Novel method for synthesis of aryl hydrazones from α-diazo esters: scope and limitations of nucleophiles

Article abstract of DOI:10.1016/j.tet.2008.11.028

Aryl hydrazones, the precursor of Fischer indole synthesis, were easily obtained by nucleophilic addition of aryllithium reagents to diazo esters. The aryl hydrazones were converted into indoles in good yields by heating with thionyl chloride in alcohol.

Full text of DOI:10.1016/j.tet.2008.11.028

Tetrahedron 65 (2009) 461–468
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Novel method for synthesis of aryl hydrazones from
limitations of nucleophiles
a-diazo esters: scope and
*
Eiko Yasui, Masao Wada, Norio Takamura
Department of Pharmaceutical Science, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo 202-8585, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 8 October 2008
Received in revised form 7 November 2008
Accepted 7 November 2008
Available online 13 November 2008
Aryl hydrazones, the precursor of Fischer indole synthesis, were easily obtained by nucleophilic addition
of aryllithium reagents to diazo esters. The aryl hydrazones were converted into indoles in good yields by
heating with thionyl chloride in alcohol. Grignard reagent was also a good nucleophile, whereas orga-
nozinc reagent did not react with diazo esters. Aryllithium reagents were prepared by reacting aryl
bromides having various substitutions at 2-, 3-, 4-, or multi positions with n-BuLi. The addition of nu-
cleophiles derived from bromopyridines to diazo esters also gave hydrazones.
Keywords:
Hydrazone
Ó 2008 Elsevier Ltd. All rights reserved.
a
-Diazo ester
Fischer indole synthesis
1. Introduction
2. Results and discussion
Due to their superior biological activities, the development of
new methods for the synthesis of indoles has been attracting a lot
of attention ever since.1 Fischer indole synthesis developed in 1883
is still being used today.2 In this synthesis, heating an aryl hydra-
zone with protic or Lewis acid yields an indole compound. Mean-
while, our group found that the terminal nitrogen of diazo ester
was easily attacked by a nucleophile.3 We thought that if many
kinds of aryl lithium compounds reacted with the diazo group,
various aryl hydrazones could be easily prepared (Scheme 1). Here
we report a novel method for the synthesis of aryl hydrazones, the
precursor of Fischer indole synthesis.
2.1. Fischer indole synthesis utilizing novel hydrazone
preparation
According to the above-mentioned strategy (Scheme 1), we
prepared several hydrazones. To diazo ester 1a derived from phe-
nylalanine ethyl ester in THF was added 1.0 equiv of phenyllithium
at ꢀ68 ꢁC. After the disappearance of the starting material, the
reaction mixture was neutralized with acetic acid and purified by
silica gel column chromatography to give desired phenyl hydrazone
2a in 86% yield. anti-Hydrazone was produced as the major product
but a small amount of syn-hydrazone 2a0 was also detected. These
isomers were easily separated by silica gel column chromatogra-
phy. The stereochemistry of the hydrazones was assigned according
to a reported procedure using NMR analysis.4 The hydrogen of syn-
hydrazone forms a hydrogen bond with the ester carbonyl group
and thus, the chemical shift of the hydrogen appears at a lower
field. The resulting anti-hydrazone 2a was heated in a sealed tube
with thionyl chloride in ethanol5 to give indole 3a in 95% yield. syn-
Hydrazone 2a06 also gave indole 3a in 97% yield (Scheme 2).
Other diazo esters were converted into corresponding hydra-
zones in the same manner. All diazo esters, which are useful syn-
thetic units comprising several functional groups and an
appropriate carbon frame, were easily prepared by our reported
CO2R'
CO2R'
CO2R'
Nu
CO2R'
R
R
R
R
N
N
N
N
N
N
N
NH
Nu
Nu
diazo ester
Nu: nucleophile
Nu = Ar : aryl hydrazone
Scheme 1.
procedure7 from
a-amino acid esters. As shown in Table 1, diazo
esters reacted with phenyllithium to give desired phenyl hydra-
zones 2a–2g in good yields. Even glutamic acid and lysine de-
rivatives (1e and 1f) having an acidic proton in the molecule gave
hydrazones 2e and 2f, respectively. From NMR analysis, the
* Corresponding author. Tel./fax: þ81 42 468 9278.
E-mail address: noritaka@musashino-u.ac.jp (N. Takamura).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.11.028

462
E. Yasui et al. / Tetrahedron 65 (2009) 461–468
Ph
CO2Et
CO2Et
SOCl2
PhLi, THF, –68 °C;
Ph
Ph
HN
Ph
EtOH
80 °C
in a sealed tube
95%
AcOH
86%
N2
N
N
H
CO2Et
1a
2a
3a
DBU
toluene
120 °C
in a sealed tube
75%
SOCl2
EtOH
80 °C
CO2Et
in a sealed tube
97%
Ph
N
NH
Ph
2a'
Scheme 2.
stereochemistry of all hydrazones except 2g was confirmed to be
anti.8 Hydrazones 2a–2g were then subjected to the indole cycli-
zation reaction. Most substrates gave the desired indoles in mod-
erate to good yields. The cyclization reaction of 2b hardly
proceeded at 80 ꢁC, whereas 3b was obtained in 86% yield when 2b
was cyclized at 100 ꢁC.
Unfortunately, several reactions ended in failure (Scheme 3).
Diazo esters derived from alanine benzyl ester 1h and aspartic acid
ester 1i did not give the desired hydrazones when they were
treated with phenyllithium. Diazo ester derived from tryptophan
methyl ester 1j gave hydrazone 2j in good yield, but Fischer indole
cyclization reaction of 2j did not proceed.
2.2. Trials on another metal reagent: examination of
nucleophile 1
Instead of lithium reagents, Grignard reagent, and an organozinc
reagent were examined. To a cooled (ꢀ68 ꢁC) solution of 1a in THF
was added phenylmagnesium bromide to give anti-hydrazone as
the major product. The reaction rate seemed to be lower than that
when lithium reagent was used. What is interesting is that the
diazo ester derived from alanine benzyl ester 1h reacted with
phenylmagnesium bromide (at 0 ꢁC) to give hydrazone 2h in 78%
yield, although it did not react with PhLi (Schemes 3 and 4). On the
other hand, 1i derived from aspartic acid ester did not produce
hydrazone despite use of Grignard reagent.
Table 1
H3C
HN
CO2Bn
H3C
CO2Bn
Amino acid
R
R0
1
2
3
PhMgBr
THF
0 °C
78%
N
N2
1h
Phenylalanine
Et
1a, 93%
2a, 86%
3a, 95%
2h
Ph
Leucine
Et
1b, 94%
2b, 67%
3b, 86%b
CO2Et
Ph
PhZnI
THF
no reaction
N2
Tyrosine
Me
Me
Et
1c, 97%
1d, 85%
1e 73%
1f, 89%
2c, 72%
2d, 79%
2e, da
3c, 70%
3d, 59%
3e, 47%c
3f, 78%
1a
BnO
MeS
Scheme 4.
Methionine
Glutamic acid
Lysine
Next, an organozinc reagent was examined to determine
whether it would work as a nucleophile with diazo ester. Phenyl-
zinc iodide (1.0 equiv) was added to a solution of diazo ester 1a in
THF at 0 ꢁC, and then the ice bath was removed. The reaction
mixture was allowed to warm to room temperature, but the re-
action did not proceed. Neither increasing reagent amount nor
heating promoted the reaction.
EtO2C
Me
2f, 88%a
ZHN
Cysteine
Et
1g 80%
2g, 97%
3g, 67%
BnS
a
PhLi (2 equiv) was used.
The reaction was performed at 100 ꢁC.
Isolation yield for two steps.
2.3. Application of hydrazone synthesis: examination of
nucleophile 2
b
c
The diversity of aryllithium reagents was examined next. If
aryllithium reagents generated in situ could react with diazo esters,
the application of this reaction would be extended because com-
mercially available aryllithium reagents are limited in number. At
first, 4-substituted aryl bromides (1.5 equiv) were treated with
n-BuLi (1.5 equiv) in THF at ꢀ68 ꢁC to produce aryllithium reagents.
To the mixture was added diazo ester 1a (1.0 equiv). Lithiation of
aryl bromides and subsequent nucleophilic addition of the lithium
reagents to diazo compound 1a proceeded successfully. Resulting
hydrazone 4 easily gave indole 5 on treatment with an acid
(Scheme 5).
H3C
CO2Bn
CO2Et
PhLi
PhLi
THF
–68 °C
EtO2C
THF
N2
1h
N2
1i
–68 °C
CO2Me
CO2Me
SOCl2
PhLi
EtOH
80 °C
THF
–68 °C
82%
N
N2
N
HN
Ph
N
H
in a sealed tube
H
1j
2j
In the same manner, 2-substituted phenyl bromides, 3-sub-
stituted phenyl bromides, and multi-substituted phenyl bromides
Scheme 3.

E. Yasui et al. / Tetrahedron 65 (2009) 461–468
463
Ph
X
n-BuLi, THF, −68 °C;
1a;
5
X
Ph
X
CO2Et
SOCl2
N
AcOH
EtOH
80 °C
N
H
CO2Et
N
H
Br
in a sealed tube
4
5
Scheme 5.
were converted into nucleophiles to give corresponding hydra-
zones. Although all lithium reagents gave the desired hydrazones,
the yield of hydrazone 6a was low compared to others. During the
cyclization of hydrazone 6b, indole 3a was also produced in 21%
yield besides major indole 7b. It seems that the methyl group was
eliminated by aromatization of the indole ring, and the same ex-
ample has already been reported.9 Hydrazone 6 derived from 2-
substituted phenyl bromides gave only one isomer, 7-substituted
indole 7, but hydrazone 8 derived from 3-substituted phenyl bro-
mides gave two isomers, 4-substituted indole 9 and 6-substituted
indole 10 (Scheme 6). The regioisomers (9 and 10) were determined
by NMR analysis. There seemed to be no rule regarding the
substituent group and the production rate (9/10). Furthermore,
multi-substituted phenyllithium prepared from 3,5-dichlorophenyl
bromide reacted with diazo ester 1a, and resulting hydrazone 11
gave desired indole 12. These results are listed in Table 2.
procedures.10 Desired hydrazones were produced after adding
a solution of 1a to pyridyl lithium reagents, although the yields
were low (Scheme 7). Subsequent cyclization did not proceed un-
der the same reaction conditions to obtain azaindoles, as
reported.11
3. Conclusion
We have developed a novel method for the synthesis of aryl
hydrazones from
a-diazo esters. As a result, many new aryl
hydrazones and indoles were synthesized utilizing this methodol-
ogy.12 The terminal nitrogen of the diazo group easily reacted with
various nucleophiles to give aryl hydrazones. Although aryl lithium
reagents and phenyl Grignard reagent worked as nucleophiles,
organozinc reagent did not react with diazo esters. Aryl lithium
reagents having substitutions at 2-, 3-, 4-, or multi positions gave
corresponding hydrazones and indoles by subsequent Fischer in-
dole cyclization. Nucleophiles derived from bromopyridines also
gave hydrazones.
Ph
Br
Ph
CO2Et
b)
X
a)
N
N
H
CO2Et
N
H
7
X
X
X
6
7
4. Experimental
4.1. General
X
Ph
4
Ph
CO2Et
N
1H and 13C NMR spectra were recorded on a JEOL JNM-ECX-400
spectrometer at 400 and 100 MHz, respectively. Chemical shifts
Br
N
H
CO2Et
N
H
a)
b)
8
9
were expressed in
internal standard (
signals were referenced to CDCl3
recorded on a JASCO FT/IR-4100. Mass spectra were recorded on
a JEOL JMS-GCmate II. Melting points were measured on a Yanaco
MP-500P micro melting point apparatus and are not corrected.
d parts per million with tetramethylsilane as an
d
Ph
X
Ph
¼0 ppm) for 1H NMR. Chemical shifts of carbon
CO2Et
(dc¼77.0 ppm). IR spectra were
6
N
X
N
H
CO2Et
X
N
H
10
Scheme 6. (a) n-BuLi, THF, ꢀ68 ꢁC, 1a, AcOH; (b) SOCl2, EtOH, 80 ꢁC in a sealed tube.
2.4. Nucleophiles derived from heteroaromatic compounds:
examination of nucleophile 3
4.2. Materials
Tetrahydrofuran (THF) and diethyl ether (Et2O) were distilled
from benzophenone ketyl immediately before use. All other re-
agents and solvents were purchased from commercial sources and
used without further purification.
Now that it has become clear that many kinds of phenyl bro-
mides can be converted into nucleophiles for diazo esters, we in-
vestigated another type of nucleophile. As a typical example of
heteroaromatic bromide, bromopyridines were examined to de-
termine if they could function as a nucleophile. Each bromopyr-
idine (2-, 3-, and 4-bromopyridine) was lithiated by known
4.3. Synthesis of aryl hydrazones
The typical procedure for synthesis of aryl hydrazones 2: diazo
ester 1a (204 mg, 1 mmol) was dissolved in THF (10 ml) and stirred
at ꢀ68 ꢁC under nitrogen atmosphere. To this solution was added
slowly phenyllithium (0.48 ml, 2.1 M in Bu2O). The reaction mix-
ture was stirred for 20 min at the same temperature, neutralized
with acetic acid (0.06 ml, 1 mmol), diluted with an aqueous satu-
rated NaHCO3 solution and extracted three times with ethyl ace-
tate. The combined organic phase was washed with brine, dried
over Na2SO4, and concentrated in vacuo. The resulting residue was
purified by silica gel column chromatography (hexane/ethyl ace-
tate: 5:1) to give 2a as pale yellow crystals (242 mg, 86%). Re-
crystallization from isopropylether afforded slightly yellow crystals,
mp (88–89 ꢁC) (lit:13 89 ꢁC, lit:4 92–94 ꢁC).
Table 2
X
4
5
X
6
7
4-
OMe
CN
n-Bu
t-Bu
Br
CF3
CN
X
4a, 79% 5a, 92% 2- OMe 6a, 28%
7a, 60%
4b, 77% 5b, 82%
4c, 74% 5c, 92%
4d, 78% 5d, 83%
4e, 69%
4f, 76%
4g, 46% 5g, 49%
11
64%
Me
Cl
F
6b, 72% 7b, 71%a
6c, 96%
6d, 72% 7d, 54%
8
7c, 50%
5e, 81%
5f, 76%
X
9/10
9a/10a, 84% (2:1)
3- OMe 8a, 66%
Me
Br
F
8b, 78% 9b/10b, 88% (1:1)
8c, 91% 9c/10c, 98% (2:3)
8d, 68% 9d/10d, 90% (2:1)
12
65%
Multi 3,5-
Dichloro
a
Compound 3a was also isolated in 21% yield.

464
E. Yasui et al. / Tetrahedron 65 (2009) 461–468
CO2Et
CO2Et
n-BuLi, Et2O, –50 °C;
N
N
1a, –60 °C;
N
HN
NH
N
AcOH
N
Br
15%
5%
13
13'
CO2Et
CO2Et
NH
n-BuLi, Et2O, –5 °C to –60 °C;
1a, –60 °C to –15 °C;
Br
N
N
N
HN
AcOH
N
42%
11%
10%
N
14
14'
Br
CO2Et
CO2Et
NH
n-BuLi, Et2O, –45 °C;1a;
N
N
HN
AcOH
N
41%
N
N
15
15'
Scheme 7.
4.3.1. (E)-Ethyl 3-phenyl-2-(2-phenylhydrazono)propanoate (2a)
1H NMR (CDCl3, 400 MHz)
8.08 (s, 1H), 7.29–7.20 (m, 7H), 7.06
J¼6.4 Hz, 2H), 2.66 (t, J¼6.4 Hz, 2H), 1.38 (t, J¼7.2 Hz, 3H), 1.23 (t,
d
J¼7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz)
d 175.14, 165.19, 143.71,
(m, 1H), 6.91 (m, 1H), 4.31 (q, J¼7.2 Hz, 2H), 3.98 (s, 2H), 1.35 (t,
134.47, 129.17, 121.74, 113.97, 61.42, 61.05, 31.45, 19.74, 14.30, 14.06;
J¼7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz)
d
165.33, 142.87, 135.00,
IR (film) 3279, 1699, 1237 cmꢀ1
; HRMS (EI) calculated for
133.59, 129.08, 129.04, 127.85, 126.93, 122.04, 113.90, 61.23, 30.87,
14.20; IR (KBr) 3300, 3244, 1701, 1669 cmꢀ1; HRMS (EI) calculated
for C17H18N2O2 (Mþ) 282.1368, found 282.1360.
C15H20N2O4 (Mþ) 292.1423, found 292.1428.
4.3.7. (E)-Methyl 6-(benzyloxycarbonylamino)-2-(2-
phenylhydrazono)hexanoate (2f)
4.3.2. (Z)-Ethyl 3-phenyl-2-(2-phenylhydrazono)propanoate (2a0)
1H NMR (CDCl3, 400 MHz)
d 9.01 (s, 1H), 7.40–7.25 (m, 9H), 6.92
1H NMR (CDCl3, 400 MHz)
d
12.14 (s, 1H), 7.31–7.18 (m, 9H), 6.95
(t, J¼7.2 Hz, 1H), 5.08 (s, 2H), 4.97 (m, 1H), 3.83 (s, 3H), 3.34 (dd,
(m, 1H), 4.18 (q, J¼7.2 Hz, 2H), 3.82 (s, 2H), 1.24 (t, J¼7.2 Hz, 3H); 13C
J¼11.2, 6.0 Hz, 1H), 2.67 (m, 1H), 1.58 (m, 2H); 13C NMR (CDCl3,
NMR (CDCl3, 100 MHz)
d
163.59, 143.45, 139.13, 129.26, 128.92,
100 MHz) d 165.97, 157.72, 143.82, 136.16, 134.78, 129.05, 128.50,
128.16, 127.85, 126.12, 121.84, 113.69, 60.57, 39.34, 13.99.
128.14, 127.79, 121.53, 114.16, 67.02, 52.11, 38.64, 30.89, 23.76, 21.18;
IR (film) 3282, 2947, 1701, 1240 cmꢀ1; HRMS (EI) calculated for
C21H25N3O4 (Mþ) 383.1845, found 383.1847.
4.3.3. (E)-Ethyl 4-methyl-2-(2-phenylhydrazono)pentanoate (2b)
1H NMR (CDCl3, 400 MHz)
d 8.14 (s, 1H), 7.28–7.19 (m, 4H), 6.92
(m, 1H), 4.29 (q, J¼7.2 Hz, 2H), 2.49 (d, J¼7.2 Hz, 2H), 2.05 (m, 1H),
4.3.8. (Z)-Ethyl 3-(benzylthio)-2-(2-phenylhydrazono)-
1.36 (t, J¼7.2 Hz, 3H), 0.97 (d, J¼6.4 Hz, 6H); 13C NMR (CDCl3,
propanoate (2g)
100 MHz)
d
165.38, 143.17, 135.52, 129.04, 121.63, 113.75, 60.82,
1H NMR (CDCl3, 400 MHz)
d 8.71 (s,1H), 7.31–7.22 (m, 7H), 7.12 (d,
32.88, 26.20, 22.64, 14.11; IR (film) 3308, 1701, 1574, 1221 cmꢀ1
;
J¼8.8 Hz, 2H), 6.96(t, J¼7.2 Hz,1H), 4.26 (q,J¼7.2 Hz,2H), 3.69(s, 2H),
HRMS (EI) calculated for C14H20N2O2 (Mþ) 248.1525, found 248.1521.
3.66 (s, 2H),1.32 (t, J¼7.2 Hz, 3H); 13C NMR (CDCl3,100 MHz)
d 164.56,
142.85, 137.31, 129.48, 129.09, 128.71, 128.53, 127.32, 122.36, 114.17,
61.23,36.00,24.26,14.15;IR(film)3295,1698,1227,1170 cmꢀ1;HRMS
(EI) calculated for C18H20N2O4S (Mþ) 328.1245, found 328.1253.
4.3.4. (E)-Methyl 3-(4-(benzyloxy)phenyl)-2-(2-
phenylhydrazono)propanoate (2c)
1H NMR (CDCl3, 400 MHz)
d
8.00 (s, 1H), 7.41–7.22 (m, 7H), 7.15
(d, J¼8.8 Hz, 2H), 7.04 (d, J¼8.8 Hz, 2H), 6.92 (m, 3H), 5.01 (s, 2H),
3.95 (s, 2H), 3.88 (s, 3H); 13C NMR (CDCl3, 100 MHz)
165.89,
4.3.9. (E)-Benzyl 2-(2-phenylhydrazono)propanoate (2h)
d
1H NMR (CDCl3, 400 MHz)
d 7.78 (s, 1H), 7.46–7.18 (m, 9H), 6.95
157.80, 142.80, 136.75, 133.82, 129.21, 128.96, 128.52, 127.94, 127.40,
126.89, 122.22, 115.59, 114.02, 69.98, 52.43, 30.25; IR (film) 3450,
1604, 1238 cmꢀ1; HRMS (EI) calculated for C23H22N2O3 (Mþ)
374.1630, found 374.1628.
(t, J¼7.2 Hz, 1H), 5.30 (s, 2H), 2.09 (s, 3H); 13C NMR (CDCl3,
100 MHz)
d 165.01, 143.11, 136.21, 131.94, 129.26, 128.45, 128.01,
127.93, 122.05, 113.99, 66.59, 10.25; IR (KBr) 3451, 3291, 1673, 1243,
1152 cmꢀ1; HRMS (EI) calculated for C16H16N2O2 (Mþ) 268.1212,
found 268.1216; mp 91.8–93.0 ꢁC.
4.3.5. (E)-Methyl 4-(methylthio)-2-(2-phenylhydrazono)-
The typical procedure for synthesis of aryl hydrazones 4, 6, 8, 11,
13–15: 4-bromoanisole (0.19 ml, 1.5 mmol) was dissolved in THF
(10 ml) and stirred at ꢀ68 ꢁC under nitrogen atmosphere. To this
solution was added slowly n-butylllithium (0.96 ml, 1.56 M in
hexane, 1.5 mmol) and stirred for 10 min at the same temperature.
Then to this solution was added 1a (1.0 ml, 1.0 M in THF, 1.0 mmol)
keeping the temperature not to rise over ꢀ60 ꢁC. After 40 min, the
reaction mixture was neutralized with acetic acid (0.09 ml,
1.5 mmol), diluted with an aqueous saturated NaHCO3 solution and
extracted three times with ethyl acetate. The combined organic
phase was washed with brine, dried over Na2SO4, and concentrated
in vacuo. The resulting residue was purified by silica gel column
butanoate (2d)
1H NMR (CDCl3, 400 MHz)
d 8.69 (s, 1H), 7.29 (m, 2H), 7.20 (m,
2H), 6.98 (m, 1H), 3.86 (s, 3H), 2.94 (t, J¼6.8 Hz, 2H), 2.72 (t,
J¼6.8 Hz, 2H), 2.18 (s, 3H); 13C NMR (CDCl3, 100 MHz)
d 165.51,
143.11, 134.33, 129.28, 122.19, 114.06, 52.28, 30.48, 25.65, 16.02; IR
(film) 1701, 1241 cmꢀ1; HRMS (EI) calculated for C12H16N2O2S (Mþ)
252.0932, found 252.0933.
4.3.6. (E)-Diethyl 2-(2-phenylhydrazono)pentanedioate (2e)
1H NMR (CDCl3, 400 MHz)
d
9.60 (s, 1H), 7.35–7.20 (m, 4H), 6.95
(m, 1H), 4.30 (q, J¼7.2 Hz, 2H), 4.14 (q, J¼7.2 Hz, 2H), 2.86 (t,

E. Yasui et al. / Tetrahedron 65 (2009) 461–468
465
chromatography (hexane/ethyl acetate: 5:1) to give 4a as pale
yellow oil (246.0 mg, 79%).
(s, 2H), 1.38 (t, J¼7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz)
d
164.82,
146.44, 137.10, 134.48, 133.47, 129.22, 127.87, 127.21, 119.35, 114.08,
104.16, 61.65, 31.20, 14.17; IR (film) 3283, 2220, 1700, 1607 cmꢀ1
;
4.3.10. (E)-Ethyl 2-(2-(4-methoxyphenyl)hydrazono)-3-
HRMS (EI) calculated for C18H17N3O2 (Mþ) 307.1321, found
307.1317.
phenylpropanoate (4a)
1H NMR (CDCl3, 400 MHz)
d 7.89 (s, 1H), 7.33–7.20 (m, 5H), 6.98
(d, J¼9.0 Hz, 2H), 6.80 (d, J¼9.0 Hz, 2H), 4.33 (q, J¼7.2 Hz, 2H), 4.00
4.3.17. (E)-Ethyl 2-(2-(2-methoxyphenyl)hydrazono)-3-
phenylpropanoate (6a)
(s, 2H), 3.74 (s, 3H),1.38 (t, J¼7.2 Hz, 3H); 13C NMR (CDCl3,100 MHz)
d
165.50, 155.19, 136.85, 135.15, 132.67, 129.16, 127.93, 127.02, 115.21,
1H NMR (CDCl3, 400 MHz)
d
8.49 (s, 1H), 7.53 (dd, J¼7.6, 1.2 Hz,
114.53, 61.26, 55.54, 31.01, 14.32; IR (film) 3298, 1698, 1514,
1231 cmꢀ1; HRMS (EI) calculated for C18H20N2O3 (Mþ) 312.1474,
found 312.1472.
1H), 7.34–7.18 (m, 5H), 6.93 (dt, J¼7.6, 1.2 Hz, 1H), 6.86 (dt, J¼8.0,
1.2 Hz, 1H), 6.76 (dd, J¼8.0, 1.2 Hz, 1H), 4.36 (q, J¼7.2 Hz, 2H), 4.01
(s, 2H), 3.72 (s, 3H),1.40 (t, J¼7.2 Hz, 3H); 13C NMR (CDCl3,100 MHz)
d
165.59, 146.13, 135.23, 134.68, 132.43, 128.90, 128.37, 126.87,
4.3.11. (E)-Ethyl 3-phenyl-2-(2-p-tolylhydrazono)propanoate (4b)
121.47, 121.46, 113.47, 110.35, 61.30, 55.60, 31.53, 14.33; IR (film)
3347, 1698 cmꢀ1; HRMS (EI) calculated for C18H20N2O3 (Mþ)
312.1474, found 312.1478.
1H NMR (CDCl3, 400 MHz)
d 7.92 (s,1H), 7.35–7.18 (m, 5H), 7.04 (d,
J¼8.0 Hz, 2H), 6.95 (d, J¼8.0 Hz, 2H), 4.34 (q, J¼7.2 Hz, 2H), 4.00 (s,
2H), 2.25 (s, 3H), 1.38 (t, J¼7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz)
d
165.47, 140.62,135.10, 133.04,131.62, 129.68, 129.17, 127.93,127.03,
4.3.18. (E)-Ethyl 3-phenyl-2-(2-o-tolylhydrazono)propanoate (6b)
113.93, 61.31, 31.01, 20.63, 14.32; IR (film) 3299, 1698, 1239 cmꢀ1
;
1H NMR (CDCl3, 400 MHz)
d
7.79 (s, 1H), 7.54 (d, J¼7.6 Hz, 1H),
HRMS (EI) calculated for C18H20N2O2 (Mþ) 296.1525, found 296.1537.
7.35–7.22 (m, 5H), 7.17 (t, J¼7.6 Hz, 1H), 6.97 (d, J¼7.2 Hz, 1H), 6.84
(dt, J¼7.2, 0.8 Hz, 1H), 4.38 (q, J¼7.2 Hz, 2H), 4.06 (s, 2H), 1.77 (s,
4.3.12. (E)-Ethyl 2-(2-(4-butylphenyl)hydrazono)-3-
3H), 1.42 (t, J¼7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz)
d 165.63,
phenylpropanoate (4c)
140.85, 134.84, 134.37, 130.32, 129.31, 128.14, 127.27, 127.23, 121.76,
121.67, 113.80, 61.43, 31.76, 16.37, 14.36; IR (KBr) 3353, 1694, 1571,
1242, 1196 cmꢀ1; HRMS (EI) calculated for C18H20N2O2 (Mþ)
296.1525, found 296.1520; mp 80.7–81.5 ꢁC.
1H NMR (CDCl3, 400 MHz)
d 7.92 (s, 1H), 7.32–7.20 (m, 5H), 7.05
(d, J¼8.8 Hz, 2H), 6.96 (d, J¼8.8 Hz, 2H), 4.34 (q, J¼6.8 Hz, 2H), 4.01
(s, 2H), 2.51 (t, J¼8.0 Hz, 2H), 1.52 (m, 2H),1.39 (t, J¼6.8 Hz, 3H),1.30
(m, 2H), 0.89 (t, J¼7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz)
d 165.50,
140.80, 136.86, 135.14, 133.08, 129.19, 129.08, 127.95, 127.04, 113.97,
61.30, 34.84, 33.74, 31.04, 22.19, 14.32, 13.90; IR (film) 3301, 2929,
1700, 1520, 1239 cmꢀ1; HRMS (EI) calculated for C21H26N2O2 (Mþ)
338.1994, found 338.2003.
4.3.19. (E)-Ethyl 2-(2-(2-chlorophenyl)hydrazono)-3-
phenylpropanoate (6c)
1H NMR (CDCl3, 400 MHz)
d
8.38 (s, 1H), 7.62 (dd, J¼8.4, 1.2 Hz,
1H), 7.36–7.16 (m, 7H), 6.83 (dt, J¼8.0, 1.6 Hz, 1H), 4.38 (q, J¼7.2 Hz,
2H), 4.04 (s, 2H), 1.41 (t, J¼7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz)
4.3.13. (E)-Ethyl 2-(2-(4-tert-butylphenyl)hydrazono)-3-
d 165.26, 139.05, 136.53, 134.46, 129.14, 129.01, 128.32, 127.88,
phenylpropanoate (4d)
127.16, 122.08, 118.66, 115.19, 61.52, 31.66, 14.29; IR (film) 3337,
1699, 1238 cmꢀ1; HRMS (EI) calculated for C17H17ClN2O2 (Mþ)
316.0979, found 316.0966.
1H NMR (CDCl3, 400 MHz)
d 7.93 (s, 1H), 7.35–7.15 (m, 7H), 7.00
(d, J¼8.8 Hz, 2H), 4.33 (q, J¼7.2 Hz, 2H), 4.00 (s, 2H), 1.38 (t,
J¼7.2 Hz, 3H), 1.26 (s, 9H); 13C NMR (CDCl3, 100 MHz)
d 165.50,
145.16, 140.56, 135.14, 133.15, 129.17, 127.95, 127.02, 125.99, 113.73,
61.27, 34.16, 31.37, 31.03, 14.32; IR (KBr) 3435, 2964, 1698, 1673,
1561, 1522, 1246, 1209, 1184 cmꢀ1; HRMS (EI) calculated for
C21H26N2O2 (Mþ) 338.1994, found 338.2005; mp 115.3–115.9 ꢁC.
4.3.20. (E)-Ethyl 2-(2-(2-fluorophenyl)hydrazono)-3-
phenylpropanoate (6d)
1H NMR (CDCl3, 400 MHz)
d
8.15 (s, 1H), 7.60 (dt, J¼8.4, 1.2 Hz,
1H), 7.50–7.20 (m, 5H), 7.07 (t, J¼8.0 Hz, 1H), 6.95 (ddd, J¼11.2, 8.0,
1.2 Hz, 1H), 6.84 (m, 1H), 4.37 (q, J¼7.2 Hz, 2H), 4.02 (s, 2H), 1.40 (t,
4.3.14. (E)-Ethyl 2-(2-(4-bromophenyl)hydrazono)-3-
J¼7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz)
d
165.21, 150.39 (d, JC–F
¼
phenylpropanoate (4e)
240.3 Hz), 136.35, 134.72, 131.38 (d, JC–F¼8.5 Hz), 129.22, 128.16,
127.15, 124.82 (d, JC–F¼2.9 Hz), 121.64 (d, JC–F¼6.7 Hz), 115.39 (d,
JC–F¼1.9 Hz), 114.85 (d, JC–F¼17.2 Hz), 61.50, 31.48, 14.29; IR (film)
3353, 1700, 1254, 1189, 1105 cmꢀ1; HRMS (EI) calculated for
C17H17FN2O2 (Mþ) 300.1274, found 300.1271.
1H NMR (CDCl3, 400 MHz)
d 7.99 (s, 1H), 7.36–7.16 (m, 7H), 6.93
(d, J¼9.2 Hz, 2H), 4.33 (q, J¼7.2 Hz, 2H), 3.99 (s, 2H), 1.37 (t,
J¼7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz)
d 165.16, 142.02, 134.75,
134.58, 132.00, 129.22, 127.87, 127.15, 115.53, 114.27, 61.46, 31.10,
14.26; IR (film) 3297, 1699, 1486, 1239 cmꢀ1; HRMS (EI) calculated
for C17H17BrN2O2 (Mþ) 360.0473, found 360.0473.
4.3.21. (E)-Ethyl 2-(2-(3-methoxyphenyl)hydrazono)-3-
phenylpropanoate (8a)
4.3.15. (E)-Ethyl 3-phenyl-2-(2-(4-(trifluoromethyl)phenyl)-
1H NMR (CDCl3, 400 MHz)
d 7.95 (s, 1H), 7.35–7.20 (m, 5H), 7.12
hydrazono)propanoate (4f)
(t, J¼8.0 Hz, 1H), 6.71 (t, J¼2.4 Hz, 1H), 6.56 (m, 1H), 6.49 (m, 1H),
1H NMR (CDCl3, 400 MHz)
d
8.06 (s, 1H), 7.48 (d, J¼8.4 Hz, 2H),
4.34 (q, J¼7.2 Hz, 2H), 4.01 (s, 2H), 3.77 (s, 3H),1.38 (t, J¼7.2 Hz, 3H);
7.36–7.22 (m, 5H), 7.10 (d, J¼8.4 Hz, 2H), 4.36 (q, J¼7.2 Hz, 2H), 4.04
13C NMR (CDCl3, 100 MHz)
d 165.38, 160.64, 144.23, 134.96, 133.82,
129.98, 129.22, 127.93, 127.10, 107.82, 106.58, 99.81, 61.39, 55.20,
31.07, 14.28; IR (film) 3300, 1699, 1600, 1200, 1152 cmꢀ1; HRMS (EI)
calculated for C18H20N2O3 (Mþ) 312.1474, found 312.1468.
(s, 2H), 1.40 (t, J¼7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz)
d
165.08,
145.57 (d, JC–F¼1.9 Hz), 135.99, 134.60, 129.37, 127.93, 127.34, 126.57
(q, JC–F¼3.8 Hz), 124.32 (q, JC–F¼269.8 Hz), 123.72 (t, JC–F¼32.5 Hz),
113.69, 61.66, 31.31, 14.28; IR (KBr) 3297, 1688, 1318 cmꢀ1; HRMS
(EI) calculated for C18H17F3N2O2 (Mþ) 333.0977, found 333.0952;
mp 104.5–105.5 ꢁC.
4.3.22. (E)-Ethyl 3-phenyl-2-(2-m-tolylhydrazono)propanoate (8b)
1H NMR (CDCl3, 400 MHz)
d 7.98 (s, 1H), 7.35–7.20 (m, 5H), 7.13
(t, J¼8.0 Hz, 1H), 6.92 (s, 1H), 6.85 (d, J¼8.0 Hz, 1H), 6.76 (d,
4.3.16. (E)-Ethyl 2-(2-(4-cyanophenyl)hydrazono)-3-
J¼8.0 Hz,1H), 4.36 (q, J¼7.2 Hz, 2H), 4.02 (s, 2H), 2.30 (s, 3H), 1.40 (t,
phenylpropanoate (4g)
J¼7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz)
d 165.40, 142.81, 139.20,
1H NMR (CDCl3, 400 MHz)
7.35–7.20 (m, 5H), 7.12 (d, J¼8.4 Hz, 2H), 4.33 (q, J¼7.2 Hz, 2H), 4.03
d
8.37 (s, 1H), 7.47 (d, J¼8.4 Hz, 2H),
135.03, 133.47, 129.16, 129.00, 127.90, 127.03, 123.05, 114.51, 111.18,
61.34, 30.99, 21.41, 14.29; IR (film) 3297, 2981, 1697, 1569,

466
E. Yasui et al. / Tetrahedron 65 (2009) 461–468
1191 cmꢀ1; HRMS (EI) calculated for C18H20N2O2 (Mþ) 296.1525,
found 296.1555.
2H), 4.04 (s, 2H), 1.40 (t, J¼7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz)
d
164.85,150.48,149.13,137.63,134.37,129.43,127.93,127.43,108.75,
61.81, 31.44, 14.26; IR (KBr) 3448, 2979, 1703, 1595 cmꢀ1; HRMS (EI)
calculated for C16H17N3O2 (Mþ) 283.1321, found 283.1328.
4.3.23. (E)-Ethyl 2-(2-(3-bromophenyl)hydrazono)-3-
phenylpropanoate (8c)
1H NMR (CDCl3, 400 MHz)
d
7.90 (s, 1H), 7.36–7.20 (m, 6H), 7.05
4.4. Synthesis of indoles
(m, 2H), 6.92 (m, 1H), 4.36 (q, J¼7.2 Hz, 2H), 4.01 (s, 2H), 1.40 (t,
J¼7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz)
d
165.16, 144.17, 135.17,
The typical procedure for synthesis of indoles 3, 5, 7, 9, 10, 12:
ethanol (1.1 ml) was cooled in an ice bath and thionyl chloride
(0.08 ml, 1.1 mmol) was added dropwise. This solution was poured
into hydrazone 2a (30.0 mg, 0.106 mmol) in a sealed tube. The re-
action solution was stirred at 80 ꢁC for 40 min, cooled, diluted with
chloroform and washed with an aqueous saturated NaHCO3 solu-
tion. The separated water phase was further extracted with chlo-
roform twice and the combined organic phase was washed with
brine, dried over Na2SO4, and concentrated in vacuo. The resulting
residue was purified by silica gel column chromatography (hexane/
ethyl acetate: 9:1) to give 3a as pale yellow crystals (26.7 mg, 95%).
Recrystallization from ethanol afforded slightly yellow crystals, mp
(137–138 ꢁC) (lit:4 137–138 ꢁC).
134.67, 130.48, 129.34, 127.90, 127.27, 125.01, 123.13, 116.95, 112.63,
61.59, 31.24,14.31; IR (film) 3298,1700,1593,1233 cmꢀ1; HRMS (EI)
calculated for C17H17N2O2 (Mþ) 360.0473, found 360.0463.
4.3.24. (E)-Ethyl 2-(2-(3-fluorophenyl)hydrazono)-3-
phenylpropanoate (8d)
1H NMR (CDCl3, 400 MHz)
d 8.01 (s, 1H), 7.35–7.10 (m, 6H), 6.89
(dt, J¼10.8, 2.0 Hz, 1H), 6.70 (dd, J¼8.0, 2.4 Hz, 1H), 6.60 (dt, J¼8.4,
2.4 Hz, 1H), 4.33 (q, J¼7.2 Hz, 2H), 4.00 (s, 2H), 1.38 (t, J¼7.2 Hz, 3H);
13C NMR (CDCl3, 100 MHz)
d
165.25, 163.71 (d, JC–F¼244.1 Hz),
144.80, 144.69, 134.85 (d, JC–F¼9.5 Hz), 130.40 (d, JC–F¼9.5 Hz),
129.30, 127.95, 127.22, 109.58 (d, JC–F¼1.9 Hz), 108.74 (d, JC–F
¼
21.9 Hz), 101.46 (d, JC–F¼26.7 Hz), 61.56, 31.18, 14.30; IR (KBr) 3451,
3289, 1698, 1670, 1136 cmꢀ1; HRMS (EI) calculated for C17H17FN2O2
(Mþ) 300.1274, found 300.1275.
4.4.1. Ethyl 3-phenylindole-2-carboxylate (3a)
1H NMR (CDCl3, 400 MHz)
d
9.34 (s, 1H), 7.63 (d, J¼7.6 Hz, 1H),
7.55 (m, 2H), 7.45–7.31 (m, 5H), 7.13 (m, 1H), 4.29 (q, J¼7.2 Hz,
4.3.25. (E)-Ethyl 2-(2-(3,5-dichlorophenyl)hydrazono)-3-
2H), 1.22 (t, J¼7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz)
d 162.22,
phenylpropanoate (11)
135.78, 133.53, 130.62, 127.86, 127.67, 127.11, 125.69, 124.16, 122.74,
121.67, 120.76, 111.72, 60.88, 13.96; IR (KBr) 3344, 1668,
1252 cmꢀ1; HRMS (EI) calculated for C17H15NO2 (Mþ) 265.1103,
found 265.1103.
1H NMR (CDCl3, 400 MHz)
d 7.92 (s, 1H), 7.36–7.18 (m, 5H), 6.93
(d, J¼2.0 Hz, 2H), 6.89 (t, J¼1.6 Hz, 1H), 4.35 (q, J¼7.2 Hz, 2H), 4.00
(s, 2H), 1.40 (t, J¼7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz)
d 164.93,
144.69, 136.32, 135.60, 134.38, 129.41, 127.86, 127.40, 121.84, 112.45,
61.74, 31.33, 14.28; IR (KBr) 3325, 1703, 1589, 1559 cmꢀ1; HRMS (EI)
calculated for C17H16Cl2N2O2 (Mþ) 350.0589, found 350.0573; mp
121.3–121.7 ꢁC.
4.4.2. Ethyl 3-isopropyl-1H-indole-2-carboxylate (3b)
1H NMR (CDCl3, 400 MHz)
d
8.70 (s, 1H), 7.89 (d, J¼8.4 Hz, 1H),
7.38 (d, J¼8.0 Hz, 1H), 7.30 (m, 1H), 7.10 (m, 1H), 4.42 (q, J¼7.2 Hz,
2H), 4.11 (m, 1H), 1.48 (d, J¼7.2 Hz, 6H), 1.43 (t, J¼7.2 Hz, 3H); 13C
4.3.26. (E)-Ethyl 3-phenyl-2-(2-(pyridin-2-yl)hydrazono)-
NMR (CDCl3, 100 MHz) d 162.41, 136.20, 130.96, 126.40, 125.08,
propanoate (13)
122.70, 121.84, 119.46, 111.89, 60.66, 25.66, 22.72, 14.37; IR (KBr)
1H NMR (CDCl3, 400 MHz)
d
8.62 (s, 1H), 8.10 (d, J¼4.4 Hz, 1H),
3327, 1678 cmꢀ1 HRMS (EI) calculated for C14H17NO2 (Mþ)
;
7.63 (m, 1H), 7.44 (d, J¼8.8 Hz, 1H), 7.34–7.19 (m, 5H), 6.86 (m, 1H),
231.1259, found 231.1256; mp 60.6–61.2 ꢁC.
4.35 (q, J¼7.2 Hz, 2H), 4.03 (s, 2H), 1.39 (t, J¼7.2 Hz, 3H); 13C NMR
(CDCl3, 100 MHz)
d
165.03, 155.32, 147.48, 138.32, 136.10, 134.62,
4.4.3. Methyl 3-(4-(benzyloxy)phenyl)-1H-indole-2-
129.10, 128.07, 127.01, 117.73, 108.48, 61.54, 31.03, 14.25; IR (film)
2980, 1702, 1595, 1577 cmꢀ1; HRMS (EI) calculated for C16H17N3O2
(Mþ) 283.1321, found 283.1296.
carboxylate (3c)
1H NMR (CDCl3, 400 MHz)
d
8.99 (s, 1H), 7.65 (d, J¼8.0 Hz, 1H),
7.51–7.34 (m, 9H), 7.14 (m, 1H), 7.08 (d, J¼8.8 Hz, 2H), 5.13 (s, 2H),
3.83 (s, 3H); 13C NMR (CDCl3, 100 MHz)
162.38, 158.16, 137.04,
d
4.3.27. (E)-Ethyl 3-phenyl-2-(2-(pyridin-3-yl)hydrazono)-
135.73, 131.65, 128.59, 127.97, 127.92, 127.56, 125.86, 125.83, 124.22,
122.13, 121.81, 120.78, 114.27, 111.65, 70.04, 51.75; IR (KBr) 3350,
propanoate (14)
1H NMR (CDCl3, 400 MHz)
1.6 Hz, 1H), 7.97 (s, 1H), 7.52 (m, 1H), 7.47–7.22 (m, 5H), 7.19 (dd,
d
8.24 (d, J¼2.8 Hz,1H), 8.18 (dd, J¼4.8,
1684, 1254 cmꢀ1 HRMS (EI) calculated for C23H19NO3 (Mþ)
;
357.1365, found 357.1355; mp 157.0–158.0 ꢁC.
J¼8.4, 4.8 Hz,1H), 4.36 (q, J¼7.2 Hz, 2H), 4.05 (s, 2H),1.40 (t, J¼7.2 Hz,
3H); 13C NMR (CDCl3, 100 MHz)
d
165.05, 143.45, 139.49, 136.51,
4.4.4. Methyl 3-(methylthiomethyl)-1H-indole-2-carboxylate (3d)
136.22, 134.60, 129.38, 127.95, 127.35, 123.84, 121.01, 61.63, 31.31,
14.29; IR (KBr) 3448,1699,1585,1100 cmꢀ1; HRMS (EI) calculated for
C16H17N3O2 (Mþ) 283.1321, found 283.1310; mp 153.0–154.0 ꢁC.
1H NMR (CDCl3, 400 MHz)
d
8.96 (s, 1H), 7.79 (dd, J¼8.4, 0.8 Hz,
1H), 7.35 (m, 2H), 7.16 (m, 1H), 4.27 (s, 2H), 3.96 (s, 3H), 2.04 (s, 3H);
13C NMR (CDCl3, 100 MHz)
162.50, 135.90, 127.33, 125.87, 123.56,
d
121.04, 120.46, 120.39, 111.83, 51.82, 26.95, 15.14; IR (KBr) 3323,
1683, 1253 cmꢀ1; HRMS (EI) calculated for C12H13NO2S (Mþ)
235.0667, found 235.0662; mp 131.0–131.5 ꢁC.
4.3.28. (Z)-Ethyl 3-phenyl-2-(2-(pyridin-3-yl)hydrazono)-
propanoate (140)
1H NMR (CDCl3, 400 MHz)
d
12.13 (s,1H), 8.46 (d, J¼2.8,1H), 8.21
(d, J¼4.8 Hz, 1H), 7.56 (m, 1H), 7.32–7.17 (m, 6H), 4.22 (q, J¼7.2 Hz,
4.4.5. Ethyl 3-(2-ethoxy-2-oxoethyl)-1H-indole-2-carboxylate (3e)
2H), 3.83 (s, 2H), 1.27 (t, J¼7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz)
1H NMR (CDCl3, 400 MHz)
d
9.22 (s, 1H), 7.63 (d, J¼8.0 Hz,
d
163.46, 142.77, 139.89, 138.46, 136.22, 130.25, 128.91, 128.22,
1H), 7.31 (m, 2H), 7.15 (m, 1H), 4.35 (q, J¼7.2 Hz, 2H), 4.19 (q,
126.29, 123.90, 120.41, 60.94, 39.30, 13.91.
J¼7.2 Hz, 2H), 4.18 (s, 2H), 1.40 (t, J¼7.2 Hz, 3H), 1.26 (t, J¼7.2 Hz,
3H); 13C NMR (CDCl3, 100 MHz)
d 171.34, 162.02, 135.77, 127.81,
4.3.29. (E)-Ethyl 3-phenyl-2-(2-(pyridin-4-yl)hydrazono)-
125.48, 124.38, 120.39 (ꢂ2), 115.58, 111.91, 60.87, 60.74, 30.67,
14.21, 14.14; IR (KBr) 3317, 1719, 1684, 1259 cmꢀ1; HRMS (EI)
calculated for C15H17NO4 (Mþ) 275.1158, found 275.1162; mp
80.0–81.0 ꢁC.
propanoate (15)
1H NMR (CDCl3, 400 MHz)
1H), 7.37–7.20 (m, 5H), 6.93 (dd, J¼5.2, 1.2 Hz, 2H), 4.37 (q, J¼7.2 Hz,
d
8.35 (dd, J¼5.2, 1.2 Hz, 2H), 8.10 (s,

E. Yasui et al. / Tetrahedron 65 (2009) 461–468
467
4.4.6. Methyl 3-(3-(benzyloxycarbonylamino)propyl)-1H-indole-2-
(CDCl3, 100 MHz)
d
161.71, 136.75, 132.53, 130.52, 127.99, 127.68,
carboxylate (3f)
127.27, 126.24, 124.93, 124.43, 123.43 (q, JC–F¼32.4 Hz), 122.24 (q,
JC–F¼3.8 Hz), 119.76 (q, JC–F¼1.9 Hz), 112.25, 61.26, 13.96; IR (KBr)
3312, 1682, 1265, 1161, 1098 cmꢀ1; HRMS (EI) calculated for
C18H14F3NO2 (Mþ) 333.0977, found 333.0952; mp 204.1–205.1 ꢁC.
1H NMR (CDCl3, 400 MHz)
d
8.79 (s, 1H), 7.65 (d, J¼8.0 Hz, 1H),
7.34 (m, 7H), 7.13 (m, 1H), 5.26 (m, 1H), 5.11 (s, 2H), 3.91 (s, 3H), 3.18
(m, 4H), 1.90 (quint, J¼6.8 Hz, 2H); 13C NMR (CDCl3, 100 MHz)
d
162.55, 156.46, 136.78, 135.94, 128.43, 128.02, 127.96, 125.81,
124.12, 122.96, 120.64, 120.20, 111.83, 66.44, 51.79, 40.08, 30.40,
4.4.14. Ethyl 5-cyano-3-phenylindole-2-carboxylate (5g)
21.38; IR (KBr) 3337, 1683 cmꢀ1
;
HRMS (EI) calculated for
1H NMR (CDCl3, 400 MHz)
d 9.51 (s, 1H), 7.99 (s, 1H), 7.57–7.40
C21H22N2O4 (Mþ) 366.1580, found 366.1588; mp 106.0–107.0 ꢁC.
(m, 7H), 4.32 (q, J¼7.2 Hz, 2H), 1.23 (t, J¼7.2 Hz, 3H); 13C NMR
(CDCl3, 100 MHz)
d 161.46, 136.92, 131.95, 130.43, 128.04, 127.99,
4.4.7. Ethyl 3-(benzylthio)-1H-indole-2-carboxylate (3g)
127.92, 127.89, 127.75, 124.78, 124.56, 119.96, 112.84, 104.27, 61.44,
13.94; IR (KBr) 3293, 2992, 2217, 1681, 1265 cmꢀ1; HRMS (EI) cal-
culated for C18H14N2O2 (Mþ) 290.1055, found 290.1051; mp 219.0–
220.0 ꢁC.
1H NMR (CDCl3, 400 MHz)
d
9.13 (s, 1H), 7.77 (dd, J¼0.8, 8.4 Hz,
1H), 7.39–7.31 (m, 2H), 7.19–7.10 (m, 6H), 4.39 (q, J¼7.2 Hz, 2H), 4.05
(s, 2H), 1.42 (t, J¼7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz)
d 161.24,
138.23, 135.26, 130.63, 128.85, 128.84, 128.09, 126.80, 125.88, 121.41,
121.12, 112.90, 111.85, 61.25, 40.87, 14.34; IR (KBr) 3320, 1677,
1252 cmꢀ1; HRMS (EI) calculated for C18H17NO2S (Mþ) 311.0980,
found 311.0983; mp 99.8–100.5 ꢁC.
4.4.15. Ethyl 7-methoxy-3-phenyl-1H-indole-2-carboxylate (7a)
1H NMR (CDCl3, 400 MHz)
d 9.17 (s, 1H), 7.57–7.33 (m, 5H), 7.22
(d, J¼8.0 Hz, 1H), 7.05 (t, J¼8.4 Hz, 1H), 6.75 (d, J¼7.6 Hz, 1H), 4.28
(q, J¼7.2 Hz, 2H), 3.98 (s, 3H), 1.23 (t, J¼7.2 Hz, 3H); 13C NMR (CDCl3,
4.4.8. Ethyl 5-methoxy-3-phenyl-1H-indole-2-carboxylate (5a)
100 MHz) d 161.72, 146.33, 133.60, 130.59, 129.03, 127.68, 127.11,
1H NMR (CDCl3, 400 MHz)
d
8.92 (s, 1H), 7.56–7.33 (m, 6H), 7.03
126.92, 124.48, 122.48, 121.21, 113.87, 104.42, 60.77, 55.45, 14.06; IR
(film) 3294, 1694 cmꢀ1; HRMS (EI) calculated for C18H17NO3 (Mþ)
295.1208, found 295.1218; mp 96.1–97.1 ꢁC.
(dd, J¼8.8, 2.4 Hz, 1H), 6.99 (d, J¼2.4 Hz, 1H), 4.27 (q, J¼7.2 Hz, 2H),
3.78 (s, 3H), 1.23 (t, J¼7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz)
d
161.87, 154.94, 133.71, 130.99, 130.52, 128.15, 127.81, 127.10, 123.74,
123.30, 117.50, 112.65, 101.47, 60.79, 55.71, 14.04; IR (KBr) 3315,
1677 cmꢀ1; HRMS (EI) calculated for C18H17NO3 (Mþ) 295.1208,
found 295.1209; mp 113.5–114.5 ꢁC.
4.4.16. Ethyl 7-methyl-3-phenyl-1H-indole-2-carboxylate (7b)
1H NMR (CDCl3, 400 MHz)
d 8.92 (s, 1H), 7.54 (m, 2H), 7.45 (m,
3H), 7.37 (m, 1H), 7.15 (d, J¼6.8 Hz, 1H), 7.06 (t, J¼7.2 Hz, 1H), 4.29
(q, J¼7.2 Hz, 2H), 2.56 (s, 3H), 1.23 (t, J¼7.2 Hz, 3H); 13C NMR (CDCl3,
4.4.9. Ethyl 5-methyl-3-phenyl-1H-indole-2-carboxylate (5b)
100 MHz) d 162.21, 135.45, 133.70, 130.63, 127.67, 127.56, 127.12,
1H NMR (CDCl3, 400 MHz)
d
8.91 (s, 1H), 7.55 (m, 2H), 7.45 (m,
125.93, 124.66, 122.60, 121.12, 120.99, 119.38, 60.87, 16.59, 14.02; IR
(KBr) 3338, 1672 cmꢀ1; HRMS (EI) calculated for C18H17NO2 (Mþ)
279.1259, found 279.1259; mp 117.8–118.3 ꢁC.
2H), 7.36 (m, 3H), 7.19 (dd, J¼8.4, 1.6 Hz, 1H), 4.28 (q, J¼6.8 Hz, 2H),
2.41 (s, 3H), 1.23 (t, J¼6.8 Hz, 3H); 13C NMR (CDCl3, 100 MHz)
d
162.02, 134.07, 133.67, 130.62, 130.26, 128.12, 127.72, 127.70,
127.08, 123.72, 122.81, 120.85, 111.34, 60.78, 21.43, 14.03; IR (KBr)
4.4.17. Ethyl 7-chloro-3-phenyl-1H-indole-2-carboxylate (7c)
3325, 1683 cmꢀ1
;
HRMS (EI) calculated for C18H17NO2 (Mþ)
1H NMR (CDCl3, 400 MHz)
d 9.11 (s, 1H), 7.53–7.20 (m, 7H), 7.08
279.1259, found 279.1245; mp 124.0–125.0 ꢁC.
(t, J¼8.4 Hz, 1H), 4.31 (q, J¼7.2 Hz, 2H), 1.24 (t, J¼7.2 Hz, 3H); 13C
NMR (CDCl3, 100 MHz)
d 161.51, 133.06, 132.97, 130.52, 129.20,
4.4.10. Ethyl 5-butyl-3-phenyl-1H-indole-2-carboxylate (5c)
127.81, 127.45, 124.92, 124.79, 123.49, 121.48, 120.36, 117.10, 61.11,
14.01; IR (KBr) 3318, 1697, 1316, 1236 cmꢀ1; HRMS (EI) calculated
for C17H14ClNO2 (Mþ) 299.0713, found 299.0709; mp 88.9–89.7 ꢁC.
1H NMR (CDCl3, 400 MHz)
d 9.21 (s, 1H), 7.55 (m, 2H), 7.45 (m,
2H), 7.36 (m, 3H), 7.18 (dd, J¼8.8, 2.0 Hz, 1H), 4.28 (q, J¼6.8 Hz, 2H),
2.65 (t, J¼7.6 Hz, 2H), 1.58 (m, 2H), 1.33 (m, 2H), 1.21 (t, J¼6.8 Hz,
3H), 0.90 (t, J¼7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz)
d
162.21,
4.4.18. Ethyl 7-fluoro-3-phenyl-1H-indole-2-carboxylate (7d)
135.48, 134.37, 133.77, 130.65, 127.99, 127.66, 127.09, 127.00, 123.78,
122.81, 120.22, 111.42, 60.77, 35.77, 34.26, 22.38, 13.97, 13.92; IR
(KBr) 3336, 1685 cmꢀ1; HRMS (EI) calculated for C21H23NO2 (Mþ)
321.1729, found 321.1690; mp 110.0–111.0 ꢁC.
1H NMR (CDCl3, 400 MHz)
d 9.22 (s, 1H), 7.54 (m, 2H), 7.45 (m,
2H), 7.38 (m, 2H), 7.04 (m, 2H), 4.31 (q, J¼7.2 Hz, 2H), 1.24 (t,
J¼7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz)
d
161.56, 149.47 (d, JC–F
¼
245 Hz), 132.98, 131.31 (d, JC–F¼4.8 Hz), 130.53, 127.80, 127.43,
124.61 (d, JC–F¼13.4 Hz), 124.60 (d, JC–F¼2.9 Hz), 123.60, 120.88 (d,
JC–F¼5.7 Hz), 117.42 (d, JC–F¼3.8 Hz), 109.89 (d, JC–F¼16.2 Hz), 61.11,
14.01; IR (KBr) 3303, 1685, 1322, 1235 cmꢀ1; HRMS (EI) calculated
for C17H14FNO2 (Mþ) 283.1009, found 283.1009; mp 160.6–161.6 ꢁC.
4.4.11. Ethyl 5-tert-butyl-3-phenyl-1H-indole-2-carboxylate (5d)
1H NMR (CDCl3, 400 MHz)
d
9.01 (s,1H), 7.56 (m, 2H), 7.46 (m, 3H),
7.39 (m, 3H), 4.28 (q, J¼7.2 Hz, 2H), 1.33 (s, 9H), 1.22 (t, J¼7.2 Hz, 3H);
13C NMR (CDCl3, 100 MHz)
162.21, 143.79, 134.06, 133.75, 130.66,
d
127.70,127.57,127.01,124.51,124.29,122.89,116.78,111.29,60.77, 34.67,
31.65,13.98; IR (KBr) 3331, 1678, 1261 cmꢀ1; HRMS (EI) calculated for
C21H23NO2 (Mþ) 321.1729, found 321.1732; mp 172.0–173.0 ꢁC.
4.4.19. Ethyl 4-methoxy-3-phenyl-1H-indole-2-carboxylate (9a)
1H NMR (CDCl3, 400 MHz)
d 9.00 (s, 1H), 7.46 (m, 2H), 7.35 (m,
3H), 7.25 (t, J¼8.0 Hz, 1H), 7.03 (d, J¼8.0 Hz, 1H), 6.47 (d, J¼8.0 Hz,
1H), 4.20 (q, J¼7.2 Hz, 2H), 3.66 (s, 3H), 1.13 (t, J¼7.2 Hz, 3H); 13C
4.4.12. Ethyl 5-bromo-3-phenyl-1H-indole-2-carboxylate (5e)
NMR (CDCl3, 100 MHz) d 161.90, 155.95, 137.09, 134.81, 130.96,
1H NMR (CDCl3, 400 MHz)
d
9.15 (s, 1H), 7.75 (d, J¼1.2 Hz, 1H),
126.59, 126.56, 126.50, 124.34, 122.30, 117.89, 104.56, 100.33, 60.63,
55.12, 13.91; IR (KþBr) 3328, 1662, 1261 cmꢀ1; HRMS (EI) calculated
for C18H17NO3 (M ) 295.1208, found 295.1217; mp 182.0–183.0 ꢁC.
7.52–7.31 (m, 7H), 4.29 (q, J¼7.2 Hz, 2H), 1.23 (t, J¼7.2 Hz, 3H); 13C
NMR (CDCl3, 100 MHz)
d 161.70, 134.15, 132.77, 130.49, 129.52,
128.75, 127.88, 127.48, 124.12, 123.76, 123.51, 114.11, 113.22, 61.11,
13.98; IR (KBr) 3311, 1684, 1258 cmꢀ1; HRMS (EI) calculated for
C17H14BrNO2 (Mþ) 343.0208, found 343.0170; mp 174.0–175.0 ꢁC.
4.4.20. Ethyl 6-methoxy-3-phenyl-1H-indole-2-carboxylate (10a)
1H NMR (CDCl3, 400 MHz)
d 9.07 (s, 1H), 7.55 (m, 2H), 7.50 (d,
J¼8.8 Hz, 1H), 7.43 (m, 2H), 7.37 (m, 1H), 6.84 (d, J¼2.4 Hz, 1H), 6.80
4.4.13. Ethyl 3-phenyl-5-(trifluoromethyl)indole-2-carboxylate (5f)
(dd, J¼8.8, 2.4 Hz, 1H), 4.27 (q, J¼7.2 Hz, 2H), 3.85 (s, 3H), 1.22 (t,
1H NMR (CDCl3, 400 MHz)
d
9.33 (s, 1H), 7.91 (s, 1H), 7.60–7.40
J¼7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz)
d 162.04, 159.14, 136.75,
(m, 7H), 4.31 (q, J¼7.2 Hz, 2H), 1.23 (t, J¼7.2 Hz, 3H); 13C NMR
133.54, 130.53, 127.67, 127.13, 124.64, 122.59, 122.30, 121.54, 112.27,

468
E. Yasui et al. / Tetrahedron 65 (2009) 461–468
93.36, 60.63, 55.45, 14.04; IR (KBr) 3324, 1670, 1261 cmꢀ1; HRMS
(EI) calculated for C18H17NO3 (Mþ) 295.1208, found 295.1208; mp
131.0–132.5 ꢁC.
4.4.26. Ethyl 6-fluoro-3-phenyl-1H-indole-2-carboxylate (10d)
1H NMR (CDCl3, 400 MHz)
9.22 (s, 1H), 7.50 (m, 3H), 7.40 (m,
d
3H), 7.24 (m, 2H), 6.76 (ddd, J¼11.2, 6.8, 1.2 Hz, 1H), 4.25 (q,
J¼7.2 Hz, 2H), 1.17 (t, J¼7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz)
4.4.21. Ethyl 4-methyl-3-phenyl-1H-indole-2-carboxylate (9b)
d
161.72, 157.93 (d, JC–F¼251.7 Hz), 137.75 (d, JC–F¼8.5 Hz), 133.54 (d,
1H NMR (CDCl3, 400 MHz)
d
8.99 (s, 1H), 7.37 (m, 5H), 7.29 (d,
JC–F¼1.9 Hz), 130.72 (d, JC–F¼1.9 Hz), 127.26, 127.10, 126.11 (d, JC–F
¼
¼
J¼8.4 Hz, 1H), 7.22 (t, J¼8.4 Hz, 1H), 6.84 (m, 1H), 4.16 (q, J¼7.2 Hz,
8.6 Hz), 123.35, 122.38, 116.97 (d, JC–F¼18.1 Hz), 107.78 (d, JC–F
2H), 2.05 (s, 3H), 1.05 (t, J¼7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz)
4.7 Hz), 105.75 (d, JC–F¼19.17 Hz), 61.03, 13.89; IR (KBr) 3317, 1672,
1258, 1243 cmꢀ1; HRMS (EI) calculated for C17H14FNO2 (Mþ)
283.1009, found 283.1008; mp 149.0–150.5 ꢁC.
d
162.05,136.14,135.71,133.67,130.61,127.17,126.99,126.49,125.59,
125.09, 123.60, 122.01, 109.54, 60.54, 20.19, 13.78; IR (KBr) 3314,
1678, 1254 cmꢀ1
;
HRMS (EI) calculated for C18H17NO2 (Mþ)
279.1259, found 279.1268; mp 157.5–158.9 ꢁC.
4.4.27. Ethyl 4,6-dichloro-3-phenyl-1H-indole-2-carboxylate (12)
1H NMR (CDCl3, 400 MHz)
d 9.36 (s, 1H), 7.36 (m, 6H), 7.10 (d,
4.4.22. Ethyl 6-methyl-3-phenyl-1H-indole-2-carboxylate (10b)
J¼1.6 Hz, 1H), 4.19 (q, J¼7.2 Hz, 2H), 1.06 (t, J¼7.2 Hz, 3H); 13C NMR
1H NMR (CDCl3, 400 MHz)
d
8.85 (s, 1H), 7.55 (m, 2H), 7.52 (d,
(CDCl3, 100 MHz) d 161.67, 136.49, 133.50, 131.09, 130.98, 129.21,
J¼8.0 Hz,1H), 7.44 (m, 2H), 7.36 (m, 1H), 7.22 (s,1H), 6.98 (dd, J¼8.0,
127.34, 126.96, 125.30, 124.10, 123.27, 122.50, 110.42, 61.12, 13.70; IR
1.2 Hz, 1H), 4.28 (q, J¼7.2 Hz, 2H), 2.49 (s, 3H), 1.23 (t, J¼7.2 Hz, 3H);
(KBr) 3303, 1683, 1248 cmꢀ1
;
HRMS (EI) calculated for
13C NMR (CDCl3, 100 MHz)
d
162.04, 159.14, 136.75, 133.54, 130.53,
C17H13Cl2NO2 (Mþ) 333.0323, found 333.0326; mp 202.2–202.7 ꢁC.
127.67, 127.13, 124.64, 122.59, 122.30, 121.54, 112.27, 93.36, 60.63,
55.45, 14.04; IR (KBr) 3335, 1677, 1255 cmꢀ1; HRMS (EI) calculated
for C18H17NO2 (Mþ) 279.1259, found 279.1270; mp 166.0–167.0 ꢁC.
Acknowledgements
This work was financially supported by MEXT. HAITEKU (2005–
2008).
4.4.23. Ethyl 4-bromo-3-phenyl-1H-indole-2-carboxylate (9c)
1H NMR (CDCl3, 400 MHz)
d
9.17 (s, 1H), 7.42 (dd, J¼8.4, 0.8 Hz,
1H), 7.38 (s, 5H), 7.31 (dd, J¼7.2, 0.8 Hz, 1H), 7.16 (t, J¼8.0 Hz, 1H),
4.17 (q, J¼7.2 Hz, 2H), 1.05 (t, J¼7.2 Hz, 3H); 13C NMR (CDCl3,
References and notes
100 MHz)
d 161.77, 136.42, 133.95, 131.36, 127.20, 126.88, 126.08,
1. (a) Gribble, G. W. J. Chem. Soc., Perkin Trans. 1 2000, 1045–1075; (b) Gilchrist, T. L.
J. Chem. Soc., Perkin Trans. 1 2001, 2491–2515.
2. (a) Fischer, E.; Jourdan, F. Ber. 1883, 16, 2241–2245; (b) Fischer, E.; Hess, O. Ber.
1884, 17, 559–568.
125.66, 125.54, 124.99, 124.70, 116.34, 111.13, 60.89, 13.71; IR (KBr)
3347, 1673, 1259 cmꢀ1; HRMS (EI) calculated for C17H14BrNO2 (Mþ)
343.0208, found 343.0221; mp 167.5–168.7 ꢁC.
3. (a) Yasui, E.; Wada, M.; Takamura, N. Tetrahedron Lett. 2006, 47, 743–746; (b)
Yasui, E.; Wada, M.; Takamura, N. Chem. Pharm. Bull. 2007, 55, 1652–1654.
4. Arata, Y.; Sakai, M.; Yasuda, S. Chem. Pharm. Bull. 1972, 20, 1745–1751.
5. (a) Przheval’skii, N. M.; Skvortsova, N. S.; Magedov, I. V. Chem. Heterocycl.
Compd. 2002, 38, 1055–1061; (b) Przheval’skii, N. M.; Skvortsova, N. S.; Mage-
dov, I. V. Chem. Heterocycl. Compd. 2003, 39, 161–167.
4.4.24. Ethyl 6-bromo-3-phenyl-1H-indole-2-carboxylate (10c)
1H NMR (CDCl3, 400 MHz)
d
8.97 (s, 1H), 7.61 (d, J¼2.0 Hz, 1H),
7.53–7.37 (m, 6H), 7.24 (dd, J¼8.4, 1.2 Hz, 1H), 4.29 (q, J¼7.2 Hz, 2H),
1.23 (t, J¼7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz)
d 161.68, 136.20,
6. syn-Fydrazone 2a0 was prepared by heating anti-hydrazone 2a with DBU in
toluene at 120 ꢁC in a sealed tube. Most of 2a isomerized to 2a0 in 2 h and 2a0
was isolated in 75% yield.
132.85,130.52,127.83,127.46,126.83,124.42, 124.28, 123.23,123.08,
119.62, 114.52, 61.07, 14.01; IR (KBr) 3429, 3314, 1678, 1237,
1049 cmꢀ1; HRMS (EI) calculated for C17H14BrNO2 (Mþ) 343.0208,
found 343.0224; mp 205.9–207.0 ꢁC.
7. (a) Takamura, N.; Mizoguchi, T.; Koga, K.; Yamada, S. Tetrahedron Lett. 1971, 12,
4495–4498; (b) Takamura, N.; Mizoguchi, T.; Koga, K.; Yamada, S. Tetrahedron
1975, 31, 227–230.
8. Although the relative positions of the substituents of 2g are the same as those
of other hydrazones, its configuration is syn because sulfur atom has higher
priority than oxygen.
9. Maddirala, S. J.; Gokak, V. S.; Rajur, S. B.; Basanagoudar, L. D. Tetrahedron Lett.
2003, 44, 5665–5668.
10. (a) Phillips, J. E.; Herber, R. H. J. Organomet. Chem. 1984, 268, 39–47; (b) Gaus, P.
L.; Haim, A.; Johnson, F. J. Org. Chem. 1977, 42, 564–565; (c) Gilman, H.; Spatz, S.
M. J. Org. Chem. 1951, 16, 1485–1494.
11. Song, J. J.; Reeves, J. T.; Gallou, F.; Tan, Z.; Yee, N. K.; Senanayake, C. H. Chem. Soc.
Rev. 2007, 36, 1120–1132.
4.4.25. Ethyl 4-fluoro-3-phenyl-1H-indole-2-carboxylate (9d)
1H NMR (CDCl3, 400 MHz)
d 9.26 (s, 1H), 7.54 (m, 3H), 7.45 (m,
2H), 7.38 (m, 1H), 7.10 (dd, J¼9.2, 2.4 Hz, 1H), 6.91 (dt, J¼9.2, 2.4 Hz,
1H), 4.29 (q, J¼7.2 Hz, 2H), 1.23 (t, J¼7.2 Hz, 3H); 13C NMR (CDCl3,
100 MHz)
d
163.25, 161.37 (d, JC–F¼108.7 Hz), 135.81 (d, JC–F
¼
¼
13.3 Hz), 133.14, 130.53, 127.79, 127.38, 124.65, 124.44 (d, JC–F
1.9 Hz), 123.21 (d, JC–F¼3.8 Hz), 123.11 (dd, JC–F¼10.4, 2.0 Hz), 110.41
(dd, JC–F¼24.8, 2.8 Hz), 97.53 (d, JC–F¼25.7 Hz), 60.96, 13.99; IR (KBr)
3316, 1671, 1260, 1240 cmꢀ1; HRMS (EI) calculated for C17H14FNO2
(Mþ) 283.1009, found 283.1012; mp 181.5–182.5 ꢁC.
12. Novel compounds are listed as follows: 2c, 2d, 2f, 2g, 2h, 3c, 3d, 3f, 3g, 4a, 4c,
4d, 4e, 4f, 4g, 5c, 5d, 5f, 5g, 6a, 6c, 6d, 7a, 8a, 8b, 8c, 8d, 9a, 9b, 9c, 9d, 10b, 10c,
10d, 11, and 12.
13. Gault, H.; Weick, R. Bull. Soc. Chim. Fr. 1922, 4, 867–892.