E. R. Bilbao et al. / Tetrahedron Letters 43 (2002) 3551–3554
3553
Scheme 2.
In order to optimize the yields of the cyclization, differ-
ent solvents, enaminones as hydrochlorides, and reac-
tion conditions were assayed. Also, triazine as
hydrochloride was reacted with different enaminones in
dioxane, dimethoxyethane or in absence of solvent
As application of this IDA reaction methodology to the
synthesis of our CNS agents precursor, we submitted
2
the enaminone 3 (NRR=NH
)
2
as hydrochloride,
obtained in 80% yield from 1, to [4+2] cycloaddition
reaction with 1,3,5-triazine in acetic acid (Scheme 2),
affording 7-methoxymethyl-5,6,7,8-tetrahydro-5-quina-
(
entries 9–12).
16
zolinone (8) in 66% yield.
Heating triazine hydrochloride with enaminone 5b in
the absence of solvent at 130°C (entry 9) led to the
formation of two products. One of them (8% yield)
proved to be the quinazolinone 6, and the other (12%
yield) was identified as the product of double cycloaddi-
tion, the 3,3,6,6-tetramethyl-1,2,3,4,5,6,7,8-octahydro-
In summary, we have demonstrated that enaminones
undergo inverse electron demand Diels–Alder reaction
with 1,3,5-triazine, allowing access to functionalised
quinazolinones as intermediates in the synthesis of CNS
agents. This reaction is highly dependent of the solvent:
1,3,5-triazine undergoes single or double [4+2] cycload-
ditions with enaminones, and quinazolinones or
acridinediones can be selectively obtained.
13
acridine-1,8-dione (7).
Also, mixtures of quinazolinone 6 and acridinodione 7
were obtained when the reaction was carried out with
5
c in dimethoxyethane (entry 12), or when the enam-
inone 5c as hydrochloride salt was treated with triazine
in dimethoxyethane (entry 17).
Acknowledgements
4
This work was supported by the Xunta de Galicia
(
Spain) under grant PGIDT01PXI20309PR. M.
The acridinodione 7 was obtained in 65% yield as the
Alvarado (on leave from Universidad de Nari n˜ o,
Colombia) is grateful to the Agencia Espa n˜ ola de Coop-
eraci o´ n Internacional (AECI) for
only product when H O was used as the solvent (entries
2
1
3 and 18). Few examples of IDA reactions performed
14
a
predoctoral
in H O have been reported so far, and, to our knowl-
2
fellowship.
edge, this is the first example of a double [4+2] cycload-
dition reported in this solvent. Both, the enaminone
hydrochloride and the triazine were soluble in H O
2
References
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1
5
presence or absence of solvent.
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4
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