Long chain β-aminoethanols as micellar catalysts for the hydrolysis of diphenyl-p-nitrophenyl phosphate. The observation of an unusual enhancement of catalysis in the presence of added polyols

Article abstract of DOI:10.1139/v99-161

The hydrolysis of p-nitrophenyldiphenyl phosphate (PNPDPP, 7) catalyzed by N-dodecylaminoethanol (6a), N-tetradecylaminoethanol (6b), N-methyl-N-tetradecylaminoethanol (6c), and N-hexadecylaminoethanol (6d) was investigated at 25°C at various pH values in aqueous media containing additives. Added ethanol or dimethoxyethane produces very little activity of 6a, b, c toward 7. The highest activities of 6a, b were found at pH 8.0 and 8.5 in solvents containing 20% glycerol or ethylene glycol. Under no conditions was N-hexadecylaminoethanol (6d) found to be active. The kinetics of the reaction of 6b with 7 were also investigated in a medium containing various amounts of glycerol, polyethylene glycol 400 (PEG 400), and water at pH 7.6-8.5. The best catalytic system comprised 3 mM 6b in 20% aqueous ethylene glycol, pH 8.5, which accelerated the hydrolysis of 7 by ~1700-fold over the blank rate. Kinetic experiments conducted using [7]/[6b] = 1 and 2 demonstrate that 6b exhibits true turnover catalysis. A mechanism for the catalyzed reaction is proposed.

Full text of DOI:10.1139/v99-161

1577
Long chain ␤-aminoethanols as micellar
catalysts for the hydrolysis of diphenyl-p-
nitrophenyl phosphate. The observation of an
unusual enhancement of catalysis in the
presence of added polyols
H. Oumar-Mahamat, H. Ðlebocka-Tilk, and R.S. Brown
Abstract: The hydrolysis of p-nitrophenyldiphenyl phosphate (PNPDPP, 7) catalyzed by N-dodecylaminoethanol (6a),
N-tetradecylaminoethanol (6b), N-methyl-N-tetradecylaminoethanol (6c), and N-hexadecylaminoethanol (6d) was
investigated at 25°C at various pH values in aqueous media containing additives. Added ethanol or dimethoxyethane
produces very little activity of 6a, b, c toward 7. The highest activities of 6a, b were found at pH 8.0 and 8.5 in
solvents containing 20% glycerol or ethylene glycol. Under no conditions was N-hexadecylaminoethanol (6d) found to
be active. The kinetics of the reaction of 6b with 7 were also investigated in a medium containing various amounts of
glycerol, polyethylene glycol 400 (PEG 400), and water at pH 7.6–8.5. The best catalytic system comprised 3 mM 6b
in 20% aqueous ethylene glycol, pH 8.5, which accelerated the hydrolysis of 7 by ~1700-fold over the blank rate.
Kinetic experiments conducted using [7]/[6b] = 1 and 2 demonstrate that 6b exhibits true turnover catalysis. A
mechanism for the catalyzed reaction is proposed.
Key words: β-aminoethanols, hydrolysis, p-nitrophenyldiphenyl phosphate, micelles, polyhydroxy alcohols.
Résumé : Opérant à 25°C, à divers pH, dans des milieux aqueux contenant des additifs, on a étudié l’hydrolyse du
phosphate de diphényle et de p-nitrophényle (7) catalysée par N-dodécylaminoéthanol (6a), N-tétradécylaminoéthanol
(6b), N-méthyl-N-tétradécylaminoéthanol (6c) et N-hexadécylaminoéthanol (6d). L’addition d’éthanol ou de
diméthoxyéthane ne produise que de faibles activités des catalyseurs 6a, b, c vis-à-vis de 7. Les activités les plus
élevées de 6a, b ont été observées à des pH de 8,0 et 8,5, dans des solvants contenant 20% de glycérol ou
d’éthylèneglycol. On n’a pas trouvé de conditions dans lesquelles le N-hexadécylaminoéthanol (6d) est actif. On a
aussi examiné la cinétique de la réaction de 6b avec 7 dans un milieu contenant diverses quantités de glycérol, de
polyéthylèneglycol 400 (PEG 400) et d’eau, à des pH allant de 7,6 à 8,5. Le meilleur système catalytique est formé de
3 mM de 6b dans de l’éthylèneglycol aqueux à 20%, à un pH de 8,5; dans ces conditions, l’hydrolyse de 7 se produit
1700 fois plus rapidement que dans l’essai à blanc. Des expériences cinétiques effectuées en utilisant un rapport
[7]/[6b] = 1 et 2 démontre que le composé 6b donne lieu à une réelle catalyse. On propose un mécanisme pour la
réaction catalysée.
Mots clés : β-aminoéthanols, hydrolyse, phosphate de diphényle et de p-nitrophényle, micelles, alcools polyhydroxylés.
[Traduit par la Rédaction] Oumar-Mahamat et al. 1588
Introduction
X
RO P
R
Activated phosphate, phosphinate, and phosphonate esters
of the general form 1 are potent acetylcholinesterase inhibi-
tors (1). These include such substances as the insecticides
parathion (RO = R = OEt; X = S; Y = OC6H4NO2) and
paraoxon (RO = R = OEt; X = O; Y = OC6H4NO2), as well
as the alkylphosphonofluoridate esters soman (RO =
Y
1
(CH3)3CCH(CH3)O; R = CH3; X = O; Y = F) and sarin (RO
= (CH3)2CHO; R = CH3; X = O; Y = F), the latter gaining
their notoriety as organophosphorus nerve agents. Due to
their potential toxicity, considerable attention has been di-
rected toward methods of facilitating the hydrolysis or de-
composition of organophosphates.
In some cases, metal chelates have been successfully
shown to catalyze the hydrolysis of neutral phosphate and
(or) phosphonate esters (2). More work has been directed to-
Received March 29, 1999.
H. Oumar-Mahamat, H. Ðlebocka-Tilk, and R.S. Brown.1
Department of Chemistry, Queen’s University, Kingston,
ON K6L 3N6, Canada.
1Author to whom correspondence may be addressed.
Telephone: (613) 533-2616. Fax: (613) 533-6669.
e-mail: rsbrown@chem.queens.ca
Can. J. Chem. 77: 1577–1588 (1999)
© 1999 NRC Canada

1578
Can. J. Chem. Vol. 77, 1999
Scheme 1.
+
R2
N+
H
6
R1
CH2CH2OH
K
K
K
1
2
4
R2
R2
+ CH2CH2O-
K
eq
R1 N CH2CH2OH
R1
N
H
o
6
6
zw
R2
K
3
CH2CH2O-
R1 N
-
6
6a R1=C12H25; R2=H
b R1=C14H29; R2=H
c R1=C14H29; R2=CH3
d R1=C16H33, R2=H
ammonium group electrostatically reduces the pKa of the at-
tached hydroxyethyl group, thereby creating appreciable
quantities of 5ZW at reduced pH. For example, while the pKa
values for alcohols normally range from 15 to 19, those of
choline and 2-(N,N,N-triethylammonium)ethanol are 12.8 (7)
and 12.9 ± 0.3 (8), while those of micellar 5 (R = C12H25
and R = C16H33) are 12.9 and 12.4 (4b). Furthermore, zwit-
terionic 5ZW has been shown in several instances (4b, 8, 9)
to be sufficiently nucleophilic to attack activated C and P es-
ters.
CH3(CH2)13
H3C
CH3
CH3
N
N
2+
Cu
2
H3C
N+
C12H25
CHO
H3C
H3C
H3C
H3O+
N+ CH2CH2O- +
N+
3
R
CH2CH2OH
R
O
H3C
H3C
5
5
zw
O
I
X
O-
Unfortunately, these hydroxyethyl quaternary ammonium
species are not true catalysts in that they possess no internal
means to subsequently regenerate 5 or 5ZW other than
through attack of external OH–. It appeared to us that one
might expand the catalytic utility of such micelles by utiliz-
ing secondary or tertiary hydroxyethyl amines related to 5.
In principle, derivatives of 6 containing a long chain alkyl
moiety should impart micellar characteristics. As shown in
Scheme 1, such species can exist in aqueous media as a pH-
dependent mixture of four species (6+, 6°, 6ZW, 6–), the rela-
tive amounts of which are controlled by the four micro-
scopic ionization constants K1–K4. Forms 6+ and 6ZW, in
which the amine is protonated, formally resemble the charge
types inherent in the more traditional quaternary ammonium
micellar species 5, 5ZW. Following nucleophilic attack of the
O– of 6– or 6ZW on the activated phosphate, a possibility ex-
ists that the β-amino group, when deprotonated, might act as
an internal nucleophile to displace phosphate to yield an
aziridine, which, under the reaction conditions, could suffer
nucleophilic ring opening to regenerate the catalyst.
4
ward micelles (3) (which may (3b–e, g–i, k, m, n) or may
not (3a, f) contain nucleophilic or general-base additives),
functionalized micelles (4), and vesicular (5) means of de-
composing organophosphate esters. Of the above surfactant
systems, only a few exhibit true catalytic properties (2e, f,
3e, k, m, o, 4g, o, q). Perhaps the most efficacious are the
systems initially discovered by Menger et al. (2e, f, 4o) (2,
3), and Moss et al. (3e, j–l) (4), various derivatives of the
latter being further investigated (6) due to the high reactivity
attributable to the iodosobenzoates.
In general, functionalized quaternary ammonium materials
containing a hydroxyethyl group (5) possess several impor-
tant features that have been exploited for the reaction with
phosphate esters. First, above the critical micelle concentra-
tion (CMC), hydrophobic substrates are attracted to the
micellar pseudophase, which increases the local concentra-
tion and the likelihood of reaction with the polar head group.
Second, the presence of the positively charged quaternary
Herein we describe our preliminary findings with surfac-
tants in which four long chain alkyl substituted derivatives
© 1999 NRC Canada

Oumar-Mahamat et al.
1579
of 6 are reacted with p-nitrophenyldiphenyl phosphate (7,
PNPDPP) under various conditions of solvent composition
and pH. Importantly, we have observed that the amino alco-
hols themselves are rather ineffective in promoting the hy-
drolysis of 7 unless added polyhydroxy cosolvents are
present. In the presence of polyols such as glycerol, ethylene
glycol, and even sorbitol, two of these derivatives, 6a, b,
probably as their zwitterionic forms, 6ZW, appear to be
effective nucleophiles toward PNPDPP, producing an O-
phosphorylated intermediate. Furthermore, under the opti-
mum conditions, 6b is shown to be catalytically active due
to its built-in turnover capabilities.
2-(N-Hexadecylamino)ethanol (6d): Yield 54.5%; mp 49–
1
50°C; IR (CHCl3 cast): 3110, 3290 cm–1; H NMR (CDCl3)
δ: 3.62 (t,
2 H, NHCH2CH2OH), 2.75 (t, 2 H,
NHCH2CH2OH), 2.60 (t, 2 H, CH2NHCH2CH2OH), 2.36
(bs, 2 H, NH + OH), 1.48 (m, 2 H, (CH2)13CH2CH2N), 1.27
(bs, 26 H, (CH2)13), 0.88 (t, 3 H, CH3). Anal. calcd. for
C18H39NO: C 75.72, H 13.77, N 4.91; found: C 75.70, H
13.46, N 4.77.
b. Kinetics
Kinetics were monitored by observing the rate of forma-
tion of p-nitrophenoxide at 400 nm (T = 25°C) using a
Hewlett–Packard 8451A diode array spectrophotometer or a
Cary 210 UV-vis. spectrophotometer. Buffers employed were
HEPPS (N-[2-hydroxyethyl]piperazine-N′-3-propanesulfonic
acid), pH 7.5–8.5; CHES (cyclohexylaminoethanesulfonic
acid), pH 8.5–10; and CAPS (cyclohexylaminopro-
panesulfonic acid), pH 10.5–11.5. Final buffer concentra-
tions were 0.01 M, µ = 0.3 (KCl). pH values were measured
using a Radiometer TTT2 titration unit with a Radiometer
GK-2321C combination electrode, which was standardized
using Fisher certified pH 7.00 and 10.00 buffers. pH values
were simply measured from solutions that contained the or-
ganic cosolvents and amino alcohols and were not corrected.
pH values measured before and after the reactions showed
no significant deviations. Organic cosolvents were commer-
cially available and used without further purification. Buffer
solutions containing the amino alcohols at various concen-
trations and cosolvents were sonicated for 5 min, and then
placed in 3 mL quartz cuvettes in the spectrophotometer cell
holder for 20 min to allow thermal equilibration. Reactions
were initiated by injecting 5 µL of a 3 × 10–2 M solution of
PNPNPP (7) in ethanol or DME into the contents of the
quartz cuvettes (final concentration of 7, 5 × 10–5 M).
Pseudo-first-order rate constants (kobs) were evaluated by fit-
ting the absorbance (Abs.) vs. time data to a standard expo-
nential model via nonlinear least-squares treatment.
Reactions were monitored in triplicate and followed to at
least 3t1/2; in most cases the reactions displayed excellent
first-order kinetics, and when they failed to do so, the reac-
tions were repeated. Kinetic data for 6a, b, c are presented
in Tables 1–3, and the error limits presented are standard de-
viations.
O
O2N
O P O
2
7
Experimental
a. Materials
p-Nitrophenyldiphenyl phosphate (7) was prepared as pre-
viously described (10). The amino alcohols 6a–d were made
by a generalized procedure (11) modified as follows. A
1130 mL acetone solution containing 300 mmol of 2-
aminoethanol (or 2(N-methyl)aminoethanol) and 20 mmol of
the C12, C14, or C16 primary alkyl bromide was heated at re-
flux for 15–18 h. After cooling, the acetone was removed at
reduced pressure, and ether was added to the residue. The
ether solution was twice washed with saturated NaHCO3,
and then H2O. Following drying (Na2SO4) of the organic so-
lution, the volatiles were removed to yield a semi-crystalline
mass that was recrystallized from ether/pet. ether (1:1). The
following physical properties were observed.
2-(N-Dodecylamino)ethanol (6a): Yield 46.5%; mp 41–
1
42°C; IR (CHCl3 cast): 3282, 3120 cm–1; H NMR (CDCl3)
80 MHz, δ: 3.64 (t, 2 H, CH2OH), 2.78 + 2.62 (2 t, 4 H,
CH2NHCH2), 1.97 (s, 2 H, NH + OH), 1.28 (bs, 20 H,
(CH2)10), 0.88 (t, 3 H, CH3). Anal. calcd. for C14H31NO: C
73.30, H 13.62, N 6.11; found: C 73.35, H 13.41, N 6.08.
2-(N-Tetradecylamino)ethanol (6b): Yield 93% in metha-
nol as solvent; mp 50–51°C; IR (KBr): 3492, 3272 cm–1;
1H NMR (CDCl3) δ: 3.6 (t, 2 H, NH2CH2CH2OH), 3.06 (bs,
2 H, NH + OH), 2.72 + 2.63 (2 t, 4 H, CH2NHCH2), 1.51
(m, 2 H, -CH2CH2NHCH2CH2OH), 1.28 (bs, 22 H, (CH2)11,
0.89 (t, 3 H, CH3). Anal. calcd. for C16H35NO: C 74.64, H
13.70, N 5.44; found: C 74.82, H 13.79, N 5.26.
c. Reactions in the presence of polyethylene glycols
One litre of polyethylene glycol (PEG) 400, having an av-
erage molecular weight of 400, was purified by mixing with
15 g of Celite followed by filtration through a medium pore
sintered glass funnel. The material was then filtered through
about 50 g of neutral alumina (~2 cm thick on sintered glass
filtration funnel). The so-purified PEG was kept in a sealed
bottle under Ar and thoroughly mixed before any use to en-
sure homogeneity. For kinetic runs, the solvent–PEG system
requires the following protocol for ensuring clear solutions.
(i) A 5 × 10–3 M mixture of 6b was prepared in a solvent
consisting of 20% v/v glycerol and 80% water containing
0.3 M KCl and 0.01 M HEPPS buffer, by shaking or
sonication for 30 min at 50°C. (ii) To this solution was
added, with agitation, the same volume of PEG 400 as the
volume of glycerol added in part (i), resulting in a final
composition of 16.5% PEG 400, 16.5% glycerol, and 67.5%
2-(N-Methyl-N-tetradecylamino)ethanol (6c): Yield 19.2%;
mp <25°C (crystallized from ether/pet. ether at low tempera-
ture and quickly filtered); IR (CHCl3 cast): 3410 cm–1;
1H NMR (CDCl3) δ: 3.54 (t, 2 H, CH2OH), 2.99 (bs, 1 H,
CH2OH), 2.48 (t, 2 H, N(CH3)CH2CH2OH), 2.37 (t, 2 H,
CH2N(CH3)CH2CH2OH), 2.20 (s, 3 H, N(CH3), 1.43 (m, 2
H, (CH2)11CH2CH2N), 1.26 (s, 22 H, (CH2)11), 0.87 (t, 3 H,
CH3). Anal. calcd. for C17H37NO: C 75.21, H 13.74, N 5.16;
found: C 74.61, H 13.74, N 4.94.
© 1999 NRC Canada

1580
Can. J. Chem. Vol. 77, 1999
Table 1. Observed pseudo-first-order rate constants, 105kobs (s–1), for the reaction of p-nitrophenyldiphenyl phosphate (7) with amino
alcohols 6a, b at 25°C in 33.3% ethylene glycol.a
103[6a] (M)
pH
8
9
10
11
0
0.54 ± 0.01
0.84 ± 0.01
0.92 ± 0.03
2.33 ± 0.05
3.08 ± 0.08
3.64 ± 0.02
9.45 ± 0.13
43.77 ± 0.63
134.0 ± 1.3
169.1 ± 2.8
0.5
1.0
1.5
2.0
117.8 ± 0.4
168.8 ± 1.4
182.8 ± 2.5
306.6 ± 2.1
149.6 ± 3.7
282.8 ± 5.9
286.2 ± 7.8
340.9 ± 5.6
103[6b] (M)
pH
8
8.5
9
10
0
0.54 ± 0.01
47.3 ± 0.2
122.2 ± 1.0
210.3 ± 1.7
234.5 ± 1.4
3.64 ± 0.02
36.5 ± 1.9
120.6 ± 2.1
200.0 ± 2.6
230.3 ± 9.9
0.5
1.0
1.5
2
18.1 ± 0.2
36.5 ± 1.5
b
250 ± 9
307 ± 10
b
apH determined from measurement in cosolvent medium and is uncorrected; [7] = 5 × 10–5 M.
bInsoluble at these concentrations.
water (v/v). The pH of the resulting solution was adjusted to
the desired value by addition of NaOH or HCl. Kinetic runs
were undertaken using these mixtures as described above,
and the results are presented in Table 4.
spectrophotometer cell holder, which was then thermally
equilibrated for 15 min. The reaction was initiated by se-
quential injection of 4 × 25µL of 3 × 10–2 M of DPPNPP in
DME (final conc. of PNPDPP after four additions = 2 × 10–3
M). For the first injection, the Abs. vs. time profile was fol-
lowed at 420 nm for 10t1/2 of reaction. The second to fourth
portions were added to the same cell, and the Abs. vs. time
profiles followed similarly but at 450, 460, and 470 nm, re-
spectively, to keep the final absorbance less than 2.0. The
pseudo-first-order rate constants for the individual runs were
calculated as above and are presented in Table 5.
d. Turnover reactions
(i) To determine the catalytic ability of these amino alco-
hols a standard protocol of conducting the reaction in 20%
(v/v) glycerol/H2O media containing HEPPS (0.01 M, µ =
0.1 (KCl)), pH = 8.0, T = 25°C was investigated. The ap-
pearance of p-nitrophenoxide was monitored at 460 or
465 nm, and to maintain the final absorbance <1, the respec-
tive initial concentrations of DPPNPP (7) were 5 × l0–4 and
1 × l0–3 M. Two sets of experiments were conducted, one
with sonication, and another without, but in each case the
[6b] was 5 × 10–4 M. With sonication, the Abs. vs. time
plots displayed an irregular and nonreproducible behavior,
which is attributable to problems of turbidity. Without
sonication, at [6b] = [7] = 5 × 10–4 M, the kinetics displayed
an approximate first-order behavior, but with a small appar-
ent burst of p-nitrophenoxide at the beginning of the reac-
tion. Importantly, at the completion of the Abs. vs. time
profile, the amount of p-nitrophenoxide liberated was
(within experimental uncertainty) equal to the initial
[PNPDPP]. When the [7] = 2[6b] ([6b] = 5 × 10–4 M), a
burst in the production of p-nitrophenoxide (amounting to
about 40% of the initial [PNPDPP] occurring within
160 min) was observed followed by a slower further release
of p-nitrophenoxide, the final concentration of which was
equivalent to the total initial [PNPDPP] (approximate time
for completion of reaction 2000 min).
Results
a. Kinetics
Amino alcohols 6a–d are not soluble in purely aqueous
media and thus require organic cosolvents to attain sufficient
solubility to conduct kinetic experiments with PNPDPP (7).
The hexadecyl derivative (6d) is the least soluble of the se-
ries and requires at least 50% added ethanol or DME to at-
tain a [6d] of 2 × 10–3 M. Even so, at pH 9 virtually no
enhancement of the decomposition of 7 is observed in the
presence of 6d relative to the blank rate. Further studies with
6d were abandoned.
Given in Tables 1–3 are the pseudo-first-order rate con-
stants for the decomposition of 7 under a variety of condi-
tions in the presence of 6a, b, and c. In 33.3% EtOH or
DME, 6b is generally a better catalyst than is 6a, but neither
provides a dramatic enhancement of the decomposition of 7
at any pH between 8 and 11. However, as shown from the
data in Tables 1 and 2, the presence of the polyhydroxy
cosolvents ethylene glycol and glycerol leads to marked en-
hancement in the reactivity of both 6a and 6b. A comparison
of these amino alcohols is given by the pseudo-first-order
rate constants for decomposition of 7 in 33.3% ethylene gly-
col in Table 1. There is no linear pH dependent trend in the
rate constants observed in the presence of either of 6a or 6b.
(ii) A series of turnover experiments was also conducted
in a solvent system comprising 16.5% glycerol, 67% water,
16.5% PEG 400 (all v/v), 0.25 M KCl, and 0.01 M HEPPS,
pH 8, T = 25°C containing three concentrations of 6b, 1.1 ×
10–3, 2.8 × 10–3, and 4.16 × 10–3 M. Three mL of the above
solutions were inserted into a quartz cuvette in the
© 1999 NRC Canada

Oumar-Mahamat et al.
1581
Table 2. Pseudo-first-order rate constants, 105kobs (s–1), for the decomposition of 7 as a function of [6b] in various media at 25°C.a
(a) 33% DME
103 [6b] (M)
pH
8
9
10
11
0.0
0.5
1.0
1.5
2.0
0.41 ± 0.02
0.41 ± 0.01
1.06 ± 0.01
1.12 ± 0.01
4.20 ± 0.03
0.41 ± 0.01
1.76 ± 0.01
13.84 ± 0.09
20.08 ± 2.00
37.10 ± 2.00
23.84 ± 0.14
40.28 ± 0.41
57.08 ± 0.69
62.82 ± 1.94
49.77 ± 0.12
71.52 ± 0.53
94.17 ± 0.94
102.86 ± 1.60
(b) 50% EtOH
103 [6b] (M)
pH
9b
8.5
9
10
11
0.0
0.5
1.0
1.5
2.0
0.19 ± 0.01
0.19 ± 0.01
0.22 ± 0.01
0.20 ± 0.01
0.23 ± 0.01
0.16 ± 0.01
0.21 ± 0.01
0.18 ± 0.01
0.24 ± 0.05
0.27 ± 0.01
0.33 ± 0.02
0.67 ± 0.01
1.03 ± 0.01
5.03 ± 0.01
8.07 ± 0.02
0.64 ± 0.02
0.78 ± 0.01
0.83 ± 0.02
1.03 ± 0.04
1.19 ± 0.03
2.78 ± 0.01
3.10 ± 0.01
3.14 ± 0.01
3.22 ± 0.01
3.3 ± 0.01
(c) 33.3% glycerol
103 [6b] (M)
pH
8.5
8
9.0
0.0
0.5
1
1.5
2.0
2.5
3.0
1.24 ± 0.04
165.2 ± 5.2
245.9 ± 5.5
239.4 ± 6.0
263.2 ± 6.3
295.2 ± 30.8
282.1 ± 6.1
3.43 ± 0.07
10.3 ± 0.1
15.5 ± 0.1
11.1 ± 0.1
19.1 ± 0.1
73.8 ± 5.0
100.2 ± 5.2
196.5 ± 4.4
196.3 ± 12.9
101.1 ± 8.7
(d) 20% glycerol
103 [6b] (M)
pH
7.5
8c
0.0
0.5
1.0
1.5
2.0
2.5
3.0
0.51 ± 0.01
147 ± 1
294 ± 11
375 ± 13
451 ± 19
486 ± 4
147.2 ± 12.3
235.7 ± 10.9
272.2 ± 3.9
276.9 ± 3.6
295.6 ± 8.6
300.0 ± 9.5
434 ± 4
(e) 20% ethylene glycol
103 [6b] (M)
pH 8.5d
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
0.44 ± 0.02
192.1 ± 8.0
380.7 ± 6.0
500.8 ± 8.4
671.7 ± 28.6e
693.6 ± 2.0
741.9 ± 13.7
675.4 ± 31.5
apH measured by electrode immersed in solution and not corrected for added cosolvent; [7] = 5 × 10–5 M.
bpH 9; 33.3% EtOH.
cMaximum activity at pH 8; insoluble below pH 7 and above pH 8.5.
dAt pH optimum for this medium.
eAt pH 8.0, same conditions, kobs = 456 ± 19 s–1.
© 1999 NRC Canada

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Can. J. Chem. Vol. 77, 1999
Table 3. Pseudo-first-order rate constants, 105kobs (s–1), for the decomposition of 7 in the presence of 6c in the presence of various
solvents, T = 25°C.a
103[6c] (M)
50% EtOHb
33% EtOHb
33% DMEb
33% ethylene glycolb
20% gycerolc
0.0
0.5
1.0
1.5
2.0
2.5
3.0
0.16 ± 0.01
0.34 ± 0.01
0.36 ± 0.01
0.40 ± 0.01
0.46 ± 0.01
0.33 ± 0.02
1.82 ± 0.11
6.38 ± 0.23
10.4 ± 0.3
13.3 ± 0.3
0.41 ± 0.01
7.58 ± 0.49
12.9 ± 0.5
18.8 ± 1.0
25.6 ± 1.0
3.64 ± 0.02
15.3 ± 0.1
48.1 ± 0.3
77.6 ± 0.7
87.4 ± 0.6
73.4 ± 3.9
99.6 ± 14.8
122.3 ± 16.3
109.1 ± 7.8
120.7 ± 4.9
142.6 ± 8.6
apH measured by electrode immersed in solution and is uncorrected for organic cosolvent. [7] = 5 × 10–5 M.
bpH 9.
cpH 8.
as effective as PEG 400 in promoting the reactions of 6b in
glycerol media, pH 7.6–8.5 (see data in Table 4).
Fig. 1. A plot of kobs for the hydrolysis of 7 vs. [6b] in various
media at 25°C, µ = 0.3 (KCl), [buffer] = 0.01 M. (᭡, 33%
ethanol, pH 9; ᭿, 33% DME, pH 9; ᭢, 20% glycerol, pH 8; —,
20% ethylene glycol, pH 8.5.)
b. Control experiments
Under no conditions is the rate of decomposition of 7 ac-
celerated markedly by simple medium effects in the absence
of 6a–c. The N-methyl derivative, 6c, was investigated at the
pH optima found for 6b in solvents of different composition.
The data for 6c in Table 3 show similar overall trends to the
reactions with 6b, but in 20% ethylene glycol the maximum
activity of 6c is 2–4 times lower than that of 6b, indicating
that both secondary and tertiary amine are active. To investi-
gate whether a simple N-substituted β-amino alcohol would
exhibit a similar marked activity for the decomposition of 7
in 20% glycerol, the effects of 2 × 10–3 M added 2(N-methyl-
amino)ethanol and 2(N,N-dimethylamino)ethanol were in-
vestigated at pH 8.0, T = 25°C, µ = 0.3 (KCl), [7] = 5 × 10–5
M. Under these conditions 7 was only slowly hydrolyzed,
and the kinetic traces were clearly not first order. Although
it is difficult to compare kinetics of dissimilar order, an ap-
proximate measure of the reactivity is the t1/2 for appearance
of the p-nitrophenoxide anion. In the presence of 6b, 6c, and
2(N-methylamino)ethanol, the respective halftimes (pH 8,
20% glycerol) were 2.55, 10.6, and 1667 min.
1000
750
500
250
0
0
1
2
3
4
103 [6b] (M)
Shown in Fig. 1 are graphical representations of the pseudo-
first-order rate constants for the decomposition of 7 as a
function of [6b] at the optimum pH in various media. While
we have not determined the critical micelle concentration
(CMC) of any of these alcohols under the reaction condi-
tions, the appearance of the kobs vs. catalyst conc. plots with
maxima at 2.5–3 mM strongly suggests micelle formation.
For 6b, ethylene glycol gives maximum activity at pH 8.5
when at 20% v/v, while 20% glycerol gives maximum activ-
ity at pH 8.0. Increasing or decreasing the amounts of these
cosolvents leads to reduced activity, as do changes in the re-
spective media pH. Given in Table 4 are rate constants for
the reaction of 6b with 7 in media containing polyethylene
glycol (PEG 400) as a cosolvent. Up to half of the glycerol
can be replaced by PEG 400 without noticeable drop in ac-
tivity (relative to 33% glycerol), and the data show that
when mixed with glycerol in a 1:1 ratio (16.5% v/v each),
the kobs for decomposition of 7 is about the same as with
33% glycerol at pH 8. In the absence of glycerol, 33% PEG
400 accelerates the reaction with 3.12 × 10–3 M 6b by about
200-fold relative to the blank rate, while 16.5% each of
added glycerol and PEG 400 accelerates the reaction with
3.33 × 10–3 M 6b by about 400-fold. Methylated PEG 350,
with the terminal OH groups replaced by CH3O, seems to be
c. Turnover experiments
The reactions of equimolar and 1:2 stoichiometry of 6b:7
were investigated in 20% glycerol, pH 8, µ = 0.1 (KCl),
10–2 M HEPPS at 25°C where [6b] = 5 × 10–4 M. These
conditions are not optimal, since the [6b] is roughly fourfold
lower than for maximal activity. Nevertheless, they were
chosen because the rate of appearance of p-nitrophenoxide
could be monitored at 460 or 465 nm where the final
absorbance was not greater than 1, (460 nm for [7] = 5 ×
10–4 M; 465 nm for [7] = 1 × 10–3 M). Concentrations of 7
in excess of 1 × l0–3 M could not be obtained for reasons of
solubility.
Shown in Fig. 2 are the Abs. vs. time plots for the above
experiments: for Fig. 2a, [7] = [6b] = 5 × 10–4 M, while for
Fig. 2b, [7] = 1 × l0–3 M = 2[6b]. The appearance of the
plots, with the initial burst followed by nearly first-order
production of p-nitrophenoxide, is consistent with a process
involving phosphorylation of the amino alcohol to form an
intermediate that decomposes on a similar time scale to re-
generate the active amino alcohol.
© 1999 NRC Canada

Oumar-Mahamat et al.
1583
Table 4. Pseudo-first-order rate constants, 104kobs (s–1), for the decomposition of 7 by 6b in the presence of PEG 400 under various
conditions at T = 25°C, µ = 0.25 (KCl), [EPPS buffer] = 0.1 M.
16.5% glycerol, 16.5% PEG 400, 67% water
103 [6b] (M)
pH
8.0
7.6
8.5
0.0
1.0
1.25
2.50
0.378 ± 0.003
0.574 ± 0.005
48.2 ± 0.8
141.8 ± 0.7
235 ± 2
0.837 ± 0.04
35.5 ± 0.5
111.8 ± 0.9
206 ± 1
198 ± 1
25.2 ± 2a
263 ± 1
243 ± 1a
303 ± 1
3.33
4.16
337 ± 2
358 ± 1
15.5% glycerol, 61.5% water, 23.0% PEG 400
103 [6b] (M)
pH
8.0
7.6
8.5
0.0
0.77
1.54
1.92
2.31
3.08
3.85
0.243 ± 0.005
14.0 ± 0.1
68.7 ± 0.2
82.7 ± 0.3
105.3 ± 0.5
140.7 ± 0.6
159.8 ± 0.9
0.387 ± 0.009
54.3 ± 0.4
50.3 ± 0.8
92.3 ± 0.7
75.1 ± 0.5
b
b
b
0% glycerol, 67% water, 40% PEG 400
103 [6b] (M)
pH
8.0
7.6
8.5
0.0
0.332 ± 0.004
0.430 ± 0.003
16.0 ± 0.1
51.8 ± 0.8
86.7 ± 0.7
118.2 ± 0.8
0.589 ± 0.003
1.04
2.08
3.12
4.16
24.1 ± 0.1
38.4 ± 0.5
74.1 ± 0.4
b
59.6 ± 0.6
16.5% glycerol, 67% water, 16.5% MPEGc
103 [6b] (M)
pH
pH 8.7 (CHES)
pH 7.6
pH 8.0
0.0
0.302 ± 0.009
0.481 ± 0.003
56.8 ± 0.4
85.3 ± 0.3
295 ± 1
0.619 ± 0.002
53.5 ± 0.9
100.1 ± 0.9
291 ± 0.8
1.04
1.56
4.16
218 ± 1
aDetermined after allowing catalyst system to stand 24 h.
bPrecipitates.
cMethyl PEG, average MW = 350, terminal groups methylated.
A second set of turnover experiments was conducted in
the PEG containing solvents under more optimal conditions.
Given in Table 5 are the pseudo-first-order rate constants for
appearance of p-nitrophenoxide in the presence of 6b in a
solvent comprising 16.5% each of glycerol and PEG 400
and 67% water. To ensure that the reactions were done under
homogeneous conditions, aliquots of 2.5 × 10–4 M 7 in DME
were injected into the solutions and the absorbance vs. time
profiles monitored for 10t1/2. After this time, another aliquot
was added, and the process repeated. To ensure that the total
absorbance of the solution did not exceed 2.0, progressively
longer wavelengths (420–470 nm) for monitoring the reac-
tion were used. The so-obtained Abs. vs. time data were an-
alyzed to obtain the pseudo-first-order rate constants, which
are seen to be the same for a given [6b], indicating that the
catalyst must turn over during the time taken for the analy-
sis.
Discussion
The choice of these long chain secondary and tertiary
aminoethanols as potential micellar turnover catalysts for the
decomposition of phosphate esters was dictated by several
considerations including simplicity of preparation, ability to
form micelles, possession of a nucleophilic pendant, and the
requirement for turnover capabilities. From the observations
and data given in the results section, 6b possesses all of the
above properties. The most surprising aspect, to our knowl-
edge, is the marked enhancement in reactivity of 6b in me-
dia containing 20–33% ethylene glycol or glycerol. Many
© 1999 NRC Canada

1584
Can. J. Chem. Vol. 77, 1999
Table 5. Pseudo-first-order rate constants, 103kobs (s–1), for the
decomposition of 7 as a function of [6b] in 16.5% glycerol, 67%
water, 16.5% PEG 400, µ = 0.25 (KCl), T = 25°C, [EPPS
buffer] = 0.01 M, pH = 8.0.a
Fig. 2. Plots of the absorbance vs. time profiles for hydrolysis of
7 by 6b in 20% glycerol (v/v), pH 8, µ = 0.1 (KC1), [buffer] =
0.01 M at 25°C. (A) [6b] = [7] = 5 × 10–4 M; (B) [7] = 2[6b] =
10–3 M.
[6b] (M)
[DPPNPP 7] (M)
1.1 × 10–3
2.8 × 10–3
4.16 × 10–3
5 × 10–5
2.5 × 10–4
5 × 10–4
0.83 ± 0.07
0.852 ± 0.021
0.865 ± 0.025
0.835 ± 0.041
3.25 ± 0.03 3.37 ± 0.20
3.23 ± 0.18 3.65 ± 0.28
7.5 × 10–4
1 × 10–3
1.035 ± 0.068b 3.25 ± 0.28 4.35 ± 0.52b
1.5 × 10–3
2 × 10–3
2.98 ± 0.31
3.52 ± 0.48
apH measured from electrode immersed in solution and not corrected
for cosolvent.
bTurbid solutions with precipitate at end of reactions.
reactions, including carboxyl (12), phosphoryl (13), and
surfuryl (14) -group transfers are accelerated in going to less
protic and less polar mixed solvent systems (15). The sol-
vent effect generally results from either transition state (TS)
stabilization or destabilization of the ground state consisting
of nucleophile plus substrate. Poor solvation of anions in
dipolar aprotic solvents leads to very marked acceleration of
nucleophilic attack if charge is dispersed in the TS (15). Re-
cently Bunton et al. (16) have investigated the attack of HO–
and the oximate of 2,3-butanedione on PNPDPP in water–
CH3CN and water–t-BuOH solvent mixtures. They found
that the rates initially drop as the percentage of water de-
creases, but that further reductions in the water conc. led to
increases in rate. This is rationalized by an initial stabiliza-
tion of the nonionic PNPDPP followed by increasing
destabilization of the anionic nucleophile resulting from its
loss of hydration. Nevertheless, the total effects are far less
than what is observed in the present study. Some work has
been done on the effects of added DMSO on the hydrolysis
of PNPDPP in media containing co-micelles of cetyltri-
methylammonium bromide and diethylheptadecylimmidazo-
lium ethylsulphate (4r), the net effect being that as the
[DMSO] was increased to 90%, substantial increases in rates
could be achieved.
Far less work appears to have been done on the effect of
polyhydroxy additives on hydrolytic reactions (17).
Nusselder and Engberts (17a) investigated the hydrolysis of
three activated amides (1-acyl-1,2,4-triazoles) in aqueous
media containing up to 4 mol% of carbohydrates such as
maltose, glucose, and ribose. Although the effect of the ad-
ditive was to slightly decrease the overall rate of reaction,
there were substantial medium effects on the ∆S‡ of reaction
attributable to alterations in the three-dimensional H-bonded
network in water. Cleve (17b) has looked at the hydrolysis
of methyl trifluoromethylacetate in water containing alco-
hols such as butanol and found only modest effects on the
reaction rates. Notably, in neither of these studies was there
observed the sort of strong rate enhancements such as seen
in the present study using the polyol additives, but the con-
centrations studied were far lower than is the case here.
The effect of the polyhydroxy solvents on the activity of
6b toward 7 is probably not simple and likely results from a
complex mixture of phenomena including changes in the
micellar pseudophase, alteration of the pKa values and Keq
associated with 6b (Scheme 1), and hydrogen bonding by
the cosolvent in a way that may lower the TS energy for
phosphoryl group transfer from 7 to the O(H) of 6b. Alter-
natively, it is possible that the polyhydroxy alcohols or
PEGs provide the right environment to promote
micellization of 6a, b, and in their absence, no micelles are
formed, but more work would be required to sort this out. It
has been suggested that strong H bonds due to the hydroxy
functions at the polar head groups of micelles are likely to
be responsible for the binding of surfactants (4b, 8). The
polyols in our case could provide such intermolecular H
bonds, which transiently bind both the DPPNPP and 6b
thereby increasing the likelihood of productive encounters.
However, since PEG 400 without glycerol and Methyl PEG
350 with 16.5% glycerol seem to promote the reactions, al-
beit somewhat less than with only glycerol or ethylene gly-
col, the additive cannot primarily be a H bond donor.
The enhancement of reactivity is not limited to the
polyols ethylene glycol or glycerol, since 0.5 M sorbitol
((HOCH2CH(OH)CH(OH))2), pH 7.5, T = 25°C, and
2.5 mM 6b gives a pseudo-first-order rate constant for reac-
tion with 7 of 3.4 × 10–3 s–1. By way of comparison, the sys-
tem containing 20% ethylene glycol at pH 8.5 gives the
highest kobs of 7.42 × 10–3 s–1. Thus, under the optimized
conditions given in Table 2, at 3 mM added [6b], the ratio of
the catalyzed to uncatalyzed process in 20% glycerol or 20%
ethylene glycol ranges from 1000- to 1700-fold, pH 8–8.5.
Turnover
The additional point of interest in decomposition of 7 me-
diated by the micelles of 6b relates to the turnover. Shown
in Fig. 2 are absorbance vs. time plots for the reaction of 6b
with 7 under at relative concentration of 1:1 and 1:2, with
[6b] = 5 × 10–4 M in 20% glycerol (v/v), pH 8, µ = 0.1
(KC1), buffer conc. = 0.01 M at 25°C. The plots are notable
for an initial burst in the production of p-nitrophenoxide fol-
© 1999 NRC Canada

Oumar-Mahamat et al.
1585
Scheme 2.
phosphorylethanolamine from base hydrolysis of 10 (eq. [4]
(19)), the hydrolysis of which undoubtedly leads to
aminoethanol. In the latter study (19a) the behavior of 10 to-
ward base can be contrasted with that of diphenyl-
phosphorylcholine, 13, the hydrolysis of which yields
phosphorylcholine, 14 (eq. [5] (19b)).
R
N+H
O
R
N+H
O-Ar
+
(PhO)2P OAr
+
O-
OP(OPh)2
O
In an analogous process, the ability of a 2-amino group to
=
act as a neighboring group in displacing OSO3 from β-
R
(aminoethyl)hydrogensulfate in NaOH solution forms the
basis of the synthesis of aziridine (21). Finally, Lazarus and
Benkovic (22) have reported a detailed analysis of the mech-
anism of hydrolysis of phosphorylethanolamine triesters,
which reveals multiple catalytic effects of the intramolecular
amino group, one of these being analogous to the process
shown in eq. [3].
R
N
N+
R
N
HO-
H2C CH2
+
-O2P(OPh)2
OH
OP(OPh)2
O
In view of the above, we envision the catalyzed decompo-
sition of 7 by 6b to follow the mechanism depicted in
Scheme 2 where the zwitterionic form (6ZW) captures 7 to
yield p-nitrophenoxide and the O-phosphorylated 6b. Loss
of the ammonium proton generates a free β-amino group,
which is capable of an internal displacement of diphenyl
phosphate to generate the aziridine/aziridinium, which sub-
sequently reacts with OH– to regenerate 6b.
Finally, it is instructive to compare the reactivity of 6b
and other catalytic entities that have been reported to hydro-
lyze 7. Given in Table 6 are the reported maximal observed
pseudo-first-order rate constants, conditions, and t1/2 values
for hydrolysis of 7 mediated by various systems. It is clear
that the best catalysts presently available are those related to
the Moss’ iodosobenzoates in cetyltrimethylammonium mi-
celles (entries 5 (3j), 6 (3d), and 7 (6e) in Table 6) which are
about two orders of magnitude better than the functionalized
micelles. Of the remainder of the series, where a comparison
can be made, the pseudo-first-order rate constants for the
formulations reported to give maximal activity all lie within
the same order of magnitude. Also, some of the better cata-
lysts exhibit maximal activity at lower catalyst conc. than
are required for our system. The Bunton surfactant
lowed by a slower process indicative of turnover. In that set
of experiments, the [6b] was less than required for optimal
activity due to the requirement of solubility and maintaining
the final absorbance <1. In a second set of experiments us-
ing 1 × 10–3 to 4.2 × 10–3 M 6b under more solubilizing
conditions (16.5% glycerol, 67% water, 16.5% PEG 400, µ
= 0.25 (KCl), T = 25°C, EPPS buffer conc. = 0.01 M, pH =
8.0) aliquots of 2.5 × 10–4 M 7 were added, and the succes-
sive pseudo-first-order rate constants for generation of p-
nitrophenoxide were determined. From the data presented in
Table 5 it is apparent that the rates of the reactions are the
same up to the point of precipitate formation, indicating that
the catalyst must be regenerating during the time of the indi-
vidual rate experiments.
Since hydroxyethyl substituted quaternary ammonium
micellar species (5) have not been demonstrated to have
turnover capabilities other than through direct OH–-mediated
hydrolysis (4b), the action of the free β-amino group in 6b is
implicated. Our belief in the free β-amino group as a poten-
tial mediator of turnover was guided by work reported by
Heath (18), Baer (19), and Mannineu (20) detailing the reac-
tion course for the decomposition of 8 (eq. [2] (18)) and 9
(eq. [3] (20)) as well as the known inability to produce a
CH2
S
S
+
SEt
CH2SEt
O CH2
+
[2]
(CH3O)2P
(CH3O)2P
O-
CH2
8
CH2
CH2
O
S
+
N(CH3)2
CH2N(CH3)2
+
[3] (CH3O)2P
(CH3O)2P
O-
O CH2
9
Ba(OH)2
Ph
O
O
∆
H3N+CH2CH2OH
=
+
H3N CH2CH2OPO3
[4]
CH2OC NHCH2CH2OP(OAr)2
Ba(OH)2
∆
12
11
10
OH-
O
[5] (CH3)3N+CH2CH2OP(OAr)2
(CH3)3N+CH2CH2OPO3
=
14
13
© 1999 NRC Canada

1586
Can. J. Chem. Vol. 77, 1999
Table 6. Pseudo-first-order rate constants, conditions, and t1/2 values for the hydrolysis of 7
mediated by various catalysts at T = 25°C.
Catalyst (conc. M)
Conditions
20% ethylene
glycol pH 8
kobs (s-1)
t1/2 (s)
93
Reference
This work
6b (3 × 10–3)
7.42 × 10–3
6b (2.5 × 10–3)
2 (1.22 × 10–4)
20% glycerol pH 8 4.85 × 10–3
143
34.2
This work
2e
pH 8, 10 mM
2.02 × 10–2
N-ethylmorpholine
3 (8 × 10–3)
4, X = H (1 × 10–4)
4, X =
pH 9
2.0 × 10–2
34.6
10.7
0.71
4o
3j
3d
pH 8, 1 mM CTACl 6.45 × 10–2
pH 8, 0.2 mM
N+Me2(CH2)2OH
CTACl
1.14
C
16H33
(1 × 10–4)
(1 × 10– 4) pH 8
0.26
2.7
6e
O
I
0.02 M phosphate
O
5 × 10–3 M CTACl
O–
pH 9
pH 8
pH 9
8.2 × 10 –3
84.4
4g
2f
2l
C16H33N+
(3 × 10–3)
N+
CH2CHO
CH3
~4.27 × 10 –3 ~162
P
N
N
Cu++
CH3
CH3
(1 × 10–3) P = polymer
(1.6 × 10–3)
1.8 × 10–3
384
~81
O
O
O
3+
Eu
O
N
N
O
~8.5 × 10 –3
4q
R
pH 9
CH3
N
N
5 × 10–4 M CTABr
(5 × 10–4)
O
(CH2)2CNH(CH2)3Me 2N+C18H37
R=
(4.5 × 10–4)
2.4 × 10–2
~1.5
28.8
~0.5
3m
4b
O
pH 8.5, 1 mM
CTACl
C
OOH
CO2H
C16H33N+Me2(CH2)2OH 0.01 M NaOH
(2.5 × 10 –5
(pH 12)
)
(C16H33N+(CH3)2CH2CH2OH) (entry 13 (4b)) is the most
closely related to 6b structurally and seems to be very reac-
tive at pH 12, but the reactivity drops linearly with pH, so
that at pH 8 it is the least effective of all the species in the
table.
cost of the formulation, long-term stability, and low toxicity
of the components. The activity of 6b is critically dependent
on the presence of polyols and (or) PEGs in the solution.
The reasons for the marked enhancement in activity in the
presence of these additives is not clear at present but could
arise from medium effects, which favour the formation of
micelles, or from a stabilization of the transition state for re-
Conclusions
action brought about by transient
H bonding with
The above study indicates that formulations of the easily
obtained 6b in 20% ethylene glycol–H2O or glycerol–H2O at
pH 8.5 or 8, respectively, provide a micellar catalyst system
that reacts with 7, giving a rate enhancement of ~1500-fold
relative to spontaneous hydrolysis. The advantages of the
present formulations with 6b include ease of preparation,
nucleophile and PNPDPP substrate. In addition, it has been
shown that 6b is catalytic in its reaction with PNPDPP, a
phenomenon that we suggest arises from neighboring group
assistance by the
N in facilitating cleavage of the
phosphorylated intermediate. It has been stated that
© 1999 NRC Canada

Oumar-Mahamat et al.
1587
Chem. 51, 4303 (1986); (l) R.A. Moss, K.W. Alwis, and J.-S.
Shin. J. Am. Chem. Soc. 106, 2651 (1984); (m) S.
Bhattacharaya and K. Snehalatha. J. Org. Chem. 62, 2198
(1997); (n) Y.Y. Kim, K.H. Lim, and M.N. Khan. Colloids
Surf. A, 121, 239 (1997); (o) I.S. Ryzhkima, R.A.
Shaqidullina, L.A. Ismaev, and I.B. Ivanov. Izv. Akad. Nauk,
Ser. Khim. 242 (1995); Chem. Abstr. 123, 83509e (1995).
DPPNPP (7) is an attractive model for study because its
spontaneous hydrolysis is slower than that of the more nox-
ious phosphorus materials such as the nerve agents (2e, f).
One expects that any catalyst capable of facilitating the hy-
drolysis of 7 should be effective for hydrolysis of the nerve
agents. However, where direct comparison can be made, al-
though certain catalysts (e.g., 4) exhibit spectacular rate en-
hancements with 7, their reactions with sarin and soman are
somewhat less spectacular, being ~20–80-fold over the
spontaneous hydrolysis (3d). Presumably this relates to dif-
ferences in partitioning of 7 and sarin or soman between the
aqueous and micellar pseudophase in which the catalytic en-
tity resides, and TS energy differences for that reaction rela-
tive to cleavage of PNPDPP. In a given case the true test for
a decontaminant is, of course, its reaction with the more
noxious agent, and it remains to be determined how effica-
cious the 6b–polyol systems are in this respect.
4. (a) J.M. Brown, C.A. Bunton, S. Diaz, and Y. lham. J. Org.
Chem. 45, 4169 (1980); (b) C.A. Bunton and L.G. Ionescu. J.
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Bodor, R. Enever, J...Sowa, and T. I-Iiguchi. J. Org. Chem. 43,
2816 (1978); (f) C.A. Bunton, A.A. Kamego, M.J. Minch, and
J.L. Wright. J. Org. Chem. 40, 1321 (1975); (g). F.M. Menger
and R.A. Persichetti. J. Org. Chem. 52, 3451 (1987); (h) C.A.
Bunton and S. Diaz. J. Am. Chem. Soc. 98, 5663 (1976);
(i) Ch. Rav-Acha, M. Chevion, J. Katzhendler, and J. Sarel. J.
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Okahata. Bull. Chem. Soc. Jpn. 49, 540 (1976); (k) T.
Kunitake, Y. Okahata, and T. Sakamoto. J. Am. Chem. Soc.
98, 7799 (1976); R.A. Moss, R.C. Nahas, and S. Ramaswami.
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and R.C. Nahas. J. Am. Chem. Soc. 100, 5920 (1978); (n)
C.D. Gutsche and G.C. Mei. J. Am. Chem. Soc. 107, 7964
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Acknowledgement
The authors gratefully acknowledge the financial support
of the Defence Research Establishment Suffield (Supply and
Services Canada contract no. W7702-9-R144/01-XSG).
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