Synthesis, NMR and X-ray characterisation of 6-substituted 4-amino-5-aryldiazenyl-1-arylpyridazinium salts

Article abstract of DOI:10.1016/j.tet.2005.06.044

A new simple method has been used to prepare 6-substituted 4-(subst. amino)-5-aryldiazenyl-1-arylpyridazinium salts from N-methyl- or N-aryl-3-amino-1-phenylbut-2-en-1-ones and 4-aminopent-3-en-2-ones and substituted benzenediazonium tetrafluoroborates or hexafluorophosphates. The structure of selected derivatives was studied by means of ¹⁵N NMR spectra and X-ray.

Full text of DOI:10.1016/j.tet.2005.06.044

Tetrahedron 61 (2005) 8130–8137
Synthesis, NMR and X-ray characterisation of 6-substituted
4
-amino-5-aryldiazenyl-1-arylpyridazinium salts
a,
a
Mark e´ ta Pe sˇ kov a´ , Valerio Bertolasi, Vladim ´ı r Mach a´ cˇ ek and Anton ´ı n Ly cˇ ka
b
a
c
ˇ
Petr Sim u˚ nek,
*
a
ˇ
Department of Organic Chemistry, University of Pardubice, N a´ m. Cs. Legi ´ı 565, CZ 532 10 Pardubice, Czech Republic
b
Universit a` di Ferrara, Dipartimento di Chimica and Centro di Strutturistica Diffrattometrica, Via L. Borsari 46, I-441 00 Ferrara, Italy
c
Research Institute for Organic Syntheses (VUOS), Rybitv ´ı 296, CZ-532 18, Pardubice 20, Czech Republic
Received 1 April 2005; revised 31 May 2005; accepted 16 June 2005
Available online 11 July 2005
Abstract—A new simple method has been used to prepare 6-substituted 4-(subst. amino)-5-aryldiazenyl-1-arylpyridazinium salts from
N-methyl- or N-aryl-3-amino-1-phenylbut-2-en-1-ones and 4-aminopent-3-en-2-ones and substituted benzenediazonium tetrafluoroborates
1
5
or hexafluorophosphates. The structure of selected derivatives was studied by means of N NMR spectra and X-ray.
q 2005 Elsevier Ltd. All rights reserved.
1
. Introduction
the hexafluorophosphates are practically identical with those
of the corresponding tetrafluoroborates (see Section 5).
1
In our previous paper, we stated that the reaction of
1
1
-phenyl-3-(2,4-dimethoxyphenylamino)but-2-en-1-one or
-phenyl-3-methylaminobut-2-en-1-one with substituted
The reaction of enaminone 1 with 4-methoxybenzene-
diazonium tetrafluoroborate did not give the respective
benzenediazonium tetrafluoroborates produces, besides the
expected products of attack of diazonium ion on methine
carbon of enaminone, also the side products 4-(2,4-dimeth-
oxyphenylamino)- or 4-methylamino-1-aryl-5-phenyldi-
azenylpyridazinium tetrafluoroborates in the yields of
1
7–22%. The mechanism for formation of these pyridazi-
nium salts has not been reliably proven. The aim of the
present paper is to explore the scope and limitations of
this reaction, inclusive of the effect of the anion of the
diazonium salt upon the yield of the pyridazinium salt, and
to find out whether the reaction can also be applied to other
enaminones than benzoylacetone derivatives.
2
. Results and discussion
In contrast to our previous findings, now we have used
benzenediazonium hexafluorophosphates instead of benz-
enediazonium tetrafluoroborates. This change in the anion
approximately doubled the yield. The X-ray diffraction
studies on a single crystal of product 10 (Figs. 1 and 2)
unequivocally proved the presumed structure of the
pyridazinium salt. The proton and carbon NMR spectra of
Keywords: Enaminones; Pyridazinium salts; Azo coupling; NMR; X-ray.
*
Corresponding author. Tel.: C420 466 037 039; fax: C420 466 037 068;
e-mail: p.simunek@email.cz
Figure 1. ORTEP view of the cation of compound 10. Thermal ellipsoids
are drawn at 30% probability level.
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.06.044

ˇ
P. Sim u˚ nek et al. / Tetrahedron 61 (2005) 8130–8137
8131
phosphate (12) was obtained in a relatively good yield
40%) when the starting material molar ratios were 2:1.
(
The pyridazinium salts can only be prepared from
diazonium salts with electropositive substituents (according
to the Hammett s constants up to the non-substituted
benzenediazonium tetrafluoroborate). With hexafluorophos-
phates the reaction applicability expanded to the 4-Cl
derivative. However, it was proved that the 4-nitro
derivative is not formed even with the application of
4-nitrobenzenediazonium hexafluorophosphate.
For a survey and characterization of the 6-arylpyridazinium
hexafluorophosphates prepared, see Scheme 1, Table 1 and
Section 5.
It was found that the reaction leading to formation of
pyridazinium salts (Scheme 1) was not limited to
enaminones derived from benzoylacetone alone. The
reaction between 4-methylaminopent-3-en-2-one 5 and
4
-methoxybenzenediazonium hexafluorophosphate also
gave the respective 6-methylpyridazinium hexafluorophos-
phate (17), shown in Figures 3 and 4. Compound 17, which
is the first representative of 6-methyl derivatives, was also
Figure 2. Crystal structure of compound 10 showing the most significant
intermolecular interactions.
1
pyridazinium salts. The increase in yield of pyridazinium
1
13
19 31
characterised by its H and C, F, P spectra (see Section
1
5
salt 10 after replacement of the tetrafluoroborate by
hexafluorophosphate of the diazonium salt led us to believe
that it could be possible to prepare the 4-methoxy derivative
too (Scheme 1). This turned out to be the case and 4-(2,4-
dimethoxyphenylamino)-1-(4-methoxyphenyl)-5-(4-meth-
oxyphenyldiazenyl)-6-phenylpyridazinium hexafluoro-
5 and Table 1) and N NMR spectra (see Table 1 and
Fig. 5). For more details about NMR of related compounds
see Ref. 1. It was found that using this method is also
possible to prepare related 6-methyl substituted pyridazi-
nium hexafluorophosphates and tetrafluoroborates with
various substituents at the amino group and aryl group,
Scheme 1.

ˇ
P. Sim u˚ nek et al. / Tetrahedron 61 (2005) 8130–8137
8132
1
5
19 31
Table 1. N, F, P and B NMR parameters of the representative pyridazinium salts
11
a
19 b
F
31
c
P
11
B
Compound
N
a
N
b
N
c
N
d
N
e
d
d
1
1
0 (CDCl
3
)
6 (DMSO)
K163.0
K164.7
K32.5
K33.6
107.7
107.7
K265.5
K276.0
K73.90
K147.87
K147.93
K69.73
K144.0
K143.1
e
f
K1.82
d
1
7 (DMSO)
K164.7
K33.6
107.7
K276.2
a
b
c
d
1 13
For H and C see Section 5.
1 19 31
Values of J( F, P): 713.4 Hz (10), 711.0 Hz (17).
1 31 19
Values of J( P, F): 712.6 Hz (10), 711.3 Hz (17).
Not detected.
F– B.
F– B.
e 19 10
f 19 11
depending on the starting enaminone and diazonium salts
substances 16–21).
(
3. Crystallography
2
ORTEP diagrams of compounds 10 and 17 are shown in
Figures 1 and 3, respectively. The structures of both organic
cations are very similar to those recently published. The
1
pyridazinium rings are essentially planar and display
extended conjugation with the positive charge mainly
located on nitrogen N4. Both compounds form short
intramolecular N–H/N hydrogen bond assisted by reso-
nance between the aminic N3–H group and the nitrogen N1
of the diazenyl moiety. The N1/N3 distances of 2.625(2)
˚
and 2.645(3) A in 10 and 17, respectively, are in agreement
with those of analogue structures recently reported.
1
In compound 17 the N3–H aminic group forms also a
bifurcated weak hydrogen bond with a fluorine atom (F2)
K
˚
of the PF anion [N3/F2Z3.083(4) A]. In both structures
6
K
the PF6 anions are involved in short electrostatic
interactions with pyridazinium rings as shown in Figures 2
and 4 and in Table 3.
Figure 3. ORTEP view of the cation of compound 17. Thermal ellipsoids
are drawn at 30% probability level.
4. Conclusions
The described way of preparation of pyridazinium salts is
simple: the reaction proceeds under mild conditions and the
separation of product being easy, too. The reaction can be
1
15
Figure 5. 500 MHz H– N gs HMBC spectrum of the compound 17 in
DMSO-d optimised for 5 Hz. One of azo nitrogens has not been detected at
the natural abundance.
6
Figure 4. Crystal structure of compound 17 showing the most significant
intermolecular interactions.

ˇ
P. Sim u˚ nek et al. / Tetrahedron 61 (2005) 8130–8137
8133
1
1
applied to both diazonium tetrafluoroborates and diazonium
hexafluorophosphates: the latter gave higher yields in the
majority of cases. The method can be used to prepare
various 1-(substituted aryl)-4-(substituted amino)pyridazi-
nium salts substituted at 6-position by a phenyl or methyl
group. The reaction is affected by substituent type both in
the diazonium salt and in the amino group of the starting
enaminone. Electron-donating substituents in diazonium
salts are usually more appropriate for the formation of the
pyridazinium salt, but exceptions were also observed in
the reactions of N-arylenaminones with diazonium tetra-
fluoroborates. The reaction is restricted to enaminones with
a secondary amino group; the compounds with a primary
amino group only give products of a single azo coupling,
and the enaminones with a tertiary amino groups show
(d 0.0). The B NMR spectra were calibrated on external
B(OCH ) placed in a co-axial capillary (d 18.1). In order to
3
3
1
1
suppress the signals of B nuclei from NMR tube glass, the
measurements were carried out in teflon sample tube liners
(Aldrich) inserted into 5 mm tubes whose bottom part of
about 25 mm length was cut off. The F NMR spectra were
calibrated on internal CFCl3 (d 0.0, central signal of
multiplet of the standard) and were measured using 5 mm
H/ F dual probehead with proton noise decoupling. The
d( N) values were measured with the help of techniques
with inversion detection ( H– N HMBC) processed in the
magnitude mode. The gradient ratios were 70:30:50.1.
Experiments were performed with the NH one-bond
coupling 90 Hz, and NH long-range coupling 5 Hz, 2k!
1
9
1
19
1
5
1
15
160k zero filled to 2k!1k, sinebell squared in both
dimensions.
3
double azo coupling.
Melting points were determined with a Kofler hot stage
microscope and were not corrected. The elemental analyses
were carried out with a FISONS EA 1108 automatic
analyser.
5
. Experimental
5
.1. General
Dichloromethane was pre-dried by standing with anhydrous
calcium chloride and subsequent distillation with phos-
phorus pentoxide. The anhydrous sodium acetate was fused
on a porcelain dish and left to cool in a desiccator. The
diazonium tetrafluoroborates used were prepared by
The NMR spectra were measured at 298 K with a Bruker
AVANCE 500 spectrometer equipped with a 5 mm broad-
band probe with a gradient of magnetic field in the direction
1
of z axis at the frequencies of 500.13 MHz ( H), 125.
1
3
15
7 MHz ( C), 50.69 MHz ( N), 470.56 MHz ( F), 202.
19
7
4
4
3
6 MHz ( P) and with a Bruker AMX 360 spectrometer at
1
procedures described elsewhere and diazonium hexa-
1
13
fluorophosphates were prepared in the same manner as
corresponding tetrafluoroborates with using sodium hexa-
fluorophosphate instead of sodium tetrafluoroborate.
the frequency of 360.14 MHz ( H), 90.57 MHz ( C), 115.
1
5 MHz ( B). The H NMR spectra were calibrated in
1
1
5
CDCl on hexamethyldisiloxane (d 0.05) and in DMSO-d
3
6
on the central signal of the solvent multiplet (d 2.55). The
C NMR spectra were calibrated on the central signal of
1
3
The crystal data for compounds 10 and 17 were collected at
room temperature using a Nonius Kappa CCD diffracto-
meter with graphite monochromated Mo K radiation and
a
the solvent multiplet (d 39.6 for DMSO and d 76.9 for
CDCl ). The carbon NMR spectra were measured in
standard way and by means of the APT pulse sequence
3
corrected for Lorentz and polarization effects. The
structures were solved by direct methods (SIR97 ) and
5
(spectral width 26.455 kHz, acquisition time 1.238 s, zero
filling to 64 K and line broadening 1 Hz prior Fourier
refined using full-matrix least-squares. In compound 10 all
non-hydrogen atoms were refined anisotropically and
hydrogens included on calculated positions, riding on their
1
transformation). The N NMR spectra were calibrated on
5
1
5
external neat N nitromethane placed in a coaxial capillary
Table 2. Crystal data
Compound
Formula
M
10
(C32
17
(C20
C
)
K
)
C
K
H
30
N
5
O
2
$(PF
6
$CHCl
3
22 5 2 6
H N O ) $(PF )
780.95
Orthorhombic
Pna2
30.1530(3)
14.4669(1)
8.2887(1)
90
90
90
3615.7(1)
4
1.435
509.40
Monoclinic
Cc
11.8255(3)
23.3472(7)
9.3110(2)
90
117.684(2)
90
2276.4(1)
4
1.486
System
Space group
1
˚
a (A)
˚
b (A)
˚
c (A)
a (8)
b (8)
g (8)
3
˚
U (A )
Z
D
K3
(g cm
c
)
T (K)
m (cm
295
3.667
295
1.978
K1
)
q
min–qmax (8)
3.9–28.0
8324
0.041
1.7–30.0
6067
0.056
Unique reflections
R
int
Observed reflections [IO2s(I)]
R (observed reflections)
wR (all reflections)
S
6986
4193
0.0624
0.1828
1.023
0.0499
0.1437
1.028
K3
˚
Drmax; Drmin (e A
)
0.38;K0.45
0.34;K0.22

ˇ
P. Sim u˚ nek et al. / Tetrahedron 61 (2005) 8130–8137
8134
carrier atoms except for N3–H hydrogen, which was refined
isotropically. The PF6 anion was found disordered and the
Ar), 126.72 (CH Ar), 127.95 (CH Ar), 130.46 (CH Ar),
131.08 (C Ar), 139.82 (C Ar), 157.51 (C Ar), 162.81
K
q
q
q
six fluorine atoms were refined with two independent
orientations with occupancies of 0.6 and 0.4, respectively.
The asymmetric unit contains also a molecule of solvent
(]C–N), 187.47 (C]O). Anal. Calcd for C H NO
17 17 2
(267.33): C, 76.38; H, 6.41; N, 5.24. Found: C, 76.34; H,
6.60; N, 5.47.
CHCl . In compound 17 all non-hydrogen atoms were
3
refined anisotropically and hydrogens isotropically.
5.1.3. 3-Phenylamino-1-phenylbut-2-en-1-one (3). Com-
pound has been prepared according to method described in
6
All the calculations were performed using SHELXL-97
Ref. 9. Yield 85%; mp 107–108.5 8C (Ref. 9; mp 110.5–
111.5 8C). H NMR (360.14 MHz, CDCl ) 2.10 (s, 3H,
7
8
1
and PARST implemented in WINGX system of programs.
The crystal data and refinement parameters are summarized
in Table 2. Selected bond and short contact distances are
given in Table 3 and hydrogen bond parameters are shown
in Table 4.
3
CH ), 5.87 (s, 1H, ]CH), 7.14 (m, 2H, Ar), 7.20 (m, 1H,
3
Ar), 7.33 (m, 2H, Ar), 7.40 (m, 3H, Ar), 7.90 (m, 2H, Ar),
13.09 (br s, 1H, NH). C NMR (90.57 MHz) 20.21 (CH3),
94.45 (]CH), 124.55 (CH Ar), 125.57 (CH Ar), 126.87
1
3
(CH Ar), 128.08 (CH Ar), 128.97 (CH Ar), 130.70 (CH Ar),
138.46 (C Ar), 139.84 (C Ar), 162.00 (]C–N), 188.47
(C]O).
CCDC-266954 and 266955 contain the supplementary
crystallographic data for this paper. These data can be
obtained free of charge at www.ccdc.cam.ac.uk/conts/
retrieving.html [or from the Cambridge Crystallographic
Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK;
fax: C44 1223 336033; e-mail: deposit@ccdc.cam.ac.uk]
q
q
5.1.4. 3-Methylamino-1-phenylbut-2-en-1-one (4). Com-
pound 4 was prepared according to the procedure described
in Ref. 10.
(
Table 4).
5.1.5. 4-Methylaminopent-3-en-2-one (5). Compound 5
was prepared according to procedure described in Ref. 11.
5
1
.1.1. 3-(2,4-Dimethoxyphenylamino)-1-phenylbut-2-en-
-one (1). Compound 1 was prepared according to the
procedure described in Ref. 1.
5.1.6. 4-(2,4-Dimethoxyphenylamino)pent-3-en-2-one
(6). A mixture of acetylacetone (0.1 mol) and 2,4-di-
methoxyaniline (0.1 mol) was heated in 50 ml toluene to
boiling. The water formed in reaction was distilled off as an
azeotrope with toluene. The toluene thus removed was
replenished by adding fresh toluene. After the reaction, the
5
.1.2. 3-(4-Methoxyphenylamino)-1-phenylbut-2-en-1-
one (2). Compound 2 was prepared by the same method
as 1. Crystallisation from toluene, yield 77%; mp 106–
1
07 8C. H NMR (360.14 MHz, CDCl ) 2.00 (s, 3H, CH ),
1
3
7
3
3
solvent was distilled off, and the residue was submitted to
.73 (s, 3H, OCH ), 5.83 (s, 1H, ]CH), 6.83 (m, 2H, Ar),
3
1
vacuum distillation. Yield 84%, bp 165 8C/5 mBar.
NMR (360.14 MHz, CDCl ): 1.87 (s, 3H, CH ), 2.07 (s, 3H,
H
.05 (m, 2H, Ar), 7.39 (m, 3H, Ar), 7.89 (m, 2H, Ar), 12.94
1
3
(
br s, 1H, NH). C NMR (90.57 MHz, CDCl ) 19.89 (CH ),
3
3
3
3
CH CO), 3.79 (s, 3H, OCH ), 3.80 (s, 3H, OCH ), 5.15 (s,
3
5
5.11 (OCH ), 93.42 (]CH), 114.02 (CH Ar), 126.19 (CH
3
3
3
1
H, ]CH), 6.42 (dd, 1H, CH , JZ8.6, 2.7 Hz), 6.48 (d,
Ar
˚
Table 3. Selected bond and short contact distances (A)
1H, CH , JZ2.6 Hz), 7.00 (d, 1H, CH , JZ8.6 Hz), 12.04
Ar
Ar
1
3
br s, 1H, NH). C NMR (90.57 MHz, CDCl ): 19.43, 28.91
(
3
1
0
17
(
2!CH ), 55.35, 55.55 (2!OCH ), 96.69, 99.08, 103.62,
3
3
N1–N2
N2–C1
C1–C2
N3–C2
C1–C4
N4–C4
N4–N5
N5–C3
C2–C3
N4/F2
C1/F1
C3/F6
C4/F2
C1/F1
C2/F1
C4/F5
1.268(3)
1.395(3)
1.431(3)
1.330(3)
1.401(3)
1.346(3)
1.348(3)
1.298(3)
1.415(3)
3.130(11)
3.196(8)
3.149(12)
3.128(11)
1.266(3)
1.405(3)
1.426(3)
1.322(4)
1.400(4)
1.361(3)
1.352(3)
1.303(4)
1.424(4)
1
1
6
20.80, 126.75 (5!CH), 154.50, 158.73, 161.70 (3!Cq),
95.48 (C]O). Anal. Calcd for C H NO (235.28): C,
6.36; H, 7.28; N, 5.95. Found: C, 66.47; H, 7.23; N, 5.99.
1
3
17
3
5
.1.7. 2,4-Dimethoxybenzaldoxime. A 250 ml three-
necked flask equipped with a reflux condenser, thermometer
and dropping funnel was charged with a solution of 2,
4-dimethoxy-benzaldehyde (16.6 g, 0.1 mol) in 75 ml
ethanol, and a solution of hydroxylamine hydrochloride
(
7 g, 0.1 mol) in 20 ml water. The mixture was stirred, and a
solution of anhydrous sodium carbonate (5.3 g, 0.05 mol) in
0 ml water was added drop by drop from the funnel. After
3.194(5)
3.187(5)
3.193(6)
2
addition of all the carbonate, the mixture was refluxed 5 h,
whereupon it was cooled in ice bath, and the separated
˚
Table 4. Hydrogen bond parameters (A and degrees)
D–H/A
D–H
H/A
D/A
D–H/A
Compound 10
N3–H/N1
C33–H33 /F4
Compound 17
0.75(4)
0.98
2.04(3)
2.18
2.625(2)
3.084(12)
135(3)
153
a
N3–H/N1
N3–H/F2(x,Ky,zK1/2)
0.70(3)
0.70(3)
2.08(3)
2.68(4)
2.645(3)
3.083(4)
140(4)
119(3)
a
Calculated hydrogen.

ˇ
P. Sim u˚ nek et al. / Tetrahedron 61 (2005) 8130–8137
8135
product was collected by suction and dried in air. Yield 10.
8
5.2. General procedure of azo coupling reactions
g (60%); mp 103–105 8C (Ref. 12; mp 104–105 8C).
Re-melted sodium acetate (30 mmol) and the respective
benzenediazonium tetrafluoroborate or hexafluorophos-
phate (10 mmol) were added to a solution of enaminone
5
.1.8. 2,4-Dimethoxybenzylamine. 2,4-Dimethoxybenzal-
doxime (10.8 g) was hydrogenated at atmospheric pressure
in ethyl acetate with RaneyNi as catalyst for 48 h. The
solvent was removed by distillation, and the evaporation
residue was distilled in vacuum to give 4.5 g (45%) liquid,
bp 110–120 8C/10 mBar (Ref. 13, bp 142–143 8C/20 mBar).
(5 mmol) in 30 ml dichloromethane with stirring. The
reaction mixture was stirred at room temperature 72 h,
whereupon the solids were collected by suction on a
sintered-glass filter and the filter cake was washed with
dichloromethane. The filtrate was evaporated in vacuum,
and the evaporation residue was either recrystallized or
submitted to column chromatography (in the case of
compounds 13 and 16–19 and 21 washing by ethylacetate
was performed instead of column chromatography). The
following compounds were prepared by the procedure
described.
1
H NMR (500.13 MHz, CDCl ): 3.73 (s, 2H, CH ), 3.78 (s,
3
2
3
2
H, OCH ), 3.80 (s, 3H, OCH ), 6.41 (dd, 1H, CH , JZ8.1,
3 3 Ar
.4 Hz), 6.44 (d, 1H, CH , JZ2.3 Hz), 7.08 (d, 1H, CH ,
Ar
Ar
1
3
JZ8.1 Hz). C NMR (125.77 MHz, CDCl ): 42.02 (CH ),
5
3
2
5.00, 5.19 (2!OCH ), 98.42, 103.44 (2!CH ), 124.38
3 Ar
(
C ), 128.83 (CH ), 158.22, 159.76 (2!C ).
q Ar q
5
.2.1. 4-(2,4-Dimethoxyphenylamino)-1-(4-methyl-
5
.1.9. 4-(2,4-Dimethoxybenzylamino)pent-3-en-2-one
7). A 100 ml three-necked flask equipped with azeotropic
phenyl)-5-(4-methylphenyldiazenyl)-6-phenylpyridazi-
nium hexafluorophosphate (10). This compound was
obtained as red crystalline solid after crystallization of
(
distillation head was charged with acetylacetone (29 mmol),
2
4
heated to boiling on an oil bath while intermittently
removing the toluene–water azeotrope, until the distillate
was clear toluene. Then a part of toluene was distilled off
and the residue was cooled. The separated crystals were
collected by suction. The product was purified by vacuum
,4-dimethoxybenzylamine (29 mmol), 30 ml toluene and
-methylbenzenesulphonic acid (1 mmol). The mixture was
evaporation residue from ethanol. Yield 43%; mp 243–
1
45 8C. H NMR (500.13 MHz, CDCl ): 2.26 (s, 3H, CH ),
2
2
6
2
7
3
3
.37 (s, 3H, CH ), 3.83 (s, 3H, OCH ), 3.92 (s, 3H, OCH ),
3
3
3
.58 (dd, 1H, CH , JZ2.6, 8.7 Hz), 6.61 (d, 1H, CH , JZ
Ar
Ar
0
.24–7.26 (m, 2H, XX ), 7.28–7.32 (m, 2H, CH ), 7.35–
0
.5 Hz), 7.04–7.05 (m, 2H, AA ), 7.18–7.20 (m, 2H, AA ),
0
Ar
1
7.42 (m, 5H, CHAr), 7.63 (d, 1H, CHAr, JZ8.7 Hz), 8.81 (s,
1
CDCl ): 20.99 (CH ), 21.55 (CH ), 55.69 (OCH ), 56.04
distillation (173–176 8C/6–7 mBar). Yield 66%. H NMR
(
13
H, CH), 12.83 (s, 1H, NH). C NMR (125.77 MHz,
360.14 MHz, CDCl ): 1.93 (s, 3H, CH ), 1.98 (s, 3H, CH ),
3 3 3
3
3
3
3
3
.77 (s, 3H, OCH ), 3.81 (s, 3H, OCH ), 4.33 (d, 2H, CH ,
3 3 2
(OCH ), 99.59, 105.35 (2!CH ), 115.70 (C ), 123.34,
3 Ar q
JZ6.4 Hz), 4.96 (s, 1H, ]CH), 6.40–6.44 (m, 2H, CH ),
Ar
3
1
126.20, 126.24, 127.72 (4!CHAr), 128.74, 128.89 (2!C ),
q
7
.06 (d, 1H, CH , JZ8.4 Hz), 11.03 (br s, 1H, NH).
C
90.57 MHz, CDCl ): 18.60 (CH ), 28.65 (CH ), 41.74
Ar
1
1
1
29.59, 130.10, 130.13, 130.69 (4!CH ), 139.28, 139.85,
Ar
(
(
3 3 3
40.32 (3!C ), 141.33 (CH), 144.35, 149.71, 154.02,
q
CH ), 55.20, 55.23 (2!OCH ), 95.23, 98.43, 103.83 (3!
2
31
58.04, 161.27 (5!Cq). P NMR (202.45 MHz, CDCl ):
3
3
CH ), 118.57 (C ), 128.54 (CH ), 157.85, 160.30, 162.84
Ar
19
q
Ar
K143.99 (sp, JZ712.6 Hz). F NMR (470.56 MHz):
K73.88 (d, JZ713.4 Hz). Anal. Calcd for C H F N O P
(
(
7
3!C ), 194.57 (C]O). Anal. Calcd for C H NO
q 14 19 3
249.31): C, 67.45; H, 7.68; N, 5.62. Found: C, 67.69; H,
.51; N, 5.64.
3
2 30 6 5 2
(661.58): C, 58.10; H, 4.57; N, 10.59. Found: C, 58.01; H,
4
.72; N, 10.31.
5.2.2. 4-(2,4-Dimethoxyphenylamino)-1-phenyl-5-phenyl-
5
.1.10. 4-(4-Chlorophenylamino)pent-3-en-2-one (8).
diazenyl-6-phenylpyridazinium hexafluorophosphate
11). This compound was obtained as red crystalline solid
after column chromatography (silica/chloroform/ethyl-
This compound has been prepared according to procedure
described in Ref. 14. Product has been purified by vacuum
distillation, (bp 123–132 8C/4 mBar) and by crystallization
(
1
acetate 3:1) and recrystallization from ethanol. Yield 38%;
mp 236–240 8C. H NMR (500.13 MHz, CDCl ): 3.85 (s,
from n-hexane; mp 55.5–57 8C (Ref. 14; mp 60–61 8C). H
NMR (360.14 MHz, CDCl ): 1.95 (s, 3H, CH ), 2.07 (s, 3H,
1
3
3
3
0
3H, OCH ), 3.92 (s, 3H, OCH ), 6.61–6.63 (m, 2H, CH ),
3 3 Ar
7.28–7.32 (m, 5H, CH ), 7.36–7.46 (m, 8H, CH ), 7.48–
Ar Ar
CH ), 5.18 (s, 1H, ]CH), 6.98–7.05 (m, 2H, AA ), 7.25–
3
0
13
.28 (m, 2H, XX ), 12.43 (br s, 1H, NH). C (90.57 MHz,
7
CDCl ): 19.44, 28.89 (2!CH ), 97.86 (]CH), 125.46,
7
1
.5 (m, 2H, CH ), 7.69 (d, 1H, CH , JZ8.72 Hz), 8.86 (s,
Ar Ar
13
3
3
H, CH ), 12.87 (br s, 1H, NH). C NMR (125.77 MHz,
Ar
1
28.88 (2!CH), 130.60, 137.06 (3!C ), 159.34 (]C–N),
q
CDCl ): 55.73 (OCH ), 56.04 (OCH ), 99.75, 105.21 (2!
3
3
3
1
96.15 (C]O).
CH ), 115.66 (C ), 123.34, 126.44, 126.57, 127.79 (4!
Ar
q
CH ), 128.57, 128.81 (2!C ), 129.11, 129.40, 129.64,
Ar
130.29, 130.75, 133.03 (6!CH ), 139.42 (C ), 141.61
Ar q
q
5
.1.11. 4-(4-Methylphenylamino)pent-3-en-2-one (9).
Compound has been prepared according to procedure
described in Ref. 14. Product has been purified by
crystallisation from n-hexane; mp 63.5–64.5 8C (Ref. 14
(CH), 142.64, 151.43, 153.98, 158.45, 161.36 (5!Cq).
Anal. Calcd for C H F N O P (633.53): C, 56.88; H,
4.14; N, 11.05. Found: C, 57.04; H, 4.15; N, 10.92.
3
0 26 6 5 2
1
6
CH ), 2.07 (s, 3H, CH ), 2.31 (s, 3H, CH ), 5.14 (s, 1H,
8–69 8C). H NMR (360.14 MHz, CDCl ): 1.93 (s, 3H,
3
3
3
3
5.2.3. 4-(2,4-Dimethoxyphenylamino)-1-(4-methoxy-
phenyl)-5-(4-methoxyphenyldiazenyl)-6-phenylpyridazi-
nium hexafluorophosphate (12). This compound was
obtained as red crystalline solid after column chromatography
(silica/chloroform/ethylacetate 4:1) and recrystallization
0
0
]
1
CH), 6.97 (m, 2H, AA ), 7.11 (m, 2H, XX ), 12.38 (br s,
H, NH). C (90.57 MHz, CDCl ): 19.64, 20.79, 29.00
3
1
3
(
3!CH ), 97.11 (]CH), 124.74, 129.55 (2!CH ),
3 Ar
1
35.37, 135.97 (2!C ), 160.56 (]C–N), 195.77 (C]O).
q

ˇ
P. Sim u˚ nek et al. / Tetrahedron 61 (2005) 8130–8137
8136
1
from ethanol. Yield 40%; mp 129–134 8C. H NMR
0
13
2H, XX ), 8.69 (s, 1H, CH), 12.71 (br s, 1H, NH). C NMR
(
500.13 MHz, CDCl ): 3.73 (s, 3H, OCH ), 3.84 (s, 6H,
3
(125.77 MHz, CDCl ): 20.88, 21.44, 55.41 (3!CH ),
3
3
3
2
CH ), 6.74–6.75 (m, 2H, AA ), 6.87–6.89 (m, 2H, AA ),
!OCH ), 3.84 (s, 3H, OCH ), 6.58–6.60 (m, 2H, 2!
115.30, 123.20 (2!CH ), 126.18 (C ), 126.33, 126.79,
Ar q
127.44 (3!CH ), 128.55, 128.79 (2!C ), 129.31, 129.81,
Ar q
129.88, 130.65 (4!CH ), 139.52, 140.21, 140.37 (3!C ),
Ar q
141.05 (CH), 144.00, 149.62, 158.35, 159.72 (4!C ). Anal.
q
3
3
0
.27–7.30 (m, 2H, XX ), 7.30–7.33 (m, 3H, CH ), 7.35–
0
Ar
0
.40 (m, 4H, CH ), 7.45–7.48 (m, 2H, XX ), 7.63 (d, 1H,
7
7
Ar
0
Ar
1
3
CH , JZ9 Hz), 8.79 (s, 1H, CH), 12.80 (br s, 1H, NH). C
NMR (125.77 MHz, CDCl ): 55.40 (OCH ), 55.70 (2!
Calcd for C H BF N O (573.40): C, 64.94; H, 4.92; N,
31 28
Ar
4 5
12.21. Found: C, 64.97; H, 4.87; N, 12.10.
3
3
OCH ), 56.02 (OCH ), 99.64, 105.20, 114.08, 114.75 (4!
3
3
CH ), 115.84 (C ), 125.61, 126.14, 127.74, 127.77 (4!
Ar
5.2.7. 1-(4-Methoxyphenyl)-4-methylamino-5-(4-meth-
oxyphenyldiazenyl)-6-methylpyridazinium tetrafluoro-
borate (16). This compound was obtained as orange solid
q
CH ), 128.93, 129.11 (2!C ), 130.05, 130.63 (2!CH ),
Ar
q
Ar
1
1
35.70, 139.28 (2!C ), 140.98 (CH), 145.96, 153.95,
q
57.58, 159.93, 161.13, 163.90 (6!C ). Anal. Calcd for
q
after recrystallization from methanol. Yield 20%; mp 210–
213.5 8C. H NMR (360.14 MHz, DMSO-d ): 2.82 (s, 3H,
1
C H F N O P (693.58): C, 55.42; H, 4.36; N, 10.10.
5
3
2
30
6
4
6
Found: C, 55.71; H, 4.25; N, 9.91.
CH ), 3.41 (d, 3H, NCH , JZ5.4 Hz), 3.92 (s, 3H, OCH ),
3
3
3
0
.94 (s, 3H, OCH ), 7.20–7.28 (m, 4H, 2!AA ), 7.65–7.70
3
3
0 0
(m, 2H, XX ), 8.18–8.22 (m, 2H, XX ), 9.18 (s, 1H, ]CH),
13
5.2.4. 1-(4-Methoxyphenyl)-4-methylamino-5-(4-meth-
oxyphenyldiazenyl)-6-phenylpyridazinium hexafluoro-
10.97 (br q, 1H, NH, JZ5.4 Hz). C NMR (90.57 MHz,
DMSO-d ): 17.04 (CH ), 30.53 (NCH ), 55.07, 56.24 (2!
phosphate (13). This compound was obtained as orange
solid after recrystallization from ethanol. Yield 33%; mp
6
3
3
OCH ), 115.18, 115.27, 125.88, 127.82 (4!CH ), 128.21,
3 Ar
135.38, 140.23 (3!C ), 140.82 (CH), 146.50, 157.18,
q
1
15–218 8C. H NMR (500.13 MHz, DMSO-d ): 3.51 (d,
2
6
3
OCH ) 6.99–7.00 (m, 2H, AA ), 7.11–7.14 (m, 2H, AA ),
H, NCH , JZ5.5 Hz), 3.78 (s, 3H, OCH ), 3.88 (s, 3H,
160.75, 163.71 (4!C ). Anal. Calcd for C H F N O B
20 22 4 5 2
(451.23): C, 53.24; H, 4.91; N, 15.52. Found: C, 53.41; H,
4.96; N, 15.27.
3
3
q
0
.44–7.52 (m, 7H, CH ), 7.74–7.77 (m, 2H, XX ), 9.39 (s,
0
3
0
7
1
Ar
1
3
H, CH), 10.97 (q, 1H, NH, JZ5.5 Hz). C NMR
(
125.77 MHz, DMSO-d ): 30.95 (NCH ), 55.82, 56.18
5.2.8. 1-(4-Methoxyphenyl)-4-methylamino-5-(4-meth-
oxyphenyldiazenyl)-6-methylpyridazinium hexafluoro-
phosphate (17). This compound was obtained as orange
6
3
(
CH ), 129.01, 129.85 (2!C ), 130.30, 130.84 (2!CH ),
2!OCH ), 114.42, 115.21, 125.60, 127.96, 128.41 (5!
3
Ar
q
Ar
1
1
36.17, 141.33 (2!C ), 141.46 (CH), 146.50, 156.72,
q
solid after recrystallization from ethanol. Yield 26%; mp
217–221 8C. H NMR (360.14 MHz, DMSO-d ): 2.84 (s,
3
1
59.92, 163.71 (4!Cq). P NMR (202.45 MHz, DMSO-
1
6
1
9
d6): K143.14 (sp, JZ711.5 Hz). F NMR (470.56 MHz,
DMSO-d ): K69.72 (d, JZ711.8 Hz). Anal. Calcd for
C H F N O P (571.46): C, 52.55; H, 4.23; N, 12.26.
Found: C, 52.79; H, 4.42; N, 12.19.
3H, CH ), 3.43 (d, 3H, NCH , JZ5.4 Hz), 3.93 (s, 3H,
3
3
0
OCH ), 3.96 (s, 3H, OCH ), 7.23–7.25 (m, 2H, AA ), 7.26–
3 3
6
0
0
2
5 24 6 5 2
7.29 (m, 2H, AA ), 7.67–7.70 (m, 2H, XX ), 8.21–8.23 (m,
0
.4 Hz). C NMR (90.57 MHz, DMSO-d ): 16.94 (CH ),
2H, XX ), 9.22 (s, 1H, ]CH), 10.97 (br q, 1H, NH, JZ
1
3
5
30.44 (NCH
6 3
5
.2.5. 4-(2,4-Dimethoxyphenylamino)-1-(4-chloro-
3
), 55.82, 56.02 (2!OCH
), 135.18 (CHAr), 139.79,
), 140.78 (CH), 146.30, 156.99, 160.48,
). Anal. Calcd for C20 P (509.39):
3
), 115.03, 125.65,
phenyl)-5-(4-chlorophenyldiazenyl)-6-phenylpyridazi-
nium hexafluorophosphate (14). This compound was
obtained as dark purple solid after column chromatography
127.55 (3!CHAr), 128.07 (C
139.95 (2!C
163.54 (4!C
q
q
H F N O
22 6 5 2
q
(
3
silica/CHCl ) and recrystallization from ethanol. Yield
3
2%; mp 245–249 8C. H NMR (500.13 MHz, CDCl ): 3.83
3
C, 47.16; H, 4.35; N, 13.75. Found: C, 47.17; H, 4.43; N,
13.98.
1
(
CH ), 7.21–7.23 (2H, m, CH ), 7.31–7.41 (m, 11H,
s, 3H, OCH ), 3.90 (s, 3H, OCH ), 6.57–6.59 (m, 2H,
3 3
5.2.9. 1-Phenyl-4-methylamino-5-phenyldiazenyl-6-
methylpyridazinium tetrafluoroborate (18). This com-
pound was obtained as orange solid after recrystallization
Ar
Ar
CH ), 7.64 (d, 1H, CH , JZ9.5 Hz), 8.83 (s, 1H, ]CH),
Ar
Ar
1
3
2.75 (br s, 1H, NH). C NMR (125.77 MHz, CDCl3):
1
1
5
5.69, 56.05 (2!OCH ), 99.65, 105.23 (2!CH ), 115.43
3
from ethanol. Yield 3%; mp 220.5–224 8C. H NMR
(360.14 MHz, DMSO-d ): 2.86 (s, 3H, CH ), 3.43 (d, 3H,
Ar
(
C ), 124.38, 126.08, 127.91, 127.96 (4!CH ), 128.27,
q
Ar
6
3
1
1
1
28.77 (2!C ), 129.25, 129.73, 130.54, 130.62 (4!CH ),
q
35.73, 139.24, 139.26, 140.99 (4!C ), 141.75 (CH),
q
49.77, 153.89, 158.47, 161.42 (4!C ). Anal. Calcd for
q
NCH , JZ5.5 Hz), 7.68–7.70 (m, 3H, CH ), 7.76–7.77 (m,
Ar
3 Ar
5H, CH ), 8.17–8.20 (m, 2H, CH ), 9.24 (s, 1H, CH),
Ar Ar
1
3
11.08 (br q, 1H, NH, JZ5.4 Hz). C NMR (90.57 MHz,
DMSO-d ): 17.16 (CH ), 30.75 (NCH ), 123.53, 126.48
(2!CH), 128.09 (C ), 130.04, 130.42, 131.13, 133.36 (4!
C H Cl F N O P (702.42): C, 51.30; H, 3.44; N, 9.97.
2
Found: C, 51.05; H, 3.40; N, 9.65.
3
0
24
2
6
5
6
3
3
q
CH), 140.23, 142.40, 152.16, 157.93 (4!C ). Anal. Calcd
q
5
.2.6. 4-(4-Methoxyphenylamino)-1-(4-methylphenyl)-5-
4-methylphenyldiazenyl)-6-phenylpyridazinium tetra-
for C18H F N BF (391.18): C, 55.27; H, 4.64; N, 17.90.
18 4 5 4
Found: C, 55.24; H, 4.53; N, 17.92.
(
fluoroborate (15). This compound was obtained as orange
solid after column chromatography (silica/CHCl /ethyl-
3
5.2.10. 1-Phenyl-4-methylamino-5-phenyldiazenyl-6-
methylpyridazinium hexafluorophosphate (19). This
compound was obtained as orange solid and were not
acetate 3:2) and washing by hot ethylacetate. Yield 9%; mp
2
CH ), 2.34 (s, 3H, CH ), 3.78 (s, 3H, OCH ), 6.92–6.94 (m,
1
07–215 8C. H NMR (500.13 MHz, CDCl ): 2.20 (s, 3H,
3
1
recrystallized. Yield 54%; mp 210–214.5 8C. H NMR
(360.14 MHz, DMSO-d ): 2.86 (s, 3H, CH ), 3.45 (d, 3H,
3
3
3
0
0
0
.23–7.26 (m, 2H, CH ), 7.30–7.32 (m, 3H, CH ), 7.34–
2
7
7
H, AA ), 6.95–6.97 (m, 2H, AA ), 7.13–7.14 (m, 2H, AA ),
6
3
NCH , JZ5.5 Hz), 7.67–7.71 (m, 3H, CH ), 7.74–7.78
Ar
Ar
3
Ar
0
.36 (m, 2H, XX ), 7.45–7.46 (m, 2H, CH ), 7.47–7.49 (m,
Ar
(m, 5H, CH ), 8.18–8.21 (m, 2H, CH ), 9.26 (s, 1H,
Ar Ar

ˇ
P. Sim u˚ nek et al. / Tetrahedron 61 (2005) 8130–8137
8137
1
3
]
(
CH), 11.09 (br q, 1H, NH, JZ5.4 Hz). C NMR
Acknowledgements
90.57 MHz, DMSO-d ): 17.04 (CH ), 30.67 (NCH ),
6
3
3
1
1
1
23.44, 126.36 (2!CH ), 127.98 (C ), 129.90, 130.32,
Ar
For financial support authors thank to the Czech Science
Foundation (Grant No. 203/03/0356) and to the Ministry of
Education, Youth and Sports of the Czech Republic
(MSM0021627501).
q
31.01, 133.24 (4!CH ), 140.12 (C ), 141.55 (CH),
Ar
q
42.31, 152.06, 157.79 (3!C ). Anal. Calcd for
q
C H F N P (449.34): C, 48.12; H, 4.04; N, 15.59.
1
8 18 6 5
Found: C, 48.33; H, 4.26; N, 15.81.
5
.2.11. 1-(4-Methoxyphenyl)-4-(2,4-dimethoxyphenyl-
amino)-5-(4-methoxyphenyldiazenyl)-6-methylpyridazi-
nium hexafluorophosphate (20). This compound was
obtained as dark red solid after column chromatography
References and notes
(
silica/chloroform/ethylacetate 4:1) and recrystallization
ˇ
1. Sim u˚ nek, P.; Pe sˇ kov a´ , M.; Bertolasi, V.; Ly cˇ ka, A.;
1
from ethanol. Yield 37%; mp 126–131 8C. H NMR
360.14 MHz, CDCl ): 2.89 (s, 3H, CH ), 3.83 (s, 3H,
Mach a´ cˇ ek, V. Eur. J. Org. Chem. 2004, 5055–5063.
(
3
3
2
. Burnett, M. N.; Johnson, C. K. ORTEP III; Report ORNL-
OCH ), 3.86 (s, 3H, OCH ), 3.90 (s, 6H, 2!OCH ), 6.56–
6
(
]
CDCl ): 16.71 (CH ), 55.51, 55.57, 55.69, 55.91 (4!
3
OCH ), 99.30, 105.21, 114.80, 114.84 (4!CH ), 115.48
Ar
3
3
3
0
.59 (m, 2H, CH ), 7.00–7.06 (m, 4H, 2!AA ), 7.46–7.50
Ar
6895, Oak Ridge National Laboratory: Oak Ridge, TN, 1996.
3. Sˇ im u˚ nek, P.; Bertolasi, V.; Ly cˇ ka, A.; Mach a´ cˇ ek, V. Org.
0 0
m, 3H, XX CCH ), 7.84–7.86 (m, 2H, XX ), 8.59 (s, 1H,
Ar
13
CH), 12.75 (br s, 1H, NH). C NMR (90.57 MHz,
Biomol. Chem. 2003, 3250–3256.
ˇ
4
. Sim u˚ nek, P.; Ly cˇ ka, A.; Mach a´ cˇ ek, V. Eur. J. Org. Chem.
2002, 2764–2769.
3
3
(
1
1
C ), 125.49, 125.61, 126.97 (3!CH ), 128.71, 134.70,
q
37.94 (3!C ), 140.29 (CH), 145.76, 153.89, 157.85,
q
60.73, 160.96, 164.00 (6!C ). Anal. Calcd for
q
5. Altomare, A.; Burla, M. C.; Camalli, M.; Cascarano, G. L.;
Giacovazzo, C.; Guagliardi, A.; Moliterni, A. G. G.; Polidori,
G.; Spagna, R. J. Appl. Crystallogr. 1999, 32, 115–119.
Ar
C H F N O P (631.51): C, 51.35; H, 4.47; N, 11.09.
2
Found: C, 51.51; H, 4.19; N, 10.97.
6. Sheldrick, G. M. SHELX-97: Program for Crystal Structure
Refinement; University of Gottingen: Gottingen, Germany,
7 28 6 5 4
1
997.
5
.2.12. 1-(4-Methylphenyl)-4-(4-methylphenylamino)-5-
4-methylphenyldiazenyl)-6-methylpyridazinium hexa-
7. Nardelli, M. J. Appl. Crystallogr. 1995, 28, 659–659.
8. Farrugia, L. J. Appl. Crystallogr. 1999, 32, 837–838.
(
fluorophosphate (21). This compound was obtained as
orange solid after recrystallization from ethanol. Yield 34%;
mp 223–227 8C. H NMR (360.14 MHz, CDCl ): 2.35 (s,
9
. Iida, H.; Yuasa, Y.; Kibayashi, C.; Iitaka, Y. J. Chem. Soc.,
Dalton Trans. 1981, 2212–2216.
1
3
10. Ribeiro Da Silva, M. A. V.; Ribeiro Da Silva, M. D. M. C.;
Paiva, J. P. A.; Nogueira, I. M. C. S.; Daman, A. M.; Barkley,
J. V.; Gardiny, M. M.; Akello, M. J.; Pilcher, G. J. Chem. Soc.,
Perkin Trans. 2 1993, 1765–1769.
3
NCH ), 7.20–7.31 (m, 8H, CH ), 7.39–7.42 (m, 2H, XX ),
H, CH ), 2.38 (s, 3H, CH ), 2.39 (s, 3H, CH ), 2.86 (s, 3H,
3 3 3
0
.69–7.72 (m, 2H, XX ), 8.51 (s, 1H, CH), 12.78 (br s, 1H,
3
Ar
0
NH). C NMR (90.57 MHz, CDCl ): 16.70, 20.96, 21.05,
7
1
3
3
1
1
1. Jirkovsky, I. Can. J. Chem. 1974, 52, 55–65.
2
1.51 (4!CH ), 123.23, 125.10, 125.44 (3!CH ), 128.31
3 Ar
2. Marshall, G. R.; Pieta, P. G.; Cavallo, P. J. Org. Chem. 1971,
(
C ), 130.07, 130.35, 130.82 (3!CH), 130.83, 138.93,
q
3
6, 3966–3970.
1
39.23, 139.52 (4!C ), 140.30 (CH), 140.90, 144.41,
q
1
1
3. Weygand, F.; Steglich, W.; Bjarnason, J.; Akhatar, R.; Chytil,
N. Chem. Ber. 1968, 101, 3623–3641.
1
49.64, 158.72 (4!C ). Anal. Calcd for C H F N P
q
26 26 6 5
(
4
553.49): C, 56.42; H, 4.73; N, 12.65. Found: C, 56.60; H,
.82; N, 12.62.
4. Roberts, E.; Turner, E. E. J. Chem. Soc. 1927, 1832–1857.