J. Chil. Chem. Soc., 56, Nº 4 (2011)
A NEW METHOD FOR ONE-POT SYNTHESIS OF ARYLOXYPHENOXYPROPIONATE HERBICIDES USING
2,4,6-TRICHLORO-1,3,5-TRIAZINE AND (n-BU)4NI AS A HOMOGENEOUS CATALYST
MEHDI KALHORA*, AKBAR DADRASB*, AKBAR MOBINIKHALEDIC, HASSAN TAJIKD
a Department of Chemistry, Payame Noor University, Tehran 19395-4697, I. R. of Iran
b Department of Chemistry, Islamic Azad University, East Tehran Branch, 33955-163, Qiamdasht, Iran
cDepartment of Chemistry, Arak University, Arak, Iran
dDepartment of Chemistry, Guilan University, Rasht, Iran, 41335-1914
(Received: September 15, 2010 - Accepted: June 20, 2011)
ABSTRACT
The one-pot reaction of halo-heterocycle, (R)-4-hydroxyphenoxy propionic acid and an alcohol, amine or sulfonamide is described as an efficient method for
the synthesis of aryloxyphenoxy propionate hrerbicides by using 2,4,6-trichloro-1,3,5-triazine in the presence of (n-Bu)4NI, as a homogeneous catalyst under mild
conditions. The present procedure offers several advantages, such as good yields, short reaction times and easy workup.
Keywords: One-pot reaction, Catalyst, Aryloxyphenoxy propionate, Cyanuric chloride
In view of this report and also due to our attention in one-pot synthesis
of organic compounds23,24, we are going to describe a practical and more
economical method for large-scale preparation of APPs herbicides 1-12.
INTRODUCTION
The one-pot reaction is known as a reaction in which three or more easily
accessible compounds are combined in a single reaction vessel.1-6 One-pot
reactions increase the efficiency of reactants by combing several operational
steps without isolation of intermediates or changing the reaction conditions.
Speed, diversity, efficiency and environmental amiability are some of the major
advantages of these reactions. They have emerged as valuable tools for the
preparation of structurally diverse chemical libraries of drug-like heterocyclic
compounds.7-9 Furthermore; aryloxyphenoxypropionates (APPs) are a highly
effective class of herbicides due to their high activity, high selectivity and low
toxicity. Up to now, more than 20 kinds of APPs such as clodinafop-propargyl
1, fenoxaprop-ethyl 2, fluazifop-butyl 3, haloxyfop-methyl 4, haloxyfop-etotyl
5, quizalofop-ethyl 6, have been commercialized and marketed by major
agrochemical companies.10-17 They are used effectively in a number of crops
including soybeans and cereal grains, such as wheat and rice, to control grass
weeds.12 Commonly, there are three pathways (route A, B and C) described
in the literature for preparation of desired APPs.14-16 These routes normally
proceed via an aromatic nucleophilic substitution of proper halo-hetero cyclic
compounds with (R)-4-hydroxyphenoxy propionic acid (4-HPPA) or it esters
(Figure 1).
EXPERIMENTAL
All used chemicals were purchased from Merck or Fluka Company.
Melting points were determined using an electro thermal digital apparatus and
are uncorrected. Infrared (IR) spectra were recorded on a Galaxy series Fourier
1
transform infrared (FT-IR) 5000 spectrometer using KBr discs. H NMR and
13C NMR spectra were recorded on Brucker spectrophotometer (300 MHZ) in
CDCl3 or DMSO-d using Me4Si as an internal standard. Elemental analyses
were performed on6a Vario EL III elemental analyzer and mass spectra were
recorded on Bruker Biflex Maldi-tof spectrometer.
General one-pot procedure
To the stirred solution of (R)-2-(4-hydroxyphenoxy)-propionic acid (1.82
g, 0.01 mol) in 10 ml of DMF, potassium phosphate (2.12 g, 0.01mol) was
added at 50ºC. Then halo-heterocycle (0.01 mol) and tetrabutylammonium
iodide (0.036 g, 1 mol %) was added, stirred at 50-60 ºC for 2 h. After cooling
the reaction mixture to 5 ºC, cyanuric chloride (0.738 g, 0.004 mol) was added
over 10 min, mixed for 1 h at 25 ºC and subsequently 0.012 mol alcohol or
amine was added. After completion of the reaction 1-2 h (monitored by thin-
layer chromatography, TLC, eluent n-hexane: EtOAc = 2:1), the mixture was
poured on 50 g of crushed ice with stirring and pH was adjusted to 8 with 25%
NaOH and stirred for 10 min at 0-5 ºC. The resulting solid was collected by
filtration, purified by recrystallization from 90% ethanol.
Spectroscopic Data for new Compounds:
2-[4-(5-Chloro-3-fluoro-pyridin-2-yloxy)-phenoxy]-propionic
acid
hydrazide (10); IR (KBr): υmax= 3356, 3277 (N-H), 1677 (C=O), 1620, 1504
(C=N), 1453, 1239 (C=C), 1197 (C-O), 851 (C-Cl) cm-1; 1H NMR (CDCl3, 300
MHz): δH 7.82 (1H, s, Ar), 7.47 (1H, s, Ar), 7.05 (2H, d, J= 8.6 Hz, Hph), 6.89
(2H, d, J= 8.6 Hz, Hph), 5.90 (1H, s, N-H), 5.25 (1H, q, J= 6.5 Hz ,CH), 4.70
(2H, br, NH ), 1.55 (3H, d, J= 6.5 Hz, CH3) ppm; 13C NMR (CDCl3, 75 MHz):
δC 18.7, 74.21, 116.3, 122.5, 125.0, 140.5, 145.1, 147.2, 148.6, 151.2, 154.1,
172.19 (C=O) ppm; [M]+ m/z = 325.72. Found: MALDI-TOF-MS: [M+Na]+ =
448.72; Anal Calcd for C H13ClFN3O3: C, 51.62; H, 4.02; N, 12.90; Found: C,
51.44; H, 4.03; N, 12.95.14
(R)-2-(4-(5-chloro-3-fluoropyridin-2-yloxy)phenoxy)-N-(4,6-dimethoxy
pyrimidin- 2-yl) propan amide (11): IR (KBr): υmax= 3409 (N-H), 2956 (C-
H.), 1719 (C=O), 1605, 1574 (C=N), 1450 (C=C), 1166 (C-O) cm-1; 1H NMR
(CDCl3, 300 MHz): δH 8.68 (1H, s, N-H), 7.81 (1H, s, Ar), 7.45 (1H, s, Ar),
7.09 (2H, d, J= 8.6 Hz, Hph), 6.99 (2H, d, J= 8.6 Hz, Hph), 5.76 (1H, s, Hpyrim.),
4.87 (1H, q, J= 6.5 Hz, CH), 3.90 (6H, s, OCH3), 1.65 (3H, d, J= 6.5 Hz,
CH3) ppm; 13C NMR (CDCl , 75 MHz): δC 18.5, 54.2, 76.0, 85.4, 116.7, 122.6,
124.1, 140.1, 145.1, 147.5,3 148.6, 151.1, 154.1, 155.5, 169.9, 172.0 (C=O)
ppm; Calcd: [M]+ m/z = 448.83; Found: MALDI-TOF-MS: [M+Na]+ = 471.83;
Anal Calcd for C20H18ClFN4O5: C, 53.52; H, 4.04; N, 12.48. Found: C, 53.71;
Figure 1. Classical pathways of APPs.
However, due to the low yield and purity of the A and B routes, commonly
route C is chosen as the synthetic strategy for the synthesis of APPs such
as clodinafop-propargyl 1 from corresponding halo-pyridine, 4-HPPA, and
propargyl halides.16 Recently, a few efficient examples have been reported
for the synthesis of APPs in ionic liquid media.18 The routes developed so far
suffer from harsh and cumbersome conditions, long reaction times, the use of
extremely anhydrous conditions, expensive and toxic reagents such as propargyl
halide, the use of large excess of reagents, tedious work-up and by product
formation. Because of the commercially importance of APPs, search for the
development of a simple, mild, and efficient method is still highly demanded.
On the other hand, over the past few years 2,4,6-Trichloro-1,3,5-triazine
(cyanuric chloride, CC) has been used in many chemical transformations19,
especially in conversion of carboxylic acid to ester or amide20-22, hence using
CC in preparation of APPs would be a challenge for the usual routes (A, B, C)
being a valid alternative route.
e-mail: adadras@guilan.ac.ir
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