Pyridazines. XXV. Formation of 2-benzoyl-2,5-dihydro-3-pyridazinecarbonitrile derivatives in the reissert reaction of pyridazines

Pyridazines 1a, b on treatment with potassium cyanide/benzoyl chloride in a mixed solvent system gave 2-benzoyl-2,5-dihydro-3-pyridazinecarbonitriles 3a, b together with products resulting from attack of one mole of cyanide ion and three moles of benzoyl chloride ( 5a, b ). The structures of these novel compounds are proved. A plausible reaction mechanism is proposed, involving rearrangement of initially formed 2a, b into 3a, b . Furthermore, the synthesis of the pyridazine Reissert compound 2a is reported.     

Pyridazines. LIX. An unusual reaction of azidoazolopyridazines with diethylamine

6-Azidoazolopyridazines and 6-azidopyridotetrazolopyridazines react in the presence of diethylamine to give various products. Among them, the corresponding diethylaminomethylene-amino derivatives were formed in a novel reaction.     

Synthesis of 4-fluoroalkyl-substituted pyridazines from fluorinated diazodiketones

Two approaches are reported for the preparation of 3,4,6-trisubstituted pyridazines from fluoroalkyl-containing diazodiketones: the sequence of Wittig/Staudinger/diaza-Wittig and Staudinger/Wittig/diaza-Wittig reactions. The implementation of the Wittig reaction at the first stage gives rise to considerably higher yields of the targeted pyridazines than through initial phosphazines. In both approaches the final stages of the synthesis (the formation of vinylphosphazines and the subsequent diaza-Wittig reaction) occur as a tandem process. R^F-activated carbonyls are much more reactive in Wittig olefination of diazodicarbonyl and 1,3-dioxophosphazine molecules, than non-fluorinated acyl and aroyl carbonyl groups (R^FCO ? COAlk, COAr), and as a result non-fluorinated diazodiketones and their phosphazines do not produce pyridazines under the same conditions.     

Synthesis of 3-amino-4-nitropyrazoles

3-Bromo-1,5-dimethyl-4-nitropyrazole does not react upon heating with aqueous ammonia, while 1,5-dimethyl-3,4-dinitropyrazole under the same conditions yields 3-amino-1,5-dimethyl-4-nitropyrazole, which is formed from 3-bromo-1,5-dimethyl-4-nitropyrazole in the presence of a copper catalyst. The amination of 1-methyl-3,4-dinitropyrazole-5-carboxylic acid is accompanied by decarboxylation, which is characteristic for 4-substituted 1-methylpyrazole-5-carboxylic acids upon heating in aqueous ammonia or water.     

Synthesis of 3-amino-4-fluoropyrazoles

Fluorinated pyrazoles bearing additional functional groups that allow further functionalization are of considerable interest as building blocks in medicinal chemistry. The developed synthetic strategy for new 3-amino-4-fluoropyrazoles consists of a monofluorination of β-methylthio-β-enaminoketones using 1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor) toward the corresponding monofluorinated enaminoketones, followed by condensation with different hydrazines.     

Pyridazines. XXXVII. Novel triazanaphthalene derivatives via intramolecular cyclization reactions of vic-disubstituted pyridazines

8-Phenylpyrido[3,4-d]pyridazines bearing various amino substituents at C-5 ( 7a-d, 8 ) were prepared from ethyl 5-benzyl-4-pyridazinecarboxylate 1 via the fused pyridone 5 . The isomeric 4-phenylpyrido[2,3-d]pyridazines having the amino functions attached to C-2 ( 10a-f ) were obtained by a one-pot cyclization of the amino ketone 1 with appropriate acetamide acetals. These novel triazanaphthalene derivatives are of interest as analogues of diuretic and antithrombotic agents.     

Pyridazines. XXVI. A novel synthesis of pyrano[2,3-d]pyridazines

A novel approach to the title ring system starting with conveniently available cinnamoylacetonitrile ( 1 ) is proposed. It involves the Japp-Klingemann reaction of 1 followed by thermally induced cyclisation of hydrazones 2 and subsequent addition of the resulting pyridazine derivatives 3 to 2-substituted cinnamonitriles 4a, 4b. The structures of the pyrano[2,3-d]pyridazines 5a, 5b , thus obtained, were established on basis of spectroscopic data.     

Pyridazines. XLI synthesis of novel pyrido[3,4-d]pyridazine derivatives from 4,5-disubstituted pyridazines

Pyrido[3,4-d]pyridazines 2–5, 21 bearing one, two, or three aryl substituents in the pyridine moiety are shown to be conveniently accessible from 4-aroyl-5-methylpyridazines or 4,5-diaroylpyridazines, respectively, by condensation reactions with appropriate C-N fragments. In addition, the novel pyridazine-annelated pyridones 24, 25 were found to be easily available from ethyl 5-methyl-4-pyridazinecarboxylate.     

Pyridazines with heteroatom substituents in position 3 and 5. 2. Regioselective introduction of mercapto groups in pyridazines

The nucleophilic substitution of halogen in 3,5-dichloro-6-phenylpyridazine 1 , 5-chloro-2-methyl-6-phenylpyridazin-3(2H)-one 13 as well as in 3-chloro-2-methyl-6-phenylpyridazin-5(2H)-one 14 with methoxy, ethoxy and the 2-methyl-2-propanethiolate anion is described. In the last type of compounds the t-butylthio groups can be eliminated regioselectively with Lewis acids, resulting in the formation of monomercapto and mono-thiopyridazines.     

Pyridazines. XV. Synthesis of 6-aryl-5-amino-3(2H)-pyridazinones as potential platelet aggregation inhibitors

Several 3(2H)-pyridazinones with amino groups at the 5-position of the pyridazine nucleus have been prepared. The 6-aryl-5-halo-3(2H)-pyridazinones obtained from mucochloric and mucobromic acid lead to the corresponding 5-alkylamino-3(2H)-pyridazinones, which were tested as platelet aggregation inhibitors.     

Synthesis of 2-amino-4,5,7-triarylimidazo[1,5-b]pyridazines

The reaction of 4-aryl-1,2-diaminoimidazoles with 1-aryl-2,3-dibromo-3-(4-nitrophenyl)propanones, 2-bromo-1-phenyl-3-(4-chlorophenyl)propenone, and 1,3-diarylpropynones yields 2-amino-4,5,7-triarylimidazo[1,5-b]pyridazines. The structure of one of these products was determined by x-ray diffraction analysis. Kharkov State University, 310077 Kharkov, Ukraine. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1397–1403, October, 1998.     

Pyridazines. XXXVIII. Pyrrolo[1,2-b] pyridazines and 4H-4a,7b-diazacyclopent[cd] indenes

Pyrrolo[1,2-b] pyridazines have been prepared and investigated for electrophilic substitutions. Depending on the electrophile and reaction conditions, mono, di, tri or tetrasubstituted derivatives were formed. Some investigations are reported also for the related 4H-4a,7b-diazacyclopent[cd]-indenes.     

Synthesis of 3-acetyl-2-amino-4-pyridone

A method hxsynthesizing 3-acetyl-2-amino-4-pyyridone has been suggested. The synthesis involves the condensation of dimethylformamide dimethylacetal at the NH₂ group of diphenylboron chelate diacetylketene aminal followed by its intramolecular cyclization under the action of NaOMe in MeOH.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 177–179. January, 1996.     

Synthesis of 3-amino-5-benzylamino-4-nitropyrazole

Conclusion A new efficient method has been developed for the synthesis of 3-amino-5-benzylamino4-nitropyrazole. The key step of this procedure is the preparation of l,l-di(alkylamino)-2nitro-2-cyanoethylenes by the condensation of nitroacetonitrile with isothiourea derivatives.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 10, pp. 2342–2344, October, 1986.     

Synthesis and properties of 4-amino-3-cyanofurazan

Deoximation of the amidoxime of 4-aminofurazan-3-carboxylic acid and dehydration of 4-aminofurazan-3-carboxamide gave 4-amino-3-cyanofurazan. Reactions of the cyano and amino groups were studied.Latvian Institute of Organic Chemistry, Riga, LV-1006. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 693–696, May, 1994.