Synthesis and characterization of (-)-menthyl containing N-alkyl cycloimmonium salts

Article abstract of DOI:10.1002/zaac.201100451

The reaction of 4-phenyl-2-aminothiazole or 2-amino pyridine with α-bromo acetic (-)-menthyl ester (2c) yields new N-alkyl cycloimmonium bromides (1c, 3) with the chiral (-)-menthyl substituent, which were isolated and fully characterized by ¹H and ¹³C NMR spectroscopy for the first time. In addition, starting from 4-phenyl-2-aminothiazole, two further N-alkyl cycloimmonium bromides (1a, 1b) were prepared. The molecular and crystal structures of all three thiazole derived N-alkyl cycloimmonium bromides (1a-c) were determined by single-crystal X-ray diffraction. In all cases the crystal structures are dominated by N-H...Br hydrogen bonds, which results in the formation of an extensive hydrogen bonded network in the crystal. Interestingly, in all structures S...Br^- distances shorter than the sum of the van der Waals radii are observed. Copyright

Full text of DOI:10.1002/zaac.201100451

ARTICLE
DOI: 10.1002/zaac.201100451
Synthesis and Characterization of (–)-Menthyl Containing N-Alkyl
Cycloimmonium Salts
Christina Hettstedt,[a] Wolfgang Betzl,[a] and Konstantin Karaghiosoff*[a]
Dedicated to Professor Wolfgang Beck on the Occasion of His 80th Birthday
Keywords: N-Alkyl cycloimmonium salts; Aminothiazole; α-Bromoacetyl (–)-menthyl ester; Crystal structure; N–H···Br– hydro-
gen bonds
Abstract. The reaction of 4-phenyl-2-aminothiazole or 2-amino pyr-
idine with α-bromo acetic (–)-menthyl ester (2c) yields new N-alkyl
azole derived N-alkyl cycloimmonium bromides (1a–c) were deter-
mined by single-crystal X-ray diffraction. In all cases the crystal struc-
tures are dominated by N–H···Br hydrogen bonds, which results in the
cycloimmonium bromides (1c, 3) with the chiral (–)-menthyl substitu-
1
ent, which were isolated and fully characterized by H and 13C NMR formation of an extensive hydrogen bonded network in the crystal.
spectroscopy for the first time. In addition, starting from 4-phenyl-2-
aminothiazole, two further N-alkyl cycloimmonium bromides (1a, 1b)
were prepared. The molecular and crystal structures of all three thi-
Interestingly, in all structures S···Br– distances shorter than the sum of
the van der Waals radii are observed.
bromides 1a–c were obtained by reaction of 2-amino-4-phen-
ylthiazole with the α-bromoesters 2a–c. While the synthesis of
1a was described by Bansal[1] the thiazolium salt 1c containing
the chiral (–)-menthyl substituent and the thiazolium salt 1b
with the CH2CO2Et substituent were obtained herein for the
first time (Scheme 1). Similarly reaction of 2-aminopyridine
with the α-bromoester 2c in acetone resulted in the formation
of the new pyridinium salt 3, which was isolated in good yields
(Scheme 1).
Introduction
N-Alkyl cycloimmonium salts are of great importance as
precursors for the synthesis of heterophospholes.[1] In the
course of systematic investigations on the synthesis of hetero-
phospholes containing chiral information we were engaged
with the preparation of N-alkyl cycloimmonium salts, which
contain the chiral (–)-menthyl substituent. No cycloimmonium
salts with the (–)-menthyl moiety are known in the literature.
Herein we report the synthesis and characterization of first
cycloimmonium salts containing the (–)-menthyl substituent.
In addition we report the molecular and crystal structures of
three thiazolium bromides. The structures are discussed with
respect to the extensive hydrogen bonding found in the crystal-
line state.
Results and Discussion
Synthesis
Cycloimmonium salts are generally prepared by the alky-
lation of corresponding 2-amino azoles or azines by appropri-
ate alkyl halides.[1–3] Following this route the thiazolium
Scheme 1. Synthesis of 2-amino-4-phenyl thiazolium salts 1a–c and
of the 2-amino pyridinium salt 3.
2-Amino-4-phenyl-1,3-thiazole
can
be
prepared
according to a synthesis published by Balalaie[4] from
2-bromo-1-phenylethanone and thiourea in a base catalyzed
condensation reaction in good yields.
* Dr. K. Karaghiosoff
Fax: +49-89-2180-77492
E-Mail: klk@cup.uni-muenchen.de
[a] Department of Chemistry
The synthesis of (1R,2S,5R)-2-(propan-2-yl)-5-methyl-cy-
clohexyl-2-bromoacetate [(–)-menthyl-2-bromoacetate] (2c) by
a carbodiimide promoted esterification – using e.g. DCC[5] or
EDC/DMAP[6] – or by the condensation of 2-bromoacetyl
chloride and (–)-menthol with pyridine[7] as base has been re-
Ludwig-Maximilians University (LMU)
Butenandtstrasse 5–13 (Haus D)
81377 Munich, Germany
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/zaac.201100451 or from the au-
thor.
Z. Anorg. Allg. Chem. 2012, 638, (2), 377–382
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
377

C. Hettstedt, W. Betzl, K. Karaghiosoff
ARTICLE
ported. We prepared 2c by reaction of 2-bromoacetyl bromide Table 2. 13C NMR chemical shifts δ /ppm of compounds 1a–c (in
CDCl3) and 3 (in [D6]DMSO).
and (–)-menthol using potassium carbonate as the base. This
route has the advantage of a much simpler workup and gives
the 2-bromoester in very good yields (95%).
1a
1b
1ca)
3b)
C2
C4
C5
N–CH2
C-i
C-o
C-m
C-p
C=O
R
169.6
140.0
105.7
48.0
128.0
129.2
130.5
129.4
166.4
53.1 (Me)
169.8
140.5
105.9
49.5
128.2
129.3
130.8
129.7
169.9
140.9
104.9
49.4
128.2
129.7
129.2
130.8
165.2
155.3
The new (–)-menthyl substituted salts 1c and 3 as well as
the esters 1a and 1b are isolated as colorless microcrystalline
solids, which are easily soluble in DMSO and CHCl3 and spar-
ingly soluble in acetonitrile, THF, and acetone. They are air
and water stable. The identities of the salts 1a–c and 3 result
54.2
1
from the H and 13C NMR spectra (see Table 1 and Table 2)
165.8
14.1 (Me)
25.7 (CH2)
165.9
and are confirmed by the results of single crystal X-ray diffrac-
tion in the case of 1a–c.
C1Ј
C2Ј
C3Ј
C4Ј
C5Ј
C6Ј
C7Ј
C8Ј
C9Ј
C10Ј
68.0
46.8
23.3
34.1
31.5
40.5
21.9
16.2
25.9
20.8
76.6
47.0
23.2
34.1
31.4
40.9
22.4
16.7
25.8
21.3
NMR Spectra
1
The H and 13C NMR spectroscopic data of the cycloim-
monium salts 1a–c and 3 are presented in Table 1 and Table 2,
respectively. The N-methylene group of the bromoacetates 2 is
a good NMR probe for the alkylation reaction as its H and
13C NMR spectroscopic data display the largest changes on
alkylation (Table 1 and Table 2).[5,8]
1
a) Spectrum measured at 40 °C. b) 113.4 (CH), 115.6 (CH), 141.1
(CH), 143.6 (CH).
Table 1. 1H NMR spectroscopic data of compounds 1a–c and 3; in
CDCl3 except 3 in [D6]DMSO; chemical shifts δ in ppm, coupling
constants J in Hz., a = axial, e = equatorial.
NMR shifts of 1a–c compare well with each other and the
corresponding shifts of the (–)-menthyl substituents in 1c and
3 are very similar. Only the 13C NMR shift of C1Ј in com-
pounds 1c and 3 differs by 18.6 ppm.
1a
1b
1ca)
3b)
5-H
7.07
6.67
6.52
6.94
J = 6.9
N–CH2 4.76
4.98
4.91, 5.28c)
JAB = 18.1
5.16, 5.27c)
JAB = 18.1
4-Ph
o-H
m-H
p-H
2-NH2 10.00
R
7.34–7.75 7.27–7.49
Molecular and Crystal Structures of 1a–c
7.26–7.31
7.40–7.45
7.46–7.52
9.94
Block-shaped single crystals of 1a–c suitable for X-ray dif-
fraction studies were obtained by recrystallization of the com-
pounds from dichloromethane.
9.84
8.66
3.66 (Me) 4.17 (OCH2)
3JHH = 7.2
Compound 1a crystallizes in the triclinic space group P1
¯
1.18 (Me)
(No. 2) with two formula units in the unit cell. Figure 1 shows
the asymmetric unit of the crystal structure of 1a, which con-
sists of two crystallographically independent molecules: mole-
cule A including sulfur atom S1 and molecule B including sul-
fur atom S2. Both molecules differ in the orientation of their
substituents relative to the thiazole ring. The phenyl substituent
3JHH = 7.2
8Ј-H
0.65
0.68
J = 6.9
0.73–0.81
0.79
J = 6.9
0.87
J = 6.9
0.80–0.89
0.84
J = 7.0
0.87
4Ј-Ha
9Ј-H
10Ј-H
J = 6.5
0.90–1.04
J = 6.5
0.92–1.08
3Ј,6Ј-
Ha
2Ј-H
5Ј-H
3Ј,4Ј-
He
1.23–1.33
1.34–1.45
1.53–1.66
1.26–1.34
1.38–1.50
1.57–1.66
7Ј-H
6Ј-He
1Ј-H
1.79–1.86
1.96–2.05
4.67, J =
1.82–1.91
1.94–2.00
4.65 J = 10.8,
10.9, J = 4.3 J = 4.2
a) Spectrum measured at 40 °C. b) 3-H: δ = 7.13 (d, J = 9.0 Hz, 1 H),
4-H: δ = 7.92 (t, J = 8.0 Hz, 1 H), 6-H: δ = 8.06 (d, J = 6.8 Hz, 1 H).
c) N–CH2: AB spin system.
The corresponding 1H NMR signals of the N-methylene
groups in 1c and 3 show an AB spin system due to the pres-
Figure 1. Molecular structure of 1a in the crystal; ORTEP view of the
asymmetric unit showing the two crystallographically independent
ence of the chiral (–)-menthyl substituent. The 1H and 13C units A and B. Thermal ellipsoids are drawn at 50% probability level.
378
www.zaac.wiley-vch.de
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Z. Anorg. Allg. Chem. 2012, 377–382

(–)-Menthyl Containing N-Alkyl Cycloimmonium Salts
as well as the CH2CO2Me group are both rotated out of the Table 3. Atom distances /Å and bond angles /° for the hydrogen bonds
and S···Br contacts in compounds 1a–c.
thiazole ring plane. Whereas the phenyl group in A is almost
perpendicular to the thiazole ring [C2–C3–C7–C12
=
X–Y···Br
d(X–Y)
d(Y–Br)
d(X–Br)
X–Y–Br
83.7(5)°], in the case of B a torsion angle C14–C15–C19–C20 1a
N2–H201···Br1 0.804(4)
N2–H202···Br1 0.925(4)
N4–H401···Br2 0.806(3)
N4–H402···Br2 0.948(3)
2.497(4)
2.475(4)
2.501(3)
2.357(4)
3.527(9)
3.485(1)
3.295(4)
3.389(3)
3.299(3)
3.287(4)
171.6(4)
169.6(3)
169.8(3)
167.0(3)
168.0(1)
163.0(1)
of 132.7(4)° is observed. The corresponding torsion angles for
the CH2CO2Me groups are C3–N1–C4–C5 = 92.2(3)° for A
and C15–N3–C16–C17 = 101.3(4)° for B, respectively.
In the crystal structure of 1a N–H···Br hydrogen bonds be-
tween the NH2 groups and the Br– anions are observed. This
results in the formation of dimers, as shown in Figure 2. The
bonding parameters of the hydrogen bonds are summarized in
Table 3 and compare well to literature values.[9] The dimers
C1–S1···Br2
C13–S2···Br1
1b
1.720(3)
1.721(3)
N2–H201···Br2a 0.848(2)
N2–H202···Br1 0.808(2)
2.519(2)
2.587(2)
2.376(3)
3.304(2)
3.380(2)
3.202(2)
154.3(2)
168.6(2)
160.4(3)
N4b–
0.864(3)
are connected by weak intermolecular interactions involving H401b···Br2a
N4b–
0.897(2)
2.489(2)
3.339(2)
158.4(2)
the sulfur atoms S1 and S2 and the bromide anions Br2 and
H402b···Br1a
Br1 (Figure 2). This arrangement results in the formation of
C2–S1···Br2a
1.729(2)
3.604(5)
3.422(5)
3.480(6)
157.6(7)
171.4(7)
169.2(7)
chains of alternating dimers of molecules A and B, which are
packed to build the crystal. The intermolecular S···Br contacts
in the crystal structure of 1a are also compiled in Table 3.
C15b–S2b···Br2a 1.726(2)
C1–S1···Br1a
1c
1.727(2)
N2–H21···Br1c
N2–H22···Br1d
C1–S1···Br1
C2–S1···Br1d
0.859(13)
0.810(3)
1.718(3)
1.734(3)
2.647(17)
2.503(3)
3.557(7)
3.639(7)
3.462(3)
3.296(3)
159.0(2)
166.5(3)
159.6(9)
172.2(0)
Symmetry operators: a) 1+x, y, z; b) 0.5+x, 0.5–y, 0.5+z; c) –1+x, y,
z; d) –0.5+x, 1.5–y, 1–z.
Figure 3. Molecular structure of 1b in the crystal; ORTEP view of the
two crystallographically independent molecules A and B. [a] 0.5+x,
0.5–y, –0.5+z. Thermal ellipsoids are drawn at 50% probability level.
As in the case of compound 1a the crystal structure of 1b
is determined by N–H···Br hydrogen bonds. Interestingly the
slight change of the substituent at oxygen (from methyl to
ethyl) obviously favors an arrangement of the cations and
Figure 2. Crystal structure of 1a; ORTEP view of the hydrogen
bonded (black dashed lines) dimers of molecules A and B linked by
weak intermolecular S···Br interactions (grey dashed lines) to form
chains. Thermal ellipsoids are drawn at 50% probability level.
Compound 1b crystallizes in the monoclinic space group anions to form chains (instead of dimers) along the a axis (Fig-
P21/n (No. 14) with eight formula units in the unit cell. As in ure 4). In this case also intermolecular S···Br distances slightly
the case of 1a the asymmetric unit of 1b is formed by two shorter than the sum of the van der Waals radii are observed.
crystallographically independent molecules A (containing S1) Atom distances and bond angles for all intermolecular interac-
and B (containing S2) and is shown in Figure 3.
tions in the crystal structure of 1b are compiled in Table 3.
Z. Anorg. Allg. Chem. 2012, 377–382
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.zaac.wiley-vch.de 379

C. Hettstedt, W. Betzl, K. Karaghiosoff
ARTICLE
The two molecules are differing in the orientation of the sub-
stituents of the planar thiazole ring. The torsion angles of the
phenyl groups are –81.7(3)° (C2–C3–C8–C13) for molecule A
and 45.7(3)° (C15–C16–C21–C22) for molecule B. Also the
CH2CO2Et groups are twisted out of the plane of the thiazole
ring. For molecule A the angle C3–N1–C4–C5 is –76.5(2)° and
for molecule B the torsion angle C16–N3–C17–C18 is 90.3(2)°
(Figure 3).
Figure 5. ORTEP drawing of the molecular structure of 1c·CH2Cl2 in
the crystal. Ellipsoids are drawn at 50% probability level.
Figure 4. Crystal structure of 1b; ORTEP view of the hydrogen
bonded (black dashed lines) chain, showing also the S···Br contacts
(grey dashed lines). Thermal ellipsoids are drawn at 50% probability
level.
Compound 1c·CH2Cl2 crystallizes in the orthorhombic
space group P212121 (No. 19) with four formula units in the
unit cell. The asymmetric unit is shown in Figure 5. As in the
case of 1a and 1b the thiazole ring in 1c is planar and both
substituents at C3 and at nitrogen are twisted out of the thi-
azole ring plane. For the phenyl ring a torsion angle C2–C3–
C4–C5 of 53.9(4)° and for the ester moiety a torsion angle
C3–N1–C11–C10 of –97.3(3)° are observed.
The most interesting feature of the structure of 1c is the
extensive hydrogen bonding involving the amino group of the
thiazole ring and the bromide anions. The oxygen atoms of
the ester function do not participate to the hydrogen bonding
Figure 6. Crystal structure of 1c·CH2Cl2; ORTEP view of the hydro-
gen bonded chain (black dashed lines), showing also the S···Br contacts
(grey dashed lines); solvent molecules omitted for clarity. Thermal el-
lipsoids are set to 50% probability level.
network. The interaction of the NH2 groups with the Br– axis. Figure 6 shows these chains in a direction formed by
anions results in the formation of zigzag chains along the a intermolecular hydrogen bonds. In addition within the chains
380
www.zaac.wiley-vch.de
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Z. Anorg. Allg. Chem. 2012, 377–382

(–)-Menthyl Containing N-Alkyl Cycloimmonium Salts
S1···Br1 distances of 3.557(7) Å and 3.639(7) Å are observed, Table 4. Crystal data and structure refinement parameters for 1a–c.
which are slightly shorter than the sum of the van der Waals
1a
1b
1c
radii (3.65 Å)[10]. This very weak interaction seems to further
stabilize the chains. The bond lengths and angles of the hydro-
gen bonds and the intermolecular S···Br distances are given in
Table 3.
Empirical formula C24H26Br2N4O4S2 C26H30Br2N4O4S2 C22H31BrCl2N2O2S
Formula weight
Cryst. size /mm3
Crystal system
Space group
a /Å
b /Å
c /Å
α /°
β /°
658.43
686.48
538.36
0.15ϫ0.15ϫ0.1 0.35ϫ0.35ϫ0.3 0.4ϫ0.1ϫ0.1
triclinic
monoclinic
P21/n (14)
9.432(3)
14.273(7)
22.406(6)
90
95.00(3)
90
3004.9(3)
4
orthorhombic
P212121 (19)
9.157(3)
16.449(5)
16.690(5)
90
¯
P1 (2)
10.1242(7)
12.2120(8)
13.024(1)
62.309(8)
74.668(7)
87.479(5)
1369.18(17)
2
1.597
3.150
664
–12 Յ h Յ 12,
–14 Յ k Յ 15,
–16 Յ l Յ 15
10656
6201
0.0362
Conclusions
90
90
Two N-alkyl cycloimmonium bromides containing the chiral
(–)-menthyl substituent were prepared starting from 4-phenyl-
2-aminothiazole and 2-aminopyridine and were fully charac-
γ /°
V /Å3
2513.9(14)
4
1.422
1.951
1112
Z
ρcalcd /g·cm–3
μ(MoKα) /cm–1
F(000), e
hkl range
1.517
2.874
1392
1
terized by H and 13C NMR spectroscopy for the first time. In
addition the synthesis of two further N-alkyl cycloimmonium
bromides is described. For all thiazole derivatives the molecu-
lar and crystal structures were determined by single-crystal X-
ray diffraction. In all cases N–H···Br hydrogen bonds are of
crucial importance in determining the crystal structures.
Whereas in the case of the methyl ester 1a hydrogen bonded
dimers are formed, in the case of 1b and 1c the hydrogen
bonds result in the formation of chains throughout the crystal.
Remarkably in all structures S···Br distances shorter than the
sum of the van der Waals radii are observed. The preparative
availability, in particular of the cycloimmonium salts having
the chiral (–)-menthyl substituent, opens now the possibility
for the synthesis of chiral heterophospholes.
–9 Յ h Յ 11, –7 –11 Յ h Յ 11,
Յ k Յ 17, –26 Յ –20 Յ k Յ 20,
l Յ 27
17421
5865
0.0259
359
4.32 Յ θ Յ
32.39
0.0252, 0.0446
–20 Յ l Յ 20
25508
4927
0.0404
279
Refl. measured
Refl. unique
Rint
Param. refined
θ Range /°
341
4.18 Յ θ Յ 26
4.12 Յ θ Յ 30.00
R1, wR2 [I Ͼ
2σ(I)]a
0.0338, 0.0465
0.0293,
R1, wR2 (all data)a 0.0708, 0.0491
0.0467, 0.0459
0.813
0.253, –0.408
0.0383,
0.893
0.679, –0.557
GooF
0.739
0.426, –0.378
δpmax, δpmin
/
e·nm–3
x (Flack)
–0.006(6)
relevant data and parameters of the X-ray measurements and refine-
ments are given in Table 4. The hydrogen atoms were found in the
difference Fourier map and refined isotropically.
Experimental Section
General: All reactions were carried out in an inert gas atmosphere
using Schlenk techniques. Argon (Messer Griesheim, purity 4.6 in
50 L steel cylinder) was used as an inert gas. Glass vessels were stored
in a 130 °C drying oven and were flame-dried at 10–3 mbar vacuum
before use. 2-Amino-4-phenyl-1,3-thiazole was prepared according to
a literature procedure[4]. All other chemicals were commercially avail-
able and were used as received. The solvents were dried using com-
monly known drying methods and were freshly distilled before use.
Crystallographic data (excluding structure factors) for the structures in
this paper have been deposited with the Cambridge Crystallographic
Data Centre, CCDC, 12 Union Road, Cambridge CB21EZ, UK. Copies
of the data can be obtained free of charge on quoting the depository
numbers CCDC-844692 (1a), CCDC-844693 (1b), and CCDC-844694
(1c) (Fax: +44-1223-336-033; E-Mail: deposit@ccdc.cam.ac.uk,
http://www.ccdc.cam.ac.uk).
NMR Spectroscopy: NMR spectra were recorded with a JEOL EX
400 Eclipse instrument operating at 400.128 MHz (1H) and 100.626
(13C). Chemical shifts are referred to Me4Si (1H, 13C) as external stan-
dards. All spectra were measured, if not mentioned otherwise, at 25 °C.
The assignment of the signals in the 1H and 13C NMR spectra is based
on 2D (1H,1H-COSY45, 1H,13C-HMQC and 1H,13C-HMBC) spectra
for 1c and comparison with the literature.
(1R,2S,5R)-2-(Propan-2-yl)-5-methylcyclohexyl 2-bromo
acetate
(2c): Compound 2c was prepared by modification of a literature pro-
cedure.[7] In a 100 mL Schlenk flask (–)-menthol [(1R,2S,5R)-2-(pro-
pan-2-yl)-5-methylcyclohexanol] (15.63 g, 100 mmol, 1.0 equiv.) and
potassium carbonate (6.91 g, 50 mmol, 0.5 equiv.) were poured in
dichloromethane (100 mL). The suspension was cooled to 0 °C and
2-bromoacetyl bromide (8.67 mL, 100 mmol, 1.0 equiv.) was added
dropwise over a period of 15 min. After warming up to room tempera-
ture the reaction mixture was stirred for 12 h. After the addition of
water (50 mL), the mixture was extracted three times with diethyl ether
(50 mL). The combined organic layers were washed with water
(100 mL) and dried over sodium sulfate. After removing the solvent
in vacuo 2c was obtained as colorless, slightly viscous oil (26.44 g,
95%). The analytic data are in good accordance to the literature known
values.[5]
Mass Spectrometry: Mass spectrometric data were obtained with a
JEOL Mstation JMS 700 spectrometer using the direct EI mode for
neutral compounds and the FAB mode for ionic compounds with (4-
nitrophenyl)methanol as matrix.
X-ray Crystallography: The molecular structures in the crystalline
state were determined with an Oxford Xcalibur3 diffraction instrument
with a Spellman generator (voltage 50 kV, current 40 mA) and a Kappa
CCD detector with an X-ray radiation wavelength of 0.71073 Å. The
data collection was performed with the CrysAlis CCD software[11] and 2-Amino-3-(2-methoxy-2-oxomethyl)-4-phenyl-1,3-thiazol-3-ium
the data reduction with the CrysAlis RED software[12]. The structures
bromide (1a): To a solution of 2-amino-4-phenyl-1,3-thiazol (3.52 g,
were solved with SIR-92, SIR-97, and SHELXS-97 and refined with 20 mmol, 1.0 equiv.) in THF (20 mL), methyl 2-bromoacetate (2a)
SHELXL-97 and finally checked using PLATON.[13–17] The absorp-
tions were corrected by SCALE3 ABSPACK multiscan method.[18] All
(1.89 mL, 20 mmol, 1.0 equiv.) was added. The reaction mixture was
stirred for five days at room temperature. During this time small
Z. Anorg. Allg. Chem. 2012, 377–382
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.zaac.wiley-vch.de
381

C. Hettstedt, W. Betzl, K. Karaghiosoff
ARTICLE
amounts of a colorless solid was formed. To complete the reaction the Supporting Information (see footnote on the first page of this article):
mixture was heated to reflux for another three days. The precipitate Tables of all bond lengths and angles observed in the crystal structures
of compounds 1a–c.
was filtered off, washed with THF (20 mL) and dried in vacuo, yield-
ing 1a as a colorless solid (3.42 g, 51.9%). For 1H and 13C NMR
spectroscopic data see Table 1 and Table 2, respectively. MS (FAB+):
m/z (%) = 249.1 (100) [M–Br]+. MS (FAB–): m/z (%) = 80.9 (97)
[Br]–, 78.9 (100) [Br]–. HRMS (FAB+): m/z = 249.0698 (calcd.
249.0692 for C12H13N2O2S+, [M–Br]+). HRMS (FAB–): m/z =
80.9163 (Br-81, 49.3%), 78.9183 (Br-79, 50.7%) [calcd. 80.916289
for Br-81 (49.31%), 78.918336 for Br-79 (50.69%)].
Acknowledgement
Financial support by the Department of Chemistry, Ludwig-Maximilian
University of Munich is gratefully acknowledged. W.B. thanks the Cus-
anuswerk for a PhD fellowship. The authors are thankful to Prof. T.
M. Klapötke for the generous allocation of diffractometer time.
2-Amino-3-(2-ethoxy-2-oxoethyl)-4-phenyl-1,3-thiazol-3-ium
bromide (1b): The compound was prepared following the procedure
described for 1a. Compound 1b was obtained as a colorless solid
References
1
(1.19 g, 17.4%). For H and 13C NMR spectroscopic data see Table 1
[1] R. K. Bansal, V. Kabra, R. Munjal, N. Gupta, Ind. J. Chem. Sect.
B 1994, 33, 992–994.
[2] K. Karaghiosoff, R. K. Bansal, N. Gupta, Z. Naturforsch. 1992,
and Table 2, respectively. MS (FAB+): m/z (%) = 263.1 (100) [M–
Br]+. MS (FAB–): m/z (%) = 80.9 (97) [Br]–, 78.9 (100) [Br]–. HRMS
(FAB+): m/z = 342.0038 (calcd. 263.0849 for C13H15N2O2S+, [M–
Br]+). HRMS (FAB–): m/z = 80.9163 (Br-81, 49.3%), 78.9183 (Br-
79, 50.7%) [calcd. 80.916289 for Br-81 (49.31%), 78.918336 for Br-
79 (50.69%)]. Elemental analysis: calcd. C 45.49, H 4.40, N 8.16%;
found C 45.72, H 4.55, N 7.86%.
47b, 373–378.
[3] R. K. Bansal, R. Mahnot, D. C. Sharma, K. Karaghiosoff, Synthe-
sis 1992, 267–269.
[4] S. Balalaie, S. Nikoo, S. Haddadi, Synth. Commun. 2008, 38,
2521–2528.
[5] L. Streinz, B. Koutek, D. Saman, Synlett 2001, 6, 809–811.
[6] T. Kurtan, N. Nesnas, Y.-Q. Li, X. Huang, K. Nakanishi, N. Be-
rova, J. Am. Chem. Soc. 2001, 123, 5962–5973.
[7] P. Deprez, J. Royer, H.-P. Husson, Tetrahedron Asymmetry 1991,
2, 1189–1192.
[8] For the NMR spectroscopic data of the starting materials for 2a
and 2b see SDBS database: http://riodb01.ibase.aist.go.jp/sdbs/
(National Institute of Advanced Industrial Science and Technol-
ogy, 11-08-2010).
2-Amino-3-(2-((1R,2S,5R)-2-(propan-2-yl)-5-methyl-cyclohexyl-
oxy)-2-oxoethyl)-4-phenyl-1,3-thiazol-3-ium bromide (1c): The
compound was prepared following the procedure described for 1a.
Compound 1c was isolated as a colorless solid (1.72 g, 19.0%). For
1H and 13C NMR spectroscopic data see Table 1 and Table 2, respec-
tively. MS (FAB+): m/z (%) = 373.2 (100) [M–Br]+. MS (FAB–): m/z
(%) = 80.9 (97) [Br]–, 78.9 (100) [Br]–. HRMS (FAB+): m/z =
373.1950 (calcd. 373.1944 for C21H29N2O2S+, [M–Br]+). HRMS
(FAB–): m/z = 80.9163 (Br-81, 49.3 %), 78.9183 (Br-79, 50.7 %)
[calcd. 80.916289 for Br-81 (49.31 %), 78.918336 for Br-79
(50.69%)]. Elemental Analysis: calcd. C 55.63, H 6.45, N 6.18%;
found C 55.30, H 6.61, N 6.24%.
[9] V. Langer, K. Huml, Acta Crystallogr., Sect. B 1978, 34, 1881–
1884.
[10] A. Bondi, J. Phys. Chem. 1964, 68, 441–451.
[11] CrysAlis CCD, version 1.171.27p5 beta (release 01–04–2005
CrysAlis171.NET; compiled Apr 1 2005,17:53:34); Oxford Dif-
fraction Ltd.: Oxfordshire, U. K.
[12] CrysAlis RED, version 1.171.27p5 beta (release 01–04–2005
CrysAlis171.NET; compiled Apr 1 2005, 17:53:34); Oxford Dif-
fraction Ltd.: Oxfordshire, U. K.
2-Amino-1-(2-((1R,2S,5R)-2-(propan-2-yl)-5-methyl cyclohexyl-
oxy)-2-oxoethyl)pyridinium bromide (3): To a solution of 2-amino-
pyridine (0.471 g, 5 mmol, 1.0 equiv.) in acetone (10 mL), (1R,2S,5R)-
2-(propan-2-yl)-5-methyl cyclohexyl 2-bromoacetate (2c) (1.39 g,
5 mmol, 1.0 equiv.) was added. From the clear orange solution a color-
less solid started to precipitate after 10 min. The mixture was heated
to reflux for 12 h. The precipitate formed was separated by filtration,
washed with 50 mL of cold acetone and dried in vacuo, yielding com-
pound 3 as colorless powder (1.38 g, 74%). For 1H and 13C NMR
spectroscopic data see Table 1 and Table 2, respectively. MS (FAB+):
m/z (%) = 291.2 (100) [M–Br]+. MS (FAB–): m/z (%) = 80.9 (97)
[Br]–, 78.9 (100) [Br]–. HRMS (FAB+): m/z = 291.2073 (calcd.
291.2067 for C17H27N2O2+, [M–Br]+). HRMS (FAB–): m/z = 80.9163
(Br-81, 49.3%), 78.9183 (Br-79, 50.7%) [calcd. 80.916289 for Br-81
(49.31%), 78.918336 for Br-79 (50.69%)] Elemental Analysis: calcd.
C 54.99, H 7.33, N 7.54%; found C 54.79, H 7.49, N 7.84%.
[13] SIR-92, A Program for Crystal Structure Solution: A. Altomare,
G. L. Cascarano, C. Giacovazzo, A. Guagliardi, J. Appl. Crys-
tallogr. 1993, 26, 343–350.
[14] A. Altomare, M. C. Burla, M. Camalli, G. L. Cascarano, C. Gia-
covazzo, A. Guagliardi, A. G. G. Moliterni, G. Polidori, R.
Spagna, J. Appl. Crystallogr. 1999, 32, 115–119.
[15] G. M. Sheldrick, SHELXS-97, Program for Crystal Structure
Solution, University of Göttingen, Göttingen, Germany, 1997.
[16] G. M. Sheldrick, SHELXL-97, Program for the Refinement of
Crystal Structures, University of Göttingen: Göttingen, Germany,
199.
[17] L. A. Spek, PLATON, A Multipurpose Crystallographic Tool,
Utrecht University: Utrecht, The Netherlands, 1999.
[18] SCALE3 ABSPACK - An Oxford Diffraction program (1.0.4,
gui:1.0.3); Oxford Diffraction Ltd.: Oxfordshire, U. K., 2005.
Received: October 12, 2011
Published Online: December 23, 2011
382
www.zaac.wiley-vch.de
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Z. Anorg. Allg. Chem. 2012, 377–382