3-Thietanones reactions

Other thietane derivatives have been obtained by isomerization of nitrogen-containing heterocycles. The reaction of an acyl isothiocyanate (RCONCS) with diphenyldiazomethane gave 20 and this isomerized in solution to the tetraphenyl-3-thietanone 21 <96BSB253>. Additionally, the isoxazolidine 22 was converted into 23 by the action of trimethylsilyl iodide and zinc iodide <96H1211>. 

Thionyl chloride undergoes a cyclization reaction with ketones. Enoli-zation of the intermediate sulfenyl chloride, followed by the base-induced intramolecular nucleophilic displacement reaction, produces the thietanone... 

The most effective synthesis for thietanones is the eliminative cyclization of halogenated ketones with hydrogen sulfide ions in the presence of bases (Eq. lOb). The reaction of 1,3-dibromoketone derivatives with sodium hydrogen sulfide produced 3-thietanones in association with a five-membered cyclic disulfide (Eq. 10c). 

The yields of thietanone depend on the number of methyl groups attached to the 1,3-dihaloketones, a relationship attributed to the gem effect. Thus the unsubstituted thietane failed to form. Thietanes have been synthesized by a series of reactions involving addition of thiolacetic acid to a vinyl ketone, reduction with LiAlH4, substitution of the acyl group by the nitrile function, and subsequent ring closure to a cis-trans mixture of 119 (Eq. 11). 

An interesting reaction related to the ring expansions of penicillin S-oxides (208) was observed in the thermal rearrangement of 2,2,4A-tetramethyl-thiethan-3-one 1-oxide to the five-membered thiolane ring 209. Oxidation attempts of these thermally unstable thietanone oxides led via ring opening to the more stable heterocycle. The reaction mechanism (Scheme 11) was... 

A ring opening of the thietanone molecule can easily be induced by thio-phile attack of hydrogen sulfide ions, which leads to the formation of an enolate ion (Eq. 56). This reaction also depends on the degree of methylation... 

In order to clarify the photolytic behavior of thietanones, Langendries et al. monitored their reactions directly by IR spectroscopy in a cryostat. With the appearance of their specific IR absorption bands the sulfenes could be instantaneously detected and a cycloreversion mechanism postulated (Eq, 57). The sulfene bands could not be observed, however, when light with wavelengths below 220 nm was used for the irradiation. 

Formation of 3-thietanones out of o,a -dibromoketones and sodium hydrogen sulfide and their ring-opening reactions. ... 

Thietanone (53) (79LA1768) and thietane (54) (72BAU505) react with sulfur-containing nucleophiles giving ring-opened products. It is thought that these reactions are initiated by nucleophilic attack by the sulfur nucleophile on the ring sulfur. 

Oxygen can be introduced into the a-positions of thietanes by treatment of the thietane with lead tetraacetate as in the formation of (204) (75JOC3046). Thietanones can be prepared by hydrolysis of thiete enamines such as (205) (65LA(684)103) or by oxidation of 3-thietanol with DMSO/benzoic anhydride (78PS(4)167>. Thietanones can be converted into various ring-substituted sulfur derivatives as already illustrated in reactions of (68) and preparation of (199). 

Only a limited number of examples are known of applications of thietanes in organic synthesis. Prominent among these examples would be electrophilic ring opening reactions leading to polyfunctional sulfur compounds (33)-(37), utilization of 3-thietanones (55) and metal complexes (87) derived therefrom as oxyallyl zwitterion equivalents in cycloaddition reactions, synthesis of dipeptide (63) with a /3-thiolactone, Raney nickel desulfurization of thietanes (e.g. 120 cf. Table 7) as a route to gem-dimethyl compounds, and desulfurization of thietanes (e.g. 17) in the synthesis of cyclopropanes (also see Table 7). 

The ring-opening reaction of thietanone la in sulfuric acid solution led to the formation of 3-mercapto-2-methylpropionic acid in 50% yield (Equation 5) <2000MRC468>. 

The ring-opening reaction of 2-thietanone la by the action of benzylamine led to the formation of Ar-benzyl-3-mercapto-2-methylpropionamide in 60% yield (Equation 6) <2000MRC468>. 

The reaction of 2,2,4,4-tetramethyl-3-thietanone 24 with hydrazine in the presence of acetic acid in methanol led to the formation of the corresponding hydrazone 25 in 91% yield (Equation 7) <2001PCA2106>. 

The reaction of 3-iodopropionyl chloride with benzyltriethylammonium tetrathiomolybdate gave /3-thiolactone 77, but in rather poor yield (Equation 21) <1997T11835>. According to the authors, the poor yield resulted from the fact that 2-thietanones easily react with various nucleophilic reagents that are present in the reaction mixture and which result in cleavage of the S—C—O bond. 

These reactions, first described by Staudinger, have received little attention. A more recent investigation shows that the C -S bond of the thiones regioselectively adds across the C—C bond of the ketenes (equation 11) to form 2-thietanones (p-thiolactones). Primary adducts have been isolated only in a few cases. Most often they spontaneously decompose to yield an ene and COS (equation 12). 

Thiete structures have been suggested as fragmentation products in the mass spectra of a thietane fused to a 3-lactam, an ortho disulfide of a thiolbenzoate ester, -propanethiol, thiirane carboxylic acid esters, isothiazoles, thiazoles, 1,3-dithiole 2-thiones, 1,3-dithiolene-2-ones, S-ethyl thio-benzoate, and thianaphthene sulfones. Tetramethylthiete may have been formed on thermolysis of the p-toluenesulfonyl-hydrazone of 2,2,4,4-tetramethyl-3-thietanone. " Thiete 2-thione may be an intermediate in the decomposition of 1,2-ditholium salts by the action of bases. " 2,2-Diphenyl-2H-thiete is suggested as an intermediate in the reaction of diphenyldiazomethane with 1,2,3-benzo-thiadiazole which yields 9-phenylthioxanthene and three other products. ... 

Treatment of 3-thietanone 1,1-dioxide with diazomethane, diazoethane, or ethyl diazoacetate gives 3-alkoxythiete 1,1-dioxides, for example, 263. ° A similar reaction occurs with 2-phenyl-3-thietanone 1,1-dioxide and diazomethane. Hydrogenation of the exocyclic double bond in 264 can be accomplished without... 

Since it has been shown that this reaction generally gives 2-thietanones ( 3-thio-lactones), reports of 3-thietanones being formed should be treated skeptically (See Section XIII.3.B.). The chemical reactions and mass spectrum of the adduct of hexafluorothioacetone with diphenylketene have been interpreted on the basis of a 3-thietanone. ... 

The carbonyl group of 3-thietanone reacts typically with nucleophiles such as hydrazine (to give 364), 2,4-dinitrophenylhydrazine, ° tosylhydrazine, semicarbazide, and phenylmagnesium bromide.It undergoes the Wittig reaction (e.g., the formation of 365) yields vary from 14 to 74%. Sodium hydroxide cleaves the presumed 2,2-bis-trifluoromethyl-4,4-diphenyl-3-thietanone to diphenylacetic acid. ... 

The hydrazone 364 of 3-thietanone reacts with hydrogen sulfide to give the dispiro derivative 384. Thermolysis of the sodium salts of p-toluenesulfonyl-hydrazones of 3-thietanone,2,2,4,4-tetramethyl-3-thietanone and 2-isopropylidene-4,4-dimethyl-3-thietanone yields allene or cumulene epi-sulfides, for example, 385. The reactions of some tris-iminothietanes are discussed in Section XV.3.B. ... 

Methylene derivatives of thietanes have been obtained by the Wittig reaction of 3-thietanones, as in the preparation of 365 and the phosphonium ylide 345 with p-nitrobenzaldehyde (to give 354). A Wittig reaction also has been applied to a 2-thietanone. ... 

Tetramethyl-3-thietanone 1-oxide 400 is obtained in 69% yield by oxidation of the thietane with peracetic acid in benzene. Amides of 3-thietanone-2,4-dicarboxylic acid 1-oxide are said to be obtained by treatment of amides of acetone dicarboxylic acid with thionyl chloride and 3-thietanone-l-oxides may be intermediate in the reaction of ketones with thionyl chloride. The -oxide of 3,3,4,4-tetraphenyl-2-thietanone may be an intermediate in the oxidation of the thietanone by nz-chloroperbenzoic acid, which is discussed in Section XIII.4.E. ... 

Thietanone 1,1-dioxide ketals and 3-aminothiete 1,1-dioxides are readily available by cycloaddition of sulfenes to ketene acetals and enamines, respectively (Section V.3.B.). Hydrolysis of these ketals " and the aminothiete sulfones (which are enamines) " " gives 3-thietanone 1,1-dioxides in fair to good yields, as exemplified by the hydrolysis of 133 and 402. Aqueous mineral acids or acidic ion-exchange resins catalyze the reaction. Cis-2-chloro-2,4,4-trimethyl-3-morpholinothietane 1,1-dioxide reacts with N sodium hydroxide to give 38% 2,2,4-trimethyl-3-thietanone 1,1-dioxide, but the trans isomer is recovered unchanged. 3-Methoxy- and 3-ethoxythiete 1,1-dioxide (enol ethers) are also hydrolyzed to 3-thietanone 1,1-dioxide. In several cases, the hydrolysis products are written as enols of the 3-thietanone sulfone. ... 

The 3-thietanone 1,1-dioxide structure proposed for the product of the reaction of azibenzil with sulfur dioxide has been shown by nmr spectroscopy to be incorrect.2,2,4,4-Tetramethyl-3-thietanethione 1,1-dioxide is obtained from the corresponding ketone (69% yield) by treatment with phosphorous penta-sulfide.5 ... 

The reaction of 3-thietanone 1,1-dioxide with methanol to give the hemiketal has been observed by nmr spectroscopy the equilibrium composition is 90% hemiketal-10% ketone.The 2,4-dinitrophenylhydrazone and the p-toluene-sulfonylhydrazone have been reported. 

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