Reaction of 3/2-formylindoles with TOSMIC: Formation of indolyloxazoles and stable indolyl primary enamines

Article abstract of DOI:10.1016/j.tet.2004.12.022

3-Formylindole and its 1-substituted and 1,5-disubstituted derivatives react with TOSMIC in presence of potassium carbonate in methanol under reflux to furnish 5-(3′-indolyl)oxazoles, new stable E-2-(3′-indolyl)-2- tosylethenamines and two diastereomers of N-[2-(3′-indolyl)-1,2-dimethoxy] ethylformamides. In contrast, 2-formylskatole furnishes N-(1-tosyl-2-skatolyl) ethenylformamide.

Full text of DOI:10.1016/j.tet.2004.12.022

Tetrahedron 61 (2005) 1793–1801
Reaction of 3/2-formylindoles with TOSMIC: formation of
indolyloxazoles and stable indolyl primary enamines
a
b
b
Manas Chakrabarty,a, Ramkrishna Basak, Yoshihiro Harigaya and Hiroaki Takayanagi
*
aDepartment of Chemistry, Bose Institute, 93/1, A.P.C. Road, Kolkata 700009, India
bSchool of Pharmaceutical Sciences, Kitasato University, Minato-ku, Tokyo 108, Japan
Received 7 September 2004; revised 17 November 2004; accepted 9 December 2004
Available online 11 January 2005
Abstract—3-Formylindole and its 1-substituted and 1,5-disubstituted derivatives react with TOSMIC in presence of potassium carbonate i0n
methanol under reflux to furnish 5-(30-indolyl)oxazoles, new stable E-2-(30-indolyl)-2-tosylethenamines and two diastereomers of N-[2-(3 -
indolyl)-1,2-dimethoxy]ethylformamides. In contrast, 2-formylskatole furnishes N-(1-tosyl-2-skatolyl)ethenylformamide.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
methylisocyanide (TOSMIC) with aldehydes. This method
was later applied to several heteroaryl16a and azole
carbaldehydes,16b mostly leading to the corresponding
5-heteroaryl and 5-azolyloxazoles, including 5-(20-indolyl)-
oxazole from 2-formylindole (Scheme 1), which is of
relevance to our objective.
1,3-Azoles are important heterocycles,1a–c of which only
oxazoles do not participate in normal biochemical pro-
cesses. Yet, bioactive secondary metabolites containing the
oxazole ring are known, specially from marine organisms.2
Our continued interest in the synthesis3 and reactions4 of
condensed nitrogen heterocycles drew our attention to a
small group of several 2-alkyl-5-(30-indolyl)oxazoles of
microbial origin. These are pimprinine5a,b or WS-30581c,5c,d
pimprinethine,5c,6 pimprinaphine,5c WS-30581a and b5d and
labradorins 1 and 2,7 which display a broad spectrum of
biological activities including anticancer properties.7–9
Some of these metabolites have already been synthesised
by three different routes, viz. the cyclisation of
3-acylaminoacetylindoles,5b,c,10 the oxidative cyclisation
of N-acetyl/benzoyltryptamine11a,b and the cycloaddition
of appropriate in situ-derived rhodium carbenoids, with
nitriles.12 A number of analogues have also been syn-
thesised by the base-catalysed reaction of 3-formylindoles
with N-tosylmethylimino synthons13 and also by a tandem
aza-Wittig/heterocumulene-mediated annulation involving
iminophosphoranes.14 However, all these methods were
multi-step syntheses and the overall yields of the indolyl-
oxazoles were as low as 10% in quite a few cases. This
motivated us to0 try to develop an efficient, one-step
synthesis of 5-(3 -indolyl)oxazoles. Towards this end, we
intended to employ van Leusen’s oxazole synthesis,15a–c
which involves the base-catalysed reaction of tosyl-
Scheme 1.
In this backdrop, our modified objective was to extend this
protocol to 3-formylindoles. Such an attempt also appeared
to have been undertaken,17 in which potassium tert-
butoxide in 1,2-dimethoxyethane (DME) was used as the
base. Surprisingly, indole-3-acetonitriles were formed
instead of the expected indolyloxazoles (Scheme 2).
Scheme 2.
Keywords: 3-Formylindoles; TOSMIC; Base; Indolyloxazoles; Indolyl
primary enamines.
* Corresponding author. Tel.: C91 33 23506619; fax: C91 33 23506790;
e-mail: chakmanas@yahoo.co.in
In our view, the use of the strong base, potassium tert-
butoxide, was responsible for this unexpected outcome, and
the use of a milder base, viz. potassium carbonate would
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.12.022

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M. Chakrabarty et al. / Tetrahedron 61 (2005) 1793–1801
have led these reactions to the desired course. Accordingly,
we carried out the reaction of a number of 3-formylindoles
with TOSMIC using potassium carbonate in refluxing
methanol. As a result, although the target molecules were
formed in certain cases, several new structurally interesting
and mechanistically significant products, including one type
of stable indolyl primary enamines, were formed. The
identification of these products, the possible mechanism
of their formation, their synthetic potential and the
significance of some of their spectral data are presented in
this paper.
This intermediate possesses a carbon center, marked with
asterisk, that might well be more electrophilic than the
carbonyl carbon.19 Consequently, a nucleophilic attack at
this center by methanol, followed by a base-induced
b-elimination of p-toluenesulphinic acid from the resulting
molecule (4), may lead to the formation of the formamido
olefin 5. Thereafter, a Michael-type addition of weakly
nucleophilic methanol to the benzylic carbon of the
indolenine tautomer (6) of 5, followed by protonation,
may result in the formation of the diastereoisomers, 2A and
2B (erythro- and threo-), as shown in Scheme 4.
2. Results and discussion
When 3-formylindole (1a) was allowed to react with 1 equiv
of TOSMIC in the presence of potassium carbonate in
methanol under reflux, two products were formed in nearly
quantitative overall yield. Each of these products were
analysed for C13H16N2O3, corroborated by mass spectral
data (MC 248), and showed (1H NMR spectroscopy) the
presence of one 3-indolyl moiety, two methoxy groups, one
formamido group and two separate aliphatic methine
protons—one (d 4.67–4.80) as a doublet (JZ2.5–4 Hz)
and the other (d 4.62–5.52) as a doublet of doublet (JZ2.5–
4, w10 Hz). All these data could0only be accommodated in
the gross structure of N-[2-(3 -indolyl)-1,2-dimethoxy]-
ethylformamide (2), the two products being the dia-
stereomers 2A and 2B (Scheme 3). Each of 2A and 2B
recorded in its EI-MS the base peak at m/z 160, formed by
cleavage of the N-(methoxymethyl)formamide moiety, thus
lending additional support to the gross structures of 2A and
2B.
Scheme 4.
Since the outcome of the reaction with 3-formylindole (1a)
was different from that with 2-formylindole,16b the present
protocol was extended to the 3-formyl derivatives of
N-methyl, N-ethyl, 5-methoxy-N-methyl, 5-methoxy-N-
Scheme 3.
The mechanism of formation of these two products was
somewhat intriguing and their NMR spectral behaviour was
indeed revealing. As regards the latter, each diastereoisomer
recorded two sets of signals with 2:1 ratio. It suggested the
presence of each diastereoisomer as an equilibrium mixture
(2:1) of two rotamers, resulting from the restricted rotation
around the N-formyl group. Further, in each of the two
diastereoisomers, the 1H NMR signal for the aldehydic
proton of the formamido group appeared as a singlet in the
major rotamer and as a doublet (JZ11.7/11.9 Hz) in the
minor rotamer. Clearly, this observation was a reflection of
the dihedral angle between the NH and the CHO protons,
which must be 908 in the major rotamer and nearly 1808 in
the minor rotamer.
ethyl
and
5-methoxy-N-isopropylindoles
(1b–f,
respectively). Different results were obtained from 1b and
1c on one hand and from 1d–f on the other hand. Thus, each
of 1b and 1c furnished two products, viz. 7b and 8b from 1b,
and 7c and 8c from 1c in 79% and 75% overall yields,
respectively. In contrast, each of 1d–f furnished only one
type of products, 8d–f in (62–73)% yields (Scheme 5,
Table 1).
As to the formation of 2A and 2B, the intermediacy of 3a
(cf. a similar species 3b, postulated as an intermediate in the
van Leusen’s base-catalysed one-step synthesis of nitriles
from ketones and TOSMIC)18 must be assumed.
Scheme 5.

M. Chakrabarty et al. / Tetrahedron 61 (2005) 1793–1801
1795
Table 1. Reaction of 3-formylindoles (1b–f; 1 mmol) with TOSMIC (1.1 mmol) in presence of potassium carbonate (1.1 mmol) in methanol under reflux
3-Formylindoles (1)
Time (h)
Yielda (%)
R0
SM
R
7
8
Overall
1b
1c
1d
1e
1f
Me
Et
H
H
OMe
OMe
OMe
6
4
4
3
3
47
33
—
—
—
32
42
62
68
73
79
75
62
68
73
Me
Et
iPr
a Refers to isolated pure products.
The less polar products from 1b and 1c, that is 7b and 7c
were identified as the expected 5-(10-methyl/ethyl-30-
Since all the critical 1H and 13C NMR spectroscopic data of
8c–f paralleled those of 8b (see Section 4), the correctness
of the structures assigned to the former group of compounds
was thus established as well.
1
indolyl)oxazoles from their diagnostic H (H-2: wd 7.87,
s; H-4: d 7.38/7.46, s; H-20: d 7.24, s) and 13C (CH-2: d
149.1; CH-4: wd 123.0; C-5: d 148.4) NMR spectral data,
typical of 5-substituted oxazolyl moieties, in addition to
those expected for the N-alkyl-3-indolyl moieties (see
Section 4).
Two aspects of 8b–f now needed to be considered—their
stability and their mechanism of formation. As regards the
former, Albrecht’s studies revealed that, inter alia, both an
electron-withdrawing group (e.g., tosyl group in 8b–f) and a
p-conjugating hydrocarbyl group (e.g., indolyl moiety in
8b–f) at the b-carbon of a primary enamine stabilise the
enamine structure in preference to its aldimine tautomer.
The stability of 8b–f is thus accounted for. Nevertheless, the
structure of 8d, again as a representative, was finally
confirmed by single crystal X-ray crystallographic
analysis.23 The ORTEP diagram of 8d is shown in Figure 2.
The more polar products from 1b and 1c, that is 8b and 8c
and the only products from 1d–1f, that is 8d–f recorded
similar NMR spectral data. Thus, each of these products
showed the presence of a b,b-disubstituted primary enamine
moiety (OC]CH–NH2: d 7.77/7.78, 1H, t, JZ10/10.5 Hz
and d 4.31–4.34, 2H, d, JZ10/10.5 Hz, D2O-exchangeable;
CHa: d 142.6/142.9; Cb: wd 105), a tosyl group (MS: base
peaks at MCK155 m.u.) and a 2-unsubstituted (H-2: d
7.09–7.23, 1H, s; CH-2: d 129.7–131.4) 3-indolyl residue
(see Section 4). The products 8b–f thus turned out to
be the novel stable 2-[30-(substituted) indolyl]-2-
tosylethenamines.
Although the X-ray crystallographic analysis of a few 1,6-
diaryl-1,3,5-trienyl-1,6-diamines has previously been
documented,24a–c this is, to the best of our knowledge, the
first X-ray crystallographic analysis of an indolylethena-
mine. Also, the formation of 8b–f constitutes the first report
of indolylethenamines, although a number of indolic25 and
bisindolic26 enamides have previously been reported as
natural products.
The formation of these primary enamines could not be
explained by any straightforward mechanism. Although
primary enamines were first implicated as reactive inter-
mediates as early as 1914,20 the first stable primary enamine
was prepared nearly half a century later.21a,b Therefore,
before discussing the stability of 8b–f in the light of the
available information on primary enamines and their
equilibrium with tautomeric imines, most of which is due
to the pioneering work of Albrecht et al.,22a–c it became all
the more desirable to settle the structures of 8b–f beyond
doubt. This was accomplished by analysing the HMQC and
HMBC spectra of 8b (as a representative compound), which
established the structure assigned to it. The observed HMBC
correlations of 8b are shown in Figure 1.
As to the mechanism of the formation of 8b–f, the N-(2-
aryl-1-tosylethenyl)formamides (A; cf. 30a in Scheme 4)
are likely to be the crucial intermediates. Compounds of
¨
type A were also independently suggested by Schollkopf et
al.27a,b as intermediates in the formation of carboxylic acids
via nitriles from the reaction of aldehydes and ketones with
TOSMIC. The lone pair of electrons on the indolic nitrogen
of A then triggers the protonation (from methanol) of the
enamidic double bond, resulting in the indoleninium species
9. Subsequently, a 1,2-shift of the tosyl group with
simultaneous neutralisation of the indoleninium cation,
followed by the loss of a proton, gives rise to the
intermidiate 10. Finally, a nucleophilic attack by methanol
to the N-formyl carbon of 10, followed by the loss of a
molecule of methyl formate and subsequent protonation,
gives rise to the enamines 8b–f (Scheme 6).
The formation of the indoleninium species 9 through the
participation of the indole ring seems to be crucial to the
formation of the enamines. This explains why increasing
electron density at the indolic C-3 either by the presence of
an alkyl group at indolic N(1) or by the additional presence
of an electron-donating methoxyl at C-5 of the indole ring
gives rise to the enamines 8b–f in increasing yields in
going from 1b to 1f (see Table 1). Indeed, the three
Figure 1. HMBC correlations of 8b.

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M. Chakrabarty et al. / Tetrahedron 61 (2005) 1793–1801
Figure 2. ORTEP diagram of 8d.
5-methoxyindoles 1d–f furnished the enamines (8d–f) as the
only products.
Whereas, the reaction with 1j, which took twice the time for
completion, provided 7j and 11j in ca. 5:14 relative yields.
When N-boc-3-formylindole (1k) was used as the substrate,
the deprotected indolyloxazole (11i) was the only product.
Strangely, when N-ethoxycarbonyl-3-formylindole (1l) was
treated with TOSMIC under similar conditions, a mixture of
2A and 2B in nearly quantitative yield was obtained as the
only products. This observation along with the lack of
formation of similar products from 1i–k pointed out that the
cyclisation preceded N-deprotection in the case of reactions
with 1i–k, whereas N-deprotection preceded subsequent
reaction with TOSMIC in the case of reaction with 1l. The
reactions with 1g–k are shown in Scheme 7 and the results
(including that from 1l) in Table 2.
With N-benzyl-3-formylindole (1g) and 5-bromo-N-methyl-
3-formylindole (1h), only the respective 5-(30-indolyl)-
oxazoles (7g,h) were formed. But with N-tosyl-3-formyl-
indole (1i) and its 5-methoxy derivative (1j), the respective
5-(30-indolyl)oxazoles (7i,j) along with their N-deprotected
analogues (11i,j) were formed in excellent overall yields. In
the case of these two substrates (1i,j), that the formation of
the indolyloxazoles and their N-deprotection were taking
place simultaneously was evident from a comparison of the
relative yields of 7i and 11i with those of 7j and 11j as
against the respective time periods for the completion of the
reactions. Thus, the reaction with 1i, which was complete in
2 h, furnished 7i and 11i in nearly 7:5 relative yields.
In this connection, the contrasting behaviour of

M. Chakrabarty et al. / Tetrahedron 61 (2005) 1793–1801
1797
N-(indolylethenyl)formamide 13 (62%) (Scheme 8),
identified spectroscopically.
Scheme 8.
1
Like 2A and 2B, 13 also showed two sets of H and 13C
NMR signals, thereby demonstrating the presence of two
rotamers in nearly 3:2 ratio.
3. Conclusions
The present work demonstrates the versatility of TOSMIC
in bringing about a wide variety of unpredictable reactions
particularly with indole-3-carbaldehydes. Besides the for-
mation of the expected 5-(30-indolyl)oxazoles (7b,c,g–j,
11i,j), the formation of the novel, rearranged stable indolyl
primary enamines (8b–f), the mechanistically conspicuous
dimethoxy-N0-formyltryptamines (2A,B) and N-(1-tosyl-2-
skatolyl)ethenylformamide (13) and the interesting spectro-
scopic behaviour (presence of rotamers) of 2A, 2B and 13
highlight the importance of our work. The present work also
provides us with a suitable substrate, 13, for preparing
indolo[1,2-c]pyrimidines, which is open to exploitation.
More importantly, on acylation/aroylation, followed by
proteodetosylation, these enamines opens up a new and
practicable synthetic route to the analogues of the naturally
occurring indolic25 and bisindolic enamides.26
Scheme 6.
Scheme 7.
2-formylindole and 2-formylimidazole towards their base-
induced reaction with TOSMIC, referred to earlier, drew our
attention. While the former, using potassium carbonate in
methanol as the base, furnished 5-(20-indolyl)oxazole,16b
the latter, using 1,3-diazabicyclo[5.4.0]undec-7-ene (DBU)
in tetrahydrofuran (THF) as the base, afforded 3-tosyl-
imidazo[1,2-c]pyrimidine, albeit in low yield (14%). These
workers similarly tried to convert 2-formylindole to
indolopyrimidine by treatment with TOSMIC using DBU
in THF, but only a tarry mass was reported to have been
formed.16b We felt that this objective could be accomplished
by blocking C-3 of 2-formylindole and carrying out the
reaction using DBU in THF. Accordingly, 2-formylskatole
(12) was treated with equimolar amounts of TOSMIC and
DBU in THF at room temperature. The reaction was
complete in 2 h, but it furnished, contrary to expectation, the
4. Experimental
4.1. General
Solvents were dried and purified using standard techniques.
Melting points were determined on a Toshniwal apparatus
and are uncorrected. IR spectra were recorded on Nicolet
Impact 410 and Magnus 750 Series II spectrophotometers,
LR EI-MS in a AEI MS 30 and LR EI-MS as well as HR
MS, both EI and FAB (m-nitrobenzyl alcohol as liquid
matrix) on JEOL JMS-AX505HA and JEOL JMS-700
1
MStation mass spectrometers and H (500 MHz) and 13C
Table 2. Reaction of 3-formylindoles (1g–l; 1 mmol) with TOSMIC (1.1 mmol) in presence of potassium carbonate (1.1 mmol) in methanol under reflux
3-Formylindoles (1)
Time (h)
Yielda (%)
R0
SM
R
7
11
Overall
1g
1h
1i
1j
1k
1lc
Bn
Me
Tos
Tos
Boc
CO2Et
H
Br
H
OMe
H
H
4
3
2
4
3
—
72
77
53
24
—
—
—
—
37
68
38b
—
72
77
90
92
38
98
a Refers to isolated pure products.
b This product is the same (11i) as that obtained from 1i.
c Furnished 2A, 2B as the only products.

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M. Chakrabarty et al. / Tetrahedron 61 (2005) 1793–1801
(125 MHz) NMR spectra, both 1D and 2D including DEPT-
135, on a Bruker DRX 500 NMR spectrometer. Individual
1H and 13C NMR assignments, wherever made, were based
on HMQC and HMBC spectral analyses. Silica gel G
(Merck, India) was used for TLCs, both analytical and
preparative, and silica gel (60–120 mesh; Qualigens, India)
was used for column chromatography (CC). Elemental
analyses were performed in a Dr. Hans Hoesli Analyser.
The 3-formylindoles 1b,28 1c,29 1g,30 1i,31 1j,32 1k33 and
2-formylskatole (12)34 were prepared following the
literature procedures. For 2A, 2B and 13, the designatory
letters mj and mn, used in presenting NMR data, stand for
the major and the minor rotamer, respectively.
4.2.5. 1-Ethoxycarbonyl-3-formylindole (1l).35 Yellow
crystals; yield: 1.04 g (96%); mp 74 8C; 1H NMR
(CDCl3): d 1.51 (3H, t, JZ7 Hz), 4.57 (2H, q, JZ7.5 Hz),
7.38 and 7.43 (1H, t each, JZ7.5 Hz), 8.18 (1H, d, JZ
7.5 Hz), 8.26 (1H, s), 8.29 (1H, d, JZ7.5 Hz), 10.10 (1H, s).
Anal. calcd for C12H11NO3: C, 66.36; H, 5.07; N, 6.45.
Found C, 66.28; H, 5.05; N, 6.43.
4.3. General procedure for the reaction of 3-formyl-
indoles (1a–l) with TOSMIC
A solution of the 3-formylindole (1a–l, 1 mmol) and
TOSMIC (0.22 g, 1.1 mmol) in dry MeOH (10 mL)
containing anhydrous K2CO3 (0.16 g, 1.1 mmol) was
refluxed until the 3-formylindole was consumed completely
(see Tables 1 and 2). The solution was then poured into
water and extracted with EtOAc (3!25 mL). The pooled
extracts were washed with water until free from of alkali,
dried (Na2SO4), solvent distilled off and the resulting
residue purified by prep. TLC [35% EtOAc/pet. ether
(double development) for 2; 35% EtOAc/pet. ether for
7b,c,j, 8b,c,e,f, 11j; 25% EtOAc/pet. ether for 7g,i, 11i;
EtOAc: pet. ether:benzene (2:4:4) for 8d] to furnish the
products, as shown in Tables 1 and 2.
4.2. General procedure for the preparation of 3-
formylindoles (1d–f,h,l)
To a solution of the 3-formylindole (5 mmol) in dry DMSO
(5 mL) was added NaH (0.22 g, 5.5 mmol, 60% dispersion
in mineral oil) and stirred at room temperature for 30 min.
The respective alkyl iodide (MeI for 1d, 1h; EtI for 1e; iPrBr
for 1f; ClCO2Et for 1l) (0.34 mL for MeI, 0.45 mL for EtI
i
and 0.52 mL for PrBr, 5.5 mmol in each case) was then
added to this suspension, which was then stirred for another
30 min. The reaction mixture was poured into crushed ice
and extracted with EtOAc (3!25 mL). The pooled extracts
were washed with water, dried (Na2SO4), solvent distilled
off and the resulting residue crystallised from pet. ether–
CH2Cl2 to furnish the 3-formylindoles (1d–f,h,l).
4.3.1. N-[2-(30-Indolyl)-1,2-dimethoxy]ethylformamide
(2A and 2B). Overall yield (2AC2B) 0.24 g (98%).
2A (mixture of two rotamers). Cream yellow solid; mp 144–
146 8C (pet. ether–CH2Cl2); nmax (nujol): 3327, 3267, 1692,
1665, 732 cmK1; 1H NMR (CDCl3): d 3.36 and 3.37 (3H, s
each, mn), 3.40 and 3.43 (3H, s each, mj), 4.62 (1H, dd, JZ
10, 2.5 Hz, mn), 4.76 (1H, d, JZ2.5 Hz, mj), 4.80 (1H, d,
JZ2.5 Hz, mn), 5.52 (1H, dd, JZ10, 2.5 Hz, mj), 6.29 (1H,
dd, JZ10, 11.9 Hz, mn), 6.33 (1H, d, JZ10 Hz, mj), 7.14
and 7.15 (1H, t each, JZ7.5 Hz, mj, mn), 7.15 (1H, s, mn),
7.19 (1H, s, mj), 7.20 (mj) and 7.22 (mn) (1H, t each, JZ
7.5 Hz), 7.36 (mj) and 7.38 (mn) (1H, d each, JZ7.5 Hz),
7.65 (mn) and 7.69 (mj) (1H, d each, JZ7.5 Hz), 7.95 (1H,
d, JZ11.9 Hz, mn), 8.26 (1H, s, mj), 8.44 (mj) and 8.50
(mn) (1H, br s each); 13C NMR: d 55.5 (mn), 56.8 (mj), 57.6
(mn), 57.8 (mj), 78.3 (mj), 78.8 (mn), 81.4 (mj), 87.4 (mn),
111.8 (mj), 111.9 (mn), 119.2 (mn), 119.5 (mj), 120.50 (mj),
120.54 (mn), 122.8 (mj), 122.9 (mn), 123.8 (mj), 124.1
(mn), 162.0 (mj), 164.2 (mn) (all CH), 111.5 (mn), 111.7
(mj), 127.1 (2!; mjCmn), 136.5 (2!; mjCmn) (all C);
EI-MS: m/z (%) 248 (MC, 7), 216 (61), 214 (25), 184 (22),
160 (100), 156 (50), 144 (38), 130 (60), 129 (29), 117 (18).
HR FAB-MS: MC, Anal. calcd for C13H16N2O3 248.1161.
Found 248.1173.
4.2.1. 3-Formyl-5-methoxy-1-methylindole (1d). Brown
crystals; yield: 0.94 g (100%); mp 128–130 8C; nmax (nujol):
1
3105, 1645, 1614, 1536, 1265, 1034, 783 cmK1; H NMR
(CDCl3): d 3.88 and 3.89 (3H, s each), 6.97 (1H, dd, JZ9,
2.5 Hz), 7.22 (1H, d, JZ9 Hz), 7.59 (1H, s), 7.78 (1H, d,
JZ2.5 Hz), 9.92 (1H, s). Anal. calcd for C11H11NO2: C,
69.84; H, 5.82; N, 7.40. Found C, 69.78; H, 5.83; N, 7.42.
4.2.2. 1-Ethyl-3-formyl-5-methoxyindole (1e). Reddish
brown flakes; yield: 1.0 g (99%); mp 98 8C; nmax (nujol):
1
1650, 1533, 1255, 1215, 724 cmK1; H NMR (CDCl3): d
1.54 (3H, t, JZ7 Hz), 3.89 (3H, s), 4.19 (2H, q, JZ7 Hz),
6.97 (1H, d, JZ8 Hz), 7.26 (1H, d, JZ8 Hz), 7.68, 7.8 and
9.95 (1H, s each). Anal. calcd for C12H13NO2: C, 70.93; H,
6.40; N, 6.89. Found C, 70.98; H, 6.38; N, 6.87.
4.2.3. 3-Formyl-1-isopropyl-5-methoxyindole (1f).
Yellow solid; yield: 1.06 g (98%); mp 108–110 8C; nmax
(nujol): 1659, 1619, 1261, 1089, 731 cmK1 1H NMR
;
(CDCl3): d 1.58 (6H, d, JZ6.5 Hz), 3.89 (3H, s), 4.64 (1H,
septet, JZ6.5 Hz), 6.96 (1H, dd, JZ9, 2 Hz), 7.29 (1H, d,
JZ9 Hz), 7.77 (1H, s), 7.80 (1H, d, JZ2 Hz), 9.96 (1H, s).
Anal. calcd for C13H15NO2: C, 71.89; H, 6.91; N, 6.45.
Found C, 71.80; H, 6.93; N, 6.43.
2B (mixture of two rotamers). White solid; mp 72–74 8C
(pet. ether–CH2Cl2); nmax (CHCl3): 3473, 3414, 1691, 1491,
1081 cmK1; 1H NMR (CDCl3): d 3.32 (3H, s, mn), 3.34 (3H
mj C3H mn, s), 3.37 (3H, s, mj), 4.67 (1H, d, JZ3.5 Hz,
mj), 4.68 (1H, d, JZ4 Hz, mn), 4.76 (1H, dd, JZ10, 4 Hz,
mn), 5.51 (1H, dd, JZ10, 3.5 Hz, mj), 6.03 (1H, dd, JZ10,
11.7 Hz, mn), 6.29 (1H, d, JZ10 Hz, mj), 7.14 (1H mj C1H
mn, t, JZ7.5 Hz), 7.20 (1H, s, mn), 7.21 (1H mj C1H mn, t,
JZ7.5 Hz), 7.27 (1H, d, JZ2 Hz, mj), 7.38 (mn) and 7.38
(mj) (1H, d each, JZ8 Hz), 7.71 (mn) and 7.74 (mj) (1H, d
each, JZ8 Hz), 8.11 (1H, d, JZ11.7 Hz, mn), 8.29 (1H, s,
mj), 8.42 (mj) and 8.46 (mn) (1H, br s each); 13C NMR: d
4.2.4. 5-Bromo-3-formyl-1-methylindole (1h). Pale
yellow solid; yield: 1.19 g (100%); mp 122–124 8C; nmax
(nujol): 1660, 1649, 1535, 1084, 731 cmK1 1H NMR
;
(CDCl3): d 3.86 (3H, s), 7.22 (1H, d, JZ8.5 Hz), 7.44 (1H,
dd, JZ8.5, 1.5 Hz), 7.66, 8.46 and 9.9 (1H, s each). Anal.
calcd for C10H8NOBr: C, 50.42; H, 3.36.; N, 5.88. Found C,
50.46; H, 3.35; N, 5.86.

M. Chakrabarty et al. / Tetrahedron 61 (2005) 1793–1801
1799
55.6 (mn), 57.0 (mj), 57.3 (mn), 57.5 (mj), 78.8 (mj), 79.2
(mn), 81.0 (mj), 86.9 (mn), 111.7 (mj), 111.8 (mn), 120.2
(2!; mjCmn), 120.4 (mj), 120.6 (mn), 122.7 (mj), 122.9
(mn), 124.4 (mj), 124.7 (mn), 161.8 (mj), 163.9 (mn) (all
CH), 111.0 (2!; mjCmn), 126.8 (mn), 127.2 (mj), 136.6
(mj), 136.8 (mn) (all C); EI-MS: m/z (%) 248 (MC, 11), 216
(50), 214 (19), 184 (14), 160 (100), 156 (40), 144 (30), 130
(51), 129 (22), 117 (17). HR FAB-MS: MC, Anal. calcd for
C13H16N2O3 248.1160. Found 248.1152.
751 cmK1; 1H NMR (d6-DMSO): d 2.27 (3H, s), 7.35 (2H,
d, JZ8 Hz), 7.36 (1H, t, JZ7.5 Hz), 7.43 (1H, t, JZ
7.5 Hz), 7.75 (1H, s), 7.91 (2H, d, JZ8 Hz), 7.93 (1H, d,
JZ8 Hz), 7.99 (1H, d, JZ8 Hz), 8.21 (1H, s), 8.48 (1H, s);
13C NMR: d 21.8 (CH3), 114.3, 121.7, 123.6, 124.1, 125.1,
126.6, 127.8 (2!), 131.2 (2!), 145.3/146.7 (all CH),
111.4, 127.1, 134.5, 135.1, 146.7/145.3, 152.2 (all C);
EI-MS: m/z (%) 338 (MC, 29), 183 (100), 155 (13), 127
(24), 91 (16). Anal. calcd for C18H14N2O3S: C, 63.90; H,
4.14; N, 8.28. Found C, 63.95; H, 4.12; N, 8.24.
4.3.2. 5-(10-Methyl-30-indolyl)oxazole (7b). Waxy; yield:
0.091 g (46%); nmax (nujol): 3128, 1632, 1527, 1332, 1089,
970, 741 cmK1; 1H NMR (CDCl3): d 3.81 (3H, s), 7.24 (1H,
s), 7.24 (1H, dt, JZ7.5, 1 Hz), 7.30 (1H, dt, JZ7.5, 1 Hz),
7.35 (1H, d, JZ8 Hz), 7.39 (1H, s), 7.83 (1H, d, JZ8 Hz),
7.87 (1H, s); 13C NMR: d 33.4 (N-CH3), 110.1, 119.5,
120.4, 121.0, 123.0, 127.0, 149.1 (all CH), 104.3, 125.0,
137.5, 148.4 (all C); EI-MS: m/z (%) 198 (MC, 100), 169
(19), 158 (14), 143 (55), 128 (12), 115 (14). Anal. calcd for
C12H10N2O: C, 72.72; H, 5.05; N, 14.14. Found C, 72.78; H,
5.03; N, 14.10.
4.3.7. 5-(50-Methoxy-10-tosyl-30-indolyl)oxazole (7j).
White amorphous solid; yield: 0.09 g (24%); mp 160–
162 8C (pet. ether–CH2Cl2); nmax (nujol): 3130, 1631, 1595,
1230, 1141, 970, 799 cmK1; 1H NMR (CDCl3): d 2.34 (3H,
s), 3.86 (3H, s), 7.0 (1H, dd, JZ9, 2 Hz), 7.18 (1H, d, JZ
2 Hz), 7.23 (2H, d, JZ8 Hz), 7.34 (1H, s), 7.78 (2H, d, JZ
8 Hz), 7.86 (1H, s), 7.93 (1H, d, JZ9 Hz), 7.95 (1H, s); 13C
NMR: d 21.9 (CH3), 56.1 (OCH3), 103.5, 114.8, 115.1,
122.4, 124.2, 127.2 (2!), 130.4 (2!), 145.7/146.1 (all
CH), 111.2, 128.3, 130.2, 135.2, 146.1/145.7, 150.3, 157.3
(all C); EI-MS: m/z (%) 368 (MC, 26), 213 (100), 199 (9),
115 (18). Anal. calcd for C19H16N2O4S: C, 61.95; H, 4.34;
N, 7.60. Found C, 61.90; H, 4.35; N, 7.57.
4.3.3. 5-(10-Ethyl-30-indolyl)oxazole (7c). Waxy; yield:
0.07 g (33%); nmax (film): 3127, 1631, 1608, 1525, 1208,
1089, 977, 741 cmK1; 1H NMR (CDCl3): d 1.50 (3H, t, JZ
7.5 Hz), 4.20 (2H, q, JZ7.5 Hz), 7.23 (1H, dt, JZ7.5,
1 Hz), 7.24 (1H, s), 7.29 (1H, dt, JZ7.5, 1 Hz), 7.38 (1H, d,
JZ8 Hz), 7.47 (1H, s), 7.84 (1H, d, JZ8 Hz), 7.87 (1H, s);
13C NMR: d 15.7 (CH3), 41.6 (N-CH2), 110.2, 119.5, 120.5,
121.0, 122.9, 125.28, 149.1 (all CH), 104.4, 125.22, 136.5,
148.4 (all C); EI-MS: m/z (%) 212 (MC, 100), 197 (52).
Anal. calcd for C13H12N2O: C, 73.58; H, 5.66; N, 13.20.
Found C, 73.43; H, 5.63; N, 13.25.
4.3.8. (E)-2-(10-Methyl-30-indolyl)-2-tosylethenamine
(8b). Reddish brown solid; yield: 0.104 g (32%); mp 92–
94 8C (pet. ether–CH2Cl2); nmax (nujol): 3463, 3354, 1641,
1
1536, 1275, 1145, 743 cmK1; H NMR (CDCl3): d 2.31
(3H, s, CH3), 3.77 (3H, s, N-CH3), 4.35 (2H, d, JZ10.5 Hz;
D2O-exchangeable; NH2), 6.99 (1H, t, JZ7.5 Hz, H-50),
7.06 (2H, d, JZ8 Hz, H-300, 500),0 7.08 (1H, d, JZ7.5 Hz,
H-40), 7.17 (1H, t, JZ7.5 Hz, H-6 ), 7.18 (1H, s, H-20), 7.29
(1H, d, JZ7.5 Hz, H-70), 7.55 (2H, d, JZ8 Hz, H-200, 600),
7.78 (1H, t, JZ10.5 Hz, ]CHNH2; collapsed to a singlet on
addition of D2O); 13C NMR: d 21.7 (CH3), 33.4 (N-CH3),
102.3 (C-30), 104.9 [ArC(Tos)]], 110.0 (CH-70), 119.94
and 119.98 (CH-40, 50), 122.1 (CH-60), 126.7 (C-30a), 1270.3
(2!; CH-200, 600), 129.4 (2!; 0C0 H-300, 500), 131.4 (CH-2 ),
137.1 (C-70a), 140.1 (C-1 ), 142.6 (C-400), 142.9
(]CHNH2); EI-MS: m/z (%) 326 (MC, 56), 171 (100),
156 (11), 144 (21), 130 (10), 91 (11). HR FAB-MS: MC,
Anal. calcd for C18H18N2O2S 326.1089. Found 326.1091.
4.3.4. 5-(10-Benzyl-30-indolyl)oxazole (7g). Orange
crystals; yield: 0.195 g (71%); mp 106–108 8C (pet. ether–
CH2Cl2); nmax (nujol): 1633, 1527, 1182, 970, 751 cmK1
;
1H NMR (CDCl3): d 5.32 (2H, s), 7.14 (2H, d, JZ7 Hz),
7.25 (2H, t, JZ7 Hz), 7.26 (1H, s), 7.2–7.27 (1H, m), 7.29
(1H, d, JZ7.5 Hz), 7.27–7.35 (2H, m), 7.45 (1H, s), 7.85
(1H, s), 7.86 (1H, d, JZ7.5 Hz); 13C NMR: d 50.7 (N-CH2),
110.7, 119.9, 120.5, 121.3, 123.3, 126.3, 127.3 (2!), 128.3,
129.3 (2!), 148.2/149.2 (all CH), 105.1, 125.3, 137.0,
137.1, 149.2/148.2 (all C); EI-MS: m/z (%) 274 (MC, 100),
234 (13), 183 (11), 120 (7), 91 (40). Anal. calcd for
C18H14N2O: C, 78.83; H, 5.10; N, 10.21. Found C, 78.91; H,
5.11; N, 10.18.
4.3.9. (E)-2-(10-Ethyl-30-indolyl)-2-tosylethenamine (8c).
Brown solid; yield: 0.14 g (41%); mp 70–72 8C (pet. ether–
CH2Cl2); nmax (nujol): 3471, 3355, 1639, 1271, 1142, 1080,
1
741 cmK1; H NMR (CDCl3): d 1.44 (3H, t, JZ6.5 Hz),
4.3.5. 5-(50-Bromo-10-methyl-30-indolyl)oxazole (7h).
Orange solid; yield: 0.214 g (77%); mp 88–90 8C (pet.
ether–CH2Cl2); nmax (nujol): 1639, 1527, 1109, 903,
2.28 (3H, s), 4.15 (2H, q, JZ6.5 Hz), 4.33 (2H, d, JZ10 Hz,
D2O-exchangeable; NH2), 6.98 (1H, t, JZ7.5 Hz), 7.05
(2H, d, JZ7 Hz), 7.10 (1H, d, JZ7.5 Hz), 7.16 (1H, t, JZ
7.5 Hz), 7.23 (1H, s), 7.31 (1H, d, JZ7.5 Hz), 7.54 (2H, d,
JZ7 Hz), 7.78 (1H, t, JZ10 Hz, ]CHNH2; collapsed to a
singlet on addition of D2O); 13C NMR: d 15.8, 21.7 (both
CH3), 41.5 (CH2), 110.0, 119.9, 120.0, 121.9, 127.4 (2!),
129.4 (2!), 129.7 (all CH), 142.6 (2!; CHCC), 102.4,
105.2, 126.9, 136.2, 140.0 (all C); FAB-MS: m/z (%) 340
(MC, 85), 313 (10), 186 (39), 185 (100), 172 (23), 158 (49),
130 (13). Anal. calcd for C19H20N2O2S: C, 67.05; H, 5.88;
N, 8.23. Found C, 67.11; H, 5.87; N, 8.26.
1
777 cmK1; H NMR (CDCl3): d 3.80 (3H, s), 7.20 (1H, s),
7.20 (1H, d, JZ8.5 Hz), 7.36 (1H, s), 7.37 (1H, dd, JZ8.5,
1.5 Hz), 7.88 (1H, s), 7.96 (1H, d, JZ1.5 Hz); 13C NMR: d
33.6 (N-CH3), 111.6, 119.8, 123.0, 125.9, 127.9, 149.3 (all
CH), 104.0, 114.4, 126.6, 136.1, 147.6 (all C); EI-MS: m/z
(%) 278 (MC, 100), 276 (100), 197 (21). Anal. calcd for
C12H9N2OBr: C, 51.98; H, 3.24; N, 10.10. Found C, 51.90;
H, 3.22; N, 10.14.
4.3.6. 5-(10-Tosyl-30-indolyl)oxazole (7i). Pale yellow
solid; yield: 0.18 g (53%); mp 144 8C (pet. ether–CH2Cl2);
nmax (nujol): 3145, 3118, 1633, 1593, 1176, 1113, 961,
4.3.10. (E)-2-(50-Methoxy-10-methyl-30-indolyl)-2-tosyl-
ethenamine (8d). Colourless prisms; yield: 0.22 g (62%);

1800
M. Chakrabarty et al. / Tetrahedron 61 (2005) 1793–1801
mp 180–182 8C (pet. ether–EtOAc); nmax (nujol): 3461,
JZ9, 2 Hz), 7.25 (1H, s), 7.29 (1H, d, JZ2 Hz), 7.32 (1H,
d, JZ9 Hz), 7.52 (1H, d, JZ2 Hz), 7.91 (1H, s), 8.72 (1H,
br s); 13C NMR: d 56.3 (OCH3), 102.1, 112.8, 113.6, 119.6,
123.2, 149.2 (all CH), 105.6, 125.0, 131.7, 148.5, 155.4 (all
C); EI-MS: m/z (%) 214 (MC, 100), 199 (33), 171 (28).
Anal. calcd for C12H10N2O2S: C, 67.28; H, 4.67; N, 13.08.
Found C, 67.35; H, 4.66; N, 13.06.
1
3347, 1639, 1533, 1269, 1215, 1134, 1082, 671 cmK1; H
NMR (CDCl3): d 2.29 (3H, s), 3.67 (3H, s), 3.73 (3H, s),
4.32 (2H, d, JZ10 Hz), 6.42 (1H, s), 6.81 (1H, d, JZ
8.5 Hz), 7.08 (2H, d, JZ8 Hz), 7.09 (1H, s), 7.16 (1H, d,
JZ8.5 Hz), 7.55 (2H, d, JZ8 Hz), 7.77 (1H, t, JZ10 Hz);
13C NMR: d 21.7, 33.5, 56.0 (all CH3), 101.4, 110.7, 112.4,
127.5 (2!), 129.4 (2!), 131.8, 142.9 (all CH), 101.7,
105.2, 127.5, 132.5, 140.2, 142.6, 154.6 (all C); EI-MS: m/z
(%) 356 (MC, 58), 202 (16), 201 (100), 186 (10), 185 (10),
174 (11). Anal. calcd for C19H20N2O3S: C, 64.04; H, 5.61;
N, 7.86. Found C, 64.15; H, 5.60; N, 7.89.
4.4. Reaction of 2-formyskatole (12) with TOSMIC
To a solution of 2-formylskatole (0.16 g, 1 mmol) in THF
(2 mL) was added TOSMIC (0.22 g, 1.1 mmol) and DBU
(0.17 mL, 1.1 mmol), the mixture stirred at room tempera-
ture for 2 h and then neutralised with acetic acid. The
solution was poured into water and extracted with EtOAc
(3!20 mL). The pooled extracts were washed with water,
dried (Na2SO4), solvent distilled off and the resulting
residue purified by prep. TLC using 20% EtOAc/pet. ether
as the developing system to furnish 13.
4.3.11. (E)-2-(10-Ethyl-50-methoxy-30-indolyl)-2-tosyl-
ethenamine (8e). Reddish brown solid; yield: 0.25 g
(68%); mp 142–144 8C (pet. ether–CH2Cl2); nmax (nujol):
3502, 3376, 1633, 1533, 1268, 1215, 1129, 1076, 671 cmK1
;
1H NMR (CDCl3): d 1.42 (3H, t, JZ7.5 Hz), 2.29 and 3.68
(3H, s each), 4.10 (2H, q, JZ7.5 Hz), 4.31 (2H, d, JZ
10.5 Hz), 6.46 (1H, d, JZ2 Hz), 6.80 (1H, dd, JZ9, 2 Hz),
7.07(2H,d,JZ8 Hz), 7.14(1H,s), 7.19(1H,d,JZ9 Hz),7.55
(2H, d, JZ8 Hz), 7.77 (1H, t, JZ10.5 Hz); 13C NMR: d 15.8,
21.7 (both CH3), 56.1 (OCH3), 41.6 (N-CH2), 101.6, 110.7,
112.2, 127.5 (2!), 129.4 (2!), 130.1 (all CH), 142.6 (2!;
CHCC), 101.9, 105.5, 127.6, 131.5, 140.1, 154.5 (all C);
EI-MS: m/z (%) 370 (MC, 93), 216 (41), 215 (100), 188
(32), 185 (18), 160 (15), 91 (20). Anal. calcd for
C20H22N2O3S: C, 64.86; H, 5.94; N, 7.56. Found C,
64.90; H, 5.95; N, 7.52.
4.4.1. N-[1-Tosyl-2-(30-methyl-20-indolyl)]ethenylforma-
mide (13; 3:2 mixture of two rotamers). Yellow solid,
yield: 0.22 g (62%); mp 74–76 8C (pet. ether–CH2Cl2); nmax
(nujol): 3362, 1712, 1639, 1225, 1137, 1076, 671 cmK1; 1H
NMR (CDCl3): d 1.70 (mj) and 1.72 (mn) (3H, s each), 2.34
(3H mj C3H mn, s), 7.11 and 7.12 (2H, d each, JZ7 Hz,
mj, mn), 7.10 (1H, d, JZ8 Hz) and 7.14 (1H, d, JZ8 Hz)
(mj, mn), 7.25 (1H mjC1H mn, t, JZ8 Hz), 7.39 (1H mj
C1H mn, t, JZ8 Hz), 7.44 (mn) and 7.43 (mj) (2H, d each,
JZ8 Hz), 7.47 (1H mjC1H mn, d, JZ8 Hz), w7.46 (1H, s,
mn), 7.65 (1H, d, JZ12 Hz, mj), 7.95 (1H, d, JZ11 Hz,
mn), 8.19 (1H, s, mj), 8.39 (1H, d, JZ12 Hz, mj), 8.51 (1H,
d, JZ8 Hz, mn), 8.67 (mn) and 8.77 (mj) (1H, br s each);
13C NMR: d 9.0 (mj), 14.5 (mn), 21.9 (mj), 23.0 (mn), 111.8
(mj), 111.9 (mn), 119.5 (mj), 119.6 (mn), 120.1 (2!; mjC
mn), 124.1 (mj), 124.2 (mn), 127.7 (2!; mn), 127.8 (2!;
mj), 130.0 (2!; mj), 130.1 (2!; mn), 131.4 (mj), 135.0
(mn), 158.8 (mj), 162.8 (mn) (all CH), 114.1 (mj), 114.2
(mn), 116.2 (mn), 117.6 (mj), 120.4 (mn), 121.1 (mj), 128.1
(2!; mjCmn), 136.6 (mn), 136.8 (mj), 137.2 (mn), 137.3
(mj), 144.6 (mj), 144.8 (mn) (all C); EI-MS: m/z (%) 354
(MC, 88), 200 (17), 199 (100), 171 (31), 158 (29), 144 (13),
130 (13). HR FAB-MS: MC, Anal. calcd for C19H18N2O3S
354.1038. Found 354.1059.
4.3.12. (E)-2-(10-Isopropyl-50-methoxy-30-indolyl)-2-
tosylethenamine (8f). Ochre yellow solid; yield: 0.28 g
(73%); mp 54–56 8C (pet. ether–CH2Cl2); nmax (KBr): 3479,
1
3375, 1637, 1483, 1276, 1218, 1147, 673 cmK1; H NMR
(CDCl3): ( 1.47 (6H, d, JZ6.5 Hz), 2.29 and 3.69 (3H, s
each), 4.32 (2H, d, JZ10.5 Hz), 4.57 (1H, septet, JZ
6.5 Hz), 6.49 (1H, d, JZ2 Hz), 6.80 (1H, dd, JZ9, 2 Hz),
7.07 (2H, d, JZ8 Hz), 7.17 (1H, s), 7.22 (1H, d, JZ9 Hz),
7.54 (2H, d, JZ8 Hz), 7.77 (1H, t, JZ10.5 Hz); 13C NMR:
d 21.7, 23.1 (2!) (all CH3), 56.1 (OCH3), 47.9, 101.5,
110.9, 112.1, 126.9, 127.6 (2!), 129.3 (2!), 142.4/142.6
(all CH), 102.0, 105.6, 127.6, 131.2, 139.9, 142.4/142.6,
154.4 (all C); EI-MS: m/z (%) 384 (MC, 50), 229 (100), 202
(21), 187 (12), 174 (9), 160 (16), 156 (12), 91 (27); Anal.
calcd for C21H24N2O3S: C, 65.62; H, 6.25; N, 7.29. Found
C, 65.73; H, 6.27; N, 7.32.
Acknowledgements
4.3.13. 5-(30-Indolyl)oxazole (11i). Pale yellow solid;
yield: 0.068 g (37%); mp 170–172 8C (pet. ether–CH2Cl2);
The authors express their sincere thanks to the Director,
Bose Institute for providing laboratory facilities, Mr. J.
Chatterjee, R.S.I.C., Mr. P. Dey, Microanalytical Labora-
tory and Mr. B. Majumdar, NMR Facilities, Bose Institute
for recording the spectra and the C.S.I.R., Govt. of India for
providing a Sr. Research Fellowship (R.B.).
nmax (nujol): 3170, 3143, 1630, 1614, 1089, 979, 738 cmK1
;
1H NMR (d6-DMSO): d 7.12 and 7.17 (1H, t each, JZ
7.5 Hz), 7.41 (1H, s), 7.45 (1H, d, JZ7.5 Hz), 7.77 (1H, s),
7.82 (1H, d, JZ7.5 Hz), 8.29 (1H, s), 11.68 (1H, br s); 13C
NMR (CDCl3): d 112.0, 119.9, 120.3, 121.4, 122.5, 123.5,
149.3 (all CH), 106.0, 124.5, 136.6, 148.3 (all C); EI-MS:
m/z (%) 184 (MC, 100), 157 (10), 141 (18), 130 (35). Anal.
calcd for C11H8N2O: C, 71.73; H, 4.34; N, 15.21. Found C,
71.83; H, 4.35; N, 15.19.
References and notes
4.3.14. 5-(50-Methoxy-30-indolyl)oxazole (11j). White
solid; yield: 0.146 g (68%); mp 154–156 8C (pet. ether–
CH2Cl2); nmax (nujol): 3159, 1639, 1633, 1252, 1090,
797 cmK1; 1H NMR (CDCl3): d 3.90 (3H, s), 6.94 (1H, dd,
1. (a) Schofield, K.; Grimmett, M. R.; Keene, B. R. T. The
Azoles; Cambridge University Press: Cambridge, 1976. (b)
Joule, J. A.; Mills, K. Heterocyclic Chemistry, 4th ed.;

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Blackwell Science: Oxford, UK, 2000; Chapter 21. (c)
Zirngibl, L. Azoles. Antifungal Active Substances—Synthesis
and Uses; Wiley-VCH: London, 1997.
Ahlbrecht, H.; Fischer, S. Tetrahedron 1973, 29, 659. (c)
Ahlbrecht, H.; Blecher, J.; Hanisch, H.; Papke, G.; Reiner,
M. T. Tetrahedron 1973, 29, 3079. (d) Ahlbrecht, H.; Papke,
G. Tetrahedron 1974, 30, 2571. (e) Ahlbrecht, H.; Funk, W.;
Reiner, M. T. Tetrahedron 1976, 32, 479.
2. (a) Roesener, J. A.; Scheuer, P. J. J. Am. Chem. Soc. 1986, 108,
846. (b) Matsunaga, S.; Fusetani, N.; Hashimoto, K. J. Am.
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23. Crystal data: crystals from petroleum ether–EtOAc,
˚
C19H20N2O3S, MZ356.44, monoclinic, aZ18.019(2) A, bZ
˚
˚
3. (a) Chakrabarty, M.; Ghosh, N.; Harigaya, Y. Tetrahedron
Lett. 2004, 45, 4955. (b) Chakrabarty, M.; Sarkar, S.;
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10.485(1) A,
cZ19.661(3) A,
3633.6(8) A , TZ296.2 K, space group P21/n, ZZ8, DcZ
1.303 g cmK3 m(Cu-Ka)Z17.51 cmK1
F(000)Z1504.00,
bZ101.98(1)8,
VZ
3
˚
,
,
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crystal dimensions: 0.40!0.40!0.40 mm, Rigaku AFC5R
diffractometer (rotating anode), Cu-Ka radiation, lZ
1.54178 A, qmaxZ70.128; 7220 reflections measured, 6682
˚
5. (a) Bhate, D. S.; Hulyalkar, R. K.; Menon, S. K. Experientia
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unique (RintZ0.082), 5092 with IO2.00 s(I), 2q!140.248, wR
(F2)Z0.1810 (all data). Two crystallographically independent
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