Synthesis and spectral characterization of N-[2-(4-halophenoxy)-3-(3- chlorophenyl)-3, 4-dihydro-2H-1,3,2-Λ5-benzoxazaphosphinin-2- yliden]-N-substituted amines by the Staudinger reaction

Article abstract of DOI:10.1002/hc.20639

The synthesis of the title compounds was accomplished in four steps. The synthetic route involves the preparation of Schiff's base by reacting salicylaldehyde with m-chloroaniline in EtOH. The Schiff's base was then reduced with NaBH₄/MeOH. In the second step, PCl₃ was reacted with p-chlorophenol/p-bromophenol in THF in the presence of Et₃N to obtain P(III) dichloride derivatives. The reduced Schiff's base and dichloride derivatives were reacted in equimolar quantities in the presence of Et ₃N in THF to get the cyclized product. Alkyl azides were prepared by reacting alkyl bromides with sodium azide, and then alkyl azides were treated with the cyclized product to obtain the title compounds. The structure of these novel compounds was elucidated by elemental analysis, IR, ¹H, ¹³C, ³¹P NMR, and mass spectroscopy.

Full text of DOI:10.1002/hc.20639

Heteroatom Chemistry
Volume 21, Number 7, 2010
Synthesis and Spectral Characterization of
N-[2-(4-Halophenoxy)-3-(3-chlorophenyl)-3,
5
4-dihydro-2H-1,3,2-λ -benzoxazaphosphinin-
2-yliden]-N-Substituted Amines by the
Staudinger Reaction
C. Venkateswarlu,1 P. V. V. Satyanarayana,2 C. V. Nageswara Rao,3
K. Reddy Mohan Naidu,4 and C. Naga Raju4
1Department of Chemistry, K. V. R. College, Nandigama 521 185, India
2Department of Chemistry, Acharya Nagarjuna University, Nagarjuna Nagar 522 510, India.
3P. G. Department of Chemistry, AG & SG Siddhartha College of Arts & Science,
Vuyyuru 521 165, India
4Department of Chemistry, Sri Venkateswara University, Tirupati 517 502, India
Received 12 February 2010; revised 22 July 2010
ABSTRACT: The synthesis of the title compounds
was accomplished in four steps. The synthetic route
involves the preparation of Schiff’s base by reacting
salicylaldehyde with m-chloroaniline in EtOH. The
Schiff’s base was then reduced with NaBH4/MeOH.
In the second step, PCl3 was reacted with p-
chlorophenol/p-bromophenol in THF in the presence
of Et3N to obtain P(III) dichloride derivatives. The
reduced Schiff’s base and dichloride derivatives were
reacted in equimolar quantities in the presence of
Et3N in THF to get the cyclized product. Alkyl azides
were prepared by reacting alkyl bromides with sodium
azide, and then alkyl azides were treated with the
cyclized product to obtain the title compounds. The
structure of these novel compounds was elucidated
by elemental analysis, IR, 1H, 13C, 31P NMR, and
INTRODUCTION
Staudinger and Meyer [1] reported the first synthe-
sis of phosphazo compounds in 1919 by the reac-
tion of tertiary phosphines with organic azides. The
Staudinger reaction, in its classical form, is a two-
step process involving the initial electrophilic addi-
tion of an azide to a trivalent phosphorus center fol-
lowed by nitrogen elimination from the intermediate
phosphazide giving the iminophosphorane.
It has not attracted the attention of the chemists
for about three to four decades after its discovery.
The landmark discovery of the imination of phos-
phorus pentachloride and its derivatives by com-
pounds containing the amino group by Kirsanov
[2] initiated an extensive development of chemistry
of phosphazo compounds and renewed the interest
to the Staudinger reaction. They examined a vari-
ety of new oxidative imination reactions of triva-
lent phosphorus compounds producing phosphazo
derivatives. A substantial contribution that extended
the area of exploration and utilization of Staudinger
reaction was made by Kabachnik et al. [3–5]. They
demonstrated that besides the tertiary phosphines,
ꢀ
C
mass spectroscopy.
2010 Wiley Periodicals, Inc. Het-
eroatom Chem 21:499–504, 2010; View this article online
at wileyonlinelibrary.com. DOI 10.1002/hc.20639
Correspondence to: C. V. Nageswara Rao; e-mail: chavavnrao@
gmail.com.
c
ꢀ
2010 Wiley Periodicals, Inc.
499

500 Venkateswarlu et al.
the esters of phosphorus acids may also be used for
the preparation of phosphazo compounds, and this
fact opened up new possibilities of the Staudinger
reaction and prompted its application.
Cl
Cl
THF
TEA
P
O
X
+
HO
X
PCl3
Warm, N2 Atm.
(2)
X = Cl, Br
The phosphazo reaction is generally used for the
synthesis of P-halogenated products. The Staudinger
reaction, on the other hand, is more convenient for
the synthesis of P-alkoxylated, P-thioalkylated, P-
aroxylated, and P-aminated phosphazo compounds.
Iminophosphoranes play an important role in
heterocyclic synthesis [6,7]. In few cases, the in-
termediate phosphazides have been isolated [8] or
trapped via an intermolecular reaction [9]. But most
of such phosphazides lose nitrogen at room temper-
ature to give the corresponding iminophosphoranes
in practically quantitative yields.
The expansion of the traditional frames of the
classical Staudinger reaction has resulted in the syn-
thesis of numerous new compounds with nitrogen–
phosphorus bonds. Even after nine decades, the re-
action is still with a lot of unspent potential and it
continues to intrigue and stimulate researchers.
In the third step, 1 was reacted with 2 in equimolar
quantities in the presence of Et3N in THF to obtain
the cyclized product 3.
H
N
CH2
OH
Cl
+
P
O
X
Cl
Cl
(2)
(1)
Et3N
THF
N
P
O
Cl
O
RESULTS AND DISCUSSION
Keeping the synthetic importance of the Staudinger
X
reaction in view,
N-[2-(4-halophenoxy)-3-(3-
chlorophenyl)-3,4-dihydro-2H-1,3,2-λ5-benzoxazaph-
osphinin-2-yliden]-N-substituted amines (5–12)
were synthesized. The synthesis of the title com-
pounds was accomplished in four steps.
(3)
Alkyl azides were prepared by reacting alkyl bro-
mides with sodium azide
By
reacting
salicylaldehyde
with
m-
chloroaniline, in ethyl alcohol, Schiff’s base
was obtained. This Schiff’s base was reduced by
using NaBH4/MeOH to afford the reduced Schiff’s
base (1).
THF
35–40oC
+
+
RBr
NaN3
R–N3
NaBr
(4)
NH2
CHO
OH
N
CH
In the fourth step, 3 was reacted with various alkyl
azides 4 to afford the title compounds 5–12 in opti-
mum yields.
EtOH
+
OH
Schiff'sbase
Cl
m-chloroaniline
Cl
The synthetic and physical data of 5–12 are
presented in Table 1. The infrared spectral study of
all the title compounds (5–12) was made with a view
to confirm the functional groups present in them.
The infrared spectral data of the compounds 5–12
are presented in Table 1. All the compounds (5–12)
exhibited characteristic absorption bands for P N
groups [10,11] in the region of 1219–1230 cm−1.
These compounds (5–12) exhibited characteristic
infrared absorption bands in the region of 1345–
1395 cm−1 for P N stretching frequencies [10–12].
All the title compounds (5–12) showed characteristic
absorption bands in the region of 1069–1093 cm−1
for N C(aliphatic) stretching frequencies [10–12].
NaBH4/MeOH
Salicyladehyde
H
N
CH2
OH
Cl
Reduced Schiff's base
(1)
In the next step, p-chlorophenol/p-bromophenol was
reacted with PCl3 in THF in the presence of triethy-
lamine under nitrogen atmosphere to get trivalent
P(III) dichloride derivative (2).
Heteroatom Chemistry DOI 10.1002/hc

Synthesis and Spectral Characterization of Benzoxazaphosphinin N-Substituted Amines by the Staudinger Reaction 501
Cl
4’
5
8
1’
4
4a
8a
N
P
6
7
N
P
3
2
N R
O
Cl
O
1
O
X
THF
O
+
RN3
1’’
40–45oC
(4)
3’’
X
(5—12)
(3)
Compound
R
X
Cl
5
2
3
CH3
CH
Cl
Cl
6
CH2 CH3
7
8
2
2
3
CH2
NO2
Cl
–CH2 –CH=CH2
–CH2–CH2–CH2–CH3
–CH2–CH3
Cl
Cl
Br
9
10
11
CH3
Br
12
CH
CH2 CH3
SCHEME 1
The proton NMR chemical shifts of the com-
pounds 5–12 are presented in Table 2. Aromatic pro-
tons of the title compounds (5–12) displayed a com-
plex multiplet in the range of δ 6.07–8.20 [12]. The
N CH2 protons of the heterocycle are resonated as
a singlet in the region of δ 4.07–4.30.
Methylene protons of CH2 CH3 in 5 are res-
onated as multiplet in the range of δ 1.43–1.62, and
methyl protons are resonated as triplet at δ 0.92.
Methylene protons of CH2 CH2 CH3 in 7 are res-
onated as multiplets in the range of δ 1.15–1.62, and
its methyl protons are resonated as a triplet at δ 0.99.
All other side chain protons are resonated in the ex-
pected regions.
The 13C NMR spectral data of the compounds
5–12 are presented in Table 3. C-4 carbons in
these compounds displayed signals in between δ
42.1 and 46.2. C-4a carbons resonated in the re-
gion of δ 129.0–130.7. C-8a carbons resonated in
the region of δ 144.9–155.8. All other aromatic
Heteroatom Chemistry DOI 10.1002/hc

502 Venkateswarlu et al.
carbons exhibited signals in the expected region.
Ethyl, n-butyl, secondary butyl, and allylic carbons
in the side chain showed signals in the expected
regions.
(mp)
R
M
31P NMR data of all the compounds 5–12 are
presented in Table 1. 31P NMR chemical shifts of the
title compounds appeared in the region of δ −4.66 to
9.22 [10,13]. Mass spectral data of 6–9 are presented
in Table 4.
P
c
i
t
a
h
p
i
al
C
–
EXPERIMENTAL
(cm
Melting points were determined in open capillary
tubes on a Mel-Temp apparatus and are uncorrected.
IR spectra were recorded in KBr pellets on a Perkin–
N
IR,
H
1
N
Elmer FT-IR 1000 spectrophotometer. The H, 13C,
and 31P NMR spectra were taken on Bruker ACF
NMR spectrophotometer operating at 400, 100, and
161.89 MHz, respectively, in CDCl3 or DMSO-d6 and
were referenced to TMS (1H and 13C) and 85% H3PO4
(31P). Mass spectral data were collected on LCMS-
2010 A Shimadzu spectrometer.
P
%)
(
N
(Calcd)
Synthesis of Allyl Azide
ound
F
H
In a dry 100 mL round-bottomed flask fitted with
a dropping funnel, calcium chloride guard tube,
sodium azide (0.33 g, 0.005 mol) in 10 mL of dry
THF was taken. Allyl bromide (0.61 g, 0.005 mol)
in 40 mL of dry THF was added to sodium azide at
room temperature with stirring. Later the reaction
temperature was raised to 40–45◦C and stirred for
4 h. The mixture was cooled to room temperature,
and NaBr was filtered off. The filtrate containing al-
lyl azide was used for the next step reaction without
further purification.
Analyis
C
Emental
N
ual
m
r
o
F
Synthesis of N-[2-(4-Chlorophenoxy)-3-
(3-chlorophenyl- 3,4-dihydro-2H-1,3,2-λ5-
benzoxazaphosphinin-2-yliden]-N-allyl Amine
(9)
Meocular
%)
2-[(3-Chlorophenylamino)methyl] phenol (reduced
Schiff’s base) (1.17 g, 0.005 mol) in 30 mL of dry THF
was added to 4-chlorophenylphosphorodichloridate
(1.15 g, 0.005 mol) in 20 mL of dry THF in the pres-
ence of TEA under N2 atmosphere at room temper-
ature. After the addition, the reaction mixture was
stirred for 4 h at 40–45◦C. The progress of the reac-
tion was judged by TLC analysis. The reaction mix-
ture was filtered to remove triethlamine hydrochlo-
ride. To the filtrate, allylazide (0.005 mol) in 10 mL of
THF was added at room temperature. The comple-
tion of the reaction was monitored by TLC analysis
(
edl
i
Y
C
(
mp
N
Cpmound
Heteroatom Chemistry DOI 10.1002/hc

Synthesis and Spectral Characterization of Benzoxazaphosphinin N-Substituted Amines by the Staudinger Reaction 503
TABLE 2 1H NMR Chemical Shifts of 5–12
Compound
Ar–H
N–CH2
Hydrogens of R
5
6
6.44–6.91 (m, 12H) 4.09 (s, 2H) 1.43–1.62 (m, 2H, –CH2–CH3), 0.92 (t, 3H, J = 11.6 Hz, CH2–CH3)
6.17–6.97 (m, 12H) 4.07 (s, 2H) 1.62–1.86 [m, CH(CH3)CH2CH3], 0.98 [d, 3H, J = 8.6 Hz,
CH(CH3)CH2CH3], 1.24–1.37 [m, 2H, CH(CH3)CH2CH3], 0.89 [t, 3H,
J = 8.2 Hz, CH(CH3)CH2CH3]
7
6.66–6.97 (m. 12H) 4.21 (s, 2H) 1.15–1.32 (m, 2H, –CH2 CH2–CH3), 1.47–1.62 (m, 2H,
CH2–CH2 CH3), 0.99 (t, 3H, J = 6.8 Hz, CH2 CH2–CH3)
8
6.62–7.26 (m, 12H) 4.12 (s, 2H) 2.81 [s, 2H, H2C C6H4 p-(NO2)], 7.47–8.2 [m, 4H, H2C
C6H4 p-(NO2), Ar–H].
9
6.66–7.77 (m, 12H) 4.27 (s, 2H) 1.86–2.89 (m, 2H , –H2C CH CH2), 5.98–6.16 (m, 1H,
H2C CH CH2), 5.25 (d, 2H, J = 12 Hz, H2C CH CH2)
10
6.08–7.05 (m, 12H) 4.21 (s, 2H) 1.12–1.27 (m, 2H, –H2C CH2 CH2 CH3), 1.31–1.38 (m, 2H,
H2C–CH2 CH2 CH3), 1.41–1.56 (m, 2H, H2C CH2–CH2 CH3),
0.88 (t, 3H, J = 6.8 Hz, H2C CH2 CH2–CH3)
11
12
6.07–7.27 (m, 12H) 4.30 (s, 2H) 1.38–1.46 (m, 2H, –CH2 CH3), 0.94 (t, 3H, J = 9.6 Hz, H2C–CH3)
6.64–7.17 (m, 12H) 4.27 (s, 2H) 1.68–1.88 [m, 1H, CH (CH3) CH2 CH3], 1.12 [d, H, J = 8.6 Hz, CH (CH3)
CH2 CH3], 1.26–1.42 [m, 2H, CH (CH3) CH2 CH3], 0.92 [t, 3H, J = 8.2
Hz, CH (CH3) CH2 CH3]
TABLE 3 13C NMR Data of 5–12
Compound
13C NMR Data
5
42.1 (C-4), 129.1 (C-5), 121. 1 (C-6), 128.9 (C-7), 115.6 (C-8), 129.0 (C-4a), 144.9 (C-8a), 144.9 (C-1ꢁ), 115.3
(C-2ꢁ), 134.4 (C-3ꢁ), 116.4 (C-4ꢁ), 129.7 (C-5ꢁ), 110.2 (C-6ꢁ), 147.1 (C-1ꢁꢁ), 116.8 (C-2ꢁꢁ and C-6ꢁꢁ),130.2 (C-3ꢁꢁ
and C-5ꢁꢁ), 127.0 (C-4ꢁꢁ), 20.2 (–H2C CH3), 16.9 ( H2C–CH3)
6
43.8 (C-4), 129.2 (C-5), 121.1 (C-6), 128.9 (C-7), 115.4 (C-8), 129.9 (C-4a), 147.2 (C-8a), 147.4 (C-1ꢁ), 115.5
(C-2ꢁ), 134.4 (C-3ꢁ), 116.9 (C-4ꢁ), 131.6 (C-5ꢁ), 111.7 (C-6ꢁ), 149.6 (C-1ꢁꢁ), 116.9 (C-2ꢁꢁ and C -6ꢁꢁ) , 130.8
(C-3ꢁꢁ and C-5ꢁꢁ), 127.2 (C-4ꢁꢁ), 30.8 [CH (CH3) CH2 CH3], 24.1 [CH (CH3) CH2 CH3], 34.6 [CH (CH3) CH2
CH3], 8.1 [CH (CH3) CH2 CH3]
7
8
44.2 (C-4), 129.2 (C-5), 121.2 (C-6), 129.0 (C-7), 115.6 (C-8), 129.2 (C-4a), 145.6 (C-8a), 147.2 (C-1ꢁ), 115.0
(C-2ꢁ), 134.7 (C-3ꢁ), 116.4 (C-4ꢁ), 130.2 (C-5ꢁ), 111.3 (C-6ꢁ), 148.9 (C-1ꢁꢁ), 116.8 (C-2ꢁꢁ and C-6ꢁꢁ), 129.5
(C-3ꢁꢁ and C-5ꢁꢁ), 127.3 (C-4ꢁꢁ), 46.0 (–H2C CH2 CH3), 27.3 ( H2C–CH2 CH3), 10.2 ( H2C CH2–CH3)
43.8 (C-4), 129.2 (C-5), 122.1 (C-6), 128.7 (C-7), 115.9 (C-8), 130.7 (C-4a), 147.2 (C-8a), 145.4 (C-1ꢁ), 113.5
(C-2ꢁ), 135.2 (C-3ꢁ), 117.8 (C-4ꢁ), 131.3 (C-5ꢁ), 116.5 (C-6ꢁ), 150.2 (C-1ꢁꢁ), 117.8 (C-2ꢁꢁ and C-6ꢁꢁ), 130.3
(C-3ꢁꢁ and C-5ꢁꢁ), 117.4 (C-4ꢁꢁ), 38.2 (CH2 Ar NO2), 145.2 (C-1ꢁꢁꢁ), 128.7 (C-2ꢁꢁꢁ and C-6ꢁꢁꢁ), 122.4 (C-3ꢁꢁꢁ and
C-5ꢁꢁꢁ), 147.2 (C-4ꢁꢁꢁ)
9
46.0 (C-4), 129.4 (C-5), 121.6 (C-6), 129.0 (C-7), 115. 6 (C-8), 129.9 (C-4a), 155.8 (C-8a), 134.9 (C-1ꢁ), 114.1
(C-2ꢁ), 134.7 (C-3ꢁ), 117.0 (C-4ꢁ), 130.7 (C-5ꢁ), 116.0 (C-6ꢁ), 31.4 (–H2C CH CH2), 130.3
( H2C–HC CH2), 116.8 ( H2C CH CH2), 155.7 (C-1ꢁꢁ), 117.3 (C-2ꢁꢁ and C-6 ꢁꢁ), 134.9 (C-3ꢁꢁ and C-5 ꢁꢁ),
117.0 (C-4 ꢁꢁ)
10
42.1 (C-4), 129.9 (C-5), 122.2 (C-6), 129.1 (C-7), 116.8 (C-8), 130.3 (C-4a), 155.0 (C-8a), 147.3 (C-1), 113.8
(C-2ꢁ), 134.8 (C-3ꢁ), 117.6 (C-4ꢁ) 130.4 (C-5ꢁ), 117.2 (C-6ꢁ), 150.0 (C-1ꢁꢁ), 119.7 (C-2ꢁꢁ and C-6ꢁꢁ), 129.9 (C-3ꢁꢁ
and C-5ꢁꢁ) 117.7 (C-4ꢁꢁ), 43.2 (–H2C CH2 CH2 CH3), 35.1 ( H2C–CH2 CH2 CH3), 20.5
( H2C CH2–CH2 CH3),13.2 ( H2C CH2 CH2–CH3)
11
12
42.3 (C-4), 129.9 (C-5), 129.4 (C-6), 121.2 (C-7), 115.8 (C-8), 130.2 (C-4a), 155.5 (C-8a), 148.5 (C-1ꢁ), 114.2
(C-2ꢁ), 134.6 (C-3ꢁ), 117.3 (C-4ꢁ), 131.9 (C-5ꢁ), 111.1 (C-6ꢁ), 150.6 (C-1ꢁꢁ), 117.3 (C-2ꢁꢁ and 6ꢁꢁ), 130.2 (C-3ꢁꢁ
and C-5ꢁꢁ), 127.1 (C-4ꢁꢁ), 27.3 (–CH2 CH3), 20.3 ( CH2–CH3)
46.2 (C-4), 129.3 (C-5), 129.0 (C-6), 120.8 (C-7), 115.9 (C-8), 130.3 (C-4a), 155.7 (C-8a), 153.7 (C-1ꢁ), 114.3
(C-2ꢁ), 135.0 (C-3ꢁ), 117.5 (C-4ꢁ), 132.0 (C-5ꢁ), 112.0 (C-6ꢁ), 154.5 (C-1ꢁꢁ), 117.5 (C-2ꢁꢁ and C-6ꢁꢁ), 130.3
(C-3ꢁꢁ and 5ꢁꢁ), 129.4 (C-4ꢁꢁ), 35.7 [CH (CH3) CH2 CH3], 23.1 [CH (CH3) CH2 CH3], 32.7 [CH (CH3) CH2
CH3], 8.5 [CH (CH3) CH2 CH3]
(hexane–ethyl acetate, 3:1). The solvent was removed
in a rota-evaporator. The crude iminophosphorane
(9) thus obtained was further purified by column
chromatography using silica gel (60–120 mesh) as
adsorbent and hexane and ethyl acetate (2:1) as an
eluent to afford analytically pure iminophosphorane
(9) as a solid. Other members of the series were pre-
pared by adopting the above procedure.
Heteroatom Chemistry DOI 10.1002/hc

504 Venkateswarlu et al.
TABLE 4 Mass Spectral Data of 6–9
[2] Kirsanov, A. V. Bull Acad Sci, USSR, Chem Sect 1950,
426.
[3] Kabachnik, M. J.; Medved, T. Izv Akad Nauk SSSR
1953, 1126.
[4] Kabachnik, M. J.; Medved, T. Izv Akad Nauk SSSR
1954, 1024.
[5] Fields, E. K. J Am Chem Soc 1952, 74, 1528.
[6] Eguchi, S.; Massushita, Y.; Yamashita, K. Org Prep
Proced Int 1992, 24, 209.
[7] Wamhoff, H.; Richardt, G.; Stoblen, S. Adv Hetero-
cyclic Chem 1995, 64, 159.
[8] (a) Staudinger, H.; Hauser, E. Helv Chim Acta 1921,
4, 861; (b) Horner, L.; Gross, A. Leibigs Ann Chem
1955, 591, 117; (c) Wittig, G.; Schwarnenabach, K.
Leibigs Ann Chem 1961, 650, 1.
[9] Molina, P.; Arques, A.; Vinadar, M. V. J Org Chem
1990, 53, 4724.
[10] Alajarin, M.; Molina, P.; Lpez-Laaro, A.; Foues-Foues,
C. Angew Chem, Int Ed Engl 1997, 36, 67.
[11] Imhoff, P.; Asselt, R. V.; Evnsting, J. M.; Vneize,
K.; Elsevier, C. J. Organometallics 1993, 12,
1523.
Compound
m/z(%)
6
7
8
9
462 [13, (M + 1)+], 461 (100, M+•), 460 [24,
(M – 1)+], 381 (37)
448 [36, (M + 1)+], 447 (100, M+•), 446 [14,
(M – 1)+], 405 (9)
541 [24, (M + 1)+], 540 (100, M+•), 478 (15),
454 (6)
446 [50, (M + 1)+], 445 (100, M+•), 431(20),
341(12), 233(30)
ACKNOWLEDGMENTS
The authors thank Prof. C. Devendranath Reddy
and Dr. C. Suresh Reddy, Department of Chemistry,
Sri Venkateswara University, Tirupati, India, for
their help and encouragement during this work. One
of the authors (CVR) also expresses his thanks to
UGC, India, for financial assistance.
[12] Silverstein, R. M.; Webster, F. X. Spectrometric Iden-
tification of Organic Compounds, 6th ed.; Wiley: New
York, 1998.
[13] Quin, L. D.; Verkade, J. G. Phosphorus-31 NMR
Spectral Properties in Compound Characterization
and Structural Analysis; VCH Publishers: New York,
1994.
REFERENCES
[1] Staudinger, H.; Meyer, J. Helv Chim Acta 1919, 2,
635.
Heteroatom Chemistry DOI 10.1002/hc