Stability and decarbonylation of 1,3-dialkyl-2-formylimidazolium perchlorate in solution

Article abstract of DOI:10.1139/cjc-2012-0497

The stability of 1,3-dialkyl-2-formylimidazolium perchlorate 1 in solution was studied in detail and found to be related to its structure and the solvent character and temperature. 1 was stable in common solvents at room temperature and unstable in protic

Full text of DOI:10.1139/cjc-2012-0497

442
ARTICLE
Stability and decarbonylation of 1,3-dialkyl-2-formylimidazolium
perchlorate in solution
Hong-Xing Xin, Qi Liu, Hong Yan, and Xiu-Qing Song
Abstract: The stability of 1,3-dialkyl-2-formylimidazolium perchlorate 1 in solution was studied in detail and found to be
related to its structure and the solvent character and temperature. 1 was stable in common solvents at room temperature
and unstable in protic solvents under reflux. In protic solvents, such as H2O, MeOH, EtOH, and AcOH, 1 decarbonylated into
1,3-dialkylimidazole perchlorates 2, which was confirmed by 1H NMR, 13C NMR, HRMS, and X-ray spectroscopy. The
decarbonylation of 1 was proposed to occur via its hemiacetal formed by the addition of solvents based on the tracking NMR
spectra of 1 in deuterated reagents.
Key words: decarbonylation, solution stability, 2-formylimidazolium, imidazolium.
Résumé : On a étudié en détail la stabilité du perchlorate de 1,3-dialkyl-2-formylimidazolium 1 en solution et constaté qu’elle
dépend de la structure du composé, ainsi que du caractère du solvant et de la température. 1 est stable dans les solvants communs
a` température ambiante et instable dans les solvants protiques sous reflux. Dans les solvants protiques, tels que H2O, MeOH,
EtOH et AcOH, 1 se décarbonyle pour former des perchlorates de 1,3-dialkylimidazole 2, dont la présence a été confirmée par
RMN 1H, RMN 13C, SMHR et spectrométrie de rayons X. L’examen des spectres RMN de 1 dans des solvants deutérés donne a` penser
que la décarbonylation de 1 a pour intermédiaire son hémiacétal formé par ajout de solvants. [Traduit par la Rédaction]
Mots-clés : décarbonylation, stabilité en solution, 2-formylimidazolium, imidazolium.
perature for 12 h, 1 was also stable in CHCl3, AcOEt, acetone, and
DMSO but unstable in MeOH, EtOH, H2O, and AcOH. The decom-
position products of 1 were 1,3-dialkylimidazolium perchlorates 2
Introduction
Imidazoles have important functionalities in biological systems
and are often used as building blocks in medicinal chemistry.
Many compounds bearing this group have been widely studied
(Scheme 1). The structure of 2 was confirmed by NMR, HRMS, and
X-ray spectroscopy. In the 1H NMR spectra of 2, the aldehyde pro-
due to their physiological activities.1–6 Formylimidazolium salts
ton signals disappeared at lower fields (␦ 10.1–10.8 ppm). Taking
are important synthons for incorporating a permanently cationic
1
compound 2a as an example, its H NMR spectrum (Fig. 1: H5)
imidazolium group into a molecular framework. The utility of
contains a singlet (s, 1H) at 9.17 ppm that was attributed to the
1,3-dimethylformylimidazolium salt was reported in a variety
proton at C2 of the imidazole ring. The signals of the two protons
of reactions, such as Knoevenagel and Wittig reactions, Schiff
at C4 and C5 of the imidazole ring exhibited one doublet with a
base formation, based-mediated electrophilic substitution, and
coupling constant of 1.2 Hz for structural symmetry. The two iso-
oxidation, including the synthesis of the natural product nor-
propyl groups showed one heptet (2H) at 4.81 ppm and one dou-
zooanemonin.7 Formylimidazolium iodide was usually pre-
blet (12H) at 1.62 ppm with the same coupling constant of 6.4 Hz
pared by the formylation of 1,3-dimethylimidazolium iodide
for structural symmetry. In addition, the 13C NMR spectrum of 2a
with ethyl formate8 or dimethylformamide.9 Furthermore,
(Fig. 1: C5) displayed four signals (120.7 and 133.6 ppm correspond-
2-formylimidazolium chloride was synthesized by the reaction of
ing to the carbons of the imidazole ring and 22.0 and 53.2 ppm
N,N=-di(tert-butyl)-1,4-diazabutadiene with HCl gas.10 When pre-
ascribed to the isopropyl groups) and no C=O peak at approximately
paring 1,3-dialkyl-2-formylimidazolium perchlorates 1 by the re-
action of N,N=-dialkyl-1,4-diazabutadiene with HClO4 in AcOH, 1
Scheme 1. Decarbonylation of 1 into 2 in solvents.
was unstable in solutions. However, few reports study the stability
of the formylimidazolium perchlorates. Herein, the solution sta-
bility of 1 was investigated in common solvents and the structures
of the decomposition products were identified by NMR, HRMS,
and X-ray spectroscopy. A decomposition mechanism was pro-
posed for the decarbonylation of 1 based on the tracking NMR
spectra of 1 in deuterated reagents.
Results and discussion
The solution stability of 1 was studied and traced by HPLC in
common solvents at room temperature and refluxing tempera-
ture. At room temperature for 1 day, 1 was stable in MeOH, EtOH,
H2O, CHCl3, AcOEt, acetone, DMSO, and AcOH. At refluxing tem-
Received 12 December 2012. Accepted 21 February 2013.
H.X. Xin, Q. Liu, H. Yan, and X.Q. Song. College of Life Science and Bio-engineering, Beijing University of Technology, Pingleyuan Street No. 100, Chaoyang District, Beijing 100124,
China.
Corresponding author: Hong Yan (e-mail: hongyan@bjut.edu.cn).
Can. J. Chem. 91: 442–447 (2013) dx.doi.org/10.1139/cjc-2012-0497
Published at www.nrcresearchpress.com/cjc on 25 February 2013.

Xin et al.
443
Fig. 1. 1H NMR and 13C NMR spectra at room temperature. (H1 and C1) 1a in DMSO-d6; (H2 and C2) 1a in MeOH-d4; (H3 and C3) 1a and 0.05 mL
of MeOH in 0.5 mL of DMSO-d6; (H4 and C4) 1a and 0.05 mL of MeOH in 0.5 mL of DMSO-d6 after heating at 65 °C for 3 h; (H5 and C5) 2a in
DMSO-d6; (H6 and C6) 2a in MeOH-d4.
␦ 177–183 ppm. The HRMS of 2a (and that for all other compounds)
revealed a strong peak at 153.1404 corresponding to [M-ClOϪ4 ]ϩ.
Single-crystal X-ray diffraction of 2b (Fig. 2) (CCDC No. 775890, see
Supplementary material section) also proved that the decomposition
products 2 were 1,3-dialkylimidazolium perchlorates.
The disappearance time of 1 under refluxing temperature is
summarized in Table 1detected by HPLC. In protic solvents,
0.01 mol L−1 of 1 fully decomposed in 4.5 h and was more unstable
in MeOH and H2O than in EtOH or AcOH. The stability order of 1
was 1b> 1a> 1c. The stability of 1 was mainly affected by imidazole
structure and the solvent character besides the solvent tempera-
ture. The influence of the imidazole structure was embodied in
the inductive effect of the nitrogen, the hyperconjugation effect,
and the steric hindrance of N-substituents. The electron-attracting
inductive effect of nitrogen in the imidazole ring is beneficial to
the decarbonylation of 1 to 2, which is in accordance with obser-
vations in other azoles.11–12 The electron-donating effect and
steric hindrance of N-substituents lead to the stability order of 1 as
1b> 1a> 1c in the same solvent. The electron-donating effect of the
Cy group in 1b and the i-Pr group in 1a weakens the electron-
attracting effect of the imidazole ring and decreases the decarbon-
ylation rate. The decarbonylation rates of 1b and 1a were greater
Published by NRC Research Press

444
Can. J. Chem. Vol. 91, 2013
Fig. 2. ORTEP of 2b, one of two independent molecules at 50%
probability.
H5 and C6 or H6 and C6 spectra. In MeOH, the mechanism of 1a
decarbonylating to 2a was the addition of a MeOH molecule to 1a
to form the intermediate 3a and the decarbonylation of 3a to
form 2a and methyl formate (Scheme 2).
The decarbonylation of 1a in H2O was also investigated by the
above method, and the spectra are shown in Fig. 3. The aldehyde
group signals of 1a vanished and new signals (␦H 6.51 ppm, ␦C 82.0 ppm,
HO-CH-OH) appeared in H7 and C7 spectra. When H2O was added
to the DMSO-d6 for 1a, a new low hydrogen signal (␦H 7.96 ppm, 2H)
appeared in the H8 spectrum relative to the H7 spectrum, and
there was no new carbon signal in the C8 spectrum compared
with the C7 spectrum. Those proved the formation of 3a= by addi-
tion of a H2O molecule joining the aldehyde group of 1a in which
a H2O molecule joined the aldehyde group of 1a to form gem-diol
(␦H 7.96 ppm). The OH groups of the gem-diol that did not appear
in the H7 spectrum due to addition by deuterated solvent (D2O)
and the CH(OD)2 carbon appeared in the C7 spectrum at 82.0 ppm.
When the sample of 1a in H2O and DMSO-d6 was heated at 100 °C
for 3 h, the signals of formic acid and 2a were detected in H9 and
C9 spectra. The signals at ␦H 8.11 ppm and ␦C 163.5 ppm were
attributed to formic acid. The mechanism of 1a decarbonylating
to 2a in H2O was the same as in MeOH and the hemiacetal 3a= was
the intermediate of decarbonylation of 1a to 2a (Scheme 3).
To investigate where the protons that end up on C2 of 2 come
from, the H11 and H12 recorded as 1H NMR spectra of 1a in
DMSO-d6 with 10% v/v MeOH-d4 and D2O after heating for 3 h are
shown in Fig. 4. Comparing the H11 and H12 spectra with the H4,
H9, and H5 spectra, the singlet (s, 1H) at C2 of 2a around 9.17 ppm
did not appear and the aldehyde group signals of methyl formate
and methanoic acid still existed. These indicate that the hydrogen
at C2 of 2a was deuterium and comes from solvents.
As observed from the differences between the NMR spectra of
1a in MeOH-d4 and MeOH, D2O, and H2O, 3a and 3a= only exist in
solvent and easily convert into 2a under heating. When 1a was
dissolved in MeOH or H2O and the solution dried in vacuo at room
temperature, the residue was still 1a. When it was dried under
refluxing, the residue was 2a but not 1a. This result shows that 3
is stable at room temperature and unstable at higher tempera-
tures such as heating. The thermal instability of 3 can further
explain the stability of 1 in solution. It also indicates that the
mechanism of decarbonylation of 1 includes the formation of
hemiacetal 3 by the nucleophilic attack of protic solvents on the
carbonyl of 1 and the decarbonylation of 3 to 2 at higher temper-
atures.
Table 1. Decomposition timea and rateb of 1 in solvents under reflux-
ing temperature.
Compound
MeOH (rate)
EtOH (rate)
H2O (rate)
AcOH (rate)
1a
1b
1c
1.5 (6.7)
2.0 (5.0)
1.0 (10.0)
3.5 (2.9)
3.0 (3.3)
1.5 (6.7)
1.5 (6.7)
1.5 (6.7)
1.0 (10.0)
3.5 (2.9)
4.5 (2.2)
2.5 (4.0)
aThe full disappearance time (h) of 0.5 mmol of 1 in 50 mL of solvent was
detected by HPLC.
bThe rate (mmol L–1 h–1) was the initial concentration of 1 divided by its
disappearance time.
than that of 1c. The steric hindrance of N-substituents hinders the
attack of the solvent on the carbonyl. The greater steric hindrance
of the Cy group relative to the i-Pr group slows the decarbon-
ylation of 1b relative to 1a. The solvent structure is an obvious
factor in the stability of 1, which is stable in nonprotic solvent and
unstable in protic solvent. Higher solvent polarities correspond to
a more rapid decomposition of 1. For example, 1a was totally
decomposed in AcOH for 3.5 h and in H2O for 1.5 h with decarbon-
ylation rates of 2.9 and 6.7 mmol L−1 h−1, respectively.
To study the decarbonylation of 1 in MeOH, 5 mg of 1a in
DMSO-d6 as the stable solvent, MeOH-d4 as the unstable solvent,
and DMSO-d6 with 10% v/v MeOH were placed into individual 10 mL
1
NMR tubes. After approximately 1 h, the H NMR and 13C NMR
spectra were recorded as H1 and C1, H2 and C2, and H3 and C3, as
shown in Fig. 1. Comparing the H2 and C2 spectra with the H1 and
C1 spectra (all solvent signals are easily recognized and sub-
tracted), the primary difference is that the signals of the aldehyde
group (␦H 10.11 ppm, 1H; ␦C 177.1 ppm) disappeared in MeOH-d4 and
new signals (␦H 6.19 ppm, 1H; ␦C 88.9 ppm) appeared. Only one
signal for the two protons at C4 and C5 of the imidazole ring
existed at ␦ 7.83 ppm, and the total number of protons remained
unchanged. These findings implied that new signals at ␦H 6.19 ppm
and at ␦C 88.9 ppm come from the conversion of the aldehyde
group, which was the only change. When MeOH was added to
DMSO-d6 for 1a, the H3 spectrum relative to the H2 spectrum
displayed greater intensities for a broad, low one-proton signal at
␦ 8.26 ppm and a sharp high three-proton singlet at ␦H 3.46 ppm.
In the C3 spectrum relative to the C2 spectrum, one new signal
appeared at ␦C 55.1 ppm. These changes indicated that the hemi-
acetal 3a was formed by addition in which a MeOH molecule
joined the aldehyde group of 1a to form an OH group (␦H 8.26 ppm)
and a CH3O group (␦H 3.46 ppm, ␦C 55.1 ppm) in MeOH. The signals
of the aldehyde group disappeared and new signals at ␦H 6.19 ppm
and ␦C 88.9 ppm (HO-CH-OCH3) appeared in MeOH. When the
sample of 1a in MeOH and DMSO-d6 was heated at 65 °C for 3 h, the
signals of methyl formate and 2a were detected in H4 and C4
spectra. The signals at ␦H 3.65, ␦H 8.19, ␦C 49.0, and ␦C 162.7 ppm
were attributed to methyl formate and the others to 2a shown in
Conclusion
1,3-Dialkyl-2-formylimidazolium perchlorate 1 was stable in
common solvents at room temperature and decarbonylated into
1,3-dialkylimidazole perchlorates 2 under reflux temperature in
protic solvents. The main factors affecting the stability of 1 were
the imidazole structure and the solvent character and tempera-
ture. By tracking the NMR spectra of 1 in deuterated reagents, the
mechanism of decarbonylation of 1 includes the addition of 1 by
solvent to form hemiacetal 3 and the decarbonylation of 3 to 2.
Experimental
All chemicals were of commercial quality; the solvents were
dried and purified by conventional methods. Melting points (un-
corrected) were determined using an X-5 instrument. NMR spectra
were recorded using a Bruker AVANCE 400 spectrometer. HRMS
spectra were recorded using an Agilent G3250AA LC/MSD TOF
mass spectrometer. HPLC instrument were the Agilent 1260 In-
finty and column was the Agilent Eclipse Plus C18 (4.6 × 100 mm,
3.5 ␮m).
Published by NRC Research Press

Xin et al.
445
Scheme 2. Reaction of 1a in MeOH.
Fig. 3. 1H NMR spectra and 13C NMR spectra at room temperature. (H1 and C1) 1a in DMSO-d6; (H7 and C7) 1a in D2O; (H8 and C8) 1a and 0.05
mL of H2O in 0.5 mL of DMSO-d6; (H9 and C9) 1a and 0.05 mL of H2O in 0.5 mL of DMSO-d6 after heating at 100 °C for 3 h; (H5 and C5) 2a in
DMSO-d6; (H10 and C10) 2a in D2O.
General synthetic procedure for
AcOH (30 mL). The clear solution was allowed to stand overnight and
the products crystallized. Filtering the resulting solid gave 1. Caution
should be used in the whole operation; higher temperatures should
be avoided because of the hazard of HClO4.
1,3-dialkyl-2-formylimidazolium perchlorate 1
A solution of HClO4 in AcOH (5.0 mL, 1.0 N) was added to a solution
of N,N=-disubstituted 1,4-diazabutadiene13 (5 mmol) dissolved in
Published by NRC Research Press

446
Can. J. Chem. Vol. 91, 2013
Scheme 3. Reaction of 1a in H2O.
Fig. 4. 1H NMR and 13C NMR spectra at room temperature (H4) 1a and 0.05 mL of MeOH in 0.5 mL of DMSO-d6 after heating at 65 °C for 3 h;
(H11) 1a and 0.05 mL of MeOH-d4 in 0.5 mL of DMSO-d6 after heating at 65 °C for 3 h; (H5) 2a in DMSO-d6; (H9) 1a and 0.05 mL of H2O in 0.5 mL
of DMSO-d6 after heating at 100 °C for 3 h; (H12) 1a and 0.05 mL of D2O in 0.5 mL of DMSO-d6 after heating at 100 °C for 3 h.
1,3-Diisopropyl-2-formylimidazolium perchlorate 1a
Yield 57% as white crystals; mp 199–201 °C; H NMR (400 MHz,
General procedure for the synthesis for
1,3-dialkylimidazolium perchlorate 2
1
DMSO-d6) ␦H (ppm) 1.54 (d, J = 6.8 Hz, 12H), 5.14 (septet, J = 6.8 Hz,
2H), 8.01 (s, 2H), 10.11 (s, 1H); 13C NMR (100 MHz, DMSO-d6) ␦C (ppm)
22.7, 51.8, 122.3, 134.6, 177.1; 1H NMR (400 MHz, MeOH-d4) ␦H (ppm)
1.54 (d, J = 6.8 Hz, 12H), 5.19 (septet, J = 6.8 Hz, 2H), 6.19 (s, 1H), 7.83
(s, 2H); 13C NMR (100 MHz, MeOH-d4) ␦C (ppm) 21.5, 51.6, 88.9, 118.9,
141.5; 1H NMR (400 MHz, D2O) ␦H (ppm) 1.38 (d, J = 6.8 Hz, 12H), 4.99
(septet, J = 6.8 Hz, 2H), 6.51 (s, 1H), 7.51 (s, 2H); 13C NMR (100 MHz,
D2O) ␦C (ppm) 22.0, 51.4, 82.0, 118.9, 141.1; HRMS (ESI) m/z calcd.:
1 (1 mmol) was refluxed in EtOH (20 mL) and the reactions were
considered complete when 1 was no longer detected by TLC. The
solvent was removed in vacuo and the residue was the products 2.
1,3-Diisopropylimidazolium perchlorate 2a
Yield 97% as white solid; mp 117–119 °C; 1H NMR (400 MHz,
DMSO-d6) ␦H (ppm) 1.62 (d, J = 6.4 Hz, 12H), 4.81 (heptet, J = 6.4 Hz,
2H), 7.87 (d, J = 1.2 Hz, 2H), 9.17 (s, 1H); 13C NMR (100 MHz, DMSO-d6)
181.1341 for C10H17N2O [M-ClOϪ]ϩ; found: 181.1338.
1
4
␦
(ppm) 22.0, 53.2, 120.7, 133.6; H NMR (400 MHz, MeOH-d4) ␦H
C
(ppm) 1.59 (d, J = 6.8 Hz, 12H), 4.67 (septet, J = 6.8 Hz, 2H), 7.76 (d,
2H, J = 1.6 Hz), 9.10 (s, 1H); 13C NMR (100 MHz, MeOH-d4) ␦C (ppm)
21.5, 53.2, 120.5, 133.2; 1H NMR (400 MHz, D2O) ␦H (ppm) 1.37 (d, J =
6.8 Hz, 12H), 4.46 (septet, J = 6.8 Hz, 2H), 7.39 (d, 2H, J = 1.6 Hz), 8.68
(s, 2H); 13C NMR (100 MHz, D2O) ␦C (ppm) 21.9, 52.98, 120.4, 132.3;
HRMS (ESI) m/z calcd.: 153.1392 for C9H17N2 [M-ClOϪ4 ]ϩ; found:
153.1404.
1,3-Dicyclohexyl-2-formylimidazolium perchlorate 1b
Yield 89% as white crystals; mp 282–283 °C; 1H NMR (400 MHz,
DMSO-d6) ␦H (ppm) 1.78 (m, 20H), 5.23 (m, 2H), 8.30 (s, 2H), 10.48 (s,
1H); 13C NMR (100 MHz, DMSO-d6) ␦C (ppm) 24.8, 25.2, 32.9, 58.4,
122.7, 134.7, 177.3; HRMS (ESI) m/z calcd.: 261.1967 for C16H25N2O
[M-ClOϪ4 ]ϩ; found: 261.1940.
1,3-Di-tert-butyl-2-formylimidazolium perchlorate 1c
Yield 61% as white solid; mp 132–133 °C; 1H NMR (400 MHz,
acetone-d6) ␦H (ppm) 1.84 (s, 18H), 8.11 (s, 2H), 10.80 (s, 1H); 13C NMR
(100 MHz, acetone-d6) ␦C (ppm) 29.9, 64.4, 122.1, 138.3, 182.4; HRMS
(ESI) m/z calcd.: 181.1699 for C11H21N2 [M-CO-ClOϪ4 ]ϩ; found:
181.1642.
1,3-Dicyclohexylimidazolium perchlorate 2b
Yield 98% as white solid; mp 174–175 °C; H NMR (400 MHz,
CDCl3) ␦H (ppm) 1.25–2.21 (m, 20H), 4.35 (m, 2H), 7.47 (d, J = 1.6, 2H),
8.99 (s, 1H); 13C NMR (100 MHz, CDCl3) ␦C (ppm) 24.8, 33.3, 60.1,
77.1, 120.5, 133.2.
1
Published by NRC Research Press

Xin et al.
447
Table 2. Crystal data of 2b.
collections, and structure refinements are summarized in Table 2.
200 Restraints used in the least-square refinement were attributed
solely to the disordered anion. The data are sufficient for confir-
mation of identity.
Crystal
2b
Empirical formula
Formula mass
Colour, habit
Crystal dimensions (mm)
Crystal system
Space group
Z
a (Å)
b (Å)
c (Å)
␴ (°)
C15H25C6N2O4
332.82
Colourless, prism
0.20 × 0.18 × 0.12
Monoclinic
P21/c
2
12.088(2)
20.922(4)
13.598(3)
90
94.57(3)
90
Stability analytical procedure
The HPLC was equipped with a diode array detector set at
267 nm and autosampler. Reversed-phase chromatography was used
with a mobile phase of 30% acetonitrile and 70% 0.1 mol L−1 so-
dium acetate buffer solution (pH 4.3), flow rate of 1.0 mL min−1,
column temperature of 25 °C, and injection volume of 5 ␮L. Sam-
ples were injected directly into the HPLC at intervals of 0.5 h. The
decomposition time was calculated by the signal disappearance
of 1. Retention time of 1 was around 3.5 min and of 2 was around
2.5 min.
␤ (°)
␥ (°)
Collection ranges
Temperature (K)
Volume (Å3)
–14 ≤ h ≤ 14, –17 ≤ k ≤ 24, –16 ≤ l ≤ 16
113(2)
3428.0(12)
1.290
Mo K␣ (␭ = 0.71073 Å)
0.242
Supplementary material
Supplementary data are available with the article through the
journal Web site at http://nrcresearchpress.com/doi/suppl/10.1139/
cjc-2012-0497. CCDC-775890 contains the supplementary crystal-
lographic data for this paper. These data can be obtained, free of
charge, via http://www.ccdc.cam.ac.uk/conts/retrieving.html.
D
calcd. (Mg m–3
)
Radiation
Absortion coefficient (␮)
(mm–1)
Absorption correction
F(000)
␪ range for data collection (°)
Observed refflections
Independent reflections
Data/restraints/parameters
Goodnes-of-fit on F2
Final R indices [I > 2␴(I)]
R indices (all data)
Semi-empirical from equivalents
1424
2.38–25.02
22765
6039 (Rint = 0.0386)
6039/200/444
Acknowledgements
This work was financially supported by the Key Projects in
the National Science
& Technology Pillar Program (No.
2012ZX10001007-008-002).
1.065
References
R1 = 0.0506, wR2 = 0.1323
R1 = 0.0630, wR2 = 0.1416
0.0184(18)
(1) Nallan, L.; Bauer, K. D.; Bendale, P.; Rivas, K.; Yokoyama, K.; Hornéy, C. P.;
Pendyala, P. R.; Floyd, D.; Lombardo, L. J.; Williams, D. K.; Hamilton, A.;
Sebti, S.; Windsor, W. T.; Weber, P. C.; Buckner, F. S.; Chakrabarti, D.;
Gelb, M. H.; VanVoorhis, W. C. J. Med. Chem. 2005, 48, 3704. doi:10.1021/
jm0491039.
Extinction coefficient
Largest diff. peak and
0.689 and –0.354
hole (e Å–3
)
(2) Oresmaa, L.; Kotikoski, H.; Haukka, M.; Salminen, J.; Oksala, O.; Pohjala, E.;
Moilanen, E.; Vapaatalo, H.; Vainiotalo, P.; Aulaskari, P. J. Med. Chem. 2005,
48, 4231. doi:10.1021/jm048949+.
(3) GwaltneyIi, S. L.O'; Connor, S. J.; Nelson, L. T. J.; Sullivan, G. M.; Imade, H.;
Wang, W.; Hasvold, L.; Li, Q.; Cohen, J.; Gu, W.-Z.; Tahir, S. K.; Bauch, J.;
Marsh, K.; Ng, S.-C.; Frost, D. J.; Zhang, H.; Muchmore, S.; Jakob, C. G.;
Stoll, V.; Hutchins, C.; Rosenberg, S. H.; Sham, H. L. Bioorg. Med. Chem. Lett.
2003, 13, 1359. doi:10.1016/s0960-894x(03)00095-7.
(4) Azami, H.; Barrett, D.; Tanaka, A.; Sasaki, H.; Matsuda, K.; Sakurai, M.;
Terasawa, T.; Shirai, F.; Chiba, T.; Matsumoto, Y.; Tawara, S. Bioorg. Med.
Chem. 2001, 9, 961. doi:10.1016/s0968-0896(00)00314-x.
(5) GwaltneyIi, S. L.O'; Connor, S. J.; Nelson, L. T. J.; Sullivan, G. M.; Imade, H.;
Wang, W.; Hasvold, L.; Li, Q.; Cohen, J.; Gu, W.-Z.; Tahir, S. K.; Bauch, J.;
Marsh, K.; Ng, S.-C.; Frost, D. J.; Zhang, H.; Muchmore, S.; Jakob, C. G.;
Stoll, V.; Hutchins, C.; Rosenberg, S. H.; Sham, H. L. Bioorg. Med. Chem. Lett.
2003, 13, 1363. doi:10.1016/s0960-894x(03)00094-5.
(6) Saha, A. K.; Liu, L.; Simoneaux, R. L.; Kukla, M. J.; Marichal, P.; Odds, F. Bioorg.
Med. Chem. Lett. 2000, 10, 2175. doi:10.1016/s0960-894x(00)00445-5.
(7) Berezin, M.; Achilefu, S. Tetrahedron Lett. 2007, 48, 1195. doi:10.1016/j.tetlet.
2006.12.051.
(8) Ricciardi, F.; Joullié, M. M. Org. Prep. Proc. Int. 1983, 15, 17. doi:10.1080/
00304948309355426.
(9) Plater, M. J.; Barnes, P.Mc; Donald, L. K.; Wallace, S.; Archer, N.; Gelbrich, T.;
Horton, P. N.; Hursthouse, M. B. Org. Biomol. Chem. 2009, 7, 1633. doi:10.1039/
b820257e.
(10) Zettlitzer, M.; TomDieck, H.; Haupt, E.; Stamp, L. Chem. Ber. 1986, 119, 1868.
doi:10.1002/cber.19861190609.
1,3-Di-tert-butylimidazolium perchlorate 2c
1
Yield 97% as white solid; mp 244–246 °C; H NMR (400 MHz,
acetone-d6) ␦H (ppm) 1.73 (s, 18H), 7.99 (s, 2H), 9.04 (s, 1H); 13C NMR
(100 MHz, acetone-d6) ␦C (ppm) 29.3, 60.7, 121.0, 132.6; HRMS (ESI)
m/z calcd.: 181.1699 for C11H21N2 [M-ClOϪ]ϩ; found: 181.1700.
4
2-(Hydroxy(methoxy)methyl)-1,3-diisopropylimidazolium
perchlorate 3a
1H NMR (400 MHz, DMSO-d6) ␦H (ppm) 1.44 (d, J = 6.8 Hz, 12H),
3.46 (s, 3H), 5.10 (heptet, J = 6.8 Hz, 2H), 6.15 (s, 1H), 7.98 (s, 2H), 8.26
(s, 1H); 13C NMR (100 MHz, DMSO-d6) ␦C (ppm) 22.4, 51.4, 55.1, 89.0,
119.7, 141.3.
2-(Dihydroxymethyl)-1,3-diisopropylimidazolium perchlorate 3a=
1H NMR (400 MHz, DMSO-d6) ␦H (ppm) 1.39 (d, J = 6.8 Hz, 12H),
5.04 (heptet, J = 6.8 Hz, 2H), 6.38 (s, 1H), 7.74 (s, 2H), 7.96 (s, 2H); 13
NMR (100 MHz, DMSO-d6) ␦C (ppm) 22.6, 51.2, 82.3, 119.1, 142.9.
C
X-ray crystallography
Crystals of 2b suitable for X-ray diffraction analysis were ob-
tained by slow evaporation of an AcOEt solution of 2b at room
temperature. The single crystal X-ray diffraction measurement
was carried out on a Rigaku Saturn CCD area-detector diffractom-
eter at 113 (2) K using graphite monochromated Mo K␣ radiation
(␭ = 0.71073 Å) in the ␻ and ␸ scans scanning mode. An empirical
absorption correction was applied using the SADABS program.14
All structures were solved by direct methods using the SHELXS-97
program15 and refined by full matrix least squares on F2 using the
SHELXL-97 program.16 All of the hydrogen atoms were geometri-
cally fixed using the riding model. Details of crystal data, data
(11) Olofson, R. A.; Landesberg, J. M.; Houk, K. N.; Michelman, J. S. J. Am. Chem.
Soc. 1966, 88, 4265. doi:10.1021/ja00970a032.
(12) Wong, J. L.; Keck, J. H.; Jr . J. Org. Chem. 1974, 39, 2398. doi:10.1021/
jo00930a015.
(13) He, J.-Y.; Xin, H.-X.; Yan, H.; Song, X.-Q.; Zhong, R.-G. Ultrason. Sonochem. 2011,
18, 466. doi:10.1016/j.ultsonch.2010.08.002.
(14) Sheldrick, G. M. SADABS, Program for Empirical Absorption Correction of Area
Detector Data; University of Göttingen: Göttingen, Germany, 1996.
(15) Sheldrick, G. M. SHELXS-97, Program for Crystal Structure Solution; University of
Göttingen: Göttingen, Germany, 1997.
(16) Sheldrick, G. M. SHELXL-97, Program for the Refinement of Crystal Structure from
Diffraction Data; University of Göttingen: Göttingen, Germany, 1997.
Published by NRC Research Press