Unexpected behaviour of tosylated and acetylated imidazolinium salts

Article abstract of DOI:10.1039/b601104g

Tosylated and acetylated imidazolinium salts revealed an unexpected reactivity when treated with methyl iodide or benzyl bromide. Moreover an unprecedented acid-catalysed rearrangement for an acetylated imidazolinium salt was observed during an anion meta

Full text of DOI:10.1039/b601104g

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www.rsc.org/obc | Organic & Biomolecular Chemistry
Unexpected behaviour of tosylated and acetylated imidazolinium salts
Nicole Clemens, Oksana Sereda and Rene´ Wilhelm*
Received 23rd January 2006, Accepted 23rd March 2006
First published as an Advance Article on the web 5th May 2006
DOI: 10.1039/b601104g
Tosylated and acetylated imidazolinium salts revealed an unexpected reactivity when treated with
methyl iodide or benzyl bromide. Moreover an unprecedented acid-catalysed rearrangement for an
acetylated imidazolinium salt was observed during an anion metathesis.
could increase the catalytic activity of these salts. Here we would
Introduction
like to discuss some unexpected results along the synthetic route
Tetrahydrofolate coenzymes, which are part of a one-carbon
towards some of the desired chiral tosyl and acetyl substituted
fragment biochemical transfer,1,2 can be mimicked by several
imidazolinium salts, which, to the best of our knowledge, have not
simple imidazolinium salts.3,4 For example, the imidazolinium
been reported so far.
iodide salt analogues 1, 2 and 3 (Scheme 1) were first prepared
from the corresponding imidazolines and MeI by Pandit’s group.5
Results and discussion
First the precursors for the desired salts were prepared. There-
fore, (+)-(R,R)-6,24 prepared from (+)-(R,R)-1,2-diphenyl-1,2-
ethylenediamine,25 was treated with tosyl chloride or acetic acid
anhydride in the presence of triethylamine to give the imidazoline
derivatives (−)-(R,R)-7 and (+)-(R,R)-8 in 90 and 77% yield,
respectively (Scheme 2). In addition imidazoline (+)-(R,R)-9 was
synthesised in 40% yield, by the reaction of methyl chloroformate
with (+)-(R,R)-6 in the presence of sodium hydride (Scheme 2).
Scheme 1
The much hindered tosylated analogue 3 revealed a different
behaviour than less hindered salts. When heated with an amine,
e.g. benzylamine, the tosyl group was attacked by the nucleophile
and the imidazoline ring left the molecule and was isolated
as the hydrolytic product 5.5 This observation is very rare for
imidazolinium analogues, however very well known for tosylated
imidazolium salts, like 1-(toluenesulfonyl)-3-methylimidazolium
triflate, which has been used as a tosylating reagent for alcohols6
and amines.7,8 The resulting imidazol ring in this reaction is not
hydrolysed.
Moreover, a few chiral imidazolinium salts have recently been
reported as chiral ionic liquids.9,10 However, the examples of this
emerging class of chiral ionic liquids remain few compared to
other types of chiral ionic liquids.11,12 In addition it is possible
to apply 2-phenyl substituted imidazolinium salts as ionic liquids
with strong bases.13
Recently, we have reported the application of some achiral
imidazolinium salts as catalysts for the aza Diels–Alder reaction.14
The salts may be considered as part of the limited number of metal-
free Lewis acids15–21 and could contribute to the important research
field of organocatalysis.22,23 In order to apply chiral analogues
of the salts as catalysts, we were interested in preparing chiral
analogues of 1 and 2, since the electron withdrawing groups
Institut fu¨r Organische Chemie der Technischen Universita¨t Clausthal, 38678
Clausthal-Zellerfeld, Germany. E-mail: rene.wilhelm@tu-clausthal.de;
Fax: +49-5323-722834; Tel: +49-5323-723886
Scheme 2
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Moreover, imidazoline (+)-(R,R)-11 was obtained via an acetyla-
tion of (+)-(R,R)-10,26 derived from (+)-(R,R)-1,2-diphenyl-1,2-
ethylenediamine,25 in 77% yield (Scheme 2).
In order to transform imidazoline 8 into the desired salt 12 the
method reported for salts 1 and 2 was applied.5 An excess of methyl
iodide was refluxed with 3 in dichloromethane for 16 h. Therefore
(+)-(4R,5R)-1-acetyl-2,4,5-triphenyl-trans-4,5-dihydroimidazole
(8) yielded (+)-(4R,5R)-1-acetyl-2,4,5-triphenyl-3-methyl-trans-
imidazolinium iodide (12) in 84% (Scheme 3).
Scheme 3
Scheme 5
Additionally, imidazolines 7 and 9 were treated the same way.
However, in both cases not the expected salts were found as the
major products. Instead the dimethylated salt 13 was observed
(Scheme 4). In the crude NMR mainly the dimethylated product 13
was detected besides the starting material and the desired product.
The latter could be isolated neither via column chromatography
nor by recrystallisation. When the reaction was performed in
dichloromethane at 85 ◦C in a sealed vessel, only 13 was obtained
from 7 and 9 in quantitative yield. The replacement of methyl
iodide with dimethyl sulfate resulted in both cases in a complex
mixture of compounds. When 11 was treated with methyl iodide
only a complex mixture of compounds was found.
react with another benzyl bromide molecule to the dibenzylated
product 14. The starting material 7 reacts with benzyl bromide far
slower then 16, due to the electron withdrawing tosyl group, which
explains, that even when just 1 equiv. of benzyl bromide was used
14 and 7 were observed. When the reaction was repeated with 0.9
equiv. of benzyl bromide and stopped after 6 h, it was possible to
isolate 16 in 5% yield through column chromatography. For the
reactions involving 9 and methyl iodide a similar mechanism could
be assumed.
In order to transform salt 12 into analogues with different
anions, 12 was stirred in the presence of 1.5 equiv. of KPF6
or LiNTf2 in a mixture of dichloromethane and water. The
organic phase was separated and washed three times with water.
The more lipophilic ion pair remains in the organic solvent. In
the case of LiNTf2 the expected salt 12c was isolated in pure
−
form in 90% yield (Scheme 6). However, the corresponding PF6
salt was isolated in only 48% yield. The result of the simple
anion exchange was quite amazing. In the NMR spectra all
aliphatic signals were twice as much as required and it was found
that the unexpected product (+)-(4R,5R)-1-benzoyl-2,3-dimethyl-
4,5-diphenyl-trans-imidazolinium hexafluorophosphate (17b) was
Scheme 4
After these unexpected results 3 equiv. of benzyl bromide was
used in the reaction with 7 and 9, respectively (Scheme 4). A
reaction in refluxing dichloromethane was not observed. When
the reaction was performed at 85 ◦C in a sealed tube, mainly the
dibenzylated product 14 was found next to some starting material.
In acetonitrile a total conversion to 14 took place. The bromide salt
14 was isolated in a yield of 74% after recrystallisation. A repeat of
the reaction in acetonitrile and 1 equiv. of benzyl bromide resulted
in the isolation of the starting material and 14 in a ratio of 1 : 1 by
NMR.
These results may be explained by the following proposed
mechanism (Scheme 5), taking the behaviour of salt 3 (Scheme 1)
into consideration. In the first step the desired product, e.g. 15
is formed. Taking the nucleophilicity of halide anions in polar
aprotic solvents into account, the bromide anion of salt 15 can
attack at the sulfonyl group in a bimolecular substitution reaction.
The formation of tosyl bromide is assisted by the generation of the
very good leaving group, the imidazole 16. In the last step 16 can
Scheme 6
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present. The ratio of the two products was calculated according to
the 1H NMR spectra with 12b : 17b = 1 : 2.
was then treated with methyl iodide and after an anion exchange
the expected product 21b was isolated. No side reactions were
observed (Scheme 7).
In conclusion, we have reported some unexpected behaviour of
tosylated and acetylated imidazolinium salts, which may be impor-
tant to consider for the preparation of new imidazolinium based
ionic liquids and tetrahydrofolate coenzyme model compounds.
After the discovery of the unexpected rearrangement product
17b, further experiments were carried out to find mechanistic
clues to describe the reaction in detail. A possible reason for
the result may be due to the use of KPF6. Considering that
potassium hexafluorophosphate contains traces of HF and can
slowly decompose further in water, a catalytic amount of acid
was used to influence the 1 : 2 ratio of the mixture 12b :
17b. Manipulation of the mixture 12b : 17b = 1 : 2 with a
catalytic amount of aqueous HCl in dichloromethane shifted
the equilibrium to 12b : 17b = 1 : 3. The reduced solubility
of HCl in dichloromethane could explain the poor movement
of the ratio. Therefore, the next reaction was carried out with
a solution of trifluoroacetic acid in dichloromethane. Now the
generation of the rearrangement product 12b : 17b was more
Experimental
General experimental
All reactions were conducted under a protective atmosphere of
dry nitrogen. Dichloromethane and acetonitrile were distilled
from calcium hydride. All other chemicals, whose preparation is
not described below, were bought from Aldrich, Fluka, Merck
or Lancaster and were used without further purification. 2-
Phenyl-4,5-dihydroimidazole (18),5 (+)-(4R,5R)-2,4,5-triphenyl-
trans-4,5-dihydro-1H-imidazole24 (6) and (+)-(4S,5S)-2-methyl-
4,5-diphenyl-trans-4,5-dihydro-1H-imidazole26 (10) were pre-
pared according to literature procedures. Reactions were moni-
tored by TLC with Merck Silica gel 60 F254 plates or with neutral
aluminium oxide 60 F254 plates. Flash column chromatography27
was performed on Sorbisil C-60 or active neutral aluminium
oxide 90. Infrared spectra were recorded on a Vector 22 FT-IR
from Bruker. NMR spectra were performed in CDCl3 at ambient
temperature on a Bruker AMX 400 and a Bruker AC 200F. The
following symbols are used to analyse the 13C-spectra: +: primary
or tertiary carbon, −: secondary carbon, q: quaternary carbon.
Mass spectra were recorded on MS 5889 B from Hewlett Packard.
Electron spray mass spectrometry was performed directly on a
MS LC/MSD 1100 MSD from Hewlett Packard. High resolution
mass spectra were recorded by Dr Dra¨ger at the Institute of
Organic Chemistry, University of Hanover. Elemental analyses
were carried out by the Institute of Pharmaceutical Chemistry,
Technical University of Braunschweig and are reported as the
average of two runs. Optical rotations were measured on a Perkin-
Elmer 243 B polarimeter. Melting points were taken with an
apparatus after Dr Tottoli and are uncorrected.
1
favoured and appeared according to H NMR spectra in a ratio
of 1 : 6 after 24 h. No total conversion of 12b to 17b was obtained,
probably an equilibrium exists, wherein an excess of 17b is ther-
modynamically favoured. In view of the empiric support, that the
rearrangement is catalysed by acidic conditions, a last procedure
was tested. (+)-(4R,5R)-1-Acetyl-2,4,5-triphenyl-3-methyl-trans-
imidazolinium trifluoromethanesulfonimide 12c was stirred with
a catalytic amount of trifluoroacetic acid in dichloromethane. The
expected mixture of 12c : 17c occurred in a ratio of 1 : 4 after 24 h.
Two possible mechanisms are imaginable: first a rearrangement
via non-ring opening. After the formation of an enol a four
membered ring could be formed followed by a 1,3-phenyl shift.
Advantages of this proposed mechanism are no ring openings,
permanently just one charge in the molecule, which can be
stabilised by tautomerism, and the necessity of a catalytic amount
of acid to form an enol in the first step. On the other hand, there is
also a disadvantage: constitution of the positively charged [3.2.0]-
system in the transition state. The second possible mechanism
would be a ring opening of the cation, followed by the formation
of the new salt with the former carbonyl carbon atom at the C-2
position.
Finally, in order to explore the behaviour of an aliphatic sulfone
rest group, (1S)-(+)-camphorsulfonyl-(2-phenyl-4,5-dihydro)-
imidazole (20) was prepared in a low yield (Scheme 7) from 2-
phenyl-4,5-dihydroimidazole (18)5 and (1S)-(+)-camphorsulfonic
acid chloride (19) under basic conditions. The imidazoline 20
(+)-(4R,5R)-1-(Toluene-4-sulfonyl)-2,4,5-triphenyl-trans-4,5-di-
hydroimidazole
(7). (+)-(4R,5R)-2,4,5-Triphenyl-trans-4,5-
dihydro-1H-imidazole (6) (2.5 g, 8.4 mmol) and triethylamine
(1.15 mL, 8.4 mmol) were dissolved in dry dichloromethane
(20 mL). After adding tosyl chloride (1.76 g, 9.2 mmol) the
resulting mixture was stirred for 2 h at r.t. The precipitate
was filtered off and the filtrate was washed with dilute sodium
bicarbonate solution and dried (Na2SO4). Evaporation yielded a
thick oil, which was purified by column chromatography on silica
with petroleum ether–ethyl acetate (5 : 1) as the eluent to give the
title compound 7 as a white solid (3.4 g, 7.5 mmol, 90%). [a]D24
=
−150 (c = 1.02, CH2Cl2), mp 122 ◦C; MS (EI), m/e 453 (M +
1, 10%), 297 (70), 91 (100); IR (KBr) 3443w, 1634s, 1368s, 1175s,
1
761s cm−1; H NMR (200 MHz) d 7.87–7.82 (m, 2 H, Ar–H),
7.56–7.40 (m, 8 H, Ar–H), 7.25–7.05 (m, 7 H, Ar–H), 6.83–6.78
(m, 2 H, Ar–H), 5.10 (s, 2 H, C–H), 2.40 (s, 3 H, Me); 13C NMR
(50 MHz) d 159.9 (q, NCN), 144.7 (q, Ar), 142.5 (q, Ar), 141.8
(q, Ar), 134.9 (q, Ar), 131.4 (+, Ar), 130.5 (q, Ar), 130.0 (+, Ar),
129.7 (Ar), 129.3 (+, Ar), 128.7 (+, Ar), 128.3 (+, Ar), 128.0 (+,
Ar), 127.9 (+, Ar), 127.4 (+, Ar), 126.2 (+, Ar), 126.0 (+, Ar),
Scheme 7
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6.5 mmol, 77%). [a]D24 = 136 (c = 1.14 in CH2Cl2), mp 133 ◦C; MS
(EI), m/e 278 (M, 10%), 236 (10), 148 (30), 131 (100), 106 (70),
89 (60); IR (KBr) 1684s, 1641m, 1379s, 1332s, 760s, 700s cm−1;
1H NMR (200 MHz) d 7.47–7.31 (m, 6 H, Ar–H), 7.23–7.17 (m,
4 H, Ar–H), 4.86 (dd, J = 1.9 Hz, J = 5.1 Hz, 2 H, C–H), 2.69
77.4 (+, C(5)–H), 72.6 (+, C(4)–H), 21.7 (+, Me). Anal. calcd for
C27H24O2N2S1: C, 73.61; H, 5.49; N, 6.36. Found: C, 73.87; H,
5.32; N, 6.33%.
(+)-(4R,5R)-1-Acetyl-2,4,5-triphenyl-trans-4,5-dihydroimidazole
(8). (+)-(4R,5R)-2,4,5-Triphenyl-trans-4,5-dihydro-1H-imida-
zole (6) (1.0 g, 3.36 mmol) was dissolved in dry dichloromethane
(12 mL). Acetic anhydride (0.32 mL, 3.36 mmol) and triethylamine
(0.32 mL, 3.36 mmol), dissolved in dichloromethane (2 mL),
were added to the mixture and left to stir for 1 h at r.t. The
mixture was washed with water and dried (Na2SO4). After
evaporation of the solvent, the crude product was purified by
column chromatography on Al2O3 using petroleum ether–ethyl
acetate (4 : 1) as the eluent to give the title compound 8 as a
colourless oil (0.88 g, 2.6 mmol, 77%). [a]2D4 = 42 (c = 1.12 in
CH2Cl2); MS (EI), m/e 340 (M, 5%), 193 (100), 91 (40); IR
(KBr) 3445m, 3029m, 1696s, 1622m, 1321s, 1273m, 1024m, 760s,
(d, J = 1.1 Hz, 3 H, N C–Me), 1.88 (s, 3 H, CO–Me); 13C NMR
=
=
(50 MHz) d 169.1 (q, C O), 159.5 (q, NCN), 141.93 (q, Ar),
141.91 (q, Ar), 129.6 (+, Ar), 129.0 (+, Ar), 128.3 (+, Ar), 127.9
(+, Ar), 126.1 (+, Ar), 125.2 (+, Ar), 77.8 (+, C(5)–H), 70.7 (+,
=
C(4)–H), 25.0 (+, N C–Me), 19.3 (+, COMe). Anal. calcd for
C18H18O1N2: C, 77.67; H, 6.52; N, 10.06. Found: C, 77.50; H,
6.57; N, 10.11%.
(+)-(4R,5R)-1-Acetyl-2,4,5-triphenyl-3-methyl-trans-imidazo-
linium iodide (12). Compound 8 (1 g, 2.9 mmol) was dissolved in
dry dichloromethane (22 mL). Methyl iodide (2.2 mL) was added
and the mixture was refluxed. After 1 h another portion of methyl
iodide (2.2 mL) was added and the mixture was refluxed overnight.
Evaporation yielded the desired product 12 as a yellowish solid
(1.2 g, 2.5 mmol, 84%). [a]2D4 = 66 (c = 0.51 in CH3CN), mp
155 ◦C; ESI, m/e 355 (M+, 100%); IR (KBr) 3048s, 3015s, 1747s,
1622s, 1497s, 1449s, 1427s, 1276s, 1225s, 756s, 701s cm−1; 1H NMR
(200 MHz) d 7.71–7.31 (m, 15 H, Ar–H), 6.01 (d, J = 11.4 Hz, 1 H,
C–H), 5.79 (d, J = 11.4 Hz, 1 H, C–H), 3.03 (s, 3 H, N–Me), 1.86
1
697s cm−1; H NMR (200 MHz) d 7.81–7.76 (m, 2 H, Ar–H),
7.52–7.28 (m, 13 H, Ar–H), 5.19 (dd, J = 3.2 Hz, J = 11.5 Hz,
2 H, C–H), 1.89 (s, 3 H, Me); 13C NMR (50 MHz) d 168.6 (q,
=
C O), 160.1 (q, NCN), 141.9 (q, Ar), 141.2 (q, Ar), 131.9 (q, Ar),
130.8 (+, Ar), 129.4 (+, Ar), 129.1 (+, Ar), 128.4 (+, Ar), 128.2
(+, Ar), 128.0 (+, Ar), 126.1 (+, Ar), 125.5 (+, Ar), 77.1 (+,
C(5)–H), 70.6 (+, C(4)–H), 25.0 (+, Me). HRMS (ESI) found:
M + H 341.1658. C23H21N2O requires: 341.1654.
(s, 3 H, CO–Me); 13C NMR (50 MHz) d 168.7 (q, C O), 166.27 (q,
=
NCN), 135.5 (q, Ar), 133.3 (+, Ar), 132.1 (q, Ar), 130.6 (+, Ar),
129.9 (+, Ar), 129.7 (+, Ar), 129.53 (+, Ar), 129.47 (+, Ar), 128.2
(+, Ar), 123.5 (q, C+), 75.8 (+, C(5)–H), 71.7 (+, C(4)–H), 35.1
(+, N–Me), 26.4 (+, COMe). HRMS (ESI) found: M+ 355.1826.
C24H23N2O requires: 355.1810.
(+)-(4R,5R)-2,4,5-Triphenyl-trans-4,5-dihydroimidazole-1-car-
boxylic acid methyl ester (9). A sodium hydride solution (60%
in petroleum) (0.17 g, 4.4 mmol) was washed with glyme (3 ×
5 mL) and then additional glyme (20 mL) was added. A
glyme solution (15 mL) of (+)-(4R,5R)-2,4,5-triphenyl-trans-4,5-
dihydro-1H-imidazole (6) (1 g, 3.36 mmol) was slowly added and
the mixture was stirred for 2 h. Methyl chloroformate (0.34 mL,
4.36 mmol) was then added quickly. The mixture was stirred at
r.t. for 19 h, filtered and the filtrate was evaporated in vacuum.
Purification by column chromatography on Al2O3 using petroleum
ether–ethyl acetate (5 : 1) as the eluent afforded the title compound
4 as a colourless oil (0.48 g, 1.3 mmol, 40%). [a]2D4 = 63 (c = 1.03
in CHCl3); MS (EI), m/e 356 (M, 50%), 193 (100); IR (KBr)
(+)-(4R,5R)-1-Acetyl-2,4,5-triphenyl-3-methyl-trans-imidazo-
linium trifluoromethanesulfonimide (12c). Salt 12 (0.2 g,
0.41 mmol) was dissolved in dry dichloromethane (5 mL). 2 equiv.
(0.24 g, 0.83 mmol) of N-lithiotrifluoromethanesulfonimide were
added and the mixture was stirred for 2 h at room temperature.
After adding water (5 mL) and additional stirring for 1 h,
the phases were separated and the organic layer was washed
three times with water, dried (Na2SO4) and evaporated under
vacuum. Drying on the vacuum line at 40 ◦C (oil bath temperature)
yielded the title compound 12c as a yellowish solid (238 mg,
0.4 mmol, 90%). [a]D24 = 115 (c = 0.35 in CH2Cl2), mp 50–51 ◦C;
ESI, m/e 355 (M+, 100%); IR (KBr) 3068w, 2360s, 2342s, 1744s,
1624s, 1502m, 1458m, 1352s, 1195s, 1132m, 1057m cm−1; 1H NMR
(200 MHz) d 7.72–7.68 (m, 3 H, Ar–H), 7.53–7.36 (m, 12 H, Ar–
H), 5.69 (d, J = 9.7 Hz, 1 H, C–H), 5.28 (d, J = 9.6 Hz, 1 H,
C–H), 2.95 (s, 3 H, N–Me), 1.80 (s, 3 H, CO–Me); 13C NMR
1
2962s, 1735m, 1331m, 1262s, 1101s, 1022s, 801s cm−1; H NMR
(200 MHz) d 7.83–7.78 (m, 2 H, Ar–H), 7.53–7.29 (m, 13 H, Ar–
H), 5.18 (d, J = 4.3 Hz, 1 H, C–H), 5.16 (d, J = 4.3 Hz, 1 H,
13
=
C–H) 3.55 (s, 3 H, Me); C NMR (50 MHz) d 160.1 (q, C O),
152.8 (q, NCN), 142.6 (q, Ar), 141.8 (q, Ar), 131.5 (q, Ar), 130.7
(+, Ar), 129.3 (+, Ar), 129.1 (+, Ar), 128.8 (+, Ar), 128.2 (+, Ar),
128.0 (+, Ar), 126.3 (+, Ar), 125.8 (+, Ar), 77.5 (+, C(5)–H), 70.6
(+, C(4)–H), 53.3 (+, Me). HRMS(ESI) found: M + H 357.1611.
C23H21N2O requires: 357.1603.
=
(50 MHz) d 168.1 (q, C O), 166.5 (q, NCN), 136.2 (q, Ar), 133.7
(+, Ar), 132.6 (q, Ar), 130.9 (+, Ar), 129.9 (+, Ar), 129.8 (+, Ar),
129.4 (+, Ar), 129.2 (+, Ar), 128.3 (+, Ar), 123.1 (q, Ar), 120.2
(q, J = 65.0 Hz, CF3), 75.9 (+, C(5)–H), 71.0 (+, C(4)–H), 34.3
(+, N–Me), 25.3 (+, COMe); HRMS(ESI) found: M+ 355.1820.
C24H23N2O requires: 355.1810.
(+)-(4S,5S)-1-Acetyl-2-methyl-4,5-diphenyl-trans-4,5-dihydro-
imidazole
(11). (+)-(4S,5S)-2-Methyl-4,5-diphenyl-trans-4,5-
dihydro-1H-imidazole (10) (2 g, 8.5 mmol) was dissolved
in absolute ethanol (15 mL). Acetic anhydride (0.8 mL,
8.5 mmol) and triethylamine (1.2 mL, 8.5 mmol) dissolved in
dichloromethane (2 mL) were added to the mixture, after which
the resulting solution was stirred for 10 h at r.t. After evaporation
of the solvent the residue was purified by column chromatography
on Al2O3 using petroleum ether–ethyl acetate (3 : 1) as the eluent
to give the crude product as a yellow solid. Recrystallisation
in ethanol gave the title compound 11 as a white solid (1.8 g,
(+)-(4R,5R)-1-Acetyl-2,4,5-triphenyl-3-methyl-trans-imidazo-
linium hexafluorophosphate (12b) and (+)-(4R,5R)-1-benzoyl-
2,3-methyl-4,5-diphenyl-trans-imidazolinium hexafluorophosphate
(17b). Salt 12 (0.2 g, 0.41 mmol) was dissolved in dry
dichloromethane (5 mL). 1.5 equiv. potassium hexafluorophos-
phate (0.11 g, 0.62 mmol) were added and the mixture was
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stirred for 24 h at room temperature. After adding water (5 mL)
the stirring was continued for another hour. The phases were
separated by using a pipette and the organic layer was washed with
water (2 × 2 mL), dried (Na2SO4) and evaporated under reduced
pressure. Crystallisation in methanol yielded white crystals (88 mg,
0.2 mmol, 48%). The ratio (17b : 12b = 2 : 1) was determined
Ar–H), 7.31 (dd, J = 1.1 Hz, J = 2.3 Hz, 6 H, Ar–H), 7.14 (dd,
J = 2.3 Hz, J = 3.5 Hz, 4 H, Ar–H), 6.90 (dd, J = 2.2 Hz, J =
3.4 Hz, 4 H, Ar–H), 4.82 (s, 2 H, C–H), 4.73 (d, J = 15.0 Hz, 2 H,
Bn–H), 4.15 (d, J = 15.0 Hz, 2 H, Bn–H); 13C NMR (50 MHz) d
166.8 (q, NCN), 134.3 (q, Ar), 134.1 (+, Ar), 131.5 (+, Ar), 131.0
(q, Ar), 130.5 (+, Ar), 130.2 (+, Ar), 129.5 (+, Ar), 129.4 (+, Ar),
129.1 (+, Ar), 128.4 (+, Ar), 127.5 (+, Ar), 121.5 (q, Ar), 71.5
(+, C(4,5)–H), 50.3 (−, CH2). Anal. calcd for C37H31N3O4S2F6: C,
58.49; H, 4.11; N, 5.53. Found: C, 58.16; H, 4.07; N, 5.39%.
1
by H NMR. Enrichment of 12b could be obtained after two
1
recrystallisations in diethyl ether–hexane (17b : 12b = 1 : 4). H
NMR (200 MHz) d 7.76–7.21 (m, 22.5 H, Ar–H of 12b + 17b),
5.73 (d, J = 10.0 Hz, 0.5 H, C–H of 12b), 5.60 (d, J = 11.6 Hz, 1 H,
C–H of 17b), 5.34 (d, J = 10.0 Hz, 0.5 H, C–H of 12b), 5.23 (d, J =
11.4 Hz, 1 H, C–H of 17b), 3.14 (s, 3 H, N–Me of 17b), 2.96 (s,
1.5 H, N–Me of 12b), 2.46 (s, 3 H, C+–Me of 17b), 1.80 (s, 1.5 H,
(4R,5R)-1-Benzyl-4,5-dihydro-2,4,5-triphenyl-1H -imidazole
(16). Compound 7 (0.158 g, 0.35 mmol) was dissolved in dry
acetonitrile (5 ml). Benzyl bromide (0.9 equiv.) was added, and the
mixture was refluxed for 6 h. After evaporation of the solvent under
reduced pressure, the residue was columned with ethyl acetate to
give the title compound 16 as a colourless oil (7 mg, 0.018 mmol,
5%). ESI m/e 389.2 (M+ + H, 100%); MS (EI), m/e 388 (M,
11%), 297 (M+ − Bn, 20), 193 (100), 91 (Bn, 93); IR (CHCl3)
CO–Me of 12b). 13C NMR (50 MHz) d 168.1 (q, C O, 12b + 17b),
=
168.0 (q, NCN, 17b), 166.5 (q, NCN, 12b), 136.2 (q, Ar, 12b), 134.5
(q, Ar, 17b), 134.1 (q, Ar, 17b), 133.7 (+, Ar, 12b), 132.6 (q, Ar,
12b), 132.5 (+, Ar, 17b), 131.0 (+, Ar, 12b), 130.7 (q, Ar, 17b),
130.0 (+, Ar, 17b), 129.9 (+, Ar, 12b), 129.7 (+, Ar, 12b), 129.5
(+, Ar, 17b), 129.3 (+, Ar, 12b), 129.2 (+, Ar, 12b + 17b), 128.5
(+, Ar, 12b + 17b), 127.8 (+, Ar, 17b), 123.1 (q, Ar, 17b), 122.9 (q,
Ar, 12b), 75.8 (+, C(5)–H, 12b), 75.2 (+, C(5)–H, 17b), 72.3 (+,
C(4)–H, 17b), 71.0 (+, C(4)–H, 12b), 34.3 (+, N–Me, 12b), 33.3
(+, N–Me, 17b), 25.3 (+, COMe, 12b), 16.0 (+, CMe, 17b).
1
3091m, 3036m, 1478s, 1036s, 637s cm−1; H NMR (200 MHz) d
7.86–7.81 (m, 2 H, Ar–H), 7.52–7.48 (m, 3 H, Ar–H), 7.40–7.20
(m, 10 H, Ar–H), 7.14–7.09 (m, 2 H, Ar–H), 6.98–6.93 (m, 2H,
Ar–H), 5.01 (d, J = 8.4 Hz, 1 H, C–H), 4.73 (d, J = 15.6 Hz, 1 H,
Bn–H), 4.35 (d, J = 8.5 Hz, 1 H, C–H), 3.94 (d, J = 15.6 Hz, 1 H,
Bn–H); 13C NMR (50 MHz) d 166.0 (NCN), 143.8 (Ar), 141.8
(Ar), 136.4 (Ar), 130.2 (Ar), 128.9 (Ar), 128.74 (Ar), 128.69 (Ar),
128.5 (Ar), 128.4 (Ar), 128.0 (Ar), 127.8 (Ar), 127.5 (Ar), 127.2
(Ar), 127.2 (Ar), 127.0 (Ar), 126.8 (Ar), 72.6 (CH), 49.6 (Bn).
(+)-(4R,5R)-1,3-Dibenzyl-2,4,5-triphenyl-trans-imidazolinium
bromide (14). Compound 7 (1 g, 2.2 mmol) was dissolved in
dry acetonitrile (10 mL). 2 equiv. freshly distilled benzyl bromide
(0.53 mL, 4.4 mmol) were added and the mixture was refluxed for
22 h. The colour was changing from colourless to yellow. After
(1S)-(−)-Camphorsulfonyl-(2-phenyl-4,5-dihydro)-imidazole
(20). 2-Phenyl-4,5-dihydroimidazole (18) (0.8 g, 5.5 mmol) was
dissolved in dry toluene (3 mL) and 1.5 equiv. triethylamine
(8.25 mmol, 0.034 mL) were added. After addition of 1.2 equiv.
(1S)-(+)-camphorsulfonic acid chloride (19) (6.6 mmol, 1.65 g)
the solution turned into a yellowish cloudy mixture, which was
stirred at r.t. for 18 h. The reaction mixture was washed with 5%
aqueous HCl (3 × 2 mL) and 10% aqueous NaHCO3 solution
(2 × 2 mL), dried (Na2SO4) and evaporated under vacuum. The
mixture was purified by column chromatography on SiO2 using
petroleum ether–ethyl acetate (1 : 2) as the eluent to give the
crude product as a colourless oil. Recrystallisation in petroleum
ether–dichloromethane gave the white pure product 20 (200 mg,
◦
evaporation of the solvent the residue was dried at 60 C under
high vacuum to remove traces of benzyl bromide. Crystallization
in ethyl acetate yielded the title compound 14 as a white solid
(920 mg, 1.6 mmol, 74%). [a]2D4 = 132 (c = 0.50 in CHCl3), mp
217 ◦C; ESI, m/e 479 (M+, 100%); IR (KBr) 3030m, 3003m, 1560s,
1454s, 1286s, 751s, 736m, 698s cm−1; 1H NMR (200 MHz) d 8.31–
8.26 (m, 2 H, Ar–H), 7.70 (dd, J = 1.1 Hz, J = 2.4 Hz, 3 H, Ar–H),
7.45–7.34 (m, 10 H, Ar–H), 7.22 (dd, J = 1.0 Hz, J = 2.4 Hz, 6 H,
Ar–H), 6.82 (dd, J = 2.2 Hz, J = 3.5 Hz, 4 H, Ar–H), 5.26 (s, 2
H, C–H), 4.69 (d, J = 15.3 Hz, 2 H, Bn–H), 4.42 (d, J = 15.3 Hz,
2 H, Bn–H); 13C NMR (50 MHz) d 167.8 (q, NCN), 133.7 (q, Ar),
133.3 (+, Ar), 132.6 (q, Ar), 130.3 (+, Ar), 130.2 (+, Ar), 129.8
(+, Ar), 129.1 (+, Ar), 129.0 (+, Ar), 128.8 (+, Ar), 128.6 (+, Ar),
122.3 (q, Ar), 73.0 (+, C(4,5)–H), 51.1 (−, CH2). Anal. calcd for
C35H31N2Br1: C, 75.13; H, 5.58; N, 5.01. Found: C, 74.86; H, 5.63;
N, 4.74%.
◦
0.6 mmol, 10%). [a]D24 = −22 (c = 1.0 in CH2Cl2), mp 91–95 C;
MS (EI), m/e 379 (M + H2O, 100%); IR (KBr) 3285s, 2955s,
1
1742s, 1726m, 1632s, 1544s, 1328s, 1144s, 697m cm−1; H NMR
(200 MHz, DMSO–D2O) d 8.54 (t, J = 5.4 Hz, 1 H), 7.81–7.76
(m, 2 H, Ar–H), 7.56–7.39 (m, 3 H, Ar–H), 3.38 (m, 2 H), 3.19–
3.13 (m, 2 H), 2.87 (d, J = 14.9 Hz, 1 H), 2.32–2.20 (m, 2 H),
2.01 (t, J = 4.3 Hz, 1 H), 1.89–1.80 (m, 2 H), 1.56–1.27 (m, 2 H),
0.93 (s, 3 H, Me), 0.70 (s, 3 H, Me); 13C NMR (50 MHz) d 168.1
(+)-(4R,5R)-1,3-Dibenzyl-2,4,5-triphenyl-trans-imidazolinium
trifluoromethanesulfonimide (14c). Salt 14 (1 g, 1.8 mmol)
was dissolved in dry dichloromethane (8 mL). 2 equiv. N-
lithiotrifluoromethanesulfonimide (1.22 g, 3.6 mmol) were added
and the mixture was stirred for 3.5 h at r.t. After adding water
(8 mL) stirring was continuing for another hour, the phases were
separated by using a pipette and the organic layer was washed
with water (3 x 2 mL), dried (Na2SO4) and evaporated in vacuum.
Drying under high vacuum yielded the title compound 14c as a
white solid (1.18 g, 1.6 mmol, 83%). [a]2D4 = 7 (c = 0.98 in CH2Cl2),
=
(q, C O), 134.2 (q, Ar), 131.7 (+, Ar), 128.6 (+, Ar), 127.2 (+,
Ar), 59.2 (q, C(1)), 49.6 (−, CH2), 49.0 (q, C(7)), 43.4 (−, CH2),
43.0 (−, CH2), 42.8 (+, C(4)), 40.5 (−, CH2), 27.1 (−, C(6)), 26.3
(−, C(5)), 19.9 (+, Me), 19.5 (+, Me). HRMS(ESI) found: M +
H2O + Na 401.1524. C19H26N2O4SNa requires: 401.1511.
(1S)-(+)-Camphorsulfonyl-(2-phenyl-3-methyl)-imidazolinium
iodide
(21). (1S)-(−)-Camphorsulfonyl-(2-phenyl)-imidazole
◦
mp 217 C; ESI, m/e 479 (M+, 100%); IR (KBr) 1591m, 1557s,
(20) (1.15 g, 3.2 mmol) was dissolved in dry dichloromethane
(15 mL). Methyl iodide (51.2 mmol, 16 equiv., 3.2 mL) was added
and the mixture was refluxed overnight. The solvent and the
excess of methyl iodide were removed on the vacuum line to yield
1
1458s, 1348s, 1323s, 1193s, 1142s, 1059s, 699s cm−1; H NMR
(200 MHz) d 8.01 (dd, J = 1.3 Hz, J = 1.6 Hz, 2 H, Ar–H),
7.90–7.78 (m, 3 H, Ar–H), 7.44 (dd, J = 0.9 Hz, J = 2.4 Hz, 6 H,
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a yellowish foam (1.3 g, 2.6 mmol, 88%). 21 was used without
further purification in the anion exchange, since it was highly
hygroscopic.
Manipulation of the PF6 salt mixture 12b : 17b with TFA.
The mixture of (+)-(4R,5R)-1-acetyl-2,4,5-triphenyl-3-methyl-
trans-imidazolinium hexafluorophosphate (12b) and (+)-(4R,5R)-
1-benzoyl-2,3-methyl-4,5-diphenyl-trans-imidazolinium hexafluo-
rophosphate (17b) (12 mg, 0.02 mmol) with a ratio of 1 : 2 was
dissolved in dry dichloromethane (0.3 mL). 20% trifluoroacetic
acid in dichloromethane (0.01 mL) was added and the mixture
was stirred for 24 h at r.t. After adding water (1 mL) the mixture
was shaken strongly, the phases were separated and the organic
layer was washed with water (2 × 0.5 mL), dried (Na2SO4) and
evaporated under vacuum. Evaporation of the remaining solvent
under high vacuum yielded a colourless oil (12 mg, 0.02 mmol,
100%). The ratio of the rearrangement products increased from
1 : 2 up to 1 : 6 according to the 1H NMR spectra.
(1S)-(+)-Camphorsulfonyl-(2-phenyl-3-methyl)-imidazolinium
hexafluorophosphate
(21b). (1S)-(+)-Camphorsulfonyl-(2-
phenyl-3-methyl)-imidazolinium iodide (21) (0.4 g, 0.78 mmol)
was dissolved in dry dichloromethane (6 mL) and 1.5 equiv.
potassium hexafluorophosphate (0.22 g, 1.17 mmol) was added.
The mixture was stirred at r.t. overnight, quenched with water
(6 mL) and stirred for an additional hour. The organic phase was
washed with water (3 x 4 mL), dried (Na2SO4) and evaporated.
Recrystallisation in ethyl acetate gave 21b as a white solid (0.230 g,
0.4 mmol, 56%). [a]D24 = 6 (c = 1.05 in CH3CN), mp 166 ◦C;
MS (EI), m/e 375 (M+, 10%); IR (KBr) 2969m, 2929m, 1738s,
1639s, 1504m, 1445m, 1374s, 1176s, 1035m, 840s cm−1; 1H NMR
(200 MHz, DMSO) d 7.69–7.66 (m, 5 H, Ar–H), 4.52–4.16 (m,
4 H), 3.79 (d, J = 3.8 Hz, 1 H), 3.40 (d, J = 2.0 Hz, 1 H), 3.00
(s, 3 H, N–Me), 2.44–2.32 (m, 1 H), 2.05–1.89 (m, 4 H), 1.37 (d,
J = 2.0 Hz, 2 H), 0.83 (s, 3 H, Me), 0.75 (s, 3 H, Me); 13C NMR
Acknowledgements
Financial support by Fonds der Chemischen Industrie and DFG
is gratefully acknowledged. In addition we would like to thank Dr
Dra¨ger for HRESI measurements.
=
(50 MHz) d 213.9 (q, C O), 164.9 (q, NCN), 133.0 (+, Ar), 128.9
(+, Ar), 121.5 (q, Ar), 58.2 (q, C(1)), 51.9 (−), 48.2 (q, C(7)), 47.9
(−), 42.0 (−, C(4)), 41.9 (+, C(3)), 35.5 (+, NMe), 26.2 (−, C(6)),
24.9 (−, C(5)), 19.2 (+, Me), 19.1 (+, Me). HRMS (ESI) found:
M 375.1756. C20H27N2O3S requires: 375.1742.
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2290 | Org. Biomol. Chem., 2006, 4, 2285–2290
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The Royal Society of Chemistry 2006
©