V. A. Savosik

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.

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.

Synthesis and properties of 5-chloro-4-nitropyrazoles

The nitration of 5-chloropyrazoles with a mixture of 100% nitric acid and 65% oleum or a mixture of 60% nitric acid and polyphosphoric acid gave substituted 5-chloro-4-nitropyrazoles in 45–91% yield. The nitration of 3-aryl-5-halopyrazoles was accompanied by introduction of a nitro group into the aromatic ring. 4-Chloropyrazoles failed to undergo nitration under these conditions. The reaction of 5-chloro-1,3-dimethyl-4-nitropyrazole with ethyl cyanoacetate in DMSO in the presence of K2CO3 led to the formation of ethyl 2-cyano-2-(1,3-dimethyl-4-nitro-1H-pyrazol-5-yl)acetate.

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.

1-Alkylpyrazoles and 1-alkyl-5-chloropyrazoles from halovinyl ketones and 1,1-dialkylhydrazines

Regioselective heterocyclization of alkyl 2-chloro-and 2,2-dichlorovinyl ketones with 1,1-dialkyl-hydrazines to 1,3-dialkyl-1H-pyrazoles and 1,3-dialkyl-5-chloro-1H-pyrazoles involves intermediate formation of the corresponding dialkylhydrazones. Fragmentation pattern of chlorine-containing pyrazoles, 3-chloromethyl-1-methyl-1H-pyrazole and 5-chloro-1-methyl-3-propyl-1H-pyrazole, depends on the position of the halogen atom.

Synthesis and structure of 4-trifluoromethylsulfonamidotrichloroethyl-5-chloropyrazoles

Reactions of trifluoromethanesulfonic acid N-(2,2,2-trichloroethylidene)amide with 1,3-dialkyl-5-chloropyrazoles and 1-phenyl-3-methylpyrazole afforded 4-(amidotrichloroethyl)-substituted pyrazole derivatives. 4-Chloropyrazoles were not involved into this process. The structure of compounds synthesized was studied by means of IR and NMR spectroscopy. The presence of intra- and intermolecular hydrogen bonds was revealed by a decrease in the absorption frequencies and a complicated form of ν(NH) and νas(SO2) absorption bands in the IR spectra, and also in splitting of signals in 1H and 13C NMR spectra.

Synthesis and reactions of 1-benzyl-3-haloalkyl-5-chloropyrazoles

Synthesized 1-benzyl-3-chloroalkyl-5-chloropyrazoles reacted with indole and pyrrole in DMSO in the presence of alkali to give 3-(heter-1-yl)alkyl-substituted 1-benzyl-5-chloropyrazoles. 1-[(1-Benzyl-5-chloropyrazol-3-yl)methyl]indole reacted regiospecifically with chloroal trifluoromethylsulfonyl- and 4-chlorophenylsulfonylimines providing the products of C-amidotrichloroethylation into the position 3 of the indole ring. {1-[(1-Benzyl-5-chloropyrazol-3-yl)methyl]indol-3-yl}sulfanylacetic acid was obtained by the reaction of 1-[(1-benzyl-5-chloropyrazol-3-yl)methyl]-indole with iodine, thiourea, and chloroacetic acid.

Synthesis and properties of 2-amino-1-chloroenones

Reactions of alkyl-, allyl-, and arylamines and o-aminophenol with 1,2-dichlorovinyl alkyl ketones involve replacement of only one chlorine atom in the β-position with respect to the carbonyl group with formation of 2-alkylamino-, 2-allylamino-, and 2-arylamino-1-chlorovinyl ketones. Diamines of the aromatic and aliphatic series react with 1,2-dichlorovinyl alkyl ketone molecules to give N,N′-bis(2-acyl-2-chlorovinyl)-substituted diamines.

C-alkyl-4-nitropyrazoles from 5-chloro-4-nitropyrazoles

Abstract5-Chloro-4-nitro-1H-pyrazoles reacted with arylsulfonyl-, cyano-, and acetylacetic acid esters in DMSO in the presence of potassium carbonate to give 5-[alkoxycarbonyl(acetyl, cyano, or arylsulfonyl)-methyl]-substituted 4-nitropyrazoles which may be promising from the viewpoint of preparation of other functionalized pyrazole derivatives and bicyclic ensembles.