Reactions of 8-(Triphenylphosphoimino)quinoline with aryl aldehydes and aryl isocyanates: Formation of 2-aryl-4H-imidazo[4,5,1-ij]quinolines and related systems1073 1474V

Article abstract of DOI:10.3987/com-06-s(o)6

The reaction of 8-(triphenylphosphoimino)quinoline with aryl aldehydes gave 2-aryl-4H-imidazo[4,5,1-ij]quinolines. In the reaction, tandem aza-Wittig reaction and cyclization attended with hydride shift occurred. The reaction of 8-(triphenylphosphoimino)q

Full text of DOI:10.3987/com-06-s(o)6

HETEROCYCLES, Vol. 69, 2006
167
HETEROCYCLES, Vol. 69, 2006, pp. 167 - 178. © The Japan Institute of Heterocyclic Chemistry
Received, 27th March, 2006, Accepted,11th May, 2006, Published online, 12th May, 2006. COM-06-S(O)6
REACTIONS OF 8-(TRIPHENYLPHOSPHOIMINO)QUINOLINE WITH
ARYL ALDEHYDES AND ARYL ISOCYANATES: FORMATION OF 2-
ARYL-4H-IMIDAZO[4,5,1-ij]QUINOLINES AND RELATED SYSTEMS†
Kentaro Nagamatsu, Erina Akiyoshi, Hidenori Ito, Hiroyuki Fujii,#
Akikazu Kakehi,§and Noritaka Abe*
Department of Chemistry, Faculty of Science, Yamaguchi University, Yoshida,
Yamaguchi 753-8512, Japan
#Science Research Center, Yamaguchi University, Yamaguchi 753-8512, Japan
§Department of Chemistry and Material Engineering, Faculty of Engineering,
Shinshu University, Wakasato, Nagano 380-8553, Japan
Abstract – The reaction of 8-(triphenylphosphoimino)quinoline with aryl
aldehydes gave 2-aryl-4H-imidazo[4,5,1-ij]quinolines.
In the reaction,
tandem aza-Wittig reaction and cyclization attended with hydride shift
occurred. The reaction of 8-(triphenylphosphoimino)quinoline with aryl
isocyanates gave 1,3-diaryl-1,2,3,9a-tetrahydro[1,3,5]triazolo[2’,3’:2,1;3’,4’-
a]imidazo[4,5,1-ij]quinolin-2-ones (11) and 2-(arylamino)imidazo[4,5,1-
ij]quinolin-4(4H)-ones (12). The structures of 11a (Ar = Ph) and 12a (Ar =
Ph) were confirmed by X-Ray structure analyses.
INTRODUCTION
4,5-Dihydro-6H-imidazo[4,5,1-ij]quinolin-6-one system, such as 1 and 2, is known to have physiological
activities such as inhibition of poly(ADP-ribosyl)transferase, inhibition of IgE antibody production, and
amelioration of the effects of stroke, head trauma, and neurodegenerative disease.1-4 It is thought that
4H-imidazo[4,5,1-ij]quinoline system (3) would have potentially physiological activities and be a good
precursor of 4,5-dihydro-6H-imidazo[4,5,1-ij]quinolin-6-one system. We previously reported the
synthesis
of
2-phenyl-2a,3-dihydro-1,2a-diazacyclopent[cd]azulene
(2-phenyl-4H-
cyclohepta[1’2’:3,2;2’,3’-d]pyrrolo[1,2-c]imidazole) system (4), which is a isomeric system of 3, by the
† Dedicated to Dr. Satoshi Omura occasion of his 70th birthday.

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HETEROCYCLES, Vol. 69, 2006
reaction of 8-(triphenylphosphoimino)-1-azaazulene (8-(triphenylphosphoimino)cyclohepta[b]pyrrole)
derivative (5) with aryl aldehyde.5
Therefore, it is considered that the reaction of 8-
(triphenylphosphoimino)quinoline (6), being an isomer of 8-(triphenylphosphoimino)-1-azaazulene
system, with aryl aldehyde would produce 2-aryl-4H-imidazo[4,5,1-ij]quinoline.
It is known that the iminophosphoranes reveal synthetic versatility for the construction of fused
heterocycles.6-9 We also reported the synthesis and some reactions of the 8-phosphoimino-1-azaazulene
derivative (5).5,10,11 In the structure of 5, the interaction between N-1 and the P atoms was observed, and
5 had a ticyclic charactor.10 Although a few researches about 2-phosphoiminoquinoline are known,12-14
the reaction of 8-phosphoiminoquinoline was not reported so far. Therefore, for the comparison of the
cases of 8-phosphoimino-1-azaazulene and 2-phosphoiminoquinoline, the studies about the synthesis and
reactions of 8-phosphoiminoquinoline, being an isomer of 8-phosphoimino-1-azaazulene, would be
meaningful.
NOSO3H
O
N
N
N
R
N
N
N
R
1
2
3
Ph
Ph
N
N
N
N
Ph3P
N
N
Ar
PPh3
5
6
4
RESULTS AND DISCUSSION
8-(Triphenylphosphoimino)quinoline (6) was prepared in good yields in two ways as follows; Method A)
a reaction of 8-aminoquinoline with dibromotriphenylphosphorane, and Method B) a reaction of 8-
aminoquinoline with triphenylphosphine and hexachloroethane in the presence of triethylamine. Thus 6
was obtained in 82% (Method A) and 94% yields (Method B), respectively, and the structure of 6 was
deduced by spectroscopic data as well as elemental analyses. Its 31P NMR spectrum showed a signal at
δP 15.955, and this chemical shift is adequate as a phosphoimine derivative.14 In the 1H NMR spectrum
of 6, the quinoline ring protons appeared at δH 7.05 (dd, J 7.6 and 1.3, H-5), 7.07 (dd, J 8.2 and 4.1, H-3),
7.29 (dd, J 7.6 and 6.7, H-6), 7.30 (dd, J 6.7 and 1.3, H-7), 7.93 (dd, J 8.2 and 1.7, H-4), and 8.18 (dd, J

HETEROCYCLES, Vol. 69, 2006
169
13
4.1 and 1.7, H-2). The conformation of phosphoimine moiety was deduced by its C NMR spectrum.
The signal of C(7) was appeared at δC 128.90 (J 14.5) as doublet, being long-range coupling with P. On
the other hand, the signal of C(2) was appeared at δC 145.51 as singlet. In the case of 8-phosphoimino-
1-azaazulene (5), where the coupling of P-C(2) was clearly observed in NMR spectra, and 5 was exist in
as cyclic structure. The results suggest that interaction between P and N(1) did not exist. For
determination of the conformation and the nature of 6, we performed the molecular orbital calculation by
Gaussian 98 using RHF / 6-31G*.15 The optimized structure of 6 is shown in Figure 1. The atomic
charge of C(2) position is rather positive, and this suggests the possibility that the further cyclization
could be occurred at C(2).
Bond lengths
atomic charges
-0.046
0.010
0.066
0.011
0.215
1.356
1.356
-0.070
0.254
1.419
1.408
1.447
1.417
1.414
1.292
1.412
1.375
-0.113
1.354
N
0.336
N
1.366
-0.558
-0.818
-0.310*
Ph
1.833
Ph
Ph
N
1.548
N
P
1.820
P
1.262
Ph
-0.292*
1.831
-0.293*
Ph
Ph
Figure 1. Calculated bond lengths (Å), atomic charges, and the optimized structure of 6.
*Atomic charges of phenyl carbon atom connected with phosphorus atom
When 6 was treated with benzaldehyde in xylene under heating at 125 ℃ for 200 h, the cycloadduct
(7a) was obtained in 73% yield as pale yellow needles. In the MS spectrum of 7a, the molecular peak
appeared at m/z 232 as a parent peak. Thus 7a was analyzed as C16H12N2 from its MS and elemental
analyses. In its 13C NMR spectrum, a methylene carbon appeared at δ47.76. In the 1H NMR spectrum
of 7a, methylene protons were appeared at δH 5.30 (dd, J 3.5 and 2.3), and two vinylic protons on
dihydropyridine ring were seen at δH 5.82 (dt, J 10.0 and 3.5, H-5) and 6.61 (dt, J 10.0 and 2.3, H-6).
Three protons of benzene moiety were seen at δH 6.86 (d, J 7.1, H-7), 7.08 (dd, J 8.2 and 7.1, H-8), and
7.54 (d, J 8.2, H-9). From the results, we assigned the structure of 7a as 2-phenyl-4H-imidazo[4,5,1-
ij]quinoline.
Similar reaction of 6 with p-cyanobenzaldehyde and p–tolualdehyde gave 7b and 7c in 52% and 68%
yields, respectively.
The reaction resembled to the case of 8-phosphoimino-1-azaazulene (5).5 Plausible reaction mechanism

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is shown in Scheme 1. Two reaction pathways are considered as follows. Cycloaddition of aryl
aldehyde with the iminophosphorane (6) would produce the intermediate (A). Eilimination of
triphenylphosphine oxide from A gives the Shiff base (B) (Aza-Wittig reaction) and successive
cyclization gives C. Hydride shift to the iminium carbon furnishes 7 (Path a). When cyclization and
elimination of triphenylphosphine oxide occurred attended with hydride shift concertedly, 7 would be
produced (Path b).
Some Shiff bases (B) are known as stable crystals and some properties were reported,16 but about the
cyclization of B was not mentioned. Therefore, we examined the synthesis and cyclization of B (Ar =
Ph, p-CNC6H4, p-CH3C6H4). Treatment of 8-aminoquinoline with benzaldehyde in the presence of p-
toluenesulfonic acid and molecular sieves 4A (MS4A) under reflux in toluene gave 8-
benzylideneiminoquinoline (B : Ar = Ph) as colorless crystals. Heating the crystals in xylene at 125 ℃
for 200 h gave 7a in an extremely low yield (0.2%). The result suggested that the cyclization of 8-
benzylideneiminoquinoline would not be preferential. Therefore, we preferred the path b as a main
route.
ArCHO
A) PPh3Br2 or
N
N
N
N
B) PPh3, C2Cl6, Et3N
N
Ph3P
Ar
NH2
Ph3P
H
O
6
A
path b
path a
– Ph3PO
– Ph3PO
N
N
N
H
N
N
N
Ar
ArHC
Ar
7a : Ar = Ph
7b : Ar = p-CNC6H4
7c : Ar = p-CH3C6H4
C
B
Scheme 1
Ph
Ph
Ph
ArNCO
+
N
H
N
N
N
N
N
N
N
NAr
NAr
PPh3
Ar
10
9
5
8

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171
We previously reported that 5 reacted with aryl isocyanate to give 8 and 9. It is thought that if similar
cyclization reaction occurred between 6 and aryl isocyanate, the twitter ion (10) would be produced.
Therefore, we next examined the reaction of 6 with some aryl isocyanates. Treatment of 6 with phenyl
isocyanate in benzene at 80 ℃ for 24 h gave 11a and 12a in 33% and 6% yields, respectively. In the
1H NMR spectrum of 11a, a methine proton was appeared δH 7.02 (t, J 2.1), and two vinylic protons on
the dihydropyridine ring were seen at δH 5.47 (dt, J 10.1 and 2.1, H-8) and 6.78 (dt, J 10.1 and 2.1, H-9).
13
In its C NMR spectrum, a methine carbon was observed at δC 65.28. In the ir spectrum of 11a, a
carbonyl signal was seen at 1690 cm-1. From the results, we assigned the structure of 11a as 1,3-
diphenyl-1,2,3,9a-tetrahydro[1,3,5]triazolo[2’,3’:2,1;3’,4’-a]imidazo[4,5,1-ij]quinolin-2-one.
Finally,
the structure of 11a was confirmed by X-Ray structure analysis. Ortep drawing16 of 11a is shown in
Figure 2.
ArNCO
ArNCO
Ar
N
N
C
O
N
N
N
N
N
C
Ph3P
N
Ar
N
Ar
D
6
10
H2O
H
H
Ar
N
N
N
N
O
O
N
N
N
N
Ar
O
H
N
Ar
NH
Ar
11a : Ar = Ph
11b : Ar = p-Tol
12a : Ar = Ph
12b : Ar = p-Tol
10
Scheme 2
In the 1H NMR spectrum of 12a, a couple of A,B-doublets signals were seen at δH 6.74 (d, J 9.4, H-5) and
7.97 (d, J 9.4, H-6) and NH proton was observed at δH 9.82. Three protons of benzene moiety were seen
at δH 7.43-7.47 (m, H-7 and 8) and 7.70 (d, J 5.9 and 2.4, H-9), along with phenyl protons at δH 7.15 (dt, J
7.4 and 1.0, H-p-phenyl), 7.42 (dd, J 8.7 and 7.4, H-m-phenyl), and 7.89 (dd, J 8.7 and 1.0, H-o-phenyl).
In the ir spectrum of 12a, an amino peak and a carbonyl peak were seen at 3268 and 1679 cm-1,
respectively. From the results, we assigned the structure of 12a as 2-(N-anilino)imidazo[4,5,1-
ij]quinolin-4(4H)-one. The structure of 12a was confirmed by X-Ray structure analysis. Ortep

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HETEROCYCLES, Vol. 69, 2006
drawing17 of 12a is shown in Figure 3.
In the similar manner, reaction of 6 with p-tolyl isocyanate gave 11b (8%) and 12b (2%).
Plausible mechanism is shown in Scheme 2. Aza-Wittig reaction of 6 with aryl isocyanate gives the
carbodiimide (D). Intramolecular cyclization of D would afford twitter ion (10). Cycloaddition of 10
C8
C6
C7
C9
C10
C5
C4
C11
N4
C2
C3
N1
C1
N3
N2
O1
Figure 2. ORTEP drawing of 11a with thermal ellipsoids (50% probability)
Selective bond length (Å): O(1)－C(1) 1.220(8), N(1)－C(10) 1.495(7), N(1)－C(1) 1.375(8),
N(2)－C(1) 1.409(7), N(2)－C(2) 1.391(8), N(3)－C(2) 1.326(8), N(3)－C(3) 1.421(9),
N(3)－C(11) 1.414(9), N(2)－C(2) 1.394(9), N(3)－C(2) 1.390(9), N(3)－C(3) 1.421(9),
N(3)－C(3) 1.404(9), N(4)－C(10) 1.395(9), N(4)－C(2) 1.350(8), N(4)－C(11) 1.368(8),
C(3)－C(4) 1.395(9), C(3)－C(11) 1.389(9), C(4)－C(5) 1.391(10), C(5)－C(6) 1.393(9),
C(6)－C(7) 1.392(9), C(7)－C(8) 1.462(9), C(7)－C(11) 1.370(9), C(8)－C(9) 1.339(9),
C(9)－C(10) 1.495(9).

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173
Figure 3. ORTEP drawing of 12a with thermal ellipsoids (50% probability)
with another molar aryl isocyanate furnishes to 11. When 10 reacts with water, 12 is produced.
Although it is thought that hydrolysis of the carbodiimide (D) could afford urea derivative, cyclization
adducts (12a,b) were obtained. Therefore, it is thought that cyclization of D would easily occur. It is
known that silica gel causes hydrolysis. Therefore we next treated 6 with p-tolyl isocyanate in the
presence of silica gel, and 12b obtained in improved yield (14%). Silica gel would facilitate the
addition of water to the twitter ion (10). In the reaction of 6 with aryl isocyanate, blue color appeared.
We assumed the color substance would be the twitter ion (10), and tried to isolate 10 under the reaction at
room temperature, but the attempt failed.
CONCLUSION
2-Aryl-4H-imidazo[4,5,1-ij]quinoline system was easily constructed in good yield by the reaction of 8-
(triphenylphosphoimino)quinoline with aryl aldehydes through tandem aza-Wittig reaction and
cyclization. The reaction of 8-(triphenylphosphoimino)quinoline with aryl isocyanates afforded 1,3-

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diaryl-1,2,3,9a-tetrahydro[1,3,5]triazolo[2’,3’:2,1;3’,4’-a]imidazo[4,5,1-ij]quinolin-2-ones (11) and 2-
(arylamino)imidazo[4,5,1-ij]quinolin-4(4H)-ones (12) via the carbodiimide and twitter ionic mediacy.
EXPERIMENTAL
Mps are measured using a Yanagimoto micro-melting apparatus and uncorrected. 1H NMR spectra
(including HH-COSY and CH-COSY NMR) were recorded on a Bruker AVANCE 400S (400 MHz) and
13C NMR spectra were recorded on a Bruker AVANCE 400S (100.6 MHz) using deuteriochloroform as a
solvent with tetramethylsilane as an internal standard; J values are recorded in Hz. 31P NMR spectra
were recorded on a Bruker AVANCE 400S using deuteriochloroform as a solvent with
triphenylphosphine as an internal standard. IR spectra were recorded for KBr pellets on a Nicolet FT-IR
Impact 410. MS spectra were taken with on an LC-MS Waters Integrity System. Elemental analyses
were taken with a Perkin Elmer 2400II. Kieselgel 60 was used for column chromatography and
Kieselgel 60G was used for thin-layer chromatography.
Synthesis of 8-(triphenylphosphoimino)qunoline (6)
Method A - Under argon atmosphere, a mixture of 8-aminoquinoline (7) (0.086 g, 0.59 mmol),
dibromotriphenylphosphorane (0.345 g, 0.82 mmol), triethylamine (0.34 mL, 2.46 mmol) in dry benzene
(3.0 mL) was stirred for 24 h at rt. The solvent was evaporated, and the residue was recrystallized from
hexane-chloroform to give 6 as yellow powder (0.196 g, 82%).
Method B - Under argon atmosphere, to a solution of 7 (0.440 g, 3.05 mmol) in dry benzene (30.0 mL)
were added consecutively triethylamine (1.0 mL, 9.9 mmol), triphenylphosphine (0.950 g, 3.62 mmol)
and hexachloroethane (0.722 g, 3.05 mmol). After refluxed for 10.5 h, the precipitate was filtered off.
The filtrate was evaporated, and the residue was chromatographed with hexane-ethyl acetate to give 6
(1.159 g, 94%).
6: Yellow powder (from hexane-dichloromethane), mp 180-182 ℃; δH 7.05 (1H, dd, J 7.6 and 1.3, H-5),
7.07 (1H, dd, J 8.2 and 4.1, H-3), 7.29 (1H, dd, J 7.6 and 6.7, H-6), 7.30 (1H, dd, J 6.7 and 1.3, H-7),
7.32-7.50 (9H, m, H-m,p-phenyl), 7.77-7.85 (6H, dddd, J 11.8 (JP-H), 8.2, 2.1, and 1.3, H-o-phenyl), 7.93
(1H, dd, J 8.2 and 1.7, H-4), and 8.18 (1H, dd, J 4.1 and 1.7, H-2); δC 116.61, 120.20 (d, J 20.3), 121.08,
128.24, 128.90 (d, J 14.5), 129.74, 131.70, 132.73 (d, J 9.7), 136.20, 142.20 (d, J 9.4), and 145.51;
δP 15.955; νmax / cm-1 1460 (P–phenyl), 750, 720, and 691 (phenyl); m/z (rel intensity) 405 (M+ + 1, 92),
404 (M+, 68), 328 (53), 262 (19), 249 (35), 183 (83), 173 (100), 144 (27). Anal. Calcd for C27H21N2P:
C, 80.18 H, 5.23; N, 6.93. Found: C, 80.05; H, 5.33; N, 6.78.
Reaction of 6 with aryl aldehyde

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175
Typical procedure - Under argon atmosphere, a mixture of 6 (0.276 g, 0.68 mmol), benzaldehyde (0.071
mL, 0.68 mmol) in dry xylene (6.0 mL) was heated at 125 ℃ for 200 h in a sealed tube, then the
mixture was evaporated. Chromatography of the residue gave 7a (0.115 g, 73%).
In the similar manner, reaction of 6 with p-cyanobenzaldehyde and p-tolyl isocyanate gave 7b (52%) and
7c (68%).
7a: Pale yellow needles (from hexane-chloroform), mp 113-114 ℃; δH 5.30 (2H, dd, J 3.5 and 2.3,
H-methylene), 5.82 (1H, dt, J 10.0 and 3.5, H-5), 6.61 (1H, dt, J 10.0 and 2.3, H-6), 6.86 (1H, d, J 7.1,
H-7), 7.08 (1H, dd, J 8.2 and 7.1, H-8), 7.47 (1H, dd, J 7.4 and 1.4, H-p-phenyl), 7.48 (2H, dd, J 7.9 and
7.4, H-m-phenyl), 7.54 (1H, d, J 8.2, H-9), and 7.87 (2H, dd, J 7.9 and 1.4, H-o-phenyl); δC 47.76, 118.23,
119.72, 119.83, 122.65, 123.46, 123.86, 128.41, 129.22, 130.09, 130.70, 133.53, 140.81, and 151.81; νmax
/ cm-1 750, 721, and 691 (phenyl); m/z (rel intensity) 232 (M+, 100), 231 (60), 157 (12), 128 (26), 115
(22), 108 (90), and 77 (11). Anal. Calcd for C16H12N2: C, 82.73; H, 5.21; N, 12.06. Found: C, 82.64;
H, 5.28; N, 12.21
7b: Pale yellow needles (from hexane-chloroform), mp 173-174 ℃; δH 5.41 (2H, dd, J 3.5 and 2.3, H-
methylene), 5.89 (1H, dt, J 10.0 and 3.5, H-5), 6.69 (1H, dt, J 10.0 and 2.3, H-6), 6.93 (1H, d, J 7.1, H-7),
7.15 (1H, dd, J 8.3 and 7.1, H-8), 7.57 (1H, d, J 8.3, H-9), 7.81, (2H, dd, J 8.6 and 1.8, H-m-phenyl), and
8.07 (2H, dd, J 8.6 and 1.8, H-o-phenyl); δC 48.07, 113.46, 118.72, 119.08, 119.91, 120.20, 122.42,
124.02, 128.73, 132.99, 133.74, 135.04, 140.92, and 149.41; νmax / cm-1 2224 (CN); m/z (rel intensity) 257
(M+, 64), 256 (100), 128 (14), and 101(24). Anal. Calcd for C17H11N3: C, 79.36; H, 4.31; N, 16.33.
Found: C, 79.26; H, 4.33; N, 16.47.
7c: Pale yellow needles (from hexane-chloroform), mp 153 - 155 ℃; δH 2.43 (3H, s, Me), 5.34 (2H, dd, J
3.4 and 2.3, H-methylene), 5.84 (1H, dt, J 9.9 and 3.4, H-5), 6.64 (1H, dt, J 9.9 and 2.3, H-6), 6.86 (1H, d,
J 7.1, H-7), 7.09 (1H, dd, J 8.2 and 7.1, H-8), 7.31 (2H, d, J 8.1, H-m-phenyl), 7.54 (1H, d, J 8.2, H-9),
and 7.80 (2H, d, J 8.1, H-o-phenyl); δC 21.82, 47.82, 118.06, 119.62, 119.78, 122.65, 123.31, 123.94,
127.93, 128.30, 133.56, 140.26, 140.88, and 152.01; m/z (rel intensity) 246 (M+, 100). Anal. Calcd for
C17H14N2: C, 82.90; H, 5.73; N, 11.37. Found: C, 82.78; H, 5.64; N, 11,54
Synthesis and reaction of 8-benzilideneiminoquinoline
Under argon atmosphere, a mixture of 8-aminoquinoline (0.4475 g, 3.1 mmol), benzaldehyde (0.31 mL,
2.97 mmol), and p-toluenesulfonic acid (0.10 g) in dry benzene (100 mL) was heated under reflux for 27
h and the water was removed azeotropically. Then the solvent was evaporated. The residue was dried
in vacuo, then dissolved in xylene (20 mL). The mixture was heated at 125 ℃ for 200 h in a sealed
tube, then the mixture was evaporated. Chromatography of the residue gave 7a (0.0016 g, 0.2%).

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Reaction of 6 with aryl isocyanate
Typical procedure - Under argon atmosphere, a mixture of 6 (0.202 g, 0.50 mmol), phenyl isocyanate
(0.17 mL, 1.5 mmol) in dry benzene (5.0 mL) was heated at 80 ℃ for 24 h in a sealed tube, then the
mixture was evaporated. Chromatography of the residue with hexane-ethyl acetate (5 : 1) and fractional
precipitation gave 11a (0.0593 g, 33%) and 12a (0.0079 g, 6%).
In the similar manner, reaction of 6 with p-tolyl isocyanate gave 11b (8%) and 12b (2%).
11a: Colorless prisms (from acetonitrile), mp 201 ℃; δH 5.47 (1H, dd, J 10.1 and 2.1, H-8), 6.78 (1H, dd,
J 10.1 and 2.1, H-9), 7.01 (1H, d, J 6.9, H-7), 7.02 (1H, t, J 2.1, H-9a), 7.13 (1H, dd, J 8.0 and 7.9, H-6),
7.35 (2H, br d, J 7.3, H-o-phenyl), 7.42 (1H, tm, J 7.4, H-p-phenyl), 7.44 (1H, tm, J 7.2, H-p-phenyl),
7.48-7.51, (4H, m, H-m-phenyl), and 7.51-7.57 (3H, m, H-5 and H-o-phenyl); δC 65.28, 116.32, 117.78,
118.71, 120.50, 123.86, 127.20, 128.46, 129.00, 129.03, 129.19, 129.81, 130.08, 135.32, 136.87, 140.36,
148.20, and 152.97; νmax / cm-1 1690 (C=O). Anal. Calcd for C23H16N4O: C, 75.81; H, 4.43; N, 15.38.
Found: C, 76.02; H, 4.39; N, 15.13.
12a: Pale yellow prisms (from acetonitrile), mp 168-170 ℃; δH 6.74 (1H, d, J 9.4, H-5), 7.15 (1H, dt, J
7.4 and 1.0, H-p-phenyl), 7.42 (1H, dd, J 8.7 and 7.4, H-m-phenyl), 7.43-7.47 (2H, m, H-7 and 8), 7.70
(1H, dd, J 5.9 and 2.4, H-9), 7.89 (2H, dd, J 8.7 and 1.0, H-o-phenyl), 7.97 (1H, d, J 9.4, H-6), and 9.82
(1H, s, NH); δC 116.25, 119.48, 120.07, 120.13, 122.98, 124.08, 126.19, 129.71, 129.84, 138.23, 141.19,
141.33, 150.78, and 161.70; νmax / cm-1 3268 (NH), 1679 (C=O) and 1641 (C=N). Anal. Calcd for
C16H11N3O: C, 73.55; H, 4.24; N, 16.08. Found: C, 73.43; H, 4.18; N, 16.02.
11b: Colorless prisms (from acetonitrile), mp 206 ℃; δH 2.39 (3H, s, Me), 2.40 (3H, s, Me), 5.46 (1H, dd,
J 10.1 and 2.0, H-8), 6.75 (1H, dd, J 10.1 and 2.1, H-9), 6.95 (1H, dd, J 2.1 and 2.0, H-9a), 6.99 (1H, d, J
7.3, H-7), 7.11 (1H, dd, J 8.0 and 7.3, H-6), 7.21 (2H, br d, J 7.9, H-o-phenyl), 7.28 (2H, d, J 7.9, H-m-
phenyl), 7.30 (2H, d, J 8.3, H-m-phenyl), 7.42, (2H, dd, J 8.3 and 1.9, H-o-phenyl), and 7.48 (1H, d, J 8.0,
H-5); δC 21.59, 21.66, 65.25, 116.31, 117.97, 118.56, 120.41, 123.74, 127.03, 128.48, 128.70, 130.48,
130.69, 132.72, 134.21, 138.97, 139.09, 140.40, 148.48, and 153.09; νmax / cm-1 1683 (C=O) and 1657
(C=N). Anal. Calcd for C25H20N4O: C, 76.51; H, 5.14; N, 14.28. Found: C, 76.73; H, 5.11; N, 14.02.
12b: Yellow needles (from hexane-chloroform), mp 173.5-174 ℃; δH 2.36 (3H, s, H-Me), 6.72 (1H, d, J
9.4, H-5), 7.24 (2H, d, J 8.4, H-m-phenyl), 7.38-7.46 (2H, m, H-7 and 8), 7.67 (1H, dd, J 6.5 and 1.7, H-
9), 7.75 (2H, d, J 8.4, H-o-phenyl), 7.96 (1H, d, J 9.4, H-6), and 9.74 (1H, s, NH); δC 21.30, 116.22,
119.57, 119.85, 119.84, 122.96, 126.15, 129.93, 130.21, 133.76, 135.69, 141.28, 141.34, 150.99, and
161.69; νmax / cm-1 3264 (NH), 1675 (C=O) and 1639 (C=N). Anal. Calcd for C17H13N3O: C, 74.17; H,
4.76; N, 15.26. Found: C, 74.44; H, 4.68; N, 14.98.

HETEROCYCLES, Vol. 69, 2006
177
Reaction of 6 with tolyl isocyanate in the presence of silica gel
Under argon atmosphere, a mixture of 6 (0.101 g, 0.25 mmol), tolyl isocyanate (0.040 mg, 0.3 mmol),
and silica gel (0.500 g) in dry benzene (5.0 mL) was heated at 80 ℃ for 24 h in a sealed tube, then the
mixture was evaporated. The residue was chromatographed with hexane-ethyl acetate (5 : 1) repeatedly
to give 12b (0.098 g, 14%).
X-Ray structure determination
Crystal data of 11a: colorless prism, C23H16N4O, M = 364.41, monoclinic, space group P21/a, a =
8.954(5) Å, b = 18.485(7) Å, c = 10.968(4) Å, β = 93.91(3)°, V = 1811.1(12) Å3, Z = 4, Dcalc = 1.336
g/cm3, crystal dimension 0.64 x 0.42 x 0.16 mm. Data were measured on a Rigaku AFC 5S radiation
diffractometer with graphite-monochromated Mo-Kα radiation. Total 4459 reflections (4363 unique)
were collected using ω-2θ scan technique with in a 2θ range of 55.0°. The structure was solved by
direct methods (SIR92),18 and refined a full-matrix least squares methods with 269 variables and 1447
observed reflections [I > 2σ(I)]. The final refinement converged to R = 0.067 and Rw = 0.051. All
calculations were performed using the CrystalStructure19,20 crystallographic software package.
Crystal data of 12a: colorless prism, C16H11N3O, M = 261.28, monoclinic, space group C2/c, a =
17.9360(19) Å, b = 7.0519(19) Å, c = 19.555(2) Å, β = 92.716(9)°, V = 2470.6(8) Å3, Z = 8, Dcalc = 1.405
g/cm3, crystal dimension 0.58 x 0.42 x 0.08 mm. Data were measured on a Rigaku AFC 5S radiation
diffractometer with graphite-monochromated Mo-Kα radiation. Total 3001 reflections (2929 unique)
were collected using ω-2θ scan technique with in a 2θ range of 55.0°. The structure was solved by
direct methods (SIR92),18 and refined a full-matrix least squares methods with 192 variables and 1252
observed reflections [I > 2σ(I)]. The final refinement converged to R = 0.0614 and Rw = 0.0441. All
calculations were performed using the CrystalStructure19,20 crystallographic software package.
REFERENCES AND NOTE
1. F. Dullweber, T. Wagner, R. Boer, and S. Weinbrebber, EP 2001-754; PCT Int. Appl., 2003, 53.
2. S. E. Webber, D. J. Skalitzky, J. G. Tikhe, R. A. Kumpf, J. T. Marakovits, and W. B. Eastman, USP
99-152142; PCT Int. Appl., 2001, 236.
3. H. Mochizuki, K. Kato, I. Yamamoto, and K. Mizuguchi, JP 92-134189; PCT Int. Appl., 1993, 107.
4. H. Ibata, K. Nishijima, K. Kato, I. Yamamoto, E. Mochida, and K. Ohtomo, JP 89-1163190; Eur.
Pat. Appl., 1991, 49.
5. N. Abe, K. Nagamatsu, K. Tahara, and H. Fujii, Heterocycles, 2004, 63, 809.

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HETEROCYCLES, Vol. 69, 2006
6. Y. G. Gololobov and L. F. Kasukhin, Tetrahedron, 1992, 48, 1353.
7. P. Molina and M. J. Vilaplana, Synthesis, 1994, 1197.
8. M. Nitta, Reviews on Heteroatom Chemistry, 1993, 9, 87.
9. A. W. Johnson, “Ylides and Imines of Phosphorus”, Wiley, New York, 1993.
10. N. Abe, H. Fujii, K. Tahara, and M. Shiro, Heterocycles, 2001, 55, 1659.
11. K. Nagamatsu , H. Fujii, N. Abe, and A. Kakehi, Heterocycles, 2004, 64, 291.
12. J. Boedeker, K. Courault, P. Koeckritz, P. Koeckritz, and R. Radeglia, J. Prakt. Chem., 1983,
327, 463.
13. J. Boedeker and A. Koeckritz, Z. Chem., 1986, 26, 100.
14. J. Boedeker, A. Koeckritz, P. Koeckritz, and R. Radeglia, J. Prakt. Chem., 1985, 327, 723.
15. M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, V. G.
Zakrezewski, J. A. Montgomery, Jr., R. E. Stratmabb, J, C. Burant, S. Dapprich, J. M. Millam, A.
D. Daniels, K. N. Kudin, M. C. Strain, O. Farkas, J. Tomasi, V. Barone, M. Cossi, R. Cammi, B.
Mennucci, C. Pommeli, C. Adamo, S. Clifford, J. Ochterski, G. A. Petersson, P. Y. Ayala, Q. Cui,
K. Malick, A. D. Rabuck, K. Raghavachari, J. B. Foresman, J. Cioslowski, J. V. Ortiz, A. G.
Baboul, B. B. Stefanov, G. Liu, A. Liashenko, P. Priskorz, I. Komaromi, R. Gomperts, R. L.
Martin, D. J. Fox, T. Keith, M. A. Al-Laham, C. Y. Peng, A. Nanayakkara, M. Challacombe, P. M.
W. Gill, B. Johnson, W. Chen, M. W. Wong, J. L. Andres, C, Gonzalez, M. Head-Gordon, E. S.
Replogle, and J. A. Pople, Gaussian 98, Revision A.7, Gaussian, Inc., Pittsburgh, PA (1998).
16. N. T. Tai, D. T. Nguyen, T. V. Tran, and D. T. Hoang, Tap Chi Hoa Hoc, 1998, 36, 10.
17. C. K. Johnson, ORTEP II, Report ORNL-5138, Oak Ridge National Laboratory, Oak Ridge,
Tennessee, 1976.
18. A. Altomare, M. Cascarano, C. Giacovazzo, and A. Guagliard, J. Appl. Cryst., 1994, 26, 343.
19. CrystalStructure 3.7.0: Crystal Structure Analysis Package, Rigaku and Rigaku/MSC (2000-
2005).9009 New Trails Dr., The Woodlands TX 77381 USA.
20. CRYSTALS Issue 10: D. J. Watkin, C. K. Prout, J. R. Carruthers, and P. W. Betteridge, Chemical
Crystallography Laboratory, Oxford, UK (1996).