The synthesis and reactions of certain pyridazine 1-oxides

Nucleophilic displacement reactions under acidic and basic conditions have been studied with 4,6-dinitro-3-methoxypyridazine 1-oxide ( 1 ) and with 6-chloro-3-methoxy-4-nitropyridazine 1-oxide ( 2 ). Depending on the nature of the nucleophilic reagent and the conditions of the reaction we have found that the chloro group, the nitro group, as well as the methoxy group of 1 and 2 may be displaced by the nucleophile. This type of compound possesses significant in vitro antifungal activity.     

Experimental and theoretical molecular and electronic structures of the N-oxides of pyridazine,pyrimidine and pyrazine

The structures of pyridazine N-oxide, pyrimidine N-oxide and pyrazine N-oxide have been determined by X-ray diffraction for the first time. Comparison with theoretical predictions of the equilibrium structures using the B3LYP method together with a cc-pVTZ basis set, show close agreement with the structural parameters observed, and experimental dipole moments, which suggests that the charge distribution is realistic. An ‘atoms in molecules’ (AIM) analysis of the computed wave-functions shows total electron densities rather different from the classical picture of a dative bond, whereas the same wave-functions subjected to Mulliken analysis show a more conventional view of the electron distribution. This latter procedure allows a bond dipole analysis of the N-oxide charge distribution.     

Photochemistry—IX : Formation of cyclopropenyl ketones and furans from pyridazine N-oxides by irradiation

Photolyses of unsubstituted and methyl substituted pyridazine 1-oxides afforded the corresponding cyclopropenyl ketones (6) and furans (7), respectively. Photolysis of 3-phenyl-, 3-methoxy-and 3-hydroxy-pyridazine 1-oxides afforded furans alone, whereas 3-aminopyridazine 1-oxides gave levulinonitriles and 3-cyanopropionaldehydes (11). Mechanism of their formation are discussed.     

Facile synthesis of multi‐functional 1,3,4‐thiadiazine derivatives bearing phthalazine,pyridazine, and pyrido‐pyridazine moieties

A series of novel, multifunctional 1,3,4‐thiadiazine derivatives bearing phthalazines, pyridazines and pyrido‐pyridazines ( 9–13 ) have been synthesized via the multicomponent reaction of (3‐(2‐bromo‐2‐[2‐chloropyrimidin‐4‐yl]acetyl)‐2‐chlorophenyl)‐2,6‐dichloro benzene‐sulfonamide with thiocarbohydrazide and various anhydrides. The reactions were performed by refluxing the components in mixed ethanol/acetic acid to afford the corresponding products in good to excellent yields. All the synthesized compounds were characterized by analytical and spectral studies. The developed method features short reaction time, simple work‐up without chromatographic separation, and a broad range of substrate applicability.     

The selenium-mercury interaction: synthesis,spectroscopic and x-ray structural studies of methylmercury-selenourea complexes

The synthesis of selenium bound selenourea complexes of methylmercury, [CH₃HgSeC(NH₂)₂]X (X=Cl, Br, NO₃, ClO₄) are described. A single crystal X-Ray analysis of the nitrate salt has provided for the first time bond length data pertinent to the biologically important mercury-selenium interaction. Crystals of [CH₃HgSeC(NH₂)₂] NO₃ belong to the space group PnZic with a = 7.524(1), b = 11.204(2), c = 9.738(2)Å, and z = 4. The structure was solved and refined using 561 observed reflections measured on a Syntex P2₁ diffractometer to a final R value of 0.037. The mercury atom is linearly coordinated to the methyl group and the selenium atom of the selenourea with Hg-Se of 2.477(3)Å. Strong Hg-Se bonding is indicated by the X-Ray data and by the ¹H - ¹⁹⁹Hg nmr coupling constants. A comparison of spectroscopic data for analogous thio and selenourea complexes is presented.     

Highly enantioselective synthesis of isoxazoline N-oxides

The reaction of cinchonidine (cinchonine)-derived ammonium salts with nitroolefins in the presence of Cs2CO3 to afford optically active isoxazoline N-oxides with excellent ee and high de values has been developed.     

Energetic heterocyclic N-oxides: synthesis and performance

Novel synthetic strategies toward construction and functionalization of nitrogen-rich energetic compounds bearing at least one heterocyclic N-oxide scaffold are briefly overviewed. The present focus review summarizes main recent advances (published in the period 2017–2022) in the chemistry of five- and six-membered heterocyclic N-oxides as well as their linear combinations and fused bi-, tri- and tetraheterocyclic frameworks which are of paramount importance for the development of next-generation energetic materials. Physicochemical properties along with detonation performance and mechanical sensitivities of the reported high-energy substances are discussed and their application potential is especially emphasized.     

A convenient and facile synthesis of pyridine,pyridazine, pyrimido‐[4,5‐c]pyridazine,pyrido[3,4‐c]pyridazine, 1,6‐naphthyridine and phthalazine derivatives

Ethyl 2‐arylhydrazono‐3‐butyrates 2 reacted with 2‐cyano‐N‐(4‐methylphenyl) acetamide 1a and 2‐cyano‐N‐(thiazol‐2‐yl)acetamide 1b to give the pyridinedione, 4 and pyridazine 5 derivatives in 3:1 ratio. The products 4 and 5 have been transformed into different phthalazine, pyrimido[4,5‐c]‐pyridazine, pyrido[3,4‐c]pyridazine and 1,6‐naphthyridine derivatives. The chemical structures have been confirmed by analytical and spectral analysis.     

Improved procedure for the synthesis of enamine N-oxides

An improved procedure for the preparation of enamine N-oxides involving aminolysis of epoxides, chlorination, N-oxidation, and dehydrochlorination is described. Although isolated beta-chloroamine N-oxides are prone to rearrangements when isolated, these side reactions can be slowed by the presence of stabilizing organic acids. The scope and limitations of this strategy are discussed.     

The synthesis of pyrazino[2,3-d]pyridazine and some of its derivatives

Pyrazino[2,3-d]pyridazine (I) was synthesized by two different routes. 5, 8-Dihydroxy-pyrazino[2, 3-d]pyridazine (IV) was converted to 5, 8-dichloropyrazino[2, 3-d]pyridazine (V) and 5, 8-dibromopyrazino[2, 3-d]pyridazine (Va). When V was treated with various benzyl mercaptans and alkoxides the corresponding disubstituted derivatives were obtained. Compound V when allowed to react with aromatic amines gave 5, 8-bisamino-pyrazino[2,3-d]pyridazines, however, with aliphatic amines only mono substituted products were obtained substituted in the 8-position. The reaction of pyrazine-2, 3-dinitrile with hydrazine gave 5, 8-diaminopyrazino[2, 3-d]pyridazine (X).     

Hydrogen bond directed synthesis of pyridazine and naphthyridine containing macrocycles

This work describes a high-yielding, one-step synthesis of pyrizadine and naphthyridine containing macrocycles directed by intramolecular H-bonding.     

Comparative theoretical studies of substituted bridged bipyridines and their N-oxides

In this work, the experimental synthesized bipyridines azo-bis(2-pyridine),4,4′-dimethyl-3,3′-dinitro-2,2′-azobipyridine, and N,N′-bis(3-nitro-2-pyridinyl)-methane-diamine and a set of designed bipyridines that have similar frameworks but different linkages and substituents were studied theoretically at the B3LYP/6-31G* level of density functional theory. The gas-phase heats of formation were predicted based on the isodesmic reactions, and the condensed-phase heats of formation and heats of sublimation were estimated in the framework of the Politzer approach. The crystal densities have been computed from molecular packing and results show that incorporation of –N=N–, –N=N(O)–, –CH=N–, and –NH–NH– into bipyridines is more favorable than –CH=CH– and –NH–CH₂–NH– for increasing the density. The predicted detonation velocities (D) and detonation pressures (P) indicate that –NH₂, –NO₂, and –NF₂ can enhance the detonation performance, and –NO₂ and –NF₂ are more favorable. Introducing –N=N–, –N=N(O)–, and –NH–NH– bridge groups into bipyridines is also favorable for improving their detonation performance. The oxidation of pyridine N always but that of –N=N– bridge does not always improve the detonation properties. E4–O, the derivative with –N=N– bridge and two –NF₂ substituent groups, has the largest D (9.90 km/s) and P (47.47 GPa). An analysis of the bond dissociation energies shows that all derivatives have good thermal stability.     

The photochemical synthesis of novel heterocyclic compounds from s-triazolo[4,3-b]pyridazine

s-Triazolo[4,3-b]pyridazine (I) photochemically reacted with cyclooctene, cyclododecene, bicyclo[2.2.2]oct-2-ene, bicyclo[2.2.1]hept-2-ene and indene to form tri and tetracyclic triazoles (II-X). Generally, two or more products were formed. For example the reaction with cyclooctene gave 4a,5,7,8,9,10,10a,11-octahydro-11-methylene-6H-cycloocta[4,5]-pyrrole[1,2-b]-s-triazole (II) and the corresponding 11-cyanomethyl product (III). When I was reacted with open chain alkenes, various isomers of the substituted pyrrolo[1,2-b]triazoles (XI-XV) were formed. Since the reaction was not stereospecific, cycloaddition must be a two step process.     

Fatty acid hydrazides in heterocyclic synthesis: Synthesis of 1,2‐diazepine and pyridazine derivatives

1,2‐Diazepinone derivatives 6a–d, 8a,b, and 10a–c were synthesized from the reaction of olefines carrying EWG as ethoxymethylene malononitrile, ethoxymethylene cyanoacetate, and tetracyanoethylene with 1a–f respectively. Also, 5‐alkyl‐6‐oxotetrahydropyridazine‐4,4‐dicarboxylate derivatives 12a–c were afforded via the reaction of 1d–f with diethyl ethoxymethylene malonate. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:259–264, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20294     

Deoxygenation and X-ray photoelectron studies on some quinoxalines and their N-oxides

Deoxygenation results of some quinoxaline dioxides with phosphorous trichloride are presented and compared with previous deoxygenations with other reagents. Differentiation between isomeric quinoxaline oxides using X-ray photoelectron spectroscopy is also discussed.     

The photolysis of berbine N-oxides

Photolysis of trans-canadine N-oxide (3) leads to lactam 5 and formamide 7. Similarly, photolysis of trans-xylopinine N-oxide (12) supplies lactam 14 and amide 15. Oxaziridine 4 is a probable intermediate in these transformations, so that selective oxidation of the berbine nucleus at C-6 has been achieved, accompanied by fission of the N-7-C-14 bond. LAH reduction of lactam 5 gives rise to dibenzazecine 8, while similar treatment of amide 7 generates dibenzazonine 10. Alternatively, acid hydrolysis of 7 furnishes dibenzazonine 11.     

Propargylamine synthesis by copper-catalyzed oxidative coupling of alkynes and tertiary amine N-oxides

An efficient method for synthesizing N,N-dimethylpropargylamines is described. The synthesis exploited the Cu(II)-catalyzed oxidative alkynylation reaction of trimethylamine N-oxides with alkynes in the absence of external oxidant. Both aromatic and aliphatic alkynes were utilized to achieve the corresponding products in moderate to excellent yields. The reaction conditions tolerated ester, hydroxy, and aldehyde groups.