Metal ion chelates of lipophilic alkyl diazinyl ketoximes as hydrolytic catalysts

Article abstract of DOI:10.1135/cccc19991159

A series of lipophilic dodecyl hetaryl ketoximes (hetaryl = pyridin-2-yl, pyridazin-3-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrazin-2-yl as well as their methyl hetaryl homologues was synthesized and hydrolytic activity of their chelates with Co²⁺, Ni²⁺, Cu²⁺ and Zn²⁺ in a micellar matrix of hexadecyltrimethylammonium bromide or in homogeneous aqueous solutions was investigated using 4-nitrophenyl acetate, 4-nitrophenyl hexanoate and 4-nitrophenyl diphenyl phosphate as model substrates. While Co²⁺ and Cu²⁺ chelates are almost inactive, those of Ni²⁺ and Zn²⁺ exhibit considerable activity. None of the studied chelates promotes hydrolysis of the used phosphate. The effective species are chelates of the metal : ligand stoichiometry 1 : 3 and 1 : 1 with Ni²⁺ and Zn²⁺, respectively, when the ester cleavage proceeds in the micellar matrix. The 1 : 2 stoichiometry was found in aqueous solutions of Ni²⁺ and Zn²⁺ chelates of methyl ketoximes.

Full text of DOI:10.1135/cccc19991159

Metal Ion Chelates
1159
METAL ION CHELATES OF LIPOPHILIC ALKYL DIAZINYL KETOXIMES
AS HYDROLYTIC CATALYSTS
a1
a2,
a
b
Radek CIBULKA , František HAMPL *, Tomáš MARTINŮ , JiříM AZÁČ ,
c
a3
Sonja TOTEVOVÁ and František LIŠKA
a
Department of Organic Chemistry, Prague Institute of Chemical Technology, 166 28 Prague 6,
1
2
3
Czech Republic; e-mail: cibulkar@vscht.cz, hamplf@vscht.cz, liskaf@vscht.cz
Ministry of Finance of the Czech Republic, Customs Technical Laboratory, 180 00 Prague 8,
Czech Republic; e-mail: mazacj@cs.mfcr.cz
Department of Biochemistry, Prague Institute of Chemical Technology, 166 28 Prague 6,
Czech Republic; e-mail: sonja.totevova@vscht.cz
b
c
Received February 22, 1999
Accepted April 12, 1999
Dedicated to Professor Milan Kratochvíl on the occasion of his 75th birthday.
A series of lipoph ilic dodecyl h etaryl ketoxim es (h etaryl = pyridin -2-yl, pyridazin -3-yl,
pyrim idin -2-yl, pyrim idin -4-yl, pyrazin -2-yl as well as th eir m eth yl h etaryl h om ologues was
2
+
2+
2+
2+
syn th esized an d h ydrolytic activity of th eir ch elates with Co , Ni , Cu
an d Zn
in a
m icellar m atrix of h exadecyltrim eth ylam m on ium brom ide or in h om ogen eous aqueous solu-
tion s was in vestigated usin g 4-n itroph en yl acetate, 4-n itroph en yl h exan oate an d
2
+
4
-n itroph en yl diph en yl ph osph ate as m odel substrates. Wh ile Co an d Cu2+ ch elates are al-
2
+
2+
m ost in active, th ose of Ni an d Zn exh ibit con siderable activity. Non e of th e studied ch e-
lates prom otes h ydrolysis of th e used ph osph ate. Th e effective species are ch elates of th e
m etal : ligan d stoich iom etry 1 : 3 an d 1 : 1 with Ni an d Zn , respectively, wh en th e ester
cleavage proceeds in th e m icellar m atrix. Th e 1 : 2 stoich iom etry was foun d in aqueous solu-
2
+
2+
2
+
2+
tion s of Ni an d Zn ch elates of m eth yl ketoxim es.
Key w ord s: Ester cleavage; Micellar catalysis; Metallom icelles; Coordin ation ch em istry;
Diazin es; Oxim es; Pyridin es; Ch elates; Nickel; Zin c; Hydrolysis; Ph osph ates.
Tran sition m etal ion s play an im portan t role in m an y types of en zym es a,1b.
Coordin ation to m etal ion s (m ost frequen tly Zn 2+) acidifies ion izable
fun ction s (e.g. covalen tly boun d h ydroxy group or coordin ated water) in
1
1
a,1c
1a,1d
h ydrolytic en zym es such as carboxypeptidase A
, alkalin e ph osph atase
an d carbon ic an h ydrase1a th us providin g n ucleoph iles readily attackin g
electroph ilic cen tres in substrates. A great n um ber of sim ple m odels of
h ydrolytic m etalloen zym es h ave been design ed an d studied over th e
2
a–2d
years
, m an y of th em possessin g h ydroph obic m oieties in th eir m ole-
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1
160
Cibulka et al.:
cules an d utilizin g th e kin etic ben efit of m icellar catalysis2e–2j. Two m ain
goals of th ese studies h ave been claim ed: (i) better un derstan din g th e
m ech an ism of th e h ydrolytic reaction s catalyzed by m etalloen zym es, (ii)
practical application s as efficien t destroyin g of organ oph osph orus pesti-
cides an d ch em ical warfare agen ts.
3
a,3b
In our previous com m un ication s
we reported m etallom icellar cata-
2
+
lysts based on Ni com plexes of alkyl pyridin -2-yl ketoxim es (1c an d 1d ).
Hydroxyim in o groups of th ese oxim es are acidified by coordin ation to th e
m etal ion . Th erefore h igh con cen tration s of ion ized ligan ds (n ucleoph iles
readily attackin g th e ester fun ction ) are presen t in aqueous solution s even
in n eutral con dition s. Com plexes of th ese ketoxim es in com icelles with
cation ic surfactan t h exadecyltrim eth ylam m on ium brom ide (CTAB) exh ib-
ited con siderable h ydrolytic efficien cy, surprisin gly even at pH ran gin g
from 4 up to 9.
R
1
a
CH3
R
N
1b
CH3(CH2)11
CH3(CH2)7
CH (CH )
1
c
N
OH
1d
3
2 12
Th e obtain ed results stim ulated th e exten sion of our study. We specu-
lated about th e possibility of “tun in g” th e h ydrolytic efficien cy of th e
m etallocatalyst by structural ch an ges in th e ch elatin g subun it of th e ligan d
an d by em ployin g differen t tran sition m etal ion s. For th is reason , we de-
cided to syn th esize ligan ds 2–5, aza an alogues of th e ligan d 1. We expected
th at th e presen ce of an oth er n itrogen in differen t position s of th e
N
N
N
N
R
R
R
R
N
N
N
N
NOH
NOH
NOH
NOH
2
3
4
5
In the formulae 2-5:
a, R = CH
3
b, R = CH (CH )
3
2 11
h eteroarom atic rin g sh ould gen tly m odify th e coordin ation ability of th e
ligan ds an d, con sequen tly, also h ydrolytic efficien cy of th eir com plexes
with tran sition m etal ion s. In addition to lipoph ilic dodecyl diazin yl
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Metal Ion Chelates
1161
ketoxim es 2b–5b, m eth yl diazin yl ketoxim es 2a–5a were in cluded in th is
study. We expected th e h ydrolytic activity of m etal ion com plexes of th e C1
h om ologues sh ould reflect th e “in trin sic” reactivity of th e m etallocatalysts,
excludin g th e con tribution of th e m icellar catalysis. Sin ce th e len gth of th e
h ydroph obic alkyl ch ain of th e ligan ds 2a–5a was n ot iden tical with th at of
th e ligan ds 1 em ployed in our previous study3
a,3b
we also prepared dodecyl
pyridin -2-yl ketoxim e 1b in order to be able to com pare th e reactivity of all
m etallom icellar catalysts based on ligan ds 1–5.
RESULTS AND DISCUSSION
Syntheses of the Ligands 1–5
Ligan ds 2–5 were prepared by addition of a Grign ard reagen t to correspon d-
in g n itriles 6–10 followed by th e reaction of th e resultin g keton es 11–16
with h ydroxylam in e (Sch em e 1). In th is way, lipoph ilic dodecyl
pyridin -2-yl (1b), dodecyl pyridazin -3-yl (2b), dodecyl pyrim idin -2-yl (3b),
dodecyl pyrim idin -4-yl (4b) an d dodecyl pyrazin -2-yl (5b) ketoxim es as
well as m eth yl pyridazin -3-yl (2a), m eth yl pyrim idin -2-yl (3a), m eth yl
pyrim idin -4-yl (4a) an d m eth yl pyrazin -2-yl (5a) ketoxim es were prepared.
1
2
. RMgX
R
+
. H O, H
2
Hetaryl CN
-9
Hetaryl
2-5
3
. H NOH
2
NOH
6
Hetaryl
Hetaryl
R
6
7
8
9
pyridazin-3-yl
pyrimidin-2-yl
pyrimidin-4-yl
pyrazin-2-yl
2a
2b
3a
3b
pyridazin-3-yl
pyridazin-3-yl
pyrimidin-2-yl
pyrimidin-2-yl
pyrimidin-4-yl
pyrimidin-4-yl
pyrazin-2-yl
CH3
CH (CH )
CH
3
2 11
3
CH (CH )
CH
3
2 11
4
4
5
5
a
b
a
b
3
CH (CH )
CH
3
2 11
3
CH (CH )
pyrazin-2-yl
3
2 11
SCHEME 1
On ly on e set of reson an ces was observed in each of th e H an d 13C NMR
spectra of th e syn th esized ligan ds 1–5 an d th erefore all th ese ketoxim es
were assum ed to be sin gle stereoisom ers. We determ in ed th eir con figura-
tion s by m ean s of IR spectroscopy. Dilution of tetrach lorom eth an e solu-
tion s of ketoxim es 1, 2, 4 an d 5 decreased th e in ten sity of th e bridged O–H
1
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1
162
Cibulka et al.:
ban ds (m axim um at ca 3 250 cm –1) wh ile th e in ten sity of th e free O–H
–
1
ban ds (ca 3 580 cm ) in creased. Th is beh aviour in dicated th e presen ce of
in term olecular h ydrogen bon ds wh ich could be expected rath er in E th an
in Z isom ers as sh own in Fig. 1. On th e oth er h an d, dilution of tetrach loro-
m eth an e solution s of alkyl pyrim idin -2-yl ketoxim es 3a, 3b did n ot ch an ge
th e in ten sity of th e bridged O–H ban ds (com pared with oth er ban ds presen t
in th e spectrum ) th us revealin g th e Z con figuration . So far, we h ave h ad n o
idea of factors con trollin g th e con figuration of th e arisin g ketoxim es.
Preparation of Metallomicellar Catalysts
In several cases, solubilization of lipoph ilic ligan ds in water after addition
2
e–2h
of a proper tran sition m etal ion h as been reported
. Ligh t scatterin g
m eth ods revealed th e presen ce of colloidal particles (m icelles an d related
aggregates) in th e resultin g solution s. Th e aggregation h as been explain ed
by form ation of com plexes, cation ic “m etallosurfactan ts”. However, n on e
3
a,3b
of th e ligan ds 1b–5b (sim ilarly to ligan ds 1c, 1d ; refs
) was soluble in
water in th e presen ce of tran sition m etal ion s. Th erefore we h ad to prepare
aqueous solution s of th eir com plexes in m icellar m atrix of th e cation ic
surfactan t CTAB.
Th e com plex form ation was con firm ed by th e appearan ce of n ew ban ds
2
+
in UV spectra (Table I). As a con sequen ce of th eir lower stability, all Zn
com plexes were observed on ly if an excess of m etal ion was added to a solu-
2
+
tion of th e ligan d. Ni com plexes of th e lipoph ilic ligan ds 2b an d 4b ap-
2
+
peared on ly in an excess of th e m etal ion as well. Th e stoich iom etry of Zn
2
+
an d Ni com plexes was determ in ed from kin etic m easurem en ts (see be-
low). We did n ot determ in e stability con stan ts of th e com plexes in an y
case. Th e rate of th e com plex form ation was stron gly depen den t on th e
m etal ion , sim ilarly to lipoph ilic pyridin -2-yl ligan ds 1c, 1d (ref. ) an d
ligan d-surfactan ts we studied previously or to 7-(4-eth yl-1-m eth yloctyl)-
3
b
4
a
4
b
2+
quin olin -8-ol com plexes m en tion ed by Ton dre . Th us wh ile Cu com -
R
R
N
N
H
N
N
O
H
O
(
E)-ketoxime
(Z)-ketoxime
FIG. 1
Structure of ketoxim e isom ers
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Metal Ion Chelates
1163
plexes were form ed im m ediately an d Co2+ com plexes in several m in utes af-
ter an addition of th e m etal ion to buffered solution s of th e ligan ds 1b–5b
in CTAB, form ation of Ni2 com plexes was on ly com pleted in m ore th an
two h ours at pH 6.5. Th is ph en om en on was on ly observed in m icellar solu-
tion s of th e ligan ds 1b–5b; in h om ogen eous solution s of th e ligan ds 1a–5a,
th e com plexes were form ed in stan tan eously after th e addition of th e m etal
ion .
+
Kinetic Measurements
Hydrolytic activity of th e prepared m icellar an d m etallom icellar catalysts
was tested by m easurin g rate con stan ts of th e m odel substrate cleavage un -
der pseudo-first-order con dition s ([ccat] >> [csubstr]). Th is approach h as been
gen erally used in th e evaluation of th e h ydrolytic en zym e m im ics effi-
2
,3
cien cy
.
In th e first series of experim en ts, screen of th e h ydrolytic activity cover-
in g all th e prepared lipoph ilic ketoxim es 1b–5b an d th eir com plexes with
TABLE I
UV absorption m axim a of oxim es 1–5 an d th eir com plexes
λm ax, n m
Oxim e
–
Co2+
Ni2+
Cu2+
Zn 2+
1
1
2
2
3
3
4
4
5
5
aa
bb
aa
bb
aa
bb
aa
bb
aa
bb
232, 272
242, 270
240
266, 340
292, 320 sh
278, 340
254 sh
318
278, 340
242, 268, 338 sh 240 sh , 300 sh d
272, 298 sh c
270
278, 362 sh
252, 312 sh
256, 292
246
244, 310 sh d
284, 356 sh
280, 316 sh
290, 334 sh
328
244, 300 sh d
238, 300 sh c
248, 300 sh d
268, 310 sh d
272, 310 sh d
280, 305 sh d
280, 366 sh d
242
252, 370 sh
256
248
256, 282, 400 sh 246, 310 sh
268
268, 362
272, 316
272, 320 sh d
276, 312 sh
280
270
282, 394
264 sh , 344
250, 346
232, 280
248, 280
276, 392 sh
280, 320 sh
256, 280, 358
a
oxim e] = [m etal] = 1 · 10 m ol l–1, pH 6.3 (0.05 M MES buffer); b [oxim e] = [m etal] =
–4
[
· 10 m ol l , [CTAB] = 8 · 10 m ol l–1, pH 6.3 (0.05 M MES buffer); [m etal] = 4 · 10
–
4
–1
–3
c
–4
1
m ol l–1; d [m etal] = 1.2 · 10 m ol l–1
–3
.
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Cibulka et al.:
several divalen t m etal ion s (Co , Ni , Cu an d Zn 2+ ) was perform ed. Th e
kin etic m easurem en ts were carried out in m icellar m atrix of CTAB at 25 °C
an d pH 6.3. 4-Nitroph en yl diph en yl ph osph ate (PNPDPP), 4-n itroph en yl
h exan oate (PNPH) an d 4-n itroph en yl acetate (PNPA) were used as m odel
substrates. Th e con dition s em ployed en able direct com parison of th e re-
2
+
2+
2+
3
sults th us obtain ed with th ose reported previously . In order to get m ore in -
form ation about th e “in trin sic” reactivity of th e com plexes, excludin g th e
con tribution of m icellar catalysis, pseudo-first-order rate con stan ts of th e
PNPA cleavage were m easured in aqueous solution s of m eth yl azin yl
ketoxim es 1a–5a an d th eir com plexes as well.
Sim ilarly to th e form erly studied pyridin -2-yl ligan ds 1a–1c an d th eir
3
b
com plexes , n eith er oxim es 2b–5b n or th eir com plexes exh ibit apparen t
reactivity towards PNPDPP an d relative rates k /k did n ot exceed th e value
Ψ
0
of 3 in an y case. k an d k are pseudo-first-order rate con stan ts of th e cata-
Ψ
0
lyzed an d un catalyzed (i.e. in th e presen ce of buffered CTAB on ly) reaction ,
respectively. Reactivity towards PNPH an d PNPA stron gly depen ds both on
th e type of th e ligan d an d th e m etal ion as eviden t from th e results sum m a-
rized in Table II.
Th e data sh own in Table II afford th e followin g in form ation : (i) Wh en
two n itrogen s are presen t in th e h eteroarom atic n ucleus of th e ligan d
(
ketoxim es 2–5), its reactivity towards esters som ewh at in creases, com pared
with pyridin e ligan d 1. Th e rate en h an cem en t of th e ester h ydrolysis corre-
spon ds to th e in crease in th e h ydroxyim in o group acidity. (ii) Wh en less
lipoph ilic substrate PNPA is em ployed in stead of PNPH, th e order of th e
h ydrolytic activity of th e m etallom icellar catalysts is virtually un ch an ged.
Th erefore, kin etic data obtain ed with both th ese substrates give th e sam e
qualitative in form ation about th e m etallocatalyst reactivity. (iii) Sim ilarly
to pyridin e ligan ds 1, coordin ation to Co2 an d Cu is with out effect or
even decreases th e reactivity of th e h ydroxyim in o group of ligan ds 2–5 an d
an acceleratin g effect on ester h ydrolysis is sh own on ly by som e of th eir
+
2+
2
+
2+
Ni an d Zn
com plexes. Metal- an d ligan d-depen den t differen ces in
h ydrolytic efficien cy of th e com plexes are in accord with th e h ypoth esis
th at th e observed reactivity of th e m etallocatalyst is a result of two con tra-
dictory con sequen ces of th e coordin ation : an in crease in th e n ucleoph ile
con cen tration an d a decrease in th e n ucleoph ilicity of th e an ion form ed
4
a
sin ce both th e effects depen d on th e n ature of th e coordin ation bon ds .
iv) Non e of th e com plexes of diazin yl ligan ds 2–5 exh ibits th e efficien cy of
an alogous com plexes of pyridin yl ligan ds 1 wh ich is really im pressive, espe-
(
2
+
cially in th e case of h om ogen eous solution s of Zn com plexes of 1a. In de-
pen den ce on h ydrolytic activity of th eir Zn 2 an d Ni2+ com plexes, diazin yl
+
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Metal Ion Chelates
1165
ligan ds 2–5 can be divided in to two groups. In each of th em , sim ilar elec-
tron distribution in th e h eteroarom atic n ucleus can be expected. In th e first
group, th ere are m ore reactive pyrim idin yl ligan ds 3 an d 4 in wh ich th e
secon d h eteroatom is located in β-position to coordin ated n itrogen an d in
α- or γ-position to carbon substituted with th e h ydroxyim in oalkyl group. In
th e oth er, th ere are less reactive pyridazin -3-yl 2 an d pyrazin -2-yl 5 ligan ds
in wh ich th e secon d h eteroatom is located in α- or γ-position to coordi-
n ated n itrogen an d in β-position to carbon substituted with th e
TABLE II
Relative rates of th e m odel substrate cleavage in th e presen ce of ketoxim es 1b–5b an d 1a–5a
an d th eir m etal ion ch elates (25 °C, pH 6.3 (0.05 M MES buffer))
k /k
Φ
0
Substrate
PNPHa
Ligan d
–
Co2+
Ni2+
Cu2+
Zn 2+
1b
1.6 · 10
3.4 · 10
3.3 · 10
8.9 · 10
3.4 · 10
2.1
4.7 · 102
9.7 · 10
2.3 · 102
4.2 · 102
8.5 · 10
1.1 · 10
1.2 · 10
1.1 · 10
9.6
1.8 · 102
3.3 · 10
2.0 · 102
8.1 · 10
2.6 · 10
2
3
4
5
b
b
b
b
6.9
2.4
9.3
8.9
1.2 · 10
PNPAb
1b
2.2 · 10
6.4 · 10
5.8 · 10
1.5 · 102
6.5 · 10
3.7
7.9 · 102
1.3 · 102
1.6 · 102
3.7 · 102
1.3 · 102
2.9 · 10
2.0 · 10
1.1 · 10
7.3
1.8 · 102
6.9 · 10
1.5 · 102
1.4 · 102
5.9 · 10
2
3
4
5
b
b
b
b
1.2 · 10
7.3
1.0 · 10
1.3 · 10
8.3
PNPAc
1a
3.3
5.0
3.7
8.5
3.8
3.0
2.3
1.9
1.6
3.4
1.2 · 103
1.3 · 102
5.2 · 102
4.7 · 102
5.5 · 102
1.9 · 10
9.3
9.6 · 103
1.1 · 102
1.8 · 103
3.8 · 102
1.9 · 102
2
3
4
5
a
a
a
a
3.4
1.6
4.3
a
ligan d] = [m etal] = 4.0 · 10 m ol l–1, [CTAB] = 8.0 · 10–3 m ol l–1, [PNPH] = 2.0 · 10 m ol l–1
–4
–5
[
,
–6
–1
b
k0 = 3.75 · 10
[
1
[
s
(rate con stan t of th e PNPH cleavage in buffered CTAB solution ); [ligan d] =
–
4
–1
–3
–1
–5
–1
m etal] = 4.0 · 10 m ol l , [CTAB] = 8.0 · 10 m ol l , [PNPA] = 2.0 · 10 m ol l , k0 =
–
6
–1
c
.92 · 10
s
(rate con stan t of th e PNPA cleavage in buffered CTAB solution ); [ligan d] =
–
3
–1
–5
–1
–6 –1
m etal] = 1.0 · 10 m ol l , [PNPA] = 4.0 · 10 m ol l , k0 = 1.29 · 10
s
(rate con stan t of
th e PNPA cleavage in buffered aqueous solution ).
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

1
166
Cibulka et al.:
h ydroxyim in oalkyl group. Neverth eless, an y un equivocal con clusion s on
th e structure-activity relation sh ips are prem ature sin ce so far we h ave n o
exact in form ation about th e electron distribution in th e con jugated system
of th e h eteroarom atic rin g an d n ucleoph ilic h ydroxyim in o group, m odified
by coordin ation with m etal ion s.
Furth er an d m ore detailed in vestigation was focused on Ni2+ an d Zn 2+
com plexes exhibiting appreciable hydrolytic activity. Being bidentate ligands,
ketoxim es 1–5 can form com plexes of differen t m etal ion : ligan d ratios. In
order to evaluate th e “effective stoich iom etry” (wh ich is n ot a defin ition of
th e n ature an d quan tity of th e com plexes presen t in solution but on ly th e
m ost effective m etal : ligan d ion ratio leadin g to th e h igh est reactivity ob-
3
b
served), we perform ed kin etic version s of Job’s plots sh own in Figs 2–5.
–
4
Th ese were obtain ed for solution s wh ere [m etal ion ] + [ligan d] = 4.0 · 10
–
1
m ol l usin g PNPH as substrate (lipoph ilic ligan ds 1b–5b) or [m etal ion ] +
ligan d] = 2.0 · 10–3 m ol l usin g PNPA as substrate (water soluble ligan ds
–1
[
1
a–5a).
As eviden t from Job’s plots in Fig. 2, Ni2+ com plexes of lipoph ilic
ketoxim es 1b an d 3b were of th e 1 : 3 m etal ion : ligan d stoich iom etry.
3
Th is ratio m ean s an im provem en t of our previous results obtain ed with
2
+
ligan ds 1c, 1d . We reported th e 1 : 2 effective stoich iom etry of Ni com -
plexes, alth ough , with respect to th e observed flat m axim a, we also adm it-
3
b
ted existen ce of oth er stoich iom etries . Job’s plot of th e pyrim idin -4-yl
1
1
0
.2
.0
.8
6.0
5.0
4.0
3
–1
4
–1
k
· 10 , s
k · 10 , s
Ψ
Ψ
0
0
0
0
.6
.4
.2
.0
3.0
2.0
1.0
0.0
1
: 2
1
: 3
0.2
0
.0
0.4
0.6
0.8
1.0
2
+
2+
[
Ni ]/([Ni ] + [oxime])
FIG. 2
Kin etic Job’s plot for th e PNPH cleavage by m icellar solution s of 1b (❍), 3b (❍) an d 4b (∇ )
2
+
2+
–4
at pH 6.3 (0.05 M MES buffer) an d 25 °C in th e presen ce of Ni ; [Ni ] + [oxim e] = 4 · 10
m ol l–1, [CTAB] = 1 · 10–2 m ol l
–1
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Metal Ion Chelates
1167
ligan d 4b is flat with th e m axim um located between th e 1 : 2 an d 1 : 3
stoich iom etry. Surprisin gly, differen t m etal ion : ligan d stoich iom etries
were foun d in h om ogen eous aqueous solution s. Job’s plots sh own in Fig. 3
2
+
give eviden ce th at Ni ion s form th e 1 : 2 com plexes with ligan ds 1a,
3
b
3
a–5a. Th is stoich iom etry is in accord with our previous results an d with
5
2+
th ose reported for sim ilar types of ligan ds . Sin ce Ni ion is h exavalen t,
form in g m ostly octah edral com plexes, we assum e coordin ation of two
water m olecules to reach th e coordin ation n um ber of six. On e m ay on ly
speculate wh ich factors are respon sible for differen t Ni : ligan d ratios in
m icellar an d h om ogen eous solution s. Most probably, lipoph ilic alkyl
ch ain s of th e ketoxim es 1b, 3b an d 4b are a h ydroph obic barrier for water
to access th e m etal ion , th us preferrin g coordin ation of th ree ligan d m ole-
cules.
2
+
Except for 3b, h ydrolytic acitivity of n on e of th e lipoph ilic diazin yl ligan ds
2
+
2
Zn
b–5b is affected by Zn . Th e reactivity an d effective stoich iom etry of th e
2
+
com plex of pyrim idin -2-yl ketoxim e 3b is sim ilar to th at observed
2
+
with lipoph ilic pyridin -2-yl ligan d 1b (Fig. 4). On th e oth er h an d, Zn ion
dram atically in creases th e reactivity of ketoxim es 1a–5a in h om ogen eous
aqueous solution s (Table II an d Fig. 5), th e m ost active bein g 1 : 2 com -
plexes of pyridin -2-yl 1a an d pyrim idin -2-yl 3a ligan ds. Th e rates of th e
PNPA cleavage catalyzed by th ese com plexes are really im pressive. In all
oth er cases (ketoxim es 2a, 4a an d 5a), Zn 2 com plexes are of 1 : 1
+
2
–1
.0
.5
.0
2.0
3
4
–1
k
· 10 , s
k · 10 , s
Ψ
Ψ
1
1
1.5
1.0
0
0
.5
.0
0.5
0.0
1
: 2
1 : 1
0
.0
0.2
0.4
0.6
0.8
1.0
2
+
2+
[
Ni ]/([Ni ] + [oxime])
FIG. 3
Kin etic Job’s plot for th e PNPA cleavage by 1a (❍), 2a (∆), 3a (❍), 4a (∇ ) an d 5a (∗ ) at pH
2
+
2+
–3
–1
6
.3 (0.05 M MES buffer) an d 25 °C in th e presen ce of Ni ; [Ni ] + [oxim e] = 2 · 10 m ol l
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

1
168
Cibulka et al.:
stoich iom etry an d th eir efficien cy is lower approxim ately by on e order of
2
+
m agn itude. Provided th at th e Zn com plexes of ligan ds 1–5 are of lower
stability (see preparation of th e m etallom icellar catalysts), th eir
stoich iom etry could be in fluen ced by th e lipoph ilicity of th e coordin ated
1
1
0
0
.5
.0
.5
.0
4
–1
k
· 10 , s
Ψ
1
: 1
0
.0
0.2
0.4
0.6
0.8
1.0
2
+
2+
[
Zn ]/([Zn ] + [oxime])
FIG. 4
Kin etic Job’s plot for th e PNPH cleavage by m icellar solution s of 1b (❍) an d 3b (❍) at pH
2
+
2+
–4
6
.3 (0.05 M MES buffer) an d 25 °C in th e presen ce of Zn ; [Zn ] + [oxim e] = 4 · 10
–
1
–2
–1
m ol l , [CTAB] = 1 · 10 m ol l
1
1
.2
.0
4.8
k · 10 , s
4
–1
2
–1
k
· 10 , s
Ψ
Ψ
4.0
3.2
0
.8
0
0
.6
.4
2.4
1.6
0
0
.2
.0
0.8
0.0
1 : 2
0.2
1 : 1
2+
0
.0
0.4
0.6
0.8
1.0
2
+
[
Zn ]/([Zn ] + [oxime])
FIG. 5
Kin etic Job’s plot for th e PNPA cleavage by 1a (❍), 2a (∆), 3a (❍), 4a (∇ ) an d 5a (∗ ) at pH
2
+
2+
–3
–1
6
.3 (0.05 M MES buffer) an d 25 °C in th e presen ce of Zn ; [Zn ] + [oxim e] = 2 · 10 m ol l
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Metal Ion Chelates
1169
ligan d. If th e tetrah edral 1 : 2 Zn 2+ com plex with lipoph ilic dodecyl ligan d
is form ed in m icellar m atrix, h ydroph obic alkyl ch ain of on e of th e ligan ds
coordin ated sh ould be orien ted in to bulk aqueous ph ase an d th e surface
free en ergy in crease m igh t be h igh er th an th e en ergy released by th e secon d
ligan d coordin ation , th us discrim in atin g th e 1 : 2 com plex form ation .
A question m ay appear about th e structure of pyridin -2-yl 1 an d
pyrim idin -2-yl 3 com plexes. In th e form er case, th e ketoxim e is of E con -
figuration wh ile in th e latter on e Z con figuration was foun d (Fig. 1).
N,N′-Ch elates can be expected wh en an (E)-ketoxim e coordin ates to m etal
ion . Coordin ation of (Z)-ketoxim es sh ould lead to less stable N,O-ch elates
2
b
2+
of quite differen t reactivity (Fig. 6). Surprisin gly, th e reactivity of Ni an d
2
+
Zn com plexes of both th ese ligan ds, 1 an d 3, was sim ilar (Table II, Figs 2–5)
th us in dicatin g th e sam e type coordin ation . We assum e th at coordin ation
to m etal ion in duced equilibration of th e ligan d 3 con figuration .
Usin g th e optim um m etal ion : ligan d ratio (see above) we studied th e in -
fluen ce of pH on th e h ydrolytic activity of th e com plexes of lipoph ilic
ketoxim es 1b an d 3b. As sh own in Figs 7 an d 8, correspon din g com plexes
of both ligan ds exh ibit sim ilar rate vs pH profiles of th e PNPH cleavage. In
2
+
th e case of Zn com plexes, on goin g from lower to h igh er pH values, th e
rate (log k ) lin early in creases, reach in g a plateau in dicatin g com plete ion -
Ψ
2
+
ization of th e h ydroxyim in o group (at pH > 8). Coordin ation to Ni ion s
acidifies h ydroxyim in o groups of ketoxim es 1b an d 3b m uch m ore th an co-
2
+
2+
ordin ation to Zn sin ce th e rate vs pH profiles of Ni com plexes already
reach a “wavin g” plateau already at pH 5. Above th is value, th e rate of
PNPH h ydrolysis is alm ost in sen sitive to pH in th e ran ge of several pH un its
(
5–11), th e ch an ges in th e rate con stan ts bein g on ly with in on e order of
m agn itude. A discon tin uity observed in alm ost all profiles aroun d pH 5 is a
con sequen ce of ch an gin g type of th e buffer (acetate an d biological below
an d above pH 5). Th e rate con stan ts of th e PNPH h ydrolysis by fully ion -
ized com plexes (above pH 5 an d 8 for Ni2 an d Zn , respectively) give evi-
+
2+
N
R
R
N
N
+
+
2
2
N
M
M
N
O
H
O
H
FIG. 6
Structure of N,N′- an d N,O-ch elates
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

1
170
Cibulka et al.:
2
+
den ce th at th e n ucleoph ilicity of th e oxim ate an ion in Zn com plexes is
2
+
h igh er th an th at in Ni com plexes. Th is observation again illustrates th e
fact th at th e m ore th e Nu–H group of th e ligan d of an y h ydrolytic
–
–
1
2
log k
Ψ
–
–
3
4
–
–
5
6
4
5
6
7
8
9
10
11
pH
FIG. 7
pH depen den ce of th e rate con stan t for th e PNPH cleavage by 1b (∆), 1b/Ni (❍, 3 : 1) an d
2
+
2
+
1
b/Zn (❍, 1 : 1). Filled an d em pty sym bols in dicate th e use of acetate an d biological buffers,
–
4
–1
2+
–4
–1
2+
respectively. Con dition s: [1b ] = 3.6 · 10
.6 · 10 m ol l , [CTAB] = 1.2 · 10 m ol l , [buffer] = 0.05 m ol l–1, 25 °C
m ol l , [Ni ] = 1.2 · 10
m ol l , [Zn ] =
–
4
–1
–2
–1
3
–
–
1
2
log k
Ψ
–
–
3
4
–
–
5
6
4
5
6
7
8
9
10
11
pH
FIG. 8
pH depen den ce of th e rate con stan t for th e PNPH cleavage by 3b (∆), 3b/Ni (❍, 3 : 1) an d
2
+
2
+
3
b/Zn (❍, 1 : 1). Filled an d em pty sym bols in dicate th e use of acetate an d biological buff-
–
4
–1
2+
–4
–1
2+
ers, respectively. Con dition s: [3b] = 3.6 · 10 m ol l , [Ni ] = 1.2 · 10 m ol l , [Zn ] =
.6 · 10 m ol l , [CTAB] = 1.2 · 10 m ol l , [buffer] = 0.05 m ol l , 25 °C
–
4
–1
–2
–1
–1
3
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Metal Ion Chelates
1171
m etallocatalyst is acidified by coordin ation to m etal ion , th e less
–
n ucleoph ilic an ion Nu is form ed.
As sh own in Fig. 9, pH rate profiles of th e PNPA h ydrolysis in h om oge-
2
+
n eous solution s of Zn com plexes of ligan ds 1a–5a follow th e sam e tren d
as was observed in th e above-m en tion ed m icellar system s. Th e
2
+
n ucleoph ilicity of th e Zn coordin ated deproton ated ketoxim es decreases
in th e followin g order: pyridin -2-yl 1a, pyrim idin -2-yl 3a, pyrim idin -4-yl
2
+
4
a, pyrazin -2-yl 5a an d pyridazin -3-yl 2a. In th e case of Zn com plex of
pyridazin -3-yl ligan d 2a, th e profile is n ot m on oton ic as it is in all oth er
cases. Most probably, decom position of th is com plex (by con curren t
h ydroxo com plexes form ation ) begin s un der weakly basic con dition s
(
above pH 8) sin ce above pH 10, th ere is an apparen t con vergen ce to th e
2
+
profile of th e free ligan d. pH rate profiles of th e Ni com plexes of ligan ds
1
Ni com plexes is m oderately in fluen ced by th e type of ligan d em ployed,
except for th e pyridazin yl ketoxim e 2a. Profiles of pyrim idin -2-yl 3a,
pyrim idin -4-yl 4a an d pyrazin -2-yl 5a com plexes are alm ost in distin guish -
able th us givin g eviden ce of th e sam e acidity of th eir h ydroxyim in o groups
2
+
a–5a are given in Fig. 10. Com pared with Zn com plexes, th e reactivity of
2
+
2
+
as well as n ucleoph ilicity of th eir an ion s. Th e Ni
com plex of th e
pyridazin -3-yl ligan d 2a is stable even in stron gly basic m edia an d th e drift
–
–
1
2
log k
Ψ
–
–
3
4
–
–
5
6
4
5
6
7
8
9
10
11
pH
FIG. 9
pH depen den ce of th e rate con stan t for th e PNPA cleavage by 1a/Zn (❍, 2 : 1), 2a/Zn 2+ (∆,
2
+
2
+
2+
2+
1
1
: 1), 3a/Zn (❍, 2 : 1), 4a/Zn (∇ , 1 : 1), 5a/Zn (∗ , 1 : 1) an d 2a (❍). Con dition s: [oxim e] =
.0 · 10 m ol l–1, [Zn ] = 5.0 · 10–4 m ol l (in th e case of 1a/Zn an d 3a/Zn ) or 1.0 · 10
m ol l (in th e case of 2a/Zn 2+, 4a/Zn 2+ an d 5a/Zn 2+), [buffer] = 0.05 m ol l–1, 25 °C
–
3
2+
–1
2+
2+
–3
–1
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

1
172
Cibulka et al.:
of its pH rate profile at pH > 10 is a con tribution of th e PNPA h ydrolysis
–
with OH ion s.
CONCLUSIONS
Detailed kin etic studies focused on h ydrolytic activity of alkyl h etaryl
ketoxim es 1–5 an d th eir com plexes both in m icellar an d in h om ogen eous
system s h as brough t m an y in terestin g pieces of in form ation . However, at
th e presen t stage of kn owledge, th eir in terpretation is speculative in several
cases an d furth er in vestigation will be n ecessary. Com pared with previously
3
studied com plexes of alkyl pyridin -2-yl ketoxim es 1, th e presen ce of th e
secon d n itrogen in th e h eteroarom atic rin g of th e diazin yl ketoxim es 2–5
rath er decreases h ydrolytic activity of th eir com plexes with m etal ion s.
Th ere exist un equivocal relation sh ips between th e position of th e
n on -coordin atin g n itrogen in th e h eteroarom atic rin gs of diazin yl ligan ds
–5 an d h ydrolytic activity of th eir Zn 2 an d Ni com plexes. Neverth eless,
+
2+
2
gen eral con clusion s in term of structure–activity relation sh ips are still pre-
m ature an d correlation s of th e calculated electron distribution s in free an d
coordin ated ligan ds with h ydrolytic activities of th eir tran sition m etal ion
com plexes will h ave to be perform ed. Th e observed in fluen ce of th e ligan d
lipoph ilicity on th e effective com plex stoich iom etry an d, con sequen tly,
–
2
3
4
5
6
log k
Ψ
–
–
–
–
3
4
5
6
7
8
9
10
11
pH
12
FIG. 10
pH depen den ce of th e rate con stan t for th e PNPA cleavage by 1a/Ni (❍, 2 : 1), 2a/Ni (∆,
2
+
2+
2
+
2+
2+
–
1
[
4
: 1), 3a/Ni
(❍, 2 : 1), 4a/Ni
(∇ , 2 : 1), 5a/Ni
(∗ , 2 : 1) an d OH (❍). Con dition s:
oxim e] = 1.0 · 10 m ol l , [Ni ] = 5.0 · 10 m ol l–1 (in th e case of 1a/Ni , 3a/Ni
a/Ni an d 5a/Ni ) or 1.0 · 10 m ol l–1 (in th e case of 2a/Ni ), [buffer] = 0.05 m ol l , 25 °C
–
3
–1
2+
–4
2+
2+
,
2
+
2+
–3
2+
–1
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Metal Ion Chelates
1173
also on its reactivity is an oth er in terestin g ph en om en on . Most probably,
determ in ation of bin din g con stan ts of th e com plexes both in h om oge-
n eous an d in m icellar solution s is th e key to its explan ation .
EXPERIMENTAL
Tem perature data were un corrected. 1H NMR an d 13C NMR spectra were recorded on a
Bruker AMX3 400 spectrom eter at 400 an d 100 MHz, respectively. Ch em ical sh ifts are re-
ported in ppm relative to tetram eth ylsilan e as an in tern al stan dard, couplin g con stan ts J in
Hz. Elem en tal an alyses were perform ed on a Perkin –Elm er 240 an alyser. IR spectra were
taken on a FTIR spectrom eter Nicolet 740. TLC an alyses were carried out on DC Alufolien
Kieselgel 60H F254 (Merck).
Chemicals: Pyridazin e-3-carbon itrile (6), pyrim idin e-2-carbon itrile7 (7) an d pyrim i-
6
7
b,8
din e-4-carbon itrile
furan -2-carbaldeh yde (purum , Lach em a), 2-ch loropyrim idin e (purum , Aldrich ) an d
-m eth ylpyrim idin e (purum , Aldrich ), respectively. All th e prepared com poun ds gave correct
(8) were syn th esized an d purified by literature m eth ods from
4
1
elem en tal an alyses an d H NMR spectra. Pyrazin e-2-carbon itrile (9) an d pyridin e-
-carbon itrile (10) were obtain ed from Aldrich an d m eth yl pyridin -2-yl keton e (11a) from
2
Fluka (all purum ). A stock solution of m eth ylm agn esium iodide was prepared from m agn e-
sium an d m eth yl iodide in eth er an d stored un der argon atm osph ere. Its con cen tration (1.7
–
1
m ol l ) rem ain ed un ch an ged for several weeks as proved by titration with butan -2-ol usin g
9
N-ph en yl-1-n aph th ylam in e as in dicator . Dodecylm agn esium brom ide (1 M eth ereal solu-
tion ) was th e product of Aldrich . 4-Nitroph en yl h exan oate (PNPH) (an alytical grade) was
1
0a
purch ased from Sigm a. 4-Nitroph en yl acetate
ph ate
(PNPA) an d 4-n itroph en yl diph en yl ph os-
1
0b
(PNPDPP) were syn th esized an d purified accordin g to described m eth ods.
Hexadecyltrim eth ylam m on ium brom ide (CTAB) (an alytical grade) was th e product of Merck.
Biological buffers, 2-(m orph olin -4-yl)eth an e-1-sulfon ic acid (MES), 2-[4-(2-h ydroxyeth yl)-
piperazin -1-yl]eth an e-1-sulfon ic acid (HEPES), 3-[4-(2-h ydroxyeth yl)piperazin -1-yl]propan e-
1
-sulfon ic acid (EPPS), 2-cycloh exylam in oeth an e-1-sulfon ic acid (CHES), 3-cycloh exylam in o-
2
+
2+
propan e-1-sulfon ic acid (CAPS) (an alytical grade) were purch ased from Sigm a. Co , Ni
Cu an d Zn
,
2
+
2+
n itrates (an alytical grade) were products of Lach em a Brn o; th eir con cen tra-
tion s in stock solution s were determ in ed by EDTA titration s followin g stan dard proce-
1
1
dures
.
Alkyl Diazin yl Keton es 11–15. Gen eral Procedure
Eth ereal solution of m eth ylm agn esium iodide or dodecylm agn esium brom ide (20% excess)
was added dropwise durin g 1 h to stirred solution of diazin ecarbon itrile 6–9 in dry eth er (ca
.2 m ol l– ) at 0 °C un der argon atm osph ere. Th e reaction m ixture was stirred at room tem -
1
0
perature for 1 h , quen ch ed with water an d n eutralized with dilute h ydroch loric acid (1 : 1)
to adjust pH 8 in aqueous ph ase. Th e eth ereal layer was separated an d th e aqueous ph ase
was several tim es extracted with eth er. Th e com bin ed organ ic layers were dried with an h y-
drous sodium sulfate (keton es 12a–15a) or potassium carbon ate (keton es 11b–15b). Evapora-
tion of th e solven t un der reduced pressure afforded crude product wh ich was purified by
colum n ch rom atograph y. An alytical sam ples were obtain ed by sublim ation un der reduced
pressure or by distillation (keton e 11b).
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

1
174
Cibulka et al.:
Methyl pyridazin-3-yl ketone (12a). Keton e 12a was prepared from n itrile 6 (1.0 g, 9.5
m m ol). Eluen t: dich lorom eth an e–m eth an ol 100 : 3. Sublim ation : 75 °C/0.8 kPa. Yield 0.65 g
56%), m .p. 85–87 °C (reported12 87–88 °C). H NMR (CDCl ): 2.90 s, 3 H (CH ); 7.66 dd,
1
(
3
3
1
H, J(5,4) = 8.8, J(5,6) = 5.0 (H-5); 8.15 dd, 1 H, J(4,5) = 8.8, J(4,6) = 1.7 (H-4); 9.34 dd, 1 H,
J(6,5) = 5.0, J(6,4) = 1.7 (H-6).
Methyl pyrimidin-2-yl ketone (13a). Keton e 13a was prepared from n itrile 7 (1.3 g, 12.4
m m ol). Eluen t: ch loroform –m eth an ol 100 : 5. Sublim ation : 80 °C/0.9 kPa. Yield 0.46 g
30%), m .p. 49–52 °C (reported13 52 °C). H NMR (CDCl ): 2.78 s, 3 H (CH ); 7.46 t, 1 H,
1
(
3
3
J(5,4) = J(5,6) = 4.9 (H-5); 8.93 d, 2 H, J(4,5) = J(6,5) = 4.9 (H-4, H-6).
Methyl pyrimidin-4-yl ketone (14a). Keton e 14a was prepared from n itrile 8 (0.3 g, 2.9
m m ol). Eluen t: dich lorom eth an e–m eth an ol 100 : 4. Sublim ation : 70 °C/0.7 kPa. Yield 0.13 g
37%), m .p. 64–67 °C (reported1 66–67 °C). H NMR (CDCl ): 2.74 s, 3 H (CH ); 7.90 d,
3
1
(
3
3
1
H, J(5,6) = 5.5 (H-5); 8.99 d, 1 H, J(6,5) = 5.0 (H-6); 9.38 s, 1 H (H-2).
Methyl pyrazin-2-yl ketone (15a). Keton e 15a was prepared from n itrile 9 (0.37 g, 3.5
m m ol). Eluen t: dich lorom eth an e–m eth an ol 100 : 2. Yield 0.18 g (42%), m .p. 76–77 °C (re-
1
4
1
ported 76–78 °C). H NMR (CDCl ): 2.74 s, 3 H (CH ); 8.67 dd, 1 H, J(6,5) = 2.2, J(6,3) =
3
3
1
.7 (H-6); 8.77 d, 1 H, J(5,6) = 2.2 (H-5); 9.25 d, 1 H, J(3,6) = 1.7 (H-3).
Dodecyl pyridin-2-yl ketone (11b). Keton e 11b was prepared from n itrile 10 (3.0 g, 28.8
m m ol). Crude product was purified by colum n ch rom atograph y (ch loroform –m eth an ol
00 : 1) an d by distillation (b.p. 125 °C/27 Pa). Yield 2.63 g (33%). For C18H29NO (275.3)
1
1
calculated: 78.49% C, 10.61% H, 5.08% N; foun d: 79.10% C, 10.78% H, 5.02% N. H NMR
CDCl ): 0.87 t, 3 H, J(12′,11′) = 6.6 (CH ); 1.25 m , 18 H (H-3′–H-11′); 1.72 qi, 2 H, J(2′,3′) =
(
3
3
J(2′,1′) = 7.2 (H-2′); 3.21 t, 2 H, J(1′,2′) = 7.3 (CH C=O); 7.46 ddd, 1H, J(5,4) = 7.7, J(5,6) =
2
5
.0, J(5,3) = 1.1 (H-5); 7.83 td, 1 H, J(4,5) = J(4,3) = 7.7, J(4,6) = 1.7 (H-4); 8.04 d, 1 H,
1
3
J(3,4) = 7.7 (H-3); 8.68 dd, 1 H, J(6,5) = 5.0, J(6,4) = 1.1 (H-6). C NMR (CDCl ): 14.8 s
3
(
CH ); 23.4 s (C-11′); 24.7 s (C-10′); 28.0 s (C-9′); 30.1 s (C-8′); 30.21 s (C-7′); 30.25 s (C-6′);
3
3
0.35 s (C-5′); 30.38 s (C-4′); 30.4 s (C-3′); 32.6 s (C-2′); 38.4 s (C-1′); 122.5 s (C-3); 127.6 s
(
C-5); 137.5 s (C-4); 149.6 s (C-6); 154.3 s (C-2); 202.9 s (C=O).
Dodecyl pyridazin-3-yl ketone (12b). Keton e 12b was prepared from n itrile 6 (0.3 g, 2.9
m m ol). Eluen t: ch loroform –m eth an ol 100 : 3. Sublim ation : 120 °C/0.04 kPa. Yield 0.27 g
(
34%), m .p. 68–70 °C. For C17H28N O (276.4) calculated: 73.86% C, 10.21% H, 10.13% N;
2
1
foun d: 73.82% C, 9.98% H, 10.12% N. H NMR (CDCl ): 0.88 t, 3 H, J(12′,11′) = 6.8 (CH );
3
3
1
.26 m , 18 H (H-3′–H-11′); 1.78 qi, 2 H, J(2′,3′) = J(2′,1′) = 7.4 (H-2′); 3.40 t, J(1′,2′) = 7.4
CH C=O); 7.64 dd, 1 H, J(5,4) = 8.4, J(5,6) = 5.1 (H-5); 8.13 dd, 1 H, J(4,5) = 8.4, J(4,6) = 1.7
(
(
(
2
1
3
H-4); 9.33 dd, 1 H, J(6,5) = 5.1, J(6,4) = 1.7 (H-6). C NMR (CDCl ): 14.8 s (CH ); 23.4 s
C-11′); 24.6 s (C-10′); 26.5 s (C-9′); 30.0–30.3 m (C-8′–C-4′); 31.1 s (C-3′); 32.6 s (C-2′);
3
3
3
8.9 s (C-1′); 125.4 s (C-5); 127.9 s (C-4); 153.9 s (C-6); 156.2 s (C-3); 201.5 s (C=O).
Dodecyl pyrimidin-2-yl ketone (13b ). Keton e 13b was prepared from n itrile 7 (0.5 g,
.7 m m ol). Eluen t: dich lorom eth an e–m eth an ol 100 : 1. Sublim ation : 140 °C/0.08 kPa. Yield
4
0
1
6
.38 g (29%), m .p. 52–56 °C. For C17H28N O (276.4) calculated: 73.86% C, 10.21% H,
2
1
0.13% N; foun d: 74.17% C, 10.25% H, 9.88% N. H NMR (CDCl ): 0.88 t, 3 H, J(12′,11′) =
3
.8 (CH ); 1.28 m , 18 H (H-3′–H-11′); 1.77 qi, 2 H, J(2′,3′) = J(2′,1′) = 7.4 (H-2′); 3.22 t,
3
J(1′,2′) = 7.5 (CH C=O); 7.44 t, 1 H, J(5,4) = J(5,6) = 4.8 (H-5); 8.93 d, 2 H, J(4,5) = J(6,5) =
2
4
2
3
.8 (H-4, H-6). 13C NMR (CDCl ): 14.8 s (CH ); 23.4 s (C-11′); 24.7 s (C-10′); 28.1 s (C-9′);
9.98 s (C-8′); 30.02 s (C-7′); 30.11 s (C-6′); 30.18 s (C-5′); 30.31 s (C-4′); 30.34 s (C-3′);
2.6 s (C-2′); 39.8 s (C-1′); 123.4 s (C-5); 158.3 s (C-4, C-6); 161.0 s (C-2); 200.6 s (C=O).
3 3
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Metal Ion Chelates
1175
Dodecyl pyrimidin-4-yl ketone (14b). Keton e 14b was prepared from n itrile 8 (0.3 g, 2.9
m m ol). Eluen t: ch loroform –m eth an ol 100 : 3. Sublim ation : 120 °C/0.04 kPa. Yield 0.29 g
(
37%), m .p. 50–52 °C. For C17H28N O (276.4) calculated: 73.86% C, 10.21% H, 10.13% N;
2
1
foun d: 74.11% C, 9.81% H, 9.86% N. H NMR (CDCl ): 0.88 t, 3 H, J(12′,11′) = 6.6 (CH );
3
3
1
(
9
2
.25 m , 18 H (H-3′–H-11′); 1.72 qi, 2 H, J(2′,3′) = J(2′,1′) = 7.2 (H-2′); 3.19 t, J(1′,2′) = 7.4
CH C=O); 7.89 dd, 1 H, J(5,6) = 5.0, J(5,2) = 1.1 (H-5); 8.98 d, 1 H, J(6,5) = 5.0 (H-6);
2
1
3
.37 d, 1 H, J(2,5) = 1.7 (H-2). C NMR (CDCl ): 14.8 s (CH ); 23.4 s (C-11′); 24.3 s (C-10′);
3 3
9.9 s (C-9′); 30.03 s (C-8′); 30.11 s (C-7′); 30.2–30.3 m (C-6′–C-3′); 32.6 s (C-2′); 38.4 s
(
C-1′); 118.0 s (C-5); 159.3 s (C-4); 159.6 s (C-6); 159.7 s (C-2); 202.3 s (C=O).
Dodecyl pyrazin-2-yl ketone (15b ). Keton e 15b was prepared from n itrile 9 (0.41 g,
3
.9 m m ol). Eluen t: ch loroform -m eth an ol 100 : 1. Sublim ation : 120 °C/0.04 kPa. Yield 0.27 g
(
25%), m .p. 61–62.5 °C. For C17H28N O (276.4) calculated: 73.86% C, 10.21% H, 10.13% N;
2
1
foun d: 73.95% C, 10.28% H, 10.11% N. H NMR (CDCl ): 0.88 t, 3 H, J(12′,11′) = 6.8 (CH );
3
3
1
(
9
3
.26 m , 18 H (H-3′–H-11′); 1.74 qi, 2 H, J(2′,3′) = J(2′,1′) = 7.2 (H-2′); 3.18 t, J(1′,2′) = 7.4
CH C=O); 8.65 dd, 1 H, J(6,5) = 2.3, J(6,3) = 1.6 (H-6); 8.75 d, 1 H, J(5,6) = 2.5 (H-5);
2
1
3
.23 d, 1 H, J(3,6) = 1.4 (H-3). C NMR (CDCl ): 14.8 s (CH ); 23.4 s (C-11′); 24.5 s (C-10′);
3 3
0.0–30.6 m (C-9′–C-3′); 32.6 s (C-2′); 38.6 s (C-1′); 144.2 s (C-5); 144.4 s (C-6); 148.4 s
(
C-3); 168.3 s (C-2); 202.2 s (C=O).
Meth yl Azin yl Ketoxim es 1a–5a. Gen eral Procedure
Keton e 11a–15a was stirred with aqueous h ydroxylam in e (prepared by m ixin g saturated
aqueous solution s of h ydroxylam in e h ydroch loride an d potassium carbon ate in
a
stoich iom etric ratio) un til th e keton e was com pletely con verted to oxim e (TLC, dich loro-
m eth an e–m eth an ol 100 : 3). Th e resultin g crystals of th e crude product were purified by col-
um n ch rom atograph y (dich lorom eth an e–m eth an ol 100 : 2) an d/or crystallization .
(
E)-Methyl pyridin-2-yl ketoxime (1a). Oxim e 1a was prepared by h eatin g keton e 11a (4.1 g,
3.9 m m ol) an d aqueous h ydroxylam in e (38.8 m m ol) at 60 °C for 1 h . Pure product was ob-
tain ed by crystallization from eth an ol–water (1 : 1). Yield 3.0 g (65%), m .p. 120–122 °C (re-
3
1
5
ported 121 °C). For C H N O (136.2) calculated: 61.75% C, 5.92% H, 20.58% N; foun d:
6
7
8
2
1
1.57% C, 6.02% H, 20.61% N. H NMR (DMSO-d ): 2.22 s, 3 H (CH ); 7.36 ddd, 1 H,
6 3
J(5,4) = 7.3, J(5,6) = 4.9, J(5,3) = 1.1 (H-5); 7.79 td, 1 H, J(4,3) = J(4,5) = 7.9, J(4,6) = 1.7
(
1
H-4); 7.86 d, 1 H, J(3,4) = 8.1 (H-3); 8.58 dd, 1 H, J(6,5) = 6.5, J(6,4) = 1.1 (H-6); 11.48 s,
1
3
H (OH). C NMR (DMSO-d ): 10.3 (CH ); 119.7 (C-4); 123.6 (C-5); 136.5 (C-3); 148.7
6 3
(
(
C-6); 154.4 (C=NOH); 154.5 (C-2). IR (CHCl ): 3 580, 3 241 (O–H); 1 616 (C=N). pK = 11.1
3 a
reported16 10.87).
E)-Methyl pyridazin-3-yl ketoxime (2a). Oxim e 2a was prepared from keton e 12a (0.3 g, 2.5
(
m m ol) an d aqueous h ydroxylam in e (4.9 m m ol). Th e reaction was com pleted in 0.5 h at
room tem perature. Pure product was obtain ed by colum n ch rom atograph y an d crystalliza-
tion from eth an ol. Yield 0.2 g (60%), m .p. 204–206 °C. For C H N O (137.1) calculated:
6
7
3
1
5
2.55% C, 5.15% H, 30.64% N; foun d: 52.83% C, 5.16% H, 31.05% N. H NMR spectrum
(
DMSO-d ): 2.33 s, 3 H (CH ); 7.69 dd, 1 H, J(5,4) = 8.5, J(5,6) = 5.0 (H-5); 8.06 dd, 1 H,
6
3
J(4,5) = 8.5, J(4,6) = 1.7 (H-4); 9.21 dd, 1 H, J(6,5) = 5.0, J(6,4) = 1.7 (H-6); 11.93 s, 1 H (OH).
1
3
C NMR (DMSO-d ): 10.1 (CH ); 123.3 (C-5); 127.0 (C-4); 151.6 (C-6); 152.7 (C-3); 156.8
6
3
(
C=NOH). pKa = 10.6.
Z)-Methyl pyrimidin-2-yl ketoxime (3a). Oxim e 3a was prepared from keton e 13a (0.45 g,
.7 m m ol) an d aqueous h ydroxylam in e (7.3 m m ol). Th e reaction was com pleted in 2 h at
(
3
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

1
176
Cibulka et al.:
room tem perature. Pure product was obtain ed by crystallization from eth an ol. Yield 0.29 g
58%), m .p. 195–198 °C. For C H N O (137.1) calculated: 52.55% C, 5.15% H, 30.64% N;
(
6
7
3
1
foun d: 52.32% C, 4.93% H, 30.52% N. H NMR (DMSO-d ): 2.22 s, 3 H (CH ); 7.47 t, 1 H,
6
3
J(5,4) = J(5,6) = 4.9 (H-5); 8.84 d, 2 H, J(4,5) = J(6,5) = 4.9 (H-4, H-6); 11.79 s, 1 H (OH).
1
3
C NMR (DMSO-d ): 11.2 (CH ); 120.6 (C-5); 153.3 (C-2); 157.2 (C-4, C-6); 162.2 (C=NOH).
6
3
pKa = 10.8.
E)-Methyl pyrimidin-4-yl ketoxime (4a). Oxim e 4a was prepared from keton e 14a (0.14 g,
.1 m m ol) an d aqueous h ydroxylam in e (2.3 m m ol). Th e reaction was com pleted in 0.5 h at
room tem perature. Pure product was obtain ed by crystallization from m eth an ol. Yield 0.11 g
(
1
1
7
(
5
70%), m .p. 182–183 °C (reported 184–185 °C). For C H N O (137.1) calculated: 52.55% C,
6 7 3
1
.15% H, 30.64% N; foun d: 52.31% C, 5.16% H, 30.56% N. H NMR (DMSO-d ): 2.19 s, 3 H
6
(
1
CH ); 7.86 dd, 1 H, J(5,6) = 5.5, J(5,2) = 1.6 (H-5); 8.76 d, 1 H, J(6,5) = 5.5 (H-6); 9.21 d,
3
H, J(2,5) = 1.6 (H-2); 12.10 s, 1 H (OH). C NMR (DMSO-d ): 9.5 (CH ); 116.3 (C-5); 153.2
6 3
1
3
(
C-4); 156.9 (C-6); 158.4 (C-2); 161.2 (C=NOH). pKa = 10.3.
E)-Methyl pyrazin-2-yl ketoxime (5a). Oxim e 5a was prepared from keton e 15a (0.18 g, 1.5
(
m m ol) an d aqueous h ydroxylam in e (2.2 m m ol). Th e reaction was com pleted in 2 h at room
tem perature. Pure product was obtain ed by sublim ation at 80 °C/2.7 Pa. Yield 0.14 g (72%),
1
4
m .p. 113–115 °C (reported
5
113–115 °C). For C H N O (137.1) calculated: 52.55% C,
6 7 3
1
.15% H, 30.64% N; foun d: 52.07% C, 5.32% H, 30.36% N. H NMR (DMSO-d ): 2.20 s, 3 H
6
(
1
CH ); 8.61 dd, 1 H, J(6,5) = 2.2, J(6,3) = 1.7 (H-6); 8.63 d, 1 H, J(5,6) = 2.2 (H-5); 9.07 d,
3
H, J(3,6) = 1.7 (H-3); 11.89 s, 1 H (OH). C NMR (DMSO-d ): 9.9 (CH ); 141.6 (C-3); 143.5
6 3
1
3
(
C-6); 143.8 (C-5); 149.9 (C-2); 153.0 (C=NOH). pKa = 10.9.
Dodecyl Azin yl Ketoxim es 1b–5b. Gen eral Procedure
Aqueous h ydroxylam in e (prepared by m ixin g saturated solution s of h ydroxylam in e h ydro-
ch loride an d potassium carbon ate in a stoich iom etric ratio) was added in th ree portion s dur-
in g 2 h to solution of keton e 11b–15b in eth an ol at 60 °C. Th en , th e reaction m ixture was
stirred at 60 °C un til th e keton e was com pletely con verted to oxim e (TLC, ch loroform –
m eth an ol 100 : 3). Form ed potassium ch loride was filtered off an d water was added to pre-
cipitate th e crude product wh ich was purified by crystallization from m eth an ol. An alytical
sam ples were obtain ed by sublim ation .
(
E)-Dodecyl pyridin-2-yl ketoxime (1b). Oxim e 1b was prepared from keton e 11b (2.45 g, 9.1
m m ol) in eth an ol (37 m l) an d aqueous h ydroxylam in e (14.4 m m ol). Pure product was ob-
tain ed by crystallization from eth an ol-water an d sublim ation at 120 °C/1.3 Pa. Yield 1.88 g
(
73%), m .p. 58–63 °C. For C18H30N O (290.5) calculated: 74.44% C, 10.41% H, 9.64% N;
2
1
foun d: 74.58% C, 10.23% H, 9.63% N. H NMR (CDCl ): 0.88 t, 3 H, J(12′,11′) = 7.2 (CH );
3
3
1
7
1
1
.24 m , 18 H (H-3′–H-11′); 1.59 qi, 2 H, J(2′,3′) = J(2′,1′) = 7.2 (H-2′); 2.99 t, 2 H, J(1′,2′) =
.6 (CH C=O); 7.27 m , 1 H (H-5); 7.69 td, 1 H, J(4,5) = J(4,3) = 7.6, J(4,6) = 1.6 (H-4); 8.04 d,
2
1
3
H, J(3,4) = 8.0 (H-3); 8.64 d, 1 H, J(6,5) = 4.4 (H-6); 8.82 s, 1 H (OH). C NMR (CDCl ):
3
4.9 s (CH ); 23.5 s (C-11′); 25.4 s (C-10′); 27.0 s (C-9′); 30.1 s (C-8′); 30.2–30.7 m
3
(
(
C-7′–C-2′); 32.7 s (C-1′); 121.7 s (C-3); 124.3 s (C-5); 137.1 s (C-4); 149.8 s (C-6); 154.8 s
C-2); 161.6 s (C=NOH). pKa = 10.9.
(
E)-Dodecyl pyridazin-3-yl ketoxime (2b). Oxim e 2b was prepared from keton e 12b (0.15 g,
0
.54 m m ol) in eth an ol (8 m l) an d aqueous h ydroxylam in e (2.7 m m ol). Pure product was ob-
tain ed by crystallization from m eth an ol an d sublim ation at 130 °C/2.7 Pa. Yield 0.083 g
(
53%), m .p. 101–103 °C. For C18H30N O (291.3) calculated: 70.06% C, 10.03% H, 14.42% N;
2
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Metal Ion Chelates
1177
foun d: 69.88% C, 10.03% H, 14.21% N. 1H NMR (CDCl ): 0.88 t, 3 H, J(12′,11′) = 6.8 (CH );
3
3
1
(
1
2
.25 m , 18 H (H-3′–H-11′); 1.64 qi, 2 H, J(2′,3′) = J(2′,1′) = 7.6 (H-2′); 3.13 t, J(1′,2′) = 7.6
CH C=O); 7.47 dd, 1 H, J(5,4) = 8.5, J(5,6) = 4.8 (H-5); 8.03 d, 1 H, J(4,5) = 8.4 (H-4); 8.44 s,
2
1
3
H (OH); 9.16 d, 1 H, J(6,5) = 4.0 (H-6). C NMR (CDCl ): 14.5 s (CH ); 23.1 s (C-11′);
3 3
4.7 s (C-10′); 26.7 s (C-9′); 29.8–30.1 m (C-8′–C-3′); 30.3 s (C-2′); 32.3 s (C-1′); 124.6 s
(
C-5); 126.7 s (C-4); 151.7 s (C-6); 157.0 s (C-3); 159.6 s (C=NOH). pKa = 10.4.
Z)-Dodecyl pyrimidin-2-yl ketoxime (3b). Oxim e 3b was prepared from keton e 13b (1.35 g,
.9 m m ol) in eth an ol (20 m l) an d aqueous h ydroxylam in e (24.4 m m ol). Pure product was
(
4
obtain ed by crystallization from eth an ol–water an d sublim ation at 130 °C/2.7 Pa. Yield
0
1
7
.25 g (18%), m .p. 89–91 °C. For C18H30N O (291.3) calculated: 70.06% C, 10.03% H,
2
1
4.42% N; foun d: 69.83% C, 9.78% H, 14.09% N. H NMR (CDCl ): 0.88 t, 3 H, J(12′,11′) =
3
.0 (CH ); 1.25 m , 18 H (H-3′–H-11′); 1.63 qi, 2 H, J(2′,3′) = J(2′,1′) = 7.6 (H-2′); 2.99 t,
3
J(1′,2′) = 7.6 (CH C=O); 7.27 m , 1 H (H-5); 8.81 d, 2 H, J(4,5) = J(6,5) = 4.8 (H-4, H-6); 9.54 s,
2
1
3
1
3
H (OH). C NMR (CDCl ): 14.8 s (CH ); 23.4 s (C-11′); 25.5 s (C-10′); 27.0 s, (C-9′);
3 3
0.1–30.4 m (C-8′–C-3′); 30.6 s (C-2′); 32.7 s (C-1′); 121.0 s (C-5); 157.9 s (C-4, C-6); 159.2 s
(
C-2); 162.8 s (C=NOH). pKa = 10.5.
E)-Dodecyl pyrimidin-4-yl ketoxime (4b). Oxim e 4b was prepared from keton e 14b (0.15 g,
.54 m m ol) in eth an ol (15 m l) an d aqueous h ydroxylam in e (2.7 m m ol). Pure product was
(
0
obtain ed by crystallization from m eth an ol an d sublim ation at 130 °C/1.3 Pa. Yield 0.98 g
(
62%), m .p. 87–88 °C. For C18H30N O (291.3) calculated: 70.06% C, 10.03% H, 14.42% N;
2
1
foun d: 70.44% C, 9.42% H, 14.30% N. H NMR (CDCl ): 0.88 t, 3 H, J(12′,11′) = 7.0 (CH );
3
3
1
(
1
2
1
.25 m , 18 H (H-3′–H-11′); 1.56 qi, 2 H, J(2′,3′) = J(2′,1′) = 7.7 (H-2′); 2.94 t, J(1′,2′) = 7.7
CH C=O); 7.82 dd, 1 H, J(5,6) = 5.3, J(5,2) = 1.1 (H-5); 8.71 d, 1 H, J(6,5) = 5.4 (H-6); 9.12 s,
2
1
3
H (OH); 9.26 s, 1 H (H-2). C NMR (CDCl ): 14.7 s (CH ); 23.4 s (C-11′); 24.6 s (C-10′);
3 3
6.9 s (C-9′); 30.0–30.3 m (C-8′–C-3′); 30.5 s (C-2′); 32.6 s (C-1′); 118.0 s (C-5); 157.4 s (C-6);
59.4 s (C-2); 160.3 s (C-4); 162.0 s (C=NOH). pKa = 10.1.
(
E)-Dodecyl-pyrazin-2-yl ketoxime (5b). Oxim e 5b was prepared from keton e 15b (0.3 g, 1.1
m m ol) in eth an ol (10 m l) an d aqueous h ydroxylam in e (5.3 m m ol). Pure product was ob-
tain ed by crystallization from m eth an ol an d sublim ation at 130 °C/2.7 Pa. Yield 0.11 g
(
35%), m .p. 80–81 °C. For C18H30N O (291.3) calculated: 70.06% C, 10.03% H, 14.42% N;
2
1
foun d: 69.55% C, 10.02% H, 14.18% N. H NMR (CDCl ): 0.88 t, 3 H, J(12′,11′) = 6.7 (CH );
3
3
1
.25 m , 18 H (H-3′–H-11′); 1.58 qi, 2 H, J(2′,3′) = J(2′,1′) = 7.5 (H-2′); 2.94 t, J(1′,2′) = 7.8
CH C=O); 8.50 s, 1 H (OH); 8.53 d, 1 H, J(6,5) = 2.5 (H-6); 8.57 m , 1 H (H-5); 9.15 s, 1 H
(
(
2
1
3
H-3).
C NMR (CDCl ): 14.7 s (CH ); 23.3 s (C-11′); 24.8 s (C-10′); 26.7 s (C-9′);
3 3
3
0.0–30.2 m (C-8′–C-3′); 30.5 s (C-2′); 32.5 s (C-1′); 143.6 s (C-5); 144.0 s (C-6); 144.3 s
(
C-3); 150.4 s (C–2); 159.9 s (C=NOH). pKa = 10.4.
Determ in ation of pKa
Values of pKa of th e ketoxim es were obtain ed as th e averages of th e values calculated from
–
th e absorban ce vs pH plots at two wavelen gth s (m axim a of th e =NOH an d =NO form s) us-
1
8
in g th e software package En zfitter . Aqueous sodium h ydroxide was used to adjust pH of
–
5
–1
aqueous solution of ketoxim es 1a–5a (70 m l, 8.0 · 10 m ol l ) or m icellar solution of
–
5
–1
–2
ketoxim es 1b–5b (70 m l, 8.0 · 10 m ol l ) in 1.0 · 10 M CTAB. Total volum e of th e NaOH
solution added did n ot exceed 0.3 m l in an y case.
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178
Cibulka et al.:
Kin etic Measurem en ts
Solution s of th e com plexes were prepared directly in spectroph otom etric cells by addition of
an appropriate am oun t of aqueous solution of th e m etal ion to a buffered h om ogen eous
aqueous solution of th e ligan d (ligan ds 1a–5a) or to a m icellar solution of th e ligan d in
CTAB (ligan ds 1b–5b). Th e cells were stan din g overn igh t to assure th e com plex form ation
reach ed th e equilibrium . 2-(Morph olin -4-yl)eth an e-1-sulfon ic acid (MES), 2-[4-(2-h ydroxy-
eth yl)piperazin -1-yl]eth an e-1-sulfon ic acid (HEPES), 3-[4-(2-h ydroxyeth yl)piperazin -1-yl]pro-
pan e-1-sulfon ic acid (EPPS), 2-cycloh exylam in oeth an e-1-sulfon ic acid (CHES), 3-cyclo-
–
1
h exylam in opropan e-1-sulfon ic acid (CAPS) an d acetate buffers (0.05 m ol l ) were used to
m ain tain th e desired pH. No ch an ges in pH were observed durin g th e kin etic run s. Th e reac-
tion s were followed on a spectroph otom eter Hewlett–Packard HP8452 equipped with a
th erm ostatted m ulticell tran sport cell h older HP89075C m ain tain in g th e reaction tem pera-
ture at 25.0 ± 0.1 °C. Th e reaction s were in itiated by in jection of a substrate solution in
aceton itrile (20 µl) in to th e spectroph otom etric cell con tain in g a buffered solution of cata-
–
5
–5
–1
lyst, th e resultin g con cen tration of th e substrate bein g 4.0 · 10 an d 2.0 · 10 m ol l in th e
case of ligan ds 1a–5a an d 1b–5b, respectively. Th e reaction s were m on itored at th e wave-
len gth s 400 n m (m axim um of th e 4-n itroph en oxide absorption ) or at 318 n m (m axim um of
th e 4-n itroph en ol absorption ) wh en pH of th e catalytic system was below 6. Th e kin etics
followed a first-order law in each case at least up to 95% con version . Th e pseudo-first-order
rate con stan ts kΨ were obtain ed by n on -lin ear regression an alysis of th e absorban ce vs tim e
1
8
data usin g software package En zfitter . Th e fit error of th e rate con stan t did n ot exceed 5%.
The authors thank the Grant Agency of the Czech Republic for financial support of this work (grant
No. 203/97/0805).
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