Unusual condensation of 6,7-dimethoxy-1,3,3-trimethyl-3,4- dihydroisoquinoline with 4-antipyrylidenebarbituric acid

Full text of DOI:10.1023/B:COHC.0000033555.76762.d8

Chemistry of Heterocyclic Compounds, Vol. 40, No. 4, 2004
UNUSUAL CONDENSATION OF
6,7-DIMETHOXY-1,3,3-TRIMETHYL-
3,4-DIHYDROISOQUINOLINE WITH
4-ANTIPYRYLIDENEBARBITURIC ACID
Yu. V. Shklyaev
Keywords: antipyrin-4-carbaldehyde, barbituric acid, 6,7-dimethoxy-1,3,3-trimethyl-3,4-dihydro-
isoquinoline.
The reaction of arylidene barbituric acids with 1-methyl-3,4-dihydroisoquinolines, leading to the
corresponding 8-azasteroid derivatives, has been described [Ref. 1, p. 208]. This reaction can be carried out both
with the arylidene barbituric acid itself and in the three-component variant: by heating a mixture of the aldehyde,
barbituric acid, and 1-methyl-3,4-dihydroisoquinoline in DMF [Ref. 1, p. 426].
Since 8-azasteroids with substituents in the 7 position have not yet been described, it was of interest to
carry out the analogous reaction with 6,7-dimethoxy-1,3,3-trimethyl-3,4-dihydroisoquinoline.
However, as we have established, the reaction of 6,7-dimethoxy-1,3,3-trimethyl-3,4-dihydroisoquinoline
(1) with a mixture of 4-antipyrin aldehyde 2 and barbituric acid 3, or with the product 4 obtained by
condensation of compounds 2 and 3, leads to formation of only 1-(6,7-dimethoxy-3,3-dimethyl-1,2,3,4-
tetrahydro-1-isoquinolylidene)-2-(3,5-diaza-2,4,6-trioxo-1-cyclohexylidene)ethane (5), which judging from the
spin–spin coupling constant of the vicinal protons (~15 Hz), exists in the trans conformation.
O
O
OHC
Me
Me
Me
MeO
MeO
+
HN
NH
+
N
N
O
N
Me
O
Ph
1
Me
3
2
MeO
MeO
Me
Me
NH
1
2
O
H
O
O
Me
Me
MeO
MeO
N
O
Me
Me
+
HN
NH
N
N
H
O
N
5
O
Me
O
N
4
Ph
__________________________________________________________________________________________
Institute of Technical Chemistry, Urals Branch of the Russian Academy of Sciences, Perm 614990;
e-mail: cheminst@mpm.ru. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 627-628,
April, 2004. Submitted June 10, 2003; revision submitted January 29, 2004.
530
0009-3122/04/4004-0530©2004 Plenum Publishing Corporation

Probably in the first step of the reaction, the antipyrylidene barbituric acid 4 undergoes Michael addition
to the enamine form of 3,4-dihydroisoquinoline 1, but the product 6 proves to be unstable under the reaction
conditions and eliminates the antipyrin moiety.
MeO
MeO
Me
Me
NH
150 oC
+
4
CH2
Me
Me
N
O
MeO
MeO
H
N
O
5
NH
O
O
Me
N
N
Ph
Me
6
1-(6,7-Dimethoxy-3,3-dimethyl-1,2,3,4-tetrahydro-1-isoquinolylidene)-2-(3,5-diaza-2,4,6-trioxo-1-
cyclohexylidene)ethane (5). Dry DMF (10 ml) was added to a mixture of compound 1 (2.21 g, 0.01 mol),
barbituric acid (1.28 g, 0.01 mol), and antipyrin carbaldehyde (2.16 g, 0.01 mol); the mixture was heated to
boiling. The mixture become homogeneous at first, but after 1-2 min abundant precipitation began. The mixture
was heated for 15 min, cooled down, and poured into 100 ml water; the red precipitate was collected, dried, and
crystallized from alcohol. Yield 59%, decomposes at ~217°C. IR spectrum, ν, cm-1: 3300 (NH); 1730, 1660
1
(C=O); 1615 (C=N). The H NMR spectrum was taken on a Bruker AM 300 (300 MHz) in DMSO-d6, internal
standard Me4Si, δ, ppm: 1.31 (6H, s, gem-CH3); 2.87 (2H, s, CH2-4); 3.83 (3H, s, OCH3-6); 3.89 (3H, s,
OCH3-7); 6.96 (1H, s, 5-H); 7.28 (1H, s, 8-H); 7.55 (1H, d, H(1) vinyl); 8.30 (1H, d, H(2) vinyl); 9.70 (1H, s,
NHisoquin); 10.01 (1H, br. s, NHbarb); 10.12 (1H, br. s, NHbarb). The mass spectrum was taken on a Finnigan MAT
under standard conditions (electron impact, 70 eV), m/z (Irel, %): 371 [M]+ (100); 356 [M - Me] (90); 341
[M - 2Me] (23); 296 (68); 283 [M-NHCONH] (20); 270 (45); 244 [M - barbituric acid] (50); 233 (60); 218
[M - barbituric acid CH=CH] (70); 191 [methoxy-3,3-dimethyl-1,2,3,4-tetrahydroisoquinoline] (40); 128
[barbituric acid] (38).
This work was done with partial financing from a Russian Federation Presidential Grant for support of
the leading scientific schools NSh-2020.2003.3 and the program of the Presidium of the Russian Academy of
Sciences on "New principles and methods for directed synthesis of compounds with specific properties."
REFERENCES
1.
A. L. Mikhal'chuk and O. V. Gulyakevich, in: Nitrogen-Containing Heterocycles and Alkaloids
[in Russian], Iridium Press, Moscow (2001), Vol. 2.
531