Synthesis of substituted methyl pyridazine-4-carboxylates via cycloaddition of diazomethane to 2,3-disubstituted 2-cyclopropenecarboxylic acids

Article abstract of DOI:10.1023/B:RUJO.0000045198.22692.97

A three-step procedure has been developed for the synthesis of 3,5-disubstituted methyl pyridazine-4-carboxylates from accessible 2,3-disubstituted 2-cyclopropenecarboxylates. In the first step, cyclopropene derivatives react with diazomethane to give add

Full text of DOI:10.1023/B:RUJO.0000045198.22692.97

Russian Journal of Organic Chemistry, Vol. 40, No. 7, 2004, pp. 1027–1032. Translated from Zhurnal Organicheskoi Khimii, Vol. 40, No. 7, 2004,
pp. 1068–1073.
Original Russian Text Copyright © 2004 by Razin, Yakovlev, Shataev, Selivanov.
Synthesis of Substituted Methyl Pyridazine-4-carboxylates
via Cycloaddition of Diazomethane to 2,3-Disubstituted
2-Cyclopropenecarboxylic Acids
V. V. Razin, M. E. Yakovlev, K. V. Shataev, and S. I. Selivanov
St. Petersburg State University, Universitetskii pr. 26, St. Petersburg, 198904 Russia
Received September 18, 2003
Abstract—A three-step procedure has been developed for the synthesis of 3,5-disubstituted methyl pyridazine-
4-carboxylates from accessible 2,3-disubstituted 2-cyclopropenecarboxylates. In the first step, cyclopropene
derivatives react with diazomethane to give adducts having 2,3-diazabicyclo[3.1.1]hex-2-ene structure. The
regio- and stereoselectivity of the cycloaddition has been determined. The second step is isomerization of the
bicyclic adducts into 1,4-dihydropyridazine derivatives by the action of sodium methoxide. Finally, oxidation
with potassium permanganate yields the target pyridazine-4-carboxylates.
The double bond in cyclopropene derivatives is
much more reactive than in acyclic olefins due to high
strain energy [1]. For example, cyclopropenes having
no acceptor substituent at the double bond are readily
involved in cycloaddition reactions with 1,3-dipoles
and conjugated dienes [2], while analogous processes
are not typical of nonactivated acyclic olefins. The
strained three-membered ring in bicyclic adducts thus
formed is capable of undergoing easy cleavage [3].
Therefore, cyclopropene derivatives may be regarded
as synthons for introduction of a three-membered
carbon fragment into cyclic molecules. In the present
work we took advantage of this property of cyclo-
propene compounds to develop a new three-step
procedure for the synthesis of substituted pyridazine-
4-carboxylates (Scheme 1).
substituted pyridazines [9], has already been reported
in the literature; however, the overall scheme of transi-
tion from 2-cyclopropenecarboxylates to pyridazine-
4-carboxylates has not been implemented previously.
As initial compounds we used 2,3-disubstituted 2-
cyclopropenecarboxylic acids I–III which are avail-
able through carbene reaction of alkyl diazoacetate
with the corresponding disubstituted acetylene [10].
The cycloaddition of diazomethane to compounds I–
III occurs at a fairly low rate. In the presence of more
than twofold excess of diazomethane, the process takes
no less than 15 days in diethyl ether at 0 to –10°C. The
progress of the reaction was monitored by TLC. In the
reaction with 2,3-dimethyl-2-cyclopropenecarboxylic
acid (I, R = R' = Me), the only product was diazabi-
cyclohexene IV; from cyclopropene II (R = R' = Ph)
we obtained two stereoisomeric diazabicyclohexenes
Va and Vb at a ratio of 4:1; and unsymmetrically
substituted cyclopropene III (R = Me, R' = Ph) gave
rise to three isomeric diazabicyclohexenes: two stereo-
isomers VIa and VIb and regioisomer VII at a ratio of
Each particular step of the proposed procedure, i.e.,
cycloaddition of diazomethane at the cyclopropene
double bond [4, 5, 6], isomerization of substituted 2,3-
diazabicyclo[3.1.0]hex-2-enes into 1,4-dihydropyrida-
zine derivatives [7, 8], and oxidation of the latter to
Scheme 1.
H
N
N
N
R
R'
N
N
N
CH2N2
MeO–
[O]
R
R'
COOMe
R
R'
COOMe
R
R'
COOMe
H
COOH
H
H
I–III
I, R = R' = Me; II, R = R' = Ph; III, R = Me, R' = Ph.
1070-4280/04/4007-1027 © 2004 MAIK “Nauka/Interperiodica”

RAZIN et al.
1028
10:1:1. In all cases, the cycloaddition of diazomethane
to cyclopropenes I–III was characterized by exo-
stereoselectivity which decreased upon replacement of
methyl substituents by phenyl groups. The regioselec-
tivity observed in the addition of diazomethane to
unsymmetrically substituted cyclopropene III is 11:1
in favor of the Auwers adduct.
COOMe
H
H
NOE
COOMe
N
H
N
H
NOE
N
N
R
R
NOE
R'
Vb, VIb
R'
H
H
IV, Va, VIa, VII
The assumed diazabicyclohexene structure of com-
pounds IV, Va, Vb, VIa, VIb, and VII satisfactorily
agrees with their 1H and 13C NMR spectra (Table 1). In
IV, R = R' = Me; Va, Vb, R = R' = Ph; VIa, VIb, R = Ph,
R' = Me; VII, R = Me, R' = Ph.
1
the H NMR spectra of these compounds we observed
a characteristic two-proton signal at δ 5.0 ppm (AB
system, CH2); the 13C NMR spectra contained four
signals from carbon atoms of the diazabicyclohexene
skeleton, two of which were displaced to the region
δC 80–90 ppm due to effect of the neighboring azo
group. The configuration of C6 was established using
2D NOESY technique. The 6-H proton in IV, Va, VIa,
and VII showed NOE with endo-4-H (but not with
phenyl or methyl protons). By contrast, the corre-
sponding proton in Vb and VIb showed NOE with
protons of the phenyl and methyl groups but not with
4-H. It should be noted that compound Va was pro-
perly assigned in [4] the exo configuration without
experimental substantiation. A specific feature of
stereoisomers Va/Vb and VIa/Vb is difference
between the chemical shifts of 6-H: In the spectra of
exo isomers Va and VIa, the 6-H signal is displaced
upfield by more than 1.2 ppm relative to the position
of the corresponding signal in the spectra of endo
isomers Vb and VIb.
The difference between regioisomers VIa and VII
is seen most clearly by comparing their 13C NMR
spectra: In the spectrum of VII, the C1 signal is located
6.2 ppm upfield, while the C5 signal, 8.2 ppm down-
field. This pattern is consistent with the positions of
the corresponding signals in the 13C NMR spectra of
compounds IV and Va. The difference in the chemical
1
shifts of the methyl protons in the H NMR spectra of
regioisomeric adducts VIa and VII also conforms to
the above assignment: in the spectrum of VII, the
methyl proton signal appears 0.45 ppm downfield due
to effect of the neighboring azo group.
The isomerization of diazabicyclohexenes IV–VII
into substituted 1,4-dihydropyridazines was effected
by the action of sodium methoxide in methanol. In all
Table 1. 1H and 13C NMR spectra of 2,3-diazabicyclohexenes IV, Va, Vb, VIa, VIb, and VII
1H NMR spectrum, δ, ppm
13C NMR spectrum, δC, ppm
Comp.
no.
4-Ha 6-H
CH3 OCH3
Ph
–
C1 C4 C5 C6 CH3 OCH3 C=O
Ph
–
4.57 0.92 s 1.38 s, 3.69 s
1.92 s
78.8 87.5 32.1 35.0 08.2, 51.5 168.7
08.8
IV
5.09 1.71 s
–
3.53 s 7.19–7.27 (2H), 84.3 91.2 42.4 38.0
7.32–7.43 (6H),
–
51.6 166.9 127.5, 127.8 (2C), 128.0,
128.2 (2C), 129.9 (2C),
Va
7.58–7.67 (2H)
130.0 (2C), 130.5, 132.1
5.27 3.23 s
–
3.71 s 7.05–7.11 (2H), 85.1 84.7 44.6 31.1
7.20–7.35 (8H)
–
51.9 166.6 127.0 (2C), 127.6, 128.0,
128.3 (2C), 128.5 (2C),
Vb
128.6 (2C), 132.3, 134.9
4.80 1.36 s 1.62 s 3.63 s 7.43 br.s
85.3 88.1 32.9 36.5 10.6 51.6 167.8 128.5 (2C), 128.7, 130.1,
130.3 (2C)
VIa
VIb
VII
4.92 2.58 s 1.19 s 3.66 s 7.30–7.39 (2H), 85.5 82.1 34.6 30.9 15.7 51.7 167.1 128.5 (2C), 128.6, 128.7
7.39–7.50 (3H) (2C), 132.2
4.84 1.33 s 2.07 s 3.63 s 7.03–7.09 (2H), 79.1 89.8 41.1 35.6 09.9 51.7 167.9 127.7, 128.6 (2C), 129.4
7.30–7.36 (3H) (2C), 133.1
a
The position of the center of the AB quartet is given, JAB = 19.5 Hz (in all cases); ∆δAB = 33, 42, 162, 15, 189, and 60 Hz for compounds
IV, Va, Vb, VIa, VIb, and VII, respectively.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 7 2004

SYNTHESIS OF SUBSTITUTED METHYL PYRIDAZINE-4-CARBOXYLATES
1029
Scheme 2.
H
COOMe
R'
H
COOMe
R'
R
R
H+
[O]
–H+
N
N
N
N
H
COOMe
R'
A
B
R
IX–XI
H+
H
–H+
N
N
XII–XV
COOMe
R'
COOMe
R'
R
R
[O]
H
H
N
NH
N
N
D
C
VIII
VIII, XII, R = R' = Me; IX, XIII, R = R' = Ph; X, XIV, R = Ph, R' = Me; XI, XV, R = Ph, R' = Me.
cases, the reaction was fast and selective, and the
products were formed in high yields. In keeping with
published data [7, 8], we believe that the process
involves formation of anionic intermediate A whose
protonation yields substituted 1,4-dihydropyridazine.
The latter may be presumed to have structure B (as
a result of protonation of anion A at the nitrogen atom)
or C (as a result of tautomeric transformation of
4,5-dihydropyridazine D arising from protonation of
anion A at the carbon atom) (Scheme 2).
isomerization of diazabicyclohexene IV leads to
formation of structure C. In all other cases, isomer B is
formed. The C structure of compound VIII follows
1
from the presence in the H NMR spectrum of
a doublet signal (J = 7 Hz) from protons of one methyl
group. The spectrum of X contained a singlet from the
methyl protons, indicating that this compound has
structure B. Structure B of IX–XI is also confirmed by
the presence of a one-proton singlet from 4-H. The
other spectral parameters of compounds VIII–XI do
not contradict the assumed structures. We believe that
the isomerization of diazabicyclohexenes IV–VII by
1
Analysis of the H and 13C NMR spectra of 1,4-di-
hydropyridazines VIII–XI (Table 2) showed that only
Table 2. 1H and 13C NMR spectra of 1,4-dihydropyridazines VIII–XI
1H NMR spectrum, δ, ppm (J, Hz)
13C NMR spectrum, δC, ppm
C5 CH3 OCH3 C=O Ph, C3, C6
Comp.
no.
4-H
6-H
CH3 OCH3 NH
Ph
–
C4
3.33 d.q 6.77 da 0.94 d 3.68 s 7.80 br.s
27.3 094.9 ,17.7, 50.6 167.6 143.6, 147.0
18.1
a
VIII
(4.8,
7.1)
(4.8) (7.1),
2.23 s
5.08 s 7.14 d
(4.2)
–
3.69 s 8.11 br.s 7.23–7.30 (1H), 41.4 103.1
7.35–7.49 (5H),
–
52.4 171.2 124.4 (2C), 124.6, 126.0
(2C), 126.2, 128.3 (2C),
128.5 (2C), 128.7, 135.4,
136.0, 136.7
IX
7.51–7.57 (2H),
7.92–7.98 (2H)
b
4.40 s 6.47 br.s 1.87 s 3.70 s
4.36 s 7.06 br.s 2.17 s 3.73 s
7.32–7.42 (3H), 44.4 101.4 18.2 52.3 170.9 123.4, 125.4 (2C), 128.2
7.72–7.80 (2H) (2C), 128.9, 134.3, 136.5
7.18–7.25 (1H), 45.1 102.1 22.4 52.4 170.4 124.0 (2C), 124.9, 126.0,
7.32–7.37 (4H) 128.5 (2C), 136.8, 137.9
X
b
XI
a
3-H.
b
No NH signal was observed in the spectrum recorded in CDCl3; in DMSO-d6, a one-proton broadened singlet appeared at δ 9.60 ppm in
both cases.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 7 2004

RAZIN et al.
1030
Table 3. 1H and 13C NMR spectra of pyridazine-4-carboxylates XII–XV
1H NMR spectrum, δ, ppm
13C NMR spectrum, δC, ppm
CH3 OCH3 C=O
Ph, C4, C5
Comp.
no.
6-H
CH3
OCH3
Ph
C3
C6
8.95 s ,2.30 s, 3.94 s
2.66 s
–
155.1 151.7 ,16.3, 52.5 166.3 131.0, 133.8
20.4
XII
9.31 s
–
3.59 s 7.43–7.58 (8H), 157.0 150.1
7.68–7.78 (2H)
–
52.5 166.5 128.0 (2C), 128.4 (2C), 128.45
(2C), 128.5, 129.0 (2C),
129.55, 129.6, 133.8, 136.1,
136.7
XIII
9.12 s 2.41 s 3.71 s 7.42–7.51 (3H), 156.6 151.8 16.3 52.6 166.7 128.3 (2C), 128.5 (2C), 129.4,
7.65–7.72 (2H) 130.9, 134.5, 136.3
XIV
XV
9.18 s 2.79 s 3.75 s 7.37–7.45 (2H), 155.5 149.8 20.3 52.6 166.6 127.9 (2C), 129.0 (2C), 129.6,
7.45–7.55 (3H)
129.8, 134.0, 136.0
ferences in the positions of the methyl group signals
were observed for compounds X and XI which are
precursors of XIV and XV.
the action of sodium methoxide is a thermodynamic-
ally controlled process. In the case of dimethyl-sub-
stituted diazabicyclohexene IV, structure C of the
isomerization product is thermodynamically more
favorable, as compared to B, for the ester group in the
former is attached to sp2-carbon atom and hence is
conjugated with the endocyclic double bond. By con-
trast, diazabicyclohexenes VIa and VIb give rise to
structure B, 1,4-dihydropiridazine X; in this case,
structure B becomes thermodynamically more favor-
able due to stabilizing effect of the phenyl group in the
imine fragment. Alternative structure C with the same
substitution pattern should be destabilized for steric
reasons (conjugation in the cis-cinnamate fragment is
hindered). Structure B is also more favorable for
isomerization products IX and XI (obtained from
diazabicyclohexenes Va, Vb, VIa, and VIb), for it
ensures conjugation between the phenyl substituent
and endocyclic double bond; in the respective structure
C, the phenyl group is forced out of conjugation with
the dihydropyridazine ring.
We conclude that the proposed three-step procedure
for the synthesis of substituted pyridazine-4-car-
boxylates via cycloaddition of diazomethane to 2,3-di-
substituted 2-cyclopropenecarboxylic acids is advan-
tageous due to high yield in each step and accessibility
of initial cyclopropene derivatives. Unfortunately, the
first step in the procedure takes a long time, and it
seems improbable to eliminate this drawback.
EXPERIMENTAL
1
The H and 13C NMR spectra were recorded on
a Bruker DPX-300 spectrometer (300.13 MHz for
1H and 75.47 MHz for 13C) using CDCl3 as solvent.
2D NOESY experiments were performed using the
same instrument. The elemental compositions were
determined on an HP-185B CHN-analyzer. Analytical
thin-layer chromatography was performed on Silufol
UV-254 plates. The products were separated and
purified by column chromatography on silica gel L
40/100 µm (Chemapol). 2,3-Disubstituted 2-cyclo-
propenecarboxylic acids I [12], II [13], and III [14]
were synthesized by known methods. A solution of
diazomethane in ether was distilled prior to use.
1,4-Dihydropyridazines VIII–XI were oxidized
with potassium permanganate in acetone. As a result,
the corresponding pyridazine-4-carboxylates XII–XV
were obtained in high yields. Their structure is con-
1
vincingly confirmed by the H and 13C NMR spectra
(Table 3). Pyridazines XII–XV characteristically
1
showed in the H NMR spectra a singlet from the 6-H
Methyl 1,5-dimethyl-2,3-diazabicyclo[3.1.0]hex-
2-ene-exo-6-carboxylate (IV). To a solution of 0.56 g
(5 mmol) of acid I in 10 ml of diethyl ether we added
at 0°C 52 ml of a 0.58 M solution of diazomethane
(30 mmol) in diethyl ether, and the mixture was kept
for 14 days at 0°C in the dark. The solvent was
removed under reduced pressure, and the residue
was recrystallized from hexane. Yield 0.75 g (89%),
proton at δ 9.0 ppm. Regioisomeric compounds XIV
and XV can be distinguished by the position of the
1
methyl group signals in the H and 13C NMR spectra:
in the spectra of 3-methylpyridazine XV, these signals
are displaced downfield by 0.38 and 4.0 ppm,
respectively, relative to the corresponding signals of
5-methylpyridazine XIV (cf. [11]). Analogous dif-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 7 2004

SYNTHESIS OF SUBSTITUTED METHYL PYRIDAZINE-4-CARBOXYLATES
1031
mp 31°C, Rf 0.25 (hexane–diethyl ether, 1:1). Found,
C 67.81; H 6.13; N 12.17. Removal of the solvent
from the filtrate gave 0.31 g of a substance which
contained compounds VIa, VIb, and VII (according
%: C 57.07; H 7.18; N 16.58. C8H12N2O2. Calculated,
1
%: C 57.13; H 7.19; N 16.66. The H NMR spectrum
1
of the residue obtained by evaporation of the mother
liquor contained no signals assignable to the endo
isomer of IV, which indicated strict exo-stereoselec-
tivity of the cycloaddition of diazomethane to 2,3-di-
methyl-2-cyclopropenecarboxylic acid (I).
to the H NMR data). It was subjected to column
chromatography on silica gel. We isolated (in the order
of elution) 59 mg (5.6%) of compound VII, Rf 0.28
(hexane–diethyl ether, 1:1); an additional portion of
VIa, 73 mg (6.9%), Rf 0.20; and compound VIb,
64 mg (6.1%), Rf 0.18.
Reaction of diazomethane with 2,3-diphenyl-2-
cyclopropenecarboxylic acid (II). To a suspension of
0.95 g (4 mmol) of acid II in 25 ml of diethyl ether we
added at 0°C 50 ml of a 0.55 M solution of diazo-
methane (27.5 mmol) in diethyl ether. The resulting
solution was kept for 20 days at –10°C in the dark. The
solvent was removed under reduced pressure to obtain
1.21 g of a substance which, according to the 1H NMR
data, was a mixture of compounds Va and Vb at a ratio
of ~4:1. Crystallization from 15 ml of hexane–diethyl
ether (1:1) (after prolonged cooling at –20°C) gave
0.86 g (73%) of methyl 1,5-diphenyl-2,3-diazabicyclo-
[3.1.0]hex-2-ene-exo-6-carboxylate (Va), mp 121°C
[4], Rf 0.29 (hexane–diethyl ether, 1:1). The mother
liquor was evaporated under reduced pressure, and the
viscous oily residue, 0.32 g, was dissolved in warm
hexane. The solution was cooled, and a portion of
crystals (a mixture of compounds Va and Vb) was
separated. The solvent was removed from the mother
liquor to obtain 0.17 g (14%) of methyl 1,5-diphenyl-
2,3-diazabicyclo[3.1.0]hex-2-ene-endo-6-carboxylate
(Vb) as a light yellow viscous oily substance, Rf 0.28.
Methyl 1-methyl-5-phenyl-2,3-diazabicyclo-
[3.1.0]hex-2-ene-exo-6-carboxylate (VII). mp 65°C.
Found, %: C 67.56; H 6.26; N 11.94. C13H14N2O2.
Calculated, %: C 67.81; H 6.13; N 12.17.
Methyl 5-methyl-1-phenyl-2,3-diazabicyclo-
[3.1.0]hex-2-ene-endo-6-carboxylate (VIb). mp 62°C.
Found, %: C 67.79; H 6.11; N 12.13. C13H14N2O2.
Calculated, %: C 67.81; H 6.13; N 12.17.
Isomerization of diazabicyclohexenes IV–VII to
1,4-dihydropyridazines VIII–XI (general procedure).
To a solution of 1.0 mmol of diazabicyclohexene IV–
VII in 3 ml of methanol we added 1 ml of a 0.2 M
solution of sodium methoxide (0.2 mmol) in methanol.
The mixture was stirred for 5 min at 20°C, diluted with
40 ml of diethyl ether, washed with water, dried over
magnesium sulfate, and evaporated under reduced
pressure.
Methyl 4,6-dimethyl-1,4-dihydropyridazine-5-
carboxylate (VIII) was obtained from diazabicyclo-
hexene IV. Colorless oily substance, yield 84%,
Rf 0.13 (hexane–diethyl ether, 1 : 1). Found, %:
C 56.81; H 7.38; N 16.38. C8H12N2O2. Calculated, %:
C 57.13; H 7.19; N 16.65.
1
According to the H NMR data, product Vb contained
~15% of exo isomer Va. Found, %: C 72.62; H 5.53;
N 9.48. C18H16N2O2. Calculated, %: C 73.95; H 5.52;
N 9.58.
Methyl 3,5-diphenyl-1,4-dihydropyridazine-4-
carboxylate (IX) was obtained from diazabicyclo-
hexene Va. Yield 96%, mp 110–111°C; published data
[4]: mp 106–109°C; Rf 0.21 (hexane–diethyl ether,
1:1). Found, %: C 73.90; H 5.52; N 9.32. C18H16N2O2.
Calculated, %: C 75.95; H 5.52; N 9.58. The same
product was formed by isomerization of compound Vb
(according to the TLC data).
Reaction of diazomethane with 2-methyl-3-
phenyl-2-cyclopropenecarboxylic acid (III). To
a suspension of 0.8 g (4.6 mmol) of acid III in 15 ml
of diethyl ether we added 52 ml of a 0.55 M solution
of diazomethane (28.6 mmol) in diethyl ether. The
mixture was kept for 15 days at –10°C in the dark. The
solvent was removed under reduced pressure to obtain
1.03 g of a colorless solid which, according to the
1H NMR data, was a mixture of compounds VIa, VIb,
and VII at a ratio of 10:1:1. This mixture was
dissolved in 10 ml of hexane–diethyl ether (1:1), the
solution was kept for 3 h at –20°C, and the precipitate
was filtered off. We thus isolated 0.72 g (68%) of
methyl 5-methyl-1-phenyl-2,3-diazabicyclo[3.1.0]hex-
2-ene-exo-6-carboxylate (VIa). mp 107°C. Found, %:
C 67.99; H 6.17; N 12.17. C13H14N2O2. Calculated, %:
Methyl 5-methyl-3-phenyl-1,4-dihydropyrida-
zine-4-carboxylate (X) was obtained from diazabi-
cyclohexene VIa. Colorless oily substance, yield 91%,
Rf 0.23 (hexane–diethyl ether, 1 : 1). Found, %:
C 67.57; H 6.38; N 12.01. C13H14N2O2. Calculated, %:
C 67.81; H 6.13; N 12.17. The same product was
formed by isomerization of compound VIb (according
to the TLC data).
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RAZIN et al.
1032
REFERENCES
Methyl 3-methyl-5-phenyl-1,4-dihydropyrida-
zine-4-carboxylate (XI) was obtained from diazabi-
cyclohexene VII. Colorless oily substance, yield 78%,
Rf 0.20 (hexane–diethyl ether, 1 : 2). Found, %:
C 67.49; H 6.40; N 11.96. C13H14N2O2. Calculated, %:
C 67.81; H 6.13; N 12.17.
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(general procedure). To a solution of 1 mmol of
1,4-dihydropyridazine VIII–XI in 5 ml of acetone we
added a solution of 0.17 g (1.1 mmol) KMnO4 in 2 ml
of water. The mixture was stirred for 0.5 h and filtered,
the filtrate was concentrated under reduced pressure,
and the residue was purified by flash chromatography
on silica gel.
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mukhametov, R.R., and Novinskii, V.G., Zh. Org. Khim.,
1976, vol. 12, p. 801.
5. Methoden der organische Chemie. Houben–Weyl, De
Meijere, A., Ed., Stuttgart: Georg Thieme, 1997,
vol. E17a, p. 175.
6. Baird, M.S. and Hussain, H.H., Tetrahedron, 1987,
vol. 43, p. 215; Al Dullayymi, A.P. and Baird, M.S.,
Tetrahedron, 1998, vol. 54, p. 12897.
7. Regitz, M., Welter, W., and Hartmann, A., Chem. Ber.,
1979, vol. 112, p. 2509; Heydt, H., Busch, K.H., and
Regitz, M., Justus Liebigs Ann. Chem., 1980, p. 590.
Methyl 3,5-dimethylpyridazine-4-carboxylate
(XII) was obtained from 1,4-dihydropyridazine VIII.
Yield 77%, mp 43–44°C, Rf 0.11 (hexane–diethyl
ether, 1:3). Found, %: C 57.71; H 6.06; N 16.54.
C8H10N2O2. Calculated, %: C 57.81; H 6.07; N 16.86.
Methyl 3,5-diphenylpyridazine-4-carboxylate
(XIII) was obtained from 1,4-dihydropyridazine IX.
Yield 95%, mp 124–125°C, Rf 0.22 (hexane–diethyl
ether, 1 : 2). Found, %: C 74.18; H 4.92; N 9.36.
C18H14N2O2. Calculated, %: C 74.47; H 4.86; N 9.65.
8. Norden, W., Sander, V., and Weyerstahl, P., Chem. Ber.,
1983, vol. 116, p. 3097.
9. Comprehensive Organic Chemistry, Barton, D. and
Ollis, W.D., Eds., Oxford: Pergamon, 1979, vol. 4.
Translated under the title Obshchaya organicheskaya
khimiya, Moscow: Khimiya, 1985, vol. 8, chap. 16.2;
The Chemistry of Heterocyclic Compounds, Castle, R.N.,
Ed., New York: Wiley, 1973, vol. 28.
10. Protopopova, M.N. and Shapiro, E.A., Usp. Khim.,
1989, vol. 58, p. 1145.
11. Tsujimoto, T., Nomura, T., Iifuru, M., and Sasaki, Y.,
Chem. Pharm. Bull., 1979, vol. 27, p. 1169.
12. Zefirov, N.S., Averina, N.V., Boganov, A.M., Koz’-
min, A.S., Anufriev, V.S., Tatevskii, V.M., Yarovoi, S.S.,
Shchelokov, R.N., and Baranovskii, I.B., Zh. Org.
Khim., 1981, vol. 17, p. 1450.
13. D’yakonov, I.A. and Komendantov, M.I., Zh. Obshch.
Khim., 1963, vol. 33, p. 2448.
Methyl 5-methyl-3-phenylpyridazine-4-car-
boxylate (XIV) was obtained from 1,4-dihydropyri-
dazine X. Yield 86%, mp 47–48°C, Rf 0.15 (hexane–
diethyl ether, 1:2). Found, %: C 68.56; H 5.39;
N 12.16. C13H12N2O2. Calculated, %: C 68.40; H 5.30;
N 12.28.
Methyl 3-methyl-5-phenylpyridazine-4-car-
boxylate (XV) was obtained from 1,4-dihydropyri-
dazine XI. Yield 74%, mp 60–61°C, Rf 0.17 (hexane–
diethyl ether, 1:2). Found, %: C 68.38; H 5.34;
N 12.21. C13H12N2O2. Calculated, %: C 68.40; H 5.30;
N 12.28.
The authors are grateful to V.A.Vasin (Mordovian
University) for his help in the preparation of acid I.
14. D’yakonov, I.A. and Komendantov, M.I., Zh. Obshch.
Khim., 1961, vol. 31, p. 3881.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 7 2004