Synthesis and herbicidal activity of -amino phosphonate derivatives containing thiazole and pyrazole moieties

Article abstract of DOI:10.1080/10426500903251373

A series of novel -amino phosphonate derivatives containing the thiazole and pyrazole moieties 3 were synthesized by the Mannich-type reaction of substituted pyrazole-aldehyde 1, 2-amino-5-ethoxycarbonyl-4-methyl-thiazole 2, and dialkyl phosphites or triphenyl phosphite in the presence of a Lewis acid such as magnesium perchlorate as the catalyst under solvent-free conditions. Their structures were clearly confirmed by spectroscopy data (IR, 1H NMR, 31P NMR, MS) and elemental analysis. The results of a preliminary bioassay (in vitro) indicated that some of the title compounds 3 possessed moderate herbicidal activities against dicotyledonous plants (Brassica campestris L) or monocotyledonous plants (Echinochloa crus-galli) at the concerntration of 100 mg/L. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426500903251373

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Synthesis and Herbicidal Activity of
α-Amino Phosphonate Derivatives
Containing Thiazole and Pyrazole
Moieties
Zhi-Hua Yu a & De-Qing Shi a
a Key Laboratory of Pesticide and Chemical Biology, Ministry of
Education, College of Chemistry, Central China Normal University,
Wuhan, Hubei, People's Republic of China
Version of record first published: 02 Aug 2010.
To cite this article: Zhi-Hua Yu & De-Qing Shi (2010): Synthesis and Herbicidal Activity of α-Amino
Phosphonate Derivatives Containing Thiazole and Pyrazole Moieties, Phosphorus, Sulfur, and Silicon
and the Related Elements, 185:8, 1746-1752
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Phosphorus, Sulfur, and Silicon, 185:1746–1752, 2010
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500903251373
SYNTHESIS AND HERBICIDAL ACTIVITY OF α-AMINO
PHOSPHONATE DERIVATIVES CONTAINING THIAZOLE
AND PYRAZOLE MOIETIES
Zhi-Hua Yu and De-Qing Shi
Key Laboratory of Pesticide and Chemical Biology, Ministry of Education, College
of Chemistry, Central China Normal University, Wuhan, Hubei, People’s Republic
of China
A series of novel α-amino phosphonate derivatives containing the thiazole and pyrazole
moieties 3 were synthesized by the Mannich-type reaction of substituted pyrazole-aldehyde
1, 2-amino-5-ethoxycarbonyl-4-methyl-thiazole 2, and dialkyl phosphites or triphenyl phos-
phite in the presence of a Lewis acid such as magnesium perchlorate as the catalyst under
solvent-free conditions. Their structures were clearly confirmed by spectroscopy data (IR, 1H
NMR, 31P NMR, MS) and elemental analysis. The results of a preliminary bioassay (in vitro)
indicated that some of the title compounds 3 possessed moderate herbicidal activities against
dicotyledonous plants (Brassica campestris L) or monocotyledonous plants (Echinochloa
crus-galli) at the concerntration of 100 mg/L.
Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental
file.
Keywords α-Amino phosphonate; herbicidal activity; pyrazole; thiazole
INTRODUCTION
Heterocyclic compounds containing nitrogen have played a major role in modern
pesticide industry; it is reported that more than 85% of pesticides with high activity and low
toxicity belong to nitrogen heterocyclic compounds. Pyrazole and thiazole are important
two kinds of heterocyclic compounds with a wide spectrum of remarkable biological
activities,1–7 and many derivatives containing pyrazole and thiazole nucleus have been
commercialized as herbicides, insecticides, and fungicides in plant protection8–11 (see
Figure 1). For example, pyraclofos and clothianidin were developed as insecticides, whereas
pyrazolate and flurazole have been used as herbicides or their safeners, and furametpyr and
ethaboxam as fungicides. Recently, α-amino phosphonic acids and their ester derivatives,
Received 22 June 2009; accepted 11 August 2009.
The authors are grateful to the Natural Science Foundation of China (Grant No. 20872046) and the Natural
Science Foundation of Hubei Province (Grant No. 2008CDB086) for financial support.
Address correspondence to De-Qing Shi, Key Laboratory of Pesticide and Chemical Biology, Ministry of
Education, College of Chemistry, Central China Normal University, Wuhan 430079, Hubei, People’s Republic of
China. E-mail: chshidq@mail.ccnu.edu.cn
1746

α-AMINO PHOSPHONATE DERIVATIVES
1747
Cl
O
Cl
O
H3C
Cl
N
N
H
H3C
N
Cl
N
O
CH3
CH3
O
P
N
N
S
C3H7
C2H5
CH3
H3C
OS
O
CH3
N
O
O
O
CH3
Furametpyr
Pyrazolate
Pyraclofos
CH CH
2
3
CF
O
3
N
N
H
N
CH CH NH
3
2
H
H
O
N
Cl
S
N
N CH
3
S
S
S
O
CN
N
NO
2
Cl
Clothianidin
Flurazole
Ethaboxam
Figure 1 Structures of some pesticides of pyrazole and thiazole derivatives.
as bioisosteres of natural amino acids, are receiving an increasing amount of attention in
medicinal chemistry and pesticide science because some of their derivatives have been
found to exhibit a wide range of biological activities such as enzyme inhibition, antibiotics,
and haptens of catalytic antibodies, fungicides, herbicides, plant regulators, and plant
virucides [for example, antiviral agent against tobacco mosaic virus (TMV)].12–18 In order
to find novel potent and selective herbicide lead compounds, we have synthesized a series
of novel α-amino phosphonate derivatives containing pyrazole and thiazole hetercycles 3
via the Mannich-type reaction under solvent-free conditions. The target compounds 3 were
evaluated for herbicidal activities. The synthetic route is listed in Scheme 1.
CHO
OAr
H3C
ArOH/KOH
H3C
CHO
Cl
H3C
POCl3/DMF
N
N
N
O
N
N
N
Ph
Ph
Ph
1b~1d
1a
F
POCl3/DMF
CHO
CH3
NNHPh
C
PhNHNH2
F
COCH3
F
N
N
Ph
1e
H C
S
NH CNH
3
N
SO Cl
2
2
2
2
NH
2
CH COCH COOC H
CH COCHCOOC H
3
2
2
5
3
2
5
C H OOC
2
5
S
Cl
2
O
H3C
C2H5OOC
P(OR)2
R2
N
Mg(ClO4)2
N
H3C
C2H5OOC
R2
HPO(OR)2
or P(OPh)3
CHO
R1
N
N
+
+
S
H
NH2
N
S
R1
N
N
Ph
Ph
3
2
1
Scheme 1 Synthetic route of the title compounds 3.

1748
Z.-H. YU AND D.-Q. SHI
RESULTS AND DISCUSSION
Synthesis and Structure Determination of Title Compounds 3
A series of novel α-amino phosphonate derivatives containing thiazole and pyrazole
moieties 3 were synthesized by the Mannich-type reactions of substituted pyrazole-aldehyde
1, 2-amino-5-ethoxycarbonyl-4-methyl-thiazole2, and dialkyl phosphites or triphenyl phos-
phite in the presence of a Lewis acid such as magnesium perchlorate as the catalyst under
solvent-free conditions. We found that the Lewis acid (magnesium perchlorate) can pro-
mote the reaction greatly, and without the use of magnesium perchlorate as the catalyst,
the reaction was greatly slowed and the yields were very low (about 25%). The Mannich
reaction might include two-step reactions: First, aldehydes are reacted with amines to form
imines in the catalyst of magnesium perchlorate; second, phosphites are added to imines
to generate α-amino phosphonates. The structures of target compounds 3 were deduced
1
from their spectral data (IR, H NMR, 31P NMR, EI-MS) and elemental analysis. In the
1H NMR spectra of 3, the CH proton linking with the phosphonyl group displayed as a
doublet due to coupling with P atom with the coupling constant of 23 Hz, while the NH
proton appeared as a singlet with chemical shift δ 5.5–6.5. In some cases, the NH signal
peaks disappeared in the 1H NMR spectrum. For 31P NMR spectra, the phosphorus atom
of all compounds displayed as a singlet, giving chemical shifts δ 11.6–22.0. The IR spectra
of compounds 3 showed normal stretching absorption bands, indicating the existence of
the NH (3200–3300 cm−1), C O (∼1700 cm−1), P O (∼1225 cm−1), P O C (∼1025
cm−1) moieties. The EI-MS of compounds 3 revealed the existence of their molecular ion
peaks, which were in accordance with the given structures of products 3.
Herbicidal Activities
The herbicidal activity values of the title compounds 3 against Brassica campestris L
(rape) and Echinochloa crus-galli (barnyard grass) have been investigated at the dosages of
100 mg/L and 10 mg/L compared with the commercially available herbicide, bispyribac-
sodium, according to the method described in the Experimental section. The results of
a preliminary bioassay (in vitro) indicated that some of the title compounds 3 possessed
moderate herbicidal activities against dicotyledonous plants (Brassica campestris L) or
monocotyledonous plants (Echinochloa crus-galli) at the concerntration of 100 mg/L. For
example, compound 3b possessed 47.2% inhibitory activity against Brassica campestris
L, and compound 3f showed 42.1% inhibitory activity against Echinochloa crus-galli;
however, compounds 3 displayed weak herbicidal activity at the concentration of 10 mg/L.
Further biological activity evaluation such as antiviral activity against TMV, herbicidal
activity (in vivo), the structure–activity relationships, and lead compound optimization are
underway.
CONCLUSION
In summary, we have synthesized a series of novel α-amino phosphonate derivatives
containing thiazole and pyrazole moieties 3 via the Mannich-type reaction of substituted
pyrazole-aldehydes 1, 2-amino-5-ethoxycarbonyl-4-methyl-thiazole 2, and dialkyl phos-
phites or triphenyl phosphite in the presence of a Lewis acid such as magnesium perchlorate
as the catalyst under solvent -free conditions. Their structures were clearly confirmed by
1
spectroscopy data (IR, H NMR, 31P NMR, MS) and elemental analysis. The results of
a preliminary bioassay (in vitro) indicated that some of the title compounds 3 possessed

α-AMINO PHOSPHONATE DERIVATIVES
1749
moderate herbicidal activities against dicotyledonous plants (Brassica campestris L) or
monocotyledonous plants (Echinochloa crus-galli) at the concerntration of 100 mg/L.
EXPERIMENTAL
Instruments
The melting points of the products were determined on an XT-4 binocular microscope
(Beijing Tech Instrument Co., Beijing, China) and were uncorrected. The IR spectra were
recorded on a Nicolet NEXUS470 spectrometer as KBr pellets with absorption given in
cm−1. 1H and 31P NMR spectra were performed on a Varian Mercury Plus-400 (400 MHz)
or Varian Mercury Plus-600 (600 MHz) spectrometer at room temperature in CDCl3 with
TMS and 85% H3PO4 as the internal and external standards, respectively. Mass spectra were
measured on a Finnigan TraceMS 2000 spectrometer at 70 eV using EI method. Elemental
analysis was taken on a Vario EL III elemental analysis instrument. Analytical TLC was
performed on silica gel GF254. Column chromatographic purification was carried out using
silica gel. Unless otherwise noted, all materials were commercially available and were used
directly without further purification. All solvents were dried and redistilled before use.
2-Amino-5-ethoxycarbonyl-4-methyl-thiazole 2 was prepared by chloridization of ethyl
acetylacetate with SO2Cl2, followed by the cyclization with thiourea according to the
reported procedure.19 Yield 79%, mp 172.6–173.2◦C; 1H NMR (CDCl3, 400 MHz): δ 1.33
(t, J = 7.2 Hz, 3H, OCH2CH3), 2.52 (s, 3H, CH3), 4.26 (q, J = 7.2 Hz, 2H, OCH2), 5.79 (s,
2H, NH2). Compound 1a was prepared by the Vilsmeier–Haack reaction of pyrazolone,20
and compounds 1b∼1d were obtained from the reaction of compound 1a and substituted
phenols under basicconditions accordingtothe reportedsyntheticprotocols.21,22 Compound
1e was obtained as a white solid by the condensation of 4-fluoroacetophenone with phenyl
hydrazine and subsequent reaction with Vilsmeier–Haak reagent according to the reported
method.23 Yield, 63%; mp 152.2–153.6◦C.
General Synthetic Procedures for O,Oꢀ-Dialkyl (Diphenyl)-N-
(5-ethoxycarbonyl-4-methyl-thiazol-2-yl)-α-amino-(substitutedpyrazol-
4-yl)methylphosphonates 3
Substituted pyrazole-aldehyde 1a∼1e (3 mmol), 2-amino-5-ethoxycarbonyl-4-
methyl-thiazole 2 (0.56 g, 3 mmol), and dialkyl phosphite or triphenyl phosphite (3 mmol)
and Mg(ClO4)2 (0.033 g, 0.15 mmol) were added to a 50 mL flask. The mixture was stirred
at 80–120◦C for 2–6 h (monitored by TLC). Acetone (10 mL) was added, the solid was
filtered off, and the solvent was removed under reduced pressure. The crude product was
purified by column chromatography on silica gel using a mixture of petroleum ether and
acetone (2:1) as an eluent to give 3 as white solids in 53–80% yields.
Data for 3a. (R = Et, R1 = PhO, R2 = CH3): yield 61%, white solid, mp
157.6–158.3◦C; IR (KBr): υ 3218 (N H), 2984 (Ph H), 1708 (C O), 1560, 1495, 1427
1
(Ph), 1270, 1245 (P O), 1036 (P O C) cm−1; H NMR (CDCl3, 600 MHz): δ 1.24 (t,
J = 7.2 Hz, 3H, CH2CH3), 1.28 (t, J = 7.2 Hz, 3H, CH2CH3), 1.32 (t, J = 7.2 Hz, 3H,
CH2CH3), 2.45 (s, 3H, CH3), 2.48 (s, 3H, CH3), 3.96–4.02 (m, 1H, OCH2), 4.09–4.14 (m,
3H, OCH2), 4.25 (q, J = 7.2 Hz, 2H, OCH2), 4.96 (d, J = 22.8 Hz, 1H, PCH), 5.90 (s,
1H, NH), 6.85 (d, J = 7.8 Hz, 2H, ArH), 6.98 (t, J = 7.2 Hz, 1H, ArH), 7.16–7.20 (m,
1
3H, ArH), 7.30 (d, J = 7.8 Hz, 2H, ArH), 7.56 (d, J = 7.2 Hz, 2H, ArH);31P { H} NMR
(CDCl3, 243 MHz): δ 19.55. Anal. Calcd for C28H33N4O6PS: C 57.52, H 5.69, N 9.58;
found C 57.60, H 5.35, N 9.81.

1750
Z.-H. YU AND D.-Q. SHI
Data for 3b. (R = n-Bu, R1 = Cl, R2
CH3): yield 59%, white solid, mp
159.7–160.5◦C; IR (KBr): υ 3257 (N H), 1701 (C O), 1552, 1491, 1418 (Ph), 1268,
1196 (P O), 1020 (P O C) cm−1; 1H NMR (CDCl3, 600 MHz): δ 0.87 (t, J = 7.8 Hz,
3H, CH2CH3), 0.91 (t, J = 7.8 Hz, 3H, CH2CH3), 1.28–1.33(m, 5H, OCH2CH3, CH2),
1.36–1.40 (m, 2H, CH2), 1.52–1.55 (m, 2H, CH2), 1.63–1.67 (m, 2H, CH2), 2.45 (s, 3H,
CH3), 2.54 (s, 3H, CH3), 3.91 (q, J = 7.8 Hz, 1H, OCH2), 4.05 (q, J = 7.8 Hz, 1H, OCH2),
4.12 (q, J = 7.2 Hz, 2H, OCH2), 4.23–4.27 (m, 2H, OCH2), 5.10 (d, J = 23.4 Hz, 1H,
PCH), 6.51 (s, 1H, NH), 7.41 (t, J = 7.2 Hz, 1H, ArH), 7.47 (t, J = 7.8 Hz, 2H, ArH),
1
7.52 (d, J = 7.8 Hz, 2H, ArH); 31P { H}NMR (CDCl3, 243 MHz): δ 20.03. Anal. Calcd
for C26H36ClN4O5PS: C 53.56, H 6.22, N 9.61; found C 53.78, H 6.01, N 9.54.
Data for 3c. (R = Ph, R1 = Cl, R2 CH3): yield 78%, white solid, mp 136–137◦C;
IR (KBr): υ 3270 (N H), 1697 (C O), 1549, 1489, 1416 (Ph), 1270, 1187 (P O), 1094,
1024 (P O C) cm−1; 1H NMR (CDCl3, 600 MHz): δ 1.33 (t, J = 7.2Hz, 3H, CH2CH3),
2.46 (s, 3H, CH3), 2.55 (s, 3H, CH3), 4.27 (q, J = 7.2 Hz, 2H, OCH2), 5.61 (d, J = 21.6
Hz, 1H, PCH), 7.04 (d, J = 7.8 Hz, 2H, ArH), 7.14–7.24 (m, 3H, ArH), 7.27–7.30 (m, 3H,
1
ArH), 7.32 (t, J = 7.8 Hz, 2H, ArH), 7.40–7.47 (m, 5H, ArH); 31P { H}NMR (CDCl3,
243 MHz): δ 21.45; EI-MS (70 eV): m/z 622 (M+, 5), 389 (30), 353 (14), 245 (14.7), 205
(15.6), 171 (22), 140 (29), 94 (100), 77 (22), 45 (53.8). Anal. Calcd for C30H28ClN4O5PS:
C 57.83, H 4.53, N 8.99; found C 58.11, H 4.27, N 9.13.
Data for 3d. (R = Ph, R1 = H, R2 = 4-FC6H4): yield 53%, white solid, mp
189.7–191.2◦C; IR (KBr): υ 3265 (N H), 1692 (C O), 1560, 1482, 1450 (Ph), 1248
(P O), 1028 (P O C) cm−1; 1H NMR (CDCl3, 400 MHz): δ 1.36 (t, J = 7.2 Hz, 3 H,
OCH2CH3), 2.63 (s, 3H, CH3), 4.31 (q, J = 7.6 Hz, 2 H, OCH2), 5.38 (d, J = 23.4 Hz,
1H, PCH), 6.78 (d, J = 7.6 Hz, 2H, ArH), 6.96–7.25 (m, 6H, ArH), 7.27–7.55 (m, 9H,
1
ArH), 7.72 (d, J = 7.6 Hz, 2H, ArH), 8.26 (s, 1H, pyrazol-H); 31P { H}NMR (CDCl3, 162
MHz): δ 22.38. Anal. Calcd for C35H30FN4O5PS: C 62.87, H 4.52, N 8.38; found C 62.57,
H 4.42, N 8.24.
Data for 3e. (R = Et, R1 = Cl, R2 = CH3): yield 68%, white solid, mp
145.4–146.7◦C; IR (KBr): υ 3268 (N H), 1691 (C O), 1552, 1484, 1453 (Ph), 1235
1
(P O), 1026 (P O C) cm−1; H NMR (CDCl3, 600 MHz): δ 1.23 (t, J = 7.2 Hz, 3H,
OCH2CH3), 1.33 (t, J = 7.2 Hz, 3H, OCH2CH3), 1.35 (t, J = 7.2 Hz, 3H, OCH2CH3),
2.44 (s, 3H, CH3), 2.55 (s, 3H, CH3), 4.00–4.02 (m, 1H, OCH2CH3), 4.10–4.14 (m, 1H,
OCH2CH3), 4.20–4.27 (m, 4H, 2OCH2CH3), 5.06 (d, J = 23.4 Hz, 1H, PCH), 5.71 (s, 1H,
NH), 7.41(t, J = 7.2 Hz, 1H, ArH), 7.48 (t, J = 7.2 Hz, 2H, ArH), 7.52 (d, J = 7.2 Hz, 2H,
1
ArH); 31P { H} NMR (CDCl3, 243 MHz): δ 21.75; EI-MS (70 eV): m/z 526 (M+, 5), 389
(8), 221 (31), 186 (100), 185 (48), 158 (83), 141 (39), 113 (43), 87 (7.0), 71 (9.5). Anal.
Calcd for C22H28ClN4O5PS: C 50.14, H 5.36, N 10.63; found C 50.35, H 5.24, N 10.40.
Data for 3f. (R = Et, R1 = 4-FC6H4O, R2 = CH3): yield 70%, white solid, mp
163.8–164.7◦C; IR (KBr): υ 3272 (N H), 1698 (C O), 1554, 1481, 1456 (Ph), 1228
1
(P O), 1032 (P O C) cm−1; H NMR (CDCl3, 600 MHz): δ 1.25 (t, J = 7.2 Hz, 3H,
OCH2CH3), 1.29 (t, J = 7.2 Hz, 3H, OCH2CH3), 1.33 (t, J = 7.2 Hz, 3H, OCH2CH3),
2.45 (s, 3H, CH3), 2.47 (s, 3H, CH3), 4.00–4.03 (m, 1H, OCH2CH3), 4.10–4.16 (m, 3H,
OCH2CH3), 4.25 (q, J = 7.2 Hz, 2H, OCH2CH3), 4.97 (d, J = 22.8 Hz, 1H, PCH), 6.78
(dd, J = 4.2 Hz, J = 9.0 Hz, 2H, ArH), 6.84 (t, J = 7.8 Hz, 2H, ArH), 7.20 (t, J = 7.2 Hz,
1
1H, ArH), 7.31 (t, J = 7.8 Hz, 2H, ArH), 7.54 (d, J = 7.8 Hz, 2H, ArH);31P { H} NMR
(CDCl3, 243 MHz): δ 23.60; EI-MS (70 eV): m/z 602.5 (M+, 2), 465 (47), 417 (6.0), 278.5
(16.0), 186 (40.1), 185 (100), 157 (6), 111 (11). Anal. Calcd for C28H32FN4O6PS: C 55.81,
H 5.35, N 9.30; found C 55.53, H 5.48, N 9.15.

α-AMINO PHOSPHONATE DERIVATIVES
1751
Data for 3g. (R = Ph, R1 = 4-FC6H4O, R2 = CH3): yield 81%, white solid, mp
142.1–143.7◦C; IR (KBr): υ 3288 (N H), 1692 (C O), 1550, 1485, 1464 (Ph), 1236
1
(P O), 1025 (P O C) cm−1; H NMR (CDCl3, 600 MHz): δ 1.32 (t, J = 7.2 Hz, 3H,
OCH2CH3), 2.47 (s, 3H, CH3), 2.49 (s, 3H, CH3), 4.25 (q, J = 7.6 Hz, 2H, OCH2CH3),
5.54 (d, J = 22.8 Hz, 1H, PCH), 6.74 (dd, J = 4.2 Hz, J = 9.0 Hz, 2H, ArH), 6.79 (t, J =
9.0 Hz, 2H, ArH), 7.02 (d, J = 8.4 Hz, 2H, ArH), 7.07 (d, J = 8.4 Hz, 2H, ArH), 7.13–7.21
1
(m, 3H, ArH), 7.25–7.31 (m, 6H, ArH), 7.46 (d, J = 7.8 Hz, 2H, ArH);31P { H} NMR
(CDCl3, 243 MHz): δ 11.66; EI-MS (70 eV): m/z 698.4 (M+, 2.5), 512 (18), 466 (40), 461
(13.1), 353 (12), 279 (31), 235 (17.2), 185 (100), 170 (11), 140 (7), 94 (3.6), 77 (3.1). Anal.
Calcd for C36H32FN4O6PS: C 61.88, H 4.62, N 8.02; found C 62.11, H 4.58, N 7.89.
Data for 3h. (R = Et, R1 = H, R2 = 4-FC6H4): yield 67%, white solid, mp
128.2–129.8◦C; IR (KBr): υ 3209 (N H), 2986 (Ph), 1702 (C O), 1557, 1554, 1494 (Ph),
1272, 1223 (P O), 1088, 1053 (P O C) cm−1; 1H NMR (CDCl3, 600 MHz): δ 1.13 (t,
J = 7.2 Hz, 3H, OCH2CH3), 1.20 (t, J = 7.2 Hz, 3H, OCH2CH3), 1.27 (t, J = 7.2 Hz,
3H, OCH2CH3), 2.51 (s, 3H, CH3), 3.91–3.95 (m, 1H, OCH2CH3), 4.02–4.09 (m, 2H,
OCH2CH3), 4.15–4.22 (m, 3H, OCH2CH3), 5.58 (d, J = 19.8 Hz, 1H, PCH), 7.18 (t, J =
7.8 Hz, 2H, ArH), 7.25 (d, J = 7.8 Hz, 1H, ArH), 7.37 (t, J = 7.8 Hz, 2H, ArH), 7.65 (t, J =
7.8 Hz, 2H, ArH), 7.81 (dd, J = 6.0 Hz, J = 8.1 Hz, 2H, ArH), 8.43 (s, 1H, pyrazol-H); 31P
1
{ H} NMR (CDCl3, 243 MHz): δ 18.35; EI-MS (70 eV): m/z 572 (M+, 3.6), 436 (11.7),
396.5 (57.1), 259 (100), 258 (61.8), 256 (47.3), 186.5 (15.2), 140 (26), 139 (37.7), 120
(15.7), 71 (7.9). Anal. Calcd for C27H30FN4O5PS: C 56.64, H 5.28, N 9.78; found C 56.70,
H 5.47, N 10.03.
Data for 3i. (R = Ph, R1 = 4-t-Bu-C6H4O, R2 = CH3): yield 58%, white solid, mp
121.4–123.0◦C; IR (KBr): υ 3238 (N H), 2975 (Ph), 1700 (C O), 1545, 1492, 1436 (Ph),
1262, 1235 (P O), 1090, 1025 (P O C) cm−1; 1H NMR (CDCl3, 600 MHz): δ 1.23 (s,
9H, 3CH3), 1.31 (t, J = 7.2 Hz, 3H, OCH2CH3), 2.47 (s, 3H, CH3), 2.48 (s, 3H, CH3),
4.23 (q, J = 7.2 Hz, 2H, OCH2CH3), 5.61(d, J = 23.4 Hz, 1H, PCH), 6.74 (d, J = 8.4 Hz,
2H, ArH), 7.02 (d, J = 8.4 Hz, 2H, ArH), 7.07 (d, J = 8.4 Hz, 2H, ArH), 7.13–7.32 (m,
1
11H, ArH), 7.52 (d, J = 7.8 Hz, 2H, ArH); 31P { H} NMR (CDCl3, 243 MHz): δ 21.47.
Anal. Calcd for C40H41N4O6PS: C 65.20, H 5.61, N 7.60; found C 64.92, H 5.54, N 7.89.
Data for 3j. (R = Et, R1 = 4-t-Bu-C6H4O, R2 = CH3): yield 61%, white solid, mp
197.1–198.3◦C; IR (KBr): υ 3243 (N H), 2966 (Ph), 1704 (C O), 1547, 1494, 1433 (Ph),
1268, 1238 (P O), 1094, 1020 (P O C) cm−1; 1H NMR (CDCl3, 600 MHz): δ 1.21 (s,
9H, 3CH3), 1.23 (t, J = 7.8 Hz, 3H, OCH2CH3), 1.27 (t, J = 7.8 Hz, 3H, OCH2CH3), 1.30
(t, J = 7.2 Hz, 3H, OCH2CH3), 2.47 (s, 3H, CH3), 2.48 (s, 3H, CH3), 3.96–4.05 (m, 1H,
OCH2CH3), 4.08–4.13 (m, 3H, OCH2CH3), 4.21–4.23 (m, 2H, OCH2CH3), 5.16 (d, J =
22.4 Hz, 1H, PCH), 5.74 (s, 1H, NH), 6.77 (d, J = 7.8 Hz, 2H, ArH), 7.20 (t, J = 8.4 Hz,
1
3H, ArH), 7.32 (t, J = 7.8 Hz, 2H, ArH), 7.59 (d, J = 8.4 Hz, 2H, ArH); 31P { H} NMR
(CDCl3, 243 MHz): δ 19.81. EI-MS (70 eV): m/z 641.6 (M+, 68.7), 487 (3.3), 355 (20.1),
353 (48.2), 344 (10.2), 287 (12.3), 275 (12.6), 208 (6.5), 135 (14.5), 109 (7.0), 91 (100), 77
(38.8). Anal. Calcd for C32H41N4O6PS: C 59.99, H 6.45, N 8.74; found C 60. 18, H 6.30,
N 8.96.
Herbicidal Activity (In Vitro)
The herbicidal evaluation of compounds 3 was carried out in the laboratory of bio-
logical activities test, Nankai University, Tianjin, China, and the results are summarized in
the Supplemental Materials and Table S1 (available online).

1752
Z.-H. YU AND D.-Q. SHI
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