Multinuclear magnetic resonance study of the structure and tautomerism of azide and iminophosphorane derivatives of chloropyridazines

Article abstract of DOI:10.1002/mrc.1055

Some azido- and iminophosphorane derivatives of 3,6-dichloro- and 3,4,5,6-tetrachloropyridazine were synthesized and studied by means of NMR measurements. Based on multinuclear data (chemical shifts, coupling constants) for compounds containing the azide group, no potentially possible tetrazole-azide equilibrium can be observed, even under acidic conditions. An unusual substitution of a chlorine atom (in position 4) of tetrachloropyridazine in the reaction with hydrazine was demonstrated by NMR measurements of two newly synthesized compounds containing azido- and iminophosphorane groups. Using multinuclear magnetic resonance data, the sites of ethylation and protonation of azido- and iminophosphorane derivatives of chloropyridazines were established. In the case of the tetrazolopyridazines, ethylation occurs at the N1′ and N2′ atoms, whereas for monocyclic compounds it takes place at the N1 and/or N2 atoms of the pyridazine ring. Preferred sites of protonation are the N1′ atom of the tetrazole ring and the N1 atom of the pyridazine ring. Moreover, the structures of potassium salts of 6-(3-cyano-1-triazeno)tetrazolo[1,5-b] pyridazine and its amido derivative were established using NMR data, especially ¹⁵N NMR chemical shifts. Copyright

Full text of DOI:10.1002/mrc.1055

MAGNETIC RESONANCE IN CHEMISTRY
Magn. Reson. Chem. 2002; 40: 507–516
Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/mrc.1055
Multinuclear magnetic resonance study of the structure
and tautomerism of azide and iminophosphorane
derivatives of chloropyridazines
Piotr Cmoch∗
Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, P.O. Box 58, 01-224 Warsaw, Poland
Received 15 January 2002; Revised 25 April 2002; Accepted 27 April 2002
Some azido- and iminophosphorane derivatives of 3,6-dichloro- and 3,4,5,6-tetrachloropyridazine were
synthesized and studied by means of NMR measurements. Based on multinuclear data (chemical shifts,
coupling constants) for compounds containing the azide group, no potentially possible tetrazole–azide
equilibrium can be observed, even under acidic conditions. An unusual substitution of a chlorine
atom (in position 4) of tetrachloropyridazine in the reaction with hydrazine was demonstrated by
NMR measurements of two newly synthesized compounds containing azido- and iminophosphorane
groups. Using multinuclear magnetic resonance data, the sites of ethylation and protonation of
azido- and iminophosphorane derivatives of chloropyridazines were established. In the case of the
tetrazolopyridazines, ethylation occurs at the N1ꢀ and N2ꢀ atoms, whereas for monocyclic compounds it
takes place at the N1 and/or N2 atoms of the pyridazine ring. Preferred sites of protonation are the N1ꢀ
atom of the tetrazole ring and the N1 atom of the pyridazine ring. Moreover, the structures of potassium
salts of 6-(3-cyano-1-triazeno)tetrazolo[1,5-b] pyridazine and its amido derivative were established using
NMR data, especially 15N NMR chemical shifts. Copyright  2002 John Wiley & Sons, Ltd.
KEYWORDS: NMR; 1H NMR; 13C NMR; 15N NMR; 31P NMR; 13C,13C, 31P,1H, 31P,13C, 31P,15N coupling; tetrazoles; azides;
ethylation; N-pyridazinium salts
therefore, derivatives 11–13 (see Fig. 3) were synthesized
and studied by NMR spectroscopy in order to determine
their structures.
INTRODUCTION
Derivatives of 3,6-dichloropyridazine (1) play an important
role in chemical synthesis, pharmacology and agroche-
mistry.1 It is known, for instance, that 3-azidopyridazine
derivatives, existing mainly as tetrazolo[1,5-b]pyridazines,
have a high cytostatic activity in KB and HeLa human cancer
cells2 and also sedative effects and anticonvulsant activity.3
All 3-azidopyridazine derivatives may exhibit tetra-
zole–azide tautomerism, but this equilibrium depends
strongly on the nature and the position of substituents,
and on temperature and polarity of the solvent. In contin-
uation of our studies of such tautomerism, compounds 3
and 5, which potentially might exist in a tetrazole–azide
equilibrium, were synthesized. Both of them reacted with
triphenylphosphine yielding 4 and 8, respectively, but only
8 containing the azide group may exhibit tetrazole–azide
equilibrium (see Fig. 1).
Our previous results8–10 demonstrate that the tetra-
zole–azide equilibrium can also be observed under acidic
conditions. Usually, the presence of strong acids increases
the relative concentration of the azide form. In order to ver-
1
ify this rule for compounds 3, 5 and 8, the H, 13C, 15N and
31P NMR spectra in trifluoroacetic acid (TFA) solution were
measured.
For compounds 1, 3–5, 8, 12 and 13, containing at least
three nitrogen atoms, protonation and ethylation studies
were undertaken, using excess of TFA and triethyloxonium
tetrafluoroborate (see Fig. 4), respectively. Protonation and
ethylation sites of 1, 3–5, 12 and 13 were recognized by the
observation of changes in the NMR parameters before and
after the reactions.
Additionally, on the basis of NMR data, mainly 15N NMR
chemical shifts, the structures of two previously synthesized
compounds, 6 and 7,4 have also been described (Fig. 1).
In contrast to 1 and its derivatives, little is known about
the reactivity of 3,4,5,6-tetrachloropyridazine (10)5–7 and,
RESULTS AND DISCUSSION
The 1H, 13C, 15N and 31P NMR data (chemical shifts
and coupling constants) for compounds 1–13 (in acetone,
chloroform or TFA solutions) are given in Tables 1, 2 and 4,
and Table 3 contains multinuclear magnetic resonance data
(in acetone) for the N-ethylated compounds 14–27.
The 1H, 13C and 15N NMR signals for all of the
compounds studied were assigned by the use of the results
ŁCorrespondence to: Piotr Cmoch, Institute of Organic Chemistry,
Polish Academy of Sciences, Kasprzaka 44/52, P.O. Box 58, 01-224
Warsaw, Poland. E-mail: piocmo@icho.edu.pl
Copyright  2002 John Wiley & Sons, Ltd.

508
P. Cmoch
Table 1. 1H, 13C and 15N NMR chemical shifts of compounds 1, 2 and 9–11 at 298 K
1
1
2
9a
10
10
11
(acetone)
(TFA)
(DMSO)
(DMSO)
(acetone)
(TFA)
(DMSO)
H4
H5
NH
NH2
C3
C4
C5
C6
N10
N20
N1
N2
7.90
7.90
—
8.00
8.00
—
7.12
7.54
9.45
8.20
7.15
8.91
—
—
—
—
—
—
—
—
8.33
—
—
4.20
4.50
—
—
4.79
156.9
132.0
132.0
156.9
—
156.2
135.8
135.8
156.2
—
159.7
117.2
129.9
147.5
ꢀ282.0
ꢀ330.8
ꢀ10.0
ꢀ52.0
140.3
122.8
119.0
157.9
155.3
138.3
138.3
155.3
—
154.6
140.0
140.0
154.6
—
142.9
141.1
113.5
154.0
ꢀ277.9b
ꢀ329.9b
ꢀ43.3b
ꢀ9.6b
b
—
—
b
—
—
—
—
C9.7
C9.7
ꢀ53.4
ꢀ53.4
ꢀ144.5
ꢀ106.8
C4.5
C4.5
ꢀ33.3
ꢀ33.3
a 15N chemical shifts in DMSO: NH, ꢀ321.2 ppm; NH2, ꢀ276.5 ppm; N30, not observed in 1H–15N gradient
selected HMBC experiment.
b Not observed in 1H–15N gradient selected HMBC experiment.
of 1H–13C and 1H–15N gradient selected HMBC and, 1H–13
C
the tetrazole form (at C16.3, ꢀ25.1 and ꢀ63.2 ppm in CDCl3
solution; Table 2)8–10 provides unambiguous evidence that 3
exists as the bicyclic form 3T, exclusively. This means that the
structure 3A suggested by Shin et al.1 does not exist; in fact,
the NMR data presented in Ref. 1 for 3A are characteristic
for 5TA.
gradient selected HSQC correlation experiments (for NMR
nomenclature of experiments, see Experimental), and the
values of 1J(13C,13C), nJ(31P,1H), nJ(31P,13C) and nJ(31P,15N)
couplings. In order to assign the NMR signals of compounds
6 and 7, selectively labeled molecules 6* and 7* (Fig. 2) were
prepared and measured in addition to the methods described
above. In the case of compound 12 and its N-ethylated salts
24 and 25, the 13C and 15N NMR signal assignment was made
using differences in chemical shifts between 1 and its N-ethyl
salt 20 = 21.
There are two main routes for the synthesis of azide
derivatives of pyridazine described in the literature.11 In
Figs 1–3, the reaction schemes leading to different deriva-
tives of 3,6-dichloro- (1) and 3,4,5,6-tetrachloropyridazine
(10) are presented.
Reaction of 3T with triphenylphosphine in chloroben-
5
°
zene at 110 C yields (6-chloropyridazin-3-yl)(triphenyl-ꢀ -
phosphanylidene)amine (4).14 Introduction of phosphorus
1
as an NPPh3 group, causes additional splittings of the H,
13C and 15N NMR signals associated with scalar spin–spin
interactions J(31P,X) (where X D H, 13C and 15N). With their
1
presence, NMR signal assignments and the determination
of the structures of the compounds studied are much eas-
ier. The most characteristic values are 1J(31P,15N) ³40 Hz,
3J(31P,15N) ³7 Hz, J(31P,13C) ³25 Hz and J(31P,13C) ³7 Hz
3
2
(Table 2).
The second route leading to azide derivatives of azines
is based on substitution of the halogen atom, located at
the ortho position to the ring nitrogen atom, by the azide
group. Reaction of 1 with excess of sodium azide leads to
5, in which two azide groups replace both chlorine atoms.
Analysis of the 1H, 13C and, especially, 15N NMR spectra
of 5 reveals only one unsymmetrical form. The presence
of eight signals in the 15N NMR spectrum of 5 taken in
acetone solution (Table 2), in a typical range for both azide
and tetrazole forms,8–10 excludes the existence of both 5AA
and 5TT and indicates the presence of 6-azidotetrazolo [1,5-
b]pyridazine 5TA. This conclusion is in agreement with
x-ray results obtained by Katrusiak et al.15 Moreover, the
13C NMR signal assignment of 5TA made by Krivopalov
et al.16 is now corrected (Table 2), using results of 1J(13C, 13C)
measurements.
Derivatives of 3,6-dichloropyridazine (1)
The pyridazine 1, similarly to 2,6-dichloropyridine, reacts
with hydrazine hydrate yielding monohydrazine 2.9,12 Treat-
ment of 2 with sodium nitrite in acidic solution leads to
derivative 3, which may exhibit tetrazole–azide tautomerism
(the numbering of the tetrazolo[1,5-b]pyridazines does not
correspond to the IUPAC system and is in accordance with
pyridazine ring). On the basis of 1H and 13C NMR spectra of
the product of reaction of 1 with sodium azide, Shin et al.1
suggested the presence of 3-azido-6-chloropyridazine (3A)
in chloroform solution. The NMR data obtained previously13
supplemented by the current results (Table 2) confirm the
1
presence of only one set of H, 13C and 15N NMR signals.
This observation excludes the presence of a tetrazole–azide
equilibrium, which is slow on NMR time-scale.9 In our previ-
ous paper9 we demonstrated in several cases the existence of
two sets of appropriate NMR signals for both forms typical
for azide and tetrazole. If only one set of signals is observed
in the NMR spectra, it means that only one tautomeric form,
azide (A) or tetrazole (T), exists in solution. The presence of
only one set of 15N NMR signals of 3 in the range typical for
6-Azidotetrazolo[1,5-b]pyridazine (5TA) reacts with
potassium cyanide yielding the potassium salt of 6-(3-cyano-
1-triazeno)tetrazolo[1,5-b]pyridazine (6) (Fig. 1). The reaction
°
of 6 with hydrochloric acid in acetone at 60 C leads to 6-(3-
carbamoylo-1-triazeno)tetrazolo [1,5-b]pyridazine (7), which
Copyright  2002 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2002; 40: 507–516

Structure and tautomerism of chloropyridazine derivatives 509
Table 2. 1H, 13C, 15N and 31P NMR chemical shifts of compounds 3–8, 12 and 13 at 298 K
3
4a,b
5c
6d
7e
8a,f
12
13a,g
(acetone)
(CDCl3)
(acetone)
(DMSO)
(DMSO)
(CDCl3)
(CDCl3)
(CDCl3)
H4
8.76 (9.5)
7.04h
8.62 (9.5)
7.86
8.54
7.83 (9.5)
[2.5]
—
—
H5
C3
7.95 (9.5)
7.04h
7.43 (9.5)
8.41
8.81
7.26 (9.5)
—
—
143.5
(70.5)i
163.9
[6.4]
143.1
(69.8)i
142.5
143.0
140.0
(69.8)i
148.6
(69.5)i
153.8
[11.7]
C4
C5
C6
N10
127.8
125.6
[24.9]
127.7
120.4
124.2
163.1
ꢀ65.2
119.4
125.9
160.3
ꢀ65.6
121.6 [4.0]
137.3
146.1
[3.1]
(60.3, 70.5)i
(61.7, 69.8)i
(69.8, 61.2)i
(69.5,71.4)i
128.6
(60.3, 61.4)i
128.3
121.8
(61.7, 64.3)i
128.4 [24.9]
(61.2, 60.1)i
128.5
(71.3,71.4)i
126.7
[9.8]
152.3
(61.4)i
145.8
155.8
(64.3)i
160.5 [6.8]
(60.1)i
154.6
(71.4)i
153.7
l
ꢀ63.2
ꢀ290.9
ꢀ63.5
ꢀ68.6
ꢀ287.8j
—
[40.2]
N20
N30
N1
N2
C16.3j
ꢀ25.1j
ꢀ80.8
ꢀ102.2
—
—
C12.3j
ꢀ27.0j
ꢀ108.8
ꢀ106.2
C10.0
ꢀ26.4
ꢀ103.0
ꢀ103.8
C13.6
ꢀ26.1
ꢀ103.7
ꢀ88.5
C3.8j
ꢀ28.6j
ꢀ121.4 [6.9]
ꢀ103.9
ꢀ150.2j
ꢀ141.1j
ꢀ7.3h,k
C0.8h,k
—
—
ꢀ9.4
ꢀ39.2j,k
ꢀ13.3j,k
ꢀ25.9
[6.1]
n
N100
N200
N300
C10
—
—
—
—
—
—
—
ꢀ276.8
ꢀ146.0
ꢀ140.3j,m
—
ꢀ29.5
C159.7
ꢀ108.3m
—
ꢀ284.0[38.8]
—
—
—
—
—
—
—
C86.9
ꢀ177.7m
—
—
—
128.7
127.0
130.6
[100.0]
[101.0]
[106.8]
C20/C60
C30/C50
C40
—
—
—
—
128.4
[12.3]
—
—
—
—
—
—
—
—
—
—
—
—
128.7
[12.5]
—
—
—
—
128.8
[12.8]
133.0
[9.8]
133.0
[10.1]
132.4
[10.6]
131.8
[2.9]
132.4
[2.9]
132.4
[2.9]
P
C17.7
C18.2
C9.3
a In parenthesis, 3J(1H, 1H) couplings; in square brackets, nJ(31P,1H), nJ(31P,13C) and nJ(31P,15N) couplings in Hz.
b υ(1H) of phenyl group: 7.39–7.43 ppm (6H), 7.47–7.50 ppm (3H), 7.79–7.84 ppm (6H).
c υ(15N) in DMSO-d6.
d υ(13C) of CN group: 123.5 ppm; υ(15N) of CN group: ꢀ168.2 ppm; 1J(15N, 13C) D 3.0 Hz.
e υ(1H) of NH group: 13.2 ppm; υ(1H) of NH2 group: 7.35 and 7.67 ppm; υ(13C) of CONH2 group: 153.2 ppm; υ(15N) of CONH2 group:
ꢀ297.9 ppm; 1J(15N, 1H) D 95.2 Hz.
f υ(1H) of phenyl group: 7.47–7.50 ppm (6H), 7.55–7.58 ppm (3H), 7.83–7.89 (6H) ppm.
g υ(1H) of phenyl group: 7.48–7.51 ppm (6H), 7.57–7.61 ppm (3H), 7.71–7.75 ppm (6H).
h Degenerate.
i 1J(13C, 13C) couplings (Hz).
j Not observed in 1H–15N gradient selected HMBC experiment.
k Assignment can be reversed.
l Not observed because of low solubility of this compound in CDCl3.
m Labeled atoms.
n Not observed in 15N inverse gated decoupling spectrum.
Copyright  2002 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2002; 40: 507–516

510
P. Cmoch
Table 3. 1H, 13C, 15N and 31P NMR chemical shifts of N-ethyl salts 14–25 in acetone at 298 K
14
77%
15
23%
16a
74%
17a
26%
18b,c
74%
19b,c
26%
20 D 21
22b,d
100%
24e
¾60%
25e
¾40%
% of N-salt
100%
H4
9.21
(9.5)
9.14
(10.0)
9.06
(10.0)
8.96
(10.0)
9.06
[0.8]
(9.9)
8.93
[1.0]
(10.0)
8.74
(9.5)
8.41
(9.3)
—
—
—
—
H5
8.65
(9.5)
8.46
(10.0)
8.08
(10.0)
7.91
(10.0)
8.41
(9.9)
8.26
(10.0)
8.85
(9.5)
8.63
[1.2]
(9.4)
CH2
CH3
C3
5.10
1.78
5.33
1.88
5.06
1.78
5.30
1.88
4.97
1.69
5.08
1.72
5.11
1.73
4.50
1.00
5.03
1.68
5.05
1.69
139.0
146.7
138.3
146.1
137.2
145.0
157.5
157.0
[3.4]
149.1
149.6
C4
C5
C6
124.4
136.1
156.6
128.7
134.1
159.0
124.2
129.0
159.5
128.3
127.2
161.2
123.5
127.8
140.7
141.2
155.7
131.6
[7.8]
134.7
147.2
155.9
138.0
146.6
153.9
128.9
[8.4]
127.1
[8.2]
140.2
155.8
[3.1]
157.4
[3.5]
150.8
CH2
CH3
N10
N20
N30
N1
48.3
13.6
55.9
13.7
48.0
13.6
55.3
13.7
47.7
13.5
54.9
13.4
61.3
13.2
—
59.9
12.6
61.8
13.3
62.3
13.4
f,g
f,g
ꢀ150.2
ꢀ16.2
ꢀ74.5
ꢀ86.3
ꢀ35.1
ꢀ82.5
ꢀ107.2
—
ꢀ150.6
ꢀ18.4
ꢀ75.2
ꢀ90.2
ꢀ37.4
ꢀ110.1
ꢀ112.3
ꢀ270.2
—
ꢀ150.8
ꢀ19.0
ꢀ75.8
ꢀ91.4
ꢀ37.6
ꢀ308.0
—
—
—
—
ꢀ153.0f ꢀ152.4f
f
f
f
—
—
—
—
—
ꢀ129.5f ꢀ129.4f
ꢀ79.6
ꢀ103.7
—
ꢀ109.1
ꢀ107.0
ꢀ272.7
—
ꢀ117.1
ꢀ109.2
ꢀ308.9
ꢀ112.3
ꢀ121.4
ꢀ36.3
—
ꢀ131.1
ꢀ74.1
—
ꢀ137.5
ꢀ44.3
—
ꢀ52.8
ꢀ126.7
—
f
N2
N100
C10
ꢀ306.0
118.1
—
—
118.0
—
118.4
—
—
[102.9]
[102.7]
[103.0]
C20 D C60
C30 D C50
C40
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
131.1
[14.1]
131.2
[14.1]
h
—
—
—
—
131.3
[14.1]
—
—
—
—
—
—
—
—
134.8
[12.1]
134.9
[12.1]
h
136.8
[3.0]
136.9
[3.2]
P
C38.0
C38.2
C37.8
a Signals of N200 and N300 nuclei of both N-ethyl salts not observed in 1H–15N gradient selected HMBC experiment.
b In parentheses, 3J(1H, 1H) couplings; in square brackets, nJ(31P,1H), nJ(31P,13C) couplings in Hz.
c 1H chemical shifts of phenyl protons of both N-ethyl salts: 7.77–7.82 ppm, 7.94–8.00, 8.06–8.12 ppm.
d 1H chemical shifts of phenyl protons: 7.81–7.85 ppm (6H), 7.97–8.00, 8.07–8.12 ppm.
e Assignment of 1H, 13C and 15N signal of both N-ethyl salts can be reversed.
f Not observed in 1H–15N gradient selected HMBC experiment.
g Not observed in 15N NMR inverse gated decoupling experiment.
h Overlaps with signals of N1-ethyl salt.
Analysis of the 1H–15
N gradient selected HMBC
may exhibit prototropic tautomerism, 7A–7B (Fig. 1).
Although both compounds and were prepared
experiment and inverse gated decoupling 15N NMR spectra
of 6/6* and 7/7* in DMSO-d6 indicates the presence of
only one form for each compound. Selective labeling with
15N isotope allows us not only to assign the N300 signals of
compounds 6 and 7, but also to recognize unambiguously
the position of the proton in the triazene part of 7. The
6
7
previously,4 their structures are still doubtful. In order to
establish the structures of these compounds, reactions of
selectively 15N-labeled 5TA* (Fig. 2) with potassium cyanide
leading to 6* and subsequent hydrolysis of 6* to amide 7*
were carried out.
Copyright  2002 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2002; 40: 507–516

Structure and tautomerism of chloropyridazine derivatives 511
Table 4. 1H, 13C, 15N and 31P NMR chemical shifts (in TFA) of compounds 3—5, 8 and 12–13 at
298 K
3a
4b,c
5
8b,d
12
13b,e
(TFA)
(TFA)
(TFA)
(TFA)
(TFA)
(TFA)
H4
H5
8.61 (9.6)
7.92 [—]
(9.5)
8.40
(9.7)
8.50
(9.5)
—
—
7.76 (9.6)
7.85 [0.9]
(9.5)
7.25
(9.7)
7.80
(9.5)
—
—
C3
141.9
125.3
130.2
154.6
ꢀ90.0f
ꢀ4.0f
ꢀ27.9f
ꢀ80.8
ꢀ104.6
—
154.9 [2.4]
128.0g [br]
134.8
149.7
ꢀ308.8
—
140.5
124.2
140.1
125.7
149.0
142.5
131.2
154.7
ꢀ279.8f
ꢀ153.4f
ꢀ133.2f
ꢀ41.1f,g
ꢀ41.1f,g
—
148.0
147.3
C4
h
C5
123.4
122.6 [8.2]
152.9 [3.1]
ꢀ90.0f
ꢀ7.7f
—
C6
157.2
140.7
ꢀ285.6f
—
N10
N20
N30
N1
N2
N100
N200
N300
C10
ꢀ96.8f
ꢀ10.6f
ꢀ29.7f
ꢀ110.4
ꢀ108.1
ꢀ275.8
ꢀ150.2
ꢀ135.7f
—
—
ꢀ30.0f
ꢀ116.8 [2.6]
ꢀ111.2
ꢀ310.0
—
—
ꢀ108.9
ꢀ67.6
—
ꢀ175.8f
ꢀ51.1f
—
—
—
—
—
—
—
—
—
—
—
116.0
116.3
—
124.1
[103.5]
[103.5]
[108.8]
C20 D C60
C30 D C50
C40
—
—
—
—
129.3
[14.1]
—
—
—
—
129.9
[14.2]
—
—
—
—
128.3
[8.8]
132.5
[11.8]
133.3
[11.8]
131.4
[11.3]
135.4
[3.0]
136.1
[3.1]
133.5
[2.6]
P
C39.6
C40.3
C50.8
a 1H and 13C NMR chemical shifts in TFA taken from Ref. 13.
b In parentheses, 3J(1H,1H) couplings; in square brackets, nJ(31P,1H), nJ(31P,13C) and nJ(31P,15N)
couplings in Hz.
c 1H chemical shifts of phenyl protons: 7.47–7.51 ppm (6H), 7.59–7.68 ppm (9H).
d 1H chemical shifts of phenyl protons: 7.47–7.50 ppm (6H), 7.55–7.59 ppm (3H), 7.84–7.89 (6H).
e 1H chemical shifts of phenyl protons: 7.42–7.58 ppm (15H).
f Not observed in 1H–15N gradient selected HMBC experiment.
g Broad signal.
h Probably overlaps with TFA signal.
1Jꢁ15N,1Hꢂ D 93.5 Hz observed in the 1H and also in the 15
N
Reaction of 5TA with triphenylphosphine in ethanol, at
room temperature, gives derivative 8 (Fig. 1) as a white
solid.19 Analysis of the 1H and 13C NMR data for 8
(Table 2) implies an unsymmetrical monoiminophosphorane
structure of this compound, but still does not explain the
type of tautomer present. In order to distinguish between
two possible forms (T and A) 1H–15N gradient-selected
HMBC and inverse gated decoupling 15N NMR spectra were
measured. Additionally, the values of 31P, X couplings were
analyzed in order to assign the 1H, 13C and 15N NMR signals
properly. The presence of typical 15N NMR tetrazole signals
(at ꢀ68, C4 and ꢀ29 ppm; Table 2) confirms that 8 exists only
in the tetrazole form 8T.
NMR spectra indicates that the tautomeric proton is bound
to the N300 atom and that in DMSO-d6 solution only tau-
tomer 7A exists. The assignment of all remaining 15N NMR
signals is based on analysis of the 15N NMR data obtained
for triazene structures, presented previously17,18 (Table 2). A
negative charge in 6 (Fig. 1) significantly distorts the elec-
tronic structure and probably causes the N300 nucleus to be
deshielded by ca 70 ppm compared with the same nucleus of
7. At the same time, the N200 nucleus of 6 is deshielded by ca
70 ppm as compared with 7. A strong decrease in shielding
of the N200 nucleus is the most significant difference between
5TA and 6/7 observed in the 15N NMR spectra.
Copyright  2002 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2002; 40: 507–516

512
P. Cmoch
1'
N
4
4
4
1′ 2′
NHNH2
4
N 1′
N2′
3
PPh3
3
3
N
3
5
5
5
N+
5
PPh3
1′
H+, NaNO2
−
2′
3′N
N2
N 2
N 2
N2
6
6
Cl
Cl
N
Cl
6
6
N1
Cl
N1
N1
N1
3′
2
3A
3T
4
NH2NH2
NaN3
N
4
4
4
4
N1′
N2′
N3′
N 1′
N2′
N 1′
N2′
N3′
3
3
3
H+
5
5
Cl
5
6
5
3
N2
N2
N 2
N 2
6
6
N
N1
N1
Cl
6
N1
N 1″
N+
N 1″
N+
H
3′
N
N1
1″
KCN
1
N+
2″ K+
2″
6
7A
2″
7B
N−3″
H
3″
4
N
4
N 3″
N1′
N2′
3
3
CN
NH2
5
NH2
N+
5
1′
O
O
N−
2′
N2
N2
3′
6
N
6
1″
N
N
N1
N
N
N
1″
3′
1
N+
2″
+
−
2″
3″
5AA
5TA
N−
3″
4
4
N 1′
PPh3
N1′
N2′
N3′
3
3
5
N+
5
6
4
N1′
N2′
2′ N−
3′
3
5
6
N 2
N2
6
Ph3P
N
N1
N
N 2
Ph3P
N
1″
1
N
1″
N1
1″ N
3′
8A
8T
N
N
3″
2″
5TT
Figure 1. Scheme of the reactions leading to different derivatives of 3,6-dichloropyridazine (1) being in azide–tetrazole equilibrium.
Atoms of all compounds are numbered in accordance with the pyridazine ring.
4
4
4
4
4
N 1′
N 2′
N3′
N 1′
N 2′
N1′
N2′
N 1′
N2′
N 1′
N2′
3
3
3
3
3
Na15NO2
5
5
5
H+
NH2NH2
KCN
K+
5
5
N2
N 2
N 2
N2
N2
6
6
N
N
Cl
6
N
N
6
6
N1
N1
N1
N1
N1
HN
NH2
N 1″
N
3′
N 1″
N+2″
3′
3′
3′
1″
N+2″
N+
2″
3T
9
5TA
6
7
H-
15
-
15N- 3″
15N
N
3″
3″
NH2
CN
O
Figure 2. Scheme of reactions leading to selectively 15N-labeled compounds 5TA, 6 and 7.
3′
4′
2′
3N′ −
2′
Ph
N+
1′
2′
1′
1′
1′N
4
P
Cl
NHNH2
N
Ph
Cl
4
4
4
Cl
Cl
Cl
Cl
Cl
Cl
3
3
Cl
3
3
5
5
5
5
H+, NaNO2
PPh3
NH2NH2
N2
N2
N2
N2
6
6
6
6
N1
11
Figure 3. Scheme of different reactions of 3,4,5,6-tetrachloropyridazine (10).
N1
12
N1
Cl
N1
13
Cl
Cl
Cl
10
reaction of 10 with hydrazine is in agreement with kinetic
data obtained by Chambers et al.6 for the reaction of 10 with
ammonia, leading to 4-amino-3,5,6-trichloropyridazine. This
path has also been confirmed by the following results of
analysis of NMR data (Table 2) obtained for compounds 12
and 13 (Fig. 3):
Derivatives of 3,4,5,6-tetrachloropyridazine (10)
3,4,5,6-Tetrachloropyridazine (10), like 3,6-dichloropyri-
dazine (1), reacts with hydrazine hydrate and yields one
hydrazinotrichloropyridazine derivative (Fig. 3). However,
analysis of a 1H–13C gradient selected HMBC correlation
spectrum of the product obtained, suggests the presence
of a structure other than the expected 3-hydrazino-4,5,6-
trichloropyridazine. Three correlation cross peaks at υ (13C)
113.5, 141.1 and 142.9 ppm caused by interaction between the
NH proton of the NHNH2group and three 13C nuclei (C3, C4,
C5; see Fig. 3) of the pyridazine ring confirm the existence of
4-hydrazino-3,5,6-trichloropyridazine (11). The path of the
3
1. The lack of J(31P,15N) couplings as observed in 4 and 8
implies a structure other than 3-iminophosphorane-4,5,6-
trichloropyridazine.
2. The increase in the N1 and N2 shieldings of the pyridazine
ring after introduction of the azide group is too small
compared with the increases observed in azidopyridine
Copyright  2002 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2002; 40: 507–516

Structure and tautomerism of chloropyridazine derivatives 513
derivatives (the N2 shielding should increase by ca
30 ppm8–10 in such a case).
In order to evaluate the results of ethylation
qualitatively,1H–15N gradient selected HMBC correlation
experiments were applied to assess the presence of the N-
ethyl salts in the mixtures, whereas quantitative estimations
of the content of the N-ethyl salts were made using integrals
of the 1H NMR spectra.
3. The shielding of nucleus N10 in 12 is different (ca 10 ppm)
from those observed for other azidoazines with the azido
group in the ortho position to the ring nitrogen atom
(Table 2). For several 2-azidopyridines the values of the
15N NMR chemical shifts of the N10 nucleus fall within
the range ꢀ270 to ꢀ280 ppm.8–10
Comparison of the 1H–15N gradient selected HMBC
results for mixtures of ethyl salts 14/15, 16/17 and 18/19
(Fig. 4, Table 3) with data for N-ethyl salts of tetrazolo[1,5-
a]pyridines20 excludes the N1 atom of the pyridazine ring
as an ethylation site. Only N10-ethyl and N20-ethyl salts are
present in the mixtures after ethylation. The increase in
shielding of the alkylated nitrogen nuclei by ca 100 ppm
compared with neutral molecules is the most characteristic
phenomenon observed in the NMR spectra of the compounds
The values of the 31P,13C couplings are different from
those observed in the case of compounds 4 and 8. The
2
3
decrease in J(31P,13C) to ca 3 Hz and increase in J(31P,13C)
to ca 10 and 12 Hz in the case of compound 13 probably
originate from the different substitution patterns connected
with the other positions of NPPh3 in the pyridazine ring,
and also from different orientations of the NPPh3 group to
the pyridazine ring plane. Both differences are caused by the
bulky chlorine atoms at positions 3 and 5.
1
obtained after the alkylation reactions (Table 3). Other H,
13C and 15N nuclei in the neighborhood of the alkylation site
also experience a shielding increase, but these changes are
smaller than the above-mentioned ones and were described
in detail in our previous paper.20
Alkylation of the compounds studied
Since all compounds studied contain at least three nitrogen
atoms and each nitrogen atom has at least one lone electron
pair, they fairly easily undergo alkylation reactions. In this
study, ethylation reactions of 1, 3–5, 8, 12 and 13 using
triethyloxonium tetrafluoroborate were carried out.
Using 1H NMR integrals of mixtures 14/15, 16/17
and 18/19, the contents of N10-ethyl salts were estimated.
Regardless of the nature of the substituent in position 6, the
content of N10-ethyl salt is ca 75% and constant for all three
ethylation mixtures.
1
Analysis of the H and 13C NMR data for the reaction
Ethylation of 1 leads to 20 D 21 owing to the substrate
symmetry, whereas derivative 4 yields only one of two
possible N-ethyl salts 22/23. The presence of a bulky NPPh3
group at position 3 of 4 probably hinders access of ethyl
mixtures after ethylation (Fig. 4) shows that in the case of
compounds 3, 5, 8, 12 and 13 two N-ethyl salts are obtained
(two sets of NMR signals), whereas 1 and 4 give only one
type of N-ethyl salt.
group to the N2 atom, and therefore ethylation occurs at
It is known from our previous work that alkylation
of tetrazolo[1,5-a]pyridine derivatives leads to two types
of N-ethyl products: N1-ethyl- and N2-ethyltetrazolo[1,5-
a] pyridinium salts.20 In comparison with tetrazolo[1,5-
a]pyridines, compounds 3, 5 and 8 contain one additional
nitrogen atom, hence alkylation is theoretically possible at
three sites: N1 atom of the pyridazine ring and both N10 and
N20 atoms of the tetrazole moiety. In the case of compounds
1, 4, 12 and 13, there are two potentially possible ethylation
sites: N1 and N2 atoms of the pyridazine ring.
1
the N1 atom. This is confirmed by analysis of the H–15
N
and 1H–13C gradient selected HMBC correlation spectra and
also by the strong nitrogen shielding increase of about ca
130–140 ppm after ethylation of 4. Ethylation also influences
N2 shieldings of compounds 1 and 4 but this effect is smaller,
ca 45–50 ppm.
In the 1H NMR spectra of mixtures of the monocyclic salts
24/25 and 26/27 derived from 12 and 13, respectively, two
sets of appropriate NMR signals are observed. This implies
4
4
4
N1′
3
3
3
N+
5
N 1′
N+2′
1′
5
5
N2′
N2
N2
(C2H5)3OBF4
N2′
+
N2
N
6
6
N
X
N1
N
6
N1
X
N1
3′
3′
X
3′
3, X = Cl
5, X = N3
8, X = NPPh3
14, X = Cl
16, X = N3
18, X = NPPh3
15, X = Cl
17, X = N3
19, X = NPPh3
Y
Y
Y
4
4
X
Z
3
X
4
Z
3
X
Z
3
5
5
5
(C2H5)3OBF4
2
N
N+2
+
N1+
6
2
N
Cl
6
N1
Cl
6
N1
Cl
1, X = Y = H, Z = Cl
4, X = Y = H, Z = NPPh3
20, X = Y = H, Z = Cl
22, X = Y = H, Z = NPPh3
21, X = Y = H, Z = Cl
23, X = Y = H, Z = NPPh3
12, X = Z = Cl, Y = N3
13, X = Z = Cl, Y = NPPh3
24, X = Z = Cl, Y = N3
26, X = Z = Cl, Y = NPPh3
25, X = Z = Cl, Y = N3
27, X = Z = Cl, Y = NPPh3
Figure 4. Scheme of ethylation of compounds 1, 3–5, 8, 12 and 13.
Copyright  2002 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2002; 40: 507–516

514
P. Cmoch
the presence of two different types of salts: N1-ethyl and
N2-ethyl.
In the case of the monocyclic compounds 1, 4, 12 and
13 and the bicyclic compounds 3, 5 and 8, for which
both alkylation and protonation reactions were carried
out, the changes in 15N chemical shifts are smaller after
protonation than the changes observed after ethylation
(Tables 3 and 4). This observation undoubtedly confirms
that proton–nitrogen interaction is of completely different
nature than the nitrogen–carbon bond in the N-ethylated
tetrazolo[1,5-b]pyridazine derivatives.
The presence of azido and iminophosphoro groups at
position 4 of chloropyridazines 12 and 13 causes only a slight
differentiation of the basicity of the ring nitrogen atoms, and
therefore the amounts of both N-ethyl salts are almost the
same. Accurate estimation of the ratio of the two N-salts in
the case of mixtures 24/25 and 26/27 is difficult since the 1H
NMR signals of appropriate CH2 and CH3 groups partially
overlap.
It is very difficult to assign 13C signals in case of the N-
ethyl salts of 12 and 13 (the mixture of salts 26/27 in acetone
is not stable enough to be measured by 13C and 15N NMR
methods and the results of such NMR measurements are not
listed in Table 3) because there are no protons attached to
ring carbons and N-ethyl protons do not correlate with ring
carbon nuclei. In the case of 15N NMR chemical shifts this
task seems to be much easier. On the basis of differences in
CONCLUSIONS
Application of NMR spectral parameters such as 1H,
13C, 15N and 31P chemical shifts and various coupling
constants proves unquestionably that the reaction of 3,6-
dichloropyridazine and 3,4,5,6-tetrachloropyridazine with
hydrazine hydrate yields derivatives in which the chlo-
rine atom is substituted in two different positions. As a
consequence, two different types of azides are produced,
from which 4-azido-3,5,6-trichloropyridazine cannot exist
in the tetrazole–azide equilibrium, whereas azide deriva-
tives of 3,6-dichloropyridazine exist exclusively in the tetra-
zole form.
NMR data [1H, 13C, 15N and 31P chemical shifts and 1J(13C,
13C) and in some cases 31P, X couplings, where X D 1H,
13C and 15N nuclei] provide sufficient evidence to assess
the tautomeric form of the azidopyridazines investigated in
solution and to determine the structure of other compounds
synthesized.
Especially the large shielding sensitivity of 15N nuclei to
different changes (tetrazole–azide equilibrium, ethylation,
protonation) allows one not only to distinguish between
tautomeric forms, existing in solution, but also to establish
ethylation and protonation sites of the compounds contain-
ing more than one nitrogen nucleus.
The strong shielding increase of the nitrogen nucleus
(ca 100 ppm and more) after ethylation precisely indicates
the site of ethylation. By the same rule, the strong nitrogen
shielding increase after protonation of monocyclic com-
pounds undoubtedly proves the site of protonation. In case
of the protonation of bicyclic compounds, the increase in
shielding after protonation is not so large but still sufficient
to assess the protonation site.
1
15N NMR chemical shifts between 1 and 20 D 21, H NMR
signals at 1.68, 5.03 ppm and 15N NMR signals at ꢀ44.3,
ꢀ137.5 ppm belong to N1-ethyl salt 24, whereas those at
1.69, 5.05, ꢀ52.8 and ꢀ126.7 ppm, respectively, correspond
to the second isomer 25 (Table 3). The estimated content of
N1-salts for both cases 24/25 and 26/27 is ca 60%.
Protonation of the compounds studied
Downing et al., using magnetic circular dichroism, examined
tetrazolo[1,5-b]pyridazine and a few other compounds
containing several nitrogen atoms in order to determine
the site of protonation.21 They suggested protonation of
unsubstituted tetrazolo[1,5-b]pyridazine at the N1 atom
but, as was reported previously for three tetrazolo[1,5-
b]pyridazines substituted at position 6, protonation occurred
at the N10 atom of the tetrazole ring.13
Application of 15N NMR spectroscopy is more effective
for the identification of the protonation site. For the wide
group of nitrogen-containing compounds the preferred site
of protonation can be found on the basis of 15N NMR chemical
shifts and their changes caused by protonation. An increase
in shielding of the nitrogen nucleus of ca 100 ppm and more
indicates that such an atom interacts strongly with a proton;
however, smaller values of such an increase do not exclude
the phenomenon of protonation.
In the case of 3, 5 and 8, the increase in N10 shielding after
protonation is 27, 33 and 21 ppm, respectively. Such results
indicate that in all three cases proton–nitrogen interaction
occurs but is rather weak.
EXPERIMENTAL
In contrast to the bicyclic compounds 3, 5 and 8,
after protonation of the monocyclic compounds 1, 4, 12
and 13 the increase in 15N shielding is 63, 100, 38 and
135 ppm, respectively. This suggests a strong dependence
of the protonation effect on the nature, position and size
of the substituent attached to the pyridazine ring. The
latter statement is additionally confirmed by the results of
protonation of compounds 12 and 13. The increase in 15N
shielding of the N1 and N2 nuclei in 12 is smaller (ca 35 ppm)
than in 13, where the bulky NPPh3 group at position 4 not
only causes a strong N1 shielding increase but also favors
the N1 atom as the protonation site (Tables 2 and 3).
Synthesis
The compounds studied were prepared according to schemes
presented in Figs 1–3.
3-Chloro-6-hydrazinopyridazine (2) and
4-hydrazino-3,5,6-trichloropyridazine (11)
Hydrazine hydrate (2.0 ml) was added to the solution of 3,6-
dichloropyridazine (1) (1.2 g, 8.1 mmol) or 3,4,5,6-tetrachloropyri-
dazine (10) (1.0 g, 4.59 mmol) in ethanol (20 ml). The reaction
mixtures were heated under reflux for 6 or 2 h, respectively, and
upon cooling the separated products were collected. Both hydrazines
were used in the next step without further purification. The 1H, 13
C
and 15N NMR chemical shifts of 2 and 11 in DMSO-d6 are collected
in Table 1.
Copyright  2002 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2002; 40: 507–516

Structure and tautomerism of chloropyridazine derivatives 515
186, 185 (25.5%), 184 (18.7%), 183 (100.0%), 170, 157, 154, 153,
152 (13.1%), 143, 141, 139, 133, 131, 115, 108 (25.9%), 107, 78, 77
(12.2%), 51. IR (KBr): 3058.1 (w), 1576.4 (m), 1539.2 (s), 1484.5 (m),
1436.2 (s), 1342.6 (m), 1229.2 (s), 1172.6 (m), 1112.4 (s), 1078.4 (m),
1051.9 (m), 1021.3 (w), 996.9 (w), 804.1 (m), 757.4 (m), 719.8 (s),
693.0 (s), 626.8 (m), 553.0 (m), 534.6 (s) cmꢀ1. Analysis: found, H
3.09, C 56.98, N 8.89%; calculated for C22H15N3Cl3P, H 3.17, C 57.38,
N 9.06%. The 1H, 13C, 15N and 31P NMR chemical shifts in CDCl3
are collected in Table 2.
6-Hydrazinotetrazolo[1,5-b]pyridazine (9)
This was prepared according to the literature.22 The 1H, 13C and 15
NMR chemical shifts in DMSO-d6 are collected in Table 1.
N
6-Tetrazolo[1,5-b]pyridazine (3)
Obtained according to literature method.11 MS: m/z 157, 155,
101, 99, 65, 64 (100%), 63, 52. IR (KBr): 3098.0 (m), 3067.0 (m),
3050.0 (m), 1531.3 (s), 1459.0 (s), 1449.0 (s), 1354.4 (s), 1291.6 (s),
1274.5 (s), 1172.7 (s), 1147.0 (s), 1128.6 (s), 1067.0 (s), 991.9 (m),
932.4 (m), 847.1 (s), 796.7 (m), 728.7 (s), 588.2 (m) cmꢀ1. Analysis:
found, H 1.10, C 30.54, N 44.67%; calculated for C4H2N5Cl, H 1.21,
C 30.87, N 45.02%. The 1H, 13C and 15N NMR chemical shifts in
acetone-d6 are collected in Table 2.
General procedure for the preparation of N-ethyl salts (14–27)
A mixture of the appropriate compound (1, 3–5, 8, 12 and
13) (2 mmol) and triethyloxonium tetrafluoroborate (2.1 mmol) in
dichloromethane (25 ml) was stirred overnight. Diethyl ether was
°
added and the mixture allowed to stand at 0 C for 2–4 h. The
(6-Chloropyridazin-3-yl)(triphenyl-ꢀ5-phosphanylidene)amine (4)
Obtained according to the literature.14 MS: m/z 392, 391, 390
(10.1%), 389 (19.4%), 388 (16.7%), 363, 362, 361, 360, 326 (12.1%),
262 (16.9%), 261, 260, 186, 185 (25.8), 184, 183 (45.6%), 172, 157,
154, 153, 152, 149, 139, 128, 125, 123, 111, 109, 108 (17.5%), 107, 97,
95, 89, 88 (25.8%), 86 (100%), 85, 84 (80.8%), 83 (10.2%), 81, 77, 71
(11.6%), 70, 69 (11.4%), 57 (23.9%). IR (KBr): 3060.8 (w), 1577.9 (m),
1512.8 (m), 1484.0 (w), 1410.0 (s), 1337.7 (m), 1276.6 (m), 1133.7 (m),
1113.9 (s), 987.3 (s), 841.4 (m), 797.2 (w), 753.2 (m), 722.9 (s), 693.4 (s),
549.3 (m), 524.1 (m) cmꢀ1. Analysis: found, H 4.28, C 67.62, N 10.42%;
calculated for C22H17N3PCl, H 4.36, C 67.78, N 10.58%. The 1H, 13C,
15N and 31P NMR chemical shifts in CDCl3 are presented in Table 2.
precipitated salts were collected, washed with diethyl ether and
dried in vacuum. All N-salts are stable as solids but decompose
in solution. The 1H, 13C, 15N and 31P NMR chemical shifts of the
prepared N-salts are collected in Table 4.
Spectra
The 1H, 13C, 15N and 31P NMR spectra were measured
at 298 K on a Bruker DRX 500 spectrometer operating at
500.133, 125.773, 50.690 and 202.456 MHz for 1H, 13C, 15N
and 31P nuclei, respectively. Typical conditions were as
follows: for 1H spectra, ca. 32 transients, relaxation delay
6-Azidotetrazolo[1,5-b]pyridazine (5)
°
2.0 s, pulse width 2.5 µs (ca 30 ), 32 K data points zero filled
Obtained according to the literature.19 MS: m/z 162, 153, 136,
134, 108, 107, 106, 89, 80, 79, 78 (100%), 77 (42.6%), 76, 64, 63,
53 (15.9%), 52, 51 (84.3%), 49. IR (KBr): 3110.8 (w), 3071.2 (m),
2148.5 (s), 2089.0 (s), 1610.6 (m), 1549.6 (s), 1472.7 (s), 1381.9 (s),
1367.4 (s), 1330.8 (s), 1295.4 (s), 1242.6 (s), 1163.2 (m), 1126.2 (m),
1081.2 (m), 977.7 (m), 965.6 (m), 869.8 (m), 850.7 (s), 756.9 (m),
669.5 (m), 590.6 (s), 540.6 (m) cmꢀ1. The 1H, 13C and 15N NMR
chemical shifts in acetone-d6 are presented in Table 2.
to 64 K, spectral width 6000 Hz, digital resolution 0.2 Hz;
for 13C spectra, 256–600 transients, relaxation delay 2.0 s,
°
pulse width 4.0 µs (ca 30 ), 32 K data points zero filled to
64 K, spectral width 20 000–24 000 Hz, digital resolution
0.2–0.5 Hz and power gated decoupling sequence; for
15N spectra, 1000–3000 transients, relaxation delay 15 s,
°
pulse width 7.0 µs (ca 30 ), 32K data points zero filled to
Tetrazolo[1,5-b]pyridazine-6-yl(triphenyl-ꢀ5-
64K, spectral width 15 000–20 000 Hz, digital resolution
0.4 Hz and inverse gated decoupling sequence; for 31P
spectra, 64–128 transients, relaxation delay 2.0 s, pulse
width 6.0 µs (ca 30 ), 32 K data points zero filled to 64 K,
spectral width 15 000 Hz, digital resolution 0.3 Hz and power
gated decoupling sequence. The J(13C, 13C) spin couplings
were obtained using the INADEQUATE sequence with
parameters as follows: ca 5000 transients, relaxation delay
2.0 s, pulse widths 7.0 µs (90 ), 14.0 µs (180 ), 64 K zero filled
phosphanylidene)amine (8)
Obtained according to the literature.19 MS: m/z 396, 288, 264,
263 (19.4%), 262 (100.0%), 261, 186, 185, 184 (10.3%), 183 (44.3%),
170, 157, 154, 108 (20.6%), 107, 78, 77, 51. IR (KBr): 3057.9 (w),
1605.3 (m), 1546.7 (s), 1451.4 (s), 1435.2 (s), 1392.3 (s), 1337.9 (m),
1235.8 (s), 1176.8 (w), 1113.7 (s), 1020.6 (m), 997.7 (m), 920.9 (s),
859.4 (m), 829.3 (s), 749.7 (m), 721.7 (s), 694.2 (s), 600.0 (m), 576.7 (s),
528.8 (s), 503.3 (m) cmꢀ1. Analysis: found, H 4.18, C 66.24, N 21.05%;
calculated for C22H17N6P, H 4.29, C 66.57, N 21.21%. The 1H, 13C,
15N and 31P NMR chemical shifts in CDCl3 are presented in Table 2.
°
1
°
°
to 128 K, spectral width ca 6000 Hz.
4-Azido-3,5,6-trichloropyridazine (12)
°
1
Two-dimensional H–13C gradient selected HSQC (het-
To a stirred mixture at 0 C containing 11 (0,64 g, 3 mmol) in
water (25 ml with 5 ml of concentrated HCl) a solution of sodium
nitrite (0.215 g, 3.12 mmol) in water (5 ml) was added dropwise. The
reaction mixture was left at room temperature for 1 h and thereafter
extracted with chloroform. Upon evaporation of the solvent, the
residue was purified by chromatography [C6H14 –CHCl3 (40 : 10)].
MS: m/z 227, 225, 223 (13.7%), 199, 197, 195, 138, 136 (35.2%), 135,
134 (57.4%), 132, 120, 118, 110, 108, 106, 101 (21.4%), 99 (68.2%),
98, 97, 96 (11.0%), 94, 87 (11.0%), 86, 85 (16.6%), 84 (26.7%),
83, 82 (75.3%), 76, 75 (42.7%), 73 (100.0%), 71 (15.4%), 64, 62,
61. IR (KBr): 2167.1 (s), 2137.9 (s), 1501.8 (s), 1482.1 (m), 1402.5 (s),
1306.8 (s), 1282.8 (m), 1241.2 (m), 1193.0 (m), 1115.4 (s), 914.9 (s),
812.0 (m), 744.6 (m), 717.3 (w), 514.3 (m) cmꢀ1. Analysis: found C
21.14, N 30.95%; calculated for C4N5Cl3, C 21.38, N 31.18%. The 1H,
13C and 15N NMR chemical shifts in CDCl3 are presented in Table 2.
eronuclear single quantum coherence) (C, H correlation
via double INEPT transfer in the phase sensitive mode)
and 1H–13C as well as 1H–15N gradient selected HMBC
(heteronuclear multiple bond coherence) (long-range corre-
lations experiments) were performed using standard Bruker
software and the following parameters: spectral widths in
F2 and F1 were ca 2–10 ppm for 1H, 80–160 ppm for 13C
and 200–400 ppm for 15N. The relaxation delay was usu-
ally ca 2.0 s, the refocusing delay in HSQC experiment
was ca 1.3 ms, whereas delays for long-range evolutions
1
1
were ca 80 and 80–320 ms for H/13C HMBC and H/15N
experiments, respectively. The 2D spectra were acquired as
2048 ð 512 or 1024 ð 256 hypercomplex files, with 4–8 tran-
(3,5,6-Trichloropyridazin-4-yl)(triphenyl-ꢀ5-
phosphanylidene)amine (13)
To a stirred solution of 12 (1.09 g, 5 mmol) in ethanol (30 ml) was
added triphenylphosphine (1.40 g, 5.34 mmol) in small portions.
Nitrogen evolution started instantly, and the yellow solution
became clear. The reaction mixture was concentrated and the
residue purified by chromatography [C6H14 –CHCl3 (60 : 10). MS:
m/z 463, 462, 461, 460 (17.5%), 459 (28.4%), 458 (20.4%), 457
(46.5%), 456 (13.8%), 426, 425, 424 (32.5%), 423, 422 (50.2%), 352,
288, 277, 263, 262 (25.5%), 261 (14.6%), 260, 259, 245, 228, 220,
sients for each 512 or 256 time increments, using appropriate
1
90 and 180 pulse widths for H, 13C and 15N channels.
°
°
For H and 13C spectra, internal TMS was used as the
1
chemical shift standard, whereas external nitromethane and
85% H3PO4 in a capillary were applied as standard for
15N and 31P measurements, respectively. In the case of TFA
Copyright  2002 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2002; 40: 507–516

516
P. Cmoch
1
solutions, H and 13C spectra were calibrated using DMSO-
d6 as an external standard. IR spectra were recorded on an
FT Spectrum 2000 (Perkin-Elmer) and mass spectra were
measured using an AMD-604 spectrometer.
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