A kinetic study of competing fragmentation and hydrolyses of phenyl hydrogen α-hydroxyiminobenzylphosphonate - A case of acid mediated inhibition of acid catalysis

Article abstract of DOI:10.1039/b010152o

The behavior of phenyl hydrogen α-hydroxyiminobenzylphosphonate (E)-2 in aqueous hydrochloric acid solution was examined by ³¹P NMR spectroscopy and by HPLC. Compound (E)-2 was found to undergo two competing acid-catalyzed reactions. 1) Fragmentation to phenyl phosphate (6) and benzonitrile, similar to the fragmentation of other hydroxyiminophosphonates to metaphosphate examined previously. The fragmentation of (E)-2 was found to be slower by a factor of 4 than that of hydrogen methyl α-hydroxyiminobenzylphosphonate ((E)-1). This phenomenon is interpreted in terms of inductive effects on the suggested metaphosphate intermediate. 2) Compound (E)-2 was found to undergo hydrolytic cleavage of the oxime group giving NH₂OH and hydrogen phenyl benzoylphosphonate (4), which was found to hydrolyze to phenol and benzoylphosphonic acid (5). The latter reacted with the NH₂OH liberated in the previous step to give α-hydroxyiminobenzylphosphonic acid ((E)-3), which fragmented to benzonitrile and phosphoric acid. The rate of a possible hydrolysis of the phenol group in oxime (E)-2 was shown to be slower by two orders of magnitude than that from ketone 4. This phenomenon is interpreted in terms of acid mediated retardation of acid catalyzed hydrolysis of phenol due to initial protonation of the oxime nitrogen in (E)-2.

Full text of DOI:10.1039/b010152o

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A kinetic study of competing fragmentation and hydrolyses
of phenyl hydrogen ꢀ-hydroxyiminobenzylphosphonate—
a case of acid mediated inhibition of acid catalysis
2
Rachel Ta-Shma, Hava Schneider, Mahmoud Mahajna, Jehoshua Katzhendler†
and Eli Breuer*†
Department of Medicinal Chemistry, The School of Pharmacy,
The Hebrew University of Jerusalem, Jerusalem, P. O. Box 12065, 91120 Israel.
E-mail: breuer@cc.huji.ac.il; Fax: 972-2-675-8934; Tel: 972-2-675-8704
Received (in Cambridge, UK) 14th December 2000, Accepted 29th May 2001
First published as an Advance Article on the web 19th June 2001
The behavior of phenyl hydrogen α-hydroxyiminobenzylphosphonate (E)-2 in aqueous hydrochloric acid solution
31
was examined by P NMR spectroscopy and by HPLC. Compound (E)-2 was found to undergo two competing
acid-catalyzed reactions. 1) Fragmentation to phenyl phosphate (6) and benzonitrile, similar to the fragmentation
of other hydroxyiminophosphonates to metaphosphate examined previously. The fragmentation of (E)-2 was
found to be slower by a factor of 4 than that of hydrogen methyl α-hydroxyiminobenzylphosphonate ((E)-1). This
phenomenon is interpreted in terms of inductive effects on the suggested metaphosphate intermediate. 2) Compound
(
E)-2 was found to undergo hydrolytic cleavage of the oxime group giving NH OH and hydrogen phenyl benzoyl-
2
phosphonate (4), which was found to hydrolyze to phenol and benzoylphosphonic acid (5). The latter reacted with
the NH OH liberated in the previous step to give α-hydroxyiminobenzylphosphonic acid ((E)-3), which fragmented
2
to benzonitrile and phosphoric acid. The rate of a possible hydrolysis of the phenol group in oxime (E)-2 was shown
to be slower by two orders of magnitude than that from ketone 4. This phenomenon is interpreted in terms of acid
mediated retardation of acid catalyzed hydrolysis of phenol due to initial protonation of the oxime nitrogen in (E)-2.
Introduction
depends considerably on the inductive effect of the esterifying
R groups (e.g. Breuer and Mahajna ), we considered it of
interest to subject hydrogen phenyl α-hydroxyiminobenzylphos-
phonate ((E)-2) to a careful kinetic study.
7
In previous reports from our laboratory, we have shown that a
variety of α-hydroxyiminophosphonic acid derivatives undergo
fragmentation and are capable of performing phosphorylation
1–9
of hydroxy compounds (Scheme 1). Recently we published a
Results and discussion
Hydrogen phenyl α-hydroxyiminobenzylphosphonate ((E)-2)
was synthesized by the reaction sequence shown in Scheme 2.
Scheme 1
detailed kinetic investigation of the fragmentation of methyl
hydrogen α-hydroxyiminobenzylphosphonate ((E)-1) and some
of its derivatives in water and in mixed alcohol–water solutions
Scheme 2
10
under acidic conditions. The results were compatible with a
dissociative mechanism (D *AN or D ϩ A ). The thermo-
N
N
N
Arbuzov reaction of benzoyl chloride with diethyl phenyl
phosphite gave ethyl phenyl benzoylphosphonate, which was
de-ethylated by treatment with NaI in acetone to phenyl sodium
benzoylphosphonate. The latter was treated with hydroxyl-
amine to yield sodium phenyl α-hydroxyiminobenzylphos-
phonate. This salt served as a stable precursor to hydrogen
phenyl α-hydroxyiminobenzylphosphonate ((E)-2).
It soon became clear that the behavior of (E)-2 is much more
complex than that of the corresponding methyl derivative (E)-
dynamics, and especially the different solvent effects on the
fragmentation rate, on the one hand, and on the products on
the other, indicated that the rate limiting step and the product
determining step do not share a common transition state, and
that the reaction coordinate includes at least one reactive
intermediate, probably methyl metaphosphate (Scheme 1).
Since our previous, synthetically oriented work showed that
the propensity of α-hydroxyiminophosphonates to fragment
11
1
. While the latter gave in aqueous HCl only methyl dihydrogen
10
†
Affiliated with the David R. Bloom Center for Pharmacy.
phosphate and benzonitrile, examination of a solution of (E)-
1
404
J. Chem. Soc., Perkin Trans. 2, 2001, 1404–1407
This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b010152o

View Article Online
31
2
by P NMR spectroscopy after 5 days in 1 M HCl at room
temperature, showed the presence of two final products: phenyl
phosphate (6) and phosphoric acid. The HPLC chromatogram
of the reaction mixture showed the presence of phenol in add-
ition to the expected 6 and benzonitrile. We ascertained that
under the same conditions and time span, 6 does not hydrolyze
noticeably to phenol and phosphoric acid. Monitoring (E)-2 in
31
1
M HCl by P NMR spectroscopy revealed after 5 and 19
hours the presence of small amounts (<20%) of three transient
products. Two of them were identified by comparing their
chemical shifts to those of authentic samples, as phenyl ben-
zoylphosphonate (4, δ = Ϫ4.0 ppm) and benzoylphosphonic
P
acid (5, δ = Ϫ1.7 ppm). The chemical shift (δ = Ϫ2.6 ppm) of
P
P
the third one (<5%) is consistent with that of the isomer (Z)-2
see Experimental section). In a separate experiment 4 was
shown by NMR and HPLC to hydrolyze relatively quickly in
M HCl to 5 and phenol, while in the presence of an equivalent
(
1
ϩ
Ϫ
amount of NH OH Cl it fragmented to benzonitrile, phenyl
phosphate (6), phosphoric acid and phenol as final products.
3
Fig. 1 Formation of benzonitrile from the reaction of 5 with NH OH
2
12
ϩ
Ϫ
in 1 M HCl at 35 ЊC. Upper line: [5] = 24 mM, [NH OH Cl ] = 26.6
3
ϩ
Ϫ
Scheme 3 shows three feasible acid catalyzed reaction paths
mM. Lower line: [5] = 12 mM, [NH OH Cl ] = 13.3 mM.
3
Fig. 2 Intermediates and products from the fragmentation and
hydrolysis of (E)-2 (33.4 mM) in 1 M HCl at 35 ЊC. (E)-2 –᭿–; 6 –᭜–;
H PO –ꢀ–; 4 –᭝–; 5 –ᮀ–.
3
4
Scheme 3
ϩ
Ϫ
from near equivalent amounts of 5 and NH OH Cl in 1 M
3
for (E)-2. These are: a) fragmentation of (E)-2 to phenyl phos-
phate (6) and benzonitrile; b) hydrolysis of (E)-2 to phenol and
HCl at 35 ЊC (Fig. 1). The time–concentration data for two
initial concentration sets were analyzed using the non-linear
18
(
E)-α-hydroxyiminobenzylphosphonic acid ((E)-3), which in
least squares regression program Dynafit and gave k =
6
Ϫ1 6 Ϫ1 Ϫ1
turn fragments to benzonitrile and phosphoric acid; and c) an
0.0067 ± 0.014 min and kϪ6 = (4.9 ± 1) × 10 M min . The
equilibrium formation of NH OH and hydrogen phenyl
benzoylphosphonate, 4, which can subsequently hydrolyze to
phenol and benzoylphosphonic acid, 5, which in turn can then
latter constant was corrected for the concentration of free
2
ϩ
ϩ
NH OH using the relation [NH OH] = K [NH OH ] / [H ] and
2 2 a 3
Ϫ7 ϩ
K = 6.8 × 10 for NH OH at 25 ЊC and ionic strength of 0.5
a
3
19
react with NH OH liberated in the previous step to give the
M. The error range in k is uncomfortably large; however, this
2
6
oxime (E)-3. The latter could not be observed by NMR due to
value decisively gave the best fit to the experimental data, as
judged by mean square and standard deviation values. The
calculated equilibrium constant for the oxime 3 formation is
15
its relatively fast fragmentation (vide infra). The noteworthy
phenomena here are: a) the noticeable hydrolysis of the oxime
group in (E)-2; and b) the fact that although the free hydroxyl-
amine concentration formed from the above hydrolysis is neces-
8
19
6
k /k = 7.3 × 10 M. Reimann and Jencks obtained 2.3 × 10
Ϫ6
Ϫ1
6
Ϫ1
M
min for the rate of formation of oxime from p-chloro-
7
Ϫ8
sarily very low in 1 M HCl (<2 × 10 M when (E)-2 is 0.03 M),
benzaldehyde and 6.1 × 10 M for the equilibrium constant in 1
M HCl and 25 ЊC, and more recently Malpica et al. observed
5 × 10 M min for the rate of formation of oxime from p-tri-
methylammoniobenzaldehyde iodide and from p-dimethyl-
aminobenzaldehyde and 1.8 × 10
acid, all in 1 M HCl and at 30 ЊC.
it is sufficient to ensure the complete formation of the oximes 2
and 3 from the ketones 4 and 5, and their subsequent fragment-
ation over the reaction time course. For clarity, Scheme 3 does
not include the isomerization of oximes (E)-2 and (E)-3 to their
geometrical isomers (Z)-2 and (Z)-3 either directly, or through
6
Ϫ1
Ϫ1
7
Ϫ1
Ϫ1
M
min from pyruvic
2
0,21
Our values for 5 are
16
the ketones 4 and 5.
therefore quite in line with relevant literature data.
31
In order to validate Scheme 3 and unravel the various rate
constants in 1 M HCl at 35 ЊC (a temperature convenient for
NMR analysis), we worked in steps. The rate constant for the
Next, we monitored by P NMR spectroscopy the changes
in the concentrations of (E)-2, 4–6 and H PO in 1 M HCl
3
4
at 35 ЊC. The results are presented in Fig. 2. We again used
fragmentation of (E)-3 (k ) at 1 M HCl and 35 ЊC could be
the Dynafit regression program with fixed values for k , k6
2
2
interpolated from measured values at other temperatures and
and kϪ6 (stated above). We obtained the following values:
Ϫ1 17
Ϫ1
Ϫ1
was found to be 0.073 min . Therefore, we first found k and
k1 = 0.00014 ± 0.00013 min , k = 0.0049 ± 0.0001 min ,
3
Ϫ1 6 Ϫ1 Ϫ1
6
kϪ6 by monitoring through HPLC the formation of benzonitrile
k = 0.0047 ± 0.0006 min , k = (2.6 ± 0.7) × 10 M min
4 Ϫ4
J. Chem. Soc., Perkin Trans. 2, 2001, 1404–1407
1405

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Fig. 4 Fragmentation products from reaction of 4 (8.4 mM) with
ϩ
Ϫ
NH OH ([NH OH Cl ] = 8.7 mM) in 1 M HCl at 35 ЊC. Benzonitrile –
Fig. 3 Fragmentation products from (E)-2 (3.67 mM) in 1 M HCl at
2
2
᭿
–; phenol –ꢀ–.
3
5 ЊC. Benzonitrile –᭿–; phenol –ꢀ–.
Ϫ1
PhOH (45% in Fig. 3) because the necessarily lower [NH OH]
favors the 4 → 5 reaction at the expense of the reverse reac-
and k = 0.0072 ± 0.0008 min . Rate constant k was cor-
2
5
Ϫ4
rected (like kϪ6 above) for the concentration of the free
NH OH. Both k and k are similar to k and k and the
equilibrium constant for the oxime (E)-3 formation (5.6 × 10
M ) is identical, within error limits, to that of (E)-2. The
hydrolysis step 4 → 5 was measured separately through HPLC
tion, 4 ϩ NH OH → (E)-2.
2
2
4
Ϫ4
6
Ϫ6
8
The question arises, why was no sign to such multiple
10
Ϫ1
reaction pathways observed in the fragmentation of (E)-1?
One obvious reason is that methanol is a much worse leaving
group than phenol, therefore in the case of (E)-1 a reaction
Ϫ1
in 1 M HCl at 35 ЊC and gave k = 0.0051 ± 0.001 min , which
5
analogous to the hydrolysis 4 → 5, ending in H PO4 form-
is not far from the value found by the Dynafit program from the
NMR results.
The numeric results found for k and k mean that the acid
catalyzed hydrolysis of phenyl hydrogen α-hydroxyiminobenzyl-
phosphonate ((E)-2) (k ) is slower by around 2 orders of mag-
nitude relative to the hydrolysis of phenyl benzoylphosphonate
4) (k ). This is also apparent from Fig. 2, which shows that
H PO formation has a long lag period and starts appearing
only after meaningful concentrations of 5 have been reached,
testifying that 5 is the main precursor of H PO . It seems
reasonable to assume that the hydrolysis of the phenol from
both phenyl esters requires protonation of a phosphorus
oxygen in the first step. From estimated pK values available in
the literature for the C᎐O and P᎐O groups and of the oxime
nitrogen (Ϫ7.2, Ϫ0.5 and 1.5, respectively ), it follows that in
the protonation of the P᎐O oxygen will take precedence over
the C᎐O, while in (E)-2 the oxime nitrogen will be protonated
first, and thus retard the second protonation on the phosphoryl
group, and the subsequent attack by water. This may be
regarded as a case of an acid mediated inhibition of acid
3
ation, would not be expected. However, we should expect
equilibrium formation of the ketone, PhCOPO(OH)OMe.
1
5
Assuming that k and k are similar for (E)-1 and (E)-2 and
4
Ϫ4
18
using Dynafit we can calculate that in the concentration
range used for NMR analysis in the case of (E)-1 (around 0.04
1
10
M), we should expect to see a maximum of 0.0048 M (12%)
of the ketone after 70 min but only an easily unnoticeable
(
5
3
4
0
.002 M (5%) after 5 hours when the reaction was actually
checked.
3
4
10
Extrapolating from values at other temperatures, we find
that in 1 M HCl the fragmentation rate of (E)-1 is 0.020 min ,
Ϫ1
22
namely 4 fold higher than k for (E)-2. This suggests that the
3
a
fragmentation of (E)-2 proceeds by a dissociative mechanism,
᎐
᎐
10
23
similar to the case of (E)-1, and leads to phenyl metaphos-
phate, whose formation should be less favored than that of
methyl metaphosphate due to inductive effects. An oxime
similar to (E)-1 in which the methoxy group was replaced by
the powerful electron withdrawing 2,2,2-trifluoroethoxy group
fragmented in 0.6 M HCl in ethanol, at least 10 times slower
4
᎐
᎐
3,7
24
than (E)-1. In summary, our results show a multifunctional
molecule, (E)-2, which in acidic solution undergoes two com-
peting reactions, fragmentation to metaphosphate and oxime to
ketone hydrolysis. Both originate from the oxime-protonated
species and are accelerated by acid, while a third reaction, the
hydrolysis of the O-phenyl group, is apparently retarded by the
protonated oxime nitrogen.
catalysis.
In order to confirm the rate constants found from the NMR
data by the non-linear program, the formation of both benzo-
nitrile and phenol from (E)-2 in 1 M HCl at 35 ЊC was moni-
tored by HPLC. Fig. 3 presents results of a representative
experiment. From this figure it can be seen that the experi-
mental points lie close to the predicted progress curves derived
from Scheme 3, and the above mentioned rate constants.
Finally, we monitored by HPLC the formation of both benzo-
nitrile and phenol from nearly equal amounts of 4 and
Experimental
ϩ
Ϫ
NH OH Cl . The results are presented in Fig. 4. Although the
3
Materials
quantitative fit between the experimental points and the calcu-
lated progress curves is not very good, they both show the same
phenomenon, namely, starting from 4 the phenol is formed
initially faster, but after 160–180 min it is overtaken by the
benzonitrile. As expected from Scheme 3, the final concen-
tration of phenol is only around two thirds of that of benzo-
nitrile, which equals the initial concentration of (E)-2. Still,
more phenol is formed when starting from 4 and NH OH Cl
than when starting from (E)-2 (compare Figs. 4 and 2; note that
in the NMR experiment [PhOH] = [H PO ] = one third of the
Reagent grade inorganic compounds were used. Organic
reagents were purified by recrystallization or distillation.
Ethyl phenyl benzoylphosphonate. To benzoyl chloride (14 g,
0.1 mol) placed in a round bottomed flask equipped with an
addition funnel was added dropwise diethyl phenyl phosphite in
an inert atmosphere with cooling. After the addition was com-
plete, the mixture was allowed to stir at room temperature over-
ϩ
Ϫ
3
night. The product was distilled in vacuo, bp 150–155 ЊC at 0.4
3
4
1
total). In addition, when the initial concentration of (E)-2 is
mmHg. H NMR (CDCl ) 7.41 (10H, m), 4.39 (2H, m), 1.38
3
lower, we obtain, as expected, a somewhat higher percentage of
(3H, t) ppm.
1
406
J. Chem. Soc., Perkin Trans. 2, 2001, 1404–1407

View Article Online
Phenyl sodium benzoylphosphonate. Ethyl phenyl benzoyl-
phosphonate (29 g, 0.1 mol) was added to a solution of sodium
iodide (16.6 g, 0.11 mol) in dry acetone (70 ml) and the reaction
mixture stirred at ambient temperature for 24 h. The precipitate
was filtered, washed with acetone and dried under vacuum
to yield 15.6 g (55%) sodium phenyl benzoylphosphonate
10 J. Katzhendler, H. Schneider, R. Ta-Shma and E. Breuer, J. Chem.
Soc., Perkin Trans. 2, 2000, 1961.
1
1 The present route is preferred over the alternative sequence in
which the reaction of hydroxylamine precedes the nucleophilic
de-ethylation. In the latter method the yield of the oxime formation
was considerably lower, because of competing C–P bond cleavage
due to the relatively good leaving group characteristics of the ethyl
phenyl phosphonate anion.
31
sufficiently pure for the next step. P NMR (D O) 2.26 ppm (s).
2
1
2 Benzoylphosphonates are known to give readily, in water or
Anal. Calcd. for C H O PNa: C, 54.92; H, 3.52. Found, C,
13
10
4
1
3,14
alcohols, hydrates or hemiketals
that can subsequently undergo
5
4.67; H, 3.78%.
fission of the C–P bond to yield benzoic acid or esters and
H-phosphonates. The fission is base catalyzed and should be
Phenyl sodium ꢀ-hydroxyiminobenzylphosphonate. To a solu-
tion of sodium phenyl benzoylphosphonate (28.4 g, 0.1 mol)
Ϫ5
Ϫ1
negligible in 1 M HCl (a rate below 10 min can be estimated
13
from results at lower acidities ), however, some hydrate could have
was added hydroxylamine (3.9 g, prepared from NH OHؒHCl
been formed in an equilibrium process from either 4 or 5, obviously
2
by the addition of an equimolar amount of sodium methoxide
in methanol and filtration of the precipitated NaCl) and the
mixture was stirred for 72 h at ambient temperature. After
evaporation of the solvent the residue was washed with dry
in quantities too small to be observed in NMR spectra.
1
1
1
3 K. S. Narayanan and K. D. Berlin, J. Am. Chem. Soc., 1979, 101,
1
09.
4 J. Katzhendler, I. Ringel, R. Karaman, H. Zaher and E. Breuer,
J. Chem. Soc., Perkin Trans. 2, 1997, 341.
5 A preliminary communication from our laboratory reported the
fragmentation of (E)-3 to metaphosphate some years ago;
detailed account of this reaction is in preparation.
31
acetone (50 ml) and dried under vacuum. Yield 41%. P NMR
D O) 4.70 ppm (s). Anal. Calcd. for C H NO PNa: C, 52.17;
2
(
a
2
13 11
4
H, 3.68; N, 4.68. Found, C, 51.97; H, 3.65; N, 4.26%. This
sodium salt served as a stable storable precursor of (E)-2 and
was converted to it by acidification of its solution in situ.
1
6 When monitoring the reaction through NMR we observed an
additional small peak, which was assigned as (Z)-2. This amounted
to 3 ± 2% of the initial oxime concentration and persisted up to 90%
reaction. The quality of the NMR data did not permit us to reach
quantitative conclusions regarding the oxime isomerization, but the
percentage seen agrees with an E/Z equilibrium ratio of 10–20,
which is consistent with the value of 9 found for dimethyl
Kinetic measurements
Reactions were initiated by dissolving the desired amount of
the sodium salt of (E)-2 or 5, or the lithium salt of 4, with or
3
ϩ
Ϫ
α-hydroxyiminobenzylphosphonate and that of 4–7 found for the
without the desired amount of NH OH Cl , in a few milliliters
10
3
monomethyl ester.
of 1 M HCl at 35 ЊC. The reactions of (E)-2 were monitored by
1
7 H. Schneider, PhD Thesis, The Hebrew University of Jerusalem,
1999.
31
P NMR using a Varian VXR-300S instrument. All spectra
were recorded using repetition times sufficiently long for com-
plete relaxation. The relative quantities of the starting material,
intermediates, and products were determined by integrating
and normalizing the appropriate NMR signals. The chemical
shifts were measured relative to an external standard (85%
H PO ). They depended on the acidity of the solution. In 1 M
18 P. Kuzmic, Anal. Biochem., 1996, 237, 260.
1
2
2
9 J. E. Reimann and W. P. Jencks, J. Am. Chem. Soc., 1966, 88,
3
973.
0 A. Malpica, M. Calzadilla, T. C. Cordova, S. Torres and G. H.
Saulny, Int. J. Chem. Kinet., 1999, 31, 387.
1 A. Malpica, M. Calzadilla and T. Cordova, J. Phys. Org. Chem.,
2000, 13, 162.
3
4
HCl we observed the following: (E)-2 δ = 2.1, 4 δ = Ϫ4.0, 5
22 (a) A. J. Kirby and S. G. Warren, The organic chemistry of
phosphorus, Elsevier, Amsterdam, 1967, pp. 322–324; (b) E. J.
Behrman, M. J. Biallas, H. J. Brass, J. O. Edwards and M. Isaks,
J. Org. Chem., 1970, 35, 3063.
3 Arnett and coworkers (E. M. Arnett, E. J. Mitchell and T. S. S. R.
Murty, J. Am. Chem. Soc., 1974, 96, 3875) give values of Ϫ7.2 for
acetone and Ϫ0.5 for trimethylphosphine oxide. Recently, Modro
and Modro (A. M. Modro and T. A. Modro, Can. J. Chem., 1999,
P
P
δ = Ϫ1.7, 6 δ = Ϫ4.6, (Z)-2 δ = Ϫ2.6, H PO δ = 0 ppm. The
P
P
P
3
4
P
NMR peaks of 3–5 and 6 were assigned by comparison with
2,25
authentic samples.
The peak of (Z)-2 was assigned by its
2
relative chemical shift (4.7 ppm upfield from that of (E)-2) that
fits the usual differences between the geometric isomers in α-
7
,9,10,26
hydroxyiminophosphonates ∆δ = 4.3–4.8 ppm).
The reac-
ϩ Ϫ
P
7
“
7, 890) estimated that the P᎐O group is about 100-fold more
effective” in hydrogen bonding than the carbonyl group in a similar
tions of (E)-2, 4 and 5 (with or without added NH OH Cl )
3
were monitored through HPLC by using Hewlett Packard’s
HP1090 system with Diode Array, the column was a Waters
µ-bondapak RP-18, 5 mm × 30 cm, mobile phase: 40 : 60
acetonitrile–water, λ = 230 nm. The peaks of phenyl phos-
phate, phenol and benzonitrile were identified by comparing
their retention times with those of authentic samples. The
concentrations of the latter two compounds were calculated by
comparing peak areas with external standards.
molecular structure. Although there is no general linear correlation
between hydrogen bonding energies and those of protonation valid
for different functional groups, qualitatively they are related. In our
case, the proximity of the two electron withdrawing groups P᎐O and
᎐
C᎐O may be expected to result in lowering of the basicity of both.
However, since the phosphoryl is more strongly electron
withdrawing (σ* = 2.65, J. Katzhendler, I. Ringel, R. Karaman,
H. Zaher and E. Breuer, J. Chem. Soc., Perkin Trans. 2, 1997, 341)
than the carbonyl (σ* = 1.65 for the acetyl group), the basicity of the
latter should be affected more than that of the former. The pK of
a
the oxime nitrogen in acetoxime was estimated to be around 1.54
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a
forming a zwitterion, in which the ionized phosphonic group will be
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1
0
previous paper we have estimated the pK ’s of the POH group in
a
protonated (E)-1 to be around 0.6, which means that in 1 M HCl
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1
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J. Chem. Soc., Perkin Trans. 2, 2001, 1404–1407
1407