The behaviour of Bis(diphenylphosphino)alkanes towards different active centres

Article abstract of DOI:10.3184/174751916X14655742365588

Benzophenones (diarylmethanones) are important starting materials in the synthesis and preparation of organic compounds such as heat-resistant resins, various drugs, and natural products.^1-7 1,1′-(Azodicarbonyl)dipiperidine has different pharmacological and biological activities.^8-13 The versatility of isatin (1H-indole-2,3-dione) in synthetic organic chemistry is shown in its biological and pharmacological properties and its extensive use in organic synthesis.¹⁴ Moreover, quinoxaline 1,4-di-N-oxide is a building block that has a broad range of biological applications.¹⁵ Bis(diphenylphosphino)alkanes have been reported as anticancer agents.^16-20The useful applications of these starting materials, coupled with our interest in organophosphorus chemistry,^21-25 encouraged us to synthesise new organophosphorus compounds and to identify the preferred site of attack of these compounds. We sought to obtain the target compounds by reacting bis(diphenylphosphino) alkanes 1a-c with some different organic compounds; namely, benzophenone2, 1,1′-(azodicarbonyl)dipiperidine (ADDP, 3), isatin 4a and 4b, and quinoxaline 1,4-di-N-oxide 5 (Scheme 1).

Full text of DOI:10.3184/174751916X14655742365588

JOURNAL OF CHEMICAL RESEARCH 2016
VOL. 40 JULY, 417–421
RESEARCH PAPER 417
The behaviour of bis(diphenylphosphino)alkanes towards different
active centres
Ewies F. Ewies, Naglaa F. El-Sayed and Leila S. Boulos*
Department of Organometallic and Organometalloid Chemistry, National Research Centre, 33 El-Bohouth St. (former El Tahrir St.), P.O. 12622, Dokki, Giza, Egypt
The reactions of bis(diphenylphosphino)alkanes with benzophenone, bis(piperidinocarbonyl)diazene, isatin, and quinoxaline1,4-di-N-
oxide have been studied and the products characterised by elemental analysis and spectroscopic measurements.
Keywords: bis(diphenylphosphino)alkanes, benzophenone, bis(piperidinocarbonyl)diazene, isatin, quinoxaline 1,4-di-N-oxide, condensation,
carbene
Benzophenones (diarylmethanones) are important starting
materials in the synthesis and preparation of organic compounds
such as heat-resistant resins, various drugs, and natural
products.1–7 1,1′-(Azodicarbonyl)dipiperidine has different
pharmacological and biological activities.8–13 The versatility
of isatin (1H-indole-2,3-dione) in synthetic organic chemistry
is shown in its biological and pharmacological properties and
its extensive use in organic synthesis.14 Moreover, quinoxaline
1,4-di-N-oxide is a building block that has a broad range of
biological applications.15 Bis(diphenylphosphino)alkanes have
been reported as anticancer agents.16–20 The useful applications
of these starting materials, coupled with our interest in
organophosphorus chemistry,21–25 encouraged us to synthesise
new organophosphorus compounds and to identify the preferred
site of attack of these compounds. We sought to obtain the target
compounds by reacting bis(diphenylphosphino) alkanes 1a–c
with some different organic compounds; namely, benzophenone
2, 1,1′-(azodicarbonyl)dipiperidine (ADDP, 3), isatin 4a and 4b,
and quinoxaline 1,4-di-N-oxide 5 (Scheme 1).
en-1-yl]piperidine-1-carbohydrazide (8) as the sole, colourless
product in 85% yield (Scheme 3).
In the same manner, (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
was
obtained when reaction of 1a and 3 was carried out in a molar
ratio of 2:1 in toluene at reflux temperature for 2 h (Scheme 3).
The structures of the new products 8 and 9 were confirmed by IR,
1H,13C, 31P NMR, MS and elemental analysis (Experimental).
It is worth mentioning that when product 8 was refluxed
in toluene for 2 h with 3 in molar ratio 1:1, 9 was formed and
purified as the sole product (identified by using m.p., mixed
m.p. and IR spectrum of an authentic sample) (Scheme 3).
The formation of products 8 and 9 can be explained in
terms of a redox reaction between trivalent phosphorus and
3 to form ethane-1,2-diylbis(diphenylphosphine oxide) and
N’-(piperidine-1-carbonyl)piperidine-1-carbohydrazide.30–36
The next step is a condensation between the active methylene
of pentavalent phosphorus26 and the carbonyl group of N’-
(piperidine-1-carbonyl)piperidine-1-carbohydrazide to give the
final products (Scheme 3).
Results and discussion
Treatment of benzophenone 2 in dry THF at reflux temperature
for 5 h with bisphosphine 1b (molar ratio 1:1) afforded the new
bis(diphenylphosphoranyl)ethane derivative 7 in good yield
together with the known bisphosphine dioxide product 6b.26
The new products were characterised by IR, 1H, 13C, 31P NMR,
MS spectrometry and elemental analysis (cf. Experimental).
These molecules could have been synthesised through a
mechanism involving carbene formation as suggested by Bird
and Wong27 and Markgrf et al.,28 (Scheme 2). The carbene A
could result from nucleophilic attack of the phosphorus lone pair
at carbon or oxygen of the carbonyl group in the benzophenone
When two moles of 1a or 1b and one mole equivalent of 3 in
THF were stirred at room temperature for 24 h, a mixture of
two known products 6a or 6b26 and 2,5-di(piperidin-1-yl)-1,3,4-
oxadiazole 1028,29 were formed, isolated and purified (Scheme
4). The structure of compounds 6a, 6b and 10 were attested by
comparison of their m.p., mixed m.p. and IR spectral data with
authentic samples (cf. Experimental Section).The mechanism
of formation of 10 is presumed to be as was first suggested
by Tusondo et al.,29 for reaction between tert-butyl phosphine
and ADDP. Compound 10 was characterised via elemental
1
microanalyses as well as IR, H, 13C NMR and mass spectral
2
27–29 via a Wittig reaction to form the final product 7.
measurements (cf. Experimental).
The reactions between bis(diphenylphosphino)alkanes 1a,b
In addition, when 4a was refluxed with 1a or 1b in dry THF
in a molar ratio of 1:1, (3Z) -3-(3-oxo-1,3-dihydro-2H-indol-
2-ylidene) -1,3-dihydro-2H-indol-2-one (indirubin, 11)37 was
separated as pink-coloured crystals in a 75% yield together with
and ADDP (3) were also investigated. Treatment of one mole
of 1a with 1 equiv. of 3 in toluene at reflux temperature for 1 h
gave N’-[2,3-bis(diphenylphosphoryl)-1-(piperidin-1-yl)prop-1-
O
O
Ph
P
Ph
O
X
N
N
C
P
N
N
Ph
N
N
n
N
H
O
N
O
NH2
MeO
OMe
O
Ph
1a c
3
4a,b
−
2
5
a, n = 1
b, n = 2
c, n = HC=CH
a, X = O
b, X = N2
Scheme 1
* Correspondent. E-mail: leilagoubran@yahoo.com

418 JOURNAL OF CHEMICAL RESEARCH 2016
MeO
OMe
Ph
P
Ph
P
Ph
Ph
Ph
Ph
O
P
P
O
1b
2
+
Ph
Ph
O
6b
MeO
MeO
A
2
1b
+
OMe
OMe
Ph
P
Ph
P
Ph
Ph
MeO
7
OMe
Scheme 2
O
O
Ph
Ph
H
Ph
P
N
N
reflux, toluene
N
N
Ph
N
N
Ph
Ph
N
N
P
+
H
O
P
O
P
+
Ph
O
Ph
O
redox reaction
(1:1)
3
1b
Ph
P
Ph
O
O
Ph
P
Ph
O
O
Ph
P
Ph
reflux, toluene
Ph
Ph
Ph
P
H
N
O
N
P Ph
3
H
N
N
O
redox reaction
(2:1)
N
H
N
H
N
O
P
N
Ph
8
Ph
9
Scheme 3
O
N
N
O
N
N
Ph
O
stir, THF
(2:1)
Ph
Ph
N
N
N
N
Ph
P
P
O
+
n
P
P
+
n
O
Ph
Ph
Ph
Ph
10
6a,b
1a,b
3
n = 1
n = 2
n = 1
n = 2
Scheme 4
the known 6a or 6b26 respectively. The mechanism of formation
of 11 can be interpreted in terms of formation of a carbene,
followed by dimerisation of this carbene and/or a Wittig
reaction (Scheme 5). This recalls the mechanism of formation
of indirubin via reaction of isatin with triphenylphosphine.37
The reaction of 4b with bisphosphines 1a and 1b was
investigated to study in comparison the results that we obtained
with isatin. When 4b was refluxed with 1a or 1b in molar ratio
2:1; the 3,3’-[methylenebis(diphenylphosphoranylylidene)]
bis(indolin-2-one) (12a); 3,3’-[ethylenebis(diphenylphospho

JOURNAL OF CHEMICAL RESEARCH 2016 419
H
N
O
O
P
Ph
P
Ph
H
Ph
P
Ph
O
P
N
+
reflux
+
Ph
n
Ph
O
n
N
H
O
O
Ph
Ph
6a,b
4a
11
1a,b
a, n = 1
b, n = 2
a, n = 1
b, n = 2
Scheme 5
Ph
Ph
n
Ph
Ph
Ph
Ph
P
N2
O
P
- N2
P
+
Ph
P
n
N
H
reflux
N
H
O
N
H
O
Ph
1a-c
12a-c
a, n = 1
b, n = 2
4b
a, n = 1
b, n = 2
c, n = HC=CH
c, n = HC=CH
Scheme 6
O
O
O
P
Ph
Ph
P
Ph
Ph
Ph
P
Ph
P
N
N
C
O
P
N
N
N
C
reflux
Ph
N
+
Ph
+
C
N
O
NH2
NH
P
NH2
Ph
Ph
Ph
Ph
O
N
NH2
C
1b
5
D
O
P
Ph
Ph
O
P
Ph
N
Ph
C
NH2
N
NH2
13
Scheme 7
ranylylidene)]bis(indolin-2-one) (12b); and/or 3,3’-[ethene-
1,2-diylbis(diphenylphosphoranylylidene)]bis(indolin-2-
one) (12c) were obtained (Scheme 6). The structures of the
phosphoranylidene derivatives 12a–c were confirmed on the
A mechanism for the formation of 13 can be proposed in
terms of deoxygenation of 5 through reduction by the trivalent
phosphorus compound38,39 to obtain 3-aminoquinoxaline-2-
carbonitrile and 6b. The active methylene of 6b could then react
with 3-aminoquinoxaline-2-carbonitrile (C) to give the final
product 13 as shown in Scheme 7 via nucleophilic attack of an
active methylene group of 6 on the carbonitrile group and the
intermediate D.
1
basis of IR, H, 13C, 31P NMR, MS and elemental analysis (cf.
Experimental).
The mechanism of formation of 12a–c can be summarised
in terms of initial evolution of dinitrogen from 4b at reflux
temperature, followed by formation of a carbene intermediate and
nucleophilic attack of trivalent phosphorus via a Wittig reaction
mechanism to form the final products 12a–c27–29,37(Scheme 6).
Finally, this study was extended to investigate the behaviour
of 1,2-bis(diphenylphosphino)ethane 1b towards quinoxaline
1,4-di-N-oxide (5) (Scheme 7). When 5 reacted with 1b in dry
THF at reflux temperature for 2 h in a molar ratio of 1:1, the
deep red crystalline [3-amino-3-(3-aminoquinoxalin-2-yl)prop-
2-ene-1,2-diyl]bis(diphenylphosphine oxide) (13) was isolated in
85% yield. The structure of the new compound 13 was confirmed
by IR, NMR, MS and elemental analysis. (Scheme 7; cf.
Experimental).
Conclusion
This study reports simple routes for the synthesis of some
organophosphorus derivatives using bis(diphenylphosphino)
alkanes as a starting organophosphorus materials. Whereas
bisphosphine 1b reacted with benzophenone 2 to give the new
bis(diphenylphosphoranyl)ethane derivative 7 and bisphosphine
dioxide 6b, 8 and 9 were obtained from the reaction of 1b with
3 in molar ratio 1:1 and 2:1, respectively, in refluxing toluene.
When two moles of 1a or 1b and 1 equiv. of 3 in THF were stirred
at room temperature for 24 h, products 6a and 6b respectively
and 10 resulted. The reaction of bisphosphines 1a and 1b with

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.

JOURNAL OF CHEMICAL RESEARCH 2016 421
6
7
8
C.M. Harris, J.S. Roberson and T.M. Harris, J. Am. Chem. Soc., 1976, 98,
5380.
3,3’-[Ethane-1,2-diylbis (diphenylphosphoranylylidene)]
bis(indolin-2-one) (12b): Eluent: petroleum ether/ethyl acetate (85/15,
v/v); brown crystals; yield 75%; m.p. 127–128 °C; IR νmax/cm–1 (KBr):
M. Kaji, Jpn Kokai Tokkyo Koho, JP 09,68,802,[97 68,802] 1997; Chem.
Abstr., 1997, 126, 310450m.
1
1654 (amide C=O), 1640 (P=C), 1432 (P–Ph); H NMR (500 MHz,
CDCl3): δ 1.71–1.81 (m, JHH = 11.9 Hz, 2JPH = 25.2 Hz, 3JPH = 11.0 Hz,
M. Tisler and B. Stanovik, Pyridazines and their benzo derivatives in
Comprehensive Heterocyclic Chemistry, eds. A.R. Katritzky, C.W. Rees,
A.J. Boulton and A. McKillop, Pergamon, Oxford, 1984, vol. 3, pp. 1–56.
H. Maher, C.M. Liu, N.J. Pelleroni, T. Smallheer, L. Todaso, T.H. Williams
and J.F. Blount, J. Antibiot., 1986, 39, 17.
4H, CH2–CH2), 6.73–7.24 (m, 28H, ArH), 8.76 (s, 2H, NH); 13C NMR
(125 MHz, CDCl3): δ 53.3 (d, JPC = 135.6 Hz, CH2–CH2), 77.5 (d, JPC
=
130.0 Hz, 2JPC = 40.1 Hz, C=P), 101.2 (d, JPC = 130.0 Hz, P–C), 112.1
(ArCH), 122.9 (ArC), 126.7 (ArC), 128.8 (ArC), 129.0 (ArC), 132.4
(ArC), 133.8 (ArC), 141.8 (ArC), 172.5 (C=O); 31P NMR (CDCl3): δ
19.72; MS (EI): m/z (%) = 660 ([M]+, 5); Anal. calcd for C42H34N2O2P2
(660.68): C, 76.35; H, 5.19; N, 4.24; P, 9.38; found: C, 76.05; H, 5.42;
N, 4.34; P, 9.53%.
9
10 A. Kleemann and J. Engel, Pharmazeutische Wirkstoffe: Synthesen.
Patente. Anwendungen, 2nd ed; Thieme–Verlag, Stuttgart, Germany, 1982.
11 H. Horiomoto, N. Shimado, H. Naganawa, T. Takita and H. Umezawa, J.
Antibiot., 1982, 35, 378.
12 J. Easmon, G. Heinisch, G. Purstinger, T. Langer and J.K. Osterreicher, J.
Med. Chem., 1997, 40, 4420.
3,3’-[Ethene-1,2-diylbis (diphenylphosphoranylylidene)]
bis(indolin-2-one) (12c): Eluent: petroleum ether/ethyl acetate (85/15,
v/v); yellow crystals; yield 75%; m.p. 159–161 °C; IR νmax/cm–1 (KBr):
13 M.A. Avery, S. Mehrotra, J.D. Bonk, J.A. Vorman, D.K. Goins and R.
Miller, J. Med. Chem., 1996, 39, 2900.
1
1654 (amide C=O), 1645 (P=C), 1435 (P–Ph); H NMR (500 MHz,
CDCl3): δ 1.90 (s, 2H, NH), 6.68–7.67 (m, 28H, ArH), 6.91 (2 × dt, JHH
14 V. Glover, S.K. Bhattacharya and M. Sandler, Indian J. Exp. Biol., 1991,
29, 1.
= 10.8, 6.5 Hz, 2JPH = 25.2 Hz, 3JPH = 11.0 Hz, 2H, CH=CH); 13C NMR
2
(125 MHz, CDCl3): δ 87.5 (d, JPC = 130.0 Hz, JPC = 40.1 Hz, C=P),
15 A. Carta, P. Corona and M. Loriga, Curr. Med. Chem., 2005, 12, 2559.
16 S.J. Berners-Price, C.K. Mirabelli, R.K. Johnson, M.R. Mattern, F.L.
McCabe, L.F. Faucette, C. MeiSung, S.-M. Mong, P.J. Sadler and S.T.
Crooke, Cancer Res., 1986, 46, 5486.
103.2 (d, JPC = 130.0 Hz, P–C), 111.1 (ArCH), 121.2 (ArC), 122.5
(ArC), 125.2 (ArC), 128.5 (ArC), 131.6 (ArC), 133.8 (ArC), 140.5
(ArC), 153.3 (d, JPC = 135.6 Hz, CH=CH), 170.5 (C=O); 31P NMR
(CDCl3): δ 22.82; MS (EI): m/z (%) = 658 ([M]+, 15); Anal. calcd for
C42H32N2O2P2 (658.66): C, 76.59; H, 4.90; N, 4.25; P, 9.41; found: C,
76.60; H, 4.95; N, 4.03; P, 9.35%.
17 C.K. Mirabelli, R.K. Johnson, D.T. Hill, L.F. Faucette, G.R. Girard, G.Y.
Keu, C.-M. Sung and S.T. Crooke, J. Med. Chem., 1986, 29, 218.
18 A. Lorber, T.M. Simon, J. Leeb, A. Peter and S.A. Wilcox, J. Rheumatol.,
1979, 6, 81.
Reaction of 1,2-Bis(diphenylphosphino)alkanes (1a and 1b) with
quinoxaline 1,4-di-N-oxide (5)
19 A.E. Finkelstein, O.R. Burrone and D.T.A. Walz Misher, J. Rheumatol.,
1977, 4, 245.
Compound 5 (0.29 g, 1 mmol) and 1b (0.39 g, 1 mmol) 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 afford 13.
[3-Amino-3- (3-aminoquinoxalin-2-yl)prop-2-ene-1,2-diyl]
bis(diphenylphosphine oxide) (13): Eluent: petroleum ether/ethyl
acetate (85/15, v/v); deep red crystals; yield 85%; m.p. 206–208 °C; IR
20 T.M. Simon, D.H. Kunishima, G.J. Vilbert and A. Lorber, Cancer Res.,
1981, 41, 94.
21 E.F. Ewies, M.F. El-Shehry and L.S. Boulos, Inter. J. Chem. Tech. Res.,
2015, 7, 2506.
22 E.F. Ewies, N.F. El-Sayed, L.S. Boulos and A.M. Soliman, J. Chem. Res.,
2014, 38, 325.
23 L.S. Boulos, E.F. Ewies, A.F.M. Fahmy and M.E. Mohram, Phosphorus
Sulfur Silicon Relat. Elem., 2013, 188, 790.
ν
max/cm–1 (KBr): 3420 (NH2), 1615 (C=C), 1549 (C=N), 1435 (P–Ph),
1
1230 (P=O); H NMR (500 MHz, CDCl3): δ 1.75 (s, 2H, NH2), 2.26
24 L.S. Boulos, E.F. Ewies, N.M. Ibrahim and M.E. Mohram, Phosphorus
Sulfur and Silicon Relat. Elem., 2014, 189, 1706.
(d, JHH = 11.9 Hz, 2JPH = 25.1 Hz, 3JPH = 11.0 Hz, 2H, CH2), 7.01–7.68
(m, J = 7.4, 1.7 Hz, 24H, ArH); 13C NMR (125 MHz, CDCl3): δ 27.5 (d,
JPC = 130.0 Hz, 2JPC = 40.1 Hz, CH2), 105.5, 159.2 (C=C), 134.1, 15.1
(cyclic C=N), 126.1 (ArCH), 127.2 (ArC), 128.5 (ArC), 128.2 (ArC),
129.5 (ArC), 131.6 (ArC), 132.8 (ArC), 141.5 (ArC); 31P NMR(CDCl3):
δ 32.82, 31.11; MS (EI): m/z (%) = 600 ([M]+, 15). Anal. calcd for
C35H30N4O2P2 (600.59): C, 69.99; H, 5.03; N, 9.33; P, 10.31; found: C,
70.10; H, 5.15; N, 9.20; P, 10.25%.
25 E.F. Ewies, N.F. El-Sayed, M. El-Hussieny, M.M. Ali and A.E. Mahmoud,
Phosphorus Sulfur Silicon Relat. Elem., 2016; http://www.tandfonline.
com/doi/abs/10.1080/10426507.2015.1119828#.Vuc1F1SLTIU,
Doi:
10.1080/10426507.2015.1119828.
26 L.S. Boulos, E.F. Ewies, A.F.M. Fahmy and M.E. Mohram, Phosphorus
Sulfur Silicon Relat. Elem., 2013, 188, 726.
27 T. Tsunoda, Y. Yamamiya and S. Ito, Tetrahedron Lett., 1993, 34, 1639.
28 L.S. Boulos, H.A. Abdel-Malek, N.F. El-Sayed and M.E. Mohram,
Phosphorus Sulfur Silicon Relat. Elem., 2012, 187, 225.
29 T. Tsunoda, J. Otsuka, Y. Yamamiya and S. Ito, Chem. Lett., 1994, 23, 539.
30 Kh. Y. Riysalu, V.V. Vasil’ev and B.I. Ionin, Zh. Obsch. Khim., 1985, 55,
2237.
The authors thank the National Research Centre for the
financial support (Project No: S10050002) and for the facilities
provided.
Received 26 March 2016; accepted 28 April 2016
Paper 1604010 doi: 10.3184/174751916X14655742365588
Published online: 16 June 2016
31 L.S. Boulos and A.A. El-Kateb, Chem. Ind., 1983, 864.
32 G.E. Lathourakis and K.E. Litinas, J. Chem. Soc., Perkin Trans. 1, 1996,
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33 J.H. Markgrf, C.I. Heller and N.L. Avery, J. Org. Chem., 1970, 35, 1588.
34 C.W. Bird and D.Y. Wong, Chem. Commun., 1969, 932.
35 O. Mitsunobu and M. Yamada, Bull. Chem. Soc., Jpn., 1967, 40, 2380.
36 O. Mitsunobu and M. Eguchi, Bull. Chem. Soc., Jpn., 1971, 44, 3427.
37 O. Mitsunobu, Synthesis, 1981, 1.
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