DBU attacks saccharin derivatives with subsequent rearrangement to give rise to 3-[3'-(1"-azepin-2"-onyl)propylamino]-1,2-benzisothiazole-1,1-dioxide 2 after work-up

Barkley, James V.

Bethell, Donald

Bulman Page, Philip C.

Vahedi, Hooshang

English

University of East Anglia digital repository

©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016SYNTHETIC COMMUNICATIONSVol. 33, No. 11, pp. 1937–1941, 2003Unexpected Nucleophilic Participation andRearrangement of DBU in Reactions withSaccharin DerivativesPhilip C. Bulman Page,1,* Hooshang Vahedi,1Donald Bethell,2 and James V. Barkley21Department of Chemistry, Loughborough University,Loughborough, Leicestershire, UK2Robert Robinson Laboratories, Department ofChemistry, University of Liverpool, Oxford Street,Liverpool, UKABSTRACTDBU attacks saccharin derivatives with subsequent rearrangementto give rise to 3-[30-(10 0-azepin-200-onyl)propylamino]-1,2-benzisothia-zole-1,1-dioxide 2 after work-up.*Correspondence: Philip C. Bulman Page, Department of Chemistry,Loughborough University, Loughborough, Leicestershire LE11 3TU, UK;Fax: þ44(0)1509 223926; E-mail: p.c.b.page@lboro.ac.uk.1937DOI: 10.1081/SCC-120020208 0039-7911 (Print); 1532-2432 (Online)Copyright & 2003 by Marcel Dekker, Inc. www.dekker.com©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016Key Words: DBU; Nucleophile.In our earlier reports,[1] it was shown that 3-substituted-1,2-benzi-sothiazole-1,1-dioxides 1 derived from saccharin are able to catalyse,in sub-stoichiometric amounts, the oxidation of sulﬁdes to sulfoxidesunder basic reaction conditions, as are certain other sulfonylimines.The reactions are carried out by addition of hydrogen peroxide (30% w/vaqueous solution; 4.0 equiv.) to a stirred solution of base (4.0 equiv.),followed by the sulfonylimine (up to 1.0 equiv.) (Sch. 1).[2] Theimine mediators 1 were prepared according to a previously reportedprocedure.[1,3] During oxidation of p-tolyl methyl sulﬁde using themediators 1a and 1b, in which the 3-substituents are Cl and OEtrespectively, yields of the sulfoxide are much lower than those observedwhen alkyl groups occupy the 3-position. Further, methyl p-tolylsulfoxide was obtained in substantially lower yield when using DBU asthe base in the oxidation reaction than when using aqueous potassiumcarbonate (see Table 1). It was observed that, in the DBU reactions,an additional product could be detected by TLC analysis. This wasseparated from the reaction mixture, crystallized, and the structure ofScheme 1.1938 Page et al.©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016the compound determined by X-ray crystallography (Fig. 1).a To oursurprise, the structure proved to be 2, containing both a saccharinresidue and an N-aminopropyl caprolactam unit, presumably derivedfrom DBU.The formation of compound 2 can be explained by nucleophilicattack by one nitrogen atom of the 6-membered ring of DBU at the3-position of pseudo-saccharin ethyl ether 1b or pseudo-saccharyl chloride1a, displacing ethoxide ion or chloride ion respectively. Attack on theFigure 1.aMolecular formula C16H21N3O3S (Mr¼ 335.42), crystal size 0.2000.200 0.450mm3, monoclinic, space group P21/c, a¼ 8.463(7) A, b¼ 16.475(9) A, c¼ 11.835 (7) A, V¼ 1646 (2) A3, Z¼ 4, D¼ 1.354 g cm3,(MoKa)¼ 2.05 cm1, F000¼ 712.2997 Unique reﬂections collected on a RigakuAFC6S sequential diﬀractometer, 2ymax¼ 50.0. The structure was solved bydirect methods and H atoms were placed geometrically and allowed to ride onthe relevant non-H atom. Reﬁnement coverged to give R¼ 0.061 and Rw¼ 0.069.Table 1. Oxidation of p-tolyl methyl sulﬁde catalysed by saccharin derivatives.Mediator Solvent BaseTemp.(C)ReactiontimeYield ofsulfoxide (%)Yield of2 (%)1a DCM DBU 25 2 days 11 121b DCM DBU 25 2 h 81b DCM DBU 25 2 days 13 251b MeOH K2CO3 25 2 days 33 01g DCM DBU 25 2 h 100 0DBU in Reactions with Saccharin Derivatives 1939©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016intermediate 3 by water, followed by opening of the bicyclic system,would aﬀord compound 2 (Sch. 2). Consistent with this interpretation,compound 2 was not observed in the product mixture when alkylsaccharin derivatives 1c–1j were used as mediators in the sulfoxidationreactions, 3-alkyl substituents not being good leaving groups. This reac-tion suggests that it would be wise to exercise caution when consideringthe use of DBU in reactions with electrophilic substrates, and particularlysubstrates containing good leaving groups.EXPERIMENTAL SECTION3-[30-(100-Azepin-200-onyl)propylamino]-1,2-benzisothiazole-1,1-dioxide 2Hydrogen peroxide (30% w/v, 0.43mL, 4 equiv.), was added to astirred solution of DBU (576mg, 3.78mmol) in dichloromethane (10mL)at room temperature, followed by 3-ethoxy-1,2-benzisothiazole-1,1-dioxide 1b (200mg, 0.946mmol). Methyl p-tolyl sulﬁde (130mg,0.94mmol) was added, and the reaction mixture was stirred at roomtemperature for 2 h, diluted with dichloromethane (30mL), washedScheme 2.1940 Page et al.©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016with brine (15mL) and saturated aqueous sodium sulﬁte (20mL),and dried over sodium sulfate. 3-[30-(100-Azepin-200-onyl)propylamino]-1,2-benzisothiazole-1,1-dioxide 2 was isolated as a colourless solid byevaporation to dryness followed by ﬂash column chromatographyusing ethyl acetate (25mg, 8%), m.p. 212–213C (from EtOH), (Found:C, 57.41; H, 6.35; N, 12.57. C16H21N3O3S requires C, 57.29; H, 6.31; N,12.53%); max(nujol)/cm1 1612, 1304 and 1152; H(400MHz; CDCl3)1.50–1.94 (8H, m), 2.55 (2H, t, J 5.6), 3.4 (2H, t, J 7.4), 3.40–3.60(4H, m), 7.50–7.70 (2H, m), 7.78–7.82 (2H, m), 8.74 (1H, s);C(300MHz; CDCl3) 23.8, 26.6, 28.5, 30.2, 37.4, 39.0, 45.4, 50.3, 122.0,122.1, 128.8, 133.1, 133.4, 142.9, 160.0, 178.6; m/z (EI) 335.13036 (Mþ,8%. C16H21N3O3S requires 335.13036), 140 (100) and 41 (44).ACKNOWLEDGMENTThis investigation has enjoyed the support of Payame NoorUniversity, Iran.REFERENCES1. (a) Page, P.C.B.; Bethell, D.; Stocks, P.A.; Heer, J.P.; Graham, A.E.;Vahedi, H.; Healy, M.; Collington, E.W.; Andrews, D.M. Sulfuroxidation mediated by imine derivatives. Synlett 1997, 1355; (b)Bethell, D.; Page, P.C.B.; Vahedi, H. Catalytic asymmetric oxidationof sulﬁdes to sulfoxides mediated by chiral 3-substituted-1,2-benzi-sothiazole 1,1-dioxides. J. Org. Chem. 2000, 65, 6756.2. (a) Page, P.C.B.; Heer, J.P.; Bethell, D.; Collington, E.W.; Andrews,D.M.; A new system for catalytic asymmetric oxidation of sulﬁdesusing a hydrogen peroxide based reagent. Tetrahedron Lett. 1994,35, 9629; (b) Page, P.C.B.; Heer, J.P.; Bethell, D.; Collington, E.W.;Andrews, D.M. Highly enantioselective catalytic asymmetric oxida-tion of sulﬁdes using hydrogen peroxide. Synlett 1995, 773; (c) Page,P.C.B.; Heer, J.P.; Bethell, D.; Collington, E.W.; Andrews, D.M.;Asymmetric sulfoxidation using [(3,3-dimethoxycamphoryl)sulfonyl]-oxaziridine. Tetrahedron: Asymmetry 1995, 6, 2911.3. Davis, F.A.; Towson, J.C.; Vashi, D.B.; ThimmaReddy, R.;McCauley, J.P., Jr.; Harakal, M.E.; Gosciniak, D.J. Chemistry ofoxaziridines. 13. Synthesis, reactions, and properties of 3-substituted1,2-benzisothiazole 1,1-dioxide oxides. J. Org. Chem. 1990, 55, 1254.Received in the USA September 16, 2002DBU in Reactions with Saccharin Derivatives 1941©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016

Unexpected nucleophilic participation and rearrangement of DBU in reactions with saccharin derivatives

Philip C. Bulman Page

Hooshang Vahedi

Donald Bethell

James V. Barkley

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Unexpected Nucleophilic Participation and Rearrangement of DBU in Reactions with Saccharin Derivatives

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Unexpected Nucleophilic Participation and Rearrangement of DBU in Reactions with Saccharin Derivatives.

Unexpected nucleophilic participation and rearrangement of DBU in reactions with saccharin derivatives

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