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Molbank 2006, M469 |
5,6,7,8-Tetrahydro-3-(1-methoxyiminoethyl)-1-methylsulfonylisoquinoline
Teodozja Lipińska* and Beata
Iwańska
Department of Chemistry,
PL-08 110
e-mail:
[email protected]
Received: 10 September 2005
/ Accepted: 9 October 2005 / Published: 28 February 2006
Keywords: 5,6,7,8-tetrahydroisoquinoline
derivatives, oxime methyl ether, 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-(methoxyiminoethyl)-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-cyclohexene as dienophile to
give 5,6,7,8-Tetrahydro-3-(1-methoxyiminoethyl)-1-methylsulfonylisoquinoline (3) in 83% 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): 3025 (CHaromat.), 2970, 2850 (CH3); 1655 (C=N); 1555, 1465, 1395 (aromat. ring); 1340, 1180 (SO2); 1070 (C-O).
1H-NMR (CDCl3,
200 MHz): δ= 9.82 (s, 1 H, CHaromat.);
4.26 (s, 3 H, CH3O); 3.45 (s. 3H, CH3SO2);
2.43 (s, 3 H, H3C=N).
Preparation of 5,6,7,8-Tetrahydro-3-(1-methyoxyiminoethyl)-1-methylsulfonyl-isoquinoline
(3):
To the solution of 2 (1 mmol)
was added 1-(N-pyrrolidine)cyclohexene (302 mg, 2 mmol).
Vigrously extrusion of N2 was observed.
The reaction mixture was stirred for 5 h at room temperature, 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 as eluent gave 235 mg (83 %) of
5,6,7,8-tetrahydro-3-(1-methyoxyiminoethyl)-1-methylsulfonylisoquinoline
(3) as a white solid after recrystalization from mixture chloroform/hexane 1:3.
Melting Point: 126-127oC
IR (KBr, ν, cm-1): 3030 (CHaromat.);
2975, 2875, 2790 (CH3 and CH2); 1660 (C=N); 1540, 1440 (aromat. ring); 1340, 1150 (SO2); 1060 (CH3O).
1H-NMR (CDCl3,
200 MHz): δ= 7.81 (s, 1 H, CHaromat.);
4.03 (s, 3 H, CH3O); 4.00 (s, 3 H, CH3SO2);
3.25 (t, J=5.5Hz, 2 H, C8H2); 2.85 (t, J=5.7 Hz, 2 H, C5H2); 2.24 (s, 3 H, CH3C=N);
1.94-1.76 (m, 4 H, C6H2C7H2).
MS (EI), m/z (% rel. int.): 282 (30) [M+.], 251 (15), 242 (11),
212 (13), 181(46), 170 (14), 170 (15), 151 (15), 149 (15), 137 (18), 135 (18),
125 (22), 123 (25), 111 (48), 109 (45), 97 (64), 95 (62), 85 (48), 83 (100), 81
(51), 71 (55), 69 (54).
HR-MS (EI): Calculated for C13H18N2O3S:
282.1038; Found: 282.1038.
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.
Sample Availability: Available from MDPI.
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