E. V. Rudyakova

Synthesis and reactions of pyrazole-4-carbaldehydes

Abstract1-, 3-, and 5-Alkylpyrazoles, as well as linearly bridged bis-pyrazoles, were converted into the corresponding 4-formyl derivatives by Vilsmeier-Haak reaction both under standard conditions and under microwave activation in DMF over a period of 10 min. 1,1′-(Hexane-1,6-diyl)bis(3,5-dimethyl-1H-pyrazole) and 1,1′-(benzene-1,4-diyldimethylene)bis(3,5-dimethyl-1H-pyrazole) gave rise to 4-formyl derivatives at both pyrazole rings. 5-Chloro-1,3-dialkyl-1H-pyrazoles failed to undergo formylation according to Vilsmeier-Haak or under microwave activation. 1,1′-Bridged bis-3,5-dimethyl-1H-pyrazoles reacted with 2-sulfanylethanol on heating in the presence of chloro(trimethyl)silane to give the corresponding bridged bis-4-(1,4,6-oxadithiocan-5-yl)-1H-pyrazoles.

Synthesis of (3-Indolylsulfanyl)alkanecarboxylic Acids

A method was developed for preparation of (3-indolylsulfanyl)alkanecarboxylic acids from 1H-, 1-methyl(benzyl)-, 2-methylindoles, thiourea, iodine, and halocarboxylic acids.

Reactions of N-(Polychloroethylidene)arene-and - trifluoromethanesulfonamides with indoles

N-(Polychloroethylidene)arene-and -trifluoromethanesulfonamides reacted with indole and N-substituted indoles to give the corresponding N-[2,2-dichloro(or 2,2,2-trichloro)-1-(1H-indol-3-yl)ethyl]-substituted sulfonamides. Unlike N-(2,2,2-trichloroethylidene)trifluoromethanesulfonamide, less electrophilic N-(poly-chloroethylidene)arenesulfonamides failed to react with 1-(4-nitrophenyl)-1H-indole. Previously unknown N,N’-bis(2,2-dichloroethylidene)biphenyl-4,4’-disulfonamide reacted with 1-benzyl-1H-indole at both azomethine fragments. Likewise, reactions of 1,6-bis(1H-indol-1-yl)hexane and 1,4-bis(1H-indol-1-ylmethyl)-benzene with N-sulfonyl trichloroacetaldehyde imines involved both indole rings in the former.

A Copper–Nitroxide Adduct Exhibiting Separate Single Crystal-to-Single Crystal Polymerization–Depolymerization and Spin Crossover Transitions

A complex cascade of solid-state processes initiated by variation of temperature was found for the heterospin complex [Cu(hfac)2L(Me/Et)] formed in the reaction of copper(II) hexafluoroacetylacetonate [Cu(hfac)2] with stable nitronyl nitroxide 2-(1-methyl-3-ethyl-1H-pyrazol-4-yl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl (L(Me/Et)). The cooling of the compound below 260 K initiated a solid-state chemical reaction, which led to a depolymerization of chains and formation of a pair heterospin complex [Cu(hfac)2L(Me/Et)2][[Cu(hfac)2]3L(Me/Et)2]. Further decrease in temperature below 144 K led to a spin transition accompanied by a drastic decrease in the effective magnetic moment from 2.52 to 2.24 μB. When the compound was heated, the order of effects was reversed: at first, the magnetic moment abruptly increased, and then the molecular fragments of the pair cluster united into polymer chains. Two hysteresis loops correspond to this cascade of temperature-induced structural transformations on the experimental dependence μeff(T): one at high (T↑ = 283 K and T↓ = 260 K) and the other at low (T↑ = 161 K, T↓ = 144 K) temperature. The spin transitions were also recorded for the [[Cu(hfac)2]3L(Bu/Et)2] and [[Cu(hfac)2]5L(Bu/Et)4] molecular complexes, which are models of the trinuclear fragment of the {[Cu(hfac)2]3L(Me/Et)2} pair cluster.

Selective synthesis of 3-[1-(organylsulfanyl)ethyl]- and 3-[2-(organylsulfanyl)ethyl]-5-chloro-1H-pyrazoles

Pyrazole ring constitutes a structural fragment of many up-do-date pharmacologically active compounds possessing analgesic, anti-inflammatory, antibacterial, and other properties. Pyrazole derivatives have found application as insectoacaricides, dyes, luminophores, ligands, etc. [1–4]. At present, search for new synthons for the preparation of pyrazole derivatives is an extensively developing field of study [1–3]. We recently synthesized 3-haloalkyl-5-chloropyrazoles which were used as starting compounds for the preparation of previously unknown 3-alkenyl-5-chloropyrazoles [5] as versatile building blocks for purposeful synthesis of materials for advanced technologies. The present communication describes a chemoselective synthesis of new regioisomeric 3-{1-[butyl(benzyl)sulfanyl]ethyl}and 3-{2-[butyl(benzyl)sulfanyl]ethyl}-5-chloropyrazoles by reaction of 3-(1-chloroethyl)and 3-vinyl-5-chloropyrazoles with butane-1-thiol and phenylmethanethiol, respectively. Radical addition of thiols to 5-chloro-3-vinyl-1Hpyrazoles Ia and Ib gave the corresponding antiMarkovnikov adducts, 3-{2-[butyl(benzyl)sulfanyl]ethyl}-5-chloro-1H-pyrazoles IIa and IIb in 77–80% yield. The reactions were carried out by heating equimolar amounts of the reactants in benzene at 60°C in the presence of azobis(isobutyronitrile) (AIBN) or under UV irradiation over a period of 6 h (Scheme 1).

Synthesis and properties of pyrazole carbaldehyde bis(2-hydroxyethyl)-dithioacetal hydrochlorides*

A simple method has been developed for the synthesis of water-soluble pyrazole derivatives, namely 4-[bis(2-hydroxyethylsulfanyl)methyl]pyrazoles hydrochlorides, by the reaction of a series of pyrazole carbaldehydes with 2-mercaptoethanol in the presence of trimethylchlorosilane. When treated with aqueous ammonia solution the pyrazole-4-carbaldehydes bis(2-hydroxyethyl)dithioacetal hydro-chlorides are converted to the 4-[bis(2-hydroxyethylsulfanyl)methyl]pyrazole free bases.

2-chlorovinyl 1,1-dichloroethyl ketone from 2-chloropropionyl chloride and 1,2-dichloroethene

We recently found [1, 2] that chloroacetyl chloride reacts with 1,2-dichloroethylene in the presence of AlCl3 to give an unexpected product, dichloromethyl 2-chlorovinyl ketone. In contrast, aliphatic carboxylic acid chlorides and dichloroacetyl chloride were reported [3, 4] to react with 1,2-dichloroethylene under analogous conditions with formation of alkyl 1,2-dichlorovinyl ketones and 1,2-dichlorovinyl dichloromethyl ketone, respectively. In continuation of our studies on the chemistry of highly reactive 2,2-, 1,2-, and 2-chlorovinyl chloroalkyl ketones [5] we examined the reaction of 2-chloropropionyl chloride with 1,2-dichloroethylene with a view to elucidate the mechanism of reactions of α-chloroalkanoyl chlorides with 1,2-dichloroethylene. We found that 2-chloropropionyl chloride reacts with commercially available mixture of cisand trans-1,2-dichloroethylenes (a large-scale chemical product) under the conditions described in [1–4] along two concurrent pathways. The first of these unexpectedly led to the formation of 49% of previously unknown 1,1-dichloroethyl 2-chlorovinyl ketone, while the second was the known process leading to diastereoisomeric 1-chloroethyl 1,2,2-trichloroethyl ketones II and 1-chloroethyl 1,2-dichlorovinyl ketone (III) at a ratio of 69 : 13; here, compound III is formed as a result of thermal dehydrochlorination of ketone II [3, 4]. The mechanism of formation of 1,1-dichloroethyl 2-chlorovinyl ketone (I) from 1,2-dichloroethylene and 2-chloropropionyl chloride, which involves chlorotropic rearrangement, is not completely clear. The product structure suggests that the mechanism proposed by us previously for the formation of dichloromethyl 2-chlorovinyl ketone [2] from chloroacetyl chloride and 1,2-dichloroethylene is not operative here. Saturated ketone II failed to undergo transformation into 2-chlorovinyl ketone I on heating in the presence of aluminum chloride. 1,4,4-Trichloropent-1-en-3-one (I). A mixture of 18.7 g (0.14 mol) of AlCl3, 17.74 g (0.14 mol) of 2-chloropropionyl chloride, and 30 ml of 1,2-dichloroethylene was heated for 6–8 h at the boiling point. The mixture was then cooled and poured onto ice. The organic phase was separated, the aqueous phase was extracted with methylene chloride, the extracts were combined with the organic phase, dried over CaCl2, and filtered, the solvent was distilled off, and the residue was distilled under reduced pressure, a fraction ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 4, pp. 617–618.

Unusual reaction of chloroacetyl chloride with 1,2-dichloroethene. Synthesis and properties of 2-chlorovinyl dichloromethyl ketone

The reaction of chloroacetyl chloride with 1,2-dichloroethene in the presence of AlCl3 unexpectedly led to the formation of (E)-1,1,4-trichlorobut-3-en-2-one whose structure was proved by 1H and 13C NMR, IR, and mass spectra and independent synthesis. A probable reaction scheme was proposed, which involves transformation of initially formed 1,2,4-trichloro-3-oxobutan-2-yl cation by the action of AlCl3. The high reactivity of the vinylic halogen atom in (E)-1,1,4-trichlorobut-3-en-2-one was demonstrated by its reactions with nitrogen-centered nucleophiles (triethylamine, aniline, 3,5-dimethyl-1H-pyrazole) and sodium sulfide. These reactions involved only the C-Cl bond in the vinyl fragment and afforded (4,4-dichloro-3-oxobut-2-en-1-yl)triethylammonium chloride, 1,1-dichloro-4-phenylaminobut-3-en-2-one, 1-(4,4-dichloro-3-oxobut-2-en-1-yl)-3,5-dimethyl-1H-pyrazole, and 4,4′-thiobis(1,1-dichlorobut-3-en-2-one), respectively. The reaction of 1,1,4-trichlorobut-3-en-2-one with benzylhydrazine gave a mixture of 1,3- and 1,5-disubstituted pyrazoles.

Synthesis of N-(Arylsulfonyl)arylglycines and Their Influence on the Growth of Bifidobacteria

Previously we developed preparative methods for the synthesis of (2,2,2-trichloro-1-arenesulfonamidoethyl)benzenes (Ia – Ig) and indoles (IIIa – IIIe) [1 – 4] and established that some of these compounds are subject to selective hydrolysis at the trichloromethyl group on heating in aqueous alkali solutions, with the formation of N-(arylsulfonyl)arylglycine salts [5]. This work continued investigations of the hydrolysis of trichloroethylarenesulfonamides I, aiming at establishing optimum conditions of this process, obtaining new N-(arylsulfonyl)arylglycines (IIa – IIg), and characterizing their biological activity. It was established that the duration of hydrolysis of compounds Ia – Ig at 90 – 95°C and a NaOH solution concentration of 0.4 mole liter varies within 3 – 5 h depending on the nature of the substituent X. The optimum amount of alkali corresponds to a fourfold excess.

Synthesis and structure of 1-tert-butyl-substituted 3(5)-alkylpyrazoles from 2-chlorovinyl ketones

Reactions of alkyl, halomethyl 2-chlorovinyl ketones with tert-butylhydrazine in the presence of triethylamine afford unsymmetrical 1-(tert-butyl)-3- and -5-disubstituted pyrazoles. The reaction direction is governed by the ketone ability of the nucleophilic substitution of chlorine and of the dehydrochlorination leading to acetylene ketones. 2-Chlorovinyl ketones react with tert-butylhydrazine along two routes giving mixtures of 1-(tert-butyl)-3- and -5-alkylpyrazoles. The content of 3-alkyl-1-(tert-butyl)pyrazole in the formed isomers mixture grows up to 73% with growing length of the alkyl chain of the ketone and up to 87 and 94% at introducing halogen atom in the alkyl fragment of the chloroenone.