A simplified approach to N- and N,N′-linked 1,2,4-triazoles by transamination

Article abstract of DOI:10.1055/s-2007-983896

A facile one-step procedure for the preparation of 4,4′-bis-1,2,4- triazole is reported. Direct transamination of N,N-dimethyl-formamide azine dihydrochloride by heating with 4-amino-1,2,4-triazole in refluxing benzene readily yields the target molecule in short duration of time with significant yield (73%). This catalyst-free method was extended to synthesise a series of 4-substituted 1,2,4-triazoles of potential interest in coordination chemistry. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-983896

PRACTICAL SYNTHETIC PROCEDURES
149
A Simplified Approach to N- and N,N¢-Linked 1,2,4-Triazoles
by Transamination
A
a
S
implifiedAppr
n
oachtoN-
a
i
ndN,N
l
¢
-Linked 1,2,
D
Unité de Chimie des Matériaux Inorganiques et Organiques, Département de Chimie, Faculté des Sciences,
Université Catholique de Louvain, Place L. Pasteur 1, 1348 Louvain-la-Neuve, Belgium
b
Unité de Chimie Organique et Médicinale, Département de Chimie, Faculté des Sciences,
Université Catholique de Louvain, Place L. Pasteur 1, 1348 Louvain-la-Neuve, Belgium
Fax +32(10)472330; E-mail: garcia@chim.ucl.ac.be
Received 15 March 2007; revised 8 June 2007
PSP
No107
Abstract: A facile one-step procedure for the preparation of 4,4¢-bis-1,2,4-triazole is reported. Direct transamination of N,N-dimethyl-
formamide azine dihydrochloride by heating with 4-amino-1,2,4-triazole in refluxing benzene readily yields the target molecule in short
duration of time with significant yield (73%). This catalyst-free method was extended to synthesise a series of 4-substituted 1,2,4-triazoles
of potential interest in coordination chemistry.
Key words: amines, amino acids, ligands, transamination, 4,4¢-bis-1,2,4-triazole
RNH2
N
N
⋅2HCl
40–75% yield
N
R
N
N
N
N
benzene, reflux, 4–14 h
Scheme 1
4-Substituted 1,2,4-triazoles are important molecules with larly when the target triazoles are oils or semi-solids with
significant properties that have found widespread applica- high molecular weight.20 In 1967, Bartlett and Humphrey
tions in foremost sectors of chemical sciences. The anti- reported a multi-step synthesis of 4,4¢-bis-1,2,4-triazole
cancer, anticonvulsant, antifungal, anti-inflammatory and (btr, 4a) by the transamination of N,N-dimethylform-
antibacterial activities of these molecules are well ac- amide azine 2 with 4-amino-1,2,4 triazole (NH2trz, 3a) in
knowledged in medicinal and pharmaceutical chemistry.1 the presence of a catalytic amount of p-toluenesulfonic
As plant growth regulators,2 herbicides and pesticides,3,4 acid in refluxing toluene for 72 hours in appreciable yield
high energy density materials,5 inhibitors for corrosion (64%) (Scheme 2).13 The reactive agent (chloromethyl-
and colour photography couplers,6 they fortify their place ene)dimethylammonium chloride [Me2N+=CHCl]Cl–,
in chemical industry. They are also largely used as which was proposed19 to be generated from a solution of
synthons7 and ligands in coordination chemistry8 finding thionyl chloride in DMF, reacts with hydrazine to produce
applications as molecular magnetic materials9,10 and dye- N,N-dimethylformamide azine dihydrochloride 1. The
molecules in regenerative solar cells.11 4-Substituted strategy followed to obtain the free base 2 from 1 is quite
1,2,4-triazoles are also used in supramolecular chemistry monotonous. The dihydrochloride in water was treated
as suitable templates for the construction of nanoporous with aqueous Na2CO3 and the solution continuously ex-
coordination networks.12
tracted with ether for 2 days from which 2 is obtained in
89% yield. Schultze et al. 21 reported a simpler alternative
for the above conversion while working on 1,3,4-thiadia-
zole where the dihydrochloride in EtOH at 0 °C was treat-
ed with a NaOEt solution. Subsequent workup gave 2 in
95% yield. Haasnoot and Groeneveld14 were also credited
for their report on the direct approach to the synthesis of
4a by a one-step reaction between NH2trz and diformyl-
hydrazine (Scheme 3). Nevertheless, this method suffers
from several drawbacks such as low yield (25%), high
temperature for the reaction, tedious workup, and uncer-
tainties in reproducibility. Therefore the synthesis of
N,N¢-bis-1,2,4-triazoles that is of high importance in coor-
dination and supramolecular chemistry on account of their
multidenticity and ability to be involved in H-bonding,22
require another procedure. We propose herein an im-
proved synthetic method for 4a that has been applied to a
series of 1,2,4-triazole derivatives 4b–m (Scheme 1,
A close literature survey reveals only few reports on the
synthesis of asymmetric or symmetric N,N¢-linked bis-
azoles and N-aryl azoles.13–19 Nowadays, there is a patented
procedure of Bayer et al. which is routinely used for pro-
ducing 4-substituted 1,2,4-triazoles.3 This procedure in-
volves the addition of a primary amine on the intermediate
formed by the reaction of formic acid hydrazide with tri-
ethyl orthoformate. This one-pot synthesis affords 4-sub-
stituted 1,2,4-triazoles in moderate to good yields
depending on the nature of the substituent R.3,4 This meth-
od suffers from the limitation of workup procedure that
can involve tedious chromatographic separations particu-
SYNTHESIS 2008, No. 1, pp 0149–0154
Advanced online publication: 11.09.2007
DOI: 10.1055/s-2007-983896; Art ID: T05507SS
© Georg Thieme Verlag Stuttgart · New York
x
x
.
x
x
.2
0
0
7

150
A. D. Naik et al.
PRACTICAL SYNTHETIC PROCEDURES
Table 1). Such efficient and rapid synthetic recipes are the ten to be faced. Rewardingly, this turns out not to be the
demands of commerce, a noteworthy example being a re- case when one starts from 1, the dihydrochloride of 2.
cently documented rapid synthesis of 1H-tetrazoles.28 As Bartlett and Humphrey13 mentioned in their report that
illustrated in Table 1, various amines including amino transamination step can also be catalysed by 1, but not as
acids turned out to be valuable exchanging partners. The effectively as by p-TsOH. Our synthetic approach is con-
results are compared and discussed with other known syn- ceptually based on this idea. As these amine exchange re-
thetic methods for the sake of comparison.
actions are generally catalysed by acids,29 we vision that
reactant 1 itself plays that role in the reaction. Yield and
duration of time were improved in benzene compared to
toluene as the effective azeotropic removal of HCl is fa-
cilitated in it, shifting the equilibrium towards the target
product.
Conventional perception advices the synthesis of 4a and
related molecules13,16–18 by engaging 2 in the crucial trans-
amination step with amines and acidic catalyst. It is how-
ever observed that, particularly in the case of 4a, the
reproducibility in terms of yield and reaction time are of-
Table 1 Reaction of Various Amines with N,N-Dimethylformamide Azine Dihydrochloride
Entry
RNH2
Entry
Product
Reaction
timea (h)
Reaction
timeb (h)
Yield
(%)a
Yield
(%)b
N
N
N
N
N
N
N
3a
3b
3c
4a
4b
4c
12
4
72
73
60
58
6413
7813
7623
H2N
H2N
H2N
N
N
3.5c
1.5d
N
N
N
N
N
N
7
NH2
O
NH2
OH
N
N
N
3d
4d
7
–
68
553,24
H2N
O
OH
N
N
N
3e
3f
4e
4f
14
8
–
17
0.5
–
45
75
40
45
<7325
9118
H2N
H2N
H2N
SO3H
SO3H
NHAc
N
N
N
NHAc
N
N
N
N
N
3g
3h
4g
4h
6
4226
27
N
N
N
N
N
N
N
8
–
NH2
N
N
O
N
N
N
H2N
3i
3j
4i
4j
9
8
–
–
50
55
–
OH
OH
O
N
N
H2N
–
N
N
N
N
N
N
3k
3l
4k
4l
7
8
–
–
70
75
CH2
NH2
CH2
CH2
NH2
NH2
H2N
H2N
N
–
–
CH2H3
N
N
2
O
S
O
S
N
3m
4m
7
–
74
NH2
N
NH2
H2N
N
O
O
a Our method.
b Reported method.
c With excess of aniline.
d Multi-step synthesis.
Synthesis 2008, No. 1, 149–154 © Thieme Stuttgart · New York

PRACTICAL SYNTHETIC PROCEDURES
Simplified Approach to N- and N,N¢-Linked 1,2,4-Triazoles
151
O
H
1. SOCl2
2. NH2NH2⋅H2O, r.t.
N
2 HCl
N
N
N
N
1
aq Na2CO3/Et2O extraction13
or NaOEt/EtOH, 0 °C21
1
2
N
N
N
N
N
2
N
N
N
NH2
(3a)
N
N
N
N
N
toluene,
PTSA
reflux, 72 h
4a
64% yield
Scheme 2 Multi-step synthesis of N,N¢-bis-1,2,4-triazole (4a)13
were performed at the University College, London (UK). Melting
points were determined with an oil bath 3937-S Büchi device (T £
220 °C) or on a Mettler Toledo analyser DSC 20.
O
mixed at 100 °C,
heated to 180 °C
N
N
H
NH2
N
+
4a
H
N
N
H
H
25% yield
O
N,N-Dimethylformamide Azine Dihydrochloride (1)
Scheme 3 One-step route to N,N¢-bis-1,2,4-triazole (4a)14
SOCl2 (28.6 mL, 0.4 mol) or oxalyl chloride (34.5 mL, 0.4 mol) was
added with stirring to freshly distilled DMF (150 mL) at 5 °C. To
the aged (24 h) solution of this mixture, was added slowly aqueous
hydrazine hydrate (5 mL, 0.1 mol) in DMF (20 mL). The mixture
was stirred at r.t. for 2 d and the white precipitate of dimethylform-
amide azine dihydrochloride was collected by filtration and washed
with DMF and Et2O;13 yield: 19.4 g (91%); mp 251 °C (Lit.13 mp
250 °C). (Caution: Benzene is potentially carcinogenic; all opera-
tions involving this solvent should be conducted in a fume hood.)
It is convenient to note that most of the transamination
products (4a–h) were reported by other methods, thus al-
lowing a suitable comparison and offering the possibility
to test our procedure. In most of the documented cases,
our method appears to be superior, being uncomplicated,
single-step, and without chromatographic separation for
the isolation of the final target molecule. It also shows a
better yield, involves shorter reaction time, avoids unnec-
essary additional step and is cheaper (Table 1). We as-
sume that this transamination reaction should permit the
exchange of a larger range of amines, which undoubtedly
would widen its synthetic interest as revealed in our amine
exchange process. Nevertheless steric factors and the ba-
sicity of amines will govern the course of the reaction.
The fact that glycine (3i), an amino acid was successfully
exchanged (to give 4i) in the amine exchange process is
promising to construct an azole moiety on the amino acid
backbone which may lead to novel biochemical applica-
tions. These molecules could also be used as potential
templates in the coordination networks of spin crossover
supramolecular assemblies. A preliminary investigation
reveals that iron(II) coordination compounds of 4e,4j and
4,4¢-Bis-1,2,4-triazole (4a)
The reaction was carried out in a dry round-bottomed flask fitted
with a reflux condenser. To a suspension of 1 (9 g, 0.042 mol, 1
equiv) in benzene (30 mL) was added rapidly solid 4-amino-1,2,4
triazole (3a; 4.24 g, 0.05 mol, 1.2 equiv) with stirring. The mixture
was gently heated at the beginning until all the suspension had dis-
solved and reappeared as a white pasty mass. The mixture was re-
fluxed then for 12 h with vigorous stirring. The reaction was
1
monitored by recording H NMR spectra of the pasty mass with-
drawn at intervals of time. The white precipitate obtained was col-
lected by filtration and washed with cold EtOH (1 × 3 mL) and Et2O
(1 × 5 mL). Recrystallisation from MeOH gave colourless crystals.
The spectroscopic data were in accord with the literature value;13,14
yield: 4.2 g (73%). Small amounts of product can also be obtained
by replacing 4-amino-1,2,4 triazole (3a) with hydrazine hydrate.
N-Linked 1,2,4-triazoles 4b–m; General Procedure
The following compounds were prepared using a general procedure
4k display a colour change from white to pink on cooling, which is essentially similar to that used for 4a with variation in re-
action time (Table 1), isolation, and purification of products.
a thermochromic behaviour that can be anticipated to be
associated to spin crossover phenomenon. Such inorganic
syntheses are in progress in our laboratories.
4-Phenyl-4H-1,2,4-triazole (4b)
A mixture of aniline (3b; 0.83 mL, 9.33 mmol, 1 equiv) and 1 (2 g,
9.33 mmol, 1 equiv) was refluxed for 4 h in benzene (20 mL). The
white solid that separated was filtered, washed with cold EtOH (1 ×
3 mL) followed by Et2O (1 × 5 mL), and dried under vacuum; yield:
Procedures
0.780 g (60%); mp 121 °C (Lit.13 mp 120 °C).
Solvents were dried prior to use. Reagents (Aldrich, Acros, Merck,
Lancaster, Avocado Research chemicals or Fischer) were used as
received. 1H and 13C NMR spectra were recorded at 250 MHz and
300 MHz on a Bruker AC 250 and Bruker AC 300 instruments, re-
spectively. TMS and sodium 3-(trimethylsilyl)-1-propane sulfonate
were used as internal references in CDCl3 and D2O, respectively.
For other solvents the residual solvent peak was used as internal ref-
erence. IR spectra were recorded on a Bio-Rad FTS 135 spectrom-
eter using KBr discs. Mass spectral data were obtained on Thermo
Finnigan LCQ Ion trap spectrometer (APCI mode). CHN analyses
4-(4-Aminophenyl)-4H-1,2,4-triazole (4c)
Freshly recrystallised 1,4-phenylenediamine (3c; 1.01 g, 9.33
mmol, 1 equiv) and 1 (2 g, 9.33 mmol, 1 equiv) were mixed and re-
fluxed in benzene (20 mL) for 7 h with vigorous stirring. The resi-
due obtained after evaporating benzene was dissolved in EtOH (6
mL) and filtered off from the insoluble solid. The filtrate was con-
centrated to obtain a white solid, which was filtered, washed with
Synthesis 2008, No. 1, 149–154 © Thieme Stuttgart · New York

152
A. D. Naik et al.
PRACTICAL SYNTHETIC PROCEDURES
1,4-Bis(4H-1,2,4-triazol-4-yl)benzene (4h)
The compound was prepared from 1 (0.668 g, 3.1 mmol, 1 equiv)
and 3h (≡ 4c) (0.5 g, 3.1 mmol, 1 equiv) in refluxing benzene (25
mL) for 8 h, as a white solid, but it can also be prepared from 1 and
p-phenylenediamine in a 2:1 stoichiometric ratio; yield: 0.28 g
(45%); mp 320 °C.
cold EtOH (1 × 1 mL), and dried under vacuum; yield: 0.863 g
(58%); mp 195 °C.
IR (KBr): 3109 (m), 1540 (s), 1501 (s), 1315 (m), 1240 (m), 1012
(m), 862 (s), 636 (m), 509 cm–1 (s).
1H NMR (250 MHz, DMSO-d6, 298 K): d = 8.86 (s, 2 H), 7.23 (d,
J = 8.7 Hz, 2 H), 6.68 (d, J = 8.7 Hz, 2 H), 5.44 (br, 2 H).
13C NMR (62.5 MHz, DMSO-d6, 298 K): d = 141.4, 134, 133.3,
131.6, 122.6.
IR (KBr): 3108 (m), 3016 (m), 1540 (s), 1508 (s), 1315 (m), 1240
(m), 1089 (m), 1037 (m), 1014 (m), 862 (s), 636 cm–1 (m).
1H NMR (250 MHz, DMSO-d6, 298 K): d = 9.22 (s, 4 H), 7.95 (s, 4
H).
4-(4H-1,2,4-Triazol-4-yl)benzoic Acid (4d)
Refluxing a mixture of 1 (2g, 9.33 mmol, 1 equiv) and 4-aminoben-
zoic acid (3d; 1.28 g, 9.33 mmol, 1 equiv) in benzene (25 mL) for 7
h gave a pale yellow solid, which was filtered and washed with
EtOH (1 × 3 mL) and Et2O (1 × 5 mL); yield: 1.19 g (68%); mp
334 °C.
13C NMR (62.5 MHz, DMSO-d6, 298 K): d = 141.3, 122.6, 121.
4-(4H-1,2,4-Triazol-4-yl)acetic Acid (4i)
Azine 1 (2 g, 9.33 mmol, 1 equiv) was suspended in benzene (30
mL) and warmed slowly to around 55–60 °C. Glycine (3i; 0.7 g,
9.33 mmol, 1 equiv) was added to this solution. The resulting mix-
ture was stirred at this temperature until all the suspension had dis-
solved and reappeared as pale yellow oil that was then refluxed for
8–9 h. The oily residue obtained after removing benzene under re-
duced pressure was dissolved in EtOH (2 mL) and filtered off from
unreacted glycine. EtOH was then removed under reduced pressure
and the colourless oil was cooled in ice to obtain white crystals;
yield: 0.59 g (50%); mp 161 °C. (Caution: Fluctuation in tempera-
ture and ineffective stirring often gave a white solid, which was
probably 4i with bonded hydrochloride of glycine.)
IR (KBr): 3423 (br), 3112 (m), 1687 (s), 1608 (s), 1533 (s), 1452
(m), 1319 (s), 1085 (s), 1014 (s), 860 (s), 769 (s), 622 cm–1 (m).
1H NMR (250 MHz, DMSO-d6, 298 K): d = 9.27 (s, 2 H), 8.11 (d,
J = 8.7 Hz, 2 H), 7.85 (d, J = 8.7 Hz, 2 H).
13C NMR (62.5 MHz, DMSO-d6, 298 K): d = 166.4, 141.3, 132.6,
131.2, 130.1, 121.
4-(4H-1,2,4-Triazol-4-yl)benzenesulfonic Acid (4e)
Azine 1 (2 g, 9.33 mmol, 1 equiv) was suspended in benzene (30
mL) and heated slowly to 60 °C. Sulfonic acid 3e (1.61 g, 9.33
mmol, 1 equiv) was added to the above solution and the mixture was
vigorously stirred and refluxed for 14 h. The creamy solid obtained
was washed with H2O (1 × 3 mL) to remove the unreacted sulfonic
acid 3e, followed by EtOH (1 × 3 mL) and Et2O (1 × 4 mL); yield:
0.94 g (45%); mp >398 °C.
IR (KBr): 3442 (br), 3110 (s), 1900 (s), 1548 (m), 1496 (m), 1257
(s), 1191 (m), 1087 (m), 1020 (s), 970 (s), 883 (s), 790 (s), 655 (s),
622 cm–1 (s).
1H NMR (300 MHz, DMSO-d6, 298 K): d = 8.49 (s, 2 H), 4.98 (s, 2
H).
13C NMR (75 MHz, DMSO-d6, 298 K): d = 170.1, 144.8, 46.3.
MS: m/z = 128.04 (M + H+).
IR (KBr): 3114 (m), 1596 (m), 1564 (s), 1423 (m), 1367 (m), 1201
(m), 1112 (m), 1035 (s), 1014 (s), 946 (m), 842 (m), 754 (m), 634
(s), 567 cm–1 (s).
1H NMR (250 MHz, DMSO-d6, 298 K): d = 9.65 (s, 2 H), 7.68–7.8
(ABq, J = 8.7 Hz, 4 H).
Anal. Calcd for C4H5N3O2 (127.10): C, 37.80; H, 3.97; N, 33.06.
Found: C, 37.57, H, 4.10, N, 32.59.
4-(Pyridin-2-yl-methyl)-4H-1,2,4-triazole (4j)
13C NMR (62.5 MHz, DMSO-d6): d = 163.1, 141.9, 131.7, 127.2,
A mixture of 1 (2 g, 9.33 mmol, 1 equiv) and 2-(aminomethylpyri-
dine) (3j; 0.96 mL, 9.33 mmol, 1 equiv) in benzene (20 mL) was re-
fluxed for 8 h. The oily residue obtained after removing benzene
under reduced pressure was dissolved in EtOH (2 mL) and the com-
pound was precipitated by dropwise addition of Et2O. The white
solid, which usually turned to pale yellow upon keeping in air, was
collected and dried under vacuum (hygroscopic); yield: 0.818 g
(55%); mp 77–80 °C.
121.3.
N-(4-(4H-1,2,4-Triazol-4-yl)phenyl)acetamide (4f)
Refluxing a mixture of 1 (2 g, 9.33 mmol, 1 equiv) and 4¢-amino-
acetanilide (3f; 1.4 g, 9.33 mmol, 1 equiv) in benzene (25 mL) for
8 h afforded a beige solid, which was washed with EtOH (1 × 3 mL)
and dried; yield: 1.4 g (75%); mp 289 °C.
1H NMR (250 MHz, DMSO-d6, 298 K): d = 10.18 (s, 1 H, NH),
9.04 (s, 2 H), 7.75 (d, J = 8.7 Hz, 2 H), 7.59 (d, J = 8.7 Hz, 2 H),
2.07 (s, 3 H).18
IR (KBr): 1646 (m), 1637 (m), 1592 (s), 1571 (m), 1529 (s), 1479
(m), 1434 (s), 1187 (s), 1076 (s), 997 (m), 871 (m), 752 (s), 700 (m),
647 cm–1 (s).
4-(Pyridin-3-yl)-4H-1,2,4-triazole (4g)
1H NMR (250 MHz, CDCl3, 298 K): d = 8.54–8.56 (m, 1 H), 8.28
(s, 2 H), 7.64–7.71 (m, 1 H), 7.22–7.27 (m, 1 H), 7.13 (d, J = 8 Hz,
1 H), 5.27 (s, 2 H).
13C NMR (62.5 MHz, CDCl3, 298 K): d = 154, 150.2, 143.2, 137.6,
123.7, 121.9, 50.6.
A mixture of 1 (2 g, 9.3 mmol, 1 equiv) and 3-aminopyridine (3g;
0.878 g, 9.3 mmol, 1 equiv) were mixed and refluxed for 6 h in ben-
zene (25 mL). The turbid solution was cooled to r.t. and the white
solid separated was filtered and suspended in a small amount of cold
EtOH (1 mL) for a short time, filtered, and dried; yield: 0.54 g
(40%); mp 158 °C.
MS: m/z = 161.22 (M + H+).
Anal. Calcd for C8H8N4 (160.18): C, 59.99; H, 5.03; N, 34.98.
Found: C, 58.10; H, 4.92; N, 33.27.
IR (KBr): 1629 (s), 1483 (m), 1430 (m), 1377 (m), 1328 (m), 1251
(m), 1097 (s), 958 (m), 883 (m), 802 (m), 729 (w), 696 cm–1 (w).
1H NMR (250 MHz, CDCl3, 298 K): d = 8.73–8.68 (m, 2 H), 8.5 (s,
4-{4-[(4-Aminophenyl)methyl]phenyl}-4H-1,2,4-triazole (4k)
4,4¢-Diaminodiphenylmethane (3k; 1.85 g, 9.33 mmol, 1 equiv)
was suspended in benzene (40 mL) and warmed to 60 °C. To this
solution was added slowly a solution of 1 (2 g, 9.33 mmol, 1 equiv)
in benzene (20 mL) with vigorous stirring. The pale yellow pasty
mass obtained was refluxed for 7 h. The solid lumps obtained were
2 H), 7.77–7.82 (m,1 H), 7.47–7.52 (m, 1 H).
13C NMR (62.5 MHz, CDCl3, 298 K): d = 153.3, 150.4, 143.4,
141.3, 130.0, 124.8.
Synthesis 2008, No. 1, 149–154 © Thieme Stuttgart · New York

PRACTICAL SYNTHETIC PROCEDURES
Simplified Approach to N- and N,N¢-Linked 1,2,4-Triazoles
153
filtered, dried, and washed with cold EtOH (2 mL). It was then dis-
solved in MeOH (10 mL) and layered with Et2O (5 mL). Pale yel-
low crystals thus obtained were filtered and dried; yield: 1.62 g
(70%); mp 222 °C.
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IR (KBr): 3348 (m), 3197 (m), 3087 (m), 1633 (s), 1616 (s), 1296
(m), 1091 (s), 1000 (s), 811 (s), 653 cm–1 (m).
1H NMR (300 MHz, DMSO-d6, 298 K): d = 9.08 (s, 2 H), 7.61 (d,
J = 8.5 Hz, 2 H), 7.38 (d, J = 8.5 Hz, 2 H), 6.91 (d, J = 8.3 Hz, 2 H),
6.52 (d, J = 8.3 Hz, 2 H), 4.92 (br, 2 H), 3.84 (s, 2 H).
13C NMR (75 MHz, DMSO-d6, 298 K): d = 147.6, 143.4, 142.1,
132.5, 130.6, 129.9, 128.5, 122, 114.8, 38.2.
MS: m/z = 251.70 (M + H+).
Anal. Calcd for C15H14N4 (250.30): C, 71.98; H, 5.64; N, 22.38.
Found: C, 72.14; H, 5.95; N, 22.48.
Bis[4-(4H-1,2,4-triazol-4-yl)phenyl]methane (4l)
The pasty mass obtained after mixing 4,4¢-diaminodiphenyl-
methane [3l (≡ 3k) 0.925 g, 4.66 mmol, 1 equiv] and 1 (2 g, 9.33
mmol, 2 equiv) in benzene (25 mL) was stirred vigorously and re-
fluxed for 8 h. The pale yellow solid obtained was filtered, and
washed with cold EtOH (1 × 3 mL). The solid was dissolved in hot
EtOH (10 mL), treated with a pinch of charcoal and filtered. White
crystals obtained was separated and dried under vacuum; yield: 2.10
g (75%); mp 262 °C.
(7) Laus, G.; Kloetzer, W. Synthesis 1989, 269.
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Dordrecht, 1996, 299. (b) Haasnoot, J. G. Coord. Chem.
Rev. 2000, 200/202, 131.
(9) Garcia, Y.; Niel, V.; Muñoz, M. C.; Real, J. A. Top. Curr.
Chem. 2004, 233, 229.
IR (KBr): 3095 (m), 2775 (m), 1635 (m), 1562 (m), 1523 (s), 1243
(s), 1095 (s), 998 (m), 867 (m), 817 (m), 792 (s), 636 cm–1 (s).
1H NMR (300 MHz, DMSO-d6, 298 K): d = 9.1 (s, 4 H), 7.65 (d,
J = 8.5 Hz, 4 H), 7.45 (d, J = 8.5 Hz, 4 H), 4.0 (s, 2 H).
(10) Ouellette, W.; Galán-Mascarós, J. R.; Dunbar, K. R.;
Zubieta, J. Inorg. Chem. 2006, 45, 1909.
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C. J.; Alebbi, M.; Bignozzi, C. A. Eur. J. Inorg. Chem. 1999,
2309.
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Chem. Soc. 2005, 127, 14162.
(13) Bartlett, R. K.; Humphrey, I. R. J. Chem. Soc. C 1967, 1664.
(14) Haasnoot, J. G.; Groeneveld, W. L. Z. Naturforsch., B:
Anorg. Chem. Org. Chem. 1979, 34, 1500.
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1549.
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M. C.; Elguero, J. J. Chem. Res., Synop. 1980, 50.
(b) Curtis, A. D. M. In Science of Synthesis, Vol. 13; Storr,
R.; Gilchrist, T., Eds.; Thieme: Stuttgart, 2004, 603.
(17) (a) Castellanos, M. L.; Llinas, M.; Bruix, M.; de Mendoza,
J.; Martin, M. R. J. Chem. Soc., Perkin Trans. 1 1985, 1209.
(b) Woisel, P.; Cazier, F.; Surpateanua, G.; Baudel, V.;
Boursier, V. Heterocycl. Commun. 2002, 8, 71.
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G.; Reeve, A. J.; Hunt, P. A.; Beer, M. S.; Held, A.; Stanton,
J. A.; Sohal, B.; Watt, A. P.; Street, L. J. J. Med. Chem. 1999,
42, 677. (b) Bouchet, P.; Coquelet, C. J. Chem. Soc., Perkin
Trans. 2 1974, 449.
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Chim. Acta 1959, 42, 1653.
(20) (a) Boland, Y.; Attout, A.; Marchand-Bryanert, J.; Garcia,
Y. J. Chromatogr., A 2007, 1141, 145. (b) Boland, Y.;
Hertsens, P.; Marchand-Bryanert, J.; Garcia, Y. Synthesis
2006, 1504.
13C NMR (75 MHz, DMSO-d6, 298 K): d = 141.6, 133, 132, 130.2,
121.8, 34.8.
MS: m/z = 303.04 (M + H+).
Anal. Calcd for C17H14N6 (302.34): C, 67.54; H, 4.67; N, 27.80.
Found: C, 67.79, H, 5.03, N, 27.36.
4-{4-[(4-Aminophenyl)sulfonyl]phenyl}-4H-1,2,4-triazole (4m)
To a warmed suspension of 1 (2 g, 9.33 mmol, 1 equiv) in benzene
(35 mL) was added slowly a solution of 4,4¢-diaminodiphenyl sul-
fone (3m; 2.317 g, 9.33 mmol, 1 equiv) in benzene (15 mL). Within
15–20 min a pale yellow semisolid appeared. The mixture was re-
fluxed with vigorous stirring for 7 h. The solid was filtered and
washed with EtOH (3 mL). Recrystallisation from hot MeOH gave
white crystals; yield: 2.06 g (74%); mp 254 °C.
IR (KBr): 3411 (br), 3323 (m), 3203 (m), 3134 (m), 1629 (m), 1590
(s), 1525 (s), 1504 (m), 1301 (s), 1150 (s), 1107 (s), 673 (s), 595 (s),
555 cm–1 (s).
1H NMR (300 MHz, DMSO-d6, 298 K): d = 9.22 (s, 2 H), 8.03 (d,
J = 8.8 Hz, 2 H), 7.93 (d, J = 8.8 Hz, 2 H) 7.62 (d, J = 8.8 Hz, 2 H),
6.65 (d, J = 8.8 Hz, 2 H), 6.25 (br, 2 H).
13C NMR (75 MHz, DMSO-d6, 298 K): d = 154.7, 143.3, 142.1,
137.7, 130.4, 129.2, 125.6, 122.8, 113.9.
MS: m/z = 301.18 (M + H+).
Anal. Calcd for C14H12N4O2S (300.34): C, 55.99; H, 4.03; N, 18.65.
Found: C, 55.40; H, 4.79; N, 17.46.
(21) Fohlisch, B.; Braun, R.; Schultze, K. W. Angew. Chem., Int.
Acknowledgment
Ed. Engl. 1967, 6, 361.
(22) (a) Garcia, Y.; Kahn, O.; Rabardel, L.; Chansou, B.;
Tuchagues, J.-P. Inorg. Chem. 1999, 38, 4663. (b) Garcia,
Y.; van Koningsbruggen, P. J.; Kooijman, H.; Spek, A. L.;
Haasnoot, J. G.; Kahn, O. Eur. J. Inorg. Chem. 2000, 307.
(c) Garcia, Y.; van Koningsbruggen, P. J.; Kooijman, H.;
Spek, A. L.; Haasnoot, J. G.; Kahn, O. Eur. J. Inorg. Chem.
We gratefully acknowledge the financial support from the Fonds
Special de Recherche of the Université Catholique de Louvain and
the IAP-VI (P6/17) programme. J. Marchand-Brynaert is a senior
research associate of the FNRS (Belgium).
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