Reactivity of the insecticide fenitrothion toward O and N nucleophiles

Article abstract of DOI:10.1021/jo100541y

The reactivity of Fenitrothion (1) toward several O- and N-based nucleophiles, including ambident and α-nucleophiles, was investigated in basic media at 25 °C in water containing 2% 1,4-dioxane. In the reactions with HO^- and HOO^- quantitative formation of 3-methyl-4-nitrophenoxide (2) was observed indicating a S_N2(P) pathway. In the reactions with NH₂OH, NH₂O^-, and BuNH₂, demethylfenitrothion (4) was formed along with 2, indicating competition between the S_N2(P) and S_N2(C) pathways; no evidence of a S_NAr pathway was observed in any case. The observed rate constants were dissected into the values corresponding to the S_N2(P) and S_N2(C) pathways. The yield of 4 depends on the nucleophile and on the pH of the reaction, being the main product in the case of BuNH₂. With HOO^-, NH₂OH, and NH ₂O^- a significant α-effect was observed, confirming the participation of the nucleophile in the rate-limiting step of the reaction.

Full text of DOI:10.1021/jo100541y

pubs.acs.org/joc
Reactivity of the Insecticide Fenitrothion toward O and N Nucleophiles
ꢀ
Natalia M. Rougier, Raquel V. Vico, Rita H. de Rossi, and Elba I. Bujan*
´
Instituto de Investigaciones en Fisicoquımica de Cordoba (INFIQC), Departamento de Quımica Organica,
Facultad de Ciencias Quımicas, Universidad Nacional de Cordoba, Medina Allende y Haya de la Torre,
ꢀ
´
ꢀ
´
ꢀ
ꢀ
X5000HUA, Cordoba, Argentina
elba@fcq.unc.edu.ar
Received March 22, 2010
The reactivity of Fenitrothion (1) toward several O- and N-based nucleophiles, including ambident
and R-nucleophiles, was investigated in basic media at 25 °C in water containing 2% 1,4-dioxane. In
the reactions with HO- and HOO- quantitative formation of 3-methyl-4-nitrophenoxide (2) was
observed indicating a SN2(P) pathway. In the reactions with NH2OH, NH2O-, and BuNH2,
demethylfenitrothion (4) was formed along with 2, indicating competition between the SN2(P) and
SN2(C) pathways; no evidence of a SNAr pathway was observed in any case. The observed rate
constants were dissected into the values corresponding to the SN2(P) and SN2(C) pathways. The yield
of 4 depends on the nucleophile and on the pH of the reaction, being the main product in the case of
BuNH2. With HOO-, NH2OH, and NH2O- a significant R-effect was observed, confirming the
participation of the nucleophile in the rate-limiting step of the reaction.
Introduction
as well as chemical treatments based on the use of strong
oxidants or nucleophiles are among the methods used for its
destruction.5,7-10 So, detailed knowledge of the reactivity of
these compounds with nucleophiles and oxidants is impor-
tant for physical organic chemistry as well as for environ-
mental chemistry. We present here our results on the
reactivity and regiochemistry of Fenitrothion (1) [O,O-di-
methyl O-(3-methyl-4-nitrophenyl) phosphorothioate] with
several O and N nucleophiles including some R-nucleophiles.
R-Nucleophiles are nucleophiles which bear nonbonding
pairs of electrons at the position R to the nucleophilic center
and whose reactivity is greater than would be expected on the
basis of the pKa values.11 They are of special interest because
their high reactivity toward phosphorus makes them re-
agents of choice for the destruction of nerve gases and other
Organophosphorus compounds such as esters and thioe-
sters of phosphoric and thiophosphoric acids are extensively
used throughout the world as insecticides and have in many
cases replaced organochlorine pesticides.1 The use of these
toxic pesticides has resulted in contamination of soils and
groundwater. Natural degradation of organophosphorus
pesticides occurs by homogeneous and heterogeneous
hydrolysis,1-3 oxidation,4 photolysis,5 and biodegradation,6
whereas thermic, enzymatic, or photochemical degradation
(1) Liu, B.; McConnell, L. L.; Torrents, A. Chemosphere 2001, 44, 1315–
1323.
(2) Macalady, D. L.; Wolfe, N. L. J. Agric. Food Chem. 1983, 31, 1139–
1147.
(3) Maguire, R. J.; Hale, E. J. J. Agric. Food Chem. 1980, 28, 372–378.
(4) Wolfe, N. L.; Zepp, R. G.; Gordon, J. A.; Baughman, G. L.; Cline,
D. M. Environ. Sci. Technol. 1977, 11, 88–93.
(8) Cristau, H. J.; Torreilles, E.; Ginieys, J. F. J. Chem. Soc., Perkin
Trans. 2 1991, 13–16.
(9) Bunton, C. A.; Gillitt, N. D.; Kumar, A. J. Phys. Org. Chem. 1997, 10,
ꢁ
(5) Bavcon Kralj, M.; Franco, M.; Trebse, P. Chemosphere 2007, 67, 99–
107.
(6) Wanner, O.; Egli, T.; Fleischman, T.; Lanz, K.; Reichert, P.;
Schwarzenbach, R. P. Environ. Sci. Technol. 1989, 23, 1232–1242.
(7) (a) Yang, Y.-C. Acc. Chem. Res. 1999, 32, 109–115. (b) Yang, Y.-C.;
Baker, J. A.; Ward, J. R. Chem. Rev. 1992, 92, 1729–1743.
221–228.
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(11) Tarkka, R. M.; Buncel, E. J. Am. Chem. Soc. 1995, 117, 1503–
1507.
DOI: 10.1021/jo100541y
r
Published on Web 04/27/2010
J. Org. Chem. 2010, 75, 3427–3436 3427
2010 American Chemical Society

Rougier et al.
JOCArticle
organophosphorus poisons.12 The plough layer of arable
soils may contain >3000 kg N ha-1; most of this is composed
of a continuum of complex organic forms. The total soluble
N in soils is composed of mineral N and soluble organic N
(SON). Studies with fresh soil have indicated that as much
SON as mineral N can exist in soil under agricultural
cropping systems. In agricultural soils, free amino acids
and amino sugars account for <5% of SON, heterocyclic
N bases up to 15%, and amino N in peptides and proteins for
35-57%.13 So, it is important to study the reactivity of
organophosphorus insecticides with N nucleophiles such as
amines because the presence of organic N compounds may
affect the effectiveness of the insecticides and their fate in
soils.
Fenitrothion (1) is a broad spectrum insecticide and
acaricide used for pest control in rice, vegetables, wheat,
cereals, and cotton;14 it is also considered by the World
Health Organization (WHO) effective for the control of the
vector of malaria.15 It has low adult mammalian toxicity but
it is a known endocrine disrupting chemical.16
7.7-11.8 proceeds through SN2(P) while in the presence of
cetyltrimethylammonium surfactants SN2(C) was also
observed.25
In the present work we studied the reactivity and regio-
chemistry of 1 with HO-, HOO-, NH2OH, NH2NH2, and
n-butylamine (BuNH2) in aqueous basic solutions. Hydro-
gen peroxide has been used for decontamination of chemical
warfare agents,7 and in advanced oxidation processes for
environmental remediation, such as Fenton and photo-
Fenton.26 This oxidant has the advantage over others that
it is environmentally friendly leading in some cases to the
total mineralization of the organic pollutant.26a Hydroxyla-
mine is an ambident R-nucleophile, readily alkylated on
nitrogen but often acylated and generally phosphorylated
on oxygen, with reaction through oxygen favored for harder
electrophiles.12 In this work, reaction at the P center was the
only pathway observed with the two O nucleophiles HO-
and HOO-, while competition by SN2(C) was found with the
other nucleophiles; no evidence of SNAr was obtained in any
case. An important R-effect was observed with HOO-,
NH2OH, and NH2O-.
Organophosphorus esters and thioesters containing
both alkyl and aryl substituents exhibit three reaction path-
ways for nucleophilic attack: attack at phosphorus, resulting
in P-OAr cleavage (SN2(P)); attack at the aliphatic car-
bon with C-O cleavage (SN2(C)); and attack on the aro-
matic moiety with Ar-O cleavage (SNAr).17-19 These three
pathways were detected in the reactions of different nucleo-
philes with 1. For instance, the hydrolysis of 1 occurs with
C-O cleavage at pH <8,20 and with P-OAr cleavage at
pH >9.3,20-22 Attack on the P center was the only pathway
observed for the reaction of 1 with several phenoxides and
some O R-nucleophiles,22 while competition of the SNAr
pathway was found in the reaction with the N nucleophiles
n-butylamine, ethanolamine, and glycyl ethyl ester.23 On the
other hand, the ethanolysis of 1 with alkali metal alkoxides in
anhydrous ethanol proceeds by nucleophilic attack at both
P and aliphatic carbon centers and a minor SNAr route
(e7%) was also detected.24 The reaction of 1 with a series
of R-nucleophile oximates having pKa values in the range of
Results and Discussion
Hydrolysis Reaction. The hydrolysis of Fenitrothion (1)
was studied under pseudo-first-order conditions in 2%
1,4-dioxane/H2O at 25 °C at several NaOH concentrations
and at constant ionic strength (I=1 M (NaCl)). The UV-vis
spectrum of the product matches that of 3-methyl-4-nitro-
phenoxide (2) at the expected concentration; therefore, as for
the reaction studied in 2% acetonitrile (ACN)/H2O,21 the
only reaction taking place is P-O bond fission, (eq 1), as was
previously demonstrated at pH >8.20 Further evidence was
obtained by following the degradation of a 9.60 ꢀ 10-3
M
solution of 1 in 1,4-dioxane/D2O/H2O (5:47.5:47.5) in the
presence of 1.40 M NaOH at room temperature by 31P NMR
over a period of 9 days. The initial reading showed a single
peak at 65.19 ppm, corresponding to 1;24,25 as the reaction
proceeded, another peak was observed at 58.13 ppm corre-
sponding to O,O-dimethylphosphorothioate (3);24,25,27 this
was the only peak remaining after all the Fenitrothion was
consumed (Figure 1).28
~
(12) Kirby, A. J.; Davies, J. E.; Brandao, T. A. S.; da Silva, P. F.; Rocha,
W. R.; Nome, F. J. Am. Chem. Soc. 2006, 128, 12374–12375.
(13) Murphy, D. V.; Macdonald, A. J.; Stockdale, E. A.; Goulding,
K. W. T.; Fortune, S.; Gaunt, J. L.; Poulton, P. R.; Wakefield, J. A.;
Webster, C. P.; Wilmer, W. S. Biol. Fertil. Soils 2000, 30, 374–387.
(14) (a) http://pmep.cce.cornell.edu/profiles/extoxnet/dienochlor-glyphosate/
fenitrothion-ext.html. (b) http://www.who.int/whopes/quality/Fenitrothion_specs_
eval_WHO_Jan_2010_ok.pdf. Accessed February 27, 2010.
(15) (a) http://www.who.int/malaria/docs/MCT_workingpaper.pdf. Malaria
Control Today. Current WHO Recommendations, Working Document, March
2005. Roll Back Malaria Department. World Health Organization, Geneva,
The value of the second-orderrateconstant for this reaction
was calculated from the slope of the linear plot of kobs vs HO-
(Figure S1, Supporting Information) as (2.50 ( 0.08) ꢀ 10-3
M-1 s-1. This value is slightly higher than that determined
before in 2%ACN/H2O ((2.0 ( 0.1) ꢀ 10-3 M-1 s-1),21 and is
in good agreement with other reported values.3,20,22
ꢀ
Switzerland, 2005. Accessed February 27, 2010. (b) Najera, J. A.; Koutznetsov,
R. L.; Delacollette, C. http://www.who.int/malaria/docs/najera_epidemics/naj8.
htm. Accessed February 27, 2010.
(16) Chanda, A.; Khetan, S. K.; Banerjee, D.; Ghosh, A.; Collins, T. J.
J. Am. Chem. Soc. 2006, 128, 12058–12059.
(17) Cox, J. R.; Ramsay, O. B. Chem. Rev. 1964, 64, 317–352.
(18) Wu, T.; Jans, U. Environ. Sci. Technol. 2006, 40, 784–790.
(19) (a) Kirby, A. J.; Younas, M. J. Chem. Soc. B 1970, 1165–1172.
(b) Khan, S. A.; Kirby, A. J. J. Chem. Soc. B 1970, 1172–1182.
(20) Greenhalgh, R.; Dhawan, K. L.; Weinberger, P. J. Agric. Food
Chem. 1980, 28, 102–105.
(25) Han, X.; Balakrishnan, V. K.; vanLoon, G. W.; Buncel, E. Langmuir
2006, 22, 9009–9017.
(26) (a) Walling, C. Acc. Chem. Res. 1975, 8, 125–131. (b) Chan, K. H.;
Chu, W. Chemosphere 2003, 51, 305–311.
ꢀ
(21) Vico, R. V.; Bujan, E. I.; de Rossi, R. H. J. Phys. Org. Chem. 2002,
15, 858–862.
ꢀ
(27) Vico, R. V.; de Rossi, R. H.; Bujan, E. I. J. Phys. Org. Chem. 2009,
(22) Omakor, J. E.; Onyido, I.; vanLoon, G. W.; Buncel, E. J. Chem. Soc.,
Perkin Trans. 2 2001, 324–330.
(23) Onyido, I.; Omakor, J. E.; vanLoon, G. W.; Buncel, E. Arkivoc,
2001, Part (xii), 134-152.
(24) Balakrishnan, V. K.; Dust, J. M.; vanLoon, G. W.; Buncel, E.
Can. J. Chem. 2001, 79, 157–173.
22, 691–702.
(28) The conversion of 1 into products is much slower than predicted by
the observed rate constant in dilute solutions. This is due to the fact that
under the conditions of the NMR experiments not all the reactant is in
solution. Besides, at this high concentration it is likely that the hydrophobic
Fenitrothion is aggregated.
3428 J. Org. Chem. Vol. 75, No. 10, 2010

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FIGURE 1. 31P NMR spectrum in 1,4-dioxane/D2O/H2O (5:47.5:47.5) at room temperature of 1 (9.60 ꢀ 10-3 M) in the presence of 1.40 M
NaOH at different reaction times: (A) 0, (B) 5, (C) 48, and (D) 213 h.
Reaction with H2O2. The reaction of 1 with H2O2 was
studied in a pH range from 9.00 to 12.40 in 2% 1,4-dioxane/
H2O at 25 °C and I = 1.00 M (NaCl); buffers of H2O2 or
0.005 M Borax were used to control the pH of the solutions.
The reaction was followed by measuring the appearance of 2
at 397 nm. Quantitative formation of 2 indicates that the only
reaction taking place is SN2(P) as was observed in the
hydrolysis reaction. As was previously proposed with other
substrates,27,29,30 we suggest that the reaction taking place is
that shown in eq 2. Evolution of bubbles was observed during
the kinetic measurements indicating the formation O2.
given by eq 3. The plots of kobs vs [H2O2]0 according to eq 3 at
each pH are linear (Figure S2, SI) and from the slope of these
plots the values of the second-order rate constants (k[H O ]
)
2
2 0
at each pH were calculated (Table S3, SI). The intercepts of
the plots of Figure S2 (SI) are indistinguishable from zero,
within experimental error, indicating that H2O and HO- ion
do not compete with H2O2. The expression for k[H O ] is
2
2 0
given by eq 6. It can be seen in Table S3 (SI) that the values of
k[H O ] obtained increase with pH.
2
2 0
-
-
-
-
kobs ¼ kH O þ kHO ½HO ꢁ þ kH O ½H2O2ꢁ þ kHOO ½HOO
ꢁ
2
2
2
-
-
¼ kH O þ kHO ½HO ꢁ þ ðkH O XH O
2
2
2
2
2
-
-
þ kHOO XHOO Þ½H2O2ꢁ0
ð3Þ
ð4Þ
½H2O2ꢁ
XH O
¼
¼
Two sets of experiments were conducted in order to
determine values of kobs for this reaction. In one of them
we worked at different pH values varying the analytical
concentration of H2O2 ([H2O2]0) at each pH; the results are
shown in Table S1 (Supporting Information). Another set of
experiments was conducted at constant [H2O2]0 = 4.76 ꢀ
10-3 M over a pH range from 9.00 to 12.38 and the results are
collected in Table S2 (SI).
2
2
½H2O2ꢁ0
½HOO-
ꢁ
-
XHOO
ð5Þ
½H2O2ꢁ0
-
-
k
¼ kH O XH O þ kHOO XHOO
½H2O2ꢁ0
2
2
2
2
The nucleophiles present in the reaction solutions were
H2O, HO-, H2O2, and HOO-, so the expression for kobs is
-
-
¼ kH O þ ðkHOO - kH O ÞXHOO
ð6Þ
2
2
2
2
From a plot of k[H O ] vs XHOO- according to eq 6, the
2
2 0
second-order rate constant for H2O2 and HOO- can be
calculated from the intercept at XHOO- = 0 and 1, respec-
tively (Figure S3, SI). The intercept at XHOO- = 0 is zero,
(29) Epstein, J.; Demek, M. M.; Rosenblatt, D. H. J. Org. Chem. 1956, 21,
796–797.
(30) Domingos, J. B.; Longhinotti, E.; Brandao, T. A. S.; Santos, L. S.;
Eberlin, M. N.; Bunton, C. A.; Nome, F. J. Org. Chem. 2004, 69, 7898–7905.
J. Org. Chem. Vol. 75, No. 10, 2010 3429

Rougier et al.
JOCArticle
(NaCl) in a pH range from 9.00 to 12.00; buffers of NH2OH
or 0.005 M Borax were used to control the pH of the solu-
tions. In this pH range the predominant form of the nucleo-
phile is neutral NH2OH (pKHa NOH = 6.19, pKHa NOH
=
3
2
13.74).34 The reaction was followed by measuring the
increase in absorbance at 397 nm corresponding to the
formation of 2, the product of attack at the phosphorus
center. It was noted that the absorbance at infinite time of the
aryloxide product (Ainf) was lower than that predicted when
the reaction occurred solely via SN2(P). The amount of 2
formed, calculated from Ainf, varied from 62% at pH 9 to
93% at pH 12. Besides, the spectra taken at different reaction
times at pH 9.00 are different from those taken at pH 12
(Figure S5, SI).
The deviation of Ainf values from the expected value
suggested the competition of another reaction pathway: a
SN2 process involving nucleophilic attack at the aliphatic
methoxy atom and/or a SNAr process in which the nucleo-
phile attacks the C-1 position of the aromatic moiety. To
fully identify the reaction products, 31P NMR and GC-MS
experiments were conducted.
The degradation of a 0.02 M solution of 1 with 0.50 M
NH2OH at pH 10.00 (buffer Borax 0.005 M) in 2% 1,4-
dioxane/D2O at room temperature was followed by 31P
NMR over 120 h. The initial reading showed a single peak
at 65.14 ppm, corresponding to the chemical shift of 1
(Figure 3). After 6 h of reaction the signal corresponding
to 1 decreased while two peaks were observed: one at 58.33
ppm and another at 53.53 ppm. After 120 h no signal
corresponding to 1 was observed and only the peaks at
58.33 and 53.53 ppm remained. The signal at 58.33 ppm
was attributed to 3 and that at 53.53 ppm to demethylfeni-
trothion (4), by comparison with reported values.24,25
By GC-MS analysis of a reaction conducted at a higher
concentration of 1 (see the Experimental Section and the
Supporting Information) the presence of 2 was detected
in the ether extract of the reaction mixture (Figure S6, SI).
With the experimental setup employed, the aqueous extract
of this reaction showed no signals by GC, but the 31P NMR
spectrum showed the presence of 4 (Figure S7, SI). No
evidence of a SNAr pathway was observed.
In Scheme 1 the reactions that lead to the formation of 2, 3,
and 4 are depicted. The formation of 4 is attributed to the
reaction of NH2OH at the aliphatic C atom by a SN2(C)
pathway. Formation of 3 can occur by two competitive
SN2(P) pathways: hydrolysis of 1 and attack of NH2OH on
P that leads to an O-phosphorylated derivative that decom-
poses in the presence of an excess of hydroxylamine. It was
previously proposed that in the reaction of NH2OH with
bis(2,4-dinitrophenyl) phosphate the initial product of at-
tack of the P center by the O of the nucleophile is converted to
2,4-dinitrophenyl phosphate by an excess of NH2OH liber-
ating N2 and NH3.34 Besides, it was demonstrated that the
reaction of NH2OH with 2,4-dinitrophenyl diethyl phos-
phate gives initially an O-phosphorylated derivative that
decomposes in the presence of an excess of NH2OH.35
Values of kobs for the reaction of 1 with NH2OH were
obtained at different pH values as a function of the analytical
FIGURE 2. Plot of kobs vs [HOO-] for the reaction of 1 with
H2O2 at a pH range from 9.00 to 12.38 at 25 °C. Solvent contains
2% 1,4-dioxane; ionic strength I = 1 M (NaCl); [1]0 = 4.76 ꢀ 10-5
to 6.10 ꢀ 10-5 M. Data from Tables S1 and S2, SI.
within experimental error; therefore H2O2 does not compete
as a nucleophile with HOO-. The value of kHOO- = 1.11 (
0.07 M-1 s-1 was obtained from the intercept at XHOO- = 1.
With the data presented in Table S2 (SI) obtained at
constant [H2O2]0 and varying the pH we calculated kHOO-
=
1.08 ( 0.05 M-1 s-1 from the slope of the straight line of
kobs/[H2O2]0 vs XHOO- (Figure S4, SI), in good agreement
with the value obtained above that corresponds to another
set of experiments. By plotting together all the values of kobs
obtained in the two series of experiments against [HOO-]
(Figure 2), kHOO-=1.25 ( 0.03 M-1 s-1 was calculated.
As the pKa of H2O2 is 11.6,22 in the pH range used for this
study, both H2O2 and HOO- are present in the reaction
solution. The results indicate that only the HOO- ion acts as
a nucleophile toward 1. Besides, this anion is 500 times more
reactive than HO- in spite of the fact that it is less basic than
the latter (pKaH O = 15.74);31 this could be attributed to the
2
fact that HOO- is an R-nucleophile.
Several studies have previously demonstrated the R-effect
in nucleophilic attack at the P center.11,17,22,27,29,30,32,33 An
R-effect of 210 for the HOO-/ HO- pair was reported before
for the reaction with 1,22 this is less than half the value that
we calculated and the difference arises from differences in the
values of kHOO- reported there. In spite of the fact that the
magnitude of the R-effect is substrate-dependent,22 we have
calculated an R-effect of 465 for the same pair of nucleophiles
for the reaction with Chlorpyrifos-methyl.27
Reaction with NH2OH. The reaction of 1 with NH2OH
was studied in 2% 1,4-dioxane/H2O at 25 °C and I = 1.00 M
(31) Smith, M. B.; March, J. Advanced Organic Chemistry, 5th ed.; John
Wiley & Sons: New York, 2001; p 330.
(32) Herschlag, D.; Jencks, W. P. J. Am. Chem. Soc. 1990, 112, 1951–
1956.
(33) Kirby, A. J.; Manfredi, A. M.; Souza, B. S.; Medeiros, M.; Priebe,
(34) Domingos, J. B.; Longinotti, E.; Bunton, C. A.; Nome, F. J. Org.
Chem. 2003, 68, 7051–7058.
(35) Kirby, A. J.; Souza, B. S.; Medeiros, M.; Priebe, J. P.; Manfredi,
A. M.; Nome, F. Chem. Commun. 2008, 4428–4429.
~
J. P.; Brandao, T. A. S.; Nome, F. Arkivoc 2009, Part (iii), 28-38.
3430 J. Org. Chem. Vol. 75, No. 10, 2010

Rougier et al.
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FIGURE 3. 31P NMR spectrum in 2% 1,4-dioxane/D2O at room temperature of 1 (0.02 M) in the presence of 0.50 M NH2OH at pH 10.00 at
different reaction times: (A) 0, (B) 6, and (C) 120 h.
SCHEME 1. Reaction Pathways for the Reaction of Fenitrothion with NH2OH
concentration of the nucleophile ([NH2OH]0) (Table S4, SI).
Combining eqs 7 and 8, the observed rate constants for the
attack at P (koPbs) and at C (koCbs) can be calculated.
[NH2OH]0 at each pH, we calculated from the slope of the
linear plots the second-order rate constant for the attack of
NH2OH at P and at the aliphatic C according to eqs 9 and 10
(Figures 4 and 5, respectively, Table S5, SI). In all cases, the
intercepts of the plots are indistinguishable from zero, within
experimental error, indicating that H2O and HO-, the other
nucleophiles present in the reaction media, do not compete
with NH2OH. From the second-order rate constant for the
hydrolysis reaction, we can calculate that the contribution of
HO- to the attack over P will be 2.5 ꢀ 10-8 s-1 at pH 9 and
2.5 ꢀ 10-5 s-1 at pH 12. Thus, the term corresponding to the
hydrolysis reaction may be neglected in eq 9.
kobs ¼ kPobs þ kCobs
ð7Þ
ð8Þ
kPobs
kCobs
½2ꢁ
½4ꢁ
¼
The concentration of 3-methyl-4-nitrophenoxide ion (2)
was determined directly from spectrophotometric measure-
ments, while the concentration of 4 was determined by
subtracting [2]inf from [1]0.
koPbs ¼ kPHO½HO- ꢁ þ kPNH OH½NH2OHꢁ þ kP
½NH2O-
ꢁ
It can be seen from the data in Table S4 (SI) that at
constant pH and variable NH2OH concentration, the yield
of products is constant and that the amount of attack at P
increases from 62% to 93% when the pH changes from 9 to
12. By plotting the values of kPobs and koCbs as a function of
NH2O-
2
¼ kPHO½HO- ꢁ þ ðkNP H OHXNH OH
2
2
P
-
-
þ kNH O XHH O Þ½NH2OHꢁ
ð9Þ
2
0
2
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Rougier et al.
JOCArticle
FIGURE 5. Plot of kCobs vs [NH2OH]0 for the reaction of Feni-
trothion (1) with NH2OH at 25 °C at different pH values. Solvent
contains 2% 1,4-dioxane; ionic strength, I = 1 M (NaCl); [1]0 =
5.88 ꢀ 10-5 to 6.60 ꢀ 10-5 M.
TABLE 1. Second-Order Rate Constants for the SN2(P) and SN2(C)
Pathways for the Reaction of Fenitrothion (1) with NH2OH at 25 °Ca
kNP H OH (M-1 s-1
)
(0.88 ( 0.01) ꢀ 10-4
kNPH O-/kPNH OH 5682
2
2
2
kNPH O- (M-1 s-1
)
0.500 ( 0.006
kNCH O-/kCNH OH
647
1.6
2
2
2
kNCH OH (M-1 s-1
)
(0.536 ( 0.008) ꢀ 10-4 kNP H OH/kNCH OH
2
2
2
kNCH O- (M-1 s-1
)
(3.47 ( 0.07) ꢀ 10-2
kNPH O-/kNCH O-
14.4
2
2
2
aSolvent contains 2% 1,4-dioxane; ionic strength, I = 1 M (NaCl);
[1]0 = 5.88 ꢀ 10-5 to 6.60 ꢀ 10-5 M.
kP[NH OH] and k[CNH OH] vs XNH O- were constructed
(Figures S8 and S9, respectively, SI) and the values obtained
2
0
2
0
2
from the intercept of the plots at XNH O- = 0 and 1 are
collected in Table S6 (SI).
2
The reaction of 1 with NH2OH was also evaluated from
another set of experiments. Several reactions were conducted
at different pH values and constant [NH2OH]0 = 0.40 M and
the results are collected in Table S7 (SI). From plots of
FIGURE 4. Plot of kPobs vs [NH2OH]0 for the reaction of Feni-
trothion (1) with NH2OH at 25 °C at different pH values. Solvent
contains 2% 1,4-dioxane; ionic strength, I = 1 M (NaCl); [1]0 =
5.88 ꢀ 10-5 to 6.60 ꢀ 10-5 M.
kPobs/[NH2OH]0 and koCbs/[NH2OH]0 vs XNH O- (Figures S10
2
and S11, respectively, SI), values for the second-order rate
constants for attack of neutral and anionic nucleophile over
P and aliphatic C atom were calculated and the results are
shown in Table S6 (SI).
kCobs ¼ kCNH OH½NH2OHꢁ þ kC
½NH2O-
ꢁ
NH2O-
It can be seen in Table S6 (SI) that the values calculated
for kNPH O- and kNCH O- from the two sets of experiments
2
¼ ðkCNH OHXNH OH þ kC
XNH O Þ½NH2OHꢁ
2
2
-
NH2O-
0
are in good agreement. So, we calculate kNPH O- = 0.500 (
2
2
2
2
0.006 M-1 s-1 and kCNH O- = (3.47 ( 0.07) ꢀ 10-2 M-1 s-1 as
ð10Þ
2
the mean value of those reported in Table S6 (SI).
On the other hand, the intercept of the plots of Figures S8
and S10 (SI) at XNH O- = 0 that gives the second-order
½NH2OHꢁ
XNH OH
¼
¼
ð11Þ
2
½NH2OHꢁ0
2
rate constant kPNH OH is zero, within experimental error,
½NH2O-
ꢁ
2
although the intercepts at XNH O- =1 that give the values
-
XNH O
ð12Þ
2
2
of kCNH OH are in good agreement. To obtain better values for
½NH2OHꢁ0
2
kNP H OH and kNCH OH we used the experiments conducted at
pH 9.00 and variable [NH2OH]0 (Table S4, SI), because at
pH 9.00 XNH O- is negligible (Table S5, SI). In Table 1 are
2
2
To calculate the second-order rate constants for the
neutral and anionic forms of the nucleophile, plots of
2
3432 J. Org. Chem. Vol. 75, No. 10, 2010

Rougier et al.
JOCArticle
FIGURE 6. 31P NMR spectrum in 1,4-dioxane/D2O/H2O (5:9.5:85.5) at room temperature of 1 (3.99 ꢀ 10-3 M) in the presence of 0.20 M
BuNH2 at pH 10.05 at different reaction times: (A) 15 min, (B) 7 h, (C) 24 h, and (D) 70 h.
collected the values of the second-order rate constants for the
neutral and anionic nucleophile reacting by the SN2(P) and
SN2(C) pathways along with their relative reactivity.
followed by measuring the appearance of 2 at 397 nm. As was
observed in the reaction with NH2OH, the absorbance at
infinite time at the wavelength maximum of the aryloxide
product (Ainf) was lower than that predicted if the reaction
occurred solely via SN2(P). The yield of 2 increases with pH
and decreases with [BuNH2] at constant pH, varying from
6% at pH 10.00 to 25% at pH 11.50.
To identify the reaction products, the degradation of a
3.99 ꢀ 10-3 M solution of 1 with 0.20 M BuNH2 at pH 10.05
in 1,4-dioxane/D2O/H2O (5:9.5:85.5) at room temperature
was followed by 31P NMR over a period of 70 h. The initial
spectrum showed a single peak at 65.28 ppm, corresponding
to 1. After 7 h of reaction another signal was observed at
53.28 ppm corresponding to 4; this signal increases with
reaction time while that of 1 decreases; at 70 h only the signal
of 4 is observed (Figure 6). No signal corresponding to 3 was
observed; this compound may be formed by hydrolysis of 1
(eq 1) or by SNAr. Considering that in the reaction with
BuNH2 at this pH the yield of 2 is less than 6%, it is not
unexpected that there is an absence of the signal correspond-
ing to the formation of 3 or other signal corresponding to a
product formed by the attack of BuNH2 at P.
It can be seen from the data in Table 1 that NH2O- is more
than 5600 times more reactive than NH2OH for the attack at
the phosphorus center, whereas for the reaction at the
aliphatic carbon atom, the anion is 600 times more reactive
than its neutral form. This difference in reactivity of the
anionic and neutral hydroxylamine is much higher than that
observed for bis(2,4-dinitrophenyl) phosphate, i.e. 103.34
Other authors reported ratios of 1900 and 3700 for diethyl
4-nitrophenyl phosphate and ethyl 4-nitrophenyl phosphate,
respectively, and 26 000 and 200 000 for 4-nitrophenyl acet-
ate and 4-nitrophenyl dimethylcarbamate, respectively.36
They have pointed out that hydroxylamine is the only
compound that in aqueous solution gives rise to two reactive
O-nucleophilic species, NH2OH and NH2O-, whose basi-
cities differ very strongly, only comparable with the differ-
ence in the basicities of oxygen in a neutral water molecule
and hydroxide ion, and that the differences in the kinetic
behavior of NH2OH and NH2O- are also surprising.36 On
the other hand, neutral NH2OH is almost as reactive toward
P as to aliphatic C, whereas NH2O- is 14 times more reactive
toward P than to aliphatic C. For the anionic nucleophile the
reaction with P is predominant.
On the other hand, when the degradation of 1 with BuNH2
was followed at pH 11.84 by 31P NMR, the presence of 3 was
evidenced after 60 min of reaction (Figure S12, SI).
Reaction with BuNH2. The reaction of 1 with BuNH2 was
studied in a pH range from 10.00 to 11.50 in 2% 1,4-dioxane/
H2O at 25 °C and I = 1.00 M (NaCl); buffers of BuNH2 were
used to control the pH of the solutions. The reaction was
By analysis of a reaction of 1 at higher concentration with
BuNH2 at pH 10.00 (see the SI) the presence of 2 was
confirmed by tlc and formation of 4 was evidenced by 31P
NMR and UV-vis spectrum. The presence of butylmethy-
lamine, which arises from the attack of BuNH2 at the
(36) Simanenko, Yu. S.; Popov, A. F.; Prokop’eva, T. M.; Karpichev,
E. A.; Savelova, V. A.; Suprun, I. P.; Bunton, C. A. Russ. J. Org. Chem. 2002,
38, 1286–1298.
1
aliphatic C atom, was detected by H NMR in a reaction
conducted with [1]0 = [BuNH2] free base (Figure S13, SI).
J. Org. Chem. Vol. 75, No. 10, 2010 3433

Rougier et al.
JOCArticle
SCHEME 2. Reaction Pathways for the Reaction of Feni-
trothion with BuNH2
The proposed reaction pathways for the reaction of 1 with
BuNH2 are shown in Scheme 2 and include SN2(P) and
SN2(C), as was observed with NH2OH.
Values of kobs for the reaction of 1 with BuNH2 were
obtained at different pH values as a function of the analytical
concentration of the nucleophile ([BuNH2]0) (Table S8, SI).
The observed rate constants were dissected into kPobs and koCbs
according to eqs 7 and 8. The yield of 2 and 4 was calculated
as described before.
The second-order rate constants for the attack of BuNH2
on P and on the aliphatic C atom were calculated from plots
of kPobs and koCbs vs [BuNH2]0 according to eqs 13 and 14
(Figures 7 and 8, respectively) and the results are collected in
Table S9 in the SI.
,
FIGURE 7. Plot of kPobs vs [BuNH2]0 for the reaction of Feni-
trothion (1) with BuNH2 at 25 °C at different pH values. Solvent
contains 2% 1,4-dioxane; ionic strength, I = 1 M (NaCl); [1]0 =
4.80 ꢀ 10-5 to 5.50 ꢀ 10-5 M.
koPbs ¼ kPHO½HO- ꢁ þ kPBuNH ½BuNH2ꢁ
2
¼ kPHO½HO- ꢁ þ kBPuNH XBuNH ½BuNH2ꢁ0
ð13Þ
2
2
kCobs ¼ kCBuNH ½BuNH2ꢁ ¼ kC
XBuNH ½BuNH2ꢁ ð14Þ
2
BuNH2
0
2
½BuNH2ꢁ
XBuNH
¼
ð15Þ
2
½BuNH2ꢁ0
By plotting the intercepts of plots in Figure 7 as a function
of [HO-] (Figure S14, SI) we obtained from its slope a value
of (2.7 ( 0.1) ꢀ 10-3 M-1 s-1 for the second-order rate
constant for the hydrolysis reaction, in very good agreement
with that calculated in the absence of BuNH2 (see above).
To calculate the second-order rate constants for the reaction
of the BuNH2 free base with P and aliphatic C atom, we
plotted kP[BuNH ] and k[CBuNH ] vs XBuNH according to
2
0
2
0
2
eqs 16 and 17 (Figures S15 and S16, respectively, in the SI).
From the intercepts of these plots at XBuNH = 1, the
FIGURE 8. Plot of kCobs vs [BuNH2]0 for the reaction of Feni-
trothion (1) with BuNH2 at 25 °C at different pH values. Solvent
contains 2% 1,4-dioxane; ionic strength, I = 1 M (NaCl); [1]0 =
4.80 ꢀ 10-5 to 5.50 ꢀ 10-5 M.
2
values of kPBuNH = (1.13 ( 0.08) ꢀ 10-5 M-1 s-1 and
2
kCBuNH =(3.16 ( 0.07) ꢀ 10-4 M-1 s-1 were calculated. The
2
ratio kPBuNH /kCBuNH = 0.0358 is 45 times smaller than that
obtained for NH2OH (see Table 1) suggesting that
2
2
1,4-dioxane/H2O at 25 °C and I = 1.00 M (NaCl). The reac-
tion was followed by measuring the appearance of 2 at
397 nm. In all the reactions the infinity absorbance was less
than that calculated for total conversion to 2. To identify the
reaction products, the reaction of 1 with NH2NH2 under
pseudo-first-order conditions at pH 9.015 was followed by
31P NMR (Figure S17, SI). At the end of the reaction in the
31P NMR spectrum was observed only one signal at 53.38
ppm corresponding to product 4; no signal corresponding to
NH2OH is reacting by the oxygen.
kP
P
BuNH2
¼ k
XBuNH
ð16Þ
ð17Þ
2
½BuNH2ꢁ0
kC
¼ kCBuNH
X
BuNH2
2
½BuNH2ꢁ0
Reaction with NH2NH2. The reaction of 1 with NH2NH2
was studied at pH 9.00 (Buffer: Borax 0.005 M) and 12.00
(Buffer: NaOH) with [NH2NH2]0 0.05 and 0.20 M in 2%
3434 J. Org. Chem. Vol. 75, No. 10, 2010

Rougier et al.
JOCArticle
TABLE 2. Kinetic Parameters for the SN2(P) and SN2(C) Pathways for the Reaction of Fenitrothion (1) with Different Nucleophiles
SN2(P)
SN2(C)
nucleophile
pKa
kP (M-1 s-1
)
kP relative
kC (M-1 s-1
)
kC relative
HO-
15.74
13.74
11.60
10.84
6.19
(2.50 ( 0.08) ꢀ 10-3
1
N.R.a
NH2O-
HOO-
BuNH2
NH2OH
H2Ob
0.504 ( 0.009
201.6
500
0.00452
0.0352
(3.52 ( 0.03) ꢀ 10-2
1
1.25 ( 0.05
N.R.a
(1.13 ( 0.08) ꢀ 10-5
(0.88 ( 0.01) ꢀ 10-4
1.24 ꢀ 10-9
(3.16 ( 0.07) ꢀ 10-4
(5.36 ( 0.08) ꢀ 10-5
4.83 ꢀ 10-10
0.00898
0.00152
-1.54
aN.R. = no reaction. bCalculated from ref 20.
product 3 was observed, probably due to low concentration.
So, as observed with the other N- based nucleophiles, com-
petition between SN2(P) and SN2(C) pathways occurs in this
reaction.
In the reactions followed by UV-vis spectrophotometry,
decomposition of 2 was detected. When the UV-vis spectra
of a solution of 2 (4.71 ꢀ 10-5 M) in the presence of 0.20 M
NH2NH2 at pH 9.00 and 12.00 were recorded at different
times, a decrease in the absorbance at 397 nm was observed.
At pH 12.00 the observed rate constant for the decomposi-
tion of 2 was calculated as (4.2 ( 0.3) ꢀ 10-6 s-1. No
attempts to identify the product were made.
The absence of evidence of a SNAr pathway could be
explained by the fact that in 1 there is only one electron-
withdrawing nitro group on the aromatic ring, so it is
unlikely to be sufficiently electron deficient to favor a SNAr
reaction.39 Consequently, little participation of this path-
way, if any, would be expected.
In Table 2 are summarized the second-order rate constants
for the SN2(P) and SN2(C) pathways of the reaction of 1 with
all the nucleophiles studied. The reactivity decreases in
the order HOO- > NH2O- > HO- > NH2OH > BuNH2
for the reaction on the P center, whereas for the reaction on
the aliphatic C it decreases in the order NH2O- > BuNH2 >
NH2OH . HOO-, HO-. The most reactive nucleophile and
the one with the largest R-effect is the peroxide anion HOO-,
which is 2.46 times more reactive than the anion of hydro-
xylamine NH2O- although the latter is over 2 orders of
magnitude more basic.
By fitting the absorbance vs time data of the reaction of 1
with NH2NH2 at pH 12.00 to a biexponential equation,
two rate constants were calculated as k1 = (7.9 ( 0.5) ꢀ
10-5 s-1 and k2 = (4.4 ( 0.7) ꢀ 10-6 s-1 (Figure S18, SI); k2 is
attributed to the decomposition of 2 because it is the same,
within experimental error, as that determined from a solu-
tion of 2 at the same pH. From standard methods37 we
calculated the time at which the maximum value of absorbance
at 397 nm will be reached and the concentration of 2 at that
time; so, we can estimate the yield of 2 as 38%. The observed
rate constant for the consumption of 1, k1, can be dissected
into kPobs and koCbs from which we calculated kPNH NH =1.51ꢀ
With the data in Table 2 for the SN2(P) pathway, we have
€
constructed the Bronsted-type plot shown in Figure 9. The
points for the different nucleophiles fall clearly in two lines:
one line is defined by the R-nucleophiles HOO-, NH2O-,
and NH2OH and the other by HO-, BuNH2, and H2O.
From the slope (least-squares) of the line drawn through the
points for the R-nucleophiles a value for βnuc of 0.55 was
calculated, whereas for the other nucleophiles a value for
βnuc of 0.356 was obtained. These values can be compared
with that reported before for the reaction of the same
substrate with a series of structurally related phenoxides,
namely 0.49; in that case the point corresponding to HO-
falls bellow the line defined by the phenoxides and was
interpreted as a different solvation of the nucleophiles.22
Values of βnuc of 0.30 and 0.61 were reported for the reaction
of O,O-dimethyl-2,4-dinitrophenyl phosphate with oxya-
nion or pyridine nucleophiles, respectively; for the reaction
of O-methyl-2,4-dinitrophenyl phosphate a value of βnuc of
0.30 was informed for both types of nucleophiles, whereas
for R-nucleophiles βnuc = 0.41 was obtained.33 A value of
βnuc = 0.3 for the reaction of bis(2,4-dinitrophenyl) phos-
phate with R-nucleophiles was also reported.30
The fact that the point for NH2OH falls in the line defined
by the other R-nucleophiles may indicate that all of them are
reacting through oxygen, as was proposed before for the
reaction of 2,4-dinitrophenyl ethyl phosphate diester.33 The
same authors proposed that ammonia oxide tautomer
NH3þ-O- is probably the active nucleophile in the reaction
of neutral NH2OH with phosphate triesters.12,35 The fact
that mono- and dimethylation of NH2OH on nitrogen does
not significantly affect rates of initial attack of NHMeOH
2
2
10-4 M-1 s-1 and kCNHNH = 2.47 ꢀ 10-4 M-1 s-1
.
2
2
Reactivity and Regioselectivity of the Reaction of Feni-
trothion with Nucleophiles. The results presented here on the
reaction of Fenitrothion in aqueous basic media with several
O- and N-based nucleophiles indicate that 1 reacts only by a
SN2(P) pathway with the O nucleophiles HO- and HOO-, as
was previously reported.3,20-22 In the reactions with the other
nucleophiles, NH2OH, NH2O-, BuNH2, and NH2NH2, com-
petition between SN2(P) and SN2(C) pathways was observed.
No evidence of a SNAr pathway was obtained in any case.
The behavior of the hard O nucleophiles HO- and HOO-
can be explained by the HSAB theory,38 in which case the
“hard” oxygen nucleophiles react mainly with the “hard” P
electrophilic center. In the case of the N-based nucleophile
BuNH2, the same theory can explain the favored reaction of
this “soft” nucleophile with the “soft” electrophile, the
aliphatic carbon atom.
In the case of the highly reactive R-nucleophile NH2O-,
the main pathway is SN2(P) although competition between
SN2(P) and SN2(C) is observed, whereas NH2OH is almost as
reactive toward P as toward the aliphatic C center.
(37) Espenson, J. H. Chemical Kinetics and Reaction Mechanisms;
McGraw-Hill, Inc.: New York, 1995; Chapter 4.
(38) Ruff, F.; Csizmadia, I. G. Organic Reactions. Equilibria, Kinetics
and Mechanism; Elsevier Science: Amsterdam, The Netherlands, 1994;
Chapter 10.
(39) Terrier, F. Nucleophilic aromatic displacement. The effect of the Nitro
Group; VCH Publisher: New York, 1991.
J. Org. Chem. Vol. 75, No. 10, 2010 3435

Rougier et al.
JOCArticle
Aqueous solutions were prepared with water purified with a
Millipore Milli-Q apparatus. BuNH241 and 1,4-dioxane42 were
purified as described previously. All of the inorganic reagents
were of analytical-reagent grade and were used without further
purification. Hydrogen peroxide solutions were titrated with
KMnO4 solution standardized by sodium oxalate. NH2OH
solutions were prepared from a commercial aqueous 50%
solution potentiometrically titrated in duplicate with HCl.
NH2NH2 solutions were prepared from a commercial sample
and were potentiometrically titrated in duplicate with HCl.
UV-vis spectra were recorded on a double beam or a diode
array spectrophotometer and the change in absorbance during a
kinetic run was measured on the same instruments.
Kinetic Procedures. Reactions were initiated by adding the
substrate dissolved in 1,4-dioxane to a solution containing
all the other constituents. The reaction temperature was 25.0
( 0.1 °C, the ionic strength was 1.0 M and NaCl was used
throughout as compensating electrolyte. The solvent contained
2% 1,4-dioxane. In the reactions with H2O2, NH2OH, and
NH2NH2, water and 1,4-dioxane were degassed and the stock
solution of NaCl was filtered by nylon membranes before the
reaction solutions were prepared. After the pH was adjusted to
the desired value, the solution was sonicated for 5 min and
thermostated to 25 °C before the substrate was added.
All kinetic runs were carried out protected from light, under
pseudo-first-order conditions, with substrate concentrations of
4.76 ꢀ 10-5 to 6.60 ꢀ 10-5 M. The reactions were followed
by measuring the increase in absorbance of the reaction mixture
at 397 nm, the λmax of 2 (ε = 17 641 cm-1 M-1).
FIGURE 9. Plot of log kNP u vs pKa of the nucleophile for the
reaction of Fenitrothion (1) with different nucleophiles in 2% 1,4-
dioxane/H2O at 25 °C.
Product Analysis Experiments. Two types of product analysis
experiments were performed. The first method involved the use
of 31P NMR, in a pseudo-first-order experiment. The 31P NMR
spectra were recorded on a spectrometer operating at 161.97
MHz. Chemical shifts were measured with respect to the ex-
ternal standard of 85% H3PO4 in D2O/H2O (75:25). Spectra
were acquired with a longitudinal relaxation time (D1) of 3 s
with 128 accumulations and proton decoupling. For sample
preparation details see the Supporting Information.
and NMe2OH on bis(2,4-dinitrophenyl) phosphate while
O-methylation blocks this reaction indicates that neutral
NH2OH can be phosphorylated through oxygen.34,40 These
considerations along with the difference in kPNu/kNCu ratios for
BuNH2 and NH2OH found in this study (see above) lead us
to believe that NH2OH is reacting with 1 through the oxygen.
Conclusions
The second method of product analysis consists of isolating
the products from reactions conducted with initial concentra-
tions of 1 > 7 ꢀ 10-3 M and identifying them by standard
methods. For details see the Supporting Information.
Fenitrothion (1) reacts with O- and N-based nucleophiles
through different reaction pathways. With the hard nucleo-
philes HO- and HOO- the reaction occurs only by a SN2(P)
pathway, whereas competition between SN2(P) and SN2(C)
pathways was observed with NH2OH, NH2O-, BuNH2, and
NH2NH2. With BuNH2, SN2(C) is the mayor pathway. No
evidence of SNAr was found in any case.
Acknowledgment. This research was supported in part by
ꢀ
´
ficas y Tecnicas.
Consejo Nacional de Investigaciones Cientı
Argentina (CONICET), Agencia Nacional de Promocion
ꢀ
An important R-effect was observed, indicating the parti-
cipation of the nucleophile in the rate-limiting step of the
bimolecular reaction.
ꢀ
´
fica y Tecnologica (FONCYT), Ministerio de Ciencia
Cientı
y Tecnologı
Ciencia y Tecnologı
ꢀ
a de la Provincia de Cordoba and Secretarıa de
´
´
ꢀ
´
a, Universidad Nacional de Cordoba,
The R-nucleophile HOO- is the most reactive nucleo-
phile of the series studied and is a good candidate for
destroying Fenitrothion since t1/2 in the presence of 1 M
HOO- is 0.55 s.
ꢀ
Argentina. N.M.R. is a Fundacion YPF fellow. R.V.V., R.
H.deR., and E.I.B. are Career Investigators of CONICET.
Supporting Information Available: Tables and plots of the
dependence of the observed rate constants on nucleophile
concentration and on pH, tables and plots of the dependence
of second-order rate constants on pH and on the free base molar
fraction, relevant spectra (UV-vis, 1H and 31P NMR) for some
compounds, and experimental details on product analysis ex-
periments. This material is available free of charge via the
Internet at http://pubs.acs.org.
Experimental Section
Materials. Fenitrothion was isolated from a commercial
sample as described before.21 A commercial sample of 3-methyl-
4-nitrophenol characterized by 1H NMR, GS-MS, and melting
point was used as reference.
~
(40) Domingos, J. B.; Longhinotti, E.; Brandao, T. A. S.; Bunton, C. A.;
Santos, L. S.; Eberlin, M. N.; Nome, F. J. Org. Chem. 2004, 69, 6024–
6033.
(41) de Vargas, E. B.; de Rossi, R. H. J. Org. Chem. 1984, 49, 3978–3983.
(42) de Rossi, R. H.; de Vargas, E. B. J. Am. Chem. Soc. 1981, 103, 1533–
1540.
3436 J. Org. Chem. Vol. 75, No. 10, 2010