New one stage synthesis of 3,3′-bis(2-methylindolyl)methane - A homolog of the marine antibiotic vibriindole [4]

Full text of DOI:10.1023/A:1017540204992

Chemistry of Heterocyclic Compounds, Vol. 37, No. 2, 2001
NEW ONE STAGE SYNTHESIS OF
3,3'-BIS(2-METHYLINDOLYL)METHANE –
A HOMOLOG OF THE MARINE
ANTIBIOTIC VIBRIINDOLE
1
1
2
T. V. Moskovkina , T. V. Pyanzin , and V. V. Isakov
Keywords: bisindolylmethane, heptandione-2,6, 2-methylcarbazole, Fischer indolization.
A group of antibiotics, derivatives of 3,3'-bisindolylmethane, have been found in marine bacteria.
Vibriindole 1 and related compounds from various bacteria of the genus Vibrio, associated with marine
organisms, are of this type [1-3].
We have shown that some 3,3'-bisindolylmethanes can be obtained by indolization of the easily obtained
1
,5-diketones. For example, we obtained 3,3'-bis(2-methylindolyl)methane (4), a homolog of vibriindole, in 55%
yield from the diketone 2 by thermal indolization of its diphenylhydrazone 3. We found compound 4 to possess
antimicrobial activity against the bacteria Staphylococcus aureus, Enterococcus faecium, and the microscopic
fungus Candida albicans. Compound 4 has been synthesized previously in low yield by condensation of
2
-methylindole with its 3-diethylamino derivative [4].
H
N
CH3
2
C H NHNH
6 5 2
H C N N CH3
H C O O CH3
3
N
H
3
C H NH NHC H
CH3 N CH3
6
5
6
5
CH3
3
N
H
2
5
NHC H
6
5
4
CH3
CH3
H
N
NHNHC H
N
H
7
N
H
6
6
5
[
O]
CH3
N
H
CH3
CH3
N
N C H
6 5
1
N
H
N
H
8
9
_
___________________________________________________________________________________________
1
2
Far Eastern State University, Vladivostok 690600, Russia; e-mail: innast@mail.primorye.ru. Pacific
Ocean Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, Vladivostok
6
9002, Russia; e-mail: piboc@stl.ru. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, 281-283,
February, 2001. Original article submitted September 15, 2000.
0009-3122/01/3702-0259$25.00©2001 Plenum Publishing Corporation
259

Isolation from the reaction mixture of compounds 8 and 9 along with compound 4 shows that the
intermediate hydrazone 5 not only underwent the Fischer indolization but was also cyclized to the intermediate
6
, which was transformed into the carbazoles 8 and 9 on oxidation and heating.
3
,3'-Bis(2-methylindolyl)methane (4). A solution of bisphenylhydrazone 3 (1.54 g, 5.0 mmol),
obtained by heating diketone 2 (10 mmol) with phenylhydrazine (20 mmol) in benzene with a Dean–Stark trap,
in ethylene glycol (15 ml) was heated at 190°C for 5 h. The reaction mass was diluted with water, ether was
added, the mixture was stirred, and the residue of 4 was separated (0.75 g, 55% yield); mp 234-236°C (ethanol).
-1
+
1
Lit. data: mp 236-237°C [4]. IR spectrum (CHCl
spectrum (CDCl
), δ, ppm, J (Hz): 2.34 (6H, s, 2CH
2H, br. s, NH). Found, %: C 83.4; H 6.7; N 10.4. C19
-Methyl-2-phenylazo-1,2,3,4-tetrahydrocarbazole (8) was isolated by column chromatography on
aluminum oxide from the ether extract of the mother liquor from the isolation of compound 4. Yield 15%;
3
), ν, cm : 3450 (NH). Mass spectrum, m/z: 274 (M ). H NMR
); 4.1 (2H, A -system, s, CH ); 6.96-7.38 (arom. H); 7.68
. Calculated, %: C 83.2; H 6.5; N 10.2.
3
3
2
2
(
H
18
N
2
2
-
1
mp 146-148°C (ethanol). IR spectrum (CHCl
3
), ν, cm : 3462 (NH), 1466 (Alk–N=N–Ph). Mass spectrum, m/z:
, 100%). H NMR spectrum (CDCl ); 2.25 (1H, m);
), δ, ppm, J (Hz): 1.4 (3H, s, CH
.36 (1H, m); 2.84 (1H, A part of AB system, d, J = 16.4); 3.45 (1H, B part of AB system, d, J = 16.4); 7.0-7.75
. Calculated, %: C 78.9; H 6.6; N 14.5.
-Methylcarbazole (9) was obtained in an analogous manner to compound 8. Yield 11%;
+
+
1
2
2
(
89 (M ), 184 (M -PhN
2
3
3
arom. H); 7.75 (br. s, NH). Found, %: C 79.0; H 6.8; N 14.7. C19
H
19
N
3
2
-
1
mp 246-248°C (ethanol), lit. data: mp 259°C [5]. IR spectrum, ν, cm : 3462 (NH), 1610, 1489, 3051 (arom).
+
1
Mass spectrum, m/z: 181 (M ). H NMR spectrum (CDCl
3
), δ, ppm: 1.5 (3H, s, CH
br. s, NH). Found, %: C 86.3; H, 6.2; N 7.9. C13H11N. Calculated, %: C 86.2; H 6.0; N 7.7.
3
); 6.9-7.3 (arom. H); 7.75
(
This work was carried out with a financial subvention from the Russian Fund for Fundamental Research
grant 98-03-32891) and grants from the US CDRF and the Ministry of Education of The Russian Federation
REC-003).
(
(
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260