Novel Tetraindoles and Unexpected Cycloalkane Indoles from the Reaction of Indoles and Aliphatic Dialdehydes

Article abstract of DOI:10.1002/jhet.2542

The reaction of indoles with dialdehydes was studied for the first time. Mild reaction conditions using glacial acetic acid led to two novel kinds of reaction products: one designated as alkyl chain-connected tetraindoles and the other one as bis(indolyl)-substituted cycloalkane indoles. The suggested reaction pathways are discussed. The indole substituents of the cycloalkane indoles were either trans or cis orientated depending from the alkyl chain length.

Full text of DOI:10.1002/jhet.2542

Month 2015
Novel Tetraindoles and Unexpected Cycloalkane Indoles from the
Reaction of Indoles and Aliphatic Dialdehydes
a
a
b
a
Mardia Telep El-Sayed, Kazem Ahmed Mahmoud, Frank W. Heinemann, and Andreas Hilgeroth *
a
Research Group of Drug Development, Institute of Pharmacy, Martin Luther University, 06120 Halle, Germany
b
Department of Pharmacy and Chemistry, Institute of Inorganic Chemistry, Friedrich Alexander University, 91058
Erlangen, Germany
E-mail: andreas.hilgeroth@pharmazie.uni-halle.de
Received January 14, 2015
*
DOI 10.1002/jhet.2542
Published online 00 Month 2015 in Wiley Online Library (wileyonlinelibrary.com).
The reaction of indoles with dialdehydes was studied for the first time. Mild reaction conditions using gla-
cial acetic acid led to two novel kinds of reaction products: one designated as alkyl chain-connected
tetraindoles and the other one as bis(indolyl)-substituted cycloalkane indoles. The suggested reaction path-
ways are discussed. The indole substituents of the cycloalkane indoles were either trans or cis orientated de-
pending from the alkyl chain length.
J. Heterocyclic Chem., 00, 00 (2015).
INTRODUCTION
at the cycloalkane ring in the case of cyclopentane and
cyclohexane and with a cis-orientation in the case of
cycloheptane and cyclooctane.
The indole nucleus belongs to the electron-rich
heteroaromatic systems because of the electron-pushing
free nitrogen atom which facilitates electrophilic substitu-
tion reactions in the preferred 3, 5, and 7 positions [1].
However, next to the nitrogen atom the 3 position of
the indole is the preferred one for electrophilic substitu-
tion reactions. Easily accessible 3-alkyl and 3-acyl in-
doles are versatile intermediates for a wide range of
further indole reactions [2]. So a simple method for the
synthesis of 3-alkylated indoles is the reaction with an
aliphatic or an aromatic aldehyde which may condense
then with a second indole [3]. Various protic as well as
Lewis acids have been described as essential catalysts
for such reactions. Used protic acids like silica sulfuric
acid, zeolites HY, or amberlyst and Lewis acids like used
The respective stereochemistry of both diastereomers
with either cis-orientation or trans-orientation of the
indolyl residues was reasoned with NMR data and con-
firmed by X-ray crystal structure analysis of one acetylated
derivative as will be discussed. Bis(indolyl)-containing
compounds have been reported to show partial antibacte-
rial activities. Most of these compounds are from natural
sources like the bisindole pyrrole 3 isolated from the ma-
rine actinomycete species Marinispora [10,11].
RESULTS AND DISCUSSION
Synthesis of tetraindole compounds (1) and of the bis
(
indolyl) cycloalkane indoles (2).
Glutardialdehyde has
pentafluorophenyl ammonium triflate, InCl , or NbCl5
3
been commercially available. Malondialdehyde and
succinaldehyde were given by acidic reaction of
are partly expensive [4–9]. However, these catalysts pro-
mote the reaction of aldehyde and indole to desired 3-
alkylated indoles in satisfying yields. We decided to
use glacial acetic acid for out intended reaction with in-
dole and various aliphatic dialdehydes, the reaction of
which has not been investigated so far. The reaction of
the dialdehydes led to the formation of tetraindole com-
pound 1 and bis(indolyl) substituted cycloalkane indole
malonaldehyde
bisdimethylacetal
and
of
2,5-
dimethoxytetrahydrofuran, respectively [12]. Finally,
adipaldehyde resulted from the reaction of cyclohexane
epoxide with sodium metaperiodate in THF at room
temperature [13]. The general synthetic procedure for the
formation of compounds 1 and 2 started with solving the
dialdehyde compound in glacial acetic acid (Scheme 1).
2
(Fig. 1) with a trans-orientation of both indole residues
©
2015 HeteroCorporation

M. T. El-Sayed, K. A. Mahmoud, F. W. Heinemann, and A. Hilgeroth
Vol 000
column chromatography using silica gel and dichlorometh-
ane as eluent.
Mechanistic aspects of the tetraindole and the bis(indolyl)
cycloalkane indole product formation. The first reaction
step will be the acid-catalyzed attack of the protonated
electrophilic aldehyde at the electron-rich C3 atom of
one indole molecule (Scheme 2a) [14,15]. After
protonation and water elimination to an azafulven-like
derivative A another indole will be attacked to give a
bis(indolyl)-derivative B [15].
The protonated second aldehyde function will attack
the third indole at the electron-rich C3 atom to give in-
termediate C. The formation of the tetraindole products
1
a–c will then proceed via the iminium intermediate D
Figure 1. Structures of given tetraindole compound 1, bis(indolyl)
cycloalkane indole 2, and bis(indolyl) pyrrole 3.
after water elimination from C and another following in-
dole attack (Scheme 2a). The formation of the bis
(indolyl) cycloalkane indole structures 2a–d may follow
an alternative attack of intermediate D at the C2 atom
of the structurally neighbored indole function similar to
the Pictet–Spengler reaction under the strong acidic reac-
tion conditions (Scheme 2b) [16,17].
Scheme 1. Product formation and acetylation procedure.
Structure discussion of the bis(indolyl) cycloalkane
1
indoles. The H NMR spectra of the cyclopentane and
the cyclohexane indole compounds 2a and 2b showed
one signal for both protons of the CH cycloalkane
groups with the attached indolyl residues of the
1
cycloalkane moieties. The H NMR spectra of the
cycloheptane and the cyclooctane indole derivatives 2c
and 2d showed two signals for each of the
corresponding CH groups of the cycloalkane moieties.
In order to solve the stereochemistry of the compounds
we succeeded in preparing a trisacetylated derivative of
the cyclohexane indole, compound 4, first and then in
analyzing the compound structure by X-ray crystal
structure analysis of a given crystal. The acetylation of
the compound was carried out in dichloromethane using
acetic anhydride and both 4-(dimethylamino)pyridine
(DMAP) and triethylamine as basic auxiliaries. The
solved structure is shown in Figure 2. Both indole
residues have a pseudoequatorial orientation at the
cyclohexene ring in its half-chair form. This means a
trans-orientation of the indoly substituents which leads
to lowest steric substituent interactions.
Then the indole compound was added in a 2.5 molar
excess.
Both respective CH atoms have the same configuration
of being either S/S or R/R, respectively. According to the
same C atom configuration the protons give just one sig-
The resulting solution was kept stirring overnight at
room temperature, and the formation of the two products
was detected by tlc. When the reaction was accomplished
according to tlc, the acidic solution was neutralized with
sodium hydroxide solution (10%) and extracted with di-
chloromethane for three times. After washing with water
and brine for each two times the organic extract was dried
over sodium sulfate, filtered, and concentrated in vacuum.
Product isolation and purification were carried out via
1
nal in the H NMR spectra. So the stereochemistry of the
corresponding CH groups with the attached indole resi-
dues in the cycloheptane and the cyclooctane indoles
2c and 2d has to be different as both protons each lead
to different signals. Consequently, the configuration of
the C atoms of these CH groups has to be either S/R
or R/S, respectively, which practically means a cis-
orientation of the attached indolyl residues.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2015
Tetraindole and Cycloalkane Indole Formation
Scheme 2. (a) Reaction pathway for product formation of compounds 1a–c. (b) Product formation of compounds 2a–d starting from intermediate D.
a
b
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

M. T. El-Sayed, K. A. Mahmoud, F. W. Heinemann, and A. Hilgeroth
Vol 000
spectrometer. Elemental analysis indicated by the symbols
of the elements was within ±0.4% of the theoretical values
and was performed using a Leco CHNS-932 apparatus.
General procedure for the synthesis of tetraindoles 1a–c
and of bis(indolyl) cycloalkanes 2a–d.
The respective
dialdehyde (2mmol) was dissolved in glacial acetic acid
15 mL). Then the corresponding indole (5 mmol) was
(
added to the solution. The mixture was left stirring
overnight, and the product was detected by tlc in CH Cl2
2
(100%). The reaction mixture was worked up by
neutralizing the acid with NaOH (10%) and then
extracted with CH Cl for three times. The organic layer
2
2
was washed with water and brine each for three times.
Then it was dried over sodium sulfate, filtered, and
concentrated in vacuum. The reaction products were
Figure 2. Molecular structure of the trisacetylated compound 4 (thermal
ellipsoid representation with 50% probability ellipsoids, hydrogen atoms
shown as spheres of arbitrary size).
given after column chromatography using CH Cl2 as
2
eluent.
1,1,3,3-Tetra(1H-indol-3-yl)propane (1a). Yield 0.686 g
1
(
(
68%); yellow powder; mp 240–244°C; H NMR
DMSO-D ) δ 10.79 (s, 4H, NH), 7.31 (d, J= 8.1 Hz, 4H,
6
CONCLUSION
aromat. H), 7.25–7.23 (m, 8H, aromat. H), 6.96 (dd,
J = 8.1, 7.5 Hz, 4H, aromat. H), 6.75 (dd, J = 8.0, 7.5Hz,
Compounds isolated from natural products play an in-
creasing role in the discovery of novel biologically active
compounds. Natural sources like marine sponges, marine
actinomycetes, or different marine bacteria led to the iden-
tification of bis(indoly)-containing antimicrobial agents of
different structures [10,11,18,19]. So a further develop-
ment of novel bis(indolyl) compounds with suspected anti-
bacterial activity can be followed with our discovered
strategy starting from indole and various aliphatic
dialdehydes. The mild method of synthesis using glacial
acetic acid at room temperature was demonstrated to be ef-
fective also concerning costs as expensive catalysts are not
needed. Isolation and purification are also simple using a
one-column chromatography method. So our bis(indolyl)
cycloalkane indoles are a novel class of compounds with
unknown structures so far and potential biological
activities.
4
H, aromat. H), 4.32 (t, J =7.2 Hz, 2H, alkyl CH), 3.11
13
(t, J= 7.2 Hz, 2H, CH2); C NMR (100MHz, DMSO-
D ) δ 136.62, 126.62, 122.17, 120.56, 119.11, 118.63,
6
1
17.75, 111.34, 40.36 (CH ), 31.88 (aliphatic CH); MS
2
+
(ESI), m/z = 505 [M +H ]; IR (ATR): 3438 (NH), 3052
À1
(CH ) cm . Anal. (C H N ) Calcd C 83.30, H 5.59, N
2
35 28 4
1
1.10. Found C 83.32, H 5.54, N 11.14.
1
,1,5,5-Tetra(1H-indol-3-yl)pentane (1b).
Yield 0.693 g
1
(
(
65%); light brownish powder; mp 219–221°C; H NMR
DMSO-D ) δ 10.62 (s, 4H, NH), 7.41 (d, J= 7.9 Hz, 4H,
6
aromat. H), 7.24 (dd, J = 7.9, 7.6 Hz, 4H, aromat. H),
.10 (s, 4H, aromat. H), 6.94 (dd, J = 7.6, 7.4 Hz, 4H,
7
aromat. H), 6.80 (d, J = 7.4 Hz, 4H, aromat. H), 4.29 (t,
J = 7.4 Hz, 2H, alkyl CH), 2.24–2.06 (m, 4H, CH ), 1.48–
2
13
1
1
1
.21 (m, 2H, CH2); C NMR (100 MHz, DMSO-D ) δ
6
36.42, 126.62, 121,79, 120.46, 118.97, 118.86, 117.76,
11.22, 34.96 (aliphatic CH), 33.41 (CH ), 26.47 (CH );
2
2
+
MS (ESI), m/z = 555 [M+ Na ]; IR (ATR): 3409 (NH),
À1
2
6
931 (CH ) cm . Anal. (C H N ) Calcd C 83.43, H
.06, N 10.52. Found C 83.39, H 6.09, N 10.61.
Yield 0.645 g
2
37 32 4
EXPERIMENTAL
Commercial reagents were used without further purifica-
tion. Succinaldehyde was given by the treatment of 2,5-
dimethoxytetrahydrofuran with hydrochloric acid in THF
after stirring under reflux for 2 h according to literature
12]. Adipaldehyde resulted from the sodium metaperiodate
oxidation of cyclohexane epoxid in THF at room tempera-
1,1,6,6-Tetra(1H-indol-3-yl)hexane (1c).
1
(59%); light-brownish powder; mp 164–168°C; H NMR
(DMSO-D ) δ 10.63 (s, 4H, NH), 7.41 (d, J= 7.9 Hz, 4H,
6
aromat. H), 7.25 (d, J = 8.1 Hz, 4H, aromat. H), 7.10 (s,
4H, aromat. H), 6.95 (dd, J = 8.1, 7.6 Hz, 4H, aromat. H),
6.79 (dd, J= 7.9, 7.6 Hz, 4H, aromat. H), 4.28 (t,
[
1
ture following literature [13]. The H NMR spectra
400 MHz) were measured using tetramethylsilane as inter-
J = 7.5 Hz, 2H, alkyl CH), 2.29–2.10 (m, 4H, CH ), 1.34–
2
13
(
1.21 (m, 4H, CH2); C NMR (100 MHz, DMSO-D ) δ
6
nal standard. TLC was performed on E. Merck 5554 silica
gel plates. The electron ionization (EI) mass spectra were
measured with an AMD 402 mass spectrometer, the ESI
spectra were recorded on a Finnigan LCQ Classic mass
spectrometer. IR spectra were recorded on a FTIR
136.42, 126.62, 121,79, 120.46, 118.97, 118.86, 117.76,
111.22, 34.96 (aliphatic CH), 33.41 (CH ), 26.47 (CH );
2
2
13
C NMR (100MHz, DMSO-D ) δ 136.29, 126.58,
6
121.66, 121.00, 120.37, 118.82, 117.69, 111.12, 35.11
(aliphatic CH), 33.30 (CH ), 27.79 (CH ); MS (ESI),
2
2
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2015
Tetraindole and Cycloalkane Indole Formation
+
m/z = 545 [M À H ]; IR (ATR): 3456 (NH), 2986 (CH )
CH), 33.71 (CH ), 33.14 (CH ), 25.66 (CH ); MS (ESI),
2 2 2
2
À1
+
cm . Anal. (C H N ) Calcd C 83.48, H 6.27, N 10.25.
m/z=414 [MÀ H ]; IR (ATR): 3416 (NH), 2925, 2825
3
8 34 4
À1
Found C 83.46, H 6.30, N 10.30.
(CH ) cm . Anal. (C H N ) Calcd C 83.82, H 6.06, N
2
29 25 3
(
1R/S, 3R/S)-1,3-Di(1H-indol-3-yl)-1,2,3,4-tetrahydrocyclopenta
Yield 0.200 g (20%); light-brownish
powder; mp 110–115°C; H NMR (acetone-D ) δ 10.19
1
0.11. Found C 83.89, H 6.05, N 10.24.
(6R/S,11S/R)-6,11-Di(1H-indol-3-yl)-6,7,8,9,10,11-hexahydro-
[b]indole (2a).
1
5H-cycloocta[b]indole (2d).
powder; mp 105–108°C; H NMR (DMSO-D ) δ 11.86
Yield 0.232g (27%); brown
6
1
(
s, 1H, NH), 9.99 (s, 1H, NH), 9.97 (s, 1H, NH), 7.58–
6
7
7
.56 (m, 1H, aromat. H), 7.39–7.37 (m, 2H, aromat. H),
.28–7.26 (m, 4H, aromat. H), 7.09–7.06 (m, 1H,
(s, 1H, NH), 10.85 (s, 1H, NH), 9.05 (s, 1H, NH), 7.65
(d, J=7.8Hz, 1H, aromat. H), 7.59-7.49 (m, 4H, aromat.
H), 7.37 (d, J=8.0Hz, 1H, aromat. H), 7.32–7.18 (m, 4H,
aromat. H), 7.18–7.15 (m, 1H, aromat. H), 7.07–7.00 (m,
2H, aromat. H), 6.95 (t, J=7.1Hz, 1H, aromat. H), 5.61–-
5.57 (m, 1H, alkyl CH), 4.61 (d, J=10.2Hz, 1H, alkyl
aromat. H), 7.03–7.01 (m, 2H, aromat. H), 6.92–6.90 (m,
H, aromat. H), 6.83–6.82 (m, 1H, aromat H), 6.47–6.45
m, 1H, aromat. H), 5.19–5.01 (m, 2H, alkyl CH), 1.89
2
(
(
1
3
d, J = 7.9 Hz, 2H, CH2); C NMR (100 MHz, DMSO-
D ) δ 159.70, 147.62, 138.46, 138.02, 129.14, 129.06,
CH), 2.07–1.98 (m, 6H, CH
C NMR (100MHz, DMSO-D ) δ 147.09, 143.61,
139.65, 136.65, 136.23, 136.13, 128.16, 127.75, 127.02,
122.46, 121.62, 121.54, 121.47, 120.64, 120.47 119.91,
119.76, 119.58, 118.99, 118.80, 118.79, 110.98, 110.85,
2
), 1.95–1.86 (m, 2H, CH
);
2
6
13
1
1
1
28.06, 128.39, 127.37, 124.50, 122.02, 121.51, 121.43,
20.99, 120.24, 119.83, 119.63, 119.29, 118.59, 116.45,
6
14.62, 112.05, 111.97, 102.26, 70.27 (CH ), 41.13
2
(
[
aliphatic CH), 30.57 (aliphatic CH); MS (EI), m/z = 387
+
À1
M ]; IR (ATR): 3404 (NH), 2923 (CH ) cm . Anal.
110.75, 49.78 (aliphatic CH), 41.23 (CH
(aliphatic CH), 34.58 (CH ), 30.37 (CH ), 24.91 (CH
2
), 36.96
2
2
(
C H N ) Calcd C 83.69, H 5.46, N 10.85. Found C
2
2
);
2
7 21 3
+
8
3.35, H 5.24, N 10.66.
MS (ESI), m/z=428 [MÀH ]; IR (ATR): 3375 (NH),
À1
(
1R/S, 4R/S)-1,4-Di(1H-indol-3-yl)-2,3,4,9-tetrahydro-1H-
2936 (CH ) cm . Anal. (C H N ) Calcd C 83.88, H
2
30 27 3
carbazole (2b).
powder; mp 139–145°C; H NMR (DMSO-D ) δ 10.88
Yield 0.683 g (85%); light-brownish
6
.34, N 9.78. Found C 83.89, H 6.36, N 9.81.
1
6
Acetylation procedure to form compound 4. Compound
(
s, 1H, NH), 10.67 (s, 1H, NH), 10.42 (s, 1H, NH), 7.59
2b (1mmol) was dissolved in CHCl3 and DMPA
(d, J =7.9 Hz, 1H, aromat. H), 7.45 (d, J= 7.9Hz, 1H,
(
(
0.1mmol). Triethylamine (1.2mmol) and acetic anhydride
1.2mmol) were added. The reaction mixture was left
aromat. H), 7.39–7.28 (m, 3H, aromat. H), 7.18 (t,
J =6.5 Hz, 1H, aromat. H), 7.05 (t, J = 7.0 Hz, 2H,
aromat. H), 6.94–6.81 (m, 4H, aromat. H), 6.67–6.60 (m,
stirring for several days. The product formation was
observed by tlc until no more changes were stated. Then
the solution was neutralized with ammonia and extraction
with CH Cl followed for three times. The organic layer
2
H, aromat. H), 4.58–4.49 (m, 2H, alkyl CH), 2.23–2.05
1
3
(m, 4H, CH2); C NMR (100MHz, DMSO-D ) δ
6
2
2
1
1
1
1
37.56, 137.33, 136.84, 136.37, 136.34, 127.07, 126.69,
26.42, 123.05, 121.09, 120.92, 120.11, 119.94, 119.39,
19.03, 118.88, 118.51, 118.29, 118.19, 117.92, 117.53,
11.80, 111.62, 111.03, 32.51 (aliphatic CH), 32.20
was washed with water and brine for three times and then
dried over sodium sulfate. After filtration the acetylated
product was given by column chromatography over silica
gel using an eluent mixture of CH Cl and methanol (98/2).
2
2
(
aliphatic CH), 30.52 (CH ), 29.75 (CH ); MS (ESI),
1,1′-(3,3′-(9-acetyl-2,3,4,9-tetrahydro-1H-carbazole-1,4-diyl)
bis(1H-indole-1,3-diyl) diethanone (4).
2
2
+
Yield 0.343 g
m/z = 402 [M + H ]; IR (ATR): 3398 (NH), 2923 (CH )
cm . Anal. (C H N ) Calcd C 83.76, H 5.77, N 10.47.
Found C 83.80, H 5.73, N 10.51.
2
À1
1
(65%); light-yellow crystals; mp 264–268°C; H NMR
(DMSO-d ) δ= 8.48–8.46 (m, 2H, aromat. H), 8.03 (d,
2
8 23 3
6
(
6R/S,10S/R)-6,10-Di(1H-indol-3-yl)-5,6,7,8,9,10-hexahy-
J = 8.3 Hz, 1H, aromat. H), 7.69–7.58 (m, 2H, aromat. H),
7.43–7.31 (m, 3H, aromat. H), 7.19–7.09 (m, 2H, aromat.
H), 6.97–6.91 (m, 2H, aromat. H), 6.76 (s, 2H, aromat.
H), 4.65–4.57 (m, 2H, alkyl CH), 2.61 (s, 3H, COCH3),
2.48 (s, 3H, COCH ), 2.42 (s, 3H, COCH ), 2.27–2.15
drocyclohepta[b]indole (2c). Yield 0.208g (25%); brown
powder; mp 152–155°C; H NMR (DMSO-D ) δ 10.97
1
6
(s, 1H, NH), 10.66 (s, 1H, NH), 9.66 (s, 1H, NH), 7.62
(d, J=7.7Hz, 1H, aromat. H), 7.43–7.33 (m, 4H, aromat.
3
3
H), 7.19 (dd, J=7.1, 2.3Hz, 1H, aromat. H), 7.10–7.05
(
m, 2H, CH ); 2.07–1.41 (m, 2H, CH ); MS (EI),
2 2
+
À1
(m, 3H, aromat. H), 6.99–6.69 (m, 2H, aromat. H), 6.85
t, J=6.9Hz, 1H, aromat. H), 6.74 (t, J=6.9Hz, 1H,
m/z = 527 [M ]; IR (ATR): 2923 (CH ), 1689 (CO) cm .
2
Anal. (C H N O ) Calcd C 77.40, H 5.54, N 7.96.
(
34 29 3 3
aromat. H), 6.66 (dd, J=7.5, 1.2Hz, 1H, aromat. H), 4.91
t, J=8.5Hz, 1H, alkyl CH), 4.66 (dd, J=9.5, 3.10Hz,
Found: C 77.25; H 5.43; N 7.75.
X-ray diffraction analysis of the trisacetylated compound
4. A colorless plate-shaped crystal of C H N O (from
DMSO), crystal size 0.12×0.08×0.02mm , was measured
at a temperature of 100°K by using a Bruker Kappa APEX
2/μS Duo diffractometer with Mo-Kα radiation (λ =
0.71073Å) and a graphite monochromator. The 21426
reflexions were collected in a ω/2Θ scanning mode in the
(
1
2
1
1
1
1
H, alkyl CH), 2.19–2.09 (m, 4H, CH ), 1.74–1.62 (m,
2
34 29 3 3
3
13
H, CH2); C NMR (100MHz, DMSO-D ) δ 139.65,
6
38.67, 137.18, 136.55, 134.31, 133.84, 129.37, 127.17,
26.87, 126.61, 123.59, 122.54, 121.70, 121.37, 120.73,
19.93, 119.11, 118.95, 118.17, 117.88, 114.95, 111.45,
11.03, 110.33, 36.23 (aliphatic CH), 35.13 (aliphatic
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

M. T. El-Sayed, K. A. Mahmoud, F. W. Heinemann, and A. Hilgeroth
Vol 000
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Tsuchiya, H.; Takahashi, Y.; Masuma, R. J Antiobiot 1977, 30, 275.
12] Armstrong, A.; Pyrokotis, C. Tetrahedron Lett 2009,
0, 3325.
13] Binder, C. M.; Dixon, D. D.; Almaraz, E.; Tius, M. A.;
Singaram, B. Tetrahedron Lett 2008, 49, 2764.
range 4.6°≤ 2Θ ≤ 52.0°, h,k,l range from À11, À13, and À14
to 11, 13, and 14. Crystal system: monoclinic space group
[
P2 /n, Z=4, a=5.6167(5) Å, b=39.258(3) Å, c= 11.931(2)
1
3
3
Å, β =95.079(2)°; V= 2620.4(4) Å ; D =1.337g x cm ;
and μ= 0.086 mm . The structure was solved by direct
x
À1
[
methods (SHELXTL NT 6.12, Bruker AXS, 2002) using
2
5
5
316 independent reflexions. Structure refinement: full-
2
matrix least squares methods on F using SHELXTL NT
.12 (Bruker AXS, 2002), all the non-hydrogen atoms with
[
6
anisotropic displacement parameters. All hydrogen atoms
[
are in calculated positions. The refinement converged to a
2
7
final wR =0.1600 for 5316 unique reflexions and
1
R = 0.0714 for 4129 observed reflections [I > 2.0σ(I )]
0
0
and 364 refined parameters.
[
5
[
Acknowledgment. Financial support of the work was given from
the Egyptian Government with a scholarship to Mardia Telep El-
Sayed.
[
[
[
14] Ehrlich, P. Med Woche 1901, 2, 151.
15] Remers, W. A. Chem Heterocyclic Comp 1972, 25, 1.
16] Pictet, A.; Spengler, T. Chem Ber 1911, 44, 2030.
REFERENCES AND NOTES
[17] Cox, E. D.; Cook, J. M. Chem Rev 1995, 95, 1797.
18] Motomasa, K.; Shunji, A.; Gato, K.; Katsuyoshi, M.; Kurosu, M.;
[
[
[
1] Raju, B. C.; Rao, J. M. Ind J Chem 2008, 47B, 623.
2] Sujatha, K.; Perumal, P. T.; Muralidharan, D.; Rajendran, M.
Isao, K. Chem Pharm Bull 1994, 42, 2449.
[19] Ravikanth, V.; Oka, I.; Wagner-Döbler, I.; Laatsch, H. J Nat
Prod 2003, 66, 1520.
Ind J Chem 2009, 48B, 267.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet