Thiocarbonylation, examples

The prefix thioxo- is used for naming =S in a thioketone. Sulfur analogs of acetals are named as alkylthio- or arylthio-. For example, CH3CH(SCH3)OCH3 is l-methoxy-l-(methylthio)ethane. Prefix forms for -carbothioic acids are hydroxy(thiocarbonyl)- when referring to the O-substituted acid and mercapto(carbonyl)- for the S-substituted acid. 

Radicals analogous to the above containing other chalcogens in place of oxygen are named by adding the prefixes thio-, seleno-, and so on for example, PS, thiophosphoryl CS, thiocarbonyl. 

The thiation procedure described here is an example of a general synthetic method for the conversion of carbonyl to thiocarbonyl groups. Similar transformations have been carried out with ketones, carboxamides,esters,thioesters, 1 actones, " thiol actones, - imides, enaminones, and protected peptides. ... 

Unusual reactions occur between diazomethane and heterocyclic thiocarbonyl compounds. For example, pyran-4-thiones give methylene ethers of 1,2-dimercaptans formed by dimerization (cf. 115 —>116). 4-Thioflavones and 4-thiochromones react similarly. 

Application of radical reactions to organic synthesis has recently received much atrendon, and various important reacdons have been discovered in this field. Alkyl halides, sulfides, seleniJes, and thiocarbonyl compounds have been used as precursors to alkyl radicals. Some examples are illustrated in Scheme 7.18. ... 

An extensive series of thiosemicarbazones obtained from 2-acetylpyridine was tested by Klayman et al. [4, 85] for antimalarial activity against Plasmodium berghei in mice. The molecular features essential for activity were found to be a 2-pyridylethylidene moiety, the presence of the thiocarbonyl sulfur, and certain, bulky or cyclic substituents at the terminal AT-atom. The most active 2-acetylpyridine thiosemicarbazones were " N-phenyl- and those with azacycUc substituents. For example, iV-substituents of 4-methylpiperidine, piperazine, and azabicyclo[3.2.2.]nonyl-, 4, were curative at a dose level as low as 20 mg/kg. 

An example of thione coordination is demonstrated with the thiocarbonyl donor ligand 2,6-dimethyl-4H-pyran-4-thione, that gives a complex with zinc chloride of the form ZnL2Cl2-The crystal structure shows the zinc is tetrahedrally coordinated by two chloride and two sulfur donors and the compound was further studied by 3H NMR and IR spectroscopy.573 Both monomeric and dimeric heterocyclic thione complexes have been formed with zinc.5 4,575... 

There is an enormous literature on thiocarbonyl compounds, due in part to the technical and industrial importance of many of them, including thioamides, thioureas, xanthates, dithiocarbamates and so forth. An excellent, and recent, general review is available.107 There are also specialized reviews germane to the present chapter Griffin, Woods, and Klayman2 discussed the use of thioureas in the synthesis of heterocycles the preparation of thiazoles from thioamides is included in a three-part volume on Thiazoles 108 the use of carbon disulfide in the synthesis of trithiones and related heterocycles has been reviewed by Mayer109 and Huisgen110 has reported numerous examples of 1,3-dipolar cycloadditions in which carbon disulfide was used. 

Reaction of lithium trimethylsilyldiazomethane (TMSC(Li)N2) with thiocarbonyl compounds has proved to be a convenient method for the preparation of 5-substituted 1,2,3-thiadiazoles. This reaction is very similar to the Pechmann-Nold reaction but probably does not proceed through a dipolar cycloaddition pathway. A number of examples of this type of reaction were described in CHEC-II(1996). More recently, it was reported that TMSCN2Li also reacts with diethylaminothiocarbonyl chloride to afford a mixture of 1,2,3-thiadiazoles 66 and 67 (Equation 19) <1997BSB533>. 

Hydrazines react with thiocarbonyl compounds, such as dithioesters, to afford directly symmetrical 1,3,4-thiadiazoles via a dithioacylhydrazine intermediate, which can be isolated and converted to the thiadiazole upon treatment with an electrophilic reagent or under thermal conditions (see Section 5.10.9.1.1). Examples of the direct formation of thiadiazoles from hydrazines and thiocarbonyls can be found in CHEC-II(1996) <1996CHEC-II(4)379>. 

Direct oxidation of thiocarbonyl compound by triflic anhydride results in stable dication salts containing disulfide framework. For example, reaction of thiocarbonate 155 with Tf2Q yields the dication salt 156 (Scheme 58).154... 

Disulfide dications are remarkably stable to water, in contrast to disulfonium dications. However, all they can be hydrolyzed by alkali water solution to give starting thiocarbonyl compound or more hydrolyzed product. For example, exposition of salt 157 to the aqueous NaOH gives formamidinium salt 158 and thiourea (Scheme 60).154... 

Another interesting example of a photochemi-cally induced domino process is the combination of the photocyclization of aryl vinyl sulfides with an intramolecular addition as described by Dittami et al. [901 as intermediate a thiocarbonyl ylide can be assumed. The domino-Norrish I-Knoevenagel-allyl-silane cyclization developed by us allows the efficient stereoselective formation of 1,2-trans-subsituted five- and six-membered carbocycles.1911 A photochemical cycloaddition of enamino-aldehydes and enamino-ketones with the intermediate formation of an iminium salt followed by addition to allylsilanes gives access to novel bicyclic heterocy-des. New examples of photochemically induced... 

The 5-dig-mode of cyclization has been applied in the synthesis of N-heterocycles. For example, treatment of the /i-allenyl dithiosemicarbazide 37 with Bu3SnH and AIBN in hot benzene furnishes the substituted 3H-pyrrole 38 in 41% yield and the isomeric heterocycle 39 in 30% yield (Scheme 11.13) [68], Iminyl radical 40 is formed via Bu3Sn addition to the thiocarbonyl group of the radical precursor 37 and fragmentation of the adduct (not shown). Nitrogen-centered radical 40 adds 5-dig-selectively to provide substituted allyl radical 41. The latter intermediate is trapped by Bu3SnH to furnish preferentially product 38 with an endocydic double bond. 

When thiocarbonyl derivatives are treated with an excess of electrophilic carbene complex, alkenes are usually obtained [1333-1336], The reaction is believed to proceed by the mechanism sketched in Figure 4.18, closely related to the thiocarbonyl olefination reaction developed by Eschenmoser [1337], Few examples have been reported in which stable thiiranes could be isolated [1338], The intermediate thiocarbonyl ylides can also undergo reactions similar to those of carhonyl ylides, e.g. 1,3-dipolar cycloadditions or 1,3-oxathiole formation [1338], Illustrative examples of these reactions are given in Table 4.22. 

The reduction of thiocarbonyl derivatives by EtsSiH can be described as a chain process under forced conditions (Reaction 4.50) [89,90]. Indeed, in Reaction (4.51) for example, the reduction of phenyl thiocarbonate in EtsSiD as the solvent needed 1 equiv of dibenzoyl peroxide as initiator at 110 °C, and afforded the desired product in 91 % yield, where the deuterium incorporation was only 48% [90]. Nevertheless, there are some interesting applications for these less reactive silanes in radical chain reactions. For example, this method was used as an efficient deoxygenation step (Reaction 4.52) in the synthesis of 4,4-difluoroglutamine [91]. 1,2-Diols can also be transformed into olefins using the Barton-McCombie methodology. Reaction (4.53) shows the olefination procedure of a bis-xanthate using EtsSiH [89]. 

Sakamoto et al. provided the first example of hydrogen abstraction by thiocarbonyl sulfur in the solid state [37,38]. Irradiation of AT-diphenylacetyl-AT-iso-propylthioaroylamides 6 in the solid state gave thioketones 7 (P-hydrogen abstraction products by thiocarbonyl sulfur), mercaptoazetidin-2-ones (y-hy-drogen abstraction products by thiocarbonyl sulfur), and aroylthioamides (y-hydrogen abstraction products by thiocarbonyl sulfur followed by cleavage). 

The effect of halogens on reactivity is also seen for fluorothiocarbonyl monomers. Thiocarbonyl fluoride is polymerized at —78°C by a trace of mild base such as dimethylforma-mide. The polymerization of hexafluorothioacetone is an extreme example of the effect of... 

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