A-thioketones

The mechanism of the Hantzsch s synthesis was studied at a very early stage by several authors. The intermediates were generally assumed to be open-chain a-thioketones, but in a series of papers by Murav eva and Schukina (470, 490) the isolation of hydroxythiazolines from the reaction between a-haloketones and a variety of thioureas was reported. 

It is interesting to note that in each of these cases only one intermediate, either the a-thioketone (93) or the hydroxythiazoline (94), was isolated from the reaction mixture, thus suggesting that hydroxythiazolines are in equilibrium with the corresponding a-thioketones. Similar conclusions are implicit in Baganz and Roger s production of 4-formylthiazoles by this synthesis (625). 

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. 

Two further compounds are on the borderline of stability. The oxathiirane (14), obtained by photorearrangement of a thioketone 5-oxide, could be characterized by its UV spectrum (76JCS(P1)1404). Thiazirine (15) was stable only at 15 K (78JCS(P1)746). 

Thiaziridines,145 thiiranes,167 and elemental sulfur168 (in the presence of Ph3P) can react with a thioketone to give thiosulfines then trapped as 1,2,4-trithiolane. 

However, for the free acid "C NMR analysis indicates the presence of a thioketone function instead of a thiol function <77JHCI4I7> (see Section 4.19.3.2). 

The reaction is of great value and most of the early work in the field is quoted and discussed in [203] by Block. As the allyl vinyl sulfide can be metallated and submitted to electrophilic substitution prior to rearrangement and the thiocarbonyl group hydrolysed in situ to a carbonyl group in the reaction product, the process has found considerable utility. The syntheses of propylure [488] and ris-jasmone [489] are early examples in which a thioaldehyde was intermediary formed (Y = H). A thioketone was involved [490] in the rearrangement of the allyl allenyl sulfide shown here. 

The desulfurdimerization reaction of dithioacetals proceeds via a thioketone intermediate. 

A stable dithiirane 223 was obtained from the oxidation of 6,7-dithiabicyclo[3.1.1]heptane 222 with oxone (2KHS0s KHS04 K2S04). Heating in solution afforded a thioketone 224 and 8-oxa-6,7-dithiabicyclo[3.2.1]octane 225 (resulted from an intramolecular [3+2] cycloaddition of the 5-thioketone J-sulfide indermediate) (Scheme 74) C1997TL1431, 1997BCJ509>. 

In a similar reaction, heating the di-fc+-butyl-tetramethyl-keto-thiirane 226 affords an analogous 8-oxa-6,7-dithia-bicyclo[3.2.1]octane 227, in competition with desulfurizing reactions yielding a thioketone 228 (X = S) and a diketone 228 (X = 0) (Scheme 74) C1997TL1431, 1997BCJ509>. 

Other dipolarophiles have been tested leading to pyrrolidines (from vinyl sulfones),219 oxazolidines (from ketones) and thiazolidine (from a thioketone) in moderate to good yields. Noteworthy is the isolation of two adducts from ethoxycrotonaldehyde a pyrrolidine carbaldehyde implying cycloaddition onto the ethylenic double bond and an oxazolidine resulting from the cycloaddition on the carbonyl moiety of the dipolarophile.219 438... 

The base catalyzed reaction of 4-phenyl-l,2-dithiole-3-thione 506 with a,P-unsaturated nitriles affords 6-aminothiopyran-2-thiones. A complex mechanism is postulated for the transformation with elimination of a thioketone from a dithiepin featuring in the key step (Scheme 189) <2003PS(178)2255>. 

The increasing utilisation of thiocarbonyl compounds brings about the necessity for efficient procedures for their transformation into carbonyl compounds. A straightforward method [172] involves the treatment of a thioketone with 4-nitrobenzaldehyde in the presence of TMSOTf. Thus thio-benzophenones and thiocamphor are converted into the corresponding ketones, but aliphatic thioketones or thioamides are resistant under these conditions. In order to convert an easily accessible bis(thiocamphor), de-... 

Although some examples have previously shown the feasibility of this reaction, very few studies have been reported recently. The isolation of a new antibiotic, leinamycin, featuring a novel dithioperoxyester S-oxide moiety, led Pattenden and Shuker [249] to a strategy based upon the [2+2] cycloaddition of a thioketone and a ketene. The expected 4-membered ring thio-lactone was obtained, albeit in modest yield, very probably due to the low thermal stability of thioacetone. The product could be transformed into a model dithiolane oxide. 

The mechanism of the Hantzsch synthesis has been established and is shown in Scheme 165. Substitution of the halogen atom of the a-halo ketone by the sulfur atom of the thioamide occurs first to give an open-chain a-thioketone (232), which under transprotonation proceeds to give a 4-hydroxy-A2-thiazoline (233) in aprotic solvents, or a thiazole (234) by acid-catalyzed dehydration of the intermediate thiazoline in protic solvents. 

The application of the Hantzsch synthesis to monosubstituted thioamides affords the corresponding N-substituted thiazolylium salts. This method is particularly valuable for the preparation of those thiazolylium compounds in which the substituent on the ring nitrogen atom cannot be introduced by direct quaternization, for example the synthesis of aryl or heteryl thiazolylium salts. In that case the intermediate a -thioketone can usually be isolated, its conversion into the thiazolylium salt occurring by simple heating (Scheme 166). 

In a reaction similar to that shown in equation (38), oxathioles may be obtained when diazobenzil is allowed to react with a thioketone (78JOC3730). A carbene intermediate is presumably not involved since addition of copper(I) sulfate gives vigorous gas evolution and tarry materials. The mechanism probably involves initial nucleophilic attack of the carbonyl oxygen at the thiocarbonyl carbon as shown in Scheme 27. 

Other new oxathiolane syntheses include reaction of an epoxide with a stable thioketone <01HCA3319>. Rhodium catalysed reaction of dimethyl diazomalonate with a thioketone has been used to prepare oxathiole 92 <02PJC551> and the iodonium ylide 8 reacts with thioketones or carbon disulfide to form oxathioles <02TL5997>. 

Episulfides, generated from diazo compounds and a thioketone, can also undergo desulfurization with phosphines to give alkenes (see section 4.3.7). 

The Barton-Kellogg reaction is a coupling reaction between a diazo compound and a thioketone to give an episulfide. Desulfurization of the episulfide to alkene can be accomplished by phosphine or by copper powder. This reaction has been pioneered by Hermann Staudinger and therefore the reaction also goes by the name Staudinger-type diazo-thioketone coupling. 

Heating allyl 2-naphthalenyl sulfoxide (7) to 120 CC for 2 hours in dimethylformamide results in quantitative isomerization to the cw-dihydrothiophene derivative 8. A possible pathway for the formation of 8 involves [3,3] sigmatropic rearrangement of 7 to a thioketone S-oxidc followed by a [1,4] sigmatropic rearrangement to a sulfenic acid intermediate and final intramolecular cis addition to give 889 92. 

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