Quaternary pyridinium ketoximes - New efficient micellar hydrolytic catalysts

Article abstract of DOI:10.1135/cccc20000227

A series of quaternized alkyl pyridyl ketoximes was synthesized and tested as micellar hydrolytic catalysts. 2-And 4-|1-(hydroxyimino)tridecyl|-1-methylpyridinium bromides were surprisingly efficient, most probably due to the location of their nucleophili

Full text of DOI:10.1135/cccc20000227

Quaternary Pyridinium Ketoximes
227
QUATERNARY PYRIDINIUM KETOXIMES – NEW EFFICIENT
MICELLAR HYDROLYTIC CATALYSTS
b
Radek CIBULKAa1, František HAMPLa2,*, Hana KOTOUČOVÁa3, Jiří MAZÁČ
a4
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, kotoucoh@vscht.cz,
liskaf@vscht.cz
4
b
Ministry of Finance, Customs Technical Laboratory, 180 00 Prague 8, Czech Republic;
e-mail: mazacj@cs.mfcr.cz
Received Novem ber 17, 1999
Accepted Jan uary 18, 2000
A series of quatern ized alkyl pyridyl ketoxim es was syn th esized an d tested as m icellar
h ydrolytic catalysts. 2- An d 4-[1-(h ydroxyim in o)tridecyl]-1-m eth ylpyridin ium brom ides were
surprisin gly efficien t, m ost probably due to th e location of th eir n ucleoph ilic h ydroxyim in o
group below th e m icellar surface. Absorban ce of th e reaction m ixture vs tim e plots exh ibited
rem arkable positive deviation from th e first-order kin etics wh en h ydrolysis of 4-n itroph en yl
ph osph ates was catalyzed by 1-dodecyl-3-[1-(h ydroxyim in o)eth yl]- or 3-[1-(h ydroxy-
im in o)tridecyl]-1-m eth ylpyridin ium brom ide.
Key w ord s: Micelles; Pyridin ium salts; Oxim es; Ph osph ates; Hydrolyses; Kin etics; Micellar
catalysis.
Fun ction al cation ic ten sides possessin g various n ucleoph ilic fun ction s h ave
been widely studied as poten tial m icellar h ydrolytic catalysts1 durin g th e
past decades.
Deproton ated h ydroxyim in o group in quatern ary pyridin ium aldoxim es
is kn own to be a powerful n ucleoph ile readily attackin g ph osph orus atom
in ph osph oric an d ph osph on ic acid derivatives. Th e 1-alkyl-[(h ydroxy-
im in o)m eth yl]pyridin ium m oiety, represen tin g a leadin g structure in
reactivators of acetylch olin esterase2, in spired m an y auth ors3 in syn th esis of
fun ction al cation ic surfactan ts of gen eral form ula 1 as m icellar catalysts for
h ydrolysis of toxic derivatives of ph osph oric an d ph osph on ic acid. Com -
poun ds 1 (especially 2-substituted isom ers) exh ibit h igh activity towards
4-n itroph en yl diph en yl ph osph ate (PNPDPP) an d oth er n ervous gases sim u-
lan ts3. In con tin uation of our previous work con cen trated on quatern ary
h eteroaren ium aldoxim es3d, we turn ed our atten tion to quatern ary
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

228
Cibulka, Hampl, Kotoučová, Mazáč, Liška:
pyridin ium ketoxim es 2. Gen eral form ula 2 com prises two series of cation ic
surfactan ts with in verse position of th e h ydroph obic alkyl ch ain . We de-
cided to syn th esize th e followin g pyridin ium brom ides: 1-dodecyl-
2-[1-(h ydroxyim in o)eth yl]- (2a), 1-dodecyl-3-[1-(h ydroxyim in o)eth yl]- (2b),
1-dodecyl-4-[1-(h ydroxyim in o)eth yl]- (2c), 1-m eth yl-2-[1-(h ydroxyim in o)-
tridecyl]- (2d ), 1-m eth yl-3-[1-(h ydroxyim in o)tridecyl]- (2e), an d 1-m eth yl-
4-[1-(h ydroxyim in o)tridecyl]- (2f). Th e aim of th e presen t study was to
evaluate th e in fluen ce of th e relative position of th e h ydroph obic alkyl
chain, polar head and nucleophilic group on the hydrolytic activity of salts 2.
CH=NOH
X
CN
N
R
n-C12H25
N
1
a
b
c
position
R
X
I
Br
Br
4
2
3
4
n-C12H25
n-C12H25
n-C12H25
RESULTS AND DISCUSSION
Syntheses of Quaternary Pyridinium Ketoximes 2
Syn th esis of th e selected quatern ary pyridin ium ketoxim es 2 from m eth yl
pyridyl keton es 3a–3c (salts 2a–2c) or from pyridin ecarbon itriles (salts
2d –2f) is outlin ed in Sch em e 1.
R2
O
R2
R2
1. R2MgBr
2. H2O
R1-X
NH2OH
C N
NOH
NOH
N
N
N
N
R1
3
5
2
X
3,5
a
b
c
d
e
f
position
R2
CH3
CH3
CH3
n-C12H25
n-C12H25
n-C12H25
2
a
b
c
d
e
f
g
h
i
position
X
Br
Br
Br
Br
Br
Br
I
R1
R2
CH3
CH3
CH3
n-C12H25
n-C12H25
n-C12H25
n-C12H25
n-C12H25
n-C12H25
2
3
4
2
3
4
2
3
4
2
3
4
2
3
4
n-C12H25
n-C12H25
n-C12H25
CH3
CH3
CH3
CH3
CH3
CH3
I
I
SCHEME 1
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

Quaternary Pyridinium Ketoximes
229
Addition of dodecylm agn esium brom ide to pyridin -2- or pyridin -
4-carbon itriles afforded th e expected dodecyl pyridin -2- (3d ) an d -4-yl (3f)
keton es in good yields. As expected, a lon ger reaction tim e at h igh er tem -
perature was n ecessary to com plete th e reaction with th e less reactive
pyridin -3-carbon itrile. As a con sequen ce, a sm all am oun t of th e 6-dodecyl-
pyridin -3-carbon itrile (4), product of th e con curren t n ucleoph ilic attack of
th e pyridin e rin g by Grign ard reagen t, was isolated from th e reaction m ix-
ture.
Ketoxim es 5a–5f were readily prepared from th e correspon din g keton es
3a–3f. On ly on e set of sign als was observed in 1H an d 13C NMR spectra of
m eth yl pyridin -2- (5a), -3- (5b), an d -4-yl (5c) ketoxim es th us givin g evi-
den ce of th e presen ce of a sin gle stereoisom er in each case. However, ex-
cept for ketoxim e 5a, we were n ot able to ascertain th e con figuration at th e
C=N bon d. In oxim e 5a, E con figuration was con firm ed by IR spectro-
scopy4a. Surprisin gly, m ixtures of E an d Z isom ers of dodecyl pyridin -2-
(5d ), -3- (5e), an d -4-yl (5f) ketoxim es resulted from th e reaction s of
lipoph ilic keton es 3d –3f with h ydroxylam in e alth ough th e reaction con di-
tion s used were sim ilar as in our previous studies4 wh ere on ly sin gle
stereoisom ers of alkyl h eteroaryl ketoxim es were obtain ed. So far, we h ave
n ot been able to explain th e factors con trollin g th e con figuration of th e
arisin g ketoxim es. In th e case of ketoxim e 5d , both stereoisom ers were
separated by colum n ch rom atograph y. Pure E isom ers of ketoxim es 5e an d
5f were obtain ed by repeated crystallization from aqueous eth an ol. Besides
th e purifyin g effect of th e crystallization , irreversible con version of Z to
m ore stable E isom ers was observed upon gen tle h eatin g of th eir eth an olic
solution s or even upon stan din g for a lon g period. Th e con figuration s
of ketoxim es 5d –5f were attributed accordin g to th e rule form ulated by
Roberts et al.5: on goin g from keton es to ketoxim es, both α-carbon reso-
n an ces in 13C NMR sh ift upfield, with th e effect for th e α-syn carbon (rela-
tive to OH) bein g greater th an th at for th e α-anti carbon . Ch em ical sh ifts of
the α-CH2 carbons in both isomers of ketoximes 5d–5f are summarized in Table I.
Th e E/Z ratio given in Table I was obtain ed from in tegrals of th e corre-
spon din g α-CH2 sign als in 1H NMR (in all cases, sign als of α-syn-CH2 pro-
ton s, relative to OH, were down field com pared to th ose of α-anti-CH2).
With th e isom er 5d , th e con figuration on th e C=N bon d was con firm ed in -
depen den tly by IR spectroscopy4a. Sin ce th e 13C NMR spectra of ketoxim es
5d–5f were n ot taken im m ediately after th eir isolation , th e Z isom ers presen t
were th e m in or com pon en ts in m ixtures of isom ers. Th erefore, we were
able to fin d th e m ost in ten sive sign als on ly (see Experim en tal).
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

230
Cibulka, Hampl, Kotoučová, Mazáč, Liška:
Quatern ization of pyridin -3-yl ketoxim es 5b , 5e an d pyridin -4-yl
ketoxim es 5c, 5f afforded th e desired pyridin ium salts 2b, 2c, 2h , an d 2i in
satisfactory yields. On th e oth er h an d, quatern ization of th e pyridin e-2-yl
ketoxim es 5a, 5d m ade a great problem . Due to th e steric h in dran ce of th e
(h ydroxyim in o)alkyl group, alkylation of th e ketoxim e 5d was very slow
an d th e arisin g pyridin ium salt 2g was obtain ed on ly in a m oderate yield.
Quatern ization of m eth yl pyridin -2-yl ketoxim e (5a) with dodecyl brom ide
failed even on 100 h h eatin g at 150 °C in a sealed tube an d in th e presen ce
of potassium iodide (Fin kelstein reaction )6. A com plex m ixture of com -
poun ds resulted from th is reaction . Meth yl pyridin -2-yl keton e (3a) was iso-
lated as th e m ajor product an d iden tified by 1H NMR. Th e origin of th e
above-m en tion ed com poun d can be explain ed by N-alkylation of th e
deproton ated h ydroxyim in o group of th e ketoxim e 5a followed by decom -
position of th e resultin g n itron e7.
Pyridin ium salts 2b, 2c, 2g–2i were isolated as sin gle isom ers. We assum e
th at n o isom erization occurred durin g th e quatern ization an d th erefore th e
prepared pyridin ium ketoxim es 2g–2i sh ould be of E con figuration .
Kinetic Studies
Hydrolytic efficien cy of th e prepared salts 2 was evaluated by m easurin g
th e kin etics of th e h ydrolysis of m odel substrates (4-n itroph en yl esters in
all cases). As usual in sim ilar studies3,4, kin etic experim en ts were perform ed
un der pseudo-first-order con dition s with an excess of th e catalyst. Th e reac-
tion s were followed spectroph otom etrically by m on itorin g th e appearan ce
of 4-n itroph en oxide ion at 400 n m .
TABLE I
Con figuration s of ketoxim es 5d –5f from th e 13C NMR spectra
α-CH2 ch em ical sh ift, ppm
E/Z
Keton e
(E)-oxim e
(Z)-oxim e
3d 38.4
3e 39.6
3f 39.6
5d 32.7
5e 32.6
5f 32.6
5d 33.7
5e 35.7
5f 35.5
5 : 4
4 : 1
4 : 1
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

Quaternary Pyridinium Ketoximes
231
In th e first series of experim en ts, 4-n itroph en yl diph en yl ph osph ate
(PNPDPP) was em ployed as a toxic organ oph osph ate sim ulan t. Th e reac-
tion s were carried out at 25 °C un der sligh tly basic con dition s (pH 7.2). Th e
obtain ed plots of th e observed pseudo-first-order rate con stan t kobs of th e
PNPDPP cleavage vs con cen tration c of salt 2 are sh own in Fig. 1. However,
we were n ot able to obtain th ese plots for 3-substituted salts 2b an d 2e. As
we h ave previously reported8, con siderable positive deviation s from th e ex-
pected first-order curves were observed in th e absorban ce vs tim e plots wh en
th e PNPDPP was h ydrolyzed in m icellar solution s of 2b an d 2e (Fig. 2).
Th e plots given in Fig. 1 clearly dem on strate th e differen ce between th e
reactivity of 1-dodecylpyridin ium salt 2c an d 1-m eth ylpyridin ium salts 2d
an d 2f with th e in verse position of th e h ydroph obic alkyl ch ain . Th e ob-
served rate con stan ts kobs of th e PNPDPP cleavage in th e presen ce of
1-m eth ylpyridin ium salt 2d an d 2f are com parable with th ose obtain ed
with 1-dodecyl-2-[(h ydroxyim in o)m eth yl]pyridin ium iodide (1a), th e m ost
efficien t h ydrolytic catalyst of th e quatern ary pyridin ium aldoxim es3d, un -
der th e sam e con dition s. Th is fact is surprisin g sin ce th e acidity of th e
h ydroxyim in o group in pyridin ium ketoxim es 2d –2f is lower by m ore th an
on e order of m agn itude th an th at of th e above-m en tion ed pyridin ium
aldoxim e an d, con sequen tly, a lower con cen tration of th e n ucleoph ile
(deproton ated h ydroxyim in o group) is presen t in solution s at th e sam e pH.
Alth ough th e an om alous absorban ce vs tim e depen den ces in th e case of th e
3-substituted salts 2b an d 2e do n ot allow to calculate th e observed rate
con stan ts kobs of th e PNPDPP cleavage, it is eviden t th at th e h ydrolysis of
12
10
8
6
4
FIG. 1
Rate con stan t kobs of th e PNPDPP h ydrolysis
2
versus surfactan t con cen tration : 2c (❏), 2d (❏),
2f (❏), an d 1a (∆) (ref.3d). Con dition s: 25 °C,
0
pH 7.2 (0.05
M HEPES buffer an d 0.04 M
0
1
2
3
3
4
Tris-HBr buffer for ketoxim es 2 an d aldoxim e
1a, respectively)
–1
c·10 , mol l
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

232
Cibulka, Hampl, Kotoučová, Mazáč, Liška:
PNPDPP is m uch faster in th e presen ce of 1-m eth ylpyridin ium salt 2e th an
in th e presen ce of its 1-dodecylpyridin ium isom er 2b (Fig. 2).
A question appears about th e source of th e h igh reactivity of 1-m eth yl-
pyridin ium salts 2d –2f towards PNPDPP. No doubt, a low critical m icelle
con cen tration (below 1.5 · 10–3 an d 5 · 10–4 m ol l–1 for salts 2d an d 2f, re-
spectively, as follows from th e kobs vs con cen tration plots sh own in Fig. 1)
affords th e kin etic ben efit of m icellar catalysis even at low con cen tration s
of salts 2d –2f. Neverth eless, th e rem arkable reactivity of 1-m eth ylpyri-
din ium salts 2d –2f could also be explain ed as follows: PNPDPP (sim ilarly to
oth er lipoph ilic com poun ds) is solubilized in th e m icellar in terior in solu-
tion s of surfactan ts. As eviden t from Fig. 3 (usin g salts 2c an d 2f as exam -
ples), if th e n ucleoph ilic group is located ben eath th e m icellar surface
(1-m eth ylpyridin ium salt 2f), th e probability of th e attack of PNPDPP sh all
1.5
A
1.0
0.5
FIG. 2
An om alous absorban ce versus tim e plot of th e
PNPDPP h ydrolysis in m icelles of 2b (dash ed)
0.0
an d 2e (full). Con dition s: [oxim e] = 3.6 . 10–3
m ol l–1, 25 °C, pH 7.2 (0.05 M HEPES buffer)
0
5 000
10 000
t, s
OH
aqueous phase
N
CH3
Br
2c
CH3
Br
micellar surface
(Stern layer)
N
N
C12H25
2f
N
C12H25
micellar interior
OH
FIG. 3
Orien tation of th e h ydroph obic alkyl ch ain , polar h ead an d n ucleoph ilic group at th e
aqueous/m icellar in terface
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

Quaternary Pyridinium Ketoximes
233
be h igh er com pared with m icelles of isom eric 1-dodecylpyridin ium salt 2c
with th e h ydroxyim in o group orien tated in to aqueous ph ase. Figure 3 also
explain s h igh solubilities an d low critical m icelle con cen tration s of salts
2d –2f: all h ydroph obic parts of th eir m olecules are “h idden ” in th e m icellar
in terior an d on ly N-m eth yl group “sticks out” from th e Stern layer in to th e
aqueous ph ase.
To verify our h ypoth esis of th e in fluen ce of th e n ucleoph ilic group posi-
tion on h ydrolytic efficien cy of salts 2, we decided to in vestigate th e activ-
ity of both types of pyridin ium ketoxim es 2 towards a series of substrates of
differen t lipoph ilicity. If our assum ption was correct, both types of salts 2
sh ould differ in th e log kobs vs log P profiles wh ere P stan ds for th e partition
coefficien t of th e substrate between octan -1-ol an d water. In an extrem e
case, th e in crease in th e m odel substrate lipoph ilicity sh ould decrease th e
rate of its h ydrolysis in m icellar solution s of 1-dodecylpyridin ium salts 2b
an d 2c an d vice versa in m icellar solution s of 1-m eth yl- pyridin ium salts
2d –2f. 4-Nitroph en yl alkan oates were ch osen as substrates for th is study
sin ce th ey are a h om ologous group of substan ces with th e lipoph ilicity de-
pen den t on ly on th e alkyl ch ain len gth . Moreover, h ydrolysis of
4-n itroph en yl alkan oates in th e presen ce of 3-substituted pyridin ium salts
2b an d 2e did n ot exh ibit th e above-m en tion ed an om aly in th e absorban ce
vs tim e plots an d, th erefore, salts 2b an d 2e could be in volved in th is study
as well. Th e followin g esters were h ydrolyzed in m icellar solution s of salts
2b–2f (25 °C, pH 6.3, con cen tration of salt 2 2.0 · 10–3 m ol l–1 in all cases):
4-n itroph en yl acetate (PNPA), 4-n itroph en yl propan oate (PNPP),
4-n itroph en yl butan oate (PNPB), 4-n itroph en yl pen tan oate (PNPV),
4-n itroph en yl h exan oate (PNPH), an d 4-n itroph en yl octan oate (PNPO).
Com pared with th e above-m en tion ed h ydrolyses of PNPDPP, pH of th e re-
action m ixtures was kept lower sin ce alkan oates are h ydrolyzed too fast in
m icelles of salts 2 at pH 7.2. All experim en ts were perform ed above th e crit-
ical m icelle con cen tration of each of th e salts 2. Th e partition coefficien ts P
of th e substrates between octan -1-ol an d water were calculated usin g th e
software Pallas 1.2 (ref.9). To ch eck th e calculated partition coefficien t val-
ues, log P was determ in ed in several cases (PNPA, PNPB, an d PNPO). Th e
calculated an d foun d values of log P are given in Table II.
Th e obtain ed log kobs vs log P profiles for all th e syn th esized salts 2 are
sh own in Fig. 4. Un fortun ately, th e plots are m ore com plicated th an ex-
pected an d, at first sigh t, th ey do n ot give un equivocal eviden ce th at th e
n ucleoph ilic group position (above or below th e m icellar surface) in flu-
en ces h ydrolytic efficien cy of salts 2. Regardless of th e structure of salt 2,
th e in crease in th e substrate lipoph ilicity also in creases th e rate of its h y-
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

234
Cibulka, Hampl, Kotoučová, Mazáč, Liška:
drolysis wh en log P value is h igh er th an 3 (pen tan oate an d h igh er carbo-
xylic acid esters). Most probably, form ation of com icelles with salts 2
occurs in th e case of substrates with lon ger alkyl ch ain s an d deform s th e
sim ple partition between th e aqueous an d m icellar ph ase. Th us, relevan t
in form ation can be obtain ed on ly if less lipoph ilic substrates of log P < 3
are em ployed. In creasin g th e lipoph ilicity of th ese esters (PNPA, PNPP, an d
PNPB), th e rates of th eir h ydrolysis (log kobs) are in varian t or rath er decreas-
in g in m icelles of 1-dodecyl salts 2b an d 2c. On th e oth er h an d, in th e case
of m icellar solution s of 1-m eth yl salts 2e an d 2f, th e rates of th e substrate
h ydrolysis sligh tly in crease with th e in creasin g lipoph ilicity of th e
above-m en tion ed 4-n itroph en yl esters. As expected, th e slopes of th e
log kobs vs log P plots differ depen din g on th e type of m icellar catalyst em -
TABLE II
Calculated an d foun d octan -1-ol : water partition coefficien t P values of selected 4-n itro-
ph en yl alkan oates
log P
Substrate
calculated
foun d
PNPA
PNPB
PNPO
1.53
2.73
4.77
1.54
2.67
4.27
–1
–2
–3
–4
FIG. 4
Rate con stan t kobs of th e h ydrolysis of various
4-n itroph en yl alkan oates versus th eir
lipoph ilicity in m icelles of 2b ( ), 2c (❏), 2d
(❏), 2e (❏), an d 2f (❏). Con dition s: [oxim e] =
2.0 . 10–3 m ol l–1, 25 °C, pH 6.3 (0.05 M MES
buffer)
1
2
3
4
5
log P
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

Quaternary Pyridinium Ketoximes
235
ployed (1-dodecyl salts 2b an d 2c or 1-m eth yl salts 2e an d 2f), n everth eless,
th e differen ces are very sm all. Surprisin gly, th e slope of th e log kobs vs log P
profile of th e 2-substituted 1-m eth yl salt 2d is alm ost th e sam e as th ose of
1-dodecyl salts 2b an d 2c. Most probably, th e proxim ity of th e n ucleoph ilic
h ydroxyim in o group to quatern ary n itrogen an d to m icellar surface is re-
spon sible for th is beh aviour.
CONCLUSION
Kin etic studies perform ed with quatern ary pyridin ium ketoxim es 2 revealed
th at th e activity of th e h ydrolytic m icellar catalysts m igh t be stron gly in flu-
en ced by th e position of th eir n ucleoph ilic group relative to th e m icellar
surface. Most likely, location of th e n ucleoph ilic fun ction ben eath th e
m icellar surface (given by relative arran gem en t of h ydroph obic alkyl ch ain ,
h ead an d fun ction al group of th e surfactan t) is th e source of th e un usual
activity of 1-m eth ylpyridin ium salts 2d –2f. Sim ilar in fluen ce of th e h ydro-
ph obic alkyl ch ain an d fun ction al group position on th e reactivity of
am ph iph ilic com poun ds was observed by Rich m on d et al.10 in th e case of
Cu2+ ch elation by isom eric lipoph ilic β-h ydroxyketoxim es. Neverth eless, to
our kn owledge, n on e of th e h ydrolytic m icellar or m etallom icellar catalyst
so far in vestigated1 h as been of an alogous structure as our pyridin ium
ketoxim es 2d –2f, i.e. with th e n ucleoph ilic group located in th e m icellar in -
terior. Th erefore, salts 2d –2f represen t a n ew an d prom issin g type of
h ydrolytic catalysts. Neverth eless, furth er studies (with surfactan ts of a lon -
ger distan ce between th e polar h ead an d n ucleoph ilic groups) are n ecessary
to verify un doubtedly our h ypoth esis of th e in fluen ce of th e n ucleoph ilic
fun ction position on th e h ydrolytic activity of m icellar catalysts.
EXPERIMENTAL
Tem perature data were un corrected. 1H NMR spectra were recorded on spectrom eters Bruker
AMX3 an d Varian Gem in i 300 at 400 an d 300 MHz, respectively. 13C NMR spectra were re-
corded on a spectrom eter Bruker AMX3 at 100 MHz. Ch em ical sh ifts are reported in ppm
relative to tetram eth ylsilan e as an in tern al stan dard, couplin g con stan ts J are in Hz. Elem en -
tal an alyses were perform ed on Perkin –Elm er 240 an alyser. IR spectra were taken on an FTIR
spectrom eter Nicolet 740; th e waven um bers are given in cm –1. TLC an alyses were carried out
on DC Alufolien Kieselgel 60 F254 (Merck). Preparative ch rom atograph ic separation s were
perform ed on Kieselgel 60H, 40–63 µm (Merck) or on Silpearl (Kavalier).
Meth yl pyridin -2-yl (3a), pyridin -3-yl (3b) an d pyridin -4-yl keton e (3c), pyridin e-2-, -3-
an d -4-carbon itrile, dodecyl brom ide an d 1 M eth ereal solution of dodecylm agn esium bro-
m ide (all purum ) were obtain ed from Fluka. 2-(Morph 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), 4-n itroph en yl propan oate
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Cibulka, Hampl, Kotoučová, Mazáč, Liška:
(PNPP), 4-n itroph en yl h exan oate (PNPH), an d 4-n itroph en yl octan oate (PNPO) (an alytical
grade) were purch ased from Sigm a. 4-Nitroph en yl acetate11a (PNPA), 4-n itroph en yl
butan oate11b (PNPB), 4-n itroph en yl pen tan oate11b (PNPV), an d 4-n itroph en yl diph en yl
ph osph ate11c (PNPDPP) were prepared an d purified accordin g to described m eth ods.
Dodecyl Pyridyl Keton es 3d –3f
Keton es 3d –3f were prepared usin g th e procedure described in our previous
com m un ication s4 from th e correspon din g pyridin ecarbon itrile (3.00 g, 28.8 m m ol) in dry
eth er (135 m l). In th e case of th e 3-isom er, refluxin g th e reaction m ixture for 1 h was n eces-
sary to com plete th e reaction . Crude products were purified by colum n ch rom atograph y
(ch loroform –m eth an ol, 100 : 2).
Dodecyl pyridin-2-yl ketone (3d ). Pure keton e 3d was obtain ed by distillation of th e product
resultin g from colum n ch rom atograph y. Yield 2.75 g (35%), b.p. 128–132 °C/40 Pa. For
C
18H29NO (275.3) calculated: 78.49% C, 10.61% H, 5.08% N; foun d: 78.50% C, 10.69% H,
4.30% N. 1H NMR (CDCl3): 0.87 t, 3 H, J(12′,11′) = 7.0 (H-12′); 1.23 bs, 18 H (H-3′–H-11′);
1.73 tt, 2 H, J(2′,1′) = J(2′,3′) = 7.7 (H-2′); 3.21 t, 2 H, J(1′,2′) = 7.6 (H-1′); 7.46 ddd, 1 H,
J(5,4) = 7.5, J(5,6) = 4.3, J(5,3) = 0.9 (H-5); 7.83 td, 1 H, J(4,5) = J(4,3) = 7.7, J(4,6) = 1.6
(H-4); 8.04 d, 1 H, J(3,4) = 7.8 (H-3); 8.68 d, 1 H, J(6,5) = 4.5 (H-6). 13C NMR (CDCl3): 14.8 s
(C-12′); 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′);
30.35 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 pyridin-3-yl ketone (3e). Yield 5.41 g (68%), m .p. 46–48 °C. For C18H29NO (275.3)
calculated: 78.49% C, 10.61% H, 5.08% N; foun d: 78.36% C, 10.41% H, 5.02% N. 1H NMR
(CDCl3): 0.87 t, 3 H, J(12′,11′) = 6.6 (H-12′); 1.25 bs, 18 H (H-3′–H-11′); 1.74 tt, 2 H, J(2′,1′) =
J(2′,3′) = 7.1 (H-2′); 2.97 t, 2 H, J(1′,2′) = 7.3 (H-1′); 7.42 dd, 1 H, J(5,4) = 7.9, J(5,6) = 4.7
(H-5); 8.23 dt, 1 H, J(4,5) = 7.9, J(4,6) = J(4,2) = 1.8 (H-4); 8.76 dd, 1 H, J(6,5) = 4.5, J(6,2) =
1.6 (H-6); 9.16 s, 1 H (H-2). 13C NMR (CDCl3): 14.8 s (C-12′); 23.4 s (C-11′); 24.8 s (C-10′);
30.0 s (C-9′); 30.2 m (C-4′–C-8′); 30.3 s (C-3′); 32.6 s (C-2′); 39.6 s (C-1′); 124.4 s (C-5); 133.0 s
(C-3); 136.1 s (C-4); 150.3 s (C-6); 154.0 s (C-2); 199.9 s (C=O).
6-Dodecylpyridine-3-carbonitrile (4). Yield 0.13 g (2%), m .p. 40–43 °C. For C18H28N2 (272.4)
calculated: 79.36% C, 10.36% H, 10.28% N; foun d: 79.68% C, 10.52% H, 9.31% N. 1H NMR
(CDCl3): 0.88 t, 3 H, J(12′,11′) = 6.6 (H-12′); 1.26 bs, 18 H (H-3′–H-11′); 1.73 tt, 2 H, J(2′,1′) =
J(2′,3′) = 7.6 (H-2′); 2.56 t, 2 H, J(1′,2′) = 7.6 (H-1′); 7.27 d, 1 H, J(5,4) = 8.0 (H-5); 7.85 dd,
1 H, J(4,5) = 8.1, J(4,2) = 2.2 (H-4); 8.80 d, 1 H, J(2,4) = 1.7 (H-2). 13C NMR (CDCl3): 14.8 s
(C-12′); 23.4 s (C-11′); 30.2 m (C-3′–C-10′); 32.6 s (C-2′); 39.4 s (C-1′); 107.8 s (C-3); 117.7 s
(C≡N); 123.5 s (C-5); 139.9 s (C-4); 152.8 s (C-2); 168.0 s (C-6).
Dodecyl pyridin-4-yl ketone (3f). Yield 4.97 g (63%), m .p. 56–60 °C. For C18H29NO (275.3)
calculated: 78.49% C, 10.61% H, 5.08% N; foun d: 78.13% C, 10.51% H, 4.77% N. 1H NMR
(CDCl3): 0.88 t, 3 H, J(12′,11′) = 7.0 (H-12′); 1.26 bs, 18 H (H-3′–H-11′); 1.74 tt, 2 H, J(2′,1′) =
J(2′,3′) = 7.3 (H-2′); 2.96 t, 2 H, J(1′,2′) = 7.3 (H-1′); 7.72 dd, 2 H, J(3,2) = J(5,6) = 4.6, J(3,5) =
J(5,3) = 1.2 (H-3, H-5); 8.81 d, 2 H, J(2,3) = J(6,5) = 4.4 (H-2, H-6). 13C NMR (CDCl3): 14.8 s
(C-12′); 23.4 s (C-11′); 24.6 s (C-10′); 30.2 m (C-3′–C-9′); 32.6 s (C-2′); 39.6 s (C-1′); 121.8 s
(C-3, C-5); 143.6 s (C-4); 151.7 s (C-2, C-6); 200.5 s (C=O).
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Quaternary Pyridinium Ketoximes
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Alkyl Pyridyl Ketoxim es 5a–5f
Ketoxim es 5a–5f were prepared from keton es 3a–3f usin g th e procedure described in our
previous com m un ication s4. Pure products were obtain ed eith er by crystallization from
eth an ol–water, 1 : 1 (ketoxim es 5a–5c) or by precipitation with water from th eir eth an olic solu-
tion s followed by colum n ch rom atograph y (ch loroform –m eth an ol, 100 : 2) an d crystallization
from eth an ol–water (5d –5f).
(E)-Methyl pyridin-2-yl ketoxime (5a). Prepared from keton e 3a (4.00 g, 0.033 m ol). Yield
2.96 g (64%), m .p. 122–123 °C (ref.12a 121 °C). 1H NMR (CDCl3): 2.43 s, 3 H (CH3); 7.28 ddd,
1 H, J(5,4) = 7.5, J(5,6) = 4.9, J(5,3) = 1.1 (H-5); 7.70 td, 1 H, J(4,5) = J(4,3) = 7.8, J(4.6) = 1.8
(H-4); 7.85 dt, 1 H, J(3,4) = 8.0, J(3,5) = J(3,6) = 0.9 (H-3); 8.66 ddd, 1 H, J(6,5) = 4.9, J(6,4) =
1.6, J(6,3) = 0.9 (H-6); 9.90 s, 1 H (OH). 13C NMR (CDCl3): 11.4 s (CH3); 121.3 s (C-3);
124.4 s (C-5); 137.1 s (C-4); 149.6 s (C-6); 155.1 s (C-2); 157.6 s (C=NOH). IR (CCl4): ν(OH)
3 240 (bridged), ν(OH) 3 580 (free).
Methyl pyridin-3-yl ketoxime (5b ). Prepared from keton e 3b (4.00 g, 0.033 m ol). Yield
3.73 g (83%), m .p. 114–118 °C (ref.12a 116 °C, ref.12b 111–113 °C). 1H NMR (CDCl3): 2.30 s,
3 H (CH3); 7.32 dd, 1 H, J(5,4) = 7.9, J(5,6) = 4.9 (H-5); 7.95 d, 1 H, J(4,5) = 8.2 (H-4); 8.61 d,
1 H, J(6,5) = 4.5 (H-6); 8.91 s, 1 H (H-2). 13C NMR (CDCl3): 12.4 s (CH3); 124.1 s (C-5);
133.7 s (C-3); 134.4 s (C-4); 147.8 s (C-6); 150.0 s (C-2); 153.3 s (C=NOH).
Methyl pyridin-4-yl ketoxime (5c). Prepared from keton e 3c (4.00 g, 0.033 m ol). Yield 3.91 g
(87%), m .p. 160–161 °C (ref.12a 157.5 °C). 1H NMR (CDCl3): 2.31 s, 3 H (CH3); 7.56 d, 2 H,
J(5,6) = J(3,2) = 6.0 (H-3, H-5); 8.64 d, 2 H, J(6,5) = J(2,3) = 6.0 (H-2, H-6). 13C NMR (CDCl3):
11.9 s (CH3); 121.1 s (C-3, C-5); 145.3 s (C-4); 150.4 s (C-2, C-6); 154.0 s (C=NOH).
Dodecyl pyridin-2-yl ketoxime (5d ). Prepared from keton e 3d (2.70 g, 9.8 m m ol). Yield
2.59 g (91%), m .p. 55–63 °C (E/Z ratio ca 5 : 4 by 1H NMR). Both stereoisom ers were separated
by colum n ch rom atograph y (ch loroform –m eth an ol, 100 : 2).
(E)-Dodecyl pyridin-2-yl ketoxime. M.p. 60–63 °C (ref.4a 58–63 °C). For C18H30N2O (290.5)
calculated: 74.44% C, 10.41% H, 9.64% N; foun d: 74.58% C, 10.23% H, 9.63% N. 1H NMR
(CDCl3): 0.87 t, 3 H, J(12′,11′) = 6.8 (H-12′); 1.24 bs, 18 H (H-11′–H-3′); 1.58 tt, 2 H, J(2′,1′) =
J(2′,3′) = 7.7 (H-2′); 2.98 t, 2 H, J(1′,2′) = 7.7 (H-1′); 7.26 m , 1 H (H-5); 7.69 td, 1 H, J(4,5) =
J(4,3) = 7.6, J(4,6) = 1.7 (H-4); 7.79 d, 1 H, J(3,4) = 8.0 (H-3); 8.22 s 1 H (OH); 8.63 d, 1 H,
J(6,5) = 4.3 (H-6). 13C NMR (CDCl3): 14.8 s (C-12′); 23.4 s (C-11′); 25.3 s (C-10′); 27.0 s
(C-9′); 30.0–30.6 m (C-8′–C-2′); 32.6 s (C-1′); 121.6 s (C-3); 124.2 s (C-5); 136.9 s (C-4);
149.7 s (C-6); 154.7 s (C-2); 161.6 s (C=NOH). IR (CCl4): ν(OH) 3 257 (bridged), ν(OH) 3 594
(free).
(Z)-Dodecyl pyridin-2-yl ketoxime. M.p. 55–59 °C. For C18H30N2O (290.5) calculated: 74.44% C,
10.41% H, 9.64% N; foun d: 74.09% C, 10.23% H, 9.31% N. 1H NMR (CDCl3): 0.87 t, 3 H,
J(12′,11′) = 6.8 (H-12′); 1.24 bs, 18 H (H-11′–H-3′); 1.62 tt, 2 H, J(2′,1′) = J(2′,3′) = 7.7 (H-2′);
2.67 t, 2 H, J(1′,2′) = 7.7 (H-1′); 7.41 dd, 1 H, J(5,4) = 7.4, J(5,6) = 4.4 (H-5); 7.51 d, 1 H,
J(3,5) = 8.1 (H-3); 7.91 td, 1 H, J(4,3) = J(4,5) = 7.5, J(4,6) = 1.6 (H-4); 8.57 d, 1 H, J(6,5) =
4.9 (H-6). 13C NMR (CDCl3): 33.7 s (C-1′).
Dodecyl pyridin-3-yl ketoxime (5e). Prepared from keton e 3e (2.10 g, 7.5 m m ol). Crude
product (E/Z ratio ca 4 : 1 by 1H NMR) was purified by crystallization from eth an ol.
(E)-Dodecyl pyridin-3-yl ketoxime. Yield 1.84 g (86%), m .p. 81.5–83 °C. For C18H30N2O
(290.5) calculated: 74.44% C, 10.41% H, 9.64% N; foun d: 74.76% C, 10.51% H, 10.10% N.
1H NMR (CDCl3): 0.88 t, 3 H, J(12′,11′) = 7.0 (H-12′); 1.25 bs, 18 H (H-11′–H-3′); 1.57 tt, 2 H,
J(2′,1′) = J(2′,3′) = 7.3 (H-2′); 2.82 t, 2 H, J(1′,2′) = 7.6 (H-1′); 7.32 dd, 1 H, J(5,4) = 7.9, J(5,6)
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Cibulka, Hampl, Kotoučová, Mazáč, Liška:
= 4.8 (H-5); 7.94 d, 1 H, J (4,5) = 8.0 (H-4); 8.61 d, 1 H, J(6,5) = 4.3 (H-6); 8.91 d, 1 H, J(2,6)
= 1.2 (H-2); 9.75 s, 1 H (OH). 13C NMR (CDCl3): 14.8 s (C-12′); 23.4 s (C-11′); 26.5 s (C-10′);
27.0 s (C-9′); 30.0–30.5 m (C-8′–C-2′); 32.6 s (C-1′); 124.1 s (C-5); 132.7 s (C-3); 134.5 s
(C-4); 148.3 s (C-6); 150.3 s (C-2); 157.9 s (C=NOH).
(Z)-Dodecyl pyridin-3-yl ketoxime. Th is com poun d was n ot isolated an d th e spectral ch arac-
teristics were deduced from th e spectra of an E/Z m ixture. 1H NMR (CDCl3): 0.88 t, 3 H,
J(12′,11′) = 7.0 (H-12′); 1.25 bs, 18 H (H-11′–H-3′); 1.46 m , 2 H (H-2′); 2.58 t, 2 H, J(1′,2′) =
7.8 (H-1′); 7.37 dd, 1H, J(5,4) = 8.2, J(5,6) = 4.3 (H-5); 7.83 d, 1 H, J(4,5) = 8.2 (H-4); 8.56 d,
1 H, J(6,5) = 4.3 (H-6); 8.73 s, 1 H (H-2); 9.29 s, 1 H (OH).13C NMR (CDCl3): 31.5 s (C-2′);
35.7 s (C-1′).
Dodecyl pyridin-4-yl ketoxime (5f). Prepared from keton e 3f (0.98 g, 3.6 m m ol). Crude product
(E/Z ratio ca 4 : 1 by 1H NMR) was purified by crystallization from eth an ol.
(E)-Dodecyl pyridin-4-yl ketoxime. Yield 0.48 g (46%), m .p. 92–94 °C. For C18H30N2O (290.5)
calculated: 74.44% C, 10.41% H, 9.64% N; foun d: 74.78% C, 10.58% H, 9.39% N. 1H NMR
(CDCl3): 0.88 t, 3 H, J(12′,11′) = 6.8 (H-12′); 1.25 bs, 18 H (H-11′–H-3′); 1.55 tt, 2 H, J(2′,1′) =
J(2′,3′) = 7.9 (H-2′); 2.79 t, 2 H, J(1′,2′) = 7.8 (H-1′); 7.52 d, 2 H, J(3,2) = J(5,6) = 5.9 (H-3,
H-5); 8.63 d, 2 H, J(2,3) = J(6,5) = 5.9 (H-2, H-6); 9.15 s, 1 H (OH). 13C NMR (CDCl3): 14.8 s
(C-12′); 23.4 s (C-11′); 26.0 s (C-10′); 26.5 s (C-9′); 27.1–30.5 m (C-8′–C-2′); 32.6 s (C-1′);
121.3 s (C-3, C-5); 144.9 s (C-4); 150.4 s (C-2, C-6); 157.8 s (C=NOH).
(Z)-Dodecyl pyridin-4-yl ketoxime. Th is com poun d was n ot isolated an d th e spectral ch arac-
teristics were deduced from th e spectra of an E/Z m ixture. 1H NMR (CDCl3): 0.88 t, 3 H,
J(12′,11′) = 6.8 (H-12′); 1.25 bs, 18 H (H-11′–H-3′); 1.44 tt, 2 H, J(2′,1′) = J(2′,3′) = 7.5 (H-2′);
2.52 t, 2 H, J(1′,2′) = 7.6 (H-1′); 7.33 d, 2 H, J(3,2) = J(5,6) = 6.0 (H-3, H-5); 8.57 s, 1 H (OH);
8.63 d, 2 H, J(2,3) = J(6,5) = 5.9 (H-2, H-6). 13C NMR (CDCl3): 14.8 s (C-12′); 23.4 s (C-11′);
26.0 s (C-10′); 26.9 s (C-9′); 27.1–30.5 m (C-8′–C-2′); 35.5 s (C-1′); 123.4 s (C-3, C-5); 142.4 s
(C-4); 150.6 s (C-2, C-6); 157.4 s (C=NOH).
Quatern ization of Meth yl Pyridyl Ketoxim es 5a–5c
Meth yl pyridyl ketoxim es 5b an d 5c (3.00 g, 22.0 m m ol) an d dodecyl brom ide (9.22 g, 37.0
m m ol) were h eated in refluxin g aceton itrile (100 m l) for 8 h . Evaporation of th e solven t un -
der reduced pressure afforded crude products wh ich were purified by crystallization from
eth an ol. Meth yl pyridin -2-yl ketoxim e (5a) did n ot react un der th e above-m en tion ed con di-
tion s. Th e reaction in th e sealed glass tube at 150 °C for 50 h led to a com plex m ixture of
products. Un reacted startin g com poun ds an d m eth yl pyridin -2-yl keton e (3a) were isolated
by colum n ch rom atograph y (ch loroform –m eth an ol, 10 : 1) from th e reaction m ixture. Sim i-
lar results were also obtain ed with oxim e 5a an d dodecyl brom ide in th e presen ce of an
equim olar am oun t of potassium iodide6 in aceton e.
Methyl pyridin-2-yl ketone (3a). Isolated by colum n ch rom atograph y (ch loroform –m eth an ol,
10 : 1). 1H NMR (CDCl3): 2.95 s, 3 H (CH3); 7.45 m , 1 H (H-5); 7.81 td, 1 H, J(4,3) = J(4,5) =
7.7, J(4,6) = 1.6 (H-4); 7.98 d, 1 H, J(3,4) = 8.2 (H-3); 8.63 dm , 1 H, J(4,3) = 5.5 (H-6).
1-Dodecyl-3-[1-(hydroxyimino)ethyl]pyridinium bromide (2b ). Yield 6.33 g (75%), m .p.
118–120 °C. For C19H33BrN2O (385.3) calculated: 59.21% C, 8.63% H, 7.27% N; foun d:
59.16% C, 8.58% H, 7.22% N. 1H NMR (CDCl3): 0.86 t, 3 H, J(12′,11′) = 6.8 (H-12′); 1.23 bs,
18 H (H-11′–H-3′); 2.04 tt, 2 H (H-2′); 2.26 s, 3 H (CH3-C=N); 4.96 t, 2 H, J(2′,1′) = 7.2 (H-1′);
8.15 m , 1 H (H-5); 8.63 d, 1 H, J(4,5) = 8.1 (H-4); 9.17 d, 1 H, J(6,5) = 5.5 (H-6); 9.39 s, 1 H
(H-2); 11.12 s, 1 H (OH). 13C NMR (CDCl3): 12.7 s (CH3C=NOH); 14.8 s (C-12′); 23.4 s
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Quaternary Pyridinium Ketoximes
239
(C-11′); 26.9 s (C-10′); 29.9 s (C-9′); 30.2 s (C-8′–C-4′); 32.6 s (C-3′); 32.7 s (C-2′); 63.1 s
(C-1′); 128.9 s (C-5); 138.5 s (C-3); 142.1 s (C-4); 142.5 s (C-6); 144.5 s (C-2); 149.6 s
(C=NOH). pKa = 10.1.
1-Dodecyl-4-[1-(hydroxyimino)ethyl]pyridinium bromide (2c). Yield 5.86 g (69%), m .p.
128–131 °C. For C19H33BrN2O (385.3) calculated: 59.21% C, 8.63% H, 7.27% N; foun d:
58.52% C, 8.77% H, 6.91% N. 1H NMR (CDCl3): 0.86 t, 3 H, J(12′,11′) = 7.0 (H-12′); 1.32 bs,
18 H (H-11′–H-3′); 2.03 m , 2 H (H-2′); 2.17 s, 3 H (CH3-C=N); 4.83 t, 2 H, J(2′,1′) = 7.2 (H-1′);
8.15 d, 2 H, J(3,2) = J(5,6) = 6.6 (H-3, H-5); 9.24 d, 2 H, J(2,3) = J(6,5) = 6.5 (H-2, H-6);
11.68 s, 1 H (OH). 13C NMR (CDCl3): 11.8 s (CH3C=NOH); 14.8 s (C-12′); 23.4 s (C-11′);
26.9 s (C-10′); 29.8 s (C-9′); 30.2 s (C-8′–C-4′); 32.4 s (C-3′); 32.6 s (C-2′); 62.1 s (C-1′);
124.5 s (C-3, C-5); 145.3 s (C-2, C-6); 150.6 s (C-4); 152.9 s (C=NOH). pKa = 9.3.
Quatern ization of Dodecyl Pyridyl Ketoxim es 5d –5f
Dodecyl pyridyl ketoxim es 5d –5f an d m eth yl iodide (5–6 m olar excess) were h eated in eth a-
n ol to 45 °C. Evaporation of th e solven t un der reduced pressure afforded crude products
wh ich were purified by crystallization from aceton e–eth er. In th e case of 2-[1-(h ydroxy-
im in o)tridecyl]-1-m eth ylpyridin ium iodide (2g), un reacted ketoxim e 5d was separated by
colum n ch rom atograph y (ch loroform –m eth an ol–aceton e–water, 30 : 5 : 5 : 1) before crystal-
lization . Iodides 2g–2i were con verted to correspon din g brom ides 2d –2f by an ion exch an ge
on Am berlite IRA-400 usin g th e previously described procedure3d
.
2-[1-(Hydroxyimino)tridecyl]-1-methylpyridinium iodide (2g). Prepared from oxim e 5d (1.0 g,
3.5 m m ol). Reaction tim e 70 h . Yield 0.39 g (23%), m .p. 80–85 °C. For C19H33IN2O (432.3)
calculated: 52.78% C, 7.69% H, 6.48% N; foun d: 53.00% C, 7.64% H, 6.30% N. 1H NMR
(CDCl3): 0.87 t, 3 H, J(12′,11′) = 6.5 (H-12′); 1.24 bs, 18 H (H-11′–H-3′); 1.44 tt, 2 H, J(2′,1′) =
J(2′,3′) = 7.7 (H-2′); 2.82 t, 2 H, J(1′,2′) = 7.8 (H-1′); 4.46 s, 3 H (CH3-N+); 8.05 m , 2 H (H-5,
H-4); 8.68 d, 1 H, J(3,4) = 7.6 (H-3); 9.55 d, 1 H, J(6,5) = 6.0 (H-6); 10.51 s, 1 H (OH).
13C NMR (CDCl3): 14.8 s (C-12′); 23.4 s (C-11′); 26.5 s (C-10′); 30.2 m (C-9′–C-2′); 32.6 s
(C-1′); 49.5 s (CH3-N+); 128.4 s (C-3); 129.6 s (C-5); 146.9 s (C-4); 148.9 s (C-6); 151.5 s
(C-2); 153.1 s (C=NOH).
3-[1-(Hydroxyimino)tridecyl]-1-methylpyridinium iodide (2h ). Prepared from oxim e 5e (1.3 g,
4.5 m m ol). Reaction tim e 20 h . Yield 1.4 g (68%), m .p. 98–101.5 °C. For C19H33IN2O (432.3)
calculated: 52.78% C, 7.69% H, 6.48% N; foun d: 51.65% C, 7.52% H, 6.49% N. 1H NMR
(CDCl3): 0.87 t, 3 H, J(12′,11′) = 6.5 (H-12′); 1.24 bs, 18 H (H-11′–H-3′); 1.46 m , 2 H (H-2′);
2.81 t, 2 H, J(1′,2′) = 7.9 (H-1′); 4.64 s, 3 H (CH3-N+); 8.11 dd, 1 H, J(5,4) = 8.0, J(5,6) = 6.2
(H-5); 8.54 d, 1 H, J(4,5) = 8.2 (H-4); 9.06 d, 1 H, J(6,5) = 5.9 (H-6); 9.24 s, 1 H (H-2); 9.93 s
1 H (OH). 13C NMR (CDCl3): 14.8 s (C-12′); 23.4 s (C-11′); 26.2 s (C-10′); 30.4 m (C-9′–C-2′);
32.6 s (C-1′); 51.1 s (CH3-N+); 129.0 s (C-5); 137.4 s (C-3); 142.2 s (C-4); 143.6 s (C-6);
145.3 s (C-2); 154.1 s (C=NOH).
4-[1-(Hydroxyimino)tridecyl]-1-methylpyridinium iodide (2i). Prepared from oxim e 5f (0.37 g,
1.28 m m ol). Reaction tim e 40 h . Yield 0.25 g (63%), m .p. 117–120.5 °C. For C19H33IN2O
(432.3) calculated: 52.78% C, 7.69% H, 6.48% N; foun d: 52.61% C, 7.49% H, 6.19% N.
1H NMR (CDCl3): 0.87 t, 3 H, J(12′,11′) = 6.6 (H-12′); 1.24 bs, 18 H (H-11′–H-3′); 1.41 tt, 2 H,
J(2′,1′) = J(2′,3′) = 7.3 (H-2′); 2.71 t, 2 H, J(1′,2′) = 7.3 (H-1′); 4.58 s, 3 H (CH3-N+); 8.09 d, 2 H,
J(3,2) = J(5,6) = 6.7 (H-3, H-5); 9.14 d, 2 H, J(2,3) = J(6,5) = 6.6 (H-2, H-6); 10.24 s, 1 H (OH).
13C NMR (CDCl3): 14.8 s (C-12′); 23.4 s (C-11′); 25.7 s (C-10′); 30.3 m (C-9′–C-2′); 32.6 s
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Cibulka, Hampl, Kotoučová, Mazáč, Liška:
(C-1′); 49.7 s (CH3-N+); 124.6 s (C-3, C-5); 146.2 s (C-2, C-6); 152.5 s (C-4); 154.9 s
(C=NOH).
2-[1-(Hydroxyimino)tridecyl]-1-methylpyridinium bromide (2d). Prepared from iodide 2g (0.34 g,
0.8 m m ol). Yield 0.30 g (78%), m .p. 126–127 °C. For C19H33BrN2O (385.3) calculated:
59.22% C, 8.63% H, 7.27% N; foun d: 58.77% C, 8.76% H, 6.90% N. 1H NMR (CDCl3):
0.87 t, 3 H, J(12′,11′) = 6.6 (H-12′); 1.24 bs, 18 H (H-11′–H-3′); 1.43 tt, 2 H, J(2′,1′) = J(2′,3′) =
7.9 (H-2′); 2.79 t, 2 H, J(1′,2′) = 7.8 (H-1′); 4.49 s, 3 H (CH3-N+); 8.00 m , 2 H (H-5, H-4);
8.65 d, 1 H, J(3,4) = 7.9 (H-3); 9.78 d, 1 H, J(6,5) = 6.1 (H-6); 11.70 s, 1 H (OH). 13C NMR
(CDCl3): 14.8 s (C-12′); 23.4 s (C-11′); 26.4 s (C-10′); 30.2 m (C-9′–C-2′); 32.6 s (C-1′); 48.8 s
(CH3-N+); 128.0 s (C-3); 129.5 s (C-5); 146.1 s (C-4); 149.6 s (C-6); 151.8 s (C-2); 152.4 s
(C=NOH). pKa = 9.6.
3-[1-(Hydroxyimino)tridecyl]-1-methylpyridinium bromide (2e). Prepared from iodide 2h
(0.35 g, 0.8 m m ol). Yield 0.37 g (84%), m .p. 106–108 °C. For C19H33BrN2O (385.3) calcu-
lated: 59.22% C, 8.63% H, 7.27% N; foun d: 59.20% C, 8.83% H, 7.01% N. 1H NMR
(DMSO-d6): 0.85 t, 3 H, J(12′,11′) = 6.5 (H-12′); 1.23 bs, 18 H (H-11′–H-3′); 1.44 m , 2 H
(H-2′); 2.79 t, 2 H, J(1′,2′) = 6.5 (H-1′); 4.41 s, 3 H (CH3-N+); 8.12 t, 1 H, J(5,4) = J(5,6) =
6.6 (H-5); 8.75 d, 1 H, J(4,5) = 7.9 (H-4); 8.98 d, 1 H, J(6,5) = 5.1 (H-6); 9.19 s, 1 H (H-2);
12.09 s, 1 H (OH). 13C NMR (DMSO-d6): 13.9 s (C-12′); 22.0 s (C-11′); 24.3 s (C-10′); 28.7 m
(C-9′–C-2′); 31.4 s (C-1′); 48.2 s (CH3-N+); 127.5 s (C-5); 135.6 s (C-3); 140.9 s (C-4); 142.7 s
(C-6); 144.8 s (C-2); 152.7 s (C=NOH). pKa = 9.4.
4-[1-(Hydroxyimino)tridecyl]-1-methylpyridinium bromide (2f). Prepared from iodide 2i
(0.37 g, 0.9 m m ol). Yield 0.34 g (98%), m .p. 134–135 °C. For C19H33BrN2O (385.3) calcu-
lated: 59.22% C, 8.63% H, 7.27% N; foun d: 59.02% C, 8.32% H, 7.29% N. 1H NMR (CDCl3):
0.88 t, 3 H, J(12′,11′) = 7.0 (H-12′); 1.24 bs, 18 H (H-11′–H-3′); 1.40 m , 2 H (H-2′); 2.68 t,
2 H, J(1′,2′) = 7.9 (H-1′); 4.61 s, 3 H (CH3-N+); 8.02 d, 2 H, J(3,2) = J(5,6) = 6.3 (H-3, H-5);
9.19 d, 2 H, J(2,3) = J(6,5) = 5.9 (H-2, H-6); 11.28 s, 1 H (OH). 13C NMR (CDCl3): 14.8 s
(C-12′); 23.4 s (C-11′); 25.5 s (C-10′); 30.3 m (C-9′–C-2′); 32.6 s (C-1′); 49.2 s (CH3-N+);
124.3 s (C-3, C-5); 146.2 s (C-2, C-6); 152.7 s (C-4); 154.5 s (C=NOH). pKa = 9.9.
Determ in ation of pKa
pKa values were determ in ed spectroph otom etrically at two wavelen gth s (m axim a of th e
=NOH an d =NO– form ) usin g th e described procedure13
.
Determ in ation of log P
4-Nitroph en yl alkan oate was dissolved in octan -1-ol saturated with water. Th is solution (of
kn own ester con cen tration ) was sh aken with redistilled water at 20 °C for 1 h . Th en , th e
con cen tration of th e 4-n itroph en yl ester in both ph ases was determ in ed as follows: an
aliquot am oun t of each ph ase was tran sferred in to th e spectroph otom etric cell. An appropri-
ate am oun t of water (with th e aqueous ph ase) or m eth an ol (with th e organ ic ph ase) was
added to obtain 1 500 µl of h om ogen eous solution . Th e excess of sodium h ydroxide (500 µl
of 4 M aqueous solution ) was added to h ydrolyze th e 4-n itroph en yl ester; th e reaction was
over im m ediately. Con cen tration of th e released 4-n itroph en oxide ion was determ in ed spec-
troph otom etrically at 400 n m . Four differen t ratios of water : octan -1-ol were used for th e
determ in ation of partition coefficien t P of each ester. Th e partition coefficien t was obtain ed
from th e calculated ratios of th e ester con cen tration in both ph ases usin g Horn procedure14
.
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Quaternary Pyridinium Ketoximes
241
Kin etic Measurem en ts
Solution s of salts 2 of th e desired con cen tration s were prepared in an appropriate 0.05
M
buffer. No ch an ges in pH were observed durin g kin etic run s. Th e reaction 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 perature at 25.0 ± 0.1 °C. Th e
reaction s were in itiated by in jection of 8.0 · 10–4 M PNPDPP solution in aceton itrile (50 µl)
in to th e spectroph otom etric cell con tain in g 1 950 µl of th e buffered solution of catalyst or
by in jection of 6.0 · 10–3 M 4-n itroph en yl alkan oate solution in aceton itrile (5.5 µl) in to th e
spectroph otom etric cell con tain in g 1 600 µl of th e buffered solution of catalyst, th e result-
in g con cen tration of th e substrate bein g 2.0 · 10–5 M in both cases. Th e reaction s were m on i-
tored at th e wavelen gth 400 n m (m axim um of 4-n itroph en oxide absorption ). 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 kobs were obtain ed by n on -lin ear regression an alysis of th e absorban ce vs tim e
data usin g software package En zfitter15. 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. 203/99/1622).
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