Design, synthesis and herbicidal activity of novel cyclic phosphonates with diaryl ethers containing pyrimidine

Article abstract of DOI:10.1080/10426507.2019.1633319

Thirteen novel cyclic phosphates were rationally designed and synthesized by introducing diary ethers containing pyrimidine. All the target compounds were characterized by ¹H, ¹³C, ³¹P NMR and HRMS. The test of herbicidal activity indicated that most of the compounds showed good herbicidal activities against Amaranthus retroflexus. The compounds IA-2 (1-(5,5-dimethyl-2-oxido-1,3,2-dioxaphosphinan-2-yl)propyl-2-((4,6-dimethoxypyrimidin-2-yl)oxy)benzoate) and IA-3 ((5,5-dimethyl-2-oxido-1,3,2-dioxaphosphinan-2-yl)(phenyl)methyl-2-((4,6-dimethoxypyrimidin-2-yl)oxy)benzoate) exhibited remarkable post-emergency herbicidal activity against the tested monocotyledonous weed at the dosage of 112.5 g ai/ha.

Full text of DOI:10.1080/10426507.2019.1633319

Phosphorus, Sulfur, and Silicon and the Related Elements
ISSN: 1042-6507 (Print) 1563-5325 (Online) Journal homepage: https://www.tandfonline.com/loi/gpss20
Design, synthesis and herbicidal activity of novel
cyclic phosphonates with diaryl ethers containing
pyrimidine
Shasha Zhang, Xinjuan Guo, Yuan Zhou, Yalan Yang, Hao Peng & Hongwu He
To cite this article: Shasha Zhang, Xinjuan Guo, Yuan Zhou, Yalan Yang, Hao Peng & Hongwu
He (2019): Design, synthesis and herbicidal activity of novel cyclic phosphonates with diaryl
ethers containing pyrimidine, Phosphorus, Sulfur, and Silicon and the Related Elements, DOI:
10.1080/10426507.2019.1633319
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PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
https://doi.org/10.1080/10426507.2019.1633319
Design, synthesis and herbicidal activity of novel cyclic phosphonates with
diaryl ethers containing pyrimidine
Shasha Zhang , Xinjuan Guo, Yuan Zhou, Yalan Yang, Hao Peng, and Hongwu He
Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education; College of Chemistry, Central China Normal University,
Wuhan, China
ABSTRACT
ARTICLE HISTORY
Received 26 February 2019
Accepted 14 June 2019
Thirteen novel cyclic phosphates were rationally designed and synthesized by introducing diary
ethers containing pyrimidine. All the target compounds were characterized by 1H, 13C, 31P NMR
and HRMS. The test of herbicidal activity indicated that most of the compounds showed good her-
bicidal activities against Amaranthus retroflexus. The compounds IA-2 (1-(5,5-dimethyl-2-oxido-
1,3,2-dioxaphosphinan-2-yl)propyl-2-((4,6-dimethoxypyrimidin-2-yl)oxy)benzoate) and IA-3 ((5,5-
dimethyl-2-oxido-1,3,2-dioxaphosphinan-2-yl)(phenyl)methyl-2-((4,6-dimethoxypyrimidin-2-yl)oxy)-
benzoate) exhibited remarkable post-emergency herbicidal activity against the tested monocotyle-
donous weed at the dosage of 112.5 g ai/ha.
KEYWORDS
Synthesis; herbicidal
activity; diary ether;
heterocyclic phosphonate
GRAPHICAL ABSTRACT
Introduction
chemical properties and biological activity, such as photo-
stability, improving efficiency and biological activ-
ity spectra.[13]
Pyruvate dehydrogenase complex (PDHc) is known to be
one target enzyme attacked by some herbicidally active com-
pounds.[1–3] a-Substituted alkylphosphonate derivatives have
received considerable attention over the past two decades in
medicine and pesticide chemistry due to their biological,
activities.[4–6]
In order to design and synthesize new phosphonate
derivatives with better herbicidal activity, the pyrimidinyl
benzoate structural unit and heterocyclic were introduced
into phosphonate molecules to design and synthesis a novel
series of 10-(5,5-dimethyl-2-oxido-1,3,2-dioxaphosphory-
l)alkyl-2-(4,6-dimethoxy-pyrimidin-2-yloxy)benzoates. Here
the preparation of the target compounds and their herbicidal
activity were reported.
Studies indicated that a-(substituted phenoxyacetoxy)al-
kylphosphonates possess excellent herbicidal activities as
potent pyruvate dehydrogenase complex (PDHc) inhibi-
tors.[7–10] Clacyfos (HW02), the only herbicide developed by
China included in The Pesticide Manual (17th version), as a
selective post-emergency herbicide, displayed outstanding
herbicidal activity on broad-leaved weeds. In our previous
work, the introduction of a cyclophosphonate moiety into
the phosphonate part of structure could promote the herbi-
Results and discussion
Synthesis
According to the reported literatures,[14–16] a-substituted-
cidal activity of the phosphonates.[11–12] Introducing diaryl 1,3,2-dioxaphosphorinane M-2 was the key intermediate for
ethers to some pesticides could improve physical and the synthesis of title compound IA. Condensation of
CONTACT Hao Peng
penghao@mail.ccnu.edu.cn; Hongwu He
he1208@mail.ccnu.edu.cn
Key Laboratory of Pesticide & Chemical Biology (CCNU),
Ministry of Education; College of Chemistry, Central China Normal University, Wuhan, 430079, China.
Supplemental data for this article is available online at https://doi.org/10.1080/10426507.2019.1633319.
ß 2019 Taylor & Francis Group, LLC

2
S. ZHANG ET AL.
Scheme 1. Synthetic route for the title compounds IA.
neopentyl glycol, phosphorus trichloride and ethanol yielded and stem against wheat, barnyard grass, broomcorn, rape,
M-1, which was then reacted with substituted aldehyde in
DCM using triethylamine as catalyst to give M-2. The title
compound IA could be synthesized by condensation of M-2
and M-4, which was prepared by the hydrolysis of com-
pound M-3. M-3 was obtained starting from methyl 2-
hydroxybenzoate by reacting with 4,6-dimethoxy-2-(methyl-
sulfonyl)pyrimidine in DMF with K2CO3 as base
(Scheme 1).
radish, and cucumber.
From the data of Tables S2 and S3, most of the title com-
pounds exhibited poor inhibitory effect on the growth of the
root and stem against the tested barnyard grass, and broom-
corn. A part of title compounds showed good to excellent
inhibitory activity on the growth of the root and stem
against rape, radish, and cucumber. Especially, compounds
IA-2 and IA-3 shown excellent inhibitory activity against
almost all the tested weeds. Compounds IA-2 and IA-3
were further tested at the rates of 450, 225, and 112.5 g ai/ha
for pre-emergency and post-emergency herbicidal activity
and against barnyard grass, crab grass, green bristlegrass,
small goosefoot, leaf mustard and common amaranth. As
shown in Tables S4 and S5, compounds IA-2 and IA-3
exhibited good to excellent inhibitory activity for pre-emer-
gency and post-emergency herbicidal activity against small
goosefoot, leaf mustard and common amaranth at the rates
of 450, 225, and 112.5 g ai/ha, which shown that compounds
IA-2 and IA-3 exhibited better herbicidal activity against the
tested monocotyledonous weeds than that against dicotyle-
donous weeds.
All the title compounds were characterized with 1H
NMR, 13C NMR, 31P NMR and HRMS, all the title com-
pounds excepted IA-2 and IA-4 were further identified via
elemental analysis. Physical properties are summarized in
Table S1 (Supplemental Materials).
1
In the H NMR spectra, the signal of pyrimidin-2-y pro-
ton appeared as singlet. The proton signals corresponding to
methyl, methoxy and methylidyne attached with phosphorus
appear as singlet, singlet and two doublets, respectively. In
1
the H NMR spectra of the title compounds, the chemical
shifts of aromatic protons appeared at 6.85–8.18 ppm. As for
the compounds with aromatic groups as R, the proton signal
corresponding to the methylidyne group attached with phos-
phorus appears at 5.37–6.92 as symmetric doublets, due to
the coupling with phosphorus. 31P NMR chemical shifts of
The herbicidal activities (Tables S2–S5) are presented in
the Supplemental Materials.
the title compounds appeared as
6.04-13.18 ppm.
a
singlet at
d
Experimental
All melting points (m.p.) were obtained with a digital model
Herbicidal activity tests
1
X-5 apparatus and are uncorrected. H, 13C, and 31P NMR
The herbicidal activities of the phosphonates IA-1-IA-13
were evaluated at a rate of 200 g ai/ha in a set of experi-
ments in a greenhouse. They were tested for a pre-emer-
gency and post-emergency inhibitory effect against Triticum
aestivum, Echinochloa crusgalli, Sorghum bicolor, Brassica
campestris, Raphanus sativus L, and Cucumis sativus.
The bioassay of the herbicidal activities of the title com-
pounds IA were carried out at a dose of 200 mg/L in a set
of experiments in a greenhouse. All the title compounds IA
spectra were recorded at Varian Mercury-Plus 600 or plus-
400 using CDCl3 or DMSO-d6 as the solvent and tetrame-
thysilane as internal standards. Infrared spectra were
recorded in potassium bromide pellets with a Nicolet Avatar
360 Fourier transform infrared (FTIR) spectrophotometer.
Elemental analysis was measured with an Elementar Vario
EL III elementary analyzer. Mass spectra were performed on
a Finnigan Trace MS 2000 spectrometer. All chemicals or
were tested for the growth inhibitory effect of the weed root reagents used for syntheses were commercially available,

PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
3
were of AR grade, and were used as received. Furfural, 2- 124.45, 123.53, 84.37, 77.76, 77.70, 77.27, 77.20, 70.25, 68.68,
thiophene formaldehyde, triethylamine are distilled before 55.37, 54.52, 32.43, 21.60, 19.93, 14.43; 31P NMR (162 MHz,
use. Dichloromethane need to be treated to be anhydrous CDCl3) d: 9.15; HRMS (ESI): calcd. for C25H27N2O8P;
before use. All other solvents and reagents were analytical [M þ H]þ 515.1578, found: 515.1574; Elemental Anal. Calcd
reagent and used directly without purification.
for C25H27N2O8P: C, 58.37; H, 5.29. N, 5.45; Found: C,
All of the compounds IA were synthesized according to 58.54; H, 5.46; N, 5.43.
the reported methods (Scheme 1).[14–16] The details of the
synthetic procedure were supplied in the Supplemental
(5,5-dimethyl-2-oxido-1,3,2-dioxaphosphinan-2-yl)(furan-2-
yl)methyl-2-((4,6-dimethoxypyrimidin-2-yl)oxy)benzoate
(IA-4)
Materials together with sample 1H and 13C NMR spectra
and HRMS of the products (Figures S1–S52).
Yellow solid; yield: 67%, 139-142 ꢀC; 1H NMR (400 MHz,
CDCl3) d: 8.03 (dd, J ¼ 7.8, 1.5 Hz, 1H, phenyl-H), 7.55 (td,
J ¼ 8.1, 1.6 Hz, 1H, furyl-H), 7.28 (d, J ¼ 7.6 Hz, 1H, phenyl-
1-(5,5-dimethyl-2-oxido-1,3,2-dioxaphosphinan-2-yl)ethyl-2-
((4,6-dimethoxypyrimidin-2-yl)oxy)benzoate (IA-1)
1
White solid; yield: 85%, m.p. 95-98 ꢀC; H NMR (400 MHz, H), 7.24 (s, 1H, phenyl-H), 7.17 (d, J ¼ 8.1 Hz, 1H, furan-2-
CDCl3) d: 8.08 (d, J ¼ 7.8 Hz, 1H, phenyl-H), 7.66 (t, yl), 6.54-6.48 (m, 2H, furyl-H), 6.23 (s, 1H, PCHO), 5.55 (s,
J ¼ 7.7 Hz, 1H, phenyl-H), 7.39 (t, J ¼ 7.6 Hz, 1H, phenyl-H), 1H, pyrimidinyl-H), 4.57-3.82 (m, 4H, 2ꢁ(OCH2)), 3.65 (s,
7.31 (s, 1H, phenyl-H), 5.80 (s, 1H, pyrimidinyl-H), 5.55 (p, 6H, 2ꢁ(OCH3)), 1.20 (s, 3H, CH3), 0.80 (s, 3H, CH3); 13C
J ¼ 7.2 Hz, 1H, PCHO), 4.12-3.93 (m, 4H, 2ꢁ(OCH2)), 3.82 NMR (101 MHz, DMSO-d6) d: 172.81, 163.73, 163.42,
(s, 6 H, 2ꢁ(OCH3)), 1.63 (s, 3H, CH3), 1.24 (s, 3H, CH3) , 163.35, 151.77, 146.20, 144.96, 135.54, 131.65, 126.52,
0.92 (s, CH3); 13C NMR (101 MHz, DMSO-d6) d: 173.06, 124.17, 123.51, 112.64, 112.58, 111.28, 84.43, 78.22, 78.16,
163.96, 151.60, 135.30, 131.63, 126.50, 124.13, 123.87, 84.42, 77.59, 77.53, 63.91, 62.27, 54.42, 32.41, 32.33, 21.57, 19.90;
77.85, 77.78, 77.15, 77.08, 65.28, 63.67, 54.63, 32.39, 32.31, 31P NMR (162 MHz, CDCl3) d: 6.04; HRMS (ESI): calcd. for
21.55, 20.16, 14.77; 31P NMR (162 MHz, CDCl3) d: 13.16; C23H25N2O9P; [M þ H]þ 505.1370, found: 505.1371.
HRMS (ESI): calcd. for C20H25N2O8P; [M þ H]þ 453.1421,
found: 453.1429. Elemental Anal. Calcd for C20H25N2O8P:
C, 53.10; H, 5.57. N, 6.19; Found: C, 53.21; H, 5.77; N, 6.01.
(5,5-dimethyl-2-oxido-1,3,2-dioxaphosphinan-2-yl)(4-
fluorophenyl)methyl-2-((4,6-dimethoxypyrimidin-2-yl)oxy)
benzoate (IA-5)
1-(5,5-dimethyl-2-oxido-1,3,2-dioxaphosphinan-2-yl)propyl-
White solid; yield: 85%, m.p. 110-112 ꢀC; 1H NMR
2-((4,6-dimethoxypyrimidin-2-yl)oxy)benzoate (IA-2)
(400 MHz, CDCl3) d: 8.03 (dd, J ¼ 7.8, 1.5 Hz, 1H, phenyl-
1
White solid; yield: 63%, m.p. 80-81 ꢀC; H NMR (400 MHz, H), 7.55 (td, J ¼ 8.1, 1.6 Hz, 1H, phenyl-H), 7.36 (td, J ¼ 6.9,
CDCl3) d: 8.06 (dd, J ¼ 7.8, 1.5 Hz, 1H, phenyl-H), 7.56 (td, 1.5 Hz, 2H, phenyl-H), 7.29 (dd, J ¼ 11.4, 3.8 Hz, 1H, phe-
J ¼ 8.1, 1.6 Hz, 1H, phenyl-H), 7.31-7.25 (m, 1H, phenyl-H), nyl-H), 7.18(s, 1H, phenyl-H),6.90 (t, J ¼ 8.6 Hz, 2H, phenyl-
7.19 (s, 1H, phenyl-H), 5.68 (s, 1H, pyrimidinyl-H), 5.44- H) , 6.35 (d, J ¼ 12.6 Hz, 1H, PCHO), 5.61 (s, 1H, pyrimi-
5.37 (m, 1H, PCHO), 4.34-3.84 (m, 4H, 2ꢁ(OCH2)), 3.71 (s, dinyl-H), 4.30-3.89 (m, 4H, 2ꢁ(OCH2)), 3.65 (s, 6H,
6H, 2ꢁ(OCH3)), 1.12 (s, 2H, CH2CH3), 0.84-0.77 (m, 3H, 2ꢁ(OCH3)), 1.11 (s, 3H, CH3), 0.80 (s, 3H, CH3); 13C NMR
CH3), 0.78 (s, 6H, CH3); 13C NMR (101 MHz, DMSO-d6) d: (101 Hz, DMSO-d6) d: 172.89, 163.87, 163.76, 163.41, 163.33,
173.10, 164.16, 164.00, 163.95, 151.98, 135.48, 131.89, 161.42, 151.84, 135.39, 131.59, 130.83, 130.75, 130.69,
126.59, 124.60, 123.26, 84.17, 77.75, 77.68, 77.01, 76.95, 129.86, 126.51, 124.33, 123.54, 84.29, 77.68, 77.60, 77.23,
69.88, 68.31, 54.59, 32.35, 32.28, 31.42, 22.81, 22.52, 21.54, 77.17, 69.17, 67.60, 54.49, 32.41, 32.33, 21.55, 19.87; 31P
20.09, 14.42, 10.24, 10.12; 31P NMR (162 MHz, CDCl3) d: NMR (162 MHz, CDCl3) d: 9.04. HRMS (ESI): calcd. for
12.66; HRMS (ESI): calcd. for C21H27N2O8P; [M þ H]þ C25H26FN2O8P; [M þ H]þ 533.1482, found:533.1486;
467.1578, found: 467.1580.
Elemental Anal. Calcd for C25H26FN2O8P: C, 56.39; H, 4.92;
N, 5.26; Found:56.67; H, 4.68; N,; 5.05.
(5,5-dimethyl-2-oxido-1,3,2-dioxaphosphinan-2-yl)(phenyl)
methyl-2-((4,6-dimethoxypyrimidin-2-yl)oxy)benzoate (IA-3) (4-bromophenyl)(5,5-dimethyl-2-oxido-1,3,2-dioxaphosphinan-
2-yl)methyl 2-((4,6-dimethoxypyrimidin-2-yl)oxy)benzoate
(IA-6)
Yellow solid; yield: 81%, m.p.107-109 ꢀC; 1H NMR
(400 MHz, CDCl3) d: 8.13 (dd, J ¼ 7.8, 1.5 Hz, 1H, phenyl-
H), 7.61 (td, J ¼ 8.1, 1.7 Hz, 1H, phenyl-H), 7.46-7.41 (m, White solid; yield: 63%, m.p. 135-137 ꢀC; 1H NMR
2H, phenyl-H), 7.35 (dd, J ¼ 11.4, 3.9 Hz, 1H, phenyl-H), (400 MHz, CDCl3) d: 8.06 (d, J ¼ 1.5 Hz, 1H, phenyl-H),
7.31-7.28 (m, 3H, phenyl-H), 7.24 (s, 1H, phenyl-H), 6.45 7.58 (td, J ¼ 8.1, 1.6 Hz, 1H, phenyl-H), 7.40 (d, J ¼ 1.5 Hz,
(d, J ¼ 12.5 Hz, 1H, PCHO), 5.67 (s, 1H, pyrimidinyl-H), 2H, phenyl-H), 7.31 (d, J ¼ 11.4, 3.8 Hz, 1H, phenyl-H),
4.32-3.95 (m, 4H, 2ꢁ(OCH2)), 3.72 (s, 6H, 2ꢁ(OCH3)), 1.18 7.20(s, 1H, phenyl-H), 6.90 (t, J ¼ 8.6 Hz, 2H, phenyl-H) ,
(s, 3H, CH3), 0.85 (s, 3H, CH3); 13C NMR (101 MHz, 6.40 (d, J ¼ 12.6 Hz, 1H, PCHO), 5.57 (s, 1H, pyrimidinyl-
DMSO-d6) d: 172.95, 163.87, 163.41, 163.32, 151.95, 135.41, H), 4.31-3.90 (m, 4H, 2ꢁ(OCH2)), 3.66 (s, 6H, 2ꢁ(OCH3)),
133.67, 131.68, 129.10, 128.76, 128.37, 128.32, 126.55, 1.14 (s, 3H, CH3), 0.83 (s, 3H, CH3); 13C NMR (101 MHz,

4
S. ZHANG ET AL.
DMSO-d6) d: 166.40, 166.31, 159.91, 136.38, 133.61, 133.59, J ¼ 12.6 Hz, 1H, PCHO), 5.68 (s, 1H, pyrimidinyl-H), 4.37-
131.94, 131.29, 130.21, 130.16, 122.48, 122.45, 120.02, 3.96 (m, 1H, 2ꢁ(OCH2)), 3.72, (s, 3H, CH3), 3.72 (s, 6H,
118.13, 113.88, 78.21, 78.14, 77.57, 77.50, 70.33, 68.75, 32.55, 2ꢁ(OCH3)), 1.18 (s, 3H, CH3), 0.87 (s, 3H, CH3); 13C NMR
32.47, 21.60, 20.01; 31P NMR (162 MHz, CDCl3) d: 9.51; (101 MHz, DMSO-d6) d: 166.70, 166.60, 160.05, 136.38,
HRMS (ESI): calcd. for C25H26BrN2O8P; [M þ H]þ 131.10, 129.86, 129.81, 125.68, 120.02, 118.08, 114.41,
593.0683, found:593.0683; Elemental Anal. Calcd for 113.73, 77.92, 77.85, 77.36, 77.29, 70.36, 68.76, 55.65, 32.52,
C25H26BrN2O8P: C, 50.60; H, 4.42; N, 4.72; Found: C, 50.63; 32.44, 21.61, 20.03; 31P NMR (162 MHz, CDCl3) d: 10.38;
H, 4.60; N, 4.60.
HRMS (ESI): calcd. for C26H29N2O9P; [M þ Na]þ 583.1242,
found: 583.1256; Elemental Anal. Calcd for C26H29N2O9P:
C, 57.35; H, 5.37; N, 5.14; Found: C, 57.46; H, 5.76; N, 5.01.
(5,5-dimethyl-2-oxido-1,3,2-dioxaphosphinan-2-yl)(3-
nitrophenyl)methyl-2-((4,6-dimethoxypyrimidin-2-yl)oxy)
benzoate (IA-7)
(3-chlorophenyl)(5,5-dimethyl-2-oxido-1,3,2-dioxaphosphinan-
2-yl)methyl-2-((4,6-dimethoxypyrimidin-2-yl)oxy)benzoate
(IA-10)
White solid; yield: 66%, m.p.150-151 ꢀC; 1H NMR
(400 MHz, CDCl3) d: 8.29 (d, J ¼ 1.6 Hz, 1H, phenyl-H),
8.18 (d, J ¼ 8.1 Hz, 1H, phenyl-H), 8.13 (dd, J ¼ 7.9, 1.5 Hz, White solid; yield: 62%, m.p. 127-130 ꢀC; 1H NMR
1H, phenyl-H), 7.83 (d, J ¼ 7.9 Hz, 1H, phenyl-H), 7.68-7.61 (400 MHz, CDCl3) d: 8.12 (dd, J ¼ 7.8, 1.4 Hz, 1H, phenyl-
(m, 1H, phenyl-H), 7.49 (t, J ¼ 8.0 Hz, 1H, phenyl-H), 7.38 H), 7.63 (td, J ¼ 8.1, 1.6 Hz, 1H, phenyl-H), 7.45 (d,
(td, J ¼ 7.8, 0.9 Hz, 1H, phenyl-H), 7.29 (d, J ¼ 0.6 Hz, 1H, J ¼ 1.3 Hz, 1H, phenyl-H), 7.39-7.32 (m, 2 H, phenyl-H),
phenyl-H), 7.23 (s, 1H, phenyl-H), 6.51 (d, J ¼ 13.5 Hz, 1H, 7.28-7.26 (m, 1H, phenyl-H), 7.25-7.20 (m, 1H, phenyl-H),
PCHO), 5.65 (s, 1H, pyrimidinyl-H), 4.47-4.01 (m, 4H, 6.41 (d, J ¼ 13.1 Hz, 1H, PCHO), 5.69 (s, 1H, pyrimidinyl-
2ꢁ(OCH2)), 3.72 (s, 6H, 2ꢁ(OCH3)), 1.20 (s, 3H, CH3), H), 4.40-3.98 (m, 3H, 2ꢁ(OCH2)), 3.73 (s, 6H, 2ꢁ(OCH3)),
0.91 (s, 3H, CH3); 13C NMR (101 MHz, DMSO-d6) d: 1.18 (s, 3H, CH3), 0.87 (s, 3H, CH3); 13C NMR (101 MHz,
172.88, 163.71, 163.45, 163.36, 151.87, 148.06, 135.88, DMSO-d6) d: 172.94, 163.80, 163.42, 163.34, 151.94, 136.08,
135.53, 135.08, 135.02, 131.56, 130.57, 126.57, 124.33, 135.50, 133.46, 131.69, 130.73, 129.19, 128.20, 128.15,
124.20, 123.36, 123.27, 84.23, 77.90, 77.83, 77.45, 77.39, 127.08, 127.03, 126.47, 124.44, 123.34, 84.40, 77.84, 77.78,
68.81, 67.26, 54.50, 32.46, 32.39, 21.55, 19.83; 31P NMR 69.35, 67.78, 54.53, 32.44, 32.37, 21.56, 19.87; 31P NMR
(162 MHz, CDCl3) d: 7.94; HRMS (ESI): calcd. for (162 MHz, CDCl3) d: 8.49; HRMS (ESI): calcd. for
C25H26N3O10P; [M þ H]þ 560.1429, found:560.1438.
C25H26ClN2O8P; [M þ H]þ 549.1188, found: 549.1185;
Elemental Anal. Calcd for C25H26ClN2O8P: C, 54.70; H,
4.77; N, 5.10; Found: C, 54.87; H, 5.15; N, 5.96.
(5,5-dimethyl-2-oxido-1,3,2-dioxaphosphinan-2-yl)(p-tolyl)
methyl-2-((4,6-dimethoxypyrimidin-2-yl)oxy)benzoate (IA-8)
(2,4-dichlorophenyl)(5,5-dimethyl-2-oxido-1,3,2-dioxaphos-
phinan-2-yl)methyl-2-((4,6-dimethoxypyrimidin-2-yl)oxy)
benzoate (IA-11)
1
White solid; yield 56%, m.p. 132-135 ꢀC; H NMR (400 MHz,
CDCl3) d: 8.10 (dd, J¼ 7.7, 1.5 Hz, 1H, phenyl-H), 7.59 (t,
J¼ 7.8 Hz, 1H, phenyl-H), 7.36-7.28 (m, 3H, phenyl-H), 7.22
1
(s, 1H, phenyl-H), 7.07 (d, J¼ 8.0 Hz, 2H, phenyl-H), 6.40 (d, White solid; yield: 67%, m.p. 141-142 ꢀC; H NMR (400 MHz,
J¼ 12.4 Hz, 1H, PCHO), 5.64 (s, 1H, pyrimidinyl-H), 4.31-3.93 CDCl3) d: 8.09 (d, J¼ 7.8 Hz, 1H, phenyl-H), 7.71 (d,
(m, 4H, 2ꢁ(OCH2)), 3.70 (s, 6H, 2ꢁ(OCH3)), 2.30 (s, 3H, J¼ 8.4 Hz, 1H, phenyl-H), 7.62 (t, J¼ 7.7 Hz, 1H, phenyl-H),
CH3), 1.16 (s, 3H, CH3), 0.84 (s, 3H, CH3); 13C NMR 7.38 (s, 1H, phenyl-H), 7.34 (d, J¼ 7.5 Hz, 1H, phenyl-H), 7.27
(101 MHz, DMSO-d6) d: 172.94, 163.84, 163.50, 163.41, 151.88, (s, 1H, phenyl-H),7.24 (d, J¼ 8.9 Hz, 1H, phenyl-H), 6.92 (d,
138.65, 138.63, 135.35, 131.64, 130.58, 130.56, 129.33, 128.45, J¼ 10.8 Hz, 1H, PCHO), 5.70 (s, 1H, pyrimidinyl-H),4.30-3.92
128.39, 126.54, 124.42, 123.67, 84.34, 77.72, 77.65, 77.24, 77.17, (m, 4H, 2ꢁ(OCH2)), 3.75 (s, 6H, 2ꢁ(OCH3)), 1.21 (s, 3H,
70.06, 68.47, 54.52, 32.44, 32.36, 21.62, 21.23, 19.94; 31P NMR CH3), 0.90 (s, 3H, CH3); 13C NMR (101 MHz, DMSO-d6) d:
(162 MHz, CDCl3) d: 9.46. HRMS (ESI): calcd. for 172.94, 163.66, 151.69, 135.53, 134.96, 134.93, 134.02, 133.90,
C26H29N2O8P; [M þ H]þ 529.1734, found: 529.1736. Elemental 131.75, 130.47, 129.32, 128.07, 126.59, 124.44, 123.30, 84.31,
Anal. Calcd for C26H29N2O8P: C, 59.09; H, 5.53; N, 5.30; 78.31, 66.83, 65.22, 54.57, 32.46, 32.39, 21.34, 20.04; 31P NMR
Found: C, 59.53; H, 5.85; N, 5.12.
(162 MHz, CDCl3) d: 7.96; HRMS (ESI): calcd. for
C25H25Cl2N2O8P; [M þ H]þ 583.0798, found: 583.0798;
Elemental Anal. Calcd for C25H25Cl2N2O8P: C, 51.47; H, 4.32;
N, 4.80; Found: C, 51. 08; H, 5.56; N, 4. 59.
(5,5-dimethyl-2-oxido-1,3,2-dioxaphosphinan-2-yl)(4-
methoxyphenyl)methyl-2-((4,6-dimethoxypyrimidin-2-yl)oxy)
benzoate (IA-9)
(3,4-dichlorophenyl)(5,5-dimethyl-2-oxido-1,3,2-dioxaphos-
phinan-2-yl)methyl-2-((4,6-dimethoxypyrimidin-2-yl)oxy)
benzoate (IA-12)
White solid; yield: 79%, m.p. 112-114 ꢀC; 1H NMR
(400 MHz, CDCl3) d: 8.10 (dd, J ¼ 7.2, 1.5 Hz, 1H, phenyl-
H), 7.62 (td, J ¼ 8.2, 1.6 Hz, 1H, phenyl-H), 7.43 (td, J ¼ 6.8,
1.5 Hz, 1H, phenyl-H), 7.36 (dd, J ¼ 11.5, 3.8 Hz, 2H, phe- White solid; yield: 82%, m.p. 131-132 ꢀC; 1H NMR
nyl-H), 6.97 (t, J ¼ 8.6 Hz, 2H, phenyl-H), 6.42 (d, (400 MHz, CDCl3) d: 7.65 (t, J ¼ 7.8 Hz, 1H, phenyl-H), 7.56

PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
5
(s, 1H, phenyl-H), 7.42-7.35 (m, 2H, phenyl-H), 7.33-7.31
(m, 2H, phenyl-H), 7.26 (s, 1H, phenyl-H), 6.40 (d,
J ¼ 13.2 Hz, 1H, PCHO), 5.71 (s, 1H, pyrimidinyl-H), 4.47-
4.01 (m, 4H, 2ꢁ(OCH2)), 3.75 (s, 6H, 2ꢁ(OCH3)), 1.21 (s,
3H, CH3), 0.91 (s, 3H, CH3); 13C NMR (101 MHz, DMSO-
d6) d: 172.91, 163.73, 163.53, 163.45, 151.85, 135.49, 134.66,
132.16, 132.14, 131.66, 131.58, 131.12, 130.48, 130.42,
128.81, 128.76, 126.56, 124.36, 123.41, 84.32, 77.87, 77.81,
77.44, 77.37, 68.58, 67.02, 54.53, 32.45, 32.38, 21.55, 19.85;
31P NMR (162 MHz, CDCl3) d: 8.14. HRMS (ESI): calcd. for
C25H25Cl2N2O8P; [M þ H]þ 583.0798, found: 583.0801;
Elemental Anal. Calcd for C25H25Cl2N2O8P: C, 51.47; H,
4.32; N, 4.80; Found: C, 51. 97; H, 4.80; N, 4. 89.
ORCID
Shasha Zhang
http://orcid.org/0000-0002-6391-8041
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Conclusions
In conclusion, novel substituted heterocyclic phosphorus
compounds containing pyrimidine structure of diaryl ethers
were rationally designed and synthesized. The herbicidal
activity of the title compounds against the growth of the
root and stem against rape, radish and cucumber was car-
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most of the compounds showed good herbicidal inhibitory
activities against Amaranthus retroflexus. The compounds
IA-2 and IA-3 exhibited remarkable post-emergency herbici-
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dosage of 112.5 g ai/ha, which will provide more useful
information for the further design and discovery of com-
pounds with high herbicidal activity.
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Activity
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(Substituted Phenoxybutyryloxy)alkyl-5,5-dimethyl-1,3,2-dioxa-
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DOI: 10.1021/acs.jafc.6b02032.
Funding
This work was supported in part by the National Natural Science
Foundation of China (21877047, 21172090), National research and
development plan (No. 2017YFD0200506), the 111 Project B17019 and
excellent doctoral dissertation cultivation grant from Central China
Normal University (No. 2016YBZZ030).
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