Chiral pyridinium-based ionic liquids containing the (1R,2S,5R)-(-)-menthyl group

Article abstract of DOI:10.1016/j.tetasy.2006.06.014

A novel class of chiral pyridinium salts in which the chirality resides in the cation have been prepared and characterized. The physicochemical and anti-microbial properties have been determined. The group of prepared salts contained chiral ionic liquids and decomposable chiral pyridinium chlorides.

Full text of DOI:10.1016/j.tetasy.2006.06.014

Tetrahedron: Asymmetry 17 (2006) 1728–1737
Chiral pyridinium-based ionic liquids containing the
(1R,2S,5R)-(ꢀ)-menthyl group
Juliusz Pernak* and Joanna Feder-Kubis
Poznan´ University of Technology, Department of Chemical Technology, pl. Skłodowskiej-Curie 2, 60-965 Poznan´, Poland
Received 11 May 2006; accepted 2 June 2006
Abstract—A novel class of chiral pyridinium salts in which the chirality resides in the cation have been prepared and characterized. The
physicochemical and anti-microbial properties have been determined. The group of prepared salts contained chiral ionic liquids and
decomposable chiral pyridinium chlorides.
ꢀ 2006 Elsevier Ltd. All rights reserved.
1. Introduction
tion of dibenzobicyclo[2.2.2]octatrienes.5 Chloromethyl
(1R,2S,5R)-(ꢀ)-menthyl ether as a chiral OH protecting
group was used in the measurement of enantiomeric
excess.6,7 Herein, we report new chiral pyridinium-based
ILs with a (1R,2S,5R)-(ꢀ)-menthyl substituent in the 1
position of the pyridine ring.
Pyridinium salts possess surface-active properties, deter-
gency, biological activities (in particular, anti-bacterial
activity), and a capacity to be adsorbed on negatively
charged solids. The most important pyridinium derivatives
occurring naturally are those of nicotinamide, which have a
coenzyme function. The most general method of forming
pyridinium halides is by nucleophilic substitution, some-
times called the Menschutkin reaction.1 Pyridinium halides
are used as synthetic precursors of ionic liquids (ILs). ILs
open up a wide field for future investigations in chemistry,
electrochemistry, biology, physics, material science, and
medicine. Recently, some chiral ionic liquids (CILs) have
been reported and a review of this newest class is avail-
able.2,3 CILs are particularly attractive due to the potential
for their chiral discrimination, as in asymmetric synthesis
and the resolution of racemates. From a structural point
of view, chirality in ILs can arise from either the anion
or the cation. Two examples of CILs containing the
(1R,2S,5R)-(ꢀ)-menthyl group as (1R,2S,5R)-(ꢀ)-menthyl-
ammonium and (1R,2S,5R)-(ꢀ)-menthylimidazolium have
been published.4,5 The preparation, characterization, and
the single-crystal X-ray structures of trialkyl[(1R,2S,5R)-
(ꢀ)-menthoxymethyl]ammonium salts have been re-
ported.4 3-[(1R,2S,5R)-(ꢀ)-menthoxymethyl]-1-methylimid-
azolium bis(trifluoromethanesulfonyl)imide has been
successfully used as a chiral solvent in the photoisomeriza-
2. Results and discussion
All pyridinium salts were prepared in the two step reaction
presented in Scheme 1. The first step was the Menschutkin
reaction. As a reagent for quaternization, chloromethyl
(1R,2S,5R)-(ꢀ)-menthyl ether was used, which was ob-
tained from (1R,2S,5R)-(ꢀ)-menthol, the inexpensive,
commercially available (ꢀ)-isomer. This ether is very reac-
tive. It requires strictly anhydrous conditions, since, other-
wise it readily becomes hydrolyzed to HCl, CH2O, and
menthol. Quaternization takes place immediately and pro-
ceeds readily at room temperature via an SN1 mechanism.
The initial rate-determining step is cation formation by
ionization. The obtained cation rapidly reacts with pyri-
dine derivatives. This specific type of Menschutkin reaction
is presented in Scheme 2. In general, the procedure is sim-
ple and the reaction has high product yield. Synthesized
pyridinium chlorides 1, presented in Table 1, are crystal-
line, except 1f which is a hygroscopic grease. They are eas-
ily soluble in water, except 1i which is poorly soluble and
can be assayed by a direct two-phase back titration accord-
ing to the EN ISO 2871-1 (2000) standard. The results of
surfactant content studies are listed in Table 1 and ranged
from 92.5% to 99.5% surfactant content. The remainder
*
Corresponding author. Tel.: +48 61 665 36 82; fax: +48 61 665 36 49;
e-mail: juliusz.pernak@put.poznan.pl
0957-4166/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2006.06.014

J. Pernak, J. Feder-Kubis / Tetrahedron: Asymmetry 17 (2006) 1728–1737
1729
The synthesized chlorides 1 were stable in air and in con-
tact with water. The only exception was 3-carbamoyl-1-
(1R,2S,5R)-(ꢀ)-menthylpyridinium chloride 1h, which eas-
ily underwent hydrolysis only above the temperature
of 40 ꢁC. The reaction products were found to include
nicotinamide hydrochloride, (1R,2S,5R)-(ꢀ)-menthol and
formaldehyde. In the studied hydrolysis reaction, the
change of chloride 1h concentration at various tempera-
tures is shown in Figure 1. The plots of the natural log
of the concentration (lnc) as the function of time repre-
sented straight lines. Therefore, it was assumed that it
was a first order reaction. The estimated rate constants
are listed in Table 2.
O
Cl
R2
R4
R1
N
R2
R4
R1
O
R3
+
R3
N
-
+
Cl
( )
1
MX
R2
R4
R1
O
R3
N
The prepared chiral pyridinium chlorides were subse-
quently employed as synthetic precursors of CILs. The
second step of the synthesis involved ion exchange. The
obtained [BF4] 2, [ClO4] 3, [I] 4, and [PF6] 5 salts were
solids, which could be easily crystallized to form plates or
needles with sharp melting points. The melting points
and specific rotations of these salts are given in Table 3.
The [NTf2] salts 6, which were CILs, are listed in Table
4. All the synthesized salts were completely miscible with
methanol, ethanol, acetone, DMF, and DMSO. However,
+
X-
(
)
-
2 6
Scheme 1.
was essentially water since the chlorides were hygroscopic.
The yield, melting point, and specific rotation of each salt
are presented in Table 1. The chirality resided in the cation.
-
(slow)
+
Cl
+
CH2
O
Cl
O
R1
N
R2
R4
R1
R2
R4
+
R3
+
(fast)
CH2
+
N
R3
O
O
Scheme 2.
Table 1. 1-[(1R,2S,5R)-(ꢀ)-Menthoxymethyl]pyridinium chlorides 1
20
Chloride
R1
R2
R3
R4
Yield [%]
Mp [ꢁC]
Surfactant content [%]
Specific rotationf ½aꢁD
1a
1b
1c
1d
1e
1
H
CH3
H
H
H
H
CH3
H
H
H
H
H
CH3
H
H
H
H
CONH2
OH
H
H
H
H
CH3
C2H5
tert-Bu
H
H
H
H
H
H
H
H
H
OH
H
H
H
H
98.0
99.0
99.5
99.0
98.5
97.0
98.0
98.5
98.0
99.0
98.5
105–106a
150–155a
142–145a
106–108a
80–81b
Hygroscopic
186–189c
145–149d
202–204e
192–197a
118–119a
96.5
97.0
98.5
96.5
99.0
92.5
99.5
93.0
99.0
96.5
99.5
ꢀ124.2 (c 0.9)
ꢀ99.7 (c 0.5)
ꢀ126.9 (c 0.6)
ꢀ117.1 (c 1.3)
ꢀ124.8 (c 1.0)
ꢀ102.7 (c 1.3)
ꢀ120.9 (c 1.1)
ꢀ122.2 (c 1.0)
ꢀ147.3 (c 1.0)
ꢀ117.8 (c 0.5)
ꢀ154.6 (c 1.0)
1g
1h
1i
1j
1k
N(CH3)2
H
H
N(CH3)2
a From ethyl acetate + chloroform; plates.
b From hexane + acetone; plates.
c From ethyl acetate + ethanol; needles.
d Plates.
e From ethyl acetate + chloroform + ethanol; needles.
f c in ethanol.

1730
J. Pernak, J. Feder-Kubis / Tetrahedron: Asymmetry 17 (2006) 1728–1737
9.5
9
The viscosities are strongly influenced by temperature, as
presented in Figure 2.
65 ºC
70 ºC
75 ºC
80 ºC
85 ºC
8.5
8
1
These new pyridinium chlorides were characterized by H
and 13C NMR, and by elemental analysis. Comparison of
the proton spectra of chlorides 1 with those of salts 2–6
indicated differences in the proton chemical shifts as listed
in Table 5.
7.5
7
6.5
6
The prepared chiral [Cl] salts 1 were tested for anti-micro-
bial activity. The minimum inhibitory concentration (MIC)
and minimum bactericidal or fungicidal concentration
(MBC) determined for chiral chlorides 1 are given in Table
6. The tested microorganisms represent cocci, rods and
fungi. The activities of these salts were similar, However,
no such broad activity was observed as that noted for benz-
alkonium chloride (BAC), the activity of which is given in
Table 6. Chlorides 1 practically remained inactive against
fungi (Candida albicans and Rhodotorula rubra). They
proved to be most active against Micrococcus luteus and,
in the cases of 1i, 1j and 1k, the activity was definitely more
pronounced than that of BAC. In general, our previous
studies of pyridinium salts with alkoxymethyl or alkylthio-
methyl hydrophobic groups show strong and wide anti-
bacterial spectra similar to the activity of BAC.8,9 The
restricted activity observed for most of chlorides 1 can be
explained by the absence of a long substituent on the pyri-
dine ring, which was accompanied by a low surface activity.
5.5
5
0
1000
2000
3000
4000
5000
6000
Time [s]
Figure 1. Logarithm of concentration as a function of time for hydrolysis
of chloride 1h.
Table 2. The rate constants of hydrolysis of chloride 1h
Temperature
k
R2
[ꢁC]
k [·104]
Standard
error [·104]
Dk 95%
confidence
level [·104]
65
70
75
80
85
1.6125
1.7674
3.0728
5.5192
8.9846
0.0594
0.0411
0.0306
0.0470
0.1219
0.2615
0.1892
0.1348
0.2072
0.5367
0.9853
0.9935
0.9989
0.9992
0.9980
Previous studies of ozonation of pyridinium salts contain-
ing alkoxymethyl or alkylthiomethyl hydrophobic groups
produced results strongly dependent on the types and posi-
tions of the substituents on the pyridine ring. The most
favorable was the third position and HO– or (CH3)2N sub-
stituents.10 For the synthesized chiral chlorides 1 at a con-
centration of 2 g/L, their stability was tested when exposed
to ozone in aqueous solution. We conducted the process
for 20 min, consistent with practices for the ozone treat-
ment of sewage (10–20 min). Only chlorides 1i and 1k re-
acted with ozone in an aqueous solution. Ozonation was
rapid and after 20 min the extent of destruction reached
their solubilities in toluene, chloroform, and ethyl acetate
strongly depended on the type of anion. For example,
[BF4] salts 2 were soluble in chloroform and [NTf2] salts
6 exhibited partial miscibility with chloroform. None of
the prepared salts dissolved in hexane or diethyl ether.
Anhydrous salts were obtained by heating the products
under vacuum. Karl Fischer measurements showed the
water content of the dried salts to be less than 200 ppm.
The densities of the dry studied ILs are weakly temperature
dependent (over 10ꢁ, the density decreases by about 2%).
Table 3. 1-[(1R,2S,5R)-(ꢀ)-Menthoxymethyl]pyridinium salts 2–5
Salt
20
R1
R2
R3
R4
Anion
Yield [%]
Mp [ꢁC]
Specific rotatione ½aꢁD
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
3
H
CH3
H
H
H
CH3
H
H
H
H
H
H
CH3
H
H
H
CONH2
OH
H
H
H
H
CH3
C2H5
H
H
H
H
H
H
H
H
OH
H
H
H
H
H
H
H
BF4
BF4
BF4
BF4
BF4
BF4
BF4
BF4
BF4
BF4
ClO4
I
98.5
99.0
99.0
99.0
98.0
99.0
97.5
98.0
99.5
99.5
97.0
90.0
99.7
110–111a
145–146a
72–73a
113–114a
82–84a
130–132a
124–127b
101–102a
105–107c
131–132a
114–115d
133–135a
140–142a
ꢀ116.5 (c 0.7)
ꢀ116.3 (c 1.0)
ꢀ116.9 (c 1.0)
ꢀ109.9 (c 0.7)
ꢀ112.2 (c 1.1)
ꢀ108.9 (c 1.0)
ꢀ111.9 (c 1.0)
ꢀ114.8 (c 1.0)
ꢀ112.6 (c 1.0)
ꢀ139.4 (c 0.5)
ꢀ110.9 (c 0.6)
ꢀ50.9 (c 0.8)
ꢀ97.6 (c 1.0)
N(CH3)2
N(CH3)2
H
H
H
H
H
H
H
H
H
H
4
5
PF6
a From water + acetone; plates.
b From chloroform + acetone; plates.
c From water + acetone + ethanol; needles.
d From water + acetone; needles.
e c in ethanol.

J. Pernak, J. Feder-Kubis / Tetrahedron: Asymmetry 17 (2006) 1728–1737
1731
Table 4. 1-[(1R,2S,5R)-(ꢀ)-Menthoxymethyl]pyridinium bis(trifluoromethanesulfonyl)imides 6
20
CIL R1
R2
R3
R4 Yield [%] Mp [ꢁC] Specific rotationf ½aꢁD
Densityg [g mLꢀ1
]
Viscosityg [mPa s] Tonset [ꢁC]
h
6a
6b
6c
6d
6e
6f
H
CH3
H
H
H
H
H
H
H
H
CH3
H
H
H
H
H
CH3
C2H5
tert-Bu
H
H
H
H
H
H
H
H
H
86.0
87.0
88.0
87.5
95.5
90.0
98.0
91.0
ꢀ33.0a
ꢀ31.4a
Grease
66–67b
70–72c
ꢀ23.2a
74–75d
30–32e
ꢀ70.9 (c 1.4)
ꢀ77.2 (c 1.1)
ꢀ70.3 (c 1.3)
ꢀ71.2 (c 1.0)
ꢀ69.7 (c 0.5)
ꢀ70.4 (c 1.6)
ꢀ75.4 (c 1.2)
ꢀ92.5 (c 0.85)
1.28
1.29
—
—
—
1.30
—
—
550
839
—
—
—
1003
—
—
180 (390)
180 (400)
205 (445)
205 (410)
208 (380)
210 (420)
165 (355)
220 (445)
H
6g
6h
CONH2
N(CH3)2
H
a Determined by DSC on heating.
b From water + ethanol; plates.
c From water + ethanol; plates.
d From water + ethanol; needles.
e Plates.
f c in ethanol.
g At 50 ꢁC.
h Decomposition temperature determined from onset to 50% mass loss.
550
500
450
400
350
300
250
200
3. Conclusion
With high efficiency, a number of chiral pyridinium salts
were prepared. The chirality resided in the cation. The
group of prepared salts contained chiral ionic liquids and
decomposable chiral pyridinium chlorides. A derivative
of vitamin PP, 3-carbamoyl-1-(1R,2S,5R)-(ꢀ)-menthyl-
pyridinium chloride easily hydrolyzed, while chlorides with
OH and N(CH3)2 groups in position three on the pyridine
ring were susceptible to ozone treatment. The estimated
microbiological activity of the obtained salts is of key
importance in selection of the appropriate chiral pyridi-
nium salts as media for reactions conducted with the
involvement of microbes.
45
50
55
60
65
Temperature [ºC]
Figure 2. Viscosity of dry CIL 7a as a function of increasing temperature.
almost 100% (Fig. 3). The extent of destruction was calcu-
lated from the relationship:
4. Experimental
D ¼ ð1 ꢀ X=X0Þ ꢂ 100ð%Þ
1H NMR spectra were recorded on a Mercury Gemini 300
spectrometer at 300 MHz with tetramethylsilane as the
standard; 13C NMR spectra were recorded using the same
instrument, at 75 MHz. Elemental CHN analyses were
where X and X0 were the concentrations in water after 20
and 0 min, respectively. The prepared chiral chlorides con-
tained compounds which could be quantitatively removed
by aqueous ozonation.
´
performed at the A. Mickiewicz University, Poznan. A
Table 5. The shifta in proton signals
9
10
8
R2
R1
13
2
5
O
12
1
3
4
14
R3
N
6
11
+
X-
15
16
R4
7
Salt
X
Characteristic proton
HC13 and HC15
HC12 and HC16
HC14
H2C11
1a
2a
3
Cl
9.75 (d)
8.94 (d)
8.99 (d)
9.52 (d)
8.82 (d)
8.96 (m)
8.81 (t)
8.60 (t)
8.63 (m)
8.79 (m)
8.56 (t)
8.61 (m)
8.33 (t)
8.11 (t)
8.15 (m)
8.30 (t)
8.07 (m)
8.13 (m)
6.38, 6.51 (d, J = 10.2)
BF4
ClO4
I
PF6
NTf2
5.92, 5.96 (d, J = 10.9; J = 10.7)
5.97, 6.00 (d, J = 10.9; J = 10.7)
6.29, 6.38 (d, J = 10.2; J = 9.9)
5.84, 5.88 (d, J = 10.2; J = 10.4)
5.90, 5.94 (d, J = 10.4)
4
5
6a
a Shift in ppm and J in hertz.

1732
J. Pernak, J. Feder-Kubis / Tetrahedron: Asymmetry 17 (2006) 1728–1737
Table 6. MIC and MBC valuesa of 1-[(1R,2S,5R)-(ꢀ)-menthoxymethyl]pyridinium chlorides 1
Strain
Chlorides
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
BACb
M. luteus
S. aureus
MIC
MBC
MIC
14
14
882
27
54
420
1681
208
840
27
27
840
27
27
840
26
51
803
5.9
12
183
736
91
198
198
>583
>583
1473 >1669
1473 >1669
368
1473
0.25
417
<0.25
12
383
>5113
12
25
383
766
49
<0.25
49
95
190
25
49
383
1531
25
25
25
1.4
11
2.8
23
>584
>2348
1595
1595
1595
MBC >1764
1681 >1681 >1605
S. epidermidis MIC
219
1764
1764
104
1681
1681
208
1681
840
51
1605
803
1669
1669
1.4
5.6
5.6
23
0.6
1.4
2.8
2.8
175
175
88
MBC
MIC
1473
368
E. faecium
1681
>4698 >1669
MBC >1764 >1681 >1681 >1681 >1605 >1473
>4698 >13,837 >1669
M. catarrhalis MIC
882
882
219
219
208
840
208
208
420
420
104
208
208
420
208
840
199
401
100
401
183
183
24
1595
>584
399
1473
1473
368
1669
1669
1669
1669
MBC
MIC
MBC
49
49
49
E. coli
47
797
736
25
S. marcescens MIC
MBC >1764 >1681 >1681 >1681 >1605 >1473
MIC >1764 >1681 >1681 >1681 >1605 >1473
MBC >1764 >1681 >1681 >1681 >1605 >1473
MIC >1764 >1681 >1681 >1681 >1605 >1473
MBC >1764 >1681 >1681 >1681 >1605 >1473
>1764 >1681 >1681 >1681 >1605 >1473
>4698 >13,837 >1669
>4698 >13,837 >1669
>4698 >13,837 >1669
>4698 >13,837 >1669
>4698 >13,837 >1669
>4698 >13,837 >1669
1595
1595
>4699 >13,840
>4698 >13,837
>4699 >13,840
>4698 >13,837
>5113
>5113
>5113
>5113
>5113
>5113
383
>15,661
>15,661
>15,661
>15,661
>15,661
>15,661
383
P. vulgaris
P. aeruginosa
B. subtilis
C. albicans
R. rubra
88
175
175
2.8
2.8
11
88
23
88
MIC
MBC
MIC
882
1764
1681
1681
208
1681 >1681
1681
803
1605
183
183
1473
>4698 >1669
>4698 >1669
383
383
>1764 >1681 >1681 >1681 >1605
1669
1669
1669
1669
>5112
>5112
1531
>5112
>15,656
>15,656
>4689
MBC >1764 >1681 >1681 >1681 >1605 >1473
MIC >1764 >1681 >1681 1681 >1605 1473
MBC >1764 >1681 >1681 1681 >1605 >1473
>15,656
a In lM.
b Benzalkonium chloride.
100
90
80
70
60
50
40
30
20
10
0
4.1. Menschutkin quaternization
A three-necked, round-bottomed flask equipped with a
magnetic stirring bar, reflux condenser, and dropping fun-
nel was charged with pyridine derivatives dried by azeotro-
pic distillation with chloroform and 30 mL of freshly
distilled solvent (hexane for 1a–f and 1k; DMF for 1g–j).
Chloromethyl (1R,2S,5R)-(ꢀ)-menthyl ether with a boiling
point of 108 ꢁC at 16 mmHg was added dropwise. The
resulting mixture was vigorously stirred at room tempera-
ture. The suspension was filtered, washed with diethyl
ether, and recrystallized.
0
5
10
15
20
Time [min]
Figure 3. Decay of 1i (j) and 1k (m) in the presence of ozone as a
function of time.
4.2. Metathesis reaction
satisfactory microanalysis was obtained (C 0.37,
H
0.36, and N 0.24). Optical rotations were measured
with a Perkin–Elmer 243 B polarimeter.
4.2.1. Preparation of solid salts. A saturated aqueous
solution of NaBF4, NaClO4, KI, KPF6, or Tf2NLi was
added to a stoichiometric amount of aqueous solution of
prepared pyridinium chloride 1. The reaction mixture was
stirred at room temperature for 24 h. The precipitated solid
was filtered off and washed with water. The crude material
was recrystallized.
Melting points were determined using a model JA 9100
electrothermal digital melting-point apparatus. A Metter
Toledo DA 110 M scale was used for the mass/density
measurements.
Water content was determined using a volumetric Aquas-
tar Karl Fischer titrator with Composite 5 solution as the
titrant and anhydrous methanol as the solvent.
4.2.2. Preparation of liquid salts. A saturated aqueous
solution of Tf2NLi was added to a stoichiometric amount
of aqueous solution of prepared pyridinium chloride 1.
The reaction mixture was stirred at room temperature for
24 h. After separation of the phases, the organic phase
was washed with distilled water until chloride ions were
no longer detected using AgNO3. The obtained liquid
was dried for 12 h at 80 ꢁC in a vacuum.
3-(Dimethylamino)pyridine was obtained according to the
procedure described earlier.11 Chloromethyl (1R,2S,5R)-
(ꢀ)-menthyl ether was prepared by passing HCl through
a
mixture of formaldehyde and (1R,2S,5R)-(ꢀ)-
menthol.4,12

J. Pernak, J. Feder-Kubis / Tetrahedron: Asymmetry 17 (2006) 1728–1737
1733
4.2.3. Anti-microbial activity. The following microorgan-
isms were used: Micrococcus luteus NCTC 7743, Staphylo-
coccus aureus NCTC 4163, Staphylococcus epidermidis
ATCC 49134, Enterococcus faecium ATCC 49474, Morax-
ella catarrhalis ATCC 25238, Escherichia coli ATCC 25922,
Serratia marcescens ATCC 8100, Proteus vulgaris MCTC
4635, Pseudomonas aeruginosa NCTC 6749, Bacillus sub-
tilis ATCC 6633, Candida albicans NCTS 4163, and Rhodo-
thorula rubra (Demml 1889, Lodder 1934). Standard
strains were supplied by the National Collection of Type
Cultures (NCTC) London, and American Type Culture
Collection (ATCC). Rhodothorula rubra was obtained from
the Department of Pharmaceutical Bacteriology, Univer-
calcd (%) for C16H26ClNO (283.88): C 67.69, H 9.25, N
4.93. Found: C 67.85, H 9.17, N 4.88.
4.3.2. 1-[(1R,2S,5R)-(ꢀ)-Menthoxymethyl]-2-methylpyrid-
inium chloride 1b. 1H NMR (CDCl3, 25 ꢁC): d = 0.36 (d,
J = 7.1 Hz, 3H, H9 or H10), 0.88 (m, 9H, Ha-4, H7, H9
or H10, Ha-6 and Ha-3), 1.25 (m, 1H, H2), 1.46 (m, 1H,
H5), 1.62 (m, 2H, Hb-3 and Hb-4), 1.78 (sept d, J = 6.9,
4.4 Hz, 1H, H8), 2.18 (m, 1H, Hb-6), 3.06 (s, 3H, CH3–
R1), 3.54 (td, J = 10.4, 4.1 Hz, 1H, H1), 6.30 and 6.50 (d,
J = 10.7 Hz, 2H, AB system, H11), 7.97 (m, 2H, H15 and
H13), 8.46 (m, 1H, H14), 10.04 (m, 1H, H16); 13C NMR
(CDCl3): d = 15.3 (C9 or C10), 20.1 (C7), 20.8 (CH3–R1),
22.0 (C9 or C10), 22.6 (C3), 25.6 (C8), 31.1 (C5), 33.9
(C4), 40.5 (C6), 47.6 (C2), 80.7 (C1), 86.0 (C11), 125.6
(C15), 129.9 (C13), 146.2 (C14), 147.0 (C16), 155.5 (C12).
Elemental analysis calcd (%) for C17H28ClNO (297.91): C
68.53, H 9.49, N 4.70. Found: C 68.33, H 9.55, N 4.80.
´
sity of Medical Sciences, Poznan.
Anti-microbial activity was determined by the tube dilution
method. A series of chiral pyridinium chlorides dilutions
were prepared in Muller–Hinton broth medium (bacteria)
¨
or Sabouraud broth medium (fungi). Bacteria strains were
cultured in a Muller–Hinton broth for 24 h and fungi on
¨
4.3.3. 1-[(1R,2S,5R)-(ꢀ)-Menthoxymethyl]-3-methylpyrid-
inium chloride 1c. 1H NMR (CDCl3, 25 ꢁC): d = 0.46 (d,
J = 7.1 Hz, 3H, H9 or H10), 0.90 (m, 9H, Ha-4, H7, H9
or H10, Ha-6 and Ha-3), 1.37 (m, 2H, H2 and H5), 1.63
(m, 2H, Hb-3 and Hb-4), 1.98 (sept d, J = 7.1, 4.7 Hz,
1H, H8), 2.16 (m, 1H, Hb-6), 2.68 (s, 3H, CH3–R2), 3.50
(td, J = 10.7, 4.4 Hz, 1H, H1), 6.26 and 6.45 (d,
J = 10.2 Hz, 2H, AB system, H11), 8.11 (m, 1H, H15),
8.40 (d, J = 7.7 Hz, 1H, H14), 9.44 (d, J = 6.0 Hz, 1H,
H16), 9.51 (s, 1H, H12); 13C NMR (CDCl3): d = 15.4
(C9 or C10), 18.6 (CH3–R2), 20.8 (C7), 21.9 (C9 or C10),
22.6 (C3), 25.4 (C8), 31.0 (C5), 33.8 (C4), 40.4 (C6), 47.6
(C2), 81.2 (C1), 87.0 (C11), 127.4 (C15), 139.2 (C13),
140.9 (C14), 143.0 (C16), 146.9 (C12). Elemental analysis
calcd (%) for C17H28ClNO (297.91): C 68.53, H 9.49, N
4.70. Found: C 68.45, H 9.52, N 4.59.
Sabouraud agar for 48 h. Suspensions of the microorgan-
isms, at the concentration of 106 cfu cmꢀ3 (cfu = colony
forming units), were prepared from each culture. Then,
to each dilution of the tested agent in the broth medium
the above-mentioned microbe suspension was inoculated,
at a 1:1 ratio. Growth (or lack thereof) of the microorgan-
isms was determined visually after incubation for 24 h at
37 ꢁC (bacteria) or 48 h at 28–30 ꢁC (fungi). The lowest
concentration at which there was no visible growth (turbid-
ity) was taken as the MIC. Then, from each tube, one loop-
ful was cultured in an agar medium with inactivates (0.3%
lecithin, 3% polysorbate 80% and 0.1% cysteine L) and
incubated for 48 h at 37 ꢁC (bacteria) or for 5 d at 28–
30 ꢁC (fungi). The lowest concentration of chiral pyridi-
nium salt supporting no colony formation was defined as
the MBC.
4.3.4. 1-[(1R,2S,5R)-(ꢀ)-Menthoxymethyl]-4-methylpyrid-
inium chloride 1d. 1H NMR (CDCl3, 25 ꢁC): d = 0.47
(d, J = 6.9 Hz, 3H, H9 or H10), 0.89 (m, 9H, Ha-4, H7,
H9 or H10, Ha-6 and Ha-3), 1.37 (m, 2H, H2 and H5),
1.62 (m, 2H, Hb-3 and Hb-4), 1.97 (sept d, J = 6.9,
4.4 Hz, 1H, H8), 2.13 (m, 1H, Hb-6), 2.73 (s, 3H, CH3–
R3), 3.50 (td, J = 10.7, 4.4 Hz, 1H, H1), 6.23 and 6.40 (d,
J = 10.2, 10.4 Hz, 2H, AB system, H11), 8.73 (d,
J = 6.6 Hz, 2H, H13 and H15), 9.48 (d, J = 6.9 Hz, 2H,
H12 and H16); 13C NMR (CDCl3): d = 15.5 (C9 or C10),
20.8 (C7), 21.9 (C9 or C10), 22.3 (CH3–R3), 22.6 (C3),
25.4 (C8), 31.0 (C5), 33.8 (C4), 40.4 (C6), 47.6 (C2), 81.2
(C1), 86.6 (C11), 128.4 (C13 and C15), 142.9 (C14), 160.3
(C12 and C16). Elemental analysis calcd (%) for
C17H28ClNO (297.91): C 68.53, H 9.49, N 4.70. Found:
C 68.38, H 9.53, N 4.77.
4.3. Ozonation
The measuring apparatus, the method of measurement,
and the measurement conditions were described by Pernak
et al.10 An aqueous ozone solution of approximately 5 mg/
L and of pH 4.2 was prepared by bubbling ozone-oxygen
gas through a 2 g/L aqueous solution of a tested chloride.
The reaction mixture was determined by a direct two-phase
back titration, according to the EN ISO 2871-1 (2000)
standard.
4.3.1. 1-[(1R,2S,5R)-(ꢀ)-Menthoxymethyl]pyridinium chlo-
ride 1a. 1H NMR (CDCl3, 25 ꢁC): d = 0.43 (d,
J = 7.1 Hz, 3H, H9 or H10), 0.89 (m, 9H, Ha-4, H7, H9
or H10, Ha-6 and Ha-3), 1.31 (m, 1H, H2), 1.43 (m, 1H,
H5), 1.62 (m, 2H, Hb-3 and Hb-4), 1.96 (sept d, J = 6.9,
4.4 Hz, 1H, H8), 2.14 (d, J = 11.8 Hz, 1H, Hb-6), 3.54
(td, J = 10.4, 4.1 Hz, 1H, H1), 6.38 and 6.51 (d,
J = 10.2 Hz, 2H, AB system, H11), 8.33 (t, J = 7.4,
6.6 Hz, 2H, H13 and H15), 8.81 (t, J = 7.7 Hz, 1H, H14),
9.75 (d, J = 5.5 Hz, 2H, H12 and H16); 13C NMR
(CDCl3): d = 14.8 (C9 or C10), 20.1 (C7), 21.3 (C9 or
C10), 21.8 (C3), 24.6 (C8), 30.3 (C5), 33.0 (C4), 39.7
(C6), 46.7 (C2), 80.3 (C1), 86.3 (C11), 127.3 (C13 and
C15), 142.9 (C14), 146.1 (C12 and C16). Elemental analysis
4.3.5.
4-Ethyl-1-[(1R,2S,5R)-(ꢀ)-menthoxymethyl]pyrid-
inium chloride 1e. 1H NMR (CDCl3, 25 ꢁC): d = 0.44 (d,
J = 6.9 Hz, 3H, H9 or H10), 0.87 (m, 9H, Ha-4, H7, H9
or H10, Ha-6 and Ha-3), 1.36 (m, 5H, H2, H5 and CH3–
R3), 1.62 (m, 2H, Hb-3 and Hb-4), 1.95 (sept d, J = 7.1,
4.4 Hz, 1H, H8), 2.14 (m, 1H, Hb-6), 3.01 (q, J = 7.7 Hz,
2H, CH2–R3), 3.50 (td, J = 10.7, 4.4 Hz, 1H, H1), 6.24
and 6.39 (d, J = 10.2 Hz, 2H, AB system, H11), 7.99 (d,
J = 6.6 Hz, 2H, H13 and H15), 9.55 (d, J = 6.6 Hz, 2H,

1734
J. Pernak, J. Feder-Kubis / Tetrahedron: Asymmetry 17 (2006) 1728–1737
H12 and H16); 13C NMR (CDCl3): d = 13.3 (CH3–R3),
15.4 (C9 or C10), 20.8 (C7), 21.9 (C9 or C10), 22.6 (C3),
25.4 (C8), 29.0 (CH2–R3), 31.0 (C5), 33.8 (C4), 40.4 (C6),
47.5 (C2), 80.8 (C1), 86.3 (C11), 126.9 (C13 and C15),
142.9 (C12 and C16), 165.4 (C14). Elemental analysis calcd
(%) for C18H30ClNO (311.94): C 69.30, H 9.71, N 4.49.
Found: C 69.18, H 9.79, N 4.56.
or H10, Ha-6 and Ha-3), 1.30 (m, 2H, H2 and H5), 1.66
(m, 2H, Hb-3 and Hb-4), 2.00 (m, 2H, H8 and Hb-6),
3.41 (td, J = 10.4, 4.1 Hz, 1H, H1), 5.86 and 5.92 (d,
J = 9.9, 10.2 Hz, 2H, AB system, H11), 7.76 (m, 1H,
H15), 8.21 (m, 2H, H14 and H16), 9.16 (s, 1H, H12);
13C NMR (CDCl3): d = 15.5 (C9 or C10), 20.8 (C7),
22.0 (C9 or C10), 22.6 (C3), 25.5 (C8), 31.3 (C5),
33.8 (C4), 40.3 (C6), 47.6 (C2), 81.9 (C1), 87.7 (C11),
127.8 (C14), 130.9 (C15), 131.7 (C12), 133.8 (C16), 159.0
(C13). Elemental analysis calcd (%) for C16H26ClNO2
(299.88): C 64.08, H 8.76, N 4.67. Found: C 64.19, H
8.70, N 4.69.
4.3.6. 4-tert-Butyl-1-[(1R,2S,5R)-(ꢀ)-menthoxymethyl]pyrid-
inium chloride 1f. 1H NMR (CDCl3, 25 ꢁC): d = 0.36 (d,
J = 7.1 Hz, 3H, H9 or H10), 0.93 (m, 9H, Ha-4, H7, H9
or H10, Ha-6 and Ha-3), 1.39 (m, 13H, H2, CH3–R3,
H5, Hb-3 and Hb-4), 1.93 (sept d, J = 6.9, 4.7 Hz, 1H,
H8), 2.24 (m, 1H, Hb-6), 3.52 (td, J = 10.7, 4.4 Hz, 1H,
H1), 6.32 and 6.43 (d, J = 9.9, 10.2 Hz, 2H, AB system,
H11), 8.17 (d, J = 6.9 Hz, 2H, H13 and H15), 9.80 (d,
J = 6.9 Hz, 2H, H12 and H16); 13C NMR (CDCl3):
d = 20.1 (C9 or C10), 20.3 (C7), 21.3 (C9 or C10), 21.8
(C3), 24.5 (C8), 29.2 (CH3–R3), 30.2 (C5), 33.1 (C4), 35.9
(C–R3), 39.6 (C6), 46.6 (C2), 79.6 (C1), 85.3 (C11), 124.2
(C13 and C15), 143.0 (C12 and C16), 171.5 (C14). Elemen-
tal analysis calcd (%) for C20H34ClNO (340.00): C 70.65, H
10.10, N 4.12. Found: C 70.73, H 9.98, N 4.07.
4.3.10.
1-[(1R,2S,5R)-(ꢀ)-Menthoxymethyl]-4-(dimethyl-
amino)pyridinium chloride 1j. 1H NMR (CDCl3, 25 ꢁC):
d = 0.50 (d, J = 6.9 Hz, 3H, H9 or H10), 1.00 (m, 9H,
Ha-4, H7, H9 or H10, Ha-6 and Ha-3), 1.25 (m, 1H,
H2), 1.40 (m, 1H, H5), 1.62 (m, 2H, Hb-3 and Hb-4),
2.03 (m, 2H, H8 and Hb-6), 3.32 (m, 7H, N(CH3)2 and
H1), 5.63 and 5.77 (d, J = 10.4 Hz, 2H, AB system, H11),
7.06 (d, J = 8.0 Hz 2H, H13 and H15), 8.58 (d,
J = 7.7 Hz, 2H, H12 and H16); 13C NMR (CDCl3):
d = 15.7 (C9 or C10), 21.0 (C7), 22.1 (C9 or C10), 22.8
(C3), 25.4 (C8), 31.2 (C5), 34.0 (C4), 40.3 (C6), 40.6
(N(CH3)2), 47.7 (C2), 79.5 (C1), 83.9 (C11), 107.7 (C13
and C15), 141.4 (C12 and C16), 156.8 (C14). Elemental
analysis calcd (%) for C18H31ClN2O (326.96): C 66.12, H
9.58, N 8.57. Found: C 66.01, H 9.63, N 8.54.
4.3.7.
5-Hydroxy-1-[(1R,2S,5R)-(ꢀ)-menthoxymethyl]-2-
methylpyridinium chloride 1g. 1H NMR (CDCl3, 25 ꢁC):
d = 0.42 (d, J = 6.9 Hz, 3H, H9 or H10), 0.91 (m, 9H,
Ha-4, H7, H9 or H10, Ha-6 and Ha-3), 1.27 (m, 1H,
H2), 1.43 (m, 1H, H5), 1.64 (m, 2H, Hb-3 and Hb-4),
1.83 (sept d, J = 6.9, 4.2 Hz, 1H, H8), 2.38 (m, 1H, Hb-
6), 2.84 (s, 3H, CH3–R1), 3.42 (td, J = 10.5, 4.2 Hz, 1H,
H1), 5.88 and 5.93 (d, J = 10.8, 10.5 Hz, 2H, AB system,
H11), 7.50 (d, J = 8.7 Hz, 1H, H13), 8.14 (m, 1H, H14),
8.97 (m, 1H, H16); 13C NMR (CDCl3): d = 15.5 (C9 or
C10), 18.9 (CH3–R1), 21.0 (C7), 22.1 (C9 or C10), 22.7
(C3), 25.7 (C8), 31.3 (C5), 34.0 (C4), 40.3 (C6), 47.7 (C2),
80.7 (C1), 86.2 (C11), 129.8 (C14), 133.1 (C13), 134.2
(C16), 143.9 (C15), 156.4 (C12). Elemental analysis calcd
(%) for C17H28ClNO2 (313.91): C 65.04, H 9.01, N 4.46.
Found: C 64.89, H 9.13, N 4.52.
4.3.11.
1-[(1R,2S,5R)-(ꢀ)-Menthoxymethyl]-3-(dimethyl-
amino)pyridinium chloride 1k. 1H NMR (CDCl3, 25 ꢁC):
d = 0.50 (d, J = 6.9 Hz, 3H, H9 or H10), 0.90 (m, 9H,
Ha-4, H7, H9 or H10, Ha-6 and Ha-3), 1.29 (m, 1H,
H2), 1.42 (m, 1H, H5), 1.62 (m, 2H, Hb-3 and Hb-4),
2.01 (sept d, J = 6.6, 4.1 Hz, 1H, H8), 2.22 (d,
J = 11.8 Hz, 1H, Hb-6), 3.24 (s, 6H, N(CH3)2), 3.53 (td,
J = 10.7, 4.4 Hz, 1H, H1), 6.14 and 6.44 (d, J = 10.2,
10.4 Hz, 2H, AB system, H11), 7.69 (m, 1H, H15), 7.82
(m, 1H, H14), 8.35 (d, J = 5.8 Hz, 1H, H16), 9.32 (m,
1H, H12); 13C NMR (CDCl3): d = 15.4 (C9 or C10), 20.7
(C7), 21.9 (C9 or C10), 22.4 (C3), 25.4 (C8), 30.9 (C5),
33.7 (C4), 40.2 (N(CH3)2), 40.3 (C6), 47.5 (C2), 80.9
(C1), 86.8 (C11), 125.1 (C15), 127.1 (C14), 127.2 (C16),
127.4 (C12), 148.0 (C13). Elemental analysis calcd (%) for
C18H31ClN2O (326.96): C 66.12, H 9.58, N 8.57. Found:
C 66.18, H 9.62, N 8.46.
4.3.8.
3-Carbamoyl-1-[(1R,2S,5R)-(ꢀ)-menthoxymethyl]-
pyridinium chloride 1h. 1H NMR (DMSO-d6, 25 ꢁC):
d = 0.27 (d, J = 6.9 Hz, 3H, H9 or H10), 0.82 (m, 9H,
Ha-4, H7, H9 or H10, Ha-6 and Ha-3), 1.21 (m, 1H,
H2), 1.43 (m, 1H, H5), 1.57 (m, 2H, Hb-3 and Hb-4),
1.87 (sept d, J = 6.0, 4.0 Hz, 1H, H8), 2.10 (d,
J = 11.7 Hz, 1H, Hb-6), 3.45 (td, J = 10.5, 4.0 Hz, 1H,
H1), 6.06 and 6.12 (d, J = 10.1 Hz, 2H, AB system, H11),
8.26 (s, 1H, NH2), 8.37 (m, 1H, H15), 9.09 (s, 1H, NH2),
9.24 (d, J = 8.5 Hz, 1H, H14), 9.44 (d, J = 6.1 Hz, 1H,
H16), 9.94 (s, 1H, H12); 13C NMR (DMSO-d6): d = 15.1
(C9 or C10), 20.9 (C7), 22.0 (C9 or C10), 22.2 (C3), 24.8
(C8), 30.6 (C5), 33.5 (C4), 40.3 (C6), 47.1 (C2), 79.0 (C1),
86.7 (C11), 127.9 (C15), 133.4 (C13), 144.2 (C14), 145.2
(C16), 145.5 (C12), 162.5 (CONH2). Elemental analysis
calcd (%) for C17H27ClN2O2 (326.91): C 62.45, H 8.34, N
8.57. Found: C 62.56, H 8.28, N 8.50.
4.3.12. 1-[(1R,2S,5R)-(ꢀ)-Menthoxymethyl]pyridinium tetra-
fluoroborate 2a. 1H NMR (CDCl3, 25 ꢁC): d = 0.43 (d,
J = 7.1 Hz, 3H, H9 or H10), 0.89 (m, 9H, Ha-4, H7, H9
or H10, Ha-6 and Ha-3), 1.35 (m, 2H, H2 and H5), 1.62
(m, 2H, Hb-3 and Hb-4), 1.96 (m, 2H, H8 and Hb-6),
3.41 (td, J = 10.7, 4.4 Hz, 1H, H1), 5.92 and 5.96 (d,
J = 10.9, 10.7 Hz, 2H, AB system, H11), 8.11 (t, J = 7.4,
6.9 Hz, 2H, H13 and H15), 8.60 (t, J = 7.7 Hz, 1H, H14),
8.94 (d, J = 5.8 Hz, 2H, H12 and H16); 13C NMR
(CDCl3): d = 15.3 (C9 or C10), 20.8 (C7), 22.0 (C9 or
C10), 22.6 (C3), 25.4 (C8), 31.0 (C5), 33.8 (C4), 40.1
(C6), 47.5 (C2), 81.2 (C1), 87.6 (C11), 128.1 (C13 and
C15), 142.7 (C14), 147.0 (C12 and C16). Elemental analysis
calcd (%) for C16H26BF4NO (335.23): C 57.32, H 7.83, N
4.18. Found: C 57.45, H 7.78, N 4.11.
4.3.9. 3-Hydroxy-1-[(1R,2S,5R)-(ꢀ)-menthoxymethyl]pyrid-
inium chloride 1i. 1H NMR (CDCl3, 25 ꢁC): d = 0.51 (d,
J = 6.9 Hz, 3H, H9 or H10), 0.80 (m, 9H, Ha-4, H7, H9

J. Pernak, J. Feder-Kubis / Tetrahedron: Asymmetry 17 (2006) 1728–1737
1735
4.3.13. 1-[(1R,2S,5R)-(ꢀ)-Menthoxymethyl]-2-methylpyrid-
inium tetrafluoroborate 2b. 1H NMR (CDCl3, 25 ꢁC):
d = 0.35 (d, J = 7.1 Hz, 3H, H9 or H10), 0.87 (m, 9H,
Ha-4, H7, H9 or H10, Ha-6 and Ha-3), 1.26 (m, 1H,
H2), 1.46 (m, 1H, H5), 1.61 (m, 2H, Hb-3 and Hb-4),
1.78 (m, 2H, H8 and Hb-6), 2.98 (s, 3H, CH3–R1), 3.43
(td, J = 10.4 Hz, J = 4.1 Hz, 1H, H1), 5.87 and 5.99 (d,
J = 10.4 Hz, 2H, AB system, H11), 7.86 (m, 2H, H15 and
H13), 8.41 (m, 1H, H14), 9.34 (m, 1H, H16); 13C NMR
(CDCl3): d = 15.1 (C9 or C10), 19.8 (C7), 20.5 (CH3–R1),
21.9 (C9 or C10), 22.3 (C3), 25.2 (C8), 30.9 (C5), 33.6
(C4), 39.9 (C6), 47.3 (C2), 80.3 (C1), 86.1 (C11), 125.5
(C15), 130.1 (C13), 145.8 (C14), 146.2 (C16), 154.9 (C12).
Elemental analysis calcd (%) for C17H28BF4NO (349.26):
C 58.46, H 8.10, N 4.01. Found: C 58.38, H 8.18, N 4.09.
for C18H30BF4NO (363.29): C 59.51, H 8.34, N 3.86.
Found: C 59.63, H 8.26, N 3.81.
4.3.17. 5-Hydroxy-1-[(1R,2S,5R)-(ꢀ)-menthoxymethyl]-2-
methylpyridinium tetrafluoroborate 2f. 1H NMR (CDCl3,
25 ꢁC): d = 0.43 (d, J = 6.9 Hz, 3H, H9 or H10), 0.89 (m,
9H, Ha-4, H7, H9 or H10, Ha-6 and Ha-3), 1.33 (m, 2H,
H2 and H5), 1.62 (m, 2H, Hb-3 and Hb-4), 1.92 (m, 2H,
H8 and Hb-6), 2.79 (s, 3H, CH3–R1), 3.31 (td, J = 10.5,
4.2 Hz, 1H, H1), 5.44 and 5.49 (d, J = 10.4 Hz, 2H, AB
system, H11), 7.45 (d, J = 8.7 Hz, 1H, H13), 8.08 (m, 1H,
H14), 8.35 (m, 1H, H16); 13C NMR (CDCl3): d = 15.3
(C9 or C10), 18.8 (CH3–R1), 20.8 (C7), 21.8 (C9 or C10),
22.5 (C3), 25.4 (C8), 31.1 (C5), 33.8 (C4), 39.8 (C6), 47.3
(C2), 80.1 (C1), 87.0 (C11), 129.7 (C14), 132.8 (C13),
133.5 (C16), 142.7 (C15), 155.8 (C12). Elemental analysis
calcd (%) for C17H28BF4NO2 (365.26): C 55.90, H 7.74,
N 3.83. Found: C 55.98, H 7.68, N 3.79.
4.3.14. 1-[(1R,2S,5R)-(ꢀ)-Menthoxymethyl]-3-methylpyrid-
inium tetrafluoroborate 2c. 1H NMR (CDCl3, 25 ꢁC):
d = 0.44 (d, J = 7.1 Hz, 3H, H9 or H10), 0.89 (m, 9H,
Ha-4, H7, H9 or H10, Ha-6 and Ha-3), 1.37 (m, 2H, H2
and H5), 1.62 (m, 2H, Hb-3 and Hb-4), 1.98 (m, 2H, H8
and Hb-6), 2.61 (s, 3H, CH3–R2), 3.40 (td, J = 10.7,
4.4 Hz, 1H, H1), 5.89 and 5.93 (d, J = 10.4, 10.2 Hz, 2H,
AB system, H11), 8.01 (m, 1H, H15), 8.41 (d, J = 8.0 Hz,
1H, H14), 8.78 (m, 2H, H16 and H12); 13C NMR (CDCl3):
d = 15.0 (C9 or C10), 18.1 (CH3–R2), 20.7 (C7), 21.7 (C9 or
C10), 22.3 (C3), 25.1 (C8), 30.8 (C5), 33.6 (C4), 39.8 (C6),
47.3 (C2), 80.8 (C1), 87.1 (C11), 127.4 (C15), 139.5 (C13),
139.9 (C14), 142.3 (C16), 147.3 (C12). Elemental analysis
calcd (%) for C17H28BF4NO (349.26): C 58.46, H 8.10, N
4.01. Found: C 58.57, H 8.13, N 3.89.
4.3.18. 3-Carbamoyl-1-[(1R,2S,5R)-(ꢀ)-menthoxymethyl]-
pyridinium tetrafluoroborate 2g. 1H NMR (DMSO-d6,
25 ꢁC): d = 0.30 (d, J = 6.9 Hz, 3H, H9 or H10), 0.90 (m,
9H, Ha-4, H7, H9 or H10, Ha-6 and Ha-3), 1.36 (m, 2H,
H2 and H5), 1.58 (m, 2H, Hb-3 and Hb-4), 1.92 (sept d,
J = 6.9, 4.9 Hz, 1H, H8), 2.09 (d, J = 11.8 Hz, 1H, Hb-
6), 3.43 (td, J = 10.4, 3.8 Hz, 1H, H1), 6.04 and 6.09 (d,
J = 10.2 Hz, 2H, AB system, H11), 8.20 (s, 1H, NH2),
8.37 (m, 1H, H15), 8.64 (s, 1H, NH2), 9.08 (d,
J = 8.2 Hz, 1H, H14), 9.34 (d, J = 6.0 Hz, 1H, H16), 9.66
(s, 1H, H12); 13C NMR (DMSO-d6): d = 15.2 (C9 or
C10), 20.8 (C7), 22.0 (C9 or C10), 22.4 (C3), 24.9 (C8),
30.7 (C5), 33.6 (C4), 40.1 (C6), 47.2 (C2), 79.5 (C1), 86.1
(C11), 128.0 (C15), 133.8 (C13), 143.8 (C14), 145.1 (C16),
145.5 (C12), 162.7 (CONH2). Elemental analysis calcd
(%) for C17H27BF4N2O2 (378.26): C 53.98, H 7.21, N
7.41. Found: C 53.91, H 7.29, N 7.50.
4.3.15. 1-[(1R,2S,5R)-(ꢀ)-Menthoxymethyl]-4-methylpyrid-
inium tetrafluoroborate 2d. 1H NMR (CDCl3, 25 ꢁC):
d = 0.45 (d, J = 6.9 Hz, 3H, H9 or H10), 0.88 (m, 9H,
Ha-4, H7, H9 or H10, Ha-6 and Ha-3), 1.34 (m, 2H, H2
and H5), 1.61 (m, 2H, Hb-3 and Hb-4), 1.99 (m, 2H, H8
and Hb-6), 2.70 (s, 3H, CH3–R3), 3.39 (td, J = 10.4,
4.1 Hz, 1H, H1), 5.80 and 5.89 (d, J = 10.4 Hz, 2H, AB
system, H11), 8.65 (d, J = 6.7 Hz, 2H, H13 and H15),
8.82 (d, J = 6.9 Hz, 2H, H12 and H16); 13C NMR
(CDCl3): d = 15.2 (C9 or C10), 20.7 (C7), 21.7 (C9 or
C10), 22.1 (CH3–R3), 22.3 (C3), 25.2 (C8), 30.8 (C5), 33.6
(C4), 39.9 (C6), 47.3 (C2), 80.8 (C1), 86.7 (C11), 128.3
(C13 and C15), 141.8 (C14), 159.6 (C12 and C16). Elemen-
tal analysis calcd (%) for C17H28BF4NO (349.26): C 58.46,
H 8.10, N 4.01. Found: C 58.41, H 8.21, N 4.13.
4.3.19. 3-Hydroxy-1-[(1R,2S,5R)-(ꢀ)-menthoxymethyl]pyr-
idinium tetrafluoroborate 2h. 1H NMR (CDCl3, 25 ꢁC):
d = 0.48 (d, J = 6.9 Hz, 3H, H9 or H10), 0.90 (m, 9H,
Ha-4, H7, H9 or H10, Ha-6 and Ha-3), 1.36 (m, 2H, H2
and H5), 1.62 (m, 2H, Hb-3 and Hb-4), 1.99 (m, 2H, H8
and Hb-6), 3.38 (td, J = 10.4, 4.1 Hz, 1H, H1), 5.80 (m,
2H, AB system, H11), 7.85 (m, 1H, H15), 8.06 (m, 1H,
H14), 8.38 (d, J = 6.0 Hz, 1H, H16), 8.50 (s, 1H, H12);
13C NMR (CDCl3): d = 15.3 (C9 or C10), 20.8 (C7), 21.9
(C9 or C10), 22.6 (C3), 25.4 (C8), 31.1 (C5), 33.8 (C4),
40.0 (C6), 47.6 (C2), 81.4 (C1), 87.7 (C11), 128.4 (C14),
130.9 (C15), 133.4 (C12), 133.7 (C16), 157.1 (C13). Elemen-
tal analysis calcd (%) for C16H26BF4NO2 (351.23): C 54.71,
H 7.48, N 3.99. Found: C 54.59, H 7.56, N 4.09.
4.3.16.
4-Ethyl-1-[(1R,2S,5R)-(ꢀ)-menthoxymethyl]pyri-
dinium tetrafluoroborate 2e. 1H NMR (CDCl3, 25 ꢁC):
d = 0.43 (d, J = 6.9 Hz, 3H, H9 or H10), 0.88 (m, 9H,
Ha-4, H7, H9 or H10, Ha-6 and Ha-3), 1.35 (m, 5H, H2,
H5 and CH3–R3), 1.62 (m, 2H, Hb-3 and Hb-4), 1.96 (m,
2H, H8 and Hb-6), 2.99 (q, J = 7.7 Hz, 2H, CH2–R3),
3.39 (td, J = 10.4, 4.1 Hz, 1H, H1), 5.80 and 5.86 (d,
J = 10.4 Hz, 2H, AB system, H11), 7.95 (d, J = 6.6 Hz,
2H, H13 and H15), 8.95 (d, J = 6.6 Hz, 2H, H12 and
H16); 13C NMR (CDCl3): d = 13.1 (CH3–R3), 15.3 (C9
or C10), 20.7 (C7), 21.7 (C9 or C10), 22.4 (C3), 25.3
(C8), 28.8 (CH2–R3), 30.8 (C5), 33.6 (C4), 39.8 (C6), 47.4
(C2), 80.4 (C1), 85.9 (C11), 126.2 (C13 and C15), 141.0
(C12 and C16), 164.9 (C14). Elemental analysis calcd (%)
4.3.20.
1-[(1R,2S,5R)-(ꢀ)-Menthoxymethyl]-4-(dimethyl-
amino)pyridinium tetrafluoroborate 2i. 1H NMR (CDCl3,
25 ꢁC): d = 0.50 (d, J = 6.9 Hz, 3H, H9 or H10), 0.89 (m,
9H, Ha-4, H7, H9 or H10, Ha-6 and Ha-3), 1.24 (m, 1H,
H2), 1.40 (m, 1H, H5), 1.61 (m, 2H, Hb-3 and Hb-4),
1.99 (m, 2H, H8 and Hb-6), 3.28 (m, 7H, N(CH3)2 and
H1), 5.44 and 5.48 (d, J = 10.4 Hz, 2H, AB system, H11),
6.94 (d, J = 7.7 Hz, 2H, H13 and H15), 8.15 (d,
J = 8.0 Hz, 2H, H12 and H16); 13C NMR (CDCl3):
d = 15.4 (C9 or C10), 20.8 (C7), 21.9 (C9 or C10), 22.6

1736
J. Pernak, J. Feder-Kubis / Tetrahedron: Asymmetry 17 (2006) 1728–1737
(C3), 25.2 (C8), 31.0 (C5), 33.9 (C4), 40.0 (C6), 40.2
(N(CH3)2), 47.6 (C2), 79.3 (C1), 83.9 (C11), 107.6 (C13
and C15), 140.9 (C12 and C16), 156.9 (C14). Elemental
analysis calcd (%) for C18H31BF4N2O (378.31): C 57.14,
H 8.28, N 7.41. Found: C 57.29, H 8.21, N 7.45.
2H, H12 and H16); 13C NMR (CDCl3): d = 15.3 (C9 or
C10), 20.9 (C7), 22.0 (C9 or C10), 22.7 (C3), 25.4 (C8),
31.0 (C5), 33.9 (C4), 40.1 (C6), 47.6 (C2), 81.4 (C1), 87.6
(C11), 128.2 (C13 and C15), 142.4 (C14), 147.1 (C12 and
C16). Elemental analysis calcd (%) for C16H26F6NOP
(393.40): C 48.85, H 6.67, N 3.56. Found: C 48.99, H
6.57, N 3.49.
4.3.21.
1-[(1R,2S,5R)-(ꢀ)-Menthoxymethyl]-3-(dimethyl-
amino)pyridinium tetrafluoroborate 2j. 1H NMR (CDCl3,
25 ꢁC): d = 0.48 (d, J = 7.1 Hz, 3H, H9 or H10), 0.90 (m,
9H, Ha-4, H7, H9 or H10, Ha-6 and Ha-3), 1.34 (m, 2H,
H2 and H5), 1.62 (m, 2H, Hb-3 and Hb-4), 2.02 (m, 2H,
H8 and Hb-6), 3.15 (s, 6H, N(CH3)2), 3.40 (td, J = 10.4,
4.1 Hz, 1H, H1), 5.81 and 5.86 (d, J = 10.2 Hz, 2H, AB
system, H11), 7.68 (m, 1H, H15), 7.77 (m, 1H, H14), 8.12
(m, 2H, H16 and H12); 13C NMR (CDCl3): d = 15.3 (C9
or C10), 20.7 (C7), 21.8 (C9 or C10), 22.5 (C3), 25.3
(C8), 30.9 (C5), 33.7 (C4), 39.6 (N(CH3)2), 39.9 (C6),
47.4 (C2), 81.0 (C1), 87.4 (C11), 124.7 (C15), 126.3 (C14),
127.4 (C16), 127.8 (C12), 148.2 (C13). Elemental analysis
calcd (%) for C18H31BF4N2O (378.31): C 57.14, H 8.28,
N 7.41. Found: C 57.25, H 8.19, N 7.42.
4.3.25. 1-[(1R,2S,5R)-(ꢀ)-Menthoxymethyl]pyridinium bis-
(trifluoromethanesulfonyl)imide 6a. 1H NMR (CDCl3,
25 ꢁC): d = 0.46 (d, J = 7.1 Hz, 3H, H9 or H10), 0.83 (m,
9H, Ha-4, H7, H9 or H10, Ha-6 and Ha-3), 1.38 (m, 2H,
H2 and H5), 1.64 (m, 2H, Hb-3 and Hb-4), 2.05 (m, 2H,
H8 and Hb-6), 3.42 (td, J = 10.4, 4.1 Hz, 1H, H1), 5.90
and 5.94 (d, J = 10.4 Hz, 2H, AB system, H11), 8.13 (m,
2H, H13 and H15), 8.61 (m, 1H, H14), 8.96 (m, 2H, H12
and H16); 13C NMR (CDCl3): d = 15.0 (C9 or C10), 20.6
(C7), 21.6 (C9 or C10), 22.4 (C3), 25.2 (C8), 30.9 (C5),
33.6 (C4), 39.9 (C6), 47.4 (C2), 81.6 (C1), 87.5 (C11),
128.2 (C13 and C15), 146.9 (C14), 147.0 (C12 and C16); an-
ion: 113.2, 117.4, 121.7, 125.9. Elemental analysis calcd (%)
for C18H26F6N2O5S2 (528.66): C 40.89, H 4.97, N 5.30.
Found: C 40.97, H 4.80, N 5.19.
4.3.22. 1-[(1R,2S,5R)-(ꢀ)-Menthoxymethyl]pyridinium per-
chlorate 3. 1H NMR (CDCl3, 25 ꢁC): d = 0.44 (d,
J = 6.9 Hz, 3H, H9 or H10), 0.90 (m, 9H, Ha-4, H7, H9
or H10, Ha-6 and Ha-3), 1.36 (m, 2H, H2 and H5), 1.62
(m, 2H, Hb-3 and Hb-4), 1.98 (m, 2H, H8 and Hb-6),
3.44 (td, J = 10.4, 4.1 Hz, 1H, H1), 5.97 and 6.00 (d,
J = 10.9, 10.7 Hz, 2H, AB system, H11), 8.15 (m, 2H,
H13 and H15), 8.63 (m, 1H, H14), 8.99 (d, J = 5.5 Hz,
2H, H12 and H16); 13C NMR (CDCl3): d = 15.4 (C9 or
C10), 20.9 (C7), 22.0 (C9 or C10), 22.6 (C3), 25.4 (C8),
31.0 (C5), 33.8 (C4), 40.1 (C6), 47.5 (C2), 81.4 (C1), 87.6
(C11), 128.2 (C13 and C15), 142.8 (C14), 147.0 (C12 and
C16). Elemental analysis calcd (%) for C16H26ClNO5
(347.88): C 55.24, H 7.55, N 4.03. Found: C 55.39, H
7.40, N 3.97.
4.3.26. 1-[(1R,2S,5R)-(ꢀ)-Menthoxymethyl]-2-methylpyrid-
inium bis(trifluoromethanesulfonyl)imide 6b. 1H NMR
(CDCl3, 25 ꢁC): d = 0.40 (d, J = 7.1 Hz, 3H, H9 or H10),
0.83 (m, 9H, Ha-4, H7, H9 or H10, Ha-6 and Ha-3), 1.30
(m, 2H, H2 and H5), 1.64 (m, 2H, Hb-3 and Hb-4), 2.03
(m, 2H, H8 and Hb-6), 3.02 (s, 3H, CH3–R1), 3.42 (td,
J = 10.4, 4.1 Hz, 1H, H1), 5.90 and 5.94 (d, J = 10.7 Hz,
2H, AB system, H11), 7.82 (m, 2H, H15 and H13), 8.28
(m, 1H, H14), 9.34 (m, 1H, H16); 13C NMR (CDCl3):
d = 15.1 (C9 or C10), 20.6 (C7), 20.7 (CH3–R1), 21.8 (C9
or C10), 22.4 (C3), 25.2 (C8), 30.9 (C5), 33.6 (C4), 40.1
(C6), 47.4 (C2), 79.2 (C1), 85.1 (C11), 124.2 (C15), 128.9
(C13), 145.6 (C14), 146.2 (C16), 154.4 (C12); anion:
113.3, 117.5, 121.8, 126.0. Elemental analysis calcd (%)
for C19H28F6N2O5S2 (542.69): C 42.05, H 5.21, N 5.16.
Found: C 42.17, H 5.19, N 5.23.
4.3.23.
1-[(1R,2S,5R)-(ꢀ)-Menthoxymethyl]pyridinium
iodide 4. 1H NMR (CDCl3, 25 ꢁC): d = 0.47 (d,
J = 7.1 Hz, 3H, H9 or H10), 0.89 (m, 9H, Ha-4, H7, H9
or H10, Ha-6 and Ha-3), 1.33 (m, 1H, H2), 1.47 (m, 1H,
H5), 1.63 (m, 2H, Hb-3 and Hb-4), 1.98 (sept d, J = 6.9,
4.4 Hz, 1H, H8), 2.16 (m, 1H, Hb-6), 3.57 (td, J = 10.4,
4.1 Hz, 1H, H1), 6.29 and 6.38 (d, J = 10.2, 9.9 Hz, 2H,
AB system, H11), 8.30 (t, J = 7.7, 6.6 Hz, 2H, H13 and
H15), 8.79 (m, 1H, H14), 9.52 (d, J = 5.5 Hz, 2H, H12
and H16); 13C NMR (CDCl3): d = 15.4 (C9 or C10), 20.6
(C7), 21.8 (C9 or C10), 22.3 (C3), 25.2 (C8), 30.7 (C5),
33.5 (C4), 40.2 (C6), 47.2 (C2), 81.0 (C1), 86.8 (C11),
127.9 (C13 and C15), 142.8 (C14), 146.8 (C12 and C16).
Elemental analysis calcd (%) for C16H26INO (375.33): C
51.20, H 7.00, N 3.73. Found: C 51.36, H 6.88, N 3.68.
4.3.27. 1-[(1R,2S,5R)-(ꢀ)-Menthoxymethyl]-3-methylpyrid-
inium bis(trifluoromethanesulfonyl)imide 6c. 1H NMR
(CDCl3, 25 ꢁC): d = 0.41 (d, J = 7.1 Hz, 3H, H9 or H10),
0.89 (m, 9H, Ha-4, H7, H9 or H10, Ha-6 and Ha-3), 1.35
(m, 2H, H2 and H5), 1.64 (m, 2H, Hb-3 and Hb-4), 2.05
(m, 2H, H8 and Hb-6), 2.67 (s, 3H, CH3–R2), 3.35 (td,
J = 10.7, 4.4 Hz, 1H, H1), 5.84 and 5.90 (d, J = 10.2 Hz,
2H, AB system, H11), 8.01 (m, 1H, H15), 8.20 (d,
J = 7.7 Hz, 1H, H14), 9.30 (d, J = 6.1 Hz, 1H, H16), 9.36
(s, 1H, H12); 13C NMR (CDCl3): d = 15.3 (C9 or C10),
18.5 (CH3–R2), 20.6 (C7), 21.7 (C9 or C10), 22.4 (C3),
25.1 (C8), 30.8 (C5), 33.6 (C4), 39.9 (C6), 47.4 (C2), 80.1
(C1), 85.8 (C11), 126.6 (C15), 138.6 (C13), 140.1 (C14),
141.7 (C16), 145.1 (C12); anion: 113.2, 117.4, 121.9,
126.0. Elemental analysis calcd (%) for C19H28F6N2O5S2
(542.69): C 42.05; H 5.21; N 5.16. Found: C 41.97; H
5.29; N 5.22.
4.3.24. 1-[(1R,2S,5R)-(ꢀ)-Menthoxymethyl]pyridinium hexa-
fluorophosphate 5. 1H NMR (CDCl3, 25 ꢁC): d = 0.43 (d,
J = 6.9 Hz, 3H, H9 or H10), 0.86 (m, 9H, Ha-4, H7, H9 or
H10, Ha-6 and Ha-3), 1.34 (m, 2H, H2 and H5), 1.60 (m,
2H, Hb-3 and Hb-4), 1.97 (m, 2H, H8 and Hb-6), 3.38
(td, J = 10.4, 4.1 Hz, 1H, H1), 5.84 and 5.88 (d, J = 10.2,
10.4 Hz, 2H, AB system, H11), 8.07 (m, 2H, H13 and
H15), 8.56 (t, J = 7.7 Hz, 1H, H14), 8.82 (d, J = 5.5 Hz,
4.3.28. 1-[(1R,2S,5R)-(ꢀ)-Menthoxymethyl]-4-methylpyrid-
inium bis(trifluoromethanesulfonyl)imide 6d. 1H NMR
(CDCl3, 25 ꢁC): d = 0.46 (d, J = 6.9 Hz, 3H, H9 or H10),

J. Pernak, J. Feder-Kubis / Tetrahedron: Asymmetry 17 (2006) 1728–1737
1737
0.88 (m, 9H, Ha-4, H7, H9 or H10, Ha-6 and Ha-3), 1.35
(m, 2H, H2 and H5), 1.63 (m, 2H, Hb-3 and Hb-4), 2.05
(m, 2H, H8 and Hb-6), 2.70 (s, 3H, CH3–R3), 3.36 (td,
J = 10.7 Hz, J = 4.4 Hz, 1H, H1), 5.77 and 5.81 (d,
J = 10.4 Hz, 2H, AB system, H11), 8.61 (d, J = 6.6 Hz,
2H, H13 and H15), 8.78 (d, J = 6.9 Hz, 2H, H12 and
H16); 13C NMR (CDCl3): d = 15.1 (C9 or C10), 20.6
(C7), 21.7 (C9 or C10), 22.2 (CH3–R3), 22.5 (C3), 25.2
(C8), 30.9 (C5), 33.7 (C4), 39.9 (C6), 47.3 (C2), 80.2
(C1), 85.9 (C11), 127.6 (C13 and C15), 141.2 (C14),
159.1 (C12 and C16); anion: 113.1, 117.5, 121.9, 125.8.
Elemental analysis calcd (%) for C19H28F6N2O5S2
(542.69): C 42.05, H 5.21, N 5.16. Found: 42.10, H 5.28,
N 5.03.
J = 7.7 Hz 1H, H15), 9.02 (d, J = 7.4 Hz, 2H, H14 and
H16), 9.38 (s, 1H, H12); 13C NMR (CDCl3): d = 15.2
(C9 or C10), 20.7 (C7), 21.7 (C9 or C10), 22.5 (C3), 25.4
(C8), 31.1 (C5), 33.7 (C4), 40.1 (C6), 47.6 (C2), 82.2
(C1), 88.0 (C11), 128.3 (C15), 134.0 (C13), 142.5 (C14),
143.9 (C16), 145.6 (C12), 163.0 (CONH2); anion: 113.1,
117.3, 121.6, 125.8. Elemental analysis calcd (%) for
C19H27F6N3O6S2 (571.69): C 39.91, H 4.77, N 7.35. Found:
C 39.99, H 4.85, N 7.21.
4.3.32.
1-[(1R,2S,5R)-(ꢀ)-Menthoxymethyl]-3-(dimethyl-
amino)pyridinium bis(trifluoromethanesulfonyl)imide 6h.
1H NMR (CDCl3, 25 ꢁC): d = 0.51 (d, J = 6.9 Hz, 3H,
H9 or H10), 0.91 (m, 9H, Ha-4, H7, H9 or H10, Ha-6
and Ha-3), 1.37 (m, 2H, H2 and H5), 1.64 (m, 2H, Hb-3
and Hb-4), 2.03 (m, 2H, H8 and Hb-6), 3.1 (s, 6H,
N(CH3)2), 3.38 (td, J = 10.7 Hz, J = 4.4 Hz, 1H, H1),
5.75 and 5.80 (d, J = 10.2 Hz, 2H, AB system, H11), 7.63
(m, 1H, H15), 7.75 (m, 1H, H14), 8.03 (m, 2H, H16 and
H12); 13C NMR (CDCl3): d = 15.3 (C9 or C10), 20.7
(C7), 21.7 (C9 or C10), 22.5 (C3), 25.4 (C8), 31.0 (C5),
33.7 (C4), 39.7 (N(CH3)2), 40.0 (C6), 47.5 (C2), 81.3
(C1), 87.4 (C11), 124.0 (C15), 126.5 (C14), 127.4 (C16),
127.8 (C12), 148.3 (C13); anion: 113.3, 117.5, 121.8,
126.0. Elemental analysis calcd (%) for C20H31F6N3O5S2
(571.74): C 42.01, H 5.48, N 7.35. Found: C 42.15, H
5.41, N 7.48.
4.3.29. 4-Ethyl-1-[(1R,2S,5R)-(ꢀ)-menthoxymethyl]pyridi-
nium bis(trifluoromethanesulfonyl)imide 6e. 1H NMR
(CDCl3, 25 ꢁC): d = 0.46 (d, J = 7.1 Hz, 3H, H9 or H10),
0.88 (m, 9H, Ha-4, H7, H9 or H10, Ha-6 and Ha-3), 1.30
(m, 5H, H2, H5 and CH3–R3), 1.64 (m, 2H, Hb-3 and
Hb-4), 1.96 (m, 2H, H8 and Hb-6), 3.00 (q, J = 7.4 Hz,
2H, CH2–R3), 3.38 (td, J = 10.4, 4.1 Hz, 1H, H1), 5.82
and 5.86 (d, J = 10.2 Hz, 2H, AB system, H11), 7.89 (d,
J = 6.3 Hz, 2H, H13 and H15), 8.78 (d, J = 6.9 Hz, 2H,
H12 and H16); 13C NMR (CDCl3): d = 13.2 (CH3–R3),
15.3 (C9 or C10), 20.8 (C7), 21.8 (C9 or C10), 22.6 (C3),
25.4 (C8), 29.1 (CH2–R3), 31.1 (C5), 33.8 (C4), 40.1 (C6),
47.6 (C2), 81.5 (C1), 86.9 (C11), 127.5 (C13 and C15),
142.1 (C12 and C16), 166.7 (C14); anion: 113.1, 117.6,
121.9, 126.0. Elemental analysis calcd (%) for
C20H30F6N2O5S2 (556.72): C 43.14, H 5.44, N 5.03. Found:
C 43.09, H 5.49, N 5.16.
Acknowledgements
This work was supported by the Polish Grant No. PBZ-
KBN-101/T09/2003.
4.3.30.
4-tert-Butyl-1-[(1R,2S,5R)-(ꢀ)-menthoxymethyl]-
pyridinium bis(trifluoromethanesulfonyl)imide 6f. 1H NMR
(CDCl3, 25 ꢁC): d = 0.40 (d, J = 7.1 Hz, 3H, H9 or H10),
0.89 (m, 9H, Ha-4, H7, H9 or H10, Ha-6 and Ha-3), 1.35
(m, 11H, H2, CH3–R3, H5), 1.63 (m, 2H, Hb-3 and Hb-4),
1.97 (m, 2H, H8 and Hb-6), 3.36 (td, J = 10.4, 4.1 Hz, 1H,
H1), 5.80 (t, J = 10.4 Hz, 2H, AB system, H11), 8.06 (d,
J = 7.1 Hz, 2H, H13 and H15), 8.83 (d, J = 6.9 Hz, 2H,
H12 and H16); 13C NMR (CDCl3): d = 14.9 (C9 or C10),
20.6 (C7), 21.7 (C9 or C10), 22.4 (C3), 25.2 (C8), 29.7
(CH3–R3), 30.9 (C5), 33.7 (C4), 36.7 (C–R3), 39.9 (C6),
47.4 (C2), 78.1 (C1), 86.5 (C11), 125.2 (C13 and C15),
142.3 (C12 and C16), 173.3 (C14); anion: 113.3, 117.5,
121.8, 126.0. Elemental analysis calcd (%) for
C22H34F6N2O5S2 (584.78): C 45.18, H 5.87, N 4.79. Found:
C 45.25, H 5.94, N 4.63.
References
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4.3.31. 3-Carbamoyl-1-[(1R,2S,5R)-(ꢀ)-menthoxymethyl]-
pyridinium bis(trifluoromethanesulfonyl)imide 6g. 1H
NMR (CDCl3, 25 ꢁC): d = 0.50 (d, J = 6.9 Hz, 3H, H9 or
H10), 0.93 (m, 9H, Ha-4, H7, H9 or H10, Ha-6 and Ha-
3), 1.35 (m, 2H, H2 and H5), 1.63 (m, 2H, Hb-3 and Hb-
4), 1.99 (m, 2H, H8 and Hb-6), 3.46 (td, J = 10.4, 4.1 Hz,
1H, H1), 5.96 and 6.01 (d, J = 10.2 Hz, 2H, AB system,
H11), 6.87 (s, 1H, NH2), 7.62 (s, 1H, NH2), 8.18 (t,