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Alkylthio)chloroacetylenes 1 react with thiosemicarbazones 2 at room temperature in a medium of aliphatic ketone to form hydrochlorides of 2-alkanone-N-[4-(organylthio)-1,3-thiazol-2-yl]hydrazones 3 in yields of up to 65%.Although poorly understood so far, the reactions of (organylthio)chloroacetylenes 1 with S,N-multinucleophiles provide a potential source of new classes of polyfunctional unsaturated compounds, including heteroatomic ones. Moreover, from a fundamental viewpoint, these present an essential source of information on some features on the nucleophilic substitution of a halogen at the triple bond in the presence of some competing nucleophilic centers during attack at a hetero-conjugated system uniting the atoms of two sp-carbons, sulfur and chlorine.It is known that (alkylthio)chloroacetylenes react with 2-aminoethane-1-thiol to form 2-{[2-(alkylthio)ethynyl]-thio}ethane-1-ammonium chlorides, 1 whereas with thiourea they give S-(alkylthioethynyl)isothiuronium chlorides and N-[1-(alkylthio)ethynylidene]thiourea. 2 Under comparable conditions the reaction of (phenylthio)chloroacetylene with thiourea leads to 4-(phenylthio)-1,3-thiazol-2(3H)-imine hydrochloride in quantitative yield. 2The reaction of haloacetylenes with thiosemicarbazones has not been studied until the present work. It has been briefly reported that bromoethynyl(organyl)ketones with thiosemicarbazine and its 1-and 4-organyl-substituted compounds form 1,3,4-thiazole derivatives. 3 The polydentate nature of thiosemicarbazones as nucleophiles (with due account taken of their tautomeric forms) suggests that during their interaction with (organylthio)chloroacetylenes diverse heterocycles can be formed. Therefore, we have first carried out and studied the reaction of (organylthio)chloroacetylenes 1 with dialkylketone thiosemicarbazones 2 in order to extend our knowledge of the reactivity and synthetic potential of the heteroconjugated S-CºC-Cl system and to synthesize novel heterocyclic polyfunctional compounds. Taking into consideration the multidentate character of the latter as well as the presence of three electrophilic centers (halogen atom and two sp-carbons) in the molecule of halogenacetylenes 1, the result of interaction of the above reagents was far from predictable.(Alkylthio)chloroacetylenes 1a,b react with thiosemicarbazones 2a-c at 20-22°C in a medium of the same aliphatic ketone to form in a chemo-and regioselective manner hydrochlorides of 2-alkanone-N-[4-(organylthio)-1,3-thiazol-2-yl]hydrazones 3a-c in 51-65% yield (Scheme 1).The thiazoles 3a-c are crystalline substances, very soluble in water, ethanol, dimethylsulfoxide, poorly soluble in chloroform and insoluble in ether. The salt nature of these compounds is confirmed by mercurometric titration: only one equivalent of ion-chloride per mole of the compound is fixed. The IR spectra of compounds 3a-c show a broad Scheme 1Downloaded by: Simon Fraser University Library. Copyrighted material.
Organylthiochloracetylenes RSC ≡ CCl (I) exhibit a high reactivity and a great synthetic potential. They represent promising syntones for a targeted synthesis of various S -[1-3]; S,Se -; S,P - [4,5], and N,S -containing acyclic and heterocyclic compounds [6][7][8][9][10]. Esters and alkanammonium salts of organylsulfanylacetic acids, which may be easily obtained on the basis of organylthiochloracetylenes, have already manifested themselves as biologically active compounds with antiagregational, cancerostatic, protective, and adaptive properties [11,12]. New convenient approaches to the synthesis of stable N -(organylthioethynyl)trialkylammonium chlorides have been developed. It was shown that all of them exhibit a broad spectrum of antibacterial activity and a strong antitumor effect both in vitro and in vivo (growth of tumors was suppressed by 82-100%) [13].Developing this new direction in chemistry of polyfunctional derivatives of acetylenes, we studied the reactivity of organylthiochloracetylenes with respect to anionic N -, O -, S -, and Se -nucleophiles; unchanged N -, P -, and S -nucleophiles; and bifunctional N,N -, N,O -, N,S -, and O,S -nucleophiles. In the course of these studies, we developed a convenient method of synthesis of 2-(alkylthiomethylene)-3,3-dialkyl-1,3-oxazolidinium chlorides with an yield of 90-96% and studied their structure [14]. Organylthiochloracetylenes readily react with N -(2-hydroxyethyl)-N,N -(dialkyl)amines in a diethyl ether medium at 20-22 ° C to form 2-(alkylthiomethylene)-3,3-dialkyl-1,3-oxazolidinium chlorides (II). The reaction apparently involves intermediate formation of quaternary in ammonium salts, which were recorded by IR spectroscopy:HO R = C 2 H 5 , R 1 = R 2 = CH 3 (IIa); R = Ì -C 4 H 9 , R 1 = R 2 = CH 3 (IIb); R = Ì -C 4 H 9 , R 1 = R 2 = C 2 H 5 (IIc); R = Ì -C 3 H 7 , R 1 = R 2 = CH 3 (IId); R = C 6 H 5 , R 1 = R 2 = CH 3 (IIe); R = C 2 H 5 , R 1 = CH 3 , R 2 = ë 2 ç 4 éç (IIf); R = Ì -C 3 H 7 , R 1 = CH 3 , R 2 = ë 2 ç 4 éç (IIg); R = R 1 = R 2 = C 2 H 5 (IIh); R = iso -C 4 H 9 , R 1 = R 2 = C 2 H 5 (IIi); R = C 2 H 5 , R 1 = C 4 H 9 , R 2 = ë 2 ç 4 éç (IIj).The 2-(alkylthiomethylene)-3,3-dialkyl-1,3-oxazolidinium chlorides (II) synthesized represented white crystalline hygroscopic compounds, stable when stored in the absence of moist and soluble in water and alcohols. The simplicity of synthesis and high yields (90-98%) allow this reaction to be proposed as a convenient preparative way of obtaining these compounds.Compounds (II) contain pharmacophore groups (the quaternary nitrogen atom, sulfur atom, and the oxazolidinium cycle) and are of interest as potential biologically active compounds. We studied the toxicity, cancerostatic, and antibacterial activity of 2-(alkylthiomethylene)-3,3-dialkyl-1,3-oxazolidinium chlorides (II). The existence of cancerostatic and antibacterial activity of chlorides (II) was not obvious, because data on similar compounds exhibiting antitumor or antimicrobial activity are absent in the literature.Fighting against infectious a...
Organylthio)chloroacetylenes react with aliphatic 1,2-dithiols in dimethyl sulfoxide at 20-25 • C in the presence of a two-fold molar excess of alkali to form 2-[(alkylthio)methyliden]-1,3-dithiolanes in up to 66% yield.Earlier, we reported the reactions of (organylthio)chloroacetylenes 1 with S-centered nucleophiles (sodium sulfide, 1 thiols, 2 thioacetic acid 3 ), which followed the addition and/or substitution schemes. (Organylthio)chloroacetylenes reacted with bidentate nucleophiles giving either functionally substituted acetylenic sulfides or organylthio substituted heterocyclic compounds. 2,4−6 Thus, 2-{[2-(alkylthio)ethynyl]thio}ethan-1-ammonium 5 and S-(alkylthioethynyl) isothiuronium 4 chlorides were prepared by the reaction of (alkylthio)-chloroacetylenes with 2-aminoethan-1-thiol and thiourea respectively. Under similar conditions, the reaction of (phenylthio)chloroacetylene with thiourea gave quantitatively 4-(phenylthio)-1,3-thiazol-2(3H)-imine hydrochloride. 4 (Organylthio)chloroacetylenes readily reacted with 2-mercaptoethan-1-ol (KOH-DMSO, 20-22 • C) to afford Financial support from the Ministry of Industry, Science and Technologies of Russian Federation (grants no. NSH-
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