Abnormal reactions of 2-methoxy-4,9-dimethyl-1-nitroacridine with selenous acid and selenium(IV) oxide. Synthesis of 1H-selenopheno[2,3,4-k,l]acridine-1- one: A new seleno-containing ring system

Article abstract of DOI:10.1002/jhet.512

Unusual course of the reaction was revealed on the oxidation of functionally substituted acridine containing the activated methyl groups by well-known oxidants, such as selenous acid and selenium(IV) oxide. Treatment of 2-methoxy-4,9-dimethyl-1-nitroacridine (5) with an excess of H ₂SeO₃ in boiling ethanol gave a mixture of the normal reaction products, 2-methoxy-4-methyl-1-nitro-9-formylacridine (11) (isolated yield 29%) and 2-methoxy-4-methyl-1-nitroacridine-9-carboxylic acid (12) (36%), together with an abnormal product, 3-methoxy-5-methyl-1H-selenopheno[2,3,4-k,l] acridine-1-one (13) (21%), which is the first example of a new seleno-containing ring system. With the use of SeO₂ the yield of selenolactone 13 was much lower.

Full text of DOI:10.1002/jhet.512

January 2011
Abnormal Reactions of 2-Methoxy-4,9-dimethyl-1-nitroacridine
with Selenous Acid and Selenium(IV) Oxide. Synthesis of
1H-Selenopheno[2,3,4-k,l]acridine-1-one: A New
Seleno-Containing Ring System
209
Oleg S. Radchenko,a* Elena N. Sigida,b Nadezhda N. Balaneva,a
Pavel S. Dmitrenok,a and Vyacheslav L. Novikova
aPacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of
Sciences, 159 Prosp. 100 let Vladivostoku, 690022, Vladivostok-22, Russian Federation
bDepartment of Chemistry, Far Eastern National University, 8 Sukhanova Str., 690050,
Vladivostok-50, Russian Federation
*E-mail: radchenko@piboc.dvo.ru
Received February 16, 2010
DOI 10.1002/jhet.512
Published online 2 September 2010 in Wiley Online Library (wileyonlinelibrary.com).
Unusual course of the reaction was revealed on the oxidation of functionally substituted acridine con-
taining the activated methyl groups by well-known oxidants, such as selenous acid and selenium(IV) ox-
ide. Treatment of 2-methoxy-4,9-dimethyl-1-nitroacridine (5) with an excess of H2SeO3 in boiling
ethanol gave a mixture of the normal reaction products, 2-methoxy-4-methyl-1-nitro-9-formylacridine
(11) (isolated yield 29%) and 2-methoxy-4-methyl-1-nitroacridine-9-carboxylic acid (12) (36%), to-
gether with an abnormal product, 3-methoxy-5-methyl-1H-selenopheno[2,3,4-k,l]acridine-1-one (13)
(21%), which is the first example of a new seleno-containing ring system. With the use of SeO2 the
yield of selenolactone 13 was much lower.
J. Heterocyclic Chem., 48, 209 (2011).
INTRODUCTION
In this communication, we wish to report the results
on using the selenium species for the oxidation of
the activated methyl groups of 4,9-dimethyl-substituted
acridine 5.
Recently, we reported a simple and effective approach
to the synthesis of pyrido[4,3,2-m,n]pyrrolo[3,2,1-
d,e]acridine skeleton of arnoamines A and B, cytotoxic
marine alkaloids from the ascidian Cystodytes sp. [1]. In
the course of developing our researches in this area we
embarked on a study of a fresh approach to the total
synthesis of arnoamines A (1) and B (2) based on the
use of acridine 5 as the key intermediate (Scheme 1).
As part of an exploration program of this synthesis it
was necessary to oxidize the activated methyl groups at
the positions 4 and 9 of acridine 5 into the formyl groups.
One solution of this problem was proposed by apply-
ing the traditional oxidants, such as selenium(IV) oxide
and selenous acid. These reagents have been success-
fully applied for various oxidations useful in practical
organic syntheses [2], including the oxidation of the
activated methyl groups of aromatic compounds to the
formyl groups [3].
RESULTS AND DISCUSSION
The synthesis of acridine 5 was carried out according
to Scheme 2 starting with commercially available 4-
bromo-3-methylanisole (6) to give the desired compound
within three steps and an overall yield of 48%.
In the first stage of this sequence, there was a need to
introduce the nitro group at the position 6 of anisole 6.
The nitration proceeded regioselectively and in good
yield only under the action of 98% HNO3 at the reduced
temperature. Under these conditions the desired product
7 was obtained in 68% yield along with a slight
amount (7%) of mononitro and trinitro derivatives 8 and
9, respectively. The formation of the latter was
C
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O. S. Radchenko, E. N. Sigida, N. N. Balaneva, P. S. Dmitrenok, and V. L. Novikov
Vol 48
Scheme 1
EtOH, methyl cellosolve, diglyme, and triglyme under
reflux conditions (66–215ꢀC). The reaction time varied
between 1 and 8 h.
Unfortunately, we failed to oxidize both of the methyl
groups of acridine 5 to the formyl groups on treatment
of substrate with H2SeO3 under experimental conditions
studied. In all cases, the formation of only a mixture of
aldehyde 11 and acid 12 was observed (Scheme 3). On
heating at high temperatures (180–215ꢀC), substrate 5
was subjected to considerable decomposition but even
under such rigid conditions the methyl group at the posi-
tion 4 was not active toward oxidizing agent.
Contrary to the usual results of such reactions we found
that the oxidation of acridine 5 with an excess of H2SeO3
in various solvents under reflux conditions leads also to a
formation of selenolactone 13, previously unknown
seleno-containing heterocyclic system, in poor yield
(Scheme 3). The most yields of this product were obtained
by the use of EtOH or diglyme, probably, owing to the
greatest solubility of H2SeO3 in these mediums. In
diglyme, the oxidation occurred faster than in ethanol (30
min and 3 h, respectively). In this case, the yields of the
products 11–13 were 12, 59, and 18%, respectively.
When using SeO2 in place of H2SeO3, the formation
of selenolactone 13 was also observed but in these cases
acridine 5 was slow to react with oxidant and the yields
of the products 11–13 were much less then are obtain-
able by the use of H2SeO3.
accompanied by cleaving the OACH3 bond and replac-
ing bromine by the nitro group. The mixture of these
products was separated by flash column chromatography
on SiO2. A copper-catalyzed coupling reaction of bro-
mide 7 with commercially available 20-aminoacetophe-
none afforded secondary amine 10 in 87% yield. The
electrophilic cyclization of amine 10 proceeded readily
under the action of a mixture of HOAc/H2SO4 (3:1, v/v)
at 85ꢀC to give the target acridine 5 in 81% yield.
The oxidation of acridine 5 with an excess of H2SeO3
was investigated in various solvents such as THF,
Scheme 2
Journal of Heterocyclic Chemistry
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January 2011
Abnormal Reactions of 2-Methoxy-4,9-dimethyl-1-nitroacridine with Selenous Acid
and Selenium(IV) Oxide. Synthesis of 1H-Selenopheno[2,3,4-k,l]acridine-1-one
211
Scheme 3
The structure of 13 was confirmed by IR, mass- and
1H and 13C NMR measurements. The molecular formula
of selenolactone 13 was deduced as C16H11NO2Se by
HRMS.
An intramolecular mechanism of nucleophilic substi-
tution of the nitro group can be represented by Scheme
5. If seleninic acid B (see Scheme 4) underwent a Pum-
merer rearrangement to selenenic acid J, the selenium
of this intermediate could act as an intramolecular
nucleophile to displace the nitro group.
Distribution of isotopes at the molecular ion peak of
13 calculated by ‘‘Isoform’’ program for formula
C16H11NO2Se was coincident with the experimental molec-
ular ion pattern, which demonstrates nine peaks with signs
of m/z equal 332 (rel. int., 3%), 331 (19), 330 (18), 329
(100), 328 (9), 327 (49), 326 (18), 325 (18), and 323 (2).
A similar ipso-replacement of NO2 group by the
amino group of hydrazone was noted in the syntheses of
1H-benzo[d,e]cinnolines (1H-1,2-diazaphenalenes) when
8-formyl-, 8-acetyl- and 8-benzoyl-1-nitronaphthalenes
were heated with hydrazine in boiling ethylene glycol or
ethanol [6].
1
Assigning resonances of H and 13C at the NMR spec-
tra of 13 was made on the basis of the results of DEPT-
135, DEPT-90, HSQC, and HMBC experiments (Fig. 1).
The formation of selenolactone 13 on the reaction of
acridine 5 with H2SeO3 or with SeO2 had come as a
surprise to us. Although these reagents are widely used
in organic chemistry as oxidants over more then 100
years, the data relative to obtaining the products of this
type are lacking.
The aforesaid raises the question about the possibility
of a Pummerer rearrangement under the reaction condi-
tions. This question presents a difficult theoretical prob-
lem. As far as we know, there is no information on such
rearrangements of a-CH2-containing selenoxides to ana-
logs of a-hydroxy sulfides as it is in the case of the clas-
sical Pummerer rearrangement of a-CH2-containing
sulfoxides.
Based on the structure of selenolactone 13, it may be
concluded that the conversion of acridine 5 to this prod-
uct involves several fundamental stages, such as the oxi-
dation of C(9)ACH3 group of substrate that must be
accompanied by the formation of a low valent selenium,
subsequent nucleophilic substitution of the nitro group
by this selenium species and lactonization. An important
key point might be whether there is an inter- or intramo-
lecular nucleophilic substitution.
To decide between an inter- or intramolecular mecha-
nism of nucleophlic substitution of NO2 group in acri-
dine 5 there is a need to make many additional
investigations.
Selenolactone 13 showed considerable antimicrobial
activity against Gram-positive bacteria Staphylococcus
aureus and Bacillus subtilis and pathogenic fungus Can-
dida albicans but it was inactive against Gram-negative
bacteria Escherichia coli and Pseudomonas aeruginosa.
The proposed intermolecular mechanism can be repre-
sented by Scheme 4.
It is conceivable that the interaction of more active
aminomethide form A of acridine 5 with the molecule
of oxidant followed by the rearrangement of seleninic
acid B to the intermediate C are the initial stages of this
process. In a similar manner, H2SeO3 oxidizes alkenes
to allylic alcohols [4,5]. If the intermediate C is turned
to aldehyde 11 via a loss of HSeOH, the reduced sele-
nium species generated by this pathway could further
act as a nucleophile. Its attack on the most electrophilic
center C(1) of aldehyde 11 could produce the r-com-
plex D, which by a loss of HNO2 would do the interme-
diate E. A loss of H2O from the latter must complete
the formation of the target compound 13.
Figure 1. The basic HMBC correlations of 1H!13C at the NMR spec-
trum of selenolactone 13.
Journal of Heterocyclic Chemistry
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O. S. Radchenko, E. N. Sigida, N. N. Balaneva, P. S. Dmitrenok, and V. L. Novikov
Vol 48
Scheme 4
EXPERIMENTAL
cmꢂ1 1H NMR (CDCl3): d 2.46 (s, 3H, CH3), 3.94 (s, 3H,
;
OCH3), 6.96 (s, 1H, 3-H), 8.07 (s, 1H, 6-H); EIMS (15 eV):
m/z (%) 248 (Mþ þ 1, 10), 247 (Mþ, 98), 246 (Mþ þ 1, 10),
Melting points were determined on a Boetius hot-stage ap-
paratus and are not corrected. 1H and 13C NMR spectra were
recorded on a Bruker AVANCE DPX 300 instrument (300
MHz for 1H, 75 MHz for 13C). The reported chemical shifts
were against TMS. Mass spectra were determined using a
AMD 604S spectrometer. IR spectra were obtained on a
Bruker Vector 22 spectrophotometer. Microanalyses were per-
formed on a Flash EA 1112 apparatus.
Scheme 5
4-Bromo-3-methylanisole (6), 20-aminoacetophenone and
copper powder were purchased from Lancaster.
Synthesis of 4-bromo-5-methyl-2-nitroanisole (7), 4-
bromo-3-methyl-2-nitroanisole (8), and 3-methyl-2,4,6-trini-
trophenol (9). To a stirred and cooled (0ꢀC) solution of 4-
bromo-3-methylanisole (6) (10.05 g, 50 mmol) in freshly dis-
tilled acetic anhydride (15 mL), 98% nitric acid (3.38 g, 55
mmol) was added dropwise for 30 min, and the reaction mix-
ture was stirred at that temperature for an additional 30 min.
The yellow precipitate of the product 7 (7.9 g) was filtered and
washed with cooled methanol (2 mL). Evaporation of filtrate
in vacuo gave the yellow solid, which was purified by flash-
chromatography on a silica gel column (2.5 ꢁ 80 cm), pre-
packed in hexane. Elution of the column with hexane:acetone
(20:1, v/v) gave an additional amount of the product 7 (0.63
g). The combined product was recrystallized from benzene to
give 8.36 g (68%) of pure 4-bromo-5-methyl-2-nitroanisole (7)
as a slight yellow needles, m.p. 111–113ꢀC; IR (CHCl3): 1039,
1106, 1174, 1192, 1210, 1220, 1257, 1285, 1347, 1372, 1444,
1463, 1483, 1524, 1575, 1606, 2835, 2944, 2976, 3041, 3083
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

January 2011
Abnormal Reactions of 2-Methoxy-4,9-dimethyl-1-nitroacridine with Selenous Acid
and Selenium(IV) Oxide. Synthesis of 1H-Selenopheno[2,3,4-k,l]acridine-1-one
213
245 (Mþ, 98), 216 (32), 214 (32), 200 (100), 198 (100), 186
(45), 184 (45), 77 (72). Anal. Calcd. for C8H8BrNO3: C,
39.05; H, 3.28; N, 5.69. Found: C, 39.13; H, 3.24; N, 5.82.
Elution of the column with hexane: acetone (8:1, v/v) gave
0.56 g (4%) of the product 8 as a slight yellow needles (ben-
zene), m.p. 97–99ꢀC (lit. [7] 98–100ꢀC); IR (CHCl3): 1037,
1111, 1169, 1196, 1213, 1231, 1249, 1291, 1349, 1370, 1446,
(7:1, v/v) gave 1.452 g (81%) of 2-methoxy-4,9-dimethyl-1-
nitroacridine 5 as a light yellow needless (ethanol), m.p. 179–
180ꢀC; IR (CHCl3): 1009, 1026, 1078, 1131, 1166, 1180,
1204, 1236, 1258, 1288, 1338, 1372, 1400, 1419, 1466, 1528,
1615, 1629, 2857, 2946, 2983, 3027, 3094, 3116 cmꢂ1 1H
;
NMR (CDCl3): d 2.79 (s, 3H, C(9)ACH3), 2.89 (d, 3H,
C(4)ACH3, J ¼ 1.2 Hz), 4.07 (s, 3H, OCH3), 7.68 (dd, 1H, 6-
H, J1 ¼ 7.5 Hz, J2 ¼ 8.0 Hz), 7.83 (dd, 1H, 7-H, J1 ¼ 7.5 Hz,
J2 ¼ 7.8 Hz), 7.93 (q, 1H, 3-H, J ¼ 1.2 Hz), 8.12 (d, 1H, 5-H,
J ¼ 7.8 Hz), 8.34 (d, 1H, 8-H, J ¼ 8.0 Hz); 13C NMR
(CDCl3): d 13.4 (q, C(9)ACH3), 19.0 (q, C(4)ACH3), 57.5 (q,
OCH3), 117.3 (d, 3-C), 117.8 (s, 9a-C), 124.1 (d, 8-C), 126.3
(s, 8a-C), 127.2 (d, 7-C), 129.9 (d, 6-C), 130.0 (d, 5-C), 131.8
(s, 4a-C), 137.6 (s, 9-C), 141.9 (s, 2-C), 143.3 (s, 4-C), 145.7
(s, 10a-C), 149.1 (s, 1-C); EIMS (15 eV): m/z (%) 284
(Mþþ2, 4), 283 (Mþ þ 1, 17), 282 (Mþ, 100), 267 [(Mþ þ 2)
- 17, 6], 266 [(Mþ þ 1) – 17, 18], 265 (Mþ - 17, 96), 252
(Mþ - 30, 11), 250 (Mþ - 32, 11), 237 (Mþ - 45, 21), 236
(Mþ - 46, 22), 235 [(Mþ - 17) - 30, 25], 209 (37), 208 (25),
207 (28), 206 (35), 205 (18), 204 (33), 195 (13), 192 (42), 191
(28), 180 (29), 178 (16), 167 (18), 165 (17), 152 (10), 120
(10), 83 (9), 77 (10), 61 (11), 44 (35), 32 (16). Anal. Calcd.
for C16H14N2O3: C, 68.06; H, 5.00; N, 9.93. Found: C, 68.19;
H, 5.04; N, 10.06.
Synthesis of 3-methoxy-5-methyl-1H-selenopheno[2,3,4-
k,l]acridine-1-one (13), 2-methoxy-4-methyl-1-nitro-9-for-
mylacridine (11) and 2-methoxy-4-methyl-1-nitroacridine-9-
carboxylic acid (12). A solution of acridine 5 (80 mg, 0.28
mmol) and selenous acid (400 mg, 3.12 mmol) in 8 mL of
ethanol was stirred at reflux for 3 h. The solvent was evapo-
rated in vacuo and the resulting residue was purified on a
silica sheet (Merck, 20 cm ꢁ 20 cm ꢁ 0.2 mm), using hexa-
ne:acetone (3:1, v/v).
1465, 1481, 1520, 1575, 1608 cmꢂ1 1H NMR (CDCl3): d
;
2.37 (s, 3H, CH3), 3.87 (s, 3H, OCH3), 6.78 (d, 1H, 5-H, J ¼
8.9 Hz), 7. 58 (d, 1H, 4-H, J ¼ 8.9 Hz); EIMS (15 eV): m/z
(%) 248 (Mþ þ 1, 12), 247 (Mþ, 100), 246 (Mþ þ 1, 12),
245 (Mþ, 100).
Elution of the column with hexane:acetone (3:1, v/v) gave
0.35 g (3%) of the product 9 as a slight yellow needles (ben-
zene), m.p. 105–106ꢀC (lit. [8] 106–108ꢀC); IR (CHCl3):
1066, 1172, 1228, 1277, 1341, 1382, 1459, 1548, 1594, 1636,
;
3109, 3207 (OH) cmꢂ1 1H NMR (CDCl3): d 2.64 (s, 3H,
CH3), 8.99 (s, 1H, 5-H), 11.14 (br. s, 1H, OH); EIMS (15 eV):
m/z (%) 243 (Mþ, 5), 242 (Mþ-1, 100), 225 (8), 224 (8), 212
(3), 196 (3), 195 (5).
1-[2-(4-Methoxy-2-methyl-5-nitrophenylamino)phenyl]e-
thanone (10). A mixture of bromide 7 (3.16 g, 12.4 mmol),
20-aminoacetophenone (1.674 g, 12.4 mmol), copper powder
(0.794 g, 12.4 g. atom), anhydrous potassium carbonate (2.422
g, 24.8 mmol), and nitrobenzene (25 mL) was stirred at 165ꢀC
for 10 h. A solid inorganic residue was separated by filtration,
filtrate was diluted by water (150 mL) and nitrobenzene was
removed by steam distillation. The product 10 was isolated
from residue by extraction with ethyl acetate (3 ꢁ 15 mL).
The organic layer was dried (Na2SO4), filtered and evaporated
to dryness. Purification of the residue by column chromatogra-
phy on a silica gel (2.5 ꢁ 80 cm) using hexane:acetone
(30:1!7:1, v/v) as eluent gave 2.74 g (87%) diphenylamine
10 as an orange powder (ethanol), m.p. 146–147ꢀC; IR
(CHCl3): 1070, 1165, 1197, 1210, 1221, 1247, 1284, 1346,
1399, 1419, 1454, 1524, 1572, 1603, 1639 (C¼¼O), 3008,
Isolation of the upper orange-red zone (Rf 0.77) gave 19 mg
(21%) of selenolactone 13. This compound was obtained as red
prisms (ethanol), m.p. 215–216ꢀC; IR (CHCl3): 1030, 1070,
1123, 1157, 1176, 1214, 1239, 1262, 1298, 1334, 1350, 1379,
1391, 1470, 1520, 1552, 1608 (C¼¼C), 1622 (C¼¼C), 1681
3018, 3034, 3256 (NH) cmꢂ1 1H NMR (CDCl3): d 2.34 (s,
;
3H, CH3), 2.67 (s, 3H, COCH3), 3.98 (s, 3H, OCH3), 6.76
(dd,1H, 50-H, J1 ¼ 7.3 Hz, J2 ¼ 8.4 Hz), 6.79 (d, 1H, 30-H, J
¼ 8.4 Hz), 6.99 (s, 1H, 300-H), 7.32 (dd, 1H, 40-H, J1 ¼ 7.3
Hz, J2 ¼ 8.0 Hz), 7.84 (d, 1H, 60-H, J ¼ 8.0 Hz), 7.89 (s, 1H,
600-H), 10.32 (s, 1H, NH); 13C NMR (CDCl3): d 18.7, 28.0,
56.7, 113.5, 115.8, 116.7, 118.7, 122.4, 131.4, 132.6, 135.0,
137.4, 141.8, 148.3, 150.3, 201.5; EIMS (15 eV): m/z (%) 300
(Mþ, 100), 285 (5), 270 (5), 252 (7), 239 (8), 225 (20), 208
(28), 196 (16), 180 (22), 167 (20), 159 (13), 149 (8), 120 (37),
83 (25), 77 (14), 57 (6), 44 (39), 32 (53). Anal. Calcd. for
C16H16N2O4: C, 63.99; H, 5.37; N, 9.33. Found: C, 64.11; H,
5.40; N, 9.50.
2-Methoxy-4,9-dimethyl-1-nitroacridine (5). A solution of
diphenylamine 10 (1.931g, 6.44 mmol) in a mixture of acetic
and sulfuric acids (20 mL, 3:1, v/v) was heated at 80–85ꢀC for
30 min. After cooling to room temperature, to a vigorously
stirred mixture a saturated solution of sodium bicarbonate (300
mL) was added dropwise. The product 5 was isolated by
extraction with ethyl acetate (3 ꢁ 10 mL). The organic layer
was washed with a saturated solution of NaCl (8 mL), dried
over anhydrous Na2SO4, and concentrated under reduced pres-
sure to give the residue, which was purified by column chro-
matography on a silica gel (2 ꢁ 60 cm) treated with a small
amount of NH4OH. Elution of the column with hexane:acetone
(C¼¼O), 2852, 2929 cmꢂ1
;
1H NMR (CDCl3): d 2.99 (d, 3H,
C(5)ACH3, J ¼ 1.1 Hz), 4.13 (s, 3H, OCH3), 7.50 (d, 1H, 4-H, J
¼ 1.1 Hz), 7.82 (m, 2H, 8-H, 9-H), 8.42 (d, 1H, 7-H, J ¼ 8.1 Hz),
9.18 (d, 1H, 10-H, J ¼ 8.1 Hz); 13C NMR (CDCl3): d 17.7 (q,
C(5)ACH3), 56.8 (q, OCH3), 110.6 (s, 2a-C), 120.4 (d, 4-C),
123.6 (s, 10a-C), 123.8 (d, 10-C), 129.1 (d, 8-C), 130.5 (d, 7-C),
130.6 (d, 9-C), 131.3 (s, 5-C), 133.5 (s, 11-C), 139.7 (s, 11a-C),
145.6 (s, 5a-C), 148.5 (s, 6a-C), 155.1 (s, 3-C), 197.8 (s, 1-C);
EIMS (15 eV): m/z (%) 332 (Mþ, 4), 331 (Mþ, 20), 330 (Mþ, 18),
329 (Mþ, 100), 328 (Mþ, 9), 327 (Mþ, 50), 326 (Mþ, 19), 325
(Mþ, 19), 323 (Mþ, 3), 314 (23), 312 (13), 288 (9), 286 (48), 284
(21), 270 (6), 258 (39), 256 (20), 190 (6), 178 (30), 177 (19), 166
(7), 151 (23), 139 (19); HREIMS. Calcd for C16H11NO2Se:
328.99547. Observed: 328.99572. Anal. Calcd. for
C16H11NO2Se: C, 58.55; H, 3.38; N, 4.27. Found: C, 58.69; H,
3.41; N, 4.38.
Isolation of the middle zone (Rf 0.36) gave 24 mg (29%) of
aldehyde 11. This compound was obtained as yellow needless
(ethanol), m.p. 193–195ꢀC; IR (CHCl3): 1079, 1131, 1297,
1337, 1359, 1374, 1401, 1471, 1529, 1537, 1557, 1602
(C¼¼C), 1614 (C¼¼C), 1630 (C¼¼C), 1679, 1703(C¼¼O), 2857,
2929, 2935, 2958 cmꢂ1 1H NMR (CDCl3): d 3.02 (d, 3H,
;
C(4)ACH3, J ¼ 1.3 Hz), 4.13 (s, 3H, OCH3), 7.59 (q, 1H, 3-
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Vol 48
REFERENCES AND NOTES
H, J ¼ 1.3 Hz), 7.69 (ddd, 1H, 6-H, J1 ¼ 7.0 Hz, J2 ¼ 6.8
Hz, J3 ¼ 1.2 Hz), 7.82 (ddd, 1H, 7-H, J1 ¼ 7.2 Hz, J2 ¼ 6.8
Hz, J3 ¼ 1.2 Hz), 8.29 (dd, 1H, 5-H, J1 ¼ 7.0 Hz, J2 ¼ 1.2
Hz), 8.31 (dd, 1H, 8-H, J1 ¼ 7.2 Hz, J2 ¼ 1.2 Hz), 10.99 (s,
1H, CHO); EIMS (15 eV): m/z (%) 296 (Mþ, 82), 279 (30),
267 (26), 252 (22), 251 (97), 250 (95), 238 (50), 236 (53), 235
(48), 222 (35), 207 (63), 195 (60), 179 (100), 167 (31), 152
(41), 140 (17). Anal. Calcd. for C16H12N2O4: C, 64.86; H,
4.08; N, 9.45. Found: C, 64.91; H, 4.03; N, 9.31.
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Chem 2008, 7, 281; (c) Gebhardt, C.; Priewisch, B.; Irran, E.; Rueck--
Braun, K. Synthesis 2008, 1889; (d) Ramoutar, R. R.; Brumaghim, J.
L. J Inorg Biochem 2007, 101, 1028; (e) Goodman, M. A.; Detty, M.
R. Synlett 2006, 1100; (f) Mlochowski, J.; Brzaszcz, M.; Giurg, M.;
Palus, J.; Wojtowicz, H. Eur J Org Chem 2003, 4329; (g) Drabowicz,
J.; Mikolajczyk, M. Top Curr Chem 2000, 208, 143; (h) No, Z.; Chae,
Y. B.; Shin, C. J.; Chung, Y. Tetrahedron Lett 1998, 39, 6191; (i)
Ernet, T.; Haufe, G. Synthesis 1997, 953; (j) Pansare, S. V.; Malusare,
M. G. Synlett 1997, 671; (k) Haroutounian, S. A. Synthesis 1995, 39;
(l) Shibuya, K. Synth Commun 1994, 24, 2923.
Isolation of the under zone (Rf 0.32) gave 32 mg (36%) of
acid 12. This compound was obtained as light yellow powder
(ethanol), m.p. 219–222ꢀC; IR (CHCl3): 1059, 1109, 1137,
1289, 1334, 1356, 1379, 1442, 1464, 1523, 1554, 1603
(C¼¼C), 1612 (C¼¼C), 1622 (C¼¼C), 1682, 1714 (C¼¼O), 1729
(C¼¼O), 2250–3400 (OH), 2857, 2902, 2930, 3013 cmꢂ1
;
1H
NMR (CDCl3): d 3.03 (d, 3H, C(4)-CH3, J ¼ 1.2 Hz), 4.15 (s,
3H, OCH3), 7.64 (q, 1H, 3-H, J ¼ 1.2 Hz), 7.85 (ddd, 1H, 6-
H, J1 ¼ 8.0 Hz, J2 ¼ 7.5 Hz, J3 ¼ 1.2 Hz), 7.88 (ddd, 1H, 7-
H, J1 ¼ 8.3 Hz, J2 ¼ 7.5 Hz, J3 ¼ 1.2 Hz), 8.32 (dd, 1H, 5-H,
J1 ¼ 8.0 Hz, J2 ¼ 1.2 Hz), 8.41 (dd, 1H, 8-H, J1 ¼ 8.3 Hz, J2
¼ 1.2 Hz); EIMS (15 eV): m/z (%) 312 (Mþ, 31), 295 (100),
294 (18), 268 (30), 267 (69), 266 (51), 251 (56), 238 (57), 208
(32), 206 (34), 205 (29), 194 (62), 167 (58). Anal. Calcd. for
C16H12N2O5: C, 61.54; H, 3.87; N, 8.97. Found: C, 61.87; H,
3.95; N, 9.11.
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Acknowledgments. This work was supported by the Grant No.
RUXO-003-VL-06 from the U.S. Civilian Research and Devel-
opment Foundation for the Independent States of the Former
Soviet Union (CRDF) and the Russian Ministry of Education and
Sciences and by a Grant from the Program of Presidium of the
Russian Academy of Sciences ‘‘Molecular and Cell Biology.’’
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet