An efficient method for the synthesis of 1-chlorophenazines based on the selective cathodic reduction of 3,3,6,6-tetrachloro-1,2-cyclohexanedione

Article abstract of DOI:10.1016/j.tet.2004.06.089

An efficient method for the synthesis of 1-chlorophenazines has been established. It is based on the use of 3,6,6-trichloro-2-hydroxy-2-cyclohexen-1- one 4 as a synthetic equivalent of 3-chloro-1,2-benzoquinone 3. The intermediate 4 was prepared in near quantitative yield by electroreductive monodechlorination of 3,3,6,6-tetrachloro-1,2-cyclohexanedione 1, which is an inexpensive and easily available starting material. Efficient reactions of 4 with primary 1,2-phenylenediamines provided the corresponding 1,1,4-trichloro-1,2,3,4-tetrahydrophenazines 6, which were directly aromatized by treatment with 2,6-lutidine to give the title compounds in high yields. X-ray crystallographic structures for 1,1,4-trichloro-1,2,3,4-tetrahydro-6- methylphenazine 6f, 8-benzoyl-1,1,4-trichloro-1,2,3,4-tetrahydro-phenazine 6ea, and 1,7-dichlorophenazine 10db have been determined.

Full text of DOI:10.1016/j.tet.2004.06.089

Tetrahedron 60 (2004) 6747–6755
An efficient method for the synthesis of 1-chlorophenazines based
on the selective cathodic reduction of
3,3,6,6-tetrachloro-1,2-cyclohexanedioneq
*
Antonio Guirado, Alfredo Cerezo, Raquel Andreu, Jose I. Lopez Sanchez and Delia Bautista
´
´
´
´ ´ ´
Departamento de Quımica Organica, Facultad de Quımica, Universidad de Murcia, Campus de Espinardo, 30071 Murcia,
Apartado 4021, Spain
Received 6 April 2004; revised 7 June 2004; accepted 16 June 2004
Available online 2 July 2004
´
Dedicated to Professor Jose Vicente on the occasion of his 60th birthday
Abstract—An efficient method for the synthesis of 1-chlorophenazines has been established. It is based on the use of 3,6,6-trichloro-2-
hydroxy-2-cyclohexen-1-one 4 as a synthetic equivalent of 3-chloro-1,2-benzoquinone 3. The intermediate 4 was prepared in near
quantitative yield by electroreductive monodechlorination of 3,3,6,6-tetrachloro-1,2-cyclohexanedione 1, which is an inexpensive and easily
available starting material. Efficient reactions of 4 with primary 1,2-phenylenediamines provided the corresponding 1,1,4-trichloro-1,2,3,4-
tetrahydrophenazines 6, which were directly aromatized by treatment with 2,6-lutidine to give the title compounds in high yields. X-ray
crystallographic structures for 1,1,4-trichloro-1,2,3,4-tetrahydro-6-methylphenazine 6f, 8-benzoyl-1,1,4-trichloro-1,2,3,4-tetrahydro-
phenazine 6ea, and 1,7-dichlorophenazine 10db have been determined.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
improved methods for the synthesis of chlorophenazines
is, therefore, of substantial interest. However, 1-chloro-
phenazines still remain almost inaccessible.4–10
Phenazines show properties with a wide range of significant
applications.1 One special interest lies in the biological
activity of certain naturally occurring phenazines or
analogues. Some of these compounds have been demon-
strated to have important therapeutic utility, mainly as
antibiotic and anticancer agents.2 This has renewed the
interest in the progress of the synthesis of phenazines.
Because of the remarkable reluctance of phenazines to
undergo electrophilic substitution reactions, the displace-
ment of the halogen atoms of chlorophenazines by a variety
of nucleophiles can play an important role in the production
of a wide variety of phenazine derivatives. However, the
difficulty in preparing the appropriate chlorinated starting
materials frequently results in a lack of applicability of the
procedure. Chlorophenazines have, in fact, provided good
entries to a number of functionalized phenazine derivatives
via nucleophilic substitution.3 The development of
The main general methods1 for the synthesis of phenazines
include cyclization of 2-nitro- and 2-aminodiphenylamines,
coupling between anilines and nitrobenzenes, treatment of
benzofuroxans with dienophiles, and double condensation
of 1,2-benzoquinones with phenylene diamines. Some other
preparative methods of less extensive use have also been
reported. However, when these approaches are applied in
preparing chlorophenazines they frequently fail in both
versatility and yield. It is apparent that the procedures
reported for synthesizing 1-chlorophenazines are remark-
ably deficient mainly because of the inherent low activity
of the aromatic intermediates implied in nucleophilic
substitution processes. The drastic experimental conditions
that are normally required to promote these reactions
cause the removal of the majority of the functional groups
present in the starting materials as well as a remarkable loss
of yields. On the other hand, direct chlorination of
phenazine by treatment with chlorine under different
conditions4 has been found to be remarkably unselective,
leading to very complex mixtures of monochloro and
polychlorophenazines. Results for chlorination reactions
applied to functionalized phenazines have not been reported
to date.
q Supplementary data associated with this article can be found in the online
version, at doi: 10.1016/j.tet.2004.06.089
Keywords: Phenazines; 1,2-Phenylenediamines; a,a0-Polychloro-1,2-
cyclohexanodiones; Electrosynthesis; Reduction; Dehydrochlorination;
Aromatization.
*
Corresponding author. Tel.: þ34-968367490; fax: þ34-968364148;
e-mail address: anguir@um.es
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.06.089

6748
A. Guirado et al. / Tetrahedron 60 (2004) 6747–6755
Regarding the above, it is clear that a good and versatile
method for preparing 1-chlorophenazines does not seem
likely to be available on this basis. Thus, the synthesis of the
parent compound 1-chlorophenazine 10a has been achieve0d
by different procedures, involving thermal cyclation of 2 -
chloro-2-nitrodiphenylamine in the presence of ferrous
oxalate5 (4.4%), a Wohl-Aue reaction6 (18%), treatment
of phenazine-N-oxide with thionyl chloride7 (23%), chlori-
nation of catechol followed by oxidation with silver oxide
and treatment with 1,2-phenylenediamine8 (16% overall
yield) or direct chlorination of phenazine4a (negligible
yield). Some low yield preparations of polychlorinated
phenazines bearing one of the chlorine substituents at C-1
have also been reported.9,10 These procedures seem to be
incompatible with the synthesis of functionalized 1-chloro-
phenazines.
basis of the search for good synthetic equivalents of
chlorinated o-quinones. It should be noted that condensation
of o-quinones with aromatic 1,2-diamines leads directly to
phenazines. However, this process appears to be unsatis-
factory since the reaction of o-phenylenediamine with
o-benzoquinone gives phenazine11 in remarkable low yield
(35%). Moreover, in most of cases the difficulty in preparing
the appropriate o-quinone is an extreme synthetic
problem.
Working in this project, we first reported12 a new, efficient
and versatile method for the synthesis of 1,4-dichloro-
phenazines by starting from 3,3,6,6-tetrachloro-1,2-cyclo-
hexanedione 1. It is a cheap, readily available compound. Its
peculiar reactivity was found to be usable as an excellent
synthetic equivalent of 3,6-dichloro-1,2-benzoquinone,
which is a practically unavailable compound, whereas this
synthetic equivalent can be easily obtained in quantitative
yield by direct treatment of commercial trans-cyclo-
hexanediol with chlorine.12,13
Given the precariousness of the reported syntheses of some
classes of chlorophenazines, we focused on the research of
improved synthetic methods for these compounds on the
Scheme 1.

A. Guirado et al. / Tetrahedron 60 (2004) 6747–6755
6749
Table 1. Preparation of 1,1,4-trichloro-1,2,3,4-tetrahydrophenazines 6a-f and 1-chlorophenazines 10a-f
Entry
Diamines 5
Intermediates 6
Yield (%)
Products 10
Yield (%)
a
85
96
93
89
b
c
90
83
d
e
f
46
35
45
41
92
96
96
91
93
91
As was reported in a preliminary communication,13 we
successfully extended the above novel synthetic method-
ology to the synthesis of 1-chlorophenazines. In this paper
we describe full details of the previous report on this subject
as well as new outcomes of this preparative procedure
which is illustrated in Scheme 1 and Table 1. The aim of this
approach is to circumvent the use of 3-chloro-1,2-benzo-
quinone 3 which is a rare and practically inaccessible
compound.8,14–16 Moreover, the advantage of a highly
efficient reaction between vicinal dicarbonyl groups with
aromatic 1,2-diamines instead of o-quinonoid ones is
another attractive feature of this procedure.
copper dichloride17 (ratio 1:20) in dioxane–water. Because
of the low yield and the requirement of a difficult
chromatographic isolation of the product, this reaction
was found to be of little synthetic use. However, this
obstacle could be satisfactorily overcome by an efficient and
highly selective electrochemical reduction of 3,3,6,6-
tetrachloro-1,2-cyclohexanedione 1. Thus, electrolysis of 1
under a constant cathodic potential in a protic medium gave
a single product quantitatively, which was isolated and
identified as the compound 4 which corresponds to the enol
form of the intended key intermediate 2.
In order to achieve the synthesis of 1,1,4-trichloro-1,2,3,4-
tetrahydrophenazines 6 to be used as precursors of the
targeted 1-chlorophenazines, reactions of 4 with 1,2-
phenylenediamines 5 were carried out. The reactivity of 4
was observed to be similar to that predictable for the dione
2. High yields in the expected products 6 were obtained by
2. Results and discussion
The preparation of 3,6,6-trichloro-2-hydroxy-2-cyclohexen-
1-one 4 was attempted by reaction of cyclohexanone with

6750
A. Guirado et al. / Tetrahedron 60 (2004) 6747–6755
Table 2. Selected bond lengths in crystal structure of 6ea
performing the reaction in benzene with continuous
azeotropic removal of water. These products were easily
obtained in a crystalline state and were stable enough to
permit prolonged storage without receiving any special care.
There are no precedents for this family of compounds. It
should be noted that reactions with symmetrical diamines
such as 5a-c gave the corresponding single products 6a-c.
However, the reactions with nonsymmetrical diamines 5d,e
gave two pairs of the possible isomeric products (6d-a,b and
6e-a,b), which were formed in a comparable ratio. All these
isomers could be definitively differentiated by X-ray
crystallographic analysis of either a member of each
product pair or a phenazine derivative, thus single crystals
of compound 6ea and 10db were analyzed by X-ray
crystallography. The molecular structures are illustrated in
Figures 1 and 2, respectively. Selected bond lengths are
given in Tables 2 and 3, respectively.
Cl(1)–C(1)
Cl(2)–C(1)
Cl(3)–C(4)
O–C(13)
1.788(2)
1.804(2)
1.824(2)
1.222(2)
1.521(3)
C(1)–C(2)
C(3)–C(4)
C(4)–C(5)
C(9)–C(13)
C(13)–C(21)
1.521(3)
1.513(3)
1.502(3)
1.503(3)
1.488(3)
C(1)–C(12)
Table 3. Selected bond lengths in crystal structure of 10db
Cl(1)–C(1)
Cl(2)–C(8)
N(1)–C(4)
N(1)–C(3)
1.740(2)
1.736(2)
1.341(2)
1.343(2)
N(2)–C(9)
N(2)–C(10)
C(3)–C(10)
C(4)–C(9)
1.340(2)
1.343(2)
1.436(2)
1.439(2)
single crystal X-ray diffraction analysis. It seems reasonable
to presume that steric factors are implied in the exclusive
formation of this product
In the search for an alternative approach to 1,1,4-trichloro-
1,2,3,4-tetrahydrophenazines 6, the electrochemical
reduction of 1,1,4,4-tetrachloro-1,2,3,4-tetrahydrophena-
zine 7a at constant potential in a protic medium was carried
out. However, this electrolysis was found to be remarkably
unselective and it led to a complex mixture of products with
a different dechlorination degree.
The first experiments, focused on establishing effective
experimental conditions to achieve the conversion of
intermediates 6 to the corresponding 1-chlorophenazines
10, gave surprising and somewhat disappointing results.
Thus, the treatment of 6a with pyridine yielded the expected
1-chlorophenazine 10a in moderate yield (62%) but
accompanied by a considerable amount of 1,4-dichloro-
phenazine 12a (26%). The reaction with sodium methoxide
gave a similar result. Some other experiments were carried
out, showing the generation of 1-chlorophenazines along
with the undesired 1,4-dichlorophenazines as a general
synthetic limitation of these reactions.
Figure 1. Molecular structure of 6ea, showing the crystallographic
numbering system used.
It was considered that the formation of the targeted
1-chlorophenazines implies an aromatization process
associated with a double elimination of hydrogen chloride
from intermediates 6. However, aromatization leading to
1,4-dichlorophenazines obviously involve a monodehydro-
halogenation process of the same intermediates. Therefore,
the collaboration of an oxidation process must be necess-
arily postulated to clarify the formation of the lateral
products 12. This hypothesis leads us to conclude that a
crucial influence of the site where the intermediates 6
undergo a first deprotonation provides the most plausible
explanation that may be offered for these facts. Thus,
deprotonation at C-3 would promote the formation of
intermediates 8, which would give the targeted products 10
exclusively. However, deprotonation at C-2 would generate
the intermediates 9, which could reasonably undergo
dehydrochlorination to give products 10, but also rearrange-
ment to 1,4-dichloro-5,10-dihydrophenazines 11, whose
oxidation explains the formation of products 12.
Figure 2. Molecular structure of 10db, showing the crystallographic
numbering system used.
The reaction with 3-methyl-1,2-phenylenediamine 5f was
found to be fully selective towards the formation of 1,1,4-
trichloro-1,2,3,4-tetrahydro-6-methylphenazine 6f. The
molecular structure of this product was corroborated by
This reaction route is well supported by the following facts:
(1) the great proclivity of 5,10-dihydrophenazines towards
undergoing oxidation yielding phenazines is well known;14
(2) a sample of 1,4-dichloro-5,10-dihydrophenazine 11a

A. Guirado et al. / Tetrahedron 60 (2004) 6747–6755
6751
was prepared by electrochemical reduction of 12a in a protic
medium. When compound 11a was exposed to a similar
experimental conditions as those operating in the conver-
sion of 6a to 10a, an almost instantaneous quantitative
formation of 1,4-dichlorophenazine 12a was observed even
when working under nitrogen atmosphere; (3) the gener-
ation of product 12a was fully prevented by treatment of 6a
with 2,6-lutidine instead of pyridine. In this case the
exclusive formation of 1-chlorophenazine 10a (96%)
occurred. This result is in excellent agreement with the
expected effect of a bulky base determining regioselectivity
towards the less hindered reactive site. It seems reasonable,
therefore, in this case to assume a process with the exclusive
generation of 10a without participation of the intermediates
9a and 11a.
hexen-1-one (4). A reductive electrolysis19 of 3,3,6,6-
tetrachloro-1,2-cyclohexanedione 1 was carried out under a
constant cathodic potential in a concentric cylindrical cell
with two compartments separated by a circular glass frit
(medium) diaphragm. A mercury pool (diameter 5 cm;
Luggin-capillary situated to the side of the pool) was used as
the cathode and a platinum plate as the anode. The current
intensity was 240 mA at the beginning, and 10 mA at the
end. The cell voltage remained below 6 V. The catholyte
was magnetically stirred. The temperature was kept at
approximately 18 8C by external cooling. The reduction was
performed in MeCN (40 mL)—AcOH (10 mL)—LiClO4
(3 g); 35 mL and 15 mL were placed in the cathodic and the
anodic compartments, respectively. Sodium acetate (0.2 g)
was placed in the anode compartment. A solution of 1
(5 mmol) was electrolyzed under a cathodic potential of
20.05 V versus SCE. The electricity consumption was
2 F/mol. Isolation of product 4 was carried out by removing
the solvent in vacuo,20 adding water (150 mL) and
extracting the mixture with chloroform (3£40 mL). The
combined organic layers were washed with cold water and
dried on anhydrous sodium sulphate. After evaporation of
chloroform under reduced pressure the solid residue was
crystallized from petroleum ether, yield 95%, white needles;
mp 120–121 8C (lit.17 119–120 8C) (Found: C, 33.30; H,
In conclusion, a simple and effective method for the
synthesis of 1-chlorophenazines 10 is reported whose
selectivity is helped by steric effects developed by the
base promoting aromatization. Nearly quantitative yields,
easy availability of starting materials are valuable, note-
worthy advantages of the method which allows the access to
previously unattainable compounds. It is also to be noted
that this work has revealed 3,6,6-trichloro-2-hydroxy-2-
cyclohexen-1-one 4 as an excellent synthetic equivalent of
3-chloro-1,2-benzoquinone 3. Since the usefulness of
quinones in organic synthesis is well known the compound
4 seems likely to be a promising intermediate in allowing
the selective synthesis of a wide variety of specifically
chlorinated compounds.
1
2.40; C6H5Cl3O2 requires: C, 33.45; H, 2.34); H NMR d
(CDCl3, 300 MHz): 2.84–2.95 (m, 4H), 6.20 (s, 1H); 13C
NMR d (CDCl3, 75.4 MHz): 30.47, 42.46, 82.70, 129.2,
140.70, 180.52; MS m/z (%) 218 [Mþþ4] (5), 216 [Mþþ2]
(15), 214 [Mþ] (18), 179 (15), 161 (7), 153 (55), 151 (100),
118 (66), 90 (43), 54 (90); IR (Nujol) 3389, 1698, 1638,
1355, 1273, 1152, 1132, 1056, 970, 910, 876, 808,
702 cm21
.
3. Experimental
3.1. General
This synthesis was found to be reproducible when using
graphite instead of mercury as cathodic material. The
preparation of 4 was achieved in 83% yield by a procedure
as described above but with an operating potential of
20.30 V versus SCE. The current intensity was 310 mA at
the beginning, and 10 mA at the end. The cell voltage
remained below 8 V. The electricity consumption was
2 F/mol.
NMR spectra were determined on Bruker AC-200 or Varian
Unity 300 Unity instruments with tetramethylsilane as
internal reference. Electron-impact mass spectra were
obtained on Hewlett–Packard 5995 and Autospect 5000
VG spectrometers under an ionizing voltage of 70 eV. IR
spectra (Nujol emulsions) were recorded on a Nicolet
Impact 400 spectrophotometer. Microanalyses were per-
formed on a Carlo Erba EA-1108 analyzer. Melting points
were determined on a Kofler hot-plate melting point
apparatus, and are uncorrected. Electrochemical experi-
ments were performed with an Amel 557 potentiostat
coupled to an Amel 558 integrator. 3,3,6,6-tetrachloro-1,2-
cyclohexanedione 1 was prepared as previously described.12
3.1.2. Preparation of 1,1,4-trichloro-1,2,3,4-tetrahydro-
phenazines (6). A benzene solution (75 mL) of 4
(5.56 mmol) and the appropriate diamine 5 (5.48 mmol)
was refluxed with a Dean–Stark water separator for 24 h.
The solvent was evaporated under reduced pressure and the
residue was shaken with ether (75 mL). The small amount
of a white solid remaining in suspension was removed by
filtration. After evaporation of ether, highly pure products 6
were isolated and crystallized in the appropriate solvent.
Products 6d-a,b and 6e-a,b were isolated by column
chromatography.
X-ray crystallographic data were collected using Mo Ka
˚
radiation (l¼0.71073 A). For compounds 6f and 6ea a
Siemens P4 diffractometer was used (v-scans, 2umax 508);
for the structure of 10db, a Bruker SMART CCD (v and
ø-scans, 2umax 568, absorption correction using multiple
scans). Structures were refined anisotropically on F 2 using
the program SHELXL-93 (G. M. Sheldrick, University of
3.1.3. 1,1,4-Trichloro-1,2,3,4-tetrahydrophenazine (6a).
(85%); Crystallization from petroleum ether gave white
prisms; mp 135–137 8C. (Found: C, 49.33; H, 3.23; N, 9.86;
C12H9Cl3N2 requires: C, 50.12; H, 3.15; N, 9.74); 1H NMR
d (CDCl3, 300 MHz): 2.49–2.59 (m, 1H), 2.81–2.94 (m,
1H), 3.05–3.14 (m, 1H), 3.41–3.53 (m, 1H), 5.53–5.56 (m,
1H), 7.80–7.87 (m, 2H), 8.09–8.15 (m, 1H) 8.19–8.26 (m,
1H); 13C NMR d (CDCl3, 75.4 MHz): 29.73, 40.77, 57.18,
¨
Gottingen). Hydrogen atoms were included using rigid
methyl groups or a riding model. Full structural information
has been deposited with the Cambridge Crystallographic
Data Centre.18
3.1.1. Preparation of 3,6,6-trichloro-2-hydroxy-2-cyclo-

6752
A. Guirado et al. / Tetrahedron 60 (2004) 6747–6755
85.59, 129.05, 129.59, 131.48, 131.86, 142.39, 142.69,
146.97, 149.65; MS, m/z (%): 290 [Mþþ4] (3), 288 [Mþþ2]
(9), 286 [Mþ] (9), 251 (21), 215 (100), 217 (31), 181 (23),
108 (21), 102 (33), 76 (67). IR (Nujol) 1556, 1356, 1235,
Crystallographic details. Yellow needle-like single crystals
were grown from a solution in chloroform. A crystal of
approximate dimensions 0.40£0.05£0.03 mm3 was selected
and mounted on a glass fiber. A total of 6632 reflections
(25#h#5, 216#k#10, 228#l#27) were collected at
T¼173(2) K in the u range from 1.88 to 28.318 of which
2509 were unique (Rint¼0.0277; Mo Ka radiation
948, 921, 900, 832, 787, 769, 689 cm21
.
3.1.4. 1,1,4-Trichloro-1,2,3,4-tetrahydro-7,8-dimethyl-
phenazine (6b). (90%); Crystallization from petroleum
ether gave white prisms; mp 197–198 8C. (Found: C, 52.97;
H, 4.09; N, 8.96; C14H13Cl3N2 requires: C, 53.28; H, 4.15;
N, 8.88);1H NMR d (CDCl3, 200 MHz) 2.41–2.58 (m, 1H),
2.50 (s, 6H), 2.77–2.95 (m, 1H), 3.00–3.13 (m, 1H), 3.37–
3.53 (m, 1H), 5.49–5.53 (m, 1H), 7.85 (s, 1H), 7.98 (s, 1H);
13C NMR d (CDCl3, 50.3 MHz) 20.49, 20.58, 29.78, 40.78,
57.45, 85.91, 127.83, 128.36, 141.49, 141.82, 142.67, 143.13,
145.81, 148.63; MS m/z (%) 318 [Mþþ4] (1), 316 [Mþþ2]
(3), 314 [Mþ] (3), 279 (15), 243 (76), 245 (25), 209 (22), 193
(13), 103 (79), 89 (25), 77 (99), 51 (100); IR (Nujol) 1357,
˚
(l¼0.71073 A). The residual peak and hole electron density
3
˚
were 0.306 and 20.200 e/A . The absorption coefficient
was 0.601 mm21. The least-squares refinement converged
normally with residuals of R1¼0.0628 (all data),
wR2¼0.0934, and GOF¼1.065 [I.2s(I)]. C12H6Cl2N2,
˚
monoclinic, space group P21/c, a¼3.9055(10) A,
˚
˚
b¼12.130(4) A, c¼21.623(8) A, a¼908, b¼92.00(3)8,
g¼908, V¼1023.7(6) A , Z¼4, rcalc¼1.616 g/cm3,
3
˚
F(0,0,0)¼504, R(F)¼0.0385, wR(F2)¼0.0835.
3.1.8. 8-Benzoyl-1,1,4-trichloro-1,2,3,4-tetrahydro-
phenazine (6ea). (45%); Chromatography (CH2Cl2/
AcOEt/hexane, 80:10:10) gave white powder; mp 161–
162 8C. (Found: C, 57.32; H, 3.21; N, 7.22; C19H13Cl3N2O
1205, 1009, 942, 922, 871, 806, 782, 760, 655 cm21
.
3.1.5. 1,1,4,7,8-Pentachloro-1,2,3,4-tetrahydrophenazine
(6c). (83%); Crystallization from petroleum ether gave
white prisms; mp 152–153 8C. (Found: C, 40.60; H, 2.04;
N, 7.99; C12H7Cl5N2 requires: C, 40.43; H, 1.98; N, 7.86);
1H NMR d (CDCl3, 200 MHz): 2.47–2.61 (m, 1H), 2.78–
2.96 (m, 1H), 3.02–3.14 (m, 1H), 3.36–3.53 (m, 1H), 5.47–
5.52 (m, 1H), 8.25 (s, 1H), 8.37 (s, 1H); 13C NMR d (CDCl3,
50.3 MHz): 29.53, 40.53, 56.73, 85.02, 129.54, 130.04,
136.64, 136.99, 140.99, 141.30, 148.25, 150.74; MS m/z (%)
354 [Mþ] (2), 321 (8), 285 (30); 283 (30), 249 (12), 213
(14), 134 (19), 124 (27), 109 (52), 100 (32), 75 (76), 61 (46),
51 (100); IR (Nujol) 1380, 1229, 1111, 985, 942, 922, 891,
1
requires: C, 58.26; H, 3.35; N, 7.15; H NMR d (CDCl3,
300 MHz) 2.52–2.62 (m, 1H), 2.84–2.97 (m, 1H), 3.06–
3.15 (m, 1H), 3.41–3.52 (m, 1H), 5.55–5.58 (m, 1H), 7.54
(tt, J¼7.5, 1.5 Hz, 2H), 7.66 (tt, J¼7.5, 1.5 Hz, 1H), 7.88
(dt, J¼7.5, 1.5 Hz, 2H), 8.25 (dd, J¼8.6, 0.6 Hz, 1H), 8.33
(dd, J¼8.6, 1.8 Hz, 1H), 8.57 (dd, J¼1.8, 0.6 Hz, 1H); 13C
NMR d (CDCl3, 75.4 MHz) 29.42, 40.46, 57.79, 85.10,
128.59, 129.53, 129.99, 131.55, 132.28, 133.04, 136.59,
139.64, 141.40, 144.06, 148.76, 150.74, 195.11; MS m/z (%)
394 [Mþþ4] (2), 392 [Mþþ2], (6), 390 [Mþ] (6), 357 (9),
355 (13), 319 (97), 321 (32), 179 (20), 105 (91), 77 (100). IR
(Nujol) 1666, 1355, 1267, 946, 894, 846, 827, 790, 711,
847, 802, 753 cm21
.
676 cm21
.
3.1.6. 1,1,4,8-Tetrachloro-1,2,3,4-tetrahydrophenazine
(6da). (46%); Chromatography (AcOEt/petroleum ether,
15:85) gave white powder; mp 150–151 8C. (Found: C,
44.61; H, 2.41; N, 8.77; C12H8Cl4N2 requires: C, 44.76; H,
2.50; N, 8.70; 1H NMR d (CDCl3, 200 MHz) 2.47–2.61 (m,
1H), 2.79–2.97 (m, 1H), 3.03–3.15 (m, 1H), 3.38–3.54 (m,
1H), 5.49–5.54 (m, 1H), 7.79 (dd, J¼9.1, 2.3 Hz, 1H), 8.12
(d, J¼2.3 Hz, 1H), 8.18 (d, J¼9.1 Hz, 1H); 13C NMR d
(CDCl3, 50.3 MHz) 29.57, 40.59, 56.86, 85.29, 127.87,
130.76, 132.74, 138.09, 140.88, 142.84, 148.01, 149.81; MS
m/z (%) 324 [Mþþ4] (3), 322 [Mþþ2] (6), 320 [Mþ] (4),
287 (21), 285 (21), 251 (62), 249 (100), 215 (38), 179 (28),
163 (20), 100 (35), 75 (99). IR (Nujol) 1607, 1354, 1188,
Crystallographic details. Colourless block-like crystals
were obtained by slow diffusion of n-hexane into a solution
of 6ea in chloroform. A crystal of approximate dimensions
0.60£0.40£0.20 mm3 was selected and mounted on a glass
fiber. A total of 3304 reflections (29#h#9, 210#k#1,
215#l#15) were collected at T¼173(2) K in the u range
from 3.16 to 24.998 of which 2989 were unique
˚
(Rint¼0.0248; Mo Ka radiation (l¼0.71073 A). The
residual peak and hole electron density were 0.239 and
.
3
21
˚
20.227 e/A . The absorption coefficient was 0.545 mm
The least-squares refinement converged normally with
residuals of R1¼0.0358 (all data), wR2¼0.0863, and
GOF¼1.087 [I.2s(I)]. C19H13Cl3N2O, triclinic, space
1064, 951, 928, 844, 836, 817, 723, 653 cm21
.
˚
˚
group P-1, a¼7.6607(7) A, b¼8.8706(6) A, c¼
˚
3.1.7. 1,1,4,7-Tetrachloro-1,2,3,4-tetrahydrophenazine
(6db). (35%); Chromatography (AcOEt/ petroleum ether,
15:85) gave white powder; mp 194–195 8C. (Found: C,
44.53; H, 2.58; N, 8.61; C12H8Cl4N2 requires: C, 44.76; H,
13.1580(12) A, a¼75.939(7)8, b¼82.475(7)8, g¼
83.248(6) 8, V¼856.5(2) A , Z¼2, rcalc¼1.519 g/cm3,
3
˚
F(0,0,0)¼400, R(F)¼0.0301, wR(F 2)¼0.0824.
1
2.50; N, 8.70.); H NMR d (CDCl3, 200 MHz) 2.48–2.61
3.1.9. 7-Benzoyl-1,1,4-trichloro-1,2,3,4-tetrahydro-
phenazine (6eb). (41%); Chromatography (CH2Cl2/
AcOEt/hexane, 80:10:10) gave white powder; mp 138–
140 8C. (Found: C, 58.59; H, 3.44; N, 7.03; C19H13Cl3N2O
(m, 1H), 2.79–2.97 (m, 1H), 3.02–3.16 (m, 1H), 3.38–3.54
(m, 1H), 5.49–5.54 (m, 1H), 7.79 (dd, J¼9.0, 2.3 Hz, 1H),
8.07 (d, J¼9.0 Hz, 1H), 8.25 (d, J¼2.3 Hz, 1H). 13C NMR d
(CDCl3, 50.3 MHz) 29.64, 40.61, 57.00, 85.24, 128.43,
130.29, 133.16, 137.80, 141.27, 142.65, 147.25, 150.63. MS
m/z (%) 324 [Mþþ4] (2), 322 [Mþþ2] (4), 320 [Mþ] (4),
287 (9), 285 (9), 251 (41), 249 (63), 215 (21), 179 (17), 163
(15), 100 (31), 75 (92), 51 (100). IR (Nujol) 1601, 1351,
1
requires: C, 58.26; H, 3.35; N, 7.15); H NMR d (CDCl3,
300 MHz) 2.52–2.61 (m, 1H), 2.83–2.96 (m, 1H), 3.07–
3.16 (m, 1H), 3.43–3.54 (m, 1H), 5.52–5.55 (m, 1H), 7.54
(tt, J¼7.4, 1.6 Hz, 2H), 7.66 (tt, J¼7.4, 1.6 Hz, 1H), 7.88
(dt, J¼7.4, 1.6 Hz, 2H), 8.31 (dd, J¼9.0, 1.8 Hz, 1H), 8.36
(dd, J¼9.0, 0.6 Hz, 1H), 8.47 (dd, J¼1.8, 0.6 Hz, 1H); 13C
1233, 1128, 1096, 955, 930, 841, 799, 753, 721, 640 cm21
.

A. Guirado et al. / Tetrahedron 60 (2004) 6747–6755
6753
NMR d (CDCl3, 75.4 MHz) 29.63, 40.63, 56.93, 85.23,
128.70, 130.13, 130.16, 131.31, 131.81, 133.22, 136.71,
140.11, 141.88, 143.95, 148.31, 151.35, 195.24; MS m/z (%)
394 [Mþþ4] (12), 392 [Mþþ2], (36), 390 [Mþ] (40), 357
(33), 355 (49), 319 (65), 290 (43), 179 (92), 105 (78), 77
(100); IR (Nujol) 1666, 1378, 1265, 949, 847, 830, 792, 730,
Crystallization from petroleum ether/Cl3CH gave yellow
needles; mp 224–225 8C. (Found: C, 69.19; H, 4.62; N,
11.60. C14H11ClN2 requires: C, 69.28; H, 4.57; N, 11.54);
1H NMR d (CDCl3, 200 MHz): 2.56 (s, 6H), 7.64–7.73 (m,
1H), 7.90 (dd, J¼7.3, 1.0 Hz, 1H), 7.95 (s, 1H), 8.11–8.16
(m, 2H). 13C NMR d (CDCl3, 50.3 MHz): 20.75, 20.83,
127.69, 128.41, 128.83, 129.05, 129.24, 132.97, 139.74,
142.73, 142.87, 142.96, 143.19, 143.57; MS m/z (%) 244
[Mþþ2] (31), 242 [Mþ] (100), 229 (8), 227 (28), 205 (16),
179 (15), 136 (10), 121 (18), 103 (37), 89 (30), 75 (81), 63
(60), 51 (85). IR (Nujol) 1505, 1380, 1353, 956, 860, 823,
715 cm21
.
3.1.10. 1,1,4-Trichloro-1,2,3,4-tetrahydro-6-methyl-
phenazine (6f). (92%); Crystallization from acetonitrile
gave white microcystals; mp 140–142 8C. (Found: C,
51.74; H, 3.74; N, 9.37; C13H11Cl3N2 requires: C, 51.77;
H, 3.68; N, 9.29); 1H NMR d (CDCl3, 300 MHz): 2.48–2.58
(m, 1H), 2.78 (s, 3H), 2.80–2.93 (m, 1H), 3.04–3.12 (m,
1H), 3.42–3.54 (m, 1H), 5.53–5.57 (m, 1H), 7.63 (br d,
J¼6.9 Hz, 1H), 7.67–7.74 (m, 1H), 8.05 (dd, J¼8.4, 0.6 Hz,
1H). 13C NMR d (CDCl3, 75.4 MHz) 17.20, 29.82, 40.87,
57.54, 85.80, 127.33, 131.35, 131.50, 137.77, 142.04,
142.59, 145.62, 149.11. MS m/z (%) 304 [Mþþ4] (3), 302
[Mþþ2] (7), 300 [Mþ] (8), 265 (16), 231 (29), 229 (100),
193 (48), 97 (40), 89 (43), 75 (25), 63 (47); IR (Nujol) 1378,
779, 743, 727 cm21
.
3.2.3. 1,7,8-Trichlorophenazine (10c). (89%); Crystal-
lization from petroleum ether gave yellow needles; mp
237–238 8C. (Found: C, 50.98; H, 1.83; N, 9.11;
C12H5Cl3N2 requires: C, 50.83; H, 1.78; N, 9.88); 1H
NMR d (CDCl3, 300 MHz): 7.73–7.79 (m, 1H), 7.96 (dd,
J¼7.5, 1.2 Hz, 1H), 8.14 (dd, J¼8.7, 1.2 Hz, 1H), 8.32 (s,
1H), 8.52 (s, 1H). 13C NMR d (CDCl3, 75.4 MHz) 129.10,
129.82, 130.43, 130.65, 130.72, 133.68, 136.42, 136.62,
140.75, 141.93, 142.37, 144.56; MS m/z (%) 286 [Mþþ4]
(7), 284 [Mþþ2] (23), 282 [Mþ] (24), 249 (7), 247 (11), 141
(10), 136 (15), 134 (11), 124 (15), 109 (31), 100 (47), 75
(100), 50 (57); IR (Nujol) 1613, 1378, 1103, 994, 958, 884,
1238, 947, 919, 817, 788, 767, 760, 679 cm21
.
Crystallographic details. Colourless block-like single
crystals were obtained by slow diffusion of petroleum
ether into a solution of 6f in chloroform. A crystal of
approximate dimensions 0.42£0.35£0.32 mm3 was selected
and mounted on a glass fiber. A total of 2836 reflections
(28#h#8, 223#k#4, 210#l#0) were collected at
T¼173(2) K in the u range from 3.12 to 24.998 of which
2235 were unique (Rint¼0.0387; Mo Ka radiation
871, 825, 775, 753, 738 cm21
.
3.2.4. 1,8-Dichlorophenazine (10da). (96%); Crystalliza-
tion from Cl3CH gave yellow needles; mp 226–227 8C (lit.6
1
219–220 8C). H NMR d (CDCl3, 300 MHz): 7.67–7.77
(m, 2H), 7.91 (dd, J¼7.2, 1.2 Hz, 1H), 8.10 (dd, J¼9.1,
1.2 Hz, 1H), 8.19 (dd, J¼1.2, 0.6 Hz, 1H), 8.26 (dd, J¼9.1,
0.6 Hz, 1H); 13C NMR d (CDCl3, 75.4 MHz): 127.92,
128.91, 130.02, 130.30, 131.41, 132.43, 133.55, 137.48,
140.20, 141.84, 143.69, 144.39; MS m/z (%) 252 [Mþþ4]
(24), 250 [Mþþ2] (87), 248 [Mþ] (100), 215 (17), 213 (50),
178 (8), 124 (15), 75 (19); IR (Nujol) 1508, 1411, 1344,
˚
(l¼0.71073 A). The residual peak and hole electron density
3
˚
were 0.428 and 20.411 e/A . The absorption coefficient
was 0.699 mm21. The least-squares refinement converged
normally with residuals of R1¼0.0619 (all data),
wR2¼0.1227, and GOF¼1.100 [I.2s(I)]. C13H11Cl3N2,
˚
monoclinic, space group P21/n, a¼7.4190(10) A,
b¼19.689(2) A, c¼8.7640(10) A, a¼908, b¼94.420(10)8,
1067, 957, 935, 888, 885, 811, 739, 713 cm21
.
˚
˚
g¼908, V¼1276.4(3) A , Z¼4, rcalc¼1.569 g/cm3,
3
˚
F(0,0,0)¼616, R(F)¼0.0447, wR(F 2)¼0.1138.
3.2.5. 1,7-Dichlorophenazine (10db). (96%); Crystalliza-
tion from Cl3CH gave yellow needles; mp 259–260 8C.
(Found: C, 58.02; H, 2.48; N, 11.20; C12H6Cl2N2 requires:
C, 57.86; H, 2.43; N, 11.25); 1H NMR d (CDCl3, 300 MHz):
7.70–7.81 (m, 2H), 7.95 (br d, J¼7.2 Hz, 1H), 8.13–8.19
(m, 2H), 8.37 (dd, J¼1.8, 0.6 Hz, 1H); 13C NMR d (CDCl3,
75.4 MHz): 128.66, 129.14, 130.02, 130.52, 130.89, 132.78,
133.52, 137.41, 140.69, 142.36, 143.41, 144.11; MS m/z (%)
252 [Mþþ4] (12), 250 [Mþþ2] (70), 248 [Mþ] (100), 215
(10), 213 (29), 124 (8), 100 (5), 75 (11); IR (Nujol) 1619,
3.2. Preparation of 1-chlorophenazines (10)
A dimethylformamide solution (30 mL) of the appropriate
intermediate 6 (3.5 mmol) and 2,6-lutidine (2 mL) was
refluxed for 2 h. After cooling the reaction products were
isolated by dropping the solution onto cold brine (400 mL)
and filtration. The directly collected solid crude products
were washed with cold water, dried and crystallized from
the appropriate solvent.
1593, 1419, 1061, 956, 946, 856, 835, 766, 738, 715 cm21
.
3.2.1. 1-Chlorophenazine (10a). (96%); Crystallization
from hexane gave yellow needles; mp 123–124 8C (lit.6
122 8C). 1H NMR d (CDCl3, 200 MHz): 7.62–7.71 (m, 1H),
7.76–7.91 (m, 3H), 8.05–8.19 (m, 2H), 8.26–8.35 (m, 1H);
13C NMR d (CDCl3, 50.3 MHz): 128.77, 129.28, 129.58,
129.69, 129.93, 130.94, 131.16, 132.97, 139.87, 143.13,
143.46, 143.67; MS m/z (%) 216 [Mþþ2] (32), 214 [Mþ]
(93), 179 (49), 152 (23), 129 (10), 125 (11), 107 (18), 100
(20), 89 (11), 75 (100), 63 (32), 50 (92). IR (Nujol) 1510,
3.2.6. 8-Benzoyl-1-chlorophenazine (10ea). (91%); Crys-
tallization from Cl3CH gave yellow needles; mp 184–
186 8C. (Found: C, 71.72; H, 3.54; N, 8.87; C19H11ClN2O
1
requires: C, 71.59; H, 3.48; N, 8.79); H NMR d (CDCl3,
300 MHz): 7.55 (tt, J¼7.5, 1.2 Hz, 2H), 7.66 (tt, J¼7.5,
1.7 Hz, 1H), 7.76–7.83 (m, 1H), 7.91–7.99 (m, 3H), 8.19
(dd, J¼9, 1.2 Hz, 1H), 8.31–8.39 (m, 2H), 8.68–8.70 (m,
1H); 13C NMR d (CDCl3, 75.4 MHz): 128.74, 129.11,
130.17, 130.43, 130.70, 130.95, 133.09, 133.53, 133.63,
137.05, 139.20, 140.91, 142.39, 144.83, 144.88, 195.59; MS
m/z (%) 320 [Mþþ2] (68), 318 [Mþ] (98), 289 (88), 243
(29), 241 (78), 215 (29), 213 (69), 178 (15), 105 (100), 77
1380, 958, 821, 762, 742, 676 cm21
.
3.2.2. 1-Chloro-7,8-dimethylphenazine (10b). (93%);

6754
A. Guirado et al. / Tetrahedron 60 (2004) 6747–6755
(90); IR (Nujol) 1658, 1380, 1321, 1244, 953, 901, 856, 825,
728, 675 cm21
4. Supporting Information Available
.
Complex X-ray crystallographic data for 6f, 6ea and 10db.
3.2.7. 7-Benzoyl-1-chlorophenazine (10eb). (93%);
Crystallization from Cl3CH gave yellow needles; mp
277–279 8C. (Found: C, 71.44; H, 3.51; N, 8.63;
Acknowledgements
1
C19H11ClN2O requires: C, 71.59; H, 3.48; N, 8.79); H
NMR d (CDCl3, 200 MHz): 7.55 (tt, J¼7.3, 1.5 Hz, 2H),
7.68 (tt, J¼7.3, 1.2 Hz, 1H), 7.91–8.04 (m, 3H), 8.17 (dd,
J¼8.8, 1.3 Hz, 1H), 8.35 (dd, J¼9.0, 1.7 Hz, 1H), 8.49 (d,
J¼9.0 Hz, 1H), 8.60 (d, J¼1.7 Hz, 1H); 13C NMR d
(CDCl3, 50.3 MHz): 128.69, 129.12, 130.20, 130.41,
130.45, 130.72, 130.97, 133.06, 133.13, 133.41, 136.85,
139.26, 140.99, 142.72, 144.38, 144.61, 195.47; MS m/z (%)
320 [Mþþ2] (34), 318 [Mþ] (100), 290 (77), 289 (58), 241
(52), 213 (42), 178 (10), 105 (84), 77 (57); IR (Nujol) 1661,
1380, 1322, 1302, 1245, 1112, 955, 899, 855, 725, 698,
´
Author J.I.-L thanks the Fundacion Seneca (Comunidad
Autonoma de Murcia) for a postgraduate grant.
´
´
References and notes
1. The chemistry of phenazines has been excellently reviewed:
(a) Swan, G. A.; Felton, D. G. I. Phenazines, Chemistry of
Heterocyclic Compounds; Weissberger, A., Ed.; Interscience:
New York, 1957; Vol. 11, p 3. (b) Porter, A. E. A.
Comprehensive Heterocyclic Chemistry; Katritzky, A., Rees,
C., Potts, K., Eds.; Pergamon: New York, 1984; Vol. 3, p 157.
(c) McCullough, K. J. Rodd’s Chemistry of Carbon
Compounds; Ansell, M. F., Ed.; Elsevier: Amsterdam, 1989;
Vol. 4, p 354, Part I J. (d) Bolton, R. Rodd’s Chemistry of
Carbon Compounds; Sainsbury, M., Ed.; Elsevier:
Amsterdam, 2000; Vol. 4, p 162, Part I J.
673 cm21
.
3.2.8. 1-Chloro-6-methylphenazine (10f). (91%); Crystal-
lization from petroleum ether /Cl3CH gave yellow
needles; mp 316–317 8C. (Found: C, 68.41; H, 3.88; N,
12.31; C13H9ClN2 requires: C, 68.28; H, 3.97; N, 12.25); 1H
NMR d (CDCl3, 300 MHz): 2.92 (s, 3H), 7.64–7.78
(m, 3H), 7.92 (dd, J¼7.4, 1.4 Hz, 1H), 8.18–8.23 (m,
2H); 13C NMR d (CDCl3, 75.4 MHz): 17.60, 128.18,
129.23, 129.49, 129.69, 130.37, 131.07, 133.22, 138.04,
140.02, 143.39, 143.62, 143.82; MS m/z (%) 230 [Mþ þ2]
(30), 228 [Mþ] (100), 193 (16), 192 (30), 165 (21), 140 (10),
114 (26), 100 (19), 89 (31), 75 (58), 63 (61). IR (Nujol)
1618, 1558, 1378, 1346, 1119, 1075, 1057, 952, 849, 805,
2. For example, (a) Kitahara, T.; Kinoshita, Y.; Aono, S. Pure
Appl. Chem. 1994, 66, 2083. (b) Tripton, C. D.; Rinehart, K. L.
J. Am. Chem. Soc. 1970, 92, 1425. (c) De Souza, A. O.; Santos,
R. R.; Melo, D. S.; Alderete, J. B. Pharmazie 2001, 56, 871.
(d) Petersen, L.; Jensen, K. J.; Nielsen, J. Synthesis 1999, 10,
1763. (e) Pathirana, C.; Jensen, P. R.; Dwight, R.; Fenical, W.
747, 721, 670 cm21
.
´
J. Org. Chem. 1992, 57, 740. (f) Wang, W.; Preville, P.; Morin,
N.; Mounir, S.; Cai, W.; Siddiqui, M. A. Bioorg. Med. Chem.
Lett. 2000, 10, 1151. (g) Sawhney, S. N.; Boykin, D. W.
J. Pharm. Sci. 1979, 68, 524. (h) Spicer, J. A.; Gamage, S. A.;
Rewcastle, G. W.; Finlay, G. J.; Bridewell, D. J.; Baguley,
B. C.; Denny, W. A. J. Med. Chem. 2000, 43, 1350.
3. For example, (a) Tada, M. Bull. Chem. Soc. Jpn 1974, 47,
1803. (b) Vivian, D. L. J. Org. Chem. 1956, 21, 565. (c) Vivian,
D. L. J. Am. Chem. Soc. 1951, 73, 457. (d) Vivian, D. L.;
Hogart, R. M.; Belkin, M. J. Org. Chem. 1961, 26, 112.
(e) Tada, M. Bull. Chem. Soc. Jpn 1978, 51, 3093. (f) Pachter,
J.; Kloetzel, M. C. J. Am. Chem. Soc. 1952, 74, 971. (g) Tada,
M. Bull. Chem. Soc. Jpn 1975, 48, 363, and references cited
therein.
3.3. Preparation of 1,4-dichloro-5,10-dihydrophenazine
(11a)
A cathodic reduction of 1,4-dichlorophenazine 12a was
carried out under a constant cathodic potential in a cell and
an electrolysis medium like that described for the electro-
chemical reduction of 3,3,6,6-tetrachloro-1,2-cyclohexane-
dione 1. The temperature was kept at approximately 18 8C
by external cooling. The reduction was performed in MeCN
(40 mL)—AcOH (10 mL)—LiClO4 (3 g); 35 and 15 mL
were placed in the cathodic and the anodic compartments,
respectively. Sodium acetate (0.2 g) was placed in the anode
compartment. A solution of 12a (5 mmol) was electrolyzed
under a cathodic potential of 20.70 V versus SCE. The
electricity consumption was 2 F/mol. It was observed that
the initial intensive yellow colour of the catholyte solution
became progressively violet according to the progress of the
electricity pass. Isolation of product 11a was carried out by
removing the solvent in vacuo,20 adding water (150 mL)
and collecting the blue solid precipitate by vacuum
filtration. Crystallization from acetonitrile gave blue
needles; mp 75 8C dec, yield 95%; (Found: C, 57.31; H,
3.18; N, 11.14; C12H8Cl2N2 requires: C, 57.40; H, 3.21; N,
4. (a) Maffei, S.; Pietra, S.; Cattaneo, A. Gazz. Chim. Ital. 1953,
83, 327. (b) Maffei, S.; Pietra, S.; Cattaneo, A. Gazz. Chim.
Ital. 1953, 83, 812. (c) Chernetskii, V. P.; Kiprianov, A. I.
Ukrain. Khim. Zhur. 1955, 21, 367. C.A. 1955, 49, 14774.
5. Vivian, D. L.; Hartwell, J. L. J. Org. Chem. 1953, 18, 1065.
6. Cross, B.; Dunn, C. L.; Payne, D. H.; Tipton, J. D. J. Sci. Food
Agric. 1969, 20, 8.
7. Nasielski, J.; Heilporn, S.; Chauveheid, E.; Poppe, K.;
Nasielski-Hinkens, R. Bull. Soc. Chim. Belg. 1990, 99, 783.
8. Wrede, F.; Mu¨hlroth, O. Chem. Ber. 1930, 63, 1931.
9. Otomasu, H. Pharm. Bull. 1955, 3, 365.
1
11.16); H NMR d (CDCl3, 200 MHz): 5.26 (br s, 2H),
10. Pachter, I. J.; Kloetzel, M. C. J. Am. Chem. Soc. 1951, 73,
4958.
11. Paquet, J.; Brassard, P. Can. J. Chem. 1989, 67, 1354.
6.16–6.21 (m, 2H), 6.38 (s, 2H), 6.46–6.53 (m, 2H); 13C
NMR d (CDCl3, 50.3 MHz): 113.07, 114.62, 121.01,
122.37, 130.75, 131.21; MS m/z (%) 254 [Mþþ4] (9), 252
[Mþþ2] (55), 250 [Mþ] (100), 214 (26), 179 (68), 152 (25),
125 (48), 102 (35), 89 (38), 76 (48); IR (Nujol) 3423, 1615,
´
12. See Guirado, A.; Cerezo, A.; Ramırez de Arellano, A.
Tetrahedron 1997, 53, 6183. and reference cited therein.
13. Guirado, A.; Cerezo, A.; Andreu, R. Tetrahedron Lett. 2000,
41, 6579.
1516, 1287, 1169, 1110, 946, 908, 769, 738 cm21
.

A. Guirado et al. / Tetrahedron 60 (2004) 6747–6755
6755
14. Voudrias, E. A.; Larson, R. A.; Snoeyink, V. L.; Chen, A. S.
C.; Stapleton, P. L. Environ. Health Perspect. 1986, 69, 97.
19. For a review about electrochemistry of halogenated organic
compounds see Peters, D. G. In Organic Electrochemistry;
Lund, H., Hammerich, O., Eds.; Marcel Dekker: New York,
2001; Chapter 8.
¨
¨
15. Willstatter, R.; Muller, H. E. Chem. Ber. 1911, 44, 2182.
16. Nazar, M. A.; Rapson, W. H.; Brook, M. A.; May, S.;
Tarhanen, J. Mutat. Res. 1981, 89, 45.
20. Caution must be exercised when handling perchlorates in
order to exclude explosion risk. Evaporation of organic
solutions containing perchlorates requires to be carried out
in vacuo and at moderate temperature. The contact with strong
acids must be avoided.
17. Nishizawa, K.; Satoh, J. Y. Bull. Chem. Soc. Jpn 1975, 48, 1276.
18. Supplementary publication number CCDC-231412 (6ea),
-231411 (6f), -231413 (10db) can be obtained from the
Director, Cambridge Crystallographic Data Centre, 12 Union
Road, Cambridge, CB12 1E2, UK (fax: þ44-1223-336033 or
e-mail: deposit@ccdc.cam.ac.uk).