Synthesis of 2-[2-(4-substituted-1,3,5-triazin-2-loxy)phenyl]-3,3-dimethoxypropanoate

Article abstract of DOI:10.14233/ajchem.2015.18227

In this article, the synthesis of a series of novel compounds, methyl 2-[2-(4-substituted-1,3,5-triazin-2-yloxy)phenyl]-3,3-dimethoxypropanoate is reported. 4,6-Dichloro-N,N-diethyl-1,3,5-triazin-2-amine reacted with methyl 2-(2-hydroxyphenyl)-3,3-dimethoxypropanoate to give methyl 2-[2-{4-chloro-6-(diethylamino)-1,3,5-triazin-2-yloxy}phenyl]-3,3-dimethoxypropanoate, which then reacted with phenols or thiophenols to give nine novel targets compounds. The structures of target compounds had been characterized by IR, 1H NMR and HRMS.

Full text of DOI:10.14233/ajchem.2015.18227

Asian Journal of Chemistry; Vol. 27, No. 8 (2015), 2836-2840
A
SIAN
J
OURNAL OF HEMISTRY
C
http://dx.doi.org/10.14233/ajchem.2015.18227
Synthesis of 2-[2-(4-Substituted-1,3,5-triazin-2-loxy)phenyl]-3,3-dimethoxypropanoate
1
,2,*
2
2
1,2
JUAN LUO , XIU YANG , YU-LIANG WANG and YU-ZHONG WANG
1
2
College of Chemical Engineering, Sichuan University, Chengdu 610064, P.R. China
College of Chemistry, Sichuan University, Chengdu 610065, P.R. China
*
Corresponding author: Tel: +86 18980715296; E-mail: loyis-luo@163.com
Received: 31 May 2014; Accepted: 12 August 2014;
Published online: 27 April 2015;
AJC-17144
In this article, the synthesis of a series of novel compounds, methyl 2-[2-(4-substituted-1,3,5-triazin-2-yloxy)phenyl]-3,3-dimethoxy-
propanoate is reported. 4,6-Dichloro-N,N-diethyl-1,3,5-triazin-2-amine reacted with methyl 2-(2-hydroxyphenyl)-3,3-dimethoxypropanoate
to give methyl 2-[2-{4-chloro-6-(diethylamino)-1,3,5-triazin-2-yloxy}phenyl]-3,3-dimethoxypropanoate, which then reacted with phenols
1
or thiophenols to give nine novel targets compounds. The structures of target compounds had been characterized by IR, H NMR and HRMS.
Keywords: Methoxyacrylate, 3,3-Dimethoxypropanoate, Synthesis.
N
N
INTRODUCTION
OCH3
O
O
H COOC
The naturally-occurring derivatives of β-methoxyacrylic
acid, such as strobilurinA (Fig. 1) has wide range of biological
activities and serve as important lead compounds for the
development of a new class of fungicides for crop protection .
In past decades, structural modification and optimization
about strobilurin A had been carried out and produced large
quantities of methoxyacrylate derivatives. Research showed
that the introduction of heterocyclic structure would help to
improve bioactivity of compounds. Many methoxyacrylate
derivatives containing nitrogenous heterocycle, such as pyri-
3
CN
N
OCH3
H COOC
3
Strobilurin A
Azoxystrobin
1-3
N(CH CH )
2
3 2
O
N
Cl
N
N
OCH3
Cl
N
O
H COOC
3
OCH3
OCH3
CH3
H COOC
3
Pyraoxystrobin
3
Fig. 1. Struture of strobilurin A, azoxystrobin, pyraoxystrobin and compound 3
4
-13
midinyl and pyrazolyl had been synthesized . Some of these
compounds showed good fungicidal activity on a wide range
of crops and was successfully commercialized. For example,
azoxystrobin and pyraoxystrobin (Fig. 1) had been widely
sold as the most significant examples among the structural
analogues of methoxyacrylate derivatives.
In our previous research on methoxyacrylates fungicide,
methyl 2-[2-{4-chloro-6-(diethylamino)-1,3,5-triazin-2-
yloxy}phenyl]-3,3-dimethoxypropanoate (3, Fig. 1) was found
to exhibit antibacterial activity and compound 3 had a certain
structural similarity to methoxyacrylates.
It can be expected that the compound 3 analogues was
one kind of novel compound with potential bioactivity. In this
study a series of novel compounds were designed and synthe-
sized on the basic moiety of 3. The synthetic route is outlined
in Scheme-I. 4,6-Dichloro-N,N-diethyl-1,3,5-triazin-2-amine
with different substituted groups or heteroatom, were linked
to compound 3 to give nine novel target compounds, methyl
2-[2-(4-substituted-1,3,5-triazin-2-yloxy)phenyl]-3,3-dimethoxy-
propanoate (4).
EXPERIMENTAL
,6-Dichloro-N,N-diethyl-1,3,5-triazin-2-amine (1) was
4
13
prepared according to literature . Methyl 2-(2-hydroxyphenyl)
3,3-dimethoxypropanoate (2) was prepared according to
-
14
literature . All the reagents were analytically pure. All of the
organic solvents used in this study were dried over appropriate
drying agents.
Melting points (m.p.) were determined with XRC-1 melting
point apparatus without correction. TLC was performed on
silica gel GF254 and spots were visualized with ultraviolet
(
1) reacted with methyl 2-(2-hydroxyphenyl)-3,3-dimethoxy-
(
1
UV) light. IR spectra were recorded with a Perkin-Elemer
6PC-FT spectrometer as pellets (KBr). Mass spectra were
propanoate (2) to give compound 3, then phenols or thiophenols,

Vol. 27, No. 8 (2015)
Synthesis of 2-[2-(4-Substituted-1,3,5-triazin-2-loxy)phenyl]-3,3-dimethoxypropanoate 2837
N(CH CH )
Cl
N
2
3 2
dry acetone, K CO
2
3
N
N
N
N
N(CH CH )
2
3 2
0
°C, 4h
Cl
N
Cl
THF,
Cl
Cl
N
N
K CO ,
2
3
1
4
0-45 °C, Cl
N
O
7
h
OCH
3
H COOC
3
COOH 1) (CH
CO)
O,CH(OCH
) ,reflux,19h; HO
3 3
3
2
OCH
3
3
OCH
3
2
) Na, dry CH
3
OH,N , 0-5°C, 3h
2
OH
H COOC
3
dioxane, K CO ,
2
3
OCH
3
7
0-100 °C,9-12h
2
N(CH CH )
2
3 2
N
N
4
4
4
4
4
a
c
e
g
i
: R=2-methoxyphenoxy ;
: R= quinolin-8-yloxy ;
: R= -tolylthio ;
: R=2-chlorophenoxy ;
: R= 4-cyanophenoxy
4b :R=naphthalen-1-yloxy ;
4d: R=pyridin-2-ylthio;
R
N
O
p
4f : R=1,3-dioxoisoindolin-5-yloxy;
4h: R= 1
-benzo[d][1,2,3]triazol-1-yloxy ;
OCH
3
H
H COOC
3
OCH
3
4
Scheme-I: Synthetic route of compound 4a-4i
recorded withAgilent 6210 (DOF-MAS) spectrometer (Agilent
Inc., Santa Clara, CA, USA) using the electrospray ionization
The residue was purified with column chromatography on
silica with mixture of petroleum ether and ethyl acetate (v/v)
to afford product 4.
+
1
(
ESI ) method. H NMR spectra were recorded with a Varian
INVOA-400 spectrometer using TMS as internal standard.
The chemical shift values (δ) were given in ppm and coupling
constants were given in Hz.
Methyl 2-[2-{4-chloro-6-(diethylamino)-1,3,5-triazin-
2-yloxy}phenyl]-3,3-dimethoxypropanoate (3): Light yellow
-1
solid, yield 64 %. IR (KBr, νmax, cm ) 2972 (Ar-H), 1728
Preparation of methyl 2-[2-{4-chloro-6-(diethylamino)-
(C=O), 1581 (Ar-N), 1500 (Ph), 1293 (C-N), 1259 (Ar-O-O),
1
1
,3,5-triazin-2-yloxy}phenyl]-3,3-dimethoxypropanoate
1209 (C-O), 1121 (C-O-C), 807 (Ar), 769 (C-Cl); H NMR
(
3): Compound 1 (4.86 g, 22 mmol), K CO (2.76, 20 mmol)
2
3
(CDCl
1.14 (t, J = 7.2, 6.8 Hz, 3 H, -NCH
3.40 (s, 3H, -OCH ), 3.51 (s, 3 H, -COOCH
-NCH CH ), 4.26 (d, J = 8.4 Hz, 1H, -CHCOOCH
J = 8.8 Hz, 1H, -CH(OCH ),7.07-7.63 (m, 4 H, Ph-H); HR-
3
, 400 MHz) δ: 0.99 (t, J = 7.2, 6.8 Hz, 3 H, -NCH
2
CH
3
),
),
and dry acetone (30 mL) were added in a flask. Then the
compound 2 (4.76 g, 20 mmol) in dry THF (20 mL) was added
dropwise to the solution slowly at room temperature. After
dropping was finished, the mixture was warmed to 35-40 °C
and stirred until completion of the reaction (monitored with
TLC, petroleum ether/ethyl acetate, 2:1,v/v). The mixture was
filtered and concentrated under reduced pressure. The residue
was dissolved in ethyl acetate (20 mL), washed with water
2
CH ), 3.16 (s, 3H, -OCH
3
3
3
3
), 3.34 (m, 4H,
), 5.04 (d,
2
3
3
)
3 2
+
MS (+ESI): Calcd. for C19
found: 447.1397.
H25ClN
4
O Na[M + Na] : 447.1411,
5
Methyl 2-[2-{4-(diethylamino)-6-(2-methoxyphenoxy)-
1,3,5-triazin-2-yloxy}phenyl]-3,3-dimethoxypropanoate
(4a): The crude product was prepared by the reaction of o-
methoxyphenol with compound 3 and was purified by TLC
on silica gel with petroleum ether and ethyl acetate (4:1, v/v)
(
10 mL × 3). The combined organic layer was dried with
anhydrous Na SO , filtered and concentrated in vacuo to give
2
4
crude product. The crude product was purified by column
chromatography (silica gel; petroleum ether/ethyl acetate, 2:1,
v/v) gave compound 3 as light yellow solid.
-1
as a viscous brown liquid. IR (KBr, νmax, cm ) 3069 (Ar-H),
1738 (C=O), 1605 (Ar-N), 1528 (Ph), 1316 (C-N), 1259 (Ar-
1
Typical procedure for the preparation of compound
O-Ar), 1215 (C-O), 1112 (C-O-C), 810 (Ar-H); H NMR
4
a-4i: Substituted phenols or thiophenols (20 mmol), K
2
CO
3
(CDCl
-OCH
-COOCH
8.5 Hz, 1H, -CHCO-OCH
-CH(OCH ), 6.87-6.93 (m, 2H, Ph-H), 7.04-7.24 (m, 5H,
Ph-H), 7.55 (d, J = 12.1 Hz, 1 H, Ph-H); HR-MS (+ESI): Calcd.
3
, 400 Hz): 0.89-1.07 (m, 6H, -NCH
), 3.26-3.44 (m, 7H, -OCH , -NCH
), 3.77 (d, J = 8.5 Hz, 3H, -OCH
), 5.04 (d, J = 8.5 Hz, 1H,
2
CH
CH
Ph), 4.31 (d, J =
3
), 3.14 (s, 3H,
), 3.55 (s, 3H,
(
2.76, 20 mmol) and dry dioxane (30 mL), KI (5 % wt) were
3
3
2
3
added in a single-necked round bottom flask. Then the
compound 3 (4.86 g, 22 mmol) in dry dioxane (20 mL) was
added dropwise to the suspension slowly at room temperature.
After dropping was finished, the mixture was warmed to 65-
3
3
3
)
3 2
+
100 °C and stirred .The end-point of the reaction was monitored
for C26
H
32
N
4
O Na [M + Na] : 535.2169 , found: 535.2160.
7
with TLC ( petroleum ether/ethyl acetate = 1:1-4:1,v/v). Then
the mixture was filtered and evaporated under reduced pressure.
The residue was dissolved in ethyl acetate (20 mL), washed
with water (10 mL × 3). The combined organic layer was dried
Methyl 2-[2-{4-(diethylamino)-6-(naphthalen-1-yloxy)-
1,3,5-triazin-2-yloxy}phenyl]-3,3-dimethoxypropanoate
(4b): The crude product was prepared by the reaction of
α-naphthol with compound 3 and was purified by TLC on
silica gel with petroleum ether and ethyl acetate (4:1, v/v) as a
with anhydrous Na
2
SO , filtered and concentrated in vacuo.
4

2
838 Luo et al.
Asian J. Chem.
-
1
viscous brown liquid. IR (KBr, νmax, cm ) 3061 (Ar-H), 1738
Methyl 2-[2-{4-(diethylamino)-6-(1,3-dioxoisoindolin-
5-yloxy)-1,3,5-triazin-2-yloxy}phenyl]-3,3-dimethoxypro-
panoate (4f): The crude product was prepared by the reaction
of 5-hydroxy-isoindole-1,3-dione and 3 and was purified by
TLC on silica gel with petroleum ether and ethyl acetate (2:1,
(
C=O), 1589 (Ar-N), 1527 (ph), 1317 (C-N), 1257 (Ar-O-Ar),
1
1
4
3
3
222 (C-O), 1105 (C-O-C), 807 (Ar-H); H NMR (CDCl
00 Hz): 0.99-0.71 (m, 6H, -NCH CH ), 3.12 (s, 3H, -OCH ),
.13-3.34 (m, 4H, -NCH CH ), 3.40 (s, 3H, -OCH ), 3.53 (s,
H, -COOCH ), 4.30 (d, 1H, J = 8.5 Hz, -CHCOOCH ), 5.03
), 7.06 (m, 1H, Phr-H), 7.16-
.29 (m, 3H, Ph-H), 7.37-7.51 (m, 3H, Naphthr-H), 7.54-7.60
3
,
2
3
3
2
3
3
-1
3
3
v/v) as a yellow solid, m.p.117 °C. IR (KBr, νmax, cm ) 3113
(
d, 1H, J = 8.5 Hz, -CH(OCH
3
)
2
(N-H), 3062 (Ar-H), 1736 (C=O), 1589 (Ar-H), 1483 (Ph),
1
7
1307 (C-N), 1215 (C-O), 1100 (C-O-C), 809 (Ar-H); H NMR
(
7
m, 1H, Naphth-H), 7.71 (d, 1H, J = 2 Hz, Naphth-H), 7.84-
.87 (m, 1H, Naphth-H), 7.90-7.98 (m, 1H, Naphthr-H); HR-
(CDCl
1.09 (t, J = 7.2, 6.8 Hz, 3H, -NCH
3.34-3.36 (m, 4H, -NCH CH ), 3.46 (s,3H, -OCH
3H, -COOCH ), 4.26 (d, J = 8.4 Hz, 1H, -CHCOOCH
(d, J = 8.4 Hz, 1H, -CH(OCH ), 7.11 (d, J = 9.2 Hz, 1H, Ph-
3
, 400 Hz): 0.99 (t, J = 7.2,7.2 Hz, 3H, -NCH
2
CH
3
),
),
2
CH ), 3.15 (s, 3H, -OCH
3
3
+
MS (+ESI): Calcd. for C29
found: 555.2212.
H
32
N O
4 6
Na [M + Na] : 555.2220,
2
3
3
), 3.53 (s,
), 5.03
3
3
Methyl 2-[2-{4-(diethylamino)-6-(quinolin-8-yloxy)-
,3,5-triazin-2-yloxy}phenyl]-3,3-dimethoxypropanoate
)
3 2
1
H), 7.27 (m, 2H, Ph-H), 7.51-7.60 (m, 2H ,Ph-H), 7.69 (s, 1H,
(
4c): The crude product was prepared by the reaction of 8-
NH), 7.85 (d, J = 8.4 Hz, 1H, Ph-H); HR-MS (+ESI): Calcd.
+
hydroxyquinoline with compound 3 and was purified by TLC
for C27
H
29
N O
5 8
Na [M + Na] : 574.1914; found: 574.1920.
on silica gel with petroleum ether and ethyl acetate (1:1, v/v)
as a yellow solid, m.p. 95 °C. IR (KBr, νmax, cm ) 3064 (Ar-
H), 1740 (C=O), 1591 (Ar-N), 1527 (Ph), 1316 (C-N), 1212
Methyl 2-[2-{4-(2-chlorophenoxy)-6-(diethylamino)-
1,3,5-triazin-2-yloxy}phenyl]-3,3-dimethoxypropanoate
(4g): The crude product was prepared by the reaction of
2-chlorophenol with compound 3 and was purified by TLC
on silica gel with petroleum ether and ethyl acetate (4:1, v/v)
-1
1
(
1
(
-
8
7
C-O), 1105 (C-O-C), 791(Ar-H); H NMR (CDCl
3
, 400 Hz):
), 3.38
), 3.07 (s, 3H,
), 4.99 (d, J =
), 6.96 (t, J = 6.8, 2 Hz, 1H, Ph-H),
.10-7.15 (m, 2H, Ph-H), 7.42-7.43 (m, 1H, Ph-H), 7.51-7.52
.24-1.27 (m, 6H, -NCH
s, 3H, -OCH ), 3.25-3,35 (m, 4H, -NCH
OCH ), 4.27 (d, J = 8.4 Hz, 1H, -CHCOOCH
.4 Hz, 1H, -CH(OCH
2
CH
3
), 3.56 (s, 3H, -COOCH
3
-1
3
2
CH
3
as a viscous yellow liquid. IR (KBr, νmax, cm ) 3068 (Ar-H),
1739 (C=O), 1589 (Ar-H), 1482 (Ph), 1318 (C-N), 1223 (C-O),
3
3
1
3
)
2
1110 (C-O-C), 810 (Ar-H), 766 (C-Cl); H NMR (CDCl
3
, 400
), 3.28-
), 3.55 (s, 3H,
), 4.32 (d, J = 8.4 Hz, 1H, -CHCOOCH ), 5.05 (d, J
= 8.4 Hz, 1H, -CH(OCH ), 7.20 (m, 6H, Ph-H), 7.41 (dd, J =
1.2, 1.2 Hz, 1H Ph-H), 7.58 (dd, J = 1.6, 1.2 Hz, 1H, Ph-H).
Hz): 0.94-1.01 (m, 6H, -NCH
3.29 (m, 4H, -NCH CH ), 3.41 (s, 3H, -OCH
-COOCH
2
CH
3
), 3.15 (s, 3H, -OCH
3
(
8
m, 3H, quinolin-H), 7.70 (t, J = 4.4, 4.8 Hz, 1H, quinolin-H),
.19 (d, J = 8 Hz, 1H, quin-olin-H), 8.89 (s, 1H, quinolin-H);
2
3
3
3
3
+
HR-MS (+ESI): Calcd. for C28
found: 534.2352.
H
32
N O
5 6
[M + H] : 534.2352,
)
3 2
+
Methyl 2-[2-{4-(diethylamino)-6-(pyridin-2-ylthio)-
,3,5-triazin-2-yloxy}phenyl]-3,3-dimethoxypropanoate
HR-MS (+ESI): Calcd. for C25
539.1674; found: 539.1979.
H
29ClN
4
6
O Na [M + Na] :
1
(
4d): The crude product was prepared by the reaction of 2-
Methyl 2-[2-{4-(1H-benzo[d][1,2,3]triazol-1-yloxy)-6-
(diethylamino)-1,3,5-triazin-2-yloxy}phenyl]-3,3-dimetho-
xypropanoate (4h): The crude product was prepared by the
reaction of benzotriazol-1-ol with compound 3 and was
purified by TLC on silica gel with petroleum ether and ethyl
mercaptopyridine with 3 and was purified by TLC on silica gel
with petroleum ether and ethyl acetate (4:1,v/v) as a yellow
solid, m.p. 85 °C. IR (KBr, νmax, cm ) 3071 (Ar-H), 1734
-1
(
(
(
-
4
1
7
C=O), 1573 (Ar-N), 1504 (Ph), 1295 (C-N), 1206 (C-O), 1117
1
C-O-C), 807 (Ar-H); H NMR (CDCl
m, 6H, -NCH CH ), 3.54 (s, 3H, -COOCH3), 3.38 (s, 3H,
OCH ), 3.35-3.37 (m, 4H, -NCH CH ), 3.13 (s, 3H, -OCH ),
.25 (d, J = 8.4 Hz, 1H, -CHCOOCH ), 5.01 (d, J = 8.8 Hz,
H, -CH(OCH ), 7.04 (m, 1H, Ph-H), 7.22 (m, 3H, Ph-H),
.55 (m, 3H, py-H), 8.53 (d, J = 4.0 Hz, 1H, py-H); HR-MS
3
, 400 Hz): 0.98-1.05
acetate (1:1, v/v) as a yellow solid, m.p. 150 °C. IR (KBr, νmax,
-1
2
3
cm ) 2976 (Ar-H), 1740 (C=O), 1599 (Ar-H), 1489 (Ph), 1316
1
3
2
3
3
(C-N), 1212 (C-O), 1100 (C-O-C), 800 (Ar-H)-1; H NMR
3
(CDCl3, 400 Hz): 1.17-1.20 (t, J = 7.2, 7.2 Hz, 3H, -NCH
1.26-1.30 (t, J = 7.6, 6.8 Hz, 3H, -NCH -CH ), 3.15 (s, 3H,
-OCH ), 3.28 (s, 3H, -OCH ), 3.40 (s, 3H, -COOCH ), 3.59
(q, J = 6.8, 7.6, 7.6 Hz, 2H, -NCH CH ), 3.77 (q, J = 7.2, 6.8, 7.2
Hz, 2H, -NCH CH ), 4.29 (d, J = 8.4 Hz, 1H, -CHCOOCH ),
5.05 (d, J = 8.8 Hz, 1H, -CH(OCH ), 7.20-7.21 (m, 1H, Ph-
2 3
CH ),
3
)
2
2
3
3
3
3
+
(
5
+ESI): Calcd. for C24
H
30
N O
5 5
S [M + H] : 500.1967, found:
2
3
00.1966.
Methyl 2-[2-{4-(diethylamino)-6-(p-tolylthio)-1,3,5-
2
3
3
)
3 2
triazin-2-yloxy}phenyl]-3,3-dimethoxypropanoate (4e):
The crude product was prepared by the reaction of p-methyl
thiophenol with 3 and was purified by TLC on silica gel with
petroleum ether and ethyl acetate (4:1, v/v) as a yellow solid,
H), 7.38-7.43 (m, 4H, benztriazol-H, Ph-H), 7.68-7.74 (m,
2H, benztriazol-H), 7.95-7.98 (m, 1H, benztriazol-H). HR-
+
MS (+ESI): Calcd. for C25
found: 546.2079.
H
29
N
7
O
6
Na [M + Na] : 546.2077;
-1
m.p. 42 °C. IR (KBr, νmax, cm ) 3063 (Ar-H), 1737 (C=O),
563 (Ar-H), 1487 (Ph), 1294 (C-N), 1206 (C-O), 1107 (C-
Methyl 2-[2-{4-(4-cyanophenoxy)-6-(diethylamino)-
1,3,5-triazin-2-yloxy}phenyl]-3,3-dimethoxypropanoate
(4i): The crude product was prepared by the reaction of
4-cyanophenol and compound 3 and was purified by TLC on
silica gel with petroleum ether and ethyl acetate (4:1, v/v) as a
1
1
O-C), 803 (Ar-H); H NMR (CDCl
3
, 400H z): 0.97-0.99 (m,
), 3.14 (s, 3H, -OCH ), 3.25-
), 3.41 (s, 3H, -OCH ), 3.54 (s, 3H,
), 5.03 (d,
), 7.02-7.05 (m, 1H, Ph-H), 7.11
d, J = 7.2 Hz, 2H, Ph-H), 7.21-7.26 (m, 2H, Ph-H), 7.38 (d,
J = 8 Hz, 2H, Ph-H), 7.56-7.59 (m, 1H, Ph-H); HR-MS (+ESI):
6H, -NCH
2
CH
3
), 2.36 (s, 3H, -CH
CH
3
3
3
.32 (m, 4H, -NCH
2
3
3
-1
-COOCH3), 4.27 (d, J = 8.8 Hz, 1H, -CHCOOCH
3
pale yellow solid, m.p. 138 °C. IR (KBr, νmax, cm ) 3068 (Ar-
J = 10.8 Hz,1H, -CH(OCH
3
)
2
H), 2233 (CN), 1743 (C=O), 1584 (Ar-H), 1496 (Ph), 1320
1
(
(C-N), 1229 (C-O), 1106 (C-O-C), 808 (Ar-H). H NMR
(CDCl
3
, 400 Hz): 0.99 (t, J = 6.8, 7.2 Hz, 3H, (s, 3H, -OCH
3
),
+
Calcd. for C26
H
33
N
4
O
5
S [M + H] : 513.2171; found: 513.2178.
3.55 (s, 3H, -COOCH
3
), -NCH CH ), 1.07 (t, J = 7.2, 6.8 Hz,
2
3

Vol. 27, No. 8 (2015)
Synthesis of 2-[2-(4-Substituted-1,3,5-triazin-2-loxy)phenyl]-3,3-dimethoxypropanoate 2839
HO
N(CH CH )
2
3 2
OCH3
Cl
N
H COOC
N(CH CH )
3
N
N
NH(CH CH )
2
3 2
2
3 2
Route-1:
N
OCH3
2
N
N
N
Cl
N
O
OCH3
OCH3
Cl
Cl
Cl
N
Cl
H
3
COOC
1
3
N(CH CH )
2
3 2
Cl
Cl
N
Route-2:
Cl
Compound
2
N
N
N
N
NH(CH CH )
2 3 2
N
N
Cl
N
O
Cl
N
Cl
O
OCH3
OCH3
OCH3
H COOC
3
H COOC
3
OCH3
Scheme-II: Two designed synthetic route for compound 3
3
3
-
(
H, -NCH
NCH CH
d, J = 8.8 Hz, 1H, -CH(OCH
2
CH
3
), 3.14 (s, 3H, -OCH
3
), 3.33-3.39 (m, 4H,
), 5.04
), 7.10 (d, J = 9.2 Hz, 1H,
12 h at 110-120 °C, only trace of product or no product were
observed. The steric hindrance was unfavorable to reaction.
The reaction between 5-hydroxyisoindoline-1,3-dione and
compound 3 required higher temperature (100 °C) and longer
time (9 h). The reaction condition for compounds 4a-4i were
listed in Table-1.
2
3
), 3.41 4.27 (d, J = 8.8 Hz, 1H, -CHCOOCH
3
)
3 2
Ph-H), 7.25-7.30 (m, 5H, Ph-H), 7.60 (d, J = 7.6 Hz, 1H, Ar-
H), 7.65 (d, J = 8.4 Hz, 1H, Ph-H). HR-MS (+ESI): Calcd. for
C
+
26
H
29
N O
5 6
Na [M + Na] : 530.2016; found: 530.2017.
RESULTS AND DISCUSSION
TABLE-1
REACTION CONDITION OF THE COMPOUNDS 4a-4i
Synthesis of compound 3: In the synthesis of compound
, two possible synthetic route were designed (Scheme-II).
Experiment showed that no compound 3 was produced when
route 2 was taken. The proper synthetic route for compound 3
3
Temp.
Time
(h)
KI
Yield
Compound
R
(
°C)
(wt %) (%)
4
a
90
7
7
5
5
56
70
should be route 1. When the ratio of compound 1, 2 and K
2
CO
3
O
O
OCH
3
was 1.1:1:1 (molar ratio) and temperature was kept between
0-45 °C, the best yield of compound 3 was observed.
4
4
b
90
In order to find better base used in the synthesis of com-
pound 3, NaH, KOH, pyridine, K
2
CO were tested. Experiment
3
showed that when NaH was used, more by-products were
produced. When pyridine was used, the color of products was
darker. When KOH was used, the yield was rather poor. When
4c
90
65
65
7
5
5
5
0
0
67
73
68
N
O
S
K
2
CO
3
was used, the yield and color of products was better
CO was used in synthesis of compound 3.
4
d
than others. So K
2
3
N
Synthesis of compound 4: The synthesis of compound
a was chosen as model to optimize the reaction conditions of
4
CH3
S
4
e
target compounds. Dioxane was used as solvent and K
was chosen as base. Better yield of compound 4a was observed
when the ratio of compound 3, phenol and K CO was 1.1:1:1
molar ratio) and the dosage of catalyst KI (if used) was 5 %
wt %) of compound 3. Different phenol exhibited different
2
CO
3
O
HN
O
2
3
(
(
4
f
100
90
9
7
5
5
51
40
O
reactivity and required different reaction temperature and time
Table-1). The results showed that thiophenols was more reactive
(
4
g
than phenols. Pyridine-2-thiol and 4-methylbenzenethiol reacted
with compound 3 at 65 °C for 5 h to give better yield without
catalyst KI. But for other phenols, the reaction temperature
was always higher than 90 °C, required catalyst KI and longer
time. For phenols containing strong electron-withdrawing
groups, such as 4-fluorophenol, 4-trifluoromethyl-phenol, 4-
nitrophenol, the reaction was difficult to take place. Even after
O
Cl
N
N
N
4h
90
90
7
7
5
5
48
53
O
4
i
NC
O

2
840 Luo et al.
Asian J. Chem.
4
5
.
.
D.G. Brooke and J.C. Morris, Tetrahedron Lett., 49, 2414 (2008).
B. Chai, S.Y. Wang, W.Q. Yu, H.C. Li, C.J. Song, Y. Xu, C.L. Liu and
J.B. Chang, Bioorg. Med. Chem. Lett., 23, 3505 (2013).
Conclusion
A series of novel 2-[2-(4-substituted-1,3,5-triazin-2-
yloxy)phenyl]-3,3-dimethoxypropanoate compounds were
synthesized. The structure of all target compounds were identi-
fied by H NMR, IR and high resolution mass spectrum (HR-MS).
6. G.H. Lu, H.B. Chu, M. Chen and C.L. Yang, Chin. Chem. Lett., 25, 61
2014).
7. H.C. Li, B.S. Chai, Z.N. Li, J.C. Yang and C.L. Liu, Chin. Chem. Lett.,
0, 1287 (2009).
(
1
2
8
.
B.S. Chai, C.L. Liu, H.C. Li, S.W. Liu, Y. Xu, Y.Q. Song and J.B.
Chang, Chin. Chem. Lett., 25, 137 (2014).
ACKNOWLEDGEMENTS
9
.
M. Li, R.l. Liu, Z.N. Li, C.L. Liu and Z.M. Li, Agrochemicals, 48, 405
This work was financially supported by the National
Science Foundation of China (No. 21072135). The H NMR
characterization was accomplished by Sichuan University
Analytical & Testing Center.
(
2009).
1
10. K. Sun, H.F. Wu, H. Zhang, F.R. Wang, W. Cao, J. Zhao, H. Yang and
J.B. Xu, Modern Agrochem., 12, 17 (2013).
1
1
1. H.Y. Wang, S.Q. Li, Z.J. Fan, J.Y. Chen, F. Chai, S. Li and C.L.Liu,
Fine Chem. Intermed., 40, 66 (2010).
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