A general one-step synthesis of multidentate (pyridylalkyl)amines from mono-, bis-, tris- and tetrakis(bromomethyl)benzenes: Potential ligands for supramolecular assembly

Article abstract of DOI:10.1055/s-2007-990904

The synthesis of new multidentate nitrogen-containing ligands is of ongoing interest. In this report, the one-step syntheses of a series of (pyridylalkyl)amine derivatives is described. The reported compounds contain both pyridine rings and sp³-hybridized nitrogen as potential donor sites. The general synthetic method involves a room temperature reaction of mono-, bis-, tris-, or tetrakis(bromomethyl)benzenes with an excess of (pyridylmethyl)amine in tetrahydrofuran. The products can be purified by distillation, chromatography or recrystallization and are obtained in fair to good yields. The advantages of this synthetic method are the procedural simplicity and the ready availability of the starting materials. The applicability of these compounds in supramolecular chemistry is demonstrated by the reaction of two of the described ligands with silver(I) salts. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-990904

PAPER
79
A General One-Step Synthesis of Multidentate (Pyridylalkyl)amines from
Mono-, Bis-, Tris- and Tetrakis(bromomethyl)benzenes: Potential Ligands for
Supramolecular Assembly
Multidentate
(a
rl)aminesbati Sengupta, Amanda E. Henkes, Mananjali K. Kumar, Hongming Zhang, David Y. Son*
Department of Chemistry, Southern Methodist University, P.O. Box 750314, Dallas, TX 75275, USA
Fax +1(214)7684089; E-mail: dson@smu.edu
Received 9 July 2007
the corresponding carbonyl compounds. As an outgrowth
Abstract: The synthesis of new multidentate nitrogen-containing
ligands is of ongoing interest. In this report, the one-step syntheses
of a series of (pyridylalkyl)amine derivatives is described. The re-
ported compounds contain both pyridine rings and sp3-hybridized
of our research involving the design of new multidentate
nitrogen-heteroaromatic ligands,40–43 we sought a short
and simple synthesis of bis(pyridylmethyl)amines (4–9)
nitrogen as potential donor sites. The general synthetic method that did not require imine intermediates. As a result of this
involves a room temperature reaction of mono-, bis-, tris-, or
tetrakis(bromomethyl)benzenes with an excess of (pyridylmeth-
yl)amine in tetrahydrofuran. The products can be purified by distil-
cedure (Figure 1). All of these compounds (most of which
lation, chromatography or recrystallization and are obtained in fair
to good yields. The advantages of this synthetic method are the pro-
cedural simplicity and the ready availability of the starting materi-
als. The applicability of these compounds in supramolecular
chemistry is demonstrated by the reaction of two of the described
ligands with silver(I) salts.
investigation, we report the syntheses of 4–9 and the relat-
ed (pyridylalkyl)amines 1–3 and 10–18 by a one-step pro-
were previously unknown) possess multiple nitrogen
binding sites and may thus serve as useful precursors of
new supramolecular materials. In this regard, two specific
examples of Ag(I)-guided supramolecular assembly are
also described.
Key words: pyridines, amines, alkylations, ligands, supramolecu-
lar chemistry
Despite the well-documented difficulty in controlling the
degree of alkylation of nitrogen nucleophiles,44 we be-
lieved a simple and direct approach to the synthesis of the
desired (pyridylmethyl)amines might be the reaction of
(bromomethyl)benzenes with 2-, 3- or 4-(aminometh-
yl)pyridine – all readily available materials. To test this
approach, we first examined the reaction of benzyl bro-
mide with 2-, 3- and 4-(aminomethyl)pyridine to give 1–
3 (Equation 1). We found that stirring an excess of 2-
(aminomethyl)pyridine with benzyl bromide in tetrahy-
drofuran (THF) for 18 hours at room temperature indeed
gave 1, isolated in 66% yield after filtration and distilla-
tion. Compound 1 was previously prepared in 46% yield
via a conventional reductive amination route45 (86% yield
Pyridylamines and structurally related compounds have
been incorporated into a variety of synthetic targets in-
cluding antitumor complexes,1–8 supramolecular com-
plexes and assemblies,9–35 and ion receptors.36–38 The
presence of both pyridine and sp3-nitrogen atoms give py-
ridylamines a high degree of versatility in the synthesis of
these materials. The prevailing method for the synthesis
of pyridylamines is the reductive amination of carbonyl
compounds.39 Although well-known, reductive amination
is a two-step process and dependent on the availability of
N
N
N
N
N
H
H
H
H
H
N
N
N
N
N
4, 2-pyridyl
5, 3-pyridyl
6, 4-pyridyl
1, 2-pyridyl
2, 3-pyridyl
3, 4-pyridyl
7, 2-pyridyl
8, 3-pyridyl
9, 4-pyridyl
N
N
N
H
N
H
N
N
N
N
N
NH
N
13, 2-pyridyl
14, 3-pyridyl
15, 4-pyridyl
10, 2-pyridyl
11, 3-pyridyl
12, 4-pyridyl
16, 2-pyridyl
17, 3-pyridyl
18, 4-pyridyl
N
Figure 1 Compounds synthesized in this study
SYNTHESIS 2008, No. 1, pp 0079–0086
x
x
.
x
x
.2
0
0
7
Advanced online publication: 15.11.2007
DOI: 10.1055/s-2007-990904; Art ID: M05007SS
© Georg Thieme Verlag Stuttgart · New York

80
P. Sengupta et al.
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using
a
polymer supported reductive amination ic, colored oils except for 5, which slowly solidified.
reaction46). This synthetic method also worked well with Reactions of a,a¢-dibromo-o-xylene with the various
the other (aminomethyl)pyridine isomers; reaction of ben- (aminomethyl)pyridines gave unexpected results. In these
zyl bromide with 3-(aminomethyl)pyridine gave 2 in 60% cases, we did not obtain the expected bis-substituted prod-
yield (prepared in 50% yield by reductive amination47), ucts, but rather the previously unknown cyclized bidentate
and reaction with 4-(aminomethyl)pyridine gave 348 in (pyridylalkyl)amines 10–12 in 48–62% purified yields.
56% yield (Table 1).
Compounds 10–12, isolated as colored oils, were clearly
formed as a result of an intramolecular cyclization of the
monosubstituted intermediate (Scheme 1).
NH2
Br
THF
1, 2, 3
+ excess
r.t., overnight
N
CH2Br
Equation 1
4
+ excess
NH2
N
Table 1 Product Yields for (Pyridylalkyl)amines
CH2Br
Product
Yield (%)a
Equation 2
1
66
60
56
20
42
42
2
Br
Br
+
NH2
3
N
4
5
H
N
6
10
b
N
7
–
HBr
Br
8
40
37
48
62
59
28
49
13
46
46
38
Scheme 1 Reaction mechanism for the synthesis of 10
9
10
Multidentate 1,3,5-trisubstituted benzenes are attractive
synthetic targets due to their utility in supramolecular
chemistry49–55 and actinide sequestration.56 Accordingly,
the reactions of 2-, 3- and 4-(aminomethyl)pyridine with
1,3,5-tris(bromomethyl)mesitylene57 proceeded in the ex-
pected fashion (Equation 3, using 13 as an example), giv-
ing the new trisubstituted compounds 13–15 in 28%, 49%
and 13% yields, respectively. Compounds 13–15 were
initially isolated as hygroscopic oils, but 14 slowly solid-
ified on standing, giving a collection of both fan-shaped
and cube-shaped crystals. Redissolving a portion of these
crystals in acetone, followed by slow evaporation, gave a
collection of colorless X-ray quality crystals. Subsequent
crystallographic analysis revealed the expected structure
of 14 as shown in Figure 2 (see also Table 2).
11
12
13
14
15
16
17
18
a Purified yields.
b Could not be purified by chromatography.
With these results in hand, we next applied this method to
reactions involving a,a¢-dibromoxylenes. We were
pleased to find that reaction of an excess of 2-(amino-
methyl)pyridine with a,a¢-dibromo-p-xylene under the
same conditions gave 4, although in modest yield (20%;
Equation 2). In subsequent experiments, this method was
applied successfully for the syntheses of 5, 6, 8 and 9, all
in reasonable yields (see Table 1). For the synthesis of 7,
we believed the product was obtained, but we were unable
to achieve a satisfactory separation using chromatogra-
phy. All of these compounds were isolated as hygroscop-
Br
Br
+
13
excess
N
CH2NH2
Br
Equation 3
The intramolecular cyclization illustrated in the syntheses
of 10–12 (Scheme 1) suggested to us that reaction of (ami-
nomethyl)pyridines with 1,2,4,5-tetrakis(bromometh-
yl)benzene could give novel polycyclic products.
Synthesis 2008, No. 1, 79–86 © Thieme Stuttgart · New York

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Multidentate (Pyridylalkyl)amines
81
NH2
Br
Br
Br
+ excess
Br
N
r.t.
THF
overnight
N
N
N
16,17,18
N
Equation 4
During the course of this investigation, we learned that the
synthetic method described herein works only with bro-
momethylbenzenes and not the corresponding chloro-
methylbenzenes. Furthermore, we found that adding an
external base instead of an excess of the (aminometh-
yl)pyridine is ineffective. Bases we have examined to this
effect include sodium hydroxide, potassium hydroxide,
pyridine and triethylamine. Therefore, an excess of the
(aminomethyl)pyridine is necessary to provide a proton
acceptor for the reaction. If so desired, the excess (ami-
nomethyl)pyridine can be recycled by distillation. Some
of the low product yields may be attributed to the fact that
the products themselves may be protonated during the re-
action and therefore removed during the filtration step. To
address this issue, we repeated the synthesis of 16 but
stirred the reaction mixture with pulverized potassium hy-
droxide for 1.5 hours before filtration. The result was a
marginal increase in yield after recrystallization (57% vs
46%), which nonetheless suggests that some protonation
of product may be occurring during the reaction.
Figure 2 ORTEP plot of 14 (50% ellipsoids); does not include two
water molecules, which are part of the unit cell
Accordingly, reactions of 2-, 3- and 4-(aminomethyl)py-
ridine with 1,2,4,5-tetrakis(bromomethyl)benzene gave
previously unknown compounds 16–18 in 46%, 46% and
38% yields, respectively (Equation 4). Compounds 16–18
were purified by recrystallization and isolated as slightly
colored crystalline solids. Besides the usual characteriza-
tion by spectroscopic and combustion analyses, the struc-
ture of 18 was confirmed by single crystal X-ray analysis.
Table 2 Selected Crystallographic Data for compounds 14, 19 and 20
14
19
C20H22N4AgNO3
20
Formula
FW
C30H36N6·2H2O
516.68
C25H26AgF3N4O3.5
635.43
S
488.30
rhombohedral
R3
Crystal system
Space group
a (Å)
triclinic
P1
triclinic
P1
10.207(3)
11.812(3)
13.956(3)
113.858(4)
100.138(5)
101.997(5)
1440.2(6)
2
32.9201(15)
32.9201(15)
9.9920(9)
90
8.836(2)
10.759(3)
15.420(4)
95.544(4)
91.344(4)
108.471(4)
1381.6(6)
2
b (Å)
c (Å)
a (°)
b (°)
90
g (°)
120
V (Å3)
9377.9(10)
18
Z
R1 [I > 2s(I)]
wR2 (all data)
0.062
0.076
0.135
0.164
0.216
0.303
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82
P. Sengupta et al.
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teraction of 5 with silver nitrate.58 Interestingly, in this
case, an infinite one-dimensional polymer was obtained in
which N–Ag–N interactions served to link individual
ligand molecules end-to-end. The difference in structure
may possibly be attributed to the different solvent system
used to grow the crystals (EtOH–H2O in this case).
In a second experiment, compound 18 was reacted with
silver triflate in a THF–H2O mixture. Within one hour,
numerous small crystals had formed on the sides of the re-
action vial. X-ray structural characterization indicated the
formation of an infinite linear polymer (20) consisting of
alternating Ag(I) ions and molecules of 18. Each Ag(I)
was bound quasi-linearly to two pyridine nitrogen atoms
from adjacent molecules of 18 (N–Ag–N 169.2°). In this
case, the sp3-hybridized nitrogen atoms of 18 were not in-
volved in Ag–N bonding. Each linear polymer chain was
tethered to a single nearby chain by Ag–Ag interactions
(Ag–Ag 3.258 Å), thus giving the overall structure the ap-
pearance of a ladder with the Ag–Ag interactions being
the rungs (Figure 4).
Figure 4 Ladder-like structure of 20; hydrogen atoms and triflate
groups are omitted for clarity
In conclusion, we have synthesized a series of (pyridyl-
alkyl)amine derivatives using a simple one-step method
based on N-alkylation chemistry. These compounds pos-
sess multiple nitrogen binding sites and therefore are at-
tractive from a ligand application standpoint, as
demonstrated by the formation of supramolecular poly-
mers from the reactions of 5 and 18 with Ag(I) salts. Al-
though our reported yields are generally modest, we
believe the simplicity of this method and the ready avail-
ability of the starting materials make this an attractive pre-
parative approach. We are continuing our investigation
into these materials as ligands for supramolecular assem-
blies.
Figure 3 (a) Subunit of three-dimensional polymer 19; (b) view
down the crystallographic c axis; in both (a) and (b), hydrogen atoms
and nitrate groups are omitted for clarity
In order to demonstrate the application of these ligands in
supramolecular assembly, we reacted 5 and 18 with Ag(I)
salts. In one experiment, compound 5 was mixed with sil-
ver nitrate in an acetone–water mixture. Visually colorless
crystals formed after three days of slow solvent evapora-
tion. X-ray crystallographic analysis (Table 2) revealed
the assembly of a three-dimensional polymer (19). A sub-
unit of the structure is shown in Figure 3(a). The silver
ions in the polymer are three-coordinate and exist in a dis-
torted T-shaped geometry, with two sp3-nitrogen atoms
from different ligand molecules forming the ends of the T-
crossbar (N1–Ag–N2 152.8°). The third donating atom to
the silver is a pyridine nitrogen (N13_B) from a third
ligand molecule. Viewing the structure down the crystal-
lographic c-axis reveals a regular repeating pattern with
well-defined channels of varying size [Figure 3(b)]. Dur-
ing the course of this work, Zhu et al. also reported the in-
All NMR spectra were obtained on a 400 MHz Bruker Avance DRX
multinuclear NMR spectrometer. Elemental analyses were obtained
from Galbraith Laboratories Inc., or by using a CE Elantech Ther-
mo-Finnigan Flash 1112 CHN elemental analyzer. 1,3,5-Tris(bro-
momethyl)mesitylene was prepared using a literature procedure.57
All other starting materials were obtained commercially from Sig-
ma–Aldrich or Acros and used as received.
Alkylation; Typical Procedure
All reactions were performed under an atmosphere of dry nitrogen.
The synthesis of compound 1 is representative of the alkylation pro-
cedure. BnBr (1.19 mL, 10 mmol) in THF (100 mL) was added to a
round-bottom flask and 2-(aminomethyl)pyridine (2.03 mL, 20
mmol) was added by syringe. The reaction mixture was stirred over-
night at r.t. then the precipitated salts were filtered off and the sol-
vent was removed under reduced pressure. Fractional distillation of
the remaining yellow-brown liquid gave 1; yield: 1.3g (66%); col-
orless liquid; bp 140 °C/1 mmHg (Lit.45 180 °C/0.1 mm Hg).
Synthesis 2008, No. 1, 79–86 © Thieme Stuttgart · New York

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Multidentate (Pyridylalkyl)amines
83
The spectral characterization data for 1 has been reported previous-
Anal. Calcd for C20H22N4·H2O: C, 71.40; H, 7.19; N, 16.65. Found:
C, 71.48; H, 7.27; N, 16.97.
ly.45
2
8
The general method was used with the following reagent amounts:
BnBr (1.19 mL, 10 mmol), 3-(aminomethyl)pyridine (2.03 mL, 20
mmol) and THF (100 mL); yield: 1.19 g (60%); pale-yellow liquid;
bp 135°C/0.05 mm Hg.
1H NMR (CDCl3, 400 MHz): d = 1.90 (br s, 1 H), 3.83 (s, 4 H),
7.26–7.36 (m, 6 H), 7.72 (d, J = 7.7 Hz, 1 H), 8.52 (d, J = 4.6 Hz,
1 H), 8.59 (s, 1 H).
The general method was used with the following reagent amounts:
a,a¢-dibromo-m-xylene (2.63 g, 10 mmol), 3-(aminomethyl)pyri-
dine (4.06 mL, 40 mmol) and THF (150 mL). Flash chromatogra-
phy on silica gel (MeOH–acetone, 1:2) gave 8; yield: 1.26 g (40%);
orange liquid.
1H NMR (CDCl3, 400 MHz): d = 3.82 (s, 4 H), 3.88 (s, 4 H), 7.23–
7.24 (m, 6 H), 7.71 (d, J = 7.7 Hz, 2 H), 8.52 (d, J = 3.5 Hz, 2 H),
8.59 (br s, 2H).
13C NMR (CDCl3, 100 MHz): d = 50.36, 53.13, 123.34, 127.11,
128.11, 128.45, 135.48, 135.79, 139.79, 148.52, 149.77.
13C NMR (CDCl3, 100 MHz): d = 50.51, 53.12, 123.34, 126.89,
127.82, 128.56, 135.51, 135.77, 140.13, 148.48, 149.72.
Anal. Calcd for C13H14N2: C, 78.75; H, 7.12; N, 14.13. Found: C,
78.99; H, 7.17; N, 14.29.
Anal. Calcd for C20H22N4·0.5H2O: C, 73.36; H, 7.08; N, 17.11.
Found: C, 73.94; H, 7.46; N, 16.81.
3
The general method was used with the following reagent amounts:
BnBr (1.19 mL, 10 mmol), 4-(aminomethyl)pyridine (2.03 mL, 20
mmol) and THF (100 mL). Flash chromatography on silica gel
(CH2Cl2–MeOH, 10:1) gave 3; yield: 1.1 g (56%); brown liquid.
9
The general method was used with the following reagent amounts:
a,a¢-dibromo-m-xylene (1.31 g, 5 mmol), 4-(aminomethyl)pyridine
(2.03 mL, 20 mmol) and THF (75 mL). Flash chromatography on
silica gel (MeOH–acetone, 1:2) gave 9; yield: 0.58 g (37%); thick
yellow oil.
1H NMR (CDCl3, 400 MHz): d = 3.81 (s, 4 H), 3.84 (s, 4 H), 7.26–
7.32 (m, 8 H), 8.54–8.55 (br, 4 H).
The spectral characterization data for 3 has been reported previous-
ly.48
4
The general method was used with the following reagent amounts:
a,a¢-dibromo-p-xylene (2.63 g, 10 mmol), 2-(aminomethyl)pyri-
dine (4.08 mL, 40 mmol) and THF (100 mL). Flash chromatogra-
phy on silica gel (MeOH–CH2Cl2, 1:9) gave 4; yield: 0.63 (20%);
thick yellow oil.
13C NMR (CDCl3, 100 MHz): d = 51.88, 53.13, 122.95, 126.94,
127.81, 128.60, 140.03, 149.31, 149.73.
Anal. Calcd for C20H22N4·1.5H2O: C, 69.54; H, 7.29; N, 16.22.
Found: C, 69.79; H, 7.09; N, 16.18.
1H NMR (CDCl3, 400 MHz): d = 3.85 (s, 4 H), 3.94 (s, 4 H), 7.17
(t, J = 5.0 Hz, 2 H), 7.31–7.33 (br, 6 H), 7.64 (dt, J = 7.7, 1.7 Hz,
2 H), 8.56 (d, J = 4.7 Hz, 2 H).
13C NMR (CDCl3, 100 MHz): d = 53.16, 54.37, 121.9, 122.33,
128.33, 136.38, 138.73, 149.27, 159.61.
10
The general method was used with the following reagent amounts:
a,a¢-dibromo-o-xylene (1.32 g, 5 mmol), 2-(aminomethyl)pyridine
(2.04 mL, 20 mmol) and THF (100 mL). Flash chromatography on
silica gel (acetone) gave 10; yield: 0.5 g (48%); thick dark-brown
oil.
1H NMR (CDCl3, 400 MHz): d = 4.05 (s, 4 H), 4.10 (s, 2 H), 7.20
(br s, 5H), 7.52 (d, J = 7.8 Hz, 1 H), 7.70 (dt, J = 7.6, 1.8 Hz, 1 H),
8.59–8.60 (m, 1 H).
Anal. Calcd for C20H22N4·0.5H2O: C, 73.36; H, 7.08. Found: C,
72.98; H, 7.35.
5
The general method was used with the following reagent amounts:
a,a¢-dibromo-p-xylene (2.64 g, 10 mmol), 3-(aminomethyl)pyri-
dine (4.06 mL, 40 mmol) and THF (100 mL). Flash chromatogra-
phy on silica gel (MeOH–acetone, 1:2) gave 5; yield: 1.33 g (42%);
thick yellow liquid that slowly solidified on standing; mp 67 °C.
13C NMR (CDCl3, 100 MHz): d = 59.05, 61.75, 122.10, 122.25,
122.98, 126.70, 136.60, 139.97, 149.15, 158.98.
Anal. Calcd for C14H14N2·0.5H2O: C, 76.68; H, 6.89; N, 12.78.
Found: C, 76.33; H, 6.41; N, 12.61.
1H NMR (CDCl3, 400 MHz): d = 3.81 (s, 4 H), 3.83 (s, 4 H), 7.25–
7.28 (m, 2 H), 7.32 (br s, 4 H), 7.70–7.72 (m, 2 H), 8.51 (dd, J = 4.8,
1.5 Hz, 2 H), 8.59 (d, J = 1.6 Hz, 2 H).
13C NMR (CDCl3, 100 MHz): d = 50.40, 52.87, 123.33, 128.23,
135.56, 135.75, 138.78, 148.49, 149.73.
11
The general method was used with the following reagent amounts:
a,a¢-dibromo-o-xylene (1.32 g, 5 mmol), 3-(aminomethyl)pyridine
(1.27 mL, 12.5 mmol) and THF (100 mL). The crude oil was dis-
solved in acetone and filtered through a silica gel column. The sol-
vent was removed under reduced pressure to give 11; yield: 0.65 g
(62%); dark oil.
1H NMR (CDCl3, 400 MHz): d = 3.95 (s, 2 H), 3.97 (s, 4 H), 7.21
(br s, 4 H), 7.29–7.32 (m, 1 H), 7.80 (d, J = 7.4 Hz, 1 H), 8.55 (d,
J = 4.5 Hz, 1 H), 8.64 (s, 1 H).
Anal. Calcd for C20H22N4·H2O: C, 71.40; H, 7.19; N, 16.65. Found:
C, 71.28; H, 6.82; N, 16.40.
6
The general method was used with the following reagent amounts:
a,a¢-dibromo-p-xylene (2.62 g, 10 mmol), 4-(aminomethyl)pyri-
dine (4.1 mL, 40 mmol) and THF (150 mL). Flash chromatography
on silica gel (MeOH–acetone, 1:2) gave 6; yield: 1.3 g (42%); thick
yellow oil.
1H NMR (CDCl3, 400 MHz): d = 3.81 (s, 4 H), 3.84 (s, 4 H), 7.30–
7.32 (m, 8 H), 8.55–8.56 (m, 4 H).
13C NMR (CDCl3, 100 MHz): d = 57.36, 58.86, 122.26, 123.42,
126.78, 134.39, 136.45, 139.69, 148.61, 149.95.
Anal. Calcd for C14H14N2·0.5H2O: C, 76.68; H, 6.89; N, 12.78.
Found: C, 76.07; H, 7.00; N, 12.40.
12
13C NMR (CDCl3, 100 MHz): d = 51.81, 52.90, 122.97, 128.26,
138.75, 149.37, 149.77.
The general method was used with the following reagent amounts:
a,a¢-dibromo-o-xylene (1.32 g, 5 mmol), 4-(aminomethyl)pyridine
(1.26 mL, 12.5 mmol) and THF (100 mL). The crude oil was dis-
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84
P. Sengupta et al.
PAPER
solved in acetone and filtered through a silica gel column. The sol-
vent was removed under reduced pressure to give 12; yield: 0.61 g
(59%); dark oil.
1H NMR (CDCl3, 400 MHz): d = 3.94 (s, 2 H), 3.98 (s, 4 H), 7.22
(br s, 4 H), 7.37 (d, J = 5.3 Hz, 2 H), 8.57–8.59 (m, 2 H).
yield: 0.39 g (46%); fine colorless crystalline solid; mp 134–136 °C
(EtOAc).
1H NMR (CDCl3, 400 MHz): d = 4.03 (s, 8 H), 4.10 (s, 4 H), 7.02
(s, 2 H), 7.21 (t, J = 6.0 Hz, 2 H), 7.52 (d, J = 7.8 Hz, 2 H), 7.70 (t,
J = 7.8 Hz, 2 H), 8.60 (d, J = 4.8 Hz, 2 H).
13C NMR (CDCl3, 100 MHz): d = 59.05, 122.32, 123.60, 126.89,
139.68, 148.23, 149.83.
13C NMR (CDCl3, 100 MHz): d = 59.3, 62.2, 116.7, 122.6, 123.5,
137.0, 139.1, 149.6, 159.2.
Anal. Calcd for C14H14N2·H2O: C, 73.66; H, 7.06; N, 12.27. Found:
C, 74.48; H, 6.38; N, 12.14.
Anal. Calcd for C22H22N4: C, 77.03; H, 6.47; N, 16.42. Found: C,
76.86; H, 6.72; N, 16.19.
13
17
The general method was used with the following reagent amounts:
1,3,5-tris(bromomethyl)mesitylene (1.006 g, 2.5 mmol), 2-(ami-
nomethyl)pyridine (1.60 mL, 15 mmol) and THF (50 mL). EtOAc
was added to the crude product and the colorless solid formed was
filtered off and the filtrate was concentrated under reduced pressure.
Flash chromatography on silica gel [acetone–MeOH (3:1) then
100% MeOH] gave 13; yield: 0.34 g (28%); thick yellow oil.
1H NMR (acetone-d6, 400 MHz): d = 2.39 (s, 9 H), 3.81 (s, 6 H),
4.03 (s, 6 H), 7.18 (t, J = 5.8 Hz, 3 H), 7.40 (d, J = 7.7 Hz, 3 H), 7.66
(t, J = 6.2 Hz, 3 H), 8.56 (d, J = 3.7 Hz, 3 H).
The general method was used with the following reagent amounts:
1,2,4,5-tetrakis(bromomethyl)benzene (3.41 g, 7.6 mmol), 3-(ami-
nomethyl)pyridine (4.6 mL, 45 mmol) and THF (150 mL). The
crude yellow solid was recrystallized (EtOAc–hexane) to give 17;
yield: 1.20 g (46%); pink needles; mp 190–198 °C.
1H NMR (CDCl3, 400 MHz): d = 3.93 (s, 12 H), 7.02 (s, 2 H), 7.31
(t, J = 5.1 Hz, 2 H), 7.80 (d, J = 7.5 Hz, 2 H), 8.55 (d, J = 4.3 Hz,
2 H), 8.64 (s, 2 H).
13C NMR (CDCl3, 100 MHz): d = 57.9, 59.1, 116.9, 123.9, 134.7,
136.9, 139.1, 149.2, 150.5.
13C NMR (acetone-d6, 100 MHz): d = 15.14, 48.45, 55.63, 122.22,
122.56, 135.16, 135.73, 136.70, 149.35, 167.05.
Anal. Calcd for C22H22N4: C, 77.03; H, 6.47; N, 16.42. Found: C,
77.09; H, 6.53; N, 16.55.
Anal. Calcd for C30H36N6·2H2O: C, 69.74; H, 7.80; N, 16.27.
Found: C, 69.30; H, 7.33; N, 16.67.
18
The general method was used with the following reagent amounts:
1,2,4,5-tetrakis(bromomethyl)benzene (1.02 g, 2.3 mmol), 4-(ami-
nomethyl)pyridine (1.6 mL, 16 mmol) and THF (50 mL). The crude
orange-red solid was recrystallized (EtOAc) to give 18; yield: 0.35
g (38%); brown needles; mp 187–190 °C.
1H NMR (CDCl3, 400 MHz): d = 3.94 (s, 4 H, NCH2), 3.96 (s, 8 H,
NCH2), 7.03 (s, 2 H, Ph-H), 7.38 (d, J = 4.7 Hz, 4 H, Py-H), 8.59 (t,
J = 5.1 Hz, 4 H, Py-H).
14
The general method was used with the following reagent amounts:
1,3,5-tris(bromomethyl)mesitylene (1.01 g, 2.5 mmol), 3-(amino-
methyl)pyridine (1.50 mL, 15 mmol) and THF (50 mL). Flash chro-
matography on silica gel [acetone–MeOH (2:1) then MeOH–
acetone (2:1)] gave 14 as a thick yellow oil in 49% yield (0.63 g).
When left exposed to air, 14 crystallized after one week to give fan-
shaped and cubic crystals. Slowly evaporating an acetone solution
of 14 gave colorless X-ray quality crystals; mp 56–59 °C
1H NMR (CDCl3, 400 MHz): d = 1.88 (br, 3 H), 2.31 (s, 9 H), 3.74
(s, 6 H), 3.91 (s, 6 H), 7.28 (d, J = 12 Hz, 3 H), 7.77 (d, J = 7.6 Hz,
3 H), 8.54 (d, J = 4.5 Hz, 3 H), 8.62 (s, 3 H).
13C NMR (CDCl3, 100 MHz): d = 59.2, 59.5, 124.0, 116.9, 139.0,
150.4.
Anal. Calcd for C22H22N4: C, 77.03; H, 6.47; N, 16.42. Found: C,
77.81; H, 6.55; N, 16.81.
13C NMR (CDCl3, 100 MHz): d = 15.89, 48.43, 52.00, 123.77,
134.98, 135.96, 136.33, 148.96, 150.16.
19
A solution of 5 (0.032 g, 0.1 mmol) in acetone (5 mL) and a solution
of silver nitrate (0.017 g, 0.1 mmol) in H2O (2 mL) were layered in
a vial. The vial was kept in the dark without a lid. After 3 days, vi-
sually colorless crystals had formed. The crystals were filtered,
washed with deionized water, and air-dried; mp 131 °C.
Anal. Calcd for C30H36N6·2H2O: C, 69.74; H, 7.80; N, 16.27.
Found: C, 70.36; H, 7.90; N, 16.11.
15
The general method was used with the following reagent amounts:
1,3,5-tris(bromomethyl)mesitylene (1.02 g, 2.5 mmol), 4-(amino-
methyl)pyridine (1.50 mL, 15 mmol) and THF (50 mL). Flash chro-
matography on silica gel (MeOH–acetone, 2:1) gave 15; yield: 0.17
g (13%); thick yellow oil.
1H NMR (acetone-d6, 400 MHz): d = 2.37 (s, 9 H), 3.72 (s, 6 H),
3.92 (s, 6 H), 7.42 (s, 6 H), 8.51 (d, J = 4.3 Hz, 6 H).
1H NMR (CDCl3, 400 MHz): d = 3.67 (s, 4 H), 3.71 (s, 4 H), 7.28
(br, 4 H), 7.34–7.37 (m, 2 H), 7.76 (d, J = 6.8 Hz, 2 H), 8.42 (d,
J = 4.7 Hz, 2 H), 8.47 (s, 2 H).
20
A solution of 18 (0.010 g, 0.029 mmol) was dissolved in boiling
THF in a vial. After the solution cooled, a solution of silver triflate
(0.029 M in H2O; 1 mL, 0.029 mmol) was added dropwise with
swirling. The solution was allowed to slowly evaporate over 1 h,
during which time numerous small clear crystals formed on the side
of the vial; mp 170 °C
13C NMR (acetone-d6, 100 MHz): d = 15.14, 48.42, 53.10, 123.48,
134.96, 135.83, 149.94, 150.52.
Anal. Calcd for C30H36N6·H2O: C, 72.26; H, 7.68; N, 16.85. Found:
C, 72.21; H, 7.60; N, 16.41.
1H NMR (CD3CN, 400 MHz): d = 3.90 (s, 8 H), 3.94 (s, 4 H), 7.06
(s, 2 H), 7.42 (d, J = 4.7 Hz, 4 H), 8.52 (d, J = 4.6 Hz, 4 H).
16
The general method was used with the following reagent amounts:
1,2,4,5-tetrakis(bromomethyl)benzene (1.11 g, 2.5 mmol), 2-(ami-
nomethyl)pyridine (2.6 mL, 25 mmol) and THF (50 mL). The crude
yellow semi-solid was rinsed thoroughly with Et2O to give 16;
X-ray Crystallography
Data for compounds 14, 19 and 2060 were collected on a Bruker
APEX diffractometer, equipped with a CCD detector. The struc-
tures were solved by direct-methods and subsequent difference
Synthesis 2008, No. 1, 79–86 © Thieme Stuttgart · New York

PAPER
Multidentate (Pyridylalkyl)amines
85
Fourier syntheses using SHELXTL program package.59 The X-ray
analysis of 19 revealed that one pyridine group [C(21)–C(26) and
C(21¢)–C(26¢)] and the nitrate counter-ion were disordered. Table 2
contains the crystal data for compounds 14, 19, and 20. Figure 3
and Figure 4 were generated using the software program ORTEP-3
for Windows, version 1.08.61
(24) Schatz, M.; Leibold, M.; Foxon, S. P.; Weitzer, M.;
Heinemann, F. W.; Hampel, F.; Walter, O.; Schindler, S.
J. Chem. Soc., Dalton Trans. 2003, 1480.
(25) Yajima, T.; Okajima, M.; Odani, A.; Yamauchi, O. Inorg.
Chim. Acta 2002, 339, 445.
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(27) Sun, W.-Y.; Fei, B.-L.; Okamura, T.; Tang, W.-X.; Ueyama,
N. Eur. J. Inorg. Chem. 2001, 1855.
Acknowledgment
(28) Schatz, M.; Becker, M.; Thaler, F.; Hampel, F.; Schindler,
S.; Jacobson, R. R.; Tyeklar, Z.; Murthy, N. N.; Ghosh, P.;
Chen, Q.; Zubieta, J.; Karlin, K. D. Inorg. Chem. 2001, 40,
2312.
The authors thank the National Science Foundation (Grant No.
0092495) and the Welch Foundation (Grant N-1375) for support of
this work.
(29) Foxon, S. P.; Walter, O.; Schindler, S. Eur. J. Inorg. Chem.
2002, 111.
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