Synthesis of Anionic Hypervalent Cyclic Selenenate Esters: Relevance to the Hypervalent Intermediates in Nucleophilic Substitution Reactions at the Selenium(II) Center

Abstract

The synthesis of a diaryl diselenide that contains 2,6-dicarboxylic acid groups, 2,2'-diselanediylbis(5-tert-butylisophthalic acid) (10), is described. Diselenide 10 undergoes intramolecular cyclization in methanol to form a cyclic selenenate ester, 5-tert-butyl-3-oxo-3H-benzo[c][1,2]oxaselenole-7-carboxylic acid (11). The cyclization reaction proceeds more rapidly in the presence of organic bases, such as pyridine, adenine, and 4,4'-bipyridine, to form pyridinium 5-tert-butyl-3-oxo-3H-benzo[c][1,2]oxaselenole-7-carboxylate (14), adeninium 5-tert-butyl-3-oxo-3H-benzo[c][1,2]oxaselenole-7-carboxylate (15), and 4,4'-bipyridiniumbis(5-tert-butyl-3-oxo-3H-benzo[c][1,2]oxaselenole-7-carboxylate) (16), respectively. However, 2,2'-diselanediyldibenzoic acid (22) does not undergo cyclization under similar conditions. Structural studies on cyclic selenenate esters 14-16 revealed that the Se···O (COO(-)) secondary distances (2.170, 2.075, and 2.176 Å) were significantly shorter than the corresponding Se···O distances (2.465, 2.472, and 2.435 Å) observed for the selenenate esters stabilized by the neutral donors (CHO, COOH, and COOEt). (1)H, (13)C, and (77)Se NMR spectroscopy of compounds 11 and 14-16 reveal that the aryl protons of compound 11 and the organic cations of compounds 14-16 exchange between the two carboxylate groups via a hypercoordinate intermediate. The corresponding hypercoordinate intermediate (14b, pyridinium selenuranide) for compound 14 was detected at low temperatures using (77)Se NMR spectroscopy. The presumed hypercoordinate intermediates in the carboxylate-exchange reactions at the selenium(II) center for a set of model reactions were optimized using DFT-B3LYP/6-311+g(d) calculations and their structural features compared with the X-ray structure of anionic selenenate esters 14-16.

Adaptive responses of sterically confined intramolecular chalcogen bonds

“… 36 A facile intramolecular cyclization of 2,6-bis(carboxyl) substituted diaryl diselenide 33 in methanol medium, leading to the formation of a cyclic selenenate ester, has also been noticed. 40 Attempted synthesis of 2,6-dioxazoline containing diselenide 34 by Mugesh and co-workers led to the formation of a cyclic selenenamide via unexpected hydrolysis of the oxazoline ring followed by a selenium centered intramolecular addition–elimination reaction. 41 Expectedly, 2,6-bis-amide substitution facilitates ( e.g.…”

“…18 ). 40 The cations such as H + and PyH + exchange between the two carboxylates via selenuranide intermediates ( 38′ / 39′ ). The fluxional behaviour observed in symmetrical selenocarboxylates ( 38 / 39 ) is further corroborated by the fluxional behaviour of symmetrical compounds ( 40–42 ) reported from Reich, 63 Martin, 64 and Back 65 groups.…”

Cyclic Seleninate Esters, Spirodioxyselenuranes and Related Compounds: New Classes of Biological Antioxidants That Emulate Glutathione Peroxidase

“…It was obtained as am ixture of meso and d,l diastereomers, with the structure of the d,l pair confirmed by X-ray crystallography. [39] When treated with hydrogen peroxidea nd benzenethiol, 23 was converted to the corresponding seleninate, which then underwent thiolysist ot he corresponding monomeric selenenate ester,f ollowed by dehydration to regenerate 23.C yclic selenenates, such as 24, [32] 25, [40] 26, [40] 27, [41] and 28, [42] (Figure 7) as well as their precursor diselenides, were similarly investigated by extensive NMR, computational and X-ray crystallographic studies, as well as in the coupled reductase assay.C ompounds 24-26 exhibitedi nitial reaction rates that werec omparable to or highert han those of ebselen in the coupled reductase assay,w hile 27 proveda lmosti nactive and no reaction rate was reportedf or 28.T hus, in addition to o-nitro groups, o-carbonyl substituents can also result in cyclic selenenate esters with significant activity,a si ndicated by initial reaction rate measurements. Furthermore,t he anion 28 displayedf luxional behaviour similart ot hat of 16 in Scheme5in variable temperature NMR experiments.…”

“…Among this class, several compounds (e.g. 36 f, 40,42,43)h ave catalytic activitiest hat are more than ah undred times greater than that of ebselen. These compounds are therefore of interestf or further development as biological antioxidants.…”

Synthesis of alpha‐methyl selenocysteine and its utilization as a glutathione peroxidase mimic

“…However, ebselen is not water soluble, making rapid intravenous administration impossible, and has shown cellular toxicity in some studies . Other selenium‐containing GPX mimics have been synthesized, and some have potent GPX‐like activity including cyclic seleninate and selenenate esters, spirodioxyselenuranes, pincer selenuranes, and spirodiazaselenuranes . However, many of these compounds are expected to be toxic, are not water soluble, are unstable, or quickly lose catalytic activity in the presence of thiols …”