Reaction of (Alkylthio)chloroacetylenes with Thiosemicarbazones: A Route to Functionalized Thiazoles

Abstract

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.

Ab Initio Study of Molecular Properties and Decomposition Products of 1-AzidoalkynesA Challenge for Experimentalists

“…As we conclude that the 13 C NMR chemical shifts given in ref are very likely not the ones of 10a , and the chemical shift of the internal standard C 1 70 given in Table might not be correct. However, comparison of the 13 C chemical shifts of similar compounds have indicated that the shift for C 1 is on the order of about 14−15 ppm ( 9a , ref : 14.8 ppm, 12 : 14.5 ppm, Et 2 S, ref : 14.8 ppm). Thus, the authors are confident that the experimental values of the real compound will be within 6 ppm deviation to the theoretical results given here.…”

The Structure of Biologically Active Functionalized Azoles: NMR Spectroscopy and Quantum Chemistry

“…In order to obtain new heterocyclic systems with potential photochromic properties and biological activity, we were the first to study the reaction of organylthiochloroacetylenes with dialkyl-substituted thiosemicarbazones, and proved the structure of the resulting products [127,128]. Considering the bidentity of thiosemicarbazones as nucleophiles and the presence of three reaction centers in the haloacetylenes molecule-the halogen atom, terminal (C α ) and internal (C β ) carbon atoms, the result of these reactions were not predictable.…”

A new route to functionally-substituted tetrazines

“…For instance, the reactions with alkylenediamines, 2 2-hydroxyethylamine 3 2-hydroxy-N,Ndimethylamine, 4 thiosemicarbazones, 5 proceed by nucleophilic substitution of the acetylenic chlorine forming ynammonium salts which further undergo cyclization. In this way it was possible to obtain imidazole, oxazolone, oxazolidine, oxazine, and thiazole derivatives which, in certain cases, display effective complex-forming properties or high antimicrobial and antitumor activity.…”