Branko Stanovnik

Synthesis of pyridazine derivatives—VIII : Imidazo(1,2,-b)pyridazines and some tricyclic aza analogs

Abstract 6-Substituted and 3,6-disubstituted imidazo(1,2-b)pyridazines have been prepared. Some of these derivatives were used for convenient syntheses of a new azaheterocycle, imidazo(1,2-b)s-triazolo(3,4-f)pyridazine (V) and its derivatives. Another new heterocyclic system, imidazo(1,2-b)-tetrazolo-(5,1-f)pyridazine (XVI) has also been prepared.

Regioselective 1,3-Dipolar Cycloadditions of (1Z)-1-(Arylmethylidene)-5,5-dimethyl-3-oxopyrazolidin-1-ium-2-ide Azomethine Imines to Acetylenic Dipolarophiles

The 5,5-dimethylpyrazolidin-3-one (4), prepared from ethyl 3-methylbut-2-enoate (3) and hydrazine hydrate, was treated with various substituted benzaldehydes 5a – i to give the corresponding (1Z)-1-(arylmethylidene)-5,5-dimethyl-3-oxopyrazolidin-1-ium-2-ide azomethine imines 6a – i. The 1,3-dipolar cycloaddition reactions of azomethine imines 6a – h with dimethyl acetylenedicarboxylate (=dimethyl but-2-ynedioate; 7) afforded the corresponding dimethyl pyrazolo[1,2-a]pyrazoledicarboxylates 8a – h, while by cycloaddition of 6 with methyl propiolate (=methyl prop-2-ynoate; 9), regioisomeric methyl pyrazolo[1,2-a]pyrazolemonocarboxylates 10 and 11 were obtained. The regioselectivity of cycloadditions of azomethine imines 6a – i with methyl propiolate (9) was influenced by the substituents on the aryl residue. Thus, azomethine imines 6a – e derived from benzaldehydes 5a – e with a single substituent or without a substituent at the ortho-positions in the aryl residue, led to mixtures of regioisomers 10a – e and 11a – e. Azomethine imines 6f – i derived from 2,6-disubstituted benzaldehydes 5f – i gave single regioisomers 10f – i.

A Simple Stereoselective Synthesis of Aplysinopsin Analogs

Simple and stereoselective syntheses of aplysinopsins and their analogs from either methyl 2-[(2,2-disubstituted ethenyl)amino]-3-(dimethylamino)prop-2-enoates 11 or 5-[(dimethylamino)methylidene]imidazolidine-2,4-diones 20 are described. The structures of products are established by 1H- and 13C-NMR, and NOESY spectroscopy, and X-ray crystal-structure analysis.

Dimethylamine substitution in N,N-dimethyl enamines. Synthesis of aplysinopsin analogues and 3-aminotetrahydrocoumarin derivatives

Abstract Some new six-membered aplysinopsin analogues were prepared from 5-dimethylaminomethylidene-2,4,6(1H,3H,5H)-pyrimidinetriones and indole derivatives. Also 2-[[(2,4,6-trioxohexahydropyrimidin-5-ylidene)methyl]amino]-3-dimethylaminopropenoates were synthesized and employed in the synthesis of fused 2H-pyran-2-ones.

Synthesis of pyridazine derivatives-XV: Some electrophilic substitutions on imidazo[1,2-b]pyridazines.

Abstract Imidazo[1,2-b]pyridazine, which has been prepared for the first time, and several of its analogs were submitted to electrophilic substitution, such as halogenation, nitration and sulphonation. NMR data for several imidazo[1,2-b]pyridazines are included and from these conclusive evidence is obtained that electrophilic substitution occurs at position 3.

Reactions of some diazoazoles with reactive methylene and other groups

Abstract Reactions of some heteroaromatic diazo compounds with 1,3-dicarbonyl compounds, amines and thiophenol to give bi- and tricyclic heterocycles are studied. Decomposition of heterocyclic diazo compounds, triazenes and related compounds are investigated.

The Tautomerism of Heterocycles: Substituent Tautomerism of Six-Membered Ring Heterocycles

Publisher Summary This chapter reviews the substituent tautomerism of six-membered heterocycles that has appeared since 1976. The most significant development since 1976 is the enormous emphasis on the computational studies. Recent advances in computer technology in combination with increasingly accurate quantum-chemical methods, allow studies of systems of up to 50 atoms on standard personal computers at relatively high levels. Computational chemistry has become increasingly important in traditional heterocyclic chemistry. It discusses the generalized approach to the tautomerism phenomenon and its studies using theoretical, physical spectroscopic, non-spectroscopic, and chemical methods. The chapter also reviews the effect of introduction of an additional heteroatom; inductive substituents, mesomeric substituents, and the effect of benzannulation on the position of the tautomeric equilibrium of azines with various functional groups were investigated by PMO semiempirical calculations.

Δ2-1,2,3-Triazolines

Publisher Summary The 1,2,3-triazolines were first discovered during their studies on the action of organic azides on quinones. Triazolines have assumed considerable importance as intermediates in a number of organic syntheses and recently as a new class of potential anticonvulsant drugs. This chapter presents a comprehensive, unified survey of the methods of synthesis and reactions of Δ 2 -1,2,3-Triazolines. The chemistry of mono-, bi-, and polycyclic triazolines, and that of spiro- and bistriazolines, is considered. A brief account of the chemistry of Δ 3 - and Δ 4 -1,2,3-triazolines is given. Triazoline aromatization to triazoles is achieved by oxidation, isomerization reactions, and elimination of stable molecular fragments, all of which require the presence of free hydrogen at position 4 and/or 5 of the triazoline ring. The aromatization reaction affords a selective, synthetic route for the preparation of triazoles of definitive structure, in as much as azide addition to acetylenes is not regioselective.

A simple synthesis of aplysinopsin analogues by dimethylamine substitution in N,N-(dimethylamino)methylidene derivatives of five-membered heterocycles

Abstract Some new aplysinopsin analogues were prepared by a simple coupling of N , N -(dimethylamino)methylidene substituted hydantoin, thiohydantoin, and thiazolone derivatives, with indole derivatives. Configuration around the exocyclic CC double bond was determined on the basis of long-range heteronuclear coupling constants using 2D HMBC correlation technique.

Advances in Pyridazine Chemistry

Publisher Summary This chapter discusses the synthetic methods for the synthesis of pyridazine. Numerous syntheses of pyridazines follow the well-known approaches, but there are some significant developments and new methods, such as syntheses of pyridazines by cycloaddition, which have become powerful synthetic tools in the hands of organic chemists. Pyridazines have been investigated intensely, from a theoretical standpoint, by spectroscopic methods. Several aspects of pyridazine chemistry and activity are included in this chapter. The chapter deals with aromaticity and antiaromaticity of azines and substituent effects in azines. The chapter covers unusual organic compounds including azoalkanes, cycloadditions of azadienes, diazoquinones, thermal and photochemical decomposition of azoalkanes, and one-electron oxidations. The pyridazine nucleosides, some biologically active pyridazines, antihypertensive 3-hydrazinopyridazines, and pyridazines with antimicrobial activity are also reviewed in the chapter