Thioketones methylation

A -Methylation of the NH of heterocycles using 1 is also known as exemplified by the methylation of indole/ The interesting mechanism is delineated below. O-methylation of weak acids such as phenols, carboxylic acids and oximes as well as 5-methylation such as A -phenylisorhodanine, certain thioketones, and dithiocarboxylic acids have also been reported." ... 

Dihydrothiopyrans have also been prepared by cycloaddition between a,jS-unsaturated thioketones and carbonyl-activated dienophiles under Lewis-acid catalysis [78]. A marked dependence of the reaction yield on the catalyst was observed. The results of the cycloaddition reaction of thioketone 77 with methyl metacrylate, catalyzed by different catalysts, are illustrated in Equation 3.24. 

Many cycloadditions of nitrones86,172 174 and thiones give cycloaddition-cycloreversion equilibria. A-Methyl-C,C-diphenyl- and A-methyl-C-phenyl-nitrones, react with aliphatic thiones forming 1,4,2-oxathiazolidines, while 4 does not afford a cycloadduct.172 A-Methyl-C,C-2,2,4,4-tetramethyl-3-cyclo-butanonenitrone reacts with alicyclic thioketones to give 1,4,2-oxathiazolidines,174 while with 4 it enters into a metathesis reaction. 

Although almost all kinds of thiocarbonyl compounds are good dienophiles, synthetic applications derived from the Diels-Alder adducts of thioketones, thionesters and dithioesters remain rather rare and focused on specific targets, as in the preparation of a fragment of the antibiotic erythronolide from the cycloadduct formed regioselectively from 2-methyl-l,3-pentadiene and an a-oxodithioester, a particularly efficient dienophile [524]. 

A related reaction is the silver(I) ion-mediated desulfurization-condensation of a number of thioketones with different active methylene compounds, such as malononitrile, methyl cyanoacetate etc.426 (equation 113), which takes place under mild basic conditions. 

Methyl iodide adducts of 2,4-diphenyl- or of 2,3,4-triphenyI-l,6,6a IV-trithiapentalene react with aniline giving a compound which can be considered as a-(l,2-dithiol-3-ylidene)aldimine (59) or perhaps also as a-(isothiazolin-5-ylidene)thioketone (60).76... 

Similarly small rate factors were obtained for 1,3-dipolar cycloadditions between diphenyl diazomethane and dimethyl fumarate [131], 2,4,6-trimethylbenzenecarbonitrile oxide and tetracyanoethene or acrylonitrile [811], phenyl azide and enamines [133], diazomethane and aromatic anils [134], azomethine imines and dimethyl acetylenedi-carboxylate [134a], diazo dimethyl malonate and diethylaminopropyne [544] or N-(l-cyclohexenyl)pyrrolidine [545], and A-methyl-C-phenylnitrone and thioketones [812]. Huisgen has written comprehensive reviews on solvent polarity and rates of 1,3-dipolar cycloaddition reactions [541, 542]. The observed small solvent effects can be easily explained by the fact that the concerted, but non-synchronous, bond formation in the activated complex may lead to the destruction or creation of partial charges, connected... 

N,N-Methyltosylhydrazones. Ketones react only slowly with N,N-methyl-tosylhydrazine (1) but hydrazones of this type can be prepared by N-alkylation of tosylhydrazones with phase-transfer catalysis. The more reactive thioketones also react sluggishly with 1, but in this case, the reaction can be catalyzed by soft Lewis acids. Thus the reaction of 2 with 1 proceeds in high yield at room temperature in the presence of 1 equiv. of silver nitrate. Mercuric acetate also promotes this reaction, but the yield of 3 is only 50% because of formation also of 4 in 44% yield. 

A reaction which is applicable to the synthesis of imidazoles substituted at C-4 by sulfur substituents is the interaction of a-chloro-a-phenyl thioketones (prepared from the corresponding diazoketones) with ammonia and carboxylic acids. Although the detailed reaction course is yet uncertain, it bears a close resemblance to the reactions of a-chloro ketones with amides. The method has been used to prepare 2-ethyl-4-methyl-5-phenylthioimidazole (145) using ammonia, propanoic acid and 1-chloro-l-phenylthiopropanone (Scheme 82). 

The addition of ZnBr2 to the tandem 1,3-azaprotio cyclotransfer-cycloaddition of a ketoxime with divinyl ketone results in rate enhancement and the exclusive formation of l-aza-7-oxabicyclo[3.2.1]octan-3-ones7 The 1,3-dipolar cycloaddition of 1-aza-l-cyclooctene 1-oxide with alkenes produces the corresponding isoxazolidines in high yields with a minimum of polymeric material. The cycloaddition of thiophene-2-carhaldehyde oxime with acetonitrile and methyl acrylate produces the 1,3-dipolar adduct, suhstituted isoxazolidines, and not the previously reported 4 - - 2-adducts. Density functional theory and semi-empirical methods have been used to investigate the 3 + 2-cycloaddition of azoxides with alkenes to produce 1,2,3-oxadiazolidines. The 3 -h 2-cycloaddition of a-nitrosostyrenes (62) with 1,3-diazabuta-1,3-dienes (63) and imines produces functionalized cyclic nitrones (64) regioselectively (Scheme 22). The first imequivocal 1,3-dipolar cycloaddition of sulfines involves the reaction of 2,2,4,4-tetramethyl-3-thioxocyclobutanone S-oxide with diaryl thioketones to produce... 

The iodonium salt 193 derived from methyl acetoacetate behaves as an a-ketocarbene equivalent and adds to methyl ketones to give the dioxoles 194. Similar addition to C=S occurs for thioketones to give 195 and with CS2 to give the oxathiole-2-thione 196 (Scheme 18) <2002TL5997>. The corresponding diazo compound 197 reacts with succin-imide and a rhodium catalyst to give the spiro dioxole 198 <2006TL2643>. 

The conversion of thioketones to sulfines (R2C=S=0) is difficult to categorize into the sections available, and it placed after oxidation of ketones and aldehydes. The reaction of a thioketone with hydrogen peroxide and a catalytic amount of MTO (methyl trioxorhenium) gives the sulfine. ... 

Enolisable thioketones (i.e. those possessing an a-hydrogen atom) like thiocyclohexanone (15) are easily methylated by treatment with diazomethane (Scheme 14a). However, non-enolisable thioketones (6) behave differently and yield the episulfides (23) (Scheme 14b). The first reaction (Scheme 14a) is the normal methylation of the acidic enethiol proton by diazomethane. The second reaction (Scheme 14b) involves initial nucleophilic attack by the diazomethane molecule on the electrophilic thiocarbonyl carbon atom... 

Aryl-substituted ketones react directly with elemental sulfur in hexa-methylphosphorus triamide with formation of l,2-dithiole-3-thiones.46,47 Aryl-substituted acetaldehydes can condense likewise with carbon disulfide to give the analogous 4-aryl-substituted l,2-dithiole-3-thiones.48 The same reaction was observed with aryl-substituted acetic acid esters, in which a methylthio group is incorporated into the reaction product (26).49 Thioketones and enthioles react analogously. 50,51 The parent l,2-dithiole-3-thione (27) has been prepared from the tetra-methyl acetal of malondialdehyde and phosphorus pentasulfide.52 In the presence of ammonia the reaction of cyclohexanone or cycloheptanone with carbon disulfide and sulfur gives as by-products the condensed 1,2-dithiole-3-thiones 28a and 28b, respectively.53... 

The preparative reduction, polarography, and cyclic voltammetry of 5-methyl-l,2-dithiole-3-thione have been studied.171 The results obtained are in agreement with a one-electron reduction of the thiocarbonyl group to a radical-anion, which could not be detected by ESR spectroscopy as it dimerizes too fast. The dimer is further reduced by a one-electron reduction to an anion in which the ring has been opened. (Scheme 12). The dianion could be isolated after methylation and was found to be identical with the compounds isolated by Maignan and Vialle by reduction with sodium sulfide.124 The dianion corresponds to the thioketonate dianion obtained by electrochemical reduction of 1,2-dithiolylium salts.172... 

The mass spectra of a series of methyl and phenyl substituted compounds have been studied.287 A general feature of these mass spectra is that the base peak is normally due to the molecular ion. 5-Monosubstituted compounds (e.g., 181) show intense peaks corresponding to M — HS2 (182), which can be formed by the fragmentation shown, such ions are also found in the mass spectra of a-(l,3-dithiole-3-ylidene)thioketones and have been used in the discussion of the structure of these compounds.204... 

---