Novel heterocyclic troponoids: Synthesis of pyridoimidazotropolones and related compounds by the reaction of 5-nitrosotropolone with several azines

Article abstract of DOI:10.3987/COM-03-S(P)48

Novel heterocyclic troponoids, such as pyridoimidazotropolones (3-4, 5-11, 12-13, 14-15 and 16) were synthesized by the reaction of 5-nitrosotropolone (1) with azines as pyridine, m- and p-substituted pyridines, pyridazine, isoquinoline and phthalazine. S

Full text of DOI:10.3987/COM-03-S(P)48

HETEROCYCLES, Vol. 62, 2004, pp. 535 - 542
Received, 4th August, 2003, Accepted, 22nd September, 2003, Published online, 4th November, 2003
NOVEL HETEROCYCLIC TROPONOIDS: SYNTHESIS OF PYRIDO-
IMIDAZOTROPOLONES AND RELATED COMPOUNDS BY THE
REACTION OF 5-NITROSOTROPOLONE WITH SEVERAL AZINES
Ohki Sato,* Kouichiro Tsurumaki, Syunnichi Tamaru, and Josuke Tsunetsugu*
Department of Chemistry, Faculty of Science, Saitama University, Sakura-ku,
Saitama 338-8570, Japan
Abstract – Novel heterocyclic troponoids, such as pyridoimidazotropolones (3–4,
5–11, 12–13, 14–15 and 16) were synthesized by the reaction of 5-
nitrosotropolone (1) with azines as pyridine, m- and p-substituted pyridines,
pyridazine, isoquinoline and phthalazine. Similarly, thiazol afforded 17. The
reaction mechanism involves multi-step reactions; acetylation of 1, Michael
addition of azines to nitrosotropolone acetate (2), cyclization and deacetoxylation.
The scope and limitation of this method are also discussed.
Non-benzenoid heterocyclic compounds containing a seven-membered ring have been receiving
attentions for their biological activities, as well as physical and chemical properties. Among them
azaazulenes and related compounds are most extensively studied family.1,2 Natural products having 1,3-
diazaazulene moieties such as zoanthoxanthins (from Parazoanthus cfr. axinellae)3,4a and paragracines
(from Parazoanthus gracilis)3,4b were found. However, not so many synthetic methods of polycyclic
azines with a 1,3-diazaazulene moiety have been investigated.1,2
MeHN
Me
H
N
Me
N
N
N
NH
N
2
NMe
2
N
N
N
N
Me N
2
Me
N
1,3-diazaazulene
zoanthoxanthin
paragracine
Here we report a new approach for the synthesis of novel heterocycle-fused troponoids,
pyridoimidazotropolones, which could be classified into 1,3-diazaazulenes, by the reaction of 5-
nitrosotropolone (1) and/or its acetate (2) with several azines.
RESULTS and DISCUSSION
5-Nitrosotropolone (1)5,6 is known to exist as an equilibrium mixture between an enol-form (1) and its
diketone-one (1’), and reacted with various amines to give quinoxaline,6 aniline-adducts7 and oxazoles.8

To investigate the reaction in the presence of azines, 1 was treated with 1.5 molar equivalents of pyridine
in acetic anhydride at room temperature for 25 hours to give pyrido[1’,2’:1,2]imidazo[4,5-e]tropolone
(3) and its acetate (4) and nitrosotropolone acetate (2) in 30, 12 and 10 % yields respectively (Scheme 1).
When 2 was treated with 10 molar equivalents of pyridine at room temperature for 34 hours, 3 was
obtained in 35 % yield, which exemplified the former is the precursor of the latter in the reaction of 1
1
with pyridine in the presence of acetic anhydride. The HNMR spectrum of 3 showed two protons at
d 7.33 and 8.10 with a characteristic coupling constant (d, J = 12.2 Hz) as a seven-membered ring. This
J value indicates the double bond character of seven-membered ring, eliminating possible isomeric
structure (3’). Calculated heats of formation for 3 and 3’ by PM39 are 8.79 and 18.46 kcal/mol
respectively, supporting the stability of the former. 13CNMR spectrum showed seven tertiary carbons and
five quarternary carbons, of which d 178.6 and 156.0 were assigned to carbonyl and hydroxyl-attached
carbons respectively. IR absorption band of n 3235 cm–1 is assigned to a hydrogen bonded hydroxyl
group of tropolone moiety. The MS spectrum showed strong molecular ion (m/z 212, M+•) and M+•–CO
ion peaks. The longest wave-maximum of UV-VIS spectrum in H2O appeared at 426 nm, whereas in
acidic solution (0.5 M aq. HCl) did at 406 nm with the characteristic hypsochromic shift of tropolone
derivatives. Together with the result of elemental analysis, those spectral data supported the proposed
structure.
5
6
4
N
NOAc
NO
7
3
Pyridine / Ac O
2
+
N
O
O
2
O
rt, 25 h
10
1
RO
O
HO
3: R = H
4: R = Ac
1
2
N
N
NOH
RO
O
O
3': R = H
4': R = Ac
O
1'
Scheme 1
The results of the similar reactions with using several o-, m- and p-substituted pyridines are shown in
Table 1. 2-Methoxypyridine did not react by some sterical reason, which will be discussed later.
3-Methoxypyridine afforded single isomer (5a), while 3-methyl-, 3-phenyl- and 3-bromopyridines
afforded two inseparable isomeric pyridoimidazotropolones (6, 7 and 8) of a- and b-series, of which the
1
formers are obtained in dominant yields. Those structures were easily discriminated by their HNMR
spectral patterns. Sterically unfavorable a-series compounds became predominant, suggesting that the
reaction proceeded by way of a kinetically controlled pathway. 3-Cyanopyridine did not react because of
the paucity of nucleophilicity. In the case of 4-substituted pyridines (4-methoxy-, 4-methyl- and 4-
phenylpyridines), pyridoimidazotropolones (9, 10 and 11) were obtained in moderate yields respectively.
The plausible reaction mechanism is shown in Scheme 2. Acetylation of 5-nitrosotropolone (1) affords

acetate (2), to which Michael addition of pyridine occurs to form addition product (A), cyclization of
which affords a tricylic intermediate (B), and successive elimination of acetic acid gives
pyridoimidazolotropolone (3).
Table 1. Reaction of 2 with substituted pyridines
R
N
R
N
N
2
O
R
HO
N
N
N
5 - 11
5a: R = OMe
6a: R = Me
7a: R = Ph
8a: R = Br
N
N
N
O
O
O
Substituted pyridine
R (mol eq.)
Conditions
Yield (%)
HO
HO
HO
2-OMe (1.5)
3-OMe (1.5)
3-Me (10)
3-Ph (1.5)
3-Br (10)
CH Cl / rt / 113 h
No Reaction
5a (28)
2
2
6b: R = Me
7b: R = Ph
8b: R = Br
CH Cl / reflux / 7 d
2
2
neat / rt / 3 d
CH Cl / rt / 8 d
6a (29) 6b (7)
7a (19) 7b (7)
8a (4) 8b (1)
No reaction
9 (46)
R
2
2
neat / 70 °C / 27 h
CH Cl / rt / 76 h
3-CN (1.5)
4-OMe (1.5)
4-Me (10)
4-Ph (1.5)
2
2
CH Cl / reflux / 69 h
R
9: R = OMe
10: R = Me
11: R = Ph
2
2
neat / rt / 21 h
CH Cl / rt / 6 d
10 (27)
11 (47)
2
2
When trifluoroacetic anhydride was used instead of acetic anhydride in the reaction of 1 and pyridine,
the reaction completed in 4.5 hours at room temperature and the yield of 3 was 22 %. Although the
reaction rate is faster on the process from 2 to A because of strong electron withdrawing force of
fluorine atoms, on the process from A to B electron donation from nitrogen atom of trifluoroacetoxime
is weaker, resulting to give 3 in less yield, as a whole. In the case of 2-methoxypyridine steric hindrance
in the formation of A is considered to be unfavorable. Calculated heats of formation by PM3 are always
larger for predominant a-series compounds derived from 3-substituted-pyridines than that for b-series
(e.g., 8a vs. 8b: 19.94 vs. 17.75 kcal/mol), indicating that the direction of cyclizaion is not controlled
thermodynamically but kinetically.
H
AcO
NOAc
AcON
N
N
N
N
Ac O
2
H
- AcOH
3
1
O
OH
O
O
OH
O
2
B
A
Scheme 2
The reaction of 5-nitrosotropolone (1) with diazines such as pyrimidine and pyrazine in acetic anhydride

did not occur but with pyridazine afforded a new heterocycle (12) and its acetate (13) in good yields as a
whole (Table 2). The structure of 12 has been determined by X-Ray crystallography and the ORTEP
diagrams are presented in Figure 1. The molecule (12) is almost flat (intramolecular torsion angle of
C(5)-N(1)-C(8)-C(9): 178.5(2)°; N(1)-C(5)-C(6)-C(7): 178.1(2)°) and the tropolone ring moiety is not
delocalized (bond length of C(1)-O(1): 1.248(1)Å; C(2)-O(2): 1.348(1)Å). Pyrimidine and pyrazine gave
an unidentifiable complex mixture under refluxed conditions, while at room temperature the latter
afforded only nitrosotropolone acetate (2). The reaction with condensed azines such as isoquinoline and
phthalazine afforded single isomeric heterocycles (14, 15 and 16) in high yields respectively but
quinoline did not react because of steric hindrance on the reaction pathway. A mixture of 14 and 15 in
CH2Cl2-MeOH-H2O solution was boiled for 68 hours to afford deacetyl compound (14) in 86 % yield.
The reaction of 2 with thiazole gave a thiazole-condensed heterocycle (17).
Table 2. Reactions of 1 and 2 with diazines, condensed azines and thiazole
Azine and thiazole
(mol eq.)
Products and yield (%)
Substrate
Conditions
N
N
Pyridazine
(1.5)
Ac O / rt / 24 h
2
O
1
N
12: R = H (32)
13: R = Ac (54)
RO
Pyrimidine
(1.5)
Ac O / rt / 28 h
2
Ac O / reflux / 8 h
1
1
No reaction
Complex mixture
2
Ac O / rt / 27 h
2
2 (93)
Complex mixture
Pyrazine
(1.5)
Ac O / reflux / 13 h
2
N
N
Ac O / rt / 56 h
2
1
Isoquinoline
(1.5)
O
14: R = H (17)
15: R = Ac (66)
RO
Complex mixture
N
2
1
Quinoline
(10)
neat / rt / 55 h
N
N
Ac O / rt / 72 h
2
Phthalazine
(1.5)
O
16 (77)
HO
O
N
S
2
Thiazole
(10)
neat / 70 °C / 27 h
N
HO 17 (13)
Nucleophilicity is not parallel with pKa value, of course, but in such a case as this where the multi-step

equilibria are considered both factors could be correlated loosely. When the pKa value of azine is less
than 2 like pyrimidine (1.31), pyrazine (0.65), 3-cyanopyridine (1.50) the reaction did not occur. On the
other hand, when that is more than 2 (e.g., pKa: 5.23 for pyridine, 4.80 for 3-phenylpyridine, 6.62 for 4-
methoxypyridine, 2.33 for pyridazine, 2.50 for thiazole), the reaction occured.
C (9)
C (10)
N (1)
C (8)
C (11)
N (3)
C (5)
N (2)
C (6)
O (1)
C (7)
C (4)
C (3)
C (7)
C (1)
O (1)
C (6)
C (1)
N (1)
C (9)
C (2)
O (2)
side view
top view
Figure 1. ORTEP diagrams of 12
Although the reaction has not been optimized well yet, it appears that this method is governed by both
steric and nucleophilic factors of azines. The wider application and development of the reaction is now
under investigation.
EXPERIMENTAL
1
13
Mps were determined with a Mitamura air-bath apparatus and are uncorrected. H and CNMR spectra
were determined with Bruker AM-400, AC-300 and/or AC-200 spectrometers. IR spectra were
determined with a Perkin Elmer System 2000 FT instrument and electronic spectra (UV-VIS) with a
JASCO V-560 spectrophotometer. MS spectra were determined with JEOL JMS-DX 303 spectrometer.
Unless otherwise stated the spectra were taken in the following solvents/media: IR, KBr; UV-VIS,
1
13
CH2Cl2 and H2O; H and CNMR, DMSO-d6; MS spectra were taken by electron impact (EI) and fast
atom bombardment (FAB) methods. The progress of most reactions was monitored by TLC using Merck
Kieselgel 60F254.
Typical experimental procedure for the reaction of 5-nitrosotropolone (1) with azines in acetic
anhydride: A solution of 1 (517 mg, 3.42 mmol) and 1.5 molar equivalents of pyridine (406 mg, 5.13
mmol) in acetic anhydride (25 mL) was stirred at rt for 25 h. The insoluble nitrosotropolone acetate (2,
68 mg, 10 % yield) was removed by filtration and the filtrate was evaporated under reduced pressure.
The residue was purified by recrystallization from CH2Cl2 to give pyrido[1’,2’:1,2]imidazo[4,5-e]
tropolone (3, 216 mg, 30 % yield) and its acetate (4, 100 mg, 12 % yield). Compounds (3 and 4) could
not be purified by column chromatography because of their lability to silica gel and aluminum oxide.
Typical experimental procedure for the reaction of nitrosotropolone acetate (2) with azines: a) A
solution of 2 (500 mg, 2.59 mmol) and 1.5 molar equivalents of 4-methoxypyridine (426 mg, 3.90
mmol) in CH2Cl2 (19 mL) was refluxed for 69 h. The solvent was removed in vacuo and the residue was
purified by recrystallization from acetonitrileto give 9 (291 mg, 46 % yield). b) A mixture of 2 (501 mg,

2.59 mmol) and 10 molar equivalents of 3-methylpyridine (2.41 g, 25.9 mmol) was stirred at rt for 72 h.
The reactant was purified by recrystallization from CH2Cl2 to give 6a and 6b (211 mg, 29 % and 7 %
yields calcd by the 1HNMR spectrum) as an inseparable mixture.
Typical experimental procedure for the transformation to pyridoimidazotropolones from their
1
acetates: A mixture of 14 and 15 (256 mg, 14 : 15 = 1 : 3.9 by HNMR spectrum) in CH2Cl2 (40 mL),
MeOH (80 mL) and H2O (20 mL) was refluxed for 68 h. The solvent was removed in vacuo and the
residue was purified by recrystallization from benzene to give 14 (196 mg, 86 % yield). All synthetic
acetates (4, 13 and 15) are relatively unstable and a part of them were converted into deacetyl
compounds (3, 12 and 14) respectively during the period of recrystallization. The structure of those
acetates was finally established by the transformation.
Physical data of synthetic heterocycles (3–17): 3: yield 30 %; yellow fine needles; mp 230 °C (sub.);
1HNMR (300 MHz, DMSO-d6, d 2.50) dH 7.15 (1H, dd, J = 7.4, 6.2, H-2), 7.33 (1H, d, J = 12.2, H-7),
7.58 (1H, dd, J = 9.2, 7.4, H-3), 7.75 (1H, d, J = 9.2, H-4), 8.10 (1H, d, J = 12.2, H-6), 8.35 (1H, s, H-
13
10), 9.14 (1H, d, J = 6.2, H-1), 9.54 (1H, br s, OH); CNMR (50 MHz, DMSO-d6, d 39.7) dC 102.7,
113.1, 117.7, 126.5, 127.4, 129.5, 129.6, 134.0, 142.1, 146.5, 156.0, 178.6; IR (KBr, cm–1) nmax 3235,
1642, 1586, 1564, 1533, 1460, 1404, 1353, 1283, 1207; MS (EI (+), %) m/z 212 (M+•, 100), 184
(M+•–CO, 100); UV-VIS (CH2Cl2, nm, log e) lmax 253 (4.56), 262 (4.55), 288 (4.44), 299 (4.58), 312
(4.58), 371 (4.06), 394 (4.19), 410 (4.35), 434 (4.25); UV-VIS (H2O, nm, log e) lmax 243 (4.20), 261
(4.18), 300 (4.17), 311 (4.21), 407 (4.00), 426 (3.95); UV-VIS (0.5M aq. HCl, nm, log e) lmax 251 (4.41),
283 (4.04), 296 (4.05), 345 (3.76), 387 (4.05), 406 (4.02); Anal. Calcd for C12H8N2O2: C, 67.92; H, 3.80;
N, 13.20. Found: C, 67.82; H, 3.73; N, 13.18. 4: yield 12 %; brown powder; mp 216–219 °C (sub.);
1HNMR (300 MHz, DMSO-d6, d 2.50) dH 2.32 (3H, s, Ac), 7.20 (1H, d, J = 12.7, H-7), 7.26 (1H, dd, J =
7.4, 7.0, H-2), 7.66 (1H, dd, J = 8.7, 7.4, H-3), 7.84 (1H, d, J = 8.7, H-4), 8.00 (1H, d, J = 12.7, H-6),
8.69 (1H, s, H-10), 9.16 (1H, d, J = 7.0, H-1); IR (KBr, cm–1) nmax 1746, 1642, 1599, 1525, 1520, 1201,
1079, 927, 857, 765; MS (FAB (+), NBA, %) m/z 255 (MH+, 56). 5a: yield 28 %; yellow fine needles;
mp 232 °C (sub.); 1HNMR (300 MHz, DMSO-d6, d 2.50) dH 4.00 (3H, s), 6.95 (1H, d, J = 7.4), 7.06 (1H,
dd, J = 7.4, 6.2), 7.31 (1H, d, J = 12.3), 8.10 (1H, d, J = 12.3), 8.30 (1H, s), 8.73 (1H, d, J = 6.2); IR
(KBr, cm–1) nmax 3267, 1566, 1456, 1399, 1331, 1282, 1225, 830, 728; MS (EI (+), %) m/z 242 (M+•,
100), 214 (M+•–CO, 100); UV-VIS (CH2Cl2, nm, log e) lmax 244 (4.61), 264 (4.42), 306 (4.55), 317
(4.64), 402 (4.29), 421 (4.20); Anal. Calcd for C13H10N2O3: C, 64.46; H, 4.16; N, 11.56. Found: C, 64.42;
1
H, 4.09; N, 11.49. 6a and 6b: yields 29 and 7 % (calcd by the HNMR spectrum); brownish yellow
powder; 1HNMR (300 MHz, DMSO-d6, d 2.50) for 6a dH 2.57 (3H, s, Me), 7.06 (1H, dd, J = 7.0, 6.6, H-
2), 7.31 (1H, d, J = 12.2, H-7), 7.38 (1H, d, J = 7.0, H-3), 8.14 (1H, d, J = 12.2, H-6), 8.32 (1H, s, H-10),
1
8.99 (1H, d, J = 6.6, H-1), 9.54 (1H, br s, OH); HNMR (300 MHz, DMSO-d6, d 2.50) for 6b dH 2.38
(3H, s, Me), 7.30 (1H, d, J = 12.1, H-7), 7.45 (1H, d, J = 9.1, H-3), 7.66 (1H, d, J = 9.1, H-4), 8.07 (1H,
d, J = 12.1, H-6), 8.28 (1H, s, H-10), 8.99 (1H, s, H-1), 9.54 (1H, br s, OH); MS (EI (+), %) m/z 226
(M+•, 100), 198 (M+•–CO, 100); HRMS (EI(+)) Calcd for C13H10N2O2: 226.0742, Found: 226.0728. 7a
1
and 7b: yields 19 and 7 % (calcd by the HNMR spectrum); brownish yellow powder; HNMR (300
1
MHz, DMSO-d6, d 2.50) for 7a dH 7.26 (1H, t, J = 7.0), 7.31 (1H, d, J = 12.5), 7.55 (3H, m), 7.76 (1H, d,

J = 7.0), 8.10 (2H, d, J = 7.0), 8.15 (1H, d, J = 12.5), 8.38 (1H, s), 9.16 (1H, d, J = 7.0), 9.58 (1H, br s,
OH); 1HNMR (300 MHz, DMSO-d6, d 2.50) for 7b dH 7.34 (1H, d, J = 12.1), 7.47 (3H, m), 7.84 (1H, d,
J = 9.6), 7.92 (2H, d, J = 7.4), 7.97 (1H, d, J = 9.6), 8.08 (1H, d, J = 12.1), 8.62 (1H, s), 9.44 (1H, s),
9.58 (1H, br s, OH); MS (EI (+), %) m/z 288 (M+•, 100), 260 (M+•–CO, 100); HRMS (EI(+)) Calcd for
C18H12N2O2: 228.0899, Found: 228.0896. 8a and 8b: yields 4 and 1 % (calcd by the 1HNMR spectrum);
reddish brown powder; 1HNMR (300 MHz, DMSO-d6, d 2.50) for 8a dH 7.06 (1H, t, J = 7.4), 7.33 (1H,
1
d, J = 12.1), 7.92 (1H, d, J = 7.4), 8.16 (1H, d, J = 12.1), 8.30 (1H, s), 9.17 (1H, d, J = 7.4); HNMR
(300 MHz, DMSO-d6, d 2.50) for 8b dH 7.32 (1H, d, J = 12.2), 7.66–7.70 (2H, m), 8.09 (1H, d, J = 12.2),
8.38 (1H, s), 9.51 (1H, s); MS (EI (+), %) m/z 292 (M+•+2, 100), 290 (M+•, 100), 264 (M+•+2–CO, 80),
262 (M+•–CO, 79); HRMS (EI(+)) Calcd for C12H779BrN2O2: 289.9691, Found: 289.9680. 9: yield 46 %;
yellow fine needles; mp 238 °C (sub.); 1HNMR (300 MHz, DMSO-d6, d 2.50) dH 3.92 (3H, s), 6.87 (1H,
d, J = 7.7), 7.07 (1H, s), 7.30 (1H, d, J = 12.3), 8.02 (1H, d, J = 12.3), 8.31 (1H, s), 9.01 (1H, d, J = 7.7);
IR (KBr, cm–1) nmax 3226, 1652, 1538, 1463, 1404, 1218, 1018, 843; MS (EI (+), %) m/z 242 (M+•, 100),
214 (M+•–CO, 100); UV-VIS (CH2Cl2, nm, log e) lmax 257 (4.47), 298 (4.29), 310 (4.26), 411 (4.21), 433
(4.15); Anal. Calcd for C13H10N2O3: C, 64.46; H, 4.16; N, 11.56. Found: C, 64.25; H, 4.11; N, 11.42. 10:
yield 27 %; mp 230 °C (sub.); brownish yellow powder; 1HNMR (300 MHz, DMSO-d6, d 2.50) dH 2.44
(3H, s), 7.02 (1H, d, J = 7.0), 7.32 (1H, d, J = 12.1), 7.53 (1H, s), 8.07 (1H, d, J = 12.1), 8.32 (1H, s),
9.04 (1H, d, J = 7.0); IR (KBr, cm–1) nmax 3250, 1655, 1561, 1541, 1459, 1259, 1214, 805; MS (EI
(+), %) m/z 226 (M+•, 83), 198 (M+•–CO, 100); Anal. Calcd for C13H10N2O2: C, 69.02; H, 4.46; N, 12.38.
Found: C, 68.75; H, 4.35; N, 12.17. 11: yield 47 %; yellow fine needles; mp 248 °C (sub.); 1HNMR (300
MHz, DMSO-d6, d 2.50) dH 7.35 (1H, d, J = 12.1), 7.49 (1H, dd, J = 7.2, 1.1), 7.53–7.59 (3H, m), 7.95
(2H, d, J = 7.7), 8.07 (1H, d, J = 1.1), 8.11 (1H, d, J = 12.1), 8.40 (1H, s), 9.22 (1H, d, J = 7.2); IR (KBr,
cm–1) nmax 3224, 1588, 1568, 1538, 1460, 1400, 1356, 1269, 866, 842, 753; MS (EI (+), %) m/z 288 (M+•,
100), 260 (M+•–CO, 100); UV-VIS (CH2Cl2, nm, log e) lmax 282 (4.63), 304 (4.57), 316 (4.50), 425
(4.40), 449 (4.33); Anal. Calcd for C18H12N2O2: C, 74.99; H, 4.20; N, 9.72. Found: C, 74.79; H, 4.15; N,
1
9.57. 12: yield 32 %; orange plates; mp 207 °C (sub.); HNMR (300 MHz, DMSO-d6, d 2.50) dH 7.32
(1H, d, J = 12.1), 7.52 (1H, dd, J = 9.2, 6.4), 7.96 (1H, s), 8.12 (1H, d, J = 12.1), 8.30 (1H, dd, J = 9.2,
13
1.5), 8.77 (1H, dd, J = 6.4, 1.5), 9.85 (1H, br s, OH); CNMR (50 MHz, DMSO-d6, d 39.7) dC 101.0,
121.8, 126.7, 129.2, 130.2, 134.2, 140.3, 141.1, 145.0, 157.0, 179.4; IR (KBr, cm–1) nmax 3202, 1585,
1538, 1463, 1344, 1271, 1224, 1173, 880, 800; MS (EI (+), %) m/z 213 (M+•, 100), 185 (M+•–CO, 100);
UV-VIS (CH2Cl2, nm, log e) lmax 251 (4.84), 271 (4.72), 293 (4.69), 302 (4.63), 339 (4.16), 355 (4.20),
422 (4.50), 445 (4.34); Anal. Calcd for C11H7N3O2: C, 61.97; H, 3.31; N, 19.71. Found: C, 61.85; H,
3.23; N, 19.56; Crystal data: C11H7N3O2, monoclinic, space group C2/c, a = 13.3320(7), b = 7.3900(5), c
= 19.7090(10) Å, a = 90, b = 109.543(4), g = 90 °, V = 1829.9(2) Å3, Z = 8, r = 1.55 g cm–3, m (Mo-Ka)
= 0.711 cm–1, F (000) = 880, R = 0.048, WR2 = 0.125, GOF = 2.722. 13: yield 54 %; brownish yellow
powder; mp 185 °C (sub.); 1HNMR (300 MHz, DMSO-d6, d 2.50) dH 2.31 (3H, s), 7.22 (1H, d, J = 12.2),
7.61 (1H, dd, J = 9.2, 6.4), 8.04 (1H, d, J = 12.2), 8.34 (1H, s), 8.40 (1H, dd, J = 9.2, 1.5), 8.85 (1H, dd,
J = 6.4, 1.5); IR (KBr, cm–1) nmax 1762, 1608, 1549, 1332, 1205, 1194, 1077, 804; MS (FAB (+),
1
NBA, %) m/z 256 (MH+, 7.6). 14: yield 17 %; yellow powder; mp 258 °C (sub.); HNMR (300 MHz,

DMSO-d6, d 2.50) dH 7.33 (1H, d, J = 12.1), 7.48 (1H, d, J = 7.7), 7.74–7.82 (2H, m), 7.99 (1H, d, J =
8.1), 8.21 (1H, d, J = 12.1), 8.35 (1H, s), 8.62 (1H, d, J = 8.8), 8.91 (1H, d, J = 7.7); IR (KBr, cm–1) nmax
3236, 1640, 1586, 1532, 1463, 1398, 1257, 1210; MS (EI (+), %) m/z 262 (M+•, 100), 234 (M+•–CO,
100); UV-VIS (CH2Cl2, nm, log e) lmax 231 (4.17), 269 (4.63), 279 (4.69), 291 (4.60), 303 (4.69), 393
(4.47), 412 (4.46); Anal. Calcd for C16H10N2O2: C, 73.27; H, 3.84; N, 10.68. Found: C, 73.05; H, 3.80; N,
1
10.71. 15: yield 66 % brownish yellow powder; mp 235 °C (sub.); HNMR (300 MHz, DMSO-d6, d
2.50) dH 2.34 (3H, s), 7.20 (1H, d, J = 12.5), 7.58 (1H, d, J = 7.4), 7.77–7.85 (2H, m), 8.00 (1H, d, J =
8.0), 8.10 (1H, d, J = 12.5), 8.63 (1H, d, J = 8.5), 8.69 (1H, s), 8.90 (1H, d, J = 7.4); IR (KBr, cm–1) nmax
1755, 1652, 1557, 1538, 1520, 1455, 1212, 1092, 857; MS (FAB (+), NBA, %) m/z 305 (MH+, 13). 16:
yield 77 %; yellow powder; mp 250 °C (sub.); 1HNMR (300 MHz, DMSO-d6, d 2.50) dH 7.32 (1H, d, J
= 12.2), 7.97–8.09 (2H, m), 8.00 (1H, s), 8.19 (1H, d, J = 12.2), 8.26 (1H, d, J = 7.5), 8.59 (1H, d, J =
7.8), 9.23 (1H, s); IR (KBr, cm–1) nmax 3255, 1586, 1540, 1467, 1378, 1253, 888, 847; MS (EI (+), %)
m/z 263 (M+•, 100), 235 (M+•–CO, 100); UV-VIS (CH2Cl2, nm, log e) lmax 279 (4.81), 292 (4.76), 304
(4.69), 368 (4.42), 400 (4.47), 419 (4.38); Anal. Calcd for C15H9N3O2: C, 68.44; H, 3.45; N, 15.96.
Found: C, 68.29; H, 3.34; N, 15.87. 17: yield 13 %; reddish brown powder; mp 169 °C (sub.); 1HNMR
(300 MHz, DMSO-d6, d 2.50) dH 7.21 (1H, d, J = 12.1), 7.53 (1H, d, J = 4.6), 7.98 (1H, d, J = 12.1),
8.21 (1H, s), 8.55 (1H, d, J = 4.6); IR (KBr, cm–1) nmax 3167, 1683, 1557, 1538, 1455, 1257, 1204, 851,
672; MS (EI (+), %) m/z 218 (M+•, 100), 190 (M+•–CO, 100); Anal. Calcd for C10H6N2O2S: C, 55.04; H,
2.77; N, 12.84. Found: C, 54.82; H, 2.63; N, 12.65.
REFERENCES
1. N. Abe, Recent Res. Devel. Org. & Bioorg. Chem., 2001, 4, 17.
2. N. Abe, Trends in Heterocyclic Chemistry, 2001, 7, 25; N. Abe, K. Odagiri, M. Otani, E. Fujinaga, H.
Fujii, and A. Kakehi, J. Chem. Soc., Perkin Trans. 1, 1999, 1339; M. Cavazza and F. Pietra,
Tetrahedron, 1998, 54, 14059.
3. J. J. Fernandez, M. L. Souto, A. H. Daranas, and M. Norte, Current Topics in Phytochemistry, 2000, 4,
105; L. Cariello, S, Crescenzi, L. Zanetti, and G. Pronta, Comparative Biochem. & Physology, Part B:
Biochem. & Molecular Biolgy, 1979, 63B, 77.
4. a) L. Cariello, S. Crescenzi, G. Pronta, F. Giordano, and L. Mazzarella, Chem. Commun., 1973, 99; L.
Cariello, S, Crescenzi, G. Pronta, S. Capasso, F. Giordano, and L. Mazzarella, Tetrahedron, 1974, 30,
3281. b) Y. Komoda, S. Kaneko, M. Yamamoto, M. Ishikawa, A. Itai, and Y. Iitaka, Chem. Pharm.
Bull., 1975, 23, 2464; Y. Komoda, M. Shimizu, S. Kaneko, M. Yamamoto, and M. Ishikawa, ibid.,
1982, 30, 502.
5. T. Nozoe and S. Seto, Proc. Japan Acad., 1951, 27, 188.
6. T. Nozoe, M. Sato, and T. Matsuda, Sci. Rep. Tohoku. Univ., Ser. 1, 1954, 37, 497.
7. T. Aasao, S. Imajo, and T. Nozoe, Bull. Chem. Soc. Jpn., 1990, 63, 3089.
8. R. Mogi, O. Sato, and J. Tsunetsugu, unpublished results.
9. MOPAC Ver.6, J. J. Stewart, QCPE Bull., 1989, 9, 10.