Formation of pyridazinium salts by azo coupling of N-substituted 3-amino-1-phenylbut-2-en-1-ones and diazonium salts

Article abstract of DOI:10.1002/ejoc.200400287

Treatment of 3-(2,4-dimethoxyphenylamino)- and 3-methylamino-1-phenylbut-2- en-1-ones with some benzenediazonium tetrafluoroborates gives, besides the usual azo coupling products [i.e., 3-(substituted imino)-1-phenylbutane-1,2-diones 2-(4-substituted phenylhydrazones) and 2-(4-methoxyphenyldiazenyl)-3- methylamino-1-phenylbut-2-en-1-one, respectively], the previously unreported 1,4,5,6-tetrasubstituted pyridazinium tetrafluoroborates. The pyridazinium salts have been identified by X-ray analysis and by their ¹H, ¹³C, ¹⁵N, ¹¹B and ¹⁹F NMR spectra. Their formation is most probably the result of nucleophilic attack on the carbonyl carbon by the nitrogen of the hydrazone group and subsequent dehydration. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.

Full text of DOI:10.1002/ejoc.200400287

FULL PAPER
Formation of Pyridazinium Salts by Azo Coupling of N-Substituted
3-Amino-1-phenylbut-2-en-1-ones and Diazonium Salts
[a]
[a]
[b]
[c]
ˇ
˚
´
ˇ
´
´
ˇ
Petr Simunek,* Marketa Peskova, Valerio Bertolasi, Antonın Lycka, and
[a]
´
´ˇ
Vladimır Machacek
Dedicated to Professor Otto Exner on the occasion of his 80th birthday[‡]
Keywords: Azo Coupling / Diazonium salts / Pyridazinium salts
1
Treatment of 3-(2,4-dimethoxyphenylamino)- and 3-methyl-
salts have been identified by X-ray analysis and by their H,
amino-1-phenylbut-2-en-1-ones with some benzenediazon- 13C, 15N, 11B and 19F NMR spectra. Their formation is most
ium tetrafluoroborates gives, besides the usual azo coupling
products [i.e., 3-(substituted imino)-1-phenylbutane-1,2-di-
ones 2-(4-substituted phenylhydrazones) and 2-(4-methoxy-
phenyldiazenyl)-3-methylamino-1-phenylbut-2-en-1-one,
respectively], the previously unreported 1,4,5,6-tetrasubsti-
probably the result of nucleophilic attack on the carbonyl
carbon by the nitrogen of the hydrazone group and sub-
sequent dehydration.
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
tuted pyridazinium tetrafluoroborates. The pyridazinium Germany, 2004)
Introduction
paper deals with a study of the reactions of the N-substi-
tuted 3-amino-1-phenylbut-2-en-1-ones 1 and 2 with ben-
zenediazonium and 4-methoxy- and 4-methylbenzenedia-
zonium cations, which give some products with structures
entirely different from those of the azo coupling products
described so far.
Enaminones are useful intermediates for syntheses of
heterocyclic compounds[1,2] and also currently serve as
medical drugs.[3Ϫ7] A typical feature of β-enaminones is
their reactions with electrophilic reagents. In previous
papers[8Ϫ12] we have dealt with reactions between various
types of β-enaminones and benzenediazonium salts from
the standpoints of the constitutions of the products and
their tautomeric behaviour, both in solution (CDCl3) and
in the crystalline state. These compounds exhibit azo-hydra-
zone and ketimine-enamine tautomerism, both fast on the
NMR timescale,[13,14] and a somewhat slower rotation
Results and Discussion
The reaction between 4-methylbenzenediazonium tetra-
fluoroborate and 3-(2,4-dimethoxyphenylamino)-1-phe-
nylbut-2-en-1-one (1) in dichloromethane gives a mixture of
two compounds. One of them is the expected azo coupling
product 3a, which according to 15N NMR spectroscopy ex-
ists in deuteriochlorofom solution predominantly as the hy-
…
around the polarised and partially double bond Cα — Cβ in
…
…
…
the N …— Cβ — Cα —
C
O grouping (ref.[9]). The positions
—
of the tautomeric equilibria depend predominantly on the
structures of the starting enaminones and, to a lesser extent,
on the substitution on the benzenediazonium ions.[15] This
drazone
[3-(2,4-dimethoxyphenylimino)-1-phenylbutane-
1,2-dione) 2-(4-methylphenyl)hydrazone]. The side product
is a dark red crystalline substance 4a, formed in a yield of
17% (Scheme 1).
[a]
University of Pardubice, Department of Organic Chemistry,
ˇ
´
´
Nam. Cs. Legiı 565, 53210 Pardubice, Czech Republic
The elemental analysis of compound 4a corresponds to
a molecular formula of C32H30BF4N5O2, which was con-
firmed by 11B and 19F NMR spectroscopy, the boron[16]
Fax: (internat.) ϩ420-466-037-068
E-mail: p.simunek@email.cz
[b]
`
Universita di Ferrara, Dipartimento di Chimica, Centro di
Ϫ
and fluorine[17] chemical shifts corresponding to the BF4
Strutturistica Diffrattometrica,
Via L. Borsari 46, 44100 Ferrara, Italy
E-mail: m38@unife.it
anion.
[c]
[‡]
The cationic moiety of the molecule was identified by X-
ray analysis of the corresponding single crystal. Compound
4a is 4-(2,4-dimethoxyphenylamino)-1-(4-methylphenyl)-
5-(4-methylphenyldiazenyl)-6-phenylpyridazinium tetra-
Research Institute for Organic Syntheses,
´
Rybitvı 296, 53218 Pardubice 20, Czech Republic
E-mail: antonin.lycka@vuosas.cz
In recognition of his outstanding contributions to physical
organic chemistry
Eur. J. Org. Chem. 2004, 5055Ϫ5063
DOI: 10.1002/ejoc.200400287
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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FULL PAPER
Figure 1. ORTEP plot of compound 4a
Figure 2. 500 MHz proton NMR spectrum of compound 4a in
CDCl3
Scheme 1
Figure 3. 50.7 MHz 15N{1H} NMR spectrum of 4c in CDCl3
fluoroborate (Scheme 1, Figure 1), and its proton NMR signment of individual 15N chemical shifts we prepared the
spectrum is shown in Figure 2.
15N isotopomer 4c with different degrees of enrichment at
A similar pyridazinium salt (compound 4b) was also ob- the nitrogen atoms of the aniline (95% 15N) and the nitrite
tained from the reaction between enaminone 1 and (55.5% 15N). The different degrees of 15N enrichment en-
benzenediazonium tetrafluoroborate. For unambiguous as- able unambiguous differentiation between the nitrogen
5056
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Eur. J. Org. Chem. 2004, 5055Ϫ5063

Formation of Pyridazinium Salts by Azo Coupling
FULL PAPER
1
Table 1. H NMR parameters of the azo-coupled enaminones 3 in CDCl3
3a (X ϭ Me)
3b (X ϭ H)
3d (X ϭ MeO)
H-4
H-6
H-7
H-8
H-10
H-11
H-12
H-15
H-17
H-18
OCH3 (C-14)
OCH3 (C-16)
Other
2.34 s
2.33 s
2.54 s
7.92Ϫ7.94 m
7.42Ϫ7.45 m
7.50Ϫ7.53 m
7.06Ϫ7.10 m
7.06Ϫ7.10 m
7.95Ϫ7.96 m
7.44Ϫ7.47 m
7.52Ϫ7.55 m
7.17Ϫ7.18 m
7.25Ϫ7.28 m
7.01Ϫ7.04 m
6.59, d, J ϭ 2.4 Hz
6.53, dd, J ϭ 2.4, 8.5 Hz
6.89, d, J ϭ 8.5 Hz
3.89, s
7.72Ϫ7.73 m
7.34Ϫ7.37 m
7.40Ϫ7.43 m
7.23Ϫ7.26 m
6.78Ϫ6.81 m
6.58, d, J ϭ 2.5 Hz
6.53, dd, J ϭ 2.6, 8.3 Hz
6.89, d, J ϭ 8.5 Hz
3.88, s
3.84, s
3.84, s
15.80, br. s (NH)
2.28, s (CH3), 15.86, br. s (NH)
3.13, s (NϪCH3), 3.75 s (OCH3),
14.59 br. s (NH)
Table 2. 13C chemical shifts of the azo-coupled enaminones 3 in shifts, and the 1J(15N,15N) coupling constants determine the
nitrogen connectivities. The 15N NMR spectrum of com-
CDCl3
pound 4c measured by direct detection with proton decoup-
ling is presented in Figure 3, and the NMR spectroscopic
3a (X ϭ Me) 3b (X ϭ H) 3d (X ϭ MeO)
data of compounds 3a and 3b and of 4a and 4b are given
in Tables 1Ϫ6.
C-1
C-2
C-3
C-4
C-5
C-6
C-7
C-8
192.99
133.34
165.00
20.79
192.91
133.99
165.10
20.52
193.77
128.48
162.51
16.07
141.56
130.00
129.93
127.01
145.08
121.06
114.01
158.39
The formation of pyridazinium salts from diazonium
salts has been described in the literature.[18Ϫ22] Among sev-
eral variants of such reactions, two alternatives can be con-
sidered in the case of the formation of compound 4a, and
we have not found any direct analogies for them in the lit-
erature:
i) [4ϩ2] cycloaddition between the enol form of com-
pound 3a and the second diazonium ion and subsequent
dehydration (Scheme 2), and
ii) azo coupling of enaminone 1, step by step, with two
diazonium salt molecules to form intermediate Im, followed
by nucleophilic attack by the hydrazone NH group on the
carbonyl of the benzoyl group and splitting off of a water
molecule (Scheme 2).
We do not know which of the given reaction pathways is
taken in the formation of pyridazinium salt 4a, because we
only know its structure and the structures of the starting
139.45
130.44
127.41
131.15
141.75
116.00
129.75
133.68
128.49
152.01
99.29
158.44
103.74
122.27
55.50
55.58
20.45 (CH3)
139.16
130.44
127.48
131.32
143.78
115.84
129.18
123.76
128.73
151.94
99.30
C-9
C-10
C-11
C-12
C-13
C-14
C-15
C-16
C-17
C-18
OCH3 (C-14)
OCH3 (C-16)
Other
158.47
103.75
122.09
55.50
55.60
30.36 (NϪCH3),
55.27 (OCH3)
Table 3. 15N NMR parameters of the azo-coupled enaminones 3 in CDCl3
3a (X ϭ Me)
3b (X ϭ H)
3d (X ϭ MeO)
1
1
1
N1
N2
N3
Ϫ183.6, J(15N,1H) ϭ 82.0 Hz
Ϫ192.3, J(15N, H) ϭ 87.9 Hz
Ϫ18.4
2
not detected
Ϫ9.4, J(15N,1H) ϭ 2.6 Hz
82.8
Ϫ90.1, J(15N, H) ϭ 10.9 Hz
Ϫ82.5
Ϫ232.2, J(15N,1H) ϭ 72.3 Hz
1
1
1
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FULL PAPER
1
Table 4. H NMR parameters of the pyridazinium salts 4
4a (CDCl3) X ϭ Me
4b (CDCl3) X ϭ H
4d ([D6]DMSO) X ϭ MeO
H-3
H-8
H-9
H-10
H-12
H-13
H-14
H-16
H-17
H-18
H-20
H-21
8.86 s
8.91 s
9.40 s
7.44Ϫ7.46 m
7.28Ϫ7.32 m
7.34Ϫ7.39 m
7.28Ϫ7.32 m
7.04Ϫ7.05 m
7.44Ϫ7.50 m
7.28Ϫ7.32 m
7.35Ϫ7.38 m
7.44Ϫ7.50 m
7.29Ϫ7.32 m
7.44Ϫ7.50 m
7.44Ϫ7.50 m
7.38Ϫ7.40 m
7.29Ϫ7.32 m
7.83, d, J ϭ 8.6 Hz
6.64, dd, J ϭ 2.5, 8.7 Hz
6.61, d, J ϭ 2.4 Hz
3.85, s
7.41Ϫ7.52 m
7.41Ϫ7.52 m
7.41Ϫ7.52 m
7.41Ϫ7.52 m
6.97Ϫ7.00 m
7.34Ϫ7.39 m
7.18Ϫ7.19 m
7.72Ϫ7.76 m
7.11Ϫ7.14 m
7.76, d, J ϭ 8.6 Hz
6.58, dd, J ϭ 2.5, 8.7 Hz
6.61, d, J ϭ 2.5 Hz
3.84, s
H-23
OCH3 (22)
OCH3 (24)
other
3.92, s
3.94, s
12.87, s, NH
2.37, s, CH3 (18)
2.26, s, CH3 (14)
12.84, s, NH
3.50, d, J ϭ 5.3 Hz, NCH3
10.94, q, J ϭ 5.5 Hz, NH
3.78, s, OCH3 (14)
3.88, s, OCH3 (18)
Table 5. 13C chemical shifts of the pyridazinium salts 4
4a (CDCl3) X ϭ Me
4b (CDCl3) X ϭ H
4d ([D6]DMSO) X ϭ MeO
C-3
C-4
C-5
C-6
C-7
C-8
C-9
141.41
128.87
139.20
158.14
128.89
130.77
127.61
126.35
140.41
130.00
129.50
139.71
149.67
123.27
130.06
144.15
115.85
126.39
105.19
161.09
99.49
141.74
128.92
139.45
158.64
128.79
130.89
127.69
126.73
142.80
129.56
129.01
130.16
151.51
123.30
129.37
132.86
115.91
126.81
105.23
161.29
99.72
141.24
128.78
140.85
156.47
129.59
130.57
127.67
130.01
135.90
128.16
114.15
159.64
146.20
125.31
114.97
163.45
C-10
C-11
C-12
C-13
C-14
C-15
C-16
C-17
C-18
C-19
C-20
C-21
C-22
C-23
C-24
OCH3 (22)
OCH3 (24)
other
153.86
55.69
56.00
21.02 CH3 (14)
21.57 CH3 (18)
153.94
55.73
56.04
30.74 N-CH3
55.61 OCH3 (14)
55.97 OCH3 (18)
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Eur. J. Org. Chem. 2004, 5055Ϫ5063

Formation of Pyridazinium Salts by Azo Coupling
FULL PAPER
Table 6. 15N, 11B and 19F NMR parameters of the pyridazinium salts 4
4a (CDCl3) X ϭ Me
4b (CDCl3) X ϭ H
4d ([D6]DMSO) X ϭ MeO
1
N-1
N-2
N-3
N-4
N-5
11B
Ϫ162.5
Ϫ33.1
not detected
106.5
Ϫ265.6
Ϫ162.8 J(15N, 15N) ϭ 14.4 Hz[a]
Ϫ165.9
Ϫ33.3
not detected
110.6
Ϫ274.9
Ϫ33.3 J(15N, 15N) ϭ 14.4 Hz[a]
1
113.4 J(15N, 15N) ϭ 15.5 Hz[a]
1
108.0 J(15N, 15N) ϭ 15.2 Hz[a]
1
Ϫ265.0
Ϫ2.19
Ϫ2.20
Ϫ1.80
19F
Ϫ153.82[b]
Ϫ153.76[c]
Ϫ153.74[b]
Ϫ153.69[c]
Ϫ148.83[b]
Ϫ148.78[c]
[a]
[b]
[c]
Obtained by measuring of 15N isotopomer 4c. Fluorine atom bound to 11B isotope. Fluorine atom bound to 10B isotope.
Scheme 2
compounds.
4-Dimethylamino-5-(phenyldiazenyl)pent-4- 4-methoxy- or 4-nitrobenzenediazonium tetrafluoroborates
ene-2,3-dione 3-phenylhydrazone, which is formed in the re- failed, only the singly coupled products analogous to 3a
action between 4-(dimethylamino)pent-3-en-2-one and two being obtained in these cases.
molecules of benzenediazonium salt, does not undergo
Products (3d and 4d) analogous to those obtained in the
case of the reaction of enaminone 1 were also isolated from
ring closure.[12]
In order to confirm that enaminone 1 can undergo [4ϩ2] azo coupling between 3-methylamino-1-phenylbut-2-en-1-
cycloaddition, we carried out the reaction in the presence one (2) and 4-methoxybenzenediazonium tetrafluoroborate
of the very reactive dienophile dimethyl butynedioate in (Scheme 1). Compound 3d exists in CDCl3 solution pre-
acetonitrile. The cycloaddition could give a derivative of di- dominantly as 2-(4-methoxyphenyldiazenyl)-3-methylam-
methyl phthalate 5-I or a derivative of 1,4-dihydropyran 5- ino-1-phenylbut-2-en-1-one. NMR parameters are given in
II (Scheme 3). However, we found that the [4ϩ2] cycload- Tables 1Ϫ6, and an ORTEP plot of compound 4d is de-
dition did not take place: only the addition of enaminone picted in Figure 4.
1 to the triple bond of butynedioate to form compound
5 occurred.
Pyridazinium salts were only formed in cases in which
With equimolar ratio of enaminones and the correspond-
ing diazonium salts, only compounds 3 were formed.
When the ratio of enaminones and diazonium salts was
enaminone 1 reacted with benzenediazonium tetrafluoro- 1:2, both compounds 3 and 4 were formed. An increase in
borate or 4-methylbenzenediazonium tetrafluoroborate. At- this ratio (1:3 and higher), however, did not result in any
tempts to obtain similar compounds from reactions with increase in the pyridazinium content in the reaction prod-
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Experimental Section
General Remarks: The NMR spectra were measured with a Bruker
AVANCE 500 spectrometer fitted with a 5-mm broad-band probe
with a magnetic field gradient in the direction of the z axis at fre-
quencies of 500.13 MHz (1 H), 125.77 MHz (13C), 50.69 MHz (15N)
and 470.56 MHz (19F), and with a Bruker AMX 360 spectrometer
at a frequency of 115.55 MHz (11B). The 1H NMR spectra were
calibrated in CDCl3 on hexamethyldisiloxane (δ ϭ 0.05 ppm) and
in [D6]DMSO on the central signal of the solvent multiplet (δ ϭ
2.55 ppm). The 13C NMR spectra were calibrated on the central
signal of the solvent multiplet (δ ϭ 39.6 ppm for [D6]DMSO and
δ ϭ 76.9 ppm for CDCl3). The 15N NMR spectra were calibrated
on external neat 15N nitromethane placed in a coaxial capillary
(δ ϭ 0.0 ppm). The 11B NMR spectra were calibrated on external
B(OCH3)3 placed in a coaxial capillary (δ ϭ 18.1 ppm). In order
to suppress the signals of 11B nuclei from glass, the measurements
were carried out in Teflon sample tube liners (Aldrich) inserted
into 5 mm tubes in which the bottom part (about 25 mm length)
had been cut off. The 19F NMR spectra were calibrated on internal
CFCl3 (δ ϭ 0.0 ppm, central signal of multiplet of the standard)
and were measured with use of a 5 mm 1H/19F dual probehead
with proton noise decoupling. The individual proton signals were
assigned by H,H-COSY spectra. The 13C signals were assigned on
the basis of APT, 1HϪ13C HMQC, 1HϪ13C HSQC and 1HϪ13C
HMBC spectra. The δ(15N) values were measured with the aid of
inversion detection techniques (1HϪ15N HMBC) and, in the case
of the 15N-labelled compounds, also by direct detection. The crystal
data for compounds 4a and 4d were collected at room temperature
on a Nonius Kappa CCD diffractometer with graphite-monochro-
mated Mo-Kα radiation and corrected for Lorentz polarization ef-
fects. The structures were solved by direct methods (SIR99[28]) and
refined by full-matrix, least-squares. All non-hydrogen atoms were
refined anisotropically and hydrogens included on calculated posi-
tions, riding on their carrier atoms, except for the N3ϪH and
C3ϪH3 hydrogen atoms, which were refined isotropically. All the
calculations were performed with SHELXL-97[29] and PARST[30]
implemented in the WINGX[31] system of programs. The 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. Dichloromethane was pre-
dried by standing over anhydrous calcium chloride and subsequent
distillation with phosphorus pentoxide. The anhydrous sodium
acetate was fused on a porcelain dish and left to cool in a dessicc-
ator. The diazonium tetrafluoroborates used were prepared by pro-
cedures described elsewhere.[10]
Scheme 3
3-(2,4-Dimethoxyphenylamino)-1-phenylbut-2-en-1-one (1): A 100
ml three-necked flask fitted with a DeanϪStark extension was
charged with toluene (30 mL), benzoylacetone (12.15 g, 75 mmol),
2,4-dimethoxyaniline ( 11.50 g, 75 mmol) and p-methylbenzenesul-
fonic acid (0.1 g). The mixture was heated at reflux for 3 h, and the
toluene distilling off was continuously replaced with fresh toluene.
Finally, the solvent was distilled off at reduced pressure. The distil-
lation residue solidified on cooling and gave a dark substance. After
recrystallisation from toluene, the yield was 16.74 g (75%) brown
green crystals melting at 105Ϫ107 °C. C18H19NO3 (297.35): calcd.
C 72.71, H 6.44, N 4.71; found C 72.93, H 6.48 and N 4.86. 1H
NMR (360 MHz, CDCl3): δ ϭ 2.00 [s, 3 H, COCH3], 3.76 [s, 3 H,
OCH3], 3.79 [s, 3 H, OCH3], 5.84 [s, 1 H, CHϭ], 6.42 [dd, 3JH,H ϭ
Figure 4. ORTEP plot of compound 4d
ucts, only increases in the decomposition products being de-
tected.
Only very small amounts of compounds 4 (besides some
diazonium salt decomposition products) were detected
when the appropriate diazonium salt was added to com-
pound 3 under the same reaction conditions as used in the
case of the reaction between compound 1 and the same
diazonium salt (see Exp. Sect.).
4
4
8.6, JH,H ϭ 2.6 Hz, 1 H], 6.48 [d, JH,H ϭ 2.6 Hz, 1 H], 7.03 [d,
3JH,H ϭ 8.6 Hz, 1 H], 7.35Ϫ7.41 [m, 3 H], 7.89Ϫ7.91 [m, 2 H],
12.65 [br. s, 1 H, NH] ppm. 13C NMR (90.56 MHz, CDCl3): δ ϭ
20.03 [CH3], 55.36, 55.61 [2 ϫ OCH3], 93.46, 99.11, 103.75 [3 ϫ
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Formation of Pyridazinium Salts by Azo Coupling
CH], 120.66 [Cq], 126.72, 126.94, 128.04, 130.48 [4 ϫ CH], 140.20, Recrystallisation from ethanol. Yield 0.26 g (17%). M.p. 255Ϫ265
FULL PAPER
154.47, 158.91, 163.61 [4 ϫ Cq], 188.07 [CϭO] ppm.
°C. C32H30BF4N5O2 (603.42): calcd. C 63.69, H 5.01, N 11.61;
found C 63.71, H 4.91, N 11.53.
3-Methylamino-1-phenylbut-2-en-1-one (2): This compound was
prepared by the procedure described in ref.[32]
4-(2,4-Dimethoxyphenylamino)-1-phenyl-5-phenyldiazenyl-6-phenyl-
pyridazinium Tetrafluoroborate (4b): Recrystallisation from ethanol.
Yield 0.25 g (17%). M.p. 260Ϫ265 °C. C30H26BF4N5O2 (575.37):
calcd. C 62.63, H 4.55, N 12.17; found C 62.75, H 4.39, N 12.04.
General Procedure Used for Azo Coupling Reactions: The enamin-
one (2.5 mmol) was dissolved in dichloromethane (20 mL) in a
100 ml Erlenmeyer flask. The reaction mixture was treated with
anhydrous sodium acetate (1.23 g, 15 mmol) with stirring, after
which the appropriate benzenediazonium tetrafluoroborate
(5 mmol) was added. The mixture was stirred at room temperature
for 72 h, and the solid was then removed by suction and washed
with a little dichloromethane. The combined dichloromethane fil-
trates were evaporated to dryness. The evaporation residue was
dried in vacuo, mixed with ethyl acetate and again filtered under
suction. The solution in ethyl acetate was placed on a silica gel
column and subjected to chromatography (silica gel/ethyl acetate).
The portion insoluble in ethyl acetate was recrystallised from etha-
nol to give the corresponding pyridazinium salt. In this way the
following compounds were prepared.
4-(2,4-Dimethoxyphenylamino)-1-phenyl-5-[15Nα,15Nβ]phenyl-
diazenyl-6-phenylpyridazinium Tetrafluoroborate (4c): The com-
pound was prepared in the same way as the unlabelled isotopomer.
Recrystallisation from ethanol. Yield 0.21 g (14%). M.p. 257Ϫ267
°C.
1-(4-Methoxyphenyl)-5-(4-methoxyphenyldiazenyl)-4-methylamino-
6-phenylpyridazinium Tetrafluoroborate (4d): Recrystallisation from
ethanol. Yield 0.28 g (22%). M.p. 211Ϫ214 °C. C25H24BF4N5O2
(513.29): calcd. C 58.50, H 4.71, N 13.64; found C 58.50, H 4.88,
N 13.81.
Methyl
4-Benzoyl-5-(2,4-dimethoxyphenylamino)-3-methoxycar-
bonylpenta-2,4-dienoate (5): A 100-ml three-necked flask was
charged with enaminone 1 (1.49 g, 5 mmol) and dry acetonitrile
(30 mL). The reaction was carried out under argon. A solution of
dimethyl butynedioate (0.71 g, 5 mmol) in dry acetonitrile (10 mL)
was added from a dropping funnel with stirring. The mixture was
further stirred at room temperature for 120 h. The solvent was then
evaporated in vacuo, and the residue was subjected to column chro-
matography (silica gel, CH2Cl2/EtAc, 5:1) to give an orange oil
(1.35 g, 61%), which gradually solidified. After recrystallisation
from ethanol, m.p. 137Ϫ139 °C. C24H25NO7 (439.46): calcd. C
65.59, H 5.73, N 3.19; found C 65.35, H 5.98, N 3.13. 1H NMR
(500.13 MHz, CDCl3): δ ϭ 1.84 [s, 3 H], 3.61 [s, 3 H], 3.70 [s, 3 H],
3-(2,4-Dimethoxyphenylimino)-1-phenylbutane-1,2-dione 2-(4-Meth-
ylphenyl)hydrazone (3a): Recrystallisation from cyclohexane. Yield
0.82 g (79%). M.p. 120Ϫ122 °C. C25H25N3O3 (415.49): calcd. C
72.27, H 6.06, N 10.11; found C 72.19, H 6.28, N 10.26.
3-(2,4-Dimethoxyphenylimino)-1-phenylbutane-1,2-dione 2-Phenyl-
hydrazone (3b): Recrystallisation from n-hexane. Yield 0.8 g (80%).
M.p. 112Ϫ115 °C. C24H23N3O3 (401.46): calcd. C 71.80, H 5.77, N
10.47; found C 71.84, H 5.96, N 10.42.
2-(4-Methoxyphenyldiazenyl)-3-methylamino-1-phenylbut-2-en-1-
one (3d): Recrystallisation from cyclohexane. Yield 0.15 g (19%).
M.p. 109Ϫ110.5 °C. C18H19N3O2 (309.36): calcd. C 69.88, H 6.19,
N 13.58; found C 69.96, H 6.49, N 13.58.
4
3
3.79 [s, 3 H], 3.85 [s, 3 H], 6.46 [dd, JH,H ϭ 2.5, JH,H ϭ 8.5 Hz,
4
3
1 H], 6.51 [d, JH,H ϭ 2.5 Hz, 1 H], 6.69 [s, 1 H], 7.09 [d, JH,H
ϭ
4-(2,4-Dimethoxyphenylamino)-1-(4-methylphenyl)-5-(4-methyl-
8.5 Hz, 1 H], 7.22Ϫ7.29 [m, 3 H], 7.35Ϫ7.37 [m, 2 H], 13.51 [s, 1
phenyldiazenyl)-6-phenylpyridazinium
Tetrafluoroborate
(4a):
H] ppm. 13C NMR (125 MHz, CDCl3): δ ϭ 17.75 [CH3], 51.51,
Table 7. Crystal data of compounds 4a and 4d
Compound
4a
4d
Empirical formula
M
System
(C32H30N5O2)ϩ·(BF4)Ϫ
603.42
monoclinic
P21/c
10.7035(2)
19.9731(4)
15.5525(3)
90
109.728(1)
90
3129.7(1)
4
1.281
295
0.97
(C25H24N5O2)ϩ·(BF4)Ϫ·1/2(CH3OH)
529.33
triclinic
¯
Space group
P1
˚
a (A)
10.0433(2)
10.5873(2)
12.5838(2)
80.512(1)
84.640(1)
88.804(1)
1314.0(1)
2
˚
b (A)
˚
c (A)
α (°)
β (°)
γ (°)
3
˚
U (A )
Z
Dcalcd. (g cmϪ3
T (K)
)
1.338
295
1.07
µ (cmϪ1
)
θ
min.Ϫθmax, (°)
2.5Ϫ27.0
6822
2.8Ϫ27.0
5714
Unique reflns.
Rint
0.030
3831
0.0562
0.1721
1.00
0.18;Ϫ0.24
0.018
4161
0.0572
0.1889
1.04
Obsd. reflns. [I Ͼ 2σ(I)]
R (obsd. reflns.)
wR (all reflns.)
S
Ϫ3
˚
∆ρmax.; ∆ρmin./e·A
0.39;Ϫ0.33
Eur. J. Org. Chem. 2004, 5055Ϫ5063
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5061

ˇ
˚
´
´
ˇ
ˇ
ˇ
P. S imunek, M. Peskova, V. Bertolasi, A. Lycka, V. Machacek
FULL PAPER
˚
52.38, 55.30, 55.58 [4 ϫ OCH3], 99.19 [CH], 102.11 [Cq], 103.92
[CH], 120.28 [Cq], 127.04, 127.15, 127.28, 128.83, 128.85 [5 ϫ CH],
142.20, 143.93, 154.60, 159.16, 163.92, 165.51, 168.02 [7 ϫ Cq],
191.64 [CϭO] ppm.
Table 9. Hydrogen bond parameters (A and degrees) of compound
4a and 4d
Compound 4a
Ϫ
X-ray Crystallographic Study: The BF4 anion in compound 4a
DϪH···A
DϪH H···A D···A
DϪH···A
was found to be disordered and the four fluorine atoms were re-
fined with two independent orientations with multiplicities of 0.6
and 0.4, respectively. In compound 4d the C7(H)C8(H)O1C11(H3)
moiety of the 4-methoxyphenyl substituent was found to be dis-
ordered, and the atoms were refined with two independent orien-
N3ϪH···N1
Compound 4d
DϪH···A
0.85(2) 1.98(2) 2.649(2) 135(2)
DϪH H···A D···A
0.83(2) 2.11(2) 2.701(2) 128(2)
DϪH···A
N3ϪH···N1
N3ϪH···F1(Ϫx, Ϫy, 1 Ϫ z) 0.83(2) 2.41(3) 3.023(3) 131(2)
Ϫ
tations with multiplicities of 0.55 and 0.45, respectively. The BF4
anion contains two disordered fluorine atoms, F3 and F4, which
were refined with two independent orientations with multiplicities
of 0.5. This crystal also includes molecules of methanol disordered
around centres of symmetry. The crystal data and refinement par-
ameters are summarized in Table 7, selected interatomic distances
and angles are given in Table 8, and hydrogen bond parameters are
listed in Table 9. ORTEP[23] views of compounds 4a and 4d are
shown in Figure 1 and 4, respectively. In both structures the pyrid-
azinium rings are essentially planar, with maximum deviations from
the least-squares planes defined by the ring atoms of 0.024(2) and
linked to the nitrogen N1 of a diazenyl moiety through a π-conju-
gated heterodienic group HN3ϪC2ϭC1ϪN2ϭN1.[11] In spite of
the very similar π-conjugation, the N1···N3 distances have signifi-
˚
cant different values of 2.649(2) and 2.701(2) A in 4a and 4d,
respectively. The lengthening and weakening of the hydrogen bond
in compound 2 can be ascribed to the formation of a second bifur-
cated N3ϪH···F1 hydrogen bond between the enaminic group and
a fluorine of the BF4 anion.[28] Furthermore, the BF4 anions in
both crystals are implicated in short interactions, with distances
less than sums of the van der Waals radii, towards atoms in the
pyridazinium rings, as shown in Table 8.
Ϫ
Ϫ
˚
0.019(2) A for 4a and 4d, respectively. Both rings display extended
˚
conjugations, and the C4ϪN4 [1.342(1) in 4a and 1.350(2) A in 4d]
˚
and N4ϪN5 [1.362(2) in 4a and 1.357(2) A in 4d] bond lengths
CCDC-229729 and -229730 contain the supplementary crystallo-
graphic 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, Cam-
bridge CB2 1EZ, UK; Fax: (internat.) ϩ44-1223-336-033; E-mail:
deposit@ccdc.cam.ac.uk].
support pyridazinum structures with positive charge mainly located
on nitrogen N4, consistently with other similar structures.[24Ϫ27]
˚
Table 8. Selected bond lengths (A), angles (°) and short contact
˚
distances (A) of compounds 4a and 4d
4a
4d
Acknowledgments
Authors are greatly indebted for financial support to the Grant
Agency of the Czech Republic (Grant No. 203/03/0356) and to the
University of Pardubice (Grant IG 340022/21).
N1ϪN2
N1ϪC5
N2ϪC1
C1ϪC2
N3ϪC2
C1ϪC4
N4ϪC4
N4ϪN5
1.262(2)
1.420(2)
1.399(2)
1.417(3)
1.335(3)
1.393(3)
1.342(2)
1.362(2)
1.297(3)
1.416(3)
1.259(2)
1.420(2)
1.403(2)
1.426(2)
1.315(2)
1.391(2)
1.350(2)
1.357(2)
1.290(3)
1.430(3)
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N1ϪN2ϪC1
N2ϪC1ϪC2
N2ϪC1ϪC4
C2ϪC1ϪC4
N3ϪC2ϪC1
C1ϪC2ϪC3
N3ϪC2ϪC3
N5ϪC3ϪC2
N4ϪC4ϪC1
N5ϪN4ϪC4
N4ϪN5ϪC3
C1···F3
114.4(2)
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126.8(2)
114.2(2)
118.5(2)
122.1(2)
115.5(2)
122.4(2)
125.5(2)
119.8(2)
123.6(2)
117.0(2)
115.9(1)
126.7(1)
114.5(1)
118.8(1)
124.8(2)
114.8(2)
120.4(2)
125.5(2)
119.9(2)
123.2(1)
117.7(2)
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C4···F3
3.107(10)
2.988(8)
3.071(8)
3.060(6)
N4···F1(x,1/2 Ϫ y,z Ϫ 1/2)
C4···F1(x,1/2 Ϫ y,z Ϫ 1/2)
C2···F1
[7]
S. Thaisrivongs, K. D. Watenpaugh, W. Jeffrey Howe, P. K.
2.982(2)
2.987(3)
Tomich, L. A. Dolak, K.-T. Chong, Ch.-Sh. C. Tomich, A. G.
Tomasselli, S. R. Turner, J. W. Strohbach, A. M. Mulichak, M.
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ˇ
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Each compound forms a short intramolecular NϪH···N hydrogen
bond assisted by resonance in which the enaminic N3ϪH group is
´ˇ
´
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5062
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 5055Ϫ5063

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Received April 27, 2004
Eur. J. Org. Chem. 2004, 5055Ϫ5063
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 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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