Carbophile Additionen von Organocupraten mit 1,3-Thiazol-5(4H)-thionen

Carbophilic Additions of Organocuprates and 1,3-Thiazole-5(4H)-thiones Organocuprates and 1,3-thiazole-5(4H)-thiones 1 react in THF at 0° via carbophilic addition onto the C? S bond to give 4,5-dihydro-1,3-thiazole-5-thiols 3 (Scheme 3). This observation is in marked contrast to the previously described reaction of organolithium compounds and 1 , which undergo a thiophilic addition onto the exocyclic S-atom. As an exception, treatment of the 1,3-thiazole-5(4H)-thione 1a with tert-butyl cuprate leads to 7a (Scheme 3).     

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 .     

Regioselektive 1,3-dipolare Cycloadditionen von Thiocarbonyl-yliden mit 1,3-Thiazol-5(4H)-thionen

Regioselective 1,3-Dipolar Cycloadditions of Thiocarbonyl Ylides with 1,3-Thiazole-5(4H)-thiones The thiocarbonyl ylides 13 and 1,3-thiazol-5(4H)-thiones 1 undergo a smooth reaction to yield spirocyclic 1,3-dithiolanes 14 – 16 (Schemes 4–6). The 1,3-dipolar cycloadditions occur in a regioselective manner, but the orientation of the thiobcnzophenone-S-methylide ( 13b ) differs from that of the cycloalkane thione-S-methylides 13a and 13c . Whereas the 1,3-cycloadduct with 13b is formed in accordance with frontier-orbital considerations, the inverse orientation in the reactions with 13a and 13c most likely is the result of steric hindrance in the transition state. The thiocarbonyl ylides have been prepared in situ from the corresponding 2,5-dihydro-1,3,4-thiadiazoles 12 . The more stable aliphatic precursors 12a and 12c undergo decomposition at 50°, the unstable 12b at ?30°.     

Umsetzung von Diazoessigsäure-ethylester mit 1,3-Thiazol-5(4H)-thionen

Reaction of Ethyl Diazoacetate with 1,3-Thiazole-5(4H)-thiones Reaction of ethyl diazoacetate ( 2a ) and 1,3-thiazole-5(4H)-thiones 1a,b in Et₂O at room temperature leads to a complex mixture of the products 5–9 (Scheme 2). Without solvent, 1a and 2a react to give 10a in addition to 5a–9a . In Et₂O in the presence of aniline, reaction of 1a,b with 2a affords the ethyl 1,3,4-thiadiazole-2-carboxylate 10a and 10b , respectively, as major products. The structures of the unexpected products 6a, 7a , and 10a have been established by X-ray crystallography. Ethyl 4H-1,3-thiazine-carboxylate 8b was transformed into ethyl 7H-thieno[2,3-e][1,3]thiazine-carboxylate 11 (Scheme 3) by treatment with aqueous NaOH or during chromatography. The structure of the latter has also been established by X-ray crystallography. In the presence of thiols and alcohols, the reaction of 1a and 2a yields mainly adducts of type 12 (Scheme 4), compounds 5a,7a , and 9a being by-products (Table 1). Reaction mechanisms for the formation of the isolated products are delineated in Schemes 4–7: the primary cycloadduct 3 of the diazo compound and the C?S bond of 1 undergoes a base-catalyzed ring opening of the 1,3-thiazole-ring to give 10 . In the absence of a base, elimination of N₂ yields the thiocarbonyl ylide A ′, which is trapped by nucleophiles to give 12 . Trapping of A ′, by H₂O yields 1,3-thiazole-5(4H)-one 9 and ethyl mercaptoacetate, which is also a trapping agent for A ′, yielding the diester 7 . The formation of products 6 and 8 can be explained again via trapping of thiocarbonyl ylide A ′, either by thiirane C (Scheme 6) or by 2a (Scheme 7). The latter adduct F yields 8 via a Demjanoff-Tiffeneau-type ring expansion of a 1,3-thiazole to give the 1,3-thiazine.     

1,3-Dipolare Cycloadditionen eines Carbonyl-ylids mit 1,3-Thiazol-5(4H)-thionen und Thioketonen

1,3-Dipolar Cycloadditions of a Carhonyl-ylide with 1,3-Thiazole-5(4H)-thiones and Thioketones Inp-xylene at 150°, 3-phenyloxirane-2,2-dicarbonitrile ( 4b ) and 2-phenyl-3-thia-1-azaspiro[4.4]non-1-ene-4-thione ( 1a ) gave the three 1:1 adduets trans- 3a , cis- 3a , and 13a in 61, 21, and 3% yield, respectively (Scheme 3). The stereoisomers trans- 3a and cis- 3a are the products of a regioselective 1,3-dipolar cycloaddition of carbonylylide 2b , generated thermally by an electrocyclic ring opening of 4b (Scheme 6), and the C?S group of 1a . Surprisingly, 13a proved not to be a regioisomeric cycloadduct of 1a and 2b , but an isomer formed via cleavage of the O? C(3) bond of the oxirane 4b . A reaction mechanism rationalizing the formation of 13a is proposed in Scheme 6. Analogous results were obtained from the reaction of 4b and 4,4-dimethyl-2-phenyl-1,3-thiazole-5 (4H)-thione ( 1b , Scheme 3). The thermolysis of 4b in p-xylene at 130° in the presence of adamantine–thione ( 10 ) led to two isomeric 1:1 adducts 15 and 16 in a ratio of ca. 2:1, however, in low yield (Scheme 4). Most likely the products are again formed viathe two competing reaction mechanisms depicted in Scheme 6. The analogous reactions of 4b with 2,2,4,4-tetramethylcyclobutane-1,3-thione ( 11 ) and 9H-xanthene-9-thione ( 12 ) yielded a single 1:1 adduct in each case (Schemes). In the former case, spirocyclic 1,3-oxathiolane 17 , the product of the 1,3-dipolar cycloaddition with 2a corresponding to 3a , was isolated in only 11 % yield. It is remarkable that no 2:1 adduct was formed even in the presence of an excess of 4b. In contrast, 4b and 12 reacted smoothly to give 18 in 81 % yield; no cycloadduct of the carbonylylide 2a could be detected. The structures of cis- 3a , 13a , 15 , and 18 , as well as the structure of 14 , which is a derivative of trans- 3a , have been established by X-ray crystallography (Figs. 1–3, Table).     

Synthese von 4,4-disubstituierten 1,3-Thiazol-5(4H)-thionen

Synthesis of 4,4-Disubstituted 1,3-Thiazol-5(4H)-thiones An easy synthesis for the 1,3-thiazol-5(4H)-thiones 5 , a class of heterocycles which have hitherto only been available with difficulty, is described. Reaction of 3-amino-2H-azirines 25 with thiocarboxylic acids at 0° yields monothiodiamides of type 20 (Scheme 6) which, on treatment with Lawesson reagent at 100°, undergo thiation and cyclization to give 5 in good yield.     

1,4-Dithiafulvene aus der Umsetzung von 4,4-disubstituierten 1,3-Thiazol-5(4H)-thionen mit Acetylenderivaten

1,4-Dithiafulvenes, Products of the Reaction of 4,4-Disubstituted 1,3-Thiazol-5(4H)-thiones and Acetylenic Compounds On heating in toluene, 4,4-disubstituted 1,3-thiazol-5(4H)-thiones 1 and acetylenecarboxylates or acetylenecarbonitriles 2 undergo a cyclosubstitution reaction to yield 2-methylidene-1,3-dithiol derivatives 3 (1,4-dithiafulvenes) and a nitrile. Further heating of 3a and 3b in the presence of excess 2a leads to the isomeric 2,3-dihydrothiophene-2-thiones 4a and 4b , respectively. The benzodithiafulvene 14 has been formed in a similar reaction from 1a and in situ generate benzyne.     

Umsetzungen von 1,3-Thiazol-5(4H)-thionen mit Grignard- und Organolithium-Verbindungen: Carbophile und Thiophile Additionen

Reactions of 1,3-Thiazole-5(4H)-thiones with Grignard- and Organolithium Compounds: Carbophilic and Thiophilic Additions Organolithium compounds and 1,3-thiazole-5(4H)-thiones 9 reacted via thiophilic addition on the exocyclic S-atom. The intermediate anion E has been trapped by protonation to give 12 and by alkylation to yield 16 , respectively (Schemes 5 and 6). In competition with protonation of E , a fragmentation to benzonitrile and a dithioester 14 was observed (Scheme 5). In some cases, the alkylation of E led to the formation of dithioacetals 17 instead of 16 (Scheme 6). Methyl, ethyl, and isopropyl Grignard reagents and 9 in THF underwent again a thiophilic addition yielding 4,5-dihydro-1,3-thiazoles of type 12 (Scheme 3). In contrast to this result, MeMgI reacted with 9a in Et₂O via carbophilic addition to 11 . Again a carbophilic attack at C(5) of 9 was observed with allylmagnesium and 2-propynylmagnesium bromide, respectively, in Et₂O.     

Reaktion von Phenyldiazomethan mit 1,3-Thiazol-5(4H)-thionen: Basenkatalysierte Ring-Öffnung des Primäradduktes

Reaction of Phenyldiazomethane with 1,3-Thiazole-5(4H)-thiones: Base-Catalyzed Ring Opening of the Primary Adduct Reaction of 1,3-thiazole-5(4H)-thiones 1 and phenyldiazomethane ( 2a ) in toluene at room temperature yields the thiiranes trans- and cis-1,4-dithia-6-azaspiro[2.4]hept-5-enes (trans- and cis- 4 ; Scheme 2). With Ph₃P in THF at 70°, these thiiranes are transformed stereospecifically into (E)- and (Z)-5-benzylidene-4,5-dihydro-1,3-thiazoles 5 , respectively. In the presence of DBU, 1 and 2a react to give 1,3,4-thiadiazole derivatives 6 or 7 via base-catalyzed ring opening of the primary cycloadduct (Scheme 3). In the case of 2-(alkylthio)-substituted 1,3-thiazole-5(4H)-thiones 1c and 1d , this ring opening proceeds by elimination of the corresponding alkylthiolate, yielding isothiocyanate 7 . The structures of (Z)- 5c and 6b have been established by X-ray crystallography.     

Additionsreaktion von 1,3-Thiazol-5(4H)-thionen und inaminen; Bildung von Thioamiden und Thioketonen

Addition Reaction of 1,3-Thiazole-5(4H)-thiones and Ynamines; Formation of Thioamides and Thioketones Ynamines and 1,3-thiazole-5(4H)-thiones of type 1 undergo an addition reaction on heating in toluene yielding mainly α,β-unsaturated 2-(4,5-dihydro-1,3-thiazol-5-yliden)thioamides of type 7 (Scheme 2 and Table). In some cases, 1-diethylamino-1-(4,5-dihydro-1,3-thiazol-5-yliden)-2-alkanethiones 8 have been isolated as minor products. In analogy to other reactions of ynamines with C?O and C?S bonds, a [2 + 2] cycloaddition to thiete intermediates, followed by an electrocyclic ring opening is suggested as reaction mechanism.     

Umsetzung von Di(tert-butyl)- und Diphenyldiazomethan mit 1,3-Thiazol-5(4H)-thionen: Isolierung und Kristallstruktur des primären Cycloadduktes

Reaction of Di(tert-butyl)- and Diphenyldiazomethane and 1,3-Thiazole-5(4H)-thiones: Isolation and Crystal Structure of the Primary Cycloadduct Reactions of diazo compounds with C?S bonds proceed via the formation of thiocarbonyl ylides, which, under the reaction conditions, undergo either 1,3-dipolar cycloadditions or electrocyclic ring closer to thiiranes (Scheme 1). With the sterically hindered di(tert-butyl)diazomethane ( 2c ), 1,3-thiazole-5(4H)-thiones 1 react to give spirocyclic 2,5-dihydro-1,3,4-thiadiazoles 3 (Scheme 2). These adducts are stable in solution at ?20°, and they could be isolated in crystalline form. The structure of 3c was established by X-ray crystallography. In CDCl₃ solution at room temperature, a cycloreversion occurs, and the adducts of type 3 are in an equilibrium with 1 and 2c . In contrast, the reaction of 1 with diphenyldiazomethane ( 2d ) gave spirocyclic thiiranes 4 as the only product in high yield (Scheme 3). The crystal structure of 4b was also determined by X-ray analysis. The desulfurization of compounds 4 to 4,5-dihydro-5-(diphenylmethylidene)-1,3-thiazoles 5 was achieved by treating 4 with triphenylphosphine in boiling THF. The crystal structure of 5f is shown.     

Synthesis of Endothiopeptides and Their Cyclization to 1,3-Thiazol-5(4H)-imines

Further investigations of the synthesis of endothio analogues of the segment 1 – 10 ( 8 ) of an apolar analogon of zervamicin IIA are described. The endothiodecapeptide Boc-Trp-Ile-Ala-Aib-Ile-Val-Aib-Leu-Aib-Ψ(CS)-Pro-OMe ( 10 ) has been prepared in good yield by our novel methodology. On the other hand, all attempts to prepare endothio analogues of 8 with the thioamide group at position 3 (Ala^t) gave not the expected linear endothiopeptides but led to epimerized 1,3-thiazol-5(4H)-imine derivatives as the main products. The mixture of epimers of the thiazolimines 27 , 30 , and 31 have been separated by means of preparative HPLC, and their structures have been established by 2D-NMR experiments.     

Acylgruppenwanderung in N-Acyl-2H-imidazol-4(3H)-thionen

On acylating 2H-imidazole-4(3H)-thiones the orange to violet crystalline N-1-acyl-2H-imidazole-4(3H)-thiones1 a–18 a are formed, the thermal stability of which depends on the acyl group and the substituents in the heterocyclic ring system. Thus the N-aroyl-2,2,5-trimethyl-2H-imidazole-4(3H)-thiones13 a–16 a are stable on being heated to the melting point, while1 a–12 a are converted quantitatively to the corresponding S-aroyl-2H-imidazole-4-thiols1–12. Rearrangement is faster when the heterocyclic ring bears bulky substituents. The aliphatic N-acyl compounds17 a and18 a are thermally unstable. This N S acyl group migration, described here for the first time, is shown to proceed by an intermolecular mechanism.

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Herrn Prof. Dr. Dr. h. c. mult.Hermann F. Mark zum 80. Geburtstag in Verehrung gewidmet.

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88. Mitt.:F. Asinger, A. Saus, H.-J. Gräber, E. Fichtner undW. Leuchtenberger, Mh. Chem.106, 1449 (1975).

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Teil der DissertationE. Fichtner, Techn. Hochschule Aachen, 1974.     

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.     

Additionsreaktionen von 2-Thiazolin-5-thionen mit Acetylenen Vorläufige Mitteilung

Addition Reactions of 2-Thiazolin-5-thiones with Acetylenes The reaction of the 2-thiazolin-5-thiones 1 and 5 , respectively, with acetylen carboxylates yields mainly 1, 4-dithiafulvenes of type 3. In the presence of the acetylenic compounds, the 1, 4-dithiafulvenes undergo an isomerization to give the corresponding 2, 3-dihydrothiophene-2-thiones 4.     

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

Russian Journal of General Chemistry -     

Synthese von 4-Benzylthio- und 4-(Arylthio)-1,3-oxazol-5(2H)-onen

Synthesis of 4-(Benzylthio)-and 4-(Arylthio)-1,3-oxazole-5(2H)-ones Following a known procedure, 4-(benzylthio)-1,3-oxazol-5(2H)-one ( 4a ) was synthesized starting from sodium cyanodithioformate ( 1 ) and cyclohexanone (Scheme 1). The structure of the intermediate 4-(benzylthio)-1,3-thiazol-5(2H)-one ( 3a ) was established by X-ray crystallography. An alternative route was developed for the synthesis of 4-(arylthio)-1,3-oxazol-5(2H)-ones which are not accessible by the former reaction. Treatment of ethyl cyanoformate ( 5 ) with a thiophenol in the presence of catalytic amounts of Et₂NH and TiCl₄, followed by addition of a ketone and BF₃.Et₂O in a one-pot-reaction, gave 4f–i in low-to-fair yields (Scheme 3). Both synthetic pathways-complementary as for benzyl–S and aryl-S derivatives–seem to be limited with respect to variation of substituents of the ketone.