Preparation and N-alkylation of 4-Aryl-1,2,4-triazoles

Article abstract of DOI:10.1055/s-0029-1218794

Heating of N,N-dimethylformamide azine dihydrochloride {N-[(dimethylamino) methylene]-N,N-dimethylhydrazonoformamide dihydrochloride} with anilines in the absence of a solvent gave a range of 4-aryl-1,2,4-triazoles by direct transamination. Ortho-substituents were tolerated. Some triazoles were converted into symmetrically and nonsymmetrically substituted bistriazolium salts, one of which was converted into a dicopper complex. Georg Thieme Verlag Stuttgart - New York.

Full text of DOI:10.1055/s-0029-1218794

2278
PAPER
Preparation and N-Alkylation of 4-Aryl-1,2,4-triazoles
4
-Aryl-1,2,4-t
triazolesefanie C. Holm, Alexander F. Siegle, Christian Loos, Frank Rominger, Bernd F. Straub*
Organisch-Chemisches Institut, Ruprecht-Karls-Universität Heidelberg, Im Neuenheimer Feld 270, 69120 Heidelberg, Germany
E-mail: straub@oci.uni-heidelberg.de
Received 13 April 2010
Dedicated to Professor Dr. Dr. h.c. mult. Rolf Huisgen on the occasion of his 90th birthday
of a primary amine. This one-pot approach affords 4-sub-
stituted 1,2,4-triazoles in moderate-to-good yields. How-
ever, this method has the disadvantage of requiring a
tedious workup procedure that includes chromatographic
Abstract: Heating of N,N-dimethylformamide azine dihydrochlo-
ride {N¢-[(dimethylamino)methylene]-N,N-dimethylhydrazonoform-
amide dihydrochloride} with anilines in the absence of a solvent
gave a range of 4-aryl-1,2,4-triazoles by direct transamination.
Ortho-substituents were tolerated. Some triazoles were converted separation. Bartlett and Humphrey13 developed a method
into symmetrically and nonsymmetrically substituted bistriazolium
salts, one of which was converted into a dicopper complex.
for synthesizing 4-substituted 1,2,4-triazoles by transami-
nation of N,N-dimethylformamide azine {N¢-[(dimethyl-
amino)methylene]-N,N-dimethylhydrazonoformamide}
with primary amines in the presence of a catalytic amount
of 4-toluenesulfonic acid in refluxing toluene. N,N-Di-
methylformamide azine is obtained as its dihydrochloride
Key words: aminations, cyclizations, heterocycles, alkylations, tri-
azoles
Although the 1,2,4-triazole fragment is unknown in any salt 1 (Scheme 1) by treating hydrazine or an N,N¢-diacyl-
natural product,1 4-substituted 1,2,4-triazoles show high hydrazine with thionyl chloride in N,N-dimethylform-
levels of biological activity. Besides their use as amide. The Bartlett and Humphrey reaction affords good
anticonvulsants2 and in cancer therapy,3 their most impor- yields of 1,2,4-triazoles, but N,N-dimethylformamide
tant application is as biocides.4 1,2,4-Triazoles are highly azine has to be liberated by treating the dihydrochloride 1
efficient fungicides, and are therefore used as broad-spec- with sodium carbonate, followed by continuous extraction
trum fungicides in agriculture. 1,2,4-Triazole fungicides with diethyl ether for two days. The free base can be ob-
exert their biological effect through inhibition of the bio- tained more rapidly and in good yield by deprotonation of
synthesis of ergosterol in fungi.5
the dihydrochloride 1 with sodium ethoxide in ethanol.14
Naik et al.15 have shown that the transamination reaction
also occurs when the dihydrochloride 1 is used directly,
thereby avoiding the need to convert the compound into
the corresponding free base. Moderate-to-good yields of
4-substituted 1,2,4-triazoles have been obtained by heat-
ing primary amines with the azine dihydrochloride 1 in
benzene for 4–14 h. The authors report that the use of ben-
zene is necessary because it permits azeotropic removal of
the hydrochloric acid byproduct, thereby shifting the equi-
librium towards the product. We propose a solvent-free
protocol for the preparation of 4-aryl 1,2,4-triazoles that
tolerates the presence of ortho-substituents and avoids the
need to use carcinogenic benzene (Scheme 1).
Besides their agricultural and pharmaceutical applica-
tions, 1,2,4-triazoles are of interest as precursors in the
synthesis of N-heterocyclic carbenes (NHCs).6 The first
NHC was isolated in 1991 by Arduengo et al.,6b and the
first stable carbene with a 1,2,4-triazolylidene structure
was reported four years later.7 Nowadays, NHCs are well-
established ligands in organometallic chemistry and catal-
ysis. However, comparatively few complexes with tria-
zolyl ligands have been synthesized. Gnanamgari et al.8
report a triazolylidene-derived iridium(I) carbene com-
plex that is catalytically active in transfer hydrogenation
and reductive amination reactions. Complexes with chiral
1,2,4-triazole-derived NHC ligands have been used as cat-
alysts in enantioselective azadiene Diels–Alder reac- The only other reported method for preparing 4-aryl-
tions,9 Oxy-Cope rearrangements,10 and Staudinger 1,2,4-triazoles under solvent-free conditions involves mi-
reactions of ketenes with imines.11
crowave heating of para-substituted anilines with N,N¢-
diformyl hydrazide.16 In our cost-efficient protocol, which
involves a simple workup, anilines are heated with N,N-
dimethylformamide azine dihydrochloride (1) in a ratio of
1:1 or 2:1 in the absence of solvent (Table 1).
Many reactions have been established for the preparation
of mono-, di-, and trisubstituted 1,2,4-triazoles. These
syntheses are generally based on hydrazine or substituted
hydrazines.12 A patented procedure developed by Bayer et
al.4 is routinely used to synthesize 4-substituted 1,2,4-tri- Unlike the reaction in refluxing benzene, both para-sub-
azoles. In this procedure, formic hydrazide is treated with stituted anilines and sterically shielded ortho-substituted
triethyl orthoformate to give N¢-ethoxymethylene-N¢- anilines were successfully converted into the correspond-
formylhydrazine, which undergoes subsequent addition ing 1,2,4-triazoles (entries 2–5). An increase of the steric
hindrance in the ortho-position resulted in a reduced yield
or a longer reaction time. Nevertheless, even 2,6-diisopro-
pylaniline was transformed into the respective triazole 2d
(entry 4) in a yield of up to 42%. Substitution of the sub-
SYNTHESIS 2010, No. 13, pp 2278–2286
Advanced online publication: 20.05.2010
DOI: 10.1055/s-0029-1218794; Art ID: C01510SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
1
0

PAPER
4-Aryl-1,2,4-triazoles
2279
O
H
1. SOCl2
N
NMe2
NMe2
2 Cl
(a)
(b)
(c)
(d)
Me2N
Me2N
N
H
Me2N
H
2. NH2NH2⋅H2O
1
Na2CO3 (aq)
RNH2, p-TsOH
N
N
R
N
1
1
1
N
N
extraction with Et2O, 2 d
toluene–benzene
reflux
RNH2
N
N
R
N
benzene, reflux
RNH2
N
N
R
N
neat, 130–160 °C
Scheme 1 (a) Preparation of N,N-dimethylformamide azine dihydrochloride; (b) Bartlett and Humphrey 1,2,4-triazole synthesis;13 (c) Direct
transamination with the N,N-dimethylformamide azine dihydrochloride 1 in refluxing benzene (Naik et al.15); (d) Direct transamination with
the N,N-dimethylformamide azine dihydrochloride in the absence of a solvent, as reported in this work.
strate by thioether (entry 5) or trifluoromethyl (entry 6) ysis of triazole 2f (Figure 1) showed that the two ring sys-
groups was also tolerated. However, the presence of tems adopt a nearly coplanar orientation (torsion angle
strongly electron-withdrawing nitro groups in the aniline 17.9°).
precursor markedly reduced the yield of the reaction (en-
tries 7 and 8).
In contrast, X-ray structure analysis of triazole 2b
(Figure 2) revealed a perpendicular orientation of the two
The steric effect of an ortho-substituent is also manifested rings (torsion angle 88.3°) as a result of steric interaction
in the torsion angle between the planes of the triazole ring between the triazole system and the methyl groups in the
and the phenyl ring. A single-crystal X-ray structure anal- ortho-positions of the phenyl ring.
Similarly, the X-ray structure analysis of triazole 2e
(Figure 3) showed the presence of twisting by 108.4°
caused by the benzylthio substituent.
1,2,4-Triazoles are valuable precursors of N-heterocyclic
carbenes. Electrophilic methylation of triazole 2e with
dimethyl sulfate gave the triazolium salt 3a in good yield.
To remove the reactive monomethyl sulfate anion, com-
pound 3a was subjected to a salt metathesis reaction by
Figure 1 ORTEP plot of the molecular structure of 4-[4-(trifluoro-
stirring a dichloromethane solution of the salt with aque-
ous 4-toluenesulfonic acid to replace the monomethyl sul-
fate counterion with a tosylate counterion (Scheme 2).
methyl)phenyl]-4H-1,2,4-triazole (2f). Bond lengths [Å]: N1–C2,
1.350; C2–N3, 1.290; N3–N4, 1.383; N4–C5, 1.296; C5–N1, 1.360;
N1–C11, 1.419. Angles [°]: C2–N1–C5, 102.7; N1–C2–N3, 112.5;
C2–N3–N4, 106.5; C2–N1–C11, 128.7; C2–N1–C11–C12, 17.9.
Table 1 Solvent-Free Direct Transamination Reactions of N,N-Dimethylformamide Azine Dihydrochloride
Entry
Aniline
Ratio aniline/1 Time (d)
Temp (°C)
140
Triazole
2a
Isolated yield (%)
58
1
2
4-MeC6H4NH2
2,6-Me2C6H3NH2
2:1
1
1:1
2:1
1
3
130
150
2b
54
68
3
4
2,4,6-Me3C6H2NH2
1:1
1
130
2c
56
2,6-i-Pr2C6H3NH2
1:1
2:1
1
6
150
150
2d
17
42
5
6
7
8
2-BnSC6H4NH2
4-F3CC6H4NH2
2-O2NC6H4NH2
4-O2NC6H4NH2
1:1
1:1
2:1
2:1
3
1
1
7
150
130
130
160
2e
2f
46
44
6
2g
2h
1
Synthesis 2010, No. 13, 2278–2286 © Thieme Stuttgart · New York

2280
S. C. Holm et al.
PAPER
Symmetrically or nonsymmetrically substituted alkyl or
aryl bisimidazolinium salts and their transition metal
complexes can be synthesized by well-established proce-
dures developed by our group.17 A similar methodology
can be applied to the triazolium system.
N
N
N
N
N
N
Figure 2 ORTEP plot of the molecular structure of 4-(2,6-di-
methylphenyl)-4H-1,2,4-triazole (2b). Bond lengths [Å]: N1–C2,
1.357; C2–N3, 1.298; N3–N4, 1.389; N4–C5, 1.302; C5–N1, 1.356;
N1–C11, 1.440. Angles [°]: C2–N1–C5, 102.9; N1–C2–N3, 111.6;
C2–N3–N4, 106.5; C2–N1–C11, 126.9; C2–N1–C11–C12, 88.3.
2 Br
4
2b (2 equiv)
MeOH
56%
reflux, 1 d
Br
Br
2e (2 equiv)
neat
130 °C, 3 h
93%
N
N
N
N
N
N
2 Br
SBn
BnS
5
Scheme 3 Synthesis of symmetrically substituted propylene-linked
bistriazolium salts 4 and 5 from 1,2,4-triazoles 2b and 2e, respective-
ly
Reactions of 1,2,4-triazoles 2b and 2e with 1,3-dibro-
mopropane gave the bistriazolium dibromides 4 and 5 in
56 and 93% yields, respectively (Scheme 3). The dica-
tions can also be linked through a more rigid a,a¢-meta-
xylylene group (Scheme 4).
Figure 3 ORTEP plot of the molecular structure of 4-[2-(benzyl-
thio)phenyl]-4H-1,2,4-triazole (2e). Bond lengths [Å]: N1–C2, 1.356;
C2–N3, 1.304; N3–N4, 1.392; N4–C5, 1.303; C5–N1, 1.361; N1–
C11, 1.439; C12–S1, 1.765; S1–C20, 1.819; C20–C21, 1.504. Angles
[°]: C2–N1–C5, 103.8; N1–C2–N3, 111.5; C2–N3–N4, 106.6; C2–
N1–C11, 127.5; C11–C12–S1, 117.5; C12–S1–C20, 103.7; S1–C20–
C21, 107.4; C5–N1–C11–C12, 69.0; C13–C12–S1–C20, 7.0; S1–
C20–C21–C22, 108.4.
Cl
Cl
2e (2 equiv)
neat
130 °C, 3 h
94%
N
N
N
N
N
Me2SO4
acetone, reflux, 3 h
N
N
N
N
N
N
N
Me
89%
MeOSO3
SBn
BnS
2 Cl
SBn
SBn
6a
3a
TsOH
CH2Cl2/H2O
r.t., 1 h
TsOH
CH2Cl2/H2O
r.t., 1 h
95%
52%
N
N
N
N
N
N
N
N
N
Me
SBn
3b
OTs
SBn
BnS
2 OTs
6b
Scheme 2 Synthesis of 1-methyltriazolium salts 3a and 3b
Scheme 4 Synthesis of symmetrically substituted bistriazolium
salts 6a and 6b from triazole 2e with an a,a¢-meta-xylylene linker
Synthesis 2010, No. 13, 2278–2286 © Thieme Stuttgart · New York

PAPER
4-Aryl-1,2,4-triazoles
2281
Because bistriazolium salts 4–6 with halides as counter-
ions are barely soluble in organic solvents, it can be bene-
ficial to exchange the halide counterions for tosylate ions,
thereby increasing the solubility of the salts. The bistria-
zolium dichloride 6a was converted into the correspond-
ing ditosylate 6b in good yield by salt metathesis, as
described above (see Scheme 2).
N
N
N
N
N
N
SBn
BnS
2 Cl
6a
CuOAc, NaH
THF, r.t., 2 h
78%
A monotriazolium salt was synthesized for use as a build-
ing block for nonsymmetrical bistriazolium salts. Treat-
ment of triazole 2b with a twentyfold excess of 1-bromo-
3-chloropropane gave the monotriazolium bromide 7. The
3-chloropropyl substituent in cation 7 is receptive to a sec-
ond nucleophilic attack by a 1,2,4-triazole (Scheme 5).
Again, N-alkylation is favored over the formation of a sul-
fonium salt. The nonsymmetrical bistriazolium dication
8a was thus obtained as a mixed bromide chloride salt. To
avoid the presence of two halide counterions, this salt was
converted into the corresponding ditosylate 8b.
SBn
SBn
N
N
N
N
N
N
Cu
Cl
Cu
Cl
9
Scheme 6 Synthesis of dicopper(I) complex 9 by deprotonation of
ligand precursor 6a in the presence of copper(I) acetate
Currently, we are working on the syntheses of other dinu-
clear transition metal bis-NHC complexes with 1,4-disub-
stituted 1,2,4-triazolylidene ligands. Heterodinuclear
complexes are of particular interest. After deprotection of
thioethers by C–S-bond cleavage, free thiophenyl triazo-
lium salts could serve as precursors of chelating NHC thi-
olate ligands. Such free ligands have not yet been
described in the literature,18 but could have a significant
impact on both bioinorganic model chemistry and biomi-
metic catalysis.
N
N
Br(CH2)3Cl
40 °C, 3 d
N
N
Cl
N
N
75%
Br
2b
7
2e (1.5 equiv)
neat, 140 °C, 2 h
95%
N
N
N
N
N
N
Starting materials as supplied by Acros Organics, Aldrich Chemical
Co., and TCI were used without further purification. Reactions in-
volving air-sensitive reagents were carried out under N2 or argon by
using standard Schlenk techniques. Solvents were dried in an
MBRAUN MB SCS-800 solvent-purification system. NMR spectra
were recorded by using Bruker ARX-250, Bruker Avance 300, or
Bruker Avance 500 spectrometers. Chemical shifts are reported in
ppm relative to TMS, and were determined by reference to the re-
sidual 1H or 13C solvent peaks. Melting points were determined by
using a Gallenkamp hot-stage microscope and are uncorrected.
Br
Cl
BnS
8a
TsOH
CH2Cl2/H2O
r.t., 1 h
64%
N
N
N
N
N
N
2 OTs
BnS
4-(4-Methylphenyl)-4H-1,2,4-triazole (2a)19
8b
4-MeC6H4NH2 (30.0 mmol, 3.22 g) was added to the azine dihydro-
chloride 1 (15.0 mmol, 3.23 g) under argon, and the mixture was
stirred at 140 °C for 24 h. The resulting melt was dissolved in tolu-
ene (150 mL) and the soln was basified with 1 M aq NaOH. The
aqueous layer was extracted with toluene (3 × 25 mL), and the com-
bined organic layers were dried (MgSO4) and concentrated in vac-
uo. Small amounts of Et2O were added to the resulting oil. A crude
product precipitated as a light brown solid; this was filtered off and
sublimed (115 °C, 0.2 mbar) to give a colorless solid; yield: 1.39 g
(58%); C9H9N3 (M = 159.19 g/mol); mp 118 °C.
Scheme 5 Synthesis of monotriazolium salt 7 and the nonsymmetri-
cally substituted bistriazolium salts 8a and 8b
The 1,2,4-triazolium salts that we prepared possess an
acidic hydrogen atom in the 5-position that can be readily
removed by a strong base to give a rather unstable tran-
sient carbene species that reacts immediately with a metal
salt. We were able to attach a bistriazolyl ligand to two
copper(I) atoms to form a dicopper(I) bis-NHC complex.
Deprotonation of the symmetrically substituted ligand
precursor 6a with sodium hydride in absolute tetrahydro-
furan containing copper(I) acetate gave complex 9 in good
IR (KBr): 3117 (m), 2955 (w), 1636 (w), 1529 (s), 1446 (w), 1369
(w), 1297 (w), 1263 (w), 1244 (w), 1092 (m), 1000 (w), 822 (m),
653 (w), 623 (w), 530 (m) cm–1.
1H NMR (300.132 MHz, CDCl3): d= 2.35 (s, 3 H, CH3), 7.21 (d,
yield (Scheme 6). The 1H and 13C NMR chemical shifts of 3JHH = 8.6 Hz, 2 H, HPh3/5), 7.26 (d, 3JHH = 8.6 Hz, 2 H, HPh2/6), 8.40
(s, 2 H, N–CH–N).
13C NMR (75.476 MHz, CDCl3): d = 20.9 (CH3), 122.0 (CPh3/5),
130.6 (CPh2/6), 131.2 (CPh1), 139.1 (CPh4), 141.4 (N–CH–N).
the SCH2 unit in copper complex 9 are within the range of
those of triazoles and triazolium salts. There is, therefore,
no direct evidence of a thioether-to-copper coordination.
MS (EI, 70 eV): m/z (%) = 159.07 (100) [C9H9N3]+, 131.05 (47)
[C9H9N1]+.
Synthesis 2010, No. 13, 2278–2286 © Thieme Stuttgart · New York

2282
S. C. Holm et al.
PAPER
Anal. Calcd for C9H9N3: C, 67.90; H, 5.70; N, 26.40. Found: C,
67.79; H, 5.76; N, 26.45.
228 °C. (The yield was increased to 42% by performing the reaction
at 150 °C for 6 d with a 2:1 starting ratio of 2,6-i-Pr2C6H3NH2 to
azine dihydrochloride 1.)
4-(2,6-Dimethylphenyl)-4H-1,2,4-triazole (2b)
IR (KBr): 3097 (s), 2963 (s), 2930 (w), 2870 (m), 1523 (s), 1508 (s),
1368 (m), 1286 (m), 1211 (m), 1117 (w), 1094 (s), 1061 (m), 996
(s), 810 (s), 766 (s), 668 (m) cm–1.
2,6-Me2C6H3NH2 (10.0 mmol, 1.21 g) was added to the azine dihy-
drochloride 1 (10.0 mmol, 2.15 g) under argon, and the mixture was
stirred at 130 °C for 24 h. The resulting melt was dissolved in tolu-
ene (50 mL) and the soln was basified with 1 M aq NaOH. The
aqueous layer was extracted with toluene (3 × 15 mL), and the com-
bined organic layers were dried (MgSO4) and concentrated in vac-
uo. The residue was washed with small amounts of Et2O, and the
resulting reddish crude product was sublimed (125 °C, 0.2 mbar) to
give a colorless solid; yield: 0.94 g, (54%); C10H11N3 (M = 173.21
g/mol); mp 173 °C. (The yield was increased to 68% by performing
the reaction at 150 °C for 3 d with a 2:1 starting ratio of 2,6-
Me2C6H3NH2 to dihydrochloride 1.)
1H NMR (300.132 MHz, CDCl3): d = 1.06 [d, 3JHH = 6.9 Hz, 12 H,
3
CH(CH3)2], 2.26 [sept, JHH = 6.9 Hz, 2 H, CH(CH3)2], 7.22 (d,
3JHH = 7.8 Hz, 2 H, HPh3/5), 7.42 (t, 3JHH = 7.8 Hz, 1 H, HPh4), 8.11
(s, 2 H, N–CH–N).
13C NMR (75.476 MHz, CDCl3): d = 24.0 [CH(CH3)2], 28.1
[CH(CH3)2], 124.1 (CPh3/5), 128.8 (CPh1), 130.7 (CPh4), 143.8 (N–
CH–N), 146.0 (CPh2/6).
MS (ESI): m/z (%) = 481.15 (100) [2M + Na]+, 268.16 [M + K]+,
252.20 [M + Na]+, 230.25 [M + H]+.
IR (KBr): 3111 (m), 2951 (w), 2921 (w), 1513 (s), 1471 (m), 1290
(m), 1213 (m), 1110 (m), 1083 (w), 1038 (w), 996 (m), 949 (w), 872
(w), 782 (s), 663 (s), 557 (w), 537 (w) cm–1.
Anal. Calcd for C14H19N3: C, 73.33; H, 8.35; N, 18.32. Found: C,
73.39; H, 8.32; N, 18.32.
1H NMR (300.132 MHz, CDCl3): d = 1.96 (s, 6 H, CH3), 7.13 (d,
3JHH = 7.5 Hz, 2 H, HPh3/5), 7.25 (d, 3JHH = 7.5 Hz, 1 H, HPh4), 8.12
(s, 2 H, N–CH–N).
13C NMR (75.476 MHz, CDCl3): d = 17.4 (CH3), 128.7 (CPh3/5),
129.8 (CPh4), 131.9 (CPh1), 135.1 (CPh2/6), 142.7 (N–CH–N).
4-(2-Benzylthiophenyl)-4H-1,2,4-triazole (2e)
2-H2NC6H4SBn21 (10.0 mmol, 2.15 g) and the azine dihydrochlo-
ride 1 (10.0 mmol, 2.15 g) were ground in a mortar and heated with-
out solvent to 150 °C for 72 h under N2. The resulting dark melt was
dissolved in CH2Cl2 (100 mL), and the soln was basified with 1 M
aq NaOH. The aqueous layer was extracted once with CH2Cl2 (50
mL). The combined organic layers were washed with H2O (2 × 50
mL), dried (MgSO4), and concentrated. The resulting dark oil was
stirred in Et2O (150 mL) to give a gray powder. The solid was fil-
tered off and sublimed (170 °C, 0.5 mbar) to yield colorless crystals;
yield: 2.47 g (46%); C15H13N3S (M = 267.35 g/mol); mp 126 °C.
MS (ESI): m/z (%) = 369.30 (55) [2M + Na]+, 212.13 (12) [M + K]+,
195.96 (25) [M + Na]+, 174.21 (10) [M + H]+.
Anal. Calcd for C10H11N3: C, 69.34; H, 6.40; N, 24.26. Found: C,
69.12; H, 6.46; N, 24.14.
4-Mesityl-4H-1,2,4-triazole (2c)20
IR (KBr): 3429 (br), 3114 (w), 1584 (w), 1520 (s), 1504 (s), 1470
(m), 1453 (m), 1434 (w), 1298 (w), 1218 (m), 1162 (w), 1095 (m),
1073 (m), 993 (m), 858 (w), 781 (w), 762 (s), 717 (s), 700 (m), 646
(s) cm–1.
1H NMR (300.132 MHz, CDCl3): d = 3.92 (s, 2 H, CH2S), 7.01–
7.04 (m, 2 H, HBn), 7.17 (dd, 3JHH = 7.7 Hz, 4JHH = 1.2 Hz, 1 H, HPh),
7.20–7.22 (m, 3 H, HBn), 7.34 (dt, 3JHH = 7.7 Hz, 4JHH = 1.2 Hz, 1 H,
HPh), 7.44 (dt, 3JHH = 7.7 Hz, 4JHH = 1.2 Hz, 1 H, HPh), 7.59 (dd,
3JHH = 7.7 Hz, 4JHH = 1.2 Hz, 1 H, HPh), 8.03 (s, 2 H, N–CH–N).
13C NMR (75.476 MHz, CDCl3): d = 39.3 (CH2S), 126.6 (CPh),
127.5 (CBn), 128.0 (CPh), 128.5 (CBn), 128.6 (CBn), 130.2 (CPh),
132.6 (CPh), 132.8 (q-C), 134.1 (q-C), 136.0 (q-C), 142.8 (N–CH–
N).
2,4,6-Me3C6H2NH2 (10.0 mmol, 1.35 g) was added to the azine di-
hydrochloride 1 (10.0 mmol, 2.15 g) under argon, and the mixture
was stirred at 130 °C for 24 h. The resulting melt was dissolved in
toluene (50 mL), and the soln was basified with 1 M aq NaOH. The
aqueous layer was extracted with toluene (3 × 15 mL), and the com-
bined organic layers were dried (MgSO4) and concentrated in
vacuo. The residue was washed with small amounts of Et2O, and the
resulting light yellow crude product was sublimed (125 °C, 0.2
mbar) to give a colorless solid; yield: 1.04 g (56%); C11H13N3 (M =
187.24 g/mol); mp 233 °C.
IR (KBr): 3137 (w), 3116 (w), 3096 (w), 2958 (w), 2923 (w), 1631
(m), 1510 (s), 1447 (w), 1379 (w), 1286 (w), 1213 (m), 1171 (w),
1095 (s), 995 (m), 962 (w), 874 (m), 667 (m), 580 (m), 558 (w)
cm–1.
1H NMR (300.132 MHz, CDCl3): d = 1.95 (s, 6 H, o-CH3), 2.31 (s,
3 H, p-CH3), 6.97 (s, 2 H, HPh4), 8.15 (s, 2 H, N–CH–N).
MS (EI, 70 eV): m/z (%) = 267.08 (100) [C15H13N3S]+, 91.05 (93)
[C7H7]+.
HRMS (EI): m/z calcd for C15H13N3S: 267.0830; found: 267.0843.
13C NMR (75.476 MHz, CDCl3): d = 17.4 (o-CH3), 20.9 (p-CH3),
129.3 (CPh1/3/5), 134.8 (CPh2/6), 139.9 (CPh4), 142.9 (N–CH–N).
Anal. Calcd for C15H13N3S: C, 67.39; H, 4.90; N, 15.72; S, 11.99.
Found: C, 67.22; H, 4.91; N, 15.78; S, 11.99.
MS (EI, 70 eV): m/z (%) = 187.11 (100) [C11H13N3]+, 159.09 (27)
[C11H13N1]+.
4-[4-(Trifluoromethyl)phenyl]-4H-1,2,4-triazole (2f)
4-F3CC6H4NH2 (10.0 mmol, 1.61 g) was added to the azine dihy-
drochloride 1 (10.0 mmol, 2.15 g) under argon, and the mixture was
stirred at 130 °C for 24 h. The resulting melt was dissolved in tolu-
ene (150 mL) and the soln was basified with 1 M aq NaOH. The
aqueous layer was extracted with toluene (3 × 20 mL), and the com-
bined organic layers were dried (MgSO4) and concentrated in vac-
uo. The residue was washed with small amounts of Et2O, and the
resulting light-yellow crude product was sublimed (140 °C, 0.2
mbar) to give a colorless solid; yield: 0.946 g (44%); C9H6F3N3
(M = 213.16 g/mol); mp 210 °C.
Anal. Calcd for C11H13N3: C, 70.56; H, 7.00; N, 22.44. Found: C,
70.64; H, 7.01; N, 22.50.
4-(2,6-Diisopropylphenyl)-4H-1,2,4-triazole (2d)
2,6-i-Pr2C6H3NH2 (10.0 mmol, 1.77 g) was added to the azine dihy-
drochloride 1 (10.0 mmol, 2.15 g) under argon, and the mixture was
stirred at 150 °C for 24 h. The resulting melt was dissolved in tolu-
ene (150 mL), and the soln was basified with 1 M aq NaOH. The
aqueous layer was extracted with toluene (3 × 20 mL), and the com-
bined organic layers were dried (MgSO4) and concentrated in
vacuo. The residue was washed with Et2O, and the resulting crude
violet product was sublimed (135 °C, 0.2 mbar) to give a faintly vi-
olet solid; yield: 0.39 g (17%); C14H19N3 (M = 229.32 g/mol); mp
IR (KBr): 3120 (m), 1619 (s), 1533 (s), 1504 (m), 1432 (w), 1376
(m), 1328 (s), 1262 (w), 1243 (s), 1170 (m), 1130 (s), 1089 (w),
1067 (s), 997 (m), 843 (m), 595 (w), 471 (m) cm–1.
Synthesis 2010, No. 13, 2278–2286 © Thieme Stuttgart · New York

PAPER
4-Aryl-1,2,4-triazoles
2283
1H NMR (300.132 MHz, CDCl3): d = 7.58 (d, 3JHH = 8.4 Hz, 2 H,
HPh2/6), 7.82 (d, 3JHH = 8.4 Hz, 2 H, HPh3/5), 8.57 (s, 2 H, N–CH–N).
HPh), 7.67 (dt, 3JHH = 7.6 Hz, 4JHH = 1.4 Hz, 1 H, HPh), 7.82–7.86 (m,
2 H, HPh), 9.02 (s, 1 H, N2–CH–N4), 10.25 (s, 1 H, N1–CH–N4).
13C NMR (75.476 MHz, CDCl3): d = 122.3 (s, CPh2/6), 123.3 (q,
1JCF = 272.5 Hz, CF3), 127.6 (q, 3JCF = 3.7 Hz, CPh3/5), 131.2 (q,
2JCF = 33.4 Hz, CPh4), 136.5 (s, CPh1), 141.0 (s, N–CH–N).
MS (ESI): m/z (%) = 449.12 (100) [2M + Na]+, 268.06 (61) [M +
Na + MeOH]+, 252.00 (55) [M + K]+, 235.93 (87) [M + Na]+,
213.79 (28) [M + H]+.
13C NMR (75.476 MHz, acetone-d6): d = 40.8 (NCH3), 41.8 (CH2S),
–
54.6 (CH3OSO3 ), 129.4 (CPh), 129.5 (CBn), 130.5 (CBn), 130.7
(CBn), 131.3 (CPh), 133.8 (CPh), 135.2 (q-C), 136.7 (CPh), 139.0 (q-
C), 145.9 (N1–CH–N4), 146.4 (N2–CH–N4), 149.0 (q-C).
MS (ESI): m/z (%) = 282.11 (85) [M – MeSO4]+, 675.19 (100) [2M
– MeSO4]+.
Anal. Calcd for C9H6F3N3: C, 50.71; H, 2.84; N, 19.71. Found: C,
50.90; H, 2.78; N, 20.00.
HRMS (ESI): m/z calcd for [C16H16N3S]+: 282.1059; found:
282.1058.
4-(2-Nitrophenyl)-4H-1,2,4-triazole (2g)
4-(2-Benzylthiophenyl)-1-methyl-4H-1,2,4-triazol-1-ium Tosy-
late (3b)
2-O2NC6H4NH2 (20.0 mmol, 2.76 g) was added to the azine dihy-
drochloride 1 (10.0 mmol, 2.15 g) under argon, and the mixture was
stirred at 130 °C for 24 h. The resulting melt was dissolved in tolu-
ene (200 mL), and the soln was basified with 1 M aq NaOH. The
aqueous layer was extracted with toluene (3 × 25 mL), the com-
bined organic layers were dried (MgSO4) and concentrated in vac-
uo. The residue was washed with small amounts of Et2O to give an
ochre yellow solid; yield: 0.106 g (6%) (Further purification was
abandoned because of the low yield.); C8H6N4O2 (M = 190.16 g/
mol); mp 126 °C.
To exchange the anion, the methyl sulfate 3a (1.19 g, 3.00 mmol)
was dissolved in CH2Cl2 (20 mL) and a soln of TsOH·H2O (1.71 g,
9.00 mmol) in H2O (20 mL) was added. The two-layer system was
thoroughly stirred for 1 h and then the layers were separated. The
aqueous layer was extracted once with CH2Cl2 (20 mL). The com-
bined organic layers were washed with H2O (3 × 15 mL) to remove
traces of TsOH and then dried (MgSO4). On addition of Et2O (40
mL) the crude product precipitated, which was washed with Et2O
(15 mL) to give a light-yellow solid; yield: 711 mg (52%);
C23H23N3O3S2 (M = 453.58 g/mol); mp 112 °C.
IR (KBr): 3117 (m), 1610 (m), 1586 (w), 1523 (s), 1347 (s), 1295
(w), 1256 (w), 1224 (m), 1105 (m), 1081 (w), 995 (m), 858 (w), 790
(m), 747 (m), 693 (w), 656 (m) cm–1.
1H NMR (300.132 MHz, CDCl3): d = 7.50 (t, 3JHH = 8.0 Hz, 1 H,
HPh4), 7.74 (d, 3JHH = 8.0 Hz, 1 H, HPh6), 7.83 (t, 3JHH = 8.0 Hz, 1 H,
HPh5), 8.16 (d, 3JHH = 8.0 Hz, 1 H, HPh3), 8.33 (s, 2 H, N–CH–N).
13C NMR (75.476 MHz, CDCl3): d = 126.0 (CPh3), 127.1 (CPh1),
129.2 (CPh4), 131.2 (CPh6), 134.5 (CPh5), 142.8 (N–CH–N), 144.8
(CPh2).
IR (KBr): 3445 (br), 3029 (br), 1633 (w), 1571 (w), 1535 (w), 1495
(w), 1479 (w), 1453 (w), 1198 (s), 1121 (m), 1073 (w), 1035 (m),
1073 (m), 1012 (m), 858 (w), 991 (w), 818 (w), 766 (w), 702 (w),
681 (m), 618 (w), 567 (m) cm–1.
1H NMR (300.132 MHz, acetone-d6): d = 2.28 (s, 3 H, OTs-CH3),
4.08 (s, 2 H, CH2S), 4.21 (s, 3 H, NCH3), 7.05 (d, 3JHH = 8.0 Hz, 2
H, OTs-CH), 7.09–7.12 (m, 2 H, HBn), 7.22–7.24 (m, 3 H, HBn), 7.44
(dt, 3JHH = 7.7 Hz, 4JHH = 1.4 Hz, 1 H, HPh), 7.55 (d, 3JHH = 8.0 Hz,
3
4
2 H, OTs-CH), 7.60 (dt, JHH = 7.6 Hz, JHH = 1.4 Hz, 1 H, HPh),
7.75–7.80 (m, 2 H, HPh), 9.15 (s, 1 H, N2–CH–N4), 10.59 (s, 1 H,
N1–CH–N4).
MS (EI, 70 eV): m/z (%) = 190.07 (7) [C8H6N4O2]+, 133.04 (46)
[C7H5N2O]+, 105.04 (100) [C5H3N3]+, 90.03 (42) [C6H4N]+.
13C NMR (75.476 MHz, acetone-d6): d = 22.2 (OTs-CH3), 40.7
(NCH3), 41.7 (CH2S), 127.6 (OTs-CH), 129.2 (CPh), 129.3 (OTs-
CH), 129.9 (CBn), 130.4 (CBn), 130.7 (CBn), 131.0 (CPh), 133.6 (CPh),
135.0 (q-C), 136.5 (CPh), 138.8 (q-C), 139.8 (q-C), 146.1 (N1–CH–
N4), 146.5 (N2–CH–N4), 147.5 (q-C).
Anal. Calcd for C8H6N4O2: C, 50.53; H, 3.18; N, 29.46. Found: C,
50.49; H, 3.27; N, 29.19.
4-(4-Nitrophenyl)-4H-1,2,4-triazole (2h)19
4-O2NC6H4NH2 (20.0 mmol, 2.76 g) was added to the azine dihy-
drochloride 1 (10.0 mmol, 2.15 g) under argon, and the mixture was
stirred at 160 °C for 7 d. The resulting melt was dissolved in toluene
(200 mL), and the soln was basified with 1 M aq NaOH. The aque-
ous layer was extracted with toluene (3 × 25 mL), and the combined
organic layers were dried (MgSO4) and concentrated in vacuo. The
residue was washed with Et2O to give a yellow solid; yield: 0.02 g
(1%) (Further purification was abandoned because of the low
yield.); C8H6N4O2 (M = 190.16 g/mol).
MS (ESI): m/z (%) = 282.11 (100) [M – OTs]+, 735.22 (23) [2M –
OTs]+.
HRMS (ESI): m/z calcd for [C16H16N3S]+: 282.1059; found:
282.1058.
Anal. Calcd for C23H23N3O3S2: C, 60.90; H, 5.11; N, 9.26; S, 14.14.
Found: C, 60.70; H, 5.08; N, 9.25; S, 14.19.
1H NMR (300.132 MHz, DMSO-d6): d = 8.04 (d, 3JHH = 9.0 Hz, 2
1,1¢-Propane-1,3-diylbis[4-(2,6-dimethylphenyl)-4H-1,2,4-tria-
zol-1-ium] Dibromide (4)
H, HPh2/6), 8.42 (d, 3JHH = 9.0 Hz, 2 H, HPh3/5), 9.32 (s, 2 H, N–CH–
N).
Br(CH2)3Br (2.6 mmol, 0.52 g) was added to a soln of triazole 2b
(5.2 mmol, 0.90 g) in MeOH (1.5 mL), and the mixture was refluxed
for 2 h until it became solid. More MeOH (10 mL) was added, and
the mixture was refluxed for a further 24 h. On addition of Et2O (20
mL), a colorless solid precipitated which was filtered off and dried
in vacuo; yield: 0.79 g (56%); C23H28Br2N6 (M = 548.32 g/mol); mp
279 °C.
13C NMR (75.476 MHz, DMSO-d6): d = 121.5 (CPh2/6), 125.4 (CPh3/
5), 138.7 (CPh1), 141.1 (N–CH–N), 146.1 (CPh4).
4-(2-Benzylthiophenyl)-1-methyl-4H-1,2,4-triazol-1-ium Meth-
yl Sulfate (3a)
Me2SO4 (0.46 mL, 4.80 mmol) was added to a soln of triazole 2e
(4.00 mmol, 1.07 g) in acetone (30 mL), and the resulting yellow
soln was refluxed for 3 h. On addition of Et2O (30 mL), a product
began to separate as a yellow oil that was washed with Et2O (20 mL)
and dried in vacuo; yield: 1.41 g (89%); C17H19N3O4S2 (M = 393.48
g/mol).
IR (KBr): 3080 (w), 2983 (br), 1628 (w), 1559 (s), 1520 (w), 1476
(s), 1451 (m), 1316 (m), 1231 (w), 1190 (m), 1108 (m), 984 (m),
788 (m), 671 (m), 641 (w), 558 (w), 537 (w) cm–1.
1H NMR (300.132 MHz, DMSO-d6): d = 2.20 (s, 12 H, CH3), 2.83
(quin, 3JHH = 6.9 Hz, 2 H, CH2CH2CH2), 4.77 (t, 3JHH = 6.9 Hz, 4 H,
NCH2CH2), 7.38 (d, 3JHH = 7.5 Hz, 4 H, HPh3/5), 7.50 (t, 3JHH = 7.5
Hz, 2 H, HPh4), 9.69 (s, 2 H, N2–CH–N4), 10.93 (s, 2 H, N1–CH–
N4).
1H NMR (300.132 MHz, acetone-d6): d = 3.43 (s, 3 H, CH3OSO3 ),
–
4.14 (s, 2 H, CH2S), 4.27 (s, 3 H, NCH3), 7.11–7.15 (m, 2 H, HBn),
7.28–7.30 (m, 3 H, HBn), 7.57 (dt, 3JHH = 7.6 Hz, 4JHH = 1.5 Hz, 1 H,
Synthesis 2010, No. 13, 2278–2286 © Thieme Stuttgart · New York

2284
S. C. Holm et al.
PAPER
13C NMR (75.476 MHz, DMSO-d6): d = 17.5 (CH3), 26.6
(CH2CH2CH2), 49.2 (NCH2CH2), 129.0 (CPh3/5), 130.4 (CPh1), 131.1
(CPh2/6), 134.8 (CPh4), 143.8 (N1–CH–N4), 145.1 (N2–CH–N4).
MS (ESI): m/z (%) = 319.11 (6) [M – 2Cl]2+, 637.22 (63) [M – Cl –
HCl]+, 673.20 (100) [M – Cl]+.
HRMS (ESI): m/z calcd for [C38H34ClN6S2]+: 673.1969; found:
673.1972.
MS (ESI): m/z (%) = 469.23 (26), 467.22 (28) [M – Br]+, 387.20
(100) [M – Br – HBr]+.
1,1¢-[1,3-Phenylenedi(methylene)]bis[4-(2-benzylthiophenyl)-
4H-1,2,4-triazol-1-ium] Ditosylate (6b)
MS (ESI negative ion): m/z (%) = 80.94 (100), 78.94 (95) [Br]–.
Anal. Calcd for C23H28Br2N6: C, 50.38; H, 5.15; N, 15.33. Found:
C, 49.89; H, 5.18; N, 14.94.
To exchange the anions, dichloride 6a (1.07 g, 1.50 mmol) was dis-
solved in CH2Cl2 (50 mL) and a soln of TsOH·H2O (1.71 g, 9.00
mmol) in H2O (50 mL) was added. The two-layer system was thor-
oughly stirred for 1 h and then the layers were separated. The aque-
ous layer was extracted once with CH2Cl2 (50 mL). The combined
organic layers were washed with H2O (3 × 30 mL) to remove traces
of TsOH, and then dried (MgSO4). On addition of Et2O (100 mL),
a product precipitated. This was washed with Et2O (50 mL) and
dried in vacuo to give a colorless foam; yield: 1.40 g (95%);
C52H48N6O6S4 (M = 981.23 g/mol); mp 90 °C.
1,1¢-Propane-1,3-diylbis[4-(2-benzylthiophenyl)-4H-1,2,4-triaz-
ol-1-ium] Dibromide (5)
Triazole 2e (18.0 mmol, 4.81 g) was melted at 130 °C. Br(CH2)3Br
(7.2 mmol, 0.73 mL) was added to the melt, and the mixture was
heated at 130 °C for 3 h. The resulting yellow melt was dissolved in
CH2Cl2 (150 mL). On addition of Et2O (100 mL), a colorless solid
precipitated which was filtered off, washed with Et2O (50 mL), and
dried in vacuo; yield: 4.90 g (93%), C33H32Br2N6S2 (M = 736.59 g/
mol); mp 235 °C.
IR (KBr): 3433 (br), 3027 (br), 1925 (w), 1634 (w), 1562 (w), 1494
(w), 1476 (w), 1453 (w), 1193 (s), 1122 (m), 1101 (w), 1034 (m),
1011 (m), 817 (w), 768 (w), 702 (w), 682 (m), 617 (w), 568 (m), 477
(w) cm–1.
IR (KBr): 3440 (br), 2996 (br), 1635 (w), 1601 (w), 1562 (s), 1495
(w), 1476 (w), 1453 (m), 1444 (m), 1319 (w), 1202 (w), 1099 (m),
1072 (w), 991 (w), 769 (s), 721 (w), 705 (m), 663 (w), 654 (w), 549
(w), 482 (w) cm–1.
1H NMR (300.132 MHz, DMSO-d6): d = 2.68 (quin, 3JHH = 6.6 Hz,
2 H, CH2CH2CH2), 4.23 (s, 4 H, SCH2), 4.72 (t, 3JHH = 6.6 Hz, 4 H,
CH2CH2CH2), 7.18–7.21 (m, 4 H, HBn), 7.24–7.28 (m, 6 H, HBn),
7.60 (dt, 3JHH = 7.5 Hz, 4JHH = 1.5 Hz, 2 H, HPh), 7.69 (dt, 3JHH = 7.5
Hz, 4JHH = 1.5 Hz, 2 H, HPh), 7.79–7.84 (m, 4 H, HPh), 9.52 (s, 2 H,
N2–CH–N4), 10.70 (s, 2 H, N1–CH–N4).
1H NMR (500.133 MHz, DMSO-d6): d = 2.28 (s, 6 H, OTs-CH3),
4.18 (s, 4 H, SCH2), 5.78 (s, 4 H, NCH2), 7.09–7.12 (m, 8 H, HBn,
3
OTs-CH), 7.21–7.23 (m, 6 H, HBn), 7.48 (d, JHH = 8.0 Hz, 4 H,
3
OTs-CH), 7.52–7.58 (m, 5 H, HXyl, HPh), 7.69 (dt, JHH = 8.0 Hz,
4JHH = 1.2 Hz, 2 H, HPh), 7.74 (dd, 3JHH = 8.0 Hz, 4JHH = 1.2 Hz, 2
4
H, HPh), 7.76 (br s, 1 H, HXyl), 7.83 (dd, 3JHH = 8.0 Hz, JHH = 1.2
Hz, 2 H, HPh), 9.41 (s, 2 H, N2–CH–N4), 10.68 (s, 2 H, N1–CH–
N4).
13C NMR (75.476 MHz, DMSO-d6): d = 27.0 (CH2CH2CH2), 38.2
(SCH2), 48.8 (CH2CH2CH2), 127.4 (CPh), 127.4 (CBn), 128.4 (CPh),
128.5 (CBn), 128.7 (CBn), 131.6 (q-C), 131.9 (CPh), 132.1 (q-C),
132.7 (CPh), 136.3 (q-C), 143.5 (N1–CH–N4), 145.1 (N2–CH–N4).
13C NMR (125.758 MHz, DMSO-d6): d = 20.7 (OTs-CH3), 38.5
(SCH2), 54.6 (NCH2), 125.4 (OTs-CH), 127.2 (CPh), 127.3 (CBn),
128.0 (OTs-CH), 128.4 (CBn), 128.5 (CPh), 128.6 (CBn), 129.4
(2 CXyl), 129.7 (CXyl), 131.8 (CPh), 131.9 (q-C), 133.1 (CPh), 133.5
(q-C), 136.3 (q-C), 137.6 (q-C), 143.5 (N1–CH–N4), 145.3 (N2–
CH–N4), 145.4 (q-C). One quarternary carbon signal not detected.
MS (ESI): m/z (%) = 288.11 (24) [M-2Br]2+, 575.20 (51) [M – HBr
– Br]+, 657.13 (100) [M – Br]+.
MS (ESI): m/z (%) = 319.11 (10) [M – 2OTs]2+, 637.22 (3) [M –
HRMS (ESI): m/z calcd for [C33H32BrN6S2]+: 655.1308; found:
655.1323.
OTs – HOTs]+, 809.24 (100) [M – OTs]+.
HRMS (ESI): m/z calcd for [C45H41N6O3S3]+: 809.2397; found:
809.2405.
1,1¢-[1,3-Phenylenedi(methylene)]bis[4-(2-benzylthiophenyl)-
4H-1,2,4-triazol-1-ium] Dichloride (6a)
Triazole 2e (10.0 mmol, 2.67 g) and 1,3-(ClCH2)2C6H4 (4.0 mmol,
0.70 g) were ground together in a mortar and then heated without
solvent to 130 °C for 2 h. The resulting yellow melt was dissolved
in CH2Cl2 (150 mL). On addition of Et2O (100 mL), a colorless sol-
id precipitated which was filtered off, washed with Et2O (50 mL),
and dried in vacuo; yield: 2.67 g (94%); C38H34Cl2N6S2 (M = 709.75
g/mol); mp 189 °C.
1-(3-Chloropropyl)-4-(2,6-dimethylphenyl)-4H-1,2,4-triazol-1-
ium Bromide (7)
Triazole 2b (11.5 mmol, 2.00 g) was dissolved in Br(CH2)3Cl (230
mmol, 23 mL), and the mixture was stirred at 40 °C for 3 d. The col-
orless solid that precipitated was filtered off, washed with Et2O (50
mL), and dried in vacuo; yield: 2.85 g (75%); C13H17BrClN3 (M =
330.65 g/mol); mp 229 °C.
IR (KBr): 3450 (br), 3006 (br), 1562 (s), 1520 (w), 1494 (m), 1476
(m), 1453 (m), 1442 (m), 1317 (m), 1240 (w), 1202 (m), 1096 (m),
1071 (m), 1001 (w), 769 (s), 744 (m), 727 (m), 703 (s), 654 (m), 544
(w), 477 (w) cm–1.
IR (KBr): 3077 (w), 3029 (s), 1559 (s), 1518 (w), 1478 (m), 1455
(w), 1436 (w), 1320 (w), 1221 (w), 1182 (m), 1103 (m), 1080 (w),
992 (w), 798 (s), 715 (w), 659 (w) cm–1.
1H NMR (500.133 MHz, DMSO-d6): d = 2.17 (s, 6 H, CH3), 2.50
1H NMR (500.133 MHz, DMSO-d6): d = 4.22 (s, 4 H, SCH2), 5.86
(s, 4 H, NCH2), 7.15–7.17 (m, 4 H, HBn), 7.22–7.23 (m, 6 H, HBn),
7.48–7.51 (m, 1 H, HXyl), 7.57 (dt, 3JHH = 7.8 Hz, 4JHH = 1.0 Hz, 2
H, HPh), 7.60–7.62 (m, 2 H, HXyl), 7.67 (dt, 3JHH = 7.8 Hz, 4JHH = 1.0
(m, 2 H, CH2CH2CH2), 3.85 (t, 3JHH = 6.3 Hz, 2 H, ClCH2CH2), 4.68
3
3
(t, JHH = 6.8 Hz, 2 H, NCH2CH2), 7.39 (d, JHH = 7.7 Hz, 2 H,
HPh3/5), 7.50 (t, 3JHH = 7.7 Hz, 1 H, HPh4), 9.63 (s, 1 H, N2–CH–N4),
10.78 (s, 1 H, N1–CH–N4).
3
4
Hz, 2 H, HPh), 7.82 (dd, JHH = 7.8 Hz, JHH = 1.0 Hz, 2 H, HPh),
7.85–7.86 (m, 3 H, HPh, HXyl), 9.52 (s, 2 H, N2–CH–N4), 11.41 (s,
2 H, N1–CH–N4).
13C NMR (125.758 MHz, DMSO-d6): d = 17.2 (CH3), 30.4
(CH2CH2CH2), 42.0 (ClCH2CH2), 49.9 (NCH2CH2), 128.9 (CPh3/5),
130.3 (CPh1), 131.0 (CPh4), 134.7 (CPh2/6), 143.7 (N1–CH–N4), 145.1
(N2–CH–N4).
13C NMR (125.758 MHz, DMSO-d6): d = 38.5 (SCH2), 54.3
(NCH2), 127.3 (CBn), 127.3 (CPh), 128.4 (CBn), 128.5 (CPh), 128.6
(CBn), 129.3 (CXyl), 129.3 (CXyl), 129.6 (CXyl), 131.8 (CPh), 132.0 (q-
C), 133.1 (CPh), 133.7 (q-C), 136.3 (q-C), 143.7 (N1–CH–N4),
145.3 (N2–CH–N4). One quaternary carbon signal not detected.
MS (ESI): m/z (%) = 581.13 (65), 579.13 (40) [2M – Br]+, 250.09
(100) [M – Br]+.
MS (ESI negative ion): m/z (%) = 412.07 (69), 409.98 (100) [M +
Br]–, 80.94 (9), 78.94 (8) [Br]–.
Synthesis 2010, No. 13, 2278–2286 © Thieme Stuttgart · New York

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4-Aryl-1,2,4-triazoles
2285
Anal. Calcd for C13H17BrClN3: C, 47.22; H, 5.18; N, 12.71. Found:
C, 47.16; H, 5.18; N, 12.75.
4JHH = 1.2 Hz, 1 H, HPh), 7.73 (dd, 3JHH = 7.8 Hz, 4JHH = 1.2 Hz, 1
H, HPh), 7.91 (dd, 3JHH = 7.8 Hz, 4JHH = 1.2 Hz, 1 H, HPh), 9.06 (s, 1
H, N2–CH–N4), 9.45 (s, 1 H, N2¢–CH–N4¢), 10.86 (s, 1 H, N1–
CH–N4), 11.05 (s, 1 H, N1¢–CH–N4¢).
13C NMR (75.476 MHz, acetone-d6): d = 19.0 (CH3), 22.2 (OTs-
CH3), 29.6 (CH2CH2CH2), 41.9 (SCH2), 51.4 (NCH2CH2CH2N¢),
51.5 (NCH2CH2CH2N¢), 127.7 (OTs-CH), 129.3 (CBn), 129.8 (CPh),
129.9 (OTs-CH), 130.5 (CBn), 130.7 (CBn), 131.0 (CXyl), 131.1
(CPh), 132.6 (q-C), 132.9 (CXyl), 133.5 (CPh), 133.6 (q-C), 135.3 (q-
C), 136.6 (CPh), 137.2 (q-C), 139.0 (q-C), 139.9 (q-C), 146.3 (N1–
CH–N4), 146.8 (N1¢–CH–N4¢), 147.0 (N2–CH–N4), 147.3 (N2¢–
CH–N4¢), 147.4 (q-C).
4-(2-Benzylthiophenyl)-1-{3-[4-(2,6-dimethylphenyl)-4H-1,2,4-
triazol-1-ium-1-yl]propyl}-4H-1,2,4-triazol-1-ium Bromide
Chloride (8a)
Triazole 2e (9.75 mmol, 2.61 g) and triazolium bromide 7 (6.50
mmol, 2.15 g) were ground together in a mortar and heated without
solvent at 140 °C for 2 h. The resulting orange melt was dissolved
in CH2Cl2 (150 mL). On addition of Et2O (100 mL), a product pre-
cipitated from the soln as a yellow oil. The oil was separated by de-
cantation, washed with Et2O (50 mL), and dried in vacuo to give a
light-yellow foam; yield: 3.67 g (95%); C28H30BrClN6S (M =
598.00 g/mol); mp 130 °C.
MS (ESI): m/z (%) = 481.22 (5) [M – HOTs – OTs]+, 653.24 (100)
[M – OTs]+.
IR (KBr): 3440 (br), 2977 (br), 1635 (w), 1589 (w), 1561 (s), 1521
(w), 1495 (w), 1476 (m), 1453 (m), 1317 (w), 1190 (w), 1105 (m),
1011 (m), 998 (w), 772 (m), 728 (w), 704 (w), 670 (w), 650 (w), 556
(w) 536 (w), 479 (w) cm–1.
1H NMR (300.132 MHz, DMSO-d6): d = 2.19 (s, 6 H, CH3), 2.76
(pseudo-quin, 2 H, CH2CH2CH2), 4.23 (s, 2 H, SCH2), 4.72–4.80
(m, 4 H, NCH2CH2CH2N¢), 7.20–7.22 (m, 2 H, HBn), 7.25–7.29 (m,
3 H, HBn), 7.38 (d, 3JHH = 7.5 Hz, 2 H, HXyl), 7.47–7.52 (m, 1 H,
HXyl), 7.59 (dt, 3JHH = 7.8 Hz, 4JHH = 1.4 Hz, 1 H, HPh), 7.68 (dt,
3JHH = 7.8 Hz, 4JHH = 1.4 Hz, 1 H, HPh), 7.81 (dd, 3JHH = 7.8 Hz,
4JHH = 1.4 Hz, 1 H, HPh), 7.87 (dd, 3JHH = 7.8 Hz, 4JHH = 1.4 Hz, 1
H, HPh), 9.54 (s, 1 H, N2–CH–N4), 9.69 (s, 1 H, N2¢–CH–N4¢),
10.94 (s, 1 H, N1–CH–N4), 11.11 (s, 1 H, N1¢–CH–N4¢).
13C NMR (75.476 MHz, DMSO-d6): d = 17.4 (CH3), 26.8
(CH2CH2CH2), 38.3 (SCH2), 48.8 (NCH2CH2CH2N¢), 48.9
(NCH2CH2CH2N¢), 127.3 (CPh), 127.4 (CBn), 128.3 (CPh), 128.4
(CBn), 128.7 (CBn), 129.0 (CXyl), 130.4 (q-C), 131.0 (q-C), 131.7
(CXyl), 131.8 (q-C), 132.1 (CPh), 132.7 (CPh), 134.7 (q-C), 136.4 (q-
C), 143.6 (N1–CH–N4), 144.0 (N1¢–CH–N4¢), 145.0 (N2–CH–
N4), 145.1 (N2¢–CH–N4¢).
MS (ESI): m/z (%) = 481.22 (100) [M – HCl – Br]+, 563.14 (19) [M
– Cl]+, 1071.36 (2) [2M – 2Br + Cl]+, 1115.31 (8) [2M – Br]+,
1159.26 (9) [2M – Cl]+, 1205.20 (3) [2M – 2Cl + Br]+.
HR-MS (ESI): m/z calculated for [C35H37N6O3S2]+: 653.2363;
found: 653.2371.
1,1¢-[1,3-Phenylenedi(methylene)]bis[4-(2-benzylthiophenyl)-
4H-1,2,4-triazolylidene]dicopper(I) Dichloride (9)
The bistriazolium dichloride 6a (0.838 mmol, 595 mg), CuOAc
(1.84 mmol, 226 mg), and NaH (1.84 mmol, 44.2 mg) were dis-
solved in anhyd THF (15 mL) under argon, and the mixture was
stirred at r.t. for 2 h. The gray precipitate was filtered off a light-blue
soln. On addition of Et2O (15 mL) to the soln, a product began to
precipitate, and the mixture was stored overnight at 4 °C. The solid
product was then filtered off, washed with Et2O (10 mL), and dried
in vacuo to give a colorless powder; yield: 548 mg (78%);
C38H32Cl2Cu2N6S2 (M = 834.83 g/mol); mp 116 °C.
IR (KBr): 3442 (br), 3132 (w), 3105 (w), 3084 (w), 3060 (w), 3027
(w), 2926 (w), 1632 (w), 1613 (w), 1588 (w), 1531 (m), 1493 (m),
1479 (s), 1452 (s), 1421 (m), 1306 (w), 1241 (w), 1158 (w), 1071
(w), 985 (m), 763 (s), 723 (m), 701 (s), 665 (w) cm–1.
1H NMR (300.132 MHz, DMSO-d6): d = 4.14 (s, 4 H, SCH2), 5.47
(s, 4 H, NCH2), 7.22 (br s, 10 H, HBn), 7.31–7.33 (m, 3 H, HXyl),
7.36–7.38 (m, 2 H, HPh), 7.47 (br s, 1 H, HXyl), 7.50–7.55 (m, 4 H,
HPh), 7.61–7.64 (m, 2 H, HPh), 9.69 (s, 2 H, N2–CH–N4).
13C NMR (75.476 MHz, DMSO-d6): d = 37.9 (SCH2), 55.5 (NCH2),
127.3 (CBn, CXyl), 127.6 (CPh), 127.7 (CPh, CXyl), 128.4 (CBn), 128.8
(CBn), 129.1 (CXyl), 130.4 (CPh), 130.5 (CPh), 132.9 (q-C), 134.8 (q-
C), 136.0 (q-C), 136.1 (q-C), 144.2 (N2–CH–N4), 178.4 (N1–C–
N4).
HRMS (ESI): m/z calcd for [C28H30BrN6S]+: 561.1431; found:
561.1440.
4-(2-Benzylthiophenyl)-1-{3-[4-(2,6-dimethylphenyl)-4H-1,2,4-
triazol-1-ium-1-yl]propyl}-4H-1,2,4-triazol-1-ium Ditosylate
(8b)
MS (ESI): m/z (%) = 699.14 (100) [M – Cu – 2Cl]+.
HRMS (ESI): m/z calcd for [C38H32CuN6S2]+: 699.1420; found:
To exchange the anion, the bromide chloride 8a (1.00 g, 1.67 mmol)
was dissolved in CH2Cl2 (50 mL) and a soln of TsOH·H2O (1.91 g,
10.00 mmol) in H2O (50 mL) was added. The two-layer system was
thoroughly stirred for 1 h and then the layers were separated. The
aqueous layer was extracted once with CH2Cl2 (50 mL). The com-
bined organic layers were washed with H2O (3 × 30 mL) to remove
traces of TsOH, then dried (MgSO4). On addition of Et2O (100 mL),
the product precipitated from the mixture as a yellow oil. The oil
was separated by decantation, washed with Et2O (50 mL), and dried
in vacuo give a light-yellow foam; yield: 769 mg (64%);
C42H44N6O6S3 (M = 825.03 g/mol); mp 73 °C.
699.1429.
Anal. Calcd for C38H32Cl2Cu2N6S2: C, 54.67; H, 3.86; N, 10.07; S,
7.68. Found: C, 54.52; H, 4.11; N, 9.90; S, 7.46.
CCDC 775622 (2b), 775623 (2e), and 775624 (2f) contain the sup-
plementary crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
Acknowledgment
IR (KBr): 3460 (br), 3027 (br), 1633 (w), 1601 (w), 1563 (m), 1495
(w), 1477 (w), 1453 (w), 1319 (w), 1192 (s), 1122 (m), 1106 (m),
1034 (s), 1012 (s), 989 (w), 817 (w), 770 (w), 703 (w), 682 (s), 618
(w), 569 (m) cm–1.
1H NMR (300.132 MHz, acetone-d6): d = 2.15 (s, 6 H, CH3), 2.26
(s, 6 H, OTs-CH3), 2.95 (pseudo-quin, 2 H, CH2CH2CH2), 4.07 (s,
2 H, SCH2), 4.97 (t, 3JHH = 6.6 Hz, 2 H, NCH2CH2CH2N¢), 5.06 (t,
3JHH = 6.9 Hz, 2 H, NCH2CH2CH2N¢), 7.00 (d, 3JHH = 7.9 Hz, 4 H,
OTs-CH), 7.08–7.11 (m, 2 H, HBn), 7.22–7.25 (m, 5 H, HBn, HXyl),
7.35 (dt, 3JHH = 7.8 Hz, 4JHH = 1.2 Hz, 1 H, HPh), 7.38–7.44 (m, 1 H,
HXyl), 7.47 (d, 3JHH = 7.9 Hz, 4 H, OTs-CH), 7.57 (dt, 3JHH = 7.8 Hz,
For financial support, we are indebted to the Deutsche Forschungs-
gemeinschaft DFG for a FRONTIER Project, the Fonds der Chemi-
schen Industrie FCI, the University of Heidelberg, and the Klaus-
Römer foundation.
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