Solvent-free microwave-assisted preparation of chiral ionic liquids from (-)-N-methylephedrine

Article abstract of DOI:10.1002/ejoc.200300601

An efficient method for the preparation of chiral ionic liquids based on (1R,2S)-(-)-ephedrinium salts under solvent-free conditions and microwave activation is described. The influence of non-specifically thermal microwave effects - consistent with mecha

Full text of DOI:10.1002/ejoc.200300601

FULL PAPER
Solvent-Free Microwave-Assisted Preparation of Chiral Ionic Liquids from
(؊)-N-Methylephedrine
[a]
[a]
[a]
´
Giang Vo Thanh,* Bruce Pegot, and Andre Loupy
Keywords: Solvent-free reactions / Microwave activation / Ionic liquids / Chirality / (Ϫ)-Ephedrine / Green chemistry
An efficient method for the preparation of chiral ionic liquids
based on (1R,2S)-(−)-ephedrinium salts under solvent-free
conditions and microwave activation is described. The influ-
ence of non-specifically thermal microwave effects − consi-
stent with mechanistic considerations − is discussed.
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2004)
Introduction
In view of the emerging importance of ILs as reaction
media in organic syntheses, and our general interest in MW-
assisted chemical processes, we report here the first syn-
thesis of chiral ILs bearing chiral ephedrinium cations using
solvent-free reactions and MW activation under green
chemistry conditions.
Ionic liquids (ILs), or room-temperature molten salts, are
being advanced as new clean media that have attracted in-
creasing interest over recent years, particularly in the area
of green chemistry and especially in synthetic and catalytic
transformations.[1] Among them, chiral ILs are particularly
attractive for their potential applications to chiral discrimi-
nation, including asymmetric syntheses and optical resolu-
tion of racemates. However, very few chiral ILs, 1Ϫ5, have
been reported so far, lead to successful chiral discrimi-
nation[2,3] and only four of them, 2Ϫ5, derived from the
‘‘chiral pool’’.[3,4] Recently, K. Saigo et al.[5] have designed
and synthesized a novel imidazolium ionic liquid with
cyclophane-type planar chirality (6), which showed poten-
tial as an ionic liquid chiral solvent for asymmetric syn-
thesis and/or optical resolution. All these ionic liquids were
prepared under classical conditions. Some of them are pre-
sented in Scheme 1.
Microwave (MW) activation as a non-conventional en-
ergy source has emerged as a powerful technique to pro-
mote a variety of chemical reactions and has become a very
popular and useful technology in organic chemistry.[6] The
combination of solvent-free conditions and MW irradiation
leads to large reductions in reaction times, enhancement in
conversions and, sometimes, in selectivity, and has several
features of the eco-friendly approach, termed green chemis-
try.[7] This method was successfully applied to the synthesis
of several ILs based on imidazolium salts.[8] Strict compari-
sons with conventional heating have been reported only rar-
ely,[8h] so specific MW effects have not been particularly
studied.
Results and Discussion
The synthesis of the chiral ephedrinium cation has al-
ready been described in the literature.[3a] However, only the
salt 3 was synthesized, by alkylation of (Ϫ)-N-methyl-
ephedrine followed by anion exchange with lithium bis(tri-
fluoromethanesulfonyl)imide (Li[(CF3SO2)2N]). In this case
all reaction steps were performed under classical conditions
and using Me2SO4 as alkylating agent, the use of which is
now very limited for organic synthesis, especially under
green chemistry conditions, owing to its carcinogenic effect
(as for all alkylating agents).
The aim of our study is to underline the potential of
coupling solvent-free reaction with focused MW activation,
and further to check nonthermal MW-specific effects by
comparing the results with those obtained using conven-
tional heating under identical conditions.
Our synthesis was initiated by the direct alkylation of
(1R,2S)-N-methylephedrine (7), easily obtained by re-
ductive amination of (1R,2S)-ephedrine using an
EschweilerϪClark procedure,[9] to N-alkylmethylephedrine
derivatives. A series of different alkyl chain lengths was
tested. All the MW reactions were performed in the CEM
Discover monomode system with strict control of power
and temperature during the reaction and in the absence of
any solvent (Scheme 2).
[a]
´
´
Laboratoire des Reactions Selectives sur Supports, ICMMO,
ˆ
´
CNRS UMR 8615, Batiment 410, Universite Paris-Sud,
91405 Orsay Cedex, France
Microwaves are electromagnetic waves generated by an
alternating electric field of high frequency. The energy as-
Fax: (internat.) ϩ 33-(0)1-69154679
E-mail: gvothanh@icmo.u-psud.fr
1112
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/ejoc.200300601
Eur. J. Org. Chem. 2004, 1112Ϫ1116

Solvent-Free Microwave-Assisted Preparation of Chiral Ionic Liquids
FULL PAPER
Scheme 1
Scheme 2
sociated with a MW photon (1 J·molϪ1 by application of temperature, vessel, profile of rise in temperature). The
Planck law E ϭ hν with ν ϭ 2450 MHz) is far too small to main results are given in Table 1.
induce any excitation of molecules. It can, however, induce
Table 1. Solvent-free N-alkylation of (1R,2S)-N-methylephedrine
with n-alkyl bromides in open vessels under monomode microwave
irradiation (CEM Discover system)
thermal effects due to some internal friction between polar
molecules during their changes in orientation with each
alternation of the electric field. In addition, they can induce
some electrostatic interactions with polar materials by
Entry
R
Time
Temperature Isolated yield (%)
dipoleϪdipole interactions, rather similar to the behaviour
of a dipolar solvent. By analogy and extension of the in-
terpretation of solvent effects, the carbonϪhalogen covalent
bond rupture can be facilitated by an increase in the po-
larity of the system during the progress of the reaction be-
tween the ground state and the transition state. An increase
in efficiency could result, therefore, from both thermal ef-
fects (which provide adequate thermal energy) and specific
polar (nonspecifically thermal) effects.[6c]
(min.) (°C)
MW
∆
[a]
1
2
3
4
5
6
7
C4H9
10
30
45
40
40
120
90
93
95
110
95
110
95
83
85
96
76
95
81
80
6
18
C8H17
C10H21
C16H33
18
71
59
110
[a]
Reactions were conducted in closed vessels owing to the low
boiling point of C4H9Br (b.p. 100 °C).
In order to check the possible intervention of nonspecifi-
cally thermal MW-specific effects, control experiments were
conducted using a thermostatted oil bath (∆ ϭ conven-
Table 1 clearly shows the influence of very important
tional heating) under identical reaction conditions (time, non-specifically thermal MW effects. This observation is
Scheme 3
Eur. J. Org. Chem. 2004, 1112Ϫ1116
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 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1113

G. Vo Thanh, B. Pegot, A. Loupy
FULL PAPER
consistent with mechanistic considerations, as the mecha- crude products (non-isolated) resulting from the quaternis-
nism involves the development of dipoles in the transition ation step (first step) were directly submitted to the anion-
state and therefore an increase in the polarity of the system exchange step (Scheme 4). All reactions were conducted in
during the progress of the reaction from the ground state the CEM Discover monomode system in open vessels and
to the transition state, which can respond to specific MW under solvent-free conditions. The more significant results
enhancement[6c,6f] (Scheme 3). This assumption was more are given in Table 2.
or less suggested by Abramovitch in the conclusion of his
The data of Table 2 generally indicate good overall yields
review in 1991[10] stating that ‘‘if the MW energy is ab- obtained within short reaction times. In the case of the bu-
sorbed selectively by a reactant, a complex or an intermedi- tyl chain, reactions were carried out in closed vessels owing
ate on the way to rate-determining transition states, then to the low boiling point of bromobutane (b.p. 100 °C).
large reaction rate increases will result’’.
Whereas the one-pot method A of mixing the three compo-
The next step in the synthesis involves transformation of nents seems to be satisfactory in the case of Entries 8Ϫ11
ephedrinium bromide salts 9 to ionic liquids 10 by anion where R ϭ C4H9, the one-pot two-step method B is better
exchange of 9 with alkaline or ammonium salts of charge- for R ϭ n-C8H17 (Entries 13 and 14). In this last case, there
delocalized soft anions (BF4Ϫ, PF6Ϫ, TfOϪ). Generally, this is no necessity to work in closed system. In order to demon-
step was carried out at reflux in a large excess of acetone strate the MW-specific effects, one representative experi-
as solvent for several hours or days.[11] Good yields were ment was conducted using a thermostatted oil bath under
generally obtained in all cases.
identical reaction conditions (see Entry 9). This effect cer-
As already reported by Varma et al.,[8g] anion-exchange tainly arises from the first step of this sequence reaction
metathesis is easily performed under MW activation using (see Table 1). The yield obtained under conventional heat-
a domestic oven. In this way, 1,3-dialkylimidazolium tetra- ing (2%) is far lower than the MW one (72%) within 10 min
fluoroborate salts were prepared within good yields for only at 93 °C.
a few minutes of reaction time. Unfortunately, no control
of power and temperature was achieved during the course 10 are viscous liquids at room temperature (except the salts
of the reaction. 10 where R ϭ C16H33, C4H9 and X ϭ PF6, which are solids
It is important to note that all chiral ephedrinium salts
In order to simplify the workup of the preparation of with m.p. of 95 and 92 °C, respectively) in contrast with the
chiral ILs, and as part of our general interest in MW-as- ephedrinium salt 3, described by Wasserscheid[3a] which is
sisted chemical processes, we decided to perform this pro- a solid (m.p. 54 °C).
cedure in a two-step but one-pot reaction sequence. All
Conclusion
In conclusion, we have developed an efficient procedure
for the preparation of chiral ILs from (1R,2S)-ephedrine, a
natural amino alcohol, using solvent-free reactions and
MW activation under green chemistry conditions. Evidence
was also obtained for an important nonthermal MW-
specific effect. The preparation of optically active ILs de-
Scheme 4
rived from natural amino acids will be discussed in a later
Table 2. One-pot solvent-free microwave-assisted preparation of (1R,2S)-N-alkyl-N-methylephedrinium salts. Method A: reaction of the
direct mixture of the three components. Method B: two-step procedure: alkylation followed by salt exchange
Entry
R
Method
MX
MW system
Time (Temp.)[a]
Yield (%)
8
9
C4H9
A
A
A
A
A
A
B
B
B
B
B
B
B
NaPF
Closed
Closed
Closed
Closed
Closed
Open
Open
Open
Open
Open
10 (93)
10 (93)
10 (93)
20 (93)
45 (95)
45 (95)
30 (110) ϩ35 (95)
30 (110) ϩ35 (95)
30 (110) ϩ35 (95)
40 (110) ϩ35 (110)
40 (110) ϩ35 (95)
120 (95) ϩ60 (95)
120 (95) ϩ60 (95)
85
NH4PF6
NH4BF4
KOTf
NH4PF6
NH4PF6
NH4PF6
NaPF6
KOTf
NaPF6
KOTf
NaPF6
KOTf
72 (2)[b]
77
10
11
12
14
13
15
16
17
18
19
20
79
10
51
80
77
91
85
84
C8H17
C10H21
C16H33
Open
Open
Open
77
88
[a]
[b]
Conditions for alkylation ϩ ion exchange; time in min and temperature in °C.
Yield obtained by conventional heating is given
in brackets.
1114
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2004, 1112Ϫ1116

Solvent-Free Microwave-Assisted Preparation of Chiral Ionic Liquids
FULL PAPER
(1R,2S)-N-Decyl-N,N-dimethylephedrinium Bromide
9
(R
؍
report. Applications of chiral ILs as green media for asym-
metric synthesis and catalysis are currently under investi-
gation.
C10H21): M.p. 92 °C. [α]2D5 ϭ Ϫ13.5 (c ϭ 2.00, CHCl3). H NMR
(CDCl3): δ ϭ 0.88 (t, J ϭ 6 Hz, 3 H), 1.10Ϫ1.15 (m, 19 H),
1.60Ϫ1.90 (m, 2 H), 3.29 (s, 3 H), 3.44 (s, 3 H), 3.60Ϫ3.95 (m, 3
H), 5.48 (d, J ϭ 5.8 Hz, 1 H), 5.75(d, J ϭ 4.8 Hz, 1 H), 7.20Ϫ7.60
(m, 5 H) ppm. 13C NMR (CDCl3) : δ ϭ 6.7, 13.5, 22.0, 22.3, 25.8,
28.6, 28.7, 28.8, 28.9, 31.2, 49.0, 49.1, 63.3, 67.3, 72.5, 125.4, 127.0,
127.9, 140.7 ppm.
1
Experimental Section
General Remarks: Microwave experiments were conducted using a
CEM Discover Synthesis Unit (monomode system) operating at
2450 MHz monitored by a PC computer.[12] Waves are focussed by
a circular wave-guide all around the cavity. The temperature was
measured by optical fibre or infrared detection with continuous-
feedback temperature control, and maintained at a constant value
by power modulation (0Ϫ300 W). Stirring was provided by an in
situ magnetic variable speed stirrer when reactions were performed
in closed vessels under controlled pressure or with mechanical stir-
ring in the case of reactions in open vessels. Reactions were per-
formed either in glass vessels (capacity 10 mL) sealed with a septum
or in open vessels (capacity 100 mL). The pressure was controlled
by a load cell connected to the vessel via a needle, which penetrated
just below the septum surface.
(1R,2S)-N-Hexadecyl-N,N-dimethylephedrinium Bromide 9 (R ؍
C16H33): M.p. 86 °C. [α]2D5 ϭ Ϫ11 (c ϭ 2.00, CHCl3). 1H NMR
(CDCl3): δ ϭ 0.88 (t, J ϭ 6.8 Hz, 3 H), 1.05Ϫ1.50 (m, 31 H),
1.51Ϫ1.95 (m, 2 H), 3.32 (s, 3 H), 3.49 (s, 3 H), 3.55Ϫ3.90 (m, 3
H), 5.47 (d, J ϭ 4.8 Hz, 1 H), 5.79(s, 1 H), 7.2Ϫ7.55 (m, 5 H) ppm.
13C NMR (CDCl3): δ ϭ 6.9, 13.7, 22.2, 22.5, 26.0, 27.8, 28.4, 28.9,
29.1, 29.2, 29.3, 31.5, 49.2, 49.2, 63.6, 67.5, 72.6, 125.6, 127.2,
128.1, 140.9 ppm.
General Procedure for the Solvent-free ‘‘One-pot’’ Preparation of
Chiral Ionic Liquids 10 from 7 under Microwave Irradiation (Method
A): A mixture of (1R,2S)-N-methylephedrine 7 (1.79 g, 10 mmol),
1-bromoalkane (10 mmol) and alkaline salt MX (10 mmol) was ir-
radiated with microwaves at the temperature and for the time given
in Table 2. The reaction mixture was brought to room temperature
and washed with EtOAc (2 ϫ 10 mL). The crude product was dis-
solved in acetone. After filtration, the solvent was evaporated under
reduced pressure. Purification by flash chromatography on silica
gel (CH2Cl2/MeOH, 98:2) gave the salt 10 as a yellow viscous oil,
except 10 R ϭ C4H9 and X ϭ PF6.
Melting points were measured with a Kofler bank. NMR spectra
were recorded in CDCl3 or [D6]acetone. 1H NMR spectra were
recorded at 250 or 200 MHz. Chemical shifts (δ) are reported in
ppm relative to TMS as internal standard. J values are given in
Hz. 13C NMR spectra were recorded at 62.5 or 50 MHz. IR spectra
were recorded with an FT-IR PerkinϪElmer instrument. TLC was
carried out with 0.2-mm thick silica-gel plates (GF254). Visualis-
ation was accomplished by UV light or phosphomolybdic acid
solution. The columns were hand packed with silica-gel 60
(200Ϫ300).
(1R,2S)-N-Butyl-N,N-dimethylephedrinium Hexafluorophosphate 10
(R ؍ C4H9, X ؍ PF6): M.p. 92 °C. [α]2D5 ϭ Ϫ10 (c ϭ 1.00, acetone).
1H NMR ([D6]acetone): δ ϭ 1.01 (t, J ϭ 7.4 Hz, 3 H), 1.35 (d, J ϭ
6.8 Hz, 3 H), 1.47 (H, J ϭ 7.4 Hz, 2 H), 1.97 (m, 2 H); 3.40 (s, 3
H), 3.47 (s, 3 H), 3.64Ϫ3.85 (m, 3 H), 5.28 (d, J ϭ 3.4 Hz, 1 H),
5.78 (s, 1 H), 7.15Ϫ7.53 (m, 5 H) ppm. 13C NMR ([D6]acetone):
δ ϭ 7.2, 14.0, 20.9, 25.7, 49.8, 50.1, 65.6, 70.6, 74.6, 126.9, 129.0,
129.7, 142.8 ppm. IR (KBr, cmϪ1): ν˜ ϭ 3582, 2969, 2880, 1477,
1424, 1084, 877, 726, 641, 557. C15H26F6NOP (381.3): calcd. C
47.24, H 6.87, F 29.89, N 3.67, P 8.12; found C 47.14, H 6.74, F
26.78, N 3.78, P, 8.12.
All reagents and solvents were purchased from commercial sources
(Acros, Aldrich) and were used without further purification.
General Procedure for the Solvent-Free N-Alkylation of 7 under Mi-
crowaves:
A mixture of (1R,2S)-N-methylephedrine 7 (1.79 g, 10 mmol) and
1-bromoalkane (10 mmol) was irradiated with microwaves at the
temperature and for the time given in Table 1. The reaction mixture
was brought to room temperature and washed with EtOAc (2 ϫ
10 mL). The crude product was dissolved in CH2Cl2. After fil-
tration, the solvent was evaporated under reduced pressure to af-
ford the solid which did not need further purification.
(1R,2S)-N-Butyl-N,N-dimethylephedrinium Trifluoromethanesulfon-
1
ate 10 (R ؍ C4H9, X ؍ OTf): [α]2D5 ϭ Ϫ11 (c ϭ 2.00, acetone). H
NMR ([D6]acetone): δ ϭ 1.01 (t, J ϭ 7.4 Hz, 3 H), 1.35 (d, J ϭ
6.8 Hz, 3 H), 1.46 (H, J ϭ 7.4 Hz, 2 H), 1.96 (m, 2 H), 3.38 (s, 3
H) 3.45 (s, 3 H), 3.6Ϫ3.84 (m, 3 H), 5.25 (d, J ϭ 4.8 Hz, 1 H),
5.78(s, 1 H), 7.15Ϫ7.54 (m, 5 H) ppm. 13C NMR ([D6]acetone):
δ ϭ 6.4, 13.2, 19.2, 24.2, 30.5, 48.7, 49.0, 63.4, 68.5, 73.1, 125.3,
127.6, 128.3, 140.6 ppm. IR (neat, cmϪ1): ν˜ ϭ 3418, 2968, 2880,
1495, 1455, 1278, 1163, 1030, 759, 721, 639, 574. C16H26F3NO4S:
calcd. C 49.86, H 6.80, F 14.79, N 3.63, S 8.32; found C 50.02, H
6.68, F 14.64, N 3.87, S 8.18.
Reactions under conventional heating were carried out with exactly
the same vessel and under similar conditions of time and tempera-
ture (see Table 1) but in a preheated oil bath.
(1R,2S)-N-Butyl-N,N-dimethylephedrinium Bromide 9 (R ؍ C4H9):
M.p. 95Ϫ96 °C. [α]D25 ϭ Ϫ12.1 (c ϭ 1.57, CHCl3). 1H NMR
(CDCl3): δ ϭ 1.01 (t, J ϭ 7.3 Hz, 3 H), 1.19 (d, J ϭ 6.8 Hz, 3 H),
1.44 (m, 2 H), 1.71 (m, 2 H), 3.30 (s, 3 H), 3.44 (s, 3 H), 3.59Ϫ3.87
(m, 3 H), 5.50 (d, J ϭ 6 Hz, 1 H), 5.76 (s, 1 H), 7.26Ϫ7.53 (m, 5
H) ppm. 13C NMR (CDCl3): δ ϭ 6.8, 13.3, 19.2, 24.3, 49.1, 49.3,
63.2, 67.4, 72.6, 125.5, 127.1, 128.0, 140.8 ppm.
General Procedure for the Solvent-free ‘‘Two-step Sequence’’ Prep-
aration of Chiral Ionic Liquids 10 from 7 under Microwaves (Method
B): A mixture of (1R,2S)-N-methylephedrine 7 (1.79 g, 10 mmol)
and 1-bromoalkane (10 mmol) was irradiated with microwaves at
(1R,2S)-N,N-Dimethyl-N-octylephedrinium Bromide 9 (R ؍ C8H17): the temperature and for the time given in Table 2. Alkaline salt MX
1
M.p. 88 °C. [α]2D5 ϭ Ϫ13.5 (c ϭ 2.00, CHCl3). H NMR (CDCl3):
(10 mmol) was added and the resulting mixture was then placed
under MW irradiation for an additional period of time and tem-
δ ϭ 0.89 (t, J ϭ 6.8 Hz, 3 H), 1.13Ϫ1.40 (m, 15 H), 1.50Ϫ1.85 (m,
2 H), 3.26 (s, 3 H), 3.38 (s, 3 H), 3.55Ϫ3.95 (m, 3 H), 5.51 (d, J ϭ perature as reported in Table 2. The reaction mixture was brought
5.6 Hz, 1 H), 5.71(s, 1 H), 7.20Ϫ7.49 (m, 5 H) ppm. 13C NMR
(CDCl3): δ ϭ 6.6, 13.4, 21.9, 22.2, 25.7, 28.4, 28.6, 31.0, 48.8, 49.0,
63.2, 67.2, 72.4, 125.3, 126.9, 127.8, 140.6 ppm.
to room temperature and washed with EtOAc (2 ϫ 10 mL). The
crude product was dissolved in acetone. After filtration, the solvent
was evaporated under reduced pressure. Purification by flash chro-
Eur. J. Org. Chem. 2004, 1112Ϫ1116
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 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1115

G. Vo Thanh, B. Pegot, A. Loupy
FULL PAPER
matography on silica gel (CH2Cl2/MeOH, 98:2) afforded the salt
C27H50F6NOP: calcd. C 59.00, H 9.17, F 20.74, N 2.55, P 5.64;
10 as a yellow viscous oil, except 10 R ϭ C16H33 and X ϭ PF6.
found C 58.85, H 9.06, F 18.94, N 2.52, P 5.60.
(1R,2S)-N,N-Dimethyl-N-octylephedrinium Hexafluorophosphate 10
(R ؍ C8H17, X ؍ PF6): [α]D25 ϭ Ϫ5.5 (c ϭ 2.00, acetone). 1H NMR
(1R,2S)-N-Hexadecyl-N,N-dimethylephedrinium Trifluoromethane-
sulfonate 10 (R ؍ C16H33, X ؍ OTf): [α]2D5 ϭ Ϫ5.5 (c ϭ 2.00, ace-
([D6]acetone): δ ϭ 0.89 (t, J ϭ 6.7 Hz, 3 H), 1.21Ϫ1.43 (m, 15 H), tone). 1H NMR ([D6]acetone): δ ϭ 0.88 (t, J ϭ 6.2 Hz, 3 H),
1.85Ϫ2.05 (m, 2 H), 3.19 (s, 3 H), 3.34 (s, 3 H), 3.59Ϫ3.82 (m, 3 1.15Ϫ1.50 (m, 31 H),1.90Ϫ2.07 (m, 2 H,), 3.40 (s, 3 H), 3.47 (s, 3
H), 5.19 (s, 1 H), 5.75(s, 1 H), 7.25Ϫ7.55 (m, 5 H) ppm. 13C NMR
H), 3.60Ϫ3.90 (m, 3 H), 5.38 (d, J ϭ 4.8 Hz, 1 H), 5.77 (s, 1 H),
([D6]acetone): δ ϭ 5.5, 12.9, 21.6, 25.4, 27.8, 28.1, 29.0, 30.9, 48.0, 7.30Ϫ7.55 (m, 5 H) ppm. 13C NMR ([D6]acetone): δ ϭ 6.4, 14.0,
48.2, 63.1, 68.5, 72.4, 125.1, 127.1, 127.7, 140.7 ppm. IR (neat, 22.5, 26.0, 29.0, 29.2, 29.3, 29.4, 29.5, 29.6, 30.7, 31.8, 48.97, 48.99,
cmϪ1) ν˜ ϭ 3582, 2929, 2859, 1492, 1454, 1047, 998, 839, 739, 720, 63.85, 68.64, 73.29, 126.0, 127.7, 128.5, 140.8 ppm. IR (neat, cmϪ1
)
676, 558. C19H34F6NOP: calcd. C 52.17, H 7.83, F 26.06, N 3.20,
P 7.08; found C 52.41, H 7.87, F 23.54, N 3.11, P 6.80.
ν˜ ϭ 3400, 2921, 2852, 1468, 1279, 1225, 1157, 1031, 764, 720,
638, 572. C28H50F3NO4S: calcd. C 60.73, H 9.10, F 10.29, N 2.53,
S 5.79; found C 60.76, H 9.42, F 10.22, N 2.48, S 5.91.
(1R,2S)-N,N-Dimethyl-N-octylephedrinium Trifluoromethanesulfon-
ate 10 (R ؍ C8H17, X ؍ OTf): [α]2D5 ϭ Ϫ7.0 (c ϭ 2.00, acetone).
1H NMR ([D6]acetone): δ ϭ 0.88 (t, J ϭ 6.6 Hz, 3 H), 1.05Ϫ1.63
(m, 15 H),1.90Ϫ2.05 (m, 2 H), 3.41 (s, 3 H), 3.48 (s, 3 H),
3.60Ϫ3.90 (m, 3 H), 5.37 (d, J ϭ 3.8 Hz, 1 H), 5.78 (s, 1 H),
7.25Ϫ7.55 (m, 5 H) ppm. 13C NMR (CDCl3): δ ϭ 6.4, 13.8, 22.3,
22.4, 25.9, 28.7, 28.8, 30.6, 31.3, 48.8, 49.0, 63.6, 68.5, 73.2, 125.4,
127.6, 128.3, 140.7 ppm. IR (neat, cmϪ1) ν˜ ϭ 3410, 2957, 2930,
1494, 1469, 1278, 1225, 1164, 1030, 759, 720, 639, 573.
C20H34F3NO4S: calcd. C 54.40, H 7.76, F 12.91, N 3.17, S 7.26;
found C 54.43, H 7.87, F 12.86, N 3.31, S 7.14.
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10 (R ؍ C10H21, X ؍ PF6): [α]2D5 ϭ Ϫ9.0 (c ϭ 2.00, acetone). H
[3b]
2002, 200Ϫ201.
F. Glorius, G. Altenhoff, R. Goddard, C.
NMR ([D6]acetone): δ ϭ 0.87 (t, J ϭ 6.4 Hz, 3 H), 1.22Ϫ1.47 (m,
19 H), 1.92Ϫ2.06 (m, 2 H), 3.40 (s, 3 H), 3.47 (s, 3 H), 3.65Ϫ3.87
(m, 3 H), 5.26 (d, J ϭ 4 Hz, 1 H), 5.78 (s, 1 H); 7.30Ϫ7.55 (m, 5
H) ppm. 13C NMR ([D6]acetone): δ ϭ 6.4, 14.0, 22.5, 22.6, 26.0,
29.0, 29.2, 29.3, 29.4, 31.8, 49.0, 49.2, 64.2, 69.4, 73.0, 125.4, 128.0,
128.7, 140.2 ppm. IR (neat, cmϪ1) ν˜ ϭ 3537, 2993, 2917, 2853,
1493, 1478, 1058, 845, 764, 721, 634, 558. C21H38F6NOP: calcd. C
54.18, H 8.23, F 24.49, N 3.01, P 6.65; found C 54.38, H 8.19, F
22.83, N 2.95, P 6.60.
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A. De la
Hoz, A. Diaz-Ortis, A. Moreno, F. Langa, Eur. J. Org. Chem.
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(1R,2S)-N-Decyl-N,N-dimethylephedrinium Trifluoromethanesul-
fonate 10 (R ؍ C10H21, X ؍ OTf): [α]2D5 ϭ Ϫ6.5 (c ϭ 2.00, acetone).
1H NMR ([D6]acetone): δ ϭ 0.87 (t, J ϭ 6.4 Hz, 3 H), 1.20Ϫ1.47
(m, 19 H), 1.95Ϫ2.05 (m, 2 H), 3.40 (s, 3 H), 3.47 (s, 3 H),
3.60Ϫ3.90 (m, 3 H), 5.37 (d, J ϭ 4.3 Hz, 1 H), 5.78 (d, J ϭ 3.8 Hz,
1 H), 7.25Ϫ7.60 (m, 5 H) ppm. 13C NMR (CDCl3): δ ϭ 6.4, 13.9,
22.4, 25.9, 28.9, 29.0, 29.1, 29.2, 30.6, 31.6, 48.8, 49.0, 63.7, 68.5,
73.2, 125.4, 127.6, 128.3, 140.7 ppm. IR (neat, cmϪ1) ν˜ ϭ 3411,
2927, 2856, 1494, 1468, 1278, 1225, 1164, 1030, 759, 721, 640, 573.
C22H38F3NO4S: calcd. C 56.27, H 8.16, F 12.14, N 2.98, S 6.83;
found C 56.31, H 7.94, F 12.41, N 2.93, S 6.86.
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(1R,2S)-N-Hexadecyl-N,N-dimethylephedrinium Hexafluorophos-
phate (R ؍ C16H33, X ؍ PF6): M.p. 95 °C. [α]2D5 ϭ Ϫ4.5 (c ϭ 2.00,
acetone). 1H NMR ([D6]acetone): δ ϭ 0.88 (t, J ϭ 6.8 Hz, 3 H),
1.15Ϫ1.45 (m, 31 H), 1.95Ϫ2.05 (m, 2 H), 3.42 (s, 3 H), 3.49 (s, 3
H), 3.65Ϫ3.90 (m, 3 H), 5.31 (d, J ϭ 3.8 Hz, 1 H), 5.79 (d, J ϭ
3.4 Hz, 1 H), 7.30Ϫ7.55 (m, 5 H) ppm. 13C NMR ([D6]acetone):
δ ϭ 6.6, 13.84, 22.8, 29.0, 29.3, 29.6, 32.1, 49.4, 49.6, 64.4, 69.8,
73.6, 126.2, 128.0, 128.8, 141.9 ppm. IR (KBr, cmϪ1) ν˜ ϭ 3534,
2994, 2916, 2848, 1493, 1476, 1419, 1051, 856, 765, 720, 557.
Res. & Develop. 2002, 6, 374Ϫ378. [8g] R. S. Varma, V. V. Nam-
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For further more information, see: www.cemsynthesis.com
Received September 25, 2003
1116
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 1112Ϫ1116