Synthesis, characterization, and structure of some new substituted 5,6-fused ring pyridazines

Article abstract of DOI:10.1080/00397911.2010.482040

Pyridazines are an important class of heterocyclic compounds as a result of their materials and commercial applications. The synthesis of 5,6-fused ring pyridazines 2a-h from 1,2-diacylcyclopentadienes (fulvenes) 1a-h is described herein. This route was quite general, and features an efficient and convenient two-step synthesis of a series of 5,6-fused ring 1,2-disubstituted pyridazines using enolized 1,2-disubstituted fulvenes in a methanolic solution of hydrazine. Full characterization of newly formed fulvene 1e and pyridazines 2a-h are reported. Single-crystal X-ray analysis confirms the molecular structure of pyridazine 2f, which displayed the expected pyridazine fused to the cyclopentadienyl moiety. Adding to their real world capabilities in electronic devices, compounds 2a-h display reasonably high stability in solution and in air at room temperature.

Full text of DOI:10.1080/00397911.2010.482040

Synthetic Communications1, 41: 1357–1369, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.482040
SYNTHESIS, CHARACTERIZATION, AND STRUCTURE
OF SOME NEW SUBSTITUTED 5,6-FUSED RING
PYRIDAZINES
Chad A. Snyder,1 Nathan C. Tice,2 Phenahas G. Sriramula,1
James L. Neathery,1 Justin K. Mobley,1 Chad L. Phillips,1
Andrew Z. Preston,2 Jacob M. Strain,1 Eric S. Vanover,1
Michael P. Starling,1 and Nilesh V. Sahi1
1Department of Chemistry, Western Kentucky University, Bowling Green,
Kentucky, USA
2Department of Chemistry, Eastern Kentucky University, Richmond,
Kentucky, USA
GRAPHICAL ABSTRACT
Abstract Pyridazines are an important class of heterocyclic compounds as a result of their
materials and commercial applications. The synthesis of 5,6-fused ring pyridazines 2a–h
from 1,2-diacylcyclopentadienes (fulvenes) 1a–h is described herein. This route was quite
general, and features an efficient and convenient two-step synthesis of a series of 5,6-fused
ring 1,2-disubstituted pyridazines using enolized 1,2-disubstituted fulvenes in a methanolic
solution of hydrazine. Full characterization of newly formed fulvene 1e and pyridazines
2a–h are reported. Single-crystal X-ray analysis confirms the molecular structure of pyrid-
azine 2f, which displayed the expected pyridazine fused to the cyclopentadienyl moiety.
Adding to their real world capabilities in electronic devices, compounds 2a–h display reason-
ably high stability in solution and in air at room temperature.
Keywords Fulvenes; heterocyclic; NMR; pyridazines; X-ray crystallography
Received December 11, 2009.
Address correspondence to Chad A. Snyder, Chemistry, Western Kentucky University, 1906
College Heights Blvd., Bowling Green, KY 42101, USA. E-mail: chad.snyder@wku.edu
1357

1358
C. A. SNYDER ET AL.
INTRODUCTION
Pyridazines, six-membered aromatic rings with two adjacent nitrogens, are
promising candidates for a variety of materials and commercial applications. These
novel heterocycles are structurally important components of several biologically
active compounds and have been explored as a-helix mimetics.[1] Pyridazines have
also been found to be efficient water oxidation catalysts when compared to dinuclear
ruthenium complexes and have shown high efficiencies in catalytic water oxidation
with turnover numbers of up to 700.[2] Additionally, pyridazines have been incorpor-
ated into iptycene frameworks,[3] compounds researched for polymer sensors,[4] gas
absorption storage,[5] and host–guest chemistry.[6] Furthermore, they continue to
serve as useful intermediates in the synthesis of several other classes of hetero-
cycles.[7] For example, Boger and coworkers reported pyrrole synthesis when treating
pyridazines to a solution of activated zinc in acetic acid.[8] Our current interests focus
on the potential role of pyridazines in next-generation electronic devices that utilize
organics as the semiconducting material. These molecular electronic materials
possess several advantages over traditional inorganic semiconducting materials,
including lower cost of production, higher processibility, and the ability to function
on flexible substrates (so-called plastic electronics).[9–11] These compounds offer new
materials suitable for a variety of real-world applications such as organic
light-emitting diodes (OLEDs) and organic photovoltaic cells (OPVs).[12] Our recent
efforts have been focused on the synthesis of a variety of 5,6-fused ring pyridazines.
These fused heterocycles will serve as synthetic models and building blocks for
potential organic or organometallic conducting polymers.
RESULTS AND DISCUSSION
The compounds presented herein were constructed from 1,2-diacylcyclopenta-
dienes (fulvenes). Fulvenes 1,2-C5H3(COR)(COHR) 1a–h were successfully synthe-
sized using a modified procedure of Linn and Sharkey (Scheme 1).[13] Three molar
equivalents of freshly cracked cyclopentadiene were added to a solution of two molar
equivalents of nBuLi in dry ethyl ether in an ice bath. The suspension was stirred for
Scheme 1. Synthetic route to fulvenes 1a–h.

SYNTHESIS OF SOME 5,6-FUSED RING PYRIDAZINES
1359
10 min, followed by dropwise addition of the appropriate acid chloride. A distinct
color change was observed with addition of each acid chloride. For example,
1,2-C5H3(COC4H3O)(COHC4H3O) (1e), prepared using 2-furoyl chloride, gave an
immediate bright orange suspension. All reaction mixtures were allowed to warm
to room temperature and were stirred for 45 min. The reactions were then hydro-
lyzed with dilute acetic acid, extracted with ethyl ether, dried over MgSO4, filtered,
and reduced to an oil or semisolid. Crude fulvenes 1a–h were filtered through a silica
plug (50:50 dichloromethane=hexane) and the solvent was reduced in vacuo. Any
semisolids were triturated using cold hexane to afford solid fulvenes 1a–h. Yields
for the fulvenes were modest but reasonable (56–86%).[13–16] The newly reported fur-
oyl fulvene, 1,2-C5H3(COC4H3O)(COHC4H3O) (1e), was produced as a bright
orange solid (10.5% yield) following elution through a silica plug. Lower than
expected yields observed for 1e were attributed to the majority of the product being
retained on the silica plug. We are currently optimizing the isolation and purification
methods for fulvene 1e.
The structure of fulvene 1e was confirmed by 1H NMR, 13C NMR, and infra-
red (IR) spectroscopy. The cyclopentadience (Cp) ring protons are observed as a
triplet (CHCHCH) and doublet (CHCHCH) with chemical shifts of 6.07 and
8.15 ppm, respectively. The coupling constants for the Cp triplet and doublet are
4.0 Hz. The furoyl protons are observed as a doublet of doublets (6.62 ppm,
3
3
3JAB ¼ 3.5 Hz, JAC ¼ 1.7 Hz, CHCHCHO), a doublet (7.40 ppm, JBC ¼ 3.5 Hz,
3
CHCHCHO), and a doublet (7.72 ppm, JAB ¼ 1.7 Hz, CHCHCHO). The Cp ring
carbons for fulvene 1e, CHCHCH and CHCHCH, are observed in their typical
range and are found at 112.5 and 119.8 ppm, respectively. IR analysis confirmed
the presence of the carbonyl functional group, with distinct stretching frequencies
at 1530 and 1565 cmꢀ1. These stretches display a shift to lower energies as a result
of the fulvene’s enolized, delocalized structure when in solution, which matches with
the corresponding values for fulvenes 1a–d,f–g.[14–17] Analysis of 1e by gas
chromatography=mass spectrometry (GC=MS) also confirmed the structure or the
furoyl fulvene 1e (Mþ ¼ 254).
The synthesis of the 5,6-fused ring pyridazines 2a–h was accomplished by treat-
ing fulvenes 1,2-C5H3(COR)(COHR) 1a–h to a solution of excess hydrazine hydrate
in methanol at room temperature (Scheme 2). Reaction times varied from 24–48 h,
followed by a water quench and then ethyl ether extraction. Pyridazines 2a–h were
purified via silica plug and=or hexane trituration. Percentage yields for compounds
2a–h ranged from 41% to 89%.
Scheme 2. Synthetic route for pyridazines 2a–h.

1360

SYNTHESIS OF SOME 5,6-FUSED RING PYRIDAZINES
1361
2h
Table 2. Selected IR data for 2a–h
Bond
2a
2b
2c
2d
2e
2f
2g
=
C
N
1592
3171
1596
3164
1592
3059
1578
3063
1612
3120
1598
3192
1573
3057
1595
3092
NꢀH
1
The structures for pyridazines 2a–h were confirmed by H NMR, 13C NMR,
and IR spectroscopy and are listed in Tables 1 and 2. The Cp ring protons
CHCHCH are observed as a doublet and found in the range 7.05–7.84 ppm, whereas
triplets are seen at 7.21–7.61 ppm corresponding to the CHCHCH proton. The
CHCHCH and CHCHCH coupling constants are observed between 3J ¼ 3.4–
4.0 Hz. Amine protons for 2a–h are observed highly downfield in the range of
11.2–12.1 ppm because of their delocalized nature in solution. The 13C NMR spec-
trum for 2a–h showed the disappearance of the carbonyl group (160.0–169.3 ppm)
=
as observed in fulvenes 1a–h. Instead, pyridazines 2a–h show a characteristic C N
carbon signal ranging from 136.5 to 144.3 ppm. The Cp ring carbons, CHCHCH
carbons, are seen in the narrow range of 108.5–114.3 ppm, whereas the CHCHCH
signals are observed between 119.5 and 120.3 ppm. Pyridazine 2d CHCHCH signal
is found higher upfield at 112.4 ppm, presumably reflecting the greater delocalized
=
nature of its C N bond because of the larger conjugation of the benzo[b]thienyl
groups. IR spectroscopy confirms the loss of carbonyl stretches and the appearance
of C N stretches seen between 1573 and 1612 cmꢀ1 (Table 2). Secondary amine sig-
=
nals for 2a–h are found between 3059 and 3192 cmꢀ1. GC=MS analysis confirms the
structures of 2a–h, with the expected parent ion peak for all cases except 2g, which
did not display an Mþ peak (298, Mþ – HOCH3).
Comparison between the thienyl and furyl substituents in the pyridazines
formed shows a relatively high degree of similarity in the chemical environment
for each proton (Table 3). For example, the signals for the heterocylic substituents
in 2a and 2e match very closely. Thienylic Ha (7.54 ppm) and furyl Ha (7.33 ppm)
Table 3. Selected 1H data for 2a–c,e substituents
Pyridazine 2 substituent
Ha
Hb
3
3
=
2a, X S, R Hc
=
7.54 (d, 1H, JAB ¼ 4.55 Hz)
7.68 (dd, 1H, JAB ¼ 4.55 Hz,
3JAC ¼ 8.0 Hz)
7.57 (d, J ¼ 4.0 Hz)
7.23 (d, J ¼ 3.4 Hz)
=
2b, X S, R Cl
=
7.03 (d, J ¼ 4.0 Hz)
7.62 (d, J ¼ 3.4 Hz)
=
2c, X S, R CH3
=
3
3
= =
2e, X O, R H
7.33 (d, 1H, JAB ¼ 3.5 Hz)
6.66 (dd, 1H, JAB ¼ 3.5 Hz,
3JAC ¼ 1.7 Hz)

1362
C. A. SNYDER ET AL.
Table 4. Selected selected 1H data for 2f–h substituents
Pyridazine 2 substituent
Ha
Hb
7.81 (d, 1H, 3J ¼ 8.55 Hz)
6.96 (d, 1H, 3J ¼ 8.6 Hz)
7.81 (d, 1H, 3J ¼ 8.0 Hz)
7.46 (d, 1H, 3J ¼ 8.55 Hz)
7.85 (d, 1H, 3J ¼ 8.6 Hz)
7.29 (d, 1H, 3J ¼ 8.0 Hz)
=
2f, R Cl
=
2g, R OCH3
=
2h, R CH3
3
protons are both seen as doublets with coupling constants at JAB ¼ 4.55 and
3JAB ¼ 3.5 Hz respectively. Protons Hb for each case are observed as a doublet of
doublets with chemical shifts 7.68 and 6.66 ppm, respectively. However, stronger
coupling interactions were observed with the thienylic Hb, with its coupling con-
3
3
stants at JAB ¼ 4.55 Hz and JAC ¼ 8.0 Hz. By comparison, the furylic Hb proton’s
3
3
coupling constants were JAB ¼ 3.5 Hz, JAC ¼ 1.7 Hz. For compounds 2b and c,
the thienylic protons Ha and Hb are seen as two doublets having coupling constants
of 3J ¼ 3.4 Hz and 4.0 Hz respectively and in observed ranges closely match those of
the corresponding protons in 2a.
1
With respect to the H NMR signals of their aryl substituents, phenyl substi-
tuted pyridazines 2f–h display similar chemical shifts and coupling constants
(Table 4). The phenyl Ha protons for each case are seen in the range 6.96–7.81 ppm
as a doublet with coupling constants ranging from 8.0 to 8.6 Hz. Phenyl Hb protons
are also observed as a doublet from 7.29 to 7.85 ppm (3J ¼ 8.0–8.6 Hz).
The structure of pyridazine 2f was determined by X-ray crystallographic meth-
ods. The crystals for which data were collected were typical of others in the batch,
which had been grown by slow evaporation from acetone at room temperature.
These crystals were mounted on glass fibers with Paratone N oil. Data were collected
at 90 K on a Nonius KappaCCD diffractometer. The main programs used were
DENZO-SMN to obtain cell parameters and for data reduction, SCALEPACK
for absorption correction, SHELXS-86 for structure solution, and SHELXL-93
for refinement.[18] Hydrogen atoms were placed in geometrically calculated positions.
Crystal data and a summary of experimental details are given in Table 5.
Recrystallization of 2f from hot acetone affords the pyridazine as
yellow-orange block crystals (Fig. 1). Pyridazine 2f crystallizes in a triclinic P-1 space
group, with one molecule in the unit cell. The average Cp carbon–carbon bond
˚
lengths for 2f are 1.4115(22) A, and the average aromatic ring carbon–carbon bond
˚
lengths are 1.3927(10) A. The N1–N2 bond length for the pyridazine portion of 2f is
˚
1.3586(15) A. The para-chloro substitutents observed a carbon–chlorine bond length
˚
˚
of 1.7437(13) A and 1.7382(13) A. X-ray analysis shows the phenyl rings are twisted
out of the plane of the central pyridazine, with the [C13–C8–C7–N2] and [C19–C14–
C1–N1] torsion angles at ꢀ36.92 ꢁ and ꢀ39.73 ꢁ respectively. One acetone solvent

SYNTHESIS OF SOME 5,6-FUSED RING PYRIDAZINES
1363
Table 5. Crystal data and structure refinement for pyridazine 2f
Empirical formula
C22H18Cl2N2O
Formula weight
Temperature
397.28
90.0(2) K
˚
0.71073 A
Triclinic, P-1
Wavelength
Crystal system, space group
Unit cell dimensions
a ¼ 97.9313(7)o
b ¼ 93.0136(7)o
c ¼ 95.8685(7)o
˚
a ¼ 8.6250(1) A
˚
b ¼ 9.8027(2) A
˚
c ¼ 11.4677(2) A
3
˚
Volume
Z
953.08(3) A
2
Calculated density
Absorption coefficient
F(000)
1.384 Mg=m3
0.355 mmꢀ1
412
Crystal size
h range for data collection
Limiting indices
0.20 ꢂ 0.15 ꢂ 0.15 mm
1.80 to 27.47o
ꢀ11 ꢃ h ꢃ 11, ꢀ12 ꢃ k ꢃ 12, ꢀ14 ꢃ l ꢃ 14
21631=4346 [R(int) ¼ 0.0195]
99.8%
Reflections collected=unique
Completeness to h ¼ 27.47
Absorption correction
Max. and min. transmission
Refinement method
Data=restraints=parameters
Goodness of fit on F2
Final R indices [I > 2 r(I)]
R indices (all data)
Largest diff. peak and hole
Semi-empirical from equivalents
0.949 and 0.932
Full-matrix least-squares on F2
4346=0=246
1.014
R1 ¼ 0.0322, wR2 ¼ 0.0856
R1 ¼ 0.0391, wR2 ¼ 0.0908
ꢀ3
˚
0.383 and ꢀ0.278 e.A
Figure 1. Molecular structure for pyridazine 2f.

1364
C. A. SNYDER ET AL.
molecule co-crystallized with pyridazine 2f and displayed a hydrogen bonding inter-
action between N1–H1 to O1. The calculated hydrogen bond (H1 . . . O1) distance is
˚
2.00 A.
EXPERIMENTAL
All reactions were carried out using standard Schlenk techniques under a
nitrogen atmosphere unless otherwise noted. NMR solvents CDCl3 and dimethyl-
n
sulfoxide (DMSO-d6; Aldrich) were used without further purification. BuLi, dicy-
clopentadiene, methanol, hydrazine hydrate, thienoyl chloride, 5-chlorothienoyl
chloride, benzo[b]thienyl chloride, 2-furoyl chloride, p-chlorobenzoyl chloride, p-
methoxybenzoyl chloride, and toluoyl chloride (Aldrich) were used without further
purification. Fulvenes 1,2-C5H3(COC4H3S)(COHC4H3S) (1a), 1,2-C5H3(COC4
H2SCl)(COHC4H2SCl) (1b), 1,2-C5H3(COC4H2SCH3)(COHC4H2SCH3) (1c), C5H3
(COC8H5S)(COHC8H5S) (1d), 1,2-C5H3(COC6H4Cl)(COHC6H4Cl) (1f), 1,2-C5H3
(COC6H4OCH3)(COHC6H4OCH3) (1g), and 1,2-C5H3(COC6H4CH3)(COHC6H4
CH3) (1h) were prepared according to the literature methods.[13–17] Ethyl ether was
dried over sodium benzophenone ketyl.
1H and 13C NMR spectra were recorded on a JEOL 500-MHz NMR spec-
trometer at ca. 22 ꢁC and were referenced to residual solvent peaks. All 13C NMR
spectra were listed as decoupled. IR spectra were recorded on a Spectrum One
Fourier transform (FT)–IR spectrometer. Electron ionization (EI) mass spectra were
recorded at 70 eV on a Varian Saturn GC=MS. Melting points were taken on a
standard Mel-Temp apparatus. X-ray diffraction data were collected at 90 K on a
Nonius KappaCCD diffractometer at the University of Kentucky X-ray Crystallo-
graphic Laboratories. Elemental analysis were performed at Western Kentucky
University’s Advanced Materials Institute.
Synthesis of 1,2-C5H3(COC4H3O)(COHC4H3O) (1d)
Freshly cracked cyclopentadiene (3.14 mL, 2.51 g, 38.1 mmol) was added drop-
wise to a cooled solution (0 ꢁC) of n-butyllithium (16.2 mL of 2.50 M, 23.4 g,
40.5 mmol) in ethyl ether (120 mL). A white precipitate of cyclopentadienyllithium
was formed immediately. The suspension was stirred for 10 min, and 2-furoyl chlor-
ide (2.48 mL, 3.29 g, 25.2 mmol) was added dropwise. A bright orange color formed
immediately. The solution was stirred for 45 min at room temperature. The reaction
mixture was hydrolyzed with dilute (3%) acetic acid (100 mL). The organic layer was
separated, and the aqueous layer was extracted twice more with ethyl ether
(2 ꢂ 10 mL). The combined ethyl ether extracts were dried (MgSO4) and removed
under reduced pressure to leave a red oil. The oil was eluted through a silica plug
(50:50 dichloromethane=hexane) to give an orange solution. The organic solution
was removed under reduced pressure to leave an orange semisolid. The solid was tri-
turated with hexane (2 ꢂ 10 mL) to leave a bright orange solid (337 mg, 1.33 mmol,
10.5%). Mp: 109–110 ꢁC. 1H NMR (500 MHz, CDCl3, ppm): d 6.07 (t, 1H, 3J ¼ 4 Hz,
3
3
Hz, CHCHCH), 6.62 (dd, 1H, JAB ¼ 3.5 Hz, JAC ¼ 1.7 Hz CHCHCHO), 7.40 (d,
3
3
1H, JBC ¼ 3.5 Hz, CHCHCHO), 7.72 (d, 1H, JAB ¼ 1.7 Hz, CHCHCHO), 8.15
(d, 1H, 3J ¼ 4 Hz, CHCHCH). 13C NMR (125 MHz, CDCl3, ppm): d 83.8

SYNTHESIS OF SOME 5,6-FUSED RING PYRIDAZINES
1365
(CHCCO), 112.5 (CHCHCH), 119.8 (CHCHCH), 123.5 (CCO), 124.1, 139.3, 146.9
(Fr), 152.0 (OCCO), 169.3 (CO). IR (KBr, cmꢀ1): 1530, 1565 (COC4H3O), 3076,
3115, 3134, 3143 (CꢀH). MS: m=z 254 (Mþ), 186 (Mþ – C4H4O), 119 (Mþ
–
2C4H4O). Anal. calcd. for C15H10O2: C, 70.86; H, 3.96. Found: C, 67.56; H, 3.56.
Synthesis of 1,2-C5H3(CC4H3SNH)(CC4H3SN) (2a)
1,2-C5H3(COC4H3S)(COHC4H3S) (1a, 164 mg, 0.573 mmol) was dissolved in
50 mL of methanol in a 200-mL round-bottom flask. An excess of hydrazine hydrate
(1.00 mL, 1.03 g, 20.6 mmol) was added to the solution. The solution was stirred 48 h.
Water (20 mL) was added to the reaction, and an orange precipitate formed immedi-
ately. The aqueous suspension was washed with ethyl ether (3 ꢂ 10 mL), and the
organic layers were collected, dried (MgSO4), and filtered. The volatiles were
removed in vacuo, and the crude product was triturated with cold hexane to give
1,2-C5H3(CC4H3SNH)(CC4H3SN) (2a, 124 mg, 0.439 mmol, 76.5%) as a red powder.
1
3
Mp: 131–134 ꢁC. H NMR (500 MHz, CDCl3, ppm): d 7.21 (t, 1H, J ¼ 4.0 Hz,
3
3
CHCHCH), 7.29 (d, 1H, JBC ¼ 4.55 Hz, CHCHCHS), 7.54 (d, 1H, JAB ¼ 4.55 Hz,
Hz, CHCHCHS), 7.68 (dd, 1H, 3JAB ¼ 4.55 Hz, 3JAC ¼ 8.0 Hz CHCHCHS), 7.84 (br
s, 1H, CHCHCH), 11.2 (br s, 1H, NH). 13C NMR (125 MHz, CDCl3, ppm): d 109.5
(CHCHCH), 119.8 (CHCHCH), 123.2 (NCCCH), 127.9, 128.1, 128.6, 132.7, 133.1,
134.0 (Tp) 139.4 (CHCHCN). IR (KBr, cmꢀ1): 1592 (CN), 3064, 3095 (CꢀH), 3171
(NꢀH). MS: m=z 282 (Mþ). Anal. calcd. for C15H10N2S2: C, 63.80; H, 3.57. Found:
C, 63.14; H, 3.92.
Synthesis of 1,2-C5H3(CC4H2SClNH)(CC4H2SClN) (2b)
1,2-C5H3(COC4H2SCl)(COHC4H2SCl) (1b, 100 mg, 0.394 mmol) was dis-
solved in 50 mL of methanol in a 200-mL round-bottom flask. An excess of hydra-
zine hydrate (1.00 mL, 1.03 g, 20.6 mmol) was added to the solution. The solution
was stirred 48 h. Water (20 mL) was added to the reaction, and an orange precipi-
tate formed immediately. The aqueous suspension was washed with ethyl ether
(3 ꢂ 10 mL), and the organic layers were collected, dried (MgSO4), and filtered.
The volatiles were removed in vacuo, and the crude product was triturated with
cold hexane to give 1,2-C5H3(CC4H2SClNH)(CC4H2SClN) (2b, 60.5 mg,
0.173 mmol, 60.8%) as an orange-red powder. Mp: 146–148 ꢁC. 1H NMR
(500 MHz, CDCl3, ppm): d 7.03 (d, 1H, 3J ¼ 4.0 Hz, ClCCHCH), 7.21 (d, 1H,
3J ¼ 3.5 Hz, CHCHCH), 7.53 (t, 1H, 3J ¼ 3.5 Hz, CHCHCH), 7.57 (d, 1H,
3J ¼ 4.0 Hz, ClCCHCH), 11.8 (br s, 1H, NH). 13C NMR (125 MHz, CDCl3,
ppm): d 109.5 (CHCHCH), 119.5 (CHCHCH), 127.3, 127.5, 133.8, 139.9 (Tp)
141.2 (CHCHCN). IR (KBr, cmꢀ1): 1596 (CN), 3054 (CꢀH), 3164 (NꢀH). MS:
m=z 350 (Mþ), 315 (Mþ – Cl). Anal. calcd. for C15H8Cl2N2S2: C, 51.29; H,
2.30. Found: C, 56.03; H, 4.01.
Synthesis of 1,2-C5H3(CC4H2SCH3NH)(CC4H2SCH3N) (2c)
1,2-C5H3(COC4H2S CH3)(COHC4H2SCH3) (1c, 329 mg, 1.05 mmol) was
dissolved in 50 mL of methanol in a 200-mL round-bottom flask. An excess of

1366
C. A. SNYDER ET AL.
hydrazine hydrate (1.00 mL, 1.03 g, 20.6 mmol) was added to the solution. The sol-
ution was stirred 48 h. Water (20 mL) was added to the reaction, and an orange pre-
cipitate formed immediately. The aqueous suspension was washed with ethyl ether
(3 ꢂ 10 mL), and the organic layers were collected, dried (MgSO4), and filtered.
The volatiles were removed in vacuo, and the crude product was triturated with cold
hexane to give 1,2-C5H3(CC4H2SClNH)(CC4H2SClN) (2c, 288 mg, 0.928 mmol,
1
88.6%) as an orange powder. Mp: 146–148 ꢁC. H NMR (500 MHz, CDCl3, ppm):
3
3
d 2.58 (s, 3H, CH3), 6.67 (d, 2H, J ¼ 4.0 Hz, CHCHCH), 7.23 (d, 1H, J ¼ 3.4 Hz,
CHCHCCH3), 7.48 (t, 1H, 3J ¼ 4.0 Hz, CHCHCH), 7.62 (d, 1H, 3J ¼ 3.4 Hz,
CHCHCCH3), 11.3 (br s, 1H, NH). 13C NMR (125 MHz, CDCl3, ppm): d 15.6
(CH3), 109.2 (CHCHCH), 119.4 (CHCHCH), 126.5, 128.2, 132.4 (Tp) 143.6
(CHCHCN). IR (KBr, cmꢀ1): 1592 (CN), 2855, 2959 (CꢀH), 3059 (NꢀH). MS:
m=z 310 (Mþ). Anal. calcd. for C17H14N2S2: C, 65.77; H, 4.55. Found: C, 62.65;
H, 5.25.
Synthesis of 1,2-C5H3(CC8H5SNH)(CC8H5SN) (2d)
1,2-C5H3(COC8H5S)(COHC8H5S) (1d, 257 mg, 0.665 mmol) was dissolved in
50 mL of methanol in a 200-mL round-bottom flask. An excess of hydrazine hydrate
(1.00 mL, 1.03 g, 20.6 mmol) was added to the solution. The solution was stirred 48 h.
Water (20 mL) was added to the reaction, and an orange precipitate formed immedi-
ately. The aqueous suspension was washed with ethyl ether (3 ꢂ 10 mL), and the
organic layers were collected, dried (MgSO4), and filtered. The volatiles were
removed in vacuo, and the crude product was triturated with cold hexane to give
1,2-C5H3(CC8H5SNH)(CC8H5SN) (2d, 60.0 mg, 0.157 mmol, 26.4%) a purple pow-
der. Mp: 168–172 ꢁC. 1H NMR (500 MHz, CDCl3, ppm): d 6.66 (dd, 1H,
3
3
3JAB ¼ 3.5 Hz, JAC ¼ 1.7 Hz, Tp), 7.25 (d, 1H, J ¼ 4 Hz, CHCHCH), 7.33 (d, 1H,
3J ¼ 4 Hz, CHCHCH), 7.53 (t, 1H, J ¼ 4 Hz, CHCHCH), 7.66 (m, 2H, Tp), 11=.2
3
(br s, 1H, NH). 13C NMR (125 MHz, CDCl3, ppm): d 108.5 (CHCHCH), 112.4
(CHCHCH), 112.7 (NCCCH), 112.6, 118.0, 133.2 (Tp) 144.3 (CHCHCN). IR
(KBr, cmꢀ1): 1578 (CN), 3006 (CꢀH), 3063 (NꢀH). MS: m=z 382 (Mþ). Anal. calcd.
for C25H14N2S2: C, 72.22; H, 3.69. Found: C, 65.74; H, 4.72.
Synthesis of 1,2-C5H3(CC4H3ONH)(CC4H3ON) (2e)
1,2-C5H3(COC4H3O)(COHC4H3O) (1e, 100 mg, 0.394 mmol) was dissolved in
50 mL of methanol in a 200-mL round-bottom flask. An excess of hydrazine hydrate
(1.00 mL, 1.03 g, 20.6 mmol) was added to the solution. The solution was stirred 48 h.
Water (20 mL) was added to the reaction, and an orange precipitate formed immedi-
ately. The aqueous suspension was washed with ethyl ether (3 ꢂ 10 mL), and the
organic layers were collected, dried (MgSO4), and filtered. The volatiles were
removed in vacuo, and the crude product was triturated with cold hexane to give
1,2-C5H3(CC4H3ONH)(CC4H3ON) (2e, 40.0 mg, 0.160 mmol, 40.6%) as a red pow-
der. Mp: 146–148 ꢁC. 1H NMR (500 MHz, CDCl3, ppm): d 6.66 (dd, 1H,
3
3JAB ¼ 3.5 Hz, JAC ¼ 1.7 Hz CHCHCHO), 7.25 (d, 1H, 3J ¼ 4.0 Hz, CHCHCH),
3
3
7.33 (d, 1H, J ¼ 3.5 Hz, CHCHCHO), 7.53 (t, 1H, J ¼ 4.0 Hz, CHCHCH), 7.66
(m, 2H, Fr), 11.2 (br s, 1H, NH). 13C NMR (125 MHz, CDCl3, ppm): d 108.5

SYNTHESIS OF SOME 5,6-FUSED RING PYRIDAZINES
1367
(CHCHCH), 112.4 (CHCHCH), 112.7 (NCCCH), 112.6, 118.0, 133.2 (Fr) 144.3
(CHCHCN). IR (KBr, cmꢀ1): 1612 (CN), 2958 (CꢀH), 3120 (NꢀH). MS: m=z
250 (Mþ), 221 (Mþ– CHO), 193 (Mþ – C2H2O2). Anal. calcd. for C15H10N2O2: C,
71.99; H, 4.03. Found: C, 74.32; H, 6.30.
Synthesis of 1,2-C5H3(CC6H4ClNH)(CC6H4ClN) (2f)
1,2-C5H3(COC6H4Cl)(COHC6H4Cl) (1f, 256 mg, 0.766 mmol) was dissolved in
50 mL of methanol in a 200-mL round-bottom flask. An excess of hydrazine hydrate
(1.00 mL, 1.03 g, 20.6 mmol) was added to the solution. The solution was stirred 24 h.
Water (20 mL) was added to the reaction, and an orange precipitate formed immedi-
ately. The aqueous suspension was washed with ethyl ether (3 ꢂ 10 mL), and the
organic layers were collected, dried (MgSO4), and filtered. The volatiles were
removed in vacuo, and the crude product was triturated with cold hexane to give
1,2-C5H3(CC6H4ClNH)(CC6H4ClN) (2f, 186 mg, 0.548 mmol, 74.0%) as
a
yellow-orange powder. Mp: 218–222 ꢁC. 1H NMR (500 MHz, CDCl3, ppm): d
3
3
7.05 (d, 1H, J ¼ 3.45 Hz, CHCHCH), 7.46 (d, 1H, J ¼ 8.55 Hz, CHCHCCl), 7.54
3
3
(t, 1H, J ¼ 3.45 Hz, CHCHCH), 7.81 (d, 1H, J ¼ 8.55 Hz, CHCHCCl), 11.8 (br s,
1H, NH). 13C NMR (125 MHz, CDCl3, ppm): d 109.2 (CHCHCH), 120.3
(CHCHCH), 129.4, 128.9, 133.4 (Ph) 136.5 (CHCHCN). IR (KBr, cmꢀ1): 1598
(CN), 3047 (CꢀH), 2931, 2965 (CH3), 3192 (NꢀH). MS: m=z 338 (Mþ), 302 (Mþ
– Cl). Anal. calcd. for C19H12N2Cl2: C, 67.27; H, 3.57. Found: C, 67.56; H, 3.56.
Synthesis of 1,2-C5H3(CC6H4OCH3NH)(CC6H4OCH3N) (2g)
1,2-C5H3(COC6H4OCH3)(COHC6H4OCH3) (1g, 383 mg, 1.15 mmol) was dis-
solved in 50 mL of methanol in a 200-mL round-bottom flask. An excess of hydra-
zine hydrate (1.00 mL, 1.03 g, 20.6 mmol) was added to the solution. The solution
was stirred 24 h. Water (20 mL) was added to the reaction, and an orange precipitate
formed immediately. The aqueous suspension was washed with ethyl ether
(3 ꢂ 10 mL), and the organic layers were collected, dried (MgSO4), and filtered.
The volatiles were removed in vacuo, and the crude product was triturated with cold
hexane to give 1,2-C5H3(CC6H4OCH3NH)(CC6H4OCH3N) (2g, 262 mg,
0.793 mmol, 69.2%) as a yellow solid. Mp: 180–184 ꢁC. 1H NMR (500 MHz, CDCl3,
ppm): d 3.90 (s, 3H, CH3), 6.96 (d, 1H, 3J ¼ 8.6 Hz, OCHCH), 7.07 (d, 1H,
3J ¼ 3.4 Hz, CHCHCH), 7.54 (t, 1H, 3J ¼ 3.4 Hz, CHCHCH), 7.85 (d, 1H,
3J ¼ 8.6 Hz, OCCHCH), 12.1 (br s, 1H, NH). 13C NMR (125 MHz, CDCl3, ppm):
d 55.4 (OCH3), 108.8 (CHCHCH), 114.3 (CHCHCH), 120.2 (CCN), 130.0, 131.9
(Ph) 161.0 (CHCHCN). IR (KBr, cmꢀ1): 1573 (CN), 2934, 2963 (CH3), 3057
(NꢀH). MS: m=z 298 (Mþ – HOCH3), 239 (Mþ – C6H4OCH3). Anal. calcd. for
C21H18N2O2: C, 76.34; H, 5.49. Found: C, 74.32; H, 6.30.
Synthesis of 1,2-C5H3(CC6H4CH3NH)(CC6H4CH3N) (2h)
1,2-C5H3(COC6H4CH3)(COHC6H4CH3) (1 h, 369 mg, 1.22 mmol) was dis-
solved in 50 mL of methanol in a 200-mL round-bottom flask. An excess of hydra-
zine hydrate (1.00 mL, 1.03 g, 20.6 mmol) was added to the solution. The solution

1368
C. A. SNYDER ET AL.
was stirred 24 h. Water (20 mL) was added to the reaction, and an orange precipitate
formed immediately. The aqueous suspension was washed with ethyl ether
(3 ꢂ 10 mL), and the organic layers were collected, dried (MgSO4), and filtered.
The volatiles were removed in vacuo, and the crude product was triturated with cold
hexane to give 1,2-C5H3(CC6H4CH3NH)(CC6H4 CH3N) (2h, 250 mg, 0.838 mmol,
1
68.9%) as a red powder. Mp: 182–186 ꢁC. H NMR (500 MHz, CDCl3, ppm): d
3
3
2.46 (s, 3H, CH3), 7.07 (d, 1H, J ¼ 4.0 Hz, CHCHCH), 7.29 (d, 1H, J ¼ 8.0 Hz,
CH3CHCH), 7.49 (t, 1H, 3J ¼ 4.0 Hz, CHCHCH), 7.81 (d, 1H, 3J ¼ 8.0 Hz,
CH3CHCH), 11.5 (br s, 1H, NH). 13C NMR (125 MHz, CDCl3, ppm): d 108.9
(CHCHCH), 120.4 (CHCHCH), 128.5, 129.0, 129.7, 130.0, 132.2 (Ph) 141.2
(CHCHCN). IR (KBr, cmꢀ1): 1595 (CN), 3031 (CꢀH), 2918 (CH3), 3092 (NꢀH).
MS: m=z 298 (Mþ), 283 (Mþ – CH3), 207 (Mþ – C6H4CH3). Anal. calcd. for
C21H18N2: C, 84.53; H, 6.08. Found: C, 81.62; H, 6.55.
ACKNOWLEDGMENTS
We acknowledge our sources of financial support, including Western Kentucky
University’s Chemistry Department, their Office of Sponsored Programs, their
Faculty Scholarship Council, and the WKU Advanced Materials Institute. In
addition, other sources of support include Eastern Kentucky University’s Chemistry
Diversity Initiative, their University Research Committee, and their Department of
Chemistry. We also thank Dr. Sean Parkin and the University of Kentucky’s X-ray
Crystallography Laboratories for their support with the crystallographic character-
ization and analysis.
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