ChemInform Abstract: RESEARCH ON COMPOUNDS WITH ANTIBLASTIC ACTIVITY PART 57, ANTHRAMYCIN AND RELATED COMPOUNDS PART 6, SYNTHESIS OF PYRROLO(1,2‐B)(1,2,5)BENZOTHIADIAZEPINE DERIVATIVES

Abstract

Nitrosulfonsäurechlorid (I) reagiert mit Kalium‐pyrrolen (II) zu den N‐Sulfonylpyrrolen (III).

Synthetic approaches to 1,2,5-benzothiadiazepine 1,1-dioxides – sulfonamide analogues of the 1,4-benzodiazepines

“…Thus, the reaction of 1-(2-aminobenzenesulfonyl)pyrrole ( 16) with alkyl 3,3-dimethoxypropionates in aqueous acetic acid furnished alkyl-10,11-dihydropyrrolo[1,2-b][1,2,5]benzothiadiazepin-11-acetate 5,5-dioxides (94), whilst the reaction with ethyl glyoxylate hemiacetal afforded the pyrrolo-benzo-thiadiazepine (95) in high yield (94 %) (Scheme 30). 1,14 Reaction of an acid chloride with 1-(2-aminobenzenesulfonyl) pyrrole ( 16) followed by phosphorus oxychloride mediated Bischler-Napieralski type ring closure gave ready access to the pyrrolobenzothiadiazepines (96), 17 whilst treatment with triphosgene has been used to provide access to the pyrrolobenzothiadiazepinones (97). 14,35…”

“…This bond formation methodology is limited to the synthesis of pyrrolobenzothiadiazepines which, by virtue of the pyrrole ring, possess the necessary reactive carbon that becomes the 3position of the 1,2,5-benzothiadiazepine ring. Thus, Artico and co-workers 21 constructed the pyrrolo[1,2-b][1,2,5]benzothiadiazepin-1,1-dioxide (18, R 1 = R 2 = H) (Scheme 3) in 47 % yield via a phosphorus oxychloride mediated Bischler-Napieralski cyclisation reaction of the formylated precursor 1-(2-formamidobenzenesulfonyl)pyrrole (17). Precursor (17) was derived quantitatively from the reaction of acetic formic anhydride ( 19) with 1-(2-aminobenzenesulfonyl) pyrrole ( 16), 21 which was in turn readily available from the reaction of the corresponding sulfonyl chloride with pyrrole.…”

“…Thus, Artico and co-workers 21 constructed the pyrrolo[1,2-b][1,2,5]benzothiadiazepin-1,1-dioxide (18, R 1 = R 2 = H) (Scheme 3) in 47 % yield via a phosphorus oxychloride mediated Bischler-Napieralski cyclisation reaction of the formylated precursor 1-(2-formamidobenzenesulfonyl)pyrrole (17). Precursor (17) was derived quantitatively from the reaction of acetic formic anhydride ( 19) with 1-(2-aminobenzenesulfonyl) pyrrole ( 16), 21 which was in turn readily available from the reaction of the corresponding sulfonyl chloride with pyrrole. This N-formylation/Bischler-Napieralski ring closure methodology has recently been utilised with similar success by other workers, who were able to access the requisite 1-(2-aminobenzenesulfonyl)pyrroles ( 16) from the 2-(o-azidobenzenesulfonyl)-1,2-thiazine 1-oxides (20), also shown in Scheme 3.…”

“…The nitro carbonyl group cyclisation approach to the tricyclic pyrrolobenzothiadiazepines was first described by Chimenti et al 17 Thus, as shown in Scheme 7, reduction of the nitro group in compound (28) with hydrogen in the presence of platinum oxide as a catalyst was accompanied by cyclisation to afford directly the pyrrolo [1,2- 29), with no over-reduction. Later, Artico and coworkers 21 showed that iron powder-acetic acid reduction of compound (28) gave the pyrrolobenzothiadiazepine ( 29), also directly, but in an improved 92 % yield.…”

“…16 Pyrrolobenzothiadiazepines (7) have also been synthesised as parts of programmes devised to access analogues of the potent antitumour antibiotic pyrrolobenzodiazepines of which DC-81 (10) is typical. 17 Tetracyclic pyrrolobenzothiadiazepine derivatives (11), which are analogues of the antidepressant aptazepine, have also attracted attention. 18 The synthesis of 1,2,5-benzothiadiazepines has been reviewed before only partially and as part of larger reviews covering diazepine heterocycles [1][2][3] in general.…”