Synthesis and biological activity of cis 2-(6-chloropyridine-3-yl) methylamino-4-substitutedphenyl-5,5-dimethyl-1,3,2-dioxaphosphinane 2-oxides

Article abstract of DOI:10.1080/104265090902697

A series of novel, asymmetric-cyclic phosphoramides containing substituted pyridine were synthesized via the condensation reactions of trans 2-chloro-4-substitutedphenyl-5, 5-dimethyl-1,3,2-dioxaphosphinane 2-oxide with 2-chloro-5-aminomethylpyridine or 3

Full text of DOI:10.1080/104265090902697

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Synthesis and Biological
Activity of Cis 2-(6-
Chloropyridine-3-
yl)methylamino-4-
substitutedphenyl-5,5-
dimethyl-1,3,2-
dioxaphosphinane 2-Oxides
De Qing Shi a , Yi Liu a , A. D. Feras a , Xiao Song Tan
a & Jian Xin Chen a
a Key Laboratory of Pesticide and Chemical Biology,
Ministry of Education of China and College of
Chemistry, Central China Normal University , Wuhan,
Hubei, P. R. China
Published online: 18 Aug 2006.
To cite this article: De Qing Shi , Yi Liu , A. D. Feras , Xiao Song Tan & Jian
Xin Chen (2005) Synthesis and Biological Activity of Cis 2-(6-Chloropyridine-3-
yl)methylamino-4-substitutedphenyl-5,5-dimethyl-1,3,2-dioxaphosphinane 2-Oxides,
Phosphorus, Sulfur, and Silicon and the Related Elements, 180:8, 1937-1946, DOI:
10.1080/104265090902697
To link to this article: http://dx.doi.org/10.1080/104265090902697
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Phosphorus, Sulfur, and Silicon, 180:1937–1946, 2005
Copyright © Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/104265090902697
Synthesis and Biological Activity of Cis
2-(6-Chloropyridine-3-yl)methylamino-4-
substitutedphenyl-5,5-dimethyl-1,3,2-dioxaphosphinane
2-Oxides
De Qing Shi
Yi Liu
A. D. Feras
Xiao Song Tan
Jian Xin Chen
Key Laboratory of Pesticide and Chemical Biology, Ministry of
Education of China and College of Chemistry, Central China Normal
University, Wuhan, Hubei, P. R. China
A
series of novel, asymmetric-cyclic phosphoramides containing substituted
pyridine were synthesized via the condensation reactions of trans 2-chloro-4-
substitutedphenyl-5, 5-dimethyl-1,3,2-dioxaphosphinane 2-oxide with 2-chloro-5-
aminomethylpyridine or 3-aminomethylpyridine. The reactions show good stereos-
electivity. Only the cis isomer from configuration inversion was obtained, which is
the thermodynamic stable product. The structures of the products were character-
1
31
ized by H NMR, P NMR, IR, MS, and elemental analysis. The configuration of
the product was determined by X-ray diffraction analysis. The results of prelimi-
nary bioassay showed that the new compounds possess potential insecticidal and
fungicidal activities.
Keywords Biological activities; configuration; cyclic phosphoramide; substituted pyri-
dine; X-ray diffraction
INTRODUCTION
Neonicotinioid insecticides as nicotinic acetylcholine receptor inhibitors
have attracted increasing attention because of its safety, low toxicity,
and high activities.1,2 A lot of new insecticides, such as imidacloprid,
acetamiprd, and nitenpyram, have been commercialized (Scheme 1).
Received August 25, 2004; accepted October 7, 2004.
We are grateful to the National Natural Science Foundation of China (20302002) and
the Key Project for Basic Research (2003CB114406) for the financial support.
Address correspondence to De Qing Shi, College of Chemistry, Central China Normal
University, Wuhan 430079, P. R. China. E-mail: chshidq@yahoo.com.cn
1937

1938
D. Q. Shi et al.
SCHEME 1
It was found that most of the biological active nicotinic compounds
contain the 3-aminomethylpyridine moiety.3 Due to their wide biologi-
cal activities, organic phosphorus-heterocyclic compounds play an im-
portant role in pesticide science; 1,3,2-dioxaphosphinane compounds
appear to be very important for their wide biological activities and
their stereochemistry.4−8 As a continuation of our research work, we
decided to introduce the structure of 1,3,2-dioxaphosphinane into 3-
aminomethylpyridine, and therefore we designed and synthesized a
number of novel asymmetric cyclic phosphoramides containing substi-
tuted pyridine 3. The synthetic route is shown in Scheme 2. The struc-
tures of the products were characterized by 1H NMR, 31P NMR, IR, MS,
and elemental analysis. The X-ray diffraction analysis shows that the
configurations of products are cis isomers.
SCHEME 2
The results of preliminary bioassay showed that the new compounds
displayed potential insecticidal and fungicidal activities.

Asymmetric Cyclic Phosphoramides
1939
RESULTS AND DISCUSSION
Preparation of the Title Compounds 3
The title compounds 3 were synthesized by the multistep route outlined
in Scheme 2. 1-Aryl-2, 2-dimethyl-1, 3-propanediols 1 are prepared by
an aldol condensation followed by a cross Cannizzaro reaction when two
equivalents of isobutyraldehyde and a substituted benzaldehyde are al-
lowed to react in basic alcoholic solution. Diols 1 react with POCl3 in the
presence of dichloromethane as solvent to obtain trans cyclic phospho-
rochloridate 2; 3-aminomethylpyridine then attacks trans compound
2 behind the chlorine atom to obtain cis isomer product 3, which was
confirmed by X-ray diffraction.
The Structures of the Title Compounds 3
All the products 3 were purified by flash column chromatography on
silica gel with a mixture of ethyl acetate and petroleum ether as the
eluent. The structures of compounds 3 were confirmed by 1H NMR, 31
P
NMR, and IR spectra, and MS and elemental analysis.
For 1H NMR spectra, the protons of the methyl groups at the 5-
position in phosphorus heterocycle appear as two single peaks, due to
the two methyl groups being in different magnetic environments. The
two protons of the 6-position methylene moiety exhibited two sets of
multiple peaks because of the coupling with the phosphorus atom with
the coupling constant of 11.6 ppm and lying in different magnetic envi-
ronments, while the 4-position proton was displayed as a set of doublet
peaks with the coupling constant of 11.2 ppm. For 31P NMR spectra, the
phosphorus atom of all compounds appeared as a single peak with the
chemical shifts in the range of 6.0–6.8. The IR spectra of all compounds
showed normal stretching absorption bands indicating the existence of
the N H (∼3200 cm−1), C N (1560–1590 cm−1), P O (∼1230 cm−1),
and P O C (∼1000 cm−1) moiety. The EI mass spectra of compound 3
revealed the existence of the molecular ion peaks and the main frag-
mentation peaks, which were in accordance with the given structures
of products 3.
X-ray diffraction analysis indicated that the single crystal of 3a is
monoclinic, with a space group P2(1)/n, cell parameter A = 6.1648(6),
˚
B = 19.943(2), C = 15.2676(16) A, α = 90, β = 99.220(2), γ = 90, V =
3
3
−1
˚
1852.8(3) A , Z = 4, Dc = 1.297 g/cm , F (000) = 748, µ = 0.309 mm
and final R = 0.0660, ωR = 0.1675 for 4436 reflections (I > 2σ(I)). X-
ray analysis revealed that the product is the cis isomer, which is the
thermodynamic stable configuration. The selected bond distances and

1940
D. Q. Shi et al.
˚
TABLE I Selected Bond Lengths [A]
Bond Dist. Bond Dist.
Bond
Dist.
Bond
Dist.
P(1)-O(1) 1.468(2) C(1)-C(2) 1.300(5) C(5)-N(1)
P(1)-O(3) 1.572(2) C(1)-N(1) 1.381(5) C(7)-C(12) 1.498(4) C(13)-C(14) 1.382(5)
P(1)-O(2) 1.587(2) C(1)-Cl(1) 1.742(4) C(7)-C(8) 1.542(4) C(14)-C(15) 1.384(6)
1.404(5) C(12)-C(13) 1.393(5)
P(1)-N(2) 1.605(3) C(2)-C(3) 1.319(5) C(8)-C(11) 1.519(5) C(15)-C(16) 1.367(5)
O(2)-C(7) 1.468(4) C(3)-C(4) 1.377(5) C(8)-C(10) 1.534(4) C(15)-Cl(2) 1.736(4)
O(3)-C(11) 1.456(4) C(4)-C(5) 1.383(5) C(8)-C(9)
1.535(5) C(16)-C(17) 1.374(5)
N(2)-C(6) 1.457(4) C(4)-C(6) 1.503(5) C(12)-C(17) 1.391(5)
angles are listed in Tables I and II. Figures 1 and 2 are the molecular
structure of compound 3a and packing of the molecules in the unit cell,
respectively.
Biological Activities
Preliminary bioassays indicate that these title compounds possess po-
tential insecticidal and fungicidal activities. For example, the death
ratio of Aphis glycine Matsumura by compound 3a, 3f, and 3g is, re-
spectively, 47.2, 18.2, and 35.7% at the concentration of 2.5 × 10−4 while
the death ratio of Tetranychus viennensis zacher by compound 3f, 3h,
and 3i is, respectively, 76.9, 47.1, and 33.3% at the same concentra-
tion. The fungicidal activities of some target compounds are listed in
Table III. Further studies are under way and will be reported in due
course.
TABLE II Selected Bond Angles (◦)
Angle
(◦)
Angle
(◦)
Angle
(◦)
O(1)-P(1)-O(3)
O(1)-P(1)-O(2)
O(3)-P(1)-O(2)
O(1)-P(1)-N(2)
O(3)-P(1)-N(2)
O(2)-P(1)-N(2)
C(7)-O(2)-P(1)
C(11)-O(3)-P(1)
C(6)-N(2)-P(1)
C(2)-C(1)-N(1)
C(2)-C(1)-Cl(1)
115.44(14) N(1)-C(1)-Cl(1)
112.80(14) C(1)-C(2)-C(3)
102.54(13) C(2)-C(3)-C(4)
114.01(15) C(3)-C(4)-C(5)
104.47(14) C(3)-C(4)-C(6)
106.46(13) C(5)-C(4)-C(6)
117.56(18) C(4)-C(5)-N(1)
118.2(3) C(12)-C(7)-C(8)
117.6(3) C(11)-C(8)-C(10) 110.5(3)
117.0(3)
124.8(3) C(11)-C(8)-C(9)
116.8(3) C(10)-C(8)-C(9)
123.4(3) C(11)-C(8)-C(7)
119.8(3) C(10)-C(8)-C(7)
119.5(3) C(9)-C(8)-C(7)
116.7(3) O(3)-C(11)-C(8)
114.2(3) C(17)-C(12)-C(13) 117.9(3)
106.5(2) C(17)-C(12)-C(7) 121.5(3)
108.7(3) C(13)-C(12)-C(7) 120.5(3)
107.4(3)
109.8(3)
108.6(3)
111.9(3)
108.5(3)
113.6(3)
116.8(2)
123.5(2)
124.7(4)
117.1(3)
C(1)-N(1)-C(5)
N(2)-C(6)-C(4)
O(2)-C(7)-C(12)
O(2)-C(7)-C(8)
C(14)-C(13)-C(12) 121.3(3)
C(13)-C(14)-C(15) 119.0(4)
C(16)-C(17)-C(12) 121.0(3)
C(16)-C(15)-C(14) 120.7(3) C(14)-C(15)-Cl(2) 119.6(3)
C(16)-C(15)-Cl(2) 119.8(3) C(15)-C(16)-C(17) 120.2(3)

Asymmetric Cyclic Phosphoramides
1941
FIGURE 1 Molecular structure of compound 3a.
EXPERIMENTAL
1H NMR and 31P NMR spectra were recorded with a VARIAN
MERCURY-PLUS400 spectrometer with TMS and an 85% H3PO4
as the internal and external reference, respectively, and CDCl3 as
the solvent, while mass spectra were obtained with a Finnigan
TRACEMS2000 spectrometer using the EI method. IR spectra were
measured by a NICOLET NEXUS470 spectrometer. Elemental anal-
yses were performed with a ELEMENTAR Vario ELIIICHNSO ele-
mentary analyzer. X-ray diffraction analysis was carried out with a
BRUKER SMART APEX CCD X-ray diffraction instrument. Melting
points were determined with a WRS-1B digital melting point appara-
tus and the thermometer was uncorrected.
The reagents and solvents were available commercially and pu-
rified according to conventional methods before use. 2-chloro-5-
chloromethylpyridine was obtained from the pesticide factory in Shashi
in Hubei province, China. Diols 1 and 2-chloro-5-aminomethylpyridine
were prepared according to references9 and10, respectively.
FIGURE 2 Packing of the molecules in the unit cell.

1942
D. Q. Shi et al.
TABLE III The Fungicidal Activities of Compounds 3 (the Plate
Method, C = 0.005%, Inhibition%)
Fungi
kind
Fusarium
oxysporium
Rhizoctonia Botrytis Gibberella Botryosphaeria Bopolaris
solani
cinerea
zeae
berengeriana
maydis
3a
3b
3c
3d
3e
3f
3g
3h
3i
33.3
47.6
66.7
71.4
38.1
61.9
61.9
57.1
61.9
57.1
86.5
83.3
93.8
92.7
78.1
92.7
93.8
88.5
87.5
90.6
88.5
92.3
100
96.2
92.3
98.1
96.2
98.1
92.3
96.2
51.9
48.1
77.8
74.1
40.7
88.9
96.3
66.7
62.9
70.4
65.0
60.0
80.0
80.0
60.0
90.0
90.0
80.0
85
88.2
94.1
94.1
94.2
82.3
94.1
97.1
88.2
97.1
88.2
3j
85.0
Synthesis of Trans 2-Chloro-4-substituted Phenyl-5,5-
dimethyl-1,3,2-dioxaphosphinane 2-Oxides
Method A: 0.02 mol of diol 1 in 10 mL of anhydrous CH2Cl2 were
added to a 50 mL three-necked flask; 0.022 mol of POCl3 was added
dropwise at 35◦, and the mixture stirred under reflux for 1.5 h. Af-
ter removing the solvent under a reduced pressure, the crude prod-
uct was purified by recrystallization with a mixture of CH2Cl2/toluene
or CHCl3/petroleum ether; a white crystal was obtained in 63–98%
yield. Method B: (when 4-methylbenzaldehyde and 4-methoxybenzal-
dehyde were used): 0.01 mol of diol 1, 0.02 mol of triethylamine and
20 mL of anhydrous CH2Cl2 were added to a 50 mL three-necked flask,
the mixture was cooled to 0◦C, and 0.01 mol of POCl3 in 5 mL of anhy-
drous CH2Cl2 was added dropwise. The mixture was stirred at 5–10◦C
for 3 h, the solid was filtered and solvent removed under a reduced
pressure. The crude product was purified by recrystallization with a
mixture of CH2Cl2 and toluene to obtain the product.
General Procedure for the Synthesis of Cis
2-(6-Chloropyridine-3-yl)methylamino-4-substituted
Phenyl-5,5-dimethyl-1,3,2-dioxaphosphinane 2-Oxides
5 mmol of compound 2, 7.5 mmol of triethylamine, and 10 mL of
anhydrous CH2Cl2 were added to a 50 mL three-necked reaction
flask; the solution of 5 mmol of 2-chloro-5-aminomethylpyridine or 3-
aminomethylpyridine in 10 mL of anhydrous CH2Cl2 was added drop-
wise with cooling in an icebath. After the addition was completed, the
mixture was stirred at room temperature, or under reflux until the
reaction was finished (monitored by TLC). The solid was filtered and

Asymmetric Cyclic Phosphoramides
1943
washed with water and the crude product was purified by flash column
chromatography on silica gel (petroleum ether/ethyl acetate 1:2 as the
eluent) to obtain compounds 3a–j.
3a (Ar = 4-ClPh, R = Cl): white solid, m.p. 185.3–186.9◦C, yield
1
81.2%; H NMR (CDCl3) δ = 0.76 (s, 3H, CH3), 0.96 (s, 3H, CH3), 3.60
(m, 1H, CH2OP), 3.87 (dd, 1H, CH2OP, 3 JH−P = 11.2 Hz), 4.32 (m, 2H,
NCH2), 4.48 (d, 1H, CH Ar, 3 JH−P = 10.8 Hz), 5.42 (s, 1H, N H), 7.02
3
(d, 2H, Ar H, JH−H = 7.6 Hz), 7.26–7.34 (m, 3H, Ar H, β-H on pyri-
dine), 7.78 (d, 1H, γ -H on pyridine, 3 JH−H = 7.6 Hz), 8.39 (s, 1H, α-H on
pyridine); 31P NMR (CDCl3) δ = 6.51; IR (KBr) (υmax/cm−1) 3199 (N H),
1568 and 1590 (C N), 1229 (P O), 1047 and 990 (P O C); MS, m/e (%)
400, 401, 403 (M+, 6.9), 347 (56.5), 344 (34.0), 205(100), 141 (39.5), 139
(30.6), 125 (20.0), 77 (20.6), 56 (56.6); Anal. Calcd. For C17H19O3N2Cl2P
(401): C, 50.87; H, 4.74; N, 6.98. Found: C, 50.56; H, 4.68; N, 7.17.
3b (Ar = Ph, R = Cl): white solid, m.p. 169.2–170.1◦C, yield 78.4%;
1H NMR (CDCl3) δ = 0.77 (s, 3H, CH3), 0.94 (s, 3H, CH3), 3.82–3.91
(dd, 1H, CH2OP, 3 JH−P = 11.2 Hz), 4.12 (m, 1H, CH2OP), 4.31 (m, 2H,
NCH2), 4.48 (d, 1H, CH Ar, 3 JH−P = 10.8 Hz), 5.42 (d, 1H, N H), 7.08
(m, 2H, Ar H), 7.25–7.34 (m, 4H, Ar H, β-H on pyridine), 7.80 (d, 1H,
3
γ -H on pyridine, JH−H = 6.8 Hz), 8.39 (s, 1H, α-H on pyridine); 31P
NMR (CDCl3) δ = 6.50; IR (KBr) (υmax/cm−1) 3195 (N H), 1567 and
1587 (C N), 1233 (P O), 1045 and 992 (P O C); MS, m/e (%) 366 (M+,
2.1), 310 (11.9), 204 (39.1), 140 (16.4), 128 (13.6), 114 (19.1), 104 (30.2),
90 (42.2), 76 (38.5), 56 (100); Anal. Calcd. For C17H20O3N2ClP (366.5):
C, 55.66; H, 5.46; N, 7.64. Found: C, 55.81; H, 5.68; N, 7.93.
3c (Ar = 3-NO2Ph, R = Cl): pale yellow solid, m.p. 210.3–210.7◦C,
yield 42.5%; 1H NMR (CDCl3) δ = 0.84 (s, 3H, CH3), 0.95 (s, 3H, CH3),
3
3.58 (m, 1H, CH2OP), 3.86–3.95 (dd, 1H, CH2OP, JH−P = 11.6 Hz),
3
4.36 (m, 2H, NCH2), 4.54 (d, 1H, CH Ar, JH−P = 11.2 Hz), 5.56 (s,
1H, N H), 7.34–7.57 (m, 3H, Ar H), 7.80 (d, 1H, β-H on pyridine,
3 JH−H = 8.0 Hz), 8.09 (s, 1H, Ar H), 8.22 (d, 1H, γ -H on pyridine,
3 JH−H = 8.0 Hz), 8.42(s, 1H, α-H on pyridine); 31P NMR (CDCl3) δ =
6.32; IR (KBr) (υmax/cm−1) 3200 (N H), 1570 and 1585 (C N), 1230
(P O), 1045 and 990 (P O C); MS, m/e (%) 412 (M+, 2.9), 356 (12.1),
223 (20.8), 221 (100), 205 (90.9), 141 (21.8), 126 (11.8), 115 (8.5), 91
(4.7), 56 (27.5); Anal. Calcd. For C17H19O5N3ClP (411.5): C, 49.57; H,
4.62; N, 10.21. Found: C, 49.32; H, 4.85; N, 10.20.
3d (Ar = 4-CH3OPh, R = Cl): white solid, m.p. 192.1–192.6◦C, yield
1
28.3%; H NMR (CDCl3) δ = 0.78 (s, 3H, CH3), 0.95 (s, 3H, CH3), 3.72
3
(s, 3H, ArOCH3), 3.80–3.92 (dd, 1H, CH2OP, JH−P = 11.6 Hz), 4.14
3
(m, 1H, CH2OP), 4.30 (m, 2H, NCH2), 4.50 (d, 1H, CH Ar, JH−P
=
11.4 Hz), 5.42 (d, 1H, N H), 6.95–7.20 (dd, 4H, Ar H, 3 JH−H = 8.0 Hz),
3
7.28–7.80 (dd, 2H, β, γ -H on pyridine, JH−H = 8.0 Hz), 8.40 (s, 1H,

1944
D. Q. Shi et al.
α-H on pyridine); 31P NMR (CDCl3) δ = 6.66; IR (KBr) (υmax/cm−1) 3202
(N H), 1572 and 1580 (C N), 1235 (P O), 1040 and 975 (P O C);
Anal. Calcd. For C18H22O4N2ClP (396.5): C, 54.48; H, 5.55; N, 7.06.
Found: C, 54.58; H, 5.34; N, 6.92.
3e (Ar = 2-CH3OPh, R = Cl): white solid, m.p. 208.1–208.9◦C, yield
31.3%; 1H NMR (CDCl3) δ = 0.76 (s, 3H, CH3), 0.93 (s, 3H, CH3), 3.78 (s,
3H, ArOCH3), 3.82–3.91 (dd, 1H, CH2OP, 3 JH−P = 11.2 Hz), 4.15 (m, 1H,
3
CH2OP), 4.33 (m, 2H, NCH2), 4.50 (d, 1H, CH Ar, JH−P = 10.8 Hz),
3
5.42 (d, 1H, N H), 6.70–7.25 (dd, 4H, Ar H, JH−H = 8.2 Hz), 7.30–
3
7.81 (dd, 2H, β, γ -H on pyridine, JH−H = 8.0 Hz), 8.45 (s, 1H, α-H on
pyridine); 31P NMR (CDCl3) δ = 6.84; IR (KBr) (υmax/cm−1) 3193 (N H),
1565 and 1580 (C N), 1230 (P O), 1045 and 990 (P O C); Anal. Calcd.
For C18H22O4N2ClP (396.5): C, 54.48; H, 5.55; N, 7.06. Found: C, 54.27;
H, 5.51; N, 7.39.
3f (Ar = 4-CH3Ph, R = Cl): white solid, m.p. 180.9–181.8◦C, yield
69.9%; 1H NMR (CDCl3) δ = 0.76 (s, 3H, CH3), 0.95 (s, 3H, CH3), 2.35 (s,
3H, ArCH3), 3.88 (m, 1H, CH2OP), 3.82–3.91 (dd, 1H, CH2OP, 3 JH−P
=
3
11.2 Hz), 4.32 (m, 2H, NCH2), 4.47 (d, 1H, CH Ar, JH−P = 10.8 Hz),
3
5.40 (d, 1H, N H), 6.97–7.14 (dd, 4H, Ar H, JH−H = 8.4 Hz), 7.28–
3
7.81 (dd, 2H, β, γ -H on pyridine, JH−H = 8.0 Hz), 8.38 (s, 1H, α-H on
pyridine); 31P NMR (CDCl3) δ = 6.06; IR (KBr) (υmax/cm−1) 3190 (N H),
1572 and 1585 (C N), 1230 (P O), 1050 and 995 (P O C); MS, m/e (%)
380 (M+, 1.27), 327 (9.2), 325 (38.7), 247 (2.2), 245 (8.4), 221 (14.8), 207
(22.2), 205 (100), 141 (19.3), 128 (24.8), 126 (37.4), 119 (45.5), 105 (27.3),
91 (40.3), 77(16.8); Anal. Calcd. For C18H22O3N2ClP (380.5): C, 56.77;
H, 5.78; N, 7.36. Found: C, 56.79; H, 5.94; N, 7.21.
3g (Ar = 4-NO2Ph, R = Cl): pale yellow solid, m.p. 212.9–213.4◦C,
yield 46.1%; 1H NMR (CDCl3) δ = 0.82 (s, 3H, CH3), 0.94 (s, 3H, CH3),
3
3.80 (m, 1H, CH2OP), 3.85–3.94 (dd, 1H, CH2OP, JH−P = 11.6 Hz),
3
4.34 (m, 2H, NCH2), 4.50 (d, 1H, CH Ar, JH−P = 11.6 Hz), 5.54 (d,
3
1H, N H), 7.28 (d, 2H, Ar H), 7.35 (d, 1H, β-H on pyridine, JH−H
=
=
3
8.4 Hz), 7.79 (d, 1H, γ -H on pyridine), 8.21 (d, 2H, Ar H, JH−H
8.8 Hz), 8.43(s, 1H, α-H on pyridine); 31P NMR (CDCl3) δ = 6.31; IR
(KBr) (υmax/cm−1) 3206 (N H), 1565 and 1587 (C N), 1225 (P O), 1040
and 991 (P O C); MS, m/e (%) 412 (M+, 33.8), 356 (12.1), 223 (22.5),
221 (72.2), 205 (100), 191 (18.0), 141 (75.7), 126 (58.4), 115 (48.3), 91
(34.5), 77 (41.0), 56 (100); Anal. Calcd. For C17H19O5N3ClP (411.5): C,
49.57; H, 4.62; N, 10.21. Found: C, 49.32; H, 4.85; N, 10.25.
3h (Ar = 4-CH3Ph, R H): white solid, m.p. 161.2–161.8◦C, yield
1
70.2%; H NMR (CDCl3) δ = 0.76 (s, 3H, CH3), 0.96 (s, 3H, CH3), 2.35
(s, 3H, CH3), 3.55 (m, 1H, CH2OP), 3.82–3.91 (dd, 1H, CH2OP, 3 JH−P
=
3
11.2 Hz), 4.34 (m, 2H, NCH2), 4.48 (d, 1H, CH Ar, JH−P = 11.6 Hz),

Asymmetric Cyclic Phosphoramides
1945
5.41 (d, 1H, N H), 6.98–7.13 (dd, 4H, Ar H, 3 JH−H = 8.0 Hz), 7.30(m,
3
1H, β-H on pyridine), 7.83 (d, 1H, γ -H on pyridine, JH−H = 8.0 Hz),
8.56 (d, 1H, α-H on pyridine, 3 JH−H = 3.6 Hz), 8.63 (s, 1H, α-H on Pyri-
dine); 31P NMR (CDCl3) δ = 6.50; IR (KBr) (υmax/cm−1) 3190 (N H),
1575 (C N), 1230 (P O), 1044 and 988 (P O C); MS, m/e (%) 346 (M+,
4.4), 291 (38.9), 226 (4.7), 209 (7.1), 187 (20.3), 171 (100), 128 (10.6),
119 (41.9), 105 (31.2), 91 (40.9), 56(17.4); Anal. Calcd. For C18H23O3N2P
(346): C, 62.43; H, 6.65; N, 8.09. Found: C, 62.59; H, 6.70; N, 8.24.
3i (Ar = 4-ClPh, R H): white solid, m.p. 162.0–162.7◦C, yield 84.4%;
1H NMR (CDCl3) δ = 0.75 (s, 3H, CH3), 0.95 (s, 3H, CH3), 3.80–3.89
(dd, 1H, CH2OP, 3 JH−P = 11.2 Hz), 4.12 (dd, 1H, CH2OP), 4.32 (m, 2H,
NCH2), 4.47 (d, 1H, CH Ar, 3 JH−P = 11.2 Hz), 5.39 (d, 1H, N H), 7.00
3
(d, 2H, Ar H, JH−H = 8.4 Hz), 7.28(m, 3H, Ar H, β-H on pyridine),
7.79 (d, 1H, γ -H on pyridine, 3 JH−H = 7.6 Hz), 8.53 (d, 1H, α-H on Pyri-
dine, 3 JH−H = 4.4 Hz), 8.60 (s, 1H, α-H on pyridine); 31P NMR (CDCl3)
δ = 6.81; IR (KBr) (υmax/cm−1) 3185 (N H), 1577 (C N), 1234 (P O),
1050 and 990 (P O C); MS, m/e (%) 367 (M + 1, 50.7), 311 (41.6), 231
(18.2), 187 (25.7), 171 (100), 141 (54.0), 107 (40.6), 105 (31.2), 92 (57.2),
77 (30.0), 56(66.0); Anal. Calcd. For C17H20O3N2ClP (366.5): C, 55.66;
H, 5.46; N, 7.64. Found: C, 55.73; H, 5.77; N, 7.47.
3j (Ar = Ph, R H): white solid, m.p. 143.3–144.3◦C, yield 79.3%;
1H NMR (CDCl3) δ = 0.77 (s, 3H, CH3), 0.95 (s, 3H, CH3), 3.82–3.91
(dd, 1H, CH2OP, 3 JH−P = 11.2 Hz), 3.95 (m, 1H, CH2OP), 4.33 (m, 2H,
NCH2), 4.48 (d, 1H, CH Ar, 3 JH−P = 11.2 Hz), 5.43 (d, 1H, N H), 7.11
(m, 1H, β-H on pyridine), 7.20–7.40 (m, 5H, Ar H), 7.81 (d, 1H, γ -H
on pyridine, 3 JH−H = 7.6 Hz), 8.53–8.61 (m, 2H, 2α-H on pyridine); 31
P
NMR (CDCl3) δ = 6.66; IR (KBr) (υmax/cm−1) 3190 (N H), 1575 (C N),
1230 (P O), 1044 and 988 (P O C); MS, m/e (%) 332 (M+, 1.7), 277
(46.3), 197 (9.3), 187 (19.7), 171 (81.9), 170 (73.3), 129 (20.2), 115 (17.1),
107 (46.0), 91 (37.7), 79 (30.4), 77 (24.7), 56(22.6), 40 (100); Anal. Calcd.
For C17H21O3N2P (332): C, 61.45; H, 6.33; N, 8.43. Found: C, 61.31; H,
6.28; N, 8.35.
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