Thioaldehydes

PART I Thioaldehydes, Thioketones, Thioketens, and their Selenium Analogues 

Reviews.—The chemistry of lluorinated thiocarbonyl compounds and enamino-thioketones has been reviewed. An important paper deals with the reaction of organomagnesium reagents with thiocarbonyl compounds. Thione photochemistry has been covered in other reviews, and the synthesis of thioketens and oligomers has been surveyed.  

The thioaldehyde (1), associated with penicillin synthesis, has been trapped chemically, but not isolated. It undergoes polymerization or thioenolization, 

R8 = alkyl) substituted with a phosphonium ylide has been reported. Syntheses of thioaldehyde dianions and of iron complexes of thioacrolein and 2-ethyl-crotonthioaldehyde have appeared. 

Reactions.—Owing to the low thermal stability of thioaldehydes obtained by flash thermolysis, their reactivity has not yet been investigated. However, one paper reports that thioformaldehyde can be trapped with cyclopentadiene to give Diels-Alder cycloadducts.  

Synthesis.—All attempts to prepare simple aliphatic thioaldehydes have until now been unsuccessful, as only the cyclic trimers or less well-defined polymeric substances have been obtained. However, Brandsma has now reported that ajS-unsaturated sulphides (1) are cleaved by alkali metals in liquid ammonia to produce the corresponding enethiols (2) in high yields. For R = H, the products (2) represent the simple aliphatic thioaldehydes (3) in what is evidently their more stable tautomeric enethiol form. Apparently the pure enethiols (2 R = H) showed no tendency to 

Janssen, The Chemistry of Carboxylic Acids and Esters , ed. S. Patai, Interscience, New York, 1969, p. 705. 

The cycloaddition reaction between l,2-dithiole-3-thiones that are not substituted in the 5-position and acetylene derivatives has been found to give the thioaldehydes (4) as brown solids or pastes. The products could not be obtained analytically pure, but were characterized spectroscopically. The yields of the thioaldehydes were rather dependent on the 

Mechanistic studies in this area are essentially nonexistent. Recently, the regiochemistry of some [4 + 2] cycloadditions of thioaldehydes has been rationalized based on FMO theory. It is difficult to generalize the resulting stereochemistry of this type of Diels-Alder reaction since systematic studies are lacking and since many structurally diverse kinds of thiocarbonyl dienophiles have been used as 27t components. 

Thioketones of various types are readily available and are well documented as effective dienophiles. Representative thioketone cycloadditions are listed in Table 5-1. In general, it appears that thioketones usually add to most dienes in high yield at exceptionally low temperatures to afford stable adducts, although some of these adducts tend to undergo retro-Diels-Alder reactions. - Very little has been done toward establishing the regiochemical selectivity of thioketone additions to unsymmetrical 1,3-dienes, and the few such entries in Table 5-1 indicate that mixtures were obtained. The exo/endo stereochemistry of [4 + 2] cycloadditions with unsymmetrical thioketones has not been probed to date. It has been reported that Diels-Alder cycloadditions of thioketones can also be pho-tochemically induced. 

Relatively little in the way of further chemistry has been performed on these adducts, although Biellmann has found an interesting rearrangement of some 6,6-disubstituted thiapyrans [Eq. (2)].  

The carbanion derived from such a system rearranges to a cyclopropane derivative which can be S-alkylated to give the cw-thioether. Several possible mechanisms have been offered for this rearrangement. 

Until recently, thioaldehydes found little application in Diels-Alder cycloadditions owing to their relative unavailability and pronounced 

Synthesis.— The condensation of acetonitrile with ethyl thionoformate by means of butyl-lithium has been reported to yield thioformylacetonitrile (1) after subsequent treatment of the intermediate lithium salt (2) with hydrochloric acid. The thioaldehyde could not be isolated, but it was reasonably stable in solution in the tautomeric enethiol form (3), and was characterized as its stable S-methyl derivative (4). Several new, stable thioaldehydes, (5) and (6), have been synthesized by solvolysis of the VUsmeier salts (7) and (8) with aqueous sodium hydrogen sulphide. Some deuteriated analogues of (6) were similarly prepared from the corresponding salts (9). The thioaldehydes (10) were isolated as amorphous solids from the cycloaddition reaction of l,2-dithiole-3-thione with propiolic acid or its 

Voss and E. Fischer, Wiss. Z. Unit). Rostock, Math.-Naturwiss. Reihe, 1972, 21, 123 (Chem. Abs., 1973, 79, 31387). 

Sulphur in Organic and Inorganic Chemistry , ed. A. Senning, Marcel Dekker, New York, 1972, Vol. 3, p. 325. 

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Nonchelation control also results from the trifluoroborane-mediated addition of the following silylketcne acetal to 2-thioaldehydes. The diastereomeric ratios of the adducts surpasses 98 2... 

Selenoaldehydes 104, like thioaldehydes, have also been generated in situ from acetals and then directly trapped with dienes, thus offering a useful one-pot procedure for preparing cyclic seleno-compounds [103,104], The construction of a carbon-selenium double bond was achieved by reacting acetal derivatives with dimethylaluminum selenide (Equation 2.30). Cycloadditions of seleno aldehydes occur even at 0 °C. In these reactions, however, the carbon-selenium bond formed by the nucleophilic attack of the electronegative selenium atom in 105 to the aluminum-coordinated acetal carbon, may require a high reaction temperature [103], The cycloaddition with cyclopentadiene preferentially gave the kinetically favorable endo isomer. 

Vallee Y., Ripoll J. L. Synthesis of Thioaldehydes, Thioketones and Thioketenes... 

The addition of H2S to an aldehyde or ketone can result in a variety of products. The most usual product is the trithiane (8). ° ot-Hydroxy thiols (5) can be prepared from polychloro and polyfluoro aldehydes and ketones.Apparently, compounds 5 are stable only when prepared from these compounds, and not even for all of them. Thioketones (6) can be prepared from certain ketones, such as diaryl ketones, by treatment with H2S and an acid catalyst, usually HCl. They are often unstable and tend to trimerize (to 8) or to react with air. Thioaldehydes are even less stable and simple ones apparently have never been isolated, though t-BuCHS has been... 

Heteroatom Diels-Alder reaction of thioketones and thioaldehydes... 

Hetero Diels-Alder reactions of 114 with thioaldehydes and thioketones were also reported to give the syn addition products exclusively [64]. 

Reaction of aliphatic aldehydes with H2S and TCS 14 at room temperature in the presence of pyridine leads to the adducts 596, which can be converted by NaH in DMF, via the adducts 597 and the intermediate thioaldehydes 598, into their sodium salts 599. These sodium salts 599 can be trapped by alkyl- or aUyl hahdes in up to 91% yield to give the vinyl sulfides 600 [147] (Scheme 5.47). 

Free intermediate thioaldehydes 598 or 602 and the selenoaldehydes 605 and HMDSO 7 are obtained in THF at 0°C on treatment of aliphatic and aromatic aldehydes with bis(trimethylsilyl)thiane 601 or bis(trimethylsilyl)selenide 604 in the presence of traces of butyllithium, while trapping the sensitive intermediate thio- or selenoaldehydes 602 and 605 with cyclopentadiene or cyclohexadiene to furnish mixtures of endo and exo Diels-Alder adducts such as 603 a and 606 a and 603 b and 603 b [148-150], the exo/endo ratio of which can be controlled [150] (Scheme 5.48). Analogous reaction of ketones such as 2-adamantanone or acetylene ketones with MesSiXSiMes 608 (a. X=S (601) b. X=Se (604)) in the presence of... 

On transforming the cyclopentenone 1431 into the trimethylsilyloxy diene 1432 the ensuing Diels-Alder cyclization gives rise to 69% tricychc compound 1433 [10] (Scheme 9.8). For Diels-Alder-reactions of thioaldehydes, selenoaldehydes, or unsaturated nitroso compounds with cyclopentadiene, see the reactions of 602 to 603 and of 605 to 606 in Scheme 5.48 and of 1092 to 1093 in Scheme 7.43. For Diels-Alder-reactions of silyloxyazadienes such as 510 with maleic anhydride to give 511, see Scheme 5.29. 

In a quite different approach, the 1,3-oxathianes 79 undergo a tandem [4++2 ] -eye 1 oaddi ti on -elimination with alkenes yielding 3,4-dihydrothiopyrans a preference for the tis-isomer was noted (Scheme 55), The oxathianes, which are readily synthesised, thus serve as a,P-unsaturated thioaldehydes <00TL371>. 

Aldehydes can be converted into thioaldehydes by a similar reaction with bis(trimethylsilyl) sulfide catalyzed by BuLi (equation II). This disilyl sulfide has been used indirectly for conversion of aldehydes into thioaldehydes via boron trisulfide (11, 63). 

The reaction of thioaldehydes, generated from phosphonium ylides and sulphur with secondary amines such as dimethylamine, leads to thioamides. If the thioaldehydes possess a a-hydrogen atom enamines are produced (equation 103)326. 

Concomitant C-Si cleavage by tetra-n-butylammonium fluoride and extrusion of a phenylthiolate anion from ot-trialkylsilyldisulphides provides a route to reactive thioaldehydes [44],... 

TBA-F in THF (0.01 M, 200 ml) is added slowly with stirring over 30-60 min to the a-silyldisulphide RCH(SiR3)SSAr (5 mmol). The mixture is stirred until all of the disulphide is consumed and the reactive thioaldehyde is reacted in situ without isolation. 

The SH bond is sufficiently weaker than the CH bonds so that the RS radical would be the dominant species formed. At high temperatures, it is likely that the RS decay leads to the thioaldehyde... 

The disappearance of the thioaldehyde at these temperatures would closely resemble that of the aldehydes namely,... 

The radical formed in reaction (8.144) then decomposes to form an alkyl radical and a thioaldehyde molecule that is,... 

Density functional and semiempirical AMI molecular orbital calculations have been used to investigate substituent effects on site selectivity in heterocumulene-hetero-diene4 + 2-cycloadditions between ketene imines and acroleins.The new and novel heterocumulenes a, /3-unsaturated thioaldehyde S -oxides (97) behave as both diene... 

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