R. Guilard, C. Lecomte et al.
FULL PAPER
tered off, washed with CH3CN and dried under vacuum. Yield 2.24 CH2), 55.64 (α-CH2), 60.21 (NϪCH2ϪPh), 127.36, 128.74, 129.60,
1
g (56%). Ϫ H NMR (D2O): δ ϭ 1.87 (m, 2 H, β-CH2), 2.3Ϫ2.7 140.62 (6 C, aromatic C). Ϫ MS (LSIMS); m/z (%): 409 [M ϩ H]ϩ.
(m, 4 H), 2.8Ϫ3.8 (m, 14 H), 4.39 (t, 2 H), 4.76 (d, 4 H, Ϫ C26H40N4 (408.3): calcd. C 76.42, H 9.87, N 13.71; found C
NϪCH2Ϫpyr.), 5.55 (d, 2 H, NϪCH2ϪN), 7.53 (t, 2 H, pyr.), 7.68 76.38, H 9.83, N 13.76.
(d, 2 H, pyr.), 8.00 (t, 2 H, pyr.), 8.61 (d, 2 H, pyr.). Ϫ 13C NMR
1
5c: H NMR (CDCl3): δ ϭ 1.60 (q, 4 H, β-CH2), 2.03 (s, 6 H,
(CDCl3): δ ϭ 22.11(β-CH2), 50.30 (α-CH2), 50.65 (α-CH2), 53.77
NϪCH3), 2.30Ϫ2.70 (m, 16 H, α-CH2), 3.66 (s, 4 H, NϪCH2-pyr.),
(α-CH2), 63.00 (NϪCH2Ϫpyr), 66.09 (α-CH2), 79.74
7.02 (t, 2 H, pyr.), 7.50 (m, 4 H, pyr.), 8.40 (d, 2 H, pyr.). Ϫ 13C
(NϪCH2ϪN), 128.44, 131.29, 141.32, 149.11, 152.73 (5 C, pyr.). Ϫ
NMR (CDCl3): δ ϭ 24.85 (β-CH2), 43,84 (NϪCH3), 52.03 (α-
C24H36Cl2N6 ·3 H2O (532.3): calcd. C 54.03, H 7.93, N 15.75;
CH2), 52.33 (α-CH2) 54.88 (α-CH2), 55.52 (α-CH2), 61.90
(NϪCH2-pyr.), 122.38, 123.68, 136.80, 149.41, 161.17 (5 C, pyr.).
found C 53.56, H, 7.92, N 15.77.
Synthesis of 1,8-Disubstitued 1,4,8,11-Tetraazacyclotetradecane Ϫ MS (LSIMS); m/z (%): 411 [M ϩ H]ϩ. Ϫ C24H38N6 (410.3):
(1): Compounds 1a, 1b, or 1c were prepared by dissolving 0.5 g of
4a (0.58 mmol), 4b (0.88 mmol), or 4c (0.93 mmol) in 100 ml of
an aqueous NaOH solution (3 mol lϪ1). After stirring for 3 h, the
solution was extracted with CHCl3 (5 ϫ 30 ml). The organic phases
were collected, dried with MgSO4, and concentrated under vacuum
to give the expected compound with a quantitative yield.
calcd. C 70.19, H 9.33, N 20.48; found C 70.15, H 9.30, N 20.13.
Supporting Information (Available on the WWW under
calculated semiempirical PM3 and molecular mechanics param-
eters for 1,4,8,11-tetraazatricyclo[9.3.1.14,8]hexadecane (bond
lengths and angles); Figure S1: PM3-calculated molecular electro-
1
1a: H NMR (CDCl3): δ ϭ 1.37 (q, 4 H, β-CH2), 1.82 (s, 6 H, static potential of 1,4,8,11-tetraazatricyclo[9.3.1.14,8]hexadecane in
NϪCH3), 2.0Ϫ2.15 (m, 8 H, α-CH2), 2.21Ϫ2.38 (m, 8 H, α-CH2), the (C6ϪN1ϪC1) plane.
2.70 (bs, 2 H, NH). Ϫ 13C NMR (CDCl3): δ ϭ 26.64 (β-CH2),
42.11 (NϪCH3), 47.86 (α-CH2), 50.47 (α-CH2), 57.29 (α-CH2),
[1]
A. K. Bazak, T. A. Kaden, Helv.Chim. Acta 1983, 66,
58.65 (α-CH2). Ϫ MS (LSIMS); m/z (%): 229 [M ϩ H]ϩ. Ϫ
2086Ϫ2092.
[2]
C12H28N4 (28.2): calcd. C 63.11, H 12.36, N 24.53; found C 63.33,
H 12.49, N 24.34.
W. Schibler, T. A. Kaden, J. Chem. Soc., Chem. Commun.
1981, 603Ϫ604.
[3]
[4]
M. Ciampolini, L. Fabbrizzi, M. Licchelli, A. Perotti, F. Pezzini,
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71, 100Ϫ106.
1b: 1H NMR (CDCl3): δ ϭ 1.82 (q, 4 H, β-CH2), 2.45Ϫ2.90 (m,
18 H, α-CH2 and NH), 3.71 (s, 4 H, NϪCH2ϪPh), 7.15Ϫ7.35 (m,
10 H, aromatic H). Ϫ 13C NMR (CDCl3): δ ϭ 26.67 (β-CH2),
48.45 (α-CH2), 50.91 (α-CH2), 52.33 (α-CH2), 54.83(α-CH2), 58.47
(NϪCH2ϪPh), 127.65, 128.79, 130.25, 138.00 (6 C, aromatic C).
Ϫ MS (EI); m/z (%): 380 [Mϩ]. Ϫ C24H36N4 (380.3): calcd. C 75.73,
H 9.54, N 14.73; found C 75.17, H 9.61, N 14.22.
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M. Lachkar, B. Andrioletti, B. Boitrel, R. Guilard, A. Atmani,
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[8]
1c: 1H NMR (CDCl3): δ ϭ 1.74 (q, 4 H, β-CH2), 2.50Ϫ2.80 (m,
16 H), 3.67 (s, 4 H, NϪCH2-pyr.), 3.80 (br. s, 2 H, NH), 7.08 (t, 2
H, pyr.), 7.39 (d, 2 H, pyr.), 7.56 (t, 2 H, pyr.), 8.47 (d, 2 H, pyr.).
I. M. Helps, D. Parker, J. Chapman, G. Ferguson, J. Chem.
Soc., Chem. Commun. 1988, 1094Ϫ1095.
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R. Guilard, A. G. Bessmertnykh, I. P. Beletskaya, Synlett
1997, 1190Ϫ1192.
[10]
[11]
[12]
Ϫ
13C NMR (CDCl3): δ ϭ 26.54 (β-CH2), 48.10 (α-CH2), 50.01(α-
E. J. Gabe, Y. Le Page, L. Prasad, Acta Crystallogr. 1982,
B38, 2752Ϫ2754.
CH2), 52.49 (α-CH2), 54.86 (α-CH2), 60.05 (NϪCH2-pyr), 122.47,
123.87, 136.73, 149.61, 159.23 (5 C, pyr.). Ϫ MS (LSIMS); m/z (%):
383 [M ϩ H]ϩ. Ϫ C22H34N6 (382.3): calcd. C 69.07, H 8.96, N
21.97; found C, 68.96, H 9.05, N 21.74.
T. Bailly, Y. Leroux, E. D. Manouni, A. Neuman, T. Prange, R.
Burgada, C. R. Acad. Sci. 1996, Ser IIB, 151Ϫ154.
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469Ϫ477.
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E. K. Barefield, F. Wagner, Inorg. Chem. 1973, 2, 2435Ϫ2439.
J. Tomasi, R. Bonaccorsi, R. Cammi, in Theoretical Models of
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1991, vol IV, p. 229.
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Molecular Mechanics (MM) and Molecular Dynamics (MD)
(DISCOVER module of the MSI Molecular Modeling Package
(Molecular Simulation, Inc., San Diego, CA, 1996, Insight II
4.00) have been used to perform an exhaustive search of low-
energy conformers of the macrocycle. The Molecular Dynamics
calculations have been carried out using the CVFF force field
within a Verlet leapfrog integration procedure. The steepest de-
Synthesis of 1,4,8,11-Tetramethyl-1,4,8,11-tetraazacyclotetra-
decane (5a), 1,8-Dimethyl-4,11-dibenzyl-1,4,8,11-tetraazacyclotetra-
decane (5b), and 1,8-Dimethyl-4,11-dipyridyl-1,4,8,11-tetraazacyclo-
tetradecane (5c): Compounds 5a, 5b, and 5c were obtained by dis-
solution of 1 mmol of 4a, 4b, or 4c in an EtOH/H2O (95:5) mixture.
10 equiv. of NaBH4 were then added and the mixture was refluxed
during 3 h. After return to room temp., 10 ml of HCl (3 in
water) was added. The mixture was concentrated to dryness and
the residue was then dissolved in 100 ml of water and concentrated
KOH was added (pH ϭ 12). After extraction with CHCl3 (5 ϫ
30ml), the organic phases were collected, dried with MgSO4 and
concentrated to give the expected tetrasubstitued tetraazamacrocy-
cle. Yields ca. 90%.
[15]
[16]
[17]
[18]
[19]
[20]
[21]
[22]
[23]
[24]
[25]
1
5a: H NMR (CDCl3): δ ϭ 1.54 (q, 4 H, β-CH2), 2.09 (s, 12 H,
NϪCH3), 2.32 (t, 16 H, α-CH2). Ϫ 13C NMR (CDCl3): δ ϭ 25.19
(β-CH2), 44.20 (NϪCH3), 54.62 (α-CH2), 54.86 (α-CH2.). Ϫ MS
(EI); m/z (%): 256 [Mϩ]. Ϫ C14H32N4 (256.3): calcd. C 65.57, H
12.58, N 21.85; found C 65.73, H 12.88, N 21.76.
1
5b: H NMR (CDCl3): δ ϭ 1.59 (q, 4 H, β-CH2), 2.10 (s, 6 H,
NϪCH3), 2.40Ϫ2.70 (m, 16 H, α-CH2), 3.55 (s, 4 H, NϪCH2ϪPh),
7.15Ϫ7.40 (m, 10 H, aromatic H). Ϫ 13C NMR (CDCl3): δ ϭ 24.84
(β-CH2), 43.97 (NϪCH3), 51.76 (α-CH2), 51.89 (α-CH2), 54.83 (α-
1974
Eur. J. Org. Chem. 1998, 1971Ϫ1975