Synthesis of a new family of bi- and polycyclic compounds via Pd-catalyzed amination of 1,7-di(3-bromobenzyl)cyclen

Article abstract of DOI:10.1016/j.tetlet.2008.04.045

New bicyclic cryptand type compounds are synthesized by reacting 1,7-di(3-bromobenzyl)cyclen with 1 equiv of linear polyamines under dilute conditions using Pd-catalyzed amination. Bis(cyclen) and tris(cyclen) compounds containing linear polyamine linkers between benzylated cyclens are obtained by a similar procedure using different reaction conditions. Cyclization of these species via intramolecular catalytic diamination led to tri- and tetracyclic polyaza compounds.

Full text of DOI:10.1016/j.tetlet.2008.04.045

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 3950–3954
Synthesis of a new family of bi- and polycyclic compounds
via Pd-catalyzed amination of 1,7-di(3-bromobenzyl)cyclen
a,
a
b
*
Alexei D. Averin , Anton V. Shukhaev , Alexei K. Buryak ,
Franck Denat c, Roger Guilard c, Irina P. Beletskaya a,*
a Lomonosov Moscow State University, Department of Chemistry, Leninskie Gory, Moscow 119992, Russia
b A. N. Frumkin Institute of Physical and Electrochemistry, 31 Leninskii Prosp., Moscow 119991, Russia
c Institut de Chimie Mole´culaire de l’Universite de Bourgogne (ICMUB-LIMRES) UMR CNRS 5260, 9 av. Alain Savary, 21078 Dijon, France
Received 16 January 2008; revised 1 April 2008; accepted 8 April 2008
Available online 11 April 2008
Abstract
New bicyclic cryptand type compounds are synthesized by reacting 1,7-di(3-bromobenzyl)cyclen with 1 equiv of linear polyamines
under dilute conditions using Pd-catalyzed amination. Bis(cyclen) and tris(cyclen) compounds containing linear polyamine linkers
between benzylated cyclens are obtained by a similar procedure using different reaction conditions. Cyclization of these species via
intramolecular catalytic diamination led to tri- and tetracyclic polyaza compounds.
Ó 2008 Elsevier Ltd. All rights reserved.
Tetraazamacrocyclic compounds, mainly cyclams and
cyclens, are of major importance due to their unique prop-
erties for the selective binding of metal ions.1 Numerous
derivatives of these molecules find application as highly
efficient sequestrating agents,2 sensors,3 catalysts,4 and
are used in biochemistry5 or medicine.6 Moreover,
bis(polyazamacrocycles) attract significant interest due to
their abilities to form binuclear complexes.7 Such macrocy-
cles can be synthesized either by attaching two tetraaza-
macrocycles to a rigid spacer via methylene groups, or by
direct Pd-catalyzed diamination of dihaloarenes with aza-
macrocycles.8 Here, we report the synthesis of a new family
of polyazamacrocycles through catalytic amination of 1,7-
di(3-bromobenzyl)cyclen with linear polyamines. This
cyclen derivative was chosen as a starting material because
the meta-position of the bromine atom pre-organizes the
ring to favor the formation of a cryptand-like molecule
through diamination.
1,7-Di(3-bromobenzyl)cyclen was obtained from cis-gly-
oxalcyclen 1 via intermediate salt 2 using a procedure
already described for similar compounds (Scheme 1).9
The reactions of 3 with a variety of linear polyamines
4a– i in equimolar ratio were carried out in boiling dioxane
using Pd(dba)2/BINAP as a catalyst10 (16/18 mol %).
Dilute conditions were applied to favor intramolecular
cyclization (c = 0.02 M). The reactions were complete
in 24 h, and the target macrocycles 5a–i were isolated in
13–65% yields (Scheme 2, Table 1).
Br
Br
Br
H
+
H
H
Br
N
N
N
N
N
N
NH
N
N
NaOH
H2O
2 equiv.
CH3CN
N
N
HN
º
80 C
+
H
2 Br-
1
Br
Br
3, 85%
*
Corresponding authors. Tel.: +7 495 939 11 39; fax: +7 495 939 36 18
2
(A.D.A.).
Scheme 1. Synthesis of 1,7-di(3-bromobenzyl)cyclen 3.
E-mail address: averin@org.chem.msu.ru (A. D. Averin).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.04.045

A. D. Averin et al. / Tetrahedron Letters 49 (2008) 3950–3954
3951
N
H
N
H
N
N
N
N
H
N
H
N
Pd(dba)2/BINAP
3
X
Br
Br
N
H
N
H
t
BuONa, dioxane
100 ºC
+
5a-i
+
H2N
NH2
X
4a-i
X
N
H
N
H
N
NH HN
N
N
NH HN
N
H
N
H
N
X
6a-d,f,h,i
Scheme 2. Synthesis of bicyclic compounds 5.
Table 1
Synthesis of bicyclic compounds 5
Entry
Polyamine
H2N(CH2)3NH2 4a
Yield of 5 (%)
Yield of cyclodimers 6a (%)
1
2
3
4
5
6
7
8
9
a
13
26
38
45
65
43
35
29
42
6a, 5
H2N(CH2)3NH(CH2)3NH2 4b
6b, 53
6c, 44
6d, 34
H2N(CH2)2NH(CH2)3NH(CH2)2NH2 4c
H2N(CH2)3NH(CH2)2NH(CH2)3NH2 4d
H2N(CH2)3NH(CH2)3NH(CH2)3NH2 4e
H2N(CH2)2[NH(CH2)2]3NH2 4f
H2N(CH2)2O(CH2)2O(CH2)2NH2 4g
H2N(CH2)3O(CH2)4O(CH2)3NH2 4h
H2N(CH2)3O[(CH2)2O]2(CH2)3NH2 4i
6f, 36
6h, 36
6i, 46
Cyclodimers 6 often contain some compounds 5.
Diaminopropane 4a was too short a linker to form the
expected cryptand in a reasonable yield, and 5a was
obtained in 13% yield; the tricyclic compound 6a resulting
from [2+2] condensation was isolated in 5% yield (Table 1,
entry 1). Almost all the other polyamines also provided tri-
cyclic compounds 6 though mixed with bicyclic species 5
(Table 1). The highest yield (65%) of the desired product,
5e, was observed in the case of tetraamine 4e (Table 1,
entry 5), whereas no dimer of type 6 was isolated. Similar
results were observed for the reaction with dioxadiamine
4g (Table 1, entry 7). Cryptand-like molecules 5 possess a
polyamine (oxadiamine) chain more or less remote from
the cyclen tetraazacycle, and differ in the number of nitro-
gen and/or oxygen atoms, which can serve as additional
donor sites for metal ion coordination. This makes such
structures very valuable ligands for coordination
chemistry.
c = 0.1 M) (Scheme 3). Target bis(cyclen) derivatives 7
were obtained in rather moderate yields (11–37%) due to
the competitive formation of tris(cyclen) derivatives 8
(yields 11–54%). Increasing the amount of starting com-
pound 3 from 2 to 3 equiv did not change the ratio of
the isolated products. Products 7 and 8 possessing two or
three macrocyclic units linked by polyamine chains are
polytopic ligands.
Bis(cyclen) derivatives 7a,g and tris(cyclen) derivatives
8a,g were used as precursors for the formation of cyclic
dimers and trimers (Schemes 4 and 5).
Reactions were run in dilute dioxane solution using 8–
16 mol% of the catalyst. Compound 7a gave tricyclic
dimer 6a in 36% yield upon reacting with an equivalent
amount of 4a. The reaction of the same derivative 7a with
trioxadiamine 4i afforded tricycle 9 in 40% yield. In con-
trast, bis(cyclen) derivative 7g did not lead to the expected
tricyclic dimer of type 6, which was also not observed by
reacting 3 with diamine 4g (Table 1, entry 7). Nevertheless,
the reaction of tris(cyclen) derivative 8g with 1 equiv of
dioxadiamine 4g afforded target tetracyclic compound 10,
though the yield was poor (13%). At the same time, tris(cy-
clen) compound 8a did not provide the corresponding
Tricyclic compounds 6 are also of interest as polyden-
tate ligands where two cyclen moieties are linked by poly-
amine chains of various lengths. We have synthesized
such compounds by a two-step procedure. In the first stage,
1,7-di(3-bromobenzyl)cyclen 3(2–3 equiv) was reacted with
polyamines 4a,d,g (Pd(dba)2/BINAP 4/4.5 mol %,

3952
A. D. Averin et al. / Tetrahedron Letters 49 (2008) 3950–3954
N
H
N
N
X
H
N
N
H
N
H
N
NH HN
N
N
NH HN
N
3, 2-3 equiv.
Br
Br
Pd(dba)2/BINAP
+
Br
Br
t
BuONa, dioxane
100 ºC
H2N
NH2
X
4a,d,g
7a (24-27%); 7d (11%), 7g (37%)
+
X
N
H
N
H
N
NH HN
N
N
NH HN
N
Br
Br
2
8a (11-14%); 8d (38%), 8g (54%)
Scheme 3. Synthesis of bis(cyclen) and tris(cyclen) compounds 7 and 8.
X
N
H
N
H
N
NH HN
N
N
NH HN
N
Pd(dba)2/BINAP
t
BuONa, dioxane
º
100 C
Br
Br
7a,g
+
X
N
H
N
H
H2N
4a, Y = CH2
4g, Y = CH2OCH2CH2OCH2
4i, Y = CH2CH2(OCH2CH2)2OCH2CH2
N
N
NH2
Y
NH HN
N
NH HN
N
H
N
H
N
Y
6a, X = Y = CH2, 36%
6g, X = Y = CH2OCH2CH2OCH2, 0%
9, X = CH2, Y = CH2CH2(OCH2CH2)2OCH2CH2, 40%
Scheme 4. Synthesis of tricyclic compounds 6 and 9.
cyclic trimer. Unexpectedly, the formation of less sterically
demanding cyclic dimers and trimers (6, 9, and 10) is sub-
ject to greater limitations than the synthesis of bicyclic
polyaza compounds 5. Studies to determine the range of
conditions for the formation of cyclic dimers and trimers
are now underway.
details and spectral data for some representative com-
pounds are given below.11
Acknowledgments
To sum up, we have elaborated an efficient one-pot
method for the synthesis of bicyclic polyaza compounds
using disubstituted cyclen as a precursor and demonstrated
that it is possible to isolate polycyclic compounds contain-
ing two, three, and four cyclen moieties. Experimental
This work was supported by RFBR Grant 06-03-32376
and by the Russian Academy of Sciences program P-8
‘Development of methods of organic synthesis and con-
struction of compounds with valuable properties’. The
authors are indebted to CHEMATECH Co for the gener-

A. D. Averin et al. / Tetrahedron Letters 49 (2008) 3950–3954
3953
O
O
N
H
N
H
N
NH HN
N
N
NH HN
N
Br
Br
2
8g
+
H2N
O
O
NH2
4g
NH
N
N
HN
N
H
N
H
O
O
N
HN
NH
N
NH
HN
O
O
O
O
NH
HN
N
H
N
N
H
N
10, 13%
Scheme 5. Synthesis of a cyclic trimer 10 from tris(cyclen) derivative 8g.
9. (a) Rohovec, J.; Gyepes, R.; Cisarova, I.; Rudovsky, J.; Lukes, I.
Tetrahedron Lett. 2000, 41, 1249; (b) Boschetti, F.; Chaux, F.; Denat,
F.; Guilard, R.; Ledon, H. WO 2005/000823 A1; Chem. Abstr. 2004,
142, 56374.
ous provision of glyoxalcyclen and personally to Dr. F.
Boschetti.
References and notes
10. Wolfe, J. P.; Buchwald, S. L. J. Org. Chem. 2000, 65, 1144.
11. Synthesis of 1,7-di(3-bromobenzyl)cyclen 3: cis-glyoxalcyclen
1
1. (a) Meyer, M.; Dahaoui-Gindrey, V.; Lecomte, C.; Guilard, R.
Coord. Chem. Rev. 1998, 180, 1313; (b) Lukes, I.; Kotek, J.; Vojtisek,
P.; Hermann, P. Coord. Chem. Rev. 2001, 216, 287.
2. (a) Barbette, F.; Rascalou, F.; Chollet, H.; Babouhot, J. L.; Denat, F.;
Guilard, R. Anal. Chim. Acta 2004, 502, 179; (b) Cuenot, F.; Meyer,
M.; Bucaille, A.; Guilard, R. J. Mol. Liq. 2005, 118, 89.
3. (a) Gunnlaugsson, T.; Leonard, J. P. Chem. Commun. 2005, 3114; (b)
Gunnlaugsson, T.; Stomeo, F. Org. Biomol. Chem. 2007, 5, 1999.
4. Reichenbach-Klinke, R.; Ko¨nig, B. J. Chem. Soc., Dalton Trans.
2002, 121.
5. (a) Aoki, S.; Kimura, E. Chem. Rev. 2004, 104, 769; (b) Ritter, S. C.;
Eiblmaier, M.; Michlova, V.; Ko¨nig, B. Tetrahedron 2005, 61, 5241.
6. (a) Liu, S.; Edwards, D. S. Bioconjugate Chem. 2001, 7; (b) Delgado,
R.; Felix, V.; Lima, L. M. P.; Price, D. W. Dalton Trans. 2007, 2734.
(0.02 mol, 3.90 g) was dissolved in acetonitrile (52 mL) and 3-
bromobenzyl bromide (0.04 mol, 10 g) was added dropwise, and the
reaction mixture was stirred at room temperature for 72 h. The
precipitate was filtered off, washed with cold acetonitrile (3 ꢀ 100 mL),
and then with hot acetonitrile (70 °C, 2 ꢀ 100 mL). The residue was
dried under vacuum and salt 2 was obtained as a white powder. Yield
12.32 g (87%). The salt was treated with NaOH (0.4 mol, 16 g) solution
in water (130 mL) for 46 h at 80 °C, then the reaction mixture was
cooled to ambient temperature and extracted with dichloromethane
(2 ꢀ 40 mL). The combined organic layers were dried over MgSO4 and
the solvent was evaporated under vacuum. Compound 3 was obtained
as a pale brown powder. Yield 8.65 g (98%). Mp 145–147 °C. 1H NMR
(400 MHz, CDCl3): d 2.42 (br s, 2H), 2.55 (br s, 8H), 2.63 (br s, 8H),
3.56 (s, 4H), 7.20–7.29 (m, 4H), 7.34–7.39 (m, 2H), 7.41–7.44 (m, 2H);
13C NMR (100.6 MHz, CDCl3): d 45.0 (4C), 51.6 (4C), 59.2 (2C),
122.4 (2C), 127.6 (2C), 131.1 (2C), 130.3 (2C), 132.0 (2C), 141.3 (2C);
MALDI-TOF m/z 508.9 [M+H]+.
`
7. (a) Brandes, S.; Gros, C.; Denat, F.; Pullumbi, P.; Guilard, R. Bull.
Soc. Chim. Fr. 1996, 133, 65; (b) Valks, G. C.; McRobbie, G.; Lewis,
E. A.; Hubin, T. J.; Hunter, T. M.; Sadler, P. J.; Pannecouque, C.; De
Clercq, E.; Archibald, S. J. J. Med. Chem. 2006, 49, 6162.
8. Beletskaya, I. P.; Bessmertnykh, A. G.; Averin, A. D.; Denat, F.;
Guilard, R. Eur. J. Inorg. Chem. 2005, 281.
Method for the synthesis of macrocycles 5a–i: A flask equipped with a
magnetic stirrer and condenser, flushed with dry argon, was charged
with 1,7-di(3-bromobenzyl)cyclen 3 (0.5 mmol, 255 mg), Pd(dba)2

3954
A. D. Averin et al. / Tetrahedron Letters 49 (2008) 3950–3954
(16 mol %, 46 mg), BINAP (18 mol %, 55 mg), abs. dioxane (25 mL),
raazadodec-1-yl]methyl]phenyl]amino]propyl]amino]phenyl]methyl]-
1,4,7,10-tetraazadodec-1-yl]methyl]phenyl]-propanediamine-1,3 8a.
Eluent: CH2Cl2/MeOH/NH3aq 100:20:3. Yellowish crystals, mp
118–120 °C, yield 101 mg (11%). 1H NMR (400 MHz, CDCl3): d
1.77 (quintet, J = 6.1 Hz, 4H), 2.58 (br s, 48H), 3.10 (br s, 8H), 3.49 (s,
4H), 3.50 (s, 4H), 3.52 (s, 4H), 6.42 (d, J = 7.9 Hz, 4H), 6.49 (s, 2H),
6.56 (s, 2H), 6.62 (d, J = 7.3 Hz, 2H), 6.64 (d, J = 7.5 Hz, 2H), 7.05–
7.36 (m, 10H), 7.42 (s, 2H) (10 NH protons were not unambiguously
assigned); 13C NMR (100.6 MHz, CDCl3): d 28.7 (2C), 41.5 (4C), 45.0
(4C), 45.1 (8C), 51.4 (12C), 59.1 (2C), 60.0 (4C), 111.0 (2C), 111.1 (2C),
113.6 (2C), 113.8 (2C), 117.7 (2C), 117.9 (2C), 122.3 (2C), 127.4 (2C),
129.1 (2C), 129.1 (2C), 129.9 (2C), 130.1 (2C), 131.7 (2C), 139.7 (2C),
139.8 (2C), 141.3 (2C), 148.3 (2C), 148.4 (2C); MALDI-TOF m/z
1353.6 [M+H]+, 1273.6 [MꢁBr]+.
and the appropriate amine (0.5 mmol) was added followed by sodium
tert-butoxide (1.5 mmol, 144 mg), and the reaction mixture was
refluxed for 24–30 h. The mixture was allowed to cool down and a
drop of water was added. Dioxane was evaporated under vacuum, and
the residue was chromatographed on silica gel using the following
sequence of eluents: CH2Cl2, CH2Cl2,/MeOH 20:1–3:1, CH2Cl2/
MeOH/NH3 aq 100:20:1–10:4:1.
Selected experimental and spectral data: 1,8,12,19,22,27-hexaazatetra-
cyclo[17.5.5.13,7.113,17]-hentriaconta-3(31),4,6,13(30),14,16-hexa-
ene 5a. Eluent: CH2Cl2/MeOH/NH3aq 100:20:1. Yellow oil, yield
28 mg (13%). 1H NMR (400 MHz, CDCl3):
d 1.87 (quintet,
J = 5.6 Hz, 2H), 2.53–2.66 (m, 16H), 3.28 (br s, 4H), 3.41 (s, 4H),
4.30 (br s, 2H), 6.49 (d, J = 7.3 Hz, 2H), 6.51 (dd, J = 8.3, 2.0 Hz, 2H),
6.69 (s, 2H), 7.06 (t, J = 7.7 Hz, 2H) (two NH protons of cyclen
were not unambiguously assigned); 13C NMR (100.6 MHz, CDCl3): d
26.6 (1C), 43.3 (2C), 45.4 (4C), 51.8(4C), 61.3 (2C), 111.0 (2C), 114.6
(2C), 118.7 (2C), 128.8 (2C), 140.4 (2C), 148.6 (2C); MALDI-TOF
m/z 423.3 [M+H]+.
1,8,12,16,23,26,31-heptaazatetracyclo[21.5.5.13,7.117,21]-pentatriacon-
ta-3(35),4,6,17(34),18,20-hexaene 5b. Eluent: CH2Cl2/MeOH/
NH3aq 100:20:2. Yellow oil, yield 64 mg (26%). 1H NMR
(400 MHz, CDCl3): d 1.72 (quintet, J = 5.5 Hz, 4H), 2.55 (br s,
8H), 2.58–2.63 (m, 8H), 2.67 (t, J = 5.7 Hz, 4H), 3.20 (t, J = 5.6 Hz,
4H), 3.48 (s, 4H), 6.48 (dd, J = 7.9, 1.5 Hz, 2H), 6.54 (d, J = 7.5 Hz,
2H), 6.66 (s, 2H), 7.08 (t, J = 7.7 Hz, 2H) (five NH protons were not
unambiguously assigned); 13C NMR (100.6 MHz, CDCl3): d 28.5
(2C), 42.9 (2C), 45.0 (4C), 48.5 (2C), 51.7 (4C), 60.6 (2C), 110.7 (2C),
113.9 (2C), 118.4 (2C), 130.0 (2C), 140.0 (2C), 149.0 (2C); MALDI-
TOF m/z 480.5 [M+H]+.
Cyclic oligomers 6a, 9, and 10 were obtained according to the same
method, starting from bis(cyclen) derivative 7a (1 equiv) or tris(cyclen)
derivative 8g, Pd(dba)2 (16 mol %), BINAP (18 mol %), the appro-
priate volume of abs. dioxane to reach 0.02 M concd amine (1 equiv)
and sodium tert-butoxide (3 equiv). The reaction mixture was refluxed
for 30 h.
1,8,12,19,22,25,32,36,43,46,51,58-Dodecaazaheptacyclo-[41.5.5.519,25
.
13,7.113,17.127,31.137,41]dohexaconta-3(62),4,6,13(61),14,16,27(55),
28,30,37(54),38,40-dodecaene 6a. Eluent: CH2Cl2/MeOH/NH3aq
100:20:2. Yellowish crystals, mp 103–105 °C, yield 53 mg (36%). 1H
NMR (400 MHz, CDCl3): d 1.74 (quintet, J = 6.3 Hz, 4H), 2.57 (br s,
16H), 2.61 (br s, 16H), 3.08 (br s, 8H), 3.50 (s, 8H), 4.30 (br s, 4H), 6.37
(d, J = 8.0 Hz, 4H), 6.56 (s, 4H), 6.60 (d, J = 7.5 Hz, 4H), 7.06 (t,
J = 7.9 Hz, 4H) (four NH protons of cyclens were not unambiguously
assigned); 13C NMR (100.6 MHz, CDCl3): d 28.9 (2C), 41.5 (4C),
45.1 (8C), 51.7 (8C), 60.0 (4C), 111.2 (4C), 113.2 (4C), 117.6 (4C),
129.0 (4C), 140.1 (4C), 148.5 (4C); MALDI-TOF m/z 845.6
[M+H]+.
Bis(cyclen) and tris(cyclen) derivatives 7a,d,g and 8a,d,g were
obtained according to the above-mentioned procedure, starting from
1,7-di(3-bromobenzyl)cyclen 3 (1.5–2 mmol), Pd(dba)2 (2–4 mol %),
BINAP (2.3–4.5 mol %), abs. dioxane (5–8 mL), the appropriate
amine (0.5–0.8 mmol), and sodium tert-butoxide (1.5–2.4 mmol).
The reaction mixture was refluxed for 5 h.
36,39,42-Trioxa-1,8,12,19,22,25,32,46,53,56,61,68-dodecaazaheptacy-
clo[51.5.5.519,25.13,7.113,17.127,31.147,51]doheptaconta-3(72),4,6,13(71),
14,16,27(65),28,30,47(64),-48,50-dodecaene 9. Eluent CH2Cl2/
MeOH/NH3aq 100:20:2. Yellow oil, yield 70 mg (40%). 1H NMR
(400 MHz, CDCl3): d 1.72–1.82 (m, 6H), 2.62 (br s, 32H), 3.06–3.25
(m, 8H), 3.45–3.60 (m, 12H), 3.57 (s, 8H), 4.31 (br s, 2H), 4.76 (br s,
2H), 6.38–6.68 (m,10H), 6.89–7.18 (m, 6H) (four NH protons of
cyclens were not unambiguously assigned); 13C NMR (100.6 MHz,
CDCl3): d 28.5 (1C), 29.0 (2C), 41.4 (4C), 47.0 (8C), 51.5 (8C), 61.2
(4C), 69.4 (2C), 70.0 (2C), 70.4 (2C), 111.0 (4C), 113.6 (4C), 117.3
(4C), 129.1 (4C), 139.6 (4C), 148.8 (4C); MALDI-TOF m/z 991.7
[M+H]+.
Cyclic trimer 10. Eluent CH2Cl2/MeOH/NH3aq 100:20:3. Yellow oil,
yield 29 mg (13%). 1H NMR (400 MHz, CDCl3): d 2.61 (s, 48H), 3.25
(br s, 12H), 3.52–3.70 (m, 36H), 6.48 (d, J = 6.2 Hz, 6H), 6.53 (s, 6H),
6.69 (d, J = 7.5 Hz, 6H), 7.13 (t, J = 7.6 Hz, 6H) (12 NH protons were
not unambiguously assigned); 13C NMR (100.6 MHz, CDCl3): d 43.4
(6C), 45.6 (12C), 51.7 (12C), 60.3 (6C), 69.6 (6C), 70.2 (6C), 111.6 (6C),
114.0 (6C), 118.2 (6C), 129.2 (6C), 139.8 (6C), 148.3 (6C); MALDI-
TOF m/z 1490.2 [M+H]+.
Selected experimental and spectral data: N,N0-(2,20-(Ethane-1,2-
diylbis(oxy))bis(ethane-2,1-diyl))di(3-((7-(3-bromobenzyl)-1,4,7,10-
tetraaza-cyclododecan-1-yl)methyl)benzenamine) 7g. Eluent: CH2Cl2/
MeOH/NH3aq 100:20:2. Yellow oil, yield 297 mg (37%). 1H NMR
(400 MHz, CDCl3): d 2.54 (br s, 32H), 3.20 (br s, 4H), 3.48 (s, 4H),
3.50 (s, 4H), 3.51 (s, 4H), 3.57 (t, J = 4.8 Hz, 4H), 4.11 (br s, 2H), 6.44
(d, J = 8.2 Hz, 2H), 6.47 (s, 2H), 6.65 (d, J = 7.2 Hz, 2H), 7.10 (t,
J = 7.6 Hz, 2H), 7.15 (t, J = 7.7 Hz, 2H), 7.21 (d, J = 7.4 Hz, 2H),
7.30 (d, J = 7.7 Hz, 2H), 7.38 (s, 2H) (four NH protons of cyclens
were not unambiguously assigned); 13C NMR (100.6 MHz, CDCl3): d
43.1 (2C), 44.9 (4C), 44.9 (4C), 51.3 (4C), 51.4 (4C), 59.0 (2C), 59.8
(2C), 69.3 (2C), 69.8 (2C), 111.2 (2C), 113.9 (2C), 118.0 (2C), 122.1
(2C), 127.3 (2C), 129.0 (2C), 129.7 (2C), 129.9 (2C), 131.6 (2C), 139.5
(2C), 141.2 (2C), 147.9 (2C); MALDI-TOF m/z 1005.5 [M+H]+.
N1-[3-[[7-[(3-Bromophenyl)methyl]-1,4,7,10-tetraazadodec-1-yl]meth-
yl]phenyl]-N3-[3-[[7-[[4-[[3-[[3-[[7-(3- bromophenyl)-1,4,7,10-tet-