Synthesis and crystal structures of new 1,3-disubstituted imidazoline-2-thiones

Article abstract of DOI:10.5560/ZNB.2013-3184

Two methods (MeOH=K²CO³, pyridine=Et³N) were assessed for the introduction of sulfur into the 2-position of 1,3-disubstituted quaternary imidazolium salts 1-9 (Cl, I, BF⁴, PF⁶, CH³OSO³ were used as anions) to yield nine 1,3-disubstituted imidazoline-2-thiones 10-18 (1, 10: R¹ = CH ³, R² = CH³; 2, 11: R¹ = OCH ²Ph, R² = CH³; 3, 12: R¹ = OCH ³, R² = CH³; 4, 13: R¹ = OCH ³, R² = OCH³; 5, 14: R¹ = NH ², R² = CH²Ph; 6, 15: R¹ = NCHPh, R² = CH³; 7, 16: R¹ = NH², R ² = CH³; 8, 17: R¹ = NCHPh, R² = NCHPh; 9, 18: R¹ = NH², R² = OCH³). Compounds 11-18 represent N-alkyloxy and N-amino imidazoline-2-thiones, whereas 10 served as reference compound. The first method was advantageous for the conversion 1 → 10 due to faster reaction, whereas in the reaction 2 → 11 considerable amounts of by-products were formed. Pure thiones 11, 14, 16, 17, and 18 were obtained only by the second method. Both methods worked for the synthesis of the methoxy derivatives 12 and 13 from 3 and 4, and the benzylideneamino derivative 15 from 6. 1-Amino-3- methylimidazoline-2-thione (16) was also prepared by hydrolysis of the benzylideneamino derivative 15. Crystal structures of seven 1,3-disubstituted imidazoline-2-thiones were determined by singlecrystal X-ray diffraction. Intermolecular C-H...S contacts were identified and, additionally, N-H...S interactions in aminothiones 14 and 16. The ¹H NMR shifts of 10 and 13 were satisfactorily correlated with the Kamlet-Abboud-Taft π^* and β parameters in ten solvents. From the lack of correlation with the a parameter and from the C=S bond length (average 1.68 A ) a significant contribution of a mesoionic imidazolium-2-thiolate resonance structure seems unlikely.

Full text of DOI:10.5560/ZNB.2013-3184

Synthesis and Crystal Structures of New 1,3-Disubstituted
Imidazoline-2-thiones
Gerhard Lausa, Volker Kahlenbergb, Klaus Wursta, Thomas Mu¨llera, Holger Kopackaa,
and Herwig Schottenbergera
a
Faculty of Chemistry and Pharmacy, University of Innsbruck, 6020 Innsbruck, Austria
Institute of Mineralogy and Petrography, University of Innsbruck, 6020 Innsbruck, Austria
b
Reprint requests to Dr. Gerhard Laus. Fax: +43 512 507 57099. E-mail: gerhard.laus@uibk.ac.at
Z. Naturforsch. 2013, 68b, 1239 – 1252 / DOI: 10.5560/ZNB.2013-3184
Received July 6, 2013
Two methods (MeOH/K2CO3, pyridine/Et3N) were assessed for the introduction of sulfur into the
2-position of 1,3-disubstituted quaternary imidazolium salts 1–9 (Cl, I, BF4, PF6, CH3OSO3 were
used as anions) to yield nine 1,3-disubstituted imidazoline-2-thiones 10–18 (1, 10: R1 = CH3, R2
= CH3; 2, 11: R1 = OCH2Ph, R2 = CH3; 3, 12: R1 = OCH3, R2 = CH3; 4, 13: R1 = OCH3, R2
= OCH3; 5, 14: R1 = NH2, R2 = CH2Ph; 6, 15: R1 = NCHPh, R2 = CH3; 7, 16: R1 = NH2, R2
= CH3; 8, 17: R1 = NCHPh, R2 = NCHPh; 9, 18: R1 = NH2, R2 = OCH3). Compounds 11–18
represent N-alkyloxy and N-amino imidazoline-2-thiones, whereas 10 served as reference compound.
The first method was advantageous for the conversion 1 → 10 due to faster reaction, whereas in the
reaction 2 → 11 considerable amounts of by-products were formed. Pure thiones 11, 14, 16, 17, and
18 were obtained only by the second method. Both methods worked for the synthesis of the methoxy
derivatives 12 and 13 from 3 and 4, and the benzylideneamino derivative 15 from 6. 1-Amino-3-
methylimidazoline-2-thione (16) was also prepared by hydrolysis of the benzylideneamino derivative
15. Crystal structures of seven 1,3-disubstituted imidazoline-2-thiones were determined by single-
crystal X-ray diffraction. Intermolecular C–H···S contacts were identified and, additionally, N–H···S
interactions in aminothiones 14 and 16. The 1H NMR shifts of 10 and 13 were satisfactorily correlated
with the Kamlet-Abboud-Taft π∗ and β parameters in ten solvents. From the lack of correlation
˚
with the α parameter and from the C=S bond length (average 1.68 A) a significant contribution of
a mesoionic imidazolium-2-thiolate resonance structure seems unlikely.
Key words: Crystal Structure, Hydrogen Bond, Imidazole, Thione
Introduction
for the synthesis of 1,3-dimethylimidazoline-2-thione
[8, 9], bridged bis(imidazoline-2-thiones) [17 – 22],
Imidazole is one of the most important heterocycles, and also for multidentate ligands [23]. Very re-
and the respective imidazoline-2-thiones are valuable cently, mixed-donor bidentate ligands based on car-
intermediates for many purposes, as discussed below. bene and thione functions have been reported [24].
Historically, heterocyclic thiones were obtained by The ‘pyridine/Et3N method’ was successfully em-
cleavage of ‘carbene dimers’ by fused sulfur [1] or sul- ployed for the preparation in high yields of 1-
fur in pyridine solution [2, 3]. Imidazoline-2-thiones benzyloxy-3-methylimidazoline-2-thione [25], 1,3-
were also synthesized by cyclization of linear precur- bis(benzylideneamino)imidazoline-2-thione [26, 27],
sor molecules [4 – 6]. The thione function was most and 1,3-di(benzyloxy)imidazoline-2-thione [28]. Al-
conveniently introduced by reaction of heterocyclic ternative thionations were performed with potassium
quaternary salts with sulfur in MeOH/K2CO3 [7 – 9], thioacetate or thiocyanate as sulfur source using mi-
or MeOH/pyridine/DBU [10, 11]. Recently, the use crowave conditions [29]. Imidazolin-2-ylidenes (car-
of CH2Cl2/Et3N [12] and THF/KOtBu [13] was re- benes) formed by deprotonation of the respective im-
ported. Pyridine is known to be an effective sol- idazolium cations were presumed to be intermedi-
vent for this reaction in the triazole and thiazole se- ates in these reactions. In fact, some imidazoline-2-
ries, often in the presence of triethylamine [14 – 16]. thiones were prepared from isolated carbenes [30],
The popular ‘MeOH/K2CO3 method’ has been used from electrolytically generated carbenes [31], and
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G. Laus et al. · Imidazoline-2-thiones
the imidazolium ion was designated as ‘proto- (10) was studied in more detail. Thionation of 1,3-
carbene’ [32]. Some 1,3-dialkylimidazoline-2-thiones dimethylimidazolium iodide (1a) in MeOH/K2CO3
were reportedly prepared by alkylation of 2-mercapto- is long known, but the reported yields are inexpli-
1-methylimidazole [33] and by thermal isomerization cably modest (58 – 62% after 40 hours at room tem-
of S-alkyl compounds [21].
perature [9]). We found that the reaction stopped at
Typical reactions of these imidazoline-2-thiones in- 60 percent conversion at 20 ◦C in accordance with
clude S-alkylation [34 – 36], addition of halogen [37, the reported yield, but 75 percent conversion was
38], oxidative desulfurization [4, 10, 39, 40], reduc- achieved at 65 ◦C after one hour (increasing only
tion to the carbene [41, 42], and formation of metal slightly to 80% after 20 hours), as judged by 1H NMR.
complexes [43 – 45]. Numerous crystal structures of In pyridine/Et3N, the iodide reacted very slowly (45%
1,3-disubstituted imidazoline-2-thione complexes with conversion after 28 hours at 20 ◦C; 40% after one hour
Al, Mn, Fe, Co, Ni, Cu, Zn, As, Mo, Ru, Rh, Ag, at 65 ◦C). More sulfur or more Et3N did not increase
Cd, In, Sb, Te, W, Re, Ir, Au, Hg, Pb, and Bi were the rate of reaction. We also tried the precursor hexa-
found in the Cambridge Structural Database (ver- fluorophosphate 1b and found that it did not react at
sion 5.33, August 2012). The crystal structure of 1,3- all in pyridine at 20 ◦C (less than 1% after 28 hours)
dimethylimidazoline-2-thione (10) [46, 47] at room and gave only 25% conversion after one hour at 65 ◦C.
temperature is known, but was now re-determined at In MeOH, conversion of 1b was 75% at 20 ◦C after
173 K to get comparable data.
3 days, 80% at 65 ◦C after one hour, where the reac-
In continuation of our studies in azole chem- tion stopped. However, the presence of KPF6 inter-
istry, we report the synthesis of 1,3-disubstituted fered with the crystallization of the thione from wa-
imidazoline-2-thiones containing N-heteroatom sub- ter, thus compromising the yield. Surprisingly, under
stituents (N or O), preferably small ones, which otherwise identical conditions the reaction slowed sig-
have not yet been described although several qua- nificantly when Na2CO3 was used instead of K2CO3
ternary precursor salts are known, and the tools (iodide gave 30%, hexafluorophosphate 15% conver-
for the synthesis of other ones are available. To sion after one hour at 65 ◦C). We confirmed that the use
our knowledge, the first representative of this class of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) inexpli-
of compounds was 1-benzyloxy-3-methylimidazoline- cably resulted in high conversion (90%) only when
2-thione (11) [25], and the second one was 1,3- two equivalents were employed [10]. Triethylamine in
bis(benzylideneamino)imidazoline-2-thione (17) with- MeOH was not effective either. Pure pyridine has been
out spectroscopic data [26]. 1-Methoxy-3-methylimid- observed to allow only slow thionation [28]. Use of
azoline-2-thione (12) was described in a patent [12]. either precipitated (‘lac sulfuris’) or sublimed sulfur
Recently, we reported the first crystal structure of did not make a significant difference. Colloidal sul-
a fourth example, 1,3-di(benzyloxy)imidazoline-2- fur sometimes caused problems during work-up. We
thione [28]. No other crystal structure of these N- observed that in the presence of 10% water (by vol-
heteroatom-substituted thiones has been disclosed ume) the reaction at 65 ◦C stopped at 15% conver-
so far. Here, we report the synthesis of nine 1,3- sion. It has been reported that the introduction of sul-
disubstituted imidazole-2-thiones and crystal struc- fur failed when ethanol or water were used as sol-
tures of three new and four known thiones.
vents [9]. Therefore, we reasoned that small amounts
of water liberated by neutralization of the carbonate
could explain this strange behavior. To our disappoint-
ment, addition of molecular sieves to trap water did
not promote the reaction, but gave lower conversion.
Attempted azeotropic removal of water using tert-
Results and Discussion
Synthetic considerations
Two methods (MeOH/K2CO3 or pyridine/Et3N, butylmethylether did not improve the yield, either. The
Scheme 1) for the transformation of quaternary salts use of the crude methylsulfate 1c unexpectedly but for-
1–9 to the thiones 10–18 were investigated. Dif- tunately resulted in 90% conversion in MeOH at 65 ◦C
ferent precursor salts (chloride, hexafluorophosphate, after one hour, where the reaction again halted (in pyri-
iodide, methylsulfate, tetrafluoroborate) were tested. dine only 40% conversion was obtained). In summary,
The synthesis of 1,3-dimethylimidazoline-2-thione use of methylsulfate as preferred anion, methanol as
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G. Laus et al. · Imidazoline-2-thiones
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cleaved into benzaldehyde and 1-methylimidazoline-
2-thione (Scheme 1), according to 1H and 13C
NMR spectra and mass spectrometry. TLC and
characteristic odor were confirmative. In contrast,
1-methoxy-3-methylimidazolium iodide (3) and
1,3-dimethoxyimidazolium hexafluorophosphate (4)
gave complete conversion after two hours at 65 ◦C in
either pyridine or methanol, yielding the thiones 12
and 13, respectively. 1,3-Dimethoxyimidazolium salts
are known to undergo degradation in alkaline aqueous
solution involving carbene formation and ring open-
ing [49]. It is interesting enough that the desired thione
was formed at all, but surprisingly no degradation
occurred in methanol as judged by the absence of the
tell-tale methyl NMR signals of the degradation prod-
uct. In pyridine again a clean reaction was observed.
On the other hand, the N-amino imidazolium chlo-
rides 5b and 7b did not tolerate the MeOH/K2CO3
conditions. Thus, attempted thionation of 5b gave
a surprising 70% isolated yield of 1-benzylimidazole
(Scheme 1). Deamination was also observed by NMR
in the case of 1-amino-3-methylimidazolium chloride
(7b). In pyridine, the thiones 14 and 16 were readily
obtained in satisfactory yields. 1-Benzylideneamino-
3-methylimidazoline-2-thione (15) was best prepared
from the tetrafluoroborate 6 in pyridine. Although
conversion was also high in MeOH/K2CO3, insoluble
KBF4 complicated work-up. However, we found that,
in this case, Na2CO3 also gave full conversion. This
compound was intended as an alternative approach to
the initially elusive 1-amino-3-methylimidazoline-2-
thione (16). Hydrolysis of 15 in dilute hydrochloric
acid proceeded smoothly at 60 ◦C to compound 16
with a free amino group (Scheme 1), whereas at 100 ◦C
only decomposition was observed. Thus, we ended
up with two synthetic pathways to 16. The previously
Scheme 1. a) 1/ S8, K2CO3/MeOH; b) 1/ S8, Et3N/pyridine;
8
8
c) 130 ◦C; d) HCl/H2O.
preferred solvent, K2CO3 as preferred base, and heat- described
1,3-bis(benzylideneamino)imidazoline-
ing in the absence of water gave the best result for the 2-thione (17) could be prepared only in pyridine.
synthesis of 10. The situation was found to be com- In methanol complete decomposition of the corre-
pletely different, however, for the thionations of other sponding quaternary chloride 8 occurred at room
quaternary salts.
temperature, whereas the thione 17 was stable under
Thus, 1-benzyloxy-3-methylimidazolium hexa- the conditions. No spectroscopic data of 17 have
fluorophosphate (2) gave complete conversion to been reported so far, and they are therefore disclosed
the respective thione 11 in pyridine/Et3N after one here. Preliminary attempts to remove the benzyli-
hour at 65 ◦C, whereas in MeOH/K2CO3 numerous dene groups from 17 (which is insoluble even in
unidentified by-products were encountered. Thermal concentrated hydrochloric acid) were not successful.
N-alkyl/S-alkyl rearrangements of imidazoline-2- Finally, 1-amino-3-methoxyimidazoline-2-thione (18),
thiones have been reported [48]. However, when a mixed N/O-substituted imidazoline-2-thione, was
thione 11 was heated at 130 ◦C, the molecule was prepared by the pyridine method from chloride 9 in
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G. Laus et al. · Imidazoline-2-thiones
˚
Fig. 1. Interatomic distances (A) and angles (deg) in imidazoline-2-thiones.
modest yield. In general, work-up comprised evap- Crystallography
oration of the solvent and extraction of the residue.
In some cases (11, 15 and 17) the products could
be precipitated by addition of water to the reaction various solvents (ranging in polarity from H2O to
mixture. CCl4) or could be purified by sublimation. The crystal-
The imidazoline-2-thiones crystallized readily from
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G. Laus et al. · Imidazoline-2-thiones
1243
Fig. 2 (color online). Interactions in the crystal structures of imidazoline-2-thiones.
lographic data and refinement details are summarized in Fig. 2, and the pertinent parameters are collected in
in Table 1. Interatomic distances and angles in the het- Table 2. Keeping in mind the potential pitfalls [50] of
erocyclic rings are displayed in Fig. 1. The hydrogen using the sum of van-der-Waals radii [51, 52] as the
bonding interactions in the crystal structures are shown threshold for hydrogen bonds and remembering that
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Table 2. Hydrogen interaction ge-
ometries (A, deg).
Compound Interaction H···A
D···A
2.9783(5) 3.923(2)
3.607(2)
D–H···A
Symmetry code (A)
1/2+x, 1/2+y, z
˚
10
11
C3–H···S
162.2(1)
168.9(1)
142.9(1)
166.1(1)
165.4(2)
148(2)
C5–H···O 2.630(1)
x, 1/2−y, 1/2+z
C2–H···S
C5–H···S
C2–H···S
N3–H···S
N3–H···S
C3–H···S
N3–H···S
2.9208(4) 3.723(2)
2.8115(4) 3.771(2)
2.7455(8) 3.673(4)
2.74(2)
2.92(2)
2−x, 1/2+y, 3/2−z
−1/2+x, 1/2−y, 1−z
1/2+x, −y, −1/2+z
1/2+x, y, 3/2−z
12
13
14
3.500(1)
3.645(1)
144(2)
157.6(1)
158(2)
129.46(8) 1/2−x, −1/2+y, z
−1/2+x, y, 3/2−z
1/2−x, 1/2+y, z
2.8014(4) 3.697(2)
2.80(1)
16
17
3.645(1)
3.259(2)
1−x, 1/2+y, 2−z
C3–H···N 2.572(1)
fect agreement. Short CH2···O and CH···S contacts
were observed in 11, CH3···S hydrogen bonds in the
direction of the crystallographic a axis in 12, and
CH···S hydrogen bonds forming zigzag chains in 13.
It is also noteworthy that 1,3-dimethoxyimidazoline-2-
thione 13 adopts the anti conformation (the methoxy
groups are rotated out of the ring plane on oppo-
Scheme 2. Alleged resonance structures of 1,3-disubstituted
imidazoline-2-thiones.
short contacts do not necessarily mean stabilizing in- site sides by 86.2◦ and 86.5◦, respectively) in the
teractions, we report here either hydrogen bonds which solid state. Previously, both syn and anti conformations
are at least 6% shorter than the sum of van-der-Waals have been observed for 1,3-dimethoxyimidazolium
radii or otherwise label them as ‘contacts’. It has been salts [54].
noted, however, that this may be too restrictive a crite-
rion for weak interactions [53].
In the structures of the N-amino-substituted thiones
14, 16 and 17, the C–N–C ring angles at the N atom
The structure of 1,3-dimethylimidazoline-2-thione bearing the amino substituent range from 110.7(2)◦ to
(10) [46, 47] was re-determined at the same tempera- 111.2(1)◦. In 1-amino-3-benzylimidazoline-2-thione
ture as the new compounds to allow comparison of the (14) two chains of intermolecular NH···S interactions
data. This turned out to be a wise decision, because the (one short, one long) propagating in opposite direc-
effect of temperature on the angles in the ring system tions lead to stacking of overlapping rings in the [100]
˚
of this compound obviously is almost as large as the direction, with a centroid–centroid distance of 3.518 A.
effect of the hetero-atom substituents in the other com- The columns are linked by CH···S hydrogen bonds.
pounds. Thus, in the reported structures of 10 at room The molecules of 1-amino-3-methylimidazoline-2-
temperature the C–N–C angles within the ring were thione (16) are parallel to the (010) plane, with an in-
108.4◦ [7] and 109.2◦ [46], whereas at 173 K we found terplanar distance of 3.276 A and connected by two
˚
110.2(2)◦. The other thiones reported here which bear chains of symmetry-related NH···S hydrogen bonds
N-alkyl substituents exhibit C–N–C ring angles from in the [010] direction, but not overlapping (shortest
110.4(1)◦ to 110.7(1)◦. The planar molecules of 10 are centroid–centroid distance 6.797 A). The small methyl
˚
arranged by weak intermolecular CH3···S contacts in groups allow an alternating arrangement of the rings
layers parallel to the (001) plane which are separated on opposite sides of the hydrogen bond ribbon (in con-
˚
by 3.363 A.
trast to the larger benzyl groups in 14 which are ori-
An N-alkyloxy substituent causes widening of ented to the left and right of the ribbon forcing the
the C–N–C ring angle at the N atom bearing the rings to one side). An intermolecular CH···N hydro-
alkyloxy substituent by approximately 3◦. Thus, in gen bond was observed in the crystal structure of the
the structures of the benzyloxy 11, methoxy 12 1,3-bis(benzylideneamino) derivative 17.
and dimethoxy derivative 13, the C–N–C ring an-
The C=S bond lengths in these seven thiones range
gles range from 112.7(1)◦ to 113.2(3)◦. In the from 1.66 to 1.69 A in agreement with the accepted
˚
˚
two independent molecules of the related 1,3- value of 1.68 A in thioureas [55]. Earlier, this C=S
di(benzyloxy)imidazoline-2-thione [28], these angles bond has been considered remarkably long (compared
are between 112.7(3)◦ and 113.5(2)◦, which is in per- with 1.60 A in a trithiocarbonate as an ill-chosen
˚
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G. Laus et al. · Imidazoline-2-thiones
mon NMR solvents covering a wide range of these pa-
rameters. The parameters for non-deuterated solvents
from a recent compilation [62] were applied to unravel
the individual contributions of the terms in the linear
solvation energy relationship (LSER) [57] by multiple
regression analysis:
δ(1H) = δ0 +sπ∗ +aα +bβ
From the data the following equations were derived
(standard errors of δ0, s, and b, correlation coefficient
r, relative standard deviation σ of the correlation, and
number N of data points given).
For 10: δ(1H) = (6.462±0.077)
+(0.252±0.120)π∗ +(0.559±0.106)β
(r = 0.95, rel. σ = 0.97%, N = 10)
For 13: δ(1H) = (6.467±0.099)
Fig. 3. Correlation of calculated and observed 1H NMR
shifts of 1,3-dimethylimidazoline-2-thione 10 (•) and
1,3-dimethoxyimidazoline-2-thione 13 (◦) in different
solvents: (1) CCl4, (2) CDCl3, (3) CD2Cl2, (4) CD3CN,
(5) [D6]acetone, (6) [D8]THF, (7) CD3OD, (8) D2O, (9)
[D7]DMF, (10) [D6]DMSO.
+(0.375±0.154)π∗ +(0.835±0.135)β
(r = 0.96, rel. σ = 1.21%, N = 10)
Both the standard deviations and correlation coef-
ficients are satisfactory. It was to be expected that
a thiolate would be affected by the hydrogen bond do-
nating strength of the solvents. However, the influ-
ence of the α term was found to be negligible. In-
terestingly, the β term is predominant, and the re-
sulting correlation of calculated vs. observed values
is shown in Fig. 3. The dimethoxy compound 13 dis-
played higher sensitivity than the dimethyl compound
10. Obviously, here the C–H···solvent interactions
dominate, which sort of validates the C–H···S contacts
observed in the crystal structures. In contrast, the α
term constituted the major contribution to the observed
solvatochromism of an unquestionable tetrazolium-5-
thiolate [63]. Thus, there is no evidence of involve-
ment of a mesoionic imidazolium-2-thiolate resonance
structure here (Scheme 2).
reference compound), and thus believed to indicate
a contribution of the mesoionic imidazolium-2-thiolate
(Scheme 2) [7, 46]. This point keeps getting reiter-
ated in the literature [38, 56]. However, a research in
the Cambridge Structural Database resulted in a mean
˚
value of 1.68 ± 0.02 A for imidazolinethiones (101
structures, no metal coordination, R ≤ 0.05) and 1.67±
˚
0.07 A for compounds containing a propanethione
fragment (105 structures, no metal coordination, R ≤
0.05). Thus, there is no evidence for an elongated C=S
bond in imidazoline-2-thiones.
1H NMR spectroscopy
The 1H NMR signals of the thione ring protons are
shifted upfield from those of the quaternary precur-
sor salts by 0.5 – 0.8 ppm, which may be attributed to
the loss of cationic character. It is noteworthy that 1H
Conclusion
The synthesis of fundamental 1,3-disubstituted
NMR shifts of the thiones depend quite significantly on imidazoline-2-thiones was investigated. The choice of
the solvent. It seemed to be of interest to analyze this method depended on the nature of the N-substituent
behavior in terms of the Kamlet-Abboud-Taft param- (C, O, or N), and work-up was adapted according to
eters [57] of solvent properties, i. e. (hydrogen bond solubility and impurities. Thus, no general method is
donor) acidity α [58], (hydrogen bond acceptor) ba- available. These thiones are valuable building blocks
sicity β [59], and dipolarity/polarizability π* [60, 61]. for other 2-substituted imidazolium systems and lig-
Thus, spectra of 10 and 13 were recorded in ten com- ands on their own. The bifunctional amino-thione
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compounds offer access to new heterocyclic systems. 747 m, 617 s, 585 s cm−1. – HRMS (FAB): m/z = 113.0662
(calcd. 113.0709 for C5H9N2O, [M]+).
Clearly, significant progress has been made in the
thriving field of imidazole chemistry, adding new in-
sights into an already flourishing area of heterocyclic
chemistry. Reactions of the new thiones will be com-
municated in due course.
1-Amino-3-benzylimidazolium 2,4-dinitrophenolate (5a)
A solution of 1-benzylimidazole (1.00 g, 6.3 mmol) and
DNPH (1.26 g, 1.0 equiv.) in CH2Cl2 (10 mL) was stirred for
20 h at 20 ◦C. The product was filtered off, washed with Et2O
(10 mL), and dried. Yield: 1.71 g (76%). M. p. 116 – 117 ◦C.
Experimental Section
– 1H NMR (300 MHz, [D6]DMSO): δ = 5.36 (s, 2H), 6.34
(d, J = 9.7 Hz, 1H), 6.9 (br, 2H), 7.40 (s, 5H), 7.65 (t, J =
1.8 Hz, 1H), 7.73 (t, J = 1.8 Hz, 1H), 7.79 (dd, J = 3.2 Hz,
J = 9.8 Hz, 1H), 8.59 (d, J = 3.2 Hz, 1H), 9.30 (t, J = 1.4 Hz,
1H) ppm. – 13C NMR (75 MHz, [D6]DMSO): δ = 52.1,
121.0, 124.2, 124.9, 126.3, 127.5, 127.6, 128.2 (2C), 128.7,
129.0 (2C), 135.0, 135.4, 136.0, 169.9 ppm. – IR (neat):
ν = 3103 w, 3057 w, 1598 m, 1551 m, 1529 m, 1466 m,
1430 m, 1373 w, 1317 s, 1260 s, 1127 s, 1053 m, 910 w, 830
m, 751 m, 715 m, 694 s, 661 s, 617 s cm−1. – HRMS (FAB):
m/z = 174.1029 (calcd. 174.1026 for C10H12N3, [M]+).
NMR spectra were recorded with a Bruker Avance DPX
300 spectrometer. IR spectra were obtained with a Nico-
let 5700 FT instrument. High-resolution mass spectra were
measured with a Finnigan MAT 95 mass spectrometer. Ele-
mental analyses were conducted at the University of Vienna,
Austria.
1-Benzylimidazole and 1-methylimidazole were
purchased from Aldrich, sulfur from Merck, and
used as received. O-(2,4-Dinitrophenyl)hydroxylamine
(DNPH) was freshly prepared according to the pub-
lished procedure [64] and used within one week.
1-(Benzylideneamino)imidazole was obtained by the
literature method [65]. 1-Methoxyimidazole and 1-
methoxyimidazolium hexafluorophosphate were synthesized
by catalytic hydrogenation of 1,3-dimethoxyimidazolium
hexafluorophosphate [54]. The quaternary precursor salts
1,3-dimethylimidazolium iodide (1a) [9, 30, 66] or hexa-
fluorophosphate (1b) [67 – 69] or methylsulfate (1c) [69],
1-Amino-3-benzylimidazolium chloride (5b)
A suspension of 5a (1.60 g, 4.5 mmol) in 1 M HCl
(45 mL) was stirred at 80 ◦C for 1 h. The mixture was fil-
tered, the solids were well washed with hot 1 M HCl (2 ×
10 mL) and H2O (10 mL). The cold filtrate was extracted
with Et2O (10 mL) and taken to dryness under reduced
pressure. The resulting oil crystallized upon treatment with
CH2Cl2 to give a colorless powder. Yield: 0.90 g (96%).
M. p. 150 – 152 ◦C. – 1H NMR (300 MHz, [D6]DMSO): δ =
5.2 (br, 2H), 5.43 (s, 2H), 7.37 – 7.44 (m, 5H), 7.67 (t, J =
1.7 Hz, 1H), 7.79 (t, J = 1.7 Hz, 1H), 9.50 (t, J = 1.4 Hz, 1H)
ppm. – 13C NMR (75 MHz, [D6]DMSO): δ = 51.8, 120.9,
124.0, 128.3 (2C), 128.7, 129.0 (2C), 135.1, 135.2 ppm. – IR
(neat): ν = 3185 w, 3085 m, 3004 m, 1656 w, 1553 m, 1455
w, 1311 w, 1209 w, 1163 m, 1069 m, 892 w, 778 w, 733 m,
712 s, 696 s, 667 m, 624 m, 615 m cm−1. – HRMS (FAB):
m/z = 174.1051 (calcd. 174.1026 for C10H12N3, [M]+).
1-benzyloxy-3-methylimidazolium
hexafluorophosphate
(2) [70], 1,3-dimethoxyimidazolium hexafluorophosphate
(4) [54], and 1,3-bis(benzylideneamino)imidazolium
chloride (8) [27] were synthesized as described. No spec-
troscopic data of 8 have been disclosed so far, and they
are therefore given here. 1-Amino-3-methylimidazolium
2,4,6-trimethylbenzenesulfonate [71] is known, but we
preferred the respective 2,4-dinitrophenolate (DNP) 7a and
the ensuing chloride 7b, because DNPH is an extremely
powerful, easy-to-prepare, and relatively inexpensive
aminating agent, and the DNP is readily converted to the
corresponding chloride.
1-Benzylideneamino-3-methylimidazolium tetrafluoroborate
(6)
1-Methoxy-3-methylimidazolium iodide (3)
To a solution of 1-(benzylideneamino)imidazole (1.71 g,
A solution of 1-methoxyimidazole (0.44 g, 4.5 mmol) and 10 mmol) in anhydrous CH2Cl2 (17 mL) Me3O BF4 (1.55 g,
methyl iodide (0.40 mL, 1.43 equiv.) in CH2Cl2 (5 mL) was 1.05 equiv.) was added. The mixture was stirred under argon
stirred for 4 days at 20 ◦C. The solvent was evaporated, and for 24 h at 20 ◦C. The colorless product was collected by fil-
the oily residue was repeatedly treated with Et2O until it tration, washed with Et2O, and dried under reduced pressure.
solidified to give a hygroscopic, tan powder. Yield: 0.79 g Yield: 2.04 g (75%). M. p. 108 ◦C. – 1H NMR (300 MHz,
(73%). M. p. 72 ◦C. – 1H NMR (300 MHz, [D6]DMSO): [D6]DMSO): δ = 3.91 (s, 3H), 7.58 – 7.69 (m, 3H), 7.89
δ = 3.84 (s, 3H), 4.22 (s, 3H), 7.75 (t, J = 1.9 Hz, 1H), (s, 2H), 7.92 (s, 1H), 8.45 (s, 1H), 9.16 (s, 1H), 9.68 (s,
8.22 (t, J = 1.9 Hz, 1H), 9.65 (unresolved t, 1H) ppm. – 13
C
1H) ppm. – 13C NMR (75 MHz, [D6]DMSO): δ = 36.3,
NMR (75 MHz, [D6]DMSO): δ = 36.6, 69.5, 118.4, 121.6, 115.7, 123.4, 129.0 (2C), 129.4 (2C), 131.0, 133.3, 135.2,
132.9 ppm. – IR (neat): ν = 3123 w, 3093 w, 2940 w, 3057 161.4 ppm. – IR (neat): ν = 3161 w, 3111 w, 1584 w, 1552
m, 1568 w, 1327 m, 1152 m, 1023 m, 1011 m, 946 s, 823 m, m, 1451 w, 1226 w, 1035 s, 970 m, 853 m, 739 m, 692 m, 618
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G. Laus et al. · Imidazoline-2-thiones
m cm−1. – HRMS (FAB): m/z = 186.1026 (calcd. 186.1026 1-Amino-3-methoxyimidazolium 2,4-dinitrophenolate (9a)
for C11H12N3, [M]+).
A solution of 1-methoxyimidazolium hexafluorophos-
phate (1.0 g, 4.1 mmol) in H2O (4 mL) was treated with
1-Amino-3-methylimidazolium 2,4-dinitrophenolate (7a)
NaHCO3 (0.35 g) and extracted with CH2Cl2 (2 × 10 mL).
A solution of 1-methylimidazole (2.00 g, 24 mmol) and
The solution was dried over MgSO4 and reduced to half its
volume. DNPH (0.86 g, 4.3 mmol) was added, and the mix-
ture was stirred for 24 h at 20 ◦C. On cooling to –30 ◦C
the product precipitated and was filtered off, washed with
Et2O (3 × 5 mL), and dried. Yield: 0.56 g (46%). M. p.
77 ◦C. – 1H NMR (300 MHz, [D6]DMSO): δ = 4.08 (s,
3H), 6.97 (d, J = 9.4 Hz, 1H), 7.02 (s, 1H), 7.65 (s, 1H),
8.17 (dd, J = 2.9 Hz, J = 9.5 Hz, 1H), 8.28 (s, 1H), 8.66 (d,
J = 2.9 Hz, 1H) ppm. – 13C NMR (75 MHz, [D6]DMSO):
δ = 68.4, 116.0, 121.9, 122.9, 123.5, 128.8, 131.1, 134.7,
136.4, 161.7 ppm. – IR (neat): ν = 3138 w, 1599 m, 1571
m, 1525 m, 1427 m, 1324 s, 1258 s, 952 s, 820 s, 608 s
cm−1. – HRMS (FAB): m/z = 114.0671 (calcd. 114.0662
for C4H8N3O, [M]+).
DNPH (5.09 g, 1.05 equiv.) in CH2Cl2 (40 mL) was stirred
for 24 h at 20 ◦C. The product was filtered off, washed with
Et2O (2 × 10 mL), and dried. Yield: 4.75 g (69%). M. p.
108 – 109 ◦C. – 1H NMR (300 MHz, [D6]DMSO): δ = 3.81
(s, 3H), 6.33 (d, J = 9.7 Hz, 1H), 6.9 (br s, 2H), 7.61 (s, 2H),
7.78 (dd, J = 3.2 Hz, J = 9.7 Hz, 1H), 8.59 (d, J = 3.1 Hz,
1H), 9.07 (s, 1H) ppm. – 13C NMR (75 MHz, [D6]DMSO):
δ = 35.9, 122.2, 123.6, 125.0, 126.5, 127.5, 135.8, 136.1,
170.3 ppm. – IR (neat): ν = 3243 w, 3135 w, 3079 w, 1596
m, 1557 m, 1536 m, 1483 w, 1466 w, 1435 w, 1376 w, 1316
s, 1246 s, 1178 s, 1127 s, 1047 m, 918 m, 851 m, 830 s, 747
s, 624 s cm−1. – C10H11N5O5 (281.22): calcd. C 42.71, H
3.94, N 24.90; found C 42.78, H 3.77, N 24.52. – HRMS
(FAB): m/z = 98.0879 (calcd. 98.0713 for C4H8N3, [M]+).
1-Amino-3-methylimidazolium chloride (7b)
1-Amino-3-methoxyimidazolium chloride (9b)
A suspension of 7a (3.00 g, 11 mmol) in 1 M HCl (90 mL)
was stirred at 80 ◦C for 1 h. The mixture was filtered, the
solids were well washed with hot 1 M HCl (2 × 20 mL) and
H2O (20 mL), and the filtrate was taken to dryness under re-
duced pressure. The resulting oil crystallized on cooling and
was washed with Et2O (2 × 10 mL). Yield: 1.33 g (93%).
M. p. 120 – 122 ◦C. – 1H NMR (300 MHz, [D6]DMSO): δ =
3.82 (s, 3H), 5.1 (br s, 2H), 7.63 (s, 1H), 7.64 (s, 1H), 9.19
(s, 1H) ppm. – 13C NMR (75 MHz, [D6]DMSO): δ = 35.8,
122.0, 123.5, 135.5 ppm. – IR (neat): ν = 3132 m, 3042 s,
3004 m, 2943 w, 1655 w, 1564 m, 1365 w, 1295 w, 1182 s,
1066 m, 1005 m, 841 m, 766 s, 617 s cm−1. – HRMS (FAB):
m/z = 98.0878 (calcd. 98.0713 for C4H8N3, [M]+).
A suspension of 9a (0.48 g, 1.6 mmol) in 1 M HCl
(20 mL) was stirred at 80 ◦C for 1 h. The mixture was fil-
tered, the solids were well washed with hot 1 M HCl (2 ×
5 mL) and H2O (5 mL). The cold filtrate was extracted with
Et2O (2 × 2 mL) and taken to dryness under reduced pres-
sure to give 0.24 g (99%) 9b as an oil. 1H NMR (300 MHz,
[D6]DMSO): δ = 4.24 (s, 3H), 7.70 (s, 1H), 8.22 (s, 1H),
9.67 (s, 1H) ppm. – 13C NMR (75 MHz, [D6]DMSO): δ =
69.2, 118.0, 118.1, 131.2 ppm. – IR (neat): ν = 3072 m, 3017
m, 2942 m, 2786 m, 2701 m, 2599 m, 1568 m, 1445 m, 1011
s, 950 s, 842 s cm−1
.
1,3-Dimethylimidazoline-2-thione (10)
1,3-Bis(benzylideneamino)imidazolium chloride (8)
A solution of 1,3-diaminoimidazolium chloride (1.0 g,
A mixture of 1c (1.0 g, 4.8 mmol), sulfur (160 mg, 1.04
7.4 mmol) in MeOH (20 mL) was treated with benzaldehyde equiv.), and K2CO3 (0.80 g, 1.2 equiv.) in MeOH (8 mL) was
(1.66 g, 2.1 equiv.) and concentrated HCl (1 drop) and stirred refluxed for 3 h. After removal of the solvent, the residue
at room temperature for 3 days. The solvent was removed, was recrystallized from boiling H2O (ca. 10 mL necessary
and the residue was stirred with H2O (20 mL) and Et2O to obtain a clear solution). The colorless product was fil-
(20 mL) for 10 min. The product was collected by filtration, tered, washed with H2O (1 mL), and dried under reduced
washed with H2O and Et2O, and dried to give 0.83 g (36%) pressure to yield 0.55 g (89%). Single crystals from hot wa-
of a tan powder. M. p. 177 ◦C (lit. 193 – 196 ◦C [27]). – ter. M. p. 183 ◦C (lit. 178 – 180 ◦C [8], 182 – 183.5 ◦C [9],
1H NMR (300 MHz, [D6]DMSO): δ = 7.59 – 7.68 (m, 6H), 182 – 183.8 ◦C [29]). – 1H NMR (300 MHz, [D6]DMSO):
7.95 – 7.97 (m, 4H), 8.82 (s, 2H), 9.50 (s, 2H), 10.63 (s, 1H) δ = 3.44 (s, 6H), 7.08 (s, 2H) ppm. – 13C NMR (75 MHz,
ppm. – 13C NMR (75 MHz, [D6]DMSO): δ = 116.7 (2C), [D6]DMSO): δ = 34.5 (2C), 118.1 (2C), 161.8 ppm. – IR
129.2 (4C), 129.5 (4C), 131.0 (2C), 132.0, 133.5 (2C), 162.3 (neat): ν = 3113 w, 1573 w, 1492 w, 1464 w, 1436 w,
(2C) ppm. – IR (neat): ν = 1615 m, 1599 m, 1574 m, 1538 1387 m, 1238 m, 1180 m, 1085 w, 749 m, 730 s, 661 s
m, 1487 m, 1227 m, 1128 m, 760 s, 689 s cm−1. – HRMS cm−1. – HRMS (FAB): m/z = 128.0437 (calcd. 128.0403 for
(FAB): m/z = 275.1280 (calcd. 275.1291 for C17H15N4, C5H8N2S, [M+]), 129.0497 (calcd. 129.0481 for C5H9N2S,
[M]+).
[M + H]+).
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1249
1-Benzyloxy-3-methylimidazoline-2-thione (11)
was stirred at 70 ◦C for 2 h. The solvent was evaporated un-
der reduced pressure, and the residue was extracted with
EtOAc (4 × 5 mL). The extract was washed with 1 M HCl
(2 × 5 mL) and passed through a SiO2 column to remove
a brown impurity. Removal of the solvent yielded 0.32 g
(55%) of a tan solid. Single crystals were obtained by cool-
ing a hot CCl4 solution to –20 ◦C. M. p. 96 – 98 ◦C. – 1H
NMR (300 MHz, [D6]DMSO): δ = 3.98 (s, 6H), 7.45 (s, 2H)
ppm. – 13C NMR (75 MHz, [D6]DMSO): δ = 64.9 (2C),
112.0 (2C), 153.1 ppm. – IR (neat): ν = 3126 w, 3098 w,
3065 w, 2992 w, 2937 w, 1545 w, 1448 m, 1396 s, 1117
m, 1011 s, 936 s, 741 m, 715 s, 646 s, 592 m, 537 s
cm−1. – HRMS (EI): m/z = 160.0244 (calcd. 160.0301 for
C5H8N2O2S, [M]+).
A mixture of 2 (1.0 g, 3.0 mmol), sulfur (96 mg, 1.0
equiv.), and Et3N (0.41 ml, 1.0 equiv.) in pyridine (5 mL) was
stirred at 70 ◦C (bath temperature) for 2 h. After addition of
H2O (50 mL) the mixture was heated until a clear solution
was obtained, filtered to remove a small amount of a brown
oil, and allowed to cool to 20 ◦C. The colorless needles were
collected by filtration, washed with H2O, and dried. Yield:
0.57 g (86%). Single crystals from acetone/H2O at ambient
temperature. M. p. 120 – 121 ◦C (dec.; lit. 121 – 122 ◦C [25]).
– 1H NMR (300 MHz, [D6]DMSO): δ = 3.45 (s, 3H), 5.26
(s, 2H), 7.04 (d, J = 2.5 Hz, 1H), 7.23 (d, J = 2.5 Hz, 1H),
7.41 (m, 3H), 7.51 (m, 2H) ppm. – 13C NMR (75 MHz,
[D6]DMSO): δ = 34.4, 78.0, 114.9, 115.4, 128.5 (2C),
129.1, 129.8 (2C), 133.7, 157.3 ppm. – IR (neat): ν = 3150
w, 3122 w, 3090 w, 1560 w, 1455 m, 1409 m, 1390 m, 1324
m, 1215 m, 1139 m, 1079 m, 1040 m, 999 w, 946 m, 907 m,
846 m, 821 m, 776 w, 742 s, 696 m, 673 s, 647 m, 592 m, 572
m cm−1. – HRMS (FAB): m/z = 221.0792 (calcd. 221.0743
for C11H13N2OS, [M + H]+).
1-Amino-3-benzylimidazoline-2-thione (14)
A mixture of 5b (0.21 g, 1.0 mmol), sulfur (34 mg, 1.05
equiv.), and Et3N (0.14 ml, 1.0 equiv.) in pyridine (2 mL)
was stirred at 90 ◦C for 4 h. After addition of cold H2O
(15 mL) the mixture was extracted with EtOAc (2 × 15 mL).
The extract was washed with 1 M HCl (2 × 10 mL) and taken
to dryness. The oily residue yielded seed crystals overnight
which were secured. The oil was heated in H2O (3 mL), and
MeOH (ca. 0.5 mL) was added until a clear solution was ob-
tained which was allowed to cool to 20 ◦C. Addition of a seed
crystal produced a precipitate which was filtered off, washed
with H2O (3 mL), and recrystallized from hot MeOH (2 mL).
Yield: 0.11 g (54%). Single crystals from hot MeOH. M. p.
105 – 106 ◦C. – 1H NMR (300 MHz, [D6]DMSO): δ = 5.17
(s, 2H), 5.4 (br, 2H), 7.09 (s, 1H, 7.13 (s, 1H), 7.31 (s, 5H)
ppm. – 13C NMR (75 MHz, [D6]DMSO): δ = 50.2, 115.0,
118.4, 127.6, 127.8 (2C), 128.5 (2C), 136.9, 160.1 ppm. –
IR (neat): ν = 3281 w, 3165 w, 3123 w, 3087 w, 3061 w,
2938 w, 1613 w, 1563 w, 1494 w, 1446 m, 1406 s, 1338 m,
1233 s, 1180 m, 1126 m, 965 m, 936 m, 817 w, 737 s, 702
s, 675 s, 651 s, 605 m, 575 m, 532 s cm−1. – HRMS (EI):
m/z = 205.0649 (calcd. 205.0668 for C10H11N3S, [M]+).
1-Methoxy-3-methylimidazoline-2-thione (12)
A mixture of 3 (300 mg, 1.25 mmol), sulfur (40 mg, 1.0
equiv.), and Et3N (0.26 mL, 1.5 equiv.) in pyridine (1.5 mL)
was stirred at 70 ◦C for 2 h. The solvent was evaporated un-
der reduced pressure, and the residue was extracted with
EtOAc (3 × 3 mL). The extract was washed with 1 M HCl
(3 × 1 mL) and filtered through a short SiO2 column to re-
move a brown impurity. The filtrate was taken to dryness
to yield 100 mg (55%) of an off-white powder. The prod-
uct was crystallized by slow evaporation of a solution in
Et2O at 20 ◦C. M. p. 55 ◦C (lit. 57 ◦C [12]). – 1H NMR
(300 MHz, [D6]DMSO): δ = 3.44 (s, 3H), 3.96 (s, 3H), 7.09
(d, J = 2.6 Hz, 1H), 7.44 (d, J = 2.6 Hz, 1H) ppm. – 13C
NMR (75 MHz, [D6]DMSO): δ = 34.3, 64.4, 113.8, 115.7,
157.1 ppm. – IR (neat): ν = 2934 w, 1549 m, 1413 s, 1390 s,
1331 m, 1261 m, 1148 m, 1084 m, 1040 m, 1019 m, 803 m
cm−1. – HRMS (EI): m/z = 144.0387 (calcd. 144.0352 for
C5H8N2OS, [M]+).
1-Benzylideneamino-3-methylimidazoline-2-thione (15)
a) A mixture of 6 (1.0 g, 3.7 mmol), sulfur (118 mg, 1.0
equiv.), and K2CO3 (0.61 g, 1.2 equiv.) in MeOH (10 mL)
was stirred at 70 ◦C for 2 h. Addition of H2O (20 mL) gave an
1,3-Dimethoxyimidazoline-2-thione (13)
a) A mixture of 4 (1.0 g, 3.6 mmol), sulfur (117 mg, 1.0 off-white precipitate which was collected by filtration. A sus-
equiv.), and K2CO3 (0.61 g, 1.2 equiv.) in MeOH (6 mL) was pension of this crude product in H2O (100 mL) was stirred
stirred at 70 ◦C for 2 h. The solids were filtered off and rinsed for 2 h at room temperature to remove inorganic salts. The
with MeOH (2 × 2 mL). The filtrate was taken to dryness product was filtered off and dried to yield 0.51 g (64%) of
under reduced pressure. The residue was mixed with H2O a yellow powder.
(5 mL) and extracted with CH2Cl2 (4 × 5 mL). The extract
was dried over MgSO4 and the solvent evaporated to give equiv.), and Et3N (0.51 ml, 1.0 equiv.) in pyridine (5 mL) was
0.29 g (50%) of a tan oil which solidified.
stirred at 80 ◦C for 2 h. Cold H2O (15 mL) was added, and
b) A mixture of 6 (1.0 g, 3.7 mmol), sulfur (118 mg, 1.0
b) A mixture of 4 (1.0 g, 3.6 mmol), sulfur (117 mg, 1.0 stirring was continued for 2 h. The yellow precipitate was
equiv.), and Et3N (0.53 mL, 1.05 equiv.) in pyridine (5 mL) filtered off, washed with H2O (5 mL), and dried. The crude
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G. Laus et al. · Imidazoline-2-thiones
product was heated in MeOH (6 mL), and acetone (12 mL) (79%). Single crystals by slow evaporation of a solution in
was added to give an almost clear solution which was filtered acetone/MeOH. M. p. 214 – 216 ◦C (lit. 215 – 218 ◦C [27]).
and set aside overnight at 20 ◦C. The crystals were collected
–
1H NMR (300 MHz, [D6]DMSO): δ = 7.56 (m, 6H),
by filtration and dried. Yield: 0.60 g (75%). M. p. 184 ◦C. 7.88 (m, 4H), 7.99 (s, 2H), 9.11 (s, 2H) ppm. – 13C NMR
– 1H NMR (300 MHz, [D6]DMSO): δ = 3.51 (s, 3H), 7.33 (75 MHz, [D6]DMSO): δ = 112.5 (2C), 128.3 (4C), 129.1
(s, 1H), 7.52 (m, 3H), 7.77 (s, 1H), 7.85 (m, 2H), 9.04 (s, (4C), 131.8 (2C), 132.9 (2C), 155.6 (2C), 159.3 ppm. –
1H) ppm. – 13C NMR (75 MHz, [D6]DMSO): δ = 34.5, IR (neat): ν = 3174 w, 3145 w, 3043 w, 1599 w, 1568
111.4, 118.9, 128.1 (2C), 129.0 (2C), 131.5, 133.0, 154.4, w, 1449 w, 1408 m, 1394 m, 1352 s, 1279 m, 1195 m,
160.8 ppm. – IR (neat): ν = 3158 w, 3116 w, 3103 w, 1448 1172 m, 1125 m, 946 m, 883 m, 756 s, 691 s, 670 m, 636
w, 1411 m, 1390 w, 1367 m, 1277 w, 1225 m, 1143 m, 958 w, m, 564 m cm−1. – HRMS (FAB): m/z = 306.0950 (calcd.
878 w, 764 s, 690 s, 657 s, 586 m, 551 m cm−1. – C11H11N3S 306.0934 for C17H14N4S, [M]+, 307.1005 (calcd. 307.1012
(217.29): calcd. C 60.80, H 5.10, N 19.34; found C 60.62, for C17H15N4S, [M + H]+).
H 5.02, N 19.11. – HRMS (FAB): m/z = 218.0781 (calcd.
218.0746 for C11H12N3S, [M + H]+).
1-Amino-3-methoxyimidazoline-2-thione (18)
A mixture of 9b (0.20 g, 1.3 mmol), sulfur (45 mg, 1.05
1-Amino-3-methylimidazoline-2-thione (16)
equiv.), and Et3N (0.28 ml, 1.5 equiv.) in pyridine (1.5 mL)
a) A mixture of 7b (200 mg, 1.5 mmol), sulfur (50 mg, was stirred at 80 ◦C for 2 h. The volatiles were removed
1.05 equiv.), and Et3N (0.42 ml, 2.0 equiv.) in pyridine under reduced pressure, and the residue was extracted with
(2 mL) was stirred at 80 ◦C for 6 h. The volatiles were re- EtOAc (3 × 3 mL). The extracts were washed with 1 M HCl
moved under reduced pressure, and the residue was ex- (2 × 2 mL) and H2O (2 mL), filtered through a short SiO2
tracted with EtOAc (5 × 3 mL). The extracts were washed column, and taken to dryness to yield 37 mg (19%) of
with 1 M HCl (2 × 2 mL), dried over MgSO4, and taken an amber powder. M. p. 120 ◦C. – 1H NMR (300 MHz,
to dryness. Crystals of 16 were obtained by sublimation at [D6]DMSO): δ = 3.97 (s, 3H), 5.7 (br, 2H), 7.09 (d, J =
130 ◦C/30 mbar. Yield: 106 mg (55%).
2.7 Hz, 1H), 7.37 (d, J = 2.7 Hz, 1H) ppm. – 13C NMR
b) A suspension of 15 (100 mg, 0.5 mmol) in 1 M HCl (75 MHz, [D6]DMSO): δ = 64.5, 111.8, 115.7, 155.8 ppm.
(10 mL) was stirred overnight at 60 ◦C in an open vessel – IR (neat): ν = 3140 w, 2935 w, 1596 m, 1398 m, 1329
for azeotropic removal of benzaldehyde. The resulting col- m, 1204 m, 1132 m, 840 s, 681 m cm−1. – HRMS (FAB):
orless solution was extracted with EtOAc (5 × 3 mL), and m/z = 145.0286 (calcd. 145.0304 for C4H7N3OS, [M]+),
the solvent was evaporated to yield 42 mg (71%) of a col- 146.0348 (calcd. 146.0383 for C4H8N3OS, [M + H]+).
orless powder. Crystals of 16 were obtained by slow cool-
ing of a hot solution in EtOAc to 20 ◦C. M. p. 157 ◦C. – 1H
Crystal structure determination
NMR (300 MHz, [D6]DMSO): δ = 3.46 (s, 3H), 5.3 (br, 2H),
The crystal structures were determined using an Oxford
7.03 (d, J = 2.3 Hz, 1H), 7.10 (d, J = 2.3 Hz, 1H) ppm. –
Diffraction Gemini-R Ultra diffractometer. X-Ray diffraction
13C NMR (75 MHz, [D6]DMSO): δ = 34.7, 115.8, 117.7,
˚
data were collected with MoKα (λ = 0.7107 A) or CuKα
159.8 ppm. – IR (neat): ν = 3266 w, 3162 w, 3143 w, 3088
˚
radiation (λ = 1.5418 A) at 173 K. Absorption corrections
m, 1458 m, 1422 w, 1383 m, 1357 m, 1230 m, 1154 m, 921
were applied in all cases (multi-scan). The structures were
m, 747 m, 660 m, 521 s, 500 m cm−1. – HRMS (FAB):
solved by Direct Methods and refined by full-matrix least-
m/z = 130.0420 (calcd. 130.0433 for C4H8N3S, [M + H]+).
squares techniques with the programs SIR2002 [72] and
SHELXL-97 [73], respectively. All non-hydrogen atoms were
assigned anisotropic displacement parameters in the refine-
1,3-Bis(benzylideneamino)imidazoline-2-thione (17)
A suspension of 8 (0.40 g, 1.3 mmol) and sulfur (41 mg, ment.
1.0 equiv.) in pyridine (4 mL) containing Et3N (0.18 mL, 1.0
CCDC 919557–919563 contain the supplementary crys-
equiv.) was stirred at room temperature for 2 days. Then tallographic data for this paper. These data can be obtained
H2O (10 mL) was added, and the precipitate was filtered free of charge from The Cambridge Crystallographic Data
off, washed with H2O (2 × 2 mL), and dried. Yield: 0.31 g Centre via www.ccdc.cam.ac.uk/data request/cif.
[1] A. Scho¨nberg, A. Rosenbach, H. Krull, U. Ostwald,
Chem. Ber. 1925, 58, 1793 – 1801.
[2] H. W. Wanzlick, B. Ko¨nig, Chem. Ber. 1964, 97,
3513 – 3516.
[3] H. W. Wanzlick, H.-J. Kleiner, I. Lasch, H. U. Fu¨ld-
ner, H. Steinmaus, Liebigs Ann. Chem. 1967, 708,
155 – 169.
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1251
[4] D. M. Wolfe, P. R. Schreiner, Eur. J. Org. Chem. 2007, [29] X.-L. Tao, M. Lei, Y.-G. Wang, Synth. Commun. 2007,
2825 – 2838. 37, 399 – 408.
[5] R.-S. Zeng, J.-P. Zou, S.-J. Zhi, J. Chen, Q. Shen, Org. [30] W. A. Herrmann, C. Ko¨cher, L. J. Gooßen, G. R. J. Ar-
Lett. 2003, 5, 1657 – 1659. tus, Chem. Eur. J. 1996, 2, 1627 – 1636.
[6] H.-J. Scho¨nherr, H.-W. Wanzlick, Chem. Ber. 1970, [31] M. Feroci, M. Orsini, A. Inesi, Adv. Synth. Catal. 2009,
103, 1037 – 1046. 351, 2067 – 2070.
[7] G. B. Ansell, D. M. Forkey, D. W. Moore, Chem. Com- [32] H. Rodriguez, G. Gurau, J. D. Holbrey, R. D. Rogers,
mun. 1970, 56 – 57. Chem. Commun. 2011, 47, 3222 – 3224.
[8] G. Roy, D. Das, G. Mugesh, Inorg. Chim. Acta 2007, [33] Q. Liu, D. Shi, K. Yu, J. Xu, Acta Crystallogr. 2003,
360, 303 – 316. E59, o356–o357.
[9] B. L. Benac, E. M. Burgess, A. J. Arduengo, Org. [34] D. J. Williams, T. A. Ly, J. W. Mudge, D. VanDerveer,
Synth. 1986, 64, 92 – 94. R. L. Jones, Inorg. Chim. Acta 1994, 218, 133 – 138.
[10] D. W. Karkhanis, L. Field, Phosphorus Sulfur 1985, 22, [35] J. Kister, G. Assef, G. Mille, J. Metzger, Can. J. Chem.
49 – 57. 1979, 57, 813 – 821.
[11] C. Williamson, J. M. D. Storey, W. T. A. Harrison, J. [36] E. M. Burgess, M. C. Pulcrano, J. Am. Chem. Soc.
Chem. Crystallogr. 2006, 36, 277 – 282. 1978, 100, 6538 – 6539.
[12] I. Suzuki, I. Erdelmeier, J.-C. Yadan, I. Pelisson, Int. [37] A. J. Arduengo, E. M. Burgess, J. Am. Chem. Soc.
Pat. WO 006824 A1, 2008. 1977, 99, 2376 – 2378.
[13] Y.-B. Huang, W.-G. Jia, G.-X. Jin, J. Organomet. [38] F. Freeman, J. W. Ziller, H. N. Po, M. C. Keindl, J. Am.
Chem. 2009, 694, 86 – 90. Chem. Soc. 1988, 110, 2586 – 2591.
[14] R. Walentowski, H. W. Wanzlick, Z. Naturforsch. 1970, [39] H.-W. Wanzlick, H.-J. Scho¨nherr, Angew. Chem., Int.
25b, 1421 – 1423. Ed. Engl. 1968, 7, 141 – 142.
[15] H. G. O. Becker, D. Nagel, H. J. Timpe, J. Prakt. Chem. [40] J. Pesch, K. Harms, T. Bach, Eur. J. Org. Chem. 2004,
1973, 315, 97 – 105. 2025 – 2035.
[16] W. Friedrich, H. Kehr, F. Kro¨hnke, P. Schiller, Chem. [41] N. Kuhn, T. Kratz, Synthesis 1993, 561 – 562.
Ber. 1965, 98, 3808 – 3818.
[17] K. P. Bhabak, K. Satheeshkumar, S. Jayavelu, G. Mu-
[42] S. Saravanakumar, A. I. Oprea, M. K. Kindermann,
P. G. Jones, J. Heinicke, Chem. Eur. J. 2006, 12,
3143 – 3154.
gesh, Org. Biomol. Chem. 2011, 9, 7343 – 7350.
[18] W.-G. Jia, Y.-B. Huang, G.-X. Jin, J. Organomet. [43] D. J. Williams, V. L. H. Bevilacqua, P. A. Morson, K. J.
Chem. 2009, 694, 3376 – 3380.
[19] W.-G. Jia, Y.-B. Huang, Y.-J. Lin, G.-X. Jin, J. Chem.
Dennison, W. T. Pennington, G. L. Schimek, D. Van-
Derveer, J. S. Kruger, N. T. Kawai, Inorg. Chim. Acta
1999, 285, 217 – 222.
Soc., Dalton Trans. 2008, 5612 – 5620.
[20] W.-G. Jia, Y.-B. Huang, Y.-J. Lin, G.-L. Wang, G.-X. [44] D. J. Williams, S. K. Tata, M. C. Koether, V. L. H.
Jin, Eur. J. Inorg. Chem. 2008, 4063 – 4073.
[21] R. M. Silva, M. D. Smith, J. R. Gardinier, J. Org. Chem.
2005, 70, 8755 – 8763.
[22] D. J. Williams, D. Vanderveer, R. L. Jones, D. S. Me-
naldino, Inorg. Chim. Acta 1989, 165, 173 – 178.
[23] W.-G. Jia, Y.-B. Huang, G.-X. Jin, J. Organomet.
Chem. 2009, 694, 4008 – 4013.
Bevilacqua, B. E. Huck, R. E. Hart, Chem. Educator
2002, 7, 167 – 172.
[45] D. J. Williams, J. J. Concepcion, M. C. Koether, K. A.
Arrowood, A. L. Carmack, T. G. Hamilton, S. M. Luck,
M. Ndomo, C. R. Teel, D. VanDerveer, J. Chem. Crys-
tallogr. 2006, 36, 453 – 457.
[46] G. B. Ansell, J. Chem. Soc., Perkin Trans. 2 1972,
841 – 843.
[24] M. Slivarichova, R. Ahmad, Y. Kuo, J. Nunn, M. F.
Haddow, H. Othman, G. R. Owen, Organometallics [47] D. V. Tomlin, D. P. Campbell, P. A. Fleitz, W. W.
2011, 30, 4779 – 4787. Adams, Acta Crystallogr. 1997, C53, 1153 – 1154.
[25] H. Hauser, W. Klo¨tzer, V. Krug, J. Rzehak, A. Sand- [48] J. Kister, G. Assef, G. Mille, J. Metzger, Can. J. Chem.
rieser, N. Singewald, Sci. Pharm. 1988, 56, 235 – 241. 1979, 57, 822 – 830.
[26] H. Link, W. Klo¨tzer, E. M. Karpitschka, M. Montavon, [49] G. Laus, V. Kahlenberg, W. Reischl, H. Schottenberger,
R. Mu¨ssner, N. Singewald, Angew. Chem., Int. Ed.
Engl. 1990, 29, 556 – 557.
[27] W. Klo¨tzer, M. Montavon, R. Mu¨ssner, N. Singewald,
Eur. Pat. EP 283857 A1, 1988.
Z. Kristallogr. NCS 2011, 226, 623 – 624.
[50] G. P. Schiemenz, Z. Naturforsch. 2007, 62b, 235 –
243.
[51] A. Bondi, J. Phys. Chem. 1964, 68, 441 – 451.
[28] G. Laus, K. Wurst, V. Kahlenberg, H. Kopacka, C. [52] R. S. Rowland, R. Taylor, J. Phys. Chem. 1996, 100,
Kreutz, H. Schottenberger, Z. Naturforsch. 2010, 65b,
7384 – 7391.
776 – 782.
[53] G. R. Desiraju, Acc. Chem. Res. 2002, 35, 565 – 573.
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1252
G. Laus et al. · Imidazoline-2-thiones
[54] G. Laus, A. Schwa¨rzler, P. Schuster, G. Bentivoglio, [65] W. Klo¨tzer, H. Baldinger, E. M. Karpitschka, J. Knof-
M. Hummel, K. Wurst, V. Kahlenberg, T. Lo¨rting, lach, Synthesis 1982, 592 – 595.
J. Schu¨tz, P. Peringer, G. Bonn, G. Nauer, H. Schotten- [66] C. G. Overberger, J. C. Salamone, S. Yaroslavsky, J.
berger, Z. Naturforsch. 2007, 62b, 295 – 308. Org. Chem. 1965, 30, 3580.
[55] F. H. Allen, O. Kennard, D. G. Watson, J. Chem. Soc., [67] S. V. Dzyuba, R. A. Bartsch, Chem. Commun. 2001,
Perkin Trans. 2 1987, S1–S19. 1466 – 1467.
[56] H. R. Kim, I. G. Jung, K. Yoo, K. Jang, E. S. Lee, [68] W. M. Reichert, J. D. Holbrey, R. P. Swatloski, K. E.
J. Yun, S. U. Son, Chem. Commun. 2010, 46, 758 –
760.
[57] M. J. Kamlet, J.-L. M. Abboud, M. H. Abraham, R. W.
Taft, J. Org. Chem. 1983, 48, 2877 – 2887.
[58] R. W. Taft, M. J. Kamlet, J. Am. Chem. Soc. 1976, 98,
2886 – 2894.
Gutowski, A. E. Visser, M. Nieuwenhuyzen, K. R. Sed-
don, R. D. Rogers, Crystal Growth Des. 2007, 7,
1106 – 1114.
[69] J. D. Holbrey, W. M. Reichert, R. P. Swatloski, G. A.
Broker, W. R. Pitner, K. R. Seddon, R. D. Rogers,
Green Chem. 2002, 4, 407 – 413.
[59] M. J. Kamlet, R. W. Taft, J. Am. Chem. Soc. 1976, 98, [70] G. Laus, A. Schwa¨rzler, G. Bentivoglio, M. Hum-
377 – 383.
mel, V. Kahlenberg, K. Wurst, E. Kristeva, J. Schu¨tz,
H. Kopacka, C. Kreutz, G. Bonn, Y. Andriyko, G. Nau-
er, H. Schottenberger, Z. Naturforsch. 2008, 63b,
447 – 464.
[60] M. J. Kamlet, J. L. Abboud, R. W. Taft, J. Am. Chem.
Soc. 1977, 99, 6027 – 6038.
[61] C. Laurence, P. Nicolet, M. T. Dalati, J.-L. M. Abboud,
R. Notario, J. Phys. Chem. 1994, 98, 5807 – 5816.
[62] Y. Marcus, Chem. Soc. Rev. 1993, 22, 409 – 416.
[63] A. Taha, A. M. Kiwan, New J. Chem. 2001, 25, 502 –
508.
[71] Y. Tamura, H. Hayashi, J. Minamikawa, M. Ikeda, J.
Heterocycl. Chem. 1974, 11, 781 – 786.
[72] M. C. Burla, B. Carrozzini, G. L. Cascarano, C. Giaco-
vazzo, G. Polidori, Z. Kristallogr. 2002, 217, 629 – 635.
[64] C. Legault, A. B. Charette, J. Org. Chem. 2003, 68, [73] G. M. Sheldrick, Acta Crystallogr. 2008, A64, 112 –
7119 – 7122.
122.
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