ChemInform Abstract: 2,1‐Benzothiazine 2,2‐Dioxides. Part 5. Hydrolysis of Alkyl 1‐R‐4‐Hydroxy‐2,2‐dioxo‐1H‐2λ ⁶,1‐benzothiazine‐3‐carboxylates.

Abstract

Hydrolysis of the title benzothiazinecarboxylates (I) is accompanied by decarboxylation both in acidic and alkaline medium.

4-Methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylic Acid. Peculiarities of Preparation, Structure, and Biological Properties

“…According to 1 Н-NMR monitoring in 4 h after the beginning of hydrolysis, the initial ester in the reaction mixture was no longer detected. Unlike 4-hydroxy analogs XII [ 8 ], in this case, highly undesirable decarboxylation of hetaryl-3-carboxylic acid initially formed in the conditions of synthesis was not observed during this time. However, this does not mean that 4-methylsubstituted 2,2-dioxo-1 H -2λ 6 ,1-benzothiazine-3-carboxylic acids are not subjected to decarboxylation at all.…”

“… Probable ( IX ) and known ( XI and XIII ) hydrolysis products of esters of 4-hydroxy-2-oxoquinoline- [ 7 ] and 4-hydroxy-2,2-dioxo-2,1-benzothiazine- [ 8 ] 3-carboxylic acids. …”

“…The main prerequisites for this research were the expressed analgesic activity demonstrated by their synthetic precursors — methyl-4-methyl-2,2-dioxo-1 H -2λ 6 ,1-benzothiazine-3-carboxylates VIII [ 6 ] as well as excellent results obtained during the transition from quinolone esters X , which are similar in terms of their structure, to acids XI [ 7 ] ( Figure 2 ). Another incentive to study the behavior of 4-methyl-substituted benzothiazine esters VIII in alkaline hydrolysis conditions was a simple scientific curiosity: as is known [ 8 ], the corresponding acids cannot be obtained from their 4-hydroxy analogs XII since in the process of their formation, they are immediately decarboxylated to 4-oxo-3,4-dihydro-1 H -2λ 6 ,1-benzothiazin-2,2-diones XIII .…”

The Effective Synthesis of N-(Arylalkyl)-1-R-4-hydroxy-2,2-dioxo-1,2-dihydro-2λ6,1-benzothiazine- 3-carboxamides as Promising Analgesics of a New Chemical Class

“…It is obvious that there is the same side reaction in amidation of benzothiazine esters 2 ; moreover, they are hydrolyzed much easier than their 2-carbonyl analogues, and we even have not had a chance to isolate the intermediate benzothiazine-3-carboxylic acids 5 yet, due to their extreme instability [ 37 ]. The only difference is that benzothiazine analogues of 4-hydroxyquinolin-2-ones unsubstituted in position 3 exist predominantly in 4-ketoform V , and it is more significant in our case, in contrast to them and their synthetic precursors, esters 2 , they possess a high reactivity in relation to N -nucleophiles.…”