Argentivorous molecules bearing three aromatic side arms: Synthesis of triple-armed cyclens and their complexing property towards Ag+

Article abstract of DOI:10.1039/c4dt02954b

Triple-armed cyclens bearing three aromatic side-arms were prepared in three steps from (3R,5S)-3,5-dimethyl-1,4,7,10-tetraazacyclododecane-2,6-dione, and the Ag⁺-ion-induced ¹H NMR and UV-vis spectral changes and X-ray structures suggested that the aromatic side-arms cover the Ag⁺ incorporated into the ligand cavities like an insectivorous plant (Venus flytrap).

Full text of DOI:10.1039/c4dt02954b

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Argentivorous molecules bearing three aromatic
side arms: synthesis of triple-armed cyclens and
their complexing property towards Ag+†
Cite this: DOI: 10.1039/c4dt02954b
Yoichi Habata,*a,b Juli Kizaki,a Yasuhiro Hosoi,a Mari Ikedab,c and
Shunsuke Kuwaharaa,b
Received 25th September 2014,
Accepted 7th November 2014
Triple-armed cyclens bearing three aromatic side-arms were prepared in three steps from (3R,5S)-3,5-
dimethyl-1,4,7,10-tetraazacyclododecane-2,6-dione, and the Ag+-ion-induced 1H NMR and UV-vis spec-
tral changes and X-ray structures suggested that the aromatic side-arms cover the Ag+ incorporated into
the ligand cavities like an insectivorous plant (Venus flytrap).
DOI: 10.1039/c4dt02954b
www.rsc.org/dalton
tron withdrawing groups such as F, NO2, and COO– groups are
introduced onto the phenyl rings, all four aromatic side-arms
Introduction
In the last decade, cyclen has been widely used as an ion rec- cover the Ag+ in the tetra-armed cyclens. On the other hand,
ognition site in metal ion sensors, as a building block for the double-armed cyclens bearing naphthalene, anthracene,
supramolecular structures, in catalytic drugs, chirality signal- and pyrene which have higher electron density than substi-
ing, MRI and fluorescent probes for imaging and so on.1 tuted benzenes cover the Ag+, however the double-armed
Recently, we have reported2 that tetra-armed and double- cyclens bearing phenyl rings as side-arms do not cover the
armed cyclens with aromatic side-arms behave like an insecti- Ag+.2d These results indicate that Ag+–π interactions between
vorous plant (Venus flytrap) when they form complexes with the Ag+ and aromatic side-arms as well as CH–π interactions
Ag+. The aromatic side-arms in the armed-cyclens cover the between neighboring aromatic rings are important for the
Ag+ incorporated into the cyclen cavities by Ag+–π and CH–π dynamic conformational changes in the armed-cyclens. In con-
interactions in an organic solvent as well as in water. The dia- tinuation of our previous work, we prepared triple-armed
meter of the cavity of cyclen, which is a 12-membered ring, is cyclens in order to answer the following questions: (i) in triple-
small for Ag+, and an Ag+ ion incorporated into the cyclen unit armed cyclens bearing three phenyl rings, whether the
is exposed on the surface of the cyclen ring to allow Ag+–π aromatic side-arms cover the Ag+ or not. (ii) If the aromatic
interactions between the Ag+ and the aromatic side-arms. This side-arms cover the Ag+ in the triple-armed cyclens, when a
behavior is not observed in Ag+ complexes with benzyl-armed combination of two kinds of aromatic rings is introduced into
diaza-18-crown-6 ethers3 because CH–π interactions between a cyclen as a side-arm, whether the substituent effects on the
aromatic rings are not possible in the diaza-18-crown-6 ether phenyl groups can be observed or not. (iii) In the tetra-armed
derivatives. We named the armed cyclens “argentivorous mole- cyclens, some Ag+ complexes were a mixture of Δ and Λ
cules”.4 The aromatic side-arms in tetra-armed cyclens cover forms in the solid state as shown in Fig. 1. The CH–π inter-
the Ag+ incorporated into the cyclen cavity, even though elec- actions in triple-armed cyclen/Ag+ complexes may be weaker
than those in tetra-armed cyclen/Ag+ complexes because triple-
armed cyclens lack one aromatic ring. Therefore, we expected
that inversion of the side-arms (Δ and Λ forms) would be
observed. During research efforts on the study of tetra-armed
cyclens with two chiral centers on the cyclen ring, we found
that (3R,5S)-3,5-dimethyl-1,4,7,10-tetraazacyclododecane-2,6-
dione (meso-6) affords triple-armed cyclens selectively.
Here, we report the synthesis of triple-armed cyclens with
two methyl groups, the structures of Ag+ complexes in
solution and in the solid state, and the inversion barrier of
the Δ and Λ forms.
aDepartment of Chemistry, Faculty of Science, Toho University, 2-2-1 Miyama,
Funabashi, Chiba 274-8510, Japan. E-mail: habata@chem.sci.toho-u.ac.jp
bResearch Center for Materials with Integrated Properties, Toho University,
2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan
cEducation Center, Faculty of Engineering, Chiba Institute of Technology,
2-1-1 Shibazono, Narashino, Chiba 275-0023, Japan
†Electronic supplementary information (ESI) available: Spectral data for the syn-
thesized compounds and (PDF); crystallographic data for meso-6, meso-9a/
AgClO4, meso-9c/AgPF6, and meso-9d/AgClO4 (CIF). CCDC 1025463–1025466. For
ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/
c4dt02954b
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Fig. 2 X-ray structure of meso-6. Steric hindrance by the two methyl
groups inhibits the reductive amination at the 10-position nitrogen (N1
and N5).
benzenes at the 1- and 7-positions was also prepared to clarify
the chemical shift of the phenyl protons at the 10-position. As
shown in Fig. 3, the aromatic Ha protons at the 10-position in
the cyclen ring shifted to a higher field ca. by 0.74 ppm while
the aromatic Hb protons at the 1- and 7-positions shifted to a
higher field ca. by 0.13 ppm.
On the other hand, the Ha protons in meso-9c and meso-9d
which have 3,5-difluorobenzenes at the 1- and 7-positions in
the cyclen shifted to a higher field ca. by 0.36 ppm (Fig. 4).
The Hb protons in meso-9c shifted to a higher field ca. by
0.13 ppm. The value is similar to that of Hb protons in meso-
9a.
Fig. 5 shows electrostatic potential maps, calculated using
the B3LYP/6-31G(*) method,8 of toluene and 1,3-difluoro-4-
methylbenzene. The electrostatic potential maps show that the
electron densities in toluene are higher than those in 1,3-
difluoro-4-methylbenzene. These chemical shift changes
strongly support the fact that the chemical shift changes in the
Ha and Hb protons are affected by the electron density on the
aromatic rings next to them. These chemical shift changes are
summarized in Table 1.
Fig. 1 Tetra-armed (a) and double-armed (b) cyclens bearing benzenes
as side-arms. Definition of the Δ and Λ forms in tetra-armed cyclens (c).
Results and discussion
Triple-armed cyclens were prepared as follows: (S)-(–)-lactic
acid tosylate ((S)-2)5 and ethyl L-alaninate ((S)-4)6 were prepared
from (S)-(–)-lactic acid and L-alanine, respectively.
(2S,2′R)-Diethyl 2,2′-iminodipropionate (meso-5)7 was pre-
pared by the reaction of (S)-2 with (S)-4 in the presence of
K2CO3. Cyclization of meso-5 with iminodiacetic acid affords
(3R,5S)-3,5-dimethyl-1,4,7,10-tetraazacyclododecane-2,6-dione
(meso-6). When reductive amination of meso-6 was carried out
using benzaldehyde and 3,5-difluorobenzaldehyde in the pres-
ence of NaBH(OAc)3, 10-substituted derivatives (meso-7a and
meso-7b) were obtained.
As we previously reported,2c,d the aromatic protons at the
2′- and 6′-positions of aromatic side-arms (the Ha protons in
Fig. 1) in the tetra-armed cyclen bearing four phenyl groups
shifted to a higher field ca. by 0.96 ppm. The higher field shift
changes in the triple-armed cyclens indicate that the aromatic
side-arms of meso-9a–9d cover the Ag+ incorporated into the
cyclen cavities. Small chemical shift changes of Hb protons at
the 1- and 7-positions would be due to the absence of an aro-
matic side-arm at the 4-position nitrogen and rapid inversion
between Δ and Λ enantiomers (Fig. 6). It is important to note
that symbols Δ and Λ refer to the helicity of the pendant arms.
To estimate the inversion barrier between Δ and Λ forms of
meso-9b, VT 1H NMR experiments on a 1 : 1 mixture of meso-9b
and Ag+ in CD2Cl2–CD3OD were carried out in the range of
293 K–193 K (Fig. 7).
The X-ray structure of meso-6 (Fig. 2) indicates that the
N atom (at the 4-position in the cyclen) between the two
methyl-substituted carbons does not react owing to the steric
hindrance of the two neighboring methyl groups. A disubsti-
tuted compound, therefore, would not be obtained. After meso-
8a and 8b were obtained by the reduction of meso-7a and 7b,
the crude meso-8a and 8b were used for reductive amination
with benzaldehyde derivatives. Finally triple-armed cyclens
(meso-9a–meso-9d) were obtained (Scheme 1).
The structure of an Ag+ complex with meso-9a was examined
1
from Ag+-induced H NMR chemical shift changes (Fig. 3). To
assign the protons at the 2′- and 6′-positions in each aromatic
ring, COSY, HMBC, and HMQC of a 1 : 1 (= meso-9a: Ag+)
mixture were measured (see Fig. S9–S12b in the ESI†). In
addition, an analogue of meso-9a (meso-9b) bearing deuterated
As shown in Fig. 7, the coalescence temperature was
observed at 243 K for the Hb protons in the phenyl rings at the
1- and 7-positions and the methyl protons. The inversion
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Scheme 1
Fig. 3 Ag+-induced 1H NMR spectral changes of meso-9c (top) and
meso-9d (bottom) in CD2Cl2–CD3OD.
Fig. 4 Ag+-induced 1H NMR spectral changes of meso-9c (top) and
meso-9d (bottom) in CD2Cl2–CD3OD.
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Fig. 5 Electrostatic potential maps of (a) toluene and (b) 1,3-difluoro-
4-methylbenzene (property range: kJ mol−1).
Fig. 8 Ag+-induced-UV-vis spectral changes of meso-9a/Ag+ in
CH3CN.
Table 1 Ag+-induced-1H NMR chemical shift changes (Δ ppm)a
Compd.
Ha (10-position)
Hb (1- and 7-positions)
Titration experiments using UV spectra were carried out to
confirm the Ag+–π interactions in CH3CN. Fig. 7 shows the
Ag+-ion-induced UV spectral changes in meso-9a (and Fig. S25
and S26 in the ESI† for meso-9c and meso-9d, respectively). An
increase in the absorbance between 242 and 267 nm was
observed with isosbestic points at 242 and 267 nm, upon the
addition of Ag+. An inflection point was observed at 1.0
(= [Ag+]/[meso-9a]), showing a 1 : 1 complex (Fig. 8). Nonlinear
least-squares analyses of the titration profiles clearly indicated
the formation of a 1 : 1 complex, and allowed us to estimate
the association constants defined as eqn (1). The log K values
between the ligands (meso-9a, meso-9c and meso-9d) and Ag+ in
CH3CN were estimated to be ca. 5.6, 6.5, and 6.5, respectively,
using the HYPERSPC calculation program.10
meso-9a
meso-9b
meso-9c
meso-9d
–0.7
–0.13
—
–0.13
–0.04
–0.74
–0.36
–0.36
a Negative values mean higher field shift.
Fig. 6 Optimized structures of Δ and Λ enantiomers of the meso-9b/
Ag+ complex (B3LYP/6-31G*). Hydrogen atoms are omitted for clarity.
Ligand þ Agþ Ð ½Ligand ꢀ Agþꢁ
ð1Þ
K ¼ ½Ligand ꢀ Agþꢁ=½Ligandꢁ½Agþꢁ
X-ray structures of Ag+ complexes with the triple-armed
cyclens were measured (Fig. 9). In meso-9b/AgPF6, three side-
arms cover the Ag+ and the C13–Ag1, C20–Ag1, and C27–Ag1
distances are 3.709, 3.179, and 3.613 Å, respectively. We
Fig. 7 VT 1H NMR experiments of meso-9b/Ag+ in CD2Cl2–CD3OD.
barrier (ΔG‡) was estimated to be 11 kcal mol−1 using the
methodology previously described by Shanan-Atidi and Bar-
Eli.9 This is the first example of an inversion barrier in Ag+
complexes with double-, triple-, and tetra-armed cyclens.
Fig. 9 X-ray structures of (a) meso-9a/AgClO4, (b) meso-9c/AgPF6,
(c) meso-9d/AgClO4, and (d) C–H–plane distances of meso-9c/AgPF6.
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reported that the typical C–Ag distance range in tetra-armed follows: (i) the 1H NMR and UV-vis titration experiments
cyclens is 3.272–3.344 Å,2b,d and the 3.6–3.7 Å is a relatively showed that the triple-armed cyclens behave like an insectivor-
long distance range. These longer distances would be due to ous plant (Venus flytrap), thus the three aromatic side-arms
the absence of an aromatic side-arm at the 4-position nitrogen. cover the Ag+ incorporated into the cyclen cavities. X-ray struc-
In addition, intramolecular CH–π interactions between the aro- tures exhibited that Ag+–π interactions as well as C–H–π inter-
matic rings are also observed in the meso-9b/AgPF6 complex actions are crucial for triple-armed cyclens to work as
(Fig. 9d). The H20–benzene plane (C12 to C17) and the H27– argentivorous molecules. (ii) When two kinds of aromatic
benzene plane (C19 to C24) distances are 2.673 and 2.879 Å, rings are introduced as side-arms, the chemical shift of the
respectively. These distances are comparable to typical CH–π protons at the 2′- and 6′-positions in the side-arms changed
distances in aromatic rings.11 On the other hand, in the meso- systematically depending on the next neighboring benzene.
9a/AgClO4 (Fig. 9a) and meso-9c/AgClO4 (Fig. 9c) complexes, (iii) The inversion barrier between Δ and Λ forms of meso-9b
two aromatic side-arms at the 1- and 10-positions cover the was estimated to be 11 kcal mol−1 by VT 1H NMR studies. Syn-
Ag+, while the third side-arm at the 7-position does not. The thesis, the complexing property towards Ag+, and chiral
Ag–ClO4 bond lengths of the meso-9a/AgClO4 (Fig. 9a) and enhancement by chiral argentivorous molecules are now in
meso-9c/AgClO4 are in the range 2.344–2.600 Å. These dis- progress in our laboratory.
tances are typical Ag–ClO4 bond distances.3a,12 The coordi-
nation of ClO4 to the Ag+ bond prevents the Ag+–π interaction
–
in the solid state. Interestingly, the mean average derivations
Experimental section
General information
of Ag+–N distances in the Ag+ complexes with 9a, 9b, and 9c
are greater than those of tetra-armed cyclens previously
reported (Table 1S in the ESI†). These deviations mean that Melting points were obtained with Mel-Temp capillary appar-
the cyclen rings are distorted in the Ag+ complexes with triple- atus and were not corrected. FAB mass spectra were obtained
1
armed cyclens. The smaller log K values of the triple-armed using a JEOL 600 H mass spectrometer. H NMR spectra were
cyclens (log K = 5.6–6.5) than those of tetra-armed cyclens measured in CDCl3, CD2Cl2, or a mixture of CD2Cl2 and
(log K = 6.8)2c,e would be due to the ring distortion.
CD3OD on a JEOL ECP400 (400 MHz) spectrometer. UV-vis
To visualize the Ag+–π interactions, the LUMOs and spectra were recorded on a JASCO V-550 spectrometer. The
HOMOs were calculated by the DFT method [B3LYP/3-21G(*)] elemental analysis was carried out on a Yanako MT-6 CHN
using the X-ray structures of the meso-9c/AgPF6 complex. As Micro Corder. All reagents were of standard analytical grade
shown in Fig. 10, the LUMO of Ag+ is in contact with the and were used without further purification. Optical rotations
HOMOs of the aromatic side-arms. However, in this case, sig- were measured on a digital polarimeter JASCO DIP-360.
nificant distortion of the LUMO like tetra-armed cyclen/Ag+
Ethyl(S)-2-[[(4-methylphenyl)sulfonyl]oxy]propionate
(S)-
complexes was not observed. This result indicates that the 2. (S)-2 was prepared according to the literature.5 Yield 97%.
Ag+–π interactions in the triple-armed cyclen/Ag+ complex Pale yellow oil. [α]D = –30.5 (c = 2.69, CHCl3). 1H NMR (CDCl3):
would not be very strong.
δ 7.82 (d, J = 8.2 Hz, 2H), 7.35 (d, J = 8.2 Hz, 2H), 4.93 (q, J =
7.1 Hz, 1H), 4.12 (dq, J1 = 7.1 Hz, J2 = 1.1 Hz, 2H), 2.45 (s, 3H),
1.51 (d, J = 7.1 Hz, 3H), 1.21 (t, J = 7.1 Hz, 3H). FAB-MS (m/z)
(matrix: dithiothreitol (DTT)–α-thioglycerol (TG) = 1 : 1): 273
([M + 1]+, 100%).
Conclusions
In the introduction part, we raised three questions about
triple-armed cyclens. Now we can answer the questions as
Ethyl L-alaninate hydrochloride (S)-4. (S)-4 was prepared
according to the literature.6 Yield 99%. Mp: 77.0–79.0 °C.
1
[α]D = +3.2 (c = 2.41, CH3OH). H NMR(CDCl3): δ 8.75 (s, 3H),
4.30–4.20 (m, 3H), 1.73 (d, J = 7.1 Hz, 3H), 1.30 (t, J = 7.1 Hz,
3H). FAB-MS (m/z) (matrix: DTT–TG = 1 : 2): 154 ([M + 1 −
HCl]+, 100%).
Diethyl (2R,2′S)-2,2′-iminodipropanoate meso-5. meso-5 was
prepared according to the literature.7 Yield 45%. Colorless oil.
1H NMR (CDCl3): δ 4.22–4.11 (m, 4H), 3.38 (q, J = 7.0 Hz, 2H),
1.31 (d, J = 7.1 Hz, 6H), 1.28 (t, J = 7.1 Hz, 6H). FAB-MS (m/z)
(matrix: DTT–TG = 1 : 1): 218 ([M + 1]+, 100%).
(3R,5S)-3,5-Dimethyl-1,4,7,10-tetraazacyclododecane-2,6-dione
meso-6. meso-5 (2.19 g, 10.1 mmol) was dissolved in absolute
CH3OH (250 mL) and then added to a solution of diethylene-
triamine (1.05 g, 10.2 mmol) in 250 mL absolute MeOH. The
reaction mixture was stirred at 70 °C under an argon atmos-
phere for 7 days, and then the solvent was removed under
reduced pressure. meso-6 was obtained as white powder by
Fig. 10 The LUMO and HOMOs calculated by the DFT method [B3LYP/
3-21G(*)] using the X-ray structures of the meso-9c/Ag+ complex (iso-
surface value is 0.02 au). LUMO (mesh) and HOMO[−4], HOMO[−5], and
HOMO[−7] (solid).
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recrystallization from a mixture of acetonitrile and methanol.
(3R,5S)-1,7,10-Tribenzyl-3,5-dimethyl-1,4,7,10-tetraazacyclo-
Yield 19%. White solid. Mp: 191–194 °C. 1H NMR (CDCl3): dodecane meso-9a. After a mixture of meso-8a (294 mg,
δ 3.55–3.47 (m, 2H), 3.20 (q, J = 7.0 Hz, 2H), 3.07–3.00 (m, 2H), 1.01 mmol), benzaldehydes (633 mg, 5.96 mmol), and NaBH
2.95–2.89 (m, 2H), 2.67–2.61 (m, 2H), 1.37 (d, J = 7.0 Hz, 6H). (OAc)3 (1.27 g, 5.99 mmol) in 1,2-dichloroethane (10 mL) was
FAB-MS (m/z) (matrix: DTT–TG = 1 : 2): 229 ([M + 1]+, 100%). stirred for 5 days at rt under an argon atmosphere (atmos-
Anal. calcd for C10H20N4O2 + 1/10H2O: C, 52.20; H, 8.85; N, pheric pressure), saturated aqueous NaHCO3 was added. The
24.35. Found: C, 52.20; H, 8.85; N, 24.35.
(3R,5S)-10-Benzyl-3,5-dimethyl-1,4,7,10-tetraazacyclododecane- extracted with CHCl3 (50 mL × 3). The combined organic layer
2,6-dione meso-7a. After mixture of meso-6 (684 mg, was washed with water, dried over Na2SO4, and concentrated.
organic layer was separated, and the aqueous layer was
a
3.00 mmol) and benzaldehydes (1.13 g, 10.6 mmol) in 1,2- The residual oil was separated and purified by column chrom-
dichloroethane was stirred for 24 h at 1 MPa (argon atmos- atography on silica-gel (CHCl3–MeOH–NH3 aq = 5/1/0.06) to
phere), NaBH(OAc)3 (1.91 g, 9.00 mmol) was added and stirred give meso-9a as a pale-yellow oil. Yield 0.142 g (30%). Pale-
1
for 24 h at atmospheric pressure (argon atmosphere). To the yellow oil. H NMR (CD2Cl2): δ 7.37–7.29 (m, 10H), 7.26–7.19
reaction mixture, saturated aqueous NaHCO3 was added, and (m, 5H), 3.82 (d, J = 14.0 Hz, 2H), 3.50 (s, 2H), 3.41 (d, J = 14.0
the organic layer was separated. The aqueous layer was Hz, 2H), 2.93–2.88 (br, 2H), 2.74–2.60 (m, 4H), 2.49–2.39 (m,
extracted with CHCl3 (50 mL × 3). The combined organic layer 6H), 2.28 (d, J = 14.0 Hz, 2H), 0.95 (d, J = 6.5 Hz, 6H). Anal.
was washed with water, dried over Na2SO4, and concentrated. Calcd for C31H42N4 + 0.25CH3OH: C, 78.41; H, 9.05; N, 11.70.
The residual solid was recrystallized from acetonitrile to give Found: C, 78.71; H, 8.86; N, 11.33. FAB-MS (m/z) (matrix: DTT–
meso-7a as a white solid. Yield 0.763 g (80%). Mp: 174–177 °C. TG = 1 : 1): 471 ([M + 1]+, 100%).
1H NMR (CDCl3): δ 7.39–7.23 (m, 5H), 3.70 (s, 2H), 3.50–3.45
(3R,5S)-10-Benzyl-3,5-dimethyl-1,7-bis[(2H5)phenyl(2H1)methyl]-
(m, 2H), 3.22 (q, J = 7.0 Hz, 2H), 3.04–3.97 (m, 2H), 2.62 (t, J = 1,4,7,10-tetraazacyclododecane meso-9b. meso-9b was prepared
5.7 Hz, 4H), 1.37 (d, J = 7.0 Hz, 6H). FAB-MS (m/z) (matrix: in a similar manner with the synthetic procedure of meso-9a
1
DTT–TG = 1 : 2): 319 ([M + 1]+, 100%). Anal. Calcd for using meso-8a and benzaldehyde-d6. Yield 14%. Brown oil. H
C17H26N4O2: C, 64.12; H, 8.23; N, 17.60. Found: C, 64.36; H, NMR (CD2Cl2): δ 7.34–7.18 (m. 5H), 3.82 (s, 0.7H), 3.54 (s,
8.27; N, 17.84.
3.3H), 2.98–2.85 (m, 2H), 2.81–2.47 (m, 8H), 2.46–2.31 (m, 4H),
(3R,5S)-10-(3,5-Difluorobenzyl)-3,5-dimethyl-1,4,7,10-tetra- 1.11 (d, J = 6.2 Hz, 6H). MS (m/z) (matrix: DTT–TG = 1 : 1): 483
azacyclododecane-2,6-dione meso-7b. meso-7b was prepared ([M + 1]+, 100%). Anal. Calcd for C31H29D12N4 + H2O: C, 74.50;
in a similar manner with the synthetic procedure of meso-7a. H, 6.25; D, 4.84; N, 11.21. The thermal conductivity of hydro-
Yield 53%. White solid. Mp: 198–201 °C. 1H NMR (CDCl3): gen is almost the same as that of deuterium. Apparent H% is
δ 6.98–6.88 (dd, J = 8.3 Hz, 2H), 6.77–6.73 (m, 1H), 3.68 (s, 1H), calculated using the following equation: Happarent% = Hcalcd
3.53–3.45 (m, 2H), 3.25–3.20 (q, J = 7.1 Hz 2H), 3.13–3.06 (m, + Dcalcd%/2 = 6.25% + (4.84/2)% = 8.67%, where Hcalcd% and
%
2H), 2.67–2.55 (m, 4H), 1.38 (d, J = 7.1 Hz, 6H). FAB-MS (m/z)
Dcalcd% are calculated H%, and calculated D%, respectively.
(matrix: DTT–TG = 1 : 2): 355 ([M + 1]+, 100%). Anal. Calcd for Therefore, C, 74.50; H, 8.67; N, 11.21. Found: C, 74.49; H, 8.64;
C17H24N4F2O2: C, 57.61; H, 6.83; N, 15.81. Found: C, 57.70; H, N, 10.88.
6.71; N, 15.49.
(3R,5S)-10-Benzyl-1,7-bis(3,5-difluorobenzyl)-3,5-dimethyl-
(6R,8S)-1-Benzyl-6,8-dimethyl-1,4,7,10-tetraazacyclododecane 1,4,7,10-tetraazacyclododecane meso-9c. meso-9c was pre-
meso-8a. A mixture of meso-7a (0.637 g, 2.00 mmol) and pared in a similar manner with the synthetic procedure of
DIBAL-H (10 mL, 1 M solution in THF) was stirred at 0 °C meso-9a using meso-8a and 3,5-difluorobenzaldehyde. Yield
under an argon atmosphere for 1 day. After NaF (3.35 g, 21%. Pale yellow solid. Mp: 90.0–91.5 °C. 1H NMR (CD2Cl2):
80.0 mmol) in water (1 mL) and benzene (60 mL) was added at δ 7.35–7.26 (m, 2H), 7.24–7.14 (m, 3H), 6.92 (d, J = 8.7 Hz, 5H),
0 °C, the mixture was stirred for 5 h. The reaction mixture was 6.71 (t, J = 8.7 Hz, 2H), 3.80 (d, J = 15.0 Hz, 2H), 3.54 (d, J =
filtered, and the filtrate was concentrated under reduced 15.0 Hz, 2H), 3.48 (s, 2H), 2.86 (br-s, 2H), 2.77–2.67 (m, 2H),
pressure. Crude meso-8a was used without further purification. 2.61–2.47 (m, 6H), 2.47–2.33 (m, 4H), 0.96 (br-s, 6H). MS (m/z)
Yield 0.413 g (71%). Mp: 89–93 °C. 1H NMR (CDCl3): (matrix: DTT–TG = 1 : 1): 543 ([M + 1]+, 100%). Anal. Calcd for
δ 7.35–7.20 (m, 5H), 3.62 (s, 2H), 2.94 (br-s, 2H), 2.70–2.47 (m, C31H38F4N4 + H2O: C, 68.61; H, 7.06; N, 10.32. Found: C, 68.70;
10H), 2.38–2.27 (m, 2H), 1.11 (d, J = 7.0 Hz, 6H). FAB-MS (m/z) H, 7.07; N, 10.22.
(matrix: DTT–TG = 1 : 2): 291 ([M + 1]+, 100%).
(6R,8S)-1-(3,5-Difluorobenzyl)-6,8-dimethyl-1,4,7,10-tetra- tetraazacyclododecane meso-9d. meso-9d was prepared in a
azacyclododecane meso-8b. meso-8b was prepared in similar manner with the synthetic procedure of meso-9a using
(3R,5S)-1,7,10-Tris(3,5-difluorobenzyl)-3,5-dimethyl-1,4,7,10-
a
similar manner with the synthetic procedure of meso-8a meso-8b and 3,5-difluorobenzaldehyde. Yield 44%. Pale yellow
using meso-7b. Yield 0.306 g (94%). Mp: 83–86 °C. 1H NMR solid. Mp: 83.0–86.0 °C. 1H NMR (CD2Cl2): δ 6.93 (d, J = 9.1 Hz,
(CDCl3) δ 6.88 (d, J = 8.6 Hz, 2H), 6.67 (t, J = 8.6 Hz, 1H), 3.60 4H), 6.84 (d, J = 9.1 Hz, 2H), 6.72 (t, J = 9.1 Hz, 2H), 6.67 (t, J =
(s, 2H), 2.98–2.90 (m, 2H), 2.71–2.56 (m, 8H), 2.55–2.47 9.1 Hz, 1H), 3.85 (J = 15.3 Hz, 2H), 3.62 (J = 15.3 Hz, 2H), 3.48
(m, 2H), 2.40–2.33 (dd, J1 = 5.6 Hz, J2 = 6.5, 2H), 1.12 (d, J = 6.5 (s, 2H), 3.66 (s, 1H), 2.95–2.83 (m, 2H), 2.82–2.69 (m, 4H),
Hz, 6H). FAB-MS (m/z) (matrix: DTT–TG = 1 : 1): 327 ([M + 1]+, 2.68–2.56 (m, 4H), 2.56–2.38 (m, 4H), 1.18–0.99 (br-s, 6H). MS
100%).
(m/z) (matrix: DTT–TG = 1 : 1): 579 ([M + 1]+, 100%). Anal.
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Table 2 Crystal data of meso-6, meso-9a/AgClO4, meso-9b/AgPF6, and meso-9c/AgClO4
Compound
Formula
M
meso-6
C10H20N4O2
228.30
meso-9a/AgClO4
C31H44AgClN4O5
696.02
meso-9b/AgPF6
C32H42AgF10N4OP
827.54
meso-9c/AgClO4
C32H37AgCl4N4O4
905.33
T/K
273
Monoclinic
P2(1)/c
173
Monoclinic
P2(1)
90
120
Monoclinic
P2(1)/c
Crystal system
Space group
Monoclinic
P2(1)/c
a/Å
b/Å
c/Å
9.6821(6)
16.7879(10)
14.9185(9)
102.0980(10)
2371.0(2)
8
8.8291(4)
10.6718(6)
15.1390(9)
23.2571(11)
116.497(2)
3362.7(3)
19.0094(10)
9.2229(5)
22.7450(12)
113.5130(10)
3656.6(3)
20.5803(10)
17.8396(8)
94.1870(10)
3232.9(3)
β/°
U/Å3
Z
4
4
4
Dc/g cm−3
1.279
0.091
1.430
0.750
1.635
0.736
1.645
0.917
μ/mm−1
Data/restraints/parameters
No. reflns used [>2σ(I)]
R1, wR2 [I > 2σ(I)]
R1, wR2 [all data]
Absolute structure parameter
GOF
6611/0/325
6611 [R(int) = 0.0354]
0.0499, 0.1162
0.0754, 0.1282
12 943/107/769
12 943 [R(int) = 0.0168]
0.0322, 0.0874
0.0347, 0.0941
−0.033(16)
1.076
7688/0/453
7688 [R(int) = 0.0234]
0.0314, 0.0822
0.0341, 0.0857
9097/0/466
9097 [R(int) = 0.0268]
0.0329, 0.0857
0.0403, 0.0965
1.030
1.051
1.130
Calcd for C31H36F6N4 + 1/2H2O: C, 63.36; H, 6.35; N, 9.53.
Found: C, 63.13; H, 6.15; N, 9.16.
Acknowledgements
Preparation of silver ion complexes. The ligand The authors thank Professor Masatoshi Hasegawa for the TG
(0.0151 mmol) in chloroform or dichloromethane (1 mL) was DTA measurements. This research was supported by Grants-in-
added to the corresponding metal salt (AgPF6 or AgClO4) Aid 08026969, 11011761 and 26410100, a High-Tech Research
(0.0153 mmol) in methanol (1 mL). Crystals were obtained Center project (2005–2009), and the Supported Program for
quantitatively on evaporation of the solvent.
Strategic Research Foundation at Private Universities
meso-9a/AgClO4. Mp: 112–115 °C (Dec.). Anal. Calcd for (2012–2016) from the Ministry of Education, Culture, Sports,
C31H42AgClN4O4 + 0.25H2O: C, 54.55; H, 6.28; N, 8.21. Found: Science and Technology of Japan for Y.H.
C, 54.50; H, 6.25; N, 8.20.
meso-9b/AgPF6. Mp: 130–133 °C (Dec.). Anal. Calcd for
C31H38F10N4AgP + CH3OH: C, 46.45; H, 5.12; N, 6.77. Found:
C, 46.79; H, 5.06; N, 6.42.
Notes and references
meso-9c/AgClO4. Mp: 143–145 °C (Dec.). Anal. Calcd for
C31H36AgClF6N4O4 + 0.1CHCl3: C, 46.82; H, 4.56; N, 7.02.
Found: C, 46.97; H, 4.88; N, 6.85.
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