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Synthesis 2008(7): 1133-1141  
DOI: 10.1055/s-2008-1066984
PAPER
© Georg Thieme Verlag Stuttgart · New York

Synthesis of N,N′-Linked Bisazaheterocycles with Sulfonamide Structure via Oxidation of S,N-Heteroaromatic Cations

Valerija M. Zakharovaa, Camino M. González Tanarrob, Michael Gütschowb, Lothar Henniga, Joachim Sielerc, Bärbel Schulze*a
a Institut für Organische Chemie, Universität Leipzig, Johannisallee 29, 04103 Leipzig, Germany
e-Mail: bschulze@chemie.uni-leipzig.de;
b Pharmazeutisches Institut, Pharmazeutische Chemie I, Universität Bonn, An der Immenburg 4, 53121 Bonn, Germany
c Institut für Anorganische Chemie, Universität Leipzig, Johannisallee 29, 04103 Leipzig, Germany
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Publikationsverlauf

Received 7 December 2007
Publikationsdatum:
06. März 2008 (online)

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Abstract

N-Phthalimidyl- and N-quinazolinyl-substituted 3-hydroperoxy-, 3-hydroxy- and 3-oxoisothiazole 1,1-dioxides have been synthesized by the sequence of oxidation reactions from N,N′-linked isothiazolium perchlorates with hydrogen peroxide, MMPP, and pyridinium dichromate. Isothiazolium salts without acceptor substituents did not give N-substituted sultams. Novel N,N′-bisazaheterocycles were investigated as inhibitors of acetylcholinesterase (AChE) and human leukocyte elastase (HLE). Two 2,3-dihydro-3-hydroperoxy-2-(phthalimid-1-yl)isothiazole 1,1-dioxides were found to inhibit AChE.

Key words

β-thiocyanatovinyl aldehydes - N-aminoheterocycles - isothiazolium salts - N,N′-linked bisazaheterocycles - sultams

19

Crystal data for 15a: C13H16N2O5S; M = 306,3: T = 213 (2) K; λ = 0.71073 Å; Colorless prism; 0.3 × 0.3 × 0.2 mm3; Triclinic; space group P-1; Unit cell dimensions α = 8.030 (2) Å, β = 8.624 (3) Å, c = 10.148 (2) Å, α = 86.81 (2)°, β = 76.02 (2)°, γ = 77.43 (2)°, V = 665.6 (3) Å3, Z = 2, Dcalcd = 1.528 gcm-3; F(000) = 316, µ = 0.267 mm-1; Theta range for data collection 2.4° to 28.2°; Index ranges -10 ≤ h ≤ 10, -11 ≤ k ≤ 11, -13 ≤ l ≤ 13; Reflections collected 6555; Independent reflections 2997 [R int = 0.052]; Final R indices [I >2σ (I)] R1 = 0.0463, wR2 = 0.0626; R indices (all data) R1 = 0.0626, wR2 = 0.1283; Largest diff. Peak/hole 0.335/-0.471 e Å-3.

20

Crystal data for 18d: C16H17N3O4S·H2O; M = 365.4; T = 213 (2) K; λ = 0.71073 Å; Colorless prism; 0.2 × 0.2 × 0.2 mm3; Triclinic; Space group P-1; Unit cell dimensions a = 8.163 (2) Å, b = 8.906 (2) Å, c = 11.862 (4) Å, α = 83.76 (2)°, β = 87.82 (2)°, γ = 81.28 (2)°, V = 847.1 (4) Å3, Z = 2, Dcalcd = 1.433 gcm-3; F(000) = 384, µ = 0.224 mm-1; Theta range for data collection 2.5° to 28.1°; Index ranges -10 ≤ h ≤ 10, -11 ≤ k ≤ 11, -15 ≤ l ≤ 15; Reflections collected 8243; Independent reflections 3779 [Rint = 0.033]; Final R indices [I >2σ(I)] R1 = 0.0363, wR2 = 0.0982; R indices (all data) R1 = 0.0463, wR2 = 0.1018; Largest diff. Peak/hole 0.262/-0.266 e Å-3.

21

Crystal data for 19b: C14H13N3O4S; M = 319.3; T = 213 (2) K; λ = 0.71073 Å; Colorless prism; 0.3 × 0.2 × 0.2 mm3; Orthorhombic; Space group Pna21; Unit cell dimensions a = 10.811 (1) Å, b = 12.632 (1) Å, c = 10.654 (1) Å, V = 1455.0(2) Å3, Z = 4, Dcalcd = 1.458 gcm-3; F(000) = 664, µ = 0.245 mm-1; Theta range for data collection 2.5° to 26.0°; Index ranges -13 ≤ h ≤ 13, -15 ≤ k ≤ 15, -13 ≤ l ≤ 13; Reflections collected 10986; Independent reflections 2828 [Rint = 0.038]; Final R indices [I >2σ (I)] R1 = 0.0259, wR2 = 0.0673; R indices (all data) R1 = 0.0281, wR2 = 0.0681; Largest diff. Peak/hole 0.183/-0.136 e Å-3.

24

The details of the structure analyses for compounds 15a, 18d, and 19b have been deposited at the Cambridge Crystallographic Data Centre with the numbers CCDC-651832, -651831 and -651833, respectively. The copies of the data can be obtained, free of charge, from CCDC, 12 Union Road, Cambridge, CB2 1EZ UK (fax: +44 1233 336033; e-Mail: deposit@ccdc.cam.ac.uk, internet: http://www.ccdc.cam.ac.uk).