Chemistry of phosphorus ylides: Part 41 synthesis of antimicrobial agents from the reaction of aminoantipyrine, coumarin- And quinoline-carbaldehyde with phosphacumulene and phosphaallene ylides

Article abstract of DOI:10.3184/174751914X14179446629855

Pyrrolo-pyrazoles were obtained from the reaction between phosphacumulenes and aminoantipyrine, while the reaction with the phosphaallene (hexaphenylcarbodiphosphorane ylide) afforded the azaphosphole and pyrazolo-phosphanylidene. The aminocoumarin carbal

Full text of DOI:10.3184/174751914X14179446629855

754 RESEARCH PAPER
VOL. 38 DECEMBER, 754–761
JOURNAL OF CHEMICAL RESEARCH 2014
Chemistry of phosphorus ylides: Part 41
Synthesis of antimicrobial agents from the reaction of aminoantipyrine,
coumarin- and quinoline-carbaldehyde with phosphacumulene and
phosphaallene ylides
Soher Said Maigalia, Mansoura Ali Abd-El-Maksouda, Marwa El-Hussienya,
Fouad Mohamed Solimana*, Mohamed Soliman Abdel-Azizb and El-Sayed Mohamed Shalabyc
aDepartment of Organometallic and Organometalloid Chemistry, National Research Centre, Dokki, Cairo, Egypt
bMicrobial Chemistry Department, National Research Centre, Dokki, Cairo, Egypt
cX‑Ray Crystallography Lab., Physics Division, National Research Centre, Dokki, Cairo, Egypt
Pyrrolo-pyrazoles were obtained from the reaction between phosphacumulenes and aminoantipyrine, while the reaction with
the phosphaallene (hexaphenylcarbodiphosphorane ylide) afforded the azaphosphole and pyrazolo-phosphanylidene. The
aminocoumarin carbaldehyde gave the chromeno-phosphanylidene and the chromeno-pyridinone, when it was allowed to
react with phosphacumulenes. The reaction of chloroquinoline carbaldehyde with the phosphacumulenes, gave chloroquinoline
phosphanylidenecyclobutane, while the reaction with phosphaallene resulted in the formation of oxaphosphetane,
phosphanylidene ethenyl- and oxaphosphetyl-quinoline. The structure of cyclobutanedione was confirmed by X-ray
crystallography. The antimicrobial activity of the new compounds is also reported.
Keywords: phosphacumulene, phosphaallene, antipyrine, coumarine, quinoline, pyrrolo-pyrazol, azaphosphole, chromeno-
pyridinone, phosphanylidene, oxaphosphetane
4-Aminoantipyrine is an important derivative of the
5-pyrazolone class which has number of biological
activities.1 It is used in the management of pain and
inflammation,2,3 antimicrobial,4 antiviral,5
and has
oxide. The key step in this transformation involves protonation
and generation of the intermediate 1:1 adduct (3a).
Intramolecular Wittig reaction of 3a, leads to the formation of the
pyrrolo-pyrazol 4a. The proposed structure of 4a was supported
a
1
by its spectroscopic data, such as IR, H NMR, 13C NMR, and
antioxidant,6,7 anticancer and antipyretic activities.9 On the
other hand, coumarins are plant-derived natural products
known for their pharmacological properties such as anti-
inflammatory, anticoagulant, antimicrobial, antiviral,
anticancer, antihypertensive, antitubercular, anticonvulsant,
8
MS spectra. The reaction of compound 1 with (2-oxovinylidene)
triphenylphosphorane (2b) was performed in dry boiling
toluene.
2,3-Dimethyl-1-phenylpyrrolo[3,2-c]pyrazol-5(4H)-
one-1,2-dihydro (4b) together with triphenylphosphane oxide
were produced.
antiadipogenic,
antihyperglycemic,
antioxidant
and
neuroprotective activities.10–12 Interesting pharmacological
properties have also been associated with 2-chloroquinoline-
3-carbaldehyde and their derivatives.13,14 These compounds
The phosphaallene ylide hexaphenylcarbodiphosphorane
(5) can be illustrated in two major resonance forms. The first
resonance form 5A, is similar to the familiar Wittig reagents
and 5B implies a molecule with heteroallene chemistry. This
bisylide was used by Bestmann32–34 in organic synthesis, in
particular products which are often difficult to prepare by other
methods. Moreover, it has attracted recent interest because
of its importance as a C-donor ligand in organometallic
chemistry and various transition metal complexes.35–37
When the pyrazolone 1 was reacted with the phosphorane
5 in boiling THF, the azaphosphole 7 and the phosphorane 8
along with triphenylphosphane oxide and triphenylphosphane
were isolated. Intramolecular cyclisation of the intermediate
adduct 6, afforded 2,3-dimethyl-1,5,5,5-tetraphenyl-1,2,4,5-
tetrahydropyrazolo[3,4-d][1,2]azaphosphole (7) together with
triphenylphosphane oxide. Triphenylphosphane is a good leaving
group, so degradation of the intermediate adduct 6, resulted
in the formation of 1,5-dimethyl-2-phenyl-4-{[(triphenyl-λ5-
phosphanylidene)methyl]amino}1,2-dihydro-3H-pyrazol-3-one
(8) along with triphenylphosphane. The most important features
in the spectroscopic data of the azaphosphole 7, is that it showed
a signal at δ 23.55 in its 31P NMR spectrum38 and the presence of
an ion peak at m/z 461 (%) [(M)+, 8] in its mass spectrum. On the
other hand, the mass spectrum of the pyrazolone 8 indicated the
presence of an ion peak at m/z 477 (%) [(M)+, 4] and a signal was
observed at δ=31.03 ppm in its 31P NMR spectrum (Scheme 1).
When 4-amino-2-oxo-2H-chromene-3-carbaldehyde (9)
was treated with the phosphacumulene 2a in THF at room
temperature, two products were isolated, namely, N-(3-
have
shown
antimicrobial,13–15
antimalarial,16,17anti-
inflammatory,18–21 antitumour,22,23and antiparasitic activities.24
As pharmacological agents, certain phosphonium compounds
have demonstrated anti-microbial activity against Gram-
negative and Gram-positive bacteria.25
Results and discussion
Ourcontinuinginterestinthereactionsofactivephosphacumulene
and phosphaallene (hexaphenylcarbodiphosphorane ylide)
ylides to prepare carbocyclic and heterocyclic phosphorus
26–31
compounds of biological interest,
led us to investigate
and compare the behaviour of these phosphonium ylides
with 4-aminoantipyrine (4-amino-1,5-dimethyl-2-phenyl-1,2-
dihydropyrazol-3-one-) (1), 4-amino-2-oxo-2H-chromene-3-
carbaldehyde (9), and 2-chloroquinoline-3-carbaldehyde (12)
to synthesise new bioactive phosphorus compounds and their
evaluation as antimicrobial agents.
The reaction of 4-amino-1,5-dimethyl-2-phenyl-1,2-
dihydropyrazol-3-one (1) with triphenyl (N-phenyl-
iminovinylidene)phosphorane (2a) in THF at room temperature
gave
N-(2,3-dimethyl-1-phenyl-1,2-dihydropyrrolo[3,2-c]
pyrazol-5(4H)-ylidene)-aniline (4a) and triphenylphosphane
* Correspondent. E-mail: solimanfma2@yahoo.com
#Part 40: ref. 26
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H
H3C
H3C
N
X
H
H
H3C
Ph3P
C C X
N
+
2a, X= N-Ph
b, X= O
X
Ph3P=O
N
C
O
Ph3P
N
N
H3C
N
Ph
Ph
3a, X= N-Ph
b, X= O
4a, X= N-Ph
b, X= O
H3C
H3C
NH2
O
N
N
Ph
1
H
H3C
N
H
PPh3
C
H3C
Ph3P
5A
C
PPh3
N
N
PPh3
Ph3P=O
O
H3C
N
H
N
PPh3
Ph3P=C=PPh3
5B
H3C
N
Ph
Ph
6
7
H
H3C
H3C
N
PPh3
C
+
Ph3P
N
H
O
N
Ph
8
Scheme 1
formyl-2-oxo-2H-chromen-4-yl)-N′-phenyl-2-(triphenyl-λ5-
phosphanylidene)ethanimidamide (10a), 2-(phenylimino)
Treatment of 2-chloroquinoline-3-carbaldehyde (12) with
the iminophosphorane 2a, furnished two compounds namely,
(N-(4-chloro-1H-cyclopenta[c]quinolin-1-ylidene)aniline (14),
N,N′-[(2-[(2-chloroquinolin-3-yl)methylidene]-4-(triphenyl-
λ5-phosphanylidene)cyclobutane-1,3-diylidene]dianiline (15a)
along with triphenylphosphane oxide. The first step in this
reaction involves the formation of the oxaphosphetane which
occurs by [2+2]-cycloaddition of the carbonyl group in 12 to
ylidic C–P bond of 2a. Expulsion of triphenylphosphane oxide
from the oxaphosphetane affords the unstable ketene 13 which
cyclises to give cyclopentaquinolineaniline 14 or followed by
[2+2]-cycloaddition to a second molecule of 2a, giving the four-
membered ring phosphanylidene-cyclobutane 15a. Structure of
the phosphanylidene cyclobutane 15a was also confirmed on the
1,2-dihydrochromeno[4,3-b]pyridin-5-one (11a) along with
triphenylphosphane oxide. This transformation involves the
generation of the phosphanylidene 10a from the reaction of
the phosphacumulene 2a with the amino group of compound
9 rather than the carbonyl groups. The phosphonium ylide
10a undergoes intramolecular Wittig reaction to give the
pyridinone 11a. When the aminochromene 9 was treated with
equimolar amounts of the phosphorane 2b in toluene at the
reflux temperature, two products, namely, N-(3-formyl-2-oxo-
2H-chromen-4-yl)-2-(triphenyl-λ5-phosphanylidene)acetamide
(10b), 1H-chromeno[4,3-b]pyridine-2,5-dione (11b) were
obtained, together with triphenylphosphane oxide (Scheme 2).
X
X
NH2
PPh3
H
CHO
HN
CH
CH
HN
O
C
H
O
+
-Ph3P=O
Ph3P
C
C
X
C
2a, X= N-Ph
b, X= O
O
O
O
O
O
11a, X= N-Ph
b, X= O
9
10a, X= N-Ph
b, X= O
Scheme 2
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756 JOURNAL OF CHEMICAL RESEARCH 2014
basis of its elemental analysis and spectral data. The 31P NMR
shift of 15a was at δ 15.96 ppm which fits with a phosphorane
on 4-membered ring.39 On the other hand, the reaction of
compound 12 with (2-oxovinylidene)-triphenylphosphorane
(2b) afforded only one product, 2-[(2-chloroquinolin-3-yl)-
methylidene]-4-(triphenyl-λ5-phosphanylidene)cyclobutane-
1,3-dione (15b) together with triphenylphosphane oxide.
Moreover, the proposed structure of 15b was further
unequivocally confirmed by X-ray crystallography (Fig. 1).
In addition, the behaviour of hexaphenylcarbodiphosphorane
(5) towards the quinoline carbaldehyde 12 was studied
to determine the site of attack. It was found that the
phosphorane 5 gave 2-chloro-3-[2,2,2-triphenyl-3-(triphenyl-
λ5-phosphanylidene)-1,2 λ5-oxaphosphetan-4-yl]quinoline (16)
and 2-chloro-3-[2-(triphenyl-λ5-phosphanylidene)ethenyl]
quinoline (17) along with triphenylphosphane oxide when
the reaction was performed in boiling toluene for 2 h. The
reaction of the phosphorane 5 and the carbaldehyde 12 in THF
at room temperature, afforded compounds 16 and 2-chloro-
3-(2,2,2-triphenyl-2H-1,2 λ5-oxaphosphet-4-yl)quinoline (18)
together with triphenylphosphane. The 31P NMR shifts of
compound 16 were δ=17.7 (O–P) and 21.5 ppm (C=P). Also,
a signal in the 31P NMR spectrum of compound 17 was
observed at δ 20.9 ppm. Moreover, the 31P NMR spectrum of
compound 18 revealed singlet signal at δ=26.1 ppm. It could be
demonstrated that formation of compound 16 from the reaction
of 5 with 12 can be explained by initial nucleophilic attack at
the carbanion centre in the bisylide 5 on the carbonyl function
in 12 to give the phosphobetaine, which is transformed to the
four-membered oxaphosphetane 16. The last compound 16 can
lose triphenylphosphane oxide which is a good leaving group
and gave phosphanylidene-ethenyl 17, when the reaction was
performed in boiling toluene. When the reaction was carried
out in THF at room temperature, the corresponding 16 was also
initially formed, which lose triphenylphosphane by Hoffmann
degradation due to the presence of hydrogen atom in the
α-position to give compound 18 (Scheme 3).
Fig. 1 An ORTEP view of 15b showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown
as small spheres of arbitrary radii. The packing diagram of compound 15b showing the hydrogen bonds can be seen in Fig. 2.
Fig. 2 Packing diagram of compound 15b; a view in the ac plane showing the h-bonds as dashed lines.
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JOURNAL OF CHEMICAL RESEARCH 2014 757
Ph
16
N
15
5
6
C
C
C X
H
4
Ph3P
C C X
7
9
Cyclization
10
11
8
3
2
+ Ph3P=O
2a, X= N-Ph
b, X= O
13
N
Cl
12
N
1
Cl
14
13a, X= N-Ph
b, X= O
14
PPh3
CHO
Cl
X
N
X
N
C
H
+2
12
Cl
Ph3P
C
PPh3
5
15a, X= N-Ph
b, X= O
O
PPh3
H
C
- Ph3P=O
C
PPh3
PPh3
N
Cl
N
Cl
16
17
H.D
O
PPh3
+ PPh3
N
Cl
18
Scheme 3
Infectious diseases caused by bacteria and fungi affect
millions of people worldwide.40 It has been found that one of
the most successful groups of antifungal agents is azoles and its
derivatives.41,42 Therefore, we studied the antimicrobial activity
of some synthesised compounds.
activity of the synthesised compounds was investigated
against four pathogenic representatives of Gram-positive
bacteria (Staphylococcus aureus), Gram-negative bacteria
(Pseudomonas aeruginosa), fungus (Aspergillus niger) and
yeast (Candida albicans).
Antimicrobial activities of the methanol extract of the
starting materials 1, 9 and 12, and some new synthesised
compounds 4a, 4b, 7, 8, 10a, 11a, 11b, 14, 15b, 16 and 18
were evaluated by disc agar plate method. The antimicrobial
As shown in Table 1, the antimicrobial activity of the tested
compounds was evaluated by measuring the zone diameters
(inhibition zone or clear zone), some of the tested compounds
showed different antimicrobial activities. Methanol was used as
Table 1 Antimicrobial activities of some synthesised compounds
Clear zone (µm)
Bacteria
Sample code
Staphylococcus aureus Pseudomonas aeruginosa
Candida albicans
(yeast)
Aspergillus niger
(fungus)
(G +ve)
(G –ve)
–
–
–
–
19
8
9
–
8
19
–
–
–
–
–
17
8
8
–
7
16
–
–
–
–
–
19
9
11
–
8
20
–
–
–
–
–
–
9
–
–
–
–
7
–
–
–
–
–
Methanol (control)
1
9
12
4a
4b
7
8
10a
11a
11b
14
15b
16
18
–
–
9
–
–
–
9
–
–
9
–
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758 JOURNAL OF CHEMICAL RESEARCH 2014
petroleum ether (60–80 °C)/ethyl acetate as eluent (85:15, v/v), gave
4a together with triphenylphosphane oxide (m.p. and mixed m.p.
151 °C).
a solvent and negative control (no clear zone was recorded). All
the compounds were tested at 1 mg/disc concentration. Among
the tested compounds it was noticed that compounds 4a and
11a revealed more significant antimicrobial activity than 4b,
7, 10a and 16. Note that the starting materials 1, 9 and 12 have
no antimicrobial activity (they were used as positive control)
but compounds 4a and 11a revealed excellent antimicrobial
activity against all of the tested microorganisms (Gram-
positive, Gram-negative bacteria, fungus and yeast). Moderate
effect was achieved by compounds 4b, 7, 10a and 16 against
bacteria and yeast but no antifungal activity was detected from
these compounds. On the other hand, no antimicrobial activity
was detected from compounds 8, 11b, 14, 15b and 18.
N-(2,3-dimethyl-1-phenyl-1,2-dihydropyrrolo[3,2-c]pyrazol-5(4H)-
ylidene)aniline (4a): Colourless crystals, yield 65%, m.p. 111–113°C,
IR (KBr, ṽ, cm–1) 3295 (NH), 1664 (C=N). 1H NMR (500 MHz,
d6-DMSO, δ, ppm): 2.46 (s, 3H, CH3), 3.30 (s, 3H, N–CH3), 5.55 (s, 1H,
CH), 7.31–7.79 (m, 10 H, arom.–H), 12.52 (s, 1H, NH, exchangeable
with D2O); 13C NMR (125 MHz, d6-DMSO, δ, ppm): 168.62 (C=N),
119.95–139.36 (arom-C), 51.25 (CH), 29.45 (N–CH3), 22.88 (CH3). MS
m/z (%): 303 [(M+H)+, 70]. Anal. calcd for C19H18N4(302.37): C, 75.47;
H, 6.00; N, 18.53; found: C, 75.34; H, 5.95; N, 18.12%
Reaction of (2-oxovinylidene)triphenylphosphorane (2b) with (4-amino-
1,5-dimethyl-2-phenyl-1,2-dihydropyrazol-3-one) (1)
A solution of (2-oxovinylidene)triphenylphosphorane (2b)45 (302 mg,
1 mmol) in 20 mL of dry toluene was added to a solution of 1 (203 mg,
1 mmol) in 20 mL of dry toluene and refluxed for 10 h, during which
the colour was changed from yellow to brown (the progress of the
reaction was monitored by TLC). Toluene was distilled off under
reduced pressure and the residue was subjected to silica gel column
chromatography using petroleum ether (60–80 °C)/ethyl acetate as
eluent (40:60, v/v) to give 4b and triphenylphosphane oxide (m.p. and
mixed m.p. 151 °C).
2,3-Dimethyl-1-phenylpyrrolo[3,2-c]pyrazol-5(4H)-one-1,2-dihydro
(4b): Buff crystals, yield 60%, m.p. 196–198°C, IR (KBr, ṽ, cm–1):
3236 (NH), 1684 (C=O).1H NMR (500 MHz, d6-DMSO, δ, ppm): 2.08
(s, 3H, CH3), 3.07 (s, 3H, N–CH3), 7.33–7.44 (m, 6 H, arom.–H), 9.33
(s, 1H, NH, exchangeable with D2O); 13C NMR (125 MHz, d6-DMSO,
δ, ppm): 170.38 (C=O), 162.16 (N–C=, pyrrol), 150.34 (N–C, pyrazol),
108.50 (CH), 124.89–134.38 (arom.–C), 35.80 (N–CH3), 23.01 (CH3).
MS m/z (%): 228 [(M+H)+, 5]. Anal. calcd for C13H13N3O (227.26): C,
68.70; H, 5.77; N, 18.49; found: C, 68.64; H, 5.65; N, 18.01%.
Conclusion
The reaction of the nucleophilic active phosphacumulene and
phosphaallene ylides with 4-amino-1,5-dimethyl-2-phenyl-1,2-
dihydropyrazol-3-one and 4-amino-2-oxo-2H-chromene-3-
carbaldehyde and 2-chloroquinoline-3-carbaldehyde represent
an interesting approach to the synthesis of new carbocyclic and
heterocyclic bioactive compounds. Cycloaddition reactions
took place and the reaction products depend on the nature of
the reagent used and the reaction conditions. Moreover, the
difference in the nucleophilic character and the reactivity of the
phosphorus reagents were noticed, while the phosphacumulenes
react smoothly with the reactants, the phosphaallene reacts less
rapidly43 2a>2b>5. This process can be considered as a simple
and efficient route for the formation of pyrrolo-pyrazoles,
azaphospholes, phosphanylidenes, chromenopyridinones,
and oxaphosphetane. Some of the tested compounds revealed
pronounced antimicrobial activity when tested against four
different microorganisms.
Interaction of hexaphenylcarbodiphosphorane (5) with (4-amino-1,5-
dimethyl-2-phenyl-1,2-dihydropyrazol-3-one) (1)
Experimental
A solution of hexaphenylcarbodiphosphorane (5)46 (536 mg, 1 mmol)
in 20 mL dry THF was added to a solution of 1 (203 mg, 1 mmol) in
20 mL dry THF. The reaction mixture was refluxed for 12 h during
which the colour changed from yellow to brown then black. THF was
distilled off under reduced pressure and the remained residue was
chromatographed on silica gel using petroleum ether (60–80 °C):
ethyl acetate as eluent (90:10, v/v), to give two compounds 7, 8
together with triphenylphosphane (m.p. and mixed m.p. 78°C) and
triphenylphosphane oxide (m.p. and mixed m.p. 151°C).
2,3-Dimethyl-1,5,5,5-tetraphenyl1,2,4,5-tetrahydro pyrazolo[3,4-d]
[1,2]azaphosphole(7): Yellow crystals, yield 62%, m.p. 233–235°C.
IR (KBr, ṽ, cm–1): 3420 (NH). 1H NMR (500 MHz, d6-DMSO, δ,
ppm): 2.46 (s, 3H, CH3), 3.31 (s, 3H, N–CH3), 5.34 (d, 1H, JHP =15 Hz,
CH=P), 7.68–7.72 (m, 21 H, arom.–H+NH); 31P NMR (202.4 MHz,
d6-DMSO, δ, ppm): 23.55. MS m/z (%): 461 [(M)+, 8], 431 [(M–2CH3)
8]+. Anal. calcd for C30H28N3P (461.54): C, 78.07; H, 6.11; N, 9.10; P,
6.71; found: C, 77.95; H, 6.07; N, 9.01; P, 6.62%.
1,5-Dimethyl-2-phenyl-4-{[(triphenyl-λ5-phosphanylidene)methyl]
amino}-1,2-dihydro-3H-pyrazol-3-one (8): Colourless crystals,
yield 22%, m.p. 96–98°C. IR (KBr, ṽ, cm–1): 3351 (NH), 1727 (C=O,
pyrazolone). 1H NMR (500 MHz, d6-DMSO, δ, ppm): 2.20 (s, 3H,
CH3), 3.72 (s, 3H, N–CH3), 4.90 (d, 1H, JHP =20 Hz, CH=P), 6.55–7.71
(m, 20 H, arom.–H), 9.83 (s, 1H, NH, exchangeable with D2O);
13C NMR (125 MHz, d6-DMSO, δ, ppm): 158.33 (C=O, pyrazolone),
153.53 (C=P), 22.81 (N–CH3), 19.80 (CH3) 31P NMR (202.4 MHz,
d6-DMSO, δ, ppm): 31.03. MS m/z (%): 477 [(M)+, 4]. Anal. calcd for
C30H28N3OP (477.54): C, 75.45; H, 5.91; N, 8.80; P, 6.49; found: C,
75.02; H, 5.79; N, 8.69; P, 6.06%.
Reaction of triphenyl(N-phenyliminovinylidene)phosphorane (2a)
with 4-amino-2-oxo-2H-chromene-3-carbaldehyde (9): A mixture
of triphenyl(N-phenyliminovinylidene)phosphorane (2a) (377 mg,
1 mmol) in 20 mL of dry THF, was added dropwise with stirring at
room temperature, to a solution of 4-amino-2-oxo-2H-chromene-
Melting points were determined with an electrothermal digital melting
point apparatus (Electro-Thermal Engineering Ltd., Essex, United
Kingdom). The IR spectra were recorded in KBr disks on a Pye
Unicam SP 3300 and Shimadzu FT IR 8101 PC IR spectrophotometers
(Pye Unicam Ltd, Cambridge, UK and Shimadzu, Tokyo, Japan,
1
respectively). H and 13C NMR spectra were obtained from a Jeol
ECA 500 MHz NMR Spectrometer (Tokyo, Japan) using deuterated
dimethylsulfoxide (d6-DMSO) as a solvent and TMS as an internal
reference at 500, 125 MHz, respectively and 31P NMR spectra were
obtained from a Jeol ECA 500 MHz NMR spectrometer at 200 MHz.
Mass spectra (EI-MS) were obtained with ISQ (Single Quadrupole
MS, Thermo Scientific). Elemental analyses (C, H, N) results were
recorded with Elementar Vario EL Germany, phosphorus was
measured by spectrophotometric methods. X-ray crystallography
was carried out on Kappa CCD Enraf Nonius FR 590 diffractometer,
National Research Center, Dokki, Cairo, Egypt. The reported yields
are of pure isolated materials obtained by column chromatography
silica gel 60 (Merck) and TLC which was performed on Merck Kiesel
gel F254 precoated plates (Merck, Darmstall, Germany). Solvents
were dried/purified according to literature procedures. The starting
material 1 from S D Fine-Chem Ltd product no. 37228, Batch no.
BO5Z/1199/2102/13.
Reaction of triphenyl(N-phenyliminovinylidene)phosphorane (2a)
with (4-amino-1,5-dimethyl-2-phenyl-1,2-dihydro pyrazol-3-one) (1)
A mixture of triphenyl(N-phenyliminovinylidene)phosphorane (2a) 44
(377 mg, 1 mmol) in 20 mL of dry THF, was added dropwise with
stirring at room temperature, to a solution of 4-amino-1,5-dimethyl-
2-phenyl-1,2-dihydropyrazol-3-one (1) (203 mg, 1 mmol) in 20 mL of
dry THF. The reaction mixture was stirred for 6 h during which the
colour changed from yellow to dark brown with the progress of the
reaction which was monitored by TLC. THF was distilled off and
the residue was subjected to silica gel column chromatography using
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3-carbaldehyde (9)47 (189 mg, 1 mmol) in 20 mL of dry THF. The
reaction mixture was stirred for 4 h during which the colour was
changed from yellow to brown then dark brown (the progress of the
reaction was monitored by TLC). THF was distilled off and the residue
was subjected to silica gel column chromatography using petroleum
ether (60–80 °C)/ethyl acetate as eluent (70:30, v/v), to give two
products 10a, 11a together with triphenylphosphane oxide (m.p. and
mixed m.p. 151 °C).
N-(3-formyl-2-oxo-2H-chromen-4-yl)-N′-phenyl-2-(triphenyl-
λ5-phosphanylidene)-ethanimidamide (10a): Yellow crystals, yield
25%, m.p. 134–136°C, IR (KBr, ṽ, cm–1): 3459 (NH), 1701 (C=O,
lactone), 1673 (C=O, formyl), 1603 (C=N), 1545 (C=P), 1473, 1414
(P-aryl). 1H NMR (500 MHz, d6-DMSO, δ, ppm): 4.58 (d, 1H,
JHP =25 Hz, CH=P), 6.86–7.83 (m, 25 H, arom.–H+NH), 10.28 (s,
1H, CHO); 31P NMR (202.4 MHz, d6-DMSO, δ, ppm): 13. 61. MS m/z
(%) 566 [(M)+, 3], 262 [Ph3P, 14.6], 278 [Ph3P=O, 5.6]. Anal. calcd for
C36H27N2O3P (566.58): C, 76.31; H, 4.80; N, 4.94; P, 5.47; found: C,
76.14; H, 4.72; N, 4.52; P, 5.40%.
2-(Phenylimino)chromeno[4,3-b]pyridin-5-one-1,2-dihydro
(11a): Buff crystals, yield 55%, m.p. 241–243°C, IR (KBr, ṽ, cm–1):
3326 (NH), 1698 (C=O, lactone), 1608 (C=N).1H NMR (500 MHz,
d6-DMSO, δ, ppm): 5.06 (d, 1H, JHH =10 Hz, CH), 7.25–7.56 (m, 10 H,
arom. –H+NH), 8.30 (d, 1H, JHH =10 Hz, CH); 13C NMR (125 MHz,
d6-DMSO, δ, ppm): 163.05 (C=N), 154.03 (C=O, lactone), 122.79 (CH),
129.60–133.91 (arom.–C). MS m/z (%) 288, [(M)+, 100], 260[(M–CO)+,
7], 244 [(M–CO2)+, 6.5]. Anal. calcd for C18H12N2O2 (288.30): C,
74.99%; H, 4.20; N, 9.72; Found: C, 74.33; H, 4.05; N, 9.12%.
monitored by (TLC). THF was distilled off under reduced pressure
and the residue was subjected to silica gel column chromatography
using petroleum ether (60–80°C)/ethyl acetate or acetone as eluent,
and affording two products 14 and 15a in case of 2a, product 15b
was obtained when 2b was used. Triphenylphosphane oxide was also
separated and identified.
N-(4-Chloro-1H-cyclopenta[c]quinolin-1-ylidene)aniline (14): Red
crystals, yield 28%, m.p. 132–134 °C, IR (KBr, ṽ, cm–1): 1608 (C=N).
1H NMR (500 MHz, d6-DMSO, δ, ppm); 5.82 (d, 1H, JHH =8 Hz, CH),
7.01–7.71 (m, 10 H, arom.–H) 13C NMR (125 MHz, d6-DMSO, δ, ppm):
161.33 (C=N), 160.75 (C-2), 137.72 (C-7), 136.19 (C-4), 129.81 (C-3),
137.72–121.50 (arom.–C), 117.66 (C-5). MS m/z (%) 288 [M–2H]+
40], 290 (18), 289 [M–1H]+ 100], 291 (30). Anal. calcd for C18H11ClN2
(290.75): C, 74.36; H, 3.81; Cl, 12.19; N, 9.63; found: C, 74.24; H, 3.75;
Cl, 12.13; N, 9.51%.
N,N′-[(2-[(2-Chloroquinolin-3-yl)methylidene]-4-(triphenyl-λ5-
phosphanylidene)-cyclobutane-1,3-diylidene]dianiline (15a): Eluent:
petroleum ether (60–80°C)/ethyl acetate (90:10, v/v), yellow crystals,
yield 52%, m.p. 199–201°C, IR (KBr, ṽ, cm–1): 1594 (2 C=N), 1548
(C=P), 1438 (P-phenyl). 1H NMR (500 MHz, d6-DMSO, δ, ppm): 6.44
(d, 1H, CH), 7.49–7.70 (m, 30 H, arom.–H); 13C NMR (125 MHz,
d6-DMSO, δ, ppm): 162.00 (2 C=N), 161.14 (N=C–Cl), 153.50
(C=P), 128.68–133.09 (arom.–C), 116.04 (C=C–H). MS m/z (%) 565
[(M–C=NPh)+, 5], 567 (1.5). Anal. calcd for C44H31ClN3P (668.16): C,
79.09; H, 4.68; Cl, 5.31; N, 6.29; P, 4.64%; found: C, 78.94; H, 4.55; Cl,
5.11; N, 6.74; P, 4.52%.
2-[(2-Chloroquinolin-3-yl)methylidene]-4-(triphenyl-λ5-phosphan-
ylidene)cyclobutane-1,3-dione (15b): Eluent: petroleum ether
(60–80 °C)/acetone (30:70, v/v), colourless crystals, yield 65%, m.p.
244–245°C. 1H NMR (500 MHz, d6-DMSO, δ, ppm): 6.67 (s, 1H, CH),
7.12–7.90 (m, 20 H, arom.–H). 31P NMR (202.4 MHz, d6-DMSO, δ,
ppm): 1.3. MS m/z (%) 482 [M–Cl]+, 278 [Ph3P=O, 16], 262 [Ph3P, 39].
Anal. calcd for C32H21ClNO2P (517.94): C, 74.21; H, 4.09; Cl, 6.84; N,
2.70; P, 5.98; found: C, 73.64; H, 4.05; Cl, 6.11; N, 2.14; P, 5.52%
Interaction of (2-oxovinylidene)triphenylphosphorane (2b) with
4-amino-2-oxo-2H-chromene-3-carbaldehyde (9):
A solution of
(2-oxovinylidene)triphenylphosphorane (2b) (302 mg, 1 mmol) in
20 mL of dry toluene was added to a solution of (189 mg, 1 mmol)
in 20 mL of toluene and refluxed for 12 h, during which the colour
was changed from yellow to red then dark red (the progress of the
reaction was monitored by TLC). Toluene was distilled off under
reduced pressure and the residue was subjected to silica gel column
chromatography using petroleum ether (60–80 °C)/ethyl acetate as
eluent (25:75, v/v) to give 10b, 11b and triphenylphosphane oxide
(m.p. and mixed m.p. 151 °C).
N-(3-formyl-2-oxo-2H-chromen-4-yl)-2-(triphenyl-λ5-phosphan-
ylidene)acetamide (10b): Colourless crystals, yield 38%,
m.p.>350°C, IR (KBr, ṽ, cm–1): 3355 (NH), 1722 (C=O, lactone),
1633 (C=O, formyl), 1620 (C=O, amide), 1485 (C=P). 1H NMR
(500 MHz, d6-DMSO, δ, ppm): 6.01 (d, 1H, JHP =20 Hz, CH=P),
7.49–7.68 (m, 20 H, arom.–H+NH), 8.28 (s, 1H, CHO); 13C NMR
(125 MHz, d6-DMSO, δ, ppm): 187.39 (CHO), 163.66 (NH–C=O),
160.04 (C=O, lactone), 156.45 (C=P), 128.56–133.83 (arom.–C).
31P NMR (202.4 MHz, d6-DMSO, δ, ppm): 16. 68 ppm. MS m/z (%)
213 [(M–Ph3P=O)+, 5]+, 278 [Ph3P=O, 25], 262 [Ph3P, 10]. Anal. calcd
for C30H22NO4P (491.47): C, 73.31; H, 4.51; N, 2.85; P, 6.30; found: C,
73.14; H, 4.45; N, 2.72; P, 6.10%.
X-Ray crystallography analysis of 15b
A single crystal of compound 15b was grown by the slow solvent
evaporation method. A suitable crystal was selected, checked and
mounted onto thin glass fibre. The X-ray single crystal diffraction
data were collected at room temperature (298 K) on an Enraf-Nonius
590 diffractometer with a Kappa CCD detector using graphite
monochromated Mo-Kα (λ=0.71073 Å) radiation, at National
Research Centre of Egypt.49,50 Reflection data were recorded in the
rotation mode using the ϕ and ω scan technique with 2θmax =27.232°.
Unit cell parameters were determined from least-squares refinement
with θ in the range 3≤θ≤27. The structure was solved by direct
methods using SHELXS-9751 and SUPERFLIP52 implemented
in the CRYSTALS program suit.53 The refinement was carried
out by the full-matrix least-squares method on the positional and
anisotropic temperature parameters of all non-hydrogen atoms
based on F2 using the CRYSTALS package. All hydrogen atoms
were positioned geometrically and were initially refined with soft
restraints on the bond lengths and angles to regularise their geometry
(C–H in the range 0.93–0.98 and N–H in the range 0.86–0.89) and
Uiso(H) (in the range 1.2–1.5 times Ueq of the parent atom). Then, the
positions were refined with riding constraints.54 The general-purpose
crystallographic tool PLATON 55 was used for the structure analysis
and presentation of the results. The molecular graphics were done
using ORTEP-3 for Windows56 and DIAMOND57 programs. Details
of the data collection conditions and the parameters of the refinement
process are given in Table 2.
1H-Chromeno[4,3-b]pyridine-2,5-dione (11b): Yellow crystals,
yield 38%, m.p. 339–341°C, IR (KBr, ṽ, cm–1): 3411 (NH), 1713 (C=O,
1
lactone), 1644 (C=O, pyridinone). H NMR (500 MHz, d6-DMSO, δ,
ppm); 7.45–7.78 (m, 6 H, arom.–H), 9.54 (s, 1H, HN, exchangeable
with D2O); 13C NMR (125 MHz, d6-DMSO, δ, ppm): 159.83 (C=O,
pyridinone), 153.29 (C=O, lactone), 119.30–138.21 (arom.–C), 116.36
(=CH). MS m/z (%) 213 [(M)+, 4], 185 [(M–CO)+, 36], 169 [(M–CO2)+,
4], 157 [(M–2CO)+, 32]. Anal. calcd for C12H7NO3 (213.19): C, 67.61; H,
3.31; N, 6.57; found: C, 67.14; H, 3.25; N, 6.02%.
Interaction of triphenyl(N-phenyliminovinylidene)phosphorane (2a) or
(2-oxovinylidene)triphenylphosphorane (2b) with 2-chloroquinoline-
3-carbaldehyde (12)
A mixture of 2a (377 mg, 1 mmol,) or 2b (302 mg, 1 mmol) in 20 mL of
dry THF, was added dropwise with stirring at room temperature, to a
solution of 2-chloroquinoline-3-carbaldehyde (12)48 (191 mg, 1 mmol)
in 20 mL of dry THF. The reaction mixture was stirred for 6 h in case
of 2a and 8 h when 2b was used (the progress of the reaction was
Crystallographic data (excluding structure factors) for the
structure in this paper have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication number
CCDC 983767. Copies of the data can be obtained, free of charge, on
application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [Fax:
+44(0)1223 336033 or E-mail: deposit@ccdc.cam.ac.uk].
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760 JOURNAL OF CHEMICAL RESEARCH 2014
Table 2 Crystal data and structure refinement parameters for 15b.
Antimicrobial test activity
Disc agar plate method was done the antimicrobial activities
of 0.5 cm-diameter filter paper disc saturated with about 1 mg
sample were tested against four different microbial strains, i.e.,
Staphylococcus aureus (G +ve bacteria), Pseudomonas aeruginosa
(G –ve bacteria), Candida albicans (yeast) and Aspergillus niger
(fungi). Both bacterial and yeast test microbes were grown on nutrient
agar (DSNZ 1) medium (g L–1): beef extract (3), peptone (10), and
agar (20). Whereas fungal test microbe was grown on Czapek-Dox
(DSMZ130) medium (g L–1): sucrose (30), NaNO3 (3), MgSO4.7H2O
(0.5), KCl (0.5), FeSO4.7H2O (0.001), K2HPO4 (1) and agar (20). The
culture of each microorganism was diluted by sterile distilled water
to 107 to 108 CFU mL–1 to be used as inoculums 0.1 mL of the previous
inoculums was used to inoculate 1l of agar medium (just before
solidification) then poured in Petri-dishes (10 cm diameter containing
25 mL). Discs (5 mm diameter) were placed on the surface of the agar
plates previously inoculated with the test microbe and incubated for
24 h for bacteria and yeast, but for 48 h for fungus at 37 and 30°C,
respectively.
Crystal data
Chemical formula
Mr
Crystal system, space group
Temperature/K
a, b, c/Å
C32H21ClNO2P·0.5(C4H4O2)
559.99
Triclinic, P-1
298
9.3420 (3), 10.8202 (5), 14.7185 (7)
101.3924 (18), 103.5506 (17),
α, β, γ/°
91.680 (2)
1413.40 (11)
V/Å3
Z
2
Radiation type
MoKα
0.23
0.22×0.17×0.12
µ/mm−1
Crystal size/mm
Data collection
Diffractometer
Absorption correction
Tmin, Tmax
Nonius KappaCCD diffractometer
Multi-scan
0.96, 0.97
No. of measured, independent and
observed [I>2.0σ(I)] reflections
9469, 5861, 2795
Received 4 August 2014; accepted 18 November 2014
Paper 1402804 doi: 10.3184/174751914X14179446629855
Published online:19 December 2014
Rint
0.050
0.644
(sin θ/λ)max /Å−1
Refinement
R[F2 >2σ(F2)], wR(F2), S
0.060, 0.139, 0.94
No. of reflections/parameters
2795/191
0.69, −0.31
References
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293–295°C. H NMR (500 MHz, d6-DMSO, δ, ppm): 7.49–7.71 (m,
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P, 6.88; found: C, 77.37; H, 4.68; Cl, 7.71; N, 2.99; P, 6.79%.
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and stirred for 10 h, products 16 and 18 were isolated together with
triphenylphosphane.
2-Chloro-3-(2,2,2-triphenyl-2H-1,2 λ5-oxaphosphet-4-yl)quinoline
(18): Pale yellow crystals, yield 20%, m.p. 172–174°C. MS m/z (%)
463 [[M–2H]+,25], 465 (7.7)], 278 [Ph3P=O, 15], 280 [Ph3P=O, 4], 201
[(M–2H) –Ph3P, 2.7], 203 (1)]. Anal. calcd for C29H21ClNOP (465.91):
C, 74.76; H, 4.54; Cl, 7.61; N, 3.01; P, 6.65; found: C, 74.54; H, 4.45; Cl,
7.31; N, 2.94; P, 6.42%.
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