Mercapto Ketones

VI. THIAZOLES FROM IVITRILES AND a-MERCAPTO-KETONES OR ACIDS 2,4-DISUBSTITUTED AND 4-HYDROXYTHIAZOLE DERIVATIVES... 

A general type of [3 + 3] heterocyclization involves initial nucleophilic attack on the electrophilic three-membered heterocycle by a 1,3-electrophile-nucleophile. Aziridines (330) with either a-mercapto ketones (329) or with a mixture of a ketone and sulfur give 5,6-dihydro-1,4-thiazines (330 — 331 — 332). Azirines (333) can be used for the preparation of pyrazinones (334) from ot-amino esters R2CH(NH2)C02Et and of 1,4-oxazinones from a-hydroxy esters (83TL1153). 

A number of /J-mercapto ketones (61 R = 2-thienyl, 2-furyl R = Ph, 2-thienyl, 2-furyl) have been reported they were prepared, in somewhat low yield, by the reaction shown in equation (6). Reaction of the o-mercapto ketone (61) with Cu" gives the yellow Cu1 complex with concomitant oxidation of the mercapto ketone to the disulfide.254 o- Mercaptoacetophenone (62) and /J-mercapto-benzophenone (63) have been prepared but are unstable 235 their chelating ability is greater than that of the ketones of type (61) because of the conjugated double bonds in the former.256... 

Synthesis from nitriles and a-mercapto ketones or acids 2,4-disubstituted and 4- 302... 

Besides a-halocarbonyl compounds, a-mercapto ketones and acids are also used for the preparation of thiazoles from nitriles and aldoximes. 

Disubstituted thiazoles are readily obtained by the action of a-mercapto ketones (278) on nitriles (279). The reaction is carried out in benzene solution at 0°C by passing a current of dry hydrogen chloride through the mixture (Scheme 199). In a variation of this reaction, by refluxing a-mercapto ketones (278) with aldoximes (280) for 2 hours at 100 °C, 2,4-di- or 2,4,5-tri-substituted thiazoles are obtained in good yields (Scheme 200). 

Cyanamide (279 R2 = NH2) condenses with a-mercapto ketones to give the corresponding 2-aminothiazoles. 

Various 1,3-dithiolylium salts (31) can be prepared by combining an excess of thioacids or thioesters with a-halo, a-hydroxy or a-mercapto ketones in the presence of hydrogen iodide or perchloric acid (71JPR722). 

Additions to conjugated triple bonds occur with facility. Thus, base-catalyzed addition of benzoin to dimethyl acetylenedicarboxylate provides a route to furans (186 187 X = 0), while pyrroles and thiophenes result from an analogous addition of -amino ketones (186 187 X = NH) and -mercapto ketones (186 187 X=S), respectively (Scheme 104) <1964JA107>. 

Reduction ofa., -enones. The a,p-enone 1 was reduced by a new two-step process after usual methods failed. Reaction of 1 with H,S and K,CO, (1 equiv.) in DMSO at 23° results in 1,4-addition to form a 3-mercapto ketone, which is desulfurized with tri-n-butylphosphine in benzene with UV irradiation the overall yield is 65%. 

The reactions of a-mercapto ketones with aziridines have been used to prepare derivatives of the dihydrothiazines 50 and 51 for example,... 

Bei der Synthese von 1,3-Thiazolen aus Cyanamiden besteht die Moglichkeit, die a-Mercapto-ketone in situ aus a-Chlor-ketonen mit Natriumhydrogensulfid91,95 herzustellen Oder stattdes-sen zugehorige 1,4-Dithiane91 einzusetzen. Letztere konnen ebenfalls aus a-Chlor-ketonen mit Natriumsulfid gewonnen werden. 

Die Herstellung von /1-Mercapto-ketonen aus Bis-[3-oxo-alkyl]-disulfanen ist mit Zink/Eisessig moglich, jedoch nur in Einzelfallen wegen der Instability der/3-Mercapto-ketone sinnvoll (Bd. VII/2c, S. 2404). 

The reactions of a-mercapto ketones with aziridines have been used to prepare derivatives of the dihydrothiazines 50 and 5144-47 for example, 2-mercaptopentan-3-one and 3-mercapto-3-methylbutan-2-one afforded the compounds 60a and 61a with aziridine, and the derivatives 60b and 61b with 2-methylaziridine. In general, good yields of dihydrothiazines are obtained by this route. 

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