A concise construction of 12H-benzo[4,5]thiazolo[2,3-b]quinazolin-12-ones via an unusual TBHP/Na₂CO₃ promoted cascade oxidative cyclization and interrupted Dimroth rearrangement

Abstract

An efficient transition-metal-free cascade reaction has been developed for the facile synthesis of 12H-benzo[4,5]thiazolo[2,3-b]quinazolin-12-one derivatives from commercially available isatins and 2-haloaryl isothiocyanates. A preliminary mechanistic study suggested an interrupted Dimroth rearrangement was the key step for the successful transformation.

FeCl3-Mediated Synthesis of 2-(Trifluoromethyl)quinazolin-4(3H)-ones from Isatins and Trifluoroacetimidoyl Chlorides

“…Finally, the decarbonylative process of intermediate A in the presence or absence of FeCl 3 occurred to enable the formation of 2-(trifluoromethyl)­quinazolin-4­(3 H )-one 3f with the extrusion of carbon monoxide, , which was successfully trapped by CO detector. The reaction proceeded smoothly in the absence of water or strong oxidant, so the decarbonylative process with the release of carbon dioxide was presumably not involved in the reaction, − which was further verified by the result of the control experiment as shown in Scheme c.…”

“…Among various isatin-based reactions, ring-expansions and decarboxylative couplings of isatins offer facile and direct routes to build structurally diverse heterocyclic compounds. For instance, Wu and co-workers developed a series of tert -butyl hydroperoxide (TBHP)-promoted oxidative cyclization reactions of isatins for the synthesis of quinazolin-4­(3 H )-ones and tryptanthrins, 12 H -benzo­[4,5]­thiazolo­[2,3- b ]­quinazolin-12-ones, and 3-carboxylate-4-quinolone derivatives, respectively. Huang and Yin described a copper-catalyzed domino reaction of isatins and 2-bromopyridines to enable the formation of 11 H -pyrido­[2,1- b ]-quinazolin-11-ones .…”

“…Furthermore, the 1 H -benzo­[ d ]­[1,3]­oxazine-2,4-dione 6 was employed as substrate to react with 2f , and only trace of the target 2-(trifluoromethyl)­quinazolin-4­(3 H )-one product 3f was detected. Therefore, the isatoic anhydride 6 did not act as the intermediate of this reaction, which was usually identified as the key intermediate in oxidant-promoted reactions of isatin (Scheme c). − Finally, the coupling product 7 of isatin 1a with 2f was submitted into the standard conditions and the desired product 3f was obtained in 76% yield. When the reaction was performed without NaH or without FeCl 3 and NaH, the product 3f was delivered in 97% or 48% yield, respectively (Scheme d).…”

Temperature‐Controlled Base‐Promoted Cyclization for the Synthesis of 2‐Amino‐4H‐benzo[d][1,3]thiazin‐4‐ones and 2‐Thioxo‐4(3H)‐quinazolinones

“…Moreover, a concise method for the synthesis of 2‐amino‐4 H ‐benzo[ d ][1,3]thiazin‐4‐ones in a step‐economy manner from commercially available substrates is still yet to be developed. In connection with our previous work, we herein report the highly selective skeletal divergence of 4 H ‐benzo[ d ][1,3]thiazin‐4‐ones and 2‐thioxo‐2,3‐dihydroquinazolin‐4(1 H )‐ones using a synergistic TBHP/Na 2 CO 3 mediated tandem oxidation/decarboxylative cyclization of isothiocyanates with isatins. This method utilizes commercially available substrates, occurs under mild conditions and is compatible with a wide substrate scope.…”

“…On the basis of above results, our previous observations and literature precedent, a mechanistic pathway is depicted in Scheme using isothiocyanatobenzene ( 1 a ) and isatin ( 2 a ) as an example. Initially, intermediate A was obtained from the TBHP/Na 2 CO 3 mediated nucleophilic attack of isatin ( 2 a ), which was then converted to isatoic anhydride ( 5 ) via a Baeyer–Villiger‐type pathway .…”