An easy and efficient method for the synthesis of 2,2-dialkyl-3-nitrochromene

Article abstract of DOI:10.1016/S0040-4039(01)00284-2

Reactions of salicylaldehyde 1, 1,4-diazabicyclo[2.2.2]octane (DABCO), with β-nitrostyrenes 2, 4, 12, 14, and 16, respectively, in the absence of solvent at 40°C gave high yields of 3-nitro-chromenes. Only 96% of trans-3-nitro-4-hydroxyflavans 7 or 98% of 10 were isolated when compounds 6 or 9 reacted with 1 and DABCO under similar conditions. When the reaction temperature was increased to 90°C, 7 and 10 underwent dehydration to generate 74% of 8 and 89% of 11.

Full text of DOI:10.1016/S0040-4039(01)00284-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 2717–2721
An easy and efficient method for the synthesis of
,2-dialkyl-3-nitrochromene
2
Ming-Chung Yan, Yeong-Jiunn Jang and Ching-Fa Yao*
Department of Chemistry, National Taiwan Normal University 88, Sec. 4, Tingchow Road, Taipei, Taiwan 116, ROC
Received 19 January 2001; accepted 16 February 2001
Abstract—Reactions of salicylaldehyde 1, 1,4-diazabicyclo[2.2.2]octane (DABCO), with b-nitrostyrenes 2, 4, 12, 14, and 16,
respectively, in the absence of solvent at 40°C gave high yields of 3-nitro-chromenes. Only 96% of trans-3-nitro-4-hydroxyflavans
7
or 98% of 10 were isolated when compounds 6 or 9 reacted with 1 and DABCO under similar conditions. When the reaction
temperature was increased to 90°C, 7 and 10 underwent dehydration to generate 74% of 8 and 89% of 11. © 2001 Elsevier Science
Ltd. All rights reserved.
1
2
The synthesis and biological activity of 3-nitro-
chromenes have been reported because of their poten-
tial as precursors to a variety of medically important
ing 3-nitro-2-phenyl-2H-chromenes, but also in our
current studies of the synthesis of 2,2-dialkyl-3-
nitrochromenes.
3
4
2
H-benzopyran derivatives such as flavonols, amines,
etc. It also has been reported that D -chromenes con-
taining electron-withdrawing substituents at the 3-posi-
3
Our recent study found that high yields of 3-
nitrochromenes 3a–d (a: Ar=Ph, 98%; b: Ar=p-
MeOC H , 75%; c: Ar=p-ClC H , 99%; d:
5
tion possess radio-protecting properties and 3-nitro-
6
4
6
4
chromenes with appropriate substituents are potentia6l
candidates for nonlinear optical applications.
However, 2,2-dialkyl-3-nitrochromenes are not well
studied yet. Herein, we provide an improved, easy, and
efficient method to prepare 2,2-dialkyl-3-nitrochrome-
nes. It is useful not only in the past works of synthesiz-
Ar=thiophene, 79%) could be generated from the reac-
tion mixture of salicylaldehyde 1 (4–10 equiv.), b-
nitrostyrenes 2a–d (1 equiv.; a: Ar=Ph, b: Ar=
p-MeOC H , c: Ar=p-ClC H , d: Ar=thiophene) and
1,4-diazabicyclo[2.2.2]octane (DABCO) (0.5–1.0 equiv.)
in the absence of solvent at 40°C for 1.5 h (Eq. (1)).
6
4
6
4
(
(
1)
2)
*
0
Corresponding author.
040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00284-2

2
718
M.-C. Yan et al. / Tetrahedron Letters 42 (2001) 2717–2721
Under similar conditions, 99% of 5 also could be
isolated when compound 4 was used (Eq. (2)). The
structures of 3 and 5 could be assigned according to
effect of the groups in the 2-position of flavan and this
effect plays an important role in both the reaction
conditions and the stability of products. To overcome
the steric effect, the temperature was increased to 90°C,
and the expected 3-nitrochromenes (74% of 8 and 89%
of 11) were produced from further dehydration of 7 or
10 (Eqs. (4) and (6)). According to the above results, we
can conclude that this method is easy for us to obtain
either 3-nitro-4-hydroxyflavans or 3-nitrochromenes
just by controlling the reaction temperature when steric
substrates 6 and 9 are used. When DABCO was
replaced by triethylamine (1 equiv.) in Eqs. (3) and (4),
similar results were also observed and the yield of 7 was
99% at 40°C for 20 h and the yields of 7 and 8 were
20% and 75% at 90°C for 77 h. This result indicates
that DABCO is superior to triethylamine under similar
conditions.
1
13
their H and C NMR.
On the basis of Eqs. (1) and (2), we then focussed our
studies on the reactions of 1 with more steric hindrance
substrates, 2,2-disubstituted-1-nitroalkenes, which were
little studied in the literatures and only the derivatives
of 2,2-dimethyl-3-nitrochromenes were mentioned in
7
these papers. When 1 reacted with compounds 6 and
8
9
, respectively, in the presence of DABCO under simi-
lar conditions, to our surprise, the isolated products
were not 3-nitrochromenes 8 and 11, but only high
yields of 3-nitro-4-hydroxyflavans 7 (96%) and 10 (98%)
were separated (Eqs. (3) and (5)). The trans structures
of the nitro alcohols 7 and 10 were also determined by
1
their H NMR spectrum; J =6.0 Hz for both 7 and
3,4
1
b
1
0. The generation of the different products 3 and 5
or 7 and 10 probably can be explained by the steric
When 1 reacted with 2,2-disubstituted-1-nitroalkenes,
8
9
12, 14, and 16, respectively, in the presence of
HO
H
NO2
NO2
DABCO
CHO
OH
o
4
0 C, 15 h
+
O
(3)
1
7 (96%)
6
H
NO2
NO2
CHO
OH
DABCO
+
o
9
0 C, 52 h
O
(4)
1
6
8 (74%)
H
NO2
HO
NO2
CHO
OH
DABCO
+
o
4
0 C, 7 h
O
(5)
1
9
10 (98%)
H
NO2
NO2
CHO
OH
DABCO
+
o
9
0 C, 71 h
O
(6)
1
9
11 (89%)

M.-C. Yan et al. / Tetrahedron Letters 42 (2001) 2717–2721
2719
9
DABCO under similar conditions, 49–99% of 2,2-
dialkyl-3-nitrochromenes, such as 13, 15, or 17, were
obtained (Eqs. (7)–(9)). It is believed that all the reac-
tions (Eqs. (7)–(9)) also proceed through the dehydra-
tion of the intermediates A–C to obtain
(3)–(9). For example, when 18–20, and 34–36 were
used, the results were complicated and the products
were 21–33 (Eqs. (10)–(11)).
To prove the equilibrium between allyl nitro com-
pounds 34–36 and nitroalkenes 18–20, 1-nitropropene
7 and 3-nitroprop-1-ene 39 were used to react with 1
3-nitrochromenes only at 40°C as described above.
3
Although this method is useful in the preparation of
some 2,2-dialkyl-3-nitrochromenes, not all 2,2-disubsti-
tuted-1-nitroalkenes generate the same results as Eqs.
under similar conditions and only the same product 38
was produced at room temperature (Eqs. (12) and (14)).
At 40°C, only 30% of 38 was obtained from the reac-
(7)
(
(
8)
9)
H
NO2
CHO
OH
DABCO
+
o
4
0 C
(
)n
1
n=1, 18
n=2, 19
n=3, 20
3h
36h
29h
OH
O
OH
O
(
)n
N
NO2
NO2
O
OH
+
+
+
O
(
)n
O
CH2NO2
(
)n
(
)n
(
)n
n=1, 21 (12%)
24 (24%)
two isomers observed
31 (4%)
26 (28%), 27 (23%)
(10)
n=2, 22 (14%)
n=3, 23 (trace)
25 (8%)
-
32 (22%)
33 (12%)
-
three isomers observed
28 (20%), 29 (20%), 30 (18%)

2
720
M.-C. Yan et al. / Tetrahedron Letters 42 (2001) 2717–2721
CH2NO2
CHO
OH
DABCO
+
o
4
0 C
(
)n
1
n=1, 34
n=2, 35
n=3, 36
1.5h
7.5h
108.5h
OH
O
(
)n
N
OH
O
NO2
NO2
O
OH
+
+
+
O
(
)n
O
(
)n
(
)n
CH2NO2
(
)n
n=1, 21 (6%)
n=2, 22 (8%)
n=3, 23 (trace)
24 (14%)
25 (trace)
-
26 (31%), 27 (27%)
31 (3%)
32 (14%)
33 (8%)
-
(
(
11)
28 (26%), 29 (22%), 30 (11%)
NO2
CHO
NO2
DABCO
r.t., 28 h
+
O
12)
OH
1
37
38 (56%)
NO2
CHO
NO2
DABCO
+
40°C, 20 min
O
OH
(13)
1
37
38 (30%)
NO2
CHO
NO2
DABCO
+
r.t., 19.5 h
O
OH
(14)
1
39
38 (24%)
tion of 1 and 37 for 20 min (Eq. (13)). The difference
between Eqs. (12) and (13) indicates that lowering the
reaction temperature can increase the yield of 38.
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in the synthesis of 3-nitro-2-phenyl-2H-chromenes but
also in the preparation of 2,2-dialkyl-3-nitrochromenes.
Our current work is focusing on the reaction mecha-
nism and the stereoselectivity and will be reported in
the future.
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