ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 10, pp. 1555–1556. © Pleiades Publishing, Ltd., 2013.
Original Russian Text © A.V. Aksenov, N.A. Aksenov, A.S. Lyakhovnenko, I.V. Aksenova, 2013, published in Zhurnal Organicheskoi Khimii, 2013, Vol. 49,
No. 10, pp. 1575–1576.
SHORT
COMMUNICATIONS
Synthesis of 6H-Pyrrolo[2,3,4-gh]perimidines
from Naphthalene-1,4,8-triamine
A. V. Aksenov, N. A. Aksenov, A. S. Lyakhovnenko, and I. V. Aksenova
North-Caucasus Federal University, ul. Pushkina 1a, Stavropol, 355009, Russia
e-mail: k-biochem-org@stavsu.ru
Received December 5, 2012
DOI: 10.1134/S1070428013100266
The importance of indole derivatives as biologi-
cally active compounds is difficult to overestimate.
Benzo[c,d]indoles are not an exception; for example,
efficient inhibitors of thymidylate synthase were found
among compounds of this series [1]. The present
communication describes the synthesis of fused benzo-
[c,d]indole derivatives, 6H-pyrrolo[2,3,4-gh]perimi-
dines IVa–IVc, from naphthalene-1,4,8-triamine (I)
and 1,3,5-triazines IIa–IIc.
We previously showed that 1,3,5-triazine in poly-
phosphoric acid (PPA) acts as efficient formylating and
acylating agent [2–5], in particular toward naphthyl-
amines [5]. Therefore, it may be expected that the use
of 1,3,5-triazine should ensure convenient synthesis of
pyrroloperimidines IVa–IVc. In fact, by heating tri-
amine I with triazines IIa–IIc in PPA first at 80–90°C
and then at 130–140°C we obtained the corresponding
pyrroloperimidines IVa–IVc in 38–48% yield. The
reaction is likely to involve intermediate formation of
aminoperimidines IIIa–IIIc.
sodium azide in acid medium, and there exists a risk of
evolution of toxic and explosive hydrazoic acid. The
procedure proposed by us is free from the said disad-
vantage.
Pyrroloperimidines IVa–IVc (general procedure).
A mixture of 0.173 g (1 mmol) of naphthalene-1,4,8-
triamine (I) and 3.1 mmol of triazine IIa–IIc in 3–4 g
of polyphosphoric acid [7] was heated under vigorous
stirring for 3 h at 80–90°C. The temperature was then
raised to 130–140°C, and the mixture was stirred for
3 h at that temperature. The mixture was cooled,
poured into 30 ml of water, heated for 10 min at the
boiling point, made alkaline by adding aqueous
ammonia, and extracted with benzene (3×100 ml). The
combined extracts were evaporated, and the residue
was purified by recrystallization from benzene (IVa,
IVb) or benzene–petroleum ether (IVc).
6H-Pyrrolo[2,3,4-gh]perimidine (IVa). Yield
0.073 g (38%), yellow crystals, mp 207–209°C (from
benzene) [6]. Found, %: C 74.71; H 4.58; N 21.64.
C12H7N3. Calculated, %: C 74.60; H 3.65; N, 21.75.
Unlike the known procedure [6], the proposed
method requires no preliminary preparation and acyla-
tion of perimidines. Furthermore, the key step in the
known procedure [6] is the Schmidt reaction utilizing
2,7-Dimethyl-6H-pyrrolo[2,3,4-gh]perimidine
(IVb). Yield 0.104 g (47%), yellow crystals, mp 271–
R
NH2 NH2
R
N
N
NH
R
N
PPA
N
N
IIa–IIc, PPA
N
+
R
R
R
N
H
NH2
NH2
I
IIa–IIc
IIIa–IIIc
IVa–IVc
R = H (a), Me (b), Ph (c).
1555