Synthesis of new benzoxaphosphole derivatives from the reaction of dialkylphosphonates and trisdialkylaminophosphines with 2,6-bis(benzylidene) cyclohexanones

Article abstract of DOI:10.1080/10426500802589956

The reaction of 2,6-bis(benzylidene)cyclohexanones with dialkylphosphonates and tris(dialkylamino)phosphines afforded the new benzoxaphosphole derivatives (5a-5d) and (9a-9f). The biological activity of the newly synthesized compounds was also examined. P

Full text of DOI:10.1080/10426500802589956

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Phosphorus, Sulfur, and Silicon
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Synthesis of New
Benzoxaphosphole Derivatives
from the Reaction of
Dialkylphosphonates and
Trisdialkylaminophosphines
with 2,6-
Bis(benzylidene)cyclohexanones
Mona H. N. Arsanious a , Nahed K. El-Din a & Leila S.
Boulos a
a National Research Centre , Dokki, Cairo, Egypt
Published online: 03 Nov 2009.
To cite this article: Mona H. N. Arsanious , Nahed K. El-Din & Leila S.
Boulos (2009) Synthesis of New Benzoxaphosphole Derivatives from the
Reaction of Dialkylphosphonates and Trisdialkylaminophosphines with 2,6-
Bis(benzylidene)cyclohexanones, Phosphorus, Sulfur, and Silicon and the Related
Elements, 184:11, 2813-2826, DOI: 10.1080/10426500802589956
To link to this article: http://dx.doi.org/10.1080/10426500802589956
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Phosphorus, Sulfur, and Silicon, 184:2813–2826, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802589956
Synthesis of New Benzoxaphosphole Derivatives
from the Reaction of Dialkylphosphonates
and Trisdialkylaminophosphines with
2,6-Bis(benzylidene)cyclohexanones
Mona H. N. Arsanious, Nahed K. El-Din, and
Leila S. Boulos
National Research Centre, Dokki, Cairo, Egypt
The reaction of 2,6-bis(benzylidene)cyclohexanones with dialkylphosphonates and
tris(dialkylamino)phosphines afforded the new benzoxaphosphole derivatives
(5a–5d) and (9a–9f). The biological activity of the newly synthesized compounds
was also examined. Possible reaction mechanisms are considered, and the struc-
tural assignments are based on analytical and spectroscopic results. The structure
of the new benzoxaphosphole 5a was confirmed by a single crystal X-ray determi-
nation.
Keywords Benzoxaphosphole; 2,6-bis(benzylidene)cyclohexanones; dialkylphospho-
nates; tris(dialkylamino)phosphonates.
INTRODUCTION
The increasing number of resistant bacterial strains, especially
the highly resistant β-lactamase producing Staphylococcus aureus
and Gram-negative strains, requires the development of new effec-
tive chemotherapeutic agents of low toxicity. α,β-Unsaturated ke-
tones are known to possess antimicrobial effects.1 This, together
with our interest in organophosphorus chemistry,2–9 has encour-
aged the synthesis of new organophosphorus compounds incorporat-
ing important nuclei that may possibly lead to further biological
activity. The present study deals with the reaction of dialkylphos-
phonates 1a–1b and tris(dialkylamino)phosphines 2a–2b with 2,6-
bis(benzylidene)cyclohexanones 3a–3c (Scheme 1).
Received 11 August 2008; accepted 22 October 2008.
Address correspondence to Leila S. Boulos, National Research Centre, Dokki, Cairo,
Egypt. E-mail: Leilagoubran@yahoo.com
2813

2814
M. H. N. Arsanious et al.
SCHEME 1
RESULTS AND DISCUSSION
We have found that 2,6-dibenzylidene cyclohexanone 3a reacts with
dimethylphosphonate 1a in refluxing toluene for 10 h to give colorless
crystals formulated as (7)-1-methoxy-3-phenyl-7-(phenylmethylidene)-
1,3,4,5,6,7-hexahydro-2,1-benzoxaphosphole-1-oxide (5a) (Scheme 2).
Compound 5a is chromatographically pure and possesses a sharp melt-
ing point. The assigned oxaphosphole structure 5a is based on the X-
1
ray structural analysis, together with correct microanalysis, IR, H,
13C, 31P NMR, and mass spectral data. The IR spectrum of compound
5a reveals the absence of a carbonyl absorption, which is recorded with
3 at 1675 cm−1. The spectrum also lacks the characteristic absorption
band attributable to the stretching frequency of an enolate carbonyl
function.10 In addition, it exhibits intense bands corresponding to the
P=O and P-O-(alkyl) stretching vibrations.11 The 1H NMR of 5a gives
3
signals at 3.86 ppm (3H, d, JHP = 11.87 Hz) for the methoxy group
attached to phosphorus, two triplets at 2.16 and 1.88 ppm and a mul-
tiplet at 1.72 ppm for the 6 methylene protons, a singlet at 5.64 ppm
for the CH proton of cyclic oxaphosphole, 6.70 for =CH, and multi-
plets at 7.26–7.39 ppm (10H, m, Ar). The 31P NMR measurement of 5a
supports the oxaphosphole structure; it exhibits a sharp signal at δ =
37.62. The mass spectrum of 5a gives a prominent peak at m/e 352 (M+,
100%). In order to identify unambiguously the structure of the reaction
product 5a, an X-ray structure determination12–15 of crystalline 5a was
performed (Figure 1, Tables I and II).
Similarly, diethylphosphonate 1b reacts with 3a to give adduct 5b
in 78% yield (Scheme 2). Structure 5b was deduced from correct micro-
analysis, IR, 1H, 13C NMR, and MS spectral data (cf. the Experimental

Synthesis of New Benzoxaphosphole Derivatives
2815
SCHEME 2
section). The reaction of 2,6-bis(4-chlorobenzylidene)cyclohexanone
(3b) with dialkylphosphonates 1a and 1b was also investigated. We
found that the reaction of 1a and 1b with 3b, in dry toluene, proceeds
at reflux temperature to give pure adducts formulated as 5c and 5d
(Scheme 2). Structure 5c and 5d were substantiated on the basis of
their elemental analysis, IR, 1H, 13C NMR, and mass spectral data (cf.
the Experimental section).
We propose the reaction course depicted in Scheme 2 to account for
these interesting results. The reaction, which is presumably initiated
by a nucleophilic attack of the phosphite-phosphorus on the most reac-
tive center carbonyl group of 3, leads to the intermediate compounds
(4), which undergoes cyclization followed by molecular rearrangements
and loss of an alcohol molecule to give compounds (5) (Scheme 2).

2816
M. H. N. Arsanious et al.
TABLE I Crystal Structure and Data Refinement Parameters
Compound
5a
10
Empirical formula
Formula weight
C21H21O3P
352.370
C20H19O3P
338.34
Crystal system/space group
Monoclinic
10.6510 (4)
11.4099 (5)
15.4764 (8)
90.00◦
Triclinic
9.6104(5)
9.6923(5)
10.4619(6)
109.231(3)
101.292(3)
99.214(2)
875.35(8)
2
a / Å
b / Å
c / Å
α / ◦
β / ◦
101.355 (2)◦
γ / ◦
90.00◦
1843.98 (14)
4
0.00126
0.16
V / Å3
Z
D calc (g/cm3)
0.001386
0.17
µ (mm−1
)
Crystal size (mm)
Color / Shape
Temp (K)
Theta range for collection
Reflections collected
Independent reflections
Data/restraints/parameters
Goodness of fit on F2
Final R indices [I > 2σ(I)]
R indices (all data)
0.10 × 0.10 × 0.12
Colorless/prismatic
298
0.17 × 0.10 × 0.10
Colorless/needles
298
2.910–25.028 0
5439
2.910–27.485◦
5029
3543
226
0.042
Rint 0.031
0.090
4402
217
0.049
Rint 0.035
0.122
FIGURE 1 Molecular structure of 5a with the atomic numbering scheme;
anisotropic displacement parameters are drawn at the 30% level, and the hy-
drogen atoms are shown as spheres of arbitrary radii.

Synthesis of New Benzoxaphosphole Derivatives
2817
Furthermore, this study was extended to include the be-
havior of 2,6-bis(benzylidene) cyclohexanones (3a–3c) toward
tris(dialkylamino)phosphines 2a–2b to determine the preferen-
tial site of attack. We have found that 2,6-dibenzylidene cyclo-
hexanone 3a reacts with tris(dimethylamino)phosphine 2a in refluxing
toluene to give (7-benzylidene-2-oxo-3-phenyl-2,3,4,5,6,7-hexahydro-
2λ5-benzo[d][1,2]oxaphosphol-2-yl)-dimethylamine (9a) (Scheme 3).
The assigned oxaphosphole structure 9a was based on the following
SCHEME 3

2818
M. H. N. Arsanious et al.
evidence: The IR spectrum of 9a exhibits intense bands at 1240 (P=O),
1320 cm−1 and 860 cm−1 due to the absorption of the P-N (CH3)2.11 The
1H NMR spectrum (in d6-DMSO) of 9a showed a doublet centered at δ
= 2.68 (JHP = 10.20 Hz) due to the 6H of the dimethylamino group, a
doublet centered at 4.26 ppm with 2JHP = 18.75 Hz due to the methine
proton attached to the phosphorus. The aromatic protons appeared as
multiplet at 7.40–7.48 (10H, Ar). The spectrum of 9a exhibits triplet
at 1.69 (t, 2H, CH2), 2.01 (t, 2H, CH2), multiplet at 1.94 (m, 2H, CH2)
and singlet at 6.73 (s, 1H, =CH). The 31P NMR gave one signal at δ =
46.02, which confirms the cyclic oxaphosphole structure.16
The 13C NMR spectrum of 9a adds good support for the proposed
structure, which reveals the methine proton attached to the phospho-
rus as doublet at 45.86 with JCP = 107.2 Hz (cf. the Experimental
section). Moreover, elemental analysis and molecular weight determi-
nation (MS) of 9a support the molecular formula. Similarly, compound
3a reacts with tris(diethylamino)phosphine 2b to give colorless crys-
talline compound formulated as 9b (Scheme 3, Experimental). More-
over, the reaction of tris(dialkylamino)phosphines 2a and 2b with 3b
and 3c, in dry toluene, proceeds at reflux temperature to give pure
adducts formulated as 9c, 9d, 9e, 9f, respectively (Scheme 3).
Structural elucidation of 9c–9f is based on elemental analysis, IR,
1H, 13C, 31P NMR, and mass spectroscopic data (cf. the Experimental
section). We propose the reaction course depicted in Scheme 3. Thus, a
nucleophilic attack of the phosphite-phosphorus on the most reactive
center of 3 leads to the dipolar adduct 6, which undergoes ring closure
giving structure 7. The latter, due to its structural features, could col-
lapse to the most stable form 9 through the rapid hydrolysis of 7 (by
the presence of unavoidable moisture) to give intermediate 8, which
undergoes further decomposition yielding 9.17
It is worthy to note that when compound 9a was boiled for
1 h in xylene, the new 7-benzyl-3-phenyl-2,4,5,6-tetrahydro-1,2-
benzoxaphosphol-2-ol-2-oxide 10 was obtained in 95% yield.
Product 10 is pure and possesses a sharp melting point. The struc-
ture of 10 was assigned based on the X-ray analysis together with mi-
croanalysis, IR, 1H NMR, and mass spectral data (cf. the Experimental

Synthesis of New Benzoxaphosphole Derivatives
2819
TABLE II Selected Bond Lengths (Å) and Angles (◦)
Compound 5a
Compound 10
P1-O2 1.593(14) P1-C15 1.779 (2)
O2-C10 1.453 (2) C9-C10 1.522(3)
C5-C9 1.335(3) P1-O3 1.454(14)
P1-O4 1.566 (2) O4-C25 1.424(3)
C5-C8 1.474 (2) C5-C9 1.335(3)
C7-C12 1.469(3) C21-C22 1.358(4)
O2-P1-O3 115.56(8)
P1-O2 1.517(2) P1-C7 1.776(3)
O4-C6 1.412(3) C6-C12 1.455(3)
C12-C7 1.357(3) P1-O3 1.501(2)
P1-O4 1.600(2) C11-C13 1.500(4)
C12-C15 1.501(4) C5-C7 1.471(4)
C5-C21 1.390(4) C13-C14 1.511(4)
P1-O4-C6 111.9(2)
O2-P1-O4 106.62(8)
O4-C6-C12 110.7(2)
O2-P1-C5 95.34(8)
P1-C7-C12 106.7(2)
P1-C5-C9 108.87(13)
O3-P1-O4 109(11)
O4-P1-C5 111.95(8)
O2-P1-O3 112.6(10)
X-Ray Crystallographic Study:12–13 The crystal structure was solved and refined,
using maXus (Nonius, Delft and Mac Science, Japan). MoKα (λ = 0.71073 Å) and
a graphite monochromator were used for data collection. A summary of the crystal
analysis parameters is given in Table I. CCDC (699015, 5a; 699016, 10) contains
the supplementary crystallographic data for this article.
These data can be obtained from The Cambridge Crystallographic Data Centre
via www.ccdc.cam.ac.uk/data request/cif.
section). In order to unambiguously identify the structure of the re-
action product 10, an X-ray structure determination was performed
(Figure 2, Tables I and II).
From the results of the present investigation, it could be con-
cluded that the reaction of 2,6-bis(benzylidene)cyclohexanones 3a–3c
with dialkylphosphonates 1a–1b proceeds in a different manner
FIGURE 2 Molecular structure of 10 with atomic numbering scheme;
anisotropic displacement parameters are drawn at the 30% level, and the hy-
drogen atoms are shown as spheres of arbitrary radii.

2820
M. H. N. Arsanious et al.
from that with tris(dialkylamino)phosphines 2a–2b. Formation
of (7)-1-alkoxy-3-phenyl-7-(phenylmethyliden)-1,3,4,5,6,7-hexahydro-
2,1-benzoxaphosphole-1-oxide 5a–5d seems to proceed via a neucle-
ophilic attack of phosphonates 1 on the carbonyl functionality in 3,
while tris(dialkylamino)phosphines 2a–2b react with 3a–3c, through
addition to the β-carbon atom of α,β-unsaturated ketone system, to give
hexahydro-1,2-benzoxaphosphole-2-oxide adducts 9a–9f. These find-
ings supplement the wide aspect for utilization of dialkylphosphonates
and tris(dialkylamino)phosphines in the synthesis of new benzoxaphos-
phole derivatives.
EXPERIMENTAL
All melting points are uncorrected. The IR spectra were measured in
KBr pellets with a Perkin-Elmer Infrared Spectrophotometer Model
1
157 (Grating). The H and 13C NMR spectra were recorded in CDCl3
and d6-DMSO as solvents on a JEOL-300 MHz Spectrometer, and the
chemical shifts were recorded in δ values relative to TMS. The 31P NMR
spectra were taken with a Varian CFT-20 (vs. external 85% H3PO4
standard). The mass spectra were performed at 70 eV on a Shimadzu
GCS-OP 1000 Ex Spectrometer. Elemental analyses were performed
using the Elementer Varu El Germany Instrument.
Reaction of Dialkylphosphonate 1a–1b with
2,6-Bis(benzylidene)cyclohexanone (3a)
Dialkylphosphonate 1a or 1b (0.002 mol) was added dropwise to a
solution of compound 3a (0.27 g, 0.001 mol) in dry toluene (30 mL), and
the reaction mixture was refluxed for 10 h. After evaporation of the
volatile materials under reduced pressure, the residue was applied to
silica gel column chromatography. The eluent, yield, and mp are given
below for adducts 5a and 5b.
(7)-1-Methoxy-3-phenyl-7-(phenylmethylidene)-2,3,4,5,6,7-
hexahydro-2,1-benzoxaphosphole-1-oxide (5a)
Eluent◦: acetone:petroleum ether (30:70, v/v), colorless crystals, mp
186–187 C, yield 85%. Anal. calcd C21H21O3P(352.37): C, 71.58, H,
6.00, P, 8.77. Found: C, 71.73, H, 6.16, P, 8.86%. IR (KBr): ν = 1240
1
(P=O) cm−1, 1040 (POMe) cm−1; H NMR (CDCl3) δ = 3.86 (d, 3H, P-
3
OCH3, JHP = 11.87 Hz), 2.16 (t, 2H, CH2), 1.88 (t, 2H, CH2), 1.72 (m,
3
2H, CH2), 5. 64 (d, 1H, P-O-CH, JHP = 5.8 Hz), 6.70 (s, 1H, =CH);
7.26–7.39 (m, 10H, Ar) ppm. 31P NMR: δ = 37.62 ppm MS m/z (%):352
(M+, 100).

Synthesis of New Benzoxaphosphole Derivatives
2821
(7)-1-Ethoxy-3-phenyl-7-(phenylmethyliden)-2,3,4,5,6,7-
hexahydro-2,1-benzoxaphosphole-1-oxide (5b)
Eluent: ethyl acetate:petroleum ether (70:30, v/v), colorless crystals,
mp 258–260◦C, yield 78%. Anal.calcd C22H23O3P (366.39): C, 72.12, H,
6.33, P, 8.45 Found: C, 72.17, H, 6.39, P, 8.53%. IR (KBr): νꢀ = 1243
1
(P=O) cm−1, 1045 (POEt) cm−1; H NMR (300 MHz,CDCl3): δ = 1.15
[t, 3H, P (OCH2CH3)], 4.02 [q, 2H, 3JHP = 11.5 Hz, P(OCH2CH3)],1.55,
3
1.37, 2.24 (3CH2), 5.62 (d, JHP = 5.4Hz,P-O-CH), 6.63 (s, 1H, =CH),
7.11–7.44 (m, 10H, Ar) ppm; 13C NMR (300 MHz,CDCl3): δ = 118.67
(C-P, 1 JCP = 70.50 Hz), 87.8 (P-O-CH), 26.6, 30.4, 23.7 (3CH2, cyclohex-
anone), 140.6 (C = C-P), 129.8, 130.5, 128.8, 131 (C6H5), 130.5, 128.8,
127.8, 126.3 (C6H5) ppm. MS: m/z (%): 366 (M+,100)
Reaction of Dialkylphosphonate 1a and/or 1b with
2,6-Bis(4-chlorobenzylidene)-cyclohexanone (3b)
A mixture of 0.002 mol dialkylphosphonate 1a or 1b and 0.001 mol
of 3b in dry toluene (30 mL) was refluxed for 18–20 h. The volatile
materials were evaporated under reduced pressure. The residue was
subjected to silica gel column chromatography to give the products.
(7)-3-(4-Chlorophenyl)-7-[(4-chlorophenyl)-methylidene]-1-
methoxy-1,3,4,5,6,7-hexahydro-2,1-benzoxaphosphole-1-
oxide (5c)
Eluent: Acetone:petroleum ether (25:75, v/v), colorless crystals, mp
187–188 ◦C, yield 80%. Anal calcd. for C21H19Cl2O3P (421.25) C, 59.87,
H, 4.55, Cl, 16.83, P, 7.35, Found. C, 59.95, H, 4.59, Cl, 16.89, P, 7.40.
1
IR (KBr): ν = 1040 (POCH3), 1250 (P=O) cm−1; H NMR (300 MHz,
3
CDCl3): δ = 3.56 (d, 3H, P-OCH3, JHP = 11.87 Hz), 2.45 (t, 2H, CH2),
1.97 (t, 2H, CH2), 1.77 (m, 2H, CH2), 5.68 (d, 1H, P-O-CH, 3JHP = 5.40
Hz), 6.78 (s, 1H, =CH), 7.50–7.29 (m, 8H, Ar) ppm; 13C NMR (300 MHz,
CDCl3): δ = 117.9 (C-P, 1JCP = 75 Hz), 53.5 (P-OCH3), 87.3 (P-O-CH, 2J
= 27 Hz), 26.6, 30.4, 23.7 (3CH2, cyclohexanone), 140.6 (C = C-P), 135.8,
130.5, 128.8, 131.3 (4-Cl-C6H4), 133.5, 128.8, 127.8, 133.3 (4-Cl-C6H4)
ppm. MS: m/z (%): 421 (M+,70).
(7)-3-(4-Chlorophenyl)-7-[(4-chlorophenyl)-methylidene]-1-
ethoxy-1,3,4,5,6,7-hexahydro-2,1-benzoxaphosphole-1-
oxide (5d)
Eluent: ethyl acetate:petroleum ether (15:85, v/v), colorless crystals,
◦
mp 203–205 C, yield 90%. Anal. calcd for C22 H21Cl2O3P (435.28): C,
60.70, H, 4.86, Cl, 16.29, P, 7.12. Found. C, 60.76, H, 4.88, Cl, 16.34,
1
P, 7.17%. IR (KBr): ν = 1242 (P=O), 1042 (POEt) cm−1; H NMR (300
MHz, CDCl3): δ = 1.39 [t, 6H, P(OCH2CH3)2], 4.23 [m, 4H, JHP = 7.4

2822
M. H. N. Arsanious et al.
Hz, P(OCH2CH3)2], 2.15, 1.90 (t, 4H, 2CH2), 1.7 (m, CH2,2H), 5.63 (d,
P-O-CH, 3JHP = 6.20 Hz), 6.86 (s, =CH), 7.25–7.35 (m, 8H, Ar) ppm. 31
P
NMR: δ = + 37.62 ppm. MS: m/z (%): 435 (M+, 85).
Reaction of 3a with Tris(dialkylamino)phosphine 2a or 2b
A mixture of 3a (0.27 g; 0.001 mol), tris(dialkylamino)phosphine 2a
or 2b (0.002 mol) and dry toluene (30 mL) was refluxed until no more
of the starting materials could be detected (TLC, 6–8 h). The reaction
mixture was evaporated under reduced pressure and then applied to
silica gel column chromatography to give products 9a and 9b.
[7-(Benzylidene)-2-oxo-3-phenyl-2,3,4,5,6,7-hexahydro-2λ5-
benzo[d][1,2]oxa-phosphol-2-yl]-dimethylamine (9a)
Eluent: ethyl acetate:petroleum ether (90:10, v/v), colorless crystals,
◦
mp 160–161 C, yield 85%. Anal. calcd. for C22H24NO2P (365.41): C,
72.31, H, 6.62, N, 3.83, P, 8.48. Found. C, 72.38, H, 7.67, N, 3.88, P,
8.50%. IR (KBr): ν = 1240 (P=O) cm−1, 1320 cm−1, 860 cm−1 (P-N(CH3)2;
1H NMR (DMSO) :δ = 2.68 (d, JHP = 7.5 Hz, 6H, P-N(CH3)2), 1.94 (m,
2
2H, CH2), 1.69 (t, 2H, CH2), 2.01 (t, 2H, CH2), 4.26 (d, JHP = 18.75
Hz, P-CH), 7.17–7.40 (m, 10H, Ar), 6.73 (s, -CH = ) ppm; 13C NMR
(DMSO): δ = 45.89 (P-CH, 1JCP = 107.2 Hz), 38.5 [P-N(CH3)2] ppm; 31
P
NMR (DMSO):δ = +46.02 ppm; MS, m/z (%): 365 (M+,100).
[7-(Benzylidene)-2-oxo-3 -phenyl)-2,3,4,5,6,7-hexahydro-2λ5-
benzo[d][1,2]oxaphosphol-2-yl]-diethylamine (9b)
Eluent: ethyl acetate:petroleum ether (10:90, v/v), colorless crystals,
mp 181–182 ◦C, yield 80%. Anal.calcd. for C24H28NO2P(393.46): C,
73.26, H, 7.17, N, 3.56, P, 7.87. Found. C, 73.29, H, 7.20, N, 3.58, P,
1
7.89%. IR (KBr): ν = 1325, 865 (P-N-CH2CH3), 1242 (P=O) cm−1; H
NMR (300 MHz, CDCl3): δ = 3.87 (d, 2JHP = 13.5 Hz, P-CH), 3.22, 3.15
[q, 4H, N(CH2CH3)2], 1.15 [t, 6H, N(CH2CH3)2], 2.06 (t, 2H, CH2), 1.62
(t, 2H, CH2), 1.77 (m, 2H, CH2), 6.89 (s, 1H, HC = ), 7.27- 7.36 (m,10H,
Ar) ppm; 13C NMR (300 MHz, CDCl3): δ = 45.1 (d, P-CH, 1JCP = 105.8
Hz), 40.6 [P-N(CH2CH3)2], 14.8 [P-N(CH2CH3)2] ppm. MS: m/z (%):
393 (M+, 100).
Reaction of Trisdialkylaminophosphine 2a and 2b with
2,6-Bis(4-chlorobenzylidene)-cyclohexanone (3b)
To a solution of 3b (0.34 g; 0.001 mol) in dry toluene (30 mL),
tris(dialkylamino)phosphine 2a or 2b (0.002 mol) was added dropwise,
and the reaction mixture was refluxed for 8–10 h. The solution was

Synthesis of New Benzoxaphosphole Derivatives
2823
evaporated under reduced pressure, and the residue was subjected to
silica gel column chromatography to give 9c and 9d.
[7-(4-Chlorobenzylidene)-3-(4-chlorophenyl)-2-oxo-2,3,4,5,6,7-
hexahydro-2λ5-benzo-[d][1,2]oxaphosphol-2-yl]-
dimethylamine (9c)
Eluent: ethyl acetate:petroleum ether (95:5, v/v), colorless crystals,
mp 245–247◦C, yield 75%. Anal. calcd. for C22H22 Cl2NO2P (434.30)
C, 60.84, H, 15.11, Cl, 16.33, N, 3.23, P, 7.13. Found. C, 60.88, H,
15.17, Cl, 16.38, N, 3.25, P, 7.17%. IR (KBr): ν = 1312,865 cm−1
P
1
2
[N(Me)2]; H NMR (300 MHz, CDCl3): δ = 3.53 (d, JHP = 13.6 Hz,
P-CH), 2.47 (d, 3JHP = 9.3 Hz, 6H, P-N(CH3)2), 1.96 (t, 2CH2), 1.37 (m,
CH2), 6.36 (s, CH, 1H), 7.15–7.24 (m, 8H, 4-Cl-Ar) ppm;13C NMR (300
1
MHz, CDCl3): δ = 45.5 (C-P, d, JCP = 104.9 Hz), 123.9, 140.6 (C6H4-
CH = C),121.30, 140.22 (C=C), 130.5, 128.8, 131.2, 135.9, 127.8,126.4,
125.8, 131.2 (2C6H4) ppm. MS, m/z (%): 434 (90, M+).
[7-(4-Chloro-benzylidene)-3-(4-chlorophenyl)-2-oxo-2,3,4,5,6,7-
hexahydro-2λ5-benzo-[d][1,2]oxaphosphol-2-yl]-diethylamine
(9d)
Eluent: acetone:petroleum ether (15:85, v/v), colorless crystals, mp
194–195 ◦C, yield 85%. Anal. calcd for. C24H26Cl2N O2P (462.35)C,
62.35, H, 5.67, Cl, 15.34, N, 3.03, P, 6.70. Found. C, 62.38, H, 5.70,
Cl, 15.37, N, 3.07, P, 6.73%. IR (KBr): ν = 1310, 854 [P-N(CH2CH3)2]
1
2
cm−1; H NMR (300 MHz, CDCl3) : δ = 3.79 (d, JHP = 13.2 Hz, P-
CH), 3.23, 3.14 [q, 4H, N(CH2CH3)2], 1.2 [t, 6H, N(CH2CH3)2], 2.01
(t, 2H, CH2), 1.77 (m, 2H, CH2), 1.58 (t, 2H, CH2), 6.82 (s, 1H, -CH
= ), 7.13–7.34 (m, 8H, Ar) ppm; 13C NMR (300 MHz, CDCl3) : δ =
47.14 (d, P-CH, JCP = 104.0 Hz), 38.97, 38.94 (2NCH2 CH3), 14.55
(2NCH2CH3), 26.71, 23.88, 22.73 (3CH2), 135.2, 130.5, 130.4, 128.8
(4-Cl-C6H4), 132.6, 133.0, 128.9, 128.63 (4-Cl-C6H4), 123.5, 148.4 (C
=CH-), 148.4 (C-O−) ppm. MS: m/z (%): 462 (M+, 85).
Reaction of 2,6-Bis(4-dimethylaminobenzylidene)
cyclohexanone (3c) with Tris(dialkylamino)phosphine 2a and
2b
Tris(dialkylamino)phosphine 2a or 2b (0.002 mol) was added dropwise
to a solution of compound 3c (0.36 g; 0.001 mol) in dry toluene (30 mL),
and the reaction mixture was refluxed for 12–15 h. After evaporation of
the volatile materials under reduced pressure, the residue was applied
to silica gel column chromatography. The eluent, yield, and mp are
given below for adducts 9e and 9f.

2824
M. H. N. Arsanious et al.
[7-(4-Dimethylaminobenzylidene)-3-(4-dimethylaminophenyl)-
2-oxo-2,3,4,5,6,7-hexahydro-2λ5-benzo[d][1,2]oxaphosphol-2-
yl]dimethylamine (9e)
Eluent: ethyl acetate:petroleum ether (12:88, v/v), yellow crystals,
◦
mp 226–228 C, yield 80%. Anal. calcd. for C26H34N3O2P (451.54) C,
69.16, H, 7.59, N, 9.31, P, 6.86. Found. C, 69.28, H, 7.64, N, 9.35, P,
6.88%. IR (KBr): ν = 1240 (P=O) cm−1, 1320, 860 (PN(CH3)2) cm−1
;
3
1H NMR (300 MHz, CDCl3) : δ = 2.79 (d, 6H, JHP = 9.9 Hz, P(N-
CH3)2), 2.98, 2.96 (12H, 2 (N(CH3)2), 3.78 (d, 1H, 2JHP = 13.2 Hz, P-CH),
6.70–7.27 (m, 9H, Ar-H, and =CH) ppm; 13C NMR (300 MHz,CDCl3): δ
= 45.86 (HC-P, d, 1JCP = 107.2 Hz), 40.1 [N(CH3)2], 38.1{d, 2JCP = 6.2
2
2
Hz, P[N (CH3)2]}, 148.60 [d, JCP = 9.7 Hz, P[O-C=C], 129.70 [d, JCP
= 5.96 Hz, Ar-C-CH-P] ppm; 31P NMR: δ = +46.02 ppm. MS, m/z (%):
451 (M+,100).
[7-(4-Dimethylaminobenzylidene)-3-(4-dimethylaminophenyl)-
2-oxo-2,3,4,5,6,7-hexahydro-2λ5-benzo[d][1,2]oxaphosphol-2-
yl]-diethylamine (9f)
Eluent: ethyl acetate:petroleum ether (18:82, v/v), colorless crystals,
mp 246–247◦C, yield 85%. Anal. calcd. for C28H38N3O2P (479.59): C,
71.32, H, 6.41, N, 8.91, P, 6.57. Found. C, 71.35, H, 6.43, N, 8.94, P,
1
6.59%. IR (KBr): ν = 1356, 898 (P-N(Et)2) cm−1; H NMR (300 MHz,
2
CDCl3) : δ = 1.21 (t, 6H, 2NCH2CH3), 3.81 (d, JHP = 10.8 Hz, P-CH),
3.00, 2.95 [12H, 2N(CH3)2], 3.16, 3.09 (m, 4H, 2NCH2CH3), 1.77 (m,
4H, 2CH2), 2.06 (t, 2H, CH2), 6.73–7.31 (m, 9H, Ar, and =CH) ppm; 13
C
NMR (300 MHz, CDCl3): δ = 46.7 (HC-P, 1JCP = 107.5 Hz), 38.78, 38.75
[P-NCH2CH3,3JCP = 4.8 Hz), 14.5 (P-NCH2CH3), 26.97, 23.92, 22.96
(3CH2), 40.7 [P-N(CH3)2], 121.4, 148.5 (C =CHAr), 148.6 (C-O), 130.3,
129.8, 125.3, 124.4 (CH-Ar), 129.7, 124.5, 124.1, 116.4 (Ar-CH =) ppm.
MS, m/z (%): 479 (100) [M+].
7-Benzyl-3-phenyl-2,4,5,6-tetrahydro-1,2-benzoxaphosphol-2-
ol-2-oxide (10)
0.36 g (0.001 mol) of 9a was refluxed in dry xylene for 1 h. After evapo-
ration of the volatile materials under reduced pressure, the residue was
crystallized from toluene to give 10 as colorless crystals, mp 134–135 ◦C.
Anal. calcd.for C20H19O3P (338.34): C, 71.00, H, 5.66, P, 9.15. Found. C,
71.05, H, 5.69, P, 9.20%. IR (KBr): ν = 2560 (P-OH) cm−1; 1H NMR (300
MHz, CDCl3): δ = 3.6 (s, 2H, CH2-benzyl), 2.17, 2.18, (2t, 4H, 2CH2),
2.70 (m, 2H, CH2), 7.22–7.55 (m, 10H, Ar), 1.7 (b, OH, exchangeable
with D2O) ppm. MS, m/z (%): 338 (M+,100).

Synthesis of New Benzoxaphosphole Derivatives
2825
TABLE III The Antibacterial and Antifungal Activities
of the Synthesized Compounds
Inhibition zone diameter mm/mg sample
Gram-negative
bacteria
Gram-positive bacteria
Compound No.
Escherichia coli
Staphylococcus aureus
Chloroform
0.0
11
12
12
14
0.0
12
12
13
15
3b
3c
9e
5d
9f
11
12
5c
9a
5a
1.0
0.6
0.4
3.0
2.6
1.1
BIOLOGICAL ACTIVITY
The antibacterial and antifungal activities were carried out in the Mi-
crobiology Division of the Microanalytical Center of Cairo University,
using the diffusion plate method.18–21 A bottomless cylinder containing
a measured quantity (1 mL, mg/mL) of the sample is placed on a plate (9
cm diameter) containing a solid bacterial medium (nutrient agar broth)
or a fungal medium (Dox’s medium), which has been seeded with the
spore suspension of the test organism. After incubation (24 h for bac-
teria and 5 days for fungi), the diameter of the clear zone of inhibition
surrounding the sample is taken as a measure of the inhibitory power of
the sample against the particular test organism (1% inhibition = sam-
ple inhibition zone (cm)/plate diameter × 100). All measurements were
done in chloroform as the solvent, which has zero inhibition activity.
The antimicrobial activity of the tested compounds was examined with
Gram-positive bacteria Staphylococcus aureus and Gram-negative bac-
teria Escherichia coli. As shown in (Table III), the cyclic adduct 5 was
found be active against Gram-negative bacteria Escherichia coli with
respect to other derivatives. The antifungal activity of compounds 4a
and 5 was found to be higher than others.
REFERENCES
[1] J. R Dimmock and M. L Wong, Can. J. Pharm. Sci., 11, 35 (1976).
[2] L. S. Boulos and H. A. Abd El-Malek, Phosphorus, Sulfur, and Silicon, 179, 97
(2004).

2826
M. H. N. Arsanious et al.
[3] L. S. Boulos and H. A. Abd El-Malek, Indian J. Heterocycl. Chem., 14, 245 (2005).
[4] L. S. Boulos, N. K. El-Din, and M. H. N. Arsanious, Phosphorus, Sulfur, and Silicon,
181, 1467 (2006).
[5] L. S. Boulos, E. M. A Yakout, and M. H. N. Arsanious, Phosphorus, Sulfur, and
Silicon, 181, 1615 (2006).
[6] M. H. N. Arsanious and L. S. Boulos, Monatsh. Chem., 137, 1177 (2006).
[7] L. S. Boulos, M. H. N. Arsanious, and E. M. A Yakout, Monatsh. Chem., 138, 979
(2007).
[8] L. S. Boulos and M. H. N. Arsanious, Synth. Commun., 32, 2779 (2001).
[9] M. H. N. Arsanious and L. S. Boulos, Heteroatom. Chem., 12, 511 (2001).
[10] M. Hesse, M. Meier, and B. Zeeh, Spektroskopische Methoden in der Organischem
Chemie (Thieme Verlag, Stuttgart, Germany, 1991), Chap. 2.1, p. 64.
[11] E. Pretsch, J. Seibl, and W. Simon, Tables of Spectral Data for Structure Determi-
nation of Organic Compounds (Springer-Verlag, Berlin, Germany, 1983).
[12] S. Mackay, C. J Gilmore, C. Edward, N. Stewart, and K. Shankland, Maxus Com-
puter Program for the Solution and Refinement of Crystal Structures Bruker Non-
ius, The Netherlands, MacSciene, Japan, and The University of Glasgow (1999).
[13] C. K. Johnson, ORTEP-11: A Fortran Thermal-Ellipsoid Plot Program. Report
ORNL-5138, Oak Ridge, Tennessee, USA (1976).
[14] W. Z. Otwinowski, In Methods in Enzymology, C. W. Minor, Jr. and R. M. Carter
Sweet, Eds. (Academic Press, New York, 1997), p. 276.
[15] A. Altomare, G. Cascarano, C. Giacovazzo, M. C. Guagliavdi Burla, G. Polidori, and
M. Camalli, J. Appl. Cryst. 27, 435 (1994).
[16] M. M. Crutchfield, C. H. Dungan, J. H. Letcher, V. Mark, and J. R. Van Wazer,
Topics in Phosphorus Chemistry, M. Graysor and E. J. Griffith, Eds. (Interscience
Publishers, New York, 1967), vol. 5, p. 227.
[17] A. A. El-Kateb, L. S. Boulos, and H. A. Abd El-Malek, Phosphorus, Sulfur, and
Silicon, 83, 105 (1993).
[18] S. Apers, D. Paper, J. Burgermeister, S. Baronikova, S. Van Dyck, G. Lemiere, A.
Vlietinck, and L. Pieters, J. Nat. Prod., 65, 718 (2002).
[19] J. A. Walker, K. Rossen, R. A. Reamer, R. P. Volante, and P. T. Reider, Tetrahedron
Lett., 40, 4917 (1999).
[20] A. G. Gamzalez, J. B Barrera, A. C. Yames, J. G. Diaz, and E. M. Rodriguez, Phyto-
chemistry, 28, 2520 (1989).
[21] C. F. Carvalho and M. V. Sargent, J. Chem. Soc., Perkin Trans. 1, 1605 (1984).