Efficient formation of a triazole ring via novel ring-opening reaction of (Z)-2-methyl-4-arylmethylene-5(4H)-oxazolones with hydrazides

Article abstract of DOI:10.3987/COM-08-11457

The ring-opening mode of the title oxazolones with hydrazide nucleophiles was investigated from both synthetic and mechanistic points of view. It was found that the novel ring-opening reaction proceeded to give (Z)-2-(3-methyl-5-substituted 1,2,4-triazol-

Full text of DOI:10.3987/COM-08-11457

HETEROCYCLES, Vol. 75, No. 12, 2008
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HETEROCYCLES, Vol. 75, No. 12, 2008, pp. 2959 - 2971. © The Japan Institute of Heterocyclic Chemistry
Received, 3rd June, 2008, Accepted, 14th July, 2008, Published online, 17th July, 2008. COM-08-11457
EFFICIENT FORMATION OF A TRIAZOLE RING VIA NOVEL
RING-OPENING REACTION OF (Z)-2-METHYL-4-ARYLMETHYLENE-
5(4H)-OXAZOLONES WITH HYDRAZIDES
Kei Maekawa, Atsushi Tomoda, Tetsutaro Igarashi, and Tadamitsu Sakurai*
Department of Material and Life Chemistry, Faculty of Engineering, Kanagawa
University, Kanagawa-ku, Yokohama 221-8686, Japan
Abstract – The ring-opening mode of the title oxazolones with hydrazide
nucleophiles was investigated from both synthetic and mechanistic points of view.
It was found that the novel ring-opening reaction proceeded to give
(Z)-2-(3-methyl-5-substituted
1,2,4-triazol-4-yl)-3-aryl-2-propenoic
acids
[1,2,4-triazole-substituted (Z)-α-dehydroarylalanines] as major products, along
with minor or negligible amounts of their isomers. Substituent and solvent
effects on the relative composition of these two isomers confirmed that this
composition was dependent on steric and electronic factors of the aryl (in the
oxazolones) and acyl (in the hydrazide nucleophiles) substituents as well as on
solvent polarity. MM2 and PM5 calculations provided a strong piece of
evidence in support of the mechanism in which the triazole ring is constructed via
the preferential nucleophilic addition of the hydrazino nitrogen to the C=N double
bond in the oxazolone ring.
INTRODUCTION
N-Acyl-α-dehydroarylalanine derivatives have been used as the starting materials in our systematic study
on the photochemistry of α-dehydroamino acids,1 being the main constituents of some antibiotics.2
These α-dehydroalanine derivatives were prepared by the nucleophilic ring-opening reactions of
substituted 5(4H)-oxazolones, which have made a great contribution to advances in the chemistry
of α-dehydroamino acids as raw materials.2,3 On the other hand, hydrazide derivatives have frequently
been utilized as convenient building blocks for the construction of various heterocyclic ring systems but
mechanism for the ring-opening reactions of the 5(4H)-oxazolones with hydrazides is not well
understood.4 It is, thus, of significance to explore these reactions from both synthetic and mechanistic
points of view. In order to pave the way for extending our study concerning the excited-state chemistry
of dehydrogenated N-acyl-α-dehydroarylalanine derivatives, (Z)-4-arylmethylene-5(4H)-oxazolones
[(Z)-1a, (Z)-1h, and (Z)-1n] were synthesized and allowed to react with acetohydrazide and related
hydrazide nucleophiles, hoping to shed much light on the mechanism of the ring-opening reactions
described above (Chart 1).

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HETEROCYCLES, Vol. 75, No. 12, 2008
O
O
O
O
NHNHCOMe
NHCOMe
O
N
O
N
O
N
Me
Me
Ph
H
H
H
H
(Z)-1a
(Z)-1h
(Z)-1n
Chart 2
RCONHNH : R = Me, H, Ph, 4-MeOC H , 4-NCC H ,
2
6
4
6 4
4-O NC H , PhCH
2
2
6 4
Chart 1
RESULTS AND DISCUSSION
Substituent effects
After an acetonitrile solution of (Z)-1a containing an equimolar amount of acetohydrazide was heated
under reflux for 0.5 h, the reaction mixture was concentrated to dryness giving the crystalline residue
1
whose H NMR spectral analysis showed that the reaction proceeded cleanly without forming any
by-products but not afford the ring-opening product, (Z)-2-acetylamino-N’-acetyl-3-(1-naphthyl)-2-
propenehydrazide, originally expected (Chart 2). The successful growth of single crystal made it
possible to establish that the novel ring-opening reaction of (Z)-1a with acetohydrazide took place to
produce quantitatively (Z)-2-(3,5-dimethyl-1,2,4-triazol-4-yl)-3-(1-naphthyl)-2-propenoic acid [(Z)-2a,
90% isolated yield; hereafter, referred to as 1,2,4-triazole-substituted (Z)-α-dehydro(1-naphthyl)alanine
derivative], as shown in Figure 1 and Scheme 1.
O
O
CO H
2
Me
Me
H
H
N
N
N
MeCONHNH2
MeCN, reflux
N
Me
(Z)-1a
(Z)-2a
Scheme 1
Figure 1. ORTEP drawing of (Z)-2a
Interestingly, on treating (Z)-1h with acetohydrazide under the same reaction conditions, the
corresponding (E)-isomer of 2 [(E)-2h] was isolated in a 7% yield, along with the (Z)-isomer [(Z)-2h,
1
88% yield] (Scheme 2 and Table 1). A careful inspection of the H NMR spectrum of this

HETEROCYCLES, Vol. 75, No. 12, 2008
2961
(Z)-1h-derived reaction mixture strongly suggested that there were minor proton signals assignable to the
originally expected ring-opening products (Z)-3h and (E)-3h (Scheme 2), although attempts to isolate
O
NHNHCOMe
NHCOMe
O
O
N
CO H
2
Me
Me
CO H
2
H
Me
H
H
N
N
MeCONHNH2
MeCN, reflux
N
N
N
Me
H
N
Me
(Z)-1h
(Z)-2h
(E)-2h
3h
Scheme 2
Table 1. Isolated yields of (Z)-2 and (E)-2 obtained from the reactions
of (Z)-1 with given hydrazide nucleophiles in refluxing acetonitrile
O
O
RCONHNH2
Me
(Z)-2a–m
(E)-2a–m
H
MeCN, reflux
N
Ar
(Z)-1
Isolated yield (%)
Reaction
time (h)
Compound
Ar
R
(Z)-2
90
89
80
87
90
88
72
88
97
74
57
92
75
(E)-2
a
a
a
a
a
a
a
b
a
b
c
d
e
f
1-Np
1-Np
1-Np
1-Np
1-Np
1-Np
1-Np
Ph
Me
H
0.5
0.5
1.0
0.5
0.5
1.0
1.0
0.5
0.5
1.0
0.5
1.0
1.0
—
b
—
b
Ph
—
b
4-MeOC H
—
6
4
b
4-NCC H
—
6
4
b
4-O NC H
—
2
6 4
g
h
i
PhCH
2
24
7
Me
H
b
Ph
—
j
Ph
Ph
17
20
k
l
Ph
4-MeOC H
6
4
b
Ph
4-O NC H
—
2
6 4
m
Ph
PhCH
2
15
a 1-Naphthyl. b Could not be detected.
1
these isomers were unsuccessful owing to their poor yields. As summarized in Table 1, H NMR
spectral analyses of the reactions of (Z)-1a and (Z)-1h with other hydrazide nucleophiles (RCONHNH2)
confirmed that while the former oxazolone gives the corresponding triazole-substituted

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HETEROCYCLES, Vol. 75, No. 12, 2008
(Z)-α-dehydroarylalanines [(Z)-2b–f], except for (Z)-2g, in quantitative yields, the (E)-isomer is formed
along with (Z)-2i–m depending on the magnitude of steric and electronic effects of the substituent R in
the reactions with the latter oxazolone. It is worth noting here that (Z)-2 is selectively obtained for any
oxazolones on reaction with hydrazides having R= H and R= 4-O2NC6H4.
O
O
N
O
H
O
RCONHNH2
–RCONHNH2
Me
Me
(E)-1
H
H
N
RCONHNH2
Ar
Ar
NHNHCOR
(Z)-1
Adduct III
(E)-2
(E)-3
RCONHNH2
RCONHN
RCONHNH2
H
O
O
O
NHNHCOR
NHCOMe
O
Me
H
O
Me
N
H
H
H
NHNHCOR
N
H
Ar
Ar
Ar
(Z)-3
Adduct I
Adduct II
CO H
CO H
CO H
2
Me
2
2
Me
Me
H
H
H
H
–H2O
N
R
N
N
N
N
N
N
N
Ar
Ar
NH
Ar
R
H
R
OH
O
(Z)-2
IV
V
Scheme 3
Since the presence of an equimolar amount of acetohydrazide induced negligible isomerization of (Z)-2 to
the corresponding (E)-isomer even in refluxing acetonitrile, the formation of (Z)-2, (E)-2 and 3
demonstrated that 4-arylmethylene-5(4H)-oxazolones had three sites for the nucleophilic addition of this
hydrazide. The first site should be the C=O double bond in the oxazolone ring, the second the C=N
double bond in this ring and the third the arylmethylene C=C double bond, allowing us to propose
Scheme 3 in order to explain the observed product distribution. In this Scheme we assumed that the
adducts I, II and III played pivotal roles in controlling the relative composition of each product. As
depicted in Scheme 3, nucleophilic addition of the hydrazino nitrogen to the C=N double bond in the ring
gives the adduct I reversibly, the ring opening of which takes place via the C–O bond cleavage to form
the iminomethylamino intermediate IV. Intramolecular nucleophilic attack of the iminomethyl nitrogen
upon the acyl carbonyl carbon generates the tetrahedral intermediate V and then the dehydration of this
intermediate eventually leads to the (Z)-isomer of 2. In competition with the addition to the C=N double
bond in the ring, the C=O double bond in this ring is also subject to the reversible addition of the
hydrazide nucleophile to produce the adduct II, and the decomposition of this cyclized tetrahedral

HETEROCYCLES, Vol. 75, No. 12, 2008
2963
intermediate provides the (Z)-isomer of 3 which is the originally expected ring-opening product. On the
other hand, the finding of negligible isomerization of (Z)-2 in the presence of a given hydrazide reveals
that geometrical isomerization of (Z)-1 into (E)-1 (proceeding through the adduct III) must precede the
nucleophilic addition to the C=N double bond of the latter isomer, which leads ultimately to (E)-2 and
(E)-3 according to reaction pathways given for the respective isomers.
Careful inspection of the data given in Table 1 confirms that replacement of the 1-naphthyl group in (Z)-1
by the phenyl has a tendency to enhance the composition of (E)-2 (which can be approximated by its
isolated yield) with a decrease in composition for (Z)-2 and then an increase in the former composition is
compensated by the lowered composition of the latter. In addition, the previous finding that the reaction
of (Z)-1 with primary amines selectively affords (Z)-N-acyl-α-dehydroarylalaninamides demonstrates that
an intermediate (corresponding to IV in Scheme 3) formed in this reaction does not undergo any
cyclization.1 These substantiate reversibilities of the processes: (Z)-1→I→IV→V, (Z)-1→II, and
(Z)-1→III→(E)-1 and are also consistent with the competitive nucleophilic addition of the hydrazino
nitrogen in the reaction between (Z)-1 and hydrazides. It is, thus, reasonable to explain a difference in
product distribution between (Z)-1a and (Z)-1h based on these reversibilities as well as on much larger
steric hindrance exerted by the naphthyl group of the former in the III-forming step. On the other hand,
molecular modeling for IV suggests that the substituents Ar and R are in close proximity to one another
in this adduct-forming transition state. Additionally, the above suggestion leads us to predict that the
composition of (Z)-2 is decreased with an increase in steric bulkiness for the latter substituent:
H>Me>Ph>CH2Ph. Thus, the fact that the results are compatible with our prediction establishes that
steric hindrance to the cyclization process in IV is one of the major factors for controlling the product
composition and also that the cyclization of IV to V should be a rate-determining step. As already
described above, there appeared a negligible amount of (E)-2l when (Z)-1h was allowed to react with
4-nitrobenzohydrazide (1H NMR spectral analysis) whereas a certain amount of the (E)-isomer was
isolated from the reaction with 4-methoxybenzohydrazide possessing R= 4-MeOC6H4 of almost the same
steric bulkiness as R= 4-O2NC6H4 (20% yield, Table 1). The latter substituent of much stronger electron
withdrawing ability than the former is considered to assist the intramolecular nucleophilic attack of the
methylimino nitrogen in IV upon the RCO carbonyl carbon causing the enhanced reactivity of this
intermediate. It is very likely that an electronic effect on the reactivity of a given hydrazide nucleophile
also contributes to the control of relative composition for (Z)-2 and (E)-2, being consistent with a
rate-determining step for the cyclization process: IV→V.
In order to elucidate the origin of the preferential formation of (Z)-2, energy-minimized conformations
(MM2) and heats of formation (ΔHf, PM5) of the adducts I, II, and III (Ar= Ph, R= Me) were calculated
and shown in Figure 2. A comparison of the ΔHf values confirms that the adduct I is the most stable
intermediate and, hence, its formation should be the major process. This analysis reveals that the
ring-opening reaction of (Z)-1 with hydrazides is a thermodynamically-controlled process. In addition
to substituent effects on the product composition, the above consideration is not in conflict with the
reversibilities of the processes: (Z)-1→I, (Z)-1→II, and (Z)-1→III→(E)-1 shown in Scheme 3.
Surprisingly, the reaction of (Z)-1n (bearing the phenyl group at the 2-position on the oxazolone ring)

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HETEROCYCLES, Vol. 75, No. 12, 2008
with acetohydrazide under the same reaction conditions afforded N-benzoyl-α-dehydronaphthylalanine
derivative (3n) as a 6:1 mixture of the (Z)- and (E)-isomers without forming the corresponding
1,2,4-triazole-substituted α-dehydroarylalanine derivative (1H NMR spectral analysis). This unexpected
observation allowed us to propose that the presence of a bulky phenyl group at the 2-position exerts a
great steric effect on the nucleophilic addition of the hydrazide to the C=N double bond resulting in an
exclusive progress of the other two addition reactions.
H
H
H
!
!
H
!
!
H
!
O
H
!
H
N
N
#
O
H
H
H
!
"
!
N
N
"
O
O
H
#
H
!
O
H
O
H
"
!
H
H
N
H
H
!
#
N
H
H
H
H
!
H
H
!
H
H
H
H
!
!
H
H
I
(!H = –290.1 kJ mol )
II
(!H = –257.0 kJ mol )
III
(!H = –272.8 kJ mol )
–1
–1
–1
f
f
f
Figure 2. Energy-minimized conformations and heats of formation (ΔHf) of the adducts I, II and III
Solvent and temperature effects
In developing a novel reaction of synthetic utility, we have to take solvent polarity and reaction
temperature into account as crucial factors affecting product compositions. For this end toluene and
1,2-dichloroethane were chosen along with acetonitrile as typical aprotic solvents. As shown in Table 2,
Table 2. Solvent and temperature effects on the isolated yields of (Z)-2h
and (E)-2h obtained from the reaction of (Z)-1h and acetolhydrazide
Isolated yield (%)
Reaction
time (h)
Reaction
temperature (°C)
Solvent
(Z)-2h
(E)-2h
Toluene
CH2ClCH2Cl
CH2ClCH2Cl
MeCN
2.5
8.0
0.5
6.5
0.5
80
78
87
76
90
88
13
6
22 (rt)
83 (reflux)
22 (rt)
16
2
MeCN
78 (reflux)
7
both solvent polarity and reaction temperature affect the product composition for the
(Z)-1h–acetohydrazide system to only a small extent. Somewhat different dependence of the overall

HETEROCYCLES, Vol. 75, No. 12, 2008
2965
rate for each reaction pathway on these two factors is considered to be responsible for a slight change in
the observed product composition. Additionally, either short column chromatography over silica gel or
recrystallization from ethanol-hexane enabled the isolation of analytical-grade (Z)-2 from a given reaction
mixture. Therefore, we were led to conclude that the reaction of (Z)-2-methyl-4-arylmethylene-5(4H)-
oxazolones with hydrazide nucleophiles in refluxing acetonitrile constitutes a novel method for the
construction of a 1,2,4-triazole ring on the amino group side of (Z)-α-dehydroarylalanines.4f,5
EXPERIMENTAL
General
1H and 13C NMR spectra were taken with a JEOL JNM-ECA500 or a JEOL JNM-ECA600 spectrometer.
Chemical shifts were determined using tetramethylsilane as an internal standard. IR spectra were
recorded on a SHIMADZU IRPrestige-21 infrared spectrophotometer. Elemental analyses were
performed on a PERKIN-ELMER PE2400 series II CHNS/O analyzer. MM2 and PM5 calculations
were accomplished by using CAChe 5.0 for Windows available from Fujitsu Ltd (2002). MeCN was
purified according to the standard procedure and freshly distilled prior to use.6 1,2-Dichloroethane and
toluene were of spectroscopic grade and used as received. All other reagents were obtained from
commercial sources and were of the highest grade available.
General procedure for the synthesis of (Z)-2-methyl-4-(1-naphthylmethylene)-5(4H)-oxazolone,
(Z)-4-benzylidene-2-methyl-5(4H)-oxazolone and (Z)-4-(1-naphthylmethylene)-2-phenyl-5(4H)-
oxazolone
N-Acetylglycine or N-benzoylglycine (50 mmol), 1-naphthaldehyde or benzaldehyde (50 mmol) and
sodium acetate (20 mmol) were added to acetic anhydride (10–30 mL) and the resulting mixture was
heated at 65–75 °C for 1–2 h with stirring. The mixture was cooled with ice and the solid separated out
was collected by filtration with suction and washed with water, a small amount of cold EtOH and then
with dry hexane. After the crude product had been air-dryed at rt, it was recrystallized from
hexane-CHCl3 to give yellow crystals (60–70%).
(Z)-2-Methyl-4-(1-naphthylmethylene)-5(4H)-oxazolone [(Z)-1a]. Mp 159.0–159.5 °C. IR (KBr):
1760, 1650, 1260 cm–1. 1H NMR (500 MHz, CDCl3): δ 2.43 (3H, s), 7.54 (1H, dd, J = 7.3, 7.9 Hz), 7.58
(1H, dd, J = 7.3, 8.6 Hz), 7.61 (1H, dd, J = 7.3, 8.6 Hz), 7.88 (1H, d, J = 7.9 Hz), 7.93 (1H, d, J = 8.6 Hz),
8.02 (1H, s), 8.24 (1H, d, J = 8.6 Hz), 8.75 (1H, d, J = 7.3 Hz). 13C NMR (125 MHz, DMSO-d6): δ 15.8,
122.8, 125.7, 126.3, 127.1, 127.4, 128.9, 129.1, 131.4, 131.8, 132.3, 133.3, 133.6, 166.8, 167.8. Anal.
Calcd for C15H11NO2: C, 75.94; H, 4.67; N, 5.90. Found: C, 75.90; H, 4.57; N, 6.19.
(Z)-4-Benzylidene-2-methyl-5(4H)-oxazolone [(Z)-1h]. Mp 152.0–152.5 °C. IR (KBr): 1779, 1659,
1266 cm–1. 1H NMR (500 MHz, CDCl3): δ 2.41 (3H, s), 7.15 (1H, s), 7.43–7.47 (3H, m), 8.06–8.09 (2H,
m). 13C NMR (125 MHz, DMSO-d6): δ 15.4, 128.9 (2C), 129.8, 131.1, 131.9 (2C), 132.6, 133.0, 166.8,
167.4. Anal. Calcd for C11H9NO2: C, 70.58; H, 4.85; N, 7.48. Found: C, 70.74; H, 4.92; N, 7.33.

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HETEROCYCLES, Vol. 75, No. 12, 2008
(Z)-4-(1-Naphthylmethylene)-2-phenyl-5(4H)-oxazolone [(Z)-1n]. Mp 166.0–167.0 °C. IR (KBr):
1797, 1647, 1167 cm–1. 1H NMR (500 MHz, CDCl3): δ 7.70–7.90 (6H, m), 8.06 (1H, d, J = 7.9 Hz),
8.08 (1H, s), 8.14 (1H, d, J = 8.6 Hz), 8.17 (2H, d, J = 7.3 Hz), 8.42 (1H, d, J = 8.6 Hz), 8.99 (1H, d, J =
7.3 Hz). 13C NMR (125 MHz, DMSO-d6): δ 123.6, 124.1, 126.2, 126.5, 127.1, 128.4, 128.7 (2C), 129.6,
129.7, 130.0 (2C), 132.0, 132.4, 132.5, 134.0, 134.5, 134.8, 164.4, 167.5. Anal. Calcd for C20H13NO2: C,
80.25; H, 4.38; N, 4.68. Found: C, 80.01; H, 4.11; N, 4.65.
General procedure for the reactions of (Z)-4-Arylmethylene-2-methyl-5(4H)-oxazolone with
acetohydrazide and related hydrazide nucleophiles
(Z)-4-Arylmethylene-2-methyl-5(4H)-oxazolone (2.7 mmol) and a given hydrazide nucleophile (3.2
mmol) were dissolved in MeCN (10 mL) and the resulting solution was heated under reflux for 0.5 or 1.0
h. After the solution was cooled to rt, it was concentrated to dryness under reduced pressure. The
crystalline residue obtained was subjected to column chromatography over silica gel (230 mesh, Merck)
eluting with EtOAc, in order to isolate analytical-grade (Z)-2 and (E)-2. When the reaction mixture
contained a negligible amount of the latter isomer, it was directly recrystallized from EtOH or
EtOH-hexane. The reaction of (Z)-1n (2.7 mmol) with acetohydrazide (3.2 mmol) in refluxing MeCN
was carried out under the same conditions as those described above and similar workup allowed us to
isolate the corresponding (Z)-3 as the major product. For examining solvent and temperature effects on
the product composition, toluene and 1,2-dichloroethane solutions containing (Z)-1h (2.7 mmol) and
acetohydrazide (3.2 mmol) were heated at 80 °C (2.5 h) and 83 °C (boiling point, 0.5 h), respectively,
while these two reactants dissolved in MeCN and 1,2-dichloroethane were allowed to stand for 6.5 and
8.0 h, respectively, at rt. Physical and spectroscopic data of (Z)-2a–m, (E)-2g,h,j,k,m, and (Z)-3n
successfully isolated are as follows.
(Z)-2-(3,5-Dimethyl-1,2,4-triazol-4-yl)-3-(1-naphthyl)-2-propenoic
acid
[(Z)-2a].
Mp
239.5–240.0 °C. IR (KBr): 3048, 1709, 1639 cm–1. 1H NMR (600 MHz, DMSO-d6): δ 1.99 (6H, s),
6.79 (1H, d, J = 7.6 Hz), 7.38 (1H, dd, J = 7.6, 8.3 Hz), 7.62 (1H, dd, J = 7.6, 7.6 Hz), 7.67 (1H, dd, J =
7.6, 8.3 Hz), 7.98 (1H, d, J = 7.6 Hz), 7.99 (1H, d, J = 8.3 Hz), 8.12 (1H, d, J = 8.3 Hz), 8.70 (1H, s).
13C NMR (150 MHz, DMSO-d6): δ 10.3 (2C), 123.4, 125.1, 125.5, 126.1, 126.8, 127.7, 128.2, 128.9,
130.8, 130.9, 133.1, 138.0, 150.5 (2C), 164.2. Anal. Calcd for C17H15N3O2: C, 69.61; H, 5.15; N, 14.33.
Found: C, 69.48; H, 4.84; N, 14.18.
(Z)-2-(3-Methyl-1,2,4-triazol-4-yl)-3-(1-naphthyl)-2-propenoic acid [(Z)-2b]. Mp 165.0–166.0 °C.
IR (KBr): 3048, 1709, 1639 cm–1. 1H NMR (600 MHz, DMSO-d6): δ 1.93 (3H, s), 6.94 (1H, d, J = 7.6
Hz), 7.39 (1H, dd, J = 6.9, 9.0 Hz), 7.62 (1H, dd, J = 7.6, 8.2 Hz), 7.66 (1H, dd, J = 6.9, 7.7 Hz), 7.98 (1H,
d, J = 8.2 Hz), 8.00 (1H, d, J = 7.7 Hz), 8.08 (1H, d, J = 9.0 Hz), 8.48 (1H, s), 8.61 (1H, s). 13C NMR
(150 MHz, DMSO-d6): δ 9.6, 123.7, 125.3, 125.8, 126.3, 126.6, 127.4, 128.5, 128.7, 130.4, 130.7, 133.0,
136.9, 144.3, 149.7, 164.1. Anal. Calcd for C16H13N3O2: C, 68.81; H, 4.69; N, 15.05. Found: C, 68.53;
H, 4.99; N, 15.29.

HETEROCYCLES, Vol. 75, No. 12, 2008
2967
(Z)-2-(3-Methyl-5-phenyl-1,2,4-triazol-4-yl)-3-(1-naphthyl)-2-propenoic acid [(Z)-2c].
Mp
227.0–227.5 °C. IR (KBr): 3055, 1709, 1638 cm–1. 1H NMR (600 MHz, DMSO-d6): δ 2.13 (3H, s),
6.76 (1H, d, J = 7.6 Hz), 7.25 (3H, m), 7.30 (1H, dd, J = 7.6, 8.3 Hz), 7.33 (2H, d, J = 7.6 Hz), 7.48 (1H,
dd, J = 7.6, 7.6 Hz), 7.53 (1H, dd, J = 7.6, 8.3 Hz), 7.77 (1H, d, J = 8.3 Hz), 7.91 (1H, d, J = 7.6 Hz), 7.92
(1H, d, J = 8.3 Hz), 8.61 (1H, s). 13C NMR (150 MHz, DMSO-d6): δ 10.3, 123.2, 125.3, 125.7, 126.0,
126.5, 126.7 (2C), 127.1, 127.2, 128.2, 128.6 (3C), 129.6, 130.7, 130.8, 132.9, 137.5, 151.7, 153.1, 164.3.
Anal. Calcd for C22H17N3O2: C, 74.35; H, 4.82; N, 11.82. Found: C, 74.16; H, 4.84; N, 11.81.
(Z)-2-[5-(4-Methoxyphenyl)-3-methyl-1,2,4-triazol-4-yl]-3-(1-naphthyl)-2-propenoic acid [(Z)-2d]. Mp
144.0–145.0 °C. IR (KBr): 3400, 1695 cm-1. 1H NMR (600 MHz, DMSO-d6): δ 2.13 (3H, s), 3.68 (3H,
s), 6.73 (1H, d, J = 7.4 Hz), 6.77 (2H, d, J = 9.2 Hz), 7.21 (2H, d, J = 9.2 Hz), 7.34 (1H, dd, J = 7.4, 8.0
Hz), 7.50 (1H, dd, J = 6.9, 8.0 Hz), 7.55 (1H, dd, J = 6.9, 8.0 Hz), 7.77 (1H, d, J = 8.0 Hz), 7.92 (1H, d, J
= 8.0 Hz), 7.93 (1H, d, J = 8.0 Hz), 8.57 (1H, s). 13C NMR (150 MHz, DMSO-d6): δ 10.4, 55.1, 114.0
(2C), 119.3, 123.2, 125.2, 125.5, 126.4 (2C), 127.0, 128.2 (2C), 128.4, 128.5, 130.6, 130.7, 132.9, 137.2,
151.3, 152.9, 160.1, 164.3. Anal. Calcd for C23H19N3O3: C, 71.68; H, 4.97; N, 10.90. Found: C, 71.40;
H, 5.27; N, 11.08.
(Z)-2-[5-(4-Cyanophenyl)-3-methyl-1,2,4-triazol-4-yl]-3-(1-naphthyl)-2-propenoic acid [(Z)-2e].
Mp
269.0–270.0 °C. IR (KBr): 3410, 2228, 1701 cm-1. 1H NMR (600 MHz, DMSO-d6): δ 2.28 (3H, s),
6.69 (1H, d, J = 7.4 Hz), 7.27 (2H, d, J = 8.6 Hz), 7.33 (1H, dd, J = 7.4, 8.0 Hz), 7.46 (1H, dd, J = 7.4,
8.0 Hz), 7.54 (1H, dd, J = 7.4, 8.0 Hz) , 7.59 (2H, d, J = 8.6 Hz), 7.90 (1H, d, J = 8.0 Hz), 7.90 (1H, d, J
= 8.0 Hz), 7.93 (1H, d, J = 8.0 Hz), 8.59 (1H, s). 13C NMR (150 MHz, DMSO-d6): δ 10.5, 99.4 (2C),
112.0, 118.0, 123.2, 125.2, 125.6, 126.4, 126.9, 127.2 (2C), 128.1, 128.4, 130.3, 130.7, 130.8, 132.4,
132.7, 138.2, 151.7, 152.6, 164.1. Anal. Calcd for C23H16N4O2: C,72.62; H, 4.24; N, 14.73. Found: C,
72.51; H, 4.21; N, 15.05.
(Z)-2-[3-Methyl-5-(4-nitrophenyl)-1,2,4-triazol-4-yl]-3-(1-naphthyl)-2-propenoic acid [(Z)-2f].
Mp
265.5–266.0 °C. IR (KBr): 3404, 1718, 1699, 1526, 1348 cm–1. 1H NMR (600 MHz, DMSO-d6): δ
2.32 (3H, s), 6.68 (1H, d, J = 7.6), 7.29 (2H, d, J = 8.9), 7.32 (1H, dd, J = 7.6, 8.9 Hz), 7.33 (1H, dd, J =
7.6, 8.3 Hz), 7.43 (1H, dd, J = 7.6, 8.9 Hz), 7.57 (1H, d, J = 8.9 Hz), 7.84 (1H, d, J = 8.3 Hz), 7.91 (1H, d,
J = 8.9 Hz), 7.91 (2H, d, J = 8.9 Hz), 8.57 (1H, s). 13C NMR (150 MHz, DMSO-d6): δ 10.5, 123.2,
123.7(2C), 125.2, 125.6, 125.8, 126.3, 126.5, 127.8(2C), 128.1, 128.4, 130.2, 130.7, 132.5, 132.7, 138.3,
147.4, 151.4, 152.8, 164.0. Anal. Calcd for C22H16N4O4: C, 65.99; H, 4.03; N, 13.99. Found: C, 65.80;
H, 3.89; N, 14.21.
(Z)-2-(3-Benzyl-5-methyl-1,2,4-triazol-4-yl)-3-(1-naphthyl)-2-propenoic acid [(Z)-2g].
Mp
165.0–166.0 °C. IR (KBr): 3048, 1709, 1639 cm–1. 1H NMR (600 MHz, DMSO-d6): δ 1.99 (3H, s),
3.68 (1H, d, J = 15.8 Hz), 3.71 (1H, d, J = 15.8 Hz), 6.41 (1H, d, J = 7.6 Hz), 7.03 (2H, d, J = 6.9 Hz),
7.08 (1H, dd, J = 7.9, 7.9 Hz), 7.14 (2H, dd, J = 6.9, 7.9 Hz), 7.20 (1H, dd, J = 7.6, 7.6 Hz), 7.60 (1H, dd,

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J = 7.6, 8.3 Hz), 7.66 (1H, dd, J = 7.6, 8.3 Hz), 7.90 (1H, d, J = 8.3 Hz), 7.97 (1H, d, J = 8.3 Hz), 8.10
(1H, d, J = 7.6 Hz), 8.57 (1H, s). 13C NMR (150 MHz, DMSO-d6): δ 10.3, 30.7, 123.2, 124.8, 125.3,
126.0, 126.6, 126.7, 127.6, 127.8, 128.2 (2C), 128.6 (2C), 128.9, 130.8, 130.9, 133.1, 135.4, 137.4, 151.0,
152.4, 164.0. Anal. Calcd for C23H19N3O2: C,74.78; H, 5.18; N, 11.37. Found: C, 74.57; H, 5.16; N,
11.53.
(Z)-2-(3,5-Dimethyl-1,2,4-triazol-4-yl)-3-phenyl-2-propenoic acid [(Z)-2h]. Mp 218.0–219.0 °C. IR
(KBr): 3431, 1708, 1691 cm–1. 1H NMR (600 MHz, DMSO-d6): δ 2.06 (6H, s), 6.95 (2H, d, J = 7.4 Hz),
7.39 (2H, dd, J = 7.4, 7.4 Hz), 7.45 (1H, dd, J = 7.4, 7.4 Hz), 8.09 (1H, s). 13C NMR (150 MHz,
DMSO-d6): δ 10.1 (2C), 122.2, 129.3 (2C), 129.7 (2C), 131.3, 131.4, 139.9, 150.0 (2C), 164.4. Anal.
Calcd for C13H13N3O2: C, 64.19; H, 5.39; N, 17.27. Found: C, 63.81; H, 5.07; N, 17.09.
(Z)-2-(3-Methyl-1,2,4-triazol-4-yl)-3-phenyl-2-propenoic acid [(Z)-2i]. Mp 245.0–246.0 °C. IR
(KBr): 3424, 1711, 1698 cm–1. 1H NMR (600 MHz, DMSO-d6): δ 2.09 (3H, s), 6.96 (2H, d, J = 6.9 Hz),
7.37 (2H, dd, J = 6.9, 7.6 Hz), 7.43 (1H, dd, J = 7.6, 7.6 Hz), 8.03 (1H, s), 8.53 (1H, s). 13C NMR (150
MHz, DMSO-d6): δ 9.4, 122.7, 129.2 (2C), 129.7 (2C), 131.1, 131.3, 139.0, 143.6, 149.6, 164.4. Anal.
Calcd for C12H11N3O2: C, 62.87; H, 4.84; N, 18.33. Found: C, 62.53; H, 4.79; N, 18.41.
(Z)-2-(3-Methyl-5-phenyl-1,2,4-triazol-4-yl)-3-phenyl-2-propenoic acid [(Z)-2j]. Mp 205.0–206.0 °C.
IR (KBr): 3058, 1714, 1642 cm–1. 1H NMR (600 MHz, DMSO-d6): δ 2.15 (3H, s), 7.01 (2H, d, J = 7.6
Hz), 7.37 (2H, dd, J = 7.6, 7.6 Hz), 7.45–7.40 (4H, m), 7.53–7.51 (2H, m), 8.07 (1H, s). 13C NMR (150
MHz, DMSO-d6): δ 10.0, 123.3, 126.8 (2C), 127.1, 128.8 (2C), 129.3 (2C), 129.8 (2C), 129.9, 131.2,
131.5, 139.8, 151.3, 152.5, 164.4. Anal. Calcd for C18H15N3O2: C, 70.81; H, 4.95; N, 13.76. Found: C,
70.43; H, 4.71; N, 13.76.
(Z)-2-[5-(4-Methoxyphenyl)-3-methyl-1,2,4-triazol-4-yl]-3-phenyl-2-propenoic acid [(Z)-2k].
An
amorphous solid. IR (KBr): 3435, 1698, 1634 cm–1. 1H NMR (600 MHz, DMSO-d6): δ 2.12 (3H, s),
3.75 (3H, s), 6.98 (2H, d, J = 8.9 Hz), 7.01 (2H, d, J = 8.9 Hz), 7.38 (2H, dd, J = 7.6, 8.9 Hz), 7.44 (1H,
dd, J = 7.6, 7.6 Hz), 7.45 (2H, d, J = 8.9 Hz), 8.05 (1H, s). 13C NMR (150 MHz, DMSO-d6): δ 10.1, 55.2,
114.3 (2C), 119.4, 123.4, 128.3 (2C), 129.4 (2C), 129.9 (2C), 131.3, 131.5, 139.7, 150.8, 152.3, 160.3,
164.5. Anal. Calcd for C19H17N3O3: C, 68.05; H, 5.11; N, 12.53. Found: C, 68.24; H, 5.07; N, 12.21.
(Z)-2-[3-Methyl-5-(4-nitrophenyl)-1,2,4-triazol-4-yl]-3-phenyl-2-propenoic acid [(Z)-2l].
Mp
266.0–267.0 °C. IR (KBr): 3446, 1762, 1703, 1531, 1339 cm–1. 1H NMR (600 MHz, DMSO-d6): δ
2.19 (3H, s), 7.01 (2H, d, J = 8.2 Hz), 7.38 (2H, dd, J = 7.6, 8.2 Hz), 7.45 (1H, dd, J = 7.6, 7.6 Hz), 7.81
(2H, d, J = 8.9 Hz), 8.14 (1H, s), 8.29 (2H, d, J = 8.9 Hz). 13C NMR (150 MHz, DMSO-d6): δ 10.0,
122.7, 124.2 (2C), 127.8 (2C), 129.4 (2C), 129.8 (2C), 131.0, 131.6, 132.9, 140.4, 148.0, 151.0, 152.4,
164.1. Anal. Calcd for C18H14N4O4: C, 61.71; H, 4.03; N, 15.99. Found: C, 61.81; H, 3.76; N, 15.95.

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(Z)-2-(5-Benzyl-3-methyl-1,2,4-triazol-4-yl)-3-phenyl-2-propenoic
acid
[(Z)-2m].
Mp
198.0–199.0 °C. IR (KBr): 3039, 1711, 1642 cm–1. 1H NMR (600 MHz, DMSO-d6): δ 2.05 (3H, s),
3.77 (2H, s), 6.82 (2H, d, J = 7.6 Hz), 7.14–7.07 (5H, m), 7.28 (2H, dd, J = 7.6, 7.6 Hz), 7.37 (1H, dd, J =
7.6, 7.6 Hz), 7.94 (1H, s). 13C NMR (150 MHz, DMSO-d6): δ 10.1, 30.8, 126.5, 128.1 (2C), 128.8 (2C),
129.0 (2C), 129.5 (2C), 130.8, 131.5, 135.5, 138.5, 148.0, 150.3, 152.3, 164.5. Anal. Calcd for
C19H17N3O2: C, 71.46; H, 5.37; N, 13.16. Found: C, 71.30; H, 5.26; N, 13.21.
(E)-2-(5-Benzyl-3-methyl-1,2,4-triazol-4-yl)-3-(1-naphthyl)-2-propenoic acid [(E)-2g].
Mp
229.0–229.5 °C. IR (KBr): 3277, 1693, 1638 cm–1. 1H NMR (600 MHz, DMSO-d6): δ 2.15 (3H, s),
3.69 (2H, s), 7.29–7.27 (1H, m), 7.36–7.34(4H, m), 7.59 (1H, dd, J = 7.6, 8.3 Hz), 7.66–7.63 (2H, m),
7.82 (1H, s), 8.00 (1H, d, J = 8.3 Hz), 8.04 (1H, d, J = 7.6 Hz), 8.30 (1H, d, J = 8.9 Hz), 8.82 (1H, d, J =
7.6 Hz), 11.06 (1H, s). 13C NMR (150 MHz, DMSO-d6): δ 14.4, 30.8, 122.2, 123.3, 126.1, 126.7, 127.3,
127.8, 128.9 (2C), 129.4, 129.5 (3C), 131.3, 131.7, 132.2, 133.7, 135.2, 137.4, 164.3, 167.4, 170.4.
Anal. Calcd for C23H19N3O2: C, 74.78; H, 5.18; N, 11.37. Found: C, 74.64; H, 5.05; N, 11.00.
(E)-2-(3,5-Dimethyl-1,2,4-triazol-4-yl)-3-phenyl-2-propenoic acid [(E)-2h]. Mp 160.0–161.0 °C.
IR (KBr) : 3309, 1726, 1689 cm–1. 1H NMR (600 MHz, DMSO-d6): δ 2.05 (3H, s), 2.20 (3H, s), 7.09
(1H, s), 7.44–7.48 (3H, m), 8.23 (2H, d, J= 6.9 Hz), 10.75 (1H, s). 13C NMR (150 MHz, DMSO-d6): δ
14.0, 20.2, 126.6, 128.7 (2C), 130.4, 132.1 (2C), 133.6, 136.1, 163.2, 167.0, 168.9. Anal. Calcd for
C13H13N3O2: C, 64.19; H, 5.39; N, 17.27. Found: C, 63.88; H, 5.14; N, 17.07.
(E)-2-(3-Methyl-5-phenyl-1,2,4-triazol-4-yl)-3-phenyl-2-propenoic acid [(E)-2j]. Mp 218.0–219.0 °C.
IR (KBr): 3138, 1736, 1656 cm–1. 1H NMR (600 MHz, DMSO-d6): δ 2.28 (3H, s), 7.16 (1H, s),
7.51–7.45 (3H, m), 7.59 (2H, dd, J = 7.6, 7.6 Hz), 7.69 (1H, dd, J = 7.6, 7.6 Hz), 7.98 (2H, d, J = 7.6 Hz),
8.27 (2H, d, J = 6.9 Hz), 11.40 (1H, s). 13C NMR (150 MHz, DMSO-d6): δ 14.0, 126.9, 127.7 (2C),
128.7 (2C), 128.8 (2C), 130.5, 130.8, 132.2 (2C), 132.8, 133.6, 136.1, 163.1, 165.6, 167.1. Anal. Calcd
for C18H15N3O2: C, 70.81; H, 4.95; N, 13.76. Found: C, 70.82; H, 4.69; N, 13.47.
(E)-2-[5-(4-Methoxyphenyl)-3-methyl-1,2,4-triazol-4-yl]-3-phenyl-2-propenoic acid [(E)-2k]. Mp
217.5–219.0 °C. IR (KBr): 3237, 1709, 1674 cm–1. 1H NMR (600 MHz, DMSO-d6): δ 2.26 (3H, s),
3.86 (3H, s), 7.12 (2H, d, J = 9.2 Hz), 7.15 (1H, s), 7.46 (1H, dd, J = 6.9, 6.9 Hz), 7.50 (2H, dd, J = 6.9,
8.0 Hz), 7.96 (2H, d, J = 9.2 Hz), 8.27 (2H, d, J = 8.0 Hz), 11.24 (1H, s). 13C NMR (150 MHz,
DMSO-d6): δ 14.1, 55.5, 114.1 (2C), 122.8, 126.9, 128.8 (2C), 129.8 (2C), 130.5, 132.2 (2C), 133.7,
136.2, 162.8, 163.4, 165.1, 167.3. Anal. Calcd for C19H17N3O3: C, 68.05; H, 5.11; N, 12.53. Found: C,
67.81; H, 5.28; N, 12.52.
(E)-2-(5-Benzyl-3-methyl-1,2,4-triazol-1-yl)-3-phenyl-2-propenoic
acid
[(E)-2m].
Mp
186.0–187.0 °C. IR (KBr): 3256, 1701, 1655 cm–1. 1H NMR (600 MHz, DMSO-d6): δ 2.13 (3H, s),
3.69 (2H, d, J = 5.5 Hz), 7.09 (1H, s), 7.30–7.26 (1H, m), 7.36–7.35 (4H, m), 7.48–7.42 (3H, m), 8.22

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(2H, d, J = 8.9 Hz), 11.02 (1H, s). 13C NMR (150 MHz, DMSO-d6): δ 13.9, 39.5, 126.7, 126.8, 128.4
(2C), 128.7 (2C), 129.0 (2C), 130.4, 132.1 (2C), 133.6, 134.7, 136.0, 163.0, 166.9, 169.9. Anal. Calcd
for C19H17N3O2: C, 71.46; H, 5.37; N, 13.16. Found: C, 71.70; H, 5.11; N, 12.87.
(Z)-2’-Acetyl-2-benzoylamino-3-(1-naphthyl)-2-propenohydrazide [(Z)-3n]. Mp 222.0–223.0 °C.
IR (KBr): 3252, 1647, 1608 cm–1. 1H NMR (600 MHz, DMSO-d6): δ 1.91 (3H, s), 7.42 (1H, dd, J = 7.6,
8.3 Hz), 7.46 (2H, dd, J = 7.6, 7.6 Hz), 7.52 (1H, dd, J = 7.6, 7.6 Hz), 7.56 (1H, dd, J = 7.6, 8.3 Hz), 7.58
(1H, dd, J = 7.6, 7.6 Hz), 7.67 (1H, d, J = 7.6 Hz), 7.76 (1H, s), 7.83 (2H, d, J = 7.6 Hz), 7.89 (1H, d, J =
8.3 Hz), 7.95 (1H, d, J = 7.6 Hz), 8.04 (1H, d, J = 8.3 Hz), 9.83 (1H, br s), 9.92 (1H, br s), 10.18 (1H, s).
X-Ray crystallographic analysis of (Z)-2a
A colourless prism (of the molecular formula C17H15N3O2) having approximate dimensions of
0.40×0.30×0.30 mm was mounted on a glass fiber in a random orientation. Preliminary examination and
data collection were performed with Mo Kα radiation (λ= 0.71069 Å) on a Rigaku RAXIS-RAPID
equipped with an imaging plate. Data collection and cell refinement: MSC/AFC diffractometer control.
Data reduction: teXsan for windows version 1.06;7 Structure solution, SIR92;8 Refinement, SHELXL97.9
Crystal data for (Z)-2a. C17H15N3O2, fw = 293.32; monoclinic, space group P21/n; a = 10.335(14) Å, b
= 9.975(17) Å, c = 14.193(19) Å, β = 96.23(8)°, V = 1455(4) Å3; Z = 4; Dcalcd = 1.339 g cm–3; R = 0.056,
wR(F2) = 0.176. Crystallographic data (excluding these structure factors) for (Z)-2a have been deposited
with the Cambridge Crystallographic Data Centre as supplementary publication number CCDC 243254.
Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge
CB2 1EZ, UK (fax: +44(0)-1223-336033 or e-mail: deposit@ccdc.cam.ac.uk).
ACKNOWLEDGMENT
This research was partially supported by a “Scientific Frontier Research Project” from the Ministry of
Education, Sports, Culture, Science and Technology, Japan.
REFERENCES
1. (a) K. Kubo, M. Koshiba, H. Hoshina, and T. Sakurai, Heterocycles, 1998, 48, 25. (b) H. Hoshina, K.
Kubo, A. Morita, and T. Sakurai, Tetrahedron, 2000, 56, 2941. (c) H. Hoshina, H. Tsuru, K. Kubo, T.
Igarashi, and T. Sakurai, Heterocycles, 2000, 53, 2261. (d) K. Maekawa, T. Igarashi, K. Kubo, and T.
Sakurai, Tetrahedron, 2001, 57, 5515. (e) T. Motohashi, K. Maekawa, K. Kubo, T. Igarashi, and T.
Sakurai, Heterocycles, 2002, 57, 269. (f) K. Maekawa, H. Kajiwara, Y. Iseya, T. Igarashi, and T.
Sakurai, Heterocycles, 2003, 60, 637. (g) K. Maekawa, K. Kubo, T. Igarashi, and T. Sakurai,
Tetrahedron, 2004, 60, 1183. (h) K. Maekawa, T. Sasaki, K. Kubo, T. Igarashi, and T. Sakurai,
Tetrahedron Lett., 2004, 45, 3663. (i) K. Maekawa, A. Shinozuka, M. Naito, T. Igarashi, and T.
Sakurai, Tetrahedron, 2004, 60, 10293. (j) K. Maekawa, K. Kubo, T. Igarashi, and T. Sakurai,
Tetrahedron, 2005, 61, 11211. (k) H. Hoshina, K. Maekawa, K. Kobayashi, T. Igarashi, and T.

HETEROCYCLES, Vol. 75, No. 12, 2008
2971
Sakurai, Heterocycles, 2006, 68, 993. (l) Y. Sasaki, K. Maekawa, H. Watanabe, T. Matsumoto, K.
Kubo, T. Igarashi, and T. Sakurai, Tetrahedron Lett., 2007, 48, 4765. (m) K. Maekawa, N. Hishikawa,
K. Kubo, T. Igarashi, and T. Sakurai, Tetrahedron, 2007, 63, 11267. (n) H. Watanabe, K. Maekawa, T.
Igarashi, and T. Sakurai, Heterocycles, 2007, 74, 149.
2. K. Noda, Y. Shimohigashi, and N. Izumiya, ‘The Peptides-Analysis, Synthesis, Biology,’ Vol. 5, ed.
by E. Gross and J. Meienhofer, Academic Press, Inc., New York, 1983, pp. 285-339.
3. (a) Y. S. Rao and R. Filler, Synthesis, 1975, 749. (b) B. Rzeszotarska, J. Karolak-Wojciechowska, M.
A. Broda, Z. Galdecki, B. Trzezwinska, and A. E. Koziol, Int. J. Peptide Protein Res., 1994, 44, 313.
4. (a) A. M. Dave, K. N. Bhatt, N. K. Undavia, and P. B. Trivedi, J. Indian Chem. Soc., 1988, 65, 294.
(b) A. A. Afify, S. EI-Nagdy, M. A. Sayed, and I. Mohey, Indian J. Chem., Sect. B, 1988, 27, 920. (c)
V. Kepe, F. Pozgan, A. Golobic, S. Polanc, and M. Kocevar, J. Chem. Soc., Perkin Trans. 1, 1998,
2813. (d) O. H. Hishmat, N. M. Fawzy, D. S. Farrag, and A. S. Abd EI-AII, Rev. Roum. Chim., 1999,
44, 161. (e) C. T. Brain, J. M. Paul, Y. Loong, and P. J. Oakley, Tetrahedron Lett., 1999, 40, 3275. (f)
S. Polanc, Targets in Heterocyclic Systems, 1999, 3, 33. (g) F. A. A. EI-Mariah, H. A. Saad, H. A.
Allimony, and R. M. Abdel-Rahman, Indian J. Chem., Sect. B, 2000, 39, 36. (h) A. V. Naidu and M.
A. Dave, Asian J. Chem., 2000, 12, 679. (i) A. V. Naidu and M. A. Dave, Asian J. Chem., 2000, 12,
914. (j) N. C. Desai, D. Dave, M. D. Shah, and G. D. Vyas, Indian J. Chem., Sect. B, 2000, 39, 277.
(k) E. C. Lawson, B. E. Maryanoff, and W. J. Hoekstra, Tetrahedron Lett., 2000, 41, 4533. (l) M. D.
Shah, N. C. Desai, K. K. Awasthi, and A. K. Saxena, Indian J. Chem., Sect. B, 2001, 40, 201. (m) F.
Pozgan, S. Polanc, and M. Kocebar, Heterocycles, 2001, 54, 1011. (n) S. D. Trivedi, H. T. Kubawat,
and H. H. Parekh, J. Indian Chem. Soc., 2002, 79, 282.
5. (a) T. L. Gilchrist, J. Chem. Soc., Perkin Trans. 1, 1999, 2849. (b) S. D. Larsen and B. A. DiPaolo,
Org. Lett., 2001, 3, 3341. (c) L. Yet, Prog. Heterocycl. Chem., 2003, 15, 206. (d) M. J. Stocks, D. R.
Cheshire, and R. Reynolds, Org. Lett., 2004, 6, 2969. (e) X.-C. Wang, J.-K. Wang, D.-Q. Wu, and
Y.-X. Zong, Synlett., 2005, 2595.
6. J. A. Riddick, W. B. Bunger, and T. K. Sakano, ‘Organic Solvents,’ 4th ed., Wiley, Chichester, 1986.
7. Molecular Structure Corporation, ‘teXan for Windows. Single Crystal Structure Analysis Software.
Ver. 1.06,’ The Woodlands, Texas, 1999.
8. A. Altomare, G. Cascarano, C. Giacovazzo, and A. Guagliardi, J. Appl. Cryst., 1994, 27, 1045.
9. G. M. Sheldrick, ‘SHELXL 97. Program for the Refinement of Crystal Structure,’ University of
Göttingen, Göttingen, 1997.