Asymmetric cyclic phosphorothonamides containing substituted pyridine

Article abstract of DOI:10.1080/10426500600864296

In order to find high-acitivity and low-toxicity pesticidal lead compounds, a type of novel, asymmetric cyclic phosphorothonamides containing substituted pyridine were synthesized via the condensation reactions of 2-chloro-4- substitutedphenyl-5,5-dimethy

Full text of DOI:10.1080/10426500600864296

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Phosphorus, Sulfur, and Silicon
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Asymmetric Cyclic
Phosphorothonamides
Containing Substituted Pyridine
De-Qing Shi a , Abudhaim Feras a & Yi Liu a
a Key Laboratory of Pesticide and Chemical Biology
of Ministry of Education , Central China Normal
University , Wuhan, Hubei, P. R. China
Published online: 01 Feb 2007.
To cite this article: De-Qing Shi , Abudhaim Feras & Yi Liu (2006) Asymmetric Cyclic
Phosphorothonamides Containing Substituted Pyridine, Phosphorus, Sulfur, and Silicon
and the Related Elements, 181:11, 2663-2673, DOI: 10.1080/10426500600864296
To link to this article: http://dx.doi.org/10.1080/10426500600864296
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Phosphorus, Sulfur, and Silicon, 181:2663–2673, 2006
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500600864296
Asymmetric Cyclic Phosphorothonamides Containing
Substituted Pyridine
De-Qing Shi
Abudhaim Feras
Yi Liu
Key Laboratory of Pesticide and Chemical Biology of Ministry
of Education, Central China Normal University, Wuhan, Hubei,
P. R. China
In order to find high-acitivity and low-toxicity pesticidal lead compounds, a type
of novel, asymmetric cyclic phosphorothonamides containing substituted pyridine
were synthesized via the condensation reactions of 2-chloro-4-substitutedphenyl-
5,5-dimethyl-1,3,2-dioxaphosphinane 2-sulfide with 3-aminomethylpyridine. The
cis and trans isomers of the products were isolated by column chromatography
1
31
on silica gel. The structures of the products were characterized by H NMR,
P
NMR, MS, and elemental analyses. The configuration of 3a was determined by X-
ray diffraction analysis. The results of the preliminary bioassay showed that the
new compounds possess potential fungicidal activities.
Keywords Cyclic phosphorothonamide; fungicidal actitity; substituted pyridine; X-ray
diffraction
INTRODUCTION
Neonicotinoid insecticides as nicotinic acetylcholine receptor inhibitors
have attracted increasing attention because of their safety, low toxi-
city, wide and high activities.1,2 A lot of new insecticides such as im-
idacloprid, acetaniprid, and nitenpyram have been commercialized.
It was found that most of the biologically active nicotinic compounds
contain the 3-aminomethylpyridine moiety.3 Due to their wide biolog-
ical activities, phosphorus heterocyclic compounds play an important
role in pesticide science; 1,3,2-dioxaphosphinane compounds appear
Received March 4, 2006; accepted March 29, 2006.
We are grateful to the Natural Science Foundation of China (20302002) for financial
support.
Address correspondence to De-Qing Shi, Key Laboratory of Pesticide and Chemical
Biology of Ministry of Education, College of Chemistry, Central China Normal University,
Wuhan 430079, Hubei, P. R. China. E-mail: chshidq@yahoo.com.cn
2663

2664
D.-Q. Shi et al.
to be very important for their wide biological activities and their
stereochemistry.4−8 As a continuation of our research work, we de-
cided to introduce the structure of 1,3,2-dioxaphosphinane into 3-
aminomethylpyridine, and therefore we designed and synthesized a
type of novel asymmetric cyclic phosphorothonamides containing sub-
stituted pyridine 3 and 4. The synthetic route is shown in Scheme 1. The
1
structures of the products were characterized by H NMR, 31P NMR,
MS, and elemental analyses. The configuration of 3a was determined by
X-ray diffraction analysis. The results of preliminary bioassay showed
that the new compounds possess potential fungicidal activities.
SCHEME 1
RESULTS AND DISCUSSION
Preparation of the Title Compounds
Title compounds 3 and 4 were synthesized by the multistep route out-
lined in Scheme 1.1-aryl-2,2-dimethyl-1,3-propanediols 1 are prepared
by an aldol condensation followed by a cross Cannizzaro reaction in
which two equivalents of isobutyraldehyde and a substituted benzalde-
hyde are allowed to react in basic alcoholic solution. Diols 1 react with
PSCl3 in a CCl4 solvent to yield cyclic phosphorochloridate 2; the ra-
tios of cis and trans isomers of compounds 2 are 1:1 approximately;9
3-aminomethylpyridine then reacts with compound 2 in the presence
of triethylamine to give products 3 and 4.
All products were purified by flash column chromatography on silica
gel using a mixture of ethyl acetate and petroleum ether as the eluent;

Cyclic Phosphorothonamides
2665
first, the trans isomers and then the cis isomers were eluted. In most
cases, the cis isomer is the major product. Moreover, when an ortho-
substituted group was attached to the aromatic rings, only cis isomer
products were obtained. However, the reason is not very clear; it maybe
due to the thermodynamic favored process.10
Structures of Title Compounds
Structures of compounds 3 and 4 were confirmed by 1H NMR, 31P NMR,
MS, and elemental analyses. Cis isomer 3a was identified by X-ray
diffraction.
In 1H NMR spectra, the two methyl protons of 1,3,2-dioxa-
phosphinane appeared as two singlets, due to the two methyl groups
lying in different magnetic environments. The two methylene pro-
tons of 1,3,2-dioxaphosphinane displayed a doublet and multiplicity
because of their different magnetic surroundings and coupling with
each other or with the adjacent phosphorus atom with the coupling
constant of 11.6 ppm and 22 ppm, respectively; the 4-position axial
proton displayed singlet without coupling with a phosphorus atom.
Interestingly, we easily can distinguish cis isomers 3 from trans iso-
1
1
mers 4 by means of H NMR and 31P NMR. In H NMR spectra, the
chemical shift difference between the two methyl groups attached to
the 1,3,2-dioxaphosphinane in trans 4 are larger than the values in
cis 3 (0.3–0.4 ppm versus 0.1–0.2 ppm), and in cis isomers, 4-position
methylene proton in phosphorus heterocycle is shifted downfield rela-
tive to that of the trans isomers, owing to the unshielded effect of P O
group, and in 31P NMR spectra, the phosphorus signal of the cis iso-
mer is downfield relative to that of the trans isomer.7 The IR spectra
of all compounds showed normal stretching absorption bands indicat-
ing the existence of the N H (∼3200 cm−1), and P=S (∼700 cm−1),
and P O C (∼1000 cm−1) moiety. The EI mass spectra of compounds
3 and 4 revealed the existence of molecular ion peaks and main frag-
mentation peaks, which were in accordance with the given structures of
products.
X-ray diffraction analysis indicated that the single crystal of 3a is
monoclinic; space group P2(1)/n, cell parameters A = 21.753(9), B =
3
˚
˚
6.879(3), C = 12.219(5) A, β = 98.980(7), V = 1806.1(1) A , Z = 4, Dc
= 1.408 g/cm3, F (000) = 800, µ = 0.428 mm−1 and final R = 0.1050,
wR = 0.2672 for 2187 reflections (I > 2σ(I)). The selected bond distances
and angles are listed in Table I. Figures 1 and 2 are the molecular
structure of compound 3a and packing of the molecules in the unit cell,
respectively.
The distorted tetrahedral configuration of the P atom can be at-
tributed to the presence of the dioxaphosphinane ring whose sterical

2666

Cyclic Phosphorothonamides
2667
Figure 1 The molecular structure of compound 3a.
and electronic properties influence coordination the values of the
. . . . . . . . . . . .
O and
P1=S1, P1 N1, and P O bonds and the angles O
P
. . . . . .
N illustrate the irregularities (Table 1). The dioxaphosphinane
O
P
ring adopts a distorted chair conformation, with the parameters Q =
◦
◦ 11
˚
0.571(6)A, θ = 172.8(6) and φ = 329(5) . The length of single bonds
. . .
. . .
of P O and P1 N1 are similar to the analogous chemical bonds ob-
12
˚
˚
˚
served previously [1.586(2) A, 1.572(2) A, and 1.598(6) A] (Table I).
. . .
. . .
The intermolecular N1 H1(A) N2 interaction joins molecules into
a chain along the b axis (Figure 2). The methylene atom C14 is in-
. . . . . .
H
˚
˚
volved in C
π interactions: C14· · · Cg2 = 3.609(8) A, H14· · ·
◦
. . .
Cg2 = 2.80A, and C14 H14. . . Cg2 = 146 . [Cg2 is the centroid of
the pyridine ring of the symmetry-related molecule at (−X, −1/2 +
Y, 1/2-Z)]. The interaction of methylene group with the aromatic sys-
tems, described by Desiraju,13 contributes to the crystal packing of cis
3a.
Figure 2 Packing of the molecules in the unit cell.

2668
D.-Q. Shi et al.
TABLE II The Fungicidal Activities of Compound, 3 and 4 (the Plate
Method,15 C = 50 ppm, Inhibitory Rate: %)
Fungi Fusarium Rhizoctonia Botrytis Gibberella Botryosphaeria Bopolaris
kind
oxysporium
solani
cinerea
zeae
berengeriana
maydis
3a
4a
3b
4b
3c
4c
3d
4d
3e
4e
3f
33.33
41.60
50.00
45.83
61.90
38.10
33.34
75.00
37.50
54.17
70.83
45.83
37.50
58.33
44.00
42.00
84.00
85.00
80.30
27.27
39.00
84.00
62.00
85.00
92.00
74.00
14.00
81.00
57.14
42.86
95.24
95.23
93.33
64.44
14.29
98.81
88.10
98.91
100
27.27
12.12
60.60
51.51
77.14
45.71
6.06
66.67
33.33
63.64
81.81
42.42
15.15
51.51
65.21
30.43
78.26
78.26
83.33
50.00
30.43
82.61
60.87
82.61
86.96
73.91
47.83
73.91
58.82
52.94
82.35
94.12
88.46
69.23
64.71
88.24
70.59
82.35
88.24
58.82
52.94
94.12
4f
3g
3h
78.57
61.90
85.71
Biological Activities
Preliminary bioassay results show that these title compounds pos-
sess weak insecticidal but potential fungicidal activities. The results
of fungicidal activities are listed in Table II.
EXPERIMENTAL
1H NMR and 31P NMR spectra were recorded with a VARIAN
MERCURY-PLUS400 spectrometer with TMS and 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 analyses were per-
formed with an ELEMENTAR Vario ELIIICHNSO elementary ana-
lyzer. X-ray diffraction analysis was carried out with an BRUKER
SMART APEX CCD X-ray diffraction instrument. Melting points were
determined with a WRS-1B digital melting point apparatus, and the
thermometer was uncorrected.
The reagents and solvents were available commercially and purified
according to conventional methods before use. Diols 1 were prepared
according to reference.14

Cyclic Phosphorothonamides
2669
The Synthesis of 2-Chloro-4-Substituted Phenyl-5,
5-Dimethyl-1,3,2-Dioxaphosphinane 2-Sulfide9
0.01 mol of diol 1, 0.01 mol of thiophosphoryl chloride, and 20 mL of car-
bon tetrachloride were taken in a 50-mL three-necked reaction flask.
The mixture was stirred under reflux for 4 h (monitored by TLC), af-
ter removal of the solvent under a reduced pressure, the residue was
dissolved in 25 mL of chloroform and washed with sodium bicarbon-
ate solution twice and then by water. The organic layer was dried over
sodium sulphate and filtered; after removal of the solvent under a re-
duced pressure, the crude product was thus obtained and used without
further purification. The ratios of the cis and trans isomer of products
1
were determined by H NMR and 31P NMR, which are listed in Table
III.
The General Procedure for the Synthesis of
2-(3-Pyridylmethylamino)-4-Substitutedphenyl-5,
5-Dimethyl-1, 3, 2-Dioxaphosphinane 2-Sulfides
5 mmol of compound 2, 5 mmol of 3-aminomethylpyridine, 7.5 mmol of
triethylamine, and 10 mL of anhydrous dichloromethane were taken in
a 50-mL three-necked reaction flask; the mixture was stirred at r.t. or
under reflux untill the reaction was complete (monitored by TLC). The
solid was filtered; after removal of the solvent, the crude product was
purified by flash column chromatography on silica gel with a mixture of
ethyl acetate and petroleum ether as the eluent. First the trans isomers
and then the cis isomers were eluted.
3a (Ar = 4-chlorophenyl, cis): white solid, m.p. 166.6–167.0◦C, yield
31.5%; 1H NMR (CDCl3) δ = 0.78 (s, 3H, CH3), 0.95 (s, 3H, CH3), 3.84
(dd, 3 J
= 23.6 Hz, 2 J
= 14.8 Hz, 1H, CH2OP), 4.45–4.58 (m, 3H,
H
P
H
H
CH2OP, NCH2), 5.46 (s, 1H, CH Ar), 7.06–7.41 (m, 5H, Ar H, β H
on pyridine), 7.91 (d,3 J
= 8.0 Hz, 1H, γ H on pyridine), 8.59 (d,
H
H
3 J
= 4.4 Hz, 1H, α H on pyridine), 8.67 (s, 1H, α H on pyridine); 31
P
H
H
NMR (CDCl3)δ = 70.13; IR (KBr) (υmax/cm−1) 3196 (N H), 1492(C N),
713 (P S), 1038 and 986 (P O C); MS, m/z (%) 382 (M+, 4.1), 203 (100),
187.1 (19), 179 (14), 165 (23), 145 (20.3), 107 (44.8), 92 (25.8); anal. calcd.
TABLE III The Ratios of Different Cyclic Thiophosphoryl Chlorides 2
Compound 2a
2b
2c
2d
2e
2f
2g
2h
Ar
Cis/trans
4-ClPh Ph 4-NO2Ph 3-FPh 4-CH3Ph 4-OCH2OPh 2-NO2Ph 2-ClPh
46/54 48/52 43/57 52/48 47/53 46/54 43/57 45/55

2670
D.-Q. Shi et al.
for C17H20ClN2O2PS (382.5): C, 53.33; H, 5.23; N, 7.32. Found: C, 53.54;
H, 5.08; N, 7.01.
4a (Ar = 4-chlorophenyl, trans): pale yellow solid, m.p. 177.5–
1
177.8◦C, yield 13.5%; H NMR (CDCl3)δ = 0.76 (s, 3H, CH3), 1.05 (s,
3H, CH3), 3.47 (sb, 1H, NH), 3.90 (dd, 3 J
= 23.6 Hz,2 J
=10.8 Hz,
H
P
H
H
1H, CH2OP), 4.20–4.26 (m, 3H, CH2OP, NCH2), 5.18 (s, 1H, CH Ar),
7.21–7.34 (m, 5H, Ar-H, β H on pyridine), 7.81 (d,3 J
=7.6 Hz, 1H,
H
H
γ -H on pyridine), 8.47 (d, 3 J
=4.0 Hz, 1H, α-H on pyridine), 8.68
H
H
(s, 1H, α-H on pyridine); 31P NMR (CDCl3)δ = 68.83; Anal. calcd. for
C17H20Cl N2O2PS (382.5): C, 53.33; H, 5.23; N, 7.32. Found: C, 53.70;
H, 5.26; N, 7.75.
3b (Ar = phenyl, cis): yellow solid, m.p. 190.2–190.7◦C, yield 40.0%;
1H NMR (CDCl3)δ = 0.81 (s, 3H, CH3), 0.97(s, 3H, CH3), 3.86 (dd,
3 J
= 26.0 Hz,2 J
= 11.4 Hz, 1H, CH2OP), 4.43–4.59 (m, 3H,
H
P
H
H
CH2OP, NCH2), 5.49 (s, 1H, CH-Ar), 7.13–7.33 (m, 6H, Ar-H, β-H on
pyridine), 7.86 (d,3 J
= 8.0 Hz, 1H, γ -H on pyridine), 8.57 (d,3 J
=
H
H
H
H
4.0 Hz, 1H, α-H on pyridine), 8.63 (s, 1H, α-H on pyridine); 31P NMR
(CDCl3)δ = 69.68; IR (KBr) (υmax/cm−1) 3193 (N H), 695 (P S), 1040
and 991 (P O C); MS, m/z (%) 348 (M+, 37.2), 205 (30.6), 203 (97.4), 187
(53.7), 145 (88.7), 128 (85.7), 117 (64.4), 91 (90.3), 79 (33.1), 77 (48.9),
65 (46.5); anal. calcd. for C17H21N2O2PS (348.0): C, 58.62; H, 6.03; N,
8.05. Found: C, 58.84; H, 6.06; N, 8.26.
4b (Ar = phenyl, trans): white solid, m.p. 207.2–208.6◦C, yield 16.6%;
1H NMR (CDCl3)δ = 0.77 (s, 3H, CH3), 1.08(s, 3H, CH3), 3.20 (d, 1H,
NH, 3 J
= 5.2 Hz), 3.90 (dd, 3 J
= 23.6 Hz,2 J
= 10.8 Hz, 1H,
H
H
H
P
H
H
CH2OP), 4.17–4.27 (m, 3H, CH2OP, NCH2), 5.20 (s, 1H, CH Ar), 7.26–
7.34 (m, 6H, Ar H, β-H on pyridine), 7.79 (d,3 J
= 7.6 Hz, 1H, γ -H on
H
H
pyridine), 8.48 (d,3 J
= 4.2 Hz, 1H, α-H on pyridine), 8.66 (s, 1H, α-H
H
H
on pyridine); 31P NMR (CDCl3)δ = 68.92; anal. calcd. for C17H21N2O2PS
(348.0): C, 58.62; H, 6.03; N, 8.05. Found: C, 53.77; H, 5.78; N, 7.98.
3c (Ar = 4-nitrophenyl, cis): pale yellow solid, m.p. 243.9–244.5◦C,
yield 36%; 1H NMR (CDCl3)δ = 0.77 (s, 3H, CH3), 0.86 (s, 3H, CH3), 3.34
(s, 1H, NH), 3.95 (dd, 3 J
= 24.0 Hz, 2 J
= 11.2 Hz, 1H, CH2OP),
H
P
H
H
4.31–4.40 (m, 3H, CH2OP, NCH2), 5.58 (s, 1H, CH Ar), 7.36–7.44 (m,
3H, Ar H, β H on pyridine), 7.81 (d, 3 J
= 7.6 Hz, 1H,γ -H on pyri-
H
H
dine), 8.21(d,3 J
= 4.4 Hz, 2H, Ar-H) 8.53(d, 3 J
= 4.8 Hz, 1H,
H
H
H
H
α H on pyridine), 8.67 (s, 1H, α-H on pyridine); 31P NMR (CDCl3)δ =
70.46; MS, m/z (%) 393 (M+, 0.5), 103 (5.24), 92 (10), 90 (100), 76 (29.1),
64 (25.8); anal. calcd. for C17H20N3O4PS (393.0): C, 51.91; H, 5.09; N,
10.69. Found: C, 51.44; H, 5.23; N, 10.63.
4c (Ar = 4-nitrophenyl, trans): white solid, m.p. 220.9–221.7◦C, yield
1
8.4%; H NMR (CDCl3)δ = 0.75 (s, 3H, CH3), 0.90 (s, 3H, CH3), 3.34
3
3
(d, J
= 8.0 Hz, 1H, NH), 3.91 (dd, J
= 24.8 Hz,2 J
= 12.0
H
H
H
P
H
H

Cyclic Phosphorothonamides
2671
Hz, 1H, CH2OP), 4.08–4.33(m, 3H, CH2OP, NCH2), 5.20 (s, 1H, CH-Ar),
7.30–7.33 (m, 4H, Ar H), 7.56 (d,3 J
= 8.4 Hz, 1H, β-H on pyridine),
H
H
7.80 (d,3 J
= 8.0 Hz, 1H, γ -H on pyridine), 8.42 (d,3 J
= 3.2 Hz,
H
H
H
H
1H, α-H on pyridine), 8.56 (s, 1H, α-H on pyridine); 31P NMR (CDCl3) δ =
70.18; anal. calcd. for C17H20N3O4PS (393.0): C, 51.91; H, 5.09; N, 10.69.
Found: C, 52.16; H, 5.45; N, 10.73.
3d (Ar = 3-fluorophenyl, cis): white crystal, m.p. 188.5–189.0◦C, yield
32%; 1H NMR (CDCl3)δ = 0.83 (s, 3H, CH3), 0.96 (s, 3H, CH3), 3.86 (dd,
3 J
= 24.0 Hz, 2 J
= 11.2 Hz, 1H, CH2OP), 4.43–4.59 (m, 3H,
H
P
H
H
CH2OP, NCH2), 5.48 (s, 1H, CH Ar), 6.83–7.36 (m, 5H, Ar H, β-H
on pyridine), 7.85 (d,3 J
= 8.0 Hz, 1H, γ -H on pyridine), 8.58 (d,
H
H
3 J
= 3.6 Hz, 1H, α-H on pyridine), 8.64 (s, 1H, α-H on pyridine); 31
P
H
H
NMR (CDCl3)δ = 70.06; MS, m/z (%) 367 (M+1, 18.3), 366 (M+, 25), 203
(37.3), 135 (39.9), 133 (35.9), 109 (76.9), 92 (100), 65 (54.6), 56 (49.2);
anal. calcd. for C17H20FN2O2PS (366): C, 55.74; H, 5.46; N, 7.65. Found:
C, 56.13; H, 5.39; N, 7.84.
4d (Ar = 3-fluorophenyl, trans): white crystal, m.p. 211.0–211.5◦C,
1
yield 7%; H NMR (CDCl3) δ = 0.79 (s, 3H, CH3), 1.26 (s, 3H, CH3),
3.14(sb, 1H, NH), 3.90 (dd, 3 J
= 23.6 Hz, 2 J
= 10.8 Hz, 1H,
H
P
H
H
CH2OP), 4.18–4.25 (m, 3H, CH2OP, NCH2), 5.15 (s, 1H, CH-Ar), 7.23–
7.33 (m, 5H, Ar-H, β-H on pyridine), 7.77 (d,3 J
= 7.6 Hz, 1H, γ -H
H
H
on pyridine), 8.50 (s, 1H, α-H on pyridine), 8.65(s, 1H, α-H on pyridine);
31P NMR (CDCl3)δ = 68.91; anal. calcd. for C17H20FN2O2PS (366): C,
55.74; H, 5.46; N, 7.65. Found: C, 55.50; H, 5.61; N, 7.97.
3e (Ar = 4-methylphenyl, cis): white solid, m.p. 189.4–189.9◦C, yield
1
29.7%; H NMR (CDCl3)δ = 0.79 (s, 3H, CH3), 0.97 (s, 3H, CH3), 2.35
(s, 3H, CH3 Ar), 3.86 (dd, 3 J
CH2OP), 4.44–4.58 (m, 3H, CH2OP, NCH2), 5.46 (s, 1H, CH Ar), 7.04
= 23.8 Hz, 2 J
= 11.2 Hz, 1H,
H
P
H
H
(d, 3 J
= 8.4 Hz, 1H, Ar H), 7.10 (d,3 J
= 8.4 Hz, 1H, Ar-H),
H
H
H
H
7.26 (s, 1H, Ar H), 7.34–7.37 (m, 2H, Ar H, β-H on pyridine), 7.90
(d,3 J
= 7.6 Hz, 1H, γ -H on pyridine), 8.59 (d, 3 J
= 4.4 Hz, 1H, α-
H
H
H
H
H on pyridine), 8.65 (s, 1H, α-H on pyridine); 31P NMR (CDCl3)δ = 69.90;
IR (KBr) (υmax/cm−1) 3082 (N H), 1517 and 1579(C N), 712 and 666
(P S), 1037 and 1022 (P O C); MS, m/z (%) 362 (M+, 4.0), 203 (86.25),
187 (46.6), 159 (100), 145 (83.3), 135 (29.4), 119 (34.5), 107 (66.8), 105
(62), 91 (58.1), 77 (36.3), 65 (22.5); anal. calcd. for C18H23N2O2PS (362):
C, 59.67; H, 6.35; N, 7.73. Found: C, 59.51; H, 6.23; N, 7.98.
4e (Ar = 4-methylphenyl, trans): white solid, m.p. 170.3–170.8◦C,
1
yield 11.5%; H NMR (CDCl3)δ = 0.75 (s, 3H, CH3), 1.08 (s, 3H, CH3),
2.38 (s, 3H, CH3 Ar), 3.47 (d, 1H, NH,3 J
= 6.0 Hz), 3.89 (dd,
H
H
3 J
= 24.0 Hz,2 J
= 10.8 Hz, 1H, CH2OP), 4.17–4.26 (m, 3H,
H
P
H
H
CH2OP, NCH2), 5.17 (s, 1H, CH-Ar), 7.14–7.29 (m, 5H, Ar-H, β-H
on pyridine), 7.78 (d,3 J
= 8.0 Hz, 1H, γ -H on pyridine), 8.50 (d,
H
H

2672
D.-Q. Shi et al.
3 J
= 4.4 Hz, 1H, α-H on pyridine), 8.64 (s, 1H, α-H on pyridine);
H
H
31P NMR (CDCl3) δ = 68.98; anal. calcd. for C18H23N2O2PS (362): C,
59.67; H, 6.35; N, 7.73. Found: C, 59.90; H, 6.44; N, 7.71.
3f (Ar = 3, 4-dioxymethylene, cis): white solid, m.p. 181.8–182.9◦C,
1
yield 33.5%; H NMR (CDCl3)δ = 0.79 (s, 3H, CH3), 0.98 (s, 3H, CH3),
3.85 (dd, 3 J
= 28.4 Hz, 2 J
= 11.4 Hz, 1H, CH2OP), 4.45–4.55
H
P
H
H
(m, 3H, CH2OP, NCH2), 5.40 (s, 1H, CH Ar), 5.98 (s, 2H, OCH2OAr),
6.60–6.76 (m, 3H, Ar-H), 7.26–7.39 (m, 1H, β-H on pyridine), 7.88–7.90
(d,3 J
= 8.0 Hz, 1H, γ -H on pyridine), 8.59 (d, 3 J
= 4.4 Hz, 1H, α-
H
H
H
H
H on pyridine), 8.65 (s, 1H, α-H on pyridine); 31P NMR (CDCl3)δ = 70.49;
MS, m/z (%) 393 (M+1, 16.7), 392 (50.2), 337 (95.78), 239 (19.9), 190
(35.2), 187 (67.9), 165 (78.4), 131 (46.8), 117 (52), 115 (67.6), 92 (100),
91 (72.5), 77 (38.4), 65 (79.7), 51 (45.8); anal. calcd. for C18H21N2O4PS
(392): C, 55.10; H, 5.36; N, 7.14. Found: C, 55.23; H, 5.09; N, 7.01.
4f (Ar = 3, 4-dioxymethylene, trans): white solid, m.p. 190.0–190.3◦C,
yield 17%; 1H NMR (CDCl3)δ = 0.76 (s, 3H, CH3), 1.09 (s, 3H, CH3), 3.34
3
(sb, 1H, NH), 3.88 (dd, J
= 24 Hz,2 J
= 14.6 Hz, 1H, CH2OP),
H
P
H
H
4.20–4.24 (m, 3H,CH2OP, NCH2), 5.12 (s, 1H, CH Ar), 5.98 (s, 2H,
OCH2OAr), 6.69–6.84 (m, 3H, Ar H), 7.27–7.32 (m, 1H, β-H on pyri-
dine), 7.80–7.82 (d,3 J
= 8Hz, 1H, γ -H on pyridine), 8.51 (d, 3 J
=
H
H
H
H
4.0 Hz, 1H, α-H on pyridine), 8.67 (s, 1H, α-H on pyridine); 31P NMR
(CDCl3)δ = 68.97; anal. calcd. for C18H21N2O4PS (392): C, 55.10; H,
5.36; N, 7.14. Found: C, 54.96; H, 5.41; N, 7.08.
3g (Ar = 2-nitrophenyl, cis): pale yellow solid, m.p. 178.3–177.8◦C,
yield 28%; 1H NMR (CDCl3)δ = 0.72 (s, 3H, CH3), 0.95 (s, 3H, CH3), 3.84
(dd, 3 J
= 23.4 Hz,2 J
= 11.4 Hz, 1H, CH2OP), 4.45–4.63 (m, 3H,
H
P
H
H
CH2OP, NCH2), 6.65 (s, 1H, CH-Ar), 7.27–7.58 (m, 5H, Ar-H, β-H on
pyridine), 7.85–7.91 (m, 1H, γ -H on pyridine), 8.59 (d, 3 J
= 4.0 Hz,
H
H
1H, α-H on pyridine), 8.66 (s, 1H, α-H on pyridine); 31P NMR (CDCl3)δ =
69.44; MS, m/z (%) 393 (M+, 0.4), 128 (13.3), 115 (24.4), 105 (24.6), 92
(100), 91 (39.4), 77 (27.9), 65 (41.8), 56 (72.1), 55 (52.5), 41 (58.1); anal.
calcd. for C17H20N3O4PS (393.0): C, 51.91; H, 5.09; N, 10.69. Found: C,
51.83; H, 5.00; N, 10.76.
3h (Ar = 2-chlorophenyl, cis): white solid, m.p. 184.7–185.1◦C, yield
1
53%; H NMR (CDCl3)δ = 0.87 (s, 3H, CH3), 1.07 (s, 3H, CH3), 3.86
(dd, 3 J
= 22.8 Hz,2 J
= 11.4 Hz, 1H, CH2OP), 4.46–4.66 (m,
H
P
H
H
3H, CH2OP, NCH2), 6.09 (s, 1H, CH-Ar), 7.17–7.41 (m, 5H, Ar-H, β-
H on pyridine), 7.94 (d, 3 J
= 7.6 Hz, 1H, γ -H on pyridine), 8.58 (d,
H
H
3 J
= 4.4 Hz, 1H, α-H on pyridine), 8.67(s, 1H, α-H on pyridine); 31
P
H
H
NMR (CDCl3)δ = 69.46; MS, m/z (%) 383 (M+1, 10.9), 202 (56.5), 128
(33.4), 114 (45), 106 (97.5), 91 (100), 76 (33.6), 64 (51), 55 (30.5); anal.
calcd. for C17H20ClN2O2PS (382.5): C, 53.33; H, 5.23; N, 7.32. Found: C,
53.67; H, 5.41; N, 7.40.

Cyclic Phosphorothonamides
2673
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