie who demonstrated that tris(benzotriazol-1yl)-
methane could act as an efficient reagent for introduction
of the bis(benzotriazol-1-yl)methyl group into nitroarenes.10
Moreover, Katritzky and Toader showed the utility of
diarylmethylbenzotriazoles for the synthesis of p-(nitro-
aryl)diarylmethanes via the VNS of hydrogen.11 The benzo-
triazolate anion also acted as a leaving group in that case.
However, the H NMR spectrum of one of the chromato-
graphic fractions from the reaction carried out in the KOH/
DMSO system did reveal signals corresponding to the VNS
product, but I was not able to isolate it in a pure form due to
its low yield (approximately 2%) and contamination with a
few side-products of close polarity.
1-Fluoro-4-nitrobenzene (14) was an exception among the
reactive species. When compound 14 was treated with
sulphone 1 in the KOH/DMSO system (Scheme 3, Table
1), only one compound, namely the product of fluorine
substitution 12c, was found in the reaction mixture in 52%
yield. However, the reaction in the t-BuOK/DMF system
afforded three compounds: the VNS (the major product),
ONSH and fluorine substitution products 14a, 14b and
12c, respectively. It should be herein added that the product
of halogen substitution (compound 12c) was also isolated
from the reaction of 1-chloro-4-nitrobenzene (15) and
sulphone 1, but its yield in the KOH/DMSO system was
much lower (6%).
However, when the reactions of sulphone 1 and nitroarenes
(Scheme 3, Table 1) or nitroheteroarenes (Scheme 4,
Table 1) were carried out in the KOH/dimethylsulphoxide
base/solvent system at room temperature (abbreviated
further in the text to ‘KOH/DMSO system’) no expected
products of the VNS, i.e. compounds containing only the
phenylsulphonylmethyl substituent, were found in the
reaction mixtures. Instead the phenylsulphinate anion was
eliminated and products with the benzotriazolylmethyl
residue (the VNS products) were isolated from the reaction
mixtures. Another type of compound was also detected in
the reaction mixtures. The compounds were identified as
products of oxidation of the s-adducts. This kind of conver-
sion of the s-complexes is known as oxidative nucleophilic
The VNS and ONSH products can be easily distinguished
by their 1H NMR spectra. The singlet for the methine proton
in the ONSH products appears at much higher frequencies
(between 8 and 9 ppm) than the one for the methylene
proton in the VNS products (between 6.1 and 6.6 ppm).
The benzotriazole protons 5-H and 6-H are observed at
about 7.5 ppm as threefold doublets with two ortho

7276
M. K. Bernard / Tetrahedron 56 (2000) 7273–7284
Scheme 4.
couplings (8.5 and 7 Hz) and one meta coupling (1 Hz). The
remaining protons 4-H and 7-H should give also the same
pattern, that is threefold doublets with ortho, meta and para
couplings. However, owing to a small difference between
the latter two couplings (both are approximately 1 Hz) and
the large half-width, the signals are not well resolved and
appear usually as a doublet of pseudotriplets, sometimes
even as distorted doublets (in the Experimental part these
signals are designated as multiplets). In the spectra of the
VNS products these signals can be seen at higher frequen-
cies (ca. 8 ppm) than the 5-H and 6-H threefold doublets,
but in the spectra of the ONSH products the signal for the 7-
H proton is shifted strongly upfield to ca. 7.2 ppm. This shift
can be attributable to the location of the 7-H proton in the
shielding zone of the tosyl group.
of 17b were assigned to the 3-H and 6-H protons of the
dinitrobenzene ring, respectively, using NOE difference
spectroscopy. Irradiation of the methine proton (8.27 ppm)
resulted in enhancement of both 3-H and 6-H protons, but
the signal at 9.07 ppm was enhanced about four times
stronger, so it was assigned to the closer 6-H proton.
The outcome of the reaction with less electrophilic arenes
was not predictable. Upon treatment with sulphone 1 in the
KOH/DMSO system nitrobenzene (12) gave several
products, but I was not able to isolate any pure compound.
The reaction in the t-BuOK/DMF system led to a similar
mixture of compounds from which only the ONSH product
12b was isolated in 4% yield. I unsuccessfully tried to shift
the reaction course toward the ONSH products by passing
oxygen through the reaction mixture in the t-BuOK/DMF
system (method D). The slow reacting carbanion of 1 was
The singlets at 8.96 and 9.07 ppm in the 1H NMR spectrum

M. K. Bernard / Tetrahedron 56 (2000) 7273–7284
7277
eliminated quickly from the reaction medium and after
30 min the reaction mixture consisted mainly of tars that
prevented isolation of any pure product. Besides, the appli-
From the above described results the following conclusions
can be drawn.
cation of KMnO4 in liquid ammonia according to van der
First, the benzotriazolate anion is indeed a poorer leaving
group in the VNS of hydrogen than the phenylsulphinate.
15,16
´
Plas and Wozniak
was ineffective for oxidation of the
s-adducts due to low solubility of sulphone 1 in this
medium. Using 10-fold excess of nitrobenzene (12) or
prolongation of the reaction time did not lead to isolable
compounds either.
Second, more preference for the oxidation of the s-adducts
in the t-BuOK/DMF system in comparison with the KOH/
DMSO one reflects greater stabilization of these adducts in
this system. It seems that the course of the reaction with
sulphone 1 shows some similarities to the VNS in which
tertiary carbanions enter the ortho position to the nitro
group in analogous conditions.20 Marginally successful
efforts were made to find a principal factor in the oxidation
of the s-complexes. The reaction of sulphone 1 and
1-chloro-4-nitrobenzene (15) carried out under argon in
deoxygenated DMF according to the method B still led to
both VNS and ONSH products 15a and 15b. Albeit the yield
of 15b dropped a bit from 41 to 32%, the yield of 15a was
again very low (4%). It means that apart from the oxygen
dissolved in a solvent also other factors, like transfer of
oxygen from nitroarene, may play an important role in the
oxidation of the s-adducts.
The reaction of 1 with 1-nitronaphthalene (13) in both base/
solvent systems provided only two products 13a and 13b
(Scheme 3, Table 1). The VNS product 13a, substituted at
the ortho position in respect to the nitro group, was obtained
in a moderate yield (25–39%). The ortho substitution was
confirmed by large coupling constants for doublets of the
3-H and 4-H protons (Jˆ8.6 Hz), and also by an NOE
difference experiment. Upon irradiation of the methylene
group resonance the difference spectrum showed enhance-
ment of the 3-H doublet and also the multiplet (distorted
doublet) of the 7-H proton of the benzotriazole ring. The
remaining protons of the naphthalene ring were unaffected.
A similar preference for the ortho substitution, even in the
KOH/DMSO system, was observed in the VNS of 1-nitro-
naphthalene (13) and chloromethyl p-tolyl sulphone.17 This
fact was explained by higher energy of the para s-adduct in
comparison with the ortho one. Another product, compound
13b, was isolated in a low yield (2–4%) from the reaction
mixtures of 1 and 13 in both systems. The high resolution
mass spectrum shows that the exact mass for the molecular
ion is 201.0432 Da/charge which corresponds to a formula
of C11H7NO3. The IR spectrum reveals a strong carbonyl
band at 1692 cmϪ1 and another intense band close to
1500 cmϪ1. The latter one can be assigned to a nitro
When tetrahydrofuran was used instead of dimethylforma-
mide in the method B (method E), the reaction rate was
significantly slower and after 90 min most of the starting
materials used in this experiment, i.e. compounds 15 and
1, were unchanged in the reaction mixture.
Third, the process that is hindered in the reaction is the
elimination step. The elimination in the VNS proceeds via
a transition state involving the anti arrangement of the
proton being abstracted by the base and the leaving group.
Moreover, transfer of charge to the leaving group is assisted
by its delocalization in the sulphonyl moiety. This would
require both oxygen atoms of the sulphonyl group to adopt a
gauche orientation with respect to the forming double bond,
exactly like it has been determined for a-sulphonyl
carbanions, where the lone pair of electrons is placed
gauche to the two sulphonyl O atoms.21 A bulky substituent,
like the benzotriazole moiety, pushes the sulphonyl group
out of this orientation and therefore retards the elimination
step. As was mentioned in the introduction, the first step of
the VNS of hydrogen is the fast and reversible formation of
s-adducts. When highly electrophilic compounds, like 16,
17 or 22, are subjected to the reaction, the equilibrium of the
first step is strongly shifted toward the s-adducts, so their
concentration is high enough to ensure satisfactory yields of
the VNS or even ONSH products. However, when
compounds of comparatively low electrophilicity, like
pyrazole 18 or imidazole 20, are used in the reaction, the
concentration of the s-adducts is insufficient for the
elimination or oxidative removal of hydrogen.
1
group. The H NMR spectrum in the 7.8–8.5 ppm region
is consistent with a 1,2-substituted nitronaphthalene, and a
singlet at 10.17 ppm may represent an aldehyde proton. On
the basis of the above data and literature information18,19 the
structure of compound 13b was established as 1-nitro-
naphthalene-2-carboxaldehyde.
1-Ethyl-5-nitroindazole (21) behaved similarly to
compound 13 upon treatment with sulphone 1 giving only
the VNS product 21a in the KOH/DMSO system. Although
the reaction in this system led to an acceptable yield (45%)
of 21a, the reaction in the t-BuOK/DMF system was domi-
nated by tars and the yield of 21a dropped to 5%. In the
latter system the presence of small amounts of the ONSH
product 21b could not be excluded.
Treatment of compounds 18 and 20 with sulphone 1
(Scheme 4, Table 1) gave unacceptable results regardless
of the system used. The prolongation of the reaction time led
to slow decomposition of the starting materials. Only the
ONSH product 18b was isolated in a poor yield (3%) from
the reaction carried out in the KOH/DMSO system.
Bulkiness of the base has no significant effect on the
elimination. Using t-BuOK instead of KOH (DMSO as a
solvent, method C) led to similar results like in method A.
For example, from the reaction of compounds 15 and 1,
according to method C, I isolated 45% of 15a and 7% of
12c.
The reaction of 5-nitroquinoline (23) and 1 afforded the
VNS product 23a as a major component of the reaction
mixture in both base/solvent systems (Scheme 4, Table 1).
Although a bit more of the ONSH product 23b was
produced in the method B, its yield was low in both
systems.
The hindered elimination step changed the reaction course

7278
M. K. Bernard / Tetrahedron 56 (2000) 7273–7284
Scheme 5.
in these cases where conventional SNAr is possible. Thus in
the KOH/DMSO system 1-fluoro-4-nitrobenzene (14) gave
only compound 12c resulted from the exchange of the
fluorine atom. The SNAr products were also isolated from
the reaction mixtures of sulphone 1 and 1-chloro-4-nitro-
benzene (15) (compound 12c) or 1-chloro-2,4-dinitro-
benzene (17) (compound 16b). This constitutes an
additional proof for the hindrance of the elimination step
as the VNS of hydrogen is known to occur faster at carbons
bearing hydrogen atoms than at those connected with other
substituents. For example, the SNAr of halogen occurred to a
negligible extent in comparison with the VNS of hydrogen
even for 1-fluoro-2,4-dinitrobenzene containing an easily
replaceable fluorine atom.22
participation of the neighbouring nitro group may play a
key role in its formation.
A further evidence for the above described hindrance in the
elimination step provided a series of reactions I performed
using sulphoxide 2 and nitroarenes 12–23 (Schemes 3 and
4, Table 1). Either in the KOH/DMSO or t-BuOK/DMF
system only the VNS products 12a–23a were isolated
from the reaction mixtures. Analysis of the 1H NMR spectra
of the reaction mixtures did not reveal signals corresponding
to the ONSH products as well as compounds resulted from
the nucleophilic substitution of halogen. The reaction was
very fast, for example it took 1–2 min to be completed for
the very reactive dinitroarenes 16 and 17. Disappointing
yields for some compounds, especially when the VNS was
carried out in the t-BuOK/DMF system, might be attributed
to side reactions like substitution of the benzotriazole resi-
due. From the reaction of 1 and 12 I isolated only the VNS
product 12a, substituted ortho to the nitro group. The low
yield (7 or 20%) was partly due to tedious purification,
which included preparative TLC. But generally the yields
were good, even for the less electrophilic heterocycles 18
and 20. Compared to the bulky sulphonyl group the steric
requirements imposed by the sulphoxide group are much
lower, so the latter one can adopt considerably easier a
favourable conformation for the anti elimination. Small
amounts of 1-nitronaphthalene-2-carboxaldehyde (13b)
were also isolated from the reactions of 13 and 2 in both
base/solvent systems.
The assumption of the hindrance of the elimination step was
further confirmed by unsuccessful attempts to react tertiary
carbanion precursors 1a and 1b, containing additional
leaving groups, with some nitroarenes (Scheme 5).
The carbanion precursors 1a and 1b were obtained by
lithiation of sulphone 1 and subsequent reactions with hexa-
chloroethane or diphenyl disulphide. Compounds 1a and 1b
were subjected to the VNS of hydrogen with nitrobenzene
(12) or 1-nitronaphthalene (13). Regardless of the system
base/solvent used only starting materials were recovered
from the reaction mixtures or, when more drastic conditions
were applied, decomposition of the carbanion precursors 1a
or 1b was observed. Steric repulsion between the sub-
stituents in the s-adduct effectively prevented their suitable
arrangement for elimination.
Finally, I conducted the VNS experiments using sulphones
4, 7, 10 and sulphoxides 5, 8, 11 (Scheme 6, Table 2).
Apart from the reaction of the triazole derivatives with
1,3-dinitrobenzene (16) and nitrobenzotriazole 22 the
results were usually disappointing. Regardless of the system
base/solvent used, only the VNS product 24 was isolated in
16–46% yield from the reaction mixtures of the carbanion
precursors 4 or 5 with 1,3-dinitrobenzene (16). The
carbanion precursor 7 treated with 16 gave both VNS and
ONSH products 25a and 25b in low yields, regardless of
conditions used, whereas the reactions of sulphoxide 8 with
16 led only to compound 25a. Apart from the difficulties in
the elimination step, the low yields of these products may be
due to low stability of carbanions derived from sulphones 4,
7 and sulphoxides 5, 8 in the strong alkaline medium.
On the basis of the above discussion it is clear why the VNS
for nitropyrazole 19 led to such poor yield of the VNS
product 19b. Coplanar alignment of the pyrazole and phenyl
rings (the advantageous arrangement)23 prohibits attainment
of the anti conformation because of the steric repulsion
between the benzotriazole residue and the phenyl (or
nitro) group. When both rings are noncoplanar, the phenyl
ring forces the sulphonyl group out of the favourable gauche
conformation.
On the other hand, the reaction of sulphone 1 and nitro-
indazole 21 led only to the VNS product 21a because of
the favourable for elimination geometry around the reaction
centre.
Similar factors like those discussed for the reaction of
sulphone 1 or sulphoxide 2 with nitroarenes seem to govern
the reaction course in the other sulphones and sulphoxides
containing azole rings. Hence, apart from compound 4, the
reactions of sulphones 7 and 10 led to both VNS and ONSH
products, while the reactions of sulphoxides 5, 8 and 11
gave only the VNS products.
A similar preference for the VNS product 13a in the reaction
of sulphone 1 and 1-nitronaphthalene (13) may be
connected with instability of the initially formed ONSH
product under the reaction conditions. The latter product
probably undergoes transformation into, inter alia, aldehyde
13b. Although compound 13b could result from hydrolysis
of the ONSH product in a similar way to the already
described synthesis of aromatic aldehydes from bis(benzo-
triazol-1-yl)methyl or dihalomethyl nitroarenes,10,19 the
In conclusion, the above discussed reactions provide some
insight into the elimination process, particularly steric

M. K. Bernard / Tetrahedron 56 (2000) 7273–7284
7279
Scheme 6.
requirements, involving the phenylsulphinate anion as
the leaving group in the VNS of hydrogen. Although the
SO2Ar and SOAr groups are common leaving groups in
aromatic nucleophilic substitution they are not generally
lost in the VNS.2,3,24 However, the SO2Ar could be forced
to leave on further transformations involving the VNS
products.4,17,23,25–27 Furthermore, the described method
afforded compounds with the benzotriazole residue. Taking
into account a plethora of possibilities of the exchange of
this group for other moieties,9 the obtained compounds may
be useful as starting materials for further synthesis. Some of
the products may be also interesting due to their biological
properties because diaryl- and dihetarylmethanes are known
as effective anti-HIV1 agents.28
Experimental
MgSO4 was used for drying extracts. Flash chromatography
(FC) was performed using silica gel 60, 230–400 mesh
(Merck). Preparative TLC was carried out on Merck PLC
plates (no 5717). Melting points were determined on a
Boetius apparatus and are uncorrected. 1H NMR were
recorded at 300 MHz on Varian Unity 300 or Varian Gemini
300 instruments in DMSO-d6. Low and high resolution mass
spectra were run on an AMD 402 instrument. IR spectra
were run in KBr on a Specord 75-IR apparatus.
Starting materials, apart from these prepared below were
obtained by known procedures7,23,27,29 or were commercially
available.
Abbreviations: sBnˆsubstituted benzyl, Btˆbenzotriazole,
FCˆflash chromatography, SMˆstarting material.
Table 2. Products of the reaction of sulphones 4, 7, 10 or sulphoxides 5, 8,
11 with nitroarenes 16, 18 or 22
Starting materials
Products
Yields (%)
Lithiation of 1 and subsequent reactions with
electrophiles: synthesis of 1a–1b. General method
Method Aa
Method B
n-BuLi (1.9 cm3 of 1.6 mol solution in THF, 3 mmol) was
added dropwise to a cooled (Ϫ50ЊC) and stirred solution of
benzotriazole 1 (0.82 g, 3 mmol) in dry THF (80 cm3). Stir-
ring was continued at this temperature for 20 min and a
solution of electrophile (3 mmol) in THF (3 cm3) was
added dropwise. The resulted mixture was stirred for 3 h
at Ϫ50ЊC, then the temperature was allowed to rise slowly
(2 h) to Ϫ10ЊC, and the reaction mixture was quenched with
saturated NH4Cl (50 cm3). The organic layer was separated,
dried and the solvent was distilled off. The residue was
crystallized from EtOH.
4ϩ16
5ϩ16
7ϩ16
24
24
43
32
18
3
4
74
0
38
78
0
46
16
10
13
10
34
29
37
46
17
3
25a
25b
25a
26a
26b
26a
27a
27b
28
8ϩ16
10ϩ16
11ϩ16
10ϩ22
11ϩ18
9
a Method A: KOH/DMSO/23ЊC; method B: t-BuOK/DMF/Ϫ30ЊC.

7280
M. K. Bernard / Tetrahedron 56 (2000) 7273–7284
1
1-[Chloro(phenylsulphonyl)methyl]benzotriazole (1a).
Yield: 69%. Pale yellow cubes, mp 176–178ЊC. H NMR,
138–139ЊC). The H NMR spectra of compounds 7 and 8
were in accordance with the published data.8
1
d: 7.54 (ddd, Jˆ8.5, 7 and 1 Hz, 1H, Bt), 7.58–7.82 (m, 6H,
BtϩPh), 7.98–8.01 (m, 1H, Bt), 8.14–8.17 (m, 1H, Bt), 8.98
(s, 1H, CH). IR: 3088, 2968, 1615, 1456, 1341, 1330, 1322,
1-(Phenylthiomethyl)-1,2,4-triazole (9). Compound 9 was
obtained from 1,2,4-triazole and chloromethyl phenyl sul-
fide in an identical manner to that described for compound
1287, 1169, 1158, 1034, 815, 771, 757, 730, 715, 688 cmϪ1
.
1
Anal. Calcd for C13H10ClN3O2S: C 50.73, H 3.28, Cl 11.52,
N 13.65; found: C 51.09, H 3.61, Cl 11.48, N 13.91.
3. Yield: 2.68 g (49%), almost colourless oil. H NMR, d:
5.77 (s, 2H, CH2), 7.30–7.44 (m, 5H, Ph), 8.00 (s, 1H, 3-H),
8.40 (s, 1H, 5-H). IR: 3105, 3052, 2990, 1504, 1486, 1440,
1276, 1199, 1133, 1011, 752, 690, 675 cmϪ1. Anal. Calcd
for C9H9N3S: C 56.52, H 4.74, N 21.97; found: C 56.18, H
4.63, N 22.34.
1-[Phenylsulphonyl(phenylthio)methyl]benzotriazole (1b).
1
Yield: 48%. Colourless needles, mp 127–129ЊC. H NMR,
d: 7.26–7.72 (m, 12H, BtϩPh), 8.03–8.07 (m, 2H, Bt), 8.28
(s, 1H, CH). IR: 3055, 2965, 1462, 1449, 1325, 1296, 1168,
1149, 1087, 1039, 748, 720, 696 cmϪ1. Anal. Calcd for
C19H15N3O2S2: C 59.82, H 3.96, N 11.02; found: C 59.94,
H 4.11, N 11.08.
1-(Phenylsulphonylmethyl)-1,2,4-triazole (10). Compound
9 (3.82 g, 20 mmol) was oxidized with m-CPBA (12.40 g,
50 mmol) in a similar manner to that described for
compounds 4 and 5. FC (hexanes–ethyl acetate 1:2) gave
2.48 g (56%) of sulphone 10 as colourless prisms (50%
3,5-Dimethyl-1-(phenylthiomethyl)pyrazole (3). Sodium
hydride (0.72 g, 30 mmol) was added portionwise under
argon to a stirred solution of 3,5-dimethylpyrazole (2.88 g,
30 mmol) in dry DMF (30 cm3). The resulted mixture was
stirred under argon at 22ЊC for 30 min and chloromethyl
phenyl sulphide (4.92 g, 31 mmol) was added dropwise
(the temperature was kept below 50ЊC). The mixture was
stirred under argon at 22ЊC for 1 h, then at 50ЊC for 2 h,
poured into water (600 cm3) and extracted with diethyl ether
(3×100 cm3). The combined ethereal extracts were washed
with water and dried. The residue after evaporation of the
solvent was flash-chromatographed (hexanes–ethyl acetate
1:1) to give 2.95 g (45%) of pyrazole 3 as thick pale yellow
1
EtOH), mp 166–167ЊC. H NMR, d: 6.12 (s, 2H, CH2),
7.62–7.82 (m, 5H, Ph), 8.00 (s, 1H, 3-H), 8.49 (s, 1H,
5-H). IR: 3099, 2966, 2915, 1510, 1446, 1364, 1327,
1297, 1275, 1159, 1133, 1123, 1080, 1000, 779, 761, 686,
675, 641 cmϪ1. Anal. Calcd for C9H9N3O2S: C 48.42, H
4.06, N 18.82; found: C 48.28, H 4.35, N 18.50.
1-(Phenylsulphinylmethyl)-1,2,4-triazole (11). Compound
9 (1.66 g, 8.7 mmol) was oxidized with NaIO4 (2.82 g,
13.2 mmol) in a similar manner to that described for
compound 2.7 FC of the crude reaction mixture (hexanes–
ethyl acetate 1:2) afforded 1.00 g (56%) of sulphoxide 11 as
1
1
oil. The H NMR spectrum was in accordance with the
colourless plates, mp 126–128ЊC. H NMR, d: 5.50 (d,
published data.30
Jˆ13 Hz, 1H, CH2), 5.71 (d, Jˆ13 Hz, 1H, CH2), 7.53–
7.63 (m, 5H, Ph), 8.01 (s, 1H, 3-H), 8.40 (s, 1H, 5-H). IR:
3126, 3111, 2994, 2932, 1510, 1452, 1280, 1209, 1129,
1088, 1040, 1016, 769, 740, 697, 672 cmϪ1. Anal. Calcd
for C9H9N3OS: C 52.16, H 4.38, N 20.28; found: C 52.38,
H 4.37, N 20.44.
3,5-Dimethyl-1-(phenylsulphonylmethyl)pyrazole (4) and
3,5-dimethyl-1-(phenylsulphinylmethyl)pyrazole
(5).
m-CPBA (5.18 g, 30 mmol) was added portionwise to a
stirred and cooled (0–4ЊC) solution of compound 3
(2.80 g, 12.8 mmol) in CHCl3 (150 cm3). Stirring was
continued for 5 h at 22ЊC, the reaction mixture was washed
with saturated NaHCO3 (3×40 cm3) followed by water, and
dried. The residue after evaporation of the solvent was flash-
chromatographed (ethyl acetate) to give 1.05 g (33%) of
pyrazole 4 (Rfˆ0.75) as colourless needles (60% EtOH),
mp 94–96ЊC, and 1.52 g (50%) of pyrazole 5 (Rfˆ0.48)
as colourless needles (hexanes–ethyl acetate 1:1), mp 80–
81ЊC (lit.30 75–76ЊC). Compound 5 can be also obtained in
66% yield by oxidation of pyrazole 3 with NaIO4 according
to a method described for compound 2.7 4: 1H NMR, d: 1.95
(s, 3H, CH3), 2.09 (s, 3H, CH3), 5.70 (s, 2H, CH2), 5.86 (s,
1H, 4-H), 7.58–7.79 (m, 5H, Ph). IR: 3060, 2975, 2911,
1559, 1445, 1388, 1315, 1296, 1136, 1076, 782, 772, 739,
680 cmϪ1. Anal. Calcd for C12H14N2O2S: C 57.58, H 5.64, N
11.19; found: C 57.71, H 5.49, N 11.31.
Reactions of nitroarenes with sulphones 1, 4, 7, 10 and
sulphoxides 2, 5, 8, 11
Method A. Finely powdered KOH (400 mg) was added in
one portion to a stirred solution of sulphone (1 mmol) or
sulphoxide (1 mmol) and nitroarene (1 mmol) in dry DMSO
(5 cm3) under argon. The resulting dark coloured mixture
was vigorously stirred under argon for 20 min at 22ЊC (if the
reaction time was different from 20 min it was given in
Table 1), quenched with 3% HCl (30 cm3) and extracted
with CHCl3 (3×20 cm3). The extract was washed with
water, dried and the solvent was removed under vacuum.
Further purification procedures are given at the description
of individual compounds.
Method B. A solution of sulphone (1 mmol) or sulphoxide
(1 mmol) and nitroarene (1 mmol) in dry DMF (4 cm3) was
added to a stirred solution of t-BuOK (336 mg, 3 mmol) in
dry DMF (3 cm3). The resulted mixture was stirred for 25
(the reaction of compounds 13–15, 19 and 21–23 with
sulphoxide 1) or 90 min at Ϫ30ЊC (if the reaction time
was different from these values it was given in Table 1),
quenched with 3% HCl (30 cm3) and extracted with CHCl3
(3×20 cm3). The extract was washed with water, dried and
the solvent was removed under vacuum. Further purification
1-(Phenylsulphonylmethyl)benzimidazole
(7)
and
1-(phenylsulphinylmethyl)benzimidazole (8). When
1-(phenylthiomethyl)benzimidazole8 (6) was oxidized with
m-CPBA according to a known procedure8 two compounds
were detected in the reaction mixture. Separation by FC
(ethyl acetate) gave 1.28 g (47%) of sulphone 7 (Rfˆ0.42)
as colourless prisms (benzene), mp 164–165ЊC (lit.8
148–150ЊC) and 1.08 g (42%) of sulphoxide 8 (Rfˆ0.12)
as colourless prisms (benzene), mp 141–143ЊC (lit.8

M. K. Bernard / Tetrahedron 56 (2000) 7273–7284
7281
procedures are given at the description of individual
compounds.
Btϩnaphthalene), 8.21 (d, Jˆ8.6 Hz, 1H, 4-H naphthalene).
IR: 3050, 1522, 1511, 1446, 1365, 1340, 1152, 1079, 830,
772, 749 cmϪ1. Anal. Calcd for C17H12N4O2: C 67.10, H
3.98, N 18.41; found: C 67.37, H 4.28, N 18.43.
Method C. Like method A, but t-BuOK (336 mg, 3 mmol)
was used instead of KOH.
1-Nitro-2-naphthalenecarboxaldehyde (13b). Purifica-
tion: see 13a, Rfˆ0.39. Yellow needles, mp 102–103ЊC
(lit.18 100–101ЊC). 1H NMR, d: 7.84–7.92 (m, 3H,
naphthalene), 8.13 (d, Jˆ8.5 Hz, 1H, 4-H naphthalene),
8.22–8.27 (m, 1H, naphthalene), 8.45 (d, Jˆ8.5 Hz, 1H,
5-H naphthalene), 10.17 (s, 1H, CHO). IR: 1692, 1511,
1502, 1355, 1210, 1046, 821, 763 cmϪ1. HRMS. Calcd for
C11H7NO3: 201.0426; found: 201.0432.
Method D. Like method B, but oxygen was passed through
the reaction mixture.
Method E. A solution of sulphone 1 (273 mg, 1 mmol) or
sulphoxide 1 (257 mg, 1 mmol) and nitroarene (1 mmol) in
dry THF (7 cm3) was added dropwise to a solution of
t-BuOK (336 mg, 3 mmol) in dry THF (3 cm3). The reaction
was carried out as for method B.
1-(5-Fluoro-2-nitrobenzyl)benzotriazole (14a). Method
B: FC (hexanes–ethyl acetate 2:1, Rf1ˆ0.58). Pale yellow
prisms (80% EtOH), mp 114–115ЊC. H NMR, d: 6.36 (s,
2H, CH2), 6.69 (dd, JHFˆ9.5 Hz, JHHˆ2.5 Hz, 1H, 6-H
sBn), 7.44–7.62 (m, 3H, 4-H sBnϩBt), 7.89–7.92 and
8.11–8.14 (2×m, 2×1H, Bt), 8.33 (dd, JHHˆ9 Hz,
JHFˆ5 Hz, 1H, 3-H sBn). IR: 3080, 2915, 1516, 1513,
1488, 1443, 1340, 1326, 1308, 1293, 1142, 1128, 1056,
741, 725, 683 cmϪ1. Anal. Calcd for C13H9FN4O2: C
57.36, H 3.33, N 20.52; found: C 57.17, H 3.58, N 20.59.
Unless otherwise stated, the purification procedure for the
particular compound applies to each starting material and
method of synthesis.
1-(2-Nitrobenzyl)benzotriazole (12a). Sulphoxide 2 as
SM. FC (hexanes–ethyl acetate 2:1, Rfˆ0.42) followed by
preparative TLC (hexanes–ethyl acetate 2:1) and crystal-
lization (70% EtOH). Almost colourless plates, mp 138–
1
139ЊC. H NMR, d: 6.35 (s, 2H, CH2), 6.81–6.84 (m, 1H,
6-H Ph), 7.44 and 7.56 (2×ddd, Jˆ8.5, 7 and 1 Hz, 2×1H,
Bt), 7.59–7.70 (m, 2H, 4- and 5-H Ph), 7.84–7.87 and 8.09–
8.13 (2×m, 2×1H, Bt), 8.19 (dd, Jˆ8 and 1.5 Hz, 1H, 3-H
Ph). IR: 3031, 2999, 1500, 1334, 1311, 1289, 1278, 1239,
1206, 1069, 835, 762, 716, 699 cmϪ1. Anal. Calcd for
C13H10N4O2: C 61.41, H 3.96, N 22.04; found: C 61.30, H
4.17, N 22.41.
1-[5-Fluoro-2-nitrophenyl(phenylsulphonyl)methyl]ben-
zotriazole (14b). Purification: see 14a, Rfˆ0.45. Tiny
1
yellow prisms (EtOH), mp 198–200ЊC (dec.). H NMR,
d: 7.34–7.47 (m, 5H, PhϩBt), 7.61–7.68 (m, 3H,
PhϩBt), 7.78 (ddd, JHHˆ9 and 3 Hz, JHFˆ7.5 Hz, 1H,
4-H sBn), 8.07–8.10 (m, 1H, Bt), 8.19 (s, 1H, CH), 8.28
(dd, JHHˆ9 Hz, JHFˆ5.5 Hz, 1H, 3-H sBn), 8.59 (dd,
JHHˆ3 Hz, JHFˆ10 Hz, 1H, 6-H sBn). IR: 3061, 3032,
2975, 1562, 1498, 1425, 1317, 1304, 1291, 1280, 1248,
1-[2-Nitrophenyl(phenylsulphonyl)methyl]benzotriazole
(12b). Sulphone 1 as SM. FC (hexanes–ethyl acetate 2:1,
Rfˆ0.34). Long yellow plates (MeOH), mp 179–181ЊC. 1H
NMR, d: 7.36–7.47 (m, 5H, PhϩBt), 7.61–7.66 (m, 3H,
PhϩBt), 7.85 (ddd, Jˆ8.5, 7 and 1 Hz, 1H, Bt), 8.01–8.14
(m, 3H, PhϩBt), 8.12 (singlet overlapped with multiplet,
1H, CH), 8.86 (dd, Jˆ8 and 1 Hz, 1H, PhNO2). MS, m/z
(relative intensity, ion): 395 (0.2%, MϩH), 253 (100%,
MϪPhSO2). IR: 3044, 2945, 1530, 1447, 1349, 1330,
1314, 1150, 1049, 742, 721 cmϪ1. Anal. Calcd for
C19H14N4O4S: C 57.86, H 3.58, N 14.21; found: C 57.94,
H 3.34, N 14.39.
1123, 1025, 824, 713, 695 cmϪ1
. Anal. Calcd for
C19H13FN4O4S: C 55.34, H 3.18, N 13.59; found: C 55.51,
H 3.10, N 13.56.
1-(5-Chloro-2-nitrobenzyl)benzotriazole
(15a).
FC
(hexanes–ethyl acetate 5:1, Rfˆ0.62). Yellow needles
1
(EtOH), mp 168–169ЊC. H NMR, d: 6.24 (s, 2H, CH2),
7.00 (d, Jˆ2.5 Hz, 1H, 6-H sBn), 7.46 and 7.60 (2×ddd,
Jˆ8.5, 7 and 1 Hz, 2×1H, Bt), 7.74 (dd, Jˆ9 and 2.5 Hz,
1H, 4-H sBn), 7.90–7.93 (m, 1H, Bt), 8.10–8.14 (m, 1H,
Bt), 8.24 (d, Jˆ9 Hz, 1H, 3-H sBn). IR: 3068, 3050, 1609,
1-[4-Nitrophenyl(phenylsulphonyl)methyl]benzotriazole
(12c). 4-Fluoronitrobenzene 14 as SM. Method A: crystal-
lization (butanone), method B: FC (hexanes–ethyl acetate
2:1, Rfˆ0.28) followed by crystallization (butanone). Pale
1571, 1530, 1524, 1340, 1272, 1096, 895, 846, 748 cmϪ1
.
Anal. Calcd for C13H9ClN4O2: C 54.09, H 3.14, Cl 12.28, N
19.41; found: C 53.94, H 3.08, Cl 12.33, N 19.51.
1
yellow prisms, mp 233–234ЊC (dec.). H NMR, d: 7.37–
1-[5-Chloro-2-nitrophenyl(phenylsulphonyl)methyl]-
benzotriazole (15b). Purification: see 15a, Rfˆ0.49. Pale
yellow needles (EtOH), mp 193–195ЊC. 1H NMR, d:
7.32–7.47 (m, 5H, BtϩPh), 7.60–7.66 (m, 3H, BtϩPh),
7.99 (dd, Jˆ9 and 2.5 Hz, 1H, 4-H sBn), 8.07–8.10 (m,
1H, Bt), 8.17 (s, 1H, CH), 8.20 (d, Jˆ9 Hz, 1H, 3-H sBn),
8.84 (d, Jˆ2.5 Hz, 1H, 6-H sBn). MS, m/z (relative inten-
sity, ion): 429 (0.3%, MϩH), 287 (100%, MϪPhSO2). IR:
3055, 3010, 1569, 1531, 1451, 1342, 1318, 1305, 1158,
7.65 (m, 7H, BtϩPh), 7.88–7.91 (m, 1H, Bt), 8.05–8.08 (m,
1H, Bt), 8.24 (s, 1H, CH), 8.32–8.36 (m, 2H, 2-H and 6-H
sBn), 8.40–8.44 (m, 2H, 3-H and 5-H sBn). IR: 3080, 1518,
1489, 1446, 1347, 1333, 1310, 1294, 1146, 1135, 1060, 748,
739, 686 cmϪ1. Anal. Calcd for C19H14N4O4S: C 57.86, H
3.58, N 14.21; found: C 57.75, H 3.93, N 14.44.
1-(1-Nitronaphthalen-2-ylmethyl)benzotriazole (13a). FC
(hexanes–ethyl acetate 5:1, Rfˆ0.30). Yellow prisms (80%
EtOH), mp 141–143ЊC. 1H NMR, d: 6.24 (s, 2H, CH2), 7.43
(ddd, Jˆ8.5, 7 and 1 Hz, 1H, Bt), 7.42 (d, Jˆ8.6 Hz, 1H,
3-H naphthalene), 7.58 (ddd, Jˆ8.5, 7 and 1 Hz, 1H, Bt),
7.71–7.83 (m, 4H, Btϩnaphthalene), 8.09–8.13 (m, 2H,
1046, 909, 746, 715, 690 cmϪ1
. Anal. Calcd for
C19H13ClN4O4S: C 53.21, H 3.06, Cl 7.48, N 13.06;
found: C 53.46, H 3.06, Cl 7.61, N 13.05.
1-(2,4-Dinitrobenzyl)benzotriazole (16a). Method A (SM:

7282
M. K. Bernard / Tetrahedron 56 (2000) 7273–7284
1): crystallization, method A (SM: 2) and method B: FC
(hexanes–ethyl acetate 2:1, Rfˆ0.44). Long pale yellow
762 cmϪ1. Anal. Calc. for C11H10N6O2: C 51.16, H 3.90, N
32.55; found: C 51.09, H 4.12, N 32.56.
1
plates (EtOH), mp 155.5–156.5ЊC. H NMR, d: 6.51 (s,
2H, CH2), 6.96 (d, Jˆ8.5 Hz, 1H, 6-H sBn), 7.49 and 7.58
(2×ddd, Jˆ8.5, 7 and 1 Hz, 2×1H, Bt), 7.89–7.92 and 8.12–
8.15 (2×m, 2×1H, Bt), 8.46 (dd, Jˆ8.5 and 2.5 Hz, 1H, 5-H
sBn), 8.88 (d, Jˆ2.5 Hz, 1H, 3-H sBn). IR: 3097, 3066,
3051, 3040, 1586, 1575, 1521, 1490, 1472, 1325, 1289,
1242, 1205, 1126, 1073, 1036, 814, 774, 766, 718,
704 cmϪ1. Anal. Calcd for C13H9N5O4: C 52.18, H 3.03, N
23.41; found: C 52.14, H 3.15, N 23.29.
1-[1-Methyl-4-nitropyrazol-5-yl(phenylsulphonyl)methyl]-
benzotriazole (18b). Sulphone 1 as SM. Purification: see
18a, Rf1ˆ0.49. Green–yellow prisms (MeOH), mp 195–
196ЊC. H NMR, d: 4.41 (s, 3H, CH3), 7.22–7.26 (m, 1H,
Bt), 7.46–7.64 (m, 4H, BtϩPh), 7.79–7.88 (m, 3H, Ph),
8.16–8.19 (m, 1H, Bt), 8.48 (s, 1H, 3-H pyrazole or CH),
8.52 (s, 1H, 3-H pyrazole or CH). IR: 3088, 3061, 2962,
1515, 1459, 1414, 1380, 1353, 1341, 1321, 1157, 1063, 772,
755, 724 cmϪ1. Anal. Calcd for C17H15N6O4S: C 51.12, H
3.79, N 21.04; found: C 51.23, H 3.58, N 21.09.
1-[2,4-Dinitrophenyl(phenylsulphonyl)methyl]benzo-
triazole (16b). Purification: see 16a, method B, Rfˆ0.40.
Yellow–orange needles (EtOH), mp 205–206ЊC. 1H NMR,
d: 7.28–7.31 (m, 1H, Bt), 7.37–7.48 (m, 4H, BtϩPh). 7.61–
7.70 (m, 3H, BtϩPh), 8.07–8.10 (m, 1H, Bt), 8.25 (s, 1H,
CH), 8.81 (d, Jˆ2.5 Hz, 1H, 3-H sBn), 8.88 (dd, Jˆ9 and
2.5 Hz, 1H, 5-H sBn), 9.16 (d, Jˆ9 Hz, 1H, 6-H sBn). IR:
3092, 3040, 2980, 1534, 1445, 1349, 1334, 1303, 1146,
1037, 748, 732, 711 cmϪ1. Anal. Calcd for C19H13N5O6S:
C 51.93, H 2.98, N 15.94; found: C 51.88, H 3.05, N 16.27.
1-[3-Methyl-4-nitro-1-(4-nitrophenyl)-pyrazol-5-ylmethyl]-
benzotriazole (19a). FC (hexanes–ethyl acetate 2:1,
Rfˆ0.34). Yellow plates (EtOH), mp 194–195ЊC. 1H
NMR, d: 2.58 (s, 3H, CH3), 6.32 (s, 2H, CH2), 7.40 and
7.57 (2×ddd, Jˆ8.5, 7 and 1 Hz, 2×1H, Bt), 7.78–7.81 (m,
1H, Bt), 7.85–7.90 (m, 2H, Ph), 7.98–8.01 (m, 1H, Bt),
8.28–8.33 (m, 2H, Ph). IR: 3089, 1574, 1525, 1501, 1446,
1349, 865, 826, 751 cmϪ1. Anal. Calcd for C17H13N7O4: C
53.82, H 3.45, N 25.85; found: C 53.91, H 3.40, N 26.14.
1-(5-Chloro-2,4-dinitrobenzyl)benzotriazole (17a). FC
(hexanes–ethyl acetate 2:1, Rfˆ0.53). Yellow plates
1-[3-Methyl-4-nitro-1-(4-nitrophenyl)pyrazol-5-yl(phenyl-
sulphonyl)methyl]benzotriazole (19b). FC (hexanes–
ethyl acetate 1:1, Rfˆ0.55). Long yellow plates (EtOH),
1
(EtOH), mp 133–134ЊC. H NMR, d: 6.41 (s, 2H, CH2),
7.32 (s, 1H, 6-H sBn), 7.48 and 7.62 (2×ddd, Jˆ8.5, 7
and 1 Hz, 2×1H, Bt), 7.92–7.95 and 8.11–8.14 (2×m,
2×1H, Bt), 8.96 (s, 1H, 3-H sBn). IR: 3090, 1619, 1588,
1
mp 188–190ЊC (dec.). H NMR, d: 2.54 (s, 3H, CH3),
7.09–7.12 (m, 1H, Bt), 7.38–7.61 (m, 6H, BtϩPhϩ4-nitro-
phenyl), 7.76–7.82 (m, 3H, BtϩPh), 8.01–8.04 (m, 1H, Bt),
8.17–8.22 (m, 2H, 4-nitrophenyl), 8.51 (s, 1H, CH). IR:
3071, 2927, 1552, 1520, 1502, 1450, 1155, 760, 751,
686 cmϪ1. Anal. Calcd for C23H17N7O6S: C 53.18, H 3.30,
N 18.87; found: C 52.90, H 3.49, N 18.75.
1535, 1348, 1325, 1273, 1166, 1095, 962, 836, 754 cmϪ1
.
Anal. Calcd for C13H8ClN5O4: C 46.79, H 2.42, Cl 10.62, N
20.99; found: C 47.02, H 2.55, Cl 10.59, N 20.84.
1-[5-Chloro-2,4-dinitrophenyl(phenylsulphonyl)methyl]-
benzotriazole (17b). Purification: see 17a, Rfˆ0.49.
Yellow needles (EtOH), mp 165–167ЊC. 1H NMR, d:
7.25–7.28 (m, 1H, Bt), 7.37–7.49 (m, 4H, BtϩPh), 7.60–
7.71 (m, 3H, BtϩPh), 8.08–8.11 (m, 1H, Bt), 8.27 (s, 1H,
CH), 8.96 (s, 1H, 3-H), 9.07 (s, 1H, 6-H). IR: 3095, 3044,
1599, 1581, 1546, 1534, 1451, 1342, 1320, 1153, 1045, 835,
741, 716, 683 cmϪ1. Anal. Calcd for C19H12ClN5O6S: C
48.66, H 2.55, Cl 7.48, N 14.78; found: C 48.87, H 2.77,
Cl 7.31, N 14.90.
1-(1-ethyl-2-methyl-4-nitroimidazol-5-yl)methylbenzo-
triazole (20a). FC (hexanes–ethyl acetate 1:1, Rfˆ0.09).
Colourless plates (70% MeOH), mp 142–144ЊC. 1H
NMR, d: 1.05 (t, Jˆ7.5 Hz, 3H, CH2CH3), 2.44 (s, 3H,
N-CH3), 4.25 (q, Jˆ7.5 Hz, 2H, CH2CH3), 6.34 (s, 2H,
Ar-CH2), 7.45 and 7.63 (2×ddd, Jˆ8.5, 7 and 1 Hz,
2×1H, Bt), 7.87–7.90 and 8.06–8.10 (2×m, 2×1H, Bt).
IR: 3050, 2990, 2969, 2930, 1572, 1539, 1514, 1458,
1431, 1420, 1393, 1356, 1336, 1293, 781, 745 cmϪ1
.
1-(2,4-Dinitro-5-phenylsulphonylbenzyl)benzotriazole
Anal. Calcd for C13H14N3O2: C 68.40, H 6.18, N 18.41;
found: C 68.29, H 6.06, N 18.66.
(17c). Purification: see 17a, Rfˆ0.27. Pale yellow needles
1
(EtOH), mp 183–186ЊC. H NMR, d: 6.48 (s, 2H, CH2),
7.52 (ddd, Jˆ8.5, 7 and 1 Hz, 1H, Bt), 7.52 (s, 1H, 6-H
sBn), 7.59–7.65 (m, 5H, BtϩPh), 7.75–7.80 (m, 1H, Ph),
7.83–7.86 and 8.17–8.20 (2×m, 2×1H, Bt), 8.95 (s, 1H, 3-H
sBn). IR: 3088, 3064, 3034, 2977, 1543, 1367, 1352, 1327,
1155, 840, 830, 757, 747, 725, 602 cmϪ1. Anal. Calcd for
C19H13N5O6S: C 51.93, H 2.98, N 15.94; found: C 51.65, H
2.82, N 15.55.
1-(1-Ethyl-5-nitroindazol-4-ylmethyl)benzotriazole (21a).
FC (hexanes–ethyl acetate 1:1, Rfˆ0.23). Yellow needles
(EtOH), mp 149–150ЊC. 1H NMR, d: 1.50 (t, Jˆ7 Hz, 3H,
CH3), 4.52 (q, Jˆ7 Hz, 2H, CH2), 6.48 (s, 2H, CH2Ar), 7.43
and 7.58 (2×ddd, Jˆ8.5, 7 and 1 Hz, 2×1H, Bt), 7.82–7.85
(m, 1H, Bt), 7.87 (d, Jˆ9.5 Hz, 1H, 7-H), 7.95 (d, Jˆ9.5 Hz,
1H, 6-H), 8.05–8.08 (m, 1H, Bt), 8.73 (s, 1H, 4-H). IR:
3142, 3109, 3032, 2989, 2977, 1618, 1519, 1467, 1352,
1340, 1321, 1298, 1239, 1091, 830, 756 cmϪ1. Anal.
Calcd for C16H14N6O2: C 59.62, H 4.38, N 26.07; found:
C 59.60, H 4.29, N 26.25.
1-(1-Methyl-4-nitropyrazol-5-ylmethyl)benzotriazole
(18a). Sulphoxide 2 as SM. FC (hexanes–ethyl acetate 1:1,
Rfˆ0.36). Almost colourless prisms (MeOH), mp 146–
1
147ЊC. H NMR, d: 4.08 (s, 3H, CH3), 6.38 (s, 2H, CH2),
7.45 and 7.65 (2×ddd, Jˆ8.5, 7 and 1 Hz, 2×1H, Bt), 7.93–
7.97 and 8.07–8.10 (2×m, 2×1H, Bt), 8.38 (s, 1H, 3-H). IR:
3113, 2994, 1560, 1501, 1456, 1440, 1408, 1376, 1318,
1304, 1291, 1229, 1190, 1158, 1134, 1093, 929, 829, 777,
1-(2-Methyl-5-nitrobenzotriazol-4-ylmethyl)benzotriazole
(22a). Method A: crystallization, method B: FC (hexanes–
ethyl acetate 1:1, Rfˆ0.37). Pale yellow needles (EtOH), mp
1
182–183ЊC. H NMR, d: 4.55 (s, 3H, CH3), 6.55 (s, 2H,

M. K. Bernard / Tetrahedron 56 (2000) 7273–7284
7283
CH2), 7.42 and 7.59 (2×ddd, Jˆ8.5, 7 and 1 Hz, 2×1H, Bt),
7.90–7.93 and 8.03–8.06 (2×m, 2×1H, Bt), 8.12 (d,
Jˆ9.5 Hz, 1H, 7-H Bt), 8.24 (d, Jˆ9.5 Hz, 1H, 6-H Bt).
IR: 3079, 2940, 1609, 1527, 1444, 1347, 1336, 1288, 839,
825, 785, 754, 741, 731 cmϪ1. Anal. Calcd for C14H11N7O2:
C 54.36, H 3.59, N 31.70; found: C 54.42, H 3.90, N 31.56.
C14H10N4O4: C 56.38, H 3.38, N 18.79; found: C 56.43, H
3.21, N 18.98.
1-[2,4-Dinitrophenyl(phenylsulphonyl)methyl]benzimi-
dazole (25b). Purification: see 25a, Rfˆ0.60. Pale yellow
cubes (80% EtOH), mp 200–201ЊC. 1H NMR, d: 6.99–7.66
(4×m, 9H, benzimidazoleϩPh), 8.51 (s, 1H, 2-H benzimi-
dazole), 8.79 (dd, Jˆ8.5 and 2.5 Hz, 1H, 5-H sBn), 8.82 (d,
Jˆ2.5 Hz, 1H, 3-H sBn), 9.03 (d, Jˆ8.5 Hz, 1H, 6-H sBn).
IR: 3107, 3086, 3054, 1614, 1553, 1539, 1499, 1462, 1352,
1328, 1315, 1275, 1151, 754, 735, 719 cmϪ1. Anal. Calcd
for C20H14N4O6S: C 54.79, H 3.22, N 12.78; found: C 54.39,
H 3.43, N 12.96.
1-[2-Methyl-5-nitrobenzotriazol-4-yl(phenylsulphonyl)-
methyl]benzotriazole (22b). Purification: see 22a, method
B, Rfˆ0.30. Pale yellow needles (EtOH), mp 183–185ЊC.
1H NMR, d: 4.31 (s, 3H, CH3), 7.40–7.53 (m, 5H, BtϩPh),
7.67–7.73 (m, 3H, BtϩPh), 8.10–8.13 (m, 1H, Bt), 8.12 (d,
Jˆ9.5 Hz, 1H, 7-H Bt), 8.35 (d, Jˆ9.5 Hz, 1H, 6-H Bt),
8.56 (s, 1H, CH). IR: 3085, 3050, 2950, 1529, 1450, 1344,
1156, 1052, 771, 752, 739 cmϪ1
.
Anal. Calcd for
1-(2,4-Dinitrobenzyl)-1,2,4-triazole (26a). FC (hexanes–
ethyl acetate 1:2, Rfˆ0.21). Pale yellow plates (50%
C20H15N7O4S: C 53.44, H 3.36, N 21.82; found: C 53.47,
H 3.64, N 21.89.
1
EtOH), mp 106–107ЊC. H NMR, d: 5.95 (s, 2H, CH2),
7.30 (d, Jˆ8.5 Hz, 1H, 6-H sBn), 8.10 (s, 1H, 3-H triazole),
8.54 (dd, Jˆ8.5 and 2.5 Hz, 1H, 5-H sBn), 8.81 (d,
Jˆ2.5 Hz, 1H, 3-H sBn). IR: 3102, 3089, 2990, 1609,
1530, 1514, 1375, 1353, 1283, 1139, 1015, 842, 781, 732,
685 cmϪ1. Anal. Calcd for C9H7N5O4: C 43.38, H 2.83, N
28.10; found: C 43.65, H 3.18, N 28.02.
5-(Benzotriazol-1-ylmethyl)-6-nitroquinoline (23a). FC
(hexanes–ethyl acetate 1:1, Rfˆ0.35). Pale yellow needles
1
(EtOH), mp 174–176ЊC. H NMR, d: 6.55 (s, 2H, CH2),
7.44 and 7.62 (2×ddd, Jˆ8.5, 7 and 1 Hz, 2×1H, Bt),
7.78–7.82 (m, 1H, 3-H quinoline), 7.90–7.93 (m, 1H, Bt),
8.04–8.07 (m, 1H, Bt), 8.33 (d, Jˆ9.5 Hz, 1H, 7-H or 8-H
quinoline), 8.36 (d, Jˆ9.5 Hz, 1H, 7-H or 8-H quinoline),
8.99 (dd, Jˆ9 and 1 Hz, 1H, 4-H quinoline), 9.15 (dd, Jˆ4
and 1 Hz, 1H, 2-H quinoline). IR: 3099–3030, 1597, 1516,
1-[2,4-Dinitrophenyl(phenylsulphonyl)methyl]-1,2,4-tri-
azole (26b). Purification: see 26a, Rfˆ0.55. Pale yellow
1
needles (50% EtOH), mp 150–152ЊC. H NMR, d: 7.59–
1492, 1468, 1338, 1318, 1080, 846, 831, 775, 743 cmϪ1
.
7.66 (m, 4H, Ph), 7.78–7.84 (m, 1H, Ph), 7.87 (s, 1H, CH),
8.25 (s, 1H, 3-H triazole), 8.75 (dd, Jˆ8.5 and 2.5 Hz, 1H,
5-H sBn), 8.78 (s, 1H, 5-H triazole), 8.82 (d, Jˆ2.5 Hz, 1H,
3-H sBn), 8.91 (d, Jˆ8.5 Hz, 1H, 6-H sBn). IR: 3112, 3056,
2989, 1602, 1537, 1376, 1345, 1309, 1277, 1151, 1130, 837,
738, 716, 642 cmϪ1. Anal. Calcd for C15H11N5O6S: C 46.27,
H 2.85, N 17.99; found: C 46.20, H 3.12, N 17.98.
Anal. Calcd for C16H11N5O2: C 62.94, H 3.63, N 22.94;
found: C 62.96, H 3.75, N 22.64.
5-[Benzotriazol-1-yl(phenylsulphonyl)methyl]-6-nitro-
quinoline (23b). Purification: see 23a, Rfˆ0.29. Colourless
1
needles (EtOH), mp 197–198ЊC. H NMR, d: 7.17–7.20
(m, 1H, Bt), 7.41–7.52 (m, 2H, Bt), 7.55–7.60 (m, 2H,
PhϩBt), 7.74–7.87 (m, 4H, Phϩquinoline), 8.13–8.16 (m,
1H, Bt), 8.32 (d, Jˆ9 Hz, 1H, 7-H quinoline), 8.33 (s, 1H,
CH), 8.45 (d, Jˆ9 Hz, 1H, 8-H quinoline), 9.12 (dd, Jˆ4
and 1.5 Hz, 1H, 2-H quinoline), 9.34 (dd, Jˆ8.5 and 1 Hz,
1H, 4-H quinoline). IR: 3056, 2972, 2915, 1494, 1457,
1449, 1333, 1318, 1291, 1227, 1154, 1085, 1068, 931,
890, 786, 773, 765, 738, 686 cmϪ1. Anal. Calcd for
C22H15N5O4S: C 59.32, H 3.39, N 15.72; found: C 59.48,
H 3.51, N 15.61.
2-Methyl-5-nitro-4-(1,2,4-triazol-1-ylmethyl)benzotriazole
(27a). Method A: crystallization; method B: FC (hexanes–
ethyl acetate 1:2, Rfˆ0.12). Yellow plates (EtOH), mp 160–
1
161ЊC. H NMR, d: 4.61 (s, 3H, CH3), 6.08 (s, 2H, CH2),
7.89 (s, 1H, 3-H triazole), 8.08 (d, Jˆ9 Hz, 1H, 7-H Bt),
8.21 (d, Jˆ9 Hz, 1H, 6-H Bt), 8.68 (s, 1H, 5-H triazole). IR:
3119, 3053, 2989, 1534, 1513, 1439, 1367, 1353, 1273,
1141, 1026, 841, 836, 752, 685 cmϪ1. Anal. Calcd for
C10H9N7O2: C 46.33, H 3.50, N 37.82; found: C 46.31, H
3.29, N 37.76.
3,5-Dimethyl-1-(2,4-dinitrobenzyl)pyrazole (24). FC
(hexanes–ethyl acetate 2:1, Rfˆ0.40). Pale yellow prisms
2-Methyl-5-nitro-4-[phenylsulphonyl(1,2,4-triazol-1-yl)-
methyl]benzotriazole (27b). Purification: see 27a, method
B, Rfˆ0.25. Almost colourless prisms (EtOH), mp 192–
1
(50% EtOH), mp 104–106ЊC. H NMR, d: 2.11 (s, 3H,
CH3), 2.16 (s, 3H, CH3), 5.69 (s, 2H, CH2), 5.97 (s, 1H,
4-H pyrazole), 6.75 (d, Jˆ8.5 Hz, 1H, 6-H sBn), 8.51 (dd,
Jˆ8.5 and 2.5 Hz, 1H, 5-H sBn), 8.81 (d, Jˆ2.5 Hz, 1H,
3-H sBn). IR: 3081, 3060–3015, 1604, 1548, 1534, 1453,
1413, 728 cmϪ1. Anal. Calcd for C12H12N4O4: C 52.17, H
4.38, N 20.28; found: C 51.93, H 4.20, N 20.33.
1
194ЊC. H NMR, d: 4.63 (s, 3H, CH3), 7.64–7.86 (m, 5H,
Ph), 7.97 (s, 1H, 3-H triazole), 8.07 (s, 1H, CH), 8.15 (d,
Jˆ9 Hz, 1H, 7-H Bt), 8.44 (d, Jˆ9 Hz, 1H, 6-H Bt), 9.48 (s,
1H, 5-H triazole). IR: 3088, 3010, 1530, 1452, 1348, 1284,
1204, 1157, 1130, 730, 680, 649 cmϪ1. Anal. Calcd for
C16H13N7O4S: C 48.12, H 3.28, N 24.55; found: C 47.84,
H 3.41, N 24.69.
1-(2,4-Dinitrobenzyl)benzimidazole (25a). FC (hexanes–
ethyl acetate 1:1, Rfˆ0.29). Cream plates (50% EtOH), mp
166–168ЊC. 1H NMR, d: 6.07 (s, 2H, CH2), 6.79 (d,
Jˆ8.5 Hz, 1H, 6-H sBn), 7.22–7.90 (4×m, 4H, benzimida-
zole), 8.38 (s, 1H, 2-H benzimidazole), 8.42 (dd, Jˆ8.5 and
2.5 Hz, 1H, 5-H sBn), 8.87 (d, Jˆ2.5 Hz, 1H, 3-H sBn). IR:
3102, 3081, 3051, 2959, 1612, 1601, 1528, 1491, 1480,
1459, 1348, 1270, 744, 740, 730 cmϪ1. Anal. Calcd for
1-(1-Methyl-4-nitropyrazol-5-ylmethyl)-1,2,4-triazole
(28). FC (hexanes–ethyl acetate 1:2, Rfˆ0.11). Pale yellow
1
prisms, mp 146–148ЊC (MeOH). H NMR, d: 4.04 (s, 3H,
CH3), 5.88 (s, 2H, CH2), 8.00 (s, 1H, 3-H triazole), 8.32 (s,
1H, 3-H pyrazole), 8.72 (s, 1H, 5-H triazole). IR: 3116,
3099, 1604, 1501, 1498, 1433, 1406, 1395, 1307, 1122,

7284
M. K. Bernard / Tetrahedron 56 (2000) 7273–7284
750, 673 cmϪ1. Anal. Calcd for C7H8N6O2: C 40.39, H 3.87,
N 40.37; found: C 40.51, H 3.89, N 40.32.
13. Chupakhin, O. N.; Charushin, V. N.; van der Plas, H. C.
Nucleophilic Aromatic Substitution of Hydrogen; Academic: San
Diego, 1994.
´
Synthesis of compound 17c from benzotriazole deriva-
tive 17a. A solution of benzotriazole derivative 17a (50 mg,
0.15 mmol) and sodium benzenesulphinate (25 mg,
0.15 mmol) in DMSO (2 cm3) was stirred at 23ЊC for 1 h
and diluted with water. The precipitated yellow solid was
filtered off and crystallized from EtOH to give 44 mg (67%)
of compound 17c as pale yellow needles, mp 182–184ЊC.
14. Adam, W.; Ma˛kosza, M.; Stalinski, K.; Zhao, C.-G. J. Org.
Chem. 1998, 63, 4390–4391.
´
15. Ma˛kosza, M.; Stalinski, K. Tetrahedron 1998, 54, 8797–8810.
16. van der Plas, H. C.; Wozniak, M. Croat. Chem. Acta 1986, 59,
´
33–49.
17. Ma˛kosza, M.; Danikiewicz, W.; Wojciechowski, K. Liebigs
Ann. Chem. 1987, 711–715.
18. Danikiewicz, W.; Ma˛kosza, M. Tetrahedron Lett. 1985, 26,
3599–3600.
19. Ma˛kosza, M.; Owczarczyk, Z. J. Org. Chem. 1989, 54, 5094–
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20. Mudryk, B.; Ma˛kosza, M. Tetrahedron 1988, 44, 209–213.
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Liebigs Ann. Chem. 1989, 545–549.
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