Synthesis of 3-(4-Methyl-phenyl)-2-phenyl-3,4-dihydro-2H-benzo[e][1,3,2] oxazaphosphinine and Its Chalcogenides

Article abstract of DOI:10.14233/ajchem.2013.13937

A simple method for the synthesis of 3-(4-methyl-phenyl)-2-phenyl-3,4- dihydro-2H-benzo[e][1,3,2]oxazaphosphinine (2) is described. P-Chalcogenides of (2) can be prepared by reacting with S, Se powder in toluene at 110°C. Whereas the tungsten pentacarbony

Full text of DOI:10.14233/ajchem.2013.13937

Asian Journal of Chemistry; Vol. 25, No. 6 (2013), 3449-3451
http://dx.doi.org/10.14233/ajchem.2013.13937
Synthesis of 3-(4-Methyl-phenyl)-2-phenyl-3,4-dihydro-
2H-benzo[e][1,3,2]oxazaphosphinine and Its Chalcogenides
*
MANJU RANI, DAVENDER KUMAR SHUKLA and ARIF ALI KHAN
University School of Basic and Applied Sciences, Guru Gobind Singh Indraprastha University, Dwarka, Sector 16C, New Delhi-110 078, India
*Corresponding author: E-mail: khanaarif@hotmail.com
(Received: 23 April 2012;
Accepted: 24 December 2012)
AJC-12612
A simple method for the synthesis of 3-(4-methyl-phenyl)-2-phenyl-3,4-dihydro-2H-benzo[e][1,3,2]oxazaphosphinine (2) is described.
P-Chalcogenides of (2) can be prepared by reacting with S, Se powder in toluene at 110 ºC. Whereas the tungsten pentacarbonyl complex
(6) can be prepared by reacting (2) with W(CO)5CH3CN in THF at 20-25 ºC.
Key Words: Phosphorous-heterocycles, Oxazaphosphinine, Phosphorous-chalcogenides.
were observed. Mass spectra were recorded on a Shimadzu
GC-MS mass spectrometer operating at an ionization potential
of 20 eV.
INTRODUCTION
Organic compounds being ubiquitous in nature have found
multifaceted applications. The chemistry of phosphorus-
heterocycles and their derivatives have received considerable
attention because of their biological activities1,2. Cyclophos-
phamide containing an oxazaphosphinine is proven alkylating
antitumor agent against a wide spectrum of human cancer
including slow-growing solid tumours3. The organophospho-
rus heterocycles containing O and N in a six-membered ring
possess high antitumor and antimicrobial activity4. The clinical
significance and unique confirmation and stereochemical
aspects of oxazaphosphinines have attracted much interest in
drug design and synthesis5. The common approach for the
synthesis of oxazaphosphinine by cyclization with phosphoryl
chloride and thiophosphoryl chloride is described in the lite-
rature6-8.
Procedure for the preparation of compounds
Synthesis of 2-[(4-methyl-phenylamino)methyl]phenol
(1): Prepared according to the literature9.
Synthesis of 3-(4-methyl-phenyl)-2-phenyl-3,4-
dihydro-2H-benzo[e][1,3,2]oxazaphosphinine (2):A solution
of phenyldichlorophosphine (2 mmol) in dry toluene (20 mL)
was added drop wise to a cooled (0-5 ºC) solution of 2-[(4-
methyl-phenylamino)methyl]phenol (2 mmol) and triethyl-
amine (4 mmol) in dry toluene (40 mL). After addition, the
reaction mixture was stirred for an additional 2-3 h at 20-25 ºC.
The salt thus formed was removed by filteration under nitrogen
and the solvent was removed under reduced pressure to obtain
semi solid material. The product thus obtained was purified
by low temperature column chromatography (SiO2, 5 ºC,
hexane:THF; 98:2). Evaporation of the solvents of the second
fraction and recrystallization from diethyl ether at 5 ºC yielded
3-(4-methyl-phenyl)-2-phenyl-3,4-dihydro-2H-benzo-
[e][1,3,2]oxazaphosphinine as offwhite crystalline solid,
yield 38 %, m.p. 116-117 ºC.
Herein, we reported a new method to synthesize
oxazaphosphinine and its chalcogenides from the readily
available starting precursors.
EXPERIMENTAL
Starting materials and solvents were obtained from Merck
and Spectrochem and were used with further purification. Low
temperature coloumn chromatography performed with dried
silica gel. IR spectra were measured on a Shimadzu IR-460
spectrophotometer. 1H and 13C NMR spectra were measured
(CDCl3 solution) with a bruker DRX-250Avance spectrometer
at 250.0 and 62.5 MHz, respectively. Progress of reaction was
monitored by TLC as well as 31P NMR and no side products
Synthesis of 3-(4-methyl-phenyl)-2-phenyl-3,4-
dihydro-2H-benzo[e][1,3,2]-oxazaphosphinine-2-oxide (3):
To a pre-cooled dichloromethane solution of 3-(4-methyl-
phenyl)-2-phenyl-3,4-dihydro-2H-benzo[e][1,3,2]oxazaphos-
phinine (2 mmol) at -80 ºC, DMSO (3 mmol) was added drop
wise and stirring was continued for 0.5 h at -80 ºC and 2 h at
20-25 ºC. The solvent was removed under reduced pressure

3450 Rani et al.
Asian J. Chem.
and the product was separated by low-temperature column
chromatography (SiO2, 5 ºC, Hexane: THF; 98:2). Evaporation
of the solvents of the second fraction and recrystallization from
diethyl ether at 5 ºC yielded 3-(4-methyl-phenyl)-2-phenyl-
3,4-dihydro-benzo[e][1,3,2]-oxazaphosphinine-2-oxide as
Creamish crystalline solid. Creamish crystalline solid, yield
80 %, m.p. 100-101 ºC.
P-chalcogenides (4) and (5) were prepared by reacting 3-(4-
methyl-phenyl)-2-phenyl-3,4-dihydro-2H-benzo[e][1,3,2]-
oxazaphosphinine with elemental sulphur and selenium powder
in dry toluene at 110 ºC. Tungten pentacarbonyl complex (6)
was prepared by reacting (2) with W(CO)5CH3CN in THF at
20-25 ºC and purified by recrystallization with diethyl ether10,11
.
They were characterized by IR, 1H, 13C, 31P NMR and GC-MS
spectroscopic data. The infrared spectra of 3-(4-methyl-phenyl)-
2-phenyl-3,4-dihydro-benzo[e][1,3,2]-oxazaphosphinine-2-
selenide (5) shows a strong and sharp absorption band at 586.3
cm-1 which has been assigned to -P=Se stretching absorption
vibrations. The proton magnetic resonance spectrum of compound
(5) shows two doublet at δ 4.454-4.906 for two methylene
protons (ArCH2N) which confirms the protons present are non
equivalent.All the aromatic protons appear as multiplet 6.998-
7.918 for 13H. The phosphorus magnetic resonance spectrum
of compound (5) shows a doublet at δ 82.932 with a coupling
constant of 871.3 Hz, due to phosphorous selenium coupling.
In the carbon magnetic resonance spectrum of compound (5)
shows fifteen carbon, which are well in accordance to the
proposed structure. A dominant peak at δ 52.08 confirms the
methylene carbon atom. Carbon bonded to endocyclic oxygen
gave signals at 140.67. Rest of thirteen peaks at δ 119.30,
123.88, 124.48, 126.49, 126.78, 128.13, 128.33, 129.09,
129.57, 131.63, 131.80, 132.58, 135.95 fairly confirms the
aromatic carbons. Mass spectral data of compound (5) shows
molecular ion peaks corresponding to the molecular mass
399.02 with further fragments at 91.00 (18.00), 135.95 (41.20),
318.00 (100.00), 319.00 (23.61), 398.90 (1.87).
Synthesis of 3-(4-methyl-phenyl)-2-phenyl-3,4-dihydro-
2H-benzo[e][1,3,2]-oxazaphosphinine-2-sulphide (4): A
solution of 3-(4-methyl-phenyl)-2-phenyl-3,4-dihydro-2H-
benzo[e][1,3,2]oxazaphosphinine (1 mmol) and elemental
sulfur (10 mmol) in 20 mL toluene was heated at 108-110 ºC
for 5-6 h. The resulting dark brown solution was filtered hot
under nitrogen and concentrated under reduced pressure. The
crude product thus obtained was separated by low-temperature
column chromatography (SiO2, 5 ºC, hexane: THF; 98:2).
Evaporation of the solvents of the second fraction and recrys-
tallization from diethyl ether at 5 ºC yielded 3-(4-methyl-
phenyl)-2-phenyl-3,4-dihydro-2H-benzo[e][1,3,2]-
oxazaphosphinine-2-sulphide as yellow crystalline solid.
Yellow crystalline solid, Yield 28 %, m.p. 92-93 ºC.
Synthesis of 3-(4-methyl-phenyl)-2-phenyl-3,4-dihydro-
2H-benzo[e][1,3,2]-oxazaphosphinine-2-selenide (5): A
solution of 3-(4-methyl-phenyl)-2-phenyl-3,4-dihydro-2H-
benzo[e][1,3,2]oxazaphosphinine (1 mmol) and elemental
selenium powder (10 mmol) in 20 mL toluene was heated at
108-110 ºC for 6-7 h. The resulting reddish brown solution
was filtered hot under nitrogen and concentrated under reduced
pressure. The crude product thus obtained was separated by
recrystallization from diethyl ether at 5 ºC yielded 3-(4-
methyl-phenyl)-2-phenyl-3,4-dihydro-2H-benzo[e][1,3,2]
oxazaphosphinine-2-selinide as orange crystalline solid.Yield
32 %, m.p. 122-123 ºC.
R
O
N
Synthesis of 3-(4-methyl-phenyl)-2-phenyl-3,4-
dihydro-2H-benzo[e][1,3,2]-oxazaphosphinine-W(CO)5
complex (6):A solution of 3-(4-methyl-phenyl)-2-phenyl-3,4-
dihydro-2H-benzo[e][1,3,2]oxazaphosphinine (1 mmol) and
W(CO)5CH3CN (1.1 mmol) in 20 mL THF was stirred at
25-30 ºC for 6-8 h. The resulting dark brown solution was
filtered under nitrogen and concentrated under reduced
pressure. The crude product thus obtained was separated by
low-temperature column chromatography (SiO2, 5 ºC, hexane:
diethyl ether; 98:2). Evaporation of the solvents of the second
fraction and recrystallization from diethyl ether at 5 ºC yielded
3-(4-methyl-phenyl)-2-phenyl-3,4-dihydro-2H-benzo[e]-
[1,3,2]oxazaphosphinine-W(CO)5 complex as off white
crystalline solid. Yield 60 %, m.p. 100-101 ºC.
H
R-NH2
MeOH
H
25-30 °C
OH
OH
R
HN
R
H
N
P
PhPCl2
Toluene
0-5 °C
NaBH4
0-5 °C
OH
O
Ph
(1)
(2)
Where
R = 4-CH3C6H4
Reaction schemes (Scheme-S1)
RESULTS AND DISCUSSION
R
N
The intermediate 3-(4-methyl-phenyl)-2-phenyl-3,4-
dihydro-2H-benzo[e][1,3,2]oxazaphosphinine (2) was obtained
from cyclocondensation of 2-[(4-methyl-phenylamino)methyl]-
phenol with dichlorophenylphosphine in equimolar quantities
in presence of triethylamine in dry toluene at room temperature
(35 ºC) overnight yielded title compound. The P-oxide deri-
vative (3) was selectively prepared by reacting 3-(4-methyl-
phenyl)-2-phenyl-3,4dihydro-2H-benzo[e][1,3,2]-
oxazaphosphinine (2) with DMSO in dry MDC at -80 ºC. The
DMSO, MDC
O
R
P
N
P
-80 °C, 2h
O
Ph
R
(3)
S, Se, Toluene
110 °C, 5-6h
O
Ph
N
(2)
Ph
P
O
X
X= S (4), Se (5)
Reaction scheme (Scheme-S2)

Vol. 25, No. 6 (2013)
Synthesis of 3-(4-Methyl-phenyl)-2-phenyl-3,4-dihydro-2H-benzo[e][1,3,2]oxazaphosphinine 3451
R
N
R
TABLE-5
N
P
W(CO)5CH3CN, THF
20-25 °C, 6-8 h
GC-MASS SPECTRAL DATA OF COMPOUNDS 2-5
Ph
P
Compound No.
GC-Mass data
O
Ph
O
m/z 319.10, mass fragments 91.10 (28.25), 136.05
(100.00), 242.05 (44.65), 318.00 (22.65), 319.10
(53.59).
2
3
4
5
W(CO)5
(2)
(6)
Reaction scheme (Scheme-S3)
m/z 335.10, mass fragments: 91.05 (21.09), 229.05
(25.61), 244.00 (42.92), 258.05 (20.76), 270.10
(20.76), 334.10(47.53), 335.10 (100.00).
m/z: 351.00, mass fragments: 91.00 (22.63), 135.95
(30.32), 318.00 (100.00), 319.00 (22.13), 351.00
(15.12).
TABLE-1
ELEMENTAL ANALYSIS OF COMPOUNDS 2-6
Elemental analysis (%) found (calcd.)
Comp.
No.
m.f.
C
H
N
m/z: 399.02, mass fragments: 91.00 (18.00), 135.95
(41.20), 318.00 (100.00), 319.00 (23.61), 398.90
(1.87).
C20H18NOP
C20H18NO2P
C20H18NOPS
75.16(75.22) 5.62 (5.68) 4.31(4.39)
71.56(71.63) 5.39 (5.41) 4.09(4.18)
68.26(68.36) 5.01 (5.16) 3.89(3.99)
2
3
4
5
6
C20H18NOPSe 60.13(60.31) 4.49 (4.56) 3.50(3.52)
C25H18NO6PW 46.56(46.68) 2.75 (2.82) 2.12(2.18)
TABLE-6
INFRARED SPECTRAL DATA OF COMPOUNDS 2-6
Compound No.
Absorption peaks (cm-1)
947.0, 1128.3 (P-O-Caromatic
1245.9 (P=O)
TABLE-2
1H NMR SPECTRAL DATA OF COMPOUNDS 2-6
)
2
3
4
5
6
Compound No
1H NMR Data
688.5 (P=S)
δ 2.260 (s, 3H, ArCH3), 4.456-4.906 (dd, 2H,
ArCH2N), 7.032-7.944 (m, 13H, aromatic).
586.3 (P=Se)
2
941.2, 1155.3, 1994.3 and 2075.3 (CO)
δ 2.265 (s, 3H, ArCH3), 4.658-4.708 (dd, 2H,
ArCH2N), 7.043-7.712 (m, 13H, aromatic).
3
4
5
6
δ 2.271(s, 3H, ArCH3), 4.509-4.820 (dd, 2H,
ArCH2N), 7.046-7.893 (m, 13H, aromatic).
Conclusion
An efficient method is described to synthesize 3-(4-methyl-
phenyl)-2-phenyl-3,4-dihydro-2H-benzo[e][1,3,2]oxazaphos-
phinine and its chalcogenides. Simple and readily available
starting materials, fairly short reaction time and good to excellent
yields of the products are advantages of this method.
δ 2.259 (s, 3H, ArCH3), 4.454-4.906 (dd, 2H,
ArCH2N), 6.998-7.918 (m, 13H, aromatic).
δ 2.342 (s, 3H, ArCH3), 4.104-4.667 (dd, 2H,
ArCH2N), 6.736-7.694 (m, 13H, aromatic).
TABLE-3
31P NMR SPECTRAL DATA OF COMPOUNDS 2-6
ACKNOWLEDGEMENTS
Compound No.
31P NMR
112.813
13.773
Coupling constant
The authors (MR,AAK) are thankful to CSIR, New Delhi
for financial assistance.
–
2
3
4
5
6
–
77.065
–
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82.932
Doublet, J = 871.3 Hz
Triplet, J = 325.620 Hz
125.254
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13C NMR SPECTRAL DATA OF COMPOUNDS 2-6
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