An efficient method for cleavage of epoxides with aromatic amines

Full text of DOI:10.1021/jo981196c

J . Org. Chem. 1999, 64, 287-289
287
An Efficien t Meth od for Clea va ge of
Ep oxid es w ith Ar om a tic Am in es
At the outset, the reaction was done using cyclohexene
oxide and aniline using 5 mol % of Cu(OTf) in ether at
2
room temperature for 30 h, and the product 1a was
obtained in almost quantitative yield. The trans stere-
ochemistry for the amino alcohol 1a (entry 1) was
deduced from the coupling constant (J ) 9.9, 9.9, and
Govindasamy Sekar and Vinod K. Singh*
Department of Chemistry, Indian Institute of Technology,
Kanpur, India 208 016
1
4.5 Hz) of the peak at 3.34 ppm (CH-OH) in H NMR
spectrum. Likewise, the peak at 3.14 ppm for CH-NHPh
showed the similar kind of splitting pattern (ddd, J )
Received J une 19, 1998
1
0.8, 9.3, 3.9 Hz). The reaction was then studied in
several solvents, and it was found that diethyl ether (95%
yield) was superior to CH Cl (90% yield), MeCN (75%
â-Amino alcohols are an important class of organic
compounds which have found much use in medicinal
chemistry.1 Classically, these were synthesized by an
opening of epoxides with an excess of amines at elevated
temperature. Since the high temperature may not be
ideal for certain functional groups, a variety of activators
have been introduced in the literature to carry out
2
2
yield), and THF (71% yield). We also carried out the
above reaction using a catalytic amount (5 mol %) of Sn-
2
(OTf) which took a little shorter time (20 h) in the
opening of epoxides with aromatic amines, and the amino
alcohol was identical by TLC and NMR with the one
obtained from the use of copper triflate. To show the
scope of the reaction, we extended it to a variety of
aromatic amines and epoxides using both catalysts. In
all cases, a very clean reaction was observed and the
amino alcohols had trans stereochemistry (Table 1).
2
epoxide opening at room temperature. During the past
few years, a variety of metal triflates have also been used
to catalyze the opening of epoxides with amines.3 How-
ever, there are still some limitations with the literature
methods. For example, deactivated aromatic amines
such as p-nitroaniline failed to open epoxides or still
required higher temperature. While working as a part
of our program on asymmetric synthesis using chiral
copper complexes of diphenylpybox ligands, we discov-
2
ered that Cu(OTf) catalyzed an epoxide opening reaction
with both deactivated and activated aromatic amines.
However, it failed to catalyze the reaction with aliphatic
amines. This observation was in a sharp contrast to the
The epoxide opening reaction tolerated a varying
amount of steric hindrance on aromatic amines such as
o-methyl and R-naphthyl. However, in case of 2,6-
dimethylaniline, the isolated yield of the epoxide opened
product was not very high (46-50%). The reaction
worked very well on five-, six-, and seven-membered
epoxides. In the case of cyclooctene oxide, the reaction
required reflux temperature in MeCN and tin triflate was
found to be a better catalyst than copper triflate (entry
4
3
results from the other known metal triflates which
worked on aliphatic and aromatic amines both.5 The
unusual preference in the epoxide cleavage with aromatic
2
1). It was gratifying to observe that unsaturated
cyclooctene oxide could be opened at room temperature
with aromatic amines (entries 22 and 23). In case of
acyclic terminal olefins such as 1-dodecene oxide (entry
2
amines using Cu(OTf) prompted us to look at the
reaction in detail, and herein we delineate our results.
We also report here that the same reaction can be carried
out using tin(II) triflate as a catalyst.
2
4), a mixture of two separable regioisomers (6a and 6b)
was obtained in a ratio of 8:1 where the major product
6a ) was formed due to the attack of amine at the
(
(
1) (a) Rogers, G. A.; Parsons, S. M.; Anderson, D. C.; Nilsson, L.
M.; Bahr, B. A.; Kornreich, W. D.; Kaufman, R.; J acobs, R. S.; Kirtman,
B. J . Med. Chem. 1989, 32, 1217. (b) For a combinatorial library of
terminal carbon. Both regioisomers were isolated and
fully characterized in order to avoid ambiguity. The
epoxide opening reaction was also smooth in a disubsti-
tuted acyclic epxoide such as cis-2,3-epoxybutane (entry
25).
â-amino alcohols using LiClO
Med. Chem. Lett. 1997, 7, 1511.
2) (a) Fu, X.-L.; Wu, S.-H. Synth. Commun. 1997, 27, 1677 (SmCl
b) V de Weghe, P.; Collin, J . Tetrahedron Lett. 1995, 36, 1649 (SmI
4
, see: Chng, B. L.; Ganesan, A. Bioorg.
(
3
2
).
).
(
(
c) Chini, M.; Crotti, P.; Macchia, F. J . Org. Chem. 1991, 56, 5939 and
The worthy feature of the reaction is that highly
deactivated amines such as p-nitroaniline also opened the
epoxides in a reasonable yield. Although the isolated
yield in the epoxide opening reaction with aromatic
references therein (metal salts). (d) Iqbal, J .; Pandey, A. Tetrahedron
Lett. 1990, 31, 575 (CoCl ). (e) Yamada, J .-I.; Yumoto, M.; Yamamoto,
Y. Tetrahedron Lett. 1989, 30, 4255 (R′ PbNR ). (f) Overman, L. E.;
2
3
2
Flippin, L. A. Tetrahedron Lett. 1981, 22, 195 (Al amide). (g) Carre,
M. C.; Houmounou, J . P.; Caubere, P. Tetrahedron Lett. 1985, 26, 3107
(
Mg amide). (h) Yamada, J .-I.; Yumoto, M.; Yamamoto, Y. Tetrahedron
2 2
amines catalyzed by Cu(OTf) and Sn(OTf) is compa-
Lett. 1989, 30, 4255 (Pb amide). (i) Papini, A.; Ricci, A.; Taddei, M.;
Seconi, G.; Dembech, P. J . Chem. Soc. Perkin Trans. 1 1984, 2261
rable, the reaction was faster with the latter catalyst.
The unusual feature of this reaction is that only aromatic
amines opened the epoxides. Aliphatic amines such as
diethylamine, n-butylamine, benzylamine, and pyrroli-
dine failed to react with epoxides at room temperature
for 2 days in the presence of a catalytic amount of copper
or tin triflate. Although we do not have any proof for
the mechanism, we feel that it is ionic in nature.
Aliphatic amines by virtue of its higher basicity made
stronger complex to the copper and tin triflate which
failed to activate the epoxides. This was deduced from
an observation that aniline failed to open cyclohexene
oxide in the presence of n-butylamine and copper or tin
triflate under the above condition.
(
silicon amides). (j) Posner, G. H.; Rogers, D. Z. J . Am. Chem. Soc.
977, 99, 8208 (amines adsorbed on alumina).
3) (a) Auge, J .; Leroy, F. Tetrahedron Lett. 1996, 37, 7715 (LiOTf).
b) Chini, M.; Crotti, P.; Favero, L.; Macchia, F.; Pineschi, M.
Tetrahedron Lett. 1994, 35, 433 [La(OTf) ]. (c) Meguro, M.; Asao, N.;
Yamamoto, Y. J . Chem. Soc., Perkin Trans. 1 1994, 2597 [(Yb(OTf) ].
d) Fujiwara, M.; Imada, M.; Baba, A.; Matsuda, H. Tetrahedron Lett.
1
(
(
3
3
(
1
989, 30, 739 (Ph
4
SbOTf).
(4) (a) Sekar, G.; DattaGupta, A.; Singh, V. K. J . Org. Chem. 1998,
6
2
5
3, 2961. (b) DattaGupta, A.; Singh, V. K. Tetrahedron Lett. 1996, 37,
633. (c) DattaGupta, A.; Bhuniya, D.; Singh, V. K. Tetrahedron 1994,
0, 13725.
(5) There are two reports (ref 2a,d) in the literature for a similar
kind of preference for aromatic amines in the opening of epoxides;
however, the yield was modest even for activated aromatic amines and
the reaction failed with deactivated aromatic amines such as p-
nitroaniline.
1
0.1021/jo981196c CCC: $18.00 © 1999 American Chemical Society
Published on Web 12/10/1998

2
88 J . Org. Chem., Vol. 64, No. 1, 1999
Notes
1H NMR (CDCl
, 300 MHz) δ 1.04 (m, 1H), 1.34 (m, 3H), 1.75
Ta ble 1. Sn (II)- a n d Cu (II) Tr ifla te Ca ta lyzed Ep oxid e
Op en in g w ith Ar om a tic Am in es in Eth er a t r t
3
(m, 2H), 2.12 (m, 2H), 3.04 (bs, 2H, NH and OH), 3.14 (ddd, J )
a
for 20-30 h
10.8, 9.3, 3.9 Hz, 1H), 3.34 (ddd, J ) 9.9, 9.9, 4.5 Hz, 1H), 6.75
(
m, 3H), 7.1 (m, 2H); 13C NMR (CDCl
3
, 75 MHz) δ 24.2, 24.9,
3
1.5, 33.1, 60.0, 74.3, 114.2, 118.2, 129.2, 147.7.
tr a n s-2-(o-Meth ylp h en yla m in o)cycloh exa n ol (1b): vis-
2
a
1
cous liquid; R
CDCl , 300 MHz) δ 1.08 (m, 1H), 1.38 (m, 3H), 1.78 (m, 2H),
.16 (m, 2H), 2.18 (s, 3H), 3.00 (bs, 2H, NH and OH), 3.23 (ddd,
f
0.37 (1:10, EtOAc in petroleum ether); H NMR
(
3
2
J ) 10.9, 9.3, 3.9 Hz, 1H), 3.44 (ddd, J ) 10.5, 10.5, 4.8 Hz,
1
3
1
H), 6.72 (m, 1H), 6.81 (d, J ) 7.8 Hz, 1H), 7.12 (m, 2H);
C
3
NMR (CDCl , 75 MHz) δ 17.62, 24.21, 24.92, 31.75, 33.17, 59.72,
4.44, 111.46, 117.73, 123.00, 127.06, 130.32, 145.62; LCMS
7
+
(APCI, m/z) 206 (M + 1).
tr a n s-2-(m -Br om op h en yla m in o)cycloh exa n ol (1c): vis-
1
cous liquid; H NMR (CDCl
3
, 300 MHz) δ 1.01 (m, 1H), 1.30 (m,
3
1
1
H), 1.72 (m, 2H), 2.08 (m, 2H), 3.07 (ddd, J ) 10.6, 9.0, 3.6 Hz,
H), 3.2 (bs, 2H, NH and OH), 3.31 (ddd, J ) 9.9, 9.9, 4.2 Hz,
H), 6.59 (ddd, J ) 8.1, 2.1, 0.9 Hz, 1H), 6.83 (m, 2H), 7.00 (dd,
1
3
J ) 8.4, 8.4 Hz, 1H); C NMR (CDCl
3
1
3
, 75 MHz) δ 24.11, 24.71,
1.39, 33.23, 59.68, 74.22, 112.69, 116.45, 120.67, 123.14, 130.46,
+
49.14; LCMS (APCI, m/z) 270 and 271 (1:1, M + 1).
2
a
tr a n s-2-(p-Meth oxyph en ylam in o)cycloh exan ol (1d): mp
8-59 °C; H NMR (CDCl , 300 MHz) δ 1.00 (m, 1H), 1.30 (m,
3
1
5
3
1
1
H), 1.71 (m, 2H), 2.05 (m, 2H), 2.97 (ddd, J ) 10.9, 9.3, 3.9 Hz,
H), 3.28 (s, 2H, NH and OH), 3.31 (ddd, J ) 9.6, 9.6, 3.9 Hz,
H), 3.73 (s, 3H), 6.68 (d, J ) 8 Hz, 2H), 6.78 (d, J ) 8 Hz 2H);
1
3
3
C NMR (CDCl , 75 MHz) δ 24.15, 24.86, 31.25, 33.07, 55.56,
1.48, 74.03, 114.67, 116.28, 141.29, 152.73; LCMS (APCI, m/z)
6
2
+
22 (M + 1).
tr a n s-2-(2,6-Dim eth ylph en ylam in o)cycloh exan ol (1f): vis-
-
1
1
cous liquid; IR (neat) 3140-3620 cm
3
; H NMR (CDCl , 300
MHz) δ 1.10 (m, 1H), 1.32 (m, 3H), 1.78 (m, 3H), 2.12 (m, 1H),
2
.30 (s, 6H), 2.87 (ddd, J ) 10.9, 9.3, 3.9 Hz, 1H), 3.42 (ddd, J
)
)
7
1
10.2, 10.2, 4.5 Hz, 1H), 3.60 (bs, 2H, NH and OH), 6.85 (dd, J
7.8, 6.9 Hz, 1H), 7.00 (d, J ) 7.8 Hz, 2H); 13C NMR (CDCl3,
5 MHz) δ 19.17, 24.26, 25.23, 32.41, 33.02, 63.36, 75.07, 122.25,
+
29.08, 129.75; LCMS (APCI, m/z) 220 (M + 1).
2
a
tr a n s-2-(r-Na p h th yla m in o)cycloh exa n ol (1g): mp 84-
-
1 1
8
1
2
(
7
3
5 °C; IR (KBr) 3100-3600 cm ; H NMR (CDCl , 300 MHz) δ
.16 (m, 1H), 1.42 (m, 3H), 1.80 (m, 2H), 2.24 (m, 2H), 2.98 (bs,
H, NH and OH), 3.39 (ddd, J ) 10.9, 9.3, 3.9 Hz, 1H), 3.54
ddd, J ) 9.6, 9.6, 4.2 Hz, 1H), 6.82 (dd, J ) 6.3, 0.9 Hz, 1H),
.30 (m, 2H), 7.45 (m, 2H), 7.84 (m, 2H); 13C NMR (CDCl
MHz) δ 24.30, 24.92, 31.23, 33.39, 59.84, 74.59, 106.41, 118.32,
19.92, 124.21, 124.87. 125.75, 126.41, 128.76, 134.44, 142.77;
3
, 75
1
+
LCMS (APCI, m/z) 242 (M + 1).
tr a n s-2-(â-Na p h th yla m in o)cycloh exa n ol (1h ): mp 97-99
-1
°
f
C; IR (KBr) 3400-3600 cm ; R 0.20 (1:10, EtOAc in petroleum
1
ether); H NMR (CDCl
1
3
, 300 MHz) δ 1.05 (m, 1H), 1.40 (m, 3H),
.78 (m, 2H), 2.20 (m, 2H), 3.02 (bs, 1H, OH), 3.30 (ddd, J )
a
9.8, 9.0, 3.9 Hz, 1H), 3.41 (ddd, J ) 9.3, 9.3, 4.2 Hz, 1H), 6.95
Entry 21 was done in MeCN at 80 °C for 20 h.
1
3
(
(
1
m, 2H), 7.23 (m, 1H), 7.38 (m, 1H), 7.65 (m, 3H).
CDCl , 75 MHz) δ 24.26, 24.97, 31.47, 33.22, 60.01, 74.59,
06.46, 118.57, 122.35, 125.96, 126.38, 127.56, 127.86, 129.05,
134.96, 145.41; LCMS (APCI, m/z) 243 (M + 2), 242 (M + 1).
Anal. Calcd for C16 19NO: C, 79.67; H, 7.88; N, 5.81. Found:
C, 79.52; H, 7.92; N, 5.88.
tr a n s-2-(4-Nitr oph en ylam in o)cycloh exan ol (1j): mp 119-
C NMR
3
Irrespective of a mechanism, the cleavage of epoxides
with aromatic amines is unique and will be highly useful
in organic synthesis. To the best of our knowledge, the
above catalysts are not known to catalyze epoxide open-
ing reaction with aromatic amines. A variety of chiral
nonracemic ligands can be complexed with copper or tin
triflate for asymmetric version of the reaction which is
in progress in our laboratory.
+
+
H
7
-
1 1
1
(
21 °C; IR (KBr) 3500 cm ; H NMR (CD
3
OD, 300 MHz) δ 1.30
bm, 4H), 1.75 (m, 2H), 2.00 (m, 2H), 3.29 (m, 1H), 3.43 (ddd, J
)
10.2, 10.2, 4.5 Hz, 1H), 4.84 (s, 2H, NH & OH), 6.65 (d, J )
9.3 Hz, 2H), 7.98 (d, J ) 9.3 Hz, 2H); 13C NMR (CD OD, 75 MHz)
3
δ 25.34, 25.53, 32.24, 35.17, 59.22, 74.70, 112.12, 127.28,137.0,
+
1
56.16; LCMS (APCI, m/z) 237 (M + 1).
Exp er im en ta l Section
tr a n s-2-(N-Meth yl-N-ph en ylam in o)cycloh exan ol (1k): vis-
Gen er a l P r oced u r e for Ep oxid e Op en in g w ith Ar om a tic
Am in es. A solution of an epoxide (1 mmol) and an aromatic
amine (1.3 mmol) in anhydrous ether (5 mL) was treated with
f
cous liquid; R 0.43 (1:10, EtOAc in petroleum ether); IR (film)
3050-3600 cm ; H NMR (CDCl , 300 MHz) δ 1.28 (m, 2H),
3
-
1
1
1.40 (m, 2H), 1.78 (m, 3H), 2.20 (m, 1H), 2.77 (s, 3H), 3.42 (ddd,
J ) 10.9, 9.6, 3.6 Hz, 1H), 3.67 (ddd, J ) 10.2, 10.2, 4.8 Hz,
1H), 6.82 (dd, J ) 6.9, 6.9 Hz, 1H), 6.96 (d, J ) 8.1 Hz, 2H),
2 2
Cu(OTf) (5 mol %) for 30 h or with Sn(OTf) (5 mol %) for 20 h
at room temperature (except entry 19 which was done in MeCN
at reflux temperature). The solvent was removed on a rotary
evaporator, and the crude product was purified over silica gel
by column chromatography to provide pure trans amino alcohol
in high yield (cf. Table 1).
7.27 (m, 2H); 13C NMR (CDCl
, 75 MHz) δ 24.27, 25.41, 25.98,
31.04, 33.29, 66.92, 69.94, 115.52, 118.45, 129.01, 151.32; LCMS
3
(6) Brown, D. W.; Ninan, A.; Sainsbury, M. Synthesis 1997, 895.
2
g
tr a n s-2-(P h en yla m in o)cycloh exa n ol (1a ): mp 58-59 °C
(7) Chinnakali, K.; Fun, H.-K.; Sriraghavan, K.; Ramakrishnan, V.
T. Acta Crystallogr., Sect. C: Cryst. Struct. Commun. 1997, C53, 1865.
2
g
(
lit. mp 60-62 °C); R
f
0.25 (1:10, EtOAc in petroleum ether);

Notes
J . Org. Chem., Vol. 64, No. 1, 1999 289
(
APCI, m/z) 206 (M+ + 1). Anal. Calcd for C16
H
19NO: C, 79.67;
tr a n s-2-(4-Nitr op h en yla m in o)cycloh ep ta n ol (3d ): semi-
H, 7.88; N, 5.81. Found: C, 79.62; H, 7.90; N, 5.90.
solid; R 0.39 (1:3, EtOAc in petroleum ether); IR (KBr) 3140-
f
-
1 1
tr a n s-2-(N-Ben zyl-N-p h en yla m in o)cycloh exa n ol (1l): vis-
3600 cm ; H NMR (CDCl
3
, 300 MHz) δ 1.42-1.90 (bm, 10H),
-
1
1
cous liquid; IR (neat) 3000-3600 cm
MHz) δ 1.38 (m, 4H), 1.80 (m, 2H), 1.94 (m, 1H), 2.19 (m, 1H),
3
; H NMR (CDCl , 300
3.43 (m, 1H), 3.55 (bs, OH), 3.69 (ddd, J ) 8.1, 3.9 Hz, 1H), 6.61
(d, J ) 9.3 Hz, 2H), 8.02 (d, J ) 9.3 Hz, 2H); 13C NMR (CDCl
,
3
2
(
(
.84 (bs, 1H, OH), 3.65 (m, 2H), 4.48 (d, J ) 10.5 Hz, 2H), 6.82
m, 1H), 7.00 (m, 2H), 7.25 (m, 3H), 7.36 (m, 4H); 13C NMR
CDCl , 75 MHz) δ 24.19, 25.38, 26.99, 33.60, 48.91, 66.38, 70.62,
16.21, 118.62, 126.62, 126.76, 128.60, 128.96, 139.58, 149.7.
Anal. Calcd for C19 23NO: C, 81.14; H, 8.19; N, 4.98. Found:
C, 81.42; H, 8.32; N, 5.08.
tr a n s-2-(P h en yla m in o)cyclop en ta n ol (2a ): mp 54-55 °C
75 MHz) δ 23.52, 25.30, 29.56, 31.26, 35.26, 61.93, 77.11, 112.32,
127.32, 140.37, 157.17; LCMS (APCI, m/z) 251 (M+ + 1).
3
tr a n s-2-(P h en yla m in o)cycloocta n ol (4): viscous liquid; IR
1
-1
1
(
8
(
neat) 3120-3620 cm ; H NMR (CDCl
3
, 300 MHz) δ 1.6 (m,
H
H), 1.86 (m, 4H), 3.22 (bs, 2H, NH and OH), 3.45 (m, 1H), 3.56
13
ddd, J ) 9.5, 6.6, 2.7 Hz, 1H), 6.78 (m, 3H), 7.24 (m, 2H);
C
2
g
3
NMR (CDCl , 75 MHz) δ 23.27, 25.17, 25.67, 26.74, 29.63, 31.10,
2
g
(
f
lit. mp 57-58 °C);); R 0.13 (1:10, EtOAc in petroleum ether);
6
2
6
0.02, 74.93, 115.11, 118.84, 129.35, 147.50; LCMS (APCI, m/z)
-
1
1
IR (KBr) 3100-3580 cm ; H NMR (CDCl
(
3
, 300 MHz) δ 1.40
+
20 (M + 1). Anal. Calcd for C14H21NO: C, 76.71; H, 9.59; N,
.39. Found: C, 76.82; H, 9.62; N, 6.28.
m, 1H), 1.62 (m, 1H), 1.78 (m, 2H), 1.98 (m, 1H), 2.10 (m, 1H),
3
3
3
.12 (bs, 2H, NH and OH), 3.60 (m, 1H), 4.03 (m, 1H), 6.70 (m,
H), 7.21 (m, 2H); 13C NMR (CDCl
tr a n s-2-(P h en yla m in o)cyclooct-5-en -1-ol (5a ): mp 48-50
3
, 75 MHz) δ 20.83, 30.95,
-1
°
f
C; IR (KBr) 3140-3580 cm ; R 0.34 (1:10, EtOAc in petroleum
2.59, 61.92, 77.94, 113.31, 117.42, 129.15, 147.63.
1
ether); H NMR (CDCl
3
, 300 MHz) δ 1.5 (m, 1H), 1.72 (m, 1H),
.04 (m, 2H), 2.38 (m, 4H), 3.45 (m, 1H + NH and OH), 3.65
ddd, J ) 8.1, 8.1, 3.3 Hz, 1H), 5.58 (m, 1H), 5.75 (m, 1H), 6.7
tr a n s-2-(N-Meth yl-N-p h en yla m in o)cyclop en ta n ol (2b):
2
(
(
f
viscous liquid; R 0.35 (1:10, EtOAc in petroleum ether); IR (neat)
-
1 1
3
6
7
100-3580 cm ; H NMR (CDCl
3
, 300 MHz) δ 1.58-2.08 (bm,
13
3
m, 2H), 6.78 (m, 1H), 7.20 (m, 1H); C NMR (CDCl , 75 MHz)
H + OH), 2.80 (s, 3H), 3.97 (m, 1H), 4.21 (m, 1H), 6.74 (dt, J )
δ 22.82, 23.35, 32.15, 33.32, 59.04, 72.94, 115.04, 119.04, 127.67,
.2, 0.6 Hz, 1H), 6.89 (d, J ) 8.7 Hz, 2H), 7.23 (m, 2H); 13C NMR
1
29.21, 130.74, 147.93. Anal. Calcd for C14 19NO: C, 77.42;
H
3
(CDCl , 75 MHz) δ 19.83, 24.39, 31.50, 32.24, 68.09, 74.49,
H, 8.76; N, 6.45. Found: C, 77.62; H, 8.72; N, 6.58.
tr a n s-2-(N-Meth yl-N-ph en ylam in o)cyclooct-5-en -1-ol (5b):
1
1
14.23, 117.44, 129.10, 151.08; LCMS (APCI, m/z) 192 (M+
).
+
-
1
viscous liquid; IR (neat) 3000-3600 cm ; R
in petroleum ether); 1H NMR (CDCl
, 300 MHz) δ 1.56-1.90
bm, 3H), 2.02 (m, 1H), 2.4 (bm, 4H), 2.77 (s, 3H), 3.42 (bs, 1H,
OH), 3.85 (m, 2H), 5.52 (m, 1H), 5.72 (m, 1H), 6.85 (m, 1H), 6.92
m, 2H), 7.27 (m, 2H); 13C NMR (CDCl
, 75 MHz) δ 22.93, 24.16,
5.98, 32.50, 64.06, 70.28, 116.08, 119.17, 126.52, 129.09, 131.54;
f
0.62 (1:10, EtOAc
tr a n s-2-(N-Eth yl-N-p h en yla m in o)cyclop en ta n ol (2c): vis-
cous liquid; R 0.37 (1:10, EtOAc in petroleum ether); IR (neat)
3
f
(
-
1 1
3
100-3580 cm ; H NMR (CDCl
Hz, 3H), 1.6 (m, 2H), 1.8 (m, 2H), 2.0 (m, 2H), 3.28 (m, 2H),
.91 (m, 1H), 4.20 (m, 1H), 6.74 (m, 1H), 6.88 (tt, J ) 7.2, 0.9
3
, 300 MHz) δ 1.19 (t, J ) 6.9
(
2
3
3
1
3
Hz, 1H), 7.23 (m, 2H); C NMR (CDCl
2
LCMS (APCI, m/z) 206 (M + 1). Anal. Calcd for C13H19NO:
C, 76.10; H, 9.27; N, 6.83. Found: C, 76.32; H, 9.22; N, 6.90.
3
, 75 MHz) δ 14.63, 19.72,
+
LCMS (APCI, m/z) 256 (M + 1). Anal. Calcd for C17H21NO:
C, 80.00; H, 8.24; N, 5.49. Found: C, 79.82; H, 8.12; N, 5.52.
5.69, 31.53, 40.55, 67.60, 74.93, 114.76, 117.33, 129.13, 149.37;
+
8
1
-(N-Meth yl-N-p h en yla m in o)d od eca n -2-ol (6a ): viscous
liquid; R
620 cm ; H NMR (CDCl
f
-
0.52 (1:5, EtOAc in petroleum ether); IR (neat) 3100-
tr a n s-2-(4-Nitr op h en yla m in o)cyclop en ta n ol (2d ): semi-
1
1
3
3
, 300 MHz) δ 0.90 (t, J ) 6.9 Hz,
solid; R
f
0.27 (1:4, EtOAc in petroleum ether); IR (KBr) 3100-
-
1
1
3H), 1.28 (bs, 16H), 1.5 (m, 2H), 1.57 (m, 1H), 2.2 (bs, 1H, OH),
.96 (s, 3H), 3.24 (m, 2H), 3.92 (m, 1H), 6.78 (dd, J ) 7.5, 7.5
Hz, 1H), 6.82 (d, J ) 8.4 Hz, 2H), 7.26 (dd, J ) 8.7, 7.5 Hz, 2H);
3
2
(
3
580 cm ; H NMR (CD OD, 300 MHz) δ 1.40-2.02 (m, 5H),
2
.22 (m, 1H), 3.65 (m, 1H), 3.75 (bs, OH), 3.85 (bs, NH), 4.02
m, 1H), 6.65 (d, J ) 9.3 Hz, 2H), 8.00 (d, J ) 9.3 Hz, 2H); 13
C
1
3
C NMR (CDCl
3
, 75 MHz) δ 14.11, 22.68, 25.69, 29.32, 29.60,
NMR (CD
3
OD, 75 MHz) δ 22.29, 31.17, 33.69, 62.48, 78.37,
12.24, 127.20, 137.92, 155.65; LCMS (APCI, m/z) 223 (M+
29.76, 31.90, 34.53, 39.27, 60.66, 69.27, 113.40, 117.50, 129.14,
50.48; LCMS (APCI, m/z) 292 (M + 1).
1
1
+
+
1
).
8
2
-(N-Meth yl-N-p h en yla m in o)d od eca n ol (6b): viscous liq-
tr a n s-2-(P h en yla m in o)cycloh ep ta n ol (3a ): mp 59-60 °C;
0.27 (1:10, EtOAc in petroleum ether); IR (KBr) 3140-3600
uid; R
f
0.47 (1:5, EtOAc in petroleum ether); IR (neat) 3100-
R
f
-
1
1
-
1
1
3620 cm ; H NMR (CDCl , 300 MHz) δ 0.88 (t, J ) 6.9 Hz,
H), 1.20 (bs, 17H), 1.5 (m, 1H), 1.95 (bs, 1H, OH), 2.74 (s, 3H),
cm ; H NMR (CDCl
3
, 300 MHz) δ 1.2-1.8 (bm, 9H), 1.98 (m,
3
3
1
(
H), 3.05 (bs, 1H, OH), 3.24 (ddd, J ) 9.3, 9.3, 3.3 Hz, 1H), 3.46
ddd, J ) 8.4, 8.4, 3.6 Hz, 1H), 6.72 (m, 3H), 7.24 (m, 2H); 13
3.62 (m, 2H), 3.95 (m, 1H), 6.78 (dd, J ) 7.5, 7.5 Hz, 1H), 6.92
C
1
3
(
d, J ) 8.4 Hz, 2H), 7.24 (dd, J ) 8.7, 7.5 Hz, 2H); C NMR
3
NMR (CDCl , 75 MHz) δ 22.13, 24.03, 27.18, 30.24, 32.79, 62.76,
14.92, 118.73, 129.36, 147.47; LCMS (APCI, m/z) 206 (M+
). Anal. Calcd for C13 19NO: C, 76.10; H, 9.27; N, 6.83.
+
(CDCl , 75 MHz) δ 14.10, 22.65, 26.45, 28.56, 29.26, 29.37, 29.51,
3
1
1
2
9.57, 29.83, 31.86, 61.56, 62.57, 114.40, 117.80, 129.12, 150.48;
H
+
LCMS (APCI, m/z) 292 (M + 1).
Found: C, 76.42; H, 9.12; N, 6.90.
tr a n s-2-(N-Meth yl-N-p h en yla m in o)cycloh ep ta n ol (3b):
viscous liquid; R 0.50 (1:10, EtOAc in petroleum ether); IR (neat)
tr a n s-3-(P h en yla m in o)bu ta n -2-ol (7): viscous liquid; IR
-1
f
1
f
(neat) 3140-3640 cm ; R 0.28 (1:10, EtOAc in petroleum ether);
-
1
1
3
9
)
(
(
140-3600 cm ; H NMR (CDCl
H), 2.08 (m, 1H), 2.74 (s, 3H), 3.06 (bs, 1H, OH), 3.48 (ddd, J
9.3, 9.3, 2.4 Hz, 1H), 3.74 (ddd, J ) 9.3, 9.3, 3.6 Hz, 1H), 6.84
tt, J ) 7.5, 0.9 Hz, 1H), 6.97 (m, 2H), 7.26 (m, 2H); 13C NMR
CDCl , 75 MHz) δ 21.74, 24.35, 25.43, 26.68, 31.35, 32.66, 69.51,
2.38, 116.21, 119.03, 129.08, 151.33; LCMS (APCI, m/z) 220
3
, 300 MHz) δ 1.38-1.80 (bm,
3
H NMR (CDCl , 300 MHz) δ 1.15 (d, J ) 6.3 Hz, 3H), 1.25 (d,
J ) 6.0 Hz, 3H), 2.82 (bs, NH and OH), 3.33 (m, 1H), 3.67 (m,
1H), 6.68 (m, 2H), 6.74 (m, 1H), 7.18 (m, 2H); MS (EI, m/z) 165
+
(M ). Anal. Calcd for C10
H
15NO: C, 72.69; H, 9.14; N, 8.48.
3
Found: C, 72.42; H, 9.02; N, 8.42.
7
+
(
M + 1). Anal. Calcd for C14H21NO: C, 76.71; H, 9.59; N, 6.39.
Ack n ow led gm en t. V.K.S. thanks DST (Govern-
ment of India) for a Swarnajayanti Fellowship (1998).
G.S. thanks CSIR for the award of a Senior Research
Fellowship.
Found: C, 76.42; H, 9.42; N, 6.20.
tr a n s-2-(N-Eth yl-N-p h en yla m in o)cycloh ep ta n ol (3c): vis-
f
cous liquid; R 0.63 (1:10, EtOAc in petroleum ether); IR (neat)
-
1
1
3
6
3
140-3600 cm
3
; H NMR (CDCl , 300 MHz) δ 1.15 (dt, J )
.9, 1.8 Hz, 3H), 1.30-1.80 (bm, 9H), 2.02 (m, 1H), 3.20 (m, 2H),
.33 (m, 1H), 3.70 (m, 1H), 6.82 (tt, J ) 7.5, 0.9 Hz, 1H), 6.97
J O981196C
1
3
3
(m, 2H), 7.25 (m, 2H); C NMR (CDCl , 75 MHz) δ 14.40, 21.68,
2
1
4.55, 26.10, 26.73, 32.57, 39.19, 70.85, 72.69, 117.77, 119.40,
(8) Shibata, K.; Shimada, S.; Matsuda, S. Kogyu Kogaku Zasshi
(J apn) 1965, 68, 957; Chem. Abstr. 1965, 63, 9761.
29.04, 149.30; LCMS (APCI, m/z) 234 (M+ + 1).