Studies on ring cleavage of aziridines with hydroxyl compounds

Article abstract of DOI:10.1016/S0040-4020(02)00609-9

Ring cleavage of a variety of N-substituted aziridines has been studied with hydroxyl compounds (primary, secondary, allylic and tertiary). It was observed that the cleavage reaction was very facile in the presence of BF₃·OEt₂ and Sn(OTf)₂. Whereas the aziridine opening reaction was facile with primary and secondary alcohols, hindered alcohols took longer (2 days). However, with the help of microwave radiation, the cleavage reaction with hindered alcohols could be achieved in a very short period (15min). Phenols could only cleave aziridines under microwave irradiation.

Full text of DOI:10.1016/S0040-4020(02)00609-9

Tetrahedron 58 (2002) 7355–7363
Studies on ring cleavage of aziridines with hydroxyl compounds
*
B. A. Bhanu Prasad, Rashmi Sanghi and Vinod K. Singh
Department of Chemistry, Indian Institute of Technology–Kanpur, Kanpur 208 016, India
Received 28 March 2002; revised 20 May 2002; accepted 13 June 2002
Abstract—Ring cleavage of a variety of N-substituted aziridines has been studied with hydroxyl compounds (primary, secondary, allylic and
tertiary). It was observed that the cleavage reaction was very facile in the presence of BF ·OEt and Sn(OTf) . Whereas the aziridine opening
3 2 2
reaction was facile with primary and secondary alcohols, hindered alcohols took longer (2 days). However, with the help of microwave
radiation, the cleavage reaction with hindered alcohols could be achieved in a very short period (15 min). Phenols could only cleave
aziridines under microwave irradiation. q 2002 Elsevier Science Ltd. All rights reserved.
Aziridines are nitrogen analogs of epoxides and their ring-
opened products are valuable intermediates in organic
synthesis. The reactivity of this strained heterocyclic ring
ZnI , ZnCl , and CoCl failed to give any product (12 h,
2 2 2
room temperature). Since Sn(OTf)2 and BF ·OEt both
3
2
1
turned out to be highly effective for aziridine opening with
MeOH, the cleavage of N-tosylcyclohexyl aziridine was
studied using other hydroxyl compounds. The reaction with
system is less than that of epoxides and dependent upon the
substitution on the nitrogen atom. The Lewis acid-induced
ring-opening of N-substituted aziridines with several
EtOH in the presence of Sn(OTf) took longer time (30 h)
2
2
3
nucleophiles such as amines and azides has been very
well studied, but aziridine opening with hydroxyl com-
pounds was unknown until we recently communicated that
less hindered alcohols such as primary and allylic alcohols
whereas the same reaction could be done in 3 h using
BF ·OEt . In both cases, a quantitative yield of the product
3
2
was obtained (entry 2). The results from allylic and
propargyl alcohols were similar (entries 3 and 4). The
ring-opening reaction was also carried out with benzyl
alcohol and water in CH Cl and MeCN, respectively, and
4
could easily open aziridines in high yield. In this paper, we
describe full details of the work and also report that
aziridines can also be opened with hindered alcohols such as
secondary and tertiary. We further report the effect of
microwave irradiation on the ring cleavage of aziridines.
2
2
the products were obtained in high yields (entries 5 and 6).
We had previously reported that aziridines were inert to
4
secondary and tertiary alcohols. On extensive study of
these cleavage reactions, we found that activated aziridines
were also opened with these hindered alcohols in an efficient
manner. Reaction of N-tosylcyclohexyl aziridine with
i-PrOH and t-BuOH in the presence of BF ·OEt provided
While working on the Sn(OTf) induced cleavage reaction
2
of N-tosylcyclohexyl aziridine with TMSCN in MeOH as a
5
solvent, we discovered that the product was b-amino ether 1
resulting from an opening of the aziridine with MeOH. The
role of TMSCN in this reaction was ruled out as it also
proceeded in its absence. Thus, following a typical
procedure, reaction of N-tosylcyclohexyl aziridine
3
2
the ring-opened products in high yields (entries 7 and 8). It
was observed that Sn(OTf) was less effective in catalyzing
2
the cleavage of aziridines with hindered alcohols. In fact, it
failed to catalyze the opening reaction with t-BuOH. The
cleavage reaction of N-tosylcyclohexyl aziridine by other
kinds of hydroxyl groups in the presence of a catalytic
amount of BF ·OEt was also facile (entries 9–14). In the
(
of Sn(OTf) gave the b-amino ether in 99% yield (Table 1,
1 mmol) with MeOH in the presence of a catalytic amount
2
entry 1). The same reaction could be done in a more efficient
manner in the presence of BF ·OEt . The trans stereo-
3
2
cases of high boiling hydroxyl compounds such as
cyclohexanol, indanol, menthol, etc., the cleavage reaction
was performed in CH Cl . Other solvents such as THF,
3
2
chemistry of the product was deduced from the coupling
constants (J¼9.0, 9.0, 3.9 Hz) of the peak at d 2.86 (CH–
2
2
1
OMe) in the H NMR spectrum. We carried out this opening
reaction with MeOH in the presence of other Lewis acids
such as CuCl (24 h, 6% yield), SnCl (24 h, 8% yield),
ether, and acetonitrile gave inferior results. Aziridine
opening with chiral alcohols such as (2)-menthol (entry
13) and (R)-3-buten-2-ol (entry 14) was efficient, but the
diastereoselectivity was poor. Unfortunately, the cleavage
of aziridines could not be achieved by other tertiary
alcohols. Similarly, a-phenyl substituted hydroxyl com-
pounds such as 1-phenyl ethanol failed to affect the
cleavage reaction, possibly due to elimination as a side
2
2
FeCl3 (24 h, 32% yield), LiClO4 (24 h, 10% yield),
Cu(OTf) (24 h, 3% yield), AlCl (12 h, 35%) but very
poor yields were obtained. Some other Lewis acids such as
2
3
Keywords: aziridines; cleavage; hydroxyl compounds; b-amino ethers.
*
6
Corresponding author. Fax: þ91-512-597436; e-mail: vinodks@iitk.ac.in
reaction.
0040–4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)00609-9

7356
B. A. Bhanu Prasad et al. / Tetrahedron 58 (2002) 7355–7363
Table 1.
Entry
Aziridine
ROH
Conventional yield, % (time)
Microwave, 70 W, 15 min,
yield (%)
Sn(OTf)
2
BF ·Et
3
2
O
Sn(OTf)
2
3 2
BF ·Et O
1
2
3
4
5
6
7
8
9
MeOH
EtOH
99 (1 h)
99 (30 h)
99 (1 h)
99 (1/2 h)
90 (20 h)
89 (15 h)
68 (48 h)
Nil (5 d)
–
99 (1/2 h)
99 (3 h)
92 (1 h)
98 (1/2 h)
94 (2 h)
90 (2 h)
92 (10 h)
72 (48 h)
72 (3 h)
93
98
97
98
90
90
91
70
83
61
–
–
–
–
CH
HCuC–CG
PhCH OH (DCM)
O (MeCN)
2
vCH–CH
2
OH
OH
2
2
H
2
–
i-PrOH
t-BuOH
Cyclohexanol (DCM)
61
60
–
1
0
1
–
–
71 (3 h)
–
–
46
1
70 (3 h)
Nil
50
57
1
1
2
3
Phenol (in DCM)
(2)-Menthol (DCM)
–
–
–
–
a
a
82
92 (3 h)
b
b
80
14
–
92 (3 h)
–
15
16
17
18
19
MeOH
EtOH
i-PrOH
t-BuOH
PhOH (DCM)
99 (5 h)
98 (65 h)
–
–
–
99 (2 h)
98 (9 h)
67 (48 h)
76 (60 h)
Nil
–
–
–
–
–
97
97
68
92
40
c
91 (1 h)
c
20
21
22
23
24
MeOH
EtOH
i-PrOH
t-BuOH
PhOH (DCM)
–
–
–
–
–
–
–
–
–
–
89
87
54
42
40
c
89 (3 h)
c
c
c
c
c
64 (60 h)
c
68 (60 h)
Nil
d
98 (1/2 h)
d
99 (10 min)
d
d
d
d
d
2
2
2
2
2
5
6
7
8
9
MeOH
EtOH
i-PrOH
t-BuOH
PhOH (DCM)
–
–
–
–
–
92
90
82
84
54
d
94 (1/2 h)
d
99 (15 min)
d
83 (3 h)
–
–
–
d
88 (3 h)
Nil
e
96 (8 h)
f
97 (3 h)
f
3
3
3
3
0
1
2
3
MeOH
EtOH
i-PrOH
t-BuOH
–
–
–
–
98
96
g
92 (24 h)
g
98 (14 h)
e
h
67 (8 h)
h
–
–
55
86
i
68 (10 h)
i
j
76 (30 h)
j
96 (4 h)
3
4
5
MeOH
EtOH
–
–
–
–
f
74 (96 h)
f
96 (20 h)
3

B. A. Bhanu Prasad et al. / Tetrahedron 58 (2002) 7355–7363
7357
Table 1 (continued)
Entry
Aziridine
ROH
Conventional yield, % (time)
Microwave, 70 W, 15 min,
yield (%)
Sn(OTf)
2
BF ·Et
3
2
O
Sn(OTf)
2
3 2
BF ·Et O
k
36
37
38
39
40
41
42
43
44
MeOH
EtOH
n-PrOH
76 (10 min)
68 (10 min)
65 (15 min)
66 (24 h)
86 (15 min)
85 (15 min)
92 (20 min)
–
92 (10 min)
94 (10 min)
90 (15 min)
86 (2 h)
91 (5 min)
93 (5 min)
90 (20 min)
78 (10 min)
72 (10 min)
–
–
–
–
–
–
–
–
–
89
–
–
–
–
–
–
74
70
PhCH
CH vCH–CH
HCuC–CH OH
O (THF)
2
OH (DCM)
2
2
OH
2
H
2
k
k
i-PrOH
tBuOH
–
a
b
c
d
e
f
Diasteromeric ration 1:1.4.
Diastereomeric ration 1:1.6.
Exclusive attack on more substituted carbon.
Exclusive attack on benzylic carbon.
Slight preference for terminal attack; ratio is 60:40.
Slight preference for terminal attack; ratio is 58:42.
Slight preference for terminal attack; ratio is 61:39.
Slight preference for internal attack; ratio is 59:41.
Slight preference for internal attack; ratio is 58:42.
Slight preference for terminal attack; ratio is 63:37.
Time required is 1 min.
g
h
i
j
k
Having obtained the success in the opening reaction of
N-tosylcyclohexyl aziridine with a range of hydroxyl
compounds, the reaction was extended to a variety of
aziridines and the results are summarized in Table 1. The
cleavage reaction of N-tosylcyclopentyl aziridine was
equally facile (entries 15–18). In the case of a trisubstituted
aziridine, the hydroxyl compounds attacked exclusively at
the more substituted carbon (entries 20–23). In the case of a
phenyl substituted N-tosyl aziridine (entries 25–28), only a
single product was obtained due to attack of the alcohols at
complete in 15 min. With most of the alcohols, yields were
comparable or little less in comparison to conventional
methods. However, the noteworthy feature was the cleavage
reaction with phenols, which under conventional conditions,
failed to open aziridines. Under MW irradiation, the
cleavage of aziridines by phenol took place and a modest
yield of the products was obtained (entries 12, 19, 24, and
29). Under MW conditions also, we observed the elimin-
ation reactions as was found in conventional process for the
a-phenyl secondary and tertiary alcohols. Except t-BuOH,
all other tertiary alcohols underwent dehydration leading to
olefins. These microwave reactions were also tried with
other Lewis acids such as Sn(OTf) and Cu(OTf) . Whereas
1
the benzylic carbon (confirmed by H NMR spectroscopy
and HPLC). In the case of alkyl substituted acyclic N-tosyl
aziridines, terminal attack was slightly favored for primary
alcohols (entries 30, 31, 34, and 35) whereas internal attack
was slightly favored for hindered alcohols (entries 32 and
2
2
moderate yields were obtained with Sn(OTf) , the reaction
2
did not proceed at all with Cu(OTf) . Since BF ·Et O was
2
3
2
3
3). N-Phenylcyclohexyl aziridine could effectively be
more efficient than Sn(OTf) , we carried out all the
2
cleaved using a variety of hydroxyl compounds in high
yield (entries 36–44). The aziridine ring-opening reaction
with hydroxyl compounds was much faster with BF ·OEt
microwave reactions with BF ·Et O (Table 1).
3
2
In summary, we have described a simple and efficient
method for cleavage of activated aziridines with a variety of
hydroxyl compounds. The noteworthy feature of the
reaction is that hindered alcohols can also cleave aziridines
in high yield. With the help of microwave irradiations,
aziridines can be opened with phenols.
3
2
in comparision with Sn(OTf) . It was also observed that
2
N-alkyl substituted azirdines could not be opened under the
above conditions. It was also noticed that phenols failed to
cleave aziridines under the above conditions.
In view of some of the failures in the above reactions, it was
thought to study the same process under microwave
irradiation. The application of microwave (MW) irradiation
to activate and accelerate organic reactions has experienced
exponential growth in the last decade. Microwave mediated
organic reactions takes place more rapidly, safely with high
yields, and are environmentally friendly. Because of its
efficiency and its potential to contribute to clean products,
MW chemistry is becoming increasingly popular both in
industry and in academia. The cleavage of aziridines by
hydroxyl compounds was studied in the presence of some
Lewis acids under MW irradiation also and the results are
compared with the conventional method (Table 1). It was
observed that most of reactions were very facile and
1. Experimental
1
H NMR spectra were recorded on Jeol and Bruker, as
mentioned in the experimental, using TMS as internal
standard. Chemical shifts are reported in ppm, and coupling
constants are reported in Hz. IR spectra were recorded on
Perkin–Elmer 580 and 1320 spectrometers. Microwave
reactions were done in MLS-1200 Mega, Milestone with
MDR (MW digestive rotor) technology. MW power
frequency 2450 MHz power of mW generating magnetron
1200 W. HPLC was done on a Perkin–Elmer machine.
7
,8

7358
B. A. Bhanu Prasad et al. / Tetrahedron 58 (2002) 7355–7363
1
Routine monitoring of reactions was performed using silica
gel-G obtained from Acme. All the chromatographic
separations were done by using silica gel (Acme’s, 100–
H NMR (CDCl , 400 MHz) d 1.01–1.35 (m, 4H), 1.49–
3
1.61 (m, 2H), 1.92–1.95 (m, 1H), 2.12–2.19 (m, 1H), 2.35
(s, 3H), 2.81 (m, 1H), 3.01 (ddd, J¼9.5, 9.3, 3.6 Hz, 1H),
3.69–3.74 (m, 1H), 3.89–3.94 (m, 1H), 4.90 (d, J¼2.7 Hz,
1H), 5.05–5.12 (m, 2H), 5.72 (m, 1H), 7.22 (d, J¼8.5 Hz,
2
8
00 mesh). Petroleum ether used was of boiling range 60–
08C. Reactions, which needed anhydrous conditions, were
1
3
run under an atmosphere of dry nitrogen or argon using
flame-dried glass wares. The organic layer was washed with
brine and stored over anhydrous Na SO for 30 min before
2H), 7.68 (d, J¼8.5 Hz, 2H); C NMR (CDCl , 100 MHz)
3
d 21.5, 23.4, 23.6, 29.3, 31.2, 57.1, 69.1, 79.3, 116.9, 127.2,
129.5, 134.5, 137.8, 143.1; LCMS (EI, m/z) 309 (M þ1).
þ
Anal. calcd for C H NO S: C, 62.33, H, 7.46, N, 4.54.
Found: C, 62.45, H, 7.51, N, 4.52.
2
4
use. Evaporation of solvents was performed at reduced
pressure, using a B u¨ chi rotary evaporator.
1
6
23
3
1
.1. General procedure for cleavage of aziridines with
hydroxyl compounds under conventional condition
1.2.4. trans-N-(2-Prop-2-ynyloxycyclohexyl)-4-methyl
benzenesulfonamide (entry 4). Colorless viscous liquid;
R 0.63 (20% EtOAc in petroleum ether); IR (neat) 3195,
f
2810, 1595, 1310, 1051 cm2 ; H NMR (CDCl , 400 MHz)
1 1
A solution of a N-tosyl aziridine (1 mmol) and a Lewis acid
10 mol%) in an alcohol (1 mL) was stirred at room
3
(
d 1.07–1.31 (m, 4H), 1.59–1.68 (m, 2H), 2.02 (m, 1H), 2.20
(m, 1H), 2.42 (s, 3H), 2.48 (t, J¼2.4 Hz, 1H), 2.87 (ddd,
J¼9.5, 8.5, 3.9 Hz, 1H), 3.2 (ddd, J¼9.5, 9.3, 3.9 Hz, 1H),
4.02 (ABq, J¼16.0, 2H), 5.09 (d, J¼3.7 Hz, 1H, NH ), 7.29
(d, J¼8.6 Hz, 2H), 7.77 (d, J¼8.3 Hz, 2H); LCMS (EI, m/z )
temperature for 1 h. Most of the alcohol was removed in
vacuo and the crude reaction mixture was directly loaded
over silica gel for column chromatography. If the hydroxyl
compound is high boiling, it (1 mmol) was dissolved in a
suitable solvent as mentioned in Table 1.
þ
307 (M þ1), 265. Anal. calcd for C H NO S: C, 62.74,
1
6
21
3
H, 6.86, N, 4.57. Found: C, 62.78, H, 6.80, N, 4.52.
1.2. General procedure for cleavage of aziridines with
hydroxyl compounds under microwave irradiation
1.2.5. trans-N-(2-Benzyloxycyclohexyl)-4-methyl ben-
zenesulfonamide (entry 5). White crystalline solid; mp
70–728C; R 0.61 (20% EtOAc in petroleum ether); IR
A solution of a N-tosyl aziridine (1 mmol) and a Lewis acid
f
(KBr) 3298, 2932, 1324, 1161 cm2 ; H NMR (CDCl ,
1
1
(
10 mol%) in an alcohol (1 mL) was taken in a teflon vessel
and irradiated in a microwave oven at 70 W power for
5 min at room temperature. Most of the alcohol was
3
400 MHz) d 1.23–1.28 (m, 4H), 1.73 (m, 2H), 2.10–2.12
(m, 1H), 2.20–2.27 (m, 1H), 2.42 (s, 3H), 2.97 (ddd, J¼9.3,
9.8, 3.6 Hz, 1H), 3.19 (ddd, J¼9.3, 9.0, 4.2 Hz, 1H), 4.34 (d,
J¼11.7 Hz, 1H), 4.56 (d, J¼11.7 Hz, 1H), 4.89 (d,
J¼3.16 Hz, 1H), 7.25 (m, 4H), 7.33–7.41 (m, 3H), 7.73
1
removed in vacuo and the crude reaction mixture was
directly loaded over silica gel for column chromatography.
If the hydroxyl compound is high boiling, it (1 mmol) was
dissolved in a suitable solvent as mentioned in Table 1.
1
3
(d, J¼8.3 Hz, 2H); C NMR (CDCl , 100 MHz) d 21.4,
3
23.4, 29.4, 31.5, 56.9, 65.0, 70.1, 79.1, 126.8, 127.5, 128.2,
129.3, 137.1, 138.1, 142.9; LCMS (EI, m/z ) 358 (M ).
þ
Anal. calcd for C H NO S: C, 67.03, H, 6.98, N, 3.91.
Found: C, 67.25, H, 6.87, N, 3.98.
1
.2.1. trans-N-(2-Methoxycyclohexyl)-4-methyl benzene-
sulfonamide (entry 1). White solid; mp 60–628C; R 0.63
f
20 25
3
(
1
20% EtOAc in petroleum ether); IR (KBr) 3263, 1317,
152, 1100 cm2 ; H NMR (CDCl , 400 MHz) d 0.99–1.18
1 1
3
(
1
(
7
m, 4H), 1.52 (m, 1H), 1.61 (m, 1H), 1.96 (m, 1H), 2.12 (m,
H), 2.35 (s, 3H), 2.78 (ddd, J¼9.0, 9.0, 3.9 Hz, 1H), 2.86
1.2.6. trans-N-(2-Hydroxycyclohexyl)-4-methyl benzene-
sulfonamide (entry 6). White solid; mp 128–1308C; Rf
0.40 (40% EtOAc in petroleum ether); IR (neat) 3547, 3266,
ddd, J¼9.0, 9.0, 3.9 Hz, 1H), 3.12 (s, 3H), 5.03 (s, 1H),
1
3
21
1
.22 (d, J¼8.3 Hz, 2H), 7.69 (d, J¼8.3 Hz, 2H); C NMR
3047, 1320, 1152 cm ; H NMR (CDCl , 400 MHz) d
3
(
CDCl , 100 MHz) d 21.5, 23.4, 23.6, 28.6, 31.0, 55.8, 57.0,
3
1.11–1.28 (m, 4H), 1.58–1.73 (m, 3H), 2.00–2.05 (m, 1H),
2.43 (s, 3H), 2.68 (bs, 1H), 2.84 (m, 1H), 3.30 (ddd,
J¼10.10, 4.4 Hz, 1H), 4.95 (d, J¼7.1 Hz, 1H), 7.32 (d,
þ
Anal. calcd for C H NO S: C, 59.57, H, 7.44, N, 4.96.
Found: C 59.75, H, 7.46, N, 4.97.
8
1.3, 127.2, 129.5, 137.3, 143; LCMS (EI, m/z) 283 (M ).
1
4
21
3
1
3
J¼8.0 Hz, 2H), 7.79 (d, J¼8.0 Hz, 2H); C NMR (CDCl ,
3
100 MHz) d 21.5, 23.7, 24.6, 31.8, 33.3, 59.6, 73.3, 127.1,
129.8, 137.2, 143.6; LCMS (EI, m/z) 268 (M ). Anal. calcd
þ
for C H NO S: C, 58.20, H, 7.08, N, 5.22. Found: C,
58.23, H, 7.00, N, 5.28.
1.2.2. trans-N-(2-Ethoxycyclohexyl)-4-methyl benzene-
sulfonamide (entry 2). White powder; mp 94–968C; Rf
0
1
13
19
3
.54 (20% EtOAc in petroleum ether); IR (KBr) 3582, 3266,
2
1 1
326, 1162, 1098 cm ; H NMR (CDCl , 400 MHz) d 1.02
3
(
(
(
4
2
2
t, J¼6.8 Hz, 3H), 1.02–1.18 (m, 4H), 1.56 (m, 2H), 1.95
m, 1H), 2.10–2.17 (m, 1H), 2.35 (s, 3H), 2.76 (m, 1H), 2.94
ddd, J¼9.7, 9.5, 3.6 Hz, 1H), 3.19 (m, 1H), 3.46 (m, 1H),
1.2.7. trans-N-(2-Isopropoxycyclohexyl)-4-methyl ben-
zenesulfonamide (entry 7). White solid; mp 89–918C; Rf
0.65, (20% EtOAc in petroleum ether); IR (KBr) 3236,
3047, 1163, 810 cm2 ; H NMR (CDCl , 400 MHz) d 1.05
1 1
.93 (s, 1H), 7.22 (d, J¼8.5 Hz, 2H), 7.69 (d, J¼8.5 Hz,
3
1
3
H); C NMR (CDCl , 100 MHz) d 15.4, 21.5, 23.6, 23.7,
3
(d, J¼6.1 Hz, 3H), 1.08 (d, J¼6.1 Hz, 3H), 1.12–1.28 (m,
4H), 1.56 (m, 1H), 1.66 (m, 1H), 1.95 (m, 1H), 2.20 (m, 1H),
2.42 (s, 3H), 2.79 (ddd, J¼9.3, 10.3, 3.7 Hz, 1H), 3.08 (ddd,
J¼9.5, 9.3, 4.4 Hz, 1H), 3.64 (heptet, J¼6.1 Hz, 1H), 4.86
9.4, 31.3, 57.2, 63.5, 79.7, 127.2, 129.5, 137.1, 143.1;
þ
LCMS (EI, m/z ) 297 (M þ1). Anal. calcd for C H NO S:
1
5
23
3
C, 60.81, H, 7.77, N, 4.72. Found: C 60.68, H, 7.81, N, 4.73.
(
d, J¼4.2 Hz, 1H), 7.29 (d, J¼8.3 Hz, 2H), 7.75 (d,
þ
for C H NO S: C, 61.93, H, 8.06, N, 4.51. Found: C,
62.15, H, 8.00, N, 4.58.
1.2.3. trans-N-(2-Allyloxycyclohexyl)-4-methyl benzene-
sulfonamide (entry 3). Viscous liquid; R 0.63 (20% EtOAc
in petroleum ether); IR (neat) 3180, 1591, 1300, 1062 cm2
J¼8.3 Hz, 2H); LCMS (EI, m/z) 310 (M ). Anal. calcd
f
16 25
3
1
;

B. A. Bhanu Prasad et al. / Tetrahedron 58 (2002) 7355–7363
7359
1.2.8. trans-N-(2-tert-Butoxycyclohexyl)-4-methyl ben-
zenesulfonamide (entry 8). White solid; mp 78–818C Rf
1.2.13. trans-N-(2)-[2-(2-Isopropyl-5-methylcyclohexyl)-
cyclohexyl]-4-methyl benzenesulfonamide (entry 13).
Diastereomeric ratio 1:1.4.
0
1
1
1
4
.65 (20% EtOAc in petroleum ether); IR (KBr) 3259, 1330,
084 cm2 ; H NMR (CDCl , 400 MHz) d 1.14 (s, 9H),
1 1
3
.18–1.33 (m, 4H), 1.52 (m, 1H), 1.62 (m, 1H), 1.86 (m,
H), 2.15 (m, 1H), 2.42 (s, 3H), 2.78 (ddd, J¼9.3, 8.3,
.2 Hz, 1H), 3.24 (ddd, J¼8.8, 8.6, 4.2 Hz, 1H), 4.74 (d,
Diastereomer I. Yield 53%; white solid; mp 130–1328C, R
2
f
5
D
0.53 (20% EtOAc in petroleum ether); [a] ¼281.4 (c 0.6,
2
1
1
CHCl ); IR (KBr) 3320, 2930, 1152 cm
3
;
H NMR
J¼3.9 Hz, 1H), 7.29 (d, J¼8.5 Hz, 2H), 7.75 (d, J¼8.5 Hz,
(CDCl , 400 MHz): d 0.62 (d, J¼7.1 Hz, 3H), 0.82 (d,
3
13
2
3
H); C NMR (CDCl , 100 MHz) d 21.5, 23.4, 28.7, 29.6,
3
J¼7.1 Hz, 3H), 0.91 (d, J¼6.6 Hz, 3H), 0.64–1.29 (m, 9H),
1.56–1.68 (m, 5H), 1.88–2.01 (m, 3H), 2.24 (m, 1H), 2.41
(s, 3H), 2.71–2.78 (m, 1H), 3.06 (ddd, J¼10.0, 10.0, 3.9 Hz,
1H), 3.15 (ddd, J¼9.7, 9.7, 4.1 Hz, 1H), 4.93 (d, J¼2.2 Hz,
0.9, 33.1, 57.2, 72.3, 74.0, 127.2, 129.5, 137.3, 143.1;
þ
LCMS (EI, m/z) 324 (M ). Anal. calcd for C H NO S:
3
1
7
27
C, 62.96, H, 8.33, N, 4.32. Found: C, 63.10, H, 8.28, N,
4
1
3
.25.
1H), 7.27 (d, J¼8.3 Hz, 2H), 7.74 (d, J¼8.3, 2H); C NMR
(CDCl , 100 MHz) d 15.8, 21.1, 21.6, 22.2, 23, 23.6, 23.6,
3
1.2.9. trans-N-(2-Cyclohexyloxycyclohexyl)-4-methyl
benzenesulfonamide (entry 9). White solid; mp 74–
24.8, 29.6, 31.3, 31.5, 34.4, 40.3, 48.1, 57.5, 73.9, 74.6,
127.3, 129.3, 136.9, 142.9; LCMS (EI, m/z) 406 (M ), 268,
þ
154, 113. Anal. calcd for C H NO S: C, 67.98, H, 9.11, N,
3.44. Found: C, 68.01, H, 9.15, N, 3.41.
7
3
68C; R 0.55 (20% EtOAc in petroleum ether); IR (KBr)
f
23 37
3
1 1
240, 1160 cm2 ; H NMR (CDCl , 400 MHz) d 1.07–1.28
3
(
2
1
(
m, 10H), 1.52–1.70 (m, 5H), 1.83 (m, 1H), 1.95 (m, 1H),
.21 (m, 1H), 2.42 (s, 3H), 2.79 (ddd, J¼10.5, 9.0, 3.2 Hz,
Diastereomer II. Yield 38%; colorless liquid; R 0.50 (20%
f
2
5
H), 3.12 (ddd, J¼9.5, 9.3, 4.1 Hz, 1H), 3.27 (m, 1H), 4.93
EtOAc in petroleum ether); [a] ¼227.6 (c 0.5, CHCl );
D
3
IR (neat) 3275, 2933, 1166 cm2
1
;
1
H NMR (CDCl ,
3
d, J¼2.2 Hz, 1H), 7.29 (d, J¼8.3 Hz, 2H), 7.70 (d,
1
3
J¼8.3 Hz, 2H); C NMR (CDCl , 100 MHz) d 21.4,
400 MHz) d 0.79 (d, J¼6.8 Hz, 3H), 0.87 (d, J¼6.6 Hz,
3H), 0.90 (d, J¼7.1 Hz, 3H), 0.72–1.30 (m, 9H), 1.49 (m,
1H), 1.57–1.67 (m, 4H), 1.85 (m, 2H), 2.11 (m, 2H), 2.42 (s,
3H), 2.93 (m, 1H), 3.06 (ddd, J¼10.2, 10.3, 4.1 Hz, 1H),
3.15 (m, 1H), 4.92 (d, J¼3.9 Hz, 1H), 7.29 (d, J¼8.0 Hz,
3
2
7
3.6, 24.0, 24.1, 25.5, 29.6, 30.6, 31.2, 32.0, 33.6, 57.4,
5.0, 77.04, 127.2, 129.5, 137.2, 143.0. Anal. calcd for
C H NO S: C, 65.14, H, 8.28, N, 4.0. Found: C, 65.20, H,
1
9
29
3
8
.31, N, 3.94.
1
3
2
H), 7.74 (d, J¼8.3 Hz, 2H); C NMR (CDCl , 100 MHz)
3
1.2.10. trans-N-[2-(1-Vinylhexyloxy)-cyclohexyl]-4-
methyl benzenesulfonamide (entry 10). Viscous liquid;
d 15.7, 21.3, 21.5, 22.3, 22.7, 25.2, 29.7, 31.0, 31.5, 34.2,
42.6, 48.7, 56.1, 77.5, 78.2, 127.2, 127.2, 129.5, 137.2,
143.2. Anal. calcd for C H NO S: C, 67.98, H, 9.11, N,
R 0.52 (20% EtOAc in petroleum ether); IR (neat) 3230,
f
23 37
3
1
1
1
3
651, 1140 cm2 ; H NMR (CDCl , 400 MHz) d 0.88 (m,
3.44. Found: C, 67.99, H, 9.09, N, 3.45.
3
H), 1.03–1.36 (m, 10H), 1.60 (m, 2H), 1.92 (m, 1H), 2.21
(
3
1
m, 1H), 2.41 (s, 3H), 2.42 (s, 3H), 2.80–2.94 (m, 1H),
1.2.14. trans-N-[2-(1-Vinylethoxy)-cyclohexyl]-4-methyl
benzenesulfonamide (entry 14). Diastereomeric ratio:
1:1.6.
.04–3.11 (m, 1H), 3.60–3.70 (m, 1H), 4.82 (d, J¼3.2 Hz,
H), 4.87 (d, J¼3.9 Hz, 1H), 5.02–5.20 (m, 2H), 5.48– 5.66
(m, 1H), 7.29 (m, 2H), 7.75 (m, 2H). Anal. calcd for
C H NO S: C, 66.84, H, 8.75, N, 3.71. Found: C, 66.97,
H, 8.77, N, 3.68.
Diastereomer I. Yield 56%; colorless liquid; R 0.52 (20%
f
2
1
33
3
2
5
EtOAc in petroleum ether); [a ] ¼þ6.67 (c 0.5, MeOH);
D
IR (KBr) 3305, 2931, 1564, 1159 cm2 ; H NMR (CDCl ,
1 1
3
1
.2.11. trans-N-[2-(Indan-2-yloxy)-cyclohexyl]-4-methyl
benzenesulfonamide (entry 11). White crystalline solid;
400 MHz) d 1.07 (d, J¼6.3 Hz, 3H), 1.08–1.22 (m, 2H),
1.59 (m, 4H), 1.97 (m, 1H), 2.21 (m, 1H), 2.42 (s, 3H), 3.08
(ddd, J¼9.8, 9.3, 4.4 Hz, 1H), 3.83–3.90 (m, 1H), 4.81 (s,
1H), 5.10–5.17 (m, 2H), 5.54–5.63 (m, 1H), 7.28 (d,
mp 118–1208C; R 0.40 (20% EtOAc in petroleum ether);
f
IR (neat) 3272, 1281, 1153, 1085 cm ; H NMR (CDCl ,
3
2
1 1
1
3
4
2
3
3
7
1
7
4
00 MHz) d 1.10–1.31 (m, 4H), 1.58 (m, 1H), 1.66 (m, 1H),
.02 (m, 1H), 2.22 (m, 1H), 2.36 (s, 3H), 2.71–2.88 (m, 3H),
.00 (dd, J¼16.1, 6.1 Hz, 2H), 3.15 (ddd, J¼9.0, 9.0,
.9 Hz, 1H), 4.36 (m, 1H), 4.84 (d, J¼3.4 Hz, 1H), 7.14–
J¼8.5 Hz, 2H), 7.75 (d, J¼8.1 Hz, 2H); C NMR (CDCl3,
100 MHz) d 21.5, 21.8, 23.6, 23.7, 29.6, 31.6, 57.3, 73.9,
76.2, 117.1, 127.2, 129.4, 137.3, 139.9, 143.0. Anal. calcd
for C H NO S: C, 63.15, H, 7.73, N, 4.33. Found: C,
1
7
25
3
1
3
.25 (m, 6H), 7.52 (d, J¼8.3 Hz, 2H); C NMR (CDCl ,
63.20, H, 7.71, N, 4.35.
3
00 MHz) d 21.4, 23.6, 29.6, 30.1, 31.5, 39.2, 40.5, 57.2,
7.8, 124.5, 124.8, 126.6, 126.7, 127.1, 129.4, 136.9, 140.1,
1.0, 142.9. Anal. calcd for C H NO S: C, 68.75, H, 7.03,
Diastereomer II. Yield 35%; white solid; mp 78–808C; R
2
f
5
D
0.48 (20% EtOAc in petroleum ether); [a] ¼þ12.0 (c
2
2
27
3
0.75, MeOH); IR (neat) 3325, 2932, 1560, 1160 cm2 ; H
1 1
N, 3.64. Found: C, 68.89, H, 7.06, N, 3.58.
NMR (CDCl , 400 MHz) d 1.14 (d, J¼6.3 Hz, 3H), 1.15–
3
1.2.12. trans-N-(2-Phenoxycyclohexyl)-4-methyl ben-
zenesulfonamide (entry 12). White solid; mp 116–
1.25 (m, 2H), 1.53–1.65 (m, 4H), 1.90 (m, 1H), 2.13
(m, 1H), 2.42 (s, 3H), 2.89 (m, 1H), 3.11 (ddd, J¼8.8,
8.8, 4.1 Hz, 1H), 3.91 (m, 1H), 4.81 (s, 1H), 4.99–5.08
(m, 2H), 5.65– 5.73 (m, 1H), 7.29 (d, J¼8.3 Hz, 2H),
1
3
1
188C; R 0.61 (20% EtOAc in petroleum ether); IR (neat)
f
286 cm2 ; H NMR (CDCl , 400 MHz) d 1.33 (m, 4H),
1 1
3
1
3
.66 (m, 2H), 2.03 (m, 1H), 2.16 (m, 1H), 2.41 (s, 3H), 3.71
7.76 (d, J¼8.3 Hz, 2H); C NMR (CDCl , 100 MHz) d
3
(
2
m, 1H), 4.03 (m, 1H), 5.22 (m, 1H), 6.69 (d, J¼7.8 Hz,
H), 6.91 (m, 5H), 7.76 (m, 2H). Anal. calcd for
C H NO S: C, 66.27, H, 6.68, N, 4.06. Found: C, 66.34,
21, 21.5, 23.4, 23.5, 30.9, 31.2, 57.2, 75.6, 77.8, 114.7,
127.2, 129.6, 137.3, 140.8, 143.2. Anal. calcd for
C H NO S: C, 63.15, H, 7.73, N, 4.33. Found: C, 63.37,
1
9
23
3
17 25
3
H, 6.62, N, 4.00.
H, 7.70, N, 4.30.

7360
B. A. Bhanu Prasad et al. / Tetrahedron 58 (2002) 7355–7363
1.2.15. trans-N-(2-Methoxycyclopentyl)-4-methyl ben-
zenesulfonamide (entry 15). White solid; mp 40–428C;
154–1568C; R 0.56 (20% EtOAc in petroleum ether); IR
f
(KBr) 3276, 1163 cm2 ; H NMR (CDCl , 400 MHz) d
1 1
3
R 0.56 (20% EtOAc in petroleum ether); IR (neat) 3250,
f
1.09 (s, 3H), 1.20–1.62 (m, 8H), 2.42 (s, 3H), 2.98 (s, 3H),
3.10 (m, 1H), 4.77 (d, J¼5.1 Hz, 1H), 7.29 (d, J¼8.3 Hz,
1 1
323, 1152 cm2 ; H NMR (CDCl , 400 MHz) d 1.23–1.31
1
3
1
3
(
3
m, 1H), 1.41–1.56 (m, 3H), 1.70–1.85 (m, 2H), 2.34 (s,
H), 3.10 (s, 3H), 3.35 (m, 1H), 3.46 (m, 1H), 5.10 (d,
2H), 7.76 (d, J¼8.3 Hz, 2H); C NMR (CDCl , 100 MHz)
3
d 18.1, 21.5, 21.9, 22.6, 28.3, 33, 48.1, 57.4, 75.8, 127.2,
129.5, 137.5, 143.1. Anal. calcd for C H NO S: C, 60.81,
H, 7.77, N, 4.72. Found: C, 60.74, H, 7.70, N, 4.80.
J¼6.3 Hz, 1H), 7.22 (d, J¼8.3 Hz, 2H), 7.72 (d, J¼8.3 Hz,
1
5
23
3
1
3
2
5
2
H); C NMR (CDCl , 100 MHz) d 20.9, 21.4, 29.0, 30.8,
3
6.8, 59, 86.8, 127.1, 129.6, 137.4, 143.3; LCMS (EI, m/z)
þ
69 (M þ1), 237, 209, 171, 154, 113, 71. Anal. calcd for
1.2.21. trans-N-(2-Ethoxy-2-methylcyclohehexyl)-4-
methyl benzenesulfonamide (entry 21). White solid; mp
85–878C; R 0.56 (20% EtOAc in petroleum ether); IR
C H NO S: C, 58.20, H, 7.08, N, 5.22. Found: C, 58.39,
1
3
19
3
H, 7.01, N, 5.17.
f
(
KBr) 3278, 1162 cm2 ; H NMR (CDCl , 400 MHz) d
1
1
3
1
.2.16. trans-N-(2-Ethoxycyclopentyl)-4-methyl benzene-
sulfonamide (entry 16). White solid; mp 55–588C; R 0.52
1.01 (t, J¼6.8 Hz, 3H), 1.11 (s, 3H), 1.23–1.63 (m, 8H),
2.42 (s, 3H), 3.06 (m, 1H), 3.11–3.20 (m, 1H),3.22–3.30
(m, 1H), 7.29 (d, J¼8.3 Hz, 2H), 7.76 (d, J¼8.3 Hz, 2H);
f
(
20% EtOAc in petroleum ether); IR (neat) 3249, 1322,
077 cm2 ; H NMR (CDCl , 400 MHz) d 1.0 (t, J¼7.0 Hz,
1 1
13
C NMR (CDCl , 100 MHz) d 15.8, 18.5, 21.5, 22, 22.6,
3
1
3
2
3
2
3
H), 1.25–1.32 (m, 1H), 1.40–1.48 (m, 1H), 1.50–1.57 (m,
H), 1.71–1.85 (m, 2H), 2.35 (s, 3H), 3.24–3.36 (m, 3H),
.55 (m, 1H), 5.06 (d, J¼6.1 Hz, 1H), 7.23 (d, J¼8.1 Hz,
28.3, 33.8, 55.6, 58.0, 75.6, 127.2, 129.5, 137.4, 143.1.
Anal. calcd for C H NO S: C, 61.93, H, 8.06, N, 4.51.
Found: C, 62.08, H, 8.13, N, 4.42.
1
6
25
3
1
3
H), 7.71 (d, J¼8.0 Hz, 2H); C NMR (CDCl , 100 MHz)
3
d 15.3, 20.9, 21.4, 29.5, 30.7, 59.3, 64.6, 84.9, 127.1, 129.5,
1
1.2.22. trans-N-(2-Isopropoxy-2-methylcyclohehexyl)-4-
methyl benzenesulfonamide (entry 22). Colorless liquid;
R 0.56 (20% EtOAc in petroleum ether); IR (neat) 3276,
þ
Anal. calcd for C H NO S: C, 59.57, H, 7.44, N, 4.96.
Found: C, 59.71, H, 7.40, N, 5.02.
37.4, 143.2; LCMS (EI, m/z) 282 (M ), 232, 155, 131.
1
4
21
3
f
1160 cm2
1
;
1
H NMR (CDCl , 400 MHz) d 0.96 (d,
3
J¼7.3 Hz, 3H), 1.02 (d, J¼6.1 Hz, 3H), 1.12 (s, 3H),
1.18–1.28 (m, 4H), 1.32–1.67 (m, 3H), 2.02 (m, 1H), 2.42
(s, 3H), 2.98 (m, 1H), 3.74 (heptet, J¼6.1 Hz, 1H), 4.88 (d,
J¼3.9 Hz, 1H), 7.28 (d, J¼8.3 Hz, 2H), 7.76 (d, J¼8.3 Hz,
1.2.17. trans-N-(2-Isopropoxycyclopentyl)-4-methyl ben-
zenesulfonamide (entry 17). Colorless viscous liquid; Rf
0
1
.61 (20% EtOAc in petroleum ether); IR (neat) 3235, 1377,
1
163, 1083 cm2 ; H NMR (CDCl , 400 MHz) d 0.95 (d,
1
2H); LCMS (EI, m/z) 324 (M ). Anal. calcd for
þ
3
J¼1.4 Hz, 3H), 0.97 (d, J¼1.5 Hz, 3H), 1.15–1.61 (m, 4H),
C H NO S: C, 63.74, H, 8.36, N, 4.30. Found: C, 62.38,
1
H, 8.33, N, 4.32.
7
27
3
1
3
4
.78 (m, 2H), 2.35 (s, 3H), 3.27 (quintet, J¼6.0 Hz, 1H),
.47 (heptet, J¼6.1 Hz, 1H), 3.63 (dt, J¼6.3, 4.6 Hz, 1H),
.66 (d, J¼5.6 Hz, 1H), 7.23 (d, J¼8.5 Hz, 2H), 7.71 (d,
1.2.23. trans-N-(2-tert-Butoxy-2-methylcyclohexyl)-4-
methyl benzenesulfonamide (entry 23). Colorless liquid;
R 0.56 (20% EtOAc in petroleum ether); IR (neat) 3275,
þ
J¼8.3, 2H); LCMS (EI, m/z) 296 (M ), 236, 141. Anal.
calcd for C H NO S: C, 60.81, H, 7.70, N, 4.72. Found: C,
1
5
23
3
f
1166 cm2 ; H NMR (CDCl , 400 MHz) d 1.23 (s, 9H),
1
1
6
0.77, H, 7.75, N, 4.77.
3
1.29 (s, 3H), 1.30 (m, 3H), 1.42–1.51 (m, 1H), 1.56–1.70
(m, 3H), 1.80–1.87 (m, 1H), 2.42 (s, 3H), 3.34 (ddd,
1.2.18. trans-N-(2-tert-Butoxycyclopentyl)-4-methyl ben-
zenesulfonamide (entry 18). Colorless liquid; R 0.61 (20%
EtOAc in petroleum ether); IR (neat) 3232, 1165,
J¼12.7, 8.3, 4.1 Hz, 1H), 5.21 (d, J¼8.3 Hz, 1H), 7.29 (d,
f
1
3
J¼8.5 Hz, 2H), 7.79 (d, J¼8.5 Hz, 2H); C NMR (CDCl ,
3
2
1
1
8
1
2
15 cm ; H NMR (CDCl , 400 MHz) d 1.02 (s, 9H),
3
100 MHz) d 21.4, 21.8, 21.9, 29.3, 29.6, 30.1, 31.3, 35.4,
35.6, 94.4, 96.2, 127, 129.5, 137.7, 143.2. Anal. calcd for
C H NO S: C, 63.90, H, 8.57, N, 4.14. Found: C, 63.94,
.26–1.37 (m, 2H), 1.45–1.63 (m, 2H), 1.75–1.87 (m, 2H),
.35 (s, 3H), 3.17 (quintet, J¼6.6 Hz, 1H), 3.70 (q,
1
8
29
3
J¼5.6 Hz, 1H), 5.14 (d, J¼6.1 Hz, 1H), 7.22 (d, J¼8 Hz,
H, 8.55, N, 4.10.
1
3
2
d 20.2, 21.4, 28.3, 29.7, 31.4, 60.7, 73.4, 77.2, 127.1, 129.4,
H), 7.73 (d, J¼8.3 Hz, 2H); C NMR (CDCl , 100 MHz)
3
1.2.24. trans-N-(2-Phenoxy-2-methylcyclohexyl)-4-
methyl benzenesulfonamide (entry 24). Viscous liquid,
R 0.55 (20% EtOAc in petroleum ether); IR (neat) 3286,
137.4, 143. Anal. calcd for C H NO S: C, 61.93, H, 8.06,
16 25 3
N, 4.51. Found: C, 62.12, H, 7.99, N, 4.55.
f
3
030 cm2 ; H NMR (CDCl , 400 MHz) d 1.21–1.33 (m,
1
1
3
1
.2.19. trans-N-(2-Phenoxycyclopentyl)-4-methyl ben-
zenesulfonamide (entry 19). White crystalline solid; mp
01–1048C; R 0.52 (20% EtOAc in petroleum ether); IR
4H), 1.53–1.64 (m, 3H), 1.60 (s, 3H), 2.13 (m, 1H), 3.36 (m,
1H), 4.98 (d, J¼5.4 Hz, 1H), 6.75 (d, J¼7.5 Hz, 2H), 7.28
(m, 5H), 7.79 (m, 2H). Anal. calcd for C H NO S: C,
1
f
20 25
3
2
1 1
(
KBr) 3285, 1326, 1084 cm ; H NMR (CDCl , 400 MHz)
3
68.82, H, 7.01, N, 3.90. Found: C, 68.68, H, 7.13, N, 3.82.
d 1.39–1.47 (m, 1H), 1.67–1.81 (m, 3H), 1.97–2.08 (m,
H), 2.38 (s, 3H), 3.67 (m, 1H), 4.51 (m, 1H), 4.93 (d,
2
1.2.25. trans-N-(2-Methoxy-2-phenylethyl)-4-methyl
benzenesulfonamide (entry 25). White solid; mp 63–
658C; R 0.56 (20% EtOAc in petroleum ether); IR (KBr)
J¼6.3 Hz, 1H), 6.75 (m, 2H), 6.91 (m, 1H), 7.23 (m, 4H),
þ
71, 154, 91. Anal. calcd for C H NO S: C, 65.45, H,
.36, N, 4.24. Found: C, 65.38, H, 6.32, N, 4.28.
7
1
6
.74 (d, J¼8.3 Hz, 2H); LCMS (EI, m/z) 330 (M ), 237,
f
3456, 1327, 1090 cm2 ; H NMR (CDCl , 400 MHz) d 2.34
1 1
1
8
21
3
3
(s, 3H), 2.87 (m, 1H), 3.09 (s, 3H), 3.09–3.16 (m, 1H), 4.12
(
dd, J¼9.3, 3.4 Hz, 1H), 4.97 (m, 1H), 7.12 (m, 2H), 7.23
1
3
1.2.20. trans-N-(2-Methoxy-2-methylcyclohehexyl)-4-
methyl benzenesulfonamide (entry 20). White solid; mp
(m, 5H), 7.65 (d, J¼8.3 Hz, 2H); C NMR (CDCl ,
3
100 MHz) d 21.4, 49.2, 56.6, 81.9, 126.5, 127, 128.3, 128.6,

B. A. Bhanu Prasad et al. / Tetrahedron 58 (2002) 7355–7363
7361
þ
Anal. calcd for C H NO S: C, 63.15, H, 6.25, N, 4.60.
Found: C, 63.20, H, 6.21, N, 4.55.
1
29.6, 136.9, 138.2, 143.3; LCMS (EI, m/z) 304 (M ).
21.4, 22.4, 22.5, 24.9, 25.4, 28.9, 29.2, 29.6, 30.5, 31.0,
31.5, 31.6, 31.9, 32.2, 45.5, 53.4, 56.7, 58.9, 73.8, 79.2, 127,
129.4, 129.6, 136.8, 138.1, 143.1, 143.3; LCMS (EI, m/z)
1
6
19
3
þ
312 (M ). Anal. calcd for C H NO S: C, 61.53, H, 8.65,
N, 4.48. Found: C, 61.58, H, 8.62, N, 4.51.
1
6
27
3
1.2.26. trans-N-(2-Ethoxy-2-phenylethyl)-4-methyl ben-
zenesulfonamide (entry 26). White solid; mp 98–1018C;
R 0.56 (20% EtOAc in petroleum ether); IR (KBr) 3286,
f
1.2.31. trans-N-(2-Ethoxyoctyl)-4-methyl benzenesul-
fonamide and trans-N-(1-ethoxymethylheptyl)-4-methyl
benzenesulfonamide (entry 31). Viscous oil, R 0.63 (20%
973, 1165 cm2 ; H NMR (CDCl , 400 MHz) d 1.06 (t,
1
1
2
3
J¼7.1 Hz, 3H), 2.34 (s, 3H), 2.87 (ddd, J¼13.1, 9.3, 3.2 Hz,
H), 3.13 (ddd, J¼13.1, 9.3, 3.9 Hz, 1H), 3.17 (m, 1H), 3.29
m, 1H), 4.23 (dd, J¼9.3, 3.7 Hz, 1H), 4.90 (dd, J¼9.3,
f
EtOAc in petroleum ether); IR (neat) 3297, 1159 cm2 ; H
1 1
1
(
NMR (CDCl , 400 MHz) d 0.75–0.81 (m, 6H), 0.99–1.15
3
2
.7 Hz, 1H), 7.12 (d, J¼8.3 Hz, 2H), 7.23 (m, 5H), 7.65 (d,
(m, 20H), 2.35 (s, 6H), 2.73 (m, 1H), 3.08 (m, 2H), 3.19–
3.27 (m, 6H), 3.36–3.54 (m, 1H), 4.84 (d, J¼7.4 Hz, 2H),
1
3
J¼8.3 Hz, 2H); C NMR (CDCl , 100 MHz) d 15.1, 21.5,
3
þ
269, 155. Anal. calcd for C H NO S: C, 62.57, H, 8.89, N,
4.29. Found: C, 62.59, H, 8.91, N, 4.25.
4
1
9.3, 64.4, 80.1, 126.4, 127.0, 128.2, 128.6, 129.7, 136.9,
38.9, 143.4; LCMS (EI, m/z ) 318 (M ). Anal. calcd for
7.22 (m, 4H), 7.68 (m, 4H); LCMS (EI, m/z) 327 (M þ1),
þ
1
7
29
3
C H NO S: C, 64.15, H, 6.60, N, 4.40. Found: C, 64.20,
1
7
21
3
H, 6.62, N, 4.35.
1
.2.32. trans-N-(1-Isopropoxymethylheptyl)-4-methyl
1.2.27. trans-N-(2-Isopropoxy-2-phenylethyl)-4-methyl
benzenesulfonamide (entry 27). White solid; mp 103–
benzenesulfonamide and trans-N-(2-isopropoxyoctyl)-4-
methyl benzenesulfonamide (entry 32). Colorless liquid,
R 0.65 (20% EtOAc in petroleum ether); IR (neat) 3294,
1
068C; R 0.61 (20% EtOAc in petroleum ether); IR (KBr)
f
f
2
1 1
21 1
3
274, 1358, 1091 cm ; H NMR (CDCl , 400 MHz) d 1.04
3
1160 cm ; H NMR (CDCl , 400 MHz) d 0.86 (m, 6H),
3
(
d, J¼6.3 Hz, 3H), 1.10 (d, J¼5.9 Hz, 3H), 2.42 (s, 3H),
1.05 (m, 6H), 1.15–1.47 (m, 20H), 2.42 (s, 6H), 2.78
(heptet, J¼6.1 Hz, 1H), 3.06 (heptet, J¼6.1 Hz, 1H), 3.17
(m,1H), 3.25 (m, 2H), 3.38 (m, 2H), 3.56 (m, 1H), 4.80 (t,
J¼7.3 Hz, 1H, NH ), 4.88 (d, J¼7.8 Hz, 1H, NH ), 7.30 (m,
2
3
3
7
.91 (ddd, J¼12.5, 9.3, 2.9 Hz, 1H), 3.17 (ddd, J¼12.9, 9.3,
.7 Hz, 1H), 3.46 (heptet, J¼6.2 Hz, 1H), 4.40 (dd, J¼9.5,
.7 Hz, 1H), 4.87 (dd, J¼9.3, 2.4 Hz, 1H), 7.21–7.33 (m,
1
3
þ
H), 7.71 (d, J¼8.3 Hz, 2H); C NMR (CDCl , 100 MHz)
4H), 7.75 (m, 4H); LCMS (EI, m/z ) 340 (M þ1), 267, 156,
3
d 21, 21.5, 23.3, 49.5, 69.3, 77.4, 126.5, 127.0, 128.1, 128.5,
91. Anal. calcd for C H NO S: C, 63.52, H, 9.11, N, 4.11.
1
8
31
3
þ
48, 106. Anal. calcd for C H NO S: C, 65.06, H, 6.92, N,
.21. Found: C, 65.20, H, 6.98, N, 4.15.
1
1
4
29.7, 137, 139.6, 143.3; LCMS (EI, m/z) 332 (M ), 273,
Found: C, 63.76, H, 9.06, N, 4.02.
1
8
23
3
1.2.33. trans-N-(1-tert-Butoxymethylheptyl)-4-methyl
benzenesulfonamide and trans-N-(2-tert-butoxyoctyl)-4-
methyl benzenesulfonamide (entry 33). Colorless liquid,
1.2.28. trans-N-(2-tert-Butoxy-2-phenylethyl)-4-methyl
benzenesulfonamide (entry 28). White powder; mp 79–
8
3
9
R 0.65 (20% EtOAc in petroleum ether); IR (neat) 3296,
f
1 1
1161 cm2 ; H NMR (CDCl , 400 MHz) d 0.85 (m, 6H),
28C; R 0.61 (20% EtOAc in petroleum ether); IR (neat)
f
3
293, 1164 cm2 ; H NMR (CDCl , 400 MHz) d 1.10 (s,
1
1
1.05 (s, 9H), 1.10 (s, 9H), 1.13–1.46 (m, 20H), 2.69 (m,
1H), 2.84 (m, 1H), 2.94 (m, 1H), 3.13 (m, 1H), 3.22 (m, 1H),
3.54 (m, 1H), 4.85 (t, J¼5.8 Hz, 1H, NH ), 4.94 (d, J¼8 Hz,
1H, NH ), 7.33 (m, 4H), 7.76 (m, 4H); LCMS (EI, m/z ) 354
3
H), 2.4 (s, 3H), 2.84 (ddd, J¼12.9, 9.0, 3.9 Hz, 1H), 3.10
(
1
ddd, J¼12.9, 9.0, 4.1 Hz, 1H), 4.60 (dd, J¼9.0, 4.1 Hz,
H), 4.74 (dd, J¼9.0, 3.4 Hz, 1H), 7.26 (m, 7H), 7.69 (d,
þ
Anal. calcd for C H NO S: C, 65.89, H, 7.22, N, 4.04.
Found: C, 65.76, H, 7.27, N, 4.00.
þ
J¼8.3 Hz, 2H); LCMS (EI, m/z) 346 (M ), 273, 162, 106.
(M ). Anal. calcd for C H NO S: C, 67.11, H, 10.04, N,
2
3
41
3
3.40. Found: C, 67.28, H, 9.93, N, 3.42.
1
9
25
3
1.2.34. trans-N-(2-Methoxydodecyl)-4-methyl benzene-
1
.2.29. trans-N-(2-Phenoxy-2-phenylethyl)-4-methyl
benzenesulfonamide (entry 29). Pale yellow solid; mp
45–1468C; R 0.60 (20% EtOAc in petroleum ether); IR
sulfonamide and trans-N-(1-methoxymethylundecyl)-4-
methyl benzenesulfonamide (entry 34). White solid; mp
34–368C; R 0.78 (20% EtOAc in petroleum ether); IR
1
f
f
2
1
1
21
1
(
KBr) 3283, 3037 cm ; H NMR (CDCl , 400 MHz) d
3
(KBr) 3288, 1159 cm ; H NMR (CDCl , 400 MHz) d
3
2
1
7
1
1
.41 (s, 3H), 3.54 (m, 2H), 4.52 (t, J¼7.8 Hz, 1H), 5.19 (bs,
0.81 (m, 6H), 1.07–1.46 (m, 36H), 2.35 (s, 6H), 2.94–3.24
(m, 6H), 3.12 (s, 3H, OCH ), 3.17 (s, 3H, OCH ), 4.72 (m,
H), 6.71 (m, 1H), 6.83 (m, 2H), 7.03 (m, 1H), 7.16 (m, 3H),
.24 (m, 5H), 7.64 (d, J¼8.3 Hz, 2H); C NMR (CDCl3,
3
3
1
3
13
2H), 7.22 (m, 4H), 7.68 (m, 4H); C NMR (CDCl3,
100 MHz) d 14.1, 21.5, 22.6, 24.9, 25.5, 29.2, 29.3, 29.4,
29.4, 29.4, 29.5, 29.6, 31.0, 31.9, 32.3, 45.5, 53.5, 56.7,
58.9, 73.8, 79.2, 127.0, 129.5, 129.6, 138.0, 143.1, 143.3.
Anal. calcd for C H NO S: C, 65.21, H, 9.51, N, 3.80.
00 MHz) d 21.3, 115.8, 119.7, 126.5, 126.9, 127.5, 127.7,
28.1, 128.2, 128.3, 129.4, 137.2, 141.0, 142.9, 154.5;
þ
8.85, H, 5.73, N, 3.82. Found: C, 68.95, H, 5.81, N, 3.85.
LCMS (EI, m/z) 366 (M ). Anal. calcd for C H NO S: C,
2
6
1
21
3
2
0
35
3
Found: C, 65.25, H, 9.52, N, 3.83.
1
.2.30. trans-N-(2-Methoxyoctyl)-4-methyl benzenesul-
fonamide and trans-N-(1-methoxymethylheptyl)-4-
methyl benzenesulfonamide (entry 30). Viscous oil, Rf
1.2.35. trans-N-(1-Ethoxymethylundecyl)-4-methyl ben-
zenesulfonamide and trans-N-(2-ethoxydodecyl)-4-
methyl benzenesulfonamide (entry 35). Viscous liquid;
0
1
3
3
4
.63 (20% EtOAc in petroleum ether); IR (neat) 3295,
161 cm2 ; H NMR (CDCl , 400 MHz) d 0.75–0.81 (m,
1
1
R 0.77 (20% EtOAc in petroleum ether); IR (neat) 3293,
f
3
1 1
1161 cm2 ; H NMR (CDCl , 400 MHz) d 0.81 (m, 6H),
H), 1.06–1.42 (m, 10H), 2.35 (s, 3H), 3.11 (s, –OCH3),
.19 (s, –OCH ), 3.09–3.30 (m, 3H), 4.81 (m, 1H), 7.22 (m,
3
1.0–1.13 (m, 36H), 2.35 (s, 3H), 2.36 (s, 3H), 3.02–3.44
13
3
1
3
H), 7.68 (m, 4H); C NMR (CDCl , 100 MHz) d 14.0,
3
(m, 6H), 4.68 (m, 2H), 7.21 (m, 4H), 7.67 (m, 4H);
C

7362
B. A. Bhanu Prasad et al. / Tetrahedron 58 (2002) 7355–7363
NMR (CDCl , 100 MHz) d 14.1, 14.9, 15.4, 21.5, 22.6,
3
31.4, 56.1, 56.7, 74.1, 79.6, 80.6, 113.5, 117.2, 119.1, 147.9.
Anal. calcd for C H NO: C, 78.60, H, 8.29, N, 6.11.
Found: C, 78.73, H, 8.31, N, 6.04.
2
4
1
5.0, 25.6, 29.3, 29.4, 29.51, 29.58, 29.6, 31.7, 31.9, 32.5,
5.9, 53.6, 64.5, 66.6, 71.5, 77.5, 127.02, 127.07, 129.5,
29.6, 138.1, 143.1. Anal. calcd for C H NO S: C, 65.96,
1
5 19
2
1
37
3
H, 9.68, N, 3.66. Found: C, 65.99, H, 9.72, N, 3.71.
1.2.42. trans-(2-Hydroxycyclohexyl) phenylamine (entry
42). Viscous liquid; R 0.42 (5% EtOAc in petroleum ether);
IR (neat) 3393 cm ; H NMR (CDCl , 400 MHz) d 1.04
f
1 1
2
1
.2.36. trans-(2-Methoxycyclohexyl) phenylamine (entry
3
3
ether); IR (neat) 3289, 1565, 1246 cm ; H NMR (CDCl ,
6). Colorless liquid; R 0.40 (2% EtOAc in petroleum
2
(m, 1H), 1.35 (m, 3H), 1.75 (m, 2H), 2.12 (m, 2H), 2.85 (bs,
1H), 3.14 (ddd, J¼11.2, 9.5, 3.9 Hz, 1H), 3.34 (ddd, J¼9.7,
9.5, 3.9 Hz, 1H), 6.73 (m, 3H), 7.17 (m, 2H); LCMS (EI,
f
1 1
3
4
2
00 MHz) d 1.09–1.32 (m, 4H), 1.55–1.70 (m, 2H), 1.99–
.14 (m, 2H), 3.04 (ddd, J¼8.8, 8.7, 3.7 Hz, 1H), 3.15 (ddd,
þ
þ
m/z) 192 (M þ1), 191 (M ), 132. Anal. calcd for
J¼8.5, 9.5, 3.9 Hz, 1H), 3.29 (s, 3H), 6.63 (m, 3H), 7.01 (m,
C H NO: C, 75.39, H, 9.90, N, 7.32. Found: C, 75.41,
1
2 17
þ
þ
Anal. calcd for C H NO: C, 76.09, H, 9.26, N, 6.82.
2
H); LCMS (EI, m/z) 206 (M þ1), 205 (M ), 132, 118, 77.
H, 8.91, N, 7.31.
13 19
Found: C, 76.12, H, 9.22, N, 6.85.
1.2.43. trans-(2-Isopropoxycyclohexyl) phenylamine
(entry 43). Colorless oily liquid, R 0.39 (2% EtOAc in
petroleum ether); IR (neat) 3397, 1167 cm ; H NMR
f
2
1
1
1
.2.37. trans-(2-Ethoxycyclohexyl) phenylamine (entry
3
ether); IR (neat) 3295, 1582, 1292, 1080 cm ; H NMR
7). Colorless liquid; R 0.39 (2% EtOAc in petroleum
2
(CDCl , 400 MHz) d 1.01 (d, J¼6.0 Hz, 3H), 1.05 (d,
f
3
1 1
J¼6.4 Hz, 3H), 1.14–1.33 (m, 4H), 1.56 (m, 1H), 1.66 (m,
1H), 1.90 (m, 1H), 2.12 (m, 1H), 3.06–3.17 (m, 2H), 3.64
(heptet, J¼6.0 Hz, 1H), 6.60 (m, 3H), 7.07 (m, 2H). Anal.
calcd for C H NO: C, 77.25, H, 9.87, N, 6.0. Found: C,
(
CDCl , 400 MHz) d 1.07 (t, J¼7.1 Hz, 3H), 1.12–1.36 (m,
3
4
3
3
H), 1.58 (m, 1H), 1.68 (m, 1H), 1.98 (m, 1H), 2.12 (m, 1H),
.05–3.16 (m, 2H), 3.38 (m, 1H), 3.55 (m, 1H), 6.61 (m,
1
5 23
þ
H), 7.08 (m, 2H); LCMS (EI, m/z) 219 (M ). Anal. calcd
77.36, H, 9.81, N, 5.77.
for C H NO: C, 76.71, H, 9.58, N, 6.39. Found: C, 76.83,
1
4 21
H, 9.49, N, 6.38.
1.2.44. trans-(2-tert-Butoxycyclohexyl) phenylamine
(entry 44). Colorless oily liquid, R 0.40 (2% EtOAc in
petroleum ether); H NMR (CDCl , 400 MHz) d 1.49 (s,
f
1
1
.2.38. trans-(2-n-Propoxycyclohexyl) phenylamine
entry 38). Colorless viscous liquid; R 0.38 (2% EtOAc
3
(
in petroleum ether); IR (neat) 3401, 1161 cm ; H NMR
9H), 1.22–1.72 (m, 6H), 1.87–2.15 (m, 2H), 3.11 (ddd,
J¼9.5, 8.3, 3.9 Hz, 1H), 3.30 (ddd, J¼9.0, 8.3, 3.9 Hz, 1H),
3.69 (bs, 1H), 6.62 (m, 3H), 7.12 (m, 2H). Anal. calcd for
C H NO: C, 77.73, H, 10.12, N, 5.66. Found: C, 77.79, H,
f
2
1 1
(
1
CDCl , 400 MHz) d 0.88 (dt, J¼7.3, 1.9 Hz, 3H), 1.23–
3
.53 (m, 4H), 1.66 (m, 1H), 1.76 (m, 1H), 2.04 (m, 1H), 2.22
1
6 25
(
1
m, 1H), 3.17 (m, 2H), 3.37 (m, 1H), 3.57 (m, 1H), 3.89 (bs,
H), 6.67 (m, 3H), 7.14 (m, 2H). Anal. calcd for C H NO:
C, 77.25, H, 9.87, N, 6.0. Found: C, 77.27, H, 9.89, N, 6.03.
10.13, N, 5.62.
1
5 23
Acknowledgments
1
(
.2.39. trans-(2-Benzyloxycyclohexyl) phenylamine
entry 39). Colorless viscous liquid; R 0.39 (2% EtOAc
f
C.S.I.R. (Government of India) is being thanked for funding
the research project and a senior research fellowship to one
2
1 1
in petroleum ether); IR (neat) 3398, 1160 cm ; H NMR
CDCl , 400 MHz) d 1.18–1.88 (m, 6H), 2.10 (m, 1H),
(
3
(
B. A. B. P.) of us.
2
4
1
2
.32–2.44 (m, 1H), 3.29 (m, 2H), 4.48 (d, J¼11.9 Hz, 1H),
.65 (d, J¼11.9 Hz, 1H), 6.62 (d, J¼8.3 Hz, 2H), 6.67 (m,
þ
31, 190, 132. Anal. calcd for C H NO: C, 81.13, H, 8.18,
H), 7.15 (m, 2H), 7.28 (m, 5H); LCMS (EI, m/z) 281 (M ),
1
9 23
References
. For reviews on aziridine chemistry, see: (a) Tanner, D. Angew.
N, 4.98. Found: C, 81.19, H, 8.21, N, 4.95.
1
1
.2.40. trans-(2-Allyloxycyclohexyl) phenylamine (entry
Chem. Int. Ed. Engl. 1994, 33, 599. (b) Padwa, A.; Woolhouse,
A. D. Comprehensive Heterocyclic Chemistry, Lwowski, W.,
Ed.; Pergamon: Oxford, 1984; Vol. 7, pp 47–93. (c) Kasai, M.;
Kono, M. Synlett 1992, 778. (d) Osborn, H. M. I.; Sweeney, J.
Tetrahedron: Asymmetry 1997, 8, 1693. (e) Rayner, C. M.
Synlett 1997, 11. (f) For application of chiral aziridines, see
McCoull, W.; Davis, F. A. Synthesis 2000, 1347.
4
ether); IR (neat) 3397, 1159 cm
0). Colorless liquid, R 0.41 (2% EtOAc in petroleum
2
f
1
1
; H NMR (CDCl3,
00 MHz) d 1.25–1.40 (m, 4H), 1.63 (m, 1H), 1.75 (m, 1H),
.03 (m, 1H), 2.19 (m, 1H), 3.24 (m, 2H), 3.94–4.13 (m,
H), 5.11–5.25 (m, 2H), 5.88 (m, 1H), 6.68 (m, 3H), 7.15
4
2
2
þ
(m, 2H); LCMS (EI, m/z ) 231 (M ). Anal. calcd for
C H NO: C, 77.92, H, 9.09, N, 6.06. Found: C, 77.95, H,
1
5 21
2. Sekar, G.; Singh, V. K. J. Org. Chem. 1999, 64, 2537, and
references cited therein.
9
.10, N, 6.02.
3
. (a) Leung, W. H.; Yu, M. T.; Wu, M. C.; Yeung, L. L.
Tetrahedron Lett. 1996, 37, 891. (b) Ferraris, D.; Drury, III
W. J.; Cox, C.; Lectka, T. J. Org. Chem. 1998, 63, 4568. (c) Wu,
J.; Hou, X. L.; Dai, L. X. J. Org. Chem. 2000, 65, 1344. (d) Li,
Z.; Fernandez, M.; Jacobsen, E. N. Org. Lett. 1999, 1, 1611.
(e) Chandrasekhar, M.; Sekar, G.; Singh, V. K. Tetrahedron
Lett. 2000, 41, 10079.
1
.2.41. trans-(2-Prop-2-ynyloxycyclohexyl) phenylamine
(
ether); IR (neat) 3405, 2348 cm
4
entry 41). Colorless liquid, R 0.4 (2% EtOA in petroleum
f
; H NMR (CDCl3,
00 MHz) d 1.15–1.43 (m, 5H), 1.64–1.67 (m, 1H), 1.77
2
1
1
(
(
1
m, 1H), 2.07 (m, 1H), 2.20 (m, 1H), 2.45 (m, 1H), 3.22
ddd, J¼9.3, 8.8, 4.4 Hz, 1H), 3.44 (ddd, J¼8.7, 8.8, 4.1 Hz,
H), 3.91 (bs, 1H), 4.14–4.31 (m, 2H), 6.68 (m, 3H), 7.16
1
4. Bhanu Prasad, B. A.; Sekar, G.; Singh, V. K. Tetrahedron Lett.
2000, 41, 4677.
3
(
m, 2H); C NMR (CDCl , 100 MHz) d 23.7, 23.7, 29.7,
3

B. A. Bhanu Prasad et al. / Tetrahedron 58 (2002) 7355–7363
7363
5
6
. For opening of aziridines with TMSCN in the presence of
lanthanoid tricyanide, see: (a) Matsubara, S.; Kodama, T.;
Utimoto, K. Tetrahedron Lett. 1990, 31, 6379. (b) Osborn, H. M.
I.; Sweeney, J. B. Synlett 1994, 145.
7. Review: Lidstrom, P.; Tierney, J.; Wathey, B.; Westman, J.
Tetrahedron 2001, 57, 9225.
8. For some recent publications, see: (a) Villemin, D.; Moreau, B.;
Simeon, F.; Maheut, G.; Fernandez, C.; Montouillout, V.;
Caignaert, V.; Jaffres, P.-A. Chem. Commun. 2001, 2060.
(b) Lee, J. C.; Choi, J.-H. Synlett 2001, 234. (c) Kiddle, J. J.
Tetrahedron Lett. 2000, 41, 1339. (d) Moghaddam, F. M.;
Mohammadi, M.; Hosseinnia, A. Synth. Commun. 2000, 30,
. (a) Posner, G. H.; Shulman-Roskes, E. R.; Ho Oh, C.; Caary,
J. C.; Green, J. V.; Clark, A. B.; Dai, H.; Anjeh, T. E. N.
Tetrahedron Lett. 1991, 32, 6489.(b)Hua,D.H.J.Am.Chem. Soc.
1986, 108, 3835. (c) Melikyan, G. G.; Mineif, A.; Vostrowsky, O.;
Bestmann, H. J. Synthesis 1991, 633. (d) Kelley, D. R.; Roberts,
S. M.; Newton, R. F. Synth. Commun. 1979, 9, 295. (e) Donaldson,
R. E.; Saddler, J. C.; Byron, S.; Mckenzie, A. T.; Fuchs, P. L.
J. Org. Chem. 1983, 48, 2167.
6
43. (e) Blettner, C. G.; Koenig, W. A.; Stenzel, W.; Schotten,
T. J. Org. Chem. 1999, 64, 3885.