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Molbank 2006, M470 |
5,6,7,8-Tetrahydro-3-(1-methoxyiminobutyl)-1-methylsulfonylisoquinoline
Teodozja Lipińska* and Ewa Olender
Department of Chemistry,
ul 3 Maja 54, PL-08
110 Siedlce,
e-mail: [email protected]
Received:
Keywords: 5,6,7,8-tetrahydroisoquinoline, 1-heteroarylbutanone oxime methylether, methysulfone, PTC-oxidation, aza-Diels-Alder
reaction.
As part of research programme
directed to the synthesis of novel heterocyclic compounds pharmacologically
interesting [1] via ring transformation of 1,2,4-triazine
derivatives, we synthesized the title compounds 3 via two step process.
Starting compounds, 5-(methoxyiminobutyl)-3-(methylsulfanyl)-1,2,4-triazine (1)
[2] was easily oxidized under PTC-conditions into the corresponding sulfone 2. The
latter compound, as reactive azadiene [3], was
subjected in crude form to [4+2]cycloaddition-retro cycloaddition with 1-pyrrolidino-1-cyclohexane as dienophile to give 5,6,7,8-Tetrahydro-3-(1-methoxyiminoethyl)-1-methylsulfonylisoquinoline
(3) in 70% yield.
Preparation of 2:
A solution of KMnO4 (474 mg, 3 mmol) in water 20 ml) was added to a solution of 1 (226 mg, 1 mmol) and Bu4N+Br- (48 mg, 1.5 mmol) in a mixture of AcOH (1.8 ml, 30 mmol) and benzene (15 ml) during stirring and cooling to 5-10oC. The reaction was continued at 10oC for 1-1.5 h, until complete oxidation process was observed with monitoring by TLC (CHCl3/acetone -50:1). A saturated solution of Na2S2O5 for decoloring, then saturated solution of K2CO3 for neutralization were added. The organic layer was separated and water phase was extracted with benzene (3 x 20 ml). The combined organic layers were washed with water (2 x 20 ml) and dried over MgSO4. After evaporation of the solvents under reduced pressure to volume of 5 ml, the solution was contained of pure product 2 (TLC monitoring) and was used for next step.
IR (KBr, ν, cm-1): 3030 (CHaromat.); 2975, 2850 (CH3); 1665 (C=N); 1565, 1460, 1395 (aromat. ring); 1335, 1155 (SO2); 1075 (C-O);
1H-NMR (CDCl3, 200 MHz); δ= 9.64 (s, 1 H, CHaromat.); 4.20 (s, 3 H, CH3O); 3.45 (s, 3H, CH3SO2); 2.90 (t, J= 7.7 Hz, 2 H, H2CC=N); 1.60 (m, 2 H, H2CCH2C=); 1.05 (t, J=7.4 Hz, 3 H, H3CCH2).
Preparation of 5,6,7,8-Tetrahydro-3-(1-methoxyiminobutyl)-1-methylsulfonylisoquinoline
(3):
To the freshly obtained solution of 2 (1 mmol), was added 1-(N-pyrrolidine)cyclohexene
(302 mg, 2 mmol). The reaction mixture was refluxed
for 1h until the substrate 2 was disappeared (TLC monitoring: CHCl3/acetone-50:1).
Removal of solvents under reduced pressure and purification of the residue by
column chromatography on silica gel (230-400 mesh, Merck type 60) using
chloroform/hexane - 3:1 as eluent gave 218 mg (70 %)
of 5,6,7,8-tetrahydro-3-(1-methyoxyiminobutyl)-1-methylsulfonylisoquinoline
(3) as a white solid after recrystalization from mixture chloroforme/hexane
1:2.
Melting point: 84-85oC
IR (KBr,
ν, cm-1): 3030 (CHaromat.);
2975, 2875, 2855 (CH3, CH2); 1660 (C=N); 1550, 1460 (aromat. ring); 1340, 1170 (SO2); 1070 (CH3O).
1H-NMR (CDCl3, 200 MHz): δ= 7.71 (s, 1
H, CHaromat.); 3.95 (s, 3 H, CH3O);
3.70 (s, 3 H, CH3SO2); 3.16 (t, J=5.5Hz, 2 H, C8H2);
2.83 (t, J=5.7 Hz, 2 H, C5H2);
2.64 (t, J=7.6 Hz, 2 H, CH2C=N); 1.94-1.76 (m,
4 H, C6H2C7H2); 1.61 (m, 2 H, H2CCH3);
0.97 (t, J=7.5 Hz, 3H, H3CCH2).
MS (EI), m/z (% rel. int.): 310
(100) [M+]; 295 (13); 279 (35); 267 (13); 250 (15); 212 (25); 181
(33).
Elemental Analysis: Calculated for C15H22N2O3S:
C, 58.04%; H, 7.14%; N, 9.03%. Found: C, 57.88%; H, 7.20%; N, 8.90%.
References and notes:
1. For
previous paper in this series, see: Lipińska T. Tetrahedron Lett. 2002, 43, 9565-9567.
2. Lipińska, T.; Branowska, D.; Rykowski, A. Khim. Geterosikl. Soedin. 1999, 381-389; Chem. Heterocycl. Compd
(Engl. Transl.) 2001, 37, 231-236.
3. For
a review on aza-DA-rDA reactions with extrusinon of small molecules see:Rickborn,
B. in Organic Reactions,
Vol. 53,
224-627. Edited by Leo A. Paguette et.al.,
J. Wiley & Sons Inc. 1998..
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