Synthesis and complex-forming properties of thiazolyl-containing organophosphorus complexone

Article abstract of DOI:10.1134/S1070363210060253

Alkaline hydrolysis of the previously prepared ethyl 2-methyl-2- [diethylamido-N-(4′-phenylthiazolyl-2-amido)phosphono]glycidate and 2-phenyl-2-[diethylamido-N-(4-phenylthiazolyl-2-amido)phosphono]glycidate accompanied by decarboxylation in situ of the ob

Full text of DOI:10.1134/S1070363210060253

ISSN 1070-3632, Russian Journal of General Chemistry, 2010, Vol. 80, No. 6, pp. 1196–1201. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © Sh.K. Amerkhanova, L.K. Sal’keeva, R.M. Shlyapov, E.V. Minaeva, A. S. Uali, 2010, published in Zhurnal Obshchei Khimii, 2010,
Vol. 80, No. 6, pp. 1028–1033.
Synthesis and Complex-Forming Properties
of Thiazolyl-Containing Organophosphorus Complexone
Sh. K. Amerkhanova, L. K. Sal’keeva, R. M. Shlyapov, E. V. Minaeva, and A. S. Uali
Buketov Karaganda State University, ul. Universitetskaya 28, Karaganda, 1000028 Kazakhstan
Received August 28, 2008
Abstract—Alkaline hydrolysis of the previously prepared ethyl 2-methyl-2-[diethylamido-N-(4'-
phenylthiazolyl-2-amido)phosphono]glycidate and 2-phenyl-2-[diethylamido-N-(4-phenylthiazolyl-2-amido)-
phosphono]glycidate accompanied by decarboxylation in situ of the obtained glycidic acids furnished 2-[diethyl-
amido-(4'-phenylthiazolyl-2'-amido)phosphono]propionic and 2-phenyl-2-[diethylamido-(4'-phenylthiazolyl-2'-
amido)phosphono]acetic aldehydes. The qualitative and quantitative evaluation of complex-forming ability of
the compounds obtained with respect to transition metal ions was carried out. For identification of copper
complex the evaluation of the stability constants of copper, cobalt, nickel, and zinc complexes was performed.
Thermodynamic parameters of complex formation reactions were calculated. Correlation dependences between
the physicochemical properties of metal ions and thermodynamic characteristics of complex formation with the
organophosphorus ligands obtained were established.
DOI: 10.1134/S1070363210060253
Ph
Investigation of complex formation between various
organic substances and metal ions has attained a new
N
H
+
level. Its determining characteristic is the poly-
functionality or universality of organic substance, in
particular, the relationship between the reactivity and
biological activity, and between thermodynamic
stability and the degree of binding of metal ions
provides also for the practical use of these compounds.
Hence, for realizing deep processes of biological and
ecological character the structural as well as the energy
features of various systems must be considered.
NH2
O
S
Ph
N
N
CH
S
I
use. The necessity of development the broad range of
complexones with the wide variety of complex-
forming properties at different pH values, in particular,
for the medicinal purpose remains the promising field
of investigation up to now [10].
Analysis of the published data [1–5] shows that the
presence of phosphorus, nitrogen, and sulfur atoms in
the molecules of organic compounds provides them
with a high physiological activity and often decreases
the toxicity. Such compounds exhibiting the bron-
cholytic, antiviral, antiphlogistic, antitumor, and some
other activity are effective drugs. Besides, compounds
of thiazole series are widely used in industry and
agriculture [6, 7]. In [8, 9] compounds were syn-
thesized inhibiting the growth of Helminthosporium
oryzae, for example substance I, and also some
substances possessing the complex-forming properties.
One of the current directions of investigation of the
organophosphorus complexones is the reaction of
derivatives of the trivalent phosphorus acids with
different electrophilic reagents. Reactions of estero-
amidites of P(III) acids with carbonyl compounds are
sufficiently thoroughly studied. It is established that
their pathway depends on the structure of starting
substances [11, 12]. Salkeeva et al. [13,14] showed
that phosphonate III prepared by the reaction of tert-
butyl tetraethyldiamidite II with 2,4-hydroxybenzalde-
hyde was capable of complex formation with different
metal cations.
As is known, the complexone chemistry opens
practically inexhaustible possibilities of modifying the
properties of cations creating wide potential for their
1196

SYNTHESIS AND COMPLEX-FORMING PROPERTIES OF THIAZOLYL-CONTAINING
OH
1197
O
P
OH
CH
Et2N
Δ
O
PhH,
+ (Et2N)2POBu-t
C
OH
HO
_Me2C=CH2
H
Et2N
HO
II
III
On the other hand, phosphite II reacts with Schiff
base IV prepared from 2-amino-4-phenylthiazole to
give phosphonate V which can be further converted
into product VI.
Ph
HO
Ph
HO
(Et2N)2POBu-t
N
N
PhH, Δ
N
CH
NH CH
OH
OH
_Me2C=CH2
S
S
P
Et2N
O
NEt2
V
IV
NEt2
O
O
Ph
P
N
PhH, Δ
_Et2NH
H
N
CH
OH
S
VI
Meanwhile, the reported data show that the number
of organophosphorus compounds exhibiting high
complex-forming properties with respect to metal ions
is not large. That is why the development of organo-
phosphorus complexones on the basis of 2-amino-4-
phenylthiazole is topical. The transamidation of phos-
phorotriamidite VII with 2-amino-4-phenylthiazole
followed by treating with tert-butanol and acid hyd-
rolysis of the reaction products VIII, IX yielded the
phosphonic acid X [14].
Synthetic potential of the amidophosphite VIII is
determined also by the possibility of its transformation
in the pentavalent phosphorus derivatives, as we
confirmed by an example of the reaction of compound
VIII with sulfur in the benzene suspension to form
product XI.
Structures of the compounds III, VI, VIII, X permit
to expect the complex-forming properties due to the
presence of phosphoryl group, of nitrogen atom, and of
hydroxy group.
Ph
N
Ph
N
NEt2
NEt2
AcOEt, Δ
+ (Et2N)3P
NH P
NH2
_2Et2NH
S
S
VII
VIII
Ph
Ph
O
N
N
H2O, H+
OBu-t
OBu-t
OH
OH
2 t-BuOH
NH
P
NH
P
_2Et2NH
Δ
S
S
IX
X
Ph
Ph
S
P
N
N
NEt2
NEt2
NEt2
NEt2
S, Δ
NH P
NH
XI
PhH
S
S
VIII
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 80 No. 6 2010

1198
AMERKHANOVA et al.
β-Dicarbonyl compounds capable of keto-enol tauto-
XIII [15] by alkaline hydrolysis accompanied by de-
carboxylation in situ of the corresponding phosphory-
lared glycidic acids. The established experimental con-
ditions require no additional and intermediate stages of
isolation and treatment significantly simplifying the
procedure. The phosphorylated aldehydes obtained
may find wide practical use [16].
merizm are good complex-forming agents. α-Phos-
phorylated aldehydes can be regarded as their hetero-
analogs.
Two representatives of phosphorylated aldehydes
XIV, XV we synthesized from the glycidyl esters XII,
Ph
Ph
O
P
R
C
O
R
N
N
O
KOHaq. sol., Δ
_K2CO3
_EtOH
NH
NH P CH
NEt2
C
CH COOEt
S
S
H
O
Et2N
XII, XIII
XIV, XV
R = CH3 (XII, XIV), Ph (XIII, XV).
Compounds XIV, XV are capable of enolization
and may be used as the effective complex-forming
agents analogously to β-diketones. It was confirmed by
our studies of thermodynamic parameters of complex
formation of some compounds synthesized. We
believe that the formation of complexes XVI, XVII
proceeds according to the following scheme.
Ph
ability of phosphorylated aldehyde XIV with respect to
the transition metal ions was studied. On the basis of
potentiometric titration in water–ethanol medium
stability constants of d-metal ions were evaluated (see
the table).
According to the data presented in [17] for the
binary solvents in the first solvate shell of the ion the
component prevails whose variation in Gibbs energy
during the solvation has the more negative value.
Therewith the near solvation shell is involved in the
complex formation. Comparative analysis of Gibbs
energies of hydration for metal ions shows that copper
ions are most hydrated, Hence, specific solvation is
characteristic of them what leads to low values of the
stability constants of complexes. On the other hand,
the behavior of ions in solution depends on their
geometric characteristics, in particular, on the ion
radius, and hence on the value of the hydration entropy
(–ΔH0, J mol–1 K–1) [18]. Considering the specific
behavior of copper(II) ions in water solution we present
here the values for the rest of ions (J mol–1 K–1): 277.2
(Ni2+), 244.9 (Zn2+), 257.6 (Co2+). This means that
nickel ion exhibits the largest structurizing effect on
water molecules, while for zinc ions the smallest
action on the molecules of solvent in the nearest
hydrate shell is characteristic. Comparative analysis of
data on the hydration entropy and the stability
constants (see the table) shows that the increase in the
absolute value of the hydration entropy leads to
decrease in the stability of complexes of d-metal ions
with the organic component. That means that the
degree of structurization of solvent affects significantly
the process of complex formation in solution.
N
O
R
O
NH
P
CH
C
S
H
Et2N
XIV, XV
EtOH_PhH, 50:50
Cu(CH3COO)2
R
Ph
Et2N
N
CH
_
P
CH
O
NH
2+
S
O
Cu
_
O
O
Ph
NEt2
N
HC
CH
P
NH
S
R
XVI, XVII
R = CH3 (XVI), Ph (XVII).
Note that the compounds synthesized may be used
for evaluation of metal ions in different media. In this
case the quantitative characteristics of complex forma-
tion are important. That is why complex forming
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 80 No. 6 2010

SYNTHESIS AND COMPLEX-FORMING PROPERTIES OF THIAZOLYL-CONTAINING
1199
Stability constants of metal ion complexes with 2-[diethyl-
amido-(4-phenylthiazolyl-2'-amido)phosphono]propionic
aldehyde in water–ethanol media
Considering the effect of temperature on the
reaction of metal ions with the organic ligand it must
be noted that at 313 K the stability of complexes
decreases in the series Ni2+ > Zn2+ > Co2+, while at 318 K)
this dependence is reversed. The above-presented data
show that the enthalpy contribution to the Gibbs
hydration energy prevails. In the first case the decrease
in the hydration enthalpy, and hence in energy of the
bond between the metal ion and the molecules of
solvent leads to the increase in the hydrate number
[19]. For large ions (Zn2+, Cu2+) this effect reveals in
the largest degree and is reflected in the stability
constants (Δlog K = log K313 – log K318 = –0.13 and
–0.09, respectively) while for Co2+ (Δlog K = –0.02).
In the second case the increase in the stability
constants for Co2+ and their decrease for Zn2+ and Ni2+
ions is caused by variation in the composition of
water–organic solvent, in particular, in the decrease in
the ethanol fraction.
298 K
303 K
308 K
313 K
M2+
log β
Co
Ni
9.02
8.19
0.56
9.33
9.39
9.01
0.46
9.79
9.32
9.71
0.37
9.66
11.00
6.79
0.28
9.17
Cu
Zn
Hence, the investigation of complex formation
between d-metal ions and the organic component in
water–ethanol media showed that linear dependences
between the stability constants of complexes and the
hydration enthalpy and entropy takes place. From the
thermodynamic data on complex formation it follows
that the structurization degree of solvent affects
significantly the process of complex formation in solu-
tion. At high temperatures it leads to increase in the
hydrate number. From the other point of view the
above-mentioned effects are caused also by the
specific features of electronic structure of the complex-
forming metal ion which are revealed in variation of
intensity of the electrostatic field of ion and reflected
in the overall dipole moment of the forming complex.
In this connection the consideration of the above-
presented effects from the thermodynamic point of
view seemed interesting. Therefore on the basis of
temperature dependence of the stability constants of
complexes we have calculated variations in the en-
thalpy contribution in the Gibbs energy (see the figure).
It was established that for nickel(II) and zinc(II) the
increase in temperature favors the increase in heat
evolution of the process meaning that the formation of
more stable complex is accompanied by variation in
the solvate surrounding, in particular, by elimination of
water molecules from the first and the second hydrate
shell of complex-forming metal. But at high tem-
peratures together with the above-mentioned variations
in heat evolution the decrease in the stability of
complexes is observed. On the one hand, it is
connected with the destruction of the solvate shell of
metal ion and binding of the greater amount of water
molecules, and on the other hand, with substitution of
water molecules in the freshly formed solvate shell of
metal by the molecules of ligand. For copper ions no
significant variations in enthalpy value take place
caused by the composition stability of the complex. In
contrast, the formation of cobalt(II) complexes is
accompanied by an increase in the heat absorption due
to the formation of associates between the molecules
of water and ethanol. Thus a stabilization of complex
with solvent takes place. This fact is connected with
weaker electrostatic field created by Co2+ ion
providing the delocalization of electronic density.
EXPERIMENTAL
IR spectra of the compounds synthesized were
recorded on a Nicolet Avatar-360 spectrometer in KBr
1
pellets (measurement error 0.2 cm–1). H NMR spectra
were taken on a Bruker DRX-500 spectrometer
(500 MHz) in DMSO-d6 against internal TMS
ΔrH0, kJ mol–1
1000
0
4
3
–1000
–2000
–3000
2
1
295
300
305
310
315
T, K
Dependence of enthalpy of complex formation of d-metal
ions with 2-[diethylamido-(4-phenylthiazolyl-2-amido)-
phosphono]propionic aldehyde on temperature. (1) Ni2+,
(2) Zn2+, (3) Cu2+, and (4) Co2+.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 80 No. 6 2010

1200
AMERKHANOVA et al.
(measurement accuracy ±0.1–0.2 ppm). Melting points
were evaluated on a Boetius apparatus (experimental
error ±0.1°C).
(CH3–CH2, 4H), 7.82 s (NH, 1H), 7.15 s (thiazole,
C5H), 8.57 s (CH=O). Found, %: C 54.56, H 6.67, N
11.45, P 8.94, S 9.42. M 351. C16H22N3PS. Calculated,
%: C 54.70, H 6.27, N 11.97, P 8.83, S 9.12.
The reaction progress and individuality of
compounds were controlled by TLC on the standard
Silufol UV-254 plates, elution with 6:1 benzene–
ethanol. Chromatograms were developed by iodine vapor.
Potentiometric studies of complex-forming pro-
perties of aldehyde XIV. Cobalt(II), nickel(II), zinc
(II) chlorides, and copper(II) sulfate of “chemically
pure” grade were used. All the substances were
dissolved in 1:1 water–ethanol mixture. Reaction of
aldehyde XIV with d-metal cations was studied
potentiometrically at 298–313 K with 5 K step by
means of Cu2S and FeS2 electrodes. Their selectivity
with respect to the transition metal ions was evaluated
in [20]. Silver chloride reference electrode was used,
and the electromotive force measurements were
performed on an I-500 pH-meter–millivoltmeter.
Potentiometric titration of 0.001 M solutions of d-
metal salts with 0.001 M solution of 2-[diethylamido-
(4'-phenylthiazolyl-2'-amido)phosphono]propionic
aldehyde was carried out according to the procedure
[20]. The temperature of the titrated mixture was
maintained by means of the UTU-2/77 thermostate
with the accuracy ±0.1 K.
Ethyl 2-methyl-2-[diethylamido-N-(4'-phenylthia-
zolyl-2'-amido)phosphono]glycidylate (XII). A solu-
tion of sodium ethylate was prepared from 0.3 mol of
sodium and 300 ml of anhydrous ethanol in a three-
neck flask equipped with a reflux condenser, a
dropping funnel, and a stirrer. After the complete dis-
solution of sodium a mixture of 3.67 g of ethyl chloro-
acetate and 6.74 g of diethylamido-N-(4'phenylthia-
zolyl-2-amido)acetylphosphonate III was added drop-
wise with stirring and cooling with the ice water. After
the reaction was complete (TLC control) the mixture
obtained was left overnight at room temperature,
neutralized with the equimolar amount of acetic acid,
and poured in 100 ml of the ice water. Water layer was
several times extracted with ether, ether extracts were
several times washed with water and dried over
sodium sulfate. The solvent was distilled off, and the
residue was crystallized from ethanol. Yield of
compound XII 6.34 g (75%), mp 202–203°C. IR spec-
trum, ν, cm–1: 1749 (COO), 1483 (C=N), 1205 (P=O),
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