Pyridazine Ring Research Articles

Pd‐ and Ni‐Catalyzed Cross‐Coupling Reactions of Functionalized Organozinc Reagents with Unsaturated Thioethers

A variety of unsaturated thioethers have been subjected to cross-coupling reactions with functionalized zinc reagents in the presence of a transition-metal catalyst. Three different catalytic systems based on Pd(OAc)(2) or [Ni(acac)(2)] and the ligands S-Phos or DPE-Phos gave the best results. N-Heterocyclic thioethers based on a pyridine, pyrimidine, pyrazine, pyridazine, triazine, benzothiazole, benzoxazole, pyrrole, or quinazoline ring, as well as thiomethylacetylenes, serve as electrophiles in this cross-coupling reaction. Aryl-, heteroaryl-, benzylic, and alkylzinc halides with sensitive functionalities, such as ester, nitrile, or ketone groups react at ambient temperature with unsaturated thioethers using a Ni catalyst. The corresponding Pd-catalyzed reactions require slightly higher temperatures. Large-scale cross-coupling experiments (10-20 mmol) with N-heterocycles are also reported.

Incorporation of pyridazine rings in the structure of functionalized π-conjugated materials

Throughout the past few decades, the development of new π-conjugated organic compounds has received a lot of attention due to their potential applications ranging from liquid crystals, light-emitting and nonlinear optical applications to self-assembly and supramolecular chemistry. Most of these applications rely on electron transfer (ET) and excitation energy transfer (EET). Introduction in these conjugated structures of N-heterocycles such as the highly electronegative pyridazine ring appeared particularly interesting since the π-deficient character of the pyridazine, used as a dipolar moiety, favored the electron transfer. Moreover, the presence of nitrogen atoms with free electron pairs allows the pyridazine ring to act like as an effective and stable complexing agent for transition metal ions and to be used in supramolecular chemistry for the construction of highly sophisticated architectures. This review highlights recent π-conjugated materials including pyridazine ring and their applications in various fields.

Monitoring the 1160 cm−1 band of pyridazine to investigate complexes with formamide

Hydrogen bonding between pyridazine (PRD) and formamide (FA) molecules has been investigated both experimentally by Raman spectroscopy on their binary mixtures and theoretically by DFT calculations on various gas-phase PRD:FA clusters. The band at 1160cm−1 of PRD was used for the first time as a marker for monitoring the degree of complexation. Upon dilution with FA, a new band at 1169cm−1 is observed and attributed to hydrogen-bonded PRD. The Raman experiments were complemented by DFT calculations and the corresponding structures, vibrational spectra and binding energies were determined. The most stable species were found to be the 1:2 PRD:FA complexes and such stoichiometry is in excellent agreement with the experimental determination. The shift to higher frequency observed to the prominent modes of PRD may be related to a shortening of the NC and CC bonds, upon complexation, which causes a decrease in the electron delocalization in PRD ring.

Diclomezine: 6-(3,5-dichloro-4-methylphenyl)pyridazin-3(2H)-one

In the title compound, C11H8Cl2N2O, the benzene and pyridazine rings are tilted by 8.6 (1)° relative to each other. In the crystal, pairs of inter­molecular N—H⋯O hydrogen bonds form centrosymmetric dimers. π–π contacts with centroid–centroid distances of 3.698 (2) and 3.751 (1) Å and halogen–halogen inter­actions [3.379 (1) Å] also stabilize the structure.

The Synthesis, X-ray Crystal Structure and Optical Properties of Novel 5-aryl-3-ferrocenyl-1-pyridazinyl-pyrazoline Derivatives

A series of novel 5-aryl-3-ferrocenyl-1-pyridazinyl pyrazoline derivatives was synthesized by the reaction of ferrocenyl chalcone and 3-chloro-6-hydrazinylpyridazine in 10-65% yields. The compounds were characterized using IR, (1)H NMR, HRMS spectroscopic techniques and representative compounds 3c and 4c were assigned based on the X-ray crystallographic structure. The absorption and fluorescence characteristics of the compounds were investigated in chloroform, tetrahydrofuran and acetonitrile, respectively. The results showed that the absorption maxima of the compounds varied from 323 to 327 nm depending on the groups bonded to benzene and pyridazine ring. The maximum emission spectra of compounds in CHCl(3) were dependent on groups in pyridazine ring in which a strong donating-electron group such as propoxyl group on pyridazine ring in N-1 position of pyrazoline made the emission wavelength of 4a-4e small red shifte than that of compounds 3a-3e with chlorine group. The intensity of absorption and fluorescence was also correlated with substituent on aryl ring in C-5 position of pyrazoline. In addition, the absorption spectra of these compounds changed very little, but the fluorescence spectra had much change with increasing solvent polarity.

Synthesis of 2-Aryl-4-(R-sulfanylmethyl)-3-methyl-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-7-ones

Bromination of ethyl 1-aryl-4-acetyl-5-methyl-1H-pyrazole-3-carboxylates gave ethyl 1-aryl-4-(bromoacetyl)-5-methyl-1H-pyrazol-3-carboxylates which were used to alkylate benzenethiol and heterocyclic thiones at the sulfur atom. Reactions of the resulting S-alkylation products with hydrazine or methylhydrazine involved closure of pyridazine ring to afford 2-aryl-3-methyl-4-[phenyl(or hetaryl)sulfanylmethyl]-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-7-ones.

3-Chloro-6-(3,5-dimethyl-1H-pyrazol-1-yl)pyridazine

In the title compound, C9H9ClN4, the dihedral angle between the aromatic rings is 6.25 (9)°. The whole mol­ecule is approximately planar (r.m.s. deviation = 0.070 Å). In the crystal, π–π inter­actions between the centroids of the pyridazine rings [separation = 3.5904 (10) Å] occur.

ChemInform Abstract: A Novel Approach to the Pyrido(4,3-c)pyridazine Ring. Synthesis of Pyrido(4,3-c)pyridazin-5(6H)-one from 3,4-Disubstituted Pyridazines.

The synthesis of new pyrido[4,3-c]pyridazin-5(6H)-one from ethyl 3-methyl-4-pyridazinecarboxylate using an enamination/ring closure sequence is described. The starting material is easily available from a hetero Diels-Alder reaction between a 1,2-diaza-1,3-diene and ethyl vinyl ether and oxidation of the resulting 1,4,5,6-tetrahydropyridazine.

ChemInform Abstract: Direct Pyridazine Ring Synthesis from β-Cyano Esters. A Facile Synthesis of the Derivatives of Tetrahydro-3,6-pyridazinedione 3- Hydrazone.

Abstract 4-Substituted tetrahydro-3,6-pyridazinedione 3-hydrazones (2) (or their 3-hydrazino tautomers 3), useful intermediates in the synthesis of bicyclic pyridazine derivatives, were prepared in satisfactory yields in the reaction of the corresponding alkyl 3-substituted 3-cyanopropionates with hydrazine hydrate.

3-Chloro-6-[(E)-2-(1-phenylethylidene)hydrazinyl]pyridazine

Two independent mol­ecules are present in the asymmetric unit of the title compound, C12H11ClN4, (Z′ = 2): the dihedral angles between the phenyl and pyridizine rings are 8.35 (10) and 37.64 (6)°. In the crystal, the two mol­ecules form inversion dimers with R 2 2(8) ring motifs through inter­molecular N—H⋯N hydrogen bonds. The crystal structure is stabilized by π–π inter­actions between the pyridazine rings of symmetry-related molecules. In one of the independent mol­ecules, the centroid–centroid separations are 3.6927 (13) and 3.7961 (13) Å, whereas in the other, the separations are 3.6909 (13) and 3.9059 (13) Å.

N-(4-Methylphenyl)-6-(pyrazol-1-yl)pyridazin-3-amine

In the title compound, C14H13N5, the pyrazole ring is disordered over two orientations in a 0.571 (10):0.429 (10) ratio and the dihedral angle between the pyridazine ring and the benzene ring is 28.07 (10)°. In the crystal, pairs of N—H⋯N and C—H⋯N hydrogen bonds link the mol­ecules into dimers, with the aid of a crystallographic twofold axis. The packing is consolidated by further C—H⋯N bonds and weak C—H⋯π inter­actions.

Synthesis of pyridazine and thiazole analogs as SGLT2 inhibitors

With anticipation of the improvement in biological aspects in our SGLT2 program, novel pyridazinyl and thiazolyl analogs were designed and efficiently synthesized. The installation of the pyridazine ring at the anomeric carbon of d-glucopyranose was carried out in a stereoselective fashion. On the other hand, a series of thiazolyl analogs was also synthesized through a coupling reaction between perbenzyl gluconolactone 9 and 2-lithiothiazole. Biological activities of the compounds thus prepared were evaluated by the in vitro SGLT2 inhibition assay. Considering assay results, the novel benzylpyridazinyl and benzylthiazolyl analogs, disclosed in this article, could be a quick reference to prospective SGLT2 inhibitors useful for pharmacotherapy.

ChemInform Abstract: Chemistry of Crown Ethers. Synthesis of New Crown Ethers Containing Pyridazine Ring.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Pyridazinopsoralens of wide chemotherapeutic interest

The synthesis of new 6,10-dimethylpyridazino[4,5-h]psoralens, carrying no (4), one (5), or two (6–9) dialkylaminoalkylcarboxamide side chains on the pyridazine ring is reported. All compounds exert a significant photoantiproliferative activity. Moreover, the derivatives characterised by the protonable side chains show a notable cytotoxicity in the dark. The investigation on the mechanism of action demonstrated the capacity to intercalate into DNA base pairs and to inhibit the relaxation activity of topoisomerase II.

ChemInform Abstract: An Unknown Route of Cyclocondensation of peri-Acetylenylquinones with Hydrazine.

Abstract Cyclocondensation of 3-diethylamino-5-phenylethynyl-l,4-naphthoquinone with NH 2 NH 2 resulting in the closure of a pyridazine ring is reported. This hydrazine condensation was unknown for peri -acetylenic derivatives of polycyclic quinones.

N-Phenyl-6-(1H-pyrazol-1-yl)pyridazin-3-amine

The mol­ecule of title compound, C13H11N5, is essentially planar (r.m.s. deviation = 0.0440 Å) and an intra­molecular C—H⋯N hydrogen bond generates an S(6) motif. In the crystal, mol­ecules are connected into chains by inter­molecular N—H⋯N and C—H⋯N hydrogen bonds. In addition, π–π stacking inter­actions are observed between the pyrazole and pyridazine rings [inter­planar distance = 3.6859 (10) Å].

3-(Piperidin-1-yl)-6-(1H-pyrazol-1-yl)pyridazine

In the title compound, C12H15N5, the piperidine ring adopts a chair conformation with the substituent C atom in an equatorial site and the dihedral angle between the pyridazine and pyrazole ring planes is 10.36 (2)°.

Some mechanistic aspects of a nickel-catalyzed electrochemical cross-coupling between aryl halides and substituted chloropyridazines

Abstract The nickel-2,2′-bipyridine catalyzed electrochemical cross-coupling reaction between an aryl halide and a chloropyridazine was investigated by an electrochemical study. The electrochemical behavior of the divalent nickel complex is affected by the presence of pyridazine rings which act as co-ligands of nickel. Cyclic voltammetry indicates that the cross-coupling reaction involves first a rapid oxidative addition of the chloropyridazine on the electrogenerated zerovalent nickel complex. The coupling product is then obtained by reaction with the aryl halide.

3-Chloro-6-{4-[3-(4-chlorophenoxy)propyl]piperazin-1-yl}pyridazine

In the title compound, C17H20Cl2N4O, the piperazine ring adopts a chair conformation and the dihedral angle between the pyridazine ring and the benzene ring is 36.3 (1)°. In the crystal, weak C—H⋯O and C—H⋯(N,N) inter­actions help to establish the packing, which also features short inter­molecular Cl⋯Cl contacts [3.331 (2) Å].

4-Benzyl-6-p-tolylpyridazin-3(2H)-one

The title compound, C18H16N2O, is a new dihydro­pyridazin-3(2H)-one derivative synthesized in one step by condensation of α-benzyl­idene-γ-tolyl­butenolide with hydrazine. The mol­ecule is not planar; the tolyl and pyridazine rings are twisted with respect to each other making a dihedral angle of 27.35 (9)° and the benzyl ring is nearly perpendicular to the pyridazine ring with a dihedral angle of 85.24 (5)°. In the crystal structure, inversion dimers arise, being linked by pairs of N—H⋯O hydrogen bonds. Weak C—H⋯O hydrogen bonds and weak offset π–π stacking stabilize the packing. The π–π stacking occurs between the pyridazine rings of symmetry-related mol­ecules, with a centroid–centroid distance of 3.748 Å, an inter­planar distance of 3.605 Å and a slippage of 1.024 Å.