Pyridinium N-heteroarylaminides: synthesis of N-heteroaryltetramines based on 1,6-bis(phenoxy)hexane and 1,3-bis(phenoxymethyl)benzene

Article abstract of DOI:10.1016/j.tetlet.2007.06.044

The synthesis of a set of new N-heteroaryltetramines is reported. A regioselective alkylation on the N-exo nitrogen of pyridinium N-(heteroaryl)aminide with the corresponding tetrabromo compounds, followed by a clean N-N bond reduction of the correspondin

Full text of DOI:10.1016/j.tetlet.2007.06.044

Tetrahedron Letters 48 (2007) 5899–5903
Pyridinium N-heteroarylaminides: synthesis
of N-heteroaryltetramines based on 1,6-bis(phenoxy)hexane
and 1,3-bis(phenoxymethyl)benzene
Rafael Castillo, M. Luisa Izquierdo and Julio Alvarez-Builla*
Departamento de Quı´mica Orga´nica, Universidad de Alcala´, 28871 Alcala´ de Henares, Madrid, Spain
Received 26 April 2007; accepted 8 June 2007
Available online 14 June 2007
Abstract—The synthesis of a set of new N-heteroaryltetramines is reported. A regioselective alkylation on the N-exo nitrogen of
pyridinium N-(heteroaryl)aminide with the corresponding tetrabromo compounds, followed by a clean N–N bond reduction of
the corresponding tetra-salts, allowed an easy and general method to obtain N,N0,N00,N000-tetrakis(2-heteroaryl)tetramines.
Ó 2007 Elsevier Ltd. All rights reserved.
Biogenic polyamines1 play an important role in various
biological and pathological processes2 and synthetic
analogs offer a wide range of therapeutic potential.3
The biological interest in these compounds has pro-
moted the development of efficient synthetic methods
for polyamine analogs and conjugates4 both in solution
and in the solid phase,5 not only for linear analogs but
also for dendrimer-like polyamines.6 In addition, the
pyridine ring takes part in many biological and chemical
reactions and the pyridine ring itself—particularly amino-
pyridinides—are interesting because of their chelating
abilities, the reason for which they are commonly used
as ligands in inorganic and organometallic chemistry.7
These characteristics are being used to develop new het-
erocyclic multidentate molecules for the use in coordina-
tion chemistry,8 and in recent years many related
references can be found in the literature that describe
2-aminopyridines,9 2-aminoquinolines,10 and 2-amino-
benzothiazoles11 as part of organometallic complexes.
Finally, 2-aminopyridine fragments have been used as
part of an abiotic receptor for the recognition of
monosaccharides.12
oxymethyl] benzene (3b) and pyridinium N-(2-hetero-
aryl)aminide 4.
The preparation of the chosen tetrabromo compounds
1,6-bis[3,5-bis(bromomethyl)phenoxy]hexane 2b and
1,3-bis[3,5-bis(bromomethyl)phenoxymethyl]benzene 3b
(Scheme 1) was achieved from the corresponding alco-
hols 2a and 3a. The preparation of these alcohols was
carried out as previously described;13 dimethyl 5-
hydroxyisophthalate, obtained by esterification of 5-
hydroxyisophthalic acid with methanol, was treated
with the corresponding dibromide in anhydrous DMF
and K2CO3 as a base14 to give tetraesters 1a, b, which
were then reduced15 using LiAlH4 in THF to give the
desired tetra-alcohols 2a and 3a. The preparation of
1,6-bis[3,5-bis(bromomethyl)phenoxy]hexane 2b was
accomplished from tetraester 1a without the isolation
of 2a, which was transformed into 2b by the addition
of hydrobromic acid in a one-pot process. As expected,
the high C–O lability in benzylic derivative 3a toward
acid media made this simple process unsuitable to pre-
pare 1,3-bis[3,5-bis(bromomethyl)phenoxymethyl]ben-
zene 3b.16 Alternatively, other bromination methods17
were tested on 3a with little or no success. Tetrabromo
compound 3b was finally obtained in good yield using
a mixture of N-bromosuccinimide (NBS) and triphenyl-
phosphine (Ph3P) in dichloromethane, treated in an
ultrasonic bath for 90 min.18 The use of ultrasound
was essential to keep the alcohol in solution.
The present Letter describes the results obtained in the
synthesis of N,N0,N00,N000-tetrakis(2-heteroaryl)tetram-
ines 7 and 8 from 1,6-bis[3,5-bis(bromomethyl)phen-
oxy]hexane (2b) or 1,3-bis[3,5-bis(bromomethyl)phen-
*
Once derivatives 2b and 3b had been prepared, alkyl-
ation with different N-pyridinium aminides 4 was tried
Corresponding author. Fax: +34 91 885 46 86; e-mail: julio.
alvarez@uah.es
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.06.044

5900
R. Castillo et al. / Tetrahedron Letters 48 (2007) 5899–5903
OMe
MeO
Y
Y
Y
OMe
OMe
O
O
O
O
O
O
(i)
OH
O
O
O
O
W
W
OMe
MeO
Y
2a W = -(CH2)4-, Y = OH
2b W = -(CH2)4-, Y = Br
3a W = m-xylyl, Y= OH
3b W = m-xylyl, Y= Br
(ii)
1a W = -(CH2)4-
1b W = m-xylyl
(iii)
Scheme 1. Reagents and conditions: (i) LiAlH4, THF; (ii) HBr–H2SO4 (2:1); (iii) PPh3, NBS, CH2Cl2, ultrasound, 90 min.
4
5
6
3
2
Het
N
Het
N
N
+
N+
N
N
Het
N
Het
+N
N
N
N
Br
Br
Br
Br
NH
Ar
HN
HN
Het
4a-e
DMF
2
6
3
4Br
W
Zn
1
O
O
4
O
O
O
O
AcOH / MeOH
W
5
W
Het
N
Het
N
NH
N
N
2b,3b
N
Het
+
N
N
+
N
Het
4a Het = pyridin-2-yl
4b Het = benzothiazol-2-yl
4c Het = 5-phenylpyridin-2-yl
4d Het = quinolin-2-yl
5a-c W = -(CH2)4-
6a-c W = -xylyl
7a-c W = -(CH2)4-
8a-c W = -xylyl
m
m
4e Het = 5-(4-hydroxymethyl)phenylpyridin-2-yl
Scheme 2.
as previously reported,19 and the products 5 and 6 were
only obtained on using DMF as a solvent, where inter-
mediate mono-, di-, and tri-salts were kept in solution
and could react to give the final product (Scheme 2). Iso-
lation of 5 and 6 was achieved by concentrating the mix-
ture to a minimum volume of solvent to keep the
products in solution, and subsequently adding the solu-
tion dropwise to vigorously stirred AcOEt. This pro-
duced precipitation of tetra-salts 5 and 6 while the
corresponding N-aminide 4 remained in solution.20
The solid obtained in this way was filtered off, washed
with AcOEt21 and dried under vacuum to give the de-
sired salt (Scheme 2). Aminides 4a–d were prepared as
described19a,b,22 and 4e was obtained by Suzuki reaction
of pyridinium N-(5-bromopyridin-2-yl)aminide23,19b and
4-hydroxymethylphenylboronic acid.24
idines was described with different reducing agents,
such as Zn/AcOH,19a,b,d Pt/C–Et3N/HCOOH,19c,e,23 or
BEt3–MeOH.25 These methods may be applied to tet-
ra-salts with slight modifications to increase the solubil-
ity of the starting materials, and the results obtained in
the reduction of 5a using three different methods are
summarized in Table 1.
Although all experiments gave similar good results (con-
versions between 80% and 90%) the metal–acid system
was chosen due to the ease of processing26 and a series
of N-heteroaryltetramines (Table 2) were successfully
obtained.
In conclusion, a viable strategy for the formation of
N,N0,N00,N000-tetrakis(2-heteroaryl)tetramines has been
developed and involves the use of a quadruple and regio-
selective alkylation and the selective reduction of an
N–N-bond. Attempts to apply this methodology to ob-
tain central cores in dendrimer synthesis are in progress.
Finally, salts 5 and 6 had to be converted into N-hetero-
aryltetramines 7 and 8. In previous papers, conversion
of related N-aminopyridinium salts into 2-aminopyr-
Table 1. Comparative chart for reduction of 5a under different conditions
Reduction conditions
Work up conditions
Extraction with NaOH (10%) and AcOEt
Salt formation with HCl (10%)
Rebasify and extract with AcOEt
Extraction with NaOH (10%) and AcOEt
Conversiona (%)
BEt3 (12 equiv)/MeOH, ꢀ30 °C, 18 h
81
90
BEt3 (12 equiv)/MeOH–10% H2O, ꢀ30 °C, 18 h
AcOH–MeOH (2:1)/Zn, rt, 12 h
a Measured by HPLC/MS.
85

R. Castillo et al. / Tetrahedron Letters 48 (2007) 5899–5903
5901
Table 2. Results obtained in the alkylation and reduction reactions. Compounds 5a–c, 6a–c, 7a–c, and 8a–c
–W–
Aminides 4
Het.
Tetra-salts 5, 6
Compound Yield (%)
Tetra-amines 7, 8
Compound Yield (%)
N
4'
N
2'
3'
6'
5'
−CH2CH2CH2CH2−
4a
5a
85
7a
85
β
γ
–CH2CH2CH2CH2–
–CH2CH2CH2CH2–
4b
5b
84
7b
68
S
N
4c
4a
5c
6a
90
87
7c
8a
74
79
N
N
2
8'
5'
2'
3'
3
1
7'
6'
4d
6b
6c
84
70
8b
8c
89
73
Xyl
5
4
6
4'
N
4e24
OH
M.; Balzani, V. Angew. Chem., Int. Ed. 2002, 41, 3595–
3598; (d) Koc¸, F.; Eilbracht, P. Tetrahedron 2004, 60,
8465–8476.
Acknowledgments
´
The authors thank the Comision Interministerial de
´
7. Pasumansky, L.; Hernandez, A. R.; Gamsey, S.; Goralski,
´
Ciencia y Tecnologıa (CTQ2005-08902) for financial
C. T.; Singaram, B. Tetrahedron Lett. 2004, 45, 6417–
6420, and references cited therein.
8. (a) Lavastre, O.; Bonnette, F.; Gallard, L. Curr. Opin.
Chem. Biol. 2004, 8, 311–318; (b) Regnier, T.; Lavastre, O.
Tetrahedron 2006, 62, 155–159; (c) Blackman, A. Polyhe-
dron 2005, 24, 1–39.
´
support, and the Ministerio de Educacion y Ciencia
(MEC) for a studentship (R.C.).
References and notes
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Kempe, R.; Noss, H.; Irrgang, T. J. Organomet. Chem.
2002, 647, 12–20; (c) Kempe, R. Eur. J. Inorg. Chem. 2003,
791–803.
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69, 7448–7462; (b) Mazik, M.; Cavga, H.; Jones, G. J. Am.
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1320–1321.
14. (a) Collman, J. P.; Brauman, J. I.; Fitzgerald, J. P.;
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nan, V.; Velmurugan, D.; Ravikumar, K. Tetrahedron
Lett. 2005, 46, 995–999.
4. (a) Bergeron, R. J. Acc. Chem. Res. 1986, 19, 105–113; (b)
Kuksa, V.; Buchan, R.; Kong, P.; Lin, T. Synthesis 2000,
9, 1189–1207; (c) Kan, T.; Fukuyama, T. Chem. Commun.
2004, 353–359.
5. (a) Karigiannis, G.; Papaioannou, D. Eur. J. Org. Chem.
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2000, 10, 1841–1863; (b) Jo¨nsson, D.; Unden, A. Tetra-
hedron Lett. 2002, 43, 3125–3128.
6. (a) Newkome, G. R.; Mishra, A.; Moorefield, C. N. J.
Org. Chem. 2002, 67, 3957–3960; (b) Tomalia, D. A.;
Huang, B.; Swanson, D. R.; Brothers, H. M., II; Klimash,
J. W. Tetrahedron 2003, 59, 3799–3813; (c) Hahn, U.;
Gorka, M.; Vo¨gtle, F.; Vicinelli, V.; Ceroni, P.; Maestri,
15. Vinod, T. K.; Hart, H. J. Org. Chem. 1991, 56, 5630–5640.
16. a,a0-Dibromo-m-xylene and 3,5-bis(bromomethyl)phenol
were recovered as the main reaction products.

5902
R. Castillo et al. / Tetrahedron Letters 48 (2007) 5899–5903
17. (a) Zoller, T.; Ducep, J. B.; Hibert, M. Tetrahedron Lett.
1,3-Bis[3,5-bis(pyridin-1-ium-quinolin-2-ylaminomethyl)phen-
oxymethyl]benzene tetrabromide (6b): Brown solid,
(259 mg, 84%), mp > 190 °C (dec); IR (KBr): mmax
(cmꢀ1) 3004, 2932, 1617, 1598, 1504, 1471, 1430, 1324,
1214, 1163, 1046, 813, 676; 1H NMR (500 MHz, CD3OD):
d (ppm) 9.18 (8H, dd, J = 6.9 and 1.3 Hz; H2(6)), 8.72
(4H, tt, J = 7.7 and 1.3 Hz, H4), 8.34 (4H, d, J = 8.9 Hz,
H40), 8.21 (8H, dd, J = 7.7 and 6.9 Hz, H3(5)), 7.89 (4H,
br d, J = 8.2 Hz, H50), 7.67 (4H, ddd, J = 8.5, 6.9 and
1.4 Hz, H70), 7.57 (4H, br d, J = 8.5 Hz, H80), 7.51 (4H,
`
2000, 41, 9985–9988; (b) Hawker, C. J.; Frechet, J. M. J.
J. Am. Chem. Soc. 1990, 112, 7638–7647; (c) Leduc, M. R.;
`
Hawker, C. J.; Dao, J.; Frechet, J. M. J. J. Am. Chem. Soc.
1996, 118, 11111–11118.
18. Synthesis
of
1,3-bis[3,5-bis(bromomethyl)phenoxy-
methyl]benzene (3b): Alcohol 3a13 (410 mg, 1 mmol) and
PPh3 (4.4 mmol) were dissolved in dichloromethane
(150 mL) in a round-bottom flask and the mixture was
cooled to 0 °C. Under vigorous stirring NBS (4.4 mmol)
was added portionwise to the reaction mixture. After the
addition, the flask was placed in an ultrasonic bath for
90 min. As soon as the starting material had been
consumed (detected by TLC) the solvent was removed in
vacuo and the residue was purified by chromatography
(silica gel/CH2Cl2). Compound 3b was isolated as a white
solid (476 mg, 72%), mp: 146–147 °C; IR (KBr): mmax
(cmꢀ1) 2938, 2882, 1593, 1443, 1335, 1296, 1212, 1179,
1040, 853, 697, 553; 1H NMR (300 MHz, CDCl3): d (ppm)
7.49 (1H, br s, H2Xyl), 7.40 (3H, m, H4Xyl(6Xyl) and 5Xyl),
7.01 (2H, t, J = 1.5 Hz, H40), 6.93 (4H, d, J = 1.5 Hz,
H20(60)), 5.07 (4H, s, CH2O), 4.41 (4H, s, CH2Br); 13C
NMR (75 MHz, CDCl3): d (ppm) 159.1 (C1Ar), 139.7
(C3Ar(5Ar)), 136.9 (C1Xyl(3Xyl)), 129.0 (C2Xyl), 127.3
(C4Xyl(6Xyl)), 126.6 (C5Xyl), 122.2 (C4Ar), 115.5
(C2Ar(6Ar)), 70.0 (CH2O), 32.8 (CH2Br). Anal. Calcd for
C24H22Br4O2: C, 43.54; H, 3.35. Found C, 43.21; H,
3.22.
ddd, J = 8.2, 6.9 and 1.3 Hz, H60), 7.35 (4H, m, H2Xyl
,
H4Xyl(6Xyl) and H5Xyl), 7.29 (4H, d, J = 8.9 Hz, H30), 7.28
(2H, ap t, J = 1.4 Hz, H4Ar), 7.15 (8H, d, J = 1.4 Hz,
H2Ar(6Ar)), 5.53 (8H, s, CH2N), 5.12 (4H, s, CH2O); 13C
NMR (75 MHz, CD3OD): d (ppm) 161.0 (C1Ar), 156.5
(C20), 149.8 (C2(6)), 149.3 (C4), 147.3 (C80a), 141.3 (C40),
138.7 (C1Xyl(3Xyl)), 138.2 (C3Ar(5Ar)), 131.9 (C70), 130.6
(C3(5)), 129.9 (C5Xyl), 128.9 (C50), 128.6 (C80), 128.3
(C4Xyl(6Xyl)), 127.9 (C2Xyl), 127.0 (C40a), 126.9 (C60),
122.8 (C4Ar), 117.1 (C2Ar(6Ar)), 111.0 (C30), 70.9 (CH2O),
58.6 (CH2N).
21. For compounds 5b and 6c, due to the low solubility of
aminides 4b and 4e in AcOEt, washing was done with
acetone.
22. (a) Reyes, M. J.; Burgos, C.; Izquierdo, M. L.; Alvarez-
Builla, J. Tetrahedron 2004, 60, 1093–1097; (b) Reyes, M.
J.; Izquierdo, M. L.; Alvarez-Builla, J. Tetrahedron Lett.
2004, 45, 8713–8715.
´
´
´
´
19. (a) Carceller, R.; Garcıa-Navıo, J. L.; Izquierdo, M. L.;
23. Burgos, C.; Delgado, F.; Garcıa-Navıo, J. L.; Izquierdo,
M. L.; Alvarez-Builla, J. Tetrahedron 1995, 31, 8649–
8654.
Alvarez-Builla, J. Tetrahedron Lett. 1993, 34, 2019–2020;
´
´
(b) Carceller, R.; Garcıa-Navıo, J. L.; Izquierdo, M. L.;
´
Alvarez-Builla, J.; Fajardo, M.; Gomez-Sal, P.; Gago, F.
24. Synthesis of N-[5-(4-hydroxymethylphenyl)pyridin-2-yl]-
pyridinium aminide (4e): Pd(PPh3)4 (57 mg, 5 mmol %), 4-
hydroxymethylphenylboronic acid (1.5 mmol) and pyrid-
inium N-(5-bromo-pyridin-2-yl) aminide23 (1 mmol) were
dissolved in a toluene:ethanol mixture (4:1, 15 mL).
K2CO3 (10 mmol) was added and the mixture was stirred
under argon and heated under reflux for 8 h. The system
was allowed to reach room temperature, the catalyst and
inorganic salts were filtered off through Celite and washed
with acetonitrile until no color was observed in the filtrate.
The combined filtrates were evaporated to dryness. The
crude residue was purified by flash chromatography on a
silica gel column with ethanol as the eluent. Compound 4e
was obtained as a red solid (255 mg, 92%, toluene), mp
168–169 °C; IR (KBr): mmax (cmꢀ1) 3233, 2850, 1599, 1465,
1374, 1328, 1146, 1042, 1008, 808, 761, 518; 1H NMR
(300 MHz, CD3OD): d (ppm) 8.80 (2H, dd, J = 7.0 and
1.2 Hz, H2(6)); 8.05 (1H, tt, J = 7.7 and 1.2 Hz, H4); 7.98
(1H, dd, J = 2.5 and 0.7 Hz, H60); 7.83 (2H, dd, J = 7.7
and 7.0 Hz, H3(5)); 7.72 (1H, dd, J = 8.8 and 2.5 Hz,
H40); 7.50 (2H, ap d, J = 8.4 Hz, H200(600)); 7.39 (2H, ap d,
J = 8.4 Hz, H300(500)); 6.62 (1H, dd, J = 8.8 and 0.7 Hz,
H30); 4.63 (2H, s, CH2); 13C NMR (75 MHz, CD3OD): d
164.9 (C20), 144.8 (C2(6)), 144.6 (C60), 140.7 (C400), 139.0
(C100), 137.8 (C4), 137.0 (C40), 128.7 (C300(500)), 128.5
(C3(5)), 126.4 (C200(600)), 125.3 (C50), 112.3 (C30), 70.0
(CH2). MS (CI, m/z): 278 (100, M + 1), 277 (47), 260 (25),
201 (65). HRMS (ESI-TOF, CH3OH): [M+H]+ calcd for
C17H16N3O, 278.12879; found, 278.13210.
´
Tetrahedron 1994, 50, 4995–5012; (c) Garcıa de Viedma,
A.; Martinez-Barrasa, V.; Burgos, C.; Izquierdo, M. L.;
Alvarez-Builla, J. J. Org. Chem. 1999, 64, 1007–1010; (d)
Martınez-Barrasa, V.; Delgado, F.; Burgos, C.; Garcıa-
´
´
´
Navıo, J. L.; Izquierdo, M. L.; Alvarez-Builla, J. Tetra-
hedron 2000, 56, 2481–2490; (e) Reyes, M. J.; Delgado, F.;
Izquierdo, M. L.; Alvarez-Builla, J. Tetrahedron 2002, 58,
8573–8579.
20. General procedure for the alkylation of pyridinium N-
aminides 4 with tetrabromo derivatives 2b or 3b: In a flame-
dried round-bottom flask under an inert atmosphere, the
corresponding tetrabromo derivative 2b or 3b (0.2 mmol)
and aminide 4 (1 mmol) were suspended in DMF (5 mL).
The reaction was stirred at room temperature for 72 h
until the halogenated derivative had been consumed
(detected by TLC). The solvent was removed under
vacuum, the crude product was redissolved in the mini-
mum volume of DMF (ꢁ1 mL) and the solution was
added to vigorously stirred AcOEt (50 mL). The solid
precipitate was filtered off and recrystallized from EtOH
and a few drops of MeOH to give the corresponding pure
tetra-salts 5 and 6 as brownish solids.
1,6-Bis[3,5-bis(pyridin-1-ium-pyridin-2-ylaminomethyl)phen-
oxy]hexane tetrabromide (5a): brownish solid (225 mg,
85%), mp > 162 °C (dec); IR (KBr): mmax (cmꢀ1): 3010,
2935, 1595, 1470, 1432, 1298, 1160, 776, 746, 685; 1H
NMR (500 MHz, CD3OD): d (ppm) 9.23 (8H, dd, J = 6.4
and 1.4 Hz, H2(6)), 8.74 (4H, tt, J = 7.8 and 1.4 Hz, H4),
8.22 (12H, m, H3(5) and 60), 7.90 (4H, ddd, J = 8.7, 7.5
and 1.7 Hz, H40), 7.19 (10H, m, H30, H50 and H4Ar), 7.00
(4H, d, J = 1.0 Hz, H2Ar (H6Ar)), 5.58 (8H, s, CH2N), 3.98
(4H, t, J = 6.4 Hz, CH2O), 1.76 (4H, m, CH2b), 1.52 (4H,
m, CH2c); 13C NMR (125 MHz, CD3OD): d (ppm) 161.6
(C1Ar), 158.3 (C20), 149.7 (C2(6)), 149.2 (C60), 149.2 (C4),
140.6 (C40), 137.8 (C3Ar(5Ar)), 130.6 (C3(5)), 122.4 (C4Ar),
120.8 (C30), 116.5 (C2Ar(6Ar)), 111.0 (C50), 69.4 (CH2O),
58.6 (CH2N), 30.2 (CH2b), 26.9 (CH2c).
´
´
25. Sanchez, A.; Nunez, A.; Burgos, C.; Alvarez-Builla, J.
˜
Tetrahedron Lett. 2006, 47, 8343–8346.
26. General procedure for the reduction of pyridinium tetrakis
salts 5 and 6: In a round-bottom flask the corresponding
tetra-salt 5 or 6 (0.1 mmol) was dissolved in AcOH/MeOH
(2:1, 30 mL). Zn dust (40 mmol) was added and the
mixture was stirred at room temperature for 12 h. During
this time a color change was observed. The crude mixture
was evaporated to dryness and treated with a mixture of

R. Castillo et al. / Tetrahedron Letters 48 (2007) 5899–5903
5903
NaOH (10%) (15 mL) and AcOEt (30 mL). Two layers
were separated and the organic phase was dried over
MgSO4, the solvent was removed in vacuo and the residue
purified by chromatography through a silica gel column,
using a suitable solvent as the eluent, and finally recrys-
tallized to give the corresponding tetra-aminopyridine 8
and 9 as a pale yellow solids.
1,6-Bis[3,5-bis(pyridin-2-ylaminomethyl)phenoxy]hexane
(7a): White solid (59 mg, 85%, ethyl acetate); mp: 92–
94 °C; IR (KBr): mmax (cmꢀ1) 3251, 2924, 1600, 1455, 1328,
1291, 1154, 1049, 979, 845, 771; 1H NMR (300 MHz,
CDCl3): d (ppm) 8.06 (4H, ap dd, J = 5.0 and 1.8 Hz, H6),
7.36 (4H, ddd, J = 8.6, 7.2 and 1.8 Hz, H4), 6.90 (2H, br s,
H4Ar), 6.78 (4H, d, J = 1.6 Hz, H2Ar(6Ar)), 6.56 (4H, ddd,
J = 7.2, 5.0 and 1.0 Hz, H5), 6.32 (4H, br d, J = 8.6 Hz,
H3), 4.94 (4H, br s, NH), 4.42 (8H, d, J = 5.7 Hz, CH2N),
3.88 (4H, t, J = 6.4 Hz, CH2O), 1.73 (4H, m, CH2b), 1.45
(4H, m, CH2c); 13C NMR (75 MHz, CDCl3): d (ppm)
159.7 (C1Ar), 158.5 (C2), 148.0 (C6), 141.1 (C3Ar(5Ar)),
137.4 (C4), 118.3 (C4Ar), 113.1 (C2Ar(6Ar)), 112.2 (C5),
106.8 (C3), 67.8 (CH2O), 46.3 (CH2N), 29.7 (CH2b), 25.8
(CH2c); HRMS (ESI-TOF, CH3OH): [M+H]+ calcd for
C42H46N8O2, 695.3812; found, 695.3860.
1,3-Bis[3,5-bis(quinolin-2-ylaminomethyl)phenoxymethyl]-
benzene (8b): Yellow solid (81 mg, 89%, ethyl acetate); mp:
133–135 °C. IR (KBr): mmax (cmꢀ1) 3417, 2925, 1618, 1400,
1290, 1154, 1049, 893, 818, 756, 456. 1H NMR (500 MHz,
(CD3)2CO): d (ppm) 7.81 (4H, d, J = 8.9 Hz, H4), 7.58
(4H, dd, J = 8.0 and 1.5 Hz, H5), 7.55 (4H, dd, J = 8.4
and 1.5 Hz, H8), 7.44 (4H, ddd, J = 8.4, 7.1 and 1.5 Hz,
H6), 7.41 (1H, br s, H2Xyl), 7.26 (3H, m, H4Xyl(6Xyl) and
H5Xyl), 7.13 (4H, ddd, J = 8.0, 6.9 and 1.1 Hz, H7), 7.10
(2H, br s, H4Ar), 6.98 (4H, d, J = 1.3 Hz, H2Ar(6Ar)), 6.81
(4H, d, J = 8.9 Hz, H3), 4.99 (4H, s, CH2O), 4.69 (4H, s,
CH2N). 13C NMR (75 MHz, (CD3)2CO): d (ppm) 159.7
(C1Ar), 157.5 (C2), 148.8 (C8a), 142.7 (C3Ar(5Ar)), 138.3
(C1Xyl(3Xyl)), 137.1 (C4), 129.5 (C7), 129.0 (C5Xyl), 128.0
(C5), 127.5 (C4Xyl(6Xyl)), 127.2 (C2Xyl), 126.7 (C8), 124.1
(C4a), 122.0 (C6), 120.1 (C4Ar), 113.3 (C3), 113.1
(C2Ar(6Ar)), 69.9 (CH2O), 44.9 (CH2N); HRMS (ESI-
TOF, CH3OH): [M+H]+ calcd for C60H50N8O2, 915.4124;
found, 915.4162.