TY - JOUR

T1 - Approach to Pyrido[2,1-b][1,3]benzothiazol-1-ones via In Situ Generation of Acyl(1,3-benzothiazol-2-yl)ketenes by Thermolysis of Pyrrolo[2,1-c][1,4]benzothiazine-1,2,4-triones

AU - Lystsova, Ekaterina A.

AU - Novikov, Alexander S.

AU - Dmitriev, Maksim V.

AU - Maslivets, Andrey N.

AU - Khramtsova, Ekaterina E.

PY - 2023/7/18

Y1 - 2023/7/18

N2 - Acyl(imidoyl)ketenes are highly reactive heterocumulenes that enable diversity-oriented synthesis of various drug-like heterocycles. Such ketenes, bearing heterocyclic substituents, afford angularly fused pyridin-2(1 H)-ones in their [4+2]-cyclodimerization reactions. We have utilized this property for the development of a new synthetic approach to pharmaceutically interesting pyrido[2,1- b][1,3]benzothiazol-1-ones via the [4+2]-cyclodimerization of acyl(1,3-benzothiazol-2-yl)ketenes generated in situ. The thermal behaviors of 3-aroylpyrrolo[2,1- c][1,4]benzothiazine-1,2,4-triones and 3-benzoylpyrrolo[2,1- b][1,3]benzothiazole-1,2-dione (two new types of [ e]-fused 1 H-pyrrole-2,3-diones reported by us recently) have been studied by thermal analysis and HPLC to elucidate their capability to be a source of acyl(1,3-benzothiazol-2-yl)ketenes. As a result, we have found that only 3-aroylpyrrolo[2,1- c][1,4]benzothiazine-1,2,4-triones are suitable for this. The experimental results are supplemented with computational studies that demonstrate that thermolysis of 3-aroylpyrrolo[2,1- c][1,4]benzothiazine-1,2,4-triones proceeds through an unprecedented cascade of two thermal decarbonylations. Based on these studies, we discovered a novel mode of thermal transformation of [ e]-fused 1 H-pyrrole-2,3-diones and developed a new pot, atom, and step economic synthetic approach to pyrido[2,1- b][1,3]benzothiazol-1-ones. The synthesized drug-like pyrido[2,1-b][1,3]benzothiazol-1-ones are of interest to pharmaceutics, since their close analogs show significant antiviral activity.

AB - Acyl(imidoyl)ketenes are highly reactive heterocumulenes that enable diversity-oriented synthesis of various drug-like heterocycles. Such ketenes, bearing heterocyclic substituents, afford angularly fused pyridin-2(1 H)-ones in their [4+2]-cyclodimerization reactions. We have utilized this property for the development of a new synthetic approach to pharmaceutically interesting pyrido[2,1- b][1,3]benzothiazol-1-ones via the [4+2]-cyclodimerization of acyl(1,3-benzothiazol-2-yl)ketenes generated in situ. The thermal behaviors of 3-aroylpyrrolo[2,1- c][1,4]benzothiazine-1,2,4-triones and 3-benzoylpyrrolo[2,1- b][1,3]benzothiazole-1,2-dione (two new types of [ e]-fused 1 H-pyrrole-2,3-diones reported by us recently) have been studied by thermal analysis and HPLC to elucidate their capability to be a source of acyl(1,3-benzothiazol-2-yl)ketenes. As a result, we have found that only 3-aroylpyrrolo[2,1- c][1,4]benzothiazine-1,2,4-triones are suitable for this. The experimental results are supplemented with computational studies that demonstrate that thermolysis of 3-aroylpyrrolo[2,1- c][1,4]benzothiazine-1,2,4-triones proceeds through an unprecedented cascade of two thermal decarbonylations. Based on these studies, we discovered a novel mode of thermal transformation of [ e]-fused 1 H-pyrrole-2,3-diones and developed a new pot, atom, and step economic synthetic approach to pyrido[2,1- b][1,3]benzothiazol-1-ones. The synthesized drug-like pyrido[2,1-b][1,3]benzothiazol-1-ones are of interest to pharmaceutics, since their close analogs show significant antiviral activity.

KW - DFT calculations

KW - acyl(imidoyl)ketene

KW - cycloaddition

KW - hetero-Diels–Alder reaction

KW - heterocumulene

KW - thermal analysis

KW - thermolysis

UR - https://www.mendeley.com/catalogue/97fb51e6-f60a-3721-a7a8-8f79987aaa96/

U2 - 10.3390/molecules28145495

DO - 10.3390/molecules28145495

M3 - Article

C2 - 37513367

VL - 28

JO - Molecules

JF - Molecules

SN - 1420-3049

IS - 14

M1 - 5495

ER -