Synthesis and herbicidal activity of novel dialkoxyphosphoryl aryl methyl 2-(4,6-dimethoxypyrimidin-2-yloxy) benzoate derivatives

Article abstract of DOI:10.1080/10426507.2010.511512

A series of dialkoxyphosphoryl aryl methyl 2-(4,6-dimethoxy-pyrimidin-2- yloxy) benzoate derivatives was designed and synthesized. All new compounds were identified by elemental analysis, infrared (IR), 1H-NMR, and mass spectrometry (MS). Their herbicidal

Full text of DOI:10.1080/10426507.2010.511512

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Phosphorus, Sulfur, and Silicon and the
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Synthesis and Herbicidal Activity of
Novel Dialkoxyphosphoryl Aryl Methyl
2-(4,6-Dimethoxypyrimidin-2-yloxy)
Benzoate Derivatives
Chuanfei Jin a & Hongwu He a
a Key Laboratory of Pesticide & Chemical Biology , Ministry of
Education, Institute of Pesticide Chemistry, Central China Normal
University , Wuhan , People's Republic of China
Published online: 04 Aug 2011.
To cite this article: Chuanfei Jin & Hongwu He (2011) Synthesis and Herbicidal Activity of Novel
Dialkoxyphosphoryl Aryl Methyl 2-(4,6-Dimethoxypyrimidin-2-yloxy) Benzoate Derivatives, Phosphorus,
Sulfur, and Silicon and the Related Elements, 186:7, 1397-1403, DOI: 10.1080/10426507.2010.511512
To link to this article: http://dx.doi.org/10.1080/10426507.2010.511512
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Phosphorus, Sulfur, and Silicon, 186:1397–1403, 2011
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2010.511512
COMMUNICATION
SYNTHESIS AND HERBICIDAL ACTIVITY OF NOVEL
DIALKOXYPHOSPHORYL ARYL METHYL
2-(4,6-DIMETHOXYPYRIMIDIN-2-YLOXY) BENZOATE
DERIVATIVES
Chuanfei Jin and Hongwu He
Key Laboratory of Pesticide & Chemical Biology, Ministry of Education,
Institute of Pesticide Chemistry, Central China Normal University, Wuhan,
People’s Republic of China
GRAPHICAL ABSTRACT
MeO
OMe
N
N
O
O
O
O
P(OR1)2
R2
Abstract A series of dialkoxyphosphoryl aryl methyl 2-(4,6-dimethoxy-pyrimidin-2-yloxy)
benzoate derivatives was designed and synthesized. All new compounds were identified by
elemental analysis, infrared (IR), 1H-NMR, and mass spectrometry (MS). Their herbicidal
activity against a set of weed species was examined. Some of the compounds showed po-
tential herbicidal activity, which provided some indications for further studies on structure
modification.
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 Herbicidal activity; phosphonate; pyrimidinyl benzoate
INTRODUCTION
Many phosphorus-containing agrochemicals have been developed and widely used all
over the world because of their high efficacy and low persistency in the natural environment.1
Recent studies on α-substituted phosphonates revealed that some of them had a wide range
of biological effects, including herbicidal activity,2 enzyme-inhibiting properties,3 anti-HIV
activity,4 antitumor properties,5 and hapten activity for catalytic antibodies.6 A wide variety
Received 17 May 2010; accepted 20 July 2010.
This work was supported by the National Natural Science Foundation of China (20772042).
Address correspondence to Hongwu He, Institute of Pesticide Chemistry, Central China Normal University,
Wuhan 430079, People’s Republic of China. E-mail: he1208@mail.ccnu.edu.cn
1397

1398
C. JIN AND H. HE
of pyrimidinyl benzoates, such as bispyriba-sodium7 and pyriftalid,8 have potent herbicidal
activity and are safe for transplanted rice crops, animals, fishes, etc.9
In order to find new phosphonate derivatives with better herbicidal activity, the
pyrimidinyl benzoate structural unit was introduced into phosphonate molecules to design
a novel series of dialkoxyphosphoryl aryl methyl 2-(4,6-dimethoxy- pyrimidin-2-yloxy)
benzoates. We were interested in finding a mild and efficient method for the synthesis
of the title compounds. Here we report the preparation of the title compounds and their
herbicidal activity.
RESULTS AND DISCUSSION
Chemistry
Compound 4 can be easily synthesized starting from methyl 2-hydroxybenzoate
1 and 4,6-dimethoxy-2-(methylsulfonyl)pyrimidine 2.10 1-Hydroxyalkylphosphonates 7
MeO
OMe
MeO
OMe
MeO
OMe
OH
K2CO3
N
N
HCl
N
N
N
N
DMF
85%
O
80%
O
COOMe
SO2Me
COOMe
COOH
1
2
4
3
R2
CHO
O
KF:Al2O3=1:1
HPO(OR1)2
P(OR1)2
OH
R2
5
6
7
7a: 90%, R1 = Me, R2 = H; 7b:89%, R1 = Me, R2 = Me;
7c: 88%, R1 = Me, R2 = OMe; 7d: 85%, R1 = Me, R2 = Cl;
6a: H
5a: Me
5b: Et
6b: Me
6c: OMe
6d: Cl
6e: F
7e: 80%, R1 = Me, R2 = F;
7g: 94%, R1 = Et, R2 = H;
7f: 69%, R1 = Me, R2 = NO2;
7h: 92%, R1 = Et, R2 = Me;
7i: 89%, R1 = Et, R2 = OMe; 7j: 87%, R1 = Et, R2 = Cl;
7k: 78%, R1 = Et, R2 = F; 7l: 65%, R1 = Et, R2 = NO2;
6f: NO2
MeO
OMe
O
MeO
OMe
R2
N
N
O
N
N
O
DCC
O
O
P(OR1)2
OH
O
DMAP
P(OR1)2
COOH
R2
4
8
7
8a: R1 = Me, R2 = H; 8b: R1 = Me, R2 = Me;
8c: R1 = Me, R2 = OMe; 8d: R1 = Me, R2 = Cl;
8e: R1 = Me, R2 = F;
8g: R1 = Et, R2 = H;
8f: R1 = Me, R2 = NO2;
8h: R1 = Et, R2 = Me;
8i: R1 = Et, R2 = OMe; 8j: R1 = Et, R2 = Cl;
8k: R1 = Et, R2 = F; 8l: R1 = Et, R2 = NO2;
Scheme 1

SYNTHESIS OF PHOSPHONATE DERIVATIVES
1399
Table 1 Preparation of dialkoxyphosphoryl aryl methyl 2-(4,6-dimethoxy-pyrimidin-2-yloxy) benzoates 8a-8l
Compound
R1
R2
Yield (%)
8a
8b
8c
8d
8e
8f
8g
8h
8i
Me
Me
Me
Me
Me
Me
Et
Et
Et
Et
Et
H
88
53
80
83
65
81
80
85
78
75
70
65
Me
OMe
Cl
F
NO2
H
Me
OMe
Cl
F
NO2
8j
8k
8l
Et
were prepared by the reaction of compound 5 and various aldehydes 6 using a dried and
ground mixture of potassium fluoride and alumina (weight ratio of 1:1) as catalyst in a
yield of 65–94% according to the literature.11,12
Subsequent reaction of compound 4 with substituted 1-hydroxyalkylphosphonates
(7a-7l) in the presence of N,Nꢁ-dicyclohexylcarbodiimide (DCC) and dimethylaminopy-
ridine (DMAP) in CH2Cl2 led to the formation of the title compounds (8a-8l) in good
yields (Table 1). Esters can be synthesized generally by treating an alcohol with the corre-
sponding acyl chloride. However, the ester group in the phosphonates 7 and 8 was easily
removed by the acid hydrolysis due to HCl, which was generated as a side product in this
method. Thus, the phosphonate esters 8a-8l were synthesized by the coupling reaction of
1-hydroxyalkylphosphonates 7a-7l with 2-(4,6-dimethoxypyrimidin-2-yloxy)benzoic acid
4 in the presence of DCC and DMAP (Scheme 1). All new compounds were purified over
silica gel column and characterized spectroscopically.
Biological Assays
Herbicidal Activity Tests in Greenhouse. The herbicidal activities of the
phosphonates 8a-8l were evaluated at a rate of 1.5 a.i. kg/ha in a set of experiments in
a greenhouse. They were tested for a preemergence and postemergence inhibitory effect
against Echinochloa crusgalli Beava (barnyard grass), Digitaria sanguinalis Scop (as-
cendant crabgrass), Brassica napus L. (rape), and Amaranthus retroflerus L. (amaranth).
Experimental details and the table of activities (Table S1) are presented in the Supplemental
Materials.
CONCLUSIONS
In conclusion, a series of novel dialkoxyphosphoryl aryl methyl 2-(4,6-dimethoxy-
pyrimidin-2-yloxy) benzoates was synthesized by coupling reaction of 1-hydroxy-alkyl
phosphonates and 2-(4,6-dimethoxypyrimidin-2-yloxy) benzoic acid. The test for herbicidal
activity in the greenhouse showed that compound 8l exhibited significant herbicidal activity
in postemergence treatments at the rate of 1.5 kg/ha and it may be of potential utility as an
herbicide. The results provided some indications for further study on the herbicidal activity

1400
C. JIN AND H. HE
and structure optimization of the title compounds. Experimental details and the table of
activities (Table S1) are presented in the Supplemental Materials (available online).
EXPERIMENTAL
Mass spectra were measured on a Finnigan Trace MS 2000 spectrometer. Infrared
spectra were recorded in potassium bromide pellets with a Nicolet Avatar 360 Fourier trans-
form infrared (FTIR) spectrophotometer. 1H-, 13C-, and 31P-NMR spectra were recorded in
CDCl3 solution at 600 MHz (1H), 125 MHz (13C), and 243 MHz (31P) using tetramethysi-
lane (1H, 13C) and 85% H3PO4 (31P) as internal standards with a Varian Mercury-Plus 600
spectrometer. Elemental analysis was performed with an Elementar Vario EL III elemen-
tary analyzer. Melting points (m.p.) were measured with an electrothermal melting point
apparatus and are uncorrected.
Synthesis of Compound 4
A mixture of 0.32 g (2.1 mmol) methyl 2-hydroxybenzoate and anhydrous K2CO3
0.59 g (4.2 mmol) in acetone (10 mL) was stirred at room temperature for 1 h. 4,6-
Dimethoxy-2-(methylsulfonyl)pyrimidine (DMSP) 0.49 g (2.25 mmol) was added and
stirring was continued for 18 h. Extraction with EtOAc (50 mL), evaporation of the solvent,
and chromatography on silica gel with EtOAc/n-hexane (4:1) gave a white solid. After the
solid was dissolved in acetone (20 mL), 2 M NaOH was added and the mixture was stirred
for another 2 h at room temperature. Addition of 2 M HCl yielded pure compound 4.
Synthesis of Compounds 7a-7l: General Procedure
Dimethyl or diethyl phosphite 5 (10 mmol) and the respective aldehyde (10 mmol)
were stirred at room temperature for 10 min and then potassium fluoride and alumina
(mass ratio 1:1.3 g) were added. The mixture was stirred for another 30 min, dissolved
in dichoromethane (15 mL), and filtered. Dichoromethane was evaporated under reduced
pressure, and the product was obtained as a white solid or colorless liquid in a yield of
60–91%.
Synthesis of Compounds 8a-8l: General Procedure
To a solution of compound 4 (1 mmol) in CH2Cl2 (10 mL) the respective intermediate
7 (1 mmol) was added with stirring. The reaction mixture was than cooled down to 0 ◦C.
1,3-Dicyclohexylcarbodiimide (DCC; 1 mmol) and DMAP (0.1 mmol) in CH2Cl2 (10 mL)
were added. The mixture was stirred for 10–24 h at 25 ◦C. The 1,3-dicyclohexylurea (DCU)
was filtered off and the solvent was evaporated to give the crude product, which was purified
by chromatography on silica using a mixture of petroleum ether and ethyl acetate (4:1) as
eluent to give compound 8 in yields of 53–88%.
Dimethoxyphosphoryl Phenyl Methyl 2-(4,6-Dimethoxypyrimidin-2-
yloxy Benzoate (8a). Yellow liquid; 1H-NMR (CDCl3, tetramethylsilane [TMS],
600 MHz): δ = 3.62–3.64 (m, 6H, OCH3), 3.74 (s, 6H, OCH3), 5.70 (s, 1H, CH), 6.34 (d,
J = 13.2 Hz, 1H, CH), 7.25 (d, J = 7.8 Hz, 2H, arom-H), 7.31–7.36 (m, 3H, arom-H),
7.49 (d, J = 7.2 Hz, 2H, arom-H), 7.60 (d, J = 7.8 Hz, 1H, arom-H), 8.13 (d, J = 7.8
Hz, 1H, arom-H); 13C-NMR (CDCl3, TMS, 125 MHz): δ = 53.8 (JPC = 17.5 Hz), 70.2

SYNTHESIS OF PHOSPHONATE DERIVATIVES
1401
(JPC = 167.3 Hz), 84.5, 123.4, 123.9, 125.5, 127.8, 128.4, 128.7, 131.7, 132.7, 134.2,
152.3, 163.8, 164.0, 172.6; 31P-NMR (CDCl3, 243 MHz): δ = 19.6; infrared (IR) (KBr,
υ/cm−1): 1736 (C O), 1269 (P O); MS (70 eV) m/z (%): 474 (18), 276 (80), 259 (100),
231 (51), 105 (13). Anal. Calcd. for C, 55.70; H, 4.89; N, 5.91%. Found: C, 55.96; H,
5.05; N, 5.65%.
Dimethoxyphosphoryl p-Tolyl Methyl 2-(4,6-Dimethoxypyrimidin-2-
yloxy) Benzoate (8b). Yellow liquid; 1H-NMR (CDCl3, TMS, 600 MHz): δ = 2.33 (s,
3H, CH3), 3.63 (d, J = 9.6 Hz, 3H, OCH3), 3.65 (d, J = 10.2 Hz, 3H, OCH3), 3.74 (s, 6H,
OCH3), 5.70 (s, 1H, CH), 6.30 (d, J = 13.2 Hz, 1H, CH), 7.13 (d, J = 8.4 Hz, 2H, arom-H),
7.24 (d, J = 9.0 Hz, 1H, arom-H), 7.34–7.38 (m, 3H, arom-H), 7.60 (d, J = 8.4 Hz,
1H, arom-H), 8.12 (d, J = 7.8 Hz, 1H, arom-H); 13C-NMR (CDCl3, TMS, 125 MHz):
δ = 21.2, 53.9 (JPC = 17.5 Hz), 70.1 (JPC = 168.4 Hz), 84.6, 123.8, 123.9, 125.5, 128.0,
129.2, 129.7, 131.7, 134.1, 138.3, 152.11, 163.8, 164.0, 172.7; 31P-NMR (CDCl3, 243
MHz): δ = 19.9; IR (KBr, υ/cm−1): 1736 (C O), 1217 (P O); MS (70 eV) m/z (%): 488
(17), 259 (100), 119 (61), 92 (43), 57 (21). Anal. Calcd. for C, 56.56; H, 5.16; N, 5.74%.
Found: C, 56.35; H, 5.50; N, 5.66%.
Dimethoxyphosphoryl 4-Methoxyphenyl Methyl 2-(4,6-Dimethoxypyrimi
1
din-2-yloxy) Benzoate (8c). Yellow liquid; H-NMR (CDCl3, TMS, 600 MHz): δ =
3.62 (d, J = 10.8 Hz, 3H, OCH3), 3.66 (d, J = 10.8 Hz, 3H, OCH3), 3.77 (s, 3H, OCH3),
3.79 (s, 6H, OCH3), 5.69 (s, 1H, CH), 6.28 (d, J = 13.2 Hz, 1H, CH), 6.85 (d, J = 8.4 Hz,
2H, arom-H), 7.24 (d, J = 8.4 Hz, 1H, arom-H), 7.30–7.35 (m, 1H, arom-H), 7.42 (d, J =
7.2 Hz, 2H, arom-H), 7.60 (d, J = 7.2 Hz, 1H, arom-H), 8.10 (d, J = 7.2 Hz, 1H, arom-H);
31P-NMR (CDCl3, 243 MHz): δ = 20.0; IR (KBr, υ/cm−1): 1734 (C O), 1218 (P O);
MS (70 eV) m/z (%): 504 (28), 318 (100), 259 (55), 225 (54), 199 (38). Anal. Calcd. for
C, 54.76; H, 5.00; N, 5.55%. Found: C, 55.08; H, 5.29; N, 5.42%.
4-Chlorophenyl Dimethoxyphosphoryl Methyl 2-(4,6-Dimethoxypyrimi
din-2-yloxy) Benzoate (8d). Yellow liquid; 1H-NMR (CDCl3, TMS, 600 MHz): 3.64
(d, J = 4.2 Hz, 3H, OCH3), 3.66 (d, J = 4.2 Hz, 3H, OCH3), 3.77 (s, 6H, OCH3), 5.71 (s,
1H, CH), 6.29 (d, J = 13.2 Hz, 1H, CH), 7.25 (d, J = 7.8 Hz, 1H, arom-H), 7.31 (d, J = 8.4
Hz, 2H, arom-H), 7.35 (t, J = 7.8 Hz, 1H, arom-H), 7.43 (d, J = 8.4 Hz, 2H, arom-H), 7.61
(d, J = 8.4 Hz, 1H, arom-H), 8.10 (d, J = 7.8 Hz, 1H, arom-H); 31P-NMR (CDCl3, 243
MHz): δ = 19.1; IR (KBr, υ/cm−1): 1736 (C O), 1216 (P O); MS (70 eV) m/z (%): 508
(12), 149 (100), 137 (76), 83 (68). Anal. Calcd. for C, 51.93; H, 4.36; N, 5.51%. Found: C,
51.61; H, 4.71; N, 5.28%.
Dimethoxyphosphoryl 4-Fluorophenyl Methyl 2-(4,6-Dimethoxypyrimi
1
din-2-yloxy) Benzoate (8e). Yellow liquid; H-NMR (CDCl3, TMS, 600 MHz): δ =
3.64 (d, J = 5.4 Hz, 3H, OCH3), 3.66 (d, J = 6.0 Hz, 3H, OCH3), 3.74 (s, 6H, OCH3), 5.71
(s, 1H, CH), 6.30 (d, J = 13.8 Hz, 1H, CH), 7.02 (t, J = 7.8 Hz, 2H, arom-H), 7.25 (d, J =
7.8 Hz, 1H, arom-H), 7.35 (t, J = 7.8 Hz, 1H, arom-H), 7.48 (t, J = 8.4 Hz, 2H, arom-H),
7.63 (d, J = 8.4 Hz, 1H, arom-H), 8.11 (d, J = 8.4 Hz, 1H, arom-H); 31P-NMR (CDCl3,
243 MHz): δ = 19.4; IR (KBr, υ/cm−1): 1737 (C O), 1219 (P O); MS (70 eV) m/z (%):
492 (4), 123 (25), 109 (100), 79 (36). Anal. Calcd. for C, 53.66; H, 4.50; N, 5.69%. Found:
C, 53.86; H, 4.78; N, 5.32%.
Dimethoxyphosphoryl 4-Nitrophenyl Methyl 2-(4,6-Dimethoxypyrimidin-
1
2-yloxy) Benzoate (8f). Yellow liquid; H-NMR (CDCl3, TMS, 600 MHz): δ = 3.66
(d, J = 10.8 Hz, 3H, OCH3), 3.71 (d, J = 10.8 Hz, 3H, OCH3), 3.76 (s, 6H, OCH3), 5.72
(s, 1H, CH), 6.41 (d, J = 14.4 Hz, 1H, CH), 7.28 (d, J = 7.8 Hz, 1H, arom-H), 7.38 (t, J =
7.8 Hz, 1H, arom-H), 7.64 (d, J = 7.8 Hz, 1H, arom-H), 7.68 (d, J = 7.8 Hz, 2H, arom-H),

1402
C. JIN AND H. HE
8.12 (d, J = 7.8 Hz, 1H, arom-H), 8.20 (d, J = 8.4 Hz, 1H, arom-H); 31P-NMR (CDCl3,
243 MHz): δ = 18.1; IR (KBr, υ/cm−1): 1739 (C O), 1218 (P O); MS (70 eV) m/z (%):
519 (2), 458 (78), 217 (100), 92 (11); Anal. Calcd. for C, 50.87; H, 4.27; N, 8.09%. Found:
C, 50.47; H, 4.65; N, 7.68%.
Diethoxyphosphoryl Phenyl Methyl 2-(4,6-Dimethoxypyrimidin-2-yloxy)
Benzoate (8g). Yellow liquid; 1H-NMR (CDCl3, TMS, 600 MHz): δ = 1.17 (t, J = 6.6
Hz, 3H, CH3), 1.20 (t, J = 6.6 Hz, 3H, CH3), 3.73 (s, 6H, OCH3), 3.93–4.07 (m, 4H,
OCH2) 5.68 (s, 1H, CH), 6.30 (d, J = 13.2 Hz, 1H, CH), 7.23 (d, J = 8.4 Hz, 1H, arom-H),
7.30–7.36 (m, 4H, arom-H), 7.48 (d, J = 8.4 Hz, 2H, arom-H), 7.59–7.62 (m, 1H, arom-H),
8.15 (d, J = 8.4 Hz, 1H, arom-H); 31P-NMR (CDCl3, 243 MHz): δ = 17.2; IR (KBr,
υ/cm−1): 1736 (C O), 1218 (P O); MS (70 eV) m/z (%): 502 (49), 364 (13), 259 (19), 56
(100). Anal. Calcd. for C, 57.37; H, 5.42; N, 5.58%. Found: C, 57.48; H, 5.08; N, 5.19%.
Diethoxyphosphoryl p-Tolyl Methyl 2-(4,6-Dimethoxypyrimidin-2-yloxy)
1
Benzoate (8h). Yellow liquid; H-NMR (CDCl3, TMS, 600 MHz): δ = 1.17–1.26 (m,
6H, CH3), 2.32 (s, 3H, CH3), 3.72 (s, 6H, OCH3), 3.91–4.08 (m, 4H, OCH2), 5.67 (s, 1H,
CH), 6.26 (d, J = 12.6 Hz, 1H, CH), 7.11 (d, J = 7.8 Hz, 2H, arom-H), 7.23 (d, J = 7.8
Hz, 1H, arom-H), 7.33–7.36 (m, 3H, arom-H), 7.60 (d, J = 7.8 Hz, 1H, arom-H), 8.12 (d,
J = 8.4 Hz, 1H, arom-H); 31P-NMR (CDCl3, 243 MHz): δ = 17.4; IR (KBr, υ/cm−1): 1720
(C O), 1218 (P O); MS (70 eV) m/z (%): 516 (8), 295 (86), 277 (100), 155 (68), 83 (60).
Anal. Calcd. for C, 58.14; H, 5.66; N, 5.42%. Found: C, 57.86; H, 5.86; N, 5.63%.
Diethoxyphosphoryl 4-Methoxyphenyl Methyl 2-(4,6-Dimethoxypyrimi
1
din-2-yloxy) Benzoate (8i). Yellow liquid; H-NMR (CDCl3, TMS, 600 MHz): δ =
1.16–1.26 (m, 6H, CH3), 3.72 (s, 3H, OCH3), 3.79 (s, 6H, OCH3), 3.91–4.08 (m, 4H,
OCH2), 5.69 (s, 1H, CH), 6.25 (d, J = 13.2 Hz, 1H, CH), 6.83 (d, J = 9.0 Hz, 2H, arom-H),
7.24 (d, J = 7.8 Hz, 1H, arom-H), 7.29–7.35 (m, 1H, arom-H), 7.42 (d, J = 8.4 Hz, 2H,
arom-H), 7.59 (d, J = 7.8 Hz, 1H, arom-H), 8.11 (d, J = 7.8 Hz, 1H, arom-H); 31P-NMR
(CDCl3, 243 MHz): δ = 17.5; IR (KBr, υ/cm−1): 1735 (C O), 1219 (P O); MS (70 eV)
m/z (%): 532 (6), 259 (100), 231 (12), 134 (23). Anal. Calcd. for C, 56.39; H, 5.49; N,
5.26%. Found: C, 56.03; H, 5.18; N, 5.47%.
4-Chlorophenyl Diethoxyphosphoryl Methyl 2-(4,6-Dimethoxypyrimidin-
1
2-yloxy) Benzoate (8j). Yellow liquid; H-NMR (CDCl3, TMS, 600 MHz): δ = 1.19
(t, J = 4.2 Hz, 3H, CH3), 1.21 (t, J = 4.2 Hz, 3H, CH3), 3.73 (s, 6H, OCH3), 3.97–4.09
(m, 4H, OCH2), 5.69 (s, 1H, CH), 6.26 (d, J = 13.8 Hz, 1H, CH), 7.25 (d, J =
8.4 Hz, 1H, arom-H), 7.29 (d, J = 7.8 Hz, 2H, arom-H), 7.34–7.36 (m, 1H, arom-H),
7.43 (d, J = 8.4 Hz, 2H, arom-H), 7.61 (d, J = 7.8 Hz, 1H, arom-H), 8.11 (d, J = 7.8
Hz, 1H, arom-H); 31P-NMR (CDCl3, 243 MHz): δ = 16.7; IR (KBr, υ/cm−1): 1739
(C O), 1219 (P O); MS (70 eV) m/z (%): 536 (6), 298 (23), 258 (100), 110 (49), 83
(89), 66 (62). Anal. Calcd. for C, 53.69; H, 4.88; N, 5.22%. Found: C, 53.92; H, 5.09; N,
4.97%.
Diethoxyphosphoryl 4-Fluorophenyl Methyl 2-(4,6-Dimethoxypyrimidin-
1
2-yloxy) Benzoate (8k). Yellow liquid; H-NMR (CDCl3, TMS, 600 MHz): δ = 1.18
(t, J = 6.6 Hz, 3H, CH3), 1.21 (t, J = 6.6 Hz, 3H, CH3), 3.73 (s, 6H, OCH3), 3.95–4.08
(m, 4H, OCH2), 5.69 (s, 1H, CH), 6.27 (d, J = 13.2 Hz, 1H, CH), 7.01 (d, J = 8.4 Hz,
2H, arom-H), 7.24 (d, J = 7.8 Hz, 1H, arom-H), 7.34–7.36 (m, 1H, arom-H), 7.47 (d, J =
7.8 Hz, 2H, arom-H), 7.61 (d, J = 7.8 Hz, 1H, arom-H), 8.11 (d, J = 7.8 Hz, 1H, arom-H);
31P-NMR (CDCl3, 243 MHz): δ = 17.0; IR (KBr, υ/cm−1): 1738 (C O), 1220 (P O);
MS (70 eV) m/z (%): 520 (3), 201 (45), 145 (100), 109 (43), 91 (18). Anal. Calcd. for C,
55.39; H, 5.04; N, 5.38%. Found: C, 55.74; H, 5.38; N, 5.04%.

SYNTHESIS OF PHOSPHONATE DERIVATIVES
1403
Diethoxyphosphoryl 4-Nitrophenyl Methyl 2-(4,6-Dimethoxypyrimidin-
2-yloxy) Benzoate (8l). Yellow liquid; 1H-NMR (CDCl3, TMS, 600 MHz): 1.19–1.37
(m, 6H, CH3), 3.75 (s, 6H, OCH3), 4.01–4.12 (m, 4H, OCH2), 5.70 (s, 1H, CH), 6.37 (d, J =
14.4 Hz, 1H, CH), 7.28 (d, J = 7.2 Hz, 1H, arom-H), 7.38 (d, J = 7.8 Hz, 1H, arom-H),
7.64–7.68 (m, 3H, arom-H), 8.13 (d, J = 7.8 Hz, 2H, arom-H), 8.18 (d, J = 9.0 Hz, 1H,
arom-H); IR (KBr, υ/cm−1): 1740 (C O), 1218 (P O); MS (70 eV) m/z (%): 547 (46),
137 (43), 108 (100), 92 (42). Anal. Calcd. for C, 52.65; H, 4.79; N, 7.68%. Found: C, 52.97;
H, 5.04; N, 7.32%.
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