1,2,3- and 1,2,4-triazolium salts, pyrazoles, and quinoxalines from diarylnitrilimines and isocyanides: A study of the scope

Article abstract of DOI:10.1002/jhet.5570400411

Formation of the four title compounds has been found to be strongly dependent on substituents: 1,2,3-Triazolium salts 6 do not arise from nitrilimines 2 that have an electron- acceptor attached to either the C- or the N-phenyl group. Likewise tert-butyl and aryl isocyanides do not afford this class of compounds; from the former isocyanide, dequaternization products 7 are obtained instead, whereas from the latter 1,2,4-triazolium salts 11 are formed. Compounds 11 with a tert-butyl group at the ring are unstable too, giving rise to triazoles 13. Pyrazole formation (analogues of 14) is completely suppressed when both tert-butyl and aryl isocyanides are used, whereas access to this ring system works best with sec-alkyl isocyanides (the influence of substituents of 2 being almost negligible in this case). Formation of quinoxalines 23 which arise from intermediary 1,2-diazets 22 by ring expansion is much favoured on employment of 2 that bears a donator substituent at the N-phenyl group, and under this premise ring closure to 22 is virtually independent on the nature of the isocyanide. Formation of 23 is not observed with 2 having acceptor groups.

Full text of DOI:10.1002/jhet.5570400411

1,2,3- and 1,2,4-Triazolium Salts, Pyrazoles, and Quinoxalines from
Diarylnitrilimines and Isocyanides: a Study of the Scope
Dietrich Moderhack * and Ali Daoud
625
Jul-Aug 2003
Institut für Pharmazeutische Chemie
der Technischen Universität Braunschweig,
D-38106 Braunschweig, Beethovenstrasse 55, Germany
Received March 28, 2003
Dedicated to Professor A. R. Katritzky on the occasion of his 75th birthday.
Formation of the four title compounds has been found to be strongly dependent on substituents: 1,2,3-
Triazolium salts 6 do not arise from nitrilimines 2 that have an electron-acceptor attached to either the C- or
the N-phenyl group. Likewisetert-butyl and aryl isocyanides do not afford this class of compounds; from the
former isocyanide, dequaternization products 7 are obtained instead, whereas from the latter 1,2,4-triazolium
salts 11 are formed. Compounds11 with a tert-butyl group at the ring are unstable too, giving rise to triazoles
13. Pyrazole formation (analogues of 14) is completely suppressed when both tert-butyl and aryl isocyanides
are used, whereas access to this ring system works best with sec-alkyl isocyanides (the influence of
substituents of 2 being almost negligible in this case). Formation of quinoxalines 23 which arise from
intermediary 1,2-diazets 22 by ring expansion is much favoured on employment of 2 that bears a donator
substituent at the N-phenyl group, and under this premise ring closure to 22 is virtually independent on the
nature of the isocyanide. Formation of 23 is not observed with 2 having acceptor groups.
J. Heterocyclic Chem., 40, 625(2003).
Introduction.
ylide 5, reverts to 4 at higher temperature (a conspicuous
exception concerns Z = Me [2]). Using cyclohexyl iso-
cyanide (3c) as a standard probe, we found that the donator-
substituted nitrilimines 2d and 2e afforded the desired
products 6h,i in reasonable yield (Table 1). However, when
3c was reacted with the nitrophenyl representatives 2f and
2g under the same conditions, instead of compounds 6 con-
siderable amounts of the pyrazole derivatives 17h,i were
obtained (Scheme 4), accompanied by the dihydrotetrazine
9b and the a -hydrazonoamides 8b,c which arise from the
intermediates 4x,z by action of moisture (cf. ref. [4]). The
failure of 4z to undergo 1/5-cyclization into the ylide 5
resembles unsuccessful attempts to prepare 1-aryl-2-(4-
nitrophenyl)-1,2,3-triazolium salts by oxidative ring clo-
sure of the respectivea -hydrazonoimines [5].
Efforts to make triazolium salts 6 with either a tert-butyl
or a phenyl group at N(1) have been reported as being
unrewarded [1]. Revisiting this finding, we observed the
following:
(i) In the case of tert-butyl isocyanide (3d), 1,2,3-triazoles
7 were formed instead of 6, perhaps via direct elimination of
isobutene from the precursor 5. Examples studied include
the couples 2a + 3d and 2d + 3d (corresponding to interme-
diates 4d,q), which afforded the derivatives 7a and 7c.
Triazolium salts 6 having a 1-adamantyl group at N(1) were
expected to be more stable, but our synthetic approach was
vitiated, since under the usual conditions (method A) the
isocyanide 3e could not be kept in solution.
Several years ago we have shown that diarylnitrilimines
2, generated from 1, are attacked by isocyanides 3 at the
C-terminus to give linear intermediates 4 (Scheme 1) which
undergo four competing reactions: (i) 1/5-cyclization (® 5;
Scheme 2), (ii) addition of 2 (® 10; Scheme 3), (iii) addi-
tion of 3 (® 14; Scheme 4), and (iv) 1/4-cyclization (® 22;
Scheme 5). These secondary species stabilize to afford the
title compounds 6, 11, 17, and 23 [1,2]. Since our findings
originate from a limited number of reactants, viz. the parent
diphenylnitrilimine (2a) (including the tolyl derivatives
2b,c) and two types of alkyl isocyanides (3a and 3b,c), the
present study is extended to nitrilimines 2 that bear an elec-
tron-donator or -acceptor group at the phenyl substituent
such as 2d-g and to isocyanides 3 that have for Z a tert-
alkyl (3d,e) or an aryl group (3g-k). The behaviour of 2
towards an isocyanide having an activated a -methylene
group (3f) [3] and also complementary work on C-acyl-N-
arylnitrilimines [4] has been reported recently. In both
cases there are major deviations in reactivity so that prod-
ucts different from the title classes were obtained.
Results and Discussion.
Experiments were performed under the conditions origi-
nally applied (Scheme 1; method A and B). As it becomes
apparent from Table 1, all pairs of reactants 2 and 3 (given in
the form of 4) produce complex mixtures, which is especially
true of runs conducted after method B. To provide an overall
picture, the results from previous work [1-3] are listed, too.
(ii) Aryl isocyanides such as 3g-i, when reacted with the
nitrilimines 2a,b (intermediates 4f-h,m), produced the
1,2,4-triazolium salts 11e-g,i (Scheme 3). No triazolium
salts 6 could be found. Their elusiveness is surprising,
since congeners having aryl substituents attached to both
1,2,3-Triazolium Salts 6.
Access to this product class requires mild conditions
(method A), because the precursor of 6, i.e. the triazolium

626
D. Moderhack and A. Daoud
Vol. 40
N(1) and N(2) are known to be reasonably stable com-
pounds [6]. Whether 6 reacts rapidly with additional nitril-
imine 2 (or the anion of 1) in a manner earlier shown for
1-alkyl congeners [7], or whether 4 fails to cyclize at all
(with the consequence of direct uptake of a second mole-
cule of 2 to give 10), remains open to discussion. Yet
another point deserves a comment: Whereas under the
mild conditions of method A only negligible amounts of
11 have been detected so far (e.g. the derivative 11b [1,2]),
the yields are remarkably high in the present case (see
Table 1).
nation, reacts with additional nitrilimine to give the deriv-
ative 12.
No triazolium salts 11 could be made from tert-butyl iso-
cyanide (3d) under the routine conditions of method B.
Again dequaternization took place so that the 1,2,4-tri-
azoles 13 were obtained as final products. This was demon-
strated by reactions of the nitrilimines 2b,d,f,g. From these
experiments arose, in addition to 13b-e, the respective
1,2,3-triazoles 7 (see starting adducts 4l,q,y,z in Table 1).
Loss of the tert-butyl group from the precursor 5 must be
rapid so as to prevent ring opening into the starting adduct
4. In contrast to the foregoing, a triazole of type 13 did not
arise from theN-donator-substituted nitrilimine 2e (see 4t),
although the corresponding derivative 7d was found. Here,
for lack of reactivity, major quantities of 1e/2e were trans-
formed into the dihydrotetrazine 9a (cf. ref. [8]).
Whereas method B proved to be inappropriate for mak-
ing tert-butyl-substituted salts 11, modified conditions as
defined in Table 1 allowed for preparation of the derivative
11c. However, when this material was dissolved in chloro-
form, it gradually decomposed into 13a. Attempts to syn-
thesize analogues from the nitrilimines 2b and 2d failed
but, interestingly, gave enhanced yields of the respective
1,2,3-triazoles 7 (Table 1, footnote [b]). Easy access to the
1,2,4-Triazolium Salts 11.
For this class of compounds procedure B is the method
of choice [2]. Using cyclohexyl isocyanide (3c), we
accordingly found that the two donator-substituted nitril-
imines 2d,e as well as the C-acceptor-substituted one 2f
gave the salts 11l,n and 11o. The yield of 11n, however, is
reduced, because the precursor 4s is more prone to 1/4-
cyclization (Scheme 5), which will be discussed later.
Thus, in the case of 2e + 3b (» 4r) the yield of 11 is lower
too (Table 1). Interestingly, a salt 11 did not result, when
3c was reacted with the N-acceptor-substituted nitrilimine
2g. Here the intermediate 10, instead of undergoing proto-

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1,2,3- and 1,2,4-Triazolium Salts
627
Table 1
Synopsis of Products (Yield, %) Obtained from Intermediate 4 [a]
4
6
7 [b]
11
13
17
23
25 [c]
27
a
b
c
d
a (63) [1]
b (57) [1]
c (73) [1]
a (<1) [2]
b (3) [2]
c (2) [2]
a (<5) [2]
b (5) [2]
c (9) [2]
a (<5) [2]
a (5) [2]
a (4) [2]
a (20) [2]
b (32) [2]
c (20 [d])
d (15)
a (12) [2]
b (34) [2]
a (44)
a (12 [d])
e [e]
f
g
h
e (25/ 66)
f (44/ 87)
g (20/ 51)
i
d (52)
a (6)
j
k
d (53) [1]
e (73) [1]
h (25) [2]
c (29) [2]
d (2) [2]
c (9) [2]
b (7) [2]
l
m
n
o
p
q
r
s [f]
t [g]
u [h]
v
b (20)
b (13)
c (6)
i (70/ 57)
j (10) [2]
k (21) [2]
l (24)
f (70) [1]
g (58) [1]
h (39)
d (<5) [2]
e (25) [2]
f (17)
e (5) [2]
f (<1) [2]
g (4)
e (14) [2]
f (9) [2]
c (17)
c (<5) [2]
c (<5) [2]
d (7)
c (42/ 57)
d (27)
m (8)
n (10)
h (15)
i (25)
j (3)
g (49)
h (43)
i (19)
e (2)
e (2)
i (50)
g (6)
k (18) [3]
l (21)
m (17)
j (37)
k (62)
e (6)
e (5)
w
x [i]
y
z [j]
z’
o (22)
h (28/ 30)
i (16/ 34)
e (74)
f (<1)
d (10)
e (84)
[a] Yield figures refer to method B or, if underlined, to method A; products obtained by the latter are not listed, if yield is below 5%; [b] with modified
method B (20 °C and reaction time of 24 hours) yields are as follows: 7a (20), 7b (44), and 7c (88); [c] yields are based on the respective urea; [d]mod-
ified conditions as with [b]; [e] also isolated: 8a (4); [f] also isolated: 9a (2); [g] also isolated: 9a (33); [h] for further products, see ref. [3]; [i] also
isolated: 8b (19); [j] alsoisolated: 8c (13/ 5), 9b (20/ 5), 12 (21), 16 (8), and 18 (<1).
starting materials and handiness of the preparative proce-
dure makes this reaction an attractive route to 2,4-diaryl-
1,2,3-triazoles, which are normally obtained from a -dike-
tone derivatives [9]. No proclivity towards dequaterniza-
tion was of course shown by the adamantyl-substituted tri-
azolium salt 11d; this compound could therefore be pre-
pared under the standard conditions of method B.
no definite material could be isolated. Also the aryl iso-
cyanides 3j,k failed to give a triazolium salt 11: the nitro-
phenyl derivative 3j turned out to be too weak a nucle-
ophile for attacking the nitrilimine carbon, whereas with
the bulky isocyanide 3k (reacted with the parent 3g) only
1/4-cyclization of the linear adduct 4i occurred.
Pyrazoles 17.
When the aryl isocyanides 3g-i and nitrilimines 2a,b
(which, as shown, produced considerable amounts of tri-
azolium salts 11e-g,i even under mild conditions) were
reacted also at higher temperature (method B), the yields
of these salts were largely enhanced. As it is evident from
Table 1, there were no products formed in addition.
Remarkably, formation of 11 was not observed with both
the N-donator- and N-acceptor-substituted nitrilimines 2e
and 2g. In the first case, the process was suppressed by
competitive 1/4-cyclization (as exemplified by the behav-
iour of the species 4v,w); in the second instance (2g + 3g),
Formation of this type of compound proceeds through the
[4 + 1] cycloadduct 14. This species readily undergoes
aromatization by 1/® 5/hydrogen-migration to give 15
whose new imine function takes up a nitrilimine to afford
the final product 17 [2]. The specific direction of the proton
5
shift is rationalized in terms of a higher basicity of N which
formally belongs to an amidrazone function. Since our
previous experiments had shown 3c to be the most propi-
tious isocyanide for making 17, we used it for studying the
behaviour towards the donator- and acceptor-substituted

628
D. Moderhack and A. Daoud
Vol. 40
1) Et3N • HCL
Et3N • HCL
Et3N • HCL
nitrilimines 2d-g. In all cases the envisaged products could
be isolated (17f-i), though of the derivative 17g (formed
from 4s) we obtained only minor quantities (cf. the low
yield of 11n). More interestingly, aromatization of the
1-(4-nitrophenyl)-substituted cycloadduct 14 turned out to
be a criss-cross process: here also 1¢/® 5¢/hydrogen-

Jul-Aug 2003
1,2,3- and 1,2,4-Triazolium Salts
629
5
migration occurred to give the imine 16. The acceptor
basicity of N so as to prevent prototropy from taking a
group at the adjacent ring position obviously reduces the
specific course. In contrast to the respective isomer 15, the

630
D. Moderhack and A. Daoud
Vol. 40
imine 16 could be separated from the reaction mixture, and
only very little was transformed into the derivative 18.
Cycloadducts 14 having for CHRR¢ a tert-alkyl or an
aryl group should be sufficiently stable for isolation and
were expected to arise from intermediates such as 4e-
i,l,m,q,t,v,w,y,z . However, we had no indications for their
occurrence in any of these cases, although analogous ring
systems have been prepared from the respective iso-
cyanides and heteroallenes comparable to 4 [10,11].
A final comment applies to structural proof of the iso-
mers 17i and 18. In the NMR experiment pyrazole-4,5-
diamines display the N - H signal downfield from the N -
H one (cf. ref. [12]). For the said compounds we found d
4.22 (17i) and 3.04 ppm (18). To confirm this assignment,
both isomers were hydrolyzed to give the (4-pyrazolyl)-
and (5-pyrazolyl)-substituted amidrazones 20 and 21,
respectively. Amidrazones of the former type are known to
undergo ring transformation into 1,2,4-triazoles of type 13
when kept in ethanolic solution or submitted to mass spec-
trometry [13]. In the present instance (20) the first method
failed, because pyrazole-4,5-diamine units that have a 4-
nitrophenyl group attached to the ring nitrogen resist the
initial oxidation step [14], but when we applied the MS
method, the reaction could be induced to proceed down to
13e. The isomeric amidrazone 21, however, produced a
pyrazolo[3,4-f][1,3,5]triazepine (m/z 476) which split out
benzonitrile to give an imidazo[4,5-c]pyrazole (m/z 373).
Quinoxalines 23.
1/4-Cyclization of the linear adduct 4 has been shown
to give a 1,2-diazet derivative (22) which, as expected for
structures of this kind [15], underwent [2 + 2] cyclorever-
sion into a nitrile (24) and a carbodiimide (25) (Scheme
5). A second mode of stabilization consisted in ring
expansion to afford a quinoxaline (23) [2]. Comparing the
yields of 23b-d,f and 25b,c,f with those of 11a-c,h,k and
17a-c,e (Table 1), the formation of 22 from 4 appeared as
a negligible process [2]. Experiments with the N-donator-
substituted nitrilimine 2e now demonstrated that 1/4-
cyclization could be the predominant step which com-
pletely suppressed the other conversions 4 is capable to
undergo. This was exemplified by reactions of 2e with the
isocyanides 3b,c,h,k (see Table 1 for precursors 4r,s,v,w).
Also on employment of the isocyanide 3f formation of 22
was shown to be important [3]; and using tert-butyl iso-
cyanide (3d), this route was still favoured to some extent,
if one compares species such as 4d,l,q which were not
transformed at all (in contrast to their cyclohexyl con-
geners 4c,k,o [2]). Generally no cyclization of 4 into 22
5
4
was observed with derivatives having 4-O NC H for Ar
or Ar¢ (4x-z ). This applied also to intermediates 4 that
have for Z an aryl substituent but are devoid of the 4-
2
6 4
MeOC H group (4f-h,m); a conspicuous exception con-
6
4
stitutes the adduct 4i which like 4r,s,v,w (see above)
underwent 1/4-cyclization only.

Jul-Aug 2003
1,2,3- and 1,2,4-Triazolium Salts
631

632
D. Moderhack and A. Daoud
Vol. 40
were identified by means of authentic samples and/or literature
data, as were the 1,2,3-triazoles 7a [25] and 7b,c [26], the
1,2,4,5-tetrazine 9b [27], the 1,2,4-triazoles13a [7] and 13b [13],
the ureas 25 c [28], 25 d [29], 25 g [30], and 25 j [31], the 1,2,4-
triazoles 27a [32], 27d [33], and 27e [34].
The pronounced propensity of 4 to give 22 when Ar¢=
4-MeOC H can be ascribed to an enhanced nucleophilicity
6
4
of the terminal azo nitrogen. But although a derivative such
–1
as 4t was observed spectroscopically (ir: n 2000 cm ; cf.
ref. [16]), there is no need for the exclusiveness of a path-
way via 4; rather, an alternate mode of combining 2 with 3
might be operative in this case: A donator group at the N-ter-
minus of a nitrilimine favours its allenic structure [17] so
that the isocyanide carbon may attack that position. The
resulting transition state can pass to 22 as well, but can also,
prior to ring closure, fragment into nitrile and carbodiimide.
As side products we found almost throughout the 1,2,4-
triazoles 27. Their way of formation is subject to specula-
tion. The well known [3 + 2] cycloaddition of 2 onto 24
[18] is not the main source, because a model experiment
with 2a and benzonitrile (conditions of method B) pro-
duced much less 27a than did the respective
nitrilimine/isocyanide reactions (see Table 1). We already
assumed [2] that the nitrilimine adds onto the ArC=N dou-
ble bond of 22 to give the bicyclic intermediate 26 which
in turn fragments into 25 and 27 (cf. ref. [19]). As shown
by the relatively constant yields of 27a-e, the process is
almost insusceptible to substituent effects.
General Procedure for the Reaction of Hydrazonoyl Chlorides 1
with Isocyanides 3 in the Presence of an Equimolar Amount of
Triethylamine (Method A).
To a solution of 1 and 3 (4 mmol each) in anhydrous acetoni-
trile (100 mL) was added triethylamine (0.40 g, 4 mmol), and the
mixture was allowed to stand at ambient temperature for 24
hours. After concentration in vacuo work-up was as follows:
(i) Starting pairs 1d + 3c and 1e + 3c (» intermediates 4p,s):
The residual solid was washed with diethyl ether (20 mL) and
dissolved in a small amount of water. Addition of a few drops of
2 N HClO4 precipitated the 2,4-diaryl-1-cyclohexyl-1,2,3-tri-
azolium perchlorate 6h or 6i which was collected by filtration
after 2 hours. For data, see Tables 1- 3.
(ii) Starting pairs 1f + 3c and 1g + 3c (» intermediates4x,z): The
ethereal washings of the solid (which was discarded) were concen-
trated and chromatographed to give, after some starting material,
1,4-bis-(4-nitrophenyl)-3,6-diphenyl-1,4-dihydro-1,2,4,5-tetrazine
(9b), the 1,3-diaryl-N-cyclohexyl-4-(1,3-diaryl-1,2,4-triaza-
spiro[4.5]dec-2-en-4-yl)pyrazol-5-amine 17h or 17i, and finally
the 2-aryl-2-(arylhydrazono)-N-cyclohexylacetamide 8b or 8c. For
data, see Tables 1- 4. – Hydrolysis of 17i: 0.17 g (ca. 0.25 mmol) of
the substrate was stirred with 12 N HCl/anhydrous ethanol (5 mL;
1/3) at ambient temperature for 6 hours. After filtration of some
starting material, the mixture was diluted with water (100 mL) and
neutralized with sodium hydrogencarbonate to precipitate the
amidrazone 20 as an amorphous solid that was collected by filtra-
tion, thoroughly washed with water and submitted to mass spec-
trometry without further purification. For data, see Table 4.
(iii) Starting pairs 1a + 3d and 1d + 3d (» intermediates 4d,q):
The ethereal washings of the solid (which was discarded) were
concentrated and chromatographed to yield, besides starting
material 1, the corresponding 2,4-diaryl-1,2,3-triazole 7a or 7c;
full separation of 7a from 1a (ca. 1:1 mixture) could not be
accomplished. For data, see Table 1.
EXPERIMENTAL
Melting points were determined on a Kofler microscope.
Elemental analyses were obtained on a Carlo-Erba C-H-N-O
Elemental Analyser 1106. The ir spectra were recorded on a Pye-
Unicam SP 1100 or Philips PU-9800 FTIR instrument. The 1H nmr
spectra were run on a Varian EM-390 or Bruker DRX-400 spec-
trometer; the 13C nmr spectra were taken on a Bruker DRX-400
instrument (tetramethylsilane or CDCl3 as internal standard). The
uv/vis spectra were determined on a Philips PU-8730 spectrometer.
The fluorescence spectra were measured on a Kontron SFM 25
instrument. The mass spectra were taken on a Finnigan MAT 8430
or MAT 90 machine. Chromatography was carried out on silca gel
using dichloromethane or (with 25 ) ethyl acetate as eluent.
(iv) Starting pairs 1a + 3g, 1a + 3h, 1a + 3i, and 1b + 3h (»
intermediates 4f-h,m): The solid was thoroughly washed with
diethyl ether and water to give the 3,4-diaryl-1-phenyl-5-
[aryl(phenylhydrazono)methyl]-1,2,4-triazolium chloride 11e,
11f, 11g or 11i. For data, see Tables 1- 4.
The hydrazonoyl chlorides 1a,b,d-g [20] and the isocyanides
3b,c [21], 3d [22], 3e [23], and 3g-k [24] were prepared accord-
ing to (or by adopting) literature procedures. Known products

Jul-Aug 2003
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633

634
D. Moderhack and A. Daoud
Vol. 40
General Procedure for the Reaction of Hydrazonoyl Chlorides 1
with the Isocyanide 3d in the Presence of Excess Triethylamine
at Room Temperature (Modified Method B).
To a solution of 1 (10 mmol) and 3d (0.83 g, 10 mmol) in
anhydrous benzene (25 mL) was added triethylamine (5 mL, ca.
36 mmol), and the mixture was kept at ambient temperature for

Jul-Aug 2003
1,2,3- and 1,2,4-Triazolium Salts
635
24 hours. Work-up was as follows:
zono)methyl]-1,2,4-triazolium chloride (11d). Chromatography
of the concentrated filtrate and organic washings from 11d
afforded crude N-(1-adamantyl)-2-phenyl-2-(phenylhydrazono)-
acetamide (8a; 0.17 g, 4%), mp 151-153 °C (from ethanol); ir
(i) Starting pair1a + 3d (» intermediate 4d): The solid was col-
lected by filtration, washed with light petroleum and water to
give 4-tert-butyl-1,3-diphenyl-5-[phenyl(phenylhydrazono)-
methyl]-1,2,4-triazolium chloride (11c). For data, see Tables 1- 3.
The filtrate and organic washings from 11c were concentrated in
vacuo, the residue was dissolved in the minimum amount of
ethanol to allow crystallization of a trace of 4,8-bis(tert-butylim-
ino)-1,3,5,7-tetraphenyl-1,4,5,8a-tetrahydro-1,2,5,6-tetrazocine
[35] and thereupon was chromatographed to yield, successively,
2,4-diphenyl-1,2,3-triazole (7a) and 1,3-diphenyl-1,2,4-triazol-5-
yl phenyl ketone phenylhydrazone (13a). For data, see Table 1.
(ii) Starting pairs 1b + 3d and 1d + 3d (» intermediates 4l,q): The
filtrate and organic washings from the solid (which was discarded)
were concentrated; the residue was chromatographed to afford the
4-aryl-2-phenyl-1,2,3-triazole 7b or 7c. For data, see Table 1.
1
(KBr): n 3201, 2909, 1694, 1601 cm-1; H nmr (CDCl3): d 6.58
(s, 1H, NH), 12.73 (s, 1H, NH); this compound could not be
obtained analytically pure. For data, see Tables 1- 3.
(v) Starting pairs 1a + 3g, 1a + 3h, 1a + 3i, 1b + 3h, 1d + 3c,
and 1e + 3c (» intermediates 4f-h,m,p,s): The solid was collected
by filtration, washed with light petroleum and water to give the 4-
substituted 1,3-diaryl-5-[aryl(phenylhydrazono)methyl]-1,2,4-
triazolium chloride 11e, 11f, 11g, 11i, 11l or 11n. The filtrates and
organic washings from 11l and 11n were concentrated and chro-
matographed to yield, after elution of some starting material and
a trace of 9a, a mixture (0.45 g or 1.14 g) consisting of very little
4-methoxybenzo- (24: Ar = 4-MeOC6H4) or benzonitrile (24: Ar
= Ph) and the respective N-aryl-N -cyclohexylcarbodiimide 25c
or 25h [ir (neat) n 2224 cm-1 (w) / 2128 (s) or 2211 (w) / 2102
cm-1 (s)] and in turn the 1,3-diaryl-N-cyclohexyl-4-(1,3-diaryl-
1,2,4-triazaspiro[4.5]dec-2-en-4-yl)pyrazol-5-amine 17f or 17g
which was crystallized by trituration with ethanol. The filtrate
from 17 was concentrated and the residue was dissolved in 12 N
General Procedure for the Reaction of Hydrazonoyl Chlorides 1
with Isocyanides 3 in the Presence of Excess Triethylamine at
Elevated Temperature (Method B).
To a stirred solution of 1 and 3 (10 mmol each) in anhydrous
benzene (25 mL) was added triethylamine (5 mL, ca. 36 mmol).
The mixture was heated under reflux for 1 hour, cooled to room
temperature, diluted with light petroleum (25 mL), and allowed
to stand for another 3-4 hours. Work-up was as follows:
(i) Starting pairs 1b + 3d and 1d + 3d (» intermediates 4l,q):
The solid was filtered off, washed with light petroleum, and dis-
carded. The filtrate was concentrated and chromatographed to
yield, successively, the 4-aryl-2-phenyl-1,2,3-triazole 7b or 7c
and the aryl 3-aryl-1-phenyl-1,2,4-triazol-5-yl ketone phenylhy-
drazone 13b or 13c. For data, see Tables 1- 3.
Table 4
Complementary Spectra of Selected New Compounds
N°
UV and Fluorescence (EtOH) l nm (log e)
17f
17g
17h
17i
202 (4.55), 259 (4.26), 325 (3.72); 468
251 (4.42), 340 (3.88); 490
223 (4.39), 264 (4.40), 308 (4.22), 407 (3.98)
235 (4.52), 320 (4.82), 438 (4.24)
(ii) Starting pair 1e + 3d (» intermediate 4t): Removal of the
solid and concentration of the filtrate gave a residue that was dis-
solved in the minimum amount of diethyl ether to deposite 1,4-bis-
(4-methoxyphenyl)-3,6-diphenyl-1,4-dihydro-1,2,4,5-tetrazine
(9a) which was collected by filtration. The concentrated filtrate
from 9a which showed a trace of tert-butyl-[(4-methoxyphenyl-
azo)phenylvinylidene]amine (4t) [ir (neat) n 2000 cm-1 (w)] was
chromatographed to afford, successively, a mixture (0.59 g) con-
sisting of a small amount of benzonitrile (24: R = Ph) and N-tert-
butyl-N -(4-methoxyphenyl)carbodiimide (25i) [ir (neat) n 2211
18
232 (4.84), 295 (3.88), 401 (4.29)
23g
23h
23i
23l
23m
232 (4.42), 264 (4.29), 397 (3.95); 450
236 (4.40), 268 (4.29), 402 (3.95); 471
237 (4.41), 266 (4.30), 401 (3.96); 468
227 (4.51), 291 (4.45), 411 (4.01); 487 [a]
230 (4.43), 271 (4.33), 397 (3.94); 462 [a]
MS (m/z, %) [b]
+
7d
7e
251 (M , 100)
+
266 (M , 100)
-1
(w) / 2105 cm (s)], 2-(4-methoxyphenyl)-4-methyl-1,2,3-triazole
11f
11g
12
13c
13e
16
17f
17g
17h
17i
18
506 (100) [c]
522 (100) [c]
(7d), and N-tert-butyl-6-methoxy-3-phenylquinoxalin-2-amine
(23j); the latter was purified through its picrate according to the
procedure given in ref. [2]. For data, see Tables 1- 4.
827 (100), 587 (6), 504 (14), 451 (57) [c]
+
475 (M , 58), 474 (100)
+
505 (M , 63), 504 (100)
(iii) Starting pairs 1f + 3d and 1g + 3d (» intermediates 4y,z ):
In the case of 1f, the solid was collected by filtration, washed
with light petroleum and water to give, after crystallization from
ethanol, 4-(4-nitrophenyl)-2-phenyl-1,2,3-triazole (7e; from the
organic filtrate and washings a second crop was obtained); for
data, see Tables 1- 4. The mother liquor of 7e showed the pres-
ence of some 4-nitrophenyl 3-(4-nitrophenyl)-1-phenyl-1,2,4-tri-
azol-5-yl ketone phenylhydrazone 13d which was not isolated. In
the case of 1g, the same procedure afforded 1-(4-nitrophenyl)-3-
phenyl-1,2,4-triazol-5-yl phenyl ketone (4-nitrophenyl)hydra-
zone (13e); the concentrated mother liquor of 13e showed a trace
of 2-(4-nitrophenyl)-4-phenyl-1,2,3-triazole (7f) which was not
isolated (ms: m/z 266). For data, see Tables 1- 4.
+
457 (M , 100), 375 (28)
+
666 (M , 100), 623 (90), 584 (48), 452 (8)
+
666 (M , 98), 623 (100), 584 (52)
+
696 (M , 70), 653 (100), 614 (64), 558 (69)
+
696 (M , 63), 653 (36), 614 (31), 558 (39), 481 (60), 96 (100)
+
696 (M , 4), 551 (14), 475 (2), 225 (100)
+
19
20
378 (26), 377 (M , 100), 294 (68)
+
616 (M , 1), 511 (63), 505 (36), 504 (24), 428 (100), 103 (81);
+
617 (M + 1, 18), 154 (100) [c]
21
476 (56) [476.1942, calcd. for C
H
N O :476.1961],
28 24
6 2
+
373 (59), 185 (100); 617 (M + 1, 92), 55 (100) [c]
+
23g
23i
23l
333 (M , 60), 251 (100)
+
333 (M , 58), 251 (100)
+
341 (M , 100), 340 (83)
355 (M , 10), 340 (16), 327 (44), 121 (100)
(iv) Starting pair 1a + 3e (» intermediate 4e): The solid was
collected by filtration, washed with light petroleum and water to
give 4-(1-adamantyl)-1,3-diphenyl-5-[phenyl(phenylhydra-
+
23m
[a] CH Cl as solvent; [b] EI (70 eV); [c] FAB (pos.).
2
2

636
D. Moderhack and A. Daoud
Vol. 40
HCl/Ethanol (10 mL; 1/4). After standing at 20 °C for 4-5 hours
the mixture was poured into water (100 mL), neutralized, and
extracted with dichloromethane. Chromatography of the concen-
trated organic phase afforded the 1,3,5-triaryl-1,2,4-triazole 27d
or 27e and then the 3-aryl-(6-methoxy)-N-cyclohexylquinoxalin-
2-amine 23g or 23i which was purified through its picrate accord-
ing to the procedure given in ref. [2]. For data, see Tables 1- 4.
(vi) Starting pair 1e + 3b (» intermediate 4r): The solid treated
as above gave 4-isopropyl-1-(4-methoxyphenyl)-5-{[(4-methoxy-
phenyl)hydrazono]phenylmethyl}-3-phenyl-1,2,4-triazolium-
chloride (11m). Chromatography of the filtrate from 11m
afforded a mixture (0.96 g) consisting of very little benzonitrile
(24: Ar = Ph) and N-isopropyl-N -(4-methoxyphenyl)carbodi-
imide (25g) [ir (neat) n 2206 (w) / 2100 cm-1 (s)]. Continued elu-
tion gave N-isopropyl-6-methoxy-3-phenylquinoxalin-2-amine
(23h) and 1-(4-methoxyphenyl)-3,5-diphenyl-1,2,4-triazole
(27e). For data, see Tables 1- 4.
(vii) Starting pairs 1f + 3c and 1g + 3c (» intermediates 4x,z):
The solid was separated and purified as above to give 4-cyclo-
hexyl-3-(4-nitrophenyl)-5-[(4-nitrophenyl)(phenylhydrazono)-
methyl]-1-phenyl-1,2,4-triazolium-chloride (11o) or 4-cyclo-
hexyl-1-(4-nitrophenyl)-5-[(4-nitrophenyl-{[(4-nitrophenyl)-
hydrazono]phenylmethyl}hydrazono)phenylmethyl]-3-phenyl-
1,2,4-triazolium-chloride (12). The filtrates and organic washings
from 11o and 12 were concentrated and chromatographed to
yield, in the case of 11o, the pyrazolamine 17h. In the case of 12,
elution gave, successively, the dihydrotetrazine 9b, the amide 8c,
the pyrazolamine 17i, and finally N4-cyclohexyl-N5-cyclohexyli-
dene-1-(4-nitrophenyl)-3-phenylpyrazole-4,5-diamine (16). The
filtrate from 12 showed a trace of N-cyclohexyl-1-(4-nitro-
phenyl)-5-[1-(4-nitrophenyl)-3-phenyl-1,2,4-triazaspiro[4.5]-
dec-2-en-4-yl]-3-phenylpyrazol-4-amine (18) which could not be
separated (identified through an authentic sample; preparation
see below). For data, see Tables 1- 4.
(viii) Starting pair 1e + 3h (» intermediate 4v): The solid was
collected by filtration and dissolved in the minimum amount of
ethanol to allow crystallization of 6-methoxy-N-(4-
methylphenyl)-3-phenylquinoxalin-2-amine (23l). The concen-
trated filtrate from 23l was chromatographed to yield a mixture
(1.13 g) consisting of very little benzonitrile (24: Ar = Ph) andN-
(4-methoxyphenyl)-N -(4-methylphenyl)carbodiimide (25j) [ir
(neat) n 2210 (w) / 2120 cm-1 (s)]. Continued elution gave a sec-
ond crop of 23l and 1-(4-methoxyphenyl)-3,5-diphenyl-1,2,4-tri-
azole (27e). For data, see Tables 1- 4.
(ix) Starting pairs 1a + 3k and 1e + 3k (» intermediates 4i,w):
The solid was filtered off, washed with light petroleum, and dis-
carded. The filtrate was concentrated and chromatographed to
yield a mixture (1.77 g or 1.90 g) consisting of a small amount of
benzonitrile (24: Ar = Ph) and the N-aryl-N -(2,6-dimethylphenyl)-
carbodiimide 25d or 25k [ir (neat) n 2210 (w) / 2120 cm-1 (s);
either mixture]. Continued elution gave, in the case of 1a, 1,3,5-
triphenyl-1,2,4-triazole (27a) and, in the case of 1e, a mixture con-
sisting of N-(2,6-dimethylphenyl)-6-methoxy-3-phenylquinoxalin-
2-amine (23m) and 1-(4-methoxyphenyl)-3,5-diphenyl-1,2,4-tri-
azole (27e) which were separated by fractional crystallization from
ethanol. For data, see Tables 1- 4.
(5 mL; 1/3) and allowed to stand at room temperature for 12
hours. Evaporation under reduced pressure gave a residue which
was chromatographed to yield the N,N -disubstituted urea 25 c,
25 d, 25 g, 25 h, 25 i, 25 j or 25 k. For data, see Tables 1- 3.
Reactions of N4-Cyclohexyl-N5-cyclohexylidene-1-(4-nitro-
phenyl)-3-phenylpyrazole-4,5-diamine (16).
(i) Reaction with 1g / triethylamine: The substrate 16 (0.11 g,
0.25 mmol) was dissolved in anhydrous benzene (5 mL) and, after
addition of triethylamine (0.2 mL), heated under reflux for 10 min-
utes. The cooled mixture was diluted with light petroleum (5 mL),
and the solid was filtered off and washed with light petroleum
(10 mL). The filtrate was concentrated and the residue was chro-
matographed to give, after trituration with ethanol, 0.07 g (40%) N-
cyclohexyl-1-(4-nitrophenyl)-5-[1-(4-nitrophenyl)-3-phenyl-
1,2,4-triazaspiro[4.5]dec-2-en-4-yl]-3-phenylpyrazol-4-amine
(18). For data, see Tables 2- 4. – Hydrolysis of 18: The substrate
was treated as described for the pyrazole 17i (see above) to give the
amidrazone 21 as an amorphous solid that was submitted to mass
spectrometry without further purification. For data, see Table 4.
(ii) Hydrolysis: The substrate 16 (0.11 g, 0.25 mmol) was
dissolved in ethanol (25 mL) and kept at room temperature for 24
hours to allow crystallization of 0.07 g (74%) N4-cyclohexyl-1-
(4-nitrophenyl)-3-phenylpyrazole-4,5-diamine (19) which was
collected by filtration. For data, see Tables 2- 4.
REFERENCES AND NOTES
[1] D. Moderhack and M. Lorke, Heterocycles, 26, 1751 (1987);
see also [7].
[2] D. Moderhack, M. Lorke, L. Ernst, and D. Schomburg, Chem.
Ber., 127, 1633 (1994).
[3] D. Moderhack, A. Daoud, and P. G. Jones, Monatsh. Chem.,
133, 1165 (2002).
[4] D. Moderhack, A. Daoud, L. Ernst, and P. G. Jones, J. Prakt.
Chem., 342, 707 (2000).
[5] A. Singh and B. Hirsch, Indian J. Chem., 8, 514 (1970).
[6] B. Hirsch and E. Förster, Naturwissenschaften, 50, 374
(1963); B. Hirsch and A. Bassl, Z. Chem., 3, 351 (1963).
[7] D. Moderhack, Liebigs Ann. Chem., 1271 (1989).
[8] R. Huisgen, K. Adelsberger, E. Aufderhaar, H. Knupfer, and
G. Wallbillich, Monatsh. Chem., 98, 1618 (1967).
[9] Overview: T. L. Gilchrist and G. E. Gymer, Adv. Heterocycl.
Chem., 16, 33 (1974).
[10] T. Eicher and U. Stapperfenne, Synthesis, 619 (1987).
[11] L. Capuano, P. Mörsdorf, and H. Scheidt, Chem. Ber., 116,
741 (1983); L. Capuano, B. Dahm, V. Port, R. Schnur, and V. Schramm,
Chem. Ber., 121, 271 (1988).
[12] C. Saitz and C. Jullian, J. Heterocyclic Chem., 36, 635 (1999).
[13] D. Moderhack, Liebigs Ann., 777 (1996).
[14] V. D. Orlov, Kh. Kiroga, and N. N. Kolos, Khim. Geterotsikl.
Soedin., 1222 (1988); Chem. Heterocycl. Compd. (USSR), 24, 1008
(1988).
[15] P. J. Macker, K. Hafner, N. Nimmerfroh, and K. Banert,
Chem. Ber., 127, 1479 (1994), and refs. cited in [2]; for a stable 1,2-diazet
derivative, see: D. Pufky, R. Beckert, M. Döring, and O. Walter,
Heterocycles, 57, 1257 (2002).
[16] Y. Ito, T. Hirao, N. Ohta, and T. Saegusa, Tetrahedron Lett.,
1009 (1977); R. Fuks, D. Baudoux, C. Piccinni-Leopardi, J.-P. Declerq,
and M. Van Meerssche,J. Org. Chem., 53, 18 (1988).
[17] K. N. Houk and K. Yamaguchi, in 1,3-Dipolar Cycloaddition
Chemistry, Vol. 2,A. Padwa, ed, Wiley, New York, 1984, pp 407-450.
[18] R. Huisgen, R. Grashey, M. Seidel, G. Wallbillich, H.
Knupfer, and R. Schmidt, Liebigs Ann. Chem., 653, 105 (1962).
General Procedure for the Conversion of the Carbodiimides 25
into the N,N -Disubstituted Ureas 25 .
The oily mixture consisting of the nitrile 24 and the carbo-
diimide 25 was dissolved in 12 N HCl/1,1-dimethoxyethane

Jul-Aug 2003
1,2,3- and 1,2,4-Triazolium Salts
637
[19] K. Hemming, D. T. Morgan, and R. K. Smalley, J. Fluorine
Chem., 106, 83 (2000), and refs. cited in [2].
[20] D. L. Rector, S. D. Folz, R. D. Conklin, L. H. Nowakowski,
and G. Kaugars, J. Med. Chem., 24, 532 (1981).
[21] I. Ugi and R. Meyr, Chem. Ber., 93, 239 (1960).
[22] G. W. Gokel, R. P. Widera, and W. P. Weber, Org. Synth., 55,
96 (1976).
[28] A. Skita and H. Rolfes, Ber. Dtsch. Chem. Ges., 53, 1242
(1920).
[29a] P. Grammaticakis, Bull. Soc. Chim. Fr., 1559 (1959); [b] M.
Miyahara, Chem. Pharm. Bull., 34, 1950 (1986).
[30] J. W. Boehmer,Recl. Trav. Chim. Pays-Bas, 55, 379 (1936).
[31] C. Naegeli, A. Tyabji, and L. Conrad, Helv. Chim. Acta, 21,
1127 (1938).
[23] T. Sasaki, S. Eguchi, and T. Katada, J. Org. Chem., 39, 1239
(1974).
[24] R. Obrecht, R. Herrmann, and I. Ugi, Synthesis, 400 (1985).
[25] H. El Khadem, M. M. El-Sadik, and M. H. Meshreki, J. Chem.
Soc. C, 2097 (1968).
[32] H. Wolchowe, Monatsh. Chem., 37, 473 (1916).
[33] J. Liebscher, East German Patent 129908 (1978); Chem.
Abstr., 89, 109514j (1978).
[34] K. Paulvannan, T. Chen, and R. Hale, Tetrahedron, 56, 8071
(2000).
[26] N. Latif and S. Abdel Meguid, J. Chem. Soc., Perkin Trans. 1,
1095 (1972).
[35] A. Daoud, Dissertation, Technische Universität, Braun-
schweig, Germany, 2003.
[27] E. Bamberger and W. Pemsel, Ber. Dtsch. Chem. Ges., 36, 347
(1903).
[36] M. A. Scialdone, S. W. Shuey, P. Soper, Y. Hamuro, and D.M.
Burns, J. Org. Chem., 63, 4802 (1998).