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DOI: 10.1055/s-0029-1219550
An Easy Access to Novel Spiro-Fused Pyrrolo Benzo[b]thiophene 1,1-Dioxide Derivatives via 1,3-Dipolar Cycloaddition Using Benzo[b]thiophene 1,1-Dioxide
Publication History
Publication Date:
26 February 2010 (online)
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Abstract
A series of spirooxindoles containing tri- and tetracyclic fused pyrrolo benzo[b]thiophene 1,1-dioxide derivatives was synthesized regioselectively via a multicomponent 1,3-dipolar cycloaddition of isatin, benzo[b]thiophene 1,1-dioxide and sarcosine or l-proline in methanol under reflux condition. Also a series of spiro frameworks having tri- and tetracyclic fused pyrrolo benzo[b]thiophene 1,1-dioxide derivatives was synthesized from ninhydrin, 11H-indeno[1,2-b]quinoxalin-11-one and acenaphthene-quinone using benzo[b]thiophene 1,1-dioxide as a dipolarophile. The methodology affords high yields of products in short reaction time.
Key words
spirooxindoles - azomethine ylide - multicomponent reaction - benzo[b]thiophene 1,1-dioxide - dipolarophile
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- Supporting Information
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References and Notes
Crystallographic data for compound 4c in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplemental publication no. CCDC 759326. Copies of the data can be obtained, free of charge on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax: +44(1223)336033 or email: deposit@ccdc.cam.ac.uk].
18
Typical Experimental
Procedure for 4a: A mixture of isatin (1a;
1.0 mmol), sarcosine (2; 1.2 mmol), and benzo[b]thiophene 1,1-dioxide (3; 1.1 mmol) in MeOH was refluxed for 60
min and cooled to r.t. The solid formed in the reaction mixture
was filtered, dried and recrystallized from EtOH to obtain the pure
product in good yield (85%).
Spectral
Data of Compound 4a (Table 1, Entry 1): white solid; mp 234-236 ˚C; R
f
0.25
(50% EtOAc-PE). IR (KBr): 3150, 3074, 1708, 1619,
1467, 1301, 1153, 1124, 755 cm-¹. ¹H
NMR (500 MHz, DMSO-d
6): δ = 1.91
(s, 3 H, Me), 3.52 (d, 1 H, J = 9.9
Hz, H1), 3.69-3.72 (m, 1 H, H2),
4.30 (t, 1 H, J = 7.6 Hz, H3),
4.53 (d, 1 H, J = 9.2 Hz, H4),
5.77 (d, 1 H, J = 7.6 Hz, ArH),
6.48 (d, 1 H, J = 8.4 Hz, ArH),
6.58 (t, 1 H, J = 7.6 Hz, ArH),
6.80 (d, 1 H, J = 7.7 Hz, ArH),
7.11 (t, 1 H, J = 7.7 Hz, ArH),
7.33 (t, 1 H, J = 7.6 Hz, ArH),
7.48 (t, 1 H, J = 7.7 Hz, ArH),
7.74 (d, 1 H, J = 7.7 Hz, ArH),
10.54 (br s, 1 H, NH, D2O
exch). ¹³C NMR (125 MHz, DMSO-d
6): δ = 35.1,
52.1, 52.3, 62.1, 74.7, 110.2, 121.1, 121.5, 125.8, 127.0, 129.9,
130.1, 130.3, 132.9, 135.7, 140.3, 143.3, 179.2. MS (ESI, LCQ-MS): m/z = 341 [M + H]+.
Anal. Calcd for C18H16N2O3S:
C, 63.51; H, 4.74; N, 8.23. Found: C, 63.57; H, 4.72; N, 8.31.
Typical Experimental
Procedure for 12: A mixture of ninhydrin 9 (1.0
mmol), sarcosine (2; 1.2 mmol), and benzo[b]thiophene 1,1-dioxide (3; 1.1 mmol) in MeOH was refluxed for 45
min and cooled to r.t. The solid formed in the reaction mixture
was filtered, dried and recrystallized from EtOH to obtain the pure
product in good yield (87%).
Spectral Data of Compound 12 (Table 3, Entry 1):
yellow solid; mp 252-254 ˚C; R
f
0.25 (50% EtOAc-PE).
IR (KBr): 1739, 1706, 1588, 1307, 1268, 1152, 1124, 768 cm-¹. ¹H NMR
(500 MHz, DMSO-d
6): δ = 2.07
(s, 3 H, Me), 3.61-3.67 (m, 2 H, H1, H2),
4.35-4.37 (m, 1 H, H3), 4.72 (d, 1 H, J = 9.9 Hz, H4),
6.68 (d, 1 H, J = 7.7 Hz, ArH),
7.42 (t, 1 H, J = 6.9 Hz, ArH),
7.50 (t, 1 H, J = 7.7 Hz, ArH),
7.72 (d, 1 H, J = 7.7 Hz, ArH),
7.83 (d, 1 H, J = 7.7 Hz, ArH),
8.02-8.07 (m, 3 H, ArH). ¹³C
NMR (125 MHz, DMSO-d
6): δ = 35.7,
52.1, 54.1, 61.6, 76.5, 121.7, 123.4, 123.9, 128.4, 130.5, 133.6,
134.8, 137.9, 138.1, 140.2, 140.6, 141.9, 199.3, 202.3. MS (ESI,
LCQ-MS): m/z = 354 [M + H]+. Anal.
Calcd for C19H15NO4S: C, 64.58;
H, 4.28; N, 3.96. Found: C, 64.52; H, 4.32; N, 3.90.
Typical Experimental
Procedure for 15: A mixture of ninhydrin 9 (1.0
mmol), l-proline (6;
1.2 mmol), and benzo[b]thiophene
1,1-dioxide (3; 1.1 mmol) in MeOH was refluxed
for 60 min and cooled to r.t. The solid formed in the reaction mixture
was filtered, dried and recrystallized from EtOH to obtain the pure
product in good yield (87%).
Spectral
Data of Compound 15 (Table 3, Entry 4): yellow solid; mp 234-236 ˚C; R
f
0.25
(50% EtOAc-PE). IR (KBr): 3435, 2958, 1713, 1591,
1286, 1143, 757 cm-¹. ¹H
NMR (500 MHz, DMSO-d
6): δ = 1.64-1.66
(m, 1 H, CH), 1.90-1.95 (m, 1 H, CH), 2.06-2.10
(m, 1 H, CH), 2.45-2.47 (m, 1 H, CH), 2.54 (t, 1 H, J = 6.9 Hz, CH), 2.98-3.01
(m, 1 H, CH), 4.29-4.32 (m, 1 H, H3), 4.42-4.44
(m, 1 H, H1), 5.05 (d, 1 H, J = 9.9
Hz, H4), 6.60 (d, 1 H, J = 8.4
Hz, ArH), 7.33 (t, 1 H, J = 7.6
Hz, ArH), 7.44 (t, 1 H, J = 7.7
Hz, ArH), 7.69 (d, 1 H, J = 8.4
Hz, ArH), 7.77 (d, 1 H, J = 7.7
Hz, ArH), 7.98 (t, 1 H, J = 7.7
Hz, ArH), 8.03 (t, 1 H, J = 6.9
Hz, ArH), 8.13 (d, 1 H, J = 7.7
Hz, ArH). ¹³C NMR (125 MHz, DMSO-d
6): δ = 24.9,
28.9, 48.8, 50.6, 67.2, 69.2, 75.6, 122.1, 124.2, 124.7, 126.2,
130.4, 134.4, 134.8, 137.5, 138.2, 140.3, 141.4, 141.7, 196.2, 197.4.
MS (ESI, LCQ-MS): m/z = 380 [M + H]+.
Anal. Calcd for C21H17NO4S: C,
66.48; H, 4.52; N, 3.69. Found: C, 66.52; H, 4.58; N, 3.71.