Synthesis and Chemistry of Benzo[e][1,2,6]thiadiazino[3,4-b][1,4]diazepin-10(11H)-ones and Related Ring Transformations

Abstract

2-[(3,5-Dichloro-4H-1,2,6-thiadiazin-4-ylidene)­amino]­benzamides are cyclized to benzo­[e]­[1,2,6]­thiadiazino­[3,4-b]­[1,4]­diazepin-10­(11H)-ones via (i) treatment with NaH and via (ii) Pd-catalyzed C-N coupling. The behavior of the latter toward nucleophiles and thermal, oxidative, and reductive conditions revealed unexpected transformations to 3,5-dioxo-4,5-dihydro-3H-benzo­[e]­[1,4]­diazepine-2-carbonitrile and 2-(4-substituted-1,2,5-thiadiazol-3-yl)­quinazolin-4­(3H)-ones.

(E)-4-Oxo-3,4-dihydroquinazoline-2-carbaldehyde Oxime

“…Our interest in quinazolines began with 3′,5′-dichloro-1H-spiro(quinazol [1,2,6]thiadiazin)-4(3H)-ones 1 that can be synthesized in 3 steps startin tetrachlorothiadiazine 2 [3] (Scheme 1). Interestingly, spirocycle 1a (R = H) can decomposed to 4-oxo-3,4-dihydroquinazoline-2-carbonitrile (3) [4] (Scheme 1 recently, while investigating the stability of 4-chlorobenzo[e] [1,2,6]thiadiaz b] [1,4]diazepin-10(11H)-one (4), we found that upon heating in MeOH/AcOH (9 was converted in 92% yield to the isomeric 2-(4-chloro-1,2,5-thiadiazol-3-yl)quin 4(3H)-one (5) [5] (Scheme 1). We attributed this transformation to an acid-ca nucleophilic addition to the thiadiazine 4 followed subsequent Wagner-Meerwe leading to the observed ring contractions [5].…”

2-Benzoyl-4-phenyl-1,2,5-thiadiazol-3(2H)-one 1,1-Dioxide

“…compound 1, Figure 1) [5]. 5) [8]. More recently, we reported the photochemically mediated oxidative ring contraction of 1,2,6-thiadiazines 6 to 1,2,5-thiadiazol-3(2H)-one 1-oxides 7 under ambient conditions [9].…”

“…Scheme 1. Ring contractions of 4H-1,2,6-thiadiazines to various 1,2,5-thiadiazole scaffolds [7][8][9].…”

The Photochemical Mediated Ring Contraction of 4H-1,2,6-Thiadiazines To Afford 1,2,5-Thiadiazol-3(2H)-one 1-Oxides

“…Recently, we reported the unexpected ring contraction of spiro(benzo[ d ][1,3]dioxole-2,4′-[1,2,6]thiadiazines) 2 to thiadiazoles 3 in high yields, under thermal and Brønsted or Lewis acid-catalyzed conditions (Scheme ), , In the current work, while investigating 3,5-diphenyl-4 H -1,2,6-thiadiazin-4-one ( 4a ) as a potential photosensitizer for singlet oxygen ( 1 O 2 ) production, rapid photobleaching of the chromophore led to a new colorless product 5a . The loss of color indicated reduced conjugation [ 5a : λ max (DCM) 296 nm (log ε = 4.26) vs 4a : λ max (DCM) 431 nm (log ε = 3.44)], while 13 C NMR spectroscopy showed 11 resonances indicating a loss of symmetry, and both MS (ESI + ) and elemental analysis suggested a molecular formula of C 15 H 10 N 2 O 3 S supporting the addition of two oxygen atoms [see the Supporting Information (SI)].…”

“…Recently, we reported the unexpected ring contraction of spiro(benzo[d] [1,3]dioxole-2,4′- [1,2,6]thiadiazines) 2 to thiadiazoles 3 in high yields, under thermal and Brønsted or Lewis acid-catalyzed conditions (Scheme 1), 9,10 In the current work, while investigating 3,5-diphenyl-4H-1,2,6-thiadiazin-4-one (4a) as a potential photosensitizer for singlet oxygen ( 1 O 2 ) production, rapid photobleaching of the chromophore led to a new colorless product 5a. The loss of color indicated reduced conjugation [5a: λ max (DCM) 296 nm (log ε = 4.26) vs 4a: λ max (DCM) 431 nm (log ε = 3.44) 11 ], while 13 The remarkable ring contraction presented herein leads to oxidation of an imine motif to an imide and the selective mono-oxidation of the ring sulfur to a stereogenic sulfoxide with only the substrate, solvent, visible light, and air present under ambient conditions.…”