1.3- Thiazine-6-thiones synthesis

Conversion of a carbonyl group to a thione group in condensed 4-thia-zolidinone can be affected by phosphorus pentasulfide, as exemplified by the synthesis of thiazolo[2,3-c]-[l.4]thiazin-3(2//)-thiones from 139 and phosphorus pentasulfide in boiling dioxane (64M1335). 

In the former case, the precursors are stable molecules that are readily prepared (Sections V,B and V,C,l,c). The procedure involves the isomerization of the exocyclic double bond at position 3 to an endocyclic location no change in the oxidation level of the system results. Examples of this type include the conversions of the thiones 12a and 12b into the derivatives 13a and 14 by triethyloxonium tetrafluoroborate and methyl iodide, respectively. A further case, resulting in the formation of the only known mono-cyclic 4/7-1,4-thiazine 15, is provided by the reaction of the thiazinium iodide 14 with potassium t-butoxide the derivative 15 is reported to be an unstable red oil. Although its generality has not been tested, the synthesis... 

In another synthesis of (fused) pyrimidine-4-thiones, o-aminonitriles were condensed with thioacetamide in ethanol that had been saturated with hydrogen chloride. Unstable 1,3-thiazines (such as 130) could be isolated as intermediates, but a final alkaline treatment gave, for example, 6-methyl-pyrazolo[3,4-d]pyrimidine-4-thione (131). When an unsubstituted 2-position was required, thioformanilide in dimethylformamide became the preferred reagent (loss of phenyl group). Yields varied from moderate to good, in favorable cases, but the reaction can be somewhat erratic.184,185 For another 4-thione-generating reaction, see Section VI,A,4. 

More recently, the same group reported an analogous cyclization for the synthesis of 21-f-benz[e]-l,3-oxazine-2-thiones [219] and functionalized 1,3-thiazines [220]. 

In yet another variation of this synthesis, 2,6-dithioxo-2,3-dihydro-4,5-benzo-l,3-thiazine ( trithioisatoic anhydride ) (231) is condensed with hydrazine at room temperature to form the intermediate (232). This is cyclized, by hot formic acid, to l,3,4-thiadiazolo[2,3-Z ]-3,4-dihydro-quinazoline-4>thione (233). The proposed structures are supported by spectral data. ... 

Finally, two examples of preparation of thiazines, the 2-thio analogues of DHPM, are depicted in Scheme 6.47. On the one hand, thiazine-2-thiones 313 have been synthesized in a one-pot procedure by Orru and coworkers via a Homer-Wadsworth-Emmons approach (Scheme 6.47a) [95]. The compounds were obtained in low to good yields (30-72%). The authors point out that the products are not very stable and slowly decompose over time in solutions, but purified products can be stored under inert conditions. And on the other hand, Shang and coworkers reported the DABCO-catalyzed synthesis of 3,4-dihydro-27f-l,4-benzo[li]thiazine derivatives 317 in good yields (62-88%) (Scheme 6.47b) [96]. 

SCHEME 6.47 Synthesis of 3,6-dihydro-2//-l,3-thiazine-2-thiones 313 and 3,4-dihydro-2//-l,4-benzo[h]thiazine derivatives 317. 

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