Reaction of β-cyano esters with hydrazine hydrate. Unexpected formation of dipyrrolo[1,2-b:1′,2′-e][1,2,4,5]tetrazine, a novel ring system

Article abstract of DOI:10.1002/jhet.5570420525

Some intermediates and by-products of the title reaction, known to yield 6-hydrazinopyridazine-3-one derivatives, were isolated or detected when the amount of hydrazine hydrate used to react with two model β-cyano esters was reduced to less than two equivalents. N′-(1-amino-4-hydrazino-4-oxo-2- phenylbutylidene)-4-hydrazino-4-oxo-2-phenylbutanehydrazonamide and 3,3,8,8-tetramethyl-2,3,7,8-tetrahydro-1H,6H-dipyrrolo[1,2-b:1′, 2′-e][1,2,4,5]tetrazine-1,6-dione were isolated as the terminal products of side-reactions; they were unreactive to hydrazine. The latter compound is a derivative of a novel ring system. Mechanism of the reaction was proposed.

Full text of DOI:10.1002/jhet.5570420525

Jul-Aug 2005
919
Reaction of β-Cyano Esters with Hydrazine Hydrate. Unexpected
Formation of Dipyrrolo[1,2-b:1',2'-e][1,2,4,5]tetrazine,
a Novel Ring System
Krystyna Wejroch [a], Aneta Wesołowska [b], Maja Sadowska [c], Janina Karolak-
Wojciechowska [c], Tadeusz Jagodziński [b], and Jerzy Lange* [a]
[a] Department of Chemistry, University of Technology, Noakowskiego 3, PL-00664 Warsaw, Poland,
e-mail: lange@ch.pw.edu.pl
[b] Institute of Chemistry and Environmental Protection, Technical University,
Piastów 42, PL-71065 Szczecin, Poland
[c] Institute of General and Ecological Chemistry, Technical University, Żwirki 36, PL-90924 Łódź, Poland
Some intermediates and by-products of the title reaction, known to yield 6-hydrazinopyridazine-3-one
derivatives, were isolated or detected when the amount of hydrazine hydrate used to react with two model
β-cyano esters was reduced to less than two equivalents. N'-(1-amino-4-hydrazino-4-oxo-2-phenylbutyli-
dene)-4-hydrazino-4-oxo-2-phenylbutanehydrazonamide and 3,3,8,8-tetramethyl-2,3,7,8-tetrahydro-
1H,6H-dipyrrolo[1,2-b:1',2'-e][1,2,4,5]tetrazine-1,6-dione were isolated as the terminal products of side-
reactions; they were unreactive to hydrazine. The latter compound is a derivative of a novel ring system.
Mechanism of the reaction was proposed.
J. Heterocyclic Chem., 42, 919 (2005).
The reaction of 3-cyanopropionic esters (1) with
triazine-4,7(3H,6H)-dione (5) as the only product. Since
the formation of 4a from 3 was considered highly
unlikely, it was assumed that 4a must have been formed in
the cyanoester-hydrazine reaction and that it passed
unchanged through the subsequent steps to be finally iso-
lated once the solubility conditions became more favor-
able (5, unlike 4, is quite readily soluble in water). In
order to verify this assumption, the title reaction was
recently reinvestigated in detail with ethyl 3-cyano-3-
methylbutyrate (1a) and ethyl 3-cyano-3-phenylpropi-
onate (1b) as the model starting esters.
hydrazine hydrate, once mistakenly believed to be a mat-
ter-of-course method for the preparation of the correspond-
ing 3-cyanopropanohydrazides [1], revealed to be a rather
complex process. As it is known now, it gives a high yield
of the appropriate 6-hydrazino-4,5-dihydro-2H-pyridazin-
3-ones (2) [2], convenient building blocks in the synthesis
of bicyclic pyridazine structures [3-5]. Unsubstituted 2 and
a phthalazine analog of 2 were also prepared earlier by ring
expansion of 5-iminopyrrolidin-2-one and an isoin-
dolinone derivative, respectively, under the action of
hydrazine hydrate [6-8].
With a sufficiently large excess of hydrazine (≥15 mol)
the reaction was routinely carried out in this laboratory by
simply leaving the reagents standing for a long time at
room temperature. Elevation of the reaction temperature
enhanced the formation of hardly removable by-products.
However, even under optimal reaction conditions, poor
solubility of the reaction products caused in the prepara-
tive-scale runs some purification problems. On the other
hand, if insufficiently pure 2 are used as the substrates in
further reactions, the results may be surprising and rather
hard to rationalize at first sight.
Thus, when a roughly purified 5,5-dimethyl-6-
hydrazino-4,5-dihydro-2H-pyridazin-3-one (2a) was once
used by us in the cyclocondensation with ethyl pyruvate
[3] and the resulting crude 3,9,9-trimethyl-8,9-dihydro-
4H-pyridazino[6,1-c][1,2,4]triazine-4,7(6H)-dione (3) was
hydrogenated on a palladium catalyst, the product isolated
in a very low yield (3.5%) was later identified by crystal-
lography as 3,3,8,8-tetramethyl-2,3,7,8-tetrahydro-1H,6H-
dipyrrolo[1,2-b:1',2'-e][1,2,4,5]-tetrazine-1,6-dione (4a),
a derivative of a novel ring system (Figure 1) [9,10]. When
thoroughly purified 2a was recently used in the same reac-
tion sequence, the final hydrogenation gave the expected
3,9,9-trimethyl-8,9-dihydro-2H-pyridazino[6,1-c][1,2,4]-
Figure 1. ORTEP drawing of the molecule of 4a. Atom labels given only
for the crystallographically independent part of the molecule [9].
Theoretically, the conversion of 1 into 2 requires two
equivalents of hydrazine hydrate whereas one is enough to
produce 4. It seemed logical, therefore, to assume that the
formation of 4 occurred mostly at the phase boundary,
where a rapid uptake of hydrazine in the main reaction

920
Vol. 42
K. Wejroch, A. Wesołowska, M. Sadowska, J. Karolak-Wojciechowska,
T. Jagodziński, and J. Lange
(1 → 2) caused a local deficiency of this reagent in the
initially heterogeneous un-agitated reaction mixture.
Following that line of reasoning, in a series of experiments
we performed presently, the cyanoester-hydrazine molar
ratio was reduced to 1:1.1-2.0. All the reactions were car-
ried out under standard conditions, i.e., without agitation
and at ambient temperature; in some experiments, a small
amount of ethanol was added in order to make the two
phases come into a better contact with one another. The
reaction progress was monitored by GC and/or GC/MS
and the reactions were arrested for the first time when the
ester content dropped by 30-35% and any amount of a
solid product appeared. Upon separation of the solid, the
homogeneous filtrate deposited slowly on standing another
portion of a solid which was separated when a reasonable
amount had accumulated. This operation was repeated 2-4
times at suitable intervals. Changes in the hydrazine
hydrate concentration (40-98%) affected the reaction rate
but had little effect upon the reaction course, if any.
Figure 3. ORTEP drawing of one of the three crystallographically
independent units of 7.
In experiments with 1a, when the amount of hydrazine
hydrate (40%) was reduced to the stoichiometry level (2
mol as required for the formation of 2a), the first portion of
the solid product revealed to be a mixture of 2a and two
other compounds. Elution with chloroform made it possi-
ble to separate the practically insoluble 2a while the
residue was resolved by column chromatography. The
structures of the new compounds, 1-amino-3,3-dimethyl-
pyrrolidine-2,5-dione 2[(3,3-dimethyl-5-oxopyrrolidin-2-
ylidene)-hydrazone] (6a, Figure 2) and 6-amino-5-
dimethyl-4,5-dihydro-2H-pyridazin-3-one (7a, Figure 3),
respectively, were elucidated by X-ray crystallography.
The second crop, filtered after a few weeks, was a mixture
of 6a and 2a (Scheme 1).
was not observed in these experiments. Both 6a and 7a
have to be considered as intermediates in the formation of
2a, into which they are readily converted upon treatment
with hydrazine hydrate.
When the cyanoester-to-hydrazine hydrate (98%) ratio
was reduced further down to 1:1.5 mol and the reaction
was carried out with a small amount of ethanol added, the
isolated solid product was pure 6a (47% yield). The filtrate
left standing for 3 weeks deposited a mixture of 6a and 2a
which was separated by column chromatography.
Finally, the reaction with 1.1 mol of hydrazine hydrate
(98%) was carried out under analogous conditions. The
solid product that gradually deposited in the reaction mix-
ture was portionwise removed by filtration at intervals of a
few weeks. The first portions contained more or less pure
6a but the last portion contained also 4a (3.5% yield)
which was isolated by column chromatography.
When 1b was treated with 1.1 mol of hydrazine hydrate
(98%) with some ethanol added, crystals which separated
after 7 days at room temperature (28% yield relative to
hydrazine) were identified by NMR and MS as N'-(1-
amino-4-hydrazino-4-oxo-2-phenylbutylidene)-4-
hydrazino-4-oxo-2-phenylbutanehydrazonamide (8b). The
filtrate left standing 18 days deposited a small amount of
6b, the phenyl analog of 6a. 8b was a terminal compound
of this reaction pathway (Scheme 1) as it did not react with
hydrazine hydrate.
The results show that the reaction of β-cyano esters with
hydrazine hydrate is a multidirectional process involving
intra- and intermolecular mechanisms. The main reaction
product, the hydrazinopyridazinone 2, is presumably
formed by an intramolecular 6-exo-trig [11] cyclization of
the intermediate 9 resulting from the addition of hydrazine
Figure 2. ORTEP drawing of one of the two independent and identical
molecules of 6a (primed atom labels).
Similar results were noted with 24% hydrazine hydrate
used without any diluent. However, the formation of 4a

Jul-Aug 2005
Reaction of β-Cyano Esters with Hydrazine Hydrate
921
which in the reaction with hydrazine hydrate either is sim-
ply converted into the corresponding dihydrazide 8b or
cyclizes with elimination of ammonia to give 12 and, fur-
ther on, 4a. It is noteworthy that the reaction course
depends here on the substituents R and R . In the reaction
starting with 1b, GC/MS monitoring revealed no trace of
the phenyl analog of 4a. Similarly, no dimethyl analog of
8b could be detected in the reaction mixture starting with
1a. The effect of substituents on the behavior of 11 is
hardly explicable; some steric and/or electronic factors
may here decide upon the reaction course.
Since 8b did not react with hydrazine hydrate, at least
under the conditions of the present experiments (room
temperature), participation of the 9 → 11 → 8 pathway in
the formation of the pyridazinones 2 and 7 can be ruled
out.
The formation of the dissymetric azines 6, readily con-
vertible by the action of hydrazine hydrate into the
hydrazinopyridazinones 2, has to be considered as another
across the C≡N nitrile bond. Isolation of the cyclization
intermediate, the aminopyridazinone 7, constitutes a
strong support for this reaction pathway since 7 is readily
converted into 2 in the reaction with hydrazine hydrate;
similar reactions were observed earlier [12]. An alternative
pathway may lead to 2 via the intermediate 10 formed
from 1 and 2 mol of hydrazine. Although the intramolecu-
lar cyclization of 10 also conforms to the Baldwin’s ring
closure rules [11] this reaction pathway seems to be disfa-
vored since the electrophilicity of the amidrazone carbon
atom in 10 is much lower than that of the ester carbon atom
in 9 [13].
As far as the formation of the dipyrrolotetrazine 4a is
concerned, it should be noticed that the formation of s-
tetrazine compounds in the reaction of hydrazine with
nitriles was observed long ago [14-16]. In our case, the
intermediate 9 may participate in this reaction. Thus, addi-
tion of 9 with its hydrazino fragment across the C≡N bond
of 1 may lead to the symmetric open-chain diester 11
1
2

922
Vol. 42
K. Wejroch, A. Wesołowska, M. Sadowska, J. Karolak-Wojciechowska,
T. Jagodziński, and J. Lange
X-Ray Structure Determination.
evidence of the key role of the intermediate 9. In the reac-
tion with hydrazine, the amidrazone moiety of 9 is con-
verted into a hydrazonohydrazine (13). Intramolecular
acylation of the secondary nitrogen atom in 13 with elimi-
nation of ethanol gives rise to the formation of the N-
aminopyrrolone 14 which subsequently reacts with 1. The
thus formed azine 15 undergoes a similar intramolecular
cyclization to yield 6. Both intramolecular cyclizations (13
→ 14 and 15 → 6) are of the favored 5-exo-trig type [11].
It is of particular interest that the conversion of 6 into 2
proceeds in yields exceeding 50%. That means that both
”halves” of 6 have active centers capable of reacting with
hydrazine. Since similar unrecognized centers may be pre-
sent in other reaction intermediates, formulation of a more
precise and fully proven mechanism is hardly possible. For
instance, an alternative pathway leading to 6 may involve
acylation of the carbon-attached nitrogen atom in 9 and in
its hydrazono tautomer (5-exo-trig cyclizations) as shown
in Scheme 1. However, the interaction of the thus formed
pyrrolones (16 and 17, respectively) is for statistical rea-
sons rather doubtful.
The crystal and molecular structures of 6a and 7a were deter-
mined by X-ray diffraction studies. Crystals were prepared by
leaving the dilute solutions in acetonitrile to evaporate freely at
room temperature. The measurements were performed at room
temperature on a Kuma 4CCDκ-axis diffractometer with
graphite-monochromated MoKα radiation (λ = 0.71073Å). Data
were corrected for Lorentz and polarization effects. No absorp-
tion correction was applied. The structures were solved by direct
methods [17] and refined using SHELXL [18]. The full-matrix
2
least-squares refinement was based on F . The positions of all H-
atoms were found from electron density ∆ρ map and refined in
riding model with the isotropic displacement parameters of 1.5
times the respective U values for the parent atoms. Atomic
eq
scattering factors were those as in SHELXL [18].
Reactions of 1a and 1b with 6 Mol of Hydrazine Hydrate.
Compound 1a (1.001 g, 6.45 mmol) and 5 mL of 40%
hydrazine hydrate (39 mmol) were left standing at room temper-
ature (20 ± 2 °C). The solid product (0.63 g), which began to sep-
th
arate on the 13 day of the experiment and was collected by fil-
tration 10 days later, was 2a (yield 62%) [2]. 2b was prepared in
an analogous procedure (yield 58%) [2]; H nmr of 2a (deuterio-
dimethyl sulfoxide): δ 1.06 (s, 6H, 2 x CH ), 2.11 (s, 2H, CH ),
1
3
2
The crystallographic determination of the enamino tau-
tomeric form in solid 7a (Figure 3) was of particular assis-
3.76 (s, 2H, NH ), 7.07 (s, 1H, exocyclic NH), 9.90 ppm (s, 1H,
2
1
endocyclic NH). H nmr of 2b (deuteriodimethyl sulfoxide): δ
1
tance in the interpretation of the H NMR spectrum. Thus,
2
3
2
2.38 (dd, 1H, J = 16.6 Hz, J = 1.6 Hz, CHH), 2.76 (dd, 1H, J =
the low-field one-proton signal at δ = 10.28 ppm observed
in a deuteriodimethylsulfoxide solution could be unequiv-
ocally attributed to the endocyclic NH group, while the
two-proton singlet at δ = 5.35 ppm, to the amino function.
Similar chemical shifts of the nitrogen-attached protons
were also noted in the spectra of 2 (e.g., 7.07 and 9.90 ppm
signals in 2a). It seems therefore legitimate to assume that
the tautomeric form found in crystals predominates also in
a solution and that it is characteristic of other 3-amino- and
3-hydrazinosubstituted pyridazin-6-ones.
3
3
16.6 Hz, J = 7.2 Hz, CHH), 3.72 (dd, 1H, J = 1.6 and 7.2 Hz,
CH), 3.91 (s, 2H, NH ), 7.22-7.32 (m, 6H, C H and exocyclic
2
6 5
13
NH), 9.92 ppm (s, 1H, endocyclic NH). C nmr of 2b (deuterio-
dimethyl sulfoxide): 27.3 (CH ), 44.7 (CH), 126.4, 127.9,
2
128.05, and 142.35 (C H ), 156.35 (C=N), 170.3 ppm (C=O).
6
5
Reaction of 1a with 2 Mol of Hydrazine Hydrate.
Compound 1a (0.997 g, 6.42 mmol) and 1.6 mL of 40%
hydrazine hydrate (13 mmol) left standing at room temperature
yielded after 35 days 0.670 g of a solid product. Trituration with
chloroform (3 x 4 mL) left 0.25 g of 2a (25% yield) as the undis-
solved fraction while evaporation of the extract yielded 0.35 g of
a mixture of two compounds (TLC). Column chromatography
made it possible to isolate 0.159 g of 6a (18.7% yield) and 0.087
g (9.6% yield) of 7a.
EXPERIMENTAL
General Methods.
1-Amino-3,3-dimethylpyrrolidine-2,5-dione 2[(3,3-Dimethyl-5-
oxopyrrolidin-2-ylidene)-hydrazone] (6a).
Melting points were determined in open glass capillaries
(Büchi apparatus) and are reported uncorrected. IR spectra were
recorded with a Carl Zeiss Specord M-80 apparatus as potassium
This compound was obtained as colorless crystals (ethanol),
1
13
mp 195-198º; ir: ν 3304, 3248, and 3188 (NH), 1728 and 1644
bromide pellets. H and C nmr spectra were taken with Varian
400 MHz or Brucker DPX 400 MHz instruments. Mass spectra
were obtained on an AMD-604 Intectra GmbH instrument by
routine electron ionization at 70 eV; in the case of thermally
unstable compounds, the liquid secondary ion (LSI) and electron
spray ionization (ESI) techniques were used. Microanalyses were
carried out on a Perkin-Elmer C-H-N analyzer. Merck AG DC-
-1
1
cm (C=O); H nmr (deuteriochloroform): δ 1.36 (s, 6H, 2 x
CH ), 1.54 (s, 6H, 2 x CH ), 2.46 (s, 2H, CH ), 2.47 (s, 2H,
3
3
2
13
CH ), 4.72 (s, 2H, NH ), 10.16 ppm (s, 1H, NH); C nmr (deu-
2
2
teriochloroform): δ 26.2 and 27.3 (CH ), 37.5 (CCH ), 44.5 and
3
3
45.2 (CH ), 163.4 and 163.7 (C=N), 170.9 and 176.5 ppm
2
+
(C=O); ms: m/z 265 (M , 45%), 233 (100%).
Anal. Calcd. for C
H N O (265.31): C, 54.32; H, 7.22; N,
Alufolien with Kieselgel 60 F were used in TLC purity moni-
12 19 5 2
254
toring. Column chromatography was performed on silicagel 60
Merck AG, granulation 0.063-0.200 mm, with chloroform gradu-
ally supplemented in 2.5% increments with ethanol up to 10%
v/v. Unless otherwise stated, all yield data refer to recrystallized,
chromatographically homogeneous compounds with consistent
elemental analysis results.
26.40. Found: C, 54.35; H, 7.18; N, 26.32.
Crystal data: C N O ; mol. mass 265.31; triclinic, P-1
H
12 19
5 2
(No. 1), a = 9.681(2), b = 11.634(2), c = 12.017(2) Å, α =
3
83.00(3), β = 89.64(3), γ = 82.83(3)°, V = 1357.6(4) Å , Z = 4,
3
-1
d = 1.298; Mg/m ; µ = 0.092 mm ; F(000) = 568; final R (F) =
x
gt
2
0.0486, wRref(F ) = 0.1425 for 3572 reflections [I>4σ(I)].

Jul-Aug 2005
Reaction of β-Cyano Esters with Hydrazine Hydrate
923
6-Amino-5-dimethyl-4,5-dihydro-2H-pyridazin-3-one (7a).
(30th day, 0.049 g; 60th day, 0.072 g; 220th day, 0.097 g). The
total yield of crude 6b was 0.218 g (8.5% relative to 1b) An ana-
lytical sample was obtained by recrystallization from methanol.
This compound was obtained as colorless crystals (acetonitrile),
-1
mp 191-194 °C; ir: ν 3500, 3436, 3316, and 3192 (NH), 1640 cm
1
(C=O); H nmr (deuteriochloroform): δ 1.21 (s, 6H, CH ), 2.29 (s,
N'-(1-Amino-4-hydrazino-4-oxo-2-phenylbutylidene)-4-hyd-
razino-4-oxo-2-phenylbutanehydrazonamide (8b).
3
13
2H, CH ), 5.35 (s, 2H, NH ), 10.28 ppm (s, 1H, NH); C nmr
2
2
(deuteriochloroform): δ 24.2 (CH ), 33.5 (CH ), 41.4 (CCH ),
3
2
3
This compound was obtained as colorless crystals (methanol),
mp 161-163 ºC (decompn); ir: ν 3476, 3352, 3304, and 3196 (NH),
159.5 (C=N), 167.9 ppm (C=O); ms (LSI, 3-nitrobenzyl alcohol):
+
+
m/z 164 [(M + Na) , 10%], 142 [(M + H) , 100%].
Anal. Calcd. for C H N O (141.17): C, 51.05; H, 7.85; N,
-1
1
1628 and 1608 cm (C=O); H nmr (deuteriodimethyl sulfoxide):
6
11 3
2
3
δ 2.34 (dd, 2H, J = 14.8 Hz, J = 7.6 Hz, 2 x CHH), 2.85 (dd, 2H,
J = 14.8 Hz, J = 7.6 Hz, 2 x CHH), 3.90 (t, 2H, J = 7.6 Hz, 2 x
CH), 4.03 (s, 4H, 2 x NH ), 5.75 (s, 4H, 2 x NH ), 7.17-7.33 (m,
29.77. Found: C, 51.07; H, 7.70; N, 29.58.
Crystal data: C H N O; mol. mass 141.18; monoclinic, P2 /c
2
3
6
11
3
1
2
2
(No. 14), a = 10.540(2), b = 21.879(4), c = 10.229(2) Å, β =
13
10H, 2 x C H ), 8.89 ppm (s, 2H, 2 x NH); C nmr (deuteriodi-
6
5
3
3
105.82(3)°, V = 2269.5(8)Å , Z = 12, d = 1.240; Mg/m ; µ =
x
methyl sulfoxide): δ 37.3 (CH ), 44.7 (CH), 126.4, 127.91 128.1,
2
-1
2
0.088 mm ; F(000) = 912; final R (F) = 0.0632, wRref(F ) =
gt
and 142.4 (C H ), 156.4 (C=N), 170.3 ppm (C=O); ms (ESI,
6
5
0.1941 for 3374 reflections [I>4σ(I)].
+
methanol/formic acid): m/z 411 [(M + H) , 100%].
Reaction of 1a with 1.5 Mol of Hydrazine Hydrate in Ethanol.
Compound 1a (1.001 g, 6.44 mmol), 0.48 mL (9.78 mmol) of
99% hydrazine hydrate and 1 mL of ethanol were left standing at
room temperature. The crystals (0.43 g) which were collected by
filtration on the 37th day of the experiment were identified as
98% pure 6a (47% yield). A small amount (0.042 g) of the sec-
ond crop, which was collected by filtration 14 days later, revealed
to be a roughly 1:1 mixture of 6a and 2a.
Anal. Calcd. for C N O (410.47): C, 58.52; H, 6.38; N,
H
20 26
8 2
27.30. Found: C, 58.41; H, 6.29; N, 27.05.
1-Amino-3-phenylpyrrolidine-2,5-dione 2-(5-Oxo-3-phenyl-
pyrrolidin-2-ylidene)hydrazone (6b).
This compound was obtained as colorless crystals (methanol),
mp 234-237º (decompn.); ir: ν 3472 and 3316 (NH), 1624 and
-1
1
1572 cm (C=O); H nmr (deuteriodimethyl sulfoxide): δ 2.23
2
3
2
Reaction of 1a with 1.1 Mol of Hydrazine Hydrate in Ethanol.
(dd, 1H, J = 18.0 Hz, J = 2.0 Hz, CHH), 2.44 (dd, 1H. J = 18.0
3
2
3
Hz, J = 5.6 Hz, CHH), 3.04 (dd, 1H, J = 18.0 Hz, J = 10.0 Hz,
CHH), 3.07 (dd, 1H, J = 18.0 Hz, J = 10.0 Hz, CHH), 4.25 (dd,
1H, J = 2.0 and 5.6 Hz, CH), 4.40 (dd, 1H, J = 10.0 Hz, CH), 5.42
The reaction of 2.001 g (12.9 mmol) of 1a with 0.70 mL (14.2
mmol) of 99% hydrazine hydrate and 2 mL of ethanol was car-
ried out as above to give after 16 days 0.474 g (27% yield) of
pure 6a. The filtrate left standing over 37 days deposited 0.196 g
of a mixture containing mostly 6a and some 4a. Extraction with
chloroform (1 x 1 mL and 2 x 0.6 mL) left 0.066 g of 4a, while
the chloroform solution was subjected to column chromatogra-
phy as above; the head fractions consisted of 4a (0.053 g)
whereas 0.067 g of 6a was obtained in the tail fractions. The total
yield of 4a was 0.119 g (7.48%), and that of 6a, 0.541 g (31.7%).
2
3
(s, 2H, NH ), 6.92-6.94 (m, 5H, C H ), 7.11-7.18 (m, 5H, C H ),
2
6
5
6 5
13
10.92 ppm (s, 1H, NH); C nmr (deuteriodimethyl sulfoxide): δ
37.12 and 38.1 (CH ), 38.3 and 41.7 (CH), 126.9, 127.3, 128.3,
2
128.4, 140.1 and 140.6 (C H ), 159.6 and 159.7 (C=N), 170.4
6
5
+
and 175.45 ppm (C=O); ms (ESI): m/z 362 ([M + H] ,100%).
Anal. Calcd. for C N O (361.40): C, 66.47; H, 5.30; N,
H
20 19
5 2
19.38). Found: C, 66.31; H, 5.22; N, 19.19.
Reaction of 6a with Hydrazine Hydrate.
3,3,8,8-Tetramethyl-2,3,7,8-tetrahydro-1H,6H-dipyrrolo[1,2-
b:1',2'-e][1,2,4,5]-tetrazine-1,6-dione (4a).
Compound 6a (0.134 g, 1.6 mmol) and 2.0 mL (16 mmol) of
40% hydrazine hydrate were left standing at room temperature.
Slow evolution of ammonia was observed although the mixture
did not turn homogeneous. First portion of the product was col-
lected by filtration on the 16th day, while the filtrate was concen-
trated in vacuo to approximately one-third of the initial volume
and left standing for 33 days to deposit the second crop of crys-
tals. The combined fractions (0.093 g) were identified as 2a of
97% purity; the contaminant was unreacted 6a. The overall yield
of 2a was 56%.
This compound was obtained as colorless crystals (ethanol),
mp 335-338 ºC (decompn.); ir: ν 2968, 2932, and 2872 (NH),
-1
1
1716 and 1656 cm (C=O); H nmr (deuteriochloroform): δ 1.40
13
(s, 12H, 4 x CH ), 2.48 ppm (s, 4H, 2 x CH ); C nmr (deuteri-
3
2
ochloroform): δ 26.4 (CH ), 35.2 (CH ), 42.9 (CCH ), 160.1
3
2
3
+
(C=N), 165.4 ppm (C=O); ms: m/z 248 (M , 79%), 233 (100%).
Anal. Calcd. for C N O (248.28): C, 58.05; H, 6.50; N,
H
12 16
4 2
22.56. Found: C, 58.12; H, 6.35; N, 22.47.
Reaction of 1b with 1.11 Mol of 99% Hydrazine Hydrate in
Hydrogenation of 3,9,9-Trimethyl-8,9-dihydro-4H-pyridazino-
[6,1-c][1,2,4]triazine-4,7(6H)-dione (3).
Ethanol.
Compound 1b (2.89 g, 14.23 mmol), 0.77 mL (15.80 mmol) of
99% hydrazine hydrate, and 3 mL of ethanol were left standing at
room temperature. The first fraction of the solid product was col-
lected by filtration after 6 days to give upon a thorough washing
with ethanol (5 x 2 mL) 0.537 g (1.31 mmol) of practically pure
8b (18.4% yield relative to 1b and 24.8% relative to hydrazine
hydrate). An analytical sample was obtained by recrystallization
from methanol. The filtrate deposited on standing another portion
of the reaction products which were removed by filtration when a
reasonable amount had accumulated. Repetition of this procedure
with successive filtrates made it possible to isolate: a mixture of
8b and 6b (15th day of the experiment, 0.111 g) and crude 6b
A mixture of 1.519 g (7.3 mmol) of 3 [3], 75 mL of acetic acid
and 0.313 g of 10% palladized carbon was hydrogenated 13 h
under 50 psig in a Parr apparatus. Upon removal of the catalyst
the filtrate was concentrated in vacuo. The solid residue was
recrystallized twice from methanol to yield 1.128 g (73% yield)
of 5.
3,9,9-Trimethyl-8,9-dihydro-2H-pyridazino[6,1-c][1,2,4triazine-
4,7(3H,6H)-dione (5).
This compound was obtained as colorless crystals (methanol),
mp 154-157º; ir: ν 3412, 3192, and 3112 (NH), 1724 and 1684

924
Vol. 42
K. Wejroch, A. Wesołowska, M. Sadowska, J. Karolak-Wojciechowska,
T. Jagodziński, and J. Lange
-1
1
[7] W. Köhler, M. Bubner and G. Ulbricht, Chem.Ber., 100, 1073
(1967).
[8] K. Körmendy, K. Á. Juhász and É. Lemberkovics, Acta Chim.
Acad. Sci. Hung., 102, 39 (1979).
cm (C=O); H nmr (deuteriochloroform): δ 1.32 (s, 3H, 9-
CH ), 1.33 (s, 3H, 9-CH ), 1.40 (d, 3H, J = 6.8 Hz, 3-CH ), 2.50
3
3
3
(s, 2H, CH ), 3.70 (q, 1H, J = 6.8 Hz, CH), 5.29 (s, 1H, 2-NH),
9.43 ppm (s, 1H, 6-NH) C nmr (deuteriochloroform): δ 13.75
2
13
[9] A. Mrozek, J. Karolak-Wojciechowska, K. Wejroch and J.
Lange, Z. Kristallogr.- New Cryst. Struct., 218, 331 (2003).
[10] The structural formulae of two perhydro analogs were pro-
duced in earlier patent specifications but neither synthetic data nor any
structure evidence nor compound characterization were included in order
to substantiate the reliability of the assignments. See: [a] Y. Kaneko,
Japanese Patent 63,229,455 (1987); Chem. Abstr., 111, 67791n (1989);
[b] T. Hioki and R. Nishimura, European Patent 554,856 (1992); Chem.
Abstr., 120, 148792b (1994).
(3-CH ), 25.6 and 25.9 (9-CH ), 34.4 (9-C), 43.6 (CH ), 51.7
3
3
2
(CH), 141.5 (C=N), 161.0 and 165.7 ppm (C=O); ms: m/z 210
+
(M , 17%), 195 (22%), 167 (100%).
Anal. Calcd. for C H N O (210.23): C, 51.42; H, 6.71; N,
9
14 4 2
26.65. Found: C, 51.59; H, 6.65; N, 26.50.
REFERENCES AND NOTES
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[14] Th. Curtius, A. Darapsky and E. Müller, Chem. Ber., 48, 1614
(1915).
[15] E. Müller and L. Herrdegen, J. Prakt. Chem., 102, 113 (1921).
[16] P. Yates and O. Meresz, Tetrahedron Lett., 77 (1967).
[17] G. M. Sheldrick, SHELXS –97-2. Program for the Solution of
Crystal Structures from Diffraction Data, University of Göttingen,
Germany (1997).
[18] G. M. Sheldrick, SHELXL-97-2. Program for the Refinement
of Crystal Structures from Diffraction Data, University of Göttingen,
Germany (1997).
[1] M. Protiva, V. Řeřicha and J. O. Jilek, Chem. Listy, 44, 231
(1950).
[2] J. Lange, H. Tondys, W. Koberda and M. Gniewosz, Synth.
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