Synthesis of 1H-1-alkyl-8-X-2,2-dioxoisothiazolo[5,4,3-d,e]-quinolines via tandem cyclization of N-alkyl-N-(2-X-5-nitrophenyl)prop-2-enyl sulfonamides

Article abstract of DOI:10.1016/S0040-4039(00)01035-2

Tandem five- and six-membered ring closure reactions to afford tricyclic sultams from N-alkyl-N-(2-X-5-nitrophenyl) prop-2-enyl sulfonamides is described. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01035-2

Tetrahedron Letters 41 (2000) 7365±7366
Synthesis of 1H-1-alkyl-8-X-2,2-dioxoisothiazolo[5,4,3-d,e]-
quinolines via tandem cyclization of N-alkyl-N-(2-X-5-
nitrophenyl)prop-2-enyl sulfonamides
Zbigniew Wrobel
Institute of Organic Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44/52, 01-224 Warsaw, Poland
Received 1 May 2000; accepted 20 June 2000
Abstract
Tandem ®ve- and six-membered ring closure reactions to a€ord tricyclic sultams from N-alkyl-N-(2-X-5-
nitrophenyl) prop-2-enyl sulfonamides is described. # 2000 Elsevier Science Ltd. All rights reserved.
Keywords: allyl nitroarylsulfonamides; tandem double cyclization; intramolecular.
Recently we reported a new method of synthesis of 2-aryl or alkyl substituted 4-arylsulfonyl-
quinolines from nitroarenes and allyl or cinnamyl sulfones on treatment with base and Lewis acid
or silylating agent in an aprotic solvent. The reaction is considered to proceed via addition of a
carbanion derived from the sulfone to the nitroarene to form a sH adduct, then the nitroso
compound which undergoes cyclization to the ®nal product.1
Now we would like to report the intramolecular version of this reaction applied to sulfonamides
and leading to sultams, namely 1H-1-alkyl-8-X-2,2-dioxoisothiazolo[5,4,3-de]quinolines, which
may be interesting as potentially biologically active compounds.2
N-Alkyl-N-(2-X-5-nitrophenyl) propen-3-yl sulfonamides 3 suitable for cyclization were
obtained from commercial 2-X-5-nitroanilines 1 (X=H, Cl) via a sulfonylation reaction with
propen-3-yl sulfonyl chloride (Py/CH2Cl2, ^30ꢀC to rt; 55±76%) to yield 2, followed by the
alkylation with alkyl halide (K2CO3/DMF/ cat. KI, rt; 70±90%). Tandem ®ve- and six-membered
ring closure was accomplished under the action of base in the presence of a catalytic amount of
MgCl2 in DMSO in moderate yields (Scheme 1).
Thus, 1 mmol of 2 dissolved in 10 mL of DMSO was treated with MgCl2 (60 mg, 0.625 mmol)
for 20 min at rt then DBU (746 mL, 5 mmol) was added and the reaction mixture was stirred at rt
for approximately 24 h. Work-up, followed by column chromatography gave 4 and 5.3
Other solvents were less e€ective in these conditions, (solvent/time/4[%]/5[%]): MeCN/30 days/
6/8; Py/7 days/43/9; CH2Cl2/21 days/3/6; DMF/1 day/59/12).
0040-4039/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01035-2

7366
Scheme 1. Reagents and conditions: (a) AllylSO2Cl, Py, CH2Cl2, ^30ꢀC to rt, 3±5 h; (b) RX, K2CO3KI (cat.), DMF,
rt, 24 h±7 days; (c) DBU, MgCl2 (cat.), DMSO, rt, 24 h
Formation of products could be rationalized according to Scheme 2. Deprotonation of 3 at the
position adjacent to the SO2 group followed by the intramolecular addition to the nitroaromatic
ring led to sH adduct 6 which is stabilized either by formal elimination of the OH^ anion1 to form
7, or oxidatively4 to 8. Further base-catalyzed intramolecular condensation1,5 led to 4 and 5.
Scheme 2. Possible formation of products
Acknowledgements
This search was funded by the State Committee of Scienti®c Research Grant No. PBZ 6.01.
References
1. (a) Wrobel, Z. Tetrahedron Lett. 1997, 38, 4913±4916; (b) Wrobel, Z. Tetrahedron 1998, 54, 2607±2618; (c)
Wrobel, Z. Eur. J. Org. Chem. 2000, 521±525.
2. For example see: Hanson, P. R.; Probst, D. A.; Robinson, R. E.; Yau, M. A. Tetrahedron Lett. 1999, 40, 4761±
4766 and references cited herein.
3. The structures of products con®rmed by 1H NMR and MS spectra, for example: 4a: NMR (CDCl3): 3.39 (s, 3H),
6.78, 7.72, 7.80 (ABX, JAB=8.8, JBX=0.5, JAX=7.4, 3H), 7.81 (d, J=4.5, 1H), 9.24 (d, J=4.5, 1H); MS (m/z, %):
221 (12.4), 220 (100), 156 (9.9), 155 (78.9), 129 (40.6), 128 (55.3); 5a: NMR (CDCl3): 3.39 (s, 3H), 6.81 (d, J=7.4,
1H), 7.70 (d, J=6.4, 1H), 7.75 ( dd, J=8.9, 7.4, 1H), 7.94 (d, J=8.9, 1H), 8.59 (d, J=6.4, 1H); MS (m/z, %): 237
(11.1), 236 (100), 220 (26.6), 189 (35.5), 171 (8.8), 155 (17.5).
4. Moskalev, N.; MacÎkosza, M. Tetrahedron Lett. 1999, 40, 5395±5398.
5. Wrobel, Z.; McaÎkosza, M. Tetrahedron 1993, 49, 5315±5323.