Flazasulfuron: Alcoholysis, Chemical Hydrolysis, and Degradation on Various Minerals

Article abstract of DOI:10.1021/jf0347970

The herbicide flazasulfuron undergoes rapid alcoholysis. High yields of the corresponding carbamate and aminopyrimidine are obtained after the alcoholysis process (methanol or ethanol) at 30 °C in the course of which the concomitant rearrangement reaction remains minor. Hydrolysis (pH ranging from 5 to 11) of flazasulfuron at 30 °C principally involves the rearrangement into urea after elimination of S0₂ and can lead, in a small proportion, to both aminopyrimidine and pyridinesulfonamide. First-order kinetics correctly describes the rates of alcoholysis and hydrolysis. The sulfonylurea-bridge contraction and final transformation into the correspondent amine were evaluated with a first-order kinetics hypothesis. Transformations in amine and urea in aqueous medium are pH dependent. The chemical degradation of flazasulfuron on various dry minerals (calcium bentonite, kaolinite, silica, montmorillonite, and alumina) was investigated at 30 °C. The rearrangement reaction is the only one observed in the presence of kaolinite and alumina. However, hydrolysis and rearrangement have the same reaction rate in the presence of silica. The hydrolysis paths of flazasulfuron are comparable to the ones described for rimsulfuron.

Full text of DOI:10.1021/jf0347970

J. Agric. Food Chem. 2003, 51, 7717−7721 7717
Flazasulfuron: Alcoholysis, Chemical Hydrolysis, and
Degradation on Various Minerals
CEÄ DRIC BERTRAND,* ANNE WITCZAK-LEGRAND, JEAN SABADIE, AND
JEAN-FRANC¸ OIS COOPER
Laboratoire de Chimie des Biomole´cules et de l’Environnement, Centre de Phytopharmacie,
Universite´ de Perpignan, 52 Avenue Paul Alduy, 66860 Perpignan Cedex, France
The herbicide flazasulfuron undergoes rapid alcoholysis. High yields of the corresponding carbamate
and aminopyrimidine are obtained after the alcoholysis process (methanol or ethanol) at 30 °C, in
the course of which the concomitant rearrangement reaction remains minor. Hydrolysis (pH ranging
from 5 to 11) of flazasulfuron at 30 °C principally involves the rearrangement into urea after elimination
of SO2 and can lead, in a small proportion, to both aminopyrimidine and pyridinesulfonamide. First-
order kinetics correctly describes the rates of alcoholysis and hydrolysis. The sulfonylurea-bridge
contraction and final transformation into the correspondent amine were evaluated with a first-order
kinetics hypothesis. Transformations in amine and urea in aqueous medium are pH dependent. The
chemical degradation of flazasulfuron on various dry minerals (calcium bentonite, kaolinite, silica,
montmorillonite, and alumina) was investigated at 30 °C. The rearrangement reaction is the only one
observed in the presence of kaolinite and alumina. However, hydrolysis and rearrangement have
the same reaction rate in the presence of silica. The hydrolysis paths of flazasulfuron are comparable
to the ones described for rimsulfuron.
KEYWORDS: Flazasulfuron; alcoholysis; hydrolysis; degradation
INTRODUCTION
Sulfonylureas are a relatively recent group of herbicides used
essentially in cereal crops. Because of their low application rates
(10-50 g ha-1), low mammalian toxicity, and high herbicidal
activity, they are of high interest worldwide. Sulfonylureas are
based on the general structure R1-SO2-NH-CO-NH-R2,
where the R1 group can be either an aliphatic chain, an aromatic,
or a heterocyclic moiety connected by the sulfonylurea bridge
to a pyrimidine or triazine heterocycle (the R2 moiety) (1).
Approximately 25 sulfonylurea herbicides are already devel-
oped, and 4 pyridylsulfonylureas (R1 ) pyridine; R2 ) pyri-
midine) have been commercialized (Figure 1).
Figure 1. Structure of some pyridylsulfonylureas.
The aim of this study is to determine the major degradation
pathway after the investigation of the alcoholysis, chemical
hydrolysis, and behavior on minerals of flazasulfuron. The
results are compared with those described for other pyridylsul-
fonylureas.
MATERIALS AND METHODS
An original hydrolysis process (SO2 elimination and rear-
rangement into an asymmetric urea) has been described for
rimsulfuron (2-6) and for flupyrsulfuron-methyl (7-9). This
reaction is not observed for the nicosulfuron, where, in this case,
hydrolysis of the sulfonylurea bridge is predominant (10).
Flazasulfuron, the fourth of this group, N-[[(4,6-dimethoxy-
2-pyrimidinyl)amino]carbonyl]-3-(trifluoromethyl)-2-pyridine-
sulfonamide, was initially developed for the control of several
grasses in pasture (11). It is, actually, the only sulfonylurea
herbicide authorized in France for use in vineyards. It is applied
on vineyards >4 years old, postwinter, at the rate of 50 g ha-1
(12).
Chemicals. For each compound, mass spectrometric data and melting
points are shown in Table 1.
Flazasulfuron (1) was isolated from the herbicide formulation
A¨IKIDO (water dispersible granules, 25% ai). An aliquot of 2 g of
A¨IKIDO was gently shaken with 40 mL of CHCl3 for 3 h and filtered
on clarsol. CHCl3 was evaporated to dryness under vacuum. Recrys-
tallization was carried out in CHCl3, and a high-purity, white crystalline
powder was obtained (yield ) 80%).
2-Amino-4,6-dimethoxypyrimidine (2) was obtained from Sigma-
Aldrich, St. Quentin, France.
3-(Trifluoromethyl)-2-pyridylsulfonylmethylcarbamate (4a) and
3-(trifluoromethyl)-2-pyridylsulfonylethylcarbamate (4b) were pre-
pared as follows: Flazasulfuron (500 mg) was dissolved in 100 mL of
dry alcohol (CH3OH or C2H5OH) and maintained at 60 °C for 12 h.
The solution was evaporated to dryness under vacuum, and the residues
* Author to whom correspondence should be addressed (telephone
+33-4-68662232; fax +33-4-68662223; e-mail cbertran@univ-perp.fr).
10.1021/jf0347970 CCC: $25.00 © 2003 American Chemical Society
Published on Web 11/05/2003

7718 J. Agric. Food Chem., Vol. 51, No. 26, 2003
Bertrand et al.
Table 1. Mass Spectrometry Data (Direct Injection, EI/70 eV), Melting Point (mp), and Relative HPLC Retention Times (tR)
compd
mp ( °C)
mass spectrometric fragments (ions m/z, relative intensity)
tR
1a
172
407 [M +, 54], 300 [CF3 − C H N − NH − C HN (OCH ) +, 45], 231 [C H N − NH − C HN (OCH ) +, 60],
1.00
1
5
3
4
2
3 2
+
5
3
4
2
3 2
155 [NH − C HN (OCH ) +, 95], 146 [CF3 − C H N , 100]
2
4
2
3 2
5 3
2
3
4a
commercial compound
0.61
1.41
1.30
+
+
147
227 [M +, 9], 162 [CF3 − C H N − NH +, 100], 146 [CF3 − C H N , 94], 126 [CF2 − C H N , 57], 69 [CF3+, 48]
3
5
3
2
5
3
5 3
284 [M +, 58], 253 [CF3 − C H N − SO − NH − CO , 44], 146 [CF3 − C H N , 100], 126 [CF2 − C H N , 49],
+
+
+
4a
5
3
2
5
3
5 3
69 [CF3+, 15]
298 [M +, 60], 253 [CF3 − C H N − SO − NH − CO , 47], 227 [CF3 − C H N − SO − NH , 36],
1.05
1.15
0.52
+
+
4b
5
4b
5
3
2
5
3
2
+
+
146 [CF3 − C H N , 100], 126 [CF2 − C H N , 60]
5
3
5 3
141
87
343 [M +, 3], 300 [CF3 − C H N − NH − C HN (OCH ) +, 21], 231 [C H N − NH − C HN (OCH ) +, 100],
5 5 3 4 2 3 2 5 3 4 2 3 2
+
+
146 [CF3 − C H N , 56], 126 [CF2 − C H N , 29]
5
3
5 3
6
300 [M +, 90], 281 [CF2 − C H N − NH − C HN (OCH ) +, 20], 231 [C H N − NH − C HN (OCH ) +, 100],
6 5 3 4 2 3 2 5 3 4 2 3 2
+
188 [?, 45], 146 [CF3 − C H N , 24]
5
3
a Retention time ) 6.5 min.
were dispersed in Na2CO3 aqueous solution (0.2 M, 40 mL) and then
extracted by diethyl ether (4 × 20 mL), giving extract EA.
The aqueous layer is then acidified with hydrochloric acid (HCl) to
pH 2 and extracted by diethyl ether (4 × 10 mL). The organic phases
were dried and partially evaporated, giving the corresponding carbamate
(4a or 4b) as crystals, which are filtered and dried.
Extract EA was washed with aqueous 0.2 M HCl solution (to
eliminate product 2) and dried. The pure urea 5 [N-(4,6-dimethoxy-
pyrimidin-2-yl)-N-[3-(trifluoromethyl)-2-pyridinyl]urea] crystals, pro-
duced after partial evaporation of diethyl ether, were collected by
filtration and vacuum-dried (20 mg).
Sulfonamide (3) [3-(trifluoromethyl)-2-pyridinesulfonamide] was
prepared from a methanolic solution of carbamate 4a (15 mL, 170 mg),
10 mL of water and 200 mg of dry Na2CO3 were added, and the mixture
was heated at 100 °C for 2 h; after cooling, the solution was extracted
by diethyl ether (4 × 10 mL). Colorless needles (90 mg) of sulfonamide
3 were obtained by crystallization and filtration.
Amine (6) [N-[(3-Trifluoromethyl)-2-pyridinyl]-4,6-dimethoxy-
2-pyrimidineamine]. Flazasulfuron (500 mg) dissolved in 100 mL of
aqueous 0.2 M Na2CO3 was heated at 40 °C for 50 h. After cooling,
the formed amine was extracted with diethyl ether (5 × 10 mL). After
evaporation of the solvent, recrystallization was carried out in diethyl
ether (320 mg).
Minerals. Commercially obtained kaolinite and calcium bentonite
(Prolabo), silica gel (Kiesegel 60, Merck), montmorillonite K 10
(Fluka), and alumina (aluminum oxide 90 active neutral, Merck), were
oven-dried (100 h at 100 °C) before use.
Experimental Conditions for Alcoholysis and Hydrolysis. All
experiments were kept in a thermoregulated water bath at 30 °C using
an initial flazasulfuron concentration of ∼0.12 mmol L-1. Dry alcohol
(CH3OH or C2H5OH) was used for alcoholysis studies. Hydrolysis
experiments were conducted using a pH ranging from 5 to 11 for
flazasulfuron (1). The pH of the unsterilized aqueous solutions was
controlled by the appropriate buffer system: phosphate 1/15 M (pH 5,
6, 7, or 8); sodium carbonate/sodium bicarbonate 0.2 M (pH 9 or 10);
sodium bicarbonate/sodium hydroxide 0.2 M (pH 11). Each test was
carried out twice.
Herbicide Deposition. Deposition on minerals (typically 10-5 mol
g-1) was performed using either a dry method (thorough crushing of
the powder mixture) or a liquid method (herbicide dissolution into
acetone, addition of the mineral, and then evaporation to dryness under
vacuum at room temperature for 60 min). The herbicide-permeated
powder (typically 3 g) was enclosed in 5-mL glass tubes that were
sealed and kept at 30 °C, under continuous rotation-stirring. Each
experiment was run in duplicate.
Figure 2. Proposed pathways of alcoholysis and chemical hydrolysis of
flazasulfuron (1) at 30 °C.
Analytical Technique. The organic solutions were analyzed in
duplicate with a high-performance liquid chromatograph using a normal
phase column (Lichrosorb, reference no. 5 m-L5-25F, 25 cm), UV
detector system (245 nm), and a mobile phase of isooctane/absolute
ethanol/acetic acid (80:20:0.3) at a flow rate of 1.5 mL min-1. Dosage
accuracy was satisfactory for compounds 1, 2, 4, 5, and 6 ((2%).
Pyridylsulfonamide 3, although detected, was generally not quantified.
Retention times are described in Table 1.
RESULTS AND DISCUSSION
Alcoholysis. Flazasulfuron (1) undergoes a rapid alcoholysis
(Figure 2) when dissolved in dry methyl alcohol (CH3OH) or
ethyl alcohol (C2H5OH) at 30 °C (Table 2). The flazasulfuron
degradation rate can be described satisfactorily by first-order
kinetics, and the rate constant (k ) 0.40 day-1; Figure 3) is
comparable to the one previously described for nicosulfuron
(10).
Preparation of Analytical Samples. Alcoholysis samples (2 mL)
were evaporated to dryness under vacuum and stirred for 30 min with
5 mL of water/chloroform/acetic acid (2:3:0.1). Hydrolysis analytical
samples (2 mL) underwent similar extraction stirring for 30 min in 3
mL of chloroform/acetic acid (3:0.1) Analytical mineral samples
(typically 30 mg) were stirred for 30 min with 5 mL of chloroform/
water/acetic acid (3:2:0.05).
The carbamate 4 (Figure 2) is the major alcoholysis product
(respectively, 88 and 91%) as already described for most of

Flazasulfuron
J. Agric. Food Chem., Vol. 51, No. 26, 2003 7719
Table 2. Alcoholysis and Hydrolysis of Flazasulfuron at 30 °C
alcoholysis
hydrolysis
CH OH
3
C H OH
pH 5
pH 6
pH 7
pH 8
pH 9
pH 10
pH 11
2
5
activity
half-life (days)
rearrangement
hydrolysis
1.7
12
2.5
9
1.3
90
10
4.0
95
5
5.7
97
3
5.6
98
2
4.1
99
1
1.3
100
0
0.19
100
0
relative selectivitya (%)
alcoholysis
88
91
a Relative selectivity measured the percentage of each observed transformation.
Figure 5. Hydrolysis of flazasulfuron at 30 °C and pH 7: concentration
of flazasulfuron (1) (b), aminopyrimidine 2 (4), and urea 5 (0) as a
function of time. First-order kinetics line was established from the loss of
flazasulfuron (- -+- -).
Figure 3. Alcoholysis of flazasulfuron-methyl alcohol at 30 °C: concentra-
tion of flazasulfuron (1) (b), ethylcarbamate 4 (2), aminopyrimidine 2
(4), and urea 5 (0) as a function of time. First-order kinetics line was
established from the loss of flazasulfuron (- -+- -).
comparable rates have been reported for rimsulfuron (3). As an
example, rate constants k (day-1) at pH 7 and 30 °C are about
0.002, 0.25, and 0.25 for nicosulfuron, flazasulfuron, and
rimsulfuron, respectively. The flazasulfuron degradation rate
reaches a minimum for pH 6-9. The degradation is quicker
under acidic condition (pH e6) and mainly in alkaline medium
(pH g9). Anyway, the reaction rates can be described with first-
order kinetics (Figure 5).
The sulfonylurea classical hydrolysis pathway (formation of
compounds 2 and 3) is minor: it represents only 10% under
acidic conditions and is not observed at pH g10 (Table 2).
The sulfonyl-bridge contraction and the rearrangement in
urea 5 are the major modes of degradation (>90%) (Figure 2).
The ratio k2/k1 corresponding to the kinetics of urea 5
transformation into amine 6 (Figures 2 and 4) was evaluated,
with a first-order kinetics hypothesis. Figure 4 shows the
important relationship between the successive transformations
1 f 5 f 6 and pH. The formation of compound 6 was
weak under acidic conditions; under neutral conditions (pH 7
or 8), the urea 5 reaches a maximum and is converted into
amine 6 (Figure 5); at pH g8, the urea 5 appears to be very
reactive and is quickly transformed into the more stable amine
6. This reaction pathway has already been described for
rimsulfuron (3).
Figure 4. Hydrolysis at 30 °C of flazasulfuron (1) as a function of pH.
Rate constant k (day-1) (b) and reaction rate ratios k2/k1 (0) were
established from the maximum measured for intermediate urea 5 (first-
order kinetic hypothesis).
the sulfonylurea herbicides (10, 13, 14). The yield for the
aminopyrimidine 2 formation is a little lower than the carbamate
(Figure 3), certainly due to analytical losses.
Concomitant rearrangement reaction remains minor and leads
to urea 5, the conversion of which into amine 6 is not observed.
No concomitant hydrolysis reaction is observed as shown by
the absence of sulfonamide in such conditions.
Hydrolysis. Flazasulfuron is relatively unstable in aqueous
solution at 30 °C. As for all sulfonylureas, there is a relationship
between the degradation rate and the pH. This effect is illustrated
in Figure 4. Under the same pH conditions, flazasulfuron
hydrolysis is faster than nicosulfuron hydrolysis (10), but
Degradation on Various Minerals. The minerals used in
this study are selected to represent a wide range of surface
properties. The sulfonylurea is deposited, either by the dry
method (thorough crushing of the powder mixture) or by the
liquid method (herbicide dissolution in acetone, then evapora-
tion to dryness of the mineral suspension). The liquid method
gives a homogeneous layer of herbicide on the mineral surface
that promoted its adsorption but reduces its extraction rate and
the half-life of the herbicide. Finally, this method gives an
acceptable correlation with pseudo-first-order kinetics. All of
the results are shown in Table 3. Calcium bentonite (Ca2+
remains completely inactive, as already observed for nicosul-
)

7720 J. Agric. Food Chem., Vol. 51, No. 26, 2003
Bertrand et al.
Table 3. Degradation of Flazasulfuron after Deposition on Various Dry Minerals at 30 °C
dry deposition method
liquid deposition method
flazasulfuron (1)
flazasulfuron (1)
selectivity
re/hya
selectivity
re/hya
initial
recovery (%)
half-life
(days)
initial
recovery (%)
half-life
(days)
k2/k1b
k2/k1b
c
c
calcium bentonite
kaolinite
silica
alumina
montmorillonite
100
90
97
97
86
∞
97
85
81
93
73
∞
60b
9.7
3.6
3.5
100/0
57/43
100/0
45
0.25
0.15
2.4
10.7
0.43
1.3
100/0
45/55
100/0
3
0.25
0.01
a Rearrangement/hydrolysis. b Approximate value. c Inactive mineral.
presence of kaolinite and alumina. However, hydrolysis and
rearrangement have the same reaction rates in the presence of
silica.
All of these results lead us to envisage numerous degradation
pathways in soils and consequently the eventual presence of
several transformation products.
As the active function of these herbicides is known to be the
sulfonylurea bridge, its seems unlikely that the degradation
products identified in this study are able to present any
phytotoxic activity.
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Figure 6. Degradation of flazasulfuron after liquid deposition on silica
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Conclusion. The alcoholysis reaction gives high yields of
the corresponding sulfonylcarbamate, as already observed for
another pyridylsulfonylurea, nicosulfuron (10). This reaction
previously described for arylsulfonylurea (13, 14) appears to
be a characteristic of all sulfonylurea herbicides.
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with first-order kinetics. The reaction rate reaches a minimum
at pH 6-9 and increases in acidic or mainly in alkaline
conditions. Hydrolysis of the sulfonylurea bridge is a minor
pathway, whereas the rearrangement into urea after elimina-
tion of SO2 is prevalent. The urea 5 can generally give the
corresponding more stable amine. This uncommon hydrolysis
pathway (15) has already been described for rimsulfuron (3,
4).
This hydrolysis and the urea transformation into amine were
pH dependent. Under acidic conditions the urea is the major
product (compounds 2, 3, and 6 appear slightly), whereas
under alkaline conditions the more stable amine 6 is largely
prevalent.
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Flazasulfuron
J. Agric. Food Chem., Vol. 51, No. 26, 2003 7721
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Received for review July 18, 2003. Revised manuscript received
September 25, 2003. Accepted October 1, 2003.
JF0347970