Synthesis, Crystal Structure, and Biological Activity of Ethyl 4-Methyl-2,2-dioxo-1H -2λ⁶,1-benzothiazine-3-carboxylate Polymorphic Forms

Scientia pharmaceutica
Igor V UkrainetsPavlo S Bondarenko

Abstract

Continuing the search for new potential analgesics among the derivatives of 4-methyl-2,2-dioxo-1H-2λ⁶,1-benzothiazine-3-carboxylic acid, the possibility of obtaining its esters by the alkylation of the corresponding sodium salt with iodoethane in dimethyl sulfoxide (DMSO) at room temperature was studied. It was found that under such conditions, together with the oxygen atom of the carboxyl group, a heteroatom of nitrogen is also alkylated. Therefore, the product of the reaction studied is a mixture of ethyl 4-methyl-2,2-dioxo-1H-2λ⁶,1-benzothiazine-3-carboxylate (major) and its 1-ethyl-substituted analog (minor). A simple but very effective method of preparative separation of these compounds was proposed. Moreover, the heterogeneous crystallization from ethanol was revealed to result in a monoclinic polymorphic form of ethyl 4-methyl-2,2-dioxo-1H-2λ⁶,1-benzothiazine-3-carboxylate, while the homogeneous crystallization results in its orthorhombic form. The molecular and crystal structures of both forms were confirmed by X-ray diffraction analysis, and the phase purity by powder diffraction study. The pharmacological tests carried out on the model of a carrageenan edema showed that the screening dose of 20 mg/kg of 1-ethyl-substi...Continue Reading

References

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Dec 25, 2007·Acta Crystallographica. Section A, Foundations of Crystallography·George M Sheldrick
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Citations

Oct 30, 2020·Acta Crystallographica. Section E, Crystallographic Communications·Svitlana V ShishkinaIgor V Ukrainets

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Methods Mentioned

BETA
acylation
nuclear magnetic resonance
X-ray

Software Mentioned

WinPLOTR
Mercury
FullProf
STATISTICA
SHELXTL
ORCA

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