QUATERNARY HETEROARENIUM ALDOXIMES AS CATALYSTS FOR CLEAVAGE OF PHOSPHATE ESTERS

Article abstract of DOI:10.1135/cccc19950883

!-Methyl- (Ia - Id) and 1-dodecyl-2-, 3- and 4-hydroxyiminomethylpyridinium salts (Ie - Ih), as well as 1-methyl- (IIa) and 1-dodecyl-3-hydroxyiminomethylpyridazinium salts (IIb, IIc), were synthesized as catalysts for hydrolytic cleavage of organophosphates.The activities of the prepared catalysts were evaluated by measuring rate constants of hydrolysis of 4-nitrophenyl diphenyl phosphate (PNPDPP) under conditions of a pseudo-first-order reaction.The observed reactivity of pyridinium aldoximes Ia - Ih towards PNPDPP in neutral or slightly basic aqueous solutions (pH 7.2 and 7.8) depends on the acidity of the hydroxyimino group.The cleavage of PNPDPP is strongly accelerated in solutions of 1-dodecylhydroxyiminomethylpyridinium salts Ie - Ih above their critical micellar concentration (CMC).Considerable effect on the velocity of PNPDPP cleavage was observed when quaternary pyridinium aldoximes Ie - Ih were comicellized with inert cationic tenside hexadecyltrimethylammonium bromide (CTAB). 1-Dodecyl-3-hydroxyiminomethylpyridazinium salts IIb and IIc were unstabel in aqueous solutions under the above-mentioned conditions.

Full text of DOI:10.1135/cccc19950883

Quaternary Heteroarenium Aldoximes
883
QUATERNARY HETEROARENIUM ALDOXIMES AS CATALYSTS FOR
CLEAVAGE OF PHOSPHATE ESTERS
a
b
a
a
c
Frantisek HAMPL , Jiri MAZAC , Frantisek LISKA , Jiri SROGL , Lubomir KABRT
c
and Miloslav SUCHANEK
a
Department of Organic Chemistry,
Prague Institute of Chemical Technology, 166 28 Prague 6, The Czech Republic
b
Central Laboratories,
Prague Institute of Chemical Technology, 166 28 Prague 6, The Czech Republic
c
Department of Analytical Chemistry,
Prague Institute of Chemical Technology, 166 28 Prague 6, The Czech Republic
Received January 24, 1995
Accepted April 2, 1995
1
-Methyl- (Ia – Id) and 1-dodecyl-2-, 3- and 4-hydroxyiminomethylpyridinium salts (Ie – Ih), as well
as 1-methyl- (IIa) and 1-dodecyl-3-hydroxyiminomethylpyridazinium salts (IIb, IIc), were
synthesized as catalysts for hydrolytic cleavage of organophosphates. The activities of the prepared
catalysts were evaluated by measuring rate constants of hydrolysis of 4-nitrophenyl diphenyl
phosphate (PNPDPP) under conditions of a pseudo-first-order reaction. The observed reactivity of
pyridinium aldoximes Ia – Ih towards PNPDPP in neutral or slightly basic aqueous solutions (pH 7.2
and 7.8) depends on the acidity of the hydroxyimino group. The cleavage of PNPDPP is strongly
accelerated in solutions of 1-dodecylhydroxyiminomethylpyridinium salts Ie – Ih above their critical
micellar concentration (CMC). Considerable effect on the velocity of PNPDPP cleavage was
observed when quaternary pyridinium aldoximes Ie – Ih were comicellized with inert cationic tenside
hexadecyltrimethylammonium bromide (CTAB). 1-Dodecyl-3-hydroxyiminomethylpyridazinium salts
IIb and IIc were unstable in aqueous solutions under the above-mentioned conditions.
A great number of phosphonic and phosphoric acid derivatives react readily with
hydroxy groups, forming relatively stable phosphonates and phosphates. This reaction
is responsible for the extreme toxicity of many organophosphorus compounds (both
neurotoxic chemical weapons as Sarin, Soman, VX, etc., and agrochemicals as
Paraoxon, Parathion etc.) which irreversibly block the serine hydroxy group in
acetylcholinesterase by phosphorylation. The problem of safe and efficient
decontamination of areas affected by these toxic compounds has been under
1
investigation for decades . The simplest way how to decompose the above-mentioned
reactive phosphates and phosphonates is their alkaline hydrolysis. Great effort has been
exerted on finding systems capable of efficient hydrolysis of phosphates and
phosphonates even under mild conditions i.e. in almost neutral water solutions at
ambient temperature. Promising results were obtained with aqueous solutions of
Collect. Czech. Chem. Commun. (Vol. 60) (1995)

8
84
Hampl, Mazac, Liska, Srogl, Kabrt, Suchanek:
cationic tensides. Their accelerating effect on alkaline hydrolysis of esters has been
2
known since the end of the sixties . The observed rate enhancement is caused by
general micellar catalysis, i.e. by the ability of micelles to bring together both a
lipophilic organic substrate and an ionic reagent (nucleophilic hydroxide anion). The
hydrolytic activity of cationic tensides is increased in cases when a nucleophilic group
2
,3
4
3
3
(
e.g. hydroxy , hydroperoxy , mercapto , amino etc.) is bound in the proximity of the
positively charged atom. These groups in the so-called functional cationic tensides are
activated by the electron withdrawing effect of the polar head group and can be easily
deprotonated to form powerful nucleophile attacking the ester bond.
Quaternary pyridinium aldoximes are efficient nucleophiles for cleavage of
phosphates, the best known of them being 1-methyl-2-hydroxyiminomethylpyridinium
5
,6
7
iodide (Ia). This reagent and many other related compounds have been used for
reactivation of acetylcholinesterase. For this reason the functional cationic tensides,
derived from oxime Ia and from its positional isomers Ib and Ic by replacing the
N-methyl group with a hydrophobic alkyl chain, were expected to be very powerful
agents for the cleavage of phosphates. The hydrolytic activity of
8
1
-dodecyl-3-hydroxyiminomethylpyridinium (Ig), 1-dodecyl-4-hydroxyiminomethyl-
9
,10
(Ih) and 1-hexadecyl-2-hydroxyiminomethylpyridinium10 (Ii) bromides
pyridinium
towards phosphate esters has been reported. Since the above-mentioned results were
obtained with different substrates at different pH values (mostly higher than 8), it was
Collect. Czech. Chem. Commun. (Vol. 60) (1995)

Quaternary Heteroarenium Aldoximes
885
impossible to compare the activity of the amphiphilic pyridinium aldoximes at neutral
conditions, suitable for practical applications. For this reason, in the present study we
have compared the reactivity of all isomeric 1-alkyl-hydroxyiminomethylpyridinium
salts Ia – Ih towards 4-nitrophenyl diphenyl phosphate (PNPDPP) as a model substrate
under neutral (pH 7.2) and slightly basic (pH 7.8) conditions. We have also tried to
modify the hydrolytic activity of the aldoximes by introduction of another ring
heteroatom. As an example we chose 1-alkyl-3-hydroxyiminomethylpyridazinium salts
II. No data have been available about the influence of an inert cationic tenside on the
velocity of pyridinium aldoximes-catalyzed cleavage of PNPDPP. Therefore we have
also studied kinetics of this cleavage in comicellar systems with cetyltrimethylammonium
bromide (CTAB).
EXPERIMENTAL
1
Temperature data are uncorrected. H NMR spectra were recorded on a Bruker AM 400 spectrometer
(
400 MHz). Chemical shifts are given in ppm relative to tetramethylsilane as internal standard,
coupling constants J in Hz. Elemental analyses were performed on a Perkin–Elmer 240 analyzer.
TLC analyses were carried out on prepared glass plates coated with 0.3 mm layer of Kieselgel G,
activity 6 according to Stahl (Merck Laboratory Chemicals), detection by 1% solution of cerium
sulfate in 10% sulfuric acid followed by carbonization.
Chemicals. 2-, 3- and 4-Pyridinealdoxime (purum) and dodecyl bromide (purum) were obtained
1
1
12
from Fluka. Dodecyl iodide , 4-nitrophenyl diphenyl phosphate
(PNPDPP) and
1
3,14
3
-pyridazinecarboxaldehyde
III were synthesized and purified by published methods. Cetyl-
trimethylammonium bromide (purum, Lachema Brno) was twice recrystallized from ethanol–ether.
Methyl iodide (purum) and tris(hydroxymethyl)methylamine, Tris (analytical grade) were Lachema
Brno products.
3
-Pyridazinealdoxime (IV)
A saturated solution of hydroxylamine hydrochloride (4.87 g, 70 mmol) and potassium carbonate
(
12.2 g, 89 mmol) in water was added to a solution of crude aldehyde III (5.00 g, 46.3 mmol) in
ethanol (150 ml). After standing overnight in a refrigerator, the deposited white crystals were
recrystallized from ethanol. Yield of oxime IV 5.06 g (89%), m.p. 142 – 143 °C. For C H N O
5
5
3
1
(
123.1) calculated: 48.78% C, 4.09% H, 34.13% N; found: 49.10% C, 4.21% H, 33.95% N. H NMR
spectrum (CDCl ): 7.74 dd, 1 H, J(5,4) = 8.7, J(5,6) = 4.9 (H-5); 8.04 d, 1 H, J(5,4) = 8.5 (H-4);
3
8
.36 s, 1 H (CH=N); 9.22 d, 1 H, J(5,6) = 4.9 (H-6).
Preparation of Quaternary Salts
A) A solution of the pyridinealdoxime (3.00 g, 24.6 mmol) and alkyl halide (37 mmol) in ethanol
(
50 ml) was refluxed until the starting oxime disappeared (TLC in chloroform–methanol 100 : 5).
The reaction mixture was cooled to room temperature, the crystalline crude product was collected
and recrystallized from ethanol.
B) Pyridinealdoxime (3.00 g, 24.6 mmol) and alkyl halide (37 mmol) in acetonitrile (100 ml) were
heated at 110 – 120 °C in a sealed tube for 8 h. Crude products, obtained by evaporation of solvent
under reduced pressure, were recrystallized from ethanol.
Collect. Czech. Chem. Commun. (Vol. 60) (1995)

8
86
Hampl, Mazac, Liska, Srogl, Kabrt, Suchanek:
Conversion of Quaternary Iodides to Bromides
A column packed with Amberlite IRA-400 (OH− form) was carefully washed with methanol. The
quaternary iodide was dissolved in methanol and applied on the column. The resulting solution of the
quaternary hydroxide was neutralized with 48% hydrobromic acid to pH 7. Evaporation of the
solvent under reduced pressure and recrystallization yielded the desired bromide.
1
-Methyl-2-hydroxyiminomethylpyridinium Iodide (Ia)
Prepared by method A. The reaction was complete after 6 h. Yield 5.27 g (81%), m.p. 230 – 232 °C
reported1 m.p. 224 – 225 °C). H NMR spectrum ((CD ) SO): 4.38 s, 3 H (CH ); 8.10 m, 1 H
5
1
(
3 2 3
(
=
H-5); 8.41 d, 1 H, J(4,3) = 8.1 (H-3); 8.56 m, 1 H (H-4); 8.69 s, 1 H (CH=N); 9.03 d, 1 H, J(5,6)
6.1 (H-6); 13.11 s (OH). pK = 7.92 (7.88 – 7.97); reported 8.0.
a
1
6
1
-Methyl-3-hydroxyiminomethylpyridinium Iodide (Ib)
Prepared by method A. The reaction was complete after 4 h. Yield 4.28 g (66%), m.p. 153 – 158 °C
reported1 m.p. 154 – 155 °C). H NMR spectrum ((CD ) SO): 4.39 s, 3 H (CH ); 8.14 dd, 1 H,
5
1
(
3 2 3
J(4,5) = 8.1, J(6,5) = 6.1 (H-5); 8.36 s, 1 H (CH=N); 8.70 d, J(5,4) = 8.1 (H-4); 8.95 d, 1 H, J(5,6)
1
6
=
6.0 (H-6); 9.18 s, 1 H (H-2). pK = 9.27 (9.22 – 9.32); reported 9.2.
a
1
-Methyl-4-hydroxyiminomethylpyridinium Iodide (Ic)
Prepared by method A. The reaction was complete after 4 h. Yield 5.57 g (86%), m.p. 178 – 181 °C
reported1 m.p. 181 – 183 °C). H NMR spectrum ((CD ) SO): 4.35 s, 3 H (CH ); 8.22 d, 2 H,
5
1
(
3
2
3
J(2,6,3,5) = 6.6 (H-3,H-5); 8.45 s, 1 H (CH=N); 8.95 d, 2 H, J(3,5,2,6) = 6.5 (H-2,H-6). pK = 8.60
a
1
6
(
8.51 – 8.70); reported 8.6.
1
-Methyl-4-hydroxyiminomethylpyridinium Bromide (Id)
Prepared from iodide Ic (2.00 g, 7.6 mmol) by anion exchange. The crude product was recrystallized
from ethanol. Yield 1.12 g (68%), m.p. 215 – 218 °C. For C H BrN O (217.0) calculated: 38.73% C,
7
9
2
1
4
.18% H, 36.81% Br, 12.91% N; found: 39.00% C, 4.44% H, 37.31% Br, 10.99% N. H NMR
spectrum ((CD ) SO): 4.38 s, 3 H (CH ); 8.25 d, 2 H, J(2,6,3,5) = 6.7 (H-3,H-5); 8.48 s, 1 H
3
2
3
(
CH=N); 9.05 d, 2 H, J(3,5,2,6) = 6.6 (H-2,H-6); 12.77 s (OH).
1
-Dodecyl-2-hydroxyiminomethylpyridinium Iodide (Ie)
A solution of 2-pyridinealdoxime (5.00 g, 40.9 mmol) and dodecyl iodide (15.00 g, 50.6 mmol) in
acetonitrile (120 ml) was stirred at 40 °C for 100 h. The solvent was removed under reduced
pressure. Column chromatography (silica gel, chloroform–methanol–NH OH 100 : 10 : 1) of the
4
residue afforded 1.94 g (39%) of unreacted 2-pyridinealdoxime and 3.17 g of crude product.
1
6
Recrystallization from acetone gave 2.28 g (13%) of iodide IVa, m.p. 127 – 130 °C (reported m.p.
1
7
59 – 160 °C). For C H IN O (418.4) calculated: 51.68% C, 7.47% H, 6.70% N; found: 51.71% C,
18 31 2
1
.63% H, 7.00% N. H NMR spectrum (CDCl ): 0.88 t, 3 H, J(12′,11′) = 7.1 (CH ); 1.33 bs, 16 H
3
3
(
(CH ) ); 1.49 m, 2 H (CH CH CH N); 1.92 qi, 2 H, J(3′,1′,2′) = 7.0 (CH CH N); 4.78 t, 2 H,
2 8 2 2 2 2 2
J(2′,1′) = 7.0 (CH N); 4.95 s, 1 H (OH); 7.84 m, 1 H (H-5); 8.36 m, 1 H (H-4); 8.52 s, 1 H (CH=N);
2
8
.55 d, 1 H, J(4,3) = 8.4 (H-3); 8.96 d, 1 H, J(5,6) = 6.0 (H-6). pK = 8.20 (8.13 – 8.27).
a
Collect. Czech. Chem. Commun. (Vol. 60) (1995)

Quaternary Heteroarenium Aldoximes
-Dodecyl-2-hydroxyiminomethylpyridinium Bromide (If)
887
1
Prepared from iodide Ie (0.600 g, 1.43 mmol) by anion exchange. The crude product was
recrystallized from acetone–ether. Yield 0.298 g (56%), m.p. 163 – 167 °C. For C H BrN O
1
8
31
2
(
371.4) calculated: 58.22% C, 8.41% H, 21.52% Br, 7.54% N; found: 56.11% C, 8.37% H, 20.68% Br,
7
1
1
.21% N. 1H NMR spectrum (CDCl ): 0.87 t, 3 H, J(11′,12′) = 6.8 (CH ); 1.24 bs, 16 H ((CH ) );
3
3
2
8
.40 m, 2 H (CH CH CH N); 1.93 m, 2 H (CH CH N); 4.94 t, 2 H, J(2′,1′) = 6.2 (CH N); 8.02 m,
2
2
2
2
2
2
H (H-5); 8.40 d, 1 H, J(4,3) = 7.6 (H-3); 8.66 m, 1 H (H-4); 8.69 s, 1 H (CH=N); 9.14 d, 1 H,
J(5,6) = 5.0 (H-6).
1
-Dodecyl-3-hydroxyiminomethylpyridinium Bromide (Ig)
Prepared by method B. Yield 3.41 g (37%), m.p. 138 – 139 °C (reported17 m.p. 141 – 143 °C).
1
H NMR spectrum (CDCl ): 0.87 t, 3 H, J(11′,12′) = 7.0 (CH ); 1.31 bs, 18 H ((CH ) ); 2.07 m, 2 H
3
3
2 9
(
CH CH N); 4.86 t, 2 H, J(2′,1′) = 7.2 (CH N); 8.18 dd, 1 H, J(6,5) = 6.2, J(4,5) = 8.0 (H-5); 8.33 s,
2 2 2
1
1
H (CH=N); 8.68 d, 1 H, J(5,4) = 8.2 (H-4); 9.05 d, 1 H, J(5,6) = 6.0 (H-6); 9.50 s, 1 H (H-2);
1.13 s, 1 H (OH). pK = 9.01 (8.92 – 9.12).
a
1
-Dodecyl-4-hydroxyiminomethylpyridinium Bromide (Ih)
9
1
Prepared by method B. Yield 5.36 g (59%), m.p. 131 – 132 °C (reported m.p. 129 – 130 °C). H NMR
spectrum (CDCl ): 0.88 t, 3 H, J(11′,12′) = 7.1 (CH ); 1.36 bs, 18 H ((CH ) ); 2.05 m, 2 H
3
3
2 9
(
(
CH CH N); 4.84 t, 2 H, J(2′,1′) = 7.2 (CH N); 8.21 d, 2 H, J(2,6,3,5) = 6.6 (H-3,H-5); 8.36 s, 1 H
2 2 2
CH=N); 9.16 d, 2 H, J(3,5,2,6) = 6.6 (H-2,H-6); 11.70 s, 1 H (OH). pK = 8.29 (8.24 – 8.34).
a
1
-Methyl-3-hydroxyiminomethylpyridazinium Iodide (IIa)
A solution of oxime IV (1.00 g, 8.1 mmol) and methyl iodide (2.32 g, 16.3 mmol) in ethanol (100 ml)
was stirred at room temperature for 30 h. Removal of the solvent under reduced pressure and
recrystallization from ethanol afforded 0.90 g (42%) of yellow crystals, m.p. 194 – 196 °C. For
C H IN O (265.1) calculated: 27.19% C, 3.04% H, 47.88% I, 15.85% N; found: 27.74% C, 3.19% H,
6
8
3
1
4
1
1
9.69% I, 13.63% N. H NMR spectrum ((CD ) SO): 4.59 s, 3 H (CH ); 8.38 s, 1 H (CH=N); 8.70 dd,
3 2 3
H, J(4,5) = 8.7, J(6,5) = 5.6 (H-5); 8.81 d, 1 H, J(5,4) = 8.5 (H-4); 9.87 d, J(5,6) = 5.5 (H-6);
2.95 s, 1 H (OH). pK = 8.48 (8.41 – 8.56).
a
1
-Dodecyl-3-hydroxyiminomethylpyridazinium Iodide (IIb)
A solution of oxime IV (2.00 g, 16.2 mmol) and dodecyl iodide (6.40 g, 21.6 mmol) in acetonitrile
(
100 ml) was stirred at 50 °C for 30 h. Evaporation the solvent and recrystallization from
ethanol–ether gave 1.83 g (27%) of yellow crystals, m.p. 142 – 149 °C. For C H IN O (419.4)
1
7
30
3
calculated: 48.69% C, 7.21% H, 30.26% I, 10.02% N; found: 49.04% C, 7.45% H, 31.60% I, 9.90% N.
1
H NMR spectrum ((CD ) SO): 0.85 t, 3 H, J(11′,12′) = 6.8 (CH ); 1.21 bs, 16 H ((CH ) ); 1.31 m,
3
2
3
2 8
2
H (CH CH CH N); 2.00 m, 2 H (CH CH N); 4.81 t, 2 H, J(2′,1′) = 7.3 (CH N); 8.38 s, 1 H
2 2 2 2 2 2
(
1
CH=N); 8.67 dd, 1 H, J(6,5) = 5.7, J(4,5) = 8.7 Hz (H-5); 8.82 d, 1 H, J(5,4) = 8.7 (H-4); 9.97 d,
H, J(5,6) = 5.7 (H-6); 13.00 s, 1 H (OH). pK = 8.32 (8.27 – 8.37).
a
1
-Dodecyl-3-hydroxyiminomethylpyridazinium Bromide (IIc)
Prepared from iodide IIb (0.500 g, 1.19 mmol) by anion exchange. The crude product was
recrystallized from acetone–ether. Yield 0.315 g (71%), m.p. 180 – 183 °C. For C H BrN O
1
7
30
3
Collect. Czech. Chem. Commun. (Vol. 60) (1995)

8
88
Hampl, Mazac, Liska, Srogl, Kabrt, Suchanek:
(372.4) calculated: 54.84% C, 8.12% H, 21.46% Br, 11.29% N; found: 53.64% C, 7.82% H, 20.96% Br,
1
0.83% N.
Determination of pKa
The pKa values of the oximes Ia
– Ih and IIa – IIc (vide supra) were determined
1
8
spectrophotometrically using the standard procedure . The oximes were titrated with sodium
−3
−1
hydroxide in 2.0 . 10 M CTAB at constant ionic strength I 0.15 mol kg at 25 °C. The pK values
a
were calculated from Eq. (1) using the absorbance–pH dependences at two wavelengths (at the
−
maxima of the =NOH and =NO forms). The confidence intervals at the significance level α = 0.05
are given in parentheses.
|
|
Amax − Aobs |
Aobs − Amin |
pKa = pHobs + log
(1)
Kinetic Measurements
Solutions of the reactants were prepared in 0.04 M tris(hydroxymethyl)methylamine–HBr buffers,
pH 7.2 or 7.8. No changes in pH were observed during the kinetic runs. The reactions were followed
on a spectrophotometer Shimadzu UV2100 or Specord M40 equipped with a thermostated cell
−3
at 25.0 ± 0.1 °C. The reactions were initiated by injection of 1.0 . 10 M solution of PNPDPP in
acetonitrile into the spectrophotometric cell containing 2 ml of buffered solution of the catalyst
(
10 µl in the case of oximes Ia – Ic and oxime IIa or 20 µl in the case of oximes Ie – Ih and IIb or
−6
in the kinetic runs in which CTAB was present; the resulting concentrations of the substrate were 5.0 . 10
−
1
−5
−1
mol l and 1.0 . 10 mol l , respectively). The concentration of the p-nitrophenoxide ion was monitored
at 400 nm. The rections invariably followed the first-order kinetics up to 90% conversion. The rate
constants were obtained by nonlinear regression analysis of the absorbance vs time data. The fit error
of the rate constant did not exceed 5% in any case.
RESULTS AND DISCUSSION
All the quaternary salts were prepared by alkylation of the corresponding aldoximes
with alkyl halides; in the case of less reactive 2-pyridinealdoxime and
3
-pyridazinealdoxime (IV) dodecyl iodide had to be used. According to NMR spectra,
all the obtained products were pure geometric isomers; however, only in the case of the
oximes Ia and Ic the configuration at the C=N bond could be assigned as (E), according
1
9,20
16
to the published melting point data
. The difference between the published and
found melting point of the quaternary aldoxime Ie indicated that our product had the
opposite configuration. 3-Pyridazinealdoxime (IV) was synthesized starting from
furfuryl acetate using the transformation of 2,5-dihydro-2,5-dimethoxyfuran to
1
3
pyridazine ring . Considering the low solubility of cetyltrimethylammonium iodide in
water all quaternary iodides had to be converted into bromides when the kinetic
measurements were performed in comicelles with CTAB. This conversion was carried
out on anion exchangers.
Collect. Czech. Chem. Commun. (Vol. 60) (1995)

Quaternary Heteroarenium Aldoximes
889
To evaluate and compare the ability of the prepared quaternary heteroarenium
aldoximes to destroy phosphates in neutral or slightly basic solutions, the apparent rate
constants kobs for the PNPDPP cleavage (Scheme 1) under pseudo-first-order conditions
(
2
[oxime] >> [PNPDPP]) were determined. All kinetic measurements were perfomed at
5 °C at two pH values (7.2 and 7.8), both in homomicelles and in comicelles with
non-functional cationic tenside cetyltrimethylammonium bromide. The reactions were
followed by quantitative determination of the liberated 4-nitrophenoxide ion. The
concentration interval in which the cleavage was studied was limited either by the
−1
solubility of the aldoxime or by the velocity of the reaction (for reactions with kobs > 0.5 s
a stopped-flow equipment is necessary). We did not take into account the contribution
of alkaline hydrolysis: under conditions of the measurements its rate constant was of
−
7
−6
21
the order 10 – 10 (see ref. ), i.e. much less than the observed rate constants in the
presence of our aldoximes. Also the difference between the rate constants in micellar
and bulk water phase and the distribution of substrate and catalyst between these
2
2
phases were neglected.
The accelerating effect of quaternary aldoximes Ia – Ic and IIa on the cleavage of
PNPDPP is evident from the pseudo-first-order rate constant kobs vs concentration plots
(
Fig. 1).
To compare the nucleophilicity of the anions formed from compounds Ia – Ic and
−
−
IIa, it is necessary to derive the plot of kobs vs [A ] (where [A ] stands for concentration
of the oximate anion) from the data in Fig. 1. The slopes of these plots represent the
formal second-order rate constants k of the cleavage, revealing thus the nucleophilicity
2
−
of the oximate anions. The [A ] values were calculated using Eq. (2) and the k values
2
−
were obtained from the kobs vs [A ] plots by linear regression
cox Ka
−
[
A ] =
,
(2)
+
[
H ] + K
a
where cox is analytical concentration of the oxime and K is dissociation constant of the
a
oxime.
The comparison of apparent reactivities of oximes Ia – Ic and IIa at given pH
(
dkobs/dcox values) with their nucleophilicities (represented by k values) is shown in
2
SCHEME 1
Collect. Czech. Chem. Commun. (Vol. 60) (1995)

8
90
Hampl, Mazac, Liska, Srogl, Kabrt, Suchanek:
Table I. It is not surprising that the order of apparent reactivities of the pyridinium
aldoximes is reverse to that of the nucleophilicities: the more the electron-withdrawing
effect of the pyridinium nitrogen increases the acidity of the hydroxyimino group, the
more it reduces the nucleophilicity of the resulting anion. Another way how to assess
nucleophilicity of the pyridinium aldoxime anions could be comparison of the
pseudo-first-order rate constants of the PNPDPP cleavage measured at pH values
1
0
higher than pK ; this method was used by Lion and revealed the same order of
a
nucleophilicity. However, the principal factor determining the observed high reactivity
of oximes towards phosphates at neutral or slightly basic conditions is the acidity of the
hydroxyimino group. A question may arise in connection with the existence of the two
isomers of aldoximes: which of these two isomers is more reactive? We suppose that in
solutions the equilibration to the thermodynamically more stable isomer proceeds
easily after deprotonation of the hydroxyimino group, and for this reason the observed
reactivity of both isomers should be the same. This assumption is supported by the fact
that the less stable isomers of the quaternary oximes Ia – Ic slowly turn to the more
1
5
stable ones at ambient temperature even in the solid state .
The order of reactivity of the amphiphilic 1-dodecylpyridinium aldoximes Ie – Ig
under neutral conditions (pH 7.2) towards PNPDPP is the same as of their 1-methyl
analogs. In all cases, the pseudo-first-order rate constant–concentration plots are
8
4
10
kobs .10
s
3
−
1
4
kobs
kobs .10
3
6
−1
.
10
s
1
4
2
0
5
0
1
2
3
cox
0
0
1
2
3
c
5
0
1
3
−1
3
−1
3
. 10 , mol l
c
. 10 , mol l
ox
ox
FIG. 1
FIG. 2
Plots of pseudo-first-order rate constants of
PNPDPP cleavage vs concentration for oximes
Ia – Id and IIa in 5.0 mM CTAB at pH 7.2
Plots of pseudo-first-order rate constants of
PNPDPP cleavage vs concentration for oximes
Ie, Ig and Ih at pH 7.2 (0.04 M Tris-HBr buffer)
and 25 °C. ❐ Ie, ❐ Ig, ∆ Ih
(
0.04 M Tris-HBr buffer) and 25 °C. ❐❐ Ia, ∇
Ib, ∆ Ic, ❐ IIa, * Id
Collect. Czech. Chem. Commun. (Vol. 60) (1995)

Quaternary Heteroarenium Aldoximes
891
markedly curved (Fig. 2). In the region of the curvature, cationic micelles of the
amphiphilic pyridinium aldoximes begin to form micelles and consequently the rate of
the cleavage dramatically increases due to the micellar catalysis. The rate profiles of
cleavage at slightly alkaline conditions (pH 7.8) are similar (Fig. 3). Their
pseudo-first-order rate constants are higher than those obtained at pH 7.2; this
demonstrates repeatedly that oximate anion is the active species in the phosphate
cleavage. We were not able to evaluate the efficiency of the pyridazinium aldoximes
IIb and IIc. These quaternary salts were unstable and decomposed under the reaction
conditions, most probably via nucleophilic attack by hydroxide anion at the positively
charged heteroaromatic nucleus. Similar instability of the amphiphilic pyridazinium
2
3
compounds was also observed by other authors .
TABLE I
Comparison of apparent activity (dkobs/dc) with nucleophilicity (k ) of oximes Ia – Ic and IIa
2
−
Ka
mol l
dkobs/dc
l mol s
k2 = dkobs/d[A ]
ox
Compound
−1
−1
−1
l mol s
−
8
−1
−1
Ia
Ib
1.20 . 10
5.37 . 10
1.6 . 10
4.4 . 10
1.1 . 10
4.1 . 10
9.9 . 10
−
10
−2,a
−1
a
5.2
−9
Id
2.51 . 10
3.31 . 10
3.0
−9
−2
−1
IIa
6.8 . 10
a
−4
−1
The distant value of kobs at cox 1.0 . 10 mol l was neglected.
25
2
kobs . 10
s
−
1
20
15
10
5
0
FIG. 3
Plots of pseudo-first-order rate con-
stants of PNPDPP cleavage vs concen-
tration for oximes Ie, Ig and Ih at pH
7
❐
.8 (0.04 M Tris-HBr buffer) and 25 °C.
Ie, ❐ Ig, ∆ Ih
0
1
3
−1
3
c
. 10 , mol l
ox
Collect. Czech. Chem. Commun. (Vol. 60) (1995)

8
92
Hampl, Mazac, Liska, Srogl, Kabrt, Suchanek:
The velocity of the PNPDPP cleavage, catalyzed by amphiphilic aldoximes If – Ih,
increased dramatically in comicelles with inert cationic tenside CTAB. The
dependences of the rate constants of the cleavage on the molar fraction of pyridinium
aldoximes in a mixture with CTAB at constant total molar concentration of tensides
(
kinetic versions of Job’s plots) are depicted in Fig. 4. In the presence of 10 – 30 mole %
of CTAB the increase of the observed rate constants was approximately one order of
magnitude. We have no plausible explanation for this phenomenon. Most probably,
changes in the structure of cationic micelles causing changes in effective concentration
of the reactants are responsible for the observed synergism.
On the other hand, PNPDPP cleavage by non-micellar 1-methylpyridinium aldoximes
was inhibited by CTAB as was shown in the case of compound Id (see Fig. 1). This fact
can be explained by “extraction” of the lipophilic substrate PNPDPP into the micelles
while the hydrophilic 1-methylpyridinium aldoxime remains in the bulk water phase.
This work was supported by the Grant Agency of the Czech Republic (grant No. 203/93/0546).
10
4
kobs . 10
s
−
1
8
6
4
FIG. 4
Dependences of the pseudo-first-order rate
constants on the molar fraction of the oximes
If, Ig and Ih in CTAB at pH 7.2 (0.04 M
Tris-HBr buffer) and 25 °C. ❐ If, [CTAB]
2
0
−3
−1
+ [oxime] = 2.0 . 10 mol l ; ❐ Ig,
0
0.2
0.4
0.6
1.0
−3
−1
[
CTAB] + [oxime] = 3.0 . 10 mol l ; ∆ Ih,
c
/(c +c
)
−3
−1
CTAB ox CTAB
[CTAB] + [oxime] = 1.0 . 10 mol l
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Collect. Czech. Chem. Commun. (Vol. 60) (1995)

Quaternary Heteroarenium Aldoximes
893
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Collect. Czech. Chem. Commun. (Vol. 60) (1995)