Multicomponent reactions in a one-pot synthesis
653
triisopropyl phosphite (2c) (3.2 mmol) in 10 cm3 tetrahy-
drofuran (THF) containing 10% FeCl3 (or 2 cm3 glacial
AcOH; best results with FeCl3) was heated under reflux for
4–6 h. After completion of the reaction (TLC), 10 cm3
AcOEt was added to the mixture. The organic phase was
separated, washed with 20 cm3 distilled water, and dried
over anhydrous sodium sulfate. Solvents were evaporated
under vacuum, and the residue was crystallized from the
proper solvent to give compounds 4a–4c.
141.3, 130.7, 129.1, 129.4, 128.5, 127.5, 126.4, 119.6, 111.8
(C–Ar, C–Ph), 118.8 (CN), 93.4 (C-300), 62.4 (d,
1
2JP–C = 8.7 Hz, (CH2O)2P), 56.4 (d, JP–C = 169.4 Hz,
HC-P), 26.3, 26.1, 23.7, 21.5 (400-, 500-, 600-, 700-C-hexene),
3
16.6 (d, JP–C = 7.7 Hz, (MeCO)2P) ppm; 31P NMR
(200.7 MHz, CDCl3): d = 25.6 ppm; MS (EI, 70 eV): m/z
(%) = 587 (28) [M? ? 1], 586 (33) [M?], 449 (62) [M?-
P(O)(OC2H5)2],
421
(27)
[M?-(2H ? CN ? P(O)
(OC2H5)2)], 409 (100) [M?-C9H8N2S], 177 (34) [C9H8N2S].
Products 4a–4c were equally obtained, in almost the
same yields, when dimethyl (6a), diethyl (6b) or diiso-
propyl phosphite (6c) replaced the trialkyl phosphite
counterpart in the above reactions, whereas experimental
conditions, stoichiometric amounts, and work-up were
exclusively used.
Diisopropyl [3-(benzofuran-2-yl)-1-phenyl-1H-pyrazol-4-
yl](3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl-
amino)methylphosphonate (4c, C33H35N4O4PS)
Yellow crystals; yield 646 mg (62%); m.p.: 228–230 °C
(AcOEt); IR (KBr): vꢀ = 3,383 (NH), 2,196 (CN), 1,235
(P=O), 1,011 (P–O–C) cm-1 1H NMR (500.7 MHz,
;
CDCl3): d = 1.11, 1.33 (2dd, JH–H = 6.6, 4JP–H = 5.8 Hz,
2 9 6H, (Me2CO)2P), 1.72, 2.43 (2 m, 8H, hexene), 4.62,
Dimethyl [3-(benzofuran-2-yl)-1-phenyl-1H-pyrazol-4-yl]-
(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl-
amino)methylphosphonate (4a, C29H27N4O4PS)
3
4.81 (2sept, JP–H = 12.4 Hz, 2 9 1H, (CHO)2P), 5.32
2
(dd, JH–H = 8.8, JP–H = 18 Hz, 1H, HC-P), 5.63 (br, 1H,
Pale-yellow crystals; yield 548 mg (58%); m.p.: 198–
NH), 7.22 (d, JP–H = 8.4 Hz, 1H, C-5-H), 7.37–7.77, 8.24
(m, 10H, Ar–H) ppm; 13C NMR (125.4 MHz, CDCl3):
d = 129.6 (d, 3JP–C = 10.6 Hz, C-3), 124.8 (d,
200 °C (EtOH); IR (KBr): vꢀ = 3,340 (NH), 2,195 (CN),
1,221 (P = O), 1,045 (P–O–C) cm-1
;
1H NMR
(500.7 MHz, CDCl3): d = 1.81, 2.88 (2 m, 8H, hexene),
3.65, 3.82 (2d, JP–H = 13.4 Hz, 2 9 3H, (MeO)2P), 5.52
2
3JP–C = 8.6 Hz, C-5), 123.4 (d, JP–C = 14.2 Hz, C-4),
3
3
2
(dd, JH–H = 8.8, JP–H = 17.5 Hz, 1H, HC–P), 6.43 (br,
168.4 (d, JP–C = 10.8 Hz, C-200), 152.9, 141.7, 130.2,
129.5, 129.7, 128.3, 127.5, 126.6, 126.3, 119.1, 111.9
1H, NH), 7.23 (d, JP–H = 8.4 Hz, 1H, C-5-H), 7.34–7.77,
8.24 (m, 10H, Ar–H) ppm; 13C NMR (125.4 MHz, CDCl3):
d = 128.3 (d, 3JP–C = 9.6 Hz, C-3), 124.8 (d,
(C–Ar, C–Ph), 116.5 (CN), 94.0 (d, 4JP–C = 3.7 Hz, C-300),
76.1
(d,
2JP–C = 9.8 Hz
(CHO)2P),
57.6
(d,
1JP–C = 164.4 Hz, HC–P), 26.4, 26.2, 23.5, 21.2 (400-, 500-,
2
3JP–C = 8.6 Hz, C-5), 123.4 (d, JP–C = 14.2 Hz, C-4),
3
3
600-, 700-C-hexene), 24.0 (d, JP–C = 8.2 Hz, (Me2CO)2P)
168.2 (d, JP–C = 11.6 Hz, C-200), 152.8, 141.6, 130.3,
129.2, 127.4, 126.5, 119.0, 111.6 (C–Ar, C–Ph), 117.5
ppm; 31P NMR (200.7 MHz, CDCl3): d = 27.3 ppm; MS
(EI, 70 eV): m/z (%) = 616 (9) [M? ? 2], 614 (15) [M?],
529 (5), 449 (100) [M?-P(O)(OC3H7)2], 419 (96) [M?-
(2H ? CN ?P(O) (OC3H7)2)], 438 (20) [M?-C9H8N2S],
177 (96) [C9H8N2S].
(CN), 94.3 (C-300), 54.6 (d, 2JP–C = 7.8 Hz, (MeO)2P), 53.4
1
(d, JP–C = 166.3 Hz, HC–P), 26.3, 26.1, 23.5, 21.7 (400-,
500-, 600-, 700-C-hexene) ppm; 31P NMR (200.7 MHz,
CDCl3): d = 23.3 ppm; MS (EI, 70 eV): m/z (%) = 559
(11) [M? ? 1], 558 (14) [M?], 449 (55) [M?–
P(O)(OCH3)2], 421 (8) [M?-(2H ? CN ? P(O)(OCH3)2)],
382 (100) [M?-C9H8N2S].
(E)-2-[[3-(Benzofuran-2-yl)-1-phenyl-1H-pyrazol-4-
yl]methyleneamino]-4,5,6,7-tetrahydrobenzo[b]-
thiophene-3-carbonitrile (5, C27H20N4OS)
To a mixture of 5 g 3-(benzofuran-2-yl)-1-phenyl-1H-
pyrazole-4-carbaldehyde (1, 17.4 mmol) and 3.1 g 2-
amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile
(3, 17.4 mmol) in 50 cm3 ethanol/dimethylformamide
(DMF) (8:2 v/v) solution was added 0.5 cm3 sulfuric acid.
The reaction mixture was refluxed for 3 h. The product
mixture was concentrated to its half, followed by filtration.
The collected material was crystallized from ethanol to
give the Schiff base 5 as yellow crystals. Yield 6.7 g
(86%); m.p.: 182–184 °C (EtOH); IR (KBr): vꢀ = 2,210
Diethyl [3-(benzofuran-2-yl)-1-phenyl-1H-pyrazol-4-yl]-
(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl-
amino)methylphosphonate (4b, C31H31N4O4PS)
Pale-yellow crystals; yield 637 mg (64%); m.p.: 224–
226 °C (AcOEt); IR (KBr): vꢀ = 3,339 (NH), 2,202 (CN),
1,223 (P = O), 1,029 (P–O–C) cm-1
;
1H NMR
(500.7 MHz, CDCl3): d = 1.12, 1.32 (2dt, JH–H = 6.6,
4JP–H = 4.5 Hz, 2 9 3H, (MeCO)2P), 1.71, 2.44 (2 m, 8H,
3
hexene), 4.23, 4.26 (2dq, JP-H = 10.8 Hz, 2 9 2H
2
(CH2O)2P), 5.43 (dd, JH–H = 8.8, JP–H = 18.4 Hz, 1H,
1
(CN), 1,612 (C=N) cm-1; H NMR (500.7 MHz, CDCl3):
HC–P), 6.36 (br, 1H, NH), 7.23 (d, JP–H = 8.4 Hz, 1H,
C-5-H), 7.27–7.78, 8.26 (m, 10H, Ar–H) ppm; 13C NMR
d = 1.74, 2.46 (2 m, 8H, hexene), 6.32 (s, 1H, HC,
exocyclic), 7.27–7.97 (m, 11H, Ar–H) ppm; 13C NMR
(125.4 MHz, CDCl3): d = 162.2 (HC=N, exocyclic),
159.7, 152.8, 140.1, 137.7, 130.4, 128.7, 126.3, 125.2,
3
(125.4 MHz, CDCl3): d = 129.8 (d, JP–C = 10.6 Hz,
3
C-3), 125.8 (d, JP–C = 8.6 Hz, C-5), 123.6 (d, JP–C
2
=
3
14.2 Hz, C-4), 168.8 (d, JP–C = 10.8 Hz, C-200), 152.8,
123