Synthesis of 4-methyl-2<i>H</i>-1,2,3-benzothiadiazine 1,1-dioxides and their further transformation <i>via</i> alkylation and reduction steps
Imre Gyűjtő
Márta Porcs-Makkay
Gyula Lukács
Gyöngyvér Pusztai
Zsófia Garádi
Gábor Tóth
Bálint Nyulasi
Gyula Simig
Balázs Volk
10.6084/m9.figshare.9976802.v1
https://tandf.figshare.com/articles/journal_contribution/Synthesis_of_4-methyl-2_i_H_i_-1_2_3-benzothiadiazine_1_1-dioxides_and_their_further_transformation_i_via_i_alkylation_and_reduction_steps/9976802
<p><i>Ortho</i> lithiation of acetophenone ketals followed by introduction of the chlorosulphonyl group and subsequent ring closure with hydrazine monohydrate or acetohydrazide gave rise to the formation of variously substituted 4-methyl-1,2,3-benzothiadiazine 1,1-dioxides. <i>N</i>(2)-Alkylation and reduction of the C=N double bond were carried out successfully to give <i>N</i>(2)-alkyl-4-methyl-3,4-dihydro-1,2,3-benzothiadiazine 1,1-dioxides. Finally, <i>N</i>(3)-alkylation was accomplished by reductive alkylation with aldehydes. Certain unsaturated and also some 3,4-dihydro derivatives exhibited a significant anxiolytic effect <i>in vivo</i>. Detailed NMR studies and DFT calculations supported the structure elucidation of the compounds.</p>
2019-10-14 13:20:55
Alkylation
DFT calculation
lithiation
NMR studies
reduction