Hete´nyi et al.
m, H-7, H-8), 1.83-1.92 (1H, m, H-10), 3.00 (1H, d, J ) 8.1
Hz, H-4), 3.35-3.43 (1H, m, H-6), 3.55 (1H, d, J ) 8.1 Hz,
H-4), 4.49 (1H, d, J ) 15.4 Hz, CH2-Ph), 4.59 (1H, d, J ) 15.4
Hz, CH2-Ph), 5.06 (1H, d, J ) 5.8 Hz, OH), 6.88-6.86 (1H, m,
N-phenyl), 7.05-7.11 (2H, m, benzyl), 7.13-7.20 (2H, m,
benzyl), 7.25-7.31 (1H, m, benzyl), 7.33-7.39 (4H, m, N-
phenyl). 13C NMR (DMSO-d6) δ: 21.0 (C-9), 23.0 (C-8), 30.5
(C-7), 34.7 (C-10), 47.6 (CH2-Ph), 51.7 (C-4), 70.7 (C-6), 83.7
(C-5), 120.3 (N-phenyl), 123.2 (N-phenyl), 126.8 (benzyl), 2 ×
127.5 (benzyl), 127.9 (N-phenyl), 137.2 (benzyl), 148.1 (N-
phenyl), 152.7 (C-2). IR (KBr) cm-1: 3225, 2937, 1624, 1085,
696. Anal. Calcd for C21H24N2O2: C, 74.97; H, 7.19; N, 8.33.
Found: C, 75.01; H, 7.01; N, 8.69.
2-(4-N it r o p h e n y l)h e x a h y d r o -1,3-b e n zo x a zin -4a -o l
(16a E). Yield: 78%. Mp: 143-147 °C. 1H NMR (CDCl3) δ:
1.20 (1H, ddd, J ) 5.0, 14.0 Hz, H-5), 1.27-1.41 (1H, m, H-7),
1.52-1.57 (1H, m, H-6), 1.63-1.75 (4H, m, H-5, H-6, 2 × H-8),
1.81-1.84 (1H, m, H-7), 2.92 (2H, s, 2 × H-4), 3.66, (1H, dd, J
) 5.0, 10.8 Hz, H-8a), 5.32 (1H, s, H-2), 7.71-7.74 (2H, m,
H-2′, H-6′), 8.19-8.22 (2H, m, H-3′, H-5′). 13C NMR (CDCl3)
δ: 20.4 (C-6), 24.2 (C-7), 26.9 (C-8), 32.4 (C-5), 55.7 (C-4), 66.3
(C-4a), 81.7 (C-8a), 88.1 (C-2), 123. (C-3′, C-5′), 127.1 (C-2′,
C-6′), 146.5 (C-1′), 147.8 (C-4′). MS (70 eV) m/z (%): 278 (M+,
15), 164 (31), 151 (100), 128 (29). Anal. Calcd for C14H18N2O4:
C, 60.42; H, 6.52; N, 10.07. Found: C, 60.11; H, 7.03; N, 10.29.
Gen er a l P r ep a r a tion of cis- a n d tr a n s-8,10-Bis(4-n itr o-
ph en yl)-7,11-dioxa-9-azatr icyclo[7.2.1.01,6]dodecan e (18aC
a n d 19a C). p-Nitrobenzaldehyde (0.45 g, 3 mmol) was added
to a solution of amino diol 4 or 6 (0.15 g, 1 mmol) in dry EtOH
(20 mL) and the solution refluxed for 10 h, after which the
solvent was removed under vacuum and the resulting crude
product recrystallized from MeOH.
cis-8,10-Bis(4-n it r op h en yl)-7,11-d ioxa -9-a za t r icyclo-
[7.2.1.01,6]d od eca n e (18a C). Yield: 54%. Mp: 206-210 °C.
1H NMR (CDCl3) δ: 1.28-1.41 (1H, m, H-3), 1.55-1.92 (7H,
m, 2 × H-2, H-3, 2 × H-4, 2 × H-5), 2.75 (1H, d, J ) 11.6 Hz,
H-12), 3.21 (1H, d, J ) 11.6 Hz, H-12), 3.81 (1H, dd, J ) 5.2,
10.8 Hz, H-1), 5.56 (1H, s, H-8), 5.61 (1H, s, H-10), 7.40-7.45
(2H, m, H-2′, H-6′), 7.84-7.89 (2H, m, H-2′′, H-6′′), 8.10-8.14
(2H, m, H-3′, H-5′), 8.26-8.30 (2H, m, H-3′′, H-5′′). 13C NMR
(CDCl3) δ: 22.5 (C-4), 23.7 (C-3), 28.5 (C-2), 30.4 (C-5), 59.2
(C-12), 78.5 (C-6), 80.2 (C-1), 89.5 (C-8), 90.6 (C-10), 123.2 (C-
3′, C-5′), 123.5 (C-3′′, C-5′′), 127.0 (C-2′, C-6′), 127.9 (C-2′′,
C-6′′), 146.1 (C-1′′), 147.5 (C-4′), 147.8 (C-4′′), 148.4 (C-1′). MS
(70 eV) m/z (%): 411 (M+, 54), 394 (32), 284 (79), 248 (100). IR
(KBr) cm-1: 2942, 1523, 1341. Anal. Calcd for C21H21N3O6: C,
61.31; H, 5.14; N, 10.21. Found: C, 61.57; H, 5.16; N, 10.45.
tr a n s-8,10-Bis(4-n itr op h en yl)-7,11-d ioxa -9-a za tr icyclo-
[7.2.1.01,6]d od eca n e (19a C). Yield: 45%. Mp: 191-193 °C.
1H NMR (CDCl3) δ: 1.21-1.45 (2H, m, H-3, H-4), 1.79-1.97
(5H, m, H-1, H-3, H-4, 2 × H-5), 2.07-2.14 (1H, m, H-2), 2.60
(1H, dd, J ) 1.8, 12.0 Hz, H-12), 3.67 (1H, d, J ) 3.8 Hz, H-12),
3.98 (1H, dd, J ) 1.7, 6.5, 12.2 Hz, H-1), 5.60 (1H, s, H-8),
5.69 (1H, s, H-10), 7.38-7.44 (2H, m, H-2′, H-6′), 7.84-7.88
(2H, m, H-2′′, H-6′′), 8.11-8.16 (2H, m, H-3′, H-5′), 8.27-8.31
(2H, m, H-3′′, H-5′′). 13C NMR (CDCl3) δ: 24.1 (C-4), 24.1 (C-
3), 29.0 (C-2), 32.6 (C-5), 53.5 (C-12), 80.7 (C-6), 81.2 (C-1),
86.9 (C-10), 88.4 (C-8), 123.2 (C-3′, C-5′), 123.4 (C-3′′, C-5′′),
127.0 (C-2′, C-5′), 128.0 (C-2′′, C-5′′), 146.2 (C-1′′), 147.6 (C-
4′), 147.8 (C-4′′), 148.2 (C-1′). MS (70 eV) m/z (%): 411 (M+,
47), 394 (37), 284 (81), 248 (100). IR (KBr) cm-1: 2937, 1521,
1346. Anal. Calcd for C21H21N3O6: C, 61.31; H, 5.14; N, 10.21.
Found: C, 61.62; H, 5.01; N, 10.63.
cis-2-P h en ylim in o-1-oxa -3-a za sp ir o[4.5]d eca n -6-ol (10).
1
Yield: 78%. Mp: 110-113 °C. H NMR (DMSO-d6) δ: 1.22-
1.73 (7H, m, 2 × H-7, 2 × H-8, 2 × H-9, H-10), 1.80-1.93 (1H,
m, H-10), 3.25-3.41 (2H, overlapped with H2O, m, H-4, H-6),
3.78 (1H, d, J ) 11.6 Hz, H-4), 4.85 (1H, d, J ) 5.8 Hz, OH),
6.81-6.87 (1H, m), 7.15-7.22 (2H, m), 7.51 (2H, d, J ) 7.8
Hz), 8.75 (1H, br s, NH). 13C NMR (DMSO-d6) δ: 21.5 (C-9),
22.7 (C-8), 31.0 (C-7), 34.4 (C-10), 59.0 (C-4), 70.7 (C-6), 85.5
(C-5), 117.6, 120.1, 128.1, 141.8, 155.3 (C-2). IR (KBr) cm-1
:
3069, 2939, 1651, 1092, 691. Anal. Calcd for C14H18N2O2: C,
68.27; H, 7.37; N, 11.37. Found: C, 68.57; H, 7.20; N, 11.66.
tr a n s-3-Ben zyl-2-p h en ylim in o-1-oxa -3-a za sp ir o[4.5]-
d eca n -6-ol (13). Yield: 77%. Mp: 152-153 °C. 1H NMR
(DMSO-d6) δ: 1.14-1.31 (3H, m, H-7, H-8, H-9), 1.47-1.60
(3H, m, H-8, H-9, H-10), 1.66-1.75 (1H, m, H-7), 1.78-1.87
(1H, m, H-10), 3.06 (1H, d, J ) 8.3 Hz, H-4), 3.51 (1H, d, J )
8.3 Hz, H-4), 3.54-3.61 (1H, m, H-6), 4.54 (2H, s, CH2-Ph),
5.23 (1H, d, J ) 4.8 Hz, OH), 6.81-6.85 (1H, m, N-phenyl),
6.99-7.03 (2H, m, N-phenyl), 7.13-7.18 (2H, m, N-phenyl),
7.26-7.32 (1H, m, benzyl), 7.35-7.38 (4H, m, benzyl). 13C NMR
(DMSO-d6) δ: 21.7 (C-8, C-9), 31.1 (C-7), 33.7 (C-10), 47.6
(CH2-Ph), 48.7 (C-4), 70.1 (C-6), 85.8 (C-5), 120.3 (phenyl),
123.1 (phenyl), 126.9 (benzyl), 2 × 127.6 (benzyl), 127.8
(phenyl), 137.2 (benzyl), 148.1 (phenyl), 152.4 (C-2). IR (KBr)
cm-1: 2936, 1662, 1589, 695. Anal. Calcd for C21H24N2O2: C,
74.97; H, 7.19; N, 8.33. Found: C, 75.32; H, 7.54; N, 8.47.
tr a n s-2-P h en ylim in o-1-oxa -3-a za sp ir o[4.5]d eca n -6-ol
(14). Yield: 74%. Mp: 145-146 °C. 1H NMR (DMSO-d6) δ:
1.18-1.33 (3H, m, H-7, H-8, H-9), 1.46-1.63 (3H, m, H-8, H-9,
H-10), 170-1.84 (2H, m, H-7, H-10), 3.29 (1H, overlapped with
H2O, m, H-4), 3.53-3.60 (1H, m, H-6), 3.78 (1H, d, J ) 11.6
Hz, H-4), 4.98 (1H, d, J ) 4.8 Hz, OH), 6.81-6.87 (1H, m),
7.15-7.22 (2H, m), 7.48 (2H, br s), 8.83 (1H, br s, NH). 13C
NMR (DMSO-d6) δ: 21.9 (C-8, C-9), 31.2 (C-7), 33.9 (C-10),
56.1 (C-4), 70.4 (C-6), 86.0 (C-5), 117.4, 120.1, 127.9, 141.4,
154.9 (C-2). IR (KBr) cm-1: 2930, 1660, 1449, 745. Anal. Calcd
for C14H18N2O2: C, 68.27; H, 7.37; N, 11.37. Found: C, 68.13;
H, 7.54; N, 11.10.
Gen er a l P r oced u r e for th e Rea ction of Am in o Diols 4
a n d 6 w ith 1 equ iv of a n Ar om a tic Ald eh yd e. Separate
solutions consisting of an aromatic aldehyde 15a -g and an
amino diol 4 or 6 were prepared by the direct addition of the
aldehyde (1 mmol) to the amino diol (1 mmol) in dry EtOH
(10 mL). Each solution was then kept at room temperature
for 2 h, after which the bulk of the solvent was removed under
vacuum at a temperature below 35 °C, followed by complete
drying under high vacuum. The resulting oily products were
used for NMR study without further purification, while
crystalline crude products were recrystallized from EtOAc-
EtOH. In each case though, only a complex mixture was
obtained, with the exception of the p-nitrophenyl substituent
whereby compound 16a E was isolated pure as a crystalline
product. Melting points: 16a , 143-147 °C; 16b, 98-100 °C;
16c, 132-138 °C; 16d , 114-118 °C; 16e, 78-82 °C; 16f,
viscous oil; 16g, 119-120 °C; 17a , 112-126 °C; 17b , 164-
170 °C; 17c, 186-188 °C; 17d , 158-160 °C; 17e, 170-173 °C;
17f, a viscous oil; 17g, 224-237 °C.
Ack n ow led gm en t . Financial support from the
PRCH Student Science Foundation; the Academy of
Finland, grant no. 4284 (K.P.); and the Centre for
International Mobility (CIMO, Finland, A.H.) is grate-
fully acknowledged. The authors are indebted to the
National Scientific Research Foundation, Hungary
(OTKA) and the Foundation for Hungarian Research
and Higher Education (AMFK). They also express their
thanks to Mr. G. Karvaly for his contribution to part of
the synthetic work.
1
Su p p or tin g In for m a tion Ava ila ble: Table of selected H
and 13C chemical shifts in ppm for compounds 16a -g in CDCl3
1
and H NMR spectra of products 16d and 17d . This material
J O026428T
2182 J . Org. Chem., Vol. 68, No. 6, 2003