Reactions of 1-hydroxyindoles with p-toluenesulfonyl chloride and p-toluenesulfonic acid

Article abstract of DOI:10.3987/COM-00-9038

1-Hydroxyindoles produced novel types of compounds such as 4-substituted indoles and 4H-1,3-dioxolo[4,5-b]indoles upon reaction with p-toluenesulfonyl chloride in acetone. Contrastively, 5-tosyloxyindole and 2H-1,2-oxazino[2,3-a]indole were generated upon reaction with p-toluenesulfonic acid in acetone.

Full text of DOI:10.3987/COM-00-9038

HETEROCYCLES, Vol. 53, No.11, 2000, pp.2487 - 2497, Received, 10th August, 2000
REACTIONS OF 1-HYDROXYINDOLES WITH p-TOLUENESULFONYL
1
CHLORIDE AND p-TOLUENESULFONIC ACID
Masanori Somei,* Fumio Yamada, Aya Goto, Masumi Hayashi, and Masakazu
Hasegawa
Faculty of Pharmaceutical Sciences, Kanazawa University,
13-1 Takara-machi, Kanazawa 920-0934, Japan
Abstract — 1-Hydroxyindoles produced novel types of compounds such as
4-substituted indoles and 4H-1,3-dioxolo[4,5-b]indoles upon reaction with
p-toluenesulfonyl chloride in acetone. Contrastively, 5-tosyloxyindole and 2H-
1,2-oxazino[2,3-a]indole were generated upon reaction with p-toluenesulfonic
acid in acetone.
2
In our ongoing project to discover reactions characteristic to 1-hydroxyindoles, we have thus far
3,4
disclosed that they undergo various types of reactions
depending on their structures, reagents, and
reaction conditions. Now, we wish to describe novel findings upon reactions of 1-hydroxyindoles (1a-c)
with p-toluenesulfonyl chloride (TsCl) and p-toluenesulfonic acid (TsOH) in either THF or acetone.
4
We reported that 1-hydroxytryptamine (1a) led to 2a, 3a, 4, 5, and 6 by the reaction with methane-
sulfonyl chloride (MsCl) in THF in the presence of triethylamine (Et N) at room temperature (Scheme 1)
3
and thereby formation of 4-mesyloxyindole (7a) was not observed at all. We therefore expected that under
similar conditions TsCl would follow the same reaction pathways as those with MsCl to give the
corresponding products. In fact, however, the reaction of 1a with TsCl in THF provided 2a, 3a, 4, 7b,
and 8a in 42, 6, 3, 0.5, and 5% yields, respectively. Though the yield was low, 4-substituted indole (7b)
2,3
was isolated for the first time among thus far variously examined reactions.
in the products is another interesting finding.
The complete absence of 6
Since the solvent plays an important role for governing reaction pathways, the reaction of 1a with TsCl
was next examined in acetone instead of THF in the presence of Et N at room temperature, resulting in
3
the formation of a novel 4H-1,3-dioxolo[4,5-b]indole derivative (9a) in 3% yield together with 2a, 3a, 4,
7b, and 8a in 14, 6, 4, 0.2, and 3% yields, respectively. In the reaction of 1b, the yield of the corre-
sponding 9b was raised up to 11% under the same reaction conditions together with 2b and 8b in the
respective yields of 58 and 6%. In the case of 1c, 9c and 3c were produced in 10 and 49% yields,
respectively. Although chromatographical separation of 7b from 8a was quite difficult, the fractions
containing 7b and 8a were readily obtained. So, the mixture of 7b and 8a was converted to the readily
separable 1-acetyl derivatives (1 0 and 11a) by the reaction with NaH followed by treatment with AcCl.
1
Alkaline hydrolysis of 1 0 afforded pure 7b in 77% yield. In the H-NMR spectrum of 1 0, ortho- and
meta-coupled C(7)-proton (dd, J=0.7 and 8.3 Hz) appeared in lower magnetic field (δ 8.39) by ca. 1 ppm
than that of 7b (δ 7.25) by the anisotropy effect of the introduced 1-acetyl group. The results clearly prove

Scheme 1
Cl
NHAc
O
H
MsO
N
H
N
N
H
Ac
5
6
MsCl (1 mol eq), Et3N,
THF, rt, 1 h
NHAc
R1
R1
N
OH
O
N
N
N
H
N
R
H
H
TsCl (1 mol eq), Et3N,
Solvent, rt, 1 h
1
2
3
4
a) R1 = CH2CH2NHAc
b) R1 = CH2CH2NHCOCF3
c) R1 = CH2CH2CH2CONH
NHAc
R2
R1
8
R1
1
8b
O
4
O
TsO
N
H
N
N
3
5
H
H
a) R2 = OMs
b) R2 = OTs
7
8
9
[3,7] sigmatropic
rearrangement
[3,5] sigmatropic
rearrangement
1) NaH
2) AcCl
1) NaH
2) AcCl
NaOH,
MeOH
Ac2O,
Pyridine
R
R
NHAc
NHAc
N
O
N
O
OTs
R1
O
O
O
O
O
O
S
S
N
Ac
TsO
N
Ac
N
Ac
12
13
10
14
11
Me
Me
Scheme 2
NHAc
NHAc
NHAc
NHAc
NaHCO3
MeOH
(ClCH2CO)2O
NaOAc,DMF
O
O
O
O
O
O
O
O
N
H
N
N
N
84%
83%
85%
COCH2Cl
COCH2OAc
COCH2OH
16
15
9a
17
that these compounds are 4-substituted indoles. Structures of 11a,b and 8a,b are determined to be 6-sub-
stituted indoles based on the similar anisotropy effect observed on the meta-coupled C(7)-proton (d, J=2.2
Hz; δ 6.97→7.98 for 8a→11a; δ 7.08→8.07 for 8b→11b). Mechanisms for the formations of 7 and 8
might be explained by the [3,7] and [3,5] sigmatropic rearrangements of the initially formed
1-tosyloxytryptamine as shown in the general formulas (1 2 and 1 3). Structural determinations of 9a-c
were carried out using 9a as a representative sample. The presence of secondary amine in the molecule
was proved by obtaining 1 4 in 71% yield by treating 9a with Ac O-pyridine. Basedon the result, 9a was
2
further derived to chloroacetyl derivative (1 5) in 84% yield by reacting it with chloroacetic anhydride
(Scheme 2). Subsequent nucleophilic substitution of chlorine of 15 for acetoxy group proceeded by
treatment with sodium acetate in DMF to give 16 in 83% yield. Mild alkaline hydrolysis of ester (1 6) with
sodium bicarbonate in MeOH produced hydroxyacetyl derivative (1 7) in 85% yield as colorless prisms.
Although spectral and elemental analyses data of 9a and 1 5 through 1 7 suggested 4H-1,3-dioxolo[4,5-
b]indole structure, the unequivocal proof was obtained by X-Ray single crystallographic analysis of 1 7 .

The results and numbering of atoms are shown in Figure 1. Positional parameters and B (eq) for 1 7 are
summarized in Table 1.
Figure 1
ORTEP Drawing of 17 (R = 0.042)
12H
Numbering of
Atoms
13H
H11
12C
11C
17
10H
2N
O3
8H
9C
H9
H2
C10
H6
O2
7H
H17
H18
C4
3H
4H
15C
5C
6C
C3
C8
2C
1C
H1
O4
H19
H16
H15
13C
14C
H14
O1
C7
5H
N1
16C
17C
5O
20H
H21
H22
Table 1. Positional Parameters and B (eq) for 1 7
atom
x
y
z
B (eq) atom
x
y
z
B (eq)
O (1)
0.7979 (1)
0.3109 (1)
1.2574 (2) 4.58 (5) C (17) 1.0353 (2)
0.4315 (2)
1.1736 (3) 4.21 (7)
1.030 (2) 3.144 (8)
0.805 (3) 5.33 (1)
0.652 (3) 6.90 (2)
0.663 (3) 6.25 (2)
0.827 (3) 4.37 (1)
0.859 (3) 4.05 (1)
0.778 (3) 4.26 (1)
0.993 (3) 4.27 (1)
1.104 (3) 4.19 (1)
0.935 (3) 4.50 (1)
0.621 (4) 8.93 (3)
0.711 (3) 5.74 (1)
0.539 (4) 5.84 (1)
1.245 (4) 7.77 (2)
1.368 (4) 6.66 (2)
1.450 (4) 8.62 (2)
1.429 (4) 7.36 (2)
1.499 (4) 7.61 (2)
1.565 (4) 7.21 (2)
1.147 (3) 4.41 (1)
1.285 (3) 5.13 (1)
1.211 (3) 6.26 (2)
O (2)
O (3)
O (4)
O (5)
N (1)
N (2)
C (1)
C (2)
C (3)
C (4)
C (5)
C (6)
C (7)
C (8)
C (9)
C (10)
C (11)
C (12)
C (13)
C (14)
C (15)
C (16)
0.6335 (1)
0.4207 (1)
1.0941 (1)
1.1487 (1)
0.8880 (1)
0.3573 (1)
0.7795 (2)
0.6621 (2)
0.7154 (2)
0.1516 (1)
0.3866 (1)
0.2759 (1)
0.5058 (1)
0.2442 (1)
0.3258 (1)
0.2883 (2)
0.1839 (1)
0.0879 (1)
1.1578 (1) 3.72 (4) H (1)
0.6575 (2) 4.95 (5) H (2)
0.9797 (2) 5.15 (6) H (3)
1.1673 (2) 5.43 (6) H (4)
1.0104 (2) 3.19 (5) H (5)
0.8872 (2) 3.92 (6) H (6)
1.0718 (2) 3.30 (6) H (7)
0.9984 (2) 3.16 (5) H (8)
0.8954 (2) 3.27 (6) H (9)
0.769 (1)
0.565 (2)
0.676 (3)
0.894 (2)
1.009 (2)
0.470 (2)
0.555 (2)
0.552 (2)
0.484 (2)
0.365 (2)
–0.046 (2)
–0.177 (2)
–0.109 (2)
0.085 (2)
0.140 (2)
0.231 (2)
0.397 (2)
0.305 (2)
0.312 (2)
0.451 (3)
0.335 (2)
0.324 (2)
0.094 (2)
0.053 (3)
0.166 (3)
0.307 (2)
0.180 (3)
0.287 (2)
0.473 (2)
0.413 (2)
0.473 (2)
0.6518 (2) –0.0242 (2)
0.7200 (2) –0.0983 (2)
0.8488 (2) –0.0589 (2)
0.8007 (2) 4.47 (7) H (10) 0.294 (2)
0.7144 (3) 5.50 (8) H (11) 0.188 (3)
0.7240 (3) 5.24 (8) H (12) 0.140 (2)
0.8175 (3) 4.16 (7) H (13) 0.170 (2)
0.9033 (2) 3.20 (5) H (14) 0.861 (3)
0.8890 (2) 3.74 (6) H (15) 0.785 (3)
0.9821 (2) 4.15 (7) H (16) 0.906 (3)
0.7322 (2) 3.58 (6) H (17) 0.613 (3)
0.6485 (4) 5.05 (9) H (18) 0.640 (3)
1.3086 (2) 4.08 (6) H (19) 0.742 (3)
1.3520 (4) 6.2 (1) H (20) 0.958 (2)
1.4620 (3) 6.1 (1) H (21) 1.044 (2)
1.0447 (2) 3.58 (6) H (22) 1.215 (3)
0.9141 (2)
0.8451 (2)
0.5385 (2)
0.4879 (2)
0.3330 (2)
0.1961 (2)
0.7360 (2)
0.8298 (3)
0.6790 (3)
1.0100 (2)
0.0532 (2)
0.1269 (1)
0.2125 (2)
0.3163 (2)
0.3602 (2)
0.3673 (3)
0.2065 (2)
0.1226 (3)
0.2503 (3)
0.3118 (2)

The mechanism for the formation of 9a might be explained as shown in Scheme 3. Initially, TsCl leads 1a
to 1-tosyloxy derivative (1 8) with a concomitant formation of HCl, which works as a proton source and
transforms 1-hydroxy moiety of the second molecule (1a) to a good leaving group as shown in 1 9.
4,5
Liberation of water from 1 9 leaves resonance stabilized indolyl cation
(2 0). Nucleophilic addition of
water to 2 0 produces 3-hydroxyindolenine (2 1) and then a sequence of reactions, such as i) protonation of
imine nitrogen, 2) nucleophilic addition of acetone to the imine carbon, and 3) addition of the 3-hydroxy
group to the acetone carbonyl, leads to the formation of 9a. Nucleophilic addition of acetone to 2 0 might
take place to produce 2 3 through 2 2. Subsequent cyclization of aminal oxygen to the positively charged
carbonyl carbon affords 9a. The attack of water at the positively charged carbonyl carbon of 2 2 followed
by cyclization of the resultant hemiketal oxygen to the imine carbon could be another possible pathway.
Scheme 3
NHAc
H2O
NHAc
NHAc
NHAc
O
O
Et3N
H2O
OH
N
N
OH
N
OTs
N
H
O
H
1a
HCl
18
20
21
9a
23
H2O
HCl
H2O
NHAc
O
H2O
NHAc
O
NHAc
NHAc
N
H
N
O
H
N
O
N
O
H
H
19 H
22
H2O
With an attempt to improve the yield of 9a, we next examined the reaction of 1a in acetone with
p-toluenesulfonic acid (TsOH) as an acid catalyst. Interestingly, the result was completely different from
the expectation. Thus, 1a afforded 2H-1,2-oxazino[2,3-a]indole (2 4), 5-tosyloxyindole (2 5), 4, and
unreacted 1a in 9, 10, 7, and 14% yields, respectively (Scheme 4).
The structure of 2 4 was proved by comparing it with the authentic sample prepared by the following
alternative route. Michael addition reaction of 1a to mesityl oxide in DMF in the presence of potassium
t-butoxide afforded 2 6 and unreacted 1a in 49 and 50% yields, respectively. Acid catalyzed cyclization of
2 6 with 8% HCl in MeOH provided 2 4 in 78% yield. The reaction of 1a with mesityl oxide at 55°C also
produced 2 4 directly in 53% yield. For the structural determination of 2 5, it was converted to 2 7 in 69%
yield by the sequential treatment with NaH and then with AcCl.
Scheme 4
AcHN
AcHN
AcHN
5
AcHN
KOtBu,
Mesityl
oxide
TsOH,
aceton e
TsO
TsO
1a
4
N
O
N
Ac
N
N
H
1) NaH
2) AcCl
4
3
O
2
HCl, MeOH
1
26
24
25
27
O

1
Comparison of the H-NMR spectrum of 2 7 with that of 2 5 exhibited the anisotropy effect of the 1-acetyl
group on the ortho-coupled C-7 proton (d, J=7.5 Hz) by ca. 1 ppm (δ 7.22 → 8.30), proving these
compounds are 5-substituted indoles. The formation of 2 5 can be explained by the regioselective
nucleophilic attack of p-toluenesulfonate at the 5-position as the 1-hydroxy leaving group departs upon
protonation. This is an additional example of nucleophilic substitution reactions characteristic to
2
1-hydroxyindoles.
In conclusion, we have found that 1-hydroxyindoles provide unprecidented types of compounds such as
4-substituted indoles and 4H-1,3-dioxolo[4,5-b]indoles upon reaction with TsCl in acetone, while the
reaction with TsOH in acetone contrastively produces 2H-1,2-oxazino[2,3-a]indole and 5-tosyloxyindole.
By choosing reaction conditions and substrates, whether we could control the reaction pathways to obtain
individual products selectively and in better yields is the next facing subject.
EXPERIMENTAL
Melting points were determined on a Yanagimoto micro melting point apparatus and are uncorrected. IR
1
spectra were determined with a Shimadzu IR-420 spectrophotometer, and H-NMR spectra with a JEOL
GSX-500 spectrometer with tetramethylsilane as an internal standard. MS were recorded on JEOL
SX-102A and JMS-GCmate spectrometers. Column chromatography was performed on silica gel (SiO ,
2
100—200 mesh, from Kanto Chemical Co. Inc.) throughout the present study.
1-Acetyl-1,2,3,8-tetrahydropyrrolo[2,3-b]indole (2a), Nb-Acetyl-2,3-dihydro-2-oxo-
tryptamine (3a), N b-Acetyltryptamine (4), N b-Acetyl-4-tosyloxytryptamine (7b), and
N b-Acetyl-6-tosyloxytryptamine (8a) from N b-Acetyl-1-hydroxytryptamine (1a) — TsCl
(181.8 mg, 0.96 mmol) was added to a solution of 1a (208.8 mg, 0.96 mmol) in anhydrous THF (8.0
mL) and Et N (0.8 mL, 5.7 mmol) at 0 °C with stirring. After additional stirring at rt for 1 h, ice and H O
3
2
was added to the reaction mixture. The whole was extracted with CHCl –MeOH (95:5, v/v). The extract
3
was washed with brine, dried over Na SO , and evaporated under reduced pressure to leave an oil, which
2
4
4
was column-chromatographed on SiO repeatedly with CHCl –MeOH (98:1—98:2, v/v) to give 2a
2
3
4
4
(80.3 mg, 42%), 4 (4.9 mg, 3%), 7b (1.7 mg, 0.5%), 8a (16.5 mg, 5%), and 3a (12.4 mg, 6%) in
the order of elution. 7b: mp 178—182 °C (pale yellow prisms, recrystallized from EtOAc–hexane). IR
-1 1
(KBr): 3303, 3216, 1624, 1570, 1371, 1177, 1023, 858 cm . H-NMR (CDCl ) δ: 1.94 (3H, s), 2.48
3
(3H, s), 3.08 (2H, t, J=7.1 Hz), 3.58 (2H, q, J=7.1 Hz), 5.85 (1H, br s), 6.48 (1H, dd, J=0.7, 8.0 Hz),
6.98 (1H, t, J=8.0 Hz), 7.04 (1H, d, J =2.4 Hz), 7.25 (1H, dd, J=0.7, 8.0 Hz), 7.37 (2H, br d, J=8.2
Hz), 7.83 (2H, br d, J=8.2 Hz), 8.23 (1H, br s). HR–MS m/z: Calcd for C H N O S: 372.1135.
19 20 2 4
Found: 372.1144. 8a: mp 190—191 °C (colorless prisms, recrystallized from EtOAc). IR (KBr): 3400,
-1 1
3182, 1660, 1542, 1361, 945 cm . H-NMR (CD OD) δ: 1.88 (3H, s), 2.43 (3H, s), 2.88 (2H, dt,
3
J=0.8, 7.5 Hz), 3.41 (2H, t, J=7.5 Hz ), 6.57 (1H, dd, J=2.2, 8.5 Hz), 6.97 (1H, dd, J=0.5, 2.2 Hz),
7.10 (1H, s), 7.37 (2H, br d, J=8.5 Hz), 7.42 (1H, dd, J=0.5, 8.5 Hz), 7.67 (2H, br d, J=8.5 Hz). MS
m/z: 372 (M+). Anal. Calcd for C H N O S: C, 61.27; H, 5.41; N, 7.52. Found: C, 61.17; H, 5.47;
19 20 2 4
N, 7.23. Although chromatographical separation of 7b from 8a was quite difficult, the fractions
containing 7b and 8a were readily obtained. So, the pure sample of 7b was prepared by the following

alkaline hydrolysis of Na,Nb-diacetyl-4-tosyloxyindole (1 0).
N a, N b-Diacetyl-4-p-tosyloxytryptamine (10) and N a, N b-Diacetyl-6-p-tosyloxytrypta-
mine (11a) from the Fractions Containing 7b and 8a — The fractions containing 7b and 8a
were collected after the similar reactions and work-up as described above. The mixture (27.5 mg, 0.07
mmol) was dissolved in anhydrous DMF (1.5 mL). The solution was added to 60% NaH (5.9 mg, 0.14
mmol, washed with dry benzene) at 0°C with stirring. After additional stirring at rt for 10 min, a solution
of AcCl (19.8 mg, 0.22 mmol) in anhydrous DMF (0.5 mL) was added to the resultant solution. The
mixture was stirred at rt for 30 min. After addition of H O under ice cooling, the whole was extracted with
2
EtOAc. The extract was washed with brine, dried over Na SO , and evaporated under reduced pressure to
2
4
leave an oil, which was column-chromatographed on SiO with CHCl –MeOH (99:1, v/v) to give 11a
2
3
(13.3 mg, 44%) and 1 0 (10.6 mg, 35%) in the order of elution. 1 0: mp 151.5—152.5 °C (colorless
-1 1
needles, recrystallized from EtOAc–hexane). IR (KBr): 3298, 1705, 1639, 1434, 1379 cm . H-NMR
(CDCl ) δ: 1.98 (3H, s), 2.49 (3H, s), 2.61 (3H, s), 3.08 (2H, t, J=7 Hz), 3.62 (2H, q, J=7 Hz,
3
collapsed to t, J=7 Hz, on addition of D O), 5.85 (1H, br s, disappeared on addition of D O), 6.58 (1H,
2
2
dd, J=0.7, 8.1 Hz), 7.15 (1H, t, J=8.1 Hz), 7.32 (1H, s), 7.39 (2H, d, J=8.1 Hz), 7.80 (2H, d, J=8.3
Hz), 8.39 (1H, dd, J=0.7, 8.3 Hz). HR–MS m/z: Calcd for C H N O S: 414.1250. Found:
21 22 2 5
414.1251.
N b-Acetyl-4-tosyloxytryptamine (7b) from 1 0 — Sat. aq. NaHCO (1.0 mL, 1.05 mmol) was
3
added to a solution of 1 0 (6.4 mg, 0.015 mmol) in MeOH (1.0 mL) and the mixture was stirred at rt for
45 min. After addition of H O, the whole was extracted with CHCl –MeOH (95:5, v/v). The extract was
2
3
washed with brine, dried over Na SO , and evaporated under reduced pressure to leave an oil, which was
2
4
column-chromatographed on SiO with CHCl –MeOH (97:3, v/v) to give pure 7b (4.4 mg, 77%).
2
3
1-Acetyl-1,2,3,8-tetrahydropyrrolo[2,3-b]indole (2a), Nb-Acetyl-2,3-dihydro-2-oxo-
tryptamine (3a), N b-Acetyltryptamine (4), N b-Acetyl- 4 -p-tosyloxytryptamine (7b), N b-
Acetyl- 6 -p-tosyloxytryptamine (8a), and 8b-(2-Acetylaminoethyl)-2,2-dimethyl-4H-1,3-
dioxolo[4,5-b]indole (9a) from 1a —p-Toluenesulfonyl chloride (88.5 mg, 0.47 mmol) was added
to a solution of 1a (101.6 mg, 0.47 mmol) in anhydrous acetone (20.0 mL) and Et N (0.65 mL, 4.7
3
mmol) at 0 °C with stirring. After additional stirring at rt for 1 h, H O was added to the reaction mixture.
2
The whole was extracted with CHCl –MeOH (95:5, v/v). The extract was washed with brine, dried over
3
Na SO , and evaporated under reduced pressure to leave an oil, which was column-chromatographed on
2
4
SiO repeatedly with CHCl –MeOH (99:1, v/v) and then with CHCl –MeOH–28% aq.NH (46:2:0.2,
2
3
3
3
4
4
v/v) to give 2a (12.8 mg, 14%), 9a (3.7 mg, 3%), 4 (3.7 mg, 4%), 7b (0.3 mg, 0.2%), 8a (5.2 mg,
4
3%), and 3a (6.5 mg, 6%) in the order of elution. 9a: pale yellow oil. IR (film): 3300, 1640 (br), 1550
-1 1
(br), 1027, 750 cm . H-NMR (DMSO-d ) δ: 1.02 (3H, s), 1.35 (3H, s), 1.76 (3H, s), 1.87 (1H,
6
ddd, J= 5.1, 10.1, 13.5 Hz), 2.05 (1H, ddd, J=6, 11, 13.5 Hz), 2.91—2.99 (1H, m), 3.04—3.12 (1H,
m), 5.44 (1H, d, J=2.5 Hz), 6.53 (1H, d, J=7.5 Hz), 6.64 (1H, dt, J=1.3, 7.5 Hz), 6.88 (1H, d, J=2.5
Hz), 7.07 (1H, dt, J=1.3, 7.5 Hz), 7.15 (1H, br d, J=7.5 Hz), 7.77 (1H, br t, J=5.0 Hz). HR–MS m/z:
Calcd for C H N O : 276.1474. Found: 276.1477.
15 20 2 3
1-Trifluoroacetyl-1,2,3,8-tetrahydropyrrolo[2,3-b]indole (2b), N b-Trifluoroacetyl-6-p-

tosyloxytryptamine (8b), and 8b-(2-Trifluoroacetylaminoethyl)-2,2-dimethyl-4H-1,3-
dioxolo[4,5-b]indole (9b) from Nb-Trifluoroacetyl-1-hydroxytryptamine (1b) — TsCl
(36.0 mg, 0.19 mmol) was added to a solution of 1b (51.1 mg, 0.19 mmol) in acetone (2.0 mL) and
Et N (0.26 mL, 1.9 mmol) at 0 °C with stirring. After additional stirring at rt for 1 h, ice and H O was
3
2
added to the reaction mixture. The whole was extracted with CHCl –MeOH (95:5, v/v). The extract was
3
washed with brine, dried over Na SO , and evaporated under reduced pressure to leave an oil, which was
2
4
4
column-chromatographed on SiO with CHCl –hexane (2:1, v/v), then with CHCl to give 2b (27.7
2
3
3
mg, 58%), 9b (6.9 mg, 11%), and 8b (4.7 mg, 6%) in the order of elution. 9b: mp 104—105 °C
(colorless fine needles, recrystallized from EtOAc–hexane). IR (KBr): 3407, 3342, 1700, 1613, 1551,
-1 1
1160 (br) cm . H-NMR (CDCl ) δ: 1.10 (3H, s), 1.47 (3H, s), 2.12 (1H, ddd, J=14.9, 7.1, 4.6 Hz),
3
2.27 (1H, ddd, J=14.9, 8.1, 4.7 Hz), 3.38—3.46 (1H, m), 3.68—3.75 (1H, m), 4.73 (1H, br s), 5.41
(1H, s), 6.66 (1H, br d, J=7.6 Hz), 6.85 (1H, dt, J=1.0, 7.6 Hz), 7.20 (1H, dt, J=1.2, 7.6 Hz), 7.25
(1H, br d, J=7.6 Hz), 7.28 (1H, br s). Anal. Calcd for C H N O F : C, 54.54; H, 5.19; N, 8.48.
15 17 2 2 3
Found: C, 54.56; H, 5.15; N, 8.44. 8b: mp 167—168 °C (colorless plates, recrystallized from CHCl ).
3
-1 1
IR (KBr): 3304, 1717, 1368, 1173, 1087 cm . H-NMR (CDCl ) δ: 2.45 (3H, s), 3.01 (2H, t, J=6.7
3
Hz), 3.65 (2H, q, J=6.7 Hz), 6.33 (1H, br s), 6.62 (1H, dd, J=8.6, 2.3 Hz), 7.08 (1H, d, J=2.3 Hz),
7.17 (1H, d, J=2 Hz), 7.30 (2H, br d, J=8.6 Hz), 7.40 (1H, d, J=8.6 Hz), 7.71 (2H, br d, J=8.6 Hz),
8.17 (1H, br s). Anal. Calcd for C H N O F S: C, 53.52; H, 4.02; N, 6.57. Found: C, 53.55; H,
19 17 2 4 3
4.03; N, 6.47.
N-Adamantyl-4-(2-oxyindol-3-yl)butanamide (3c) and N-Adamantyl-4-(2,2-dimethyl-
4H-1,3-dioxolo[4,5-b]indol-8b-yl)butanamide (9c) from N-Adamantyl-4-(1-hydroxyin-
dol-3-yl)butanamide (1c) — TsCl (16.6 mg, 0.08 mmol) was added to a solution of 1c (29.3 mg,
0.08 mmol) in acetone (1.5 mL) and Et N (0.12 mL, 0.9 mmol) at 0 °C with stirring. After additional
3
stirring at rt for 30 min, ice and H O was added to the reaction mixture. The whole was extracted with
2
CHCl –MeOH (95:5, v/v). The extract was washed with brine, dried over Na SO , and evaporated under
3
2
4
reduced pressure to leave an oil, which was column-chromatographed on SiO with EtOAc–hexane (1:2—
2
1:1, v/v) to give 9c (3.4 mg, 10%) and 3c (14.3 mg, 49%) in the order of elution. 3c: mp 227.0—228.5 °C
-1
(colorless powder, recrystallized from CHCl ). IR (KBr): 3292, 2904, 1712, 1628, 1550, 750 cm .
3
1
H-NMR (CDCl ) δ: 1.64—1.68 (6H, m), 1.67—1.72 (2H, m), 1.96—1.99 (6H, m), 1.97—2.03
3
(2H, m), 2.06 (3H, br s), 2.10 (2H, t, J=7.4 Hz), 3.47 (1H, br t, J=6.1 Hz), 5.18 (1H, br s), 6.85 (1H,
d, J=7.6 Hz), 7.02 (1H, dt, J=1.0, 7.6 Hz), 7.20 (1H, br t, J=7.6 Hz), 7.25 (1H, t, J=7.6 Hz), 7.79
(1H, br s, disappeared on addition of D O). MS m/z: 352 (M+). Anal. Calcd for C H N O ·1/2 H O:
2
22 28 2 2
2
C, 73.10; H, 8.09; N, 7.75. Found: C, 72.97; H, 7.81; N, 7.70. 9c: pale yellow oil. IR (KBr): 3292,
-1 1
1643, 1613, 1543, 1017, 746 cm . H-NMR (CDCl ) δ: 1.11 (3H, s), 1.45 (3H, s), 1.49—1.61 (1H,
3
m), 1.64—1.68 (6H, m), 1.64—1.78 (1H, m), 1.85—2.03 (3H, m), 1.95—1.98 (6H, m), 2.06 (3H, br
s), 2.03—2.16 (1H, m), 4.66 (1H, br s), 5.06 (1H, br s), 5.44 (1H, s), 6.61 (1H, d, J=7.5 Hz), 6.79
(1H, dt, J=0.9, 7.5 Hz), 7.14 (1H, dt, J=1.2, 7.5 Hz), 7.23 (1H, dd, J=0.9, 7.5 Hz). HR–MS m/z:
Calcd for C H N O : 410.2569. Found: 410.2578.
25 34 2 3
N a, N b-Diacetyl-6-p-tosyloxytryptamine (11a) from 8a — A solution of 8a (39.8 mg, 0.11

mmol) in DMF (1.5 mL) was added to 60% NaH (9.3 mg, 0.23 mmol, washed with dry benzene) at 0 °C
with stirring. After additional stirring at rt for 10 min, a solution of AcCl (30.2 mg, 0.38 mmol) in DMF
(0.5 mL) was added to the resultant solution and the mixture was stirred at rt for 1 h. After addition of
H O under ice cooling, the whole was extracted with EtOAc. The extract was washed with brine, dried
2
over Na SO , and evaporated under reduced pressure to leave an oil, which was column-
2
4
chromatographed on SiO with EtOAc to give unreacted 8a (5.9 mg, 14.8%) and 11a (37.6 mg, 84.9%)
2
in the order of elution. 11a: mp 155.0—156.5 °C (colorless prisms, recrystallized from EtOAc–hexane).
-1 1
IR (KBr): 3256, 1706, 1658, 1634, 1172, 905, 834 cm . H-NMR (CD OD) δ: 1.89 (3H, s), 2.44
3
(3H, s), 2.58 (3H, s), 2.87 (2H, dt, J=1.0, 7.1 Hz), 3.47 (2H, t, J=7.1 Hz), 6.91 (1H, dd, J=2.2, 8.5
Hz), 7.39 (2H, br d, J=8.5 Hz), 7.51 (1H, d, J=8.5 Hz), 7.57 (1H, s), 7.68 (2H, br d, J=8.5 Hz), 7.98
(1H, d, J=2.2 Hz). Anal. Calcd for C H N O S: C, 60.85; H, 5.35; N, 6.76. Found: C, 60.63; H,
21 22 2 5
5.38; N, 6.65.
N a-Acetyl-N b-trifluoroacetyl-6-p-tosyloxytryptamine (11b) from 8b — A solution of 8b
(40.2 mg, 0.09 mmol) in DMF (2.0 mL) was added to 60% NaH (8.0 mg, 0.18 mmol, washed with dry
benzene) at 0 °C with stirring. After additional stirring at rt for 15 min, a solution of AcCl (24.0 mg, 0.31
mmol) in DMF (1.0 mL) was added to the resultant solution and the mixture was stirred at rt for 1 h. After
addition of H O under ice cooling, the whole was extracted with EtOAc. The extract was washed with
2
brine, dried over Na SO , and evaporated under reduced pressure to leave an oil, which was
2
4
column-chromatographed on SiO with EtOAc-hexane (1:1, v/v) to give unreacted 8b (9.4 mg, 23%) and
2
11b (15.5 mg, 35%) in the order of elution. 11b: mp 162.5—164.0 °C (colorless powder, recrystallized
-1 1
from CHCl –hexane). IR (KBr): 3328, 1698, 1371, 1174 cm . H-NMR (CDCl ) δ: 2.45 (3H, s),
3
3
2.54 (3H, s), 2.98 (2H, dt, J=1.0, 7.1 Hz), 3.68 (2H, q, J=7.1 Hz, collapsed to t, J=7.1 Hz on addition
of D O), 6.45 (1H, br s, disappeared on addition of D O), 7.01 (1H, dd, J=2.2, 8.5 Hz), 7.29 (1H, br
2
2
s), 7.33 (2H, br d, J=8.5 Hz), 7.42 (1H, d, J=8.5 Hz), 7.75 (2H, br d, J=8.5 Hz), 8.07 (1H, br s).
Anal. Calcd for C H N O F S: C, 53.84; H, 4.09; N, 5.98. Found: C, 53.56; H, 4.03; N, 5.87.
21 19 2 5 3
4-Acetyl-8b-(2-acetylaminoethyl)-2,2-dimethyl-4H-1,3-dioxolo[4,5-b]indole (14) from
9a — Ac O (1 mL) was added to a solution of 9a (23.3 mg, 0.08 mmol) in pyridine (2.0 mL) and the
2
mixture was stirred at rt for 8.5 h. Evaporation of the solvent under reduced pressure afforded an oil,
which was column-chromatographed on SiO with CHCl –MeOH (98:2, v/v) to give 1 4 (19.0 mg,
2
3
-1 1
71%). 1 4: colorless oil. IR (film): 3300, 1663 (br), 1553 (br), 760 cm . H-NMR (CDCl ) δ: 1.00
3
(3H, s), 1.50 (3H, s), 1.96 (3H, s), 2.07—2.14 (1H, m), 2.28—2.35 (1H, m), 2.43 (3H, s), 3.25—
3.33 (1H, m), 3.43—3.52 (1H, m), 5.85 (1H, br s), 5.87 (1H, s), 7.13 (1H, t, J=7.5 Hz), 7.32—7.37
(2H, m), 8.20 (1H, d, J=7.5 Hz). HR–MS m/z: Calcd for C H N O : 318.1580. Found: 318.1580.
17 22 2 4
8b-(2-Acetylaminoethyl)-4-chloroacetyl-2,2-dimethyl-4H-1,3-dioxolo[4,5-b]indole (15)
from 9a — A solution of chloroacetic anhydride (28.1 mg, 0.15 mmol) in CHCl (0.5 mL) was added to
3
a solution of 9a (14.1 mg, 0.05 mmol) in CHCl (1.0 mL) and the mixture was stirred at rt for 3 h. Sat.
3
aq. NaHCO and CHCl were added to the reaction mixture. The organic layer was washed with brine,
3
3
dried over Na SO , and evaporated under reduced pressure to leave an oil, which was column-
2
4
chromatographed on SiO with EtOAc to give 1 5 (17.0 mg, 84%). 1 5: colorless oil. IR (film): 3292,
2

-1 1
1656 (br), 1550, 1480, 1400, 1059, 760 cm . H-NMR (CDCl ) δ: 1.01 (3H, s), 1.50 (3H, s), 1.95
3
(3H, s), 2.11—2.18 (1H, m), 2.31—2.38 (1H, m), 3.25—3.32 (1H, m), 3.41—3.49 (1H, m), 4.34
(1H, d, J= 13.2 Hz), 4.55 (1H, d, J=13.2 Hz), 5.76 (1H, br s), 6.04 (1H, s), 7.19 (1H, dt, J=1.0, 7.4
Hz), 7.37 (1H, br d, J=7.4 Hz), 7.38 (1H, ddd, J=8.1, 7.4, 1.3 Hz), 8.21 (1H, br d, J=8.1 Hz). HR–
MS m/z: Calcd for C H N O Cl: 354.1160 and 352.1190. Found: 354.1189 and 352.1185.
17 21 2 4
4-(2-Acetoxy)acetyl-8b-(2-acetylaminoethyl)-2,2-dimethyl-4H-1,3-dioxolo[4,5-b]indole
(16) from 1 5 — A solution of NaOAc (7.6 mg, 0.09 mmol) in H O (0.2 mL) was added to a solution of
2
1 5 (16.5 mg, 0.047 mmol) in DMF (2.0 mL) and the mixture was stirred at 55–57 °C for 8 h. After
evaporation of the solvent under reduced pressure, H O was added to the residue. The whole was
2
extracted with CHCl –MeOH (95:5, v/v). The extract was washed with brine, dried over Na SO , and
3
2
4
evaporated under reduced pressure to leave an oil, which was column-chromatographed on SiO with
2
CHCl –MeOH (98:2, v/v) to give 1 6 (14.6 mg, 83%). 1 6: colorless oil. IR (film): 3287, 1747, 1691,
3
-1 1
1655, 763 cm . H-NMR (CDCl ) δ: 1.02 (3H, s), 1.50 (3H, s), 1.96 (3H, s), 2.10—2.17 (1H, m),
3
2.24 (3H, s), 2.31—2.38 (1H, m), 3.20—3.27 (1H, m), 3.44—3.52 (1H, m), 4.93 (1H, d, J=15.1 Hz),
5.06 (1H, d, J=15.1 Hz), 5.82 (1H, br s, disappeared on addition of D O), 5.97 (1H, s), 7.16 (1H, dt,
2
J= 1.0, 7.4 Hz), 7.36 (1H, dd, J=7.4, 1.3 Hz), 7.36 (1H, ddd, J=8.5, 7.4, 1.3 Hz), 8.18 (1H, br d,
J=8.5 Hz). HR–MS m/z: Calcd for C H N O : 376.1634. Found: 376.1630.
19 24 2 6
8b-(2-Acetylaminoethyl)-4-hydroxyacetyl-2,2-dimethyl-4H-1,3-dioxolo[4,5-b]indole
(17) from 1 6 — Sat. aq. NaHCO (0.5 mL, 0.5 mmol) was added to a solution of 1 6 (3.3 mg, 0.009
3
mmol) in MeOH (0.5 mL) and the mixture was stirred at rt for 45 min. After addition of H O to the
2
reaction mixture, the whole was extracted with CHCl –MeOH (95:5, v/v). The extract was washed with
3
brine, dried over Na SO , and evaporated under reduced pressure to leave an oil, which was column-
2
4
chromatographed on SiO with CHCl –MeOH (95:5, v/v) to give 1 7 (2.5 mg, 85%). 1 7: mp 130.0—
2
3
130.5 °C (colorless prisms, recrystallized from EtOAc). IR (KBr): 3455, 3284, 1676, 1625, 1562, 1055,
-1 1
756 cm . H- NMR (CDCl ) δ: 1.00 (3H, s), 1.49 (3H, s), 1.95 (3H, s), 2.07—2.15 (1H, m), 2.28—
3
2.36 (1H, m), 3.23—3.31 (1H, m), 3.35 (1H, br t, J=4 Hz, disappeared on addition of D O), 3.41—
2
3.49 (1H, m), 4.46 (1H, dd, J=4.3, 16.1 Hz, collapsed to d, J=16.1 Hz on addition of D O), 4.58 (1H,
2
dd, J=4.5, 16.1 Hz, collapsed to d, J=16.1 Hz on addition of D O), 5.75 (1H, br s, disappeared on
2
addition of D O), 5.80 (1H, br s), 7.18 (1H, dt, J=1.0, 7.6 Hz), 7.38 (1H, br d, J=7.9 Hz), 7.39 (1H,
2
ddd, J=7.9, 7.6, 1.2 Hz), 8.21 (1H, br d, J=7.6 Hz). Anal. Calcd for C H N O : C, 61.06; H, 6.63;
17 22 2 5
N, 8.38. Found: C, 60.90; H, 6.58; N, 8.26.
Nb-Acetyl-1-(1,1-dimethyl-3-oxo)butoxytryptamine (26) from 1a — Potassium t-butoxide
(74.8 mg, 0.67 mmol) was added to a solution of 1a (50.0 mg, 0.23 mmol) in DMF (2.5 mL) under Ar
atmosphere and then mesityl oxide (9 mL) was added to the reaction mixture at 0 °C. The mixture was
stirred at rt for 72 h. After addition of H O under ice cooling, the whole was extracted with EtOAc. The
2
extract was washed with brine, dried over Na SO , and evaporated under reduced pressure to leave an oil,
2
4
which was column-chromatographed on SiO with CHCl –MeOH (98:2, v/v) and then with EtOAc to
2
3
give 2 6 (35.5 mg, 49%) and unreacted 1a (25.1 mg, 50%) inthe order of elution. 2 6: pale yellow oil. IR
-1 1
(film) : 3300, 1713, 1653, 1553, 745 cm . H-NMR (CDCl ) δ: 1.53 (6H, s), 1.98 (3H, s), 2.22 (3H,
3

s), 2.93 (2H, s), 2.93 (2H, t, J=6.3 Hz), 3.56 (2H, t, J=6.3 Hz), 7.06 (1H, s), 7.11 (1H, t, J=7.5 Hz),
7.24 (1H, t, J=7.5 Hz), 7.38 (1H, d, J=7.5 Hz), 7.53 (1H, d, J=7.5 Hz). HR–MS m/z: Calcd for
C H N O : 316.1787. Found: 316.1791.
18 24 2 3
5-(2-Acetylaminoethyl)-2,2,4-trimethyl-2H-1,2-oxazino[2,3-a]indole (24), N b-Acetyl-
5-tosyloxytryptamine (25) and 4 from 1a — p-Toluenesulfonic acid (181 mg, 1.05 mmol) was
added to a solution of 1a (202 mg, 0.93 mmol) in acetone (16.0 mL) and the mixture was refluxed for 24
h with stirring. Evaporation of the solvent under reduced pressure afforded an oil, which was
column-chromatographed repeatedly on SiO with CHCl –MeOH–28% kaq. NH (46:1:0.1, v/v) and
2
3
3
CHCl –MeOH (95:5, v/v) to give 2 4 (25.1 mg, 9%), 4 (16.2 mg, 7%), 2 5 (33.3 mg, 10%), and
3
unreacted 1a (27.6 mg, 14%) in the order of elution. 2 4: pale yellow oil. IR (film) : 3250, 1653, 1553,
-1 1
755, 735 cm . H-NMR (Me SO-d ) δ: 1.41 (6H, s), 1.77 (3H, s), 2.20 (3H, d, J=1.9 Hz), 2.98
2
6
(2H, dd, J= 6.9, 7.5 Hz), 3.22 (2H, dt, J=6.9, 7.5 Hz), 5.76 (1H, q, J=1.9 Hz), 7.02 (1H, ddd, J=1.3,
6.9, 7.5 Hz), 7.16 (1H, ddd, J=1.3, 6.9, 7.5 Hz), 7.27 (1H, d, J=7.5 Hz), 7.57 (1H, d, J=7.5 Hz),
8.00 (1H, t, J=6.9 Hz). HR–MS m/z: Calcd for C H N O : 298.1681. Found: 298.1685. 2 5: Pale
18 22 2 2
-1 1
yellow oil. IR (film) : 3400, 3250, 1645, 1360, 930 cm . H-NMR (CDCl ) δ: 1.94 (3H, s), 2.44 (3H,
3
s), 2.85 (2H, t, J=6.3 Hz), 3.48 (2H, q, J=6.3 Hz), 5.50 (1H, br s), 6.79 (1H, dd, J=2.5, 8.1 Hz), 7.07
(1H, d, J=2.5 Hz), 7.18 (1H, d, J=2.5 Hz), 7.22 (1H, d, J=8.1 Hz), 7.30 (2H, d, J=7.5 Hz), 7.72 (2H,
d, J=7.5 Hz), 8.20 (1H, br s). HR–MS m/z: Calcd for C H N O S: 372.1144. Found: 372.1125.
19 20 2 4
5-(2-Acetylaminoethyl)-2,2,4-trimethyl-2H-1,2-oxazino[2,3-a]indole (24) from 1a — A
solution of 1a (70.5 mg, 0.32 mmol) and p-toluenesulfonic acid (70.4 mg, 0.41 mmol) in mesityl oxide
(5.5 mL) was heated at 55 °C for 2 h with stirring. Evaporation of the solvent under reduced pressure
afforded an oil, which was column-chromatographed on SiO with CHCl to give 2 4 (51.2 mg, 53%).
2
3
5-(2-Acetylaminoethyl)-2,2,4-trimethyl-2H-1,2-oxazino[2,3-a]indole (24) from 2 6 — 8%
Aq. HCl (2.5 mL) was added to a solution of 2 6 (34.0 mg, 0.11 mmol) in MeOH (5.0 mL) at 0 °C and the
mixture was stirred at rt for 1 h. After addition of H O to the reaction mixture under ice cooling, the whole
2
was extracted with CHCl –MeOH (95:5, v/v). The extract was washed with brine, dried over Na SO ,
3
2
4
and evaporated under reduced pressure to leave an oil, which was column-chromatographed on SiO with
2
CHCl –MeOH (99:1, v/v) to give 24 (25.0 mg, 78%).
3
N a, N b-Diacetyl-5-p -tosyloxytryptamine (27) from 2 5 — A solution of 2 5 (31.6 mg, 0.09
mmol) in anhydrous DMF (3.0 mL) was added to 60% NaH (10.0 mg, 0.25 mmol, washed with dry
benzene) at 0 °C with stirring. After additional stirring at rt for 10 min, a solution of AcCl (31.2 mg, 0.39
mmol) in anhydrous DMF (0.5 mL) was added to the resultant solution. The mixture was stirred at rt for
30 min. After addition of H O under ice cooling, the whole was extracted with EtOAc. The extract was
2
washed with brine, dried over Na SO , and evaporated under reduced pressure to leave an oil, which was
2
4
column-chromatographed on SiO with CHCl –MeOH (98:2, v/v) to give 2 7 (24.2 mg, 69%) and
2
3
unreacted 2 5 (9.5 mg, 30%) in the order of elution. 2 7: mp 66 °C (colorless needles, recrystallized from
-1 1
CH Cl –hexane). IR (KBr): 3380, 1698, 1680, 1660, 1550 cm . H-NMR (CDCl ) δ: 1.99 (3H, s),
2 2
3
2.45 (3H, s), 2.60 (3H, s), 2.87 (2H, t, J=6.3 Hz), 3.56 (2H, q, J=6.3 Hz, collapsed to t, J=6.3 Hz on
addition of D O), 5.66 (1H, br s, disappeared on addition of D O), 6.79 (1H, dd, J=2.5, 7.5 Hz), 7.28
2
2

(1H, d, J=2.5 Hz), 7.31 (2H, d, J=7.5 Hz), 7.35 (1H, s), 7.70 (2H, d, J=7.5 Hz), 8.30 (1H, d, J=7.5
Hz). Anal. Calcd for C H N O S: C, 60.86; H, 5.35; N, 6.76. Found: C, 60.80; H, 5.45; N, 6.75.
21 22 2 5
X-Ray Single Crystallographic Analysis of 17 — The reflection data were collected on a Rigaku
AFC5R diffractometer over the range of 79.66°<2θ<80.03° using CuK radiation (λ=1.54178 Å) and the
α
ω–2θ scan method at a 2θ scan speed of 6°/min. The structure of 1 7 was solved by the direct method
6
using MITHRIL and refined by the full-matrix least-squares method with anisotropic thermal factors for
non-hydrogen atoms and with isotropic ones for hydrogen atoms. The final R- and R -factors were 0.042
w
and 0.063 for 2511 observed reflections [I>3.00σ (I)], respectively. The atomic parameters are listed in
Table 1. Crystal data for 1 7: C H N O ; M=334.37; triclinic; space group, P1 (#2); a=10.7201 (9) Å,
17 22 2 5
3
b=11.4019 (9) Å, c=7.8385 (6) Å; α=99.204 (6)°, β=102.615 (7)°, γ =97.892 (6)° ; V=908.1 (1) Å ,
3
Z=2, D
=1.223 g/cm .
calc.
REFERENCES AND NOTES
1. This is Part 102 of a series entitled “The Chemistry of Indoles”. Part 101: F. Yamada, T. Hayashi, K.
Yamada, and M. Somei, Heterocycles, 2000, 5 3, 1881.
2. M. Somei, Heterocycles, 1999, 5 0, 1157 and references cited therein.
3. M. Somei, M. Nakajou, T. Teramoto, A. Tanimoto, and F. Yamada, Heterocycles, 1999, 5 1, 1949;
M. Hasegawa, K. Yamada, Y. Nagahama, and M. Somei, ibid., 1999, 5 1, 2815; M. Somei, K.
Noguchi, R. Yamagami, Y. Kawada, K. Yamada, and F. Yamada, ibid., 2000, 5 3, 7; T. Kurauchi,
Y. Nagahama, M. Hasegawa, K. Yamada, and M. Somei, ibid., 2000, 5 3, 1017; F. Yamada, A.
Goto, and M. Somei, ibid., 2000, 5 3, 1255.
4. M. Hasegawa, Y. Nagahama, K. Kobayashi, M. Hayashi, and M. Somei, Heterocycles, 2000, 5 2,
483.
5. M. Somei, N. Oshikiri, M. Hasegawa, and F. Yamada, Heterocycles, 1999, 5 1, 1237.
6. C. J. Gilmore, J. Appl. Cryst., 1984, 1 7, 42.