Unexpected formation of pyrazolecarbaldehyde dithioacetal hydrochlorides

Abstract

SHORT COMMUNICATIONSPyrazoles are important building blocks in the synthesis of novel pharmaceutical agents possessing analgesic, antiphlogistic, antibacterial, antidepressant, and other kinds of biological activity [1], as well as of insectoacaricides [2], dyes, luminophores, and ligands [3]. Water-soluble pyrazole derivatives are of particular significance. The ability of pyrazoles to form hydrohalides is determined by the presence of a pyridinetype nitrogen atom in their molecules, which possesses enhanced nucleophilicity [4]. It is known that pyrazole hydrochlorides are unstable. If pyrazole molecule contains another nucleophilic center, e.g., double C=C bond, their reactions with hydrohalic acids could follow two pathways. Hydrochlorination of 1-alkenylpyrazoles occurs at the N 2 atom only on cooling (-70°C), whereas at room temperature the process involves the alkenyl substituent [5,6].We were the first to reveal that acetalization of pyrazole-4-carbaldehydes Ia-Ic with 2-sulfanylethanol in the presence of 5-6 equiv of chlorotrimethylsilane at room temperature leads to the formation of the corresponding dithioacetal hydrochlorides IIa-IIc in good yield. Protonation of the N 2 atom in the heteroring of compounds IIa-IIc is indicated by the presence in their IR spectra of a broadened NH + absorption bands at 2500-2800 cm -1 . Hydrochlorides IIa-IIc are colorless water-soluble oily substances that are stable under usual conditions. 4-Bis(2-hydroxyethylsulfanyl)methyl-3,5-dimethyl-1H-pyrazole hydrochlorides IIa-IIc (general procedure). 2-Sulfanylethanol, 0.156 g (2 mmol), was added dropwise under stirring to a mixture of 1 mmol of pyrazolecarbaldehyde Ia-Ic and 0.77 ml (6 mmol) of chlorotrimethylsilane. The reaction was accompanied by heat evolution, and the mixture divided into two layers. The mixture was stirred for 15-20 min at room temperature, the upper layer was separated, and the viscous residue was washed with hot hexane and with diethyl ether and dried under reduced pressure. S,S′-[(1-Isopropyl-3,5-dimethyl-1H-pyrazol-4-yl)-methanediyl]bis(2-sulfanylethanol) hydrochloride (IIa). Yield 0.315 g (93%). IR spectrum (film), ν, cm -1 : 3339 br (OH), 2713-2540 br (NH + ). 1 H NMR spectrum, δ, ppm: 1.57 d [6H, CH(CH 3 ) 2 , 3 J = 6.7 Hz], 2.55 s and 2.56 s (3H each, CH 3 ), 2.69 d.t and 2.82 d.t (2H each, CH 2 S, 2 J = 14.1, 3 J = 6.3 Hz), 3.70 d.t and 3.76 d.t (2H each, CH 2 O, 2 J = 11.3, 3 J = 6.3 Hz), 4.91 m (1H, NCH), 5.44 s (1H, SCHS). 13 C NMR spectrum, δ C , ppm: 10.43 and 10.63 (CH 3 ), 21.47 [CH (CH 3 ) 2 ], 36.20 (CH 2 S), 43.54 (SCHS), 53.67 (NCH), 62.79 (OCH 2 ), 119.96 (C 4 ), 144.70 and 145.56 (C 3 , C 5 ). Found, %: C 45.76; H 7.38; Cl 10.38; N 8.21; R = i-Pr (a), CH 2 =CHCH 2 (b), PhCH 2 (c).

Fragmentation of pyrazolecarbaldehyde thio- and dithioacetals under electron impact and chemical ionization

“…Pyrazolecarbaldehyde bis(2-hydroxyethyl) dithioacetals Ia-Ie were obtained by dehydrochlorination with aqueous ammonia of the corresponding dithioacetal salts synthesized from pyrazolecarbaldehydes and 2-sulfanylethanol at a ratio of 1 : 2 [12]. Pyrazolyl-1,4,6-oxadithiocanes IIa-IIe were synthesized by reaction of aldehydes IVa-IVe with 2,2′-oxydiethanethiol at room temperature according to the procedure described in [12].…”

“…Pyrazolyl-1,4,6-oxadithiocanes IIa-IIe were synthesized by reaction of aldehydes IVa-IVe with 2,2′-oxydiethanethiol at room temperature according to the procedure described in [12]. 2-Pyrazolyl-1,3-oxathiolanes IIIaIIIe were isolated by column chromatography (silica gel, 0.060-0.2 mm; diethyl ether-methanol, 25 : 1) from the reaction mixtures obtained by reaction of pyrazolecarbaldehydes with an equimolar amount of 2-sulfanylethanol in the presence of Me 3 SiCl.…”

“…Therefore, their fragmentation under electron DOI: 10.1134/S1070428011120116 X = Me (a), Pr (b), i-Pr (c), CH 2 =CHCH 2 (d), PhCH 2 (e). (5), 82 (7), 81 (7), 80 (7), 79 (4), 78 (12), 77 (4), 69 (3), 68 (5), 67 (8), 66 (7), 65 (8) impact can follow pathways typical of both classes of compounds or take a quite different pathway.…”

2‐(Pyrazol‐4‐yl)‐1,3‐oxaselenolanes from Pyrazole Сarbaldehydes and 2‐Selanyl‐1‐ethanol

“…1‐i‐Propyl‐3,5‐dimethylpyrazole carbaldehyde ( 1d ) . Yield 64%, mp 115–116°С (in literature the yields and physical–chemical constants of carbaldehydes 1a–e were not given).…”

5-Chloropyrazole-4-carboxaldehydes as synthon in heterocyclic synthesis

“…Unlike 2-mercaptoethanol, 2-selenoetanol reacts with pyrazole aldehydes in a different manner. The reaction is implemented with equimolar amounts of reagents in four-to sixfold excess [99]) exclusively to deliver 2-(pirazol-4-yl)-1,3-oxaselenolane hydrochlorides 372a-f in 68-94 % yields (Scheme 78). The synthesized hydrochlorides 372a-f are unstable and upon storage in air or during the treatment with solvents and admixtures of water undergo hydrolysis to give the initial aldehydes and other unidentified compounds, probably, products of 2-selanyl-1-ethanol oxidation.…”