A new prearranged tripodant ligand N,N′,N″-trimethyl-N,N′,N″-tris(3-pyridyl)-1,3, 5-benzene tricarboxamide is easily obtained via the N-methyl amide effect

Article abstract of DOI:10.1016/S0040-4039(01)00800-0

The N-methyl amide cis generating effect has been utilised to create a new prearranged tripodant ligand in two synthetic steps from benzene-1,3,5-tricarboxylic acid. Crystals of the ligand itself and of complexes with metal salts such as silver(I) triflate, copper(I) and copper(II) chloride and ruthenium(II) chloride have been prepared and the crystal structures solved by analysis of X-ray diffraction data.

Full text of DOI:10.1016/S0040-4039(01)00800-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 4717–4720
A new prearranged tripodant ligand
N,N%,N¦-trimethyl-N,N%,N¦-tris(3-pyridyl)-1,3,5-benzene
tricarboxamide is easily obtained via the N-methyl amide effect
Mikkel Jørgensen* and Frederik C. Krebs
The Danish Polymer Centre, Risø National Laboratory, PO Box 49, DK-4000 Roskilde, Denmark
Received 2 April 2001; revised 2 May 2001; accepted 11 May 2001
Abstract—The N-methyl amide cis generating effect has been utilised to create a new prearranged tripodant ligand in two
synthetic steps from benzene-1,3,5-tricarboxylic acid. Crystals of the ligand itself and of complexes with metal salts such as
silver(I) triflate, copper(I) and copper(II) chloride and ruthenium(II) chloride have been prepared and the crystal structures solved
by analysis of X-ray diffraction data. © 2001 Elsevier Science Ltd. All rights reserved.
Yamaguchi et al. and others have shown in a number
of papers that N-methylation of benzoylanilides
changes the normal trans-amide configuration to a cis
configuration with the aryl groups arranged in a V-
shaped plane-to-plane geometry.1,2 In the following we
will call this interesting effect the ‘methyl amide effect’.
The Cambridge Structural Database (CSD) has been
searched for NH and N-methyl biaryl-carboxamide
occurrences2 showing that the conformational change
from trans to cis is strictly adhered to. While the effect
has been substantiated through numerous crystal struc-
tures of model compounds, there have been few reports
that take specific advantage of the N-methyl effect. In
the present work, we describe how to use the effect in a
very simple way to create a new pre-arranged tripodal
ligand.
C3-axis. Substitution with nitrogen atoms in these posi-
tions would clearly aid in the construction of a tripo-
dant ligand molecule. The orientation of the ligand
atoms could thus be rigidly fixed to accommodate
tetrahedral or octahedral complexes of transition metal
ions.
The new tripodant ligand N,N%,N¦-trimethyl-N,N%,N¦-
tris(3-pyridyl)-1,3,5-benzene tricarboxamide (2a) with
three pyridine moieties prearranged to bind metal ions
has been prepared in a one-step reaction between 3-
methylamino-pyridine and 1,3,5-benzene tricarboxylic
acid chloride. Crystals of the ligand itself and of com-
plexes with metal salts such as silver(I) triflate, cop-
per(I) and copper(II) chloride have been prepared and
the crystal structures solved by analysis of X-ray dif-
fraction data.
In the special case of 1,3,5-benzene tricarboxamide with
three N-methyl-aniline groups, all three anilide sub-
stituents were found to be orientated to the same side
of the central benzene triamide ring.1 The question was
whether this structural feature would be preserved if the
three aniline moieties were functionalised. In the case of
such a general structure generating element it would be
possible to make prearranged ligands for metal ions.
Careful inspection of the native 1,3,5-benzene tricar-
boxamide structure showed that the three carbon atoms
meta to the amide groups are close to the central
We set out to test the generality of being able direct all
three anilide substituents to the same side of the central
benzene ring by synthesising various substituted
molecules according to Scheme 1. 1,3,5-Benzene tricar-
boxylic acid chloride was treated with either 4-nitroani-
line or 4-amino-benzoic acid ethyl ester to prepare the
corresponding NH amides. N-Methylation was carried
out with potassium t-butoxide/methyl iodide in THF.2
Alternatively, the aniline part could be methylated first,
followed by reaction with the benzene tricarboxylic acid
chloride. This route was investigated using 3-amino-
pyridine, which was N-methylated according to the
procedure of Clarke–Lewis and Thompson.3
Keywords: amides; complexes; transition metals; X-ray crystallo-
graphy.
* Corresponding author. E-mail: mikkel.joergensen@risoe.dk
Proton NMR spectra of the N-methylated amides 2a–c
are very simple (and different from the corresponding
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00800-0

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M. Jørgensen, F. C. Krebs / Tetrahedron Letters 42 (2001) 4717–4720
R
1a R=EtOOC- (95%)
1b R=NO2 (93%)
X
O
NH
i
R
NH2
H
N
O
O
HN
R
iii
ii
R
R
N
CH3
O
N
X
X
CH3
NH
X
i
R
R
O
H3C
O
N
CH3
R
X
2a R=H and X=N (71%)
2b R=EtOOC- and X=CH (51%)
2c R=NO2 and X=CH (67%)
Scheme 1. i. C6H3(COCl)3, Et2N; ii. KO-t-Bu, THF, CH3I; iii. (a) TsCl, py.; (b) (CH3O)2SO2; (c) H2SO4.
NH amides 1a–c) suggesting that they have C3 symme-
structure determinant. In all cases, the three aniline
try regardless of the preparation route and substituents.
substituents bend to the same side of the central ring in
a propeller like arrangement. The edge of each ring
makes contact with the neighbouring ring plane, sug-
gesting that the C3 symmetric conformer is especially
stabilised by these Van der Waals interactions.
1
Dramatic shielding effects are observed in the H NMR
spectra when comparing the NH amides 1a–b to the
N-methylated amides 2a–c. For the NH amide triester
1a, signals due to the 12 aryl protons on the three
aniline rings occur together at 8.01 ppm, while in the
N-methyl amide 2a, two doublets are seen at 8.00 and
6.61 ppm. The signals from six of these protons have
thus changed by 1.4 ppm upfield in accordance with the
magnetic shielding expected for the protons orientated
towards the plane of adjacent rings.4 Similar effects are
observed for the other triamides prepared. The struc-
tures in solution of the N-methyl amides are therefore
in accordance with the crystal structure obtained by
Yamaguchi for the native compound.
The molecular geometry as established from the X-ray
structures for the neutral compounds 2a, 2b and 2c is
very similar to the previously reported parent triben-
zenoid system.1 In the case of 2a we found a cubic
space group in contrast to the original authors, and as
suggested in a recent errata5 for this parent compound.
While 2a is different (differing with three less hydrogen
atoms) it is reasonable to expect that these compounds
could be isostructural. The complexes with Ag(I) and
Ru(II) have a near perfect octahedral coordination
environment around the metal ion. It is noticeable that
the ruthenium complex is more contracted due to the
doubly charged cation. This is reflected in the plane-to-
plane distance between the benzene rings in the com-
Crystals of sufficient quality for X-ray diffraction were
grown from acetonitrile/ethanol. The crystal structures
of these compounds (see Figs. 1–3) clearly show that
the N-methyl amide effect is a general and powerful
Figure 1. A stereoview of the molecular geometry as determined from the X-ray structure of the ligand 2a. Compounds 2b and
2c have a very similar molecular geometry. The solvent molecule of 2a has been omitted for clarity.

M. Jørgensen, F. C. Krebs / Tetrahedron Letters 42 (2001) 4717–4720
4719
Figure 2. A Stereoview of the molecular geometry of the transition metal complex of 2a with Ag(I). The counter ion and solvent
molecule are omitted for clarity. The geometry of the Ru(II) complex is very similar.
Figure 3. Stereoviews of the molecular geometry of the transition metal complexes of 2a with Cu(I) (above) and Cu(II) (below).
Counter ions, solvent molecules and the disordered chlorine atom for the Cu(II) salt are omitted for clarity.
,
,
plex 11.047(2) A for the Ag(I) complex and 10.362(8) A
for the Ru(II) complex. The Cu(I) complex shows a
near tetrahedral coordination of the metal ion, whereas
the Cu(II) complex shows a near square pyramidal
coordination of the metal ion involving two chloride
ions and two pyridine nitrogen atoms in the square.
The typical pyridine nitrogen to metal distances
observed are 2.524(3), 2.137(12), 2.068(2) and 2.104(3)
Experimental procedures
1a: 1,3,5-Benzenetricarboxylic acid (2.10 g, 10 mmol)
was refluxed together with thionyl chloride (25 mL) for
1 h. Excess thionyl chloride was distilled at reduced
pressure leaving the benzenetricarboxylic acid chloride
as an oil. This oil was dissolved in methylene chloride
(20 mL) and added slowly to a mixture of 4-aminoben-
zoic acid ethyl ester (5 g, 30 mmol) and triethyl amine
(3 mL) in methylene chloride (50 mL). The mixture was
stirred at ambient temperature for an additional 30 min
to complete the reaction, whereupon the solvents were
,
A for the Ag(I), Ru(II), Cu(I) and Cu(II) complexes,
respectively. The data shows that the ligand 2a can
adapt to varying coordination numbers, as well as
metal-to-ligand distances.

4720
M. Jørgensen, F. C. Krebs / Tetrahedron Letters 42 (2001) 4717–4720
removed in vacuum. The residue was recrystallised
7 Hz), 3.39 (9H, s), 1.40 (9H, s) ppm. 13C NMR (62.9
MHz, CDCl3) l: 14.7, 38.1, 61.8, 127.1, 129.0, 130.7,
131.0, 136.1, 148.7, 165.8, 169.0 ppm. Crystal data:
C39H39N3O9, M=693.73, trigonal space group R-3c, a,
from 96% ethanol to give N,N%,N¦-tris(4-ethoxycar-
bonylphenyl)-1,3,5-benzenetricarboxamide 1a as
a
white crystalline powder (6.25 g, 95% yield). Mp 238–
, ,
b=14.2571(15) A, c=61.462(9) A, h, i=90°, k=120°,
3 −3
9°C. Anal. found: C, 64.25; H, 5.37; N, 6.16. Calcd for
1
,
C36H33N3O9
·
H2O: C, 64.57; H, 5.27; N, 6.27; H NMR
V=10819(2) A , Z=12, Dc=1.278 g cm , T=120(2)
K, v=0.091 cm−1, wR2=0.1293 (1915 unique reflec-
tions [I>2|(I)]), R=0.0421.
lH (250.1 MHz, CDCl3–DMSO-d6, 1:1): 10.62 (3H, s),
8.87 (3H, s), 8.01 (12H, s), 4.34 (6H, q, J 7 Hz), 1.40
(9H, t, J 7 Hz) ppm. 13C NMR (62.9 MHz, CDCl3–
DMSO-d6, 1:1) l: 14.4, 60.7, 119.8, 125.6, 130.4, 130.6,
135.5, 143.4, 165.1, 165.9.
2c: Prepared from 1b, potassium t-butoxide and methyl
iodide as above. Recrystalised from dilute ethanol to
give N,N%,N¦-trimethyl-N,N%,N¦-tris(4-nitrophenyl)-1,3,
5-benzene tricarboxamide (yield: 67%). Mp 131–132°C.
Anal. found: C, 56.86; H, 4.13; N, 13.06. Calcd for
C30H24N6O9·H2O: C, 57.14; H, 4.16; N, 13.33; 1H
NMR (250.1 MHz, CDCl3–DMSO-d6, 1:1) l: 3.33 (9H,
s), 7.16 (6H, d, J 9 Hz), 7.25 (3H, s), 8.14 (6H, d, J 9
Hz) ppm. 13C NMR (62.9 MHz, CDCl3–DMSO-d6, 1:1)
l: 38.2, 125.0, 127.9, 130.3, 136.5, 145.7, 150.3, 168.5
ppm. Crystal data: C32H30N6O10, M=658.62, trigonal
1b: Obtained from 4-nitroaniline and benzene-1,3,5-tri-
carboxylic acid chloride, as described in Reference 6.
2a: 3-Methylaminopyridine (3.3 g, 30.5 mmol) and tri-
ethylamine (3.5 g, 35 mmol) were dissolved in chloro-
form (150 mL). 1,3,5-Benzene tricarboxylic acid
chloride (2.65 g, 10 mmol) in chloroform (50 mL) was
added dropwise. The reaction mixture was stirred at
ambient temperature for a further hour and then the
solvents were evaporated in vacuum. The residue was
triturated with methanol (100 mL), filtered and washed
with methanol and petrol. Finally, the product
N,N%, N¦-trimethyl-N,N%,N¦-tris(3-pyridyl)-1,3,5-ben-
zene tricarboxamide was crystallised from methylene
chloride/acetonitrile (yield: 3.4 g, 71%.). Mp 199–
200°C. Anal. found: C, 59.40; H, 4.74; N, 14.76. Calcd
for C27H24N6O3·CH2Cl2: C, 59.47; H, 4.63; N, 14.86.
1H NMR (250.1 MHz, CDCl3) l: 3.39 (9H, s), 7.04
(3H, d, J 7 Hz), 7.12 (3H, s), 7.26–7.32 (3H, m), 8.05
(3H, s), 8.48 (3H, d, J 7 Hz). 13C NMR (62.9 MHz,
CDCl3) l: 38.6, 124.4, 130.8, 134.3, 135.8, 141.1,
148.19, 148.24, 168.7 ppm. Crystal data: C29H30N6O4,
,
,
space group R-3, a, b=12.1180(12) A, c=37.310(5) A,
h, i=90°, k=120°, V=4744.8(9) A , Z=6, Dc=1.383
3
,
g cm−3, T=120(2) K, v=0.105 cm−1, wR2=0.2863
(1479 unique reflections [I>2|(I)]), R=0.0968.
Crystallographic data (excluding structure factors) for
the structures reported in this paper have been
deposited with the Cambridge Crystallographic Data
Centre. Copies of the data can be obtained free of
charge on application to CCDC, 12 Union Road, Cam-
bridge CB2 1EZ, UK [Fax: (internat.) +44-1223/
336033; e-mail: deposit@ccdc.cam.ac.uk] on quoting
the depository numbers CCDC-162962 (2a), CCDC-
162963 (2b), CCDC-162964 (2c), CCDC-162965
(Ag(2a)2), CCDC-162966 (Cu(I)2a), CCDC-162967
(Cu(II)2a), CCDC-162968 (Ru(2a)2).
M=526.59, cubic space group Pa-3, a, b, c=
3
,
,
17.4437(13) A, h, i, k=90°, V=5307.8(7) A , Z=8,
Dc=1.318 g cm−3, T=120(2) K, v=0.090 cm−1, wR2=
0.2658 (1702 unique reflections [I>2|(I)]), R=0.0774.
2b: Triamide 1a (3.0 g, 4.7 mmol) was dissolved in THF
(200 mL) together with methyl iodide (2 mL). Potas-
sium t-butoxide (1.8 g) was added and the reaction
mixture was stirred 48 h whereupon the solvent was
removed. The remaining solid was partitioned between
cold dilute hydrochloric acid (50 mL) and methylene
chloride (100 mL). The slightly yellow organic phase
was evaporated to dryness and crystallised from etha-
nol (20 mL) to give 2b as colourless crystals of
N,N%,N¦ - trimethyl - N,N%,N¦ - tris(4 - ethoxycarbonyl-
phenyl)-1,3,5-benzene tricarboxamide (1.65 g, 51%).
Mp 218–219°C. Anal. found: C, 66.99; H, 5.74; N, 6.15.
Calcd for C39H39N3O9·0.5EtOH: C, 67.03; H, 5.91; N,
References
1. Azumaya, I.; Kagechika, H.; Yamaguchi, K.; Shudo, K.
Tetrahedron 1995, 51, 5277.
2. Krebs, F. C.; Larsen, M.; Jørgensen, M.; Jensen, P. R.;
Bielecki, M.; Schaumburg, K. J. Org. Chem. 1998, 63,
9872.
3. Clark-Lewis, J. W.; Thompson, M. J. J. Chem. Soc. 1957,
442.
4. Gu¨nther, H. NMR Spectroscopy; John Wiley and Sons:
New York, 1980.
5. Herbstein, F. H. Acta Crystallogr., Sect. C (Cr. Str.
Comm.) 1999, 55, 1196.
6. Ishida, Y.; Jikei, M.; Kakimoto, M. Macromolecules 2000,
33, 3202.
1
5.86; H NMR (250.1 MHz, CDCl3) l: 8.00 (6H, d, J 8
Hz), 7.08 (3H, s), 6.61 (6H, d, J 8 Hz), 4.39 (6H, q, J
.