420 JOURNAL OF CHEMICAL RESEARCH 2016
N’-[2,3-bis(diphenylphosphoryl)-1-(piperidin-1-yl)prop-1-en-1-
yl]piperidine-1-carbohydrazide (8): Eluent: petroleum ether/ethyl
acetate (90/10, v/v); colourless crystals; yield 85%; m.p. 171–172 °C;
IR νmax/cm–1 (KBr): 3320 (NH), 1640 (C=O), 1635 (P=C), 1437
isatin yields 6a or 6b respectively, together with indirubin (11).
Moreover, 4b reacts with bisphosphines 1a–c in refluxing
toluene in molar ratio 2:1 to give 12a–c respectively. On the other
hand, when 5 was refluxed with 1b in molar ratio of 1:1, 13 was
produced.
1
(P–Ph), 1225 (P=O); H NMR (500 MHz, CDCl3): δ 1.57, 1.58, 1.59,
1.70, 2.16, 2.27 (m, 12H, 6 × CH2 pip.), 2.51, 2.52 (dd, JHH = 6.8 Hz,
2JPH = 25.3 Hz, 3JPH = 11.0 Hz, 2H, CH2–P), 3.38 (m, 8H, 4 × CH2, pip.),
6.51 (d, 2H, 2NH), 7.26–7.70 (m, 20H, ArH); 13C NMR (125 MHz,
Experimental
All chemicals were supplied by either Fluka or Aldrich chemical
companies and were used without further purification. Melting points
were determined in open glass capillaries using an Electrothermal IA
9000 series digital melting point apparatus (Electrothermal, Essex,
UK) and are uncorrected. The IR spectra were measured in KBr pellets
with a Perkin-Elmer Infracord Spectrophotometer model 157(Grating).
1H NMR (500 MHz), 13C{1H} NMR (125 MHz) and 31P{1H} NMR
(202.48 MHz) spectra were recorded at room temperature on a JEOL-
500 MHz spectrometer as solutions in deuterated chloroform (CDCl3)/ or
dimethyl sulfoxide (DMSO). All chemical shifts are quoted in δ relative
to the trace resonance of protonated chloroform (δ 7.25 ppm), CDCl3 (δ
77.0 ppm), protonated dimethyl sulfoxide (δ 2.50 ppm), DMSO-d6 (δ
39.51 ppm) and external 85% aqueous H3PO4 (δ 0.0 ppm). Mass spectra
(EI) were measured at 70 eV on a Shimada GCS-OP 1000 Ex spectrometer
provided with a data system. Elemental analyses were performed using an
Elmenter Varu EL Germany instrument. The reported yields are based
upon pure materials isolated by column chromatography. Solvents were
dried/purified according to conventional procedures.
CDCl3): δ 24.4 (s, 4 × CH2, Pip.), 25.4 (s, 4 × CH2, Pip.), 26.1 (d, JPC
=
=
130.0 Hz, CH2), 44.9 (s, 2 × CH2, Pip.), 67.1 (d, JPC = 130.0 Hz, 2JPC
40.1 Hz, =C–P), 128.8 (ArC), 128.9 (ArC), 130.7 (ArC), 130.8 (ArC),
132.0 (ArC), 134.4 (ArC), 135.8 (ArC), 136.8 (ArC), 158.1 (C=O),
161.5 (N=C); 31P NMR (CDCl3): δ 33.26, 33.48; MS (EI): m/z (%)
= 666 ([M]+, 5). Anal. calcd for C38H44N4O3P2 (666.73): C, 68.45; H,
6.65; N, 8.40; P, 9.29; found: C, 68.56; H, 6.42; N, 8.55; P, 9.02%.
(3-{2-[2,3-Bis(diphenylphosphoryl)-1-(piperidin-1-yl)prop-
1-en-1-yl]hydrazinyl}-3- (piperidin-1-yl)prop-2-ene-1,2-diyl)
bis(diphenylphosphine oxide) (9): Eluent: petroleum ether/ethyl
acetate (80/20, v/v); colourless crystals; yield 35%; m.p. 227–230 °C;
IRνmax/cm–1 (KBr): 3324 (NH), 1630 (P=C), 1432 (P–Ph), 1223 (P=O);
1H NMR (500 MHz, CDCl3): δ 0.88, 0.91, 0.93, 1.25 (m, 12H, 6 × CH2
pip.), 1.29, 1.34 (dd, JHH = 6.8 Hz, 2JPH = 25.3 Hz, 3JPH = 11.0 Hz, 4H,
2 × CH2–P), 2.23, 2.52 (m, 8H, 4 × CH2, pip.), 4.38 (d, 2H, 2 × NH),
7.25–7.69 (m, 40H, ArH); 13C NMR (125 MHz, CDCl3): δ 24.3 (s, 4
× CH2, Pip.), 25.2 (s, 4 × CH2, Pip.), 26.2, 26.4 (d, JPC = 130.0 Hz, 2 ×
CH2), 45.5 (s, 2 × CH2, Pip.), 80.0 (d, JPC = 130.0 Hz, 2JPC = 40.1 Hz,
=C–P), 126.8 (ArC), 126.9 (ArC), 128.7 (ArC), 130.8 (ArC), 132.0
(ArC), 134.4 (ArC), 135.8 (ArC), 136.8 (ArC), 171.5 (N=C); 31P NMR
(CDCl3): δ 33.13; MS (FAB+): m/z (%) = 1078 ([M]+, 5). Anal. calcd
for C64H66N4O4P4 (1079.13): C, 71.23; H, 6.16; N, 5.19; P, 11.48; found:
C, 71.42; H, 6.20; N, 5.32; P, 11.23%.
Synthesis of 1,2-Bis{[bis(4-methoxyphenyl)methylene]diphenylphos-
phoranyl}ethane (7)
Compounds 2 (0.24 g, 1 mmol) and 1b (0.39 g, 1 mmol) were refluxed
in dry THF (30 mL) at ambient temperature for 5 h. The course of
the reaction was monitored by TLC. The volatile materials were
evaporated under reduced pressure. The residue was chromatographed
on silica gel column to give two products; 7 and the known 6b.26
2,5-Di(piperidin-1-yl)-1,3,4-oxadiazole (10): Eluent: petroleum ether/
ethyl acetate (80/20, v/v); colourless crystals; yield 65%; m.p. 75–76 °C
(lit. 75 °C).28,29 1H NMR (500 MHz, δ ppm, CDCl3): 1.62 (m, 12H, CH2-
pip.), 3.30 (m, 8H, CH2-pip.), MS (EI): m/z (%) = 236 ([M]+, 80).
Ethane-1,2-diylbis(diphenylphosphene)dioxide
(6b):
Eluent:
petroleum ether/acetone (50/50, v/v); colourless crystals; yield 25%;
m.p. 276–277 °C.26
Reaction of 1,2-Bis(diphenylphosphino)alkane (1a or 1b) with Isatin
(4a)
1,2-Bis{[bis(4-methoxyphenyl)methylene]diphenylphosphoranyl}
ethane (7): Eluent: petroleum ether/acetone (90/10, v/v); colourless
crystals; yield 45%, m.p. 185–187 °C; IR νmax/cm–1 (KBr): 1630
Isatin (4a) (0.29 g, 2 mmol) and (1a or 1b) were refluxed in dry THF
(30 mL) for 2 h. The course of the reaction was monitored by TLC. The
volatile materials were evaporated under reduced pressure. The residue
was chromatographed on a silica gel column to give the products
Indirubin, 1137 and 6a or 6b26 respectively.
(3Z)-3-(3-oxo-1,3-dihydro-2H-indol-2-ylidene)-1,3-dihydro-2H-
indol-2-one (Indirubin, 11): Eluent: petroleum ether/ethyl acetate
(80/20, v/v); pink crystals; yield 75%.37 M.p. 350 °C (lit.28,29 m.p
350 °C). 1H NMR (500 MHz, DMSO): δ = 6.87–7.01 (m, 8H, H arom.),
9.01, 10.08 (2s, 2 NH exchangeable with D2O) ppm. MS (EI): m/z (%)
= 262 (75) [M]+.
1
(P=C), 1437 (P–Ph); H NMR (500 MHz, CDCl3): δ 2.92–2.99 (ddd,
2
3
JHH = 6.8 Hz, JPH = 25.3 Hz, JPH = 11.0 Hz, 4H, CH2–CH2), 3.38 (s,
12H, OCH3), 7.26–7.74 (m, 36H, ArH); 13C NMR (125 MHz, CDCl3):
δ 40.1 (d, JPC = 130.0 Hz, CH2–CH2), 50.6 (4 × OCH3), 67.0 (d,
JPC = 130.0 Hz, 2JPC = 40.1 Hz, C=P), 128.6 (ArCH), 128.9 (ArC), 130.7
(ArC), 130.8 (ArC), 132.0 (ArC), 134.4 (ArC), 135.8 (ArC), 136.8
(ArC), 159.5 (C–O); 31P NMR (CDCl3): δ 33.24 ppm; MS (FAB+): m/z
(%) = 850 ([M]+, 10); Anal. calcd for C56H52O4P2 (850.96): C, 79.04; H,
6.16; P, 7.28; found: C, 79.21; H, 6.20; P, 7.15%.
Reactions of 1,2-Bis(diphenylphosphino)alkanes (1a and 1b) with
1,1’(azodicarbonyl)dipiperidine (ADDP, 3); general procedure
Reaction of 1,2-Bis(diphenylphosphino)alkane (1a–c) with
Diazoisatin (4b); general procedure
•
After 1b (0.39 g, 1 mmol) and 3 (0.25 g, 1 mmol) were refluxed in
dry toluene (30 mL) for 1 h the sole product, N’-(2,3-bis(diphenyl-
phosphoryl)-1-(piperidin-1-yl)prop-1-en-1-yl)piperidine-1-
carbohydrazide (8), was separated.
Diazoisatin (4b) (0.31 g, 2 mmol) and 1a–c (1 mmol) were refluxed in
dry THF (30 mL) for 1–4 h. The course of the reaction was monitored
by TLC. The volatile materials were evaporated under reduced
pressure. The residue was chromatographed on a silica gel column to
give the products 12a–c respectively.
•
After 1b (0.78 g, 2 mmol) and 3 (0.25 g, 1 mmol) were refluxed in
dry toluene (30 mL) for 2 h, (3-{2-[2,3-Bis(diphenyl-phosphoryl)-
1-(piperidin-1-yl)prop-1-en-1-yl]hydrazinyl}3-(piperidin-1-
yl)-prop-2-ene-1,2-diyl)bis(diphenylphosphine oxide) (9) was
separated.
3,3’-[Methylenebis(diphenylphosphoranylylidene)]bis(indolin-2-
one) (12a): Eluent: petroleum ether/ethyl acetate (80/20, v/v); yellow
crystals; yield 65%; m.p. 185–187 °C; IR νmax/cm–1 (KBr): 1655 (amide
1
•
•
After 8 (0.66 g, 1 mmol) and 3 (0.25 g, 1 mmol) were refluxed in
dry toluene (30 mL) for 2 h, compound 9 was separated.
After 1a or 1b (2 mmol) and 3 (0.25 g, 1 mmol) were stirred in dry
THF (30 mL) for 24 h, compounds 10, 6a and 6b were separated
respectively.
C=O), 1632 (P=C), 1437 (P–Ph); H NMR (500 MHz, CDCl3): δ 2.16
2
3
(t, JHH = 11.9 Hz, JPH = 24.9 Hz, JPH = 11.0 Hz, 2H, CH2), 6.78–7.24
(m, 28H, ArH), 8.56 (s, 2H, NH); 13C NMR (125 MHz, CDCl3): δ 29.5
(t, JPC = 135.6 Hz, CH2), 67.5 (d, JPC = 130.0 Hz, 2JPC = 40.1 Hz, C=P),
95.2 (d, JPC = 130.0 Hz, P–C), 113.1 (ArCH), 121.9 (ArC), 125.7 (ArC),
127.8 (ArC), 128.0 (ArC), 131.4 (ArC), 132.8 (ArC), 140.8 (ArC), 171.5
(C=O); 31P NMR (CDCl3): δ 31.14; MS (EI): m/z (%) = 646 ([M]+, 25);
Anal. calcd for C41H32N2O2P2 (646.65): C, 76.15; H, 4.99; N, 4.33; P,
9.58; found: C, 76.02; H, 5.05; N, 4.22; P, 9.75%.
The course of each reaction was monitored by TLC. The volatile
materials were evaporated under reduced pressure. The residues were
chromatographed on a silica gel column to give the product.