Synthesis of some naphthyl-substituted nitrogen heterocycles on the basis of (Z)-3-chloro-3-(2-naphthyl)propenal

Abstract

β-Naphthyl-substituted derivatives of pyrazole, benzodiazepine, isoxazole, and pyrimidine were synthesized by reactions of (Z)-3-chloro-3-(2-naphthyl)propenal with hydrazine, o-phenylenediamine, hydroxylamine, and formamide, respectively.(Z)-3-Chloro-3-(2-naphthyl)propenal (I), which is readily available from 2-acetylnaphthalene via Vilsmeier-Haack reaction [1], is a reactive synthon for the preparation of various organic compounds containing a naphthalene fragment. The chlorine atom at the C=C bond in molecule I is activated due to conjugation with the electron-acceptor carbonyl group, and it can readily be replaced by other functional groups. The presence in molecule I of two reactive centers (C=O and =C-Cl) makes it possible to build up various heterocyclic systems. We recently showed that (Z)-3-chloro-3-(2-naphthyl)propenal readily reacts with primary aromatic amines to give naphthylimino enamines which undergo intramolecular cyclization to naphthyl-substituted quinolines [2]. The goal of the present study was to develop methods of synthesis of various nitrogen-containing heterocycles by reactions of (Z)-3-chloro-3-(2-naphthyl)propenal (I) with a series of nucleophiles. As the latter we used hydrazine, 2,4-dinitrophenylhydrazine, o-phenylenediamine, hydroxylamine, and formamide.It is known [3] that the reaction of β-chlorovinyl ketones with hydrazine underlies a preparative procedure for the synthesis of pyrazole derivatives. We expected that analogous reaction of chloropropenal I should also lead to formation of the corresponding naphthyl-substituted heterocycle. In fact, aldehyde I reacted with hydrazine hydrate to afford 74% of 5-(2-naphthyl)pyrazole (II) which was identified on the basis of its spectral data and elemental composition. The 13 C NMR spectrum of pyrazole II was reported in [4]; however, neither procedure for preparation of this compound nor its other spectral data were given (although the authors noted that this compound was previously unknown). The molecule of naphthylpyrazole II contains an N-nucleophilic center (NH); therefore, we examined its alkylation with 2-nitropentachloro-1,3-butadiene (III) which is known as a highly reactive electrophilic agent toward various amines [5]. The reaction involved replacement of both geminal chlorine atoms in the dichloronitrovinyl fragment of III and resulted in formation of a bis-pyrazole structure, 3,4,4-trichloro-1,1-bis[5-(2-naphthyl)pyrazol-1-yl]-2-nitro-1,3-butadiene (IV) (Scheme 1).(Z)-3-Chloro-3-(2-naphthyl)propenal (I) was converted into the corresponding 2,4-dinitrophenylhydrazone (V) in 77% yield by treatment with 2,4-dinitrophenylhydrazine in ethanol in the presence of sodium acetate. However, our attempts to effect heterocyclization of hydrazone V by the action of triethylamine or pyridine or by heating at 200°C (15 h) were unsuccessful. In all cases, the initial hydrazone was recovered from the reaction mixtures. Presumably, the presence of two electron-acceptor nitro groups in the benzene ring leads to electron density transfer from the...

Uncommon Heterocyclization into a Pyrazole System of Z-3-(2-Naphthyl)-3-chloro-2-propenal Semicarbazone and Thiosemicarbazone

“…The IR and 1 H NMR spectra of compound IV essentially differ from the spectra of 5-(2-naphthyl)-pyrazole (V) we have synthesized previously [2]. In the 1 H NMR spectrum of compound IV alongside the multiplet belonging to the protons of the naphthyl fragment two doublets were identified located at d 6.85 and 7.77 ppm with a coupling constant J 2.2 Hz corresponding to the =CH groups of the pyrazole ring, whereas in the spectrum of 5-(2-naphthyl)pyrazole (V) the protons of the heterocycle appeared as doublets at d 7.0 and 7.95 ppm, 3 J 6 Hz [2]. The relatively small value of the coupling constant observed for compound IV suggests by analogy with the published data on the spectra of related substances [4,5] that it is 4 J , and thus VASHKEVICH et al…”

“…prepared from 2-acetonaphthone by VilsmeierHaack reaction [1] contains two reactive sites (C=O and =CCl) that permits an effective application of the compound to building up versatile heterocyclic systems including a naphthalene fragment: benzodiazepine, isoxazole, pyrimidine [2], and quinoline [3]. We formerly demonstrated that the reaction between chloropropenal I and hydrazine hydrate was a convenient procedure for preparation of 5-(2-naphthyl)pyrazole [2].…”

“…It turned out that pyrazole IV was less active in the reaction with nitrodiene VI than its isomer V which readily reacted with the nitrodiene at room temperature [2]. With pyrazole IV a boiling of reagents in benzene for 15 h was required to obtain the reaction product 1,1-bis[4-(2-naphthyl)pyrazol-1-yl]-2-nitrotrichloro-1,3-butadiene (VII).…”

“…We formerly demonstrated that the reaction between chloropropenal I and hydrazine hydrate was a convenient procedure for preparation of 5-(2-naphthyl)pyrazole [2].…”

Synthesis of Diheteroatomic Five‐Membered Heterocyclic Compounds from α,β‐Unsaturated Aldehydes

“…Another essential limitation of this reaction (Scheme ) was the structure of the starting 2‐alkenal. It was established that 3‐chloro‐propenal 32 and 2‐substituted amino‐propenal 34 reacted with aromatic and aliphatic 1,2‐diamines to deliver diazepine derivatives 33 and 35 , respectively (Scheme ); this reactivity could be explained by the participation of alternative reaction sites in the process. For comparison, it should be noted that such a result is characteristic of the reaction between 2‐enones and 1,2‐diamines, as supported by numerous experiments…”