Palladium-catalyzed amination in the synthesis of polyazamacrocycles containing a 1,3-disubstituted benzene moiety

Article abstract of DOI:10.1055/s-2007-990779

The synthesis of a new family of polyaza- and polyoxapolyazamacrocycles by a simple and efficient one-pot palladium-catalyzed diamination of 1,3-dibromobenzene is described. The dependence of the nature of the starting polyamines on the yield of the produ

Full text of DOI:10.1055/s-2007-990779

PAPER
2995
Palladium-Catalyzed Amination in the Synthesis of Polyazamacrocycles
Containing a 1,3-Disubstituted Benzene Moiety
P
olyazamacrocycl
l
e
s
Cont
e
aining
a
1,3
x
-Disubstitut
e
edBenzene
i
Moiety D. Averin,*a Anton V. Shukhaev,a Svetlana L. Golub,b Alexei K. Buryak,b Irina P. Beletskaya*a
a
Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory, 119992 Moscow, Russian Federation
Fax +7(495)9393618; E-mail: averin@org.chem.msu.ru, beletska@org.chem.msu.ru
b
A. N. Frumkin Institute of Physical Chemistry and Electrochemistry, 31 Leninskii prosp., 119991 Moscow, Russian Federation
Received 23 May 2007; revised 5 July 2007
rocycle based on 1,3-diaminated benzene is as yet
known,21 we focused on the synthesis of macrocycles
starting from 1,3-dibromobenzene. It was thought inter-
esting to develop the synthesis of such macrocycles with
Abstract: The synthesis of a new family of polyaza- and polyoxa-
polyazamacrocycles by a simple and efficient one-pot palladium-
catalyzed diamination of 1,3-dibromobenzene is described. The de-
pendence of the nature of the starting polyamines on the yield of the
products is demonstrated. The synthesis of Na,Nw-bis(3-bromophe- different polyamine chains and also to synthesize com-
nyl)-substituted polyamines is elaborated to obtain intermediates
pounds containing two polyamine and two benzene moi-
for the synthesis of polyazamacrocycles consisting of two
eties, thus increasing both the cavity of the macrocycle
polyamine and two benzene fragments (cyclodimers). The forma-
and the number of donor nitrogen and oxygen atoms. We
tion of tri- and tetraarylated polyamines is studied and regularities
have chosen the Pd(dba)2/BINAP catalytic system for our
of the process are established. The synthesis of 1,3-bis(polyamino)-
synthesis due to its versatility and convenience.22
substituted benzenes is also described.
The reactions between equimolar amounts of 1,3-dibro-
mobenzene (1) and a polyamine 2a–j were conducted in
the presence of the Pd(dba)2/BINAP catalytic system (4–
8/4.5–9 mol%), in boiling 1,4-dioxane (concn = 0.02 M),
using sodium tert-butoxide as base (Scheme 1). The reac-
tions ran to completion in 24–30 hours, and the composi-
tion of the reaction mixtures was monitored using 1H and
13C NMR spectroscopy. The compounds were isolated us-
ing column chromatography on silica gel. The data con-
cerning yields and reaction conditions are given in
Table 1; byproducts formed in these reactions are indicat-
ed in Figure 1.
Key words: amines, aminations, haloarenes, homogenous cataly-
sis, macrocycles
Polyazamacrocycles (or azacrown ethers) attract a keen
and constant interest of researchers due to their unique
ability of selective complexation with various metals, or-
ganic and inorganic anions, and some polar compounds.
During the last decades hundreds of such compounds,
which contain nitrogen, oxygen, and sulfur atoms, have
been synthesized.1 The main problem in these syntheses is
the use of laborious multistep methods which result in
rather low yields of the target products.2–5 Many
polyazamacrocycles can serve as molecular sensors due to
their photochemical or redox properties; they contain aro-
matic moieties which can be present as substituents at ni-
trogen atoms or can be incorporated in the cycle. In the
majority of cases, aromatic groups are separated from the
nitrogen atom by at least one methylene or methine
group.6–11 According to literature data, a better response to
the complexation is achieved when the nitrogen atom is
directly linked to an aromatic substituent, but such com-
pounds are still rare.12–14
The yield of target macrocycles 3 was found to be strongly
dependent on the nature of the starting polyamines 2. Tri-
amine 2a did not provide the corresponding cycle 3a, not
HN
NH
X
Br
Br
3b–j, 15–56%
1
Pd(dba)2/BINAP
+
t-BuONa, dioxane
reflux, 24–30 h
+
Recently, using the method of palladium-catalyzed ami-
nation of haloarenes proposed by Buchwald and
Hartwig,15 we have elaborated an efficient approach to the
synthesis of polyazamacrocycles using palladium-cata-
lyzed diamination of dihaloarenes with linear polyamines.
Thus, macrocycles containing 1,8- and 1,5-disubstituted
anthracene and anthraquinone,16 2,6- and 3,5-disubstitut-
ed pyridine,17–20 and 1,2-disubstituted benzene21 have
been synthesized. As only one example of a tetraazamac-
HN
HN
X
NH
H2N
X
NH2
2a–j
X
NH
4a–e,h–j, 5–74%
2a: X = NH; 2b: X = CH2NHCH2; 2c: X = NH(CH2)2NH;
2d: X = NH(CH2)3NH; 2e: X = CH2NH(CH2)2NHCH2;
2f: X = CH2NH(CH2)3NHCH2; 2g: X = NH(CH2)2NH(CH2)2NH;
2h: X = O(CH2)2O; 2i: X = CH2O(CH2)4OCH2;
2j: X = CH2O(CH2)2O(CH2)2OCH2
SYNTHESIS 2007, No. 19, pp 2995–3012
x
x.
x
x
.
2
0
0
7
Advanced online publication: 11.09.2007
DOI: 10.1055/s-2007-990779; Art ID: Z12707SS
© Georg Thieme Verlag Stuttgart · New York
Scheme 1 Synthesis of macrocycles 3b–j

2996
A. D. Averin et al.
PAPER
H
N
NH
X
Br
N
N
H
NH2
H
X
NH
6a, 44%
H
N
n
5a–c,j (n = 2)
5h (n = 2–4)
O
O
O
O
NH
HN
NH
NH
R
n
7: R = Ph, n = 0, 8%
8: R = Ph, n = 1, 5–11%
9: R = H, n = 0, 11–13%
10: R = H, n = 1, 23–24%
11: R = H, n = 2, 6%
Figure 1 Byproducts in the synthesis of macrocycles 3
Table 1 Synthesis of Macrocycles 3b–j
2g, gave the desired macrocycles in moderate to good
yield (entries 5–10).
Entry Amine Pd(dba)2/BINAP Yield (%)
Yield (%)
The formation of the macrocycles 3h–j in the reactions
with oxadiamines proceeded successfully though yields
were somewhat lower (Table 1, entries 11–14). The main
byproducts in most cases were cyclodimers 4 which con-
sist of two benzene and two polyamine moieties; in the
case of triamines 2a,b, dimers 4a,b were the main prod-
ucts of the reaction (entries 2–4). In some cases cyclotri-
mers 5a–c,h,j (n = 2) and even cyclooligomers with
higher masses (5h; n = 3, 4) were also detected in the
MALDI–TOF spectra as admixtures to the corresponding
cyclodimers, but they could not be separated chromato-
graphically. Moreover, their NMR spectra are almost the
same as those of cyclodimers 4, and thus they cannot be
distinguished spectroscopically. The use of 4 mol% of the
catalyst was quite sufficient in many cases: in the reaction
with tetraamine 2d, NMR investigations demonstrated
that there was no difference in the reaction mixture com-
positions when either 4 mol% or 8 mol% of the catalyst
was used. However, in the case of triamines 2a,b, the in-
crease in the catalyst loading favored amination (entries 2
and 4).
(mol%/mol%) of 3a–j
of other products
1
2
2a
2a
4/4.5
8/9
3a, 0
3a, 0
6a, 44
4a + 5a
(n = 2), 74
3
4
2b
2b
2c
2d
2d
2e
2f
4/4.5
8/9
3b, 0
4b, 56
4b, 60
4c, 14
4d, 26
3b, 15
3c, 39
3d, 31
5
8/9
6
4/4.5
8/9
7
8
4/4.5
4/4.5
8/9
3e, 29
3f, 56
3g, 33
3h, 27
3i, 19
4e, 36
4h, 28
9
10
11
12
2g
2h
2i
4/4.5
4/4.5
4i, 8; 8, 14; 9, 11;
10, 23
The reaction of dioxadiamine 2i with 1,3-dibromoben-
zene (1) gave a number of noncyclic byproducts 7–11 (en-
tries 12 and 13); the corresponding byproducts were not
registered in the reactions with other polyamines. These
compounds resulted from reduction of the bromine atom,
and no linear byproducts with a remaining bromine atom,
such as 6a, were isolated. An increase in the catalyst load-
ing from 4 mol% to 8 mol% provided a better yield of the
target macrocycle 3i, as well as of other products of ben-
zene diamination (10,11).
13
14
2i
2j
8/9
3i, 26
3j, 26
4i, 5; 7, 8; 8, 3; 9,
13; 10, 24; 11, 6
4/4.5
4j, 23
even in trace amounts, giving either linear derivative 6a or
cyclic dimer 4a (Table 1, entries 1 and 2), whereas tri-
amine 2b with a longer chain afforded target 3b in low
yield (entry 4). Probably macrocycle 3a does not form due
to an unfavorable conformation of the triamine chain in
this compound. Tetraamines 2c–f, as well as pentaamine
1H NMR spectra of the macrocycles 3 are characterized by
a strong dependence of the chemical shift of the 2-H atom
Synthesis 2007, No. 19, 2995–3012 © Thieme Stuttgart · New York

PAPER
Polyazamacrocycles Containing a 1,3-Disubstituted Benzene Moiety
2997
in the benzene ring on the macrocycle ring size. In the ceed 90%. To synthesize these interesting macrocycles
compounds with smaller cycles the signal of this hydro- with larger cavities in a pure state, in the first stage we ob-
gen atom is shifted relatively downfield (d2-H 7.31 in 3b tained Na,Nw-bis(3-bromophenyl)-substituted polyamines
and 6.96 in 3h), while an increase in the cycle size leads 15b,d–f,h–k starting from 1,3-dibromobenzene (1) and
to a substantial upfield shift (d2-H 6.48 in 3c, 6.30 in 3d, linear polyamines 2 taken in ca. 2:1 ratio. The reactions
and 6.09 in 3f). It means that this hydrogen atom is sensi- were conducted in the presence of the Pd(dba)2/BINAP
tive to the close proximity of the nitrogen or oxygen atoms catalytic system, in boiling 1,4-dioxane, using sodium
of the aliphatic part of the molecule in smaller cycles. In tert-butoxide as base (Scheme 3). The reactions ran to
cyclodimers 4 where these nitrogen atoms are most distant completion in 6–8 hours and the composition was moni-
from the 2-H atom, the chemical shift d2-H lies between 5.8 tored using 1H and 13C NMR spectroscopy. In all cases the
and 5.9 ppm.
yield of the target product 15 was found to be no less than
70–80% in the reaction mixture. The compounds were
isolated using column chromatography on silica gel; the
data concerning yields and reaction conditions are given
in Table 2.
Previously, we have synthesized two series of
polyazamacrocycles based on 2,6- and 3,5-disubstituted
pyridines.17,19,20 The yields of the present macrocycles de-
rived from 1,3-dibromobenzene were found to be notably
higher than the yields of pyridine-based macrocycles. The
latter were formed in lower yields in the reaction mix-
tures, and the losses during column chromatography were
also greater. While the reaction of 1,3-dibromobenzene
(1) with triethylenetetraamine (2c) and tetraethylenepen-
taamine (2g) led to a 33–39% yield of the corresponding
macrocycles (Table 1, entries 5 and 10), polyamines of
such type provided very humble yields (3–5%) of macro-
cycles with dibromopyridines. Also, the formation of cy-
clic oligomers like 4 was not observed in almost all
reactions of dihalopyridines with polyamines. These facts
mean that the reactions of 1,3-dibromobenzene (1) with
polyamines are more selective than similar reactions of di-
bromopyridines.
Br
Br
HN
X
NH
n
Pd(dba)2/BINAP
1
+
t-BuONa, dioxane
reflux, 6–8 h
Br
Br
15b,d–f,h–k
70–80% (raw)
H2N
X
NH2
n
29–64% (isolated)
2b,d–f,h–k
2b: n = 1, X = CH2NHCH2; 2d: n = 1, X = NH(CH2)3NH;
2e: n = 1, X = CH2NH(CH2)2NHCH2; 2f: n = 1, X = CH2NH(CH2)3NHCH2;
2h: n = 1, X = O(CH2)2O; 2i: n = 1, X = CH2O(CH2)4OCH2;
2j: n = 1, X = CH2O(CH2)2O(CH2)2OCH2; 2k: n = 0
Scheme 3 Synthesis of Na,Nw-bis(3-bromophenyl)-substituted po-
lyamines 15b,d–f,h–k
O
O
O
Cl
Cl
Pd(dba)2/BINAP
8/9 mol%
H
H
In the majority of cases the diarylated polyamines 15 were
isolated in yields from moderate to good (29–64%), but in
all reactions the formation of byproducts was noted
(Figure 2). Yields of compounds 15 and that of byprod-
ucts were shown to be strongly dependent on the reaction
conditions and on the nature of the starting polyamines 2.
Application of 2–4 mol% of the catalyst, 2.2 equivalents
of 1,3-dibromobenzene (1), and a polyamine concentra-
tion of 0.1 M provided the highest yields of desired prod-
ucts 15; these conditions can be proposed as optimal,
though in all cases the formation of linear byproducts 16
was observed. They were formed due to partial diamina-
tion of the benzene fragment. In some cases moderate
yields of the target compounds after chromatography
were due to very close Rf values of compounds 15 and 16.
N
N
12
R
t-BuONa, dioxane
reflux, 30 h
+
O
O
O
NH2
H2N
Cl
13: R = H, 59%
14: R = 3-ClC6H4, 24%
2j
Scheme 2 Arylation of trioxadiamine 2j with 1,3-dichlorobenzene
(12)
We also used 1,3-dichlorobenzene (12) in the reaction
with trioxadiamine 2j using 8 mol% of the catalyst, but in
this case the corresponding macrocycle 3j was only regis-
tered in trace amounts according to the 1H NMR spectrum
of the reaction mixture. Instead of 3j, the mono- and diaryl
derivatives 13 and 14 were isolated in 59% and 24% yield, In several cases the products of N,N-diarylation 17 were
respectively (Scheme 2).
formed in small amounts (Table 2, entries 2 and 6–9); ap-
plication of a greater excess of 1,3-dibromobenzene (1)
led to an increase in the formation of 17 and a diminished
yield of the target product (entry 2). Increasing the con-
centration of the polyamine 2 up to 0.2 M led to a substan-
tial decrease in the yield of 15 caused by the formation of
oligomers such as 18 (entries 6 and 12). Application of a
greater amount of the catalyst (entry 10) did not improve
the yield of the target product, but caused the formation of
oligomeric products of homocoupling, according to the
In contrast to 1,3-dichlorobenzene (12), 1-bromo-2,6-
dichlorobenzene has been shown to provide macrocycles
containing the 1,2-disubstituted benzene moiety in suffi-
cient yields.21
While macrocycles 3 were isolated in pure state using col-
umn chromatography, cyclodimers 4 contained admix-
tures which could not be sufficiently separated by
chromatography, and the purity of 4 generally did not ex-
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2998
A. D. Averin et al.
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Table 2 Synthesis of Na,Nw-Bis(3-bromophenyl)-Substituted Polyamines 15b,d–f,h–k
Entry
Amine
2b
Pd(dba)2/BINAP Ratio 1:2
(mol%/mol%)
Concn (M) of 2
Isolated yield (%)
1
2
3
4
4/4.5
2.2:1
3:1
0.1
0.1
0.1
0.1
15b, 46
16b, 13
2b
12/13.5
2/2.5
15b, 38
17b, 3
2d
2.2:1
2.2:1
15d, 64
16d, 21
2e
2/2.5
15e, 52
16e, 10
6e, 7
5
6
2f
4/4.5
4/4.5
2.2:1
2.5:1
0.1
0.2
15f, 39
16f, 12
2h
15h, 11a
16h, 14
17h, 4
7
2h
4/4.5
2.2:1
0.1
15h, 42
16h, 14
17h, 12
8
9
2h
2h
2/2.5
8/9
2.2:1
2.2:1
0.1
0.1
15h, 46
16h, 16
17h, 8
10
11
12
13
2h
2i
4/4.5
4/4.5
4/4.5
4/4.5
1:1
0.1
0.1
0.2
0.1
15h, 0b
4h, 7
2.2:1
2.2:1
2.5:1
15i, 59c
16i, 11
2i
15i, 38d
19i, 9
2j
15j, 29
16j, 10
19j, 5
14
2k
4/4.5
2.2:1
0.1
15k, 32
16k, 14
a 18h (2%) was also isolated in a mixture with higher linear oligomers.
b A complex mixture of linear oligomers was isolated (53%).
c 17i and 19i were isolated as admixtures to 15i.
d 18i (2%) was also isolated in a mixture with higher linear oligomers.
NMR spectroscopic data of the reaction mixture. (Scheme 4). Enough diluted solutions of equimolar
Amounts of the catalyst lower than 2 mol% were not test- amounts of the reagents were used to suppress the forma-
ed as monoarylated products such as 6e may be obtained tion of linear byproducts. The amount of catalyst was in-
(entry 4). The formation of small amounts of the products creased to 8 mol%, and the reactions ran to completion in
19 of partial reduction of the bromine atom was observed 24–30 hours. In all cases (except the reaction between 2d
in only two cases (entries 12 and 13), which is in good ac- and 15d) formation of the desired macrocycles was ob-
cordance with the fact that primary amines normally do served and, after chromatography on silica gel, they were
not cause the reduction of haloarenes provided BINAP is isolated in 16–44% yield (Table 3). In the reaction with
used. A change in the reagent ratio of 1:2 from 2.2:1 to 1:1 polyamine 2d, standard conditions led to a low 6% yield
dramatically decreased the yield of 15 giving rise to oligo- of the corresponding cyclodimer 4d, while the formation
mers of complex composition (entry 10).
of a linear derivative 20 was observed (entry 2). Applica-
tion of the donor phosphane 2-dicyclohexylphosphano-2¢-
(dimethylamino)biphenyl, which was shown by Buch-
wald to be more efficient than BINAP,23 did not improve
Starting from diarylated polyamines 15b,d–f,h–j we at-
tempted the synthesis of the cyclodimers 4b,d–f,h–j con-
taining two benzene and two polyamine fragments
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Polyazamacrocycles Containing a 1,3-Disubstituted Benzene Moiety
2999
Table 3 Synthesis of Cyclodimers 4b,d–f,h–j
Entry
Reagents
Pd(dba)2/BINAP Isolated yield (%)
(mol%/mol%)
HN
X
N
N
H
X
NH
n
n
H
1
2
3
4
5
6
7
8
9
2b + 15b
2d + 15d
2d + 15d
2e + 15e
2e + 15e
2f + 15f
2h + 15h
2i + 15i
8/9
4b, 44
Br
Br
X
16b,d–f,h–k
8/9
4d, 6; 20, 30
4d, 0; 20, 10
4e, 36b
4/4.5a
8/9
HN
NH
Br
N
X
NH
n
4/4.5
8/9
Br
Br
Br
4f, 30
4h, 16
4i, 38
4j, 21
19i,j
17b,h–k
8/9
8/9
HN
X
N
N
X
NH
H
2j + 15j
8/9
a 2-Dicyclohexylphosphano-2¢-(dimethylamino)biphenyl was used
instead of BINAP.
Br
Br
Br
b Result of combined chromatography; composition of both reaction
mixtures was identical.
18h,i
N
N
H
H
dium, which is thus eliminated from the catalytic cycle. In
the case of triamine 2b or tetraamine 2f, only less stable
six-membered chelates can be formed. It was also shown
that lower catalyst loadings may be used for the synthesis
of cyclodimers with normal yields (Table 3, entry 5).
NH
H2N
Br
6e
Figure 2 Isolated byproducts in the synthesis of Na,Nw-bis(3-bro-
mophenyl)-substituted polyamines 15
1
All cyclodimers 4 were characterized by H NMR, 13C
NMR, and MALDI–TOF spectroscopy. It is worth noting
that the 1,3-diaminobenzene fragments possess hydrogen
and carbon atoms with signals shifted strongly upfield (dH
5.8–6.0 and dC 96–102, respectively), which is useful for
the identification of these compounds in the reaction mix-
tures. Signals for aliphatic hydrogen atoms are often
broad, and singlets are sometimes observed instead of
multiplets. In the NMR spectra of cyclodimers 4b,d–f in
CDCl3 we observed the duplication of some or even all
signals of the compounds; the chemical shifts of doubled
signals are close, but they may differ in intensity and
width. Sometimes duplication of the signals can also be
noted in the reaction mixtures. The following is proposed
as a possible explanation for these facts: four nitrogen at-
oms linked to benzene rings are formally chiral and, pro-
vided the inversion at these atoms is slow in CDCl3, the
cyclodimers can be viewed as dl- and meso-diastereomers
which would possess different chemical shifts in their
NMR spectra. This effect was not observed in the case of
cyclodimers 4h–j because, unlike compounds 4b,d–f,
they do not possess secondary aliphatic amino groups
which can form intramolecular hydrogen bonds, thus hin-
dering the inversion at the nitrogen atoms. The depen-
HN
X
NH
HN
X
NH
X
Br
Br
15b,d–f,h–j
Pd(dba)2/BINAP
+
t-BuONa, dioxane
reflux, 24–30 h
HN
NH
H2N
X
NH2
2b,d–f,h–j
4b,d–f,h–j, 6–44%
NH
N
N
NH2
Br
NH
N
N
HN
H
H
H
H
20
Scheme 4 Synthesis of cyclodimers 4
the result and the desired product was not isolated at all in
this case (entry 3).
This reluctance of tetraamine 2d to form a cyclodimer in dence of the mentioned effect on the concentration of the
the reaction with 15d might be explained by the fact that macrocycle in the NMR sample, and on the solvent used,
it contains two ethylenediamine fragments which can supports this suggestion.
form stable five-membered chelate complexes with palla-
Synthesis 2007, No. 19, 2995–3012 © Thieme Stuttgart · New York

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A. D. Averin et al.
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Br
Br
Table 4 Synthesis of Polyarylated Polyamines 21b,h–k
H2N
X
NH2
n
Entry
Amine
Equiv
of 1
Pd(dba)2/BINAP Isolated yield
2b,h–j, n = 1; 2k, n = 0
(mol%/mol%)
(%)
N
X
N
Pd(dba)2/BINAP
n
+
1
2
3
2b
2h
2i
6
6
5
16/18
21b, 37
21h, 31
t-BuONa, dioxane
reflux, 24–30 h
16/18
Br
Br
Br
Br
21b,h–j (n = 1), 21k, (n = 0),
21–37%
8/9
21i, 33; 17i, 11;
22i, 9; 23i, 5
1 (5–6 equiv)
4
5
6
2j
2j
2k
5
6
5
16/18
16/18
16/18
21j, 29; 17j, 5;
22j, 9
N
X
N
Br
Br
N
X
N
21j, 21; 17j, 25;
22j, 5; 23j, 5
21k, 25
Br
Br
Br
Br
22i,j
sicity.24 As in the synthesis of diarylated derivatives 15,
we did not observe the reduction of the bromine atom
even though generous catalyst loadings were applied.
N
X
N
Br
Br
N
X
N
H
An alternative method for the synthesis of cyclodimers 4
could include the formation of 1,3-bis(polyamino)-substi-
tuted benzenes, followed by their reaction with a second
molecule of 1,3-dibromobenzene. Therefore, we elaborat-
ed the synthesis of some 1,3-bis(polyamino)-substituted
derivatives 24h–j (Scheme 6). The reactions were con-
ducted using 2.5–4 equivalents of polyamines 2h–j in the
presence of 8/9 mol% of the Pd(dba)2/BINAP catalytic
system. Only oxadiamines were chosen for this process
because of the difficulties of separating bis(polyamino)-
substituted arene derivatives from the starting polyamines
when tetraamines are used. Experimental data are collect-
ed in Table 5.
Br
Br
Br
23i,j
Scheme 5 Synthesis of polyarylated polyamines 21b,h–k
In the course of the synthesis of diarylated polyamines 15,
we observed the formation of triaryl derivatives 17 as
byproducts in some cases. It was decided to specially in-
vestigate the exhaustive polyarylation of polyamines with
1,3-dibromobenzene as it may lead to the formation of
valuable intermediates for the synthesis of polyamine-
containing dendrimers. Previously we studied the palladi-
um-mediated tetraarylation of ethane-1,2-diamine and
propane-1,3-diamine and established that BINAP was
suitable for this purpose.24 Diamines 2h–k and triamine
2b were reacted with 5–6 equivalents of 1,3-dibromoben-
zene (1) in the presence of 16 mol% of the Pd(dba)2/
BINAP catalytic system (Scheme 5). Studies of the reac-
tion mixture revealed that the target products of tetraary-
lation 21b,h–k were formed in all cases in yields no less
than 50%. They were isolated using column chromatogra-
phy in 21–37% yield (Table 4). In the case of 21i,j,
byproducts of an oligomeric nature, 22i,j and 23i,j, were
also obtained (entries 3–5). These compounds were prob-
ably formed via further amination of the tetraarylated
compounds 21i,j, like compounds 16 which were ob-
tained by substitution of the remaining bromine atom in
15.
In some cases an increase in the diamine/1,3-dibromoben-
zene ratio and the use of less concentrated solutions can
lead to higher yields of the target product (Table 5, entries
1 and 2). In all cases the formation of oligomeric byprod-
ucts 25h–j was observed; they were isolated as mixtures
and their masses were established by MALDI–TOF spec-
troscopy. The NMR spectra of compounds 24h–j show
H2N
X
NH2
2h–j (2.5–4 equiv)
NH
HN
Pd(dba)2/BINAP
+
t-BuONa, dioxane
reflux, 8 h
X
X
NH2
H2N
Br
Br
24h–j, 36–62%
1
A decrease in the catalyst loading (Table 4, entry 3) did
not lead to a lower yield of the product; also, the use of a
greater excess of 1 does not result in a higher yield (entry
5). It is important to note that the reaction of triamine 2b
with six equivalents of 1 did not lead to the arylation of the
central nitrogen atom due to very low reactivity of the sec-
ondary amino group in linear amines. Alkylarylamines
proved to be more reactive possibly due to their lower ba-
N
H
N
X
N
N
H
H
n
H
X
X
25h–j, n = 1–4
H2N
NH2
Scheme 6 Synthesis of 1,3-bis(polyamino)-substituted benzenes
24h–j
Synthesis 2007, No. 19, 2995–3012 © Thieme Stuttgart · New York

PAPER
Polyazamacrocycles Containing a 1,3-Disubstituted Benzene Moiety
3001
Macrocycles 3b–j; General Procedure
Table 5 Synthesis of 1,3-Bis(polyamino)-Substituted Benzenes
24h–j
A flask flushed with dry argon and equipped with a magnetic stirrer
and condenser was charged with 1,3-dibromobenzene (1) (0.5
mmol), Pd(dba)2 (4–8 mol%), BINAP (4.5–9 mol%), the appropri-
ate amine 2b–j (0.5 mmol), and abs 1,4-dioxane (25 mL). t-BuONa
(1.5 mmol) was added and the mixture was stirred under reflux for
24–30 h; then, the mixture was cooled to r.t., the 1,4-dioxane was
evaporated under reduced pressure, and the residue was chromato-
graphed on silica gel using various eluents: CH2Cl2–MeOH, 200:1–
3:1; CH2Cl2–MeOH–aq NH3, 100:20:1–10:4:1.
Entry Amine Equiv Pd(dba)2/BINAP Concn (M) Isolatedyield
of 2
(mol%/mol%) of 1
(%)
1
2
3
4
5
2h
2h
2i
3
8/9
8/9
8/9
8/9
8/9
0.2
0.1
0.1
0.2
0.2
24h, 36a
24h, 59
24i, 62b
24i, 37
24j, 56c
4
3
2i
4
2,6,10-Triazabicyclo[9.3.1]pentadeca-1(15),11,13-triene (3b)
Obtained from 1 (118 mg, 0.5 mmol) and triamine 2b (66 mg, 0.5
mmol), in the presence of Pd(dba)2 (24 mg, 8 mol%), BINAP (28
mg, 9 mol%), and t-BuONa (144 mg, 1.5 mmol), in abs 1,4-dioxane
(25 mL).
2j
2.5
a Contains an admixture of 25h (n = 1).
b Contains an admixture of 25i (n = 1).
c A mixture of oligomers 25j (n = 1–4) was isolated in 28% yield.
Yield: 15 mg (15%); pale-yellow oil; eluent: CH2Cl2–MeOH,
100:1.
1H NMR (400 MHz, CDCl3): d = 1.60 (br s, 4 H), 2.65 (t, J = 5.6
Hz, 4 H), 3.38 (br s, 4 H), 5.91 (dd, J = 7.9, 2.2 Hz, 2 H), 6.84 (t,
J = 7.9 Hz, 1 H), 7.31 (br s, 1 H) (the signals of the three NH protons
were not unambiguously assigned).
13C NMR (100.6 MHz, CDCl3): d = 30.46 (2 C), 39.83 (2 C), 45.88
(2 C), 96.19 (1 C), 102.45 (2 C), 129.04 (1 C), 149.72 (2 C).
the similar peculiarities as those described for cy-
clodimers 4: in CDCl3 the signals of the hydrogen and car-
bon atoms are often doubled, and after a change of the
solvent to DMSO or after simple addition of an excess of
free oxadiamine this effect fully disappears. Despite rea-
sonable yields of 24 they were not used in the synthesis of
cyclodimers as they turned out to be inconvenient to han-
dle, being very viscous oils, insufficiently soluble in 1,4-
dioxane, and unstable upon storage. Also, their isolation
by column chromatography is much more laborious than
that of diarylated derivatives 15.
MALDI–TOF: m/z [M + H]+ calcd for C12H19N3: 206.17; found:
206.29.
Cyclodimer 4b (vide infra) was obtained as a second product in this
reaction.
Yield: 62 mg (60%); yellow oil; eluent: CH2Cl2–MeOH–aq NH3,
100:20:3, 10:4:1.
To sum up, we have elaborated a convenient one-step
method for the synthesis of polyazamacrocycles contain-
ing a 1,3-disubstituted benzene moiety and an easy proce-
dure for obtaining cyclodimers consisting of two benzene
and two polyamine moieties via intermediate formation of
diarylated polyamines, and we have synthesized a number
of such compounds with different numbers of nitrogen
and oxygen atoms and different cavity sizes. We have
found that the regularities of these processes and the prod-
uct yields, as well as the formation of byproducts, depend
on the nature of the starting polyamines and on the reac-
tion conditions. Investigation of the complexing proper-
ties of the new macrocycles is underway. We have also
studied the possibilities of polyarylation of the
polyamines with 1,3-dibromobenzene and the synthesis of
1,3-bis(polyamino)-substituted benzenes. As these com-
pounds possess several reaction centers, they may well
find further applications in organic synthesis.
Contains an admixture of cyclotrimer 5b (n = 2): MALDI–TOF:
m/z [M + H]+ calcd for C36H57N9: 616.48; found: 616.49.
The use of Pd(dba)2 (12 mg, 4 mol%) and BINAP (14 mg, 4.5
mol%) in this reaction gave no macrocycle 3b and led only to the
formation of cyclodimer 4b.
Yield: 57 mg (56%); eluent: CH2Cl2–MeOH–aq NH3, 100:20:3,
10:4:1.
2,5,8,11-Tetraazabicyclo[10.3.1]hexadeca-1(16),12,14-triene
(3c)
Obtained from 1 (118 mg, 0.5 mmol) and tetraamine 2c (72 mg, 0.5
mmol), in the presence of Pd(dba)2 (24 mg, 8 mol%), BINAP (28
mg, 9 mol%), and t-BuONa (144 mg, 1.5 mmol), in abs 1,4-dioxane
(25 mL).
Yield: 43 mg (39%); pale-yellow oil; eluent: CH2Cl2–MeOH–
aq NH3, 100:20:2, 100:20:3.
1H NMR (400 MHz, CDCl3): d = 2.77 (s, 4 H), 2.80 (t, J = 5.7 Hz,
4 H), 3.32 (t, J = 5.7 Hz, 4 H), 5.99 (dd, J = 7.9, 2.1 Hz, 2 H), 6.48
(s, 1 H), 6.88 (t, J = 7.9 Hz, 1 H) (the signals of the four NH protons
were not unambiguously assigned).
NMR spectra were recorded on a Bruker Avance-400 spectrometer
at room temperature; the chemical shifts (d) were measured in ppm
with respect to TMS. MALDI–TOF mass spectra were registered
using a Bruker Daltonics Ultraflex spectrometer with dithranol
(1,8,9-anthracenetriol) as matrix. Column chromatography was per-
formed on silica gel (40–60 mesh) purchased from Fluka. 1,3-Di-
bromobenzene, 1,3-dichlorobenzene, amines, and phosphane
ligands were purchased from Acros and Aldrich and used without
special purification, except for pentaamine 2g, whose adduct with
water was recrystallized several times from toluene to increase its
purity from ca. 60 to 90%. 1,4-Dioxane was distilled successively
over NaOH and Na; CH2Cl2, MeOH, and petroleum ether were used
freshly distilled. Pd(dba)2 was obtained by a described method.25
13C NMR (100.6 MHz, CDCl3): d = 44.96 (2 C), 48.06 (2 C), 49.86
(2 C), 97.76 (1 C), 104.89 (2 C), 129.63 (1 C), 149.24 (2 C).
MALDI–TOF: m/z [M + H]+ calcd for C12H20N4: 221.18; found:
221.18.
2,5,8,11,17,20,23,26-Octaazatricyclo[25.3.1.112,16]dotriaconta-
1(31),12,14,16(32),27,29-hexaene (4c)
Obtained as a byproduct in the synthesis of 3c.
Yield: 15 mg (14%); yellow oil; eluent: CH2Cl2–MeOH–aq NH3,
10:4:1.
1H NMR (400 MHz, CDCl3): d = 2.70 (br s, 8 H), 2.80 (br s, 8 H),
3.15 (br s, 8 H), 5.89 (s, 2 H), 6.00 (d, J = 7.1 Hz, 4 H), 6.94 (t,
Synthesis 2007, No. 19, 2995–3012 © Thieme Stuttgart · New York

3002
A. D. Averin et al.
PAPER
J = 8.0 Hz, 2 H) (the signals of the eight NH protons were not un-
ambiguously assigned).
MALDI–TOF: m/z [M + H]+ calcd for C24H40N8: 441.35; found:
441.33.
1H NMR (400 MHz, CDCl3): d = 1.73 (quin, J = 6.0 Hz, 2 H), 1.75
(quin, J = 6.4 Hz, 4 H), 2.71 (t, J = 5.6 Hz, 4 H), 2.76 (t, J = 5.9 Hz,
4 H), 3.29 (t, J = 7.3 Hz, 4 H), 3.81 (br s, 2 H), 5.91 (dd, J = 7.8, 1.6
Hz, 2 H), 6.09 (s, 1 H), 6.89 (t, J = 7.8 Hz, 1 H) (the signals of two
of the NH protons were not unambiguously assigned).
13C NMR (100.6 MHz, CDCl3): d = 28.65 (1 C), 29.16 (2 C), 42.29
(2 C), 47.50 (2 C), 49.32 (2 C), 95.43 (1 C), 103.28 (2 C), 129.82 (1
C), 149.51 (2 C).
Contains an admixture of cyclotrimer 5c (n = 2): MALDI–TOF:
m/z [M + H]+ calcd for C36H60N12: 661.51; found: 661.48.
2,5,9,12-Tetraazabicyclo[11.3.1]heptadeca-1(17),13,15-triene
(3d)
MALDI–TOF: m/z [M + H]+ calcd for C15H26N4: 263.22; found:
Obtained from 1 (118 mg, 0.5 mmol) and tetraamine 2d (80 mg, 0.5
mmol), in the presence of Pd(dba)2 (24 mg, 8 mol%), BINAP (28
mg, 9 mol%), and t-BuONa (144 mg, 1.5 mmol), in abs 1,4-dioxane
(25 mL). Combined with the portion obtained from the same
amounts of starting compounds in the presence of Pd(dba)2 (12 mg,
4 mol%) and BINAP (14 mg, 4.5 mol%).
263.16.
2,5,8,11,14-Pentaazabicyclo[13.3.1]nonadeca-1(19),15,17-triene
(3g)
Obtained from 1 (118 mg, 0.5 mmol) and pentaamine 2g (95 mg, 0.5
mmol), in the presence of Pd(dba)2 (24 mg, 8 mol%), BINAP (28
mg, 9 mol%), and t-BuONa (144 mg, 1.5 mmol), in abs 1,4-dioxane
(25 mL).
Yield: 72 mg (31%); pale-yellow oil; eluent: CH2Cl2–MeOH–aq
NH3, 100:20:3.
Yield: 44 mg (33%); pale-yellow oil; eluent: CH2Cl2–MeOH–aq
NH3, 100:20:3, 10:4:1.
1H NMR (400 MHz, CDCl3): d = 2.64 (s, 4 H), 2.71 (s, 8 H), 3.32
(br s, 4 H), 5.96 (d, J = 7.7 Hz, 2 H), 6.24 (s, 1 H), 6.88 (t, J = 7.9
Hz, 1 H) (the signals of the five NH protons were not unambiguous-
ly assigned).
13C NMR (100.6 MHz, CDCl3): d = 43.74 (2 C), 48.29 (2 C), 48.48
(2 C), 49.59 (2 C), 96.55 (1 C), 103.84 (2 C), 129.70 (1 C), 149.65
(2 C).
1H NMR (400 MHz, CDCl3): d = 1.54 (quin, J = 5.6 Hz, 2 H), 2.69
(t, J = 6.0 Hz, 4 H), 2.74 (t, J = 5.6 Hz, 4 H), 3.33 (t, J = 6.0 Hz, 4
H), 5.93 (dd, J = 8.0, 2.1 Hz, 2 H), 6.30 (s, 1 H), 6.85 (t, J = 8.0 Hz,
1 H) (the signals of the four NH protons were not unambiguously
assigned).
13C NMR (100.6 MHz, CDCl3): d = 26.36 (1 C), 43.50 (2 C), 49.00
(2 C), 49.30 (2 C), 95.64 (1 C), 104.06 (2 C), 129.58 (1 C), 149.09
(2 C).
MALDI–TOF: m/z [M + H]+ calcd for C13H22N4: 235.19; found:
235.26.
MALDI–TOF: m/z [M + H]+ calcd for C14H25N5: 264.22; found:
264.30.
Cyclodimer 4d (vide infra) was obtained as a byproduct in this re-
action.
5,8-Dioxa-2,11-diazabicyclo[10.3.1]hexadeca-1(16),12,14-triene
(3h)
Obtained from 1 (118 mg, 0.5 mmol) and dioxadiamine 2h (74 mg,
0.5 mmol), in the presence of Pd(dba)2 (12 mg, 4 mol%), BINAP
(14 mg, 4.5 mol%), and t-BuONa (144 mg, 1.5 mmol), in abs 1,4-
dioxane (25 mL).
Yield: 60 mg (26%); yellow oil; eluent: CH2Cl2–MeOH–aq NH3,
10:4:1.
2,6,9,13-Tetraazabicyclo[12.3.1]octadeca-1(18),14,16-triene
(3e)
Obtained from 1 (944 mg, 4 mmol) and tetraamine 2e (696 mg, 4
mmol), in the presence of Pd(dba)2 (92 mg, 4 mol%), BINAP (110
mg, 4.5 mol%), and t-BuONa (1152 mg, 12 mmol), in abs 1,4-diox-
ane (150 mL).
Yield: 30 mg (27%); pale-yellow oil; eluent: CH2Cl2–MeOH, 50:1.
1H NMR (400 MHz, CDCl3): d = 3.40 (t, J = 5.1 Hz, 4 H), 3.62 (s,
4 H), 3.62 (t, J = 5.1 Hz, 4 H), 3.91 (br s, 2 H), 6.03 (dd, J = 7.8, 1.8
Hz, 2 H), 6.88 (t, J = 7.8 Hz, 1 H), 6.96 (t, J = 1.8 Hz, 1 H).
13C NMR (100.6 MHz, CDCl3): d = 45.28 (2 C), 70.11 (2 C), 71.61
(2 C), 99.71 (1 C), 105.24 (2 C), 129.12 (1 C), 149.08 (2 C).
MALDI–TOF: m/z [M+] calcd for C12H18N2O2: 222.14; found:
222.17.
Yield: 288 mg (29%); pale-yellow oil; eluent: CH2Cl2–MeOH–aq
NH3, 100:20:2.
1H NMR (400 MHz, CDCl3): d = 1.66 (quin, J = 5.8 Hz, 4 H), 2.65
(t, J = 5.4 Hz, 4 H), 2.66 (s, 4 H), 2.94 (br s, 2 H), 3.31 (t, J = 6.3
Hz, 4 H), 5.88 (dd, J = 7.9, 2.1 Hz, 2 H), 6.26 (s, 1 H), 6.83 (t,
J = 7.9 Hz, 1 H) (the signals of two of the NH protons were not un-
ambiguously assigned).
13C NMR (100.6 MHz, CDCl3): d = 31.35 (2 C), 41.34 (2 C), 46.01
(2 C), 49.21 (2 C), 94.34 (1 C), 103.63 (2 C), 129.62 (1 C), 150.32
(2 C).
Cyclodimer 4h (vide infra) was obtained as a byproduct in this re-
action.
Yield: 31 mg (28%); yellow oil; eluent: CH2Cl2–MeOH, 20:1.
Contains an admixture of cyclotrimer 5h (n = 2): MALDI–TOF:
m/z [M+] calcd for C36H54N6O6: 666.41; found: 666.16; cyclotet-
ramer 5h (n = 3): MALDI–TOF: m/z [M+] calcd for C48H72N8O8:
888.55; found: 888.40; and cyclopentamer 5h (n = 4): MALDI–
TOF: m/z [M+] calcd for C60H90N10O10: 1110.68; found: 1110.70.
Cyclodimer 4e (vide infra) was obtained as a byproduct in this reac-
tion.
Yield: 358 mg (36%); yellow oil; eluent: CH2Cl2–MeOH–aq NH3,
100:20:3, 10:4:1.
6,11-Dioxa-2,15-diazabicyclo[14.3.1]eicosa-1(20),16,18-triene
(3i)
Obtained from 1 (118 mg, 0.5 mmol) and dioxadiamine 2i (102 mg,
0.5 mmol), in the presence of Pd(dba)2 (12 mg, 4 mol%), BINAP
(14 mg, 4.5 mol%), and t-BuONa (144 mg, 1.5 mmol), in abs 1,4-
dioxane (25 mL).
2,6,10,14-Tetraazabicyclo[13.3.1]nonadeca-1(19),15,17-triene
(3f)
Obtained from 1 (118 mg, 0.5 mmol) and tetraamine 2f (94 mg, 0.5
mmol), in the presence of Pd(dba)2 (12 mg, 4 mol%), BINAP (14
mg, 4.5 mol%), and t-BuONa (144 mg, 1.5 mmol), in abs 1,4-diox-
ane (25 mL).
Yield: 26 mg (19%); pale-yellow oil; eluent: CH2Cl2–MeOH, 20:1.
Yield: 73 mg (56%); pale-yellow oil; eluent: CH2Cl2–MeOH–aq
NH3, 100:20:3, 10:4:1.
1H NMR (400 MHz, CDCl3): d = 1.74–1.80 (m, 4 H), 1.85 (quin,
J = 6.0 Hz, 4 H), 3.28 (t, J = 6.1 Hz, 4 H), 3.42–3.48 (m, 4 H), 3.56
Synthesis 2007, No. 19, 2995–3012 © Thieme Stuttgart · New York

PAPER
Polyazamacrocycles Containing a 1,3-Disubstituted Benzene Moiety
3003
(t, J = 5.0 Hz, 4 H), 4.26 (br s, 2 H), 5.94 (dd, J = 7.9, 1.5 Hz, 2 H),
6.19 (s, 1 H), 6.95 (t, J = 7.9 Hz, 1 H).
13C NMR (100.6 MHz, CDCl3): d = 26.41 (2 C), 29.98 (2 C), 42.41
(2 C), 69.82 (4 C), 96.09 (1 C), 101.83 (2 C), 129.59 (1 C), 150.16
(2 C).
C), 69.35 (1 C), 70.62 (1 C), 70.72 (4 C), 96.63 (1 C), 102.53 (2 C),
112.61 (2 C), 116.95 (1 C), 129.14 (2 C), 129.82 (1 C), 148.53 (1
C), 149.66 (2 C).
MALDI–TOF: m/z [M + H]+ calcd for C32H54N4O4: 559.42; found:
559.20.
MALDI–TOF: m/z [M+] calcd for C16H26N2O2: 278.20; found:
278.08.
Synthesis of 3i Using a Double Amount of the Catalyst
Obtained from 1 (236 mg, 1 mmol) and dioxadiamine 2i (204 mg, 1
mmol), in the presence of Pd(dba)2 (48 mg, 8 mol%), BINAP (56
mg, 9 mol%), and t-BuONa (288 mg, 3 mmol), in abs 1,4-dioxane
(50 mL).
Cyclodimer 4i (vide infra) was obtained as a byproduct in this reac-
tion.
Yield: 11 mg (8%); yellow oil; eluent: CH2Cl2–MeOH, 50:1.
Yield: 73 mg (26%); pale-yellow oil; eluent: CH2Cl2–MeOH,
100:1.
N1,N3-Bis(3-{4-[3-(phenylamino)propoxy]butoxy}propyl)ben-
zene-1,3-diamine (8)
Obtained as a byproduct in the synthesis of 3i.
Cyclodimer 4i (vide infra) was obtained as a byproduct in this reac-
tion.
Yield: 12 mg (11%); pale-yellow oil; eluent: CH2Cl2–MeOH, 50:1,
20:1.
Yield: 14 mg (5%); yellow oil; eluent: CH2Cl2–MeOH, 50:1.
Compound 8 (vide supra) was also obtained as a byproduct in this
reaction.
1H NMR (400 MHz, CDCl3): d = 1.65–1.70 (m, 8 H), 1.82–1.90 (m,
8 H), 3.15–3.22 (m, 8 H), 3.40–3.45 (m, 8 H), 3.51–3.56 (m, 8 H),
5.85 (s, 1 H), 5.98 (dd, J = 7.9, 1.7 Hz, 2 H), 6.59 (d, J = 8.2 Hz, 4
H), 6.67 (t, J = 7.0 Hz, 2 H), 6.95 (t, J = 7.9 Hz, 1 H), 7.15 (t, J = 7.7
Hz, 4 H) (the signals of the four NH protons were not unambiguous-
ly assigned).
13C NMR (100.6 MHz, CDCl3): d = 26.54 (2 C), 26.65 (2 C), 29.38
(2 C), 29.47 (2 C), 41.88 (2 C), 41.97 (2 C), 69.32 (2 C), 69.37 (2
C), 70.77 (4 C), 96.97 (1 C), 102.58 (2 C), 112.65 (4 C), 116.99 (2
C), 129.15 (4 C), 129.84 (1 C), 148.56 (2 C), 149.69 (2 C).
Yield: 11 mg (5%).
Compounds 9, 10, and 11 were obtained as fractionated mixtures in
total yields of 35 mg (13%), 68 mg (24%), and 17 mg (6%), respec-
tively; eluents: CH2Cl2–MeOH, 3:1; CH2Cl2–MeOH–aq NH3,
10:4:1.
N1-{3-[4-(3-Aminopropoxy)butoxy]propyl}-N3-[3-(4-{3-[3-(3-
{4-[3-(phenylamino)propoxy]butoxy}propylamino)phenylami-
no]propoxy}butoxy)propyl]benzene-1,3-diamine (11)
MALDI–TOF: m/z [M+] calcd for C38H58N4O4: 634.45; found:
634.53.
1H NMR (400 MHz, CDCl3): d = 1.57–1.68 (m, 12 H), 1.81–1.90
(m, 10 H), 1.94 (br s, 2 H), 3.08 (br s, 2 H), 3.13–3.22 (m, 10 H),
3.37–3.54 (m, 24 H), 5.84 (s, 1 H), 5.88 (s, 1 H), 5.97 (br s, 4 H),
6.59 (d, J = 7.9 Hz, 2 H), 6.65 (t, J = 7.2 Hz, 1 H), 6.93 (t, J = 7.9
Hz, 2 H), 7.14 (t, J = 7.8 Hz, 2 H) (the signals of the seven NH pro-
tons were not unambiguously assigned).
N-{3-[4-(3-Aminopropoxy)butoxy]propyl}benzenamine (9)
Obtained as a byproduct in the synthesis of 3i as an inseparable mix-
ture with 10.
Yield: 16 mg (11%); yellow oil; eluent: CH2Cl2–MeOH–aq NH3,
10:4:1.
13C NMR (100.6 MHz, CDCl3): d = 26.2–26.8 (m, 6 C), 29.3–29.4
(m, 6 C), 39.10 (1 C), 41.7–41.9 (m, 5 C), 69.0–71.1 (m, 12 C),
97.24 (1 C), 97.35 (1 C), 102.68 (2 C), 102.74 (2 C), 112.62 (2 C),
116.99 (1 C), 129.12 (2 C), 129.83 (2 C), 148.48 (1 C), 149.55 (2
C), 149.61 (2 C).
MALDI–TOF: m/z [M + H]+ calcd for C48H80N6O6: 837.62; found:
837.45.
1H NMR (400 MHz, CDCl3): d = 1.59–1.64 (m, 4 H), 1.72 (quin,
J = 6.4 Hz, 2 H), 1.86 (quin, J = 6.2 Hz, 2 H), 2.85 (t, J = 6.6 Hz, 2
H), 3.17 (t, J = 6.3 Hz, 2 H), 3.37–3.54 (m, 8 H), 4.35 (br s, 1 H),
6.58 (d, J = 7.7 Hz, 2 H), 6.65 (t, J = 7.3 Hz, 1 H), 7.14 (t, J = 7.9
Hz, 2 H) (the signals of two of the NH protons were not unambigu-
ously assigned).
13C NMR (100.6 MHz, CDCl3): d = 26.45 (2 C), 29.35 (1 C), 29.44
(1 C), 39.25 (1 C), 41.85 (1 C), 68.80 (1 C), 69.30 (1 C), 70.62 (1
C), 70.72 (1 C), 112.61 (2 C), 116.95 (1 C), 129.14 (2 C), 148.53 (1
C).
MALDI–TOF: m/z [M+] calcd for C16H28N2O2: 280.22; found:
280.14.
N,N¢-{3,3¢-[Butane-1,4-diylbis(oxy)]bis(propane-3,1-
diyl)}dibenzenamine (7)
Obtained as a byproduct in the synthesis of 3i using a double
amount of the catalyst.
Yield: 14 mg (8%); yellowish oil; eluent: CH2Cl2–MeOH, 100:1.
1H NMR (400 MHz, CDCl3): d = 1.67–1.72 (m, 4 H), 1.90 (quin,
J = 6.3 Hz, 4 H), 3.24 (t, J = 6.5 Hz, 4 H), 3.28 (t, J = 5.7 Hz, 4 H),
3.56 (t, J = 5.0 Hz, 4 H), 6.61 (d, J = 7.8 Hz, 4 H), 6.69 (t, J = 7.3
Hz, 2 H), 7.18 (t, J = 7.7 Hz, 4 H) (the signals of the two NH protons
were not unambiguously assigned).
13C NMR (100.6 MHz, CDCl3): d = 26.41 (2 C), 29.27 (2 C), 41.86
(2 C), 69.28 (2 C), 70.68 (2 C), 112.54 (4 C), 116.87 (2 C), 129.05
(4 C), 148.45 (2 C).
N1-{3-[4-(3-Aminopropoxy)butoxy]propyl}-N3-(3-{4-[3-(phen-
ylamino)propoxy]butoxy}propyl)benzene-1,3-diamine (10)
Obtained as a byproduct in the synthesis of 3i as an inseparable mix-
ture with 9.
Yield: 32 mg (23%); yellow oil; eluent: CH2Cl2–MeOH–aq NH3,
10:4:1.
1H NMR (400 MHz, CDCl3): d = 1.58–1.66 (m, 8 H), 1.72 (quin,
J = 6.4 Hz, 2 H), 1.82–1.90 (m, 6 H), 2.80 (t, J = 6.6 Hz, 2 H), 3.17
(t, J = 6.3 Hz, 2 H), 3.20 (t, J = 6.6 Hz, 4 H), 3.35–3.55 (m, 16 H),
4.35 (br s, 3 H), 5.84 (s, 1 H), 5.97 (d, J = 7.8 Hz, 2 H), 6.58 (d,
J = 7.7 Hz, 2 H), 6.65 (t, J = 7.3 Hz, 1 H), 6.93 (t, J = 7.9 Hz, 1 H),
7.14 (t, J = 7.9 Hz, 2 H) (the signals of two of the NH protons were
not unambiguously assigned).
MALDI–TOF: m/z [M+] calcd for C22H32N2O2: 356.25; found:
356.07.
6,9,12-Trioxa-2,16-diazabicyclo[15.3.1]heneicosa-1(21),17,19-
triene (3j)
Obtained from 1 (118 mg, 0.5 mmol) and trioxadiamine 2j (110 mg,
0.5 mmol), in the presence of Pd(dba)2 (12 mg, 4 mol%), BINAP
13C NMR (100.6 MHz, CDCl3): d = 26.45 (4 C), 29.33 (2 C), 29.44
(2 C), 39.25 (1 C), 41.85 (1 C), 41.92 (2 C), 68.80 (1 C), 69.30 (1
Synthesis 2007, No. 19, 2995–3012 © Thieme Stuttgart · New York

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A. D. Averin et al.
PAPER
(14 mg, 4.5 mol%), and t-BuONa (144 mg, 1.5 mmol), in abs 1,4-
(28 mg, 9 mol%), and t-BuONa (144 mg, 1.5 mmol), in abs 1,4-di-
dioxane (25 mL).
oxane (25 mL).
Yield: 38 mg (26%); pale-yellow oil; eluent: CH2Cl2–MeOH, 50:1.
Yield: 98 mg (59%); pale-yellow oil; eluents: CH2Cl2–MeOH, 3:1;
CH2Cl2–MeOH–aq NH3, 100:20:1.
1H NMR (400 MHz, CDCl3): d = 1.81 (quin, J = 5.7 Hz, 4 H), 3.30
(t, J = 6.3 Hz, 4 H), 3.58 (t, J = 5.2 Hz, 4 H), 3.59–3.62 (m, 4 H),
3.67–3.70 (m, 4 H), 4.24 (br s, 2 H), 5.93 (dd, J = 7.9, 2.1 Hz, 2 H),
6.19 (s, 1 H), 6.91 (t, J = 8.0 Hz, 1 H).
13C NMR (100.6 MHz, CDCl3): d = 29.60 (2 C), 41.87 (2 C), 69.53
(2 C), 70.06 (2 C), 70.92 (2 C), 96.88 (1 C), 102.16 (2 C), 129.57 (1
C), 150.23 (2 C).
1H NMR (400 MHz, CDCl3): d = 1.70 (quin, J = 6.4 Hz, 2 H), 1.84
(quin, J = 6.1 Hz, 2 H), 2.77 (t, J = 6.6 Hz, 2 H), 2.87 (br s, 2 H),
3.17 (t, J = 6.4 Hz, 2 H), 3.50 (t, J = 6.1 Hz, 2 H), 3.56 (t, J = 6.1
Hz, 2 H), 3.55–3.58 (m, 4 H), 3.59–3.62 (m, 4 H), 4.91 (br s, 1 H),
6.43 (dd, J = 8.2, 1.3 Hz, 1 H), 6.53 (s, 1 H), 6.57 (d, J = 8.0 Hz, 1
H), 7.00 (t, J = 8.0 Hz, 1 H).
13C NMR (100.6 MHz, CDCl3): d = 26.86 (1 C), 28.74 (1 C), 39.18
(1 C), 41.30 (1 C), 69.50 (1 C), 69.68 (1 C), 69.82 (1 C), 69.95 (2
C), 70.38 (1 C), 111.07 (1 C), 112.14 (1 C), 116.50 (1 C), 130.04 (1
C), 134.80 (1 C), 149.84 (1 C).
MALDI–TOF: m/z [M+] calcd for C16H26N2O3: 294.19; found:
294.12.
Cyclodimer 4j (vide infra) was obtained as a byproduct in this reac-
tion.
HRMALDI–TOF: m/z [M+] calcd for C16H27ClN2O3: 330.1710;
found: 330.1702.
Yield: 34 mg (23%); yellow oil; eluent: CH2Cl2–MeOH, 20:1.
Contains an admixture of cyclotrimer 5j (n = 2): MALDI–TOF:
m/z [M+] calcd for C48H78N6O9: 882.58; found: 882.53.
N,N¢-{3,3¢-[2,2¢-Oxybis(ethane-2,1-diyl)bis(oxy)]bis(propane-
3,1-diyl)}bis(3-chlorobenzenamine) (14)
Obtained as a byproduct in the reaction of 1,3-dichlorobenzene (12)
N1-(2-Aminoethyl)-N2-(3-bromophenyl)ethane-1,2-diamine
(6a)
with trioxadiamine 2j.
Obtained from 1 (118 mg, 0.5 mmol) and triamine 2a (52 mg, 0.5
mmol), in the presence of Pd(dba)2 (12 mg, 4 mol%), BINAP (14
mg, 4.5 mol%), and t-BuONa (144 mg, 1.5 mmol), in abs 1,4-diox-
ane (25 mL).
Yield: 26 mg (24%); pale-yellow oil; eluent: CH2Cl2–MeOH,
200:1.
1H NMR (400 MHz, CDCl3): d = 1.86 (quin, J = 6.1 Hz, 4 H), 3.19
(t, J = 6.5 Hz, 4 H), 3.59 (t, J = 5.7 Hz, 4 H), 3.59–3.62 (m, 4 H),
3.65–3.69 (m, 4 H), 4.25 (br s, 2 H), 6.43 (dd, J = 8.2, 2.0 Hz, 2 H),
6.55 (t, J = 2.0 Hz, 2 H), 6.61 (dd, J = 7.8, 1.8 Hz, 2 H), 7.03 (t,
J = 8.0 Hz, 2 H).
13C NMR (100.6 MHz, CDCl3): d = 28.85 (2 C), 41.77 (2 C), 69.79
(2 C), 70.25 (2 C), 70.62 (2 C), 110.95 (2 C), 112.18 (2 C), 116.64
(2 C), 130.06 (2 C), 134.91 (2 C), 149.72 (2 C).
Yield: 57 mg (44%); pale-yellow oil; eluent: CH2Cl2–MeOH–aq
NH3, 10:4:1.
1H NMR (400 MHz, CDCl3): d = 2.66 (t, J = 5.2 Hz, 2 H), 2.79 (t,
J = 5.5 Hz, 2 H), 2.81 (t, J = 5.4 Hz, 2 H), 3.12 (t, J = 5.3 Hz, 2 H),
6.50 (d, J = 7.9 Hz, 1 H), 6.73 (s, 1 H), 6.76 (d, J = 7.9 Hz, 1 H),
6.96 (t, J = 7.9 Hz, 1 H) (the signals of the four NH protons were not
unambiguously assigned).
13C NMR (100.6 MHz, CDCl3): d = 41.04 (1 C), 43.04 (1 C), 47.98
(1 C), 50.96 (1 C), 111.52 (1 C), 115.16 (1 C), 119.77 (1 C), 123.14
(1 C), 130.37 (1 C), 149.74 (1 C).
HRMALDI–TOF: m/z [M+] calcd for C22H30Cl2N2O3: 440.1633;
found: 440.1613.
Na,Nw-Bis(3-bromophenyl)-Substituted Polyamines
15b,d–f,h–k; General Procedure
MALDI–TOF: m/z [M + H]+ calcd for C10H16BrN3: 258.06; found:
A two-necked flask flushed with argon and equipped with a con-
denser and magnetic stirrer was charged with 1,3-dibromobenzene
(1) (519 mg, 2.2 mmol), Pd(dba)2 (23 mg, 0.04 mmol), BINAP (28
mg, 0.045 mmol), and abs 1,4-dioxane (10 mL). The mixture was
stirred at r.t. for 1–2 min, then the appropriate polyamine 2 (1
mmol) and t-BuONa (150 mg, ca. 1.5 mmol) were added, and the
reaction mixture was stirred under reflux for 6–8 h. After the reac-
tion mixture was cooled to r.t., 1 drop of H2O was added, the 1,4-
dioxane was evaporated under reduced pressure, and the residue
was chromatographed on silica gel using various eluents: CH2Cl2–
petroleum ether, 1:1–4:1; CH2Cl2; CH2Cl2–MeOH, 500:1–10:1;
CH2Cl2–MeOH–aq NH3, 100:20:1–10:4:1.
257.99.
2,5,8,14,17,20-Hexaazatricyclo[19.3.1.19,13]hexacosa-
1(25),9(26),10,12,21,23-hexaene (4a)
Obtained from 1 (118 mg, 0.5 mmol) and triamine 2a (52 mg, 0.5
mmol), in the presence of Pd(dba)2 (24 mg, 8 mol%), BINAP (28
mg, 9 mol%), and t-BuONa (144 mg, 1.5 mmol), in abs 1,4-dioxane
(25 mL).
Yield: 66 mg [as a mixture with cyclotrimer 5a (n = 2)] (74%); pale-
yellow oil; eluent: CH2Cl2–MeOH–aq NH3, 10:4:1.
1H NMR (400 MHz, CDCl3): d = 2.41 (br s, 2 H), 2.81 (t, J = 5.5
Hz, 8 H), 3.15 (t, J = 5.5 Hz, 8 H), 4.79 (br s, 4 H), 5.83 (s, 2 H),
6.01 (dd, J = 8.0, 2.0 Hz, 4 H), 6.96 (t, J = 7.9 Hz, 2 H).
13C NMR (100.6 MHz, CDCl3): d = 43.44 (br s, 4 C), 48.43 (br s, 4
C), 98.17 (1 C), 99.30 (1 C), 102.79 (2 C), 102.99 (2 C), 130.05 (1
C), 130.14 (1 C), 149.43 (2 C), 149.53 (2 C).
N1-(3-Bromophenyl)-N3-[3-(3-bromophenylamino)propyl]pro-
pane-1,3-diamine (15b)
From triamine 2b (131 mg, 1 mmol) and other reagents according
to the procedure stated above, 15b was obtained as a yellowish vis-
cous oil.
MALDI–TOF: m/z [M + H]+ calcd for C20H30N6: 355.26; found:
355.25.
Yield: 202 mg (46%); eluent: CH2Cl2–MeOH, 20:1, 10:1.
1H NMR (400 MHz, CDCl3): d = 1.93 (quin, J = 6.5 Hz, 4 H), 2.86
(t, J = 6.7 Hz, 4 H), 3.14 (t, J = 6.4 Hz, 4 H), 3.68 (br s, 2 H), 6.46
(dd, J = 8.2, 2.0 Hz, 2 H), 6.68 (t, J = 2.0 Hz, 2 H), 6.76 (d, J = 8.2
Hz, 2 H), 6.95 (t, J = 8.2 Hz, 2 H) (the signal of the central NH pro-
ton was not unambiguously assigned).
13C NMR (100.6 MHz, CDCl3): d = 26.64 (2 C), 41.15 (2 C), 46.63
(2 C), 111.53 (2 C), 115.12 (2 C), 119.98 (2 C), 123.20 (2 C), 130.52
(2 C), 149.41 (2 C).
Contains cyclotrimer 5a (n = 2): MALDI–TOF: m/z [M + H]+ calcd
for C30H45N9: 532.39; found: 532.50.
N-(3-{2-[2-(3-Aminopropoxy)ethoxy]ethoxy}propyl)-3-chloro-
benzenamine (13)
Obtained according to the procedure stated above using 1,3-dichlo-
robenzene (12) (74 mg, 0.5 mmol) and trioxadiamine 2j (110 mg,
0.5 mmol), in the presence of Pd(dba)2 (24 mg, 8 mol%), BINAP
Synthesis 2007, No. 19, 2995–3012 © Thieme Stuttgart · New York

PAPER
Polyazamacrocycles Containing a 1,3-Disubstituted Benzene Moiety
3005
MALDI–TOF: m/z [M+] calcd for C18H23Br2N3: 439.03; found:
438.98.
1H NMR (400 MHz, CDCl3): d = 1.65 (quin, J = 6.6 Hz, 4 H), 2.36
(br s, 4 H), 2.62–2.70 (m, 8 H), 2.81 (t, J = 5.1 Hz, 8 H), 3.08–3.19
(m, 8 H), 4.40 (br s, 4 H), 5.90 (s, 1 H), 6.00 (d, J = 8.0 Hz, 2 H),
6.49 (d, J = 7.9 Hz, 2 H), 6.71 (s, 2 H), 6.75 (d, J = 7.9 Hz, 2 H),
6.92–6.98 (m, 3 H).
N1,N1¢-(1,3-Phenylene)bis{N3-[3-(3-bromophenylamino)pro-
pyl]propane-1,3-diamine} (16b)
Obtained as a byproduct in the synthesis of 15b.
13C NMR (100.6 MHz, CDCl3): d = 29.61 (2 C), 42.95 (2 C), 43.23
(2 C), 47.95 (4 C), 48.18 (2 C), 48.61 (2 C), 97.40 (1 C), 102.81 (2
C), 111.57 (2 C), 115.12 (2 C), 119.73 (2 C), 123.14 (2 C), 129.95
(1 C), 130.37 (2 C), 149.51 (2 C), 149.71 (2 C).
Yield: 41 mg (13%); eluent: CH2Cl2–MeOH–aq NH3, 10:4:1.
1H NMR (400 MHz, CDCl3): d = 1.81 (quin, J = 6.1 Hz, 4 H), 1.82
(quin, J = 6.1 Hz, 4 H), 2.76 (t, J = 6.4 Hz, 8 H), 3.11 (t, J = 6.6 Hz,
4 H), 3.13 (t, J = 6.6 Hz, 4 H), 4.43 (br s, 4 H), 5.87 (s, 1 H), 5.96
(d, J = 7.9 Hz, 2 H), 6.45 (d, J = 8.0 Hz, 2 H), 6.68 (s, 2 H), 6.74 (d,
J = 7.6 Hz, 2 H), 6.92 (t, J = 7.5 Hz, 1 H), 6.94 (t, J = 7.8 Hz, 2 H)
(the signals of the two central NH protons were not unambiguously
assigned).
MALDI–TOF: m/z [M + H]+ calcd for C32H48Br2N8: 703.25; found:
703.04, 623.12 [M – Br]+.
N1,N1¢-(Ethane-1,2-diyl)bis[N3-(3-bromophenyl)propane-1,3-
diamine] (15e)
From tetraamine 2e (435 mg, 2.5 mmol) and other reagents accord-
ing to the procedure stated above, 15e was obtained as a yellowish
viscous oil.
13C NMR (100.6 MHz, CDCl3): d = 28.10 (2 C), 28.60 (2 C), 42.01
(2 C), 42.19 (2 C), 47.55 (2 C), 47.63 (2 C), 97.29 (1 C), 102.76 (2
C), 111.46 (2 C), 115.03 (2 C), 119.65 (2 C), 123.23 (2 C), 130.04
(1 C), 130.44 (2 C), 149.51 (2 C), 149.75 (2 C).
MALDI–TOF: m/z [M + H]+ calcd for C30H42Br2N6: 645.19; found:
644.97.
Yield: 632 mg (52%); eluent: CH2Cl2–MeOH–aq NH3, 100:20:1,
100:20:2.
1H NMR (400 MHz, CDCl3): d = 1.77 (quin, J = 6.5 Hz, 4 H), 2.74
(s, 4 H), 2.75 (t, J = 6.5 Hz, 4 H), 3.13 (t, J = 6.5 Hz, 4 H), 6.48 (dd,
J = 8.2, 1.4 Hz, 2 H), 6.70 (s, 2 H), 6.75 (dd, J = 7.8, 1.4 Hz, 2 H),
6.97 (t, J = 8.0 Hz, 2 H) (the signals of the four NH protons were not
unambiguously assigned).
N1,N1-Bis(3-bromophenyl)-N3-[3-(3-bromophenylamino)pro-
pyl]propane-1,3-diamine (17b)
Obtained as a byproduct in the synthesis of 15b.
Yield: 14 mg (3%); eluent: CH2Cl2–MeOH, 20:1.
13C NMR (100.6 MHz, CDCl3): d = 28.87 (2 C), 42.34 (2 C), 48.20
(2 C), 49.07 (2 C), 112.39 (2 C), 115.94 (2 C), 120.02 (2 C), 124.04
(2 C), 131.46 (2 C), 151.75 (2 C).
1H NMR (400 MHz, CDCl3): d = 1.77 (quin, J = 6.5 Hz, 2 H), 1.80
(quin, J = 7.1 Hz, 2 H), 2.64 (t, J = 6.8 Hz, 2 H), 2.70 (t, J = 6.6 Hz,
2 H), 3.13 (t, J = 6.6 Hz, 2 H), 3.73 (t, J = 7.2 Hz, 2 H), 6.45 (dd,
J = 8.0, 2.0 Hz, 1 H), 6.69 (t, J = 2.0 Hz, 1 H), 6.78 (d, J = 8.0 Hz,
1 H), 6.89–6.91 (m, 2 H), 6.96 (t, J = 8.0 Hz, 1 H), 7.04–7.10 (m, 4
H), 7.14 (br s, 2 H) (the signals of the two NH protons were not un-
ambiguously assigned).
MALDI–TOF: m/z [M + H]+ calcd for C20H28Br2N4: 483.08; found:
483.06, 403.12 [M – Br]+.
N1,N1¢-(1,3-Phenylene)bis(N3-{2-[3-(3-bromophenylamino)pro-
pylamino]ethyl}propane-1,3-diamine) (16e)
Obtained as a byproduct in the synthesis of 15e.
13C NMR (100.6 MHz, CDCl3): d = 27.49 (1 C), 28.80 (1 C), 42.32
(1 C), 46.97 (1 C), 47.94 (1 C), 50.17 (1 C), 111.52 (1 C), 114.99 (1
C), 119.77 (3 C), 123.15 (2 C), 123.28 (1 C), 123.95 (2 C), 124.84
(2 C), 130.39 (1 C), 130.64 (2 C), 148.78 (2 C), 149.74 (1 C).
MALDI–TOF: m/z [M + H]+ calcd for C24H26Br3N3: 593.98; found:
593.84.
Yield: 90 mg (10%); eluent: CH2Cl2–MeOH–aq NH3, 100:20:3.
1H NMR (400 MHz, CDCl3): d = 1.73 (quin, J = 6.6 Hz, 4 H), 1.75
(quin, J = 6.4 Hz, 4 H), 2.71 (br s, 16 H), 3.11 (t, J = 6.6 Hz, 4 H),
3.13 (t, J = 6.8 Hz, 4 H), 5.85 (s, 1 H), 5.99 (dd, J = 8.0, 1.9 Hz, 2
H), 6.46 (dd, J = 8.1, 1.3 Hz, 2 H), 6.69 (d, J = 1.9 Hz, 2 H), 6.74
(d, J = 7.0 Hz, 2 H), 6.94 (t, J = 7.9 Hz, 1 H), 6.96 (t, J = 8.1 Hz, 2
H) (the signals of the NH protons were not unambiguously as-
signed).
N1,N1¢-(Propane-1,3-diyl)bis[N2-(3-bromophenyl)ethane-1,2-di-
amine] (15d)
From tetraamine 2d (400 mg, 2.5 mmol) and other reagents accord-
ing to the procedure stated above, 15d was obtained as a yellowish
viscous oil.
13C NMR (100.6 MHz, CDCl3): d = 28.99 (2 C), 29.52 (2 C), 42.50
(4 C), 48.00 (4 C), 49.21 (4 C), 96.97 (1 C), 102.52 (2 C), 111.29 (2
C), 114.88 (2 C), 119.41 (2 C), 123.13 (2 C), 129.81 (1 C), 130.32
(2 C), 149.60 (2 C), 149.80 (2 C).
Yield: 753 mg (64%); eluent: CH2Cl2–MeOH–aq NH3, 100:20:1,
100:20:3.
1H NMR (400 MHz, CDCl3): d = 1.65 (quin, J = 6.5 Hz, 2 H), 2.07
(br s, 2 H), 2.71 (t, J = 6.5 Hz, 4 H), 2.84 (t, J = 5.6 Hz, 4 H), 3.16
(t, J = 5.4 Hz, 4 H), 4.47 (br s, 2 H), 6.50 (d, J = 8.0 Hz, 2 H), 6.73
(s, 2 H), 6.77 (d, J = 7.8 Hz, 2 H), 6.97 (t, J = 8.0 Hz, 2 H).
MALDI–TOF: m/z [M + H]+ calcd for C34H52Br2N8: 731.28; found:
731.07, 651.12 [M – Br]+.
N1-[2-(3-Aminopropylamino)ethyl]-N3-(3-bromophenyl)pro-
pane-1,3-diamine (6e)
Obtained as a byproduct in the synthesis of 15e.
13C NMR (100.6 MHz, CDCl3): d = 29.01 (1 C), 42.77 (2 C), 48.07
(4 C), 111.60 (2 C), 115.12 (2 C), 119.89 (2 C), 123.19 (2 C), 130.43
(2 C), 149.59 (2 C).
Yield: 56 mg (7%); eluent: CH2Cl2–MeOH–aq NH3, 10:4:1.
1H NMR (400 MHz, CDCl3): d = 1.65 (quin, J = 6.4 Hz, 2 H), 1.75
(quin, J = 6.4 Hz, 2 H), 2.67 (t, J = 6.7 Hz, 2 H), 2.72 (br s, 6 H),
2.80 (t, J = 6.1 Hz, 2 H), 3.10 (t, J = 5.6 Hz, 2 H), 6.46 (d, J = 7.4
Hz, 1 H), 6.68 (s, 1 H), 6.72 (d, J = 7.8 Hz, 1 H), 6.95 (t, J = 7.4 Hz,
1 H) (the signals of the five NH protons were not unambiguously as-
signed).
13C NMR (100.6 MHz, CDCl3): d = 28.45 (1 C), 31.40 (1 C), 40.16
(1 C), 42.11 (1 C), 47.61 (1 C), 47.74 (1 C), 48.60 (1 C), 48.70 (1
C), 111.28 (1 C), 114.88 (1 C), 119.37 (1 C), 123.15 (1 C), 130.36
(1 C), 149.84 (1 C).
MALDI–TOF: m/z [M + H]+ calcd for C19H26Br2N4: 469.06; found:
469.12, 389.21 [M – Br]+.
N1,N1¢-{2,2¢-[1,3-Phenylenebis(azanediyl)]bis(ethane-2,1-
diyl)}bis{N3-[2-(3-bromophenylamino)ethyl]propane-1,3-di-
amine} (16d)
Obtained as a byproduct in the synthesis of 15d.
Yield: 188 mg (21%); eluent: CH2Cl2–MeOH–aq NH3, 10:4:1.
Synthesis 2007, No. 19, 2995–3012 © Thieme Stuttgart · New York

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A. D. Averin et al.
PAPER
MALDI–TOF: m/z [M + H]+ calcd for C14H25BrN4: 329.14; found:
6.73 (t, J = 2.0 Hz, 2 H), 6.79 (dd, J = 7.9, 2.0 Hz, 2 H), 6.97 (t,
J = 8.1 Hz, 1 H), 6.98 (t, J = 8.0 Hz, 2 H) (the signals of the four NH
protons were not unambiguously assigned).
13C NMR (100.6 MHz, CDCl3): d = 43.28 (2 C), 43.50 (2 C), 69.36
(2 C), 69.74 (2 C), 70.14 (2 C), 70.25 (2 C), 97.96 (1 C), 103.33 (2
C), 111.86 (2 C), 115.41 (2 C), 120.13 (2 C), 123.20 (2 C), 129.96
(1 C), 130.41 (2 C), 149.29 (2 C), 149.51 (2 C).
329.04, 249.10 [M – Br]+.
N1,N1¢-(Propane-1,3-diyl)bis[N3-(3-bromophenyl)propane-1,3-
diamine] (15f)
From tetraamine 2f (187 mg, 1 mmol) and other reagents according
to the procedure stated above, 15f was obtained as a yellowish vis-
cous oil.
MALDI–TOF: m/z [M + H]+ calcd for C30H40Br2N4O4: 679.15;
Yield: 191 mg (39%); eluent: CH2Cl2–MeOH–aq NH3, 100:20:1,
100:20:2.
found: 678.89, 599.01 [M – Br]+.
1H NMR (400 MHz, CDCl3): d = 1.68 (quin, J = 6.7 Hz, 2 H), 1.74
(quin, J = 6.5 Hz, 4 H), 2.68 (t, J = 6.7 Hz, 4 H), 2.71 (t, J = 6.6 Hz,
4 H), 3.11 (t, J = 6.5 Hz, 4 H), 4.51 (br s, 2 H), 6.46 (dd, J = 8.1, 1.4
Hz, 2 H), 6.69 (t, J = 2.0 Hz, 2 H), 6.75 (dd, J = 7.8, 1.8 Hz, 2 H),
6.96 (t, J = 8.0 Hz, 2 H) (the signals of the two central NH protons
were not unambiguously assigned).
13C NMR (100.6 MHz, CDCl3): d = 28.77 (2 C), 29.70 (1 C), 42.60
(2 C), 48.20 (2 C), 48.40 (2 C), 111.29 (2 C), 114.86 (2 C), 119.40
(2 C), 123.12 (2 C), 130.30 (2 C), 149.79 (2 C).
3-Bromo-N-(3-bromophenyl)-N-(2-{2-[2-(3-bromophenylami-
no)ethoxy]ethoxy}ethyl)benzenamine (17h)
Obtained as a byproduct in the synthesis of 15h.
Yield: 17 mg (4%); eluent: CH2Cl2–petroleum ether, 1:1.
1H NMR (400 MHz, CDCl3): d = 3.23 (t, J = 5.0 Hz, 2 H), 3.59 (br
s, 4 H), 3.65 (t, J = 5.9 Hz, 2 H), 3.66 (t, J = 5.1 Hz, 2 H), 3.88 (t,
J = 5.8 Hz, 2 H), 4.10 (br s, 1 H), 6.47 (dd, J = 7.9, 1.8 Hz, 1 H),
6.71 (br s, 1 H), 6.79 (d, J = 7.8 Hz, 1 H), 6.91–6.95 (m, 2 H), 7.10
(t, J = 8.0 Hz, 1 H), 7.06–7.10 (m, 4 H), 7.20 (br s, 2 H).
13C NMR (100.6 MHz, CDCl3): d = 43.24 (1 C), 51.80 (1 C), 68.07
(1 C), 69.44 (1 C), 70.32 (1 C), 70.75 (1 C), 111.77 (1 C), 115.40 (1
C), 119.79 (2 C), 120.10 (1 C), 123.04 (1 C), 124.00 (2 C), 124.81
(2 C), 130.32 (2 C), 130.42 (1 C), 130.54 (2 C), 148.57 (2 C), 149.43
(1 C).
MALDI–TOF: m/z [M + H]+ calcd for C21H30Br2N4: 497.09; found:
497.23, 417.27 [M – Br]+.
N1,N1¢-(1,3-Phenylene)bis(N3-{3-[3-(3-bromophenylamino)pro-
pylamino]propyl}propane-1,3-diamine) (16f)
Obtained as a byproduct in the synthesis of 15f.
MALDI–TOF: m/z [M+] calcd for C24H25Br3N2O2: 609.95; found:
Yield: 48 mg (12%); eluent: CH2Cl2–MeOH–aq NH3, 10:3:1.
610.05, 531.10 [M – Br]+, 452.18 [M – 2 Br]+.
1H NMR (400 MHz, CDCl3): d = 1.74 (br s, 12 H), 2.73 (br s, 16 H),
3.05–3.35 (m, 8 H), 4.17 (br s, 4 H), 5.90 (s, 1 H), 5.96 (d, J = 6.9
Hz, 2 H), 6.47 (d, J = 7.4 Hz, 2 H), 6.68 (s, 2 H), 6.72 (d, J = 6.8 Hz,
2 H), 6.92–6.97 (m, 3 H) (the signals of the four central NH protons
were not unambiguously assigned).
N1-(3-Bromophenyl)-N1,N3-bis(2-{2-[2-(3-bromophenylami-
no)ethoxy]ethoxy}ethyl)benzene-1,3-diamine (18h)
Obtained as a byproduct in the synthesis of 15h. Isolated together
with higher-mass oligomers.
13C NMR (100.6 MHz, CDCl3): d = 27.99 (2 C), 28.29 (2 C), 28.68
(2 C), 42.20 (2 C), 42.30 (2 C), 47.63 (2 C), 47.70 (2 C), 48.51 (2
C), 48.57 (2 C), 97.25 (1 C), 102.53 (2 C), 111.36 (2 C), 114.89 (2
C), 119.39 (2 C), 123.15 (2 C), 129.89 (1 C), 130.38 (2 C), 149.59
(2 C), 149.86 (2 C).
Yield: 10 mg (2%); eluent: CH2Cl2–MeOH, 200:1.
1H NMR (400 MHz, CDCl3): d = 3.20–3.27 (m, 6 H), 3.58–3.70 (m,
16 H), 3.85 (t, J = 6.1 Hz, 2 H), 4.11 (br s, 3 H), 6.37 (s, 1 H), 6.46
(d, J = 8.2 Hz, 1 H), 6.48 (d, J = 8.7 Hz, 1 H), 6.68–6.83 (m, 6 H),
6.89–7.22 (m, 7 H).
MALDI–TOF: m/z [M + H]+ calcd for C36H56Br2N8: 759.31; found:
MALDI–TOF: m/z [M+] calcd for C36H43Br3N4O4: 832.08; found:
759.22, 679.13 [M – Br]+.
832.22, 753.30 [M – Br]+, 674.38 [M – 2 Br]+.
N,N¢-{2,2¢-[Ethane-1,2-diylbis(oxy)]bis(ethane-2,1-diyl)}bis(3-
bromobenzenamine) (15h)
From dioxadiamine 2h (148 mg, 1 mmol) and other reagents ac-
cording to the procedure stated above, 15h was obtained as a yel-
lowish viscous oil.
N,N¢-{3,3¢-[Butane-1,4-diylbis(oxy)]bis(propane-3,1-
diyl)}bis(3-bromobenzenamine) (15i)
From dioxadiamine 2i (204 mg, 1 mmol) and other reagents accord-
ing to the procedure stated above, 15i was obtained as a yellowish
viscous oil.
Yield: 210 mg (46%); eluent: CH2Cl2–petroleum ether, 1:1–2:1.
Yield: 306 mg (59%); eluent: CH2Cl2–MeOH, 200:1.
1H NMR (400 MHz, CDCl3): d = 3.26 (t, J = 5.2 Hz, 4 H), 3.64 (s,
4 H), 3.68 (t, J = 5.2 Hz, 4 H), 4.17 (br s, 2 H), 6.51 (ddd, J = 8.3,
2.0, 1.0 Hz, 2 H), 6.74 (t, J = 2.0 Hz, 2 H), 6.81 (ddd, J = 7.8, 2.0,
1.0 Hz, 2 H), 6.99 (t, J = 8.0 Hz, 2 H).
13C NMR (100.6 MHz, CDCl3): d = 43.12 (2 C), 69.25 (2 C), 70.08
(2 C), 111.68 (2 C), 115.26 (2 C), 119.99 (2 C), 123.07 (2 C), 130.32
(2 C), 149.36 (2 C).
1H NMR (400 MHz, CDCl3): d = 1.68 (quin, J = 4.3 Hz, 4 H), 1.86
(quin, J = 6.1 Hz, 4 H), 3.18 (t, J = 6.4 Hz, 4 H), 3.45 (br s, 4 H),
3.53 (t, J = 5.8 Hz, 4 H), 4.17 (br s, 2 H), 6.48 (ddd, J = 8.1, 2.2, 0.8
Hz, 2 H), 6.71 (t, J = 2.0 Hz, 2 H), 6.77 (ddd, J = 7.8, 1.8, 0.8 Hz, 2
H), 6.98 (t, J = 8.0 Hz, 2 H).
13C NMR (100.6 MHz, CDCl3): d = 26.52 (2 C), 29.09 (2 C), 41.90
(2 C), 69.36 (2 C), 70.79 (2 C), 111.35 (2 C), 114.91 (2 C), 119.55
(2 C), 123.20 (2 C), 130.35 (2 C), 149.78 (2 C).
MALDI–TOF: m/z [M + H]+ calcd for C18H22Br2N2O2: 457.01;
found: 456.92, 377.03 [M – Br]+.
MALDI–TOF: m/z [M+] calcd for C22H30Br2N2O2: 512.07; found:
512.23, 433.28 [M – Br]+.
N1,N3-Bis(2-{2-[2-(3-bromophenylamino)ethoxy]ethoxy}eth-
yl)benzene-1,3-diamine (16h)
Obtained as a byproduct in the synthesis of 15h.
N1,N3-Bis(3-{4-[3-(3-bromophenylamino)propoxy]butoxy}pro-
pyl)benzene-1,3-diamine (16i)
Yield: 54 mg (16%); eluent: CH2Cl2–MeOH, 100:1.
Obtained as a byproduct in the synthesis of 15i.
1H NMR (400 MHz, CDCl3): d = 3.25 (t, J = 5.2 Hz, 4 H), 3.26 (t,
J = 5.1 Hz, 4 H), 3.63 (s, 8 H), 3.67 (t, J = 5.2 Hz, 8 H), 5.89 (s, 1
H), 6.03 (dd, J = 7.9, 2.1 Hz, 2 H), 6.51 (dd, J = 8.1, 2.0 Hz, 2 H),
Yield: 44 mg (11%); eluent: CH2Cl2–MeOH, 50:1.
1H NMR (400 MHz, CDCl3): d = 1.66 (br s, 8 H), 1.85 (quin, J = 5.8
Hz, 8 H), 3.18 (t, J = 5.9 Hz, 8 H), 3.44 (br s, 8 H), 3.52 (t, J = 5.6
Synthesis 2007, No. 19, 2995–3012 © Thieme Stuttgart · New York

PAPER
Polyazamacrocycles Containing a 1,3-Disubstituted Benzene Moiety
3007
Hz, 8 H), 4.15 (br s, 4 H), 5.85 (s, 1 H), 5.98 (d, J = 8.0 Hz, 2 H),
6.47 (d, J = 7.8 Hz, 2 H), 6.70 (s, 2 H), 6.76 (d, J = 7.6 Hz, 2 H),
6.96 (t, J = 8.0 Hz, 1 H), 6.98 (t, J = 8.0 Hz, 2 H).
13C NMR (100.6 MHz, CDCl3): d = 26.53 (4 C), 29.10 (2 C), 29.45
(2 C), 41.90 (4 C), 69.35 (4 C), 70.72 (2 C), 70.84 (2 C), 96.92 (1
C), 102.57 (2 C), 111.38 (2 C), 114.93 (2 C), 119.56 (2 C), 123.23
(2 C), 129.85 (1 C), 130.36 (2 C), 149.67 (2 C), 149.82 (2 C).
MALDI–TOF: m/z [M+] calcd for C22H30Br2N2O3: 528.06; found:
527.93, 449.04 [M – Br]+.
N1,N3-Bis[3-(2-{2-[3-(3-bromophenylamino)propoxy]eth-
oxy}ethoxy)propyl]benzene-1,3-diamine (16j)
Obtained as a byproduct in the synthesis of 15j.
Yield: 43 mg (10%); eluent: CH2Cl2–MeOH, 50:1.
MALDI–TOF: m/z [M+] calcd for C38H56Br2N4O4: 790.27; found:
1H NMR (400 MHz, CDCl3): d = 1.85 (quin, J = 6.0 Hz, 8 H), 3.18
(t, J = 6.4 Hz, 8 H), 3.55–3.62 (m, 16 H), 3.64–3.69 (m, 8 H), 4.21
(br s, 4 H), 5.85 (s, 1 H), 5.97 (d, J = 7.8 Hz, 2 H), 6.47 (d, J = 7.8
Hz, 2 H), 6.71 (s, 2 H), 6.75 (d, J = 7.8 Hz, 2 H), 6.95 (t, J = 8.1 Hz,
1 H), 6.97 (t, J = 7.9 Hz, 2 H).
13C NMR (100.6 MHz, CDCl3): d = 28.87 (2 C), 29.36 (2 C), 41.57
(2 C), 41.70 (2 C), 69.62 (2 C), 69.72 (2 C), 70.24 (4 C), 70.62 (4
C), 97.03 (1 C), 102.56 (2 C), 111.34 (2 C), 115.06 (2 C), 119.47 (2
C), 123.19 (2 C), 129.82 (1 C), 130.33 (2 C), 149.67 (2 C), 149.91
(2 C).
790.18, 711.20 [M – Br]+.
N1-(3-Bromophenyl)-N1,N3-bis(3-{4-[3-(3-bromophenylami-
no)propoxy]butoxy}propyl)benzene-1,3-diamine (18i)
Obtained as a byproduct in the synthesis of 15i. Isolated together
with higher-mass oligomers.
Yield: 10 mg (2%); eluent: CH2Cl2–MeOH, 200:1.
1H NMR (400 MHz, CDCl3): d = 1.67 (br s, 8 H), 1.77–1.90 (m, 8
H), 3.14–3.30 (m, 8 H), 3.38–3.48 (m, 8 H), 3.52 (t, J = 5.5 Hz, 4
H), 3.54 (t, J = 5.0 Hz, 4 H), 4.14 (br s, 3 H), 6.32 (s, 1 H), 6.35 (d,
J = 8.1 Hz, 1 H), 6.43 (d, J = 9.0 Hz, 1 H), 6.48 (dd, J = 8.1, 1.6 Hz,
2 H), 6.59 (d, J = 7.6 Hz, 2 H), 6.71 (s, 2 H), 6.74–6.80 (m, 1 H),
6.90–7.18 (m, 6 H).
13C NMR (100.6 MHz, CDCl3): d = 26.56 (4 C), 27.85 (1 C), 29.14
(2 C), 29.37 (1 C), 41.97 (2 C), 42.53 (1 C), 48.97 (1 C), 69.39 (4
C), 69.92 (1 C), 70.72 (1 C), 70.80 (1 C), 70.92 (1 C), 108.63 (1 C),
108.84 (1 C), 111.40 (2 C), 113.44 (1 C), 114.96 (2 C), 117.01 (1
C), 119.60 (2 C), 119.86 (1 C), 121.36 (1 C), 122.94 (1 C), 123.26
(2 C), 130.08 (1 C), 130.37 (2 C), 132.21 (1 C), 147.75 (1 C), 149.83
(2 C), 150.08 (1 C), 150.26 (1 C).
MALDI–TOF: m/z [M+] calcd for C38H56Br2N4O6: 822.26; found:
822.16.
3-Bromo-N-[3-(2-{2-[3-(phenylamino)propoxy]eth-
oxy}ethoxy)propyl]benzenamine (19j)
Obtained as a byproduct in the synthesis of 15j.
Yield: 24 mg (5%); eluent: CH2Cl2–MeOH, 100:1.
1H NMR (400 MHz, CDCl3): d = 1.86 (quin, J = 6.1 Hz, 2 H), 1.87
(quin, J = 6.3 Hz, 2 H), 3.17 (t, J = 6.5 Hz, 2 H), 3.22 (t, J = 6.4 Hz,
2 H), 3.55–3.63 (m, 8 H), 3.65–3.70 (m, 4 H), 4.20 (br s, 2 H), 6.47
(dd, J = 7.6, 1.5 Hz, 1 H), 6.59 (d, J = 7.8 Hz, 2 H), 6.67 (t, J = 7.5
Hz, 1 H), 6.71 (t, J = 2.0 Hz, 1 H), 6.75 (d, J = 7.6 Hz, 1 H), 6.97 (t,
J = 8.0 Hz, 1 H), 7.15 (dd, J = 8.4, 7.6 Hz, 2 H).
MALDI–TOF: m/z [M+] calcd for C44H59Br3N4O4: 944.21; found:
944.41.
13C NMR (100.6 MHz, CDCl3): d = 28.89 (2 C), 41.76 (2 C), 69.77
(2 C), 70.26 (2 C), 70.64 (2 C), 111.36 (1 C), 112.69 (2 C), 115.11
(1 C), 116.99 (1 C), 119.54 (1 C), 123.23 (1 C), 129.15 (2 C), 130.35
(1 C), 149.91 (2 C).
3-Bromo-N-(3-{4-[3-(phenylamino)propoxy]butoxy}pro-
pyl)benzenamine (19i)
Obtained as a byproduct in the synthesis of 15i.
Yield: 38 mg (9%); eluent: CH2Cl2–MeOH, 500:1.
MALDI–TOF: m/z [M+] calcd for C22H31BrN2O3: 450.15; found:
1H NMR (400 MHz, CDCl3): d = 1.68 (quin, J = 4.3 Hz, 4 H), 1.86
(quin, J = 6.1 Hz, 4 H), 3.18 (t, J = 6.4 Hz, 2 H), 3.21 (t, J = 6.4 Hz,
2 H), 3.45 (br s, 4 H), 3.53 (t, J = 5.8 Hz, 4 H), 4.17 (br s, 2 H), 6.48
(dd, J = 8.0, 1.3 Hz, 1 H), 6.60 (d, J = 8.2 Hz, 2 H), 6.68 (t, J = 7.4
Hz, 1 H), 6.71 (s, 1 H), 6.77 (d, J = 7.7 Hz, 1 H), 6.98 (t, J = 7.9 Hz,
1 H), 7.16 (t, J = 7.7 Hz, 2 H).
450.06.
N1,N3-Bis(3-bromophenyl)propane-1,3-diamine (15k)
From diamine 2k (74 mg, 1 mmol) and other reagents according to
the procedure stated above, 15k was obtained as a yellowish viscous
oil.
13C NMR (100.6 MHz, CDCl3): d = 26.30 (2 C), 29.08 (2 C), 41.87
(2 C), 69.33 (2 C), 70.77 (2 C), 111.34 (1 C), 112.59 (2 C), 114.90
(1 C), 116.95 (1 C), 119.52 (1 C), 123.19 (1 C), 129.12 (2 C), 130.33
(1 C), 148.47 (1 C), 149.78 (1 C).
Yield: 121 mg (32%); eluent: CH2Cl2–petroleum ether, 4:1.
1H NMR (400 MHz, CDCl3): d = 1.88 (quin, J = 6.7 Hz, 2 H), 3.19
(br s, 4 H), 3.75 (br s, 2 H), 6.51 (ddd, J = 8.2, 2.0, 1.0 Hz, 2 H), 6.74
(t, J = 2.0 Hz, 2 H), 6.83 (ddd, J = 7.8, 2.0, 1.0 Hz, 2 H), 7.03 (t,
J = 8.0 Hz, 2 H).
MALDI–TOF: m/z [M + H]+ calcd for C22H31BrN2O2: 435.17;
found: 435.22.
13C NMR (100.6 MHz, CDCl3): d = 28.73 (1 C), 41.50 (2 C), 111.54
(2 C), 115.14 (2 C), 120.11 (2 C), 123.23 (2 C), 130.48 (2 C), 149.27
(2 C).
MALDI–TOF: m/z [M+] calcd for C15H16Br2N2: 382.00; found:
382.03.
N,N¢-{3,3¢-[2,2¢-Oxybis(ethane-2,1-diyl)bis(oxy)]bis(propane-
3,1-diyl)}bis(3-bromobenzenamine) (15j)
From trioxadiamine 2j (220 mg, 1 mmol) and other reagents accord-
ing to the procedure stated above, 15j was obtained as a yellowish
viscous oil.
N1,N1¢-(1,3-Phenylene)bis[N3-(3-bromophenyl)propane-1,3-di-
amine] (16k)
Obtained as a byproduct in the synthesis of 15k.
Yield: 156 mg (29%); eluent: CH2Cl2–MeOH, 200:1.
1H NMR (400 MHz, CDCl3): d = 1.85 (quin, J = 6.1 Hz, 4 H), 3.18
(t, J = 6.5 Hz, 4 H), 3.48 (t, J = 5.5 Hz, 4 H), 3.59–3.62 (m, 4 H),
3.66–3.69 (m, 4 H), 4.24 (br s, 2 H), 6.48 (dd, J = 8.1, 2.0 Hz, 2 H),
6.71 (t, J = 2.0 Hz, 2 H), 6.76 (dd, J = 7.8, 2.0 Hz, 2 H), 6.97 (t,
J = 8.0 Hz, 2 H).
13C NMR (100.6 MHz, CDCl3): d = 28.69 (2 C), 41.60 (2 C), 69.63
(2 C), 70.10 (2 C), 70.47 (2 C), 111.22 (2 C), 114.90 (2 C), 119.33
(2 C), 123.08 (2 C), 130.27 (2 C), 149.78 (2 C).
Yield: 37 mg (14%); eluent: CH2Cl2–MeOH, 200:1.
1H NMR (400 MHz, CDCl3): d = 1.89 (quin, J = 6.7 Hz, 4 H), 3.15
(t, J = 6.8 Hz, 8 H), 5.86 (s, 1 H), 6.02 (dd, J = 8.0, 2.0 Hz, 2 H),
6.49 (dd, J = 8.3, 2.0 Hz, 2 H), 6.72 (t, J = 2.0 Hz, 2 H), 6.79 (dd,
J = 8.0, 2.0 Hz, 2 H), 6.98 (t, J = 8.0 Hz, 1 H), 6.99 (t, J = 8.0 Hz, 2
H) (the signals of the four NH protons were not unambiguously as-
signed).
Synthesis 2007, No. 19, 2995–3012 © Thieme Stuttgart · New York

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A. D. Averin et al.
PAPER
13C NMR (100.6 MHz, CDCl3): d = 29.01 (2 C), 41.71 (2 C), 41.83
(2 C), 97.21 (1 C), 103.09 (2 C), 111.54 (2 C), 115.17 (2 C), 120.00
(2 C), 123.27 (2 C), 130.10 (1 C), 130.47 (2 C), 149.30 (2 C), 149.46
(2 C).
MALDI–TOF: m/z [M+] calcd for C24H28Br2N4: 530.07; found:
529.97.
MALDI–TOF: m/z [M + H]+ calcd for C26H44N8: 469.38; found:
469.51.
N1-[2-({3-[(2-Aminoethyl)amino]propyl}amino)ethyl]-N3-(2-
{[3-({2-[(3-bromophenyl)amino]ethyl}amino)propyl]ami-
no}ethyl)benzene-1,3-diamine (20)
Obtained as a byproduct in the synthesis of 4d.
N1,N1,N3-Tris(3-bromophenyl)propane-1,3-diamine (17k)
Detected as an admixture to 15k; eluent: CH2Cl2–petroleum ether,
2:1.
1H NMR (400 MHz, CDCl3): d = 1.93 (quin, J = 6.7 Hz, 2 H), 3.15
(t, J = 6.8 Hz, 2 H), 3.77 (t, J = 7.0 Hz, 2 H), 3.78 (br s, 1 H), 6.47
(d, J = 8.0 Hz, 1 H), 6.70 (s, 1 H), 6.82 (d, J = 8.0 Hz, 1 H), 6.89–
6.92 (m, 2 H), 7.01 (t, J = 8.0 Hz, 1 H), 7.07–7.14 (m, 6 H).
Yield: 50 mg (30%); eluent: CH2Cl2–MeOH–aq NH3, 10:4:1.
1H NMR (400 MHz, CDCl3): d = 1.64 (br s, 2 H), 1.65 (br s, 2 H),
2.55–2.85 (m, 18 H), 3.05–3.20 (m, 6 H), 5.90 (s, 1 H), 5.98 (d,
J = 7.0 Hz, 2 H), 6.48 (d, J = 7.6 Hz, 1 H), 6.70 (s, 1 H), 6.74 (d,
J = 7.2 Hz, 1 H), 6.93 (t, J = 7.6 Hz, 1 H), 6.95 (t, J = 8.0 Hz, 1 H)
(the signals of the nine NH protons were not unambiguously as-
signed).
13C NMR (100.6 MHz, CDCl3): d = 27.19 (1 C), 41.15 (1 C), 49.84
(1 C), 111.58 (1 C), 115.30 (1 C), 119.73 (2 C), 120.31 (1 C), 122.97
(2 C), 123.89 (2 C), 124.99 (2 C), 130.49 (1 C), 130.69 (3 C), 148.58
(2 C), 149.27 (1 C).
13C NMR (100.6 MHz, CDCl3): d = 29.65 (1 C), 29.76 (1 C), 42.94
(1 C), 43.01 (1 C), 43.23 (2 C), 47.86 (2 C), 48.12 (1 C), 48.17 (1
C), 48.45 (1 C), 48.60 (2 C), 52.07 (1 C), 97.35 (1 C), 102.69 (1 C),
102.75 (1 C), 111.52 (1 C), 115.07 (1 C), 119.95 (1 C), 123.09 (1
C), 129.86 (1 C), 130.33 (1 C), 149.49 (3 C).
Macrocycles 4b,d–f,h–j; General Procedure
MALDI–TOF: m/z [M + H]+ calcd for C26H45BrN8: 549.31; found:
A two-necked flask flushed with argon and equipped with a mag-
netic stirrer and condenser was charged with a Na,Nw-bis(3-bro-
mophenyl)-substituted polyamine 15 (1 mmol), Pd(dba)2 (46 mg, 8
mol%), BINAP (56 mg, 9 mol%), and abs 1,4-dioxane (50 mL). The
mixture was stirred for several minutes, then the appropriate
polyamine 2 (1 mmol) was added followed by t-BuONa (150 mg,
ca. 1.5 mmol), and the reaction mixture was stirred under reflux for
24–30 h. After the reaction mixture was cooled to r.t., 1 drop of H2O
was added, the 1,4-dioxane was evaporated under reduced pressure,
and the residue was chromatographed on silica gel using various
eluents: CH2Cl2; CH2Cl2–MeOH, 200:1–10:1; CH2Cl2–MeOH–aq
NH3, 100:20:3–10:4:1.
549.47.
2,6,9,13,19,23,26,30-Octaazatricyclo[29.3.1.114,18]hexatriacon-
ta-1(35),14(36),15,17,31,33-hexaene (4e)
From compound 15e (338 mg, 0.7 mmol) and other reagents ac-
cording to the procedure stated above, 4e was obtained as a yellow
viscous oil.
Yield: 125 mg (36%); eluent: CH2Cl2–MeOH–aq NH3, 10:3:1.
1H NMR (400 MHz, CDCl3): d = 1.70 (quin, J = 6.0 Hz, 8 H), 2.71
(br s, 16 H), 3.11 (t, J = 5.9 Hz, 8 H), 5.90 (s, 2 H), 5.95 (d, J = 7.9
Hz, 4 H), 6.92 (t, J = 7.9 Hz, 2 H) (the signals of the eight NH pro-
tons were not unambiguously assigned).
13C NMR (100.6 MHz, CDCl3): d = 29.00 (4 C), 42.72 (4 C), 47.79
(4 C), 48.49 (4 C), 97.55 (2 C), 102.30 (4 C), 129.80 (2 C), 149.65
(4 C).
2,6,10,16,20,24-Hexaazatricyclo[23.3.1.111,15]triaconta-
1(29),11(30),12,14,25,27-hexaene (4b)
From compound 15b (146 mg, 0.33 mmol) and other reagents ac-
cording to the procedure stated above, 4b was obtained as a yellow
viscous oil.
MALDI–TOF: m/z [M + H]+ calcd for C28H48N8: 497.41; found:
497.50.
Yield: 60 mg (44%); eluent: CH2Cl2–MeOH–aq NH3, 10:3:1.
1H NMR (400 MHz, CDCl3): d = 1.75 (quin, J = 6.0 Hz, 8 H), 2.68
(br s, 4 H), 2.72 (t, J = 6.0 Hz, 4 H), 3.14 (t, J = 6.3 Hz, 4 H), 3.19
(t, J = 6.2 Hz, 4 H), 5.85 (s, 2 H), 5.98 (dd, J = 7.8, 1.9 Hz, 4 H),
6.94 (t, J = 7.9 Hz, 2 H) (the signals of the six NH protons were not
unambiguously assigned).
2,6,10,14,20,24,28,32-Octaazatricyclo[31.3.1.115,19]octatriacon-
ta-1(37),15(38),16,18,33,35-hexaene (4f)
From compound 15f (190 mg, 0.38 mmol) and other reagents ac-
cording to the procedure stated above, 4f was obtained as a yellow
viscous oil.
13C NMR (100.6 MHz, CDCl3): d = 29.01 (2 C), 29.36 (br s, 2 C),
42.68 (br s, 2 C), 42.75 (2 C), 48.22 (4 C), 97.10 (br s, 1 C), 97.37
(1 C), 102.43 (2 C), 102.49 (br s, 2 C), 129.87 (2 C), 149.68 (4 C).
Yield: 60 mg (30%); eluent: CH2Cl2–MeOH–aq NH3, 100:20:3–
10:3:1.
1H NMR (400 MHz, CDCl3): d = 1.73 (br s, 12 H), 2.47 (br s, 8 H),
2.60–2.90 (m, 8 H), 2.95–3.20 (m, 8 H), 5.81–6.02 (m, 6 H), 6.91
(br s, 2 H) (the signals of the eight NH protons were not unambigu-
ously assigned).
13C NMR (100.6 MHz, CDCl3): d = 26.37 (4 C), 27.67 (2 C), 43.34
(4 C), 52.92 (4 C), 53.51 (4 C), 97.58 (2 C), 101.83 (4 C), 129.77 (2
C), 149.47 (4 C).
MALDI–TOF: m/z [M+] calcd for C24H38N6: 410.32; found: 410.31.
2,5,9,12,18,21,25,28-Octaazatricyclo[27.3.1.113,17]tetratriacon-
ta-1(33),13(34),14,16,29,31-hexaene (4d)
From compound 15d (141 mg, 0.3 mmol) and other reagents ac-
cording to the procedure stated above, 4d was obtained as a yellow
viscous oil.
MALDI–TOF: m/z [M+] calcd for C30H52N8: 524.43; found: 524.37.
Yield: 9 mg (6%); eluent: CH2Cl2–MeOH–aq NH3, 10:4:1.
1H NMR (400 MHz, CDCl3): d = 1.64 (br s, 4 H), 2.63 (br s, 8 H),
2.80 (br s, 8 H), 3.11 (br s, 8 H), 5.85 (s, 2 H), 5.98 (d, J = 7.0 Hz,
4 H), 6.92 (t, J = 7.0 Hz, 2 H) (the signals of the eight NH protons
were not unambiguously assigned).
13C NMR (100.6 MHz, CDCl3): d = 28.16 (2 C), 41.26 (4 C), 48.03
(4 C), 48.36 (4 C), 97.93 (2 C), 102.39 (4 C), 129.86 (2 C), 149.70
(4 C).
5,8,20,23-Tetraoxa-2,11,17,26-tetraazatricyclo[25.3.1.112,16]do-
triaconta-1(31),12(32),13,15,27,29-hexaene (4h)
From compound 15h (194 mg, 0.424 mmol) and other reagents ac-
cording to the procedure stated above, 4h was obtained as a yellow
viscous oil.
Yield: 30 mg (16%); eluent: CH2Cl2–MeOH, 200:1, 100:1.
1H NMR (400 MHz, CDCl3): d = 3.24 (t, J = 4.9 Hz, 8 H), 3.64 (s,
8 H), 3.68 (t, J = 4.9 Hz, 8 H), 5.86 (s, 2 H), 6.03 (d, J = 7.9 Hz, 4
Synthesis 2007, No. 19, 2995–3012 © Thieme Stuttgart · New York

PAPER
Polyazamacrocycles Containing a 1,3-Disubstituted Benzene Moiety
3009
H), 6.98 (t, J = 8.0 Hz, 2 H) (the signals of the four NH protons were
not unambiguously assigned).
13C NMR (100.6 MHz, CDCl3): d = 43.49 (4 C), 69.44 (4 C), 70.05
(4 C), 98.85 (2 C), 102.69 (4 C), 129.90 (2 C), 149.30 (4 C).
13C NMR (100.6 MHz, CDCl3): d = 27.83 (2 C), 46.82 (2 C), 50.11
(2 C), 119.76 (4 C), 123.15 (4 C), 123.93 (4 C), 124.81 (4 C), 130.61
(4 C), 148.74 (4 C).
MALDI–TOF: m/z [M+] calcd for C30H29Br4N3: 746.91; found:
746.96.
MALDI–TOF: m/z [M+] calcd for C24H36N4O4: 444.27; found:
444.00.
N,N¢-{2,2¢-[Ethane-1,2-diylbis(oxy)]bis(ethane-2,1-diyl)}bis[3-
bromo-N-(3-bromophenyl)benzenamine] (21h)
From dioxadiamine 2h (37 mg, 0.25 mmol) and other reagents stat-
ed above, 21h was obtained as a yellow oil.
6,11,25,30-Tetraoxa-2,15,21,34-tetraazatricy-
clo[33.3.1.116,20]tetraconta-1(39),16(40),17,19,35,37-hexaene (4i)
From compound 15i (132 mg, 0.257 mmol) and other reagents ac-
cording to the procedure stated above, 4i was obtained as a yellow
viscous oil.
Yield: 60 mg (31%); eluent: CH2Cl2–petroleum ether, 2:1.
1H NMR (400 MHz, CDCl3): d = 3.54 (s, 4 H), 3.63 (t, J = 5.9 Hz,
4 H), 3.85 (t, J = 5.9 Hz, 4 H), 6.89–6.93 (m, 4 H), 7.05–7.10 (m, 8
H), 7.17–7.20 (m, 4 H).
13C NMR (100.6 MHz, CDCl3): d = 51.83 (2 C), 68.15 (2 C), 70.86
(2 C), 119.79 (4 C), 123.07 (4 C), 124.03 (4 C), 124.80 (4 C), 130.54
(4 C), 148.61 (4 C).
Yield: 54 mg (38%); eluent: CH2Cl2–MeOH, 50:1, 20:1.
1H NMR (400 MHz, CDCl3): d = 1.68 (br s, 8 H), 1.85 (quin, J = 6.1
Hz, 8 H), 3.19 (t, J = 6.5 Hz, 8 H), 3.45 (br s, 8 H), 3.53 (t, J = 5.7
Hz, 8 H), 3.99 (br s, 4 H), 5.88 (t, J = 1.8 Hz, 2 H), 5.98 (dd, J = 7.9,
2.1 Hz, 4 H), 6.95 (t, J = 7.9 Hz, 2 H).
13C NMR (100.6 MHz, CDCl3): d = 26.62 (4 C), 29.36 (4 C), 42.11
(4 C), 69.49 (4 C), 70.77 (4 C), 97.32 (2 C), 102.39 (4 C), 129.84 (2
C), 149.79 (4 C).
MALDI–TOF: m/z [M+] calcd for C30H28Br4N2O2: 763.89; found:
763.67, 684.78 [M – Br]+, 605.90 [M – 2 Br]+, 526.99 [M – 3 Br]+.
N,N¢-{3,3¢-[Butane-1,4-diylbis(oxy)]bis(propane-3,1-
diyl)}bis[3-bromo-N-(3-bromophenyl)benzenamine] (21i)
From dioxadiamine 2i (51 mg, 0.25 mmol) and other reagents stated
above, 21i was obtained as a yellow oil.
MALDI–TOF: m/z [M+] calcd for C32H52N4O4: 556.40; found:
556.26.
6,9,12,26,29,32-Hexaoxa-2,16,22,36-tetraazatricy-
clo[35.3.1.117,21]dotetraconta-1(41),17(42),18,20,37,39-hexaene
(4j)
From compound 15j (400 mg, 0.75 mmol) and other reagents ac-
cording to the procedure stated above, 4j was obtained as a yellow
viscous oil.
Yield: 68 mg (33%); eluent: CH2Cl2–petroleum ether, 2:1.
1H NMR (400 MHz, CDCl3): d = 1.69 (br s, 4 H), 1.86 (quin, J = 6.2
Hz, 4 H), 3.44 (br s, 8 H), 3.80 (t, J = 7.0 Hz, 4 H), 6.90–6.94 (m, 4
H), 7.02–7.12 (m, 8 H), 7.17 (br s, 4 H).
13C NMR (100.6 MHz, CDCl3): d = 26.56 (2 C), 27.63 (2 C), 49.00
(2 C), 67.42 (2 C), 70.82 (2 C), 119.68 (4 C), 123.09 (4 C), 123.83
(4 C), 124.58 (4 C), 130.48 (4 C), 148.77 (4 C).
Yield: 93 mg (21%); eluent: CH2Cl2–MeOH, 20:1, 10:1
1H NMR (400 MHz, CDCl3): d = 1.85 (br s, 8 H), 3.16 (br s, 8 H),
3.45–3.70 (m, 24 H), 3.99 (br s, 4 H), 5.85 (s, 2 H), 5.98 (d, J = 7.5
Hz, 4 H), 6.94 (t, J = 7.5 Hz, 2 H).
13C NMR (100.6 MHz, CDCl3): d = 29.14 (4 C), 41.35 (4 C), 69.44
(4 C), 70.05 (4 C), 70.45 (4 C), 97.23 (2 C), 102.30 (4 C), 129.61 (2
C), 149.55 (4 C).
MALDI–TOF: m/z [M+] calcd for C34H36Br4N2O2: 819.95; found:
819.81, 740.87 [M – Br]+.
3-Bromo-N-(3-bromophenyl)-N-(3-{4-[3-(3-bromophenylami-
no)propoxy]butoxy}propyl)benzenamine (17i)
Obtained as a byproduct in the synthesis of 21i.
MALDI–TOF: m/z [M+] calcd for C32H52N4O6: 588.39; found:
588.52.
Yield: 19 mg (11%); eluents: CH2Cl2; CH2Cl2–MeOH, 500:1.
1H NMR (400 MHz, CDCl3): d = 1.55 (br s, 2 H), 1.57 (br s, 2 H),
1.87 (quin, J = 6.1 Hz, 2 H), 1.93 (quin, J = 6.4 Hz, 2 H), 3.19 (t,
J = 6.3 Hz, 2 H), 3.37 (t, J = 6.0 Hz, 2 H), 3.40–3.51 (m, 4 H), 3.53
(t, J = 5.8 Hz, 2 H), 3.79 (t, J = 6.9 Hz, 2 H), 4.17 (br s, 1 H), 6.47
(ddd, J = 8.2, 2.3, 0.9 Hz, 1 H), 6.71 (t, J = 2.0 Hz, 1 H), 6.77 (ddd,
J = 6.8, 1.8, 0.9 Hz, 1 H), 6.90–6.94 (m, 2 H), 6.97 (t, J = 8.0 Hz, 1
H), 7.03–7.12 (m, 4 H), 7.15–7.17 (m, 2 H).
13C NMR (100.6 MHz, CDCl3): d = 26.20 (1 C), 26.59 (1 C), 28.15
(1 C), 29.15 (1 C), 42.02 (1 C), 49.42 (1 C), 67.49 (1 C), 69.44 (1
C), 70.46 (1 C), 70.96 (1 C), 111.41 (1 C), 114.98 (1 C), 119.65 (1
C), 119.73 (2 C), 123.12 (2 C), 123.28 (1 C), 123.88 (2 C), 124.63
(2 C), 130.38 (1 C), 130.52 (2 C), 148.83 (2 C), 149.83 (1 C).
Tetraarylated Polyamines 21b,h–k; General Procedure
A two-necked flask flushed with argon and equipped with a con-
denser and magnetic stirrer was charged with 1,3-dibromobenzene
(1) (1.18–1.42 g, 5–6 mmol), Pd(dba)2 (46–92 mg, 0.08–0.16
mmol), BINAP (56–112 mg, 0.09–0.18 mmol), and abs 1,4-dioxane
(10 mL). The mixture was stirred at r.t. for 1–2 min, then the appro-
priate polyamine 2 (1 mmol) and t-BuONa (576 mg, 6 mmol) were
added, and the reaction mixture was stirred under reflux for 24–30
h. After the reaction mixture was cooled to r.t., 1 drop of H2O was
added, the 1,4-dioxane was evaporated under reduced pressure, and
the residue was chromatographed on silica gel using various elu-
ents: CH2Cl2–petroleum ether, 1:2–4:1; CH2Cl2; CH2Cl2–MeOH,
500:1–100:1.
MALDI–TOF: m/z [M+] calcd for C28H33Br3N2O2: 666.01; found:
665.88.
N1-{3-[Bis(3-bromophenyl)amino]propyl}-N3,N3-bis(3-bromo-
phenyl)propane-1,3-diamine (21b)
N1,N3-Bis[3-(4-{3-[bis(3-bromophenyl)amino]propoxy}but-
oxy)propyl]-N1,N3-bis(3-bromophenyl)benzene-1,3-diamine
(22i)
From triamine 2b (33 mg, 0.25 mmol) and other reagents stated
above, 21b was obtained as a yellow oil.
Obtained as a byproduct in the synthesis of 21i.
Yield: 70 mg (37%); eluent: CH2Cl2–MeOH, 200:1, 100:1.
1H NMR (400 MHz, CDCl3): d = 1.80 (quin, J = 7.1 Hz, 4 H), 2.62
(t, J = 6.9 Hz, 4 H), 3.72 (t, J = 7.2 Hz, 4 H), 6.88–6.91 (m, 4 H),
7.07–7.12 (m, 8 H), 7.14 (br s, 4 H) (the signal of the NH proton was
not unambiguously assigned).
Yield: 33 mg (9%); eluent: CH2Cl2–MeOH, 500:1.
1H NMR (400 MHz, CDCl3): d = 1.66 (br s, 8 H), 1.85 (quin, J = 6.1
Hz, 8 H), 3.37–3.45 (m, 16 H), 3.77 (t, J = 6.6 Hz, 4 H), 3.79 (t,
J = 6.8 Hz, 4 H), 6.71 (t, J = 2.0 Hz, 1 H), 6.74–6.78 (m, 2 H), 6.83–
Synthesis 2007, No. 19, 2995–3012 © Thieme Stuttgart · New York

3010
A. D. Averin et al.
PAPER
6.86 (m, 2 H), 6.90–6.95 (m, 4 H), 6.97 (t, J = 8.0 Hz, 1 H), 7.02–
7.12 (m, 12 H), 7.15–7.17 (m, 6 H).
C), 70.63 (2 C), 111.33 (1 C), 115.04 (1 C), 119.50 (1 C), 119.73 (2
C), 123.07 (2 C), 123.20 (1 C), 123.84 (2 C), 124.60 (2 C), 130.54
(2 C), 130.55 (1 C), 148.77 (2 C), 149.86 (1 C).
13C NMR (100.6 MHz, CDCl3): d = 26.58 (4 C), 27.67 (2 C), 27.74
(2 C), 48.96 (2 C), 49.05 (2 C), 67.47 (2 C), 67.72 (2 C), 70.82 (2
C), 70.86 (2 C), 117.29 (2 C), 117.59 (2 C), 118.08 (1 C), 119.73 (4
C), 121.47 (2 C), 122.70 (2 C), 123.00 (2 C), 123.12 (4 C), 123.88
(4 C), 124.63 (4 C), 130.28 (2 C), 130.52 (5 C), 148.04 (2 C), 148.83
(4 C), 149.53 (2 C).
MALDI–TOF: m/z [M+] calcd for C28H33Br3N2O3: 682.00; found:
681.82, 602.93 [M – Br]+, 524.05 [M – 2 Br]+.
N1,N3-Bis{3-[2-(2-{3-[bis(3-bromophenyl)amino]prop-
oxy}ethoxy)ethoxy]propyl}-N1,N3-bis(3-bromophenyl)benzene-
1,3-diamine (22j)
MALDI–TOF: m/z [M+] calcd for C62H68Br6N4O4: 1406.03; found:
Obtained as a byproduct in the synthesis of 21j.
1405.94, 1327.03 [M – Br]+.
Yield: 31 mg (9%); eluent: CH2Cl2–MeOH, 200:1.
N1-[3-(4-{3-[Bis(3-bromophenyl)amino]propoxy}butoxy)pro-
pyl]-N1,N3-bis(3-bromophenyl)-N3-(3-{4-[3-(3-bromophenyl-
amino)propoxy]butoxy}propyl)benzene-1,3-diamine (23i)
Obtained as a byproduct in the synthesis of 21i.
1H NMR (400 MHz, CDCl3): d = 1.85 (quin, J = 6.3 Hz, 8 H), 3.47
(t, J = 5.7 Hz, 8 H), 3.53–3.61 (m, 8 H), 3.64–3.70 (m, 8 H), 3.76 (t,
J = 8.1 Hz, 4 H), 3.78 (t, J = 7.3 Hz, 4 H), 6.70 (s, 1 H), 6.73–6.76
(m, 2 H), 6.82–6.85 (m, 2 H), 6.89–6.93 (m, 4 H), 6.96 (t, J = 7.9
Hz, 1 H), 7.01–7.12 (m, 12 H), 7.14–7.16 (m, 6 H).
Yield: 15 mg (5%); eluent: CH2Cl2–MeOH, 200:1.
1H NMR (400 MHz, CDCl3): d = 1.65 (br s, 4 H), 1.66 (br s, 4 H),
1.80–1.90 (m, 8 H), 3.18 (t, J = 6.4 Hz, 2 H), 3.35–3.48 (m, 14 H),
3.53 (t, J = 5.8 Hz, 2 H), 3.73–3.81 (m, 6 H), 4.32 (br s, 1 H), 6.47
(d, J = 8.4 Hz, 1 H), 6.70 (t, J = 2.0 Hz, 2 H), 6.73–6.78 (m, 3 H),
6.84 (d, J = 8.4 Hz, 2 H), 6.90–6.98 (m, 4 H), 7.00–7.12 (m, 8 H),
7.16 (br s, 4 H).
13C NMR (100.6 MHz, CDCl3): d = 26.58 (4 C), 27.67 (2 C), 27.74
(2 C), 42.00 (1 C), 48.95 (2 C), 49.04 (1 C), 67.46 (1 C), 67.72 (1
C), 69.43 (1 C), 70.81 (3 C), 70.87 (2 C), 111.41 (1 C), 114.98 (1
C), 117.28 (2 C), 117.58 (2 C), 118.08 (1 C), 119.65 (1 C), 119.73
(2 C), 121.39 (1 C), 121.46 (2 C), 122.70 (2 C), 123.00 (2 C), 123.12
(2 C), 123.88 (2 C), 124.63 (2 C), 130.22 (1 C), 130.28 (2 C), 130.39
(1 C), 130.52 (2 C), 148.03 (2 C), 148.83 (4 C), 149.83 (1 C).
13C NMR (100.6 MHz, CDCl3): d = 27.65 (2 C), 27.69 (2 C), 48.89
(2 C), 49.00 (2 C), 68.05 (2 C), 68.28 (2 C), 70.34 (4 C), 70.69 (4
C), 117.40 (2 C), 117.62 (2 C), 118.08 (1 C), 119.79 (4 C), 121.55
(2 C), 122.78 (2 C), 123.00 (2 C), 123.12 (4 C), 123.93 (4 C), 124.68
(4 C), 130.32 (3 C), 130.55 (4 C), 148.07 (4 C), 148.86 (4 C).
MALDI–TOF: m/z [M+] calcd for C62H68Br6N4O6: 1438.02; found:
1437.72, 1358.82 [M – Br]+.
N1-{3-[2-(2-{3-[Bis(3-bromophenyl)amino]propoxy}eth-
oxy)ethoxy]propyl}-N1,N3-bis(3-bromophenyl)-N3-[3-(2-{2-[3-
(3-bromophenylamino)propoxy]ethoxy}ethoxy)propyl]ben-
zene-1,3-diamine (23j)
Obtained as a byproduct in the synthesis of 21j.
MALDI–TOF: m/z [M+] calcd for C56H65Br5N4O4: 1252.09; found:
1252.21, 1173.15 [M – Br]+, 1094.21 [M – 2 Br]+, 1015.32 [M – 3
Br]+.
Yield: 18 mg (5%); eluent: CH2Cl2–MeOH, 200:1.
1H NMR (400 MHz, CDCl3): d = 1.86 (quin, J = 6.1 Hz, 8 H), 3.18
(t, J = 6.5 Hz, 2 H), 3.47 (t, J = 5.8 Hz, 8 H), 3.54–3.62 (m, 10 H),
3.63–3.70 (m, 8 H), 3.76 (t, J = 8.1 Hz, 2 H), 3.78 (t, J = 7.0 Hz, 2
H), 6.48 (dd, J = 8.3, 2.3 Hz, 1 H), 6.71 (t, J = 2.2 Hz, 2 H), 6.72–
6.77 (m, 3 H), 6.84 (dd, J = 8.1, 2.3 Hz, 2 H), 6.89–6.94 (m, 2 H),
6.97 (t, J = 8.0 Hz, 2 H), 7.00–7.12 (m, 8 H), 7.14–7.16 (m, 4 H)
(the signal of the NH proton was not unambiguously assigned).
N,N¢-{3,3¢-[2,2¢-Oxybis(ethane-2,1-diyl)bis(oxy)]bis(propane-
3,1-diyl)}bis[3-bromo-N-(3-bromophenyl)benzenamine] (21j)
From trioxadiamine 2j (55 mg, 0.25 mmol) and other reagents stat-
ed above, 21j was obtained as a yellow oil.
Yield: 60 mg (29%); eluent: CH2Cl2.
13C NMR (100.6 MHz, CDCl3): d = 27.54 (2 C), 27.59 (2 C), 41.77
(1 C), 48.82 (2 C), 48.92 (1 C), 69.80 (2 C), 70.25 (2 C), 70.30 (4
C), 70.63 (2 C), 70.66 (2 C), 111.36 (1 C), 115.08 (1 C), 117.31 (2
C), 117.60 (2 C), 118.07 (1 C), 119.54 (1 C), 119.75 (2 C), 121.43
(3 C), 122.70 (2 C), 122.97 (2 C), 123.10 (2 C), 123.86 (2 C), 124.63
(2 C), 130.37 (4 C), 130.55 (2 C), 147.98 (2 C), 148.79 (2 C), 149.51
(2 C), 149.88 (1 C).
1H NMR (400 MHz, CDCl3): d = 1.86 (quin, J = 5.8 Hz, 4 H), 3.49
(t, J = 5.3 Hz, 4 H), 3.58 (t, J = 4.3 Hz, 4 H), 3.71 (t, J = 4.3 Hz, 4
H), 3.79 (t, J = 6.5 Hz, 4 H), 6.90–6.94 (m, 4 H), 7.04–7.12 (m, 8
H), 7.16 (br s, 4 H).
13C NMR (100.6 MHz, CDCl3): d = 27.51 (2 C), 48.89 (2 C), 67.96
(2 C), 70.32 (2 C), 70.66 (2 C), 119.71 (4 C), 123.07 (4 C), 123.83
(4 C), 124.60 (4 C), 130.53 (4 C), 148.76 (4 C).
MALDI–TOF: m/z [M+] calcd for C56H65Br5N4O6: 1284.02; found:
1283.79, 1204.78 [M – Br]+.
MALDI–TOF: m/z [M+] calcd for C34H36Br4N2O3: 835.95; found:
835.69, 756.80 [M – Br]+, 677.99 [M – 2 Br]+.
N1,N1,N3,N3-Tetrakis(3-bromophenyl)propane-1,3-diamine
(21k)
From diamine 2k (37 mg, 0.5 mmol) and other reagents stated
above, 21k was obtained as a yellow oil.
3-Bromo-N-(3-bromophenyl)-N-[3-(2-{2-[3-(3-bromophenyl-
amino)propoxy]ethoxy}ethoxy)propyl]benzenamine (17j)
Obtained as a byproduct in the synthesis of 21j.
Yield: 85 mg (25%); eluent: CH2Cl2.
1H NMR (400 MHz, CDCl3): d = 1.98 (quin, J = 7.0 Hz, 2 H), 3.74
(t, J = 7.0 Hz, 4 H), 6.83–6.88 (m, 4 H), 7.07–7.13 (m, 12 H).
13C NMR (100.6 MHz, CDCl3): d = 25.40 (1 C), 49.84 (2 C), 119.76
(4 C), 123.01 (4 C), 124.00 (4 C), 125.14 (4 C), 130.71 (4 C), 148.55
(4 C).
Yield: 9 mg (5%); eluent: CH2Cl2–MeOH, 500:1.
1H NMR (400 MHz, CDCl3): d = 1.86 (quin, J = 6.1 Hz, 4 H), 3.19
(t, J = 6.5 Hz, 2 H), 3.48 (t, J = 5.8 Hz, 2 H), 3.55–3.62 (m, 6 H),
3.66–3.72 (m, 4 H), 3.79 (t, J = 7.0 Hz, 2 H), 4.27 (s, 1 H), 6.48 (dd,
J = 8.1, 2.3 Hz, 1 H), 6.71 (t, J = 2.0 Hz, 1 H), 6.75 (dd, J = 7.8, 1.8
Hz, 1 H), 6.89–6.94 (m, 2 H), 6.96 (t, J = 8.0 Hz, 1 H), 7.05–7.12
(m, 4 H), 7.16 (t, J = 1.9 Hz, 2 H).
MALDI–TOF: m/z [M + H]+ calcd for C27H22Br4N2: 690.86; found:
13C NMR (100.6 MHz, CDCl3): d = 27.51 (1 C), 28.82 (1 C), 41.79
(1 C), 48.91 (1 C), 68.00 (1 C), 69.80 (1 C), 70.24 (1 C), 70.31 (1
690.68, 610.85 [M – Br]+.
Synthesis 2007, No. 19, 2995–3012 © Thieme Stuttgart · New York

PAPER
Polyazamacrocycles Containing a 1,3-Disubstituted Benzene Moiety
3011
1,3-Bis(polyamino)-Substituted Benzenes 24h–j; General Pro-
cedure
MALDI–TOF: m/z [M + H]+ calcd for C26H50N4O4: 483.39; found:
483.20.
A two-necked flask flushed with argon and equipped with a con-
denser and magnetic stirrer was charged with 1,3-dibromobenzene
(1) (236 mg, 1 mmol), Pd(dba)2 (46 mg, 0.08 mmol), BINAP (56
mg, 0.09 mmol), and abs 1,4-dioxane (5–10 mL). The mixture was
stirred at r.t. for 1–2 min, then the appropriate polyamine 2 (2.5–4
mmol) and t-BuONa (150 mg, ca. 1.5 mmol) were added, and the
reaction mixture was stirred under reflux for 8 h. After the reaction
mixture was cooled to r.t., 1 drop of H2O was added, the 1,4-diox-
ane was evaporated under reduced pressure, and the residue was
chromatographed on silica gel using various eluents: CH2Cl2;
CH2Cl2–MeOH, 50:1–3:1; CH2Cl2–MeOH–aq NH3, 100:20:1–
10:4:1.
N1,N3-Bis(3-{2-[2-(3-aminopropoxy)ethoxy]ethoxy}propyl)ben-
zene-1,3-diamine (24j)
From trioxadiamine 2j (550 mg, 2.5 mmol), 1,3-dibromobenzene
(1) (236 mg, 1 mmol), and other reagents stated above, 24j was ob-
tained as a yellow oil.
Yield: 288 mg (56%); eluent: CH2Cl2–MeOH–aq NH3, 10:4:1.
1H NMR (400 MHz, CDCl3): d = 1.70 (quin, J = 6.4 Hz, 4 H), 1.85
(quin, J = 6.2 Hz, 4 H), 2.36 (br s, 4 H), 2.77 (t, J = 6.7 Hz, 4 H),
3.17 (t, J = 6.5 Hz, 4 H), 3.52 (t, J = 6.3 Hz, 4 H), 3.55–3.65 (m, 20
H), 5.84 and 5.86 (s, 1 H), 5.98 (d, J = 7.9 Hz, 2 H), 6.92 (t, J = 7.9
Hz, 1 H) (the signals of some of the NH protons were not unambig-
uously assigned).
13C NMR (100.6 MHz, CDCl3): d = 29.23 (2 C), 32.71 (2 C), 39.49
(2 C), 41.49 (2 C), 69.40 (2 C), 69.56 (2 C), 70.07 (2 C), 70.14 (2
C), 70.51 (4 C), 97.01 (1 C), 102.50 (2 C), 129.77 (1 C), 149.62 (2
C).
N1,N3-Bis{2-[2-(2-aminoethoxy)ethoxy]ethyl}benzene-1,3-di-
amine (24h)
From dioxadiamine 2h (592 mg, 4 mmol), 1,3-dibromobenzene (1)
(236 mg, 1 mmol), and other reagents stated above, 24h was ob-
tained as a yellow oil.
MALDI–TOF: m/z [M + H]+ calcd for C26H50N4O6: 515.38; found:
Yield: 220 mg (59%); eluent: CH2Cl2–MeOH, 5:1.
1H NMR (400 MHz, CDCl3): d = 2.83 (t, J = 4.9 Hz, 4 H), 3.20 (t,
J = 4.9 Hz, 4 H), 3.48 (t, J = 4.9 Hz, 4 H), 3.55 (br s, 8 H), 3.62 (t,
J = 4.9 Hz, 4 H), 3.70 (br s, 4 H), 5.89 and 5.94 (br s, 1 H), 5.98 (d,
J = 7.9 Hz, 2 H), 6.89 (t, J = 7.9 Hz, 1 H) (the signals of some of the
NH protons were not unambiguously assigned).
13C NMR (100.6 MHz, CDCl3): d = 40.86 and 40.94 (2 C), 43.32 (2
C), 69.52 (2 C), 69.93 (4 C), 71.18 and 72.10 (2 C), 97.88 and 98.04
(1 C), 102.82 and 102.98 (2 C), 129.71 (1 C), 149.18 (2 C).
515.19.
Acknowledgment
This work was supported by RFBR grants N 06-03-32376, 05-03-
32905, and 03-03-22001, and by the Russian Academy of Sciences
program P-8 ‘Development of the methods of organic synthesis and
construction of the compounds with valuable properties’.
In the presence of a twofold excess of dioxadiamine 2h, the dupli-
cation of proton and carbon signals disappears:
References
1H NMR (400 MHz, CDCl3 + 2 equiv of 2h): d = 2.82 (t, J = 5.0 Hz,
4 H), 3.18 (t, J = 5.0 Hz, 4 H), 3.47 (t, J = 5.0 Hz, 4 H), 3.56 (br s,
8 H), 3.60 (t, J = 5.0 Hz, 4 H), 3.72 (br s, 4 H), 5.88 (br s, 1 H), 5.99
(d, J = 7.8 Hz, 2 H), 6.92 (t, J = 7.8 Hz, 1 H) (the signals of some of
the NH protons were not unambiguously assigned).
13C NMR (100.6 MHz, CDCl3 + 2 equiv of 2h): d = 41.15 (2 C),
43.00 (2 C), 69.26 (2 C), 69.81 (4 C), 72.94 (2 C), 97.40 (1 C),
102.76 (2 C), 129.46 (1 C), 148.95 (2 C).
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Hz, 4 H), 1.84 (quin, J = 6.0 Hz, 4 H), 2.87 (t, J = 6.6 Hz, 4 H), 3.16
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Synthesis 2007, No. 19, 2995–3012 © Thieme Stuttgart · New York

3012
A. D. Averin et al.
PAPER
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Synthesis 2007, No. 19, 2995–3012 © Thieme Stuttgart · New York