Reaction of 1,3-Thiazole-5(4H)-thiones with 1,2-Epoxycycloalkanes: Formation of Spirocyclic 1,3-Oxathiolanes

Treatment of solutions of 1,3-thiazole-5(4H)-thiones 1 in CH₂Cl₂ at room temperature with BF₃⋅Et₂O and 1,2-epoxycyclohexane (7-oxabicyclo[4.1.0]heptane; 2a ) or 1,2-epoxycyclopentane (6-oxabicyclo[3.1.0]hexane; 2b ) yielded mixtures of diastereoisomeric spirocyclic 1,3-oxathiolanes ( 3 / 4 and 8 / 9 , respectively). In addition, the corresponding 1,3-dithiolane 6 was formed as a minor product in the reaction of 4,4-dimethyl-2-phenyl-1,3-thiazole-5(4H)-thione ( 1a ) with 2a . The structures of the different types of products have been established by X-ray crystal-structure analysis. An ionic two-step mechanism via nucleophilic ring-opening of the complexed oxirane by the attack of the thiocarbonyl S-atom is proposed. This proposal is supported by the formation of the propellane 10 with a Wagner-Meerwein rearrangement as the key step.     

Synthesis and Addition Reactions of 1,3-Thiazole-5(4H)-thione Oxides

1,3-Thiazole-5(4H)-thione oxides 2 were prepared by oxidation of the corresponding 1,3-thiazole-5(4H)-thiones 1 with m-chloroperbenzoic acid (Table 1). Addition reactions of 2 with organolithium and Grignard reagents yielded 4,5-dihydro-4,4-dimethyl-1,3-thiazol-5-yl methyl sulfoxides of type 4 via thiophilic attack (Table 2). Whereas the reaction with the organolithium compounds proceeded with fair-to-excellent yields, the Grignard reagents reacted only very sluggishly. The sulfoxides 4 could also be prepared via oxidation of 4,5-dihydro-4,4-dimethyl-5-(methylthio)-1,3-thiazoles of type 3 with m-chloroperbenzoic acid, together with the corresponding sulfones 5 (Scheme 1).     

New Addition Reactions of Organometal Compounds with 4,4-Dimethyl-1,3-thiazole-5(4H)-thiones

Addition reactions of organometallic reagents with 4,4-disubstituted 1,3-thiazole-5(4H)-thiones were studied. Whereas the reactions with alkyllithium and alkyl Grignard reagents occurred in the thiophilic manner, the carbophilic addition was observed with allyllithium and allyl Grignard reagents. A radical reaction mechanism is proposed for rationalizing these observations (Scheme 5). A radical cyclization of the prepared 5-allyl-4,5-dihydro-1,3-thiazole-5-thiol derivatives yielded 1,6-dithia-3-azaspiro[4.4]non-2-enes (Table 4).     

Synthesis and reactions of 2-(alkylthio)-4,4-dimenthyl-1,3-thiazole-5(4H)-thiones

Six 2-(alkylthio)-substituted 4,4-dimethyl-1,3-thiazole-5(4H)-thiones were synthesized according to a new method. The reactions of these compounds with allyl- and benzyllithium reagents, 1,3-dipoles, and dimethyl acetylenedicarboxylate proceeded in a similar manner to 2-alkyl-substituted analogues, while methyllithium reacted in a different way yielding trithio-orthoester derivatives.     

N-(1,3-Thiazol-5(4H)-yliden)amine aus 1,3-dipolaren Cycloadditionen von Aziden mit 1,3-Thiazol-5(4H)-thionen

N-(1,3-Thiazol-5(4H)-ylidene)amines via 1,3-Dipolar Cycloaddition of Azides and 1,3-Thiazol-5(4H)-thiones Organic azides 5 and 4,4-dimethyl-2-phenyl-1,3-thiazol-5(4H)-thione ( 2 ) in toluene at 90° react to give the corresponding N-(1,3-thiazol-5(4H)-ylidene)amines (= 1,3-thiazol-5(4H)-imines) 6 in good yield (Table). A reaction mechanism for the formation of these scarcely investigated thiazole derivatives is formulated in Scheme 3: 1,3-Dipolar azide cycloaddition onto the C?S group of 2 leads to the 1:1 adduct C . Successive elimination of N₂ and S yields 6 , probably via an intermediate thiaziridine E .     

Reactions of Thioketones with Dichlorocarbene

The reactions of sterically crowded cycloalkanethiones of type 2 with CHCl₃/NaOH under phase-transfer catalysis (PTC) with benzyl(triethyl)ammonium chloride (TEBA) as catalyst afforded the corresponding `gem.-dichlorothiiranes' of type 3 in good yields (cf. Scheme 2 and Table). The desulfurization, which, in some cases, occurred spontaneously, led to (dichloromethylidene)cycloalkanes of type 4 . Similar results were obtained using Seyferth's reagent in boiling benzene. In the case of 2,2,6,6-tetramethylcyclohexanethione, reaction under PTC conditions after 3 h yielded only the corresponding dichloromethylidene derivative; on the other hand, workup after 1 h gave (2,2,6,6-tetramethylcyclohexylidene)methanethione (thioketene 9 ; Scheme 5).     

Reaction of 4-Dichloromethylene-p-tolyl-1,3-oxazol-5(4H)-one with o-Aminothiophenol

Russian Journal of General Chemistry -     

Hetero-Diels-Alder-Reaktion mit 1,3-Thiazol-5(4H)-thionen

Hetro-Diels-Alder Reaction with 1,3-Thiazol-5(4H)-thiones On heating in toluene to 180° and on treatment with BF₃·Et₂O in CH₂Cl₂ room temperature, 1,3-dienes react with the C?S group of 1,3-thiazol-5(4H)-thiones 1 in a reversible Diels-Alder reaction to give spiro[4.5]-heterocycles of type 6. A 1:1 mixture of two regioisomeric cycloadducts is formed in the thermal reaction with 2-methylbuta-1,3-diene (isoprene, 5b ). In contrast, the formation of one regioisomer is strongly preferred in the BF₃-catalyzed reaction. Frontier-orbital control as well as steric factors seem to be responsible for the observed regioselectivity. BF₃-Catalyzed, cyclic 1,3-dienes and 1 also undergo a smooth Diels-Alder reaction. Whereas cyclohexa-1,3-diene ( 5c ) reacts with 1a and 1b to give a single isomer (presumably the ‘exo’-adduct), cyclopenta-1,3-diene ( 5d ) leads to a ca. 3:1 mixture of ‘exo’-and ‘endo’-isomer.     

4-Phosphoranylidene-5(4H)-oxazolones II. Reactions with alkylating agents

Summary When treated with alkyl halides at 20–90°C without solvent or in acetonitrile, 4-phosphoranylidene-5(4H)-oxazolones (1) give 4-C-alkylation products4 in good yields. Alkylation of1 with alkyl triflates in CH₂Cl₂ at room temperature results in O-alkylation products5. No O-to 4-C-alkylation rearrangement can be observed. The spectroscopic properties of the alkylation products are reported and discussed.

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4-Phosphoranyliden-5(4H)-oxazolone, 2. Mitt. Reaktionen mit Alkylierungsreagentien

Zusammenfassung Behandlung von 4-Phosphoranyliden-5(4H)-oxazolonen (1) mit Alkylhalogeniden bei 20–90°C ohne Lösungsmittel oder in Acetonitril liefert in guten Ausbeuten die 4-C-alkylierten Produkte4. Alkylierung von1 mit Alkyltriflaten in CH₂Cl₂ bei Raumtemperatur ergibt O-alkylierte Produkte (5). E6 wurde keine Umlagerung von O-alkylierten zu C-alkylierten Verbindungen beobachtet. Die spektroskopischen Eigenschaften der Alkylierungsprodukte werden berichtet und diskutiert.

     

Synthesis of 5-substituted 4-methylthio-1,3-thiazoline-2-thiones

Translated from Khimiya Geterotsiklicheskih Soedinenii, No. 2, pp. 276–277, February, 1989.     

New Reactions of Sulfur-Centered 1,3-Dipoles Generated from Thioketones in Three-Component Reactions with Phenyl Azide and an Electron-Deficient Dipolarophile

ABSTRACT:

Reactions of cycloaliphatic thioketones with phenyl azide in the presence of an electron-deficient C-C-dipolarophile have been studied. It was shown that the course of the reactions and the structures of the products depend strongly on the type of the dipolarophile used. Only in the case of fumaronitrile the interception product of the intermediate thiocarbonyl-S-imide was obtained.     

Bildung von 5,6-Dihydro-1,3(4H)-thiazin-4-carbonsäure-estern aus 4-Allyl-1,3-thiazol-5(4H)-onen

Formation of Methyl 5,6-Dihydro-l, 3(4H)-thiazine-4-carboxyiates from 4-Allyl-l, 3-thiazol-5(4H)-ones . The reaction of N-[1-(N, N-dimethylthiocarbamoyl)-1-methyl-3-butenyl]benzamid ( 1 ) with HCl or TsOH in MeCN or toluene yields a mixture of 4-allyl-4-methyl-2-phenyl-1,3-thiazol-5(4H)-one ( 5a ) and allyl 4-methyl-2-phenyl-1,3-thiazol-2-yl sulfide ( 11 ; Scheme 3). Most probably, the corresponding 1,3-oxazol-5(4H)-thiones B are intermediates in this reaction. With HCl in MeOH, 1 is transformed into methyl 5,6-dihydro-4,6-dimethyl-2-phenyl-1,3(4H)-thiazine-4-carboxylate ( 12a ). The same product 12a is formed on treatment of the 1,3-thiazol-5(4H)-one 5a with HCl in MeOH (Scheme 4). It is shown that the latter reaction type is common for 4-allyl-substituted 1,3-thiazol-5(4H)-ones.     

Reactions of Enone Ethylene Ketals with Methyl Diazomalonate/Bis(acetylacetonato)copper(II)

Several cyclic and acyclic enones and their ethylene ketals/acetals were reacted with dimethyl diazomalonate under bis(acetylacetonato)copper(II) catalysis. Cyclohex-2-en-1-one ( 1 ) yielded only C–H insertion products 2 and 3 , whereas but-3-en-2-one gave a cyclopropane albeit in very low yield. The ethylene ketals 6 of cyclopent-2-en-1-one and cyclohex-2-en-1-one gave the corresponding cyclopropanes 7 , which were in turn cleaved to the ketones 8 . The acetals 9 and 10 of crotonaldehyde ((E)-but-2-enal) and cinnamaldehyde ((E)-3-phenylprop-2-enal), respectively, yielded C–O insertion and [2,3]-sigmatropic rearrangement products 11b, c and 12b, c , as well as cyclopropanes 11a and 11b , all of which are polyfunctional and synthetically useful compounds.     

Synthesis of Substituted 1,3-Cyclohexadienes,Pyridine-2(1H)-thiones,and Thieno[2,3-d]pyrimidine- 4(3H)-thiones by the Michael Reaction

Cyclopentylidene- and cyclohexylidene(cyano)acetamides reacted with malononitrile and cyano-(thioacetamide) according to the Michael pattern with exchange of the methylene components to give substituted 1-amino-2,6,6-tricyano-1,3-cyclohexadienes and thieno[2,3-d]pyrimidine-4(3H)-thiones. Condensation of cyclopentylidene- and cyclohexylidene(cyano)acetamide with 1,3-dicarbonyl compounds afforded 4,6-di-methyl-3-cyanopyridine-2(1H)-thione and morpholinium 4-methyl-6-oxo-3-cyano-1,6-dihydropyridine-2-thiolate which were converted into substituted 2-alkylsulfanylpyridines, thieno[2,3-b]pyridines, thiazolo[3,2-a]pyridine, and 2H-[1,3]thiazino[3,2-a]pyridine.     

1,3‐Oxathiolanes from the Reaction of Aromatic and Enolized Thioketones with Monosubstituted Oxiranes

The reactions of 4,4′‐dimethoxythiobenzophenone ( 1 ) with (S)‐2‐methyloxirane ((S)‐ 2 ) and (R)‐2‐phenyloxirane ((R)‐ 6 ) in the presence of a Lewis acid such as BF₃?Et₂O, ZnCl₂, or SiO₂ in dry CH₂Cl₂ led to the corresponding 1 : 1 adducts, i.e., 1,3‐oxathiolanes (S)‐ 3 with Me at C(5), and (S)‐ 7 and (R)‐ 8 with Ph at C(4) and C(5), respectively. A 1 : 2 adduct, 1,3,6‐dioxathiocane (4S,8S)‐ 4 and 1,3‐dioxolane (S)‐ 9 , respectively, were formed as minor products (Schemes 3 and 5, Tables 1 and 2). Treatment of the 1 : 1 adduct (S)‐ 3 with (S)‐ 2 and BF₃?Et₂O gave the 1 : 2 adduct (4S,8S)‐ 4 (Scheme 4). In the case of the enolized thioketone 1,3‐diphenylprop‐1‐ene‐2‐thiol ( 10 ) with (S)‐ 2 and (R)‐ 6 in the presence of SiO₂, the enesulfanyl alcohols (1′Z,2S)‐ 11 and (1′E,2S)‐ 11 , and (1′Z,2S)‐ 13 , (1′E,2S)‐ 13 , (1′Z,1R)‐ 15 , and (1′E,1R)‐ 15 , respectively, as well as a 1,3‐oxathiolane (S)‐ 14 were formed (Schemes 6 and 8). In the presence of HCl, the enesulfanyl alcohols (1′Z,2S)‐ 11 , (1′Z,2S)‐ 13 , (1′E,2S)‐ 13 , (1′Z,1R)‐ 15 , and (1′E,1R)‐ 15 cyclize to give the corresponding 1,3‐oxathiolanes (S)‐ 12 , (S)‐ 14 , and (R)‐ 16 , respectively (Schemes 7, 9, and 10). The structures of (1′E,2S)‐ 11 , (S)‐ 12 , and (S)‐ 14 were confirmed by X‐ray crystallography (Figs. 1–3). These results show that 1,3‐oxathiolanes can be prepared directly via the Lewis acid‐catalyzed reactions of oxiranes with non‐enolizable thioketones, and also in two steps with enolized thioketones. The nucleophilic attack of the thiocarbonyl or enesulfanyl S‐atom at the Lewis acid‐complexed oxirane ring proceeds with high regio‐ and stereoselectivity via an S_n 2‐type mechanism.     

Isovaleric Aldehyde in the Synthesis of 4-Isobutyl-Substituted Pyridine-2(1H)-thiones, 4H-Pyrans, and 1,3-Cyclohexadiene

Cyclocondensation of isovaleric aldehyde with various CH acids [benzoylacetonitrile, malononitrile, cyanothioacetamide, 4-hydroxycoumarin, resorcinol, 3-phenylpyrazol-5(1H)-one, 3-morpholinocrotonanilide] in the presence of amines yields isobutyl-substituted 4H-pyrans, 1,3-cyclohexadiene, and pyridine-2(1H)-thiones. The latter compounds were used in the synthesis of substituted 2-pyridino thioethers and thieno[2,3-b]pyridine.__________Translated from Zhurnal Obshchei Khimii, Vol. 75, No. 3, 2005, pp. 476–482.Original Russian Text Copyright © 2005 by Dyachenko.     

Reactions of 3-hydrazino-5,6-diphenyl-1,2,4-triazine with 4-arylidene-2-phenyl-5(4H)-oxazolones and 4-benzylidene-3-methyl-5(4H)-isoxazolone

3-Hydrazino-5,6-diphenyl-1,2,4-triazine reacts with 4-arylidene-2-phenyl-5(4H)-oxazolones in toluene to give substituted acrylic acid hydrazides, and in glacial acetic acid to give substituted imidazolones. On the other hand the hydrazinotriazine reacts with 4-benzylidene-3-methyl-5(4H)-isoxazolone, probably via a 1,4 addition reaction followed by an elimination reaction, to give benzaldehyde 5,6-diphenyl-1,2,4-triazin-3-ylhydrazone and 3-methyl-5(4H)-isoxazolone.     

Reactions of 1,3-thiazine-2,6-dithiones. Part 5. Novel synthesis of 3,5-dicyano-4-thiopyridones via 2-cyanomethyldihydro-1,3-thiazine-6-thiones

A novel synthesis of a series of 2,6-disubstituted 3,5-dicyano-4-thiopyridones 4 by the decomposition of 2,4-disubstituted 5-cyano-2-cyanomethyldihydro-1,3-thiazine-6-thiones 2 , which are synthesized from 4-substituted 5-cyano-1,3-thiazine-2,6-dithiones and enaminonitriles, is described.