A new class of C3-symmetrical hemicryptophane hosts: Triamide- and tren-hemicryptophanes

Article abstract of DOI:10.1021/jo100052r

Chemical Equation Presented The first hemicryptophanes derived from tris(N-alkylcarbamoylmethyl)amine and tris(2-aminoethyl)amine (tren) have been synthesized following a single synthetic pathway that allows the subsequent formation of the two heteroditopic hosts 3 and 4. X-ray crystal structures show a well-defined cavity encapsulating a solvent guest for both compounds emphasizing their complexation properties.

Full text of DOI:10.1021/jo100052r

pubs.acs.org/joc
introducing dissymmetry at the molecular cavity level, are
A New Class of C3-Symmetrical Hemicryptophane
Hosts: Triamide- and Tren-hemicryptophanes
ditopic host molecules with all ingredients to produce cata-
lytic and recognition properties.4,5 We have previously
reported the synthesis of the diastereomeric hemicrypto-
phanes 1 and 2 (C3 symmetry), which contain a CTV unit,
providing a rigid scaffold with a lipophilic cavity, and a
chiral C3-symmetrical trialkanolamine moiety, a potential
metalloreceptor with catalytic properties if proper metal and
reactant(s) are used (Chart 1).6 The related oxidovanadium-
(V) complexes, including the vanatrane structure, have been
synthesized. They showed interesting stereochemical proper-
ties7 and were found to be a novel class of efficient supra-
molecular catalysts.8 These promising results led us to
investigate the design of new hemicryptophane hosts by
varying the nature of the tripodal amino group. The replace-
ment of the trialkanolamine unit in 1 and 2 by C3-symme-
trical ligands derived from tris(N-alkylcarbamoyl-methyl)-
amine and from tris(2-aminoethyl)-amine (tren), was
expected to give rise to original derivatives exhibiting com-
plexation properties related to the triamide or the tren
structures. Indeed, these structures have been widely used
to recognize, respectively, anions9 and cations.10 They have
been also used to complex metal ions such as cobalt, zinc,11
and copper.12 For instance, the calix[6]arenes capped with a
C3v-symmetrical azacrown bridge13 were designed to rein-
force the complexation ability toward ammonium cations,14
as well as neutral molecules.14,15 They were found to be
efficient in recognition and metal complexation, opening the
way to interesting and unexpected reactivity. Herein, we wish
to report the synthesis of the first C3-symmetrical triamide-
and tren-hemicryptophane derivatives 3 and 4, the first
members of a new class of hemicryptophane hosts (Chart 1).
The amide functions in hemicryptophane 3 should be
easily reduced to afford derivative 4. It was thus convenient
to envision a general synthetic pathway for the subsequent
synthesis of compounds 3 and 4 (Scheme 1). Starting from
Pascal Dimitrov Raytchev, Olivier Perraud,
Christophe Aronica, Alexandre Martinez,* and
Jean-Pierre Dutasta*
ꢀ
Laboratoire de Chimie, CNRS, Ecole Normale Supeꢀrieure de
ꢀ
Lyon, 46, Allee d’Italie, F-69364 Lyon 07, France
alexandre.martinez@ens-lyon.fr;
jean-pierre.dutasta@ens-lyon.fr
Received January 15, 2010
The first hemicryptophanes derived from tris(N-alkyl-
carbamoylmethyl)amine and tris(2-aminoethyl)amine
(tren) have been synthesized following a single synthetic
pathway that allows the subsequent formation of the two
heteroditopic hosts 3 and 4. X-ray crystal structures show
a well-defined cavity encapsulating a solvent guest for
both compounds emphasizing their complexation prop-
erties.
(4) (a) Canceill, J.; Collet, A.; Gabard, J.; Kotzyba-Hibert, F.; Lehn,
J.-M. Helv. Chim. Acta 1982, 65, 1894–1897. (b) Smeets, J. W. H.; Coolen,
H. K. A. C.; Zwikker, J. W.; Nolte, R. J. M. Recl. Trav. Chim. Pays-Bas 1989,
108, 215–218. (c) Rapenne, G.; Crassous, J.; Collet, A.; Echegoyen, L.;
Diederich, F. Chem. Commun. 1999, 1121–1122. (d) Gosse, I.; Dutasta, J.-P.;
Perrin, M.; Thozet, A. New J. Chem. 1999, 23, 545–548.
The use of molecular containers for the design of metal-
loreceptors is very attractive, as they can act as supramole-
cular catalysts and can mimic biological entities such as
enzymes.1 The cryptophane hosts, which are constructed
from cyclotriveratrylene (CTV) units, have remarkable bind-
ing properties toward neutral or charged guests2 and are
efficient in chiral recognition.3 The related hemicryptophanes,
€
(5) Collet, A. In Comprehensive Supramolecular Chemistry; Vogtle, F.,
Ed.; Pergamon Press: New York, 1996; Vol. 2, pp 325-365.
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2005, 7, 1207–1210.
(7) Martinez, A.; Robert, V.; Gornitzka, H.; Dutasta, J.-P. Chem.;Eur.
J. 2010, 16, 520–527.
(8) Martinez, A.; Dutasta, J-P J. Catal. 2009, 267, 188–192.
(9) (a) Valiyaveettil, S.; Engbersen, J. F. J.; Verboom, W.; Reinhoudt,
D. N. Angew. Chem., Int. Ed. Engl. 1993, 32, 900–901. (b) Voloshin, Ya. Z.;
Belov, A. S. Russ. Chem. Rev. 2008, 77, 161–175.
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(11) (a) Hammes, B. S.; Ramos-Maldonado, D.; Yap, G. P. A.;
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Chem. 1997, 36, 3210–3211. (b) Darbost, U.; Zeng, X.; Rager, M.-N.; Giorgi,
M.; Jabin, I.; Reinaud, O. Eur. J. Inorg. Chem. 2004, 22, 4371–4374.
(1) (a) Kirby, A. J. Angew. Chem., Int. Ed. Engl. 1996, 35, 707–724. (b)
Sanders, J. K. M. Chem.;Eur. J. 1998, 4, 1378–1383. (c) Lehn, J.-M. Rep.
Prog. Phys. 2004, 67, 245–249.
(2) (a) Garel, L.; Dutasta, J.-P.; Collet, A. Angew. Chem., Int. Ed. Engl.
1993, 32, 1169–1171. (b) Collet, A.; Dutasta, J.-P; Lozach, B.; Canceill, J.
Top. Curr. Chem. 1993, 165, 103–129. (c) Garel, L.; Lozach, B.; Dutasta,
J.-P.; Collet, A. J. Am. Chem. Soc. 1993, 115, 11652–11653. (d) Fogarty, H.
A.; Berthault, P.; Brotin, T.; Huber, G.; Desvaux, H.; Dutasta, J.-P. J. Am.
Chem. Soc. 2007, 129, 10332–10333. (e) Brotin, T.; Dutasta, J.-P. Chem. Rev.
2009, 109, 88–130.
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(12) Izzet, G.; Douziech, B.; Prange, T.; Tomas, A.; Jabin, I.; Le Mest, Y.;
Reinaud, O. Proc. Nat. Acad. Sci. U.S.A. 2005, 102, 6831–6836.
(13) Jabin, I.; Reinaud, O. J. Org. Chem. 2003, 68, 3416–3419.
(14) Darbost, U.; Rager, M-.N.; Petit, S.; Jabin, I.; Reinaud, O. J. Am.
Chem. Soc. 2005, 127, 8517–8525.
(15) Garrier, E.; Le Gac, S.; Jabin, I. Tetrahedron: Asymmetry 2005, 16,
3767–3771.
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6996. (b) Costante-Crassous, J.; Marrone, T. J.; Briggs, J. M.; McGammon, J. A.;
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DOI: 10.1021/jo100052r
r
Published on Web 02/18/2010
J. Org. Chem. 2010, 75, 2099–2102 2099
2010 American Chemical Society

Raytchev et al.
JOCNote
CHART 1. Structures of Hemicryptophanes 1-4
FIGURE 1. 1H NMR spectra (497.8 MHz, CDCl3, 293 K) of
hemicryptophanes 3 (a) and 4 (b).
conducted under standard conditions by reacting 7 with 10 in
DMF in presence of Cs2CO3. Compound 11 was obtained
in 58% yield after selective precipitation in diethyl ether.
The formation of the cup-shaped cyclotriveratrilene unit
was first investigated using Sc(OTf)3 as Lewis acid, following
the synthetic procedure reported for the synthesis of CTVs,
cryptophane,18 and hemicryptophane derivatives.6 There-
fore, the intramolecular cyclization of the tripodal triamide
11 was first attempted by using a stoichiometric amount of
Sc(OTf)3 in CH3CN. Although standard dilution conditions
for the hemicryptophane and cryptophane syntheses were
used (10-3 M) to favor intramolecular reactions, only poly-
meric products were obtained. Changing the solvent to
CH2Cl2 or the temperature conditions did not allow the
formation of the expected product. This lack of selectivity
and the formation of polymers could be due to the poor
preorganization of the tripodal precursor 11. The cyclization
was then performed in formic acid, which is frequently used
for the synthesis of cryptophanes.2e Under these strong
acidic conditions, hemicryptophane 3 was obtained in 30%
yield. The tripodal unit may complex a proton via the
triamide and amine functions, and hence a preorganized
system and a template effect could account for the improve-
ment of the reaction yield.19 Surprisingly, the reduction of
the triamide 3 was not straightforward. Reduction using
LiAlH4 gave only mixtures of inseparable products. The
reduction of the amide functions and the deprotection of the
methoxy groups of the CTV moieties occurred at the same
rate. Lowering the temperature or decreasing the amount
of LiAlH4 also led to a mixture of partially reduced and
deprotected compounds. The reduction of the amide func-
tions was successfully performed with BH3/THF and
afforded the desired hemicryptophane 4 in 30% yield.
The 1H NMR spectra of hemicryptophanes 3 and 4
indicate that both molecules are on average of C3 symmetry
(Figure 1). Both spectra display the usual features of the
SCHEME 1a
aReagents and conditions: (a) BrCH2CH2Br, K2CO3, EtOH, 80°C, 21 h,
34%; (b) DHP, pyridinium p-toluenesulfonate, THF/CH2Cl2, rt, 3 d,
79%; (c) p-methoxybenzylamine, P(OPh)3, pyridine, 110°C, 15 h, 70%;
(d) BBr3, CH2Cl2, -78°C f rt, 18 h, 87%; (e) Cs2CO3, DMF, 80°C, 18 h,
58%; (f) HCOOH, rt, 24 h, 30%; (g) BH3 SMe2, THF, 30%.
3
vanillyl alcohol 5, compound 6 was obtained and protected
with THP to give 7 in 27% overall yield, according to a well-
known two-step sequence.16 Nitrilotriacetic acid 8 was con-
densed at 100 °C with 3 equiv of p-methoxy benzylamine in
the presence of P(OPh)3 using pyridine as solvent to give the
tripodal triamidoamine derivative 9.17 Compound 9 was
purified by crystallization from CHCl3/pentane (70% yield).
The amide functions act as amine protecting groups so that
both protection and skeleton construction are performed
during this step. Deprotection, i.e., amide reduction, will be
performed only in the last step, thus avoiding side reactions
during the next sequences of the synthesis. The methoxy
groups in compound 9 were then removed by using BBr3
(1 M solution in CH2Cl2) to give the triphenol derivative 10.
The preparation of the hemicryptophane precursor 11 was
(16) Brotin, T.; Devic, T.; Lesage, A.; Emsley, L.; Collet, A. Chem.;Eur.
J. 2001, 7, 1561–1573.
(18) Brotin, T.; Roy, V.; Dutasta, J.-P. J. Org. Chem. 2005, 70, 6187–
6195.
€
(19) Renaud, F.; Piguet, C.; Bernadinelli, G.; Bunzli, J-C. G.; Hopfgartner,
G. J. Am. Chem. Soc. 1999, 121, 9326–9342.
(17) Liu, X.; Ilankumaran, P.; Guzei, I. A.; Verkade, J. G. J. Org. Chem.
2000, 65, 701–706.
2100 J. Org. Chem. Vol. 75, No. 6, 2010

Raytchev et al.
JOCNote
FIGURE 3. Stereoview of the X-ray molecular structure of
4 C5H12 (encapsulated pentane is omitted for clarity).
FIGURE 2. Stereoview of the X-ray molecular structure of
3 CH2Cl2.
3
3
Furthermore, the CTV-triamide (3) and CTV-tren (4) plat-
forms seem particularly well suited for the recognition of new
cationic/anionic guests. Such studies will be reported in due
course.
CTV unit, i.e., two singlets for the aromatic protons, one
singlet for the OCH3 groups, and the characteristic AB
system for the ArCH2 bridges. Two doublets for the
H3-H4 aromatic protons of the linkers and the multiplets
for the OCH2 groups are also observed in the spectra.
Changing the tripodal triamide unit by the tren structure
induces modifications in the spectra with a particular effect
on the NCH2 protons in compound 4, which appear as a
complex pattern between 2.2 and 2.3 ppm (see Supporting
Information).
Single crystals of 3 suitable for X-ray analysis were
obtained by slow evaporation from a CH2Cl2 solution. A
representation of the structure is shown in Figure 2. Hemi-
cryptophane 3 exhibits an asymmetric structure with respect
to the C3 axis of the CTV cap, introduced by the inward
orientation of one CdO amide bond stabilized by H-bonds
with the adjacent NH groups. The two other CdO groups
are oriented outward and participate in the crystalline cohe-
sion through intermolecular H-bonding. One CH2Cl2 guest
molecule is encapsulated in the host cavity and localized
close to the CTV unit in the more lipophilic environment of
the cavity. This is an interesting feature that anticipates the
ditopic character of 3.
Slow diffusion of pentane in a solution of 4 in CH2Cl2 gave
crystals suitable for X-ray analysis (Figure 3). The most
striking observations are on one hand the conservation of the
C3-symmetrical axis in the crystal structure and on the other
hand the well-preorganized cavity defined by the cyclotri-
veratrylene and the tren moieties. Moreover, a molecule of
n-pentane is imprisoned in this cavity, underlining the mole-
cular receptor properties of 4. It can be noticed that the
host-guest complex is not detected by NMR spectroscopy
since the guest is small enough to enter and depart the
interior of the host so that mass-law driven exchange of
guest with solvent occurs in solution at room temperature.
The asymmetric crystal unit is constituted by one-third of the
host molecule due to the R-3 space group, which leads to the
presence of a C3 axis colinear to that one of the CTV unit and
aligned with the c parameter. As a consequence, the central
carbon atom of the pentane guest lies on the C3 axis, and the
two CH2CH3 groups apart the central atom are delocalized
on the three equivalent positions according to the C3 repeti-
tion.
Experimental Section
Synthesis of Tris(p-methoxybenzylcarbamoylmethyl)-amine 9.
To a solution of nitrilotriacetic acid (9.00 g, 47.1 mmol) in
pyridine (80 mL) was added under vigorous stirring p-methoxy-
benzyl amine. (19 mL, 145.6 mmol). The solution was warmed
to 50 °C, and triphenyl phosphite (49 mL, 187.2 mmol) was
added. The mixture was heated at 110 °C for 1 day, and then the
pyridine was removed under vacuum. The orange residue was
dissolved in chloroform (400 mL) and was successively washed
with 10% aq NaHCO3 (2 ꢀ 200 mL) and distilled water (1 ꢀ
200 mL). The organic layers were dried with Na2SO4, and
chloroform was removed under reduced pressure. The white
solid obtained was dissolved in chloroform, precipitated, and
washed with petroleum ether to give pure 9 as a white powder
(18.1 g, 70%). ESI-MS m/z obsd 571.2548 ([M þ Na]þ, calcd
571.2533 for C30H36N4O6Na). 1H NMR (CDCl3, 297 K, 497.80
MHz): δ 7.36 (t, 3H, 3J = 5.83 Hz, NHCdO), 7.11 (d, 6H, 3J =
3
8.66 Hz, ArH), 6.80 (d, 6H, J=8.66 Hz, ArH), 4.26 (d, 6H,
3J = 5.83 Hz, ArCH2), 3.76 (s, 9H, ArOMe), 3.26 (s, 6H,
N(CH2)3). 13C NMR (CDCl3, 297 K, 125.17 MHz): δ 170.0
(NHCdO), 158.9 (CArO), 130.0 (CAr), 129.0 (CAr), 114.0 (CAr),
60.3 (NCH2CdO), 55.2 (OMe), 42.8 (NHCH2Ar). Anal. Calcd
for C30H36N4O6: C, 65.68; H, 6.61; N, 10.21. Found: C, 65.72;
H, 6.54; N, 9.83.
Synthesis of Tris(p-hydroxybenzylcarbamoylmethyl)-amine
10. A 1 M boron tribromide solution in CH2Cl2 (200 mL, 200
mmol) was added dropwise at - 78 °C to a well-stirred solution
of 9 (19.7 g, 35.9 mmol) in CH2Cl2 (450 mL). The mixture was
allowed to warm to room temperature and stirred for 1 day. The
solution was cooled to 0 °C, and 10% aqueous solution of
NaHCO3 (600 mL) was added slowly. After addition of metha-
nol (10 mL) the organic layer was separated, and the aqueous
phase was extracted with ethyl acetate (3 ꢀ 500 mL). The
combined organic layers were dried over Na2SO4, and the
organic solvent was removed to give 10 as a white solid (15.8
g, 87%). ESI-MS m/z obsd 529.2075 ([M þ Na]þ, calcd 529.2063
for C27H30N4O6Na). 1H NMR (d6-DMSO, 297 K, 497.80
MHz): δ 9.30 (s, 3H, ArOH), 8.53 (t, 3H, 3J = 5.47 Hz,
NHCdO), 7.025 (d, 6H, 3J = 8.22 Hz, ArH), 6.68 (d, 6H,
3J = 8.22 Hz, ArH), 4.165 (d, 6H, 3J = 5.47 Hz, ArCH2),
3.27 (s, 6H, N(CH2)3). 13C NMR (d6-DMSO, 297 K, 125.17
MHz): δ 169.8 (NHCdO), 156.2 (CArO), 129.4 (CAr), 128.4
(CAr), 115.0 (CAr), 58.0 (NCH2), 41.4 (NCH2).
In summary, we have developed the synthesis of a new
class of ditopic hosts, where a triamide or tren moiety faces a
CTV unit to form a new class of hemicryptophanes. These
chiral molecules could provide a suitable environment for the
formation of metal complexes with catalytic properties.
Synthesis of Hemicryptophane Precursor 11. Compounds 10
(6.63 g, 13.1 mmol) and 7 (14.87 g, 43.1 mmol) and Cs2CO3
(18.89 g, 57.9 mmol) were dissolved in DMF (60 mL). The
solution was heated at 80 °C for 1 day. The mixture was cooled
J. Org. Chem. Vol. 75, No. 6, 2010 2101

Raytchev et al.
JOCNote
to room temperature, and distilled water (250 mL) was added.
The aqueous mixture was then extracted with ethyl acetate (4 ꢀ
150 mL). The combined organic layers were washed with
distilled water (2 ꢀ 150 mL), dried over Na2SO4, and concen-
trated under vacuum. The crude product was dissolved in
CH2Cl2 and precipitated with diethyl ether to give pure 11 as a
white powder (9.9 g, 58%). ESI-MS m/z obsd 1321.6171 ([M þ
Na]þ, calcd 1321.6148 for C72H90N4O18Na). 1H NMR (CDCl3,
297 K, 497.80 MHz): δ 7.41 (t, 3H, 3J = 5.52 Hz, NHCdO), 7.10
(d, 6H, 3J = 8.62 Hz, ArH), 6.86-6.90 (m, 9H, ArH), 6.83 (d,
6H, 3J = 8.66 Hz, ArH), 4.70 (d, 3H, 2J = 11.71 Hz, ArCH2O),
4.66 (t, 3H, 3J = 3.64 Hz, OTHP), 4.42 (d, 3H, 2J = 11.71 Hz,
ArCH2O), 4.23-4.34 (m, 18H, ArCH2N ; O(CH2)2O), 3.91 (m,
3H, OTHP), 3.82 (s, 9H, ArOMe), 3.53 (m, 3H, OTHP), 3.25 (s,
6H, N(CH2)3) 1.47-1.89 (m, 18H, OTHP). 13C NMR (CDCl3,
297 K, 125.17 MHz): δ 170.1 (NHCdO), 158.0 (CArO), 149.6
(CArO), 147.5 (CArO),131.8 (CAr), 130.4 (CAr), 129.0 (CAr),
120.5 (CAr), 114.8 (CAr), 114.0 (CAr), 112.0 (CAr), 97.6 (OCO),
68.7 (CH2O), 67.8 (CH2O), 66.5 (CH2O), 62.3 (CH2O), 60.2
(NCH2), 55.9 (OMe), 42.8 (NCH2), 30.6, 25.4, 19.5 (OTHP).
Synthesis of Tren-hemicryptophane 4. Compound 3 (310 mg)
was dissolved under vigorous stirring in a 2 M solution of
H3B SMe2 in THF (15 mL). The solution was stirred for 1 week
3
at 65 °C. After the mixture cooled to room temperature,
methanol (6 mL) and aqueous 1 M HCl (1 mL) were successively
added dropwise. The solution was then heated at 40 °C for 1 day.
The solvents were removed under vacuum, and the residue was
dissolved in chloroform (10 mL). Methanol (7 mL) and aqueous
1 M HCl (1 mL) were then added, and the mixture was stirred for
2 days at 60 °C. The solvents were removed, and the residue
was dissolved in chloroform (50 mL) and aqueous 1 M NaOH
(50 mL). The organic layer was separated, and the aqueous
phase was extracted with chloroform (3 ꢀ 40 mL).The combined
organic layers were dried over Na2SO4, and the solvent was
removed under vacuum. The crude product was purified by
column chromatography on silica gel using a 90:10:2 mixture of
CH2Cl2, methanol, and triethylamine to give 4 as a white solid
(89 mg, 30%). Crystals suitable for X-ray crystallography were
obtained by allowing pentane to slowly diffuse in a concentrated
solution of 4 in CH2Cl2 at 5 °C. ESI-MS m/z obsd 951.4916
([M þ H]þ, calcd 951.4908 for C57H67N4O9). 1H NMR (CDCl3,
297 K, 497.80MHz): δ 7.01 (s, 3H, ArH), 6.91(br, 6H, ArH), 6.82
(s, 3H, ArH), 6.48 (d, 6H, 3J = 7.56 Hz, ArH), 4.75 (d, 3H, 2J =
13.63 Hz, Ha), 4.14-4.42 (m, 12H, O(CH2)2O), 3.65 (s, 9H,
OMe), 3.54 (d, 3H, 2J = 13.63 Hz, He), 3.43-3.54 (br, 6H,
ArCH2N), 2.48-2.70 (br, 12H, N(CH2)2N). 13C NMR (CDCl3,
297 K, 125.17 MHz): δ 157.4 (NHCdO), 148.3 (CArO), 146.4
(CArO), 133.0 (CAr), 132.9 (CAr), 131.7 (CAr), 129.1 (CAr), 116.8
(CAr), 114.7 (CAr), 113.5 (CAr), 67.7 (OCH2), 67.6 (OCH2), 55.9
(OMe), 55.6 (NCH2), 53.0 (NCH2), 47.0 (NCH2), 36.5 (ArCAr).
Anal. Calcd for C72H90N4O18 CH2Cl2: C, 63.33; H, 6.70; N,
3
4.05. Found: C, 63.65; H, 6.68; N, 4.21.
Synthesis of Triamide-hemicryptophane 3. Precursor 11 (2.50
g, 1.93 mmol) was dissolved in formic acid (2.5 L). The mixture
was stirred for 1 day at room temperature, and then the formic
acid was removed under vacuum. The brown residue was
dissolved in chloroform (100 mL), and aqueous K2CO3 (10%,
50 mL) was added. The organic layer was separated, and the
aqueous phase was extracted with chloroform (2 ꢀ 100 mL). The
combined organic layers were dried with Na2SO4, and then the
organic solvent was removed under vacuum. The crude product
was purified by column chromatography on silica gel using a
15:3 mixture of chloroform and methanol as eluent to give 3
(575 mg, 30%) as a white powder. Crystallization from CH2Cl2
gave suitable material for X-ray crystallography analysis.
ESI-MS m/z obsd 1015.4093 ([M þ Na]þ, calcd 1015.4105 for
X-ray Crystallography. 3 CH2Cl2: C58H62Cl2N4O12, Mw
3
˚
1078.05 monoclinic P21/n, a = 10.997(5) A, b = 18.282(5) A,
˚
3
˚
˚
c = 28.996(5) A, β = 95.320(5)°, V = 5804(3) A , Dc = 1.230 g
cm-3, Z = 4, μ = 0.17 mm-1, R1 = 0.136, wR2 = 0.144 for 3218
reflections with I > 2σ(I). 4 Pentane: C62H78N4O9, Mw 1023.32
3
˚
˚
˚
trigonal R-3, a = 16.61(2) A, b = 16.61(8) A, c = 37.24(1) A, V =
1
3
8897(3) A , Dc =1.148gcm-3, Z=2, μ=0.08mm-1, R1 = 0.139,
˚
C57H60N4O12Na). H NMR (CDCl3, 297 K, 497.80 MHz): δ
7.04 (s, 3H, ArH), 6.82 (s, 3H, ArH), 6.75 (l, 3H, NHCdO),
wR2 = 0.171 for 1469 reflections with I > 2σ(I). Details on data
collections and refinements are reported in Supporting Information.
3
6.655 (d, 6H, 3J = 8.56 Hz, ArH), 6.35 (d, 6H, J = 8.56 Hz,
ArH), 4.77 (d, 3H, 2J = 13.69 Hz, Ha), 4.49-4.55 (m, 3H,
O(CH2)2O), 4.31-4.37 (m, 3H, O(CH2)2O), 4.20-4.28 (m, 6H,
O(CH2)2O; ArCH2N), 4.13-4.19 (m, 3H, O(CH2)2O), 3.70
Acknowledgment. The authors thank Dr. Erwann Jeanneau
ꢀ
(Centre de Diffractometrie Henri Longchambon, University of
Lyon) for X-ray assistance and facilities.
2
(dd, 3H, ArCH2N), 3.64 (s, 9H, ArOMe), 3.55 (d, 3H, J =
13.69 Hz, He), 3.18 (d, 3H, 2J = 16.49 Hz, N(CH2)3), 3.12 (d,
3H, 2J = 16.49 Hz, N(CH2)3). 13C NMR (CDCl3, 297 K, 125.17
MHz): δ 169.5 (NHCdO), 157.7 (CArO), 148.3 (CArO), 146.3
(CArO), 132.9 (CAr), 131.8 (CAr), 130.35 (CAr), 128.76 (CAr),
116.61 (CAr), 114.92 (CAr), 113.6 (CAr), 67.9 (OCH2), 67.3 (OCH2),
60.9 (NCH2), 55.8 (OMe), 42.7 (NCH2), 36.5 (ArCAr). Anal.
Supporting Information Available: General experimental
methods for compounds 3, 4, and 9-11; 1H and 13C NMR
spectra for all new compounds; crystallographic information
files in CIF format for 3 CH2Cl2 (CCDC 758472) and
4 pentane (CCDC 758471). This material is available free of
charge via the Internet at http://pubs.acs.org.
3
Calcd for C57H60N4O12 2CH2Cl2: C, 60.93; H, 5.55; N, 4.82.
3
3
Found: C, 60.63; H, 5.58; N, 5.01.
2102 J. Org. Chem. Vol. 75, No. 6, 2010