Facile regiodivergent synthesis of spiro pyrrole-substituted pseudothiohydantoins and thiohydantoins via reaction of [e]-fused 1H-pyrrole-2,3-diones with thiourea

Abstract

A highly divergent synthesis of regioisomeric thiohydantoins and pseudothiohydantoins spiro-fused to a pharmacologically valuable pyrrole-2-one fragment involving the reaction of [e]-fused 1H-pyrrole-2,3-diones with thioureas was developed. The obtained spiro pseudothiohydantoin derivatives were found to undergo a pseudothiohydantoin–thiohydantoin rearrangement. The reactions were shown to proceed under catalyst-free conditions in good yields, and the products were isolated without applying preparative chromatography methods.

Switchable Synthesis of Benzothiazoles, Benzothiazines and Benzothiazepines through the Reaction of Hetareno[e]pyrrole‐2,3‐Diones with o‐Aminothiophenol

“…It should be noted that the initial Michael (thia-or aza-Michael) addition of binucleophiles to pyrrolobenzoxazinetriones followed by opening the benzoxazine ring is a typical reaction route that has been discussed previously. [11,26] The similar reactivity was observed for oxazine-and benzoxazepinefused pyrrole-2,3-diones. [27] Using reagents in a ratio of 1 : 1 did not allow for the complete conversion of compound 1 a (the necessary discoloration of intensely colored compound 1 a) (Table 1, Entry 1).…”

“…It should be noted that the initial Michael (thia‐ or aza‐Michael) addition of binucleophiles to pyrrolobenzoxazinetriones followed by opening the benzoxazine ring is a typical reaction route that has been discussed previously [11,26] . The similar reactivity was observed for oxazine‐ and benzoxazepine‐fused pyrrole‐2,3‐diones [27]…”

Reaction of Hetareno[e]pyrrole‐2,3‐diones with Thiols: An Approach to Two Distinct 5‐Thio‐Substituted Pyrrole‐2‐one Derivatives

“…The analysis of possible substituents, which were reported to be installed into 3‐hydroxy‐1,5‐dihydro‐2 H ‐pyrrol‐2‐ones, revealed that their 5‐thio‐substituted derivatives were extremely poorly explored. Relevant to the present study, few reports are available in the literature for the synthesis of conformationally restricted 5‐thio‐substituted 3‐hydroxy‐1,5‐dihydro‐2 H ‐pyrrol‐2‐ones, i. e. spiro‐fused at C‐5 A [10–16] or fused at [ e ]‐side B [17,18] with a thioheterocycle. Conformationally free 5‐thio‐substituted 3‐hydroxy‐1,5‐dihydro‐2 H ‐pyrrol‐2‐ones C fused at [ d ]‐side have been previously investigated [19] (Figure 2).…”