Cyclocondensation of 2-fluoro-5-nitrobenzaldehyde with amidines [2]

Full text of DOI:10.1023/A:1020946202893

Chemistry of Heterocyclic Compounds, Vol. 38, No. 8, 2002
CYCLOCONDENSATION OF 2-FLUORO-
5
-NITROBENZALDEHYDE WITH AMIDINES
D. V. Dar'in, S. I. Selivanov, P. S. Lobanov, and A. A. Potekhin
Keywords: amidines as N,N- and C,N-nucleophiles, 2-fluoro-5-nitrobenzaldehyde, cyclocondensation.
Kotsuki et al. [1] have recently reported the synthesis of 4-unsubstituted quinazolines by the
cyclocondensation of o-fluorobenzaldehydes with amidines. Waring [2] and Mohamed [3] have reported that
amidines containing α-hydrogen atoms may undergo cyclocondensation with esters of 3-oxocarboxylic acids
and conjugated enols by acting not only as N,N-dinucleophiles but also as C,N-dinucleophiles. These findings
have led us to study the reaction of 2-fluoro-5-nitrobenzaldehyde (1) with acetamidine under the same
conditions as in the work of Kotsuki [1] and thoroughly separated the reaction mixture by column
chromatography. The major reaction product, as expected, was 2-methyl-6-nitroquinazoline. Furthermore,
isomeric 2-amino-6-nitroquinone formed in the nucleophilic attack of the amidine α-carbon atom on the
benzaldehyde carbonyl group was obtained in trace amounts. Examples of cyclocondensation featuring
unsubstituted acetamidine as a C,N-dinucleophile have not yet been reported.
O N
CHO
F
O N
O N
2
2
2
MeC(=NH)NH2
K CO
N
2
3
N
Me+
N
NH2
1
58%
1.5%
When amidine 2, containing an active methyl group, was introduced into the same reaction,
-aminoisoquinoline 3 was the major cyclocondensation product.
3
NH
O N
2
6
5%
N
1
+
NH2
CONH2
NH2
CONH2
2
3
Isoquinoline structure was assigned for 3 on the basis of the chemical shifts for 1-H and C(1) and the
1
1
1
J(C –H ) coupling constant. These values are characteristic for a C–H fragment in the α-position to the
nitrogen atom in azines [5].
2
-Methyl-6-nitroquinazoline was isolated in 58% yield by chromatography on a silica gel column with
1
1
(
:2 ether–hexane as the eluent; mp 152-154°C. H NMR spectrum (300 MHz, DMSO-d
6
), δ, ppm, J (Hz): 2.84
3H, s, CH
Found, %: C 57.21; H 3.72; N 22.10. C
3
); 8.05 (1H, d, J = 9, 8-H); 8.61 (1H, m, J = 9, 2-, 5-, 7-H); 9.12 (1H, d, J = 5-H); 9.78 (1H, s, 4-H).
9
H
7
N
3
O . Calculated, %: C 57.14; H 3.73; N 22.21.
2
_
_________________________________________________________________________________________
St. Petersburg State University, 198904 St. Petersburg, Russia; e-mail: psl@pisem.net. Translated from
Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1155-1156, August, 2002. Original article submitted
April 24, 2002.
1
014
0009-3122/02/3808-1014$27.00©2002 Plenum Publishing Corporation

2
-Amino-6-nitroquinoline [14] was isolated in 1.5% yield by chromatography on a silica gel column
1
with 3:1:1 ether–hexane–ethyl acetate as the eluent; mp 250°C (dec.). H NMR spectrum, δ, ppm, J (Hz): 6.89
(
1H, d, J = 9, 3-H); 7.23 (2H, NH
2
); 7.50 (1H, d, J = 9, 8-H); 8.13 (1H, d, J = 9, 4-H); 8.22 (1H, m, J = 9, 2-, 5-,
7
-H); 8.68 (1H, d, J = 2.5, 5-H).
3
-Amino-7-nitroisoquinoline-4-carboxamide (3) was isolated in 65% yield by reprecipitation from
1
DMF using 1:1 ether–ethanol; mp ~350°C. H NMR spectrum, δ, ppm, J (Hz): 6.86 (2-H, 3-NH
2
); 7.83 (2H, d,
J = 9, 5-H); 7.85 (1H, CONH); 8.06 (1H, CONH); 8.24 (1H, m, J = 9, 2-, 5-, 6-H); 8.93 (1H, d, J = 2.5, 8-H);
13
9
.19 (1H, s, 1-H). C NMR spectrum, δ, ppm: 104.35 (C(4)), 119.79 (C(8a)), 123.83 (C(6)), 126.14 (C(8)), 137.41
1
(
C
(4a)), 140.98 (C(7)), 155.98 (C(3)), 156.12 (C(1), J(C–H) = 181.5 Hz), 168.08 (CO). Found, %: C 51.66; H 3.52;
N 24.19. C10
H
8
H
4
O . Calculated, %: C 51.73; H 3.47; N 24.13.
3
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015