One-pot synthesis of fluorescent 2,5-dihydro-1,2,3-triazine derivatives from a cascade rearrangement sequence in the reactions of 1,2,3-triazolium-1- aminide 1,3-dipoles with propiolate esters

Article abstract of DOI:10.1021/jo060752x

The reactions of 1,2,3-triazolium-1-aminides 1 (readily available from benzil bishydrazones) with propiolate esters leads to fluorescent 2,5-dihydro-1,2,3-triazine derivatives 2, 3 in one pot. These synthetic reactions can be carried out in acetone, in wa

Full text of DOI:10.1021/jo060752x

One-Pot Synthesis of Fluorescent 2,5-Dihydro-1,2,3-triazine
Derivatives from a Cascade Rearrangement Sequence in the
Reactions of 1,2,3-Triazolium-1-aminide 1,3-Dipoles with Propiolate
Esters
Richard N. Butler,*,† Aoife M. Fahy,† Anthony Fox,† John C. Stephens,† P. McArdle,†
D. Cunningham,† and A. Ryder†,‡
Chemistry Department and National Centre for Biomedical Engineering Science, National UniVersity of
Ireland, Galway, Ireland
r.debuitleir@nuigalway.ie
ReceiVed April 10, 2006
The reactions of 1,2,3-triazolium-1-aminides 1 (readily available from benzil bishydrazones) with propiolate
esters leads to fluorescent 2,5-dihydro-1,2,3-triazine derivatives 2, 3 in one pot. These synthetic reactions
can be carried out in acetone, in water, or under solvent-free conditions. The reactions involve a Huisgen
cycloaddition followed by a sequence of rearrangements. The final ring-expansion step was blocked by
linking a six-methylene hydrocarbon chain between the prospective 1,2,3-triazine C-4 and C-6 atoms,
using substrate 8 which gave the fused tricyclic azapropellane product 9 exclusively. X-ray crystal structures
were determined for two 2,5-dihydro-1,2,3-triazine derivatives and for compound 9. The UV absorption
of the 1,2,3-triazine derivatives showed a dual absorption at ca. 310 and ca. 390 nm with fluorescent
emission at ca. 480 and 528 nm (for excitation at 317 nm). The significant Stokes shift of ca. 200 nm
shows the potential for biological fluorescent labeling experiments.
Introduction
Among the triazine series, the 1,2,3-triazine system is the least
studied by comparison with 1,2,4- and 1,3,5- triazine structures
because the ring system is the least stable of the three and
synthetic routes are limited.9 Herein we describe10 an experi-
Fluorescent molecules with reactive functional groups have
received considerable recent interest because of their potential
for incorporation as real-time sensors in biomolecular systems.1-8
(4) Krishnamoorthy, S.; Fang, X.; Brandon, M. C.; Su, L.; Hannah, N.
B.; Qian, W. Org. Lett. 2004, 6, 4603-4606.
† Chemistry Department.
‡ National Centre for Biomedical Engineering Science.
(1) Wiskur, S. L.; Ait-Haddou, H.; Anslyn, E. V.; Lavigne J. J. Acc.
Chem. Res. 2001, 34, 963-972.
(5) Moerner, W. E.; Orrit, M. Science 1999, 283, 1670-1676.
(6) Willets, K. A.; Ostroverkhova, O.; He, M.; Twieg, R. J.; Moerner,
W. E. J. Am. Chem. Soc. 2003, 125, 1174-1175.
(2) Han, M. S.; Kim, D. H. Angew. Chem., Int. Ed. 2002, 41, 3809-
3811.
(3) Li-Li, Z.; Hao, S.; Hua-Ping, L.; Hui, W.; Xiao-Hong, Z.; Shi-Kang,
W.; Shuit-Tong, L. Org. Lett. 2004, 6, 1071-1074.
(7) Rigler, R., Orrit, M., Basche, T., Eds.; Single Molecule Spectroscopy;
Nobel Conference Lectures; Springer-Verlag: Berlin, Germany, 2001; Vol.
67.
(8) Weiss, S. Science 1999, 283, 1676-1683.
10.1021/jo060752x CCC: $33.50 © 2006 American Chemical Society
Published on Web 06/28/2006
J. Org. Chem. 2006, 71, 5679-5687
5679

Butler et al.
1
SCHEME 1. Some Key H and 13C NMR Shifts in CDCl3 for 2a and 4a
TABLE 1. 2,5-Dihydro-1,2,3-triazines and Pyrrolo Triazoline
mentally simple one-pot reaction which produces new fluoro-
phore derivatives of the 2,5-dihydro-1,2,3-triazine structure
containing reactive functional groups of an ester and an imine
suitable for bonding. We explore the multistep synthetic pathway
which produces these products. This work has developed from
our studies11 of azolium ylide systems where two of the four π
electrons of a potential 1,3-dipole12 are embedded in an azole
ring.
Products
yield
(%)a
yield
(%)a
entry
product
mp °C
product
mp °C
1
2
3
4
5
6
7
8
2a
2b
2c
2d
2e
3a
3b
3c
3d
3e
6
52
52
35
45
38
38
33
26
33
29
72
92
46
85
122-123
140-141
193-194
179-180
165-167
146-147
144-145
163-164
158-159
213-214
142-143
193-194
173-174
159-161
4a
4b
4c
4d
4e
5a
5b
5c
5d
5e
8
0
186-187
23
27
33
13
8
35
25
25
157-158
174-175
172-174
164-166
145-146
169-170
163-164
143-144
Results and Discussion
9
1. Synthesis and Mechanism. When solutions of the 1,2,3-
triazolium-1-aminide 1,3-dipoles 1 were treated with unsym-
metrical alkyl propiolates in dry acetone and heated for 24 h
under reflux, the substituted 1,2,3-triazine derivatives 2 and 3
were obtained in reasonable yields along with lesser yields of
the fused pyrrolo[2,3-d]-triazoline derivatives 4 and 5 (Scheme
1, Table 1). When the reaction was carried out in undried
acetone quantities of a third product, 6 and 7 were also
encountered from hydrolytic degradation of 2 and 3. This
degradation could also be carried out in high yield by separately
heating solutions of 2 and 3 in 1:1 (v/v) aqueous ethanol. The
10
11
12
13
14
7
8
9
a Yield of isolated product after recrystallization.
degradation occurred either under nitrogen or in air and produced
formanilide and aniline along with triazines 6 and 7.
It probably involved acid catalyzed addition of water to the
imine and competitive fragmentation as shown in Scheme 2
giving formanilide (path A) as well as a formyl group at the
triazine C-5 (path B). Both formanilide and aniline were isolated
as products from the degradation. In path B, air oxidation of
the formyl group and ready decarboxylation gives the 5-H
triazine 6. These reactions are probably driven by the special
leaving-group ability of the extensively delocalized anion of
2,4,6-triaryl-5-alkoxycarbonyl-2-5-dihydro-1,2,3-triazines 6 and
7. These compounds exhibit proton deuterium exchange at C-5
when dissolved in ROD solvents containing alkoxide base but
not in the absence of the base. When the degradation was carried
out in a 1:1 (v/v) EtOD-D2O mixture, compound 7, deuterated
(9) For a review see the following: Ahsawa, A.; Itoh, T. 1,2,3-Triazines
and their Benzo Derivatives. In ComprehensiVe Heterocyclic Chemistry II;
Katritzky, A. R., Rees, C. W., Scriven, E. F., Eds.; Elsevier Science: New
York, 1996; Vol. 6, pp 483-505.
(10) Part of this work has been published in preliminary communication
form: Butler, R. N.; Fahy, A. M.; Fox, A.; Stephens, J. C.; McArdle, P.;
Cunningham, D.; Ryder, A. G. Tetrahedron Lett. 2006, 47, 1721-1724.
(11) Butler, R. N.; Cloonan, O. M.; McArdle, P.; Cunningham, D. J.
Chem. Soc., Perkin Trans. 1 1998, 1295-1297. Butler, R. N.; Wallace, L.
M. J. Chem. Soc., Perkin Trans. 1 2000, 4335-4338.
(12) A survey of 1,3-dipolar cycloadditions can be found in the
following: Huisgen, R. In 1,3-Dipolar Cycloaddition Chemistry; Padwa,
A., Ed.; John Wiley & Sons : New York, 1984; vVol. 1, pp 1-176.
5680 J. Org. Chem., Vol. 71, No. 15, 2006

Synthesis of 2,5-Dihydro-1,2,3-triazine DeriVatiVes
SCHEME 2. Tr-H Is Compound 6 or 7
TABLE 2. Fluorescent Properties, Absorption, and Emission of
the Series 3 and Compound 7
the experimental requirements for these one-pot multistep
synthetic reactions are particularly beneficial as to both labora-
tory and environmental considerations.
λ
abs maxa
band 1
(nm)
ꢀabs max
band 1
λ
abs maxa
λ λ
em maxc em maxc
band 2 area ratiob band 1
band 2
The formation of the products 2 and 3 involves a cascade-
type sequence of rearrangements from the initial cycloadduct
11 (Scheme 3). We have established15 that the 1,2,3-triazolium-
1-aminide 1,3-dipole 1 undergoes HOMOdipole controlled Huis-
gen cycloaddition12 reactions. The exclusive regiochemistry in
the products 2-5, observed herein for the first time, where the
N- terminus has bonded to the unsubstituted carbon of the
alkyne, is in agreement with this. The initial cycloadduct 11
undergoes a symmetry-allowed suprafacial 1,4-sigmatropic
rearrangement to give the products 4 and 5. We have character-
ized12,15 more stable examples of these types of products from
both alkene and general XdY dipolarophiles (where there is
now no CdC in the analogous species 11). We have recently
commented16 on the significance of this rearrangement which
is a nitrogen analogue of the ubiquitous 1,5-rearrangements of
1,3-diene systems allowed by Woodward-Hofmann HOMO
symmetry. In the present reactions the products 4 and 5 are the
first cases with both an H atom at C-5 (Scheme 1) and a double
bond at C-5 and C-6 and they are highly labile, rearranging in
situ with ring expansion. We envisage that this ring expansion
occurs through the dipolar intermediate 12 (Scheme 3) which
arises from heterolytic cleavage of the C(3a)-N(4) bond in the
products 4 and 5 (Scheme 3).
It was of interest to explore whether the ring expansion to
the 1,2,3-triazine derivative would still occur if the C-3a and
C-6a bridgeheads of compounds 5 were linked with a suf-
ficiently long chain, for example, six methylene groups (indi-
cated by Dreiding models). This would give the product 10
(Scheme 4). The 1,3-dipole 8 was synthesized from DL trans-
1,2-cyclooctanediol by oxidation followed by bisarylhydrazone
formation and subsequent oxidation of the bisarylhydrazone to
the 1,3-dipole 8. The sole product from the reaction of 8 with
methyl propiolate was the tricyclic compound 9 (85%), formed
from the cycloaddition and 1,4-rearrangement steps. This
product could not be induced to rearrange to the structure 10.
A referee has pointed out that this result is not surprising since
the structure may force the dihydrotriazine ring toward planarity
thereby becoming approximately isosteric with the strained [4]
meta cyclophane.17 However since there are six methylene
groups linking the triazine C-3 to C-5 in structure 10, the strain
should be lessened as inferred by the Dreiding models, but it
still could be significant. Another effect of the six methylene
chain may be to destabilize the intermediate 12 both sterically
and by loss of phenyl stabilization of the cationic terminus of
the ylide thereby preventing the ring expansion.
compd
(M-1 cm-1
)
(nm)
(est)
1.5
2.0
3.1
1.7
(nm)
(nm)
3a
3b
3c
3d
3e
7
307
307
310
309
378
322
19914
18213
25971
26540
30548
19192
392
391
391
391
483.6
483.7
482.6
482.8
499
528.7
528.2
528.1
528.1
377
1.1 (est)
478.9
516.7
a Steady-state excitation data recorded with the irradiation set at 470
nm and at a concentration of 10-6 M in MeOH. b Estimated approximate
area ratios band 1/band 2 from best fit Gaussian functions at the offset
baseline. c Steady-state emission data recorded with 317 nm excitation at a
concentration of 10-6 M in MeOH.
at C-5, was obtained thereby confirming the presence of the
carbanion in the reaction.
The compounds 2 and 3 displayed a green fluorescence (Table
2) which was a property of the dihydrotriazine unit. This
fluorescence was retained in compounds 6 and 7. The pyrrolo-
[2,3-d]-1,2,3-triazoline products 4 and 5 were precursors to the
2,5-dihydro-1,2,3-triazine products 2 and 3. When compounds
5a and 5d were separately heated under reflux in acetone for
24 h, the triazines 3a and 3d were obtained in 24 and 20%
yields, respectively. In the overall reaction from substrates 1,
the yields of the fluorescent triazines were increased and reduced
by the presence of electron donating and electron withdrawing
X-substituents, respectively, for standard synthetic conditions
(Scheme 1, Table 1) (suggesting that stabilization of the
triazolium terminus of the intermediate 12, Scheme 3, facilitates
the ring expansion). For the reaction of the parent substrate 1a
with methyl propiolate, it was found that with water as the
medium, where both reactants are insoluble, a reaction at 90
°C for 24 h gave the product 3a in 79-81% yield along with
only 6-7% of 7a. Interestingly, water enhanced the in situ
conversion of the pyrrolo[2,3-d]-1,2,3-triazoline 5a to the
triazine 3a but without an organic cosolvent did not significantly
hydrolyze the imine group in the latter. Breslow13 first estab-
lished the beneficial effects of water as a solvent for organic
synthetic reactions where the hydrophobic effect13 plays a key
role.
We have also recently observed14 successful cycloadditon
reactions in water with insoluble phthalazinium dicyanomethanide
1,3-dipoles and liquid dipolarophiles. Under solvent-free condi-
tions when the solid 1,3-dipole 1a was mixed with an equimolar
quantity of liquid methyl propiolate (neither in excess as
potential solvent) in a glass tube and heated at 60 °C for 1 h,
the fluorescent product 3a was obtained in 71% yield. Hence,
(15) Butler, R. N.; Lysaght, F. A.; Burke, L. A. J. Chem. Soc., Perkin
Trans. 2 1992, 1103-1106.
(16) Butler, R. N.; Coyne, A. G.; Cunningham, W. J.; Moloney, E. M.;
Burke, L. A. HelV. Chim. Acta 2005, 88, 1626-1628.
(17) Tsuji, T. In Modern Cyclophane Chemistry; Gleiter, R., Hopf, H.,
Eds.; Wiley: New York, 2004; pp 81-104.
(13) Breslow, R.; Rideout, D. J. Am. Chem. Soc. 1980, 102, 7816-7817.
Biscoe, M. R.; Breslow, R. J. Am. Chem. Soc. 2002, 125, 12718-12719.
Breslow, R. Acc. Chem. Res. 2004, 37, 471-478.
(14) Butler, R. N.; Coyne, A. G.; Cunningham, W. J.; Burke, L. A. J.
Chem. Soc., Perkin Trans. 2 2002, 1807-1815.
J. Org. Chem, Vol. 71, No. 15, 2006 5681

Butler et al.
SCHEME 3
1
SCHEME 4. Ar, p-NO2-C6H4. H and 13C NMR Shifts in CDCl3
2. Product Structures. The structures of the products 2-7
and 9 were established from microanalyses, IR, and proton and
carbon-13 NMR spectra which showed all of the expected
signals and multiplicities. Representative examples of some key
chemical shifts are shown in Schemes 1 and 4. The carbon-13
NMR assignments were supported by DEPT spectra. The
structures 4, 5, and 9 contain an embedded enamine moiety at
N-4, C-5, and C-6 within the dihydropyrrole ring. The R- and
â- enamine sites (C-5 and C-6, respectively) showed the
expected deshielding and shielding associated with the enamine
resonance,
Analysis of the emission spectra (Tables 2 and 3) indicate
that the 390 nm absorption band is associated with the emission
band centered at approximately 480 nm, whereas the more
intense absorption band near 320 nm is related to the longer
wavelength emission at ca. 520 nm. The large Stokes shift of
∼120 nm with 400 nm excitation, and even larger separation
of ∼200 nm with 317 nm excitation, makes these molecules
attractive fluorescent labels for a wide variety of applications.
The large separation between excitation and emission enables
the use of simple optics and filters. The utility of these molecules
as potential biological probes is also derived from the sensitivity
of the emission to the local environment as evident from the
The regiochemistry of the cycloaddition in the structures 4 and
5 was established by locating the original alkyne proton at C-5
through carbon-13 distortionless enhancement by polarization
transfer (DEPT) spectra and by proton nuclear Overhauser effect
(NOE) difference spectra which showed strong enhancements
(11-13%) between H-5 and the 4-N-phenyl Hortho signals. The
product structures were further supported with X-ray crystal
structure determinations on compounds 3a, 7a, and 9 (Figures
1-3, respectively, in Supporting Information). The X-ray
structures of compounds 3a and 7a show some crowding and
twisting of the substituents on the C-4, C-5, and C-6 carbons
of the dihydro-1,2,3-triazine ring so that there is no plane of
symmetry through the N-2, C-5 axis, and the carbons at C-4
and C-6 show slightly different carbon-13 NMR signals.
3. Fluorescent Properties. Compounds 3a-d display two
strong absorption bands below ca. 400 nm, the first at ca. 300
nm and the second at ca. 400 nm (Table 2). Excitation of
compounds 3a-d and 7 at ca. 300 nm (Figure 1) or ca. 400
nm results in a dual band (480 and 530 nm bands) emission
centered at ca. 520 nm, which is sensitive to the excitation
wavelength used (Figure 2A). The nitro substituted compound
3e has only a single very weak emission band. Excitation at ca.
320 nm leads to more intense emission than 400 nm excitation
(about 2.5 times), and the ratio is approximately equal to the
intensity ratio of the absorption bands. The wavelength of
excitation also influences the ratio of the two emission bands
(Figure 2A). In the case of 3a the ratio between band 1 (480
nm) and band 2 (530 nm) increases from 0.6 to 1.2 on going
from 317 to 400 nm excitation (Table 3, column 7 and 8).
FIGURE 1. Normalized excitation (500 nm emission) and emission
(excitation at 317 nm) spectra for 3a in MeOH. Spectra are uncorrected
for instrumental effects.
FIGURE 2. (A) Normalized fluorescence emission spectra of 3a, 10-6
M in MeOH using 317 nm (solid) and 400 nm (dashed) excitation,
showing difference in emission profile; (B) normalized fluorescence
emission spectra of 3a and 3d in MeOH and toluene.
5682 J. Org. Chem., Vol. 71, No. 15, 2006

Synthesis of 2,5-Dihydro-1,2,3-triazine DeriVatiVes
TABLE 3. Steady State Emission Data
λ
em maxa
band 1 (nm)
λ
em maxa
band 2 (nm)
area ratio
(317 nm ex)
areac ratio
(400 nm ex)
compd
solvent
fwhmb (nm)
fwhmb (nm)
3a
MeOH
toluene
483.6
481.1
48
43
528.7
519.2
75
62
0.6
0.7
1.2
0.9
3b
3c
3d
3ed
7
MeOH
toluene
483.7
481.1
48
43
528.2
519.3
72
62
0.6
0.7
1.2
0.9
MeOH
toluene
482.6
481.7
49
43
528.1
521.3
74
64
0.6
0.7
1.1
1.0
MeOH
toluene
482.8
481.7
48
43
528.1
521.3
76
64
0.6
0.7
1.1
1.0
MeOH
toluene
499
498
∼106
∼82
MeOH
toluene
478.9
479.2
42
40
516.7
516.9
58
53
1.4
1.7
1.5
1.5
a Steady-state emission data recorded with 317 nm excitation at a concentration of 10-6 M in MeOH and toluene. b fwhm, full width at half-maximum.
c Area ratio for compounds 3a-d and compound 7, recorded with 400 nm excitation (ex) at a concentration of 10-6 M in MeOH and toluene. d Compound
3e displays a very weak single emission band.
TABLE 4. Fluorescent Lifetime Data for 3aa
component, whose fractional contribution does not vary sig-
wavelength solvent A1 (%) τ1 A2 (%) τ2 A3 (%) τ3
ø2
τ
f
nificantly with emission wavelength, has not yet been identified.
The most interesting point in the lifetime measurements is
that the 520 nm band has a much longer lifetime than the 480
nm band. This 2-fold to 3-fold difference in lifetimes indicates
that the excited state that emits at 520 nm is significantly more
stable than the excited state which emits at 480 nm. The
interconversion between the two excited states is dependent on
the local environment (Table 4), and this yields a potential
lifetime based sensor for solvent polarity and/or hydrogen
bonding ability.
The observed fluorescence properties are indicative of excited
states involving an interaction between the carbonyl oxygen and
the imine unit and may involve a proton transfer.19 In the case
of 3a the X-ray structure shows that the carbonyl oxygen is
close to the hydrogen atom on the imine carbon C(24). In the
case of compound 7 the acidic 5-CH on the triazine ring should
readily transfer to the carbonyl oxygen giving an excited-state
involving keto-enol tautomerism. A deeper photophysical
characterization of these new interesting fluorophores, and in
particular the excited-state dynamics, will necessitate further
extensive spectroscopic work.
470
520
540
570
toluene 30.8
toluene 45.2
toluene 58.2
toluene 76.1
9.6 69.2 3.9
9.8 54.8 3.9
9.5 41.8 3.8
9.8 23.9 4.0
1.32 5.64
1.31 7.85
1.44 8.20
1.42 9.18
470
490
520
540
570
MeOH
MeOH
MeOH
MeOH
MeOH
4.3 11.2 89.3 4.0
16.0 10.7 78.9 4.0
28.5 11.6 67.4 4.0
35.6 11.8 60.6 4.0
42.9 12.0 53.6 4.0
6.4
5.1
4.1
3.8
3.5
1.1 1.34 4.09
0.9 1.40 4.89
0.8 1.40 6.05
0.8 1.46 6.65
0.8 1.68 7.36
a Fluorescence lifetime data for compound 3a in MeOH and toluene at
different emission wavelengths using a 405 nm excitation source. Ai
represents the fractional intensities, τi represents the individual lifetime
components, and τ f is the intensity-averaged lifetime.18 The ø2 (goodness
of fit) values are a little high, but this is mostly due to misfits at the
beginning of the decay traces and is largely attributed to light scatter and
small mismatches between the instrument response and fluorescence decay
data.
measurements in different solvents (Table 3). This could be
utilized, for example, to study structural changes in macromol-
ecules.
The emission is also sensitive to the solvent environment
(Figure 2B) with the emission intensity becoming weaker by a
factor of ca. 2 in methanol. The other significant differences
are broadening of the emission in methanol compared to toluene
and the red shift in the positions of both peaks. For 3a-d, the
longer wavelength emission band is shifted by ca. 10 nm and
broadened by ca. 10 nm in methanol. Compound 7 does not
display this degree of solvent sensitivity with regard to shifting
of band positions/shape although the emission intensity is ca.
6-8 times stronger in toluene when compared to methanol.
The fluorescence lifetime behavior of these compounds is
complex and is dependent on the emission and excitation
wavelengths. Table 4 displays a fluorescence lifetime analysis
of compound 3a in methanol and toluene.
Experimental Section Procedures
General. Solvents were distilled prior to use and dried by
standard methods. CH2Cl2 and acetone were dried from CaH2 and
KMnO4, respectively, and stored over molecular sieves. Proton
NMR spectra were measured on a 400 MHz spectrometer (carbon-
13 spectra at 100 MHz on the same machine) using tetramethyl-
silane as an internal reference for 1H shifts. Coupling constants, J,
are reported in Hz. Chemical shifts are given in ppm; multiplicities
are indicated by s (singlet), d (doublet), t (triplet), q (quartet), m
(multiplet), and bs (broad signal). NMR spectra were recorded at
probe temperature (19 ( 1 °C) unless otherwise stated. All structural
assignments were supported by DEPT, NOEDS, and COSY. For
prochiral CH2, HA and HB indicate stereochemistry not determined.
IR spectra were measured on neat samples. Flash chromatography
was performed on 230-400 mesh silica gel. TLC was performed
on 0.25 mm silica gel 60 F254 plates and visualized by UV (254
nm).
In both cases the intensity averaged lifetime τ increases
f
on going to longer emission wavelength. This is a consequence
of the two emission bands having different lifetimes. In this
study of 3a we measured the lifetime of the first band (ca. 480
nm) to be 3.9 ( 0.1 ns in toluene and only slightly longer, at
ca. 4.0 ns, in methanol. The second band (ca. 520 nm) in toluene
has a lifetime of 9.7 ( 0.2 ns, but is significantly longer at
11.5 ( 0.5 ns in methanol. The source of the third decay
(18) Sillen, A.; Engelberts, Y. Photochem. Photobiol. 1998, 67 (5), 475-
486.
(19) Moriyama, M.; Kosuge, M.; Tobita, S.; Shizuka, H. Chem. Phys.
2000, 253 (1), 91-103.
J. Org. Chem, Vol. 71, No. 15, 2006 5683

Butler et al.
Measurement of Fluorescence Data. For UV-visible absorp-
tion data, all optical measurements were made using the nonde-
gassed sample held in 1 cm path length, Teflon stoppered, quartz
cuvettes at room temperature. Fluoresence steady-state emission
data were collected on a spectrometer with slit widths set to 5 nm
resolution and a scan speed of 600 nm/min. Emission data were
collected at an excitation wavelength of 317 nm with a concentration
of 10-6 M in spectroscopic grade methanol or toluene. Excitation
spectra were collected at emissions of 470 and 520 nm using the
same instrumental settings. The emission spectra were deconvoluted
by fitting log-normal functions using the GRAMS-AI software
package. Spectra are not corrected for instrument response. The
fluoresence lifetime data were collected on a lifetime spectrometer
using a 405 nm laser diode excitation source. Fluoresence lifetimes
were obtained by deconvolution of the decay data using the fluofit
program.
General Procedure for the Synthesis of 1a, 2a, and 4a. A
suspension of 1,2-bis(phenyl)hydrazone of benzil (1 g, 2.56 mmol)
in dichloromethane (25 mL) was treated with lead dioxide (0.73 g,
3.07 mmol) and stirred for 18 h at ambient temperature. Insoluble
salts were removed and washed thoroughly with dichloromethane.
Evaporation of the combined mother liquor and washings gave 1a
(80%): mp 178-179 °C (from toluene-petroleum spirit bp 60-80
°C).20 The following substrates were similarly prepared and purified;
1b (mp 205-207 °C, 82%), 1c (mp 197-199 °C, 88%),20 1d (mp
187-188 °C, 65%), 1e (mp 180-182 °C, (from Et2O) 73%).20
The following products were synthesized using similar experi-
mental conditions.
5-Ethoxycarbonyl-5-(N-p-methoxyphenylformimidoyl)-2-p-
methoxyphenyl-4,6-diphenyl-2,5-dihydro-1,2,3-triazine 2b. Com-
pound 2b was isolated as a yellow solid which fluoresced intensely
when exposed to UV light (52%): mp 140-141 °C (from ethanol).
1H NMR (400 MHz CDCl3): δ 0.81 (t, 3H, CO2CH2CH3), 3.75 (s,
3H, iminyl N-C6H4-OCH3-p), 3.83 (s, 3H, 2-N-C6H4-OCH3-
p), 3.94 (q, 2H, CO2CH2CH3), 6.78-6.80 (d), 6.89-6.91 (d),
(iminyl N-C6H4-OCH3-p, AA′BB′ JAB 8.7 Hz), 6.94-6.96 (d),
7.81-7.83 (d), (2-N-C6H4-OCH3-p, AA′BB′ JAB 9 Hz), 7.36-
7.38 (m, 4H, aromatics), 7.75-7.76 (m, 6H, aromatics), 8.4 (s, 1H,
-NdCH). 13C NMR (CDCl3): 13.4 (CO2CH2CH3), 54.1 (C-5),
55.5 and 55.7 (OCH3 of iminyl-N-C6H4-OCH3-p and OCH3 of
2-N-C6H4-OCH3-p), 62.6 (CO2CH2CH3), 143.9, 122.0, 117.4,
158.5 (C-1′, C-2′, C-3′, C-4′, respectively, iminyl-N-C6H4-OCH3-
p), 139.4, 129.3, 114.1, 156.1 (C-1′, C-2′, C-3′, C-4′, respectively,
2-N-C6H4-OCH3-p), 134.1, (C-6), 135.1 (C-4), 157.7 (-NdCH),
169.8 (CdO). IR (neat, cm-1): 1728 (CdO), 1598 (CdN). Anal.
Calcd for C33H30N4O4: C, 72.5; H, 5.5; N, 10.2. Found: C, 72.1;
H, 5.3; N, 10.5.
5-Ethoxycarbonyl-5-(N-p-bromophenylformimidoyl)-4,6-di-
phenyl-2-p-bromo-2,5-dihydro-1,2,3-triazine 2c. Compound 2c
was isolated as a solid with intense yellow color (35%): mp 193-
1
194 °C (from ethanol). H NMR (400 MHz CDCl3): δ 0.78 (t,
3H, CO2CH2CH3), 3.93 (q, 2H, CO2CH2CH3), 6.68-6.70 (d),
7.35-7.37 (d), (iminyl N-C6H4-Br-p, AA′BB′ JAB 8.7 Hz), 7.38-
7.40 (m, 6H, aromatic), 7.47-7.50 (d), 7.75-7.78 (d), (2-N-C6H4-
Br-p, AA′BB′ JAB 9.2 Hz), 7.71-7.78 (m, 4H, aromatic), 8.52 (s,
1H -NdCH). 13C NMR (CDCl3): δ 13.3 (CO2CH2CH3), 53.6 (C-
5), 62.5 (CO2CH2CH3), 134.7 (C-6), 135.9 (C-4), 144.2, 117.6,
128.5, 116.4 (C-1′, C-2′, C-3′, C-4′, respectively, 2-N-C6H4-Br-
p), 149.8, 122.1, 129.7, 120.0 (C-1′, C-2′, C-3′, C-4′, respectively,
iminyl -N- C6H4-Br-p), 128.4, 132.1, 131.8 (remaining aromat-
ics), 160.3 (-NdCH), 169.3 (CdO). Anal. Calcd for C31H24-
Br2N4O2: C, 57.7; H, 3.7; N, 8.7. Found: C, 57.9; H, 3.8; N, 8.5.
Synthesis of 5-Ethoxycarbonyl-5-(N-phenylformimidoyl)-
2,4,6-triphenyl-2,5-dihydro-1,2,3-triazine 2a. A suspension of
2,4,5-triphenyl-1,2,3-triazolium-1-phenyl aminide 1a (0.3 g, 0.77
mmol) in dry acetone (10 cm3) was treated with an excess of methyl
propiolate (0.14 cm3, 1.57 mmol). The reaction mixture was stirred
under reflux for 24 h after which time the solvent was removed
under reduced pressure. The residue (in 2 cm3 of methylene
chloride) was placed on a silica gel column (230-400 mesh
ASTM). The column was eluted with a gradient mixture (1:0 to
0:1) (v/v) of petroleum spirit (bp 40-60 °C)/methylene chloride,
using a 2.5% (v/v) changing gradient, to give the product 2a as a
5-Ethoxycarbonyl-5-(N-p-chlorophenylformimidoyl)-2-p-chlo-
rophenyl-4,6-diphenyl-2,5-dihydro-1,2,3-triazine 2d. Compound
2d was isolated as a solid with intense yellow color (45%): mp
179-180 °C (from ethanol). 1H NMR (400 MHz CDCl3): δ 0.78
(t, CO2CH2CH3, 3H), 3.93 (q, CO2CH2CH3, 2H), 6.78-6.81 (d),
7.22-7.24 (d), (iminyl-N-C6H4-Cl-p, AA′BB′ JAB 8.7 Hz), 7.35-
7.38 (d), 7.84-7.87 (d), (2-N-C6H4-Cl-p, AA′BB′ JAB 9.1 Hz),
7.41-7.42 (m, 6H, aromatic), 7.72-7.73 (m, 4H, aromatic), 8.53
(s, 1H -NdCH). 13C NMR (CDCl3): δ 13.4 (CO2CH2CH3), 53.6
(C-5), 61.9 (CO2CH2CH3), 134.7 (C-6), 135.9 (C-4), 149.4, 121.7,
129.2, 132.1 (C-1′, C-2′, C-3′, C-4′, respectively, iminyl -N-
C6H4-Cl-p), 144.6, 117.2, 129.7, 128.7 (C-1′, C-2′, C-3′, C-4′,
respectively, 2-N-C6H4-Cl-p), 128.9, 128.7, 128.5 (remaining
aromatics), 159.7 (-NdCH), 169.7 (CdO). Anal. Calcd for C31H24-
Cl2N4O2: C, 67.0; H, 4.3; N, 10.0. Found: C, 66.7; H, 4.4; N,
10.1.
5-Ethoxycarbonyl-5-(N-p-nitrophenylformimidoyl)-2-p-nitro-
phenyl-4,6-diphenyl-2,5-dihydro-1,2,3-triazine 2e. Compound 2e
was isolated as a solid with an intense yellow color (38%): mp
165-167 °C (from ethanol). 1H NMR (400 MHz CDCl3): δ 0.80
(t, 3H, CO2CH2CH3), 3.98 (q, 2H, CO2CH2CH3), 6.76-6.79 (d),
8.03-8.06 (d), (iminyl-N-C6H4-NO2-p, AA′BB′ JAB 8.9 Hz),
7.93-7.95 (d), 8.20-8.22 (d), (2-N-C6H4-NO2-p, AA′BB′ JAB
9.4 Hz), 7.36-7.41 (m, 6H, aromatics), 7.71-7.73 (m, 4H,
aromatics), 8.73 (s, 1H, -NdCH). 13C NMR (CDCl3): 13.3 (CO2-
CH2CH3), 53.2 (C-5), 63.1 (CO2CH2CH3), 134.1 (C-6), 138.3 (C-
4), 149.1, 115.5, 124.9, 143.4 (C-1′, C-2′, C-3′, C-4′, respectively,
2-N-C6H4-NO2-p), 156.2, 120.6, 125.3, 145.9, (C-1′, C-2′, C-3′,
C-4′, respectively, iminyl-N-C6H4-NO2-p), 128.2, 128.8, 130.4
(remaining aromatics), 162.9 (-NdCH), 168.7 (CdO). Anal. Calcd
for C31H24N6O6: C, 64.5; H, 4.1; N, 14.5. Found: C, 64.3; H, 4.0;
N, 14.5.
1
yellow solid (52%): mp 122-123 °C (from ethanol). H NMR
(400 MHz CDCl3): δ 0.87 (t, CO2CH2CH3, 3H), 4.0 (q, CO2CH2-
CH3, 2H), 6.93-6.95 (d, J ) 7.7 Hz, 2H Hortho iminyl-N-Ph),
7.18-7.49 (m, 10H, Ar-H), 7.86-7.89 (m, 4H, Ar-H), 8.0-8.02
(d, J ) 7.7 Hz, 2H, aromatics), 8.51 (1H, s, -NdCH). 13C NMR
(CDCl3): δ 13.5 (CO2CH2CH3), 53.7 (C-5), 62.5 (CO2CH2CH3),
135.0 (C-6), 135.4 (C-4), 145.4, 116.2, 128.7, 123.7 (C-1′, C-2′,
C-3′, C-4′ respectively, 2-N-Ph), 151.1, 120.5, 129.6, 126.3 (C-
1′, C-2′, C-3′, C-4′ respectively, iminyl-N-Ph), 129.0, 129.1
(remaining aromatics), 159.9 (-NdCH), 169.7 (CdO). IR (NaCl)
ν cm-1: 1729.6 (CdO), 1598.1 (CdN). Anal. Calcd for C31H26N4O2:
C, 76.5; H, 5.3; N, 11.5. Found: C, 76.1; H, 5.0; N, 11.3.
6-Ethoxycarbonyl-2,3a,4,6a-tetraphenyl-3,3a,4,6a-tetrahydro-
pyrrolo[2,3-d]-[1,2,3]-triazol-2-ium-3-ide 4a. Compound 4a, a
second product, was isolated subsequently from the column as a
yellow solid (8%): mp 186-187 °C (from ethanol). 1H NMR (400
MHz CDCl3): δ 1.12 (t, 3H, CO2CH2CH3), 4.03-4.08 (m, 1H,
HA of CH2), 4.18-4.23 (m, 1H, HB of CH2), 6.92-6.98 (m, 10H,
Ar-H), 7.1-7.2 (m, 4H, aromatics), 7.5-7.6 (m, 4H, aromatics),
8.40 (s, 1H, 5-CH), 8.42-8.44 (m, 2H, aromatics). 13C NMR
(CDCl3): δ 14.5 (CO2CH2CH3), 59.6 (CO2CH2CH3), 93.0 (C-6a),
105.7 (C-3a), 107.6 (C-6), 135.9 (C-1′, 6a-Ph), 137.7 (C-1′, 3a-
Ph), 140.6, 123.2, 126.8, 129.0 (C-1′, C-2′, C-3′, C-4′, respectively,
2-N-Phenyl), 139.3, 118.1, 127.5, 129.1 (C-1′, C-2′, C-3′, C-4′,
respectively, 4-N-Ar), 148.6 (C-5), 131.9, 127.7, 127.5 (remaining
aromatics), 165.0 (CdO). IR (neat, cm-1): 1705 (Cd0). Anal.
Calcd for C31H26N4O2: C, 76.5; H, 5.4; N, 11.5. Found: C, 76.6;
H, 5.5; N, 11.8. The remaining eluents were intractable resins.
(20) Butler, R. N.; Gillan, A. M.; Collier, S.; James, J. P. J. Chem. Res.
Synop. 1987, 332-333.
5684 J. Org. Chem., Vol. 71, No. 15, 2006

Synthesis of 2,5-Dihydro-1,2,3-triazine DeriVatiVes
6-Ethoxycarbonyl-3a,6a-diphenyl-2,4-bis(p-bromophenyl)-
3,3a,4,6a-tetrahydropyrrolo[2,3-d][1,2,3]triazol-2-ium-3-ide 4c.
Compound 4c was isolated as a yellow solid (23%): mp 157-158
C6H4-OCH3-p, AA′BB′ JAB 8.7 Hz), 6.95-6.97 (d), 7.83-7.86
(d), (2-N-C6H4-OCH3-p, AA′BB′ JAB 9.1 Hz), 7.36-7.38 (m, 6H,
aromatics), 7.78-7.80 (m, 4H, aromatics), 8.39 (s, 1H, -NdCH).
13C NMR (CDCl3): δ 52.9 (CO2CH3), 53.7 (C-5), 55.2 and 55.4
(OCH3 of 2-N-C6H4-OCH3-p and OCH3 of iminyl-N-C6H4-
OCH3-p), 134.6 (C-6), 135.1 (C-4), 144.0, 121.9, 114.0, 158.5 (C-
1′, C-2′, C-3′, C-4′, respectively, iminyl-N- C6H4-OCH3-p), 139.5,
117.3, 114.1, 156.3 (C-1′, C-2′, C-3′, C-4′, respectively, 2-N-
C6H4-OCH3-p), 128.2, 128.8, 129.2 (remaining aromatics), 158.2
(-NdCH), 169.3 (CdO). Anal. Calcd C32H28N4O4: C, 72.2; H,
5.2; N, 10.5. Found: 72.3; H, 4.9; N, 10.7.
5-Methoxycarbonyl-5-(N-p-bromophenylformimidoyl)-2-p-
bromophenyl-4,6-diphenyl-2,5-dihydro-1,2,3-triazine 3c. Com-
pound 3c was isolated as a yellow solid which fluoresced intensely
when exposed to UV light (26%): mp 163-164 °C (from ethanol).
1H NMR (400 MHz CDCl3): δ 3.5 (s, OCH3, 3H), 6.65-6.67 (d),
7.35-7.37 (d), (iminyl-N-C6H4-Br-p, AA′BB′ JAB 8.7 Hz), 7.40-
7.42 (m, 6H, aromatic), 7.49-7.52 (d), 7.78-7.80 (d), (2-N-C6H4-
Br-p, AA′BB′ JAB 9.1 Hz), 7.75-7.76 (m, 4H, aromatic), 8.51 (s,
1H, -NdCH). 13 C NMR (CDCl3): δ 53.4, 53.5 (C-5 and OCH3),
134.6, 135.9 (C-6 and C-4), 149.4, 122.1, 129.8, 120.0 (C-1′, C-2′,
C-3′, C-4′, respectively, iminyl-N-C6H4-Br-p), 144.2, 117.7,
128.5, 116.5 (C-1′, C-2′, C-3′, C-4′, respectively, 2-N-C6H4-Br-
p), 131.8, 132.8 (overlapping aromatics), 161.0 (-NdCH), 170.0
(CdO). Anal. Calcd for C30H22Br2N4O2: C, 57.1; H, 3.4; N, 8.9.
Found: C, 57.2; H, 3.6; N, 9.1.
5-Methoxycarbonyl-5-(N-p-chlorophenylformimidoyl)-2-p-
chlorophenyl-4,6-diphenyl-2,5-dihydro-1,2,3-triazine 3d. Com-
pound 3d was isolated as a yellow solid that fluoresced intensely
when exposed to UV light (33%): mp 158-159 °C (from ethanol).
1H NMR (400 MHz CDCl3): δ 3.54 (s, 3H, OCH3), 6.70-6.72
(d), 7.19-7.21 (d), (iminyl N-C6H4-Cl-p, AA′BB′ JAB 8.4 Hz),
7.35-7.37 (d), 7.83-7.85 (d), (2-N-C6H4-Cl-p, AA′BB′ JAB 9.1
Hz), 7.40-7.42 (m, 6H, aromatic), 7.74-7.75 (m, 4H, aromatic),
8.48 (s, 1H, -NdCH); 13C NMR (CDCl3): δ 53.4 and 53.5 (C-5
and OCH3), 134.6 (C-6), 135.7 (C-4), 149.3, 121.7, 129.1, 132.1,
(C-1′, C-2′, C-3′, C-4′, respectively, iminyl-N-C6H4-Cl-p) 143.7,
117.2, 128.9, 128.8 (C-1′, C-2′, C-3′, C-4′, respectively, 2-N-
C6H4-Cl-p), 129.8, 128.4, 128.5 (remaining aromatics), 160.9
(-NdCH), 170.0 (CdO). IR (neat, cm-1): 1740 (CdO), 1598 (Cd
N). Anal. Calcd for C30H22Cl2N4O2: C, 66.6; H, 4.1; N, 10.3.
Found: C, 66.4; H, 4.1; N, 10.2.
1
°C (from ethanol). H NMR (400 MHz CDCl3): δ 1.13 (t, 3H,
CO2CH2CH3), 4.03-4.11 (m, 1H, HA of CO2CH2CH3), 4.16-4.24
(m, 1H, HB of CO2CH2CH3), 6.89-7.0 (m, 5H, aromatics), 7.08-
7.10 (d), 7.65-7.68 (d), (4-N-C6H4-Br-p, AA′BB′ JAB 8.9 Hz),
7.25-7.28 (d), 8.31-8.33 (d), (2-N-C6H4-Br-p, AA′BB′ JAB 8.9
Hz), 6.89-7.0 (m, 10H, aromatics), 8.33 (s, 1H, 5-CH). 13 C NMR
(CDCl3): δ 14.4 (CO2CH2CH3), 59.8 (CO2CH2CH3), 93.1 (C-6a),
105.5 (C-3a), 108.5 (C-6), 135.3 (C-1′, 6a-Ph), 137.2 (C-1′, 3a-
Ph), 139.3, 124.7, 132.2, 126.4 (C-1′, C-2′, C-3′, C-4′, respectively,
2-N-C6H4-Br-p), 138.4, 119.5, 132.1, 115.4 (C-1′, C-2′, C-3′,
C-4′, respectively, 4-N-C6H4-Br-p), 127.1, 127.6, 127.8 (remain-
ing aromatics), 147.9 (C-5), 164.7 (CdO). IR (neat, cm-1): 1705
(CdO). Anal. Calcd for C31H24Br2N4O2: C, 57.8; H, 3.7; N, 8.7.
Found: C, 57.7; H, 3.9; N, 8.4.
6-Ethoxycarbonyl-3a,6a-diphenyl-2,4-bis(p-chlorophenyl)-
3,3a,4,6a-tetrahydropyrrolo[2,3-d][1,2,3]triazol-2-ium-3-ide 4d.
Compound 4d was isolated as a yellow solid (27%): mp 174-
1
175 °C (from ethanol). H NMR (400 MHz CDCl3): δ 1.13 (t,
CO2CH2CH3, 3H), 4.05-4.11 (m, 1H, HA of CO2CH2CH3), 4.17-
4.23 (m, 1H, HB of CO2CH2CH3), 6.89-7.00 (m, 8H, aromatic),
7.11-7.14 (m, 6H, aromatic), 7.50-7.52 (d), 8.38-8.41 (d), (2-
N-C6H4-Cl-p, AA′BB′ JAB 9.1 Hz), 8.33 (s, 1H, 5-CH). 13C NMR
(CDCl3): δ 14.4 (CO2CH2CH3), 59.7 (CO2CH2CH3), 93.1 (C-6a),
105.6 (C-3a), 108.4 (C-6), 135.4 (C-1′, 6a-Ph), 137.3 (C-1′, 3a-
Ph), 138.9, 124.5, 127.6, 137.9 (C-1′, C-2′, C-3′, C-4′, respectively,
2-N-C6H4-Cl-p), 138.1, 119.1, 129.2, 127.0, (C-1′, C-2′, C-3′,
C-4′, respectively, 4-N-C6H4-Cl-p), 127.8 (remaining aromatic)
148.0 (C-5), 164.7 (CdO). Anal. Calcd for C31H24Cl2N4O2: C,
67.05; H, 4.3; N, 10.0. Found: C, 66.75; H, 4.4; N, 9.9.
6-Ethoxycarbonyl-3a,6a-diphenyl-2,4-bis(p-nitrophenyl)-
3,3a,4,6a-tetrahydropyrrolo[2,3-d][1,2,3]triazol-2-ium-3-ide 4e.
Compound 4e was isolated as a yellow solid (33%): mp 172-174
1
°C (from ethanol). H NMR (400 MHz CDCl3): δ 1.15 (t, 3H,
CO2CH2CH3), 4.09-4.15 (m, 1H, HA of CO2CH2CH3), 4.18-4.25
(m, 1H, HB of CO2CH2CH3), 6.90-6.92 (m, 4H, aromatic), 6.97-
7.02 (m, 6H, aromatic), 7.23-7.26 (d), 8.05-8.07 (d), (4-N-C6H4-
NO2-p, AA′BB′ JAB 9.4 Hz), 8.40-8.42 (d), 8.65-8.67 (d), (2-
N-C6H4-NO2-p, AA′BB′ JAB 9.1 Hz), 8.44 (s, 1H, 5-CH). 13C
NMR (CDCl3): δ 14.4 (CO2CH2CH3), 60.4 (CO2CH2CH3), 93.2
(C-6a), 105.6 (C-3a), 112.2 (C-6), 134.5 (C-1′, 6a-Ph), 136.3 (C-
1′, 3a-Ph), 144.0, 124.5, 125.4, 146.3 (C-1′, C-2′, C-3′, C-4′,
respectively, 2-N-C6H4-NO2-p), 144.4, 117.0, 124.4, 142.0 (C-
1′, C-2′, C-3′, C-4′, respectively, 4-N-C6H4-NO2-p), 127.8, 128.2,
128.4 (remaining aromatics), 150.3 (C-5), 164.0 (CdO). Anal.
Calcd for C31H24N6O6: C, 64.5; H, 4.1; N, 14.6. Found: C, 64.8;
H, 3.9; N, 14.7.
5-Methoxycarbonyl-5-(N-p-nitrophenylformimidoyl)-2-p-ni-
trophenyl-4,6, diphenyl-2,5-dihydro-1,2,3-triazine 3e: Compound
3e was isolated as a yellow solid which fluoresced intensely when
1
exposed to UV light (29%): mp 213-214 °C (from ethanol). H
NMR (400 MHz CDCl3): δ 3.58 (s, OCH3, 3H), 6.69-6.72 (d),
8.08-8.10 (d), (iminyl-N-C6H4-NO2-p, AA′BB′ JAB 8.7 Hz),
7.45-7.46 (m, 6H, aromatic), 7.73-7.75 (m, 4H, aromatic), 7.97-
8.0 (d), 8.27-8.29 (d), (2-N-C6H4-NO2-p, AA′BB′ JAB 9.6 Hz).
8.71 (s, 1H, -NdCH). 13C NMR (CDCl3): δ 53.9 (OCH3), 53.1
(C-5), 134.1 (C-6), 138.2 (C-4), 156.1, 120.5, 128.9, 145.9 (C-1′,
C-2′, C-3′, C-4′, respectively, iminyl-N-C6H4-NO2-p), 149.1,
115.4, 128.5, 143.4 (C-1′, C-2′, C-3′, C-4,′ respectively, 2-N-
C6H4-NO2-p), 118.8, 124.9, 125.2, 130.5 (remaining aromatics),
163.6 (-NdCH), 169.4 (CdO). Anal. Calcd for C30H22N6O6: C,
64.0; H, 3.9; N, 14.9. Found: C, 64.11; H, 3.67; N, 14.74.
6-Methoxycarbonyl-2,3a,4,6a-tetraphenyl-3,3a,4,6a-tetrahy-
dropyrrolo[2,3-d]-[1,2,3]-triazol-2-ium-3-ide 5a. Compound 5a
was isolated as a yellow solid (13%): mp 164-166 °C (from
5-Methoxycarbonyl-5-(N-phenylformimidoyl)-2,4,6-triphenyl-
2,5-dihydro-1,2,3-triazine 3a. Compound 3a was isolated as a
yellow solid which fluoresced intensely when exposed to UV light
(38%): mp 146-147 °C (from ethanol). 1H NMR (400 MHz
CDCl3): δ 3.54 (s, 3H, OCH3), 6.77-6.79 (d, J ) 8.3 Hz, 2H,
H
ortho 4-N-phenyl ring), 7.11-7.42 (m, 12H, aromatic), 7.76-7.92
(m, 6H, aromatic), 8.47 (s, 1H, -NdCH). 13C NMR (CDCl3): δ
53.6 (-OCH3), 53.7 (C-5), 134.9 (C-6), 135.3 (C-4), 150.0, 120.3,
129.5, 126.3 (C-1′, C-2′, C-3′, C-4′, respectively, iminyl-N-phenyl
ring), 145.4, 116.1, 128.9, 123.6 (C-1′, C-2′, C-3′, C-4′, respectively,
2-N-phenyl ring), 160.5 (-NdCH), 170.2 (CdO). IR (NaCl)
ν cm-1
:
1739.9 (CdO), 1598.8 (CdN). Anal. Calcd for
1
ethanol). H NMR (400 MHz CDCl3): δ 3.6 (s, 3H, CO2CH3),
C30H24N4O2: C, 76.3; H, 5.1; N, 11.9. Found: C, 76.3; H, 4.8; N,
11.6.
6.89-7.0 (m, 10H, aromatic), 7.06-7.09 (m, 4H, aromatic), 7.25-
7.26 (m, 4H, aromatic), 7.66-7.68 (m, 2H, 2-N-Ph, Hortho), 8.40
(s, 1H, 5-CH). 13C NMR (CDCl3): δ 51.2 (OCH3), 92.9 (C-6a),
105.8 (C-3a), 107.4 (C-6), 135.9 (C-1′, 6a-Ph), 137.6 (C-1′, 3a-
Ph), 140.6, 127.0, 123.2, 129.1 (C-1′, C-2′, C-3′, C-4′, respectively,
2-N-phenyl ring), 139.5, 118.2, 122.9, 128.5 (C-1′, C-2′, C-3′, C-4′,
respectively, 4-N-phenyl ring), 132.0, 129.2, 127.7, 127.6, (remain-
ing aromatics), 149.1 (C-5), 165.5 (CdO). IR (NaCl) V cm-1: 1705
5-Methoxycarbonyl-5-(N-p-methoxyphenylformimidoyl)-4,6-
diphenyl-2,5-dihydro-1,2,3-triazine 3b. Compound 3b was iso-
lated as a solid with intense yellow color (33%): mp 144-145 °C
1
(from ethanol). H NMR (400 MHz CDCl3): δ 3.53 (s, 3H, CO2-
CH3), 3.74 (s, 3H), 3.82 (s, 3H), (2-N-C6H4-OCH3-p and iminyl-
N-C6H4-OCH3-p), 6.77-6.79 (d), 6.86-6.88 (d), (iminyl-N-
J. Org. Chem, Vol. 71, No. 15, 2006 5685

Butler et al.
(C)0). Anal. Calcd for C30H24N4O2: C, 76.3; H, 5.1; N, 11.9.
Found: C, 76.1; H, 4.9; N, 11.6.
on a silica gel column (230-400 mesh ASTM), and the column
was eluted with a gradient mixture (1:0 to 1:1) (v/v) of petroleum
spirit (bp 40-60 °C)/ethyl acetate using a 2.5% (v/v) changing
gradient to give the product 6 (0.08 g, 72%): mp 142-143 °C
6-Methoxycarbonyl-3a,6a-diphenyl-2,4-bis(p-methoxyphenyl)-
3,3a,4,6a-tetrahydropyrrolo[2,3-d][1,2,3]triazol-2-ium-3-ide 5b.
Compound 5b was isolated as a yellow solid (8%): mp 145-146
1
(from CH2Cl2: hexane). H NMR (400 MHz CDCl3): δ 0.86 (t,
1
3H, CO2CH2CH3), 4.1 (q, 2H, CO2CH2CH3), 5.28 (s, 1H, 5-CH),
7.38-7.48 (m, 9H, aromatic), 7.88-8.04 (m, 6H, aromatic). 13C
NMR (CDCl3): δ 14.0 (OCH3), 38.8 (C-5) 62.3 (CO2CH2CH3),
134.1, 134.6 (C-4, C-6), 144.3, 117.3, 128.8, 126.8 (C-1′, C-2′,
C-3′, C-4′, respectively, 2-N-Ph), 126.8, 128.8, 130.0 (remaining
aromatics). IR (NaCl) V cm-1, 1742 (CdO). Anal. Calcd for
C24H21N3O2: C, 75.1; H, 5.5; N, 10.9. Found: C, 74.9; H, 5.3; N,
11.1. Formanilide (ca. 60%) and aniline were detected by TLC and
°C (from ethanol). H NMR (400 MHz CDCl3): δ 3.64 (s, 3H),
3.69 (s, 3H), (2-N-C6H4-OCH3-p and 4-N-C6H4-OCH3-p), 3.89
(s, 3H, CO2CH3), 6.70-6.72 (d), 8.37-8.39 (d), (2-N-C6H4-
OCH3-p, AA′BB′ JAB 9.1 Hz), 6.90-7.0 (m, 10H, aromatic), 6.98-
7.0 (d), 7.17-7.19 (d), (4-N-C6H4-OCH3-p, AA′BB′ JAB 9.1 Hz),
8.28 (s, 1H, 5-CH). 13C NMR (CDCl3): δ 51.0 (CO2CH3), 55.4,
55.8 (2-N-C6H4-OCH3-p and 4-N-C6H4-OCH3-p), 92.9 (C-6a),
105.7 (C-3a), 107.4 (C-6), 127.0 (C-1′, 6a-Ph), 131.9 (C-1′, 3a-
Ph), 137.8, 122.9, 129.0, 162.3 (C-1′, C-2′, C-3′, C-4′, respectively,
2-N-C6H4-OCH3-p), 136.0, 123.2, 118.2, 155.6 (C-1′, C-2′, C-3′,
C-4′, respectively, 4-N- C6H4-OCH3-p), 127.6, 129.2 (remain-
ing aromatics), 149.0 (C-5), 165.5 (CdO). Anal. Calcd for
C32H28N4O4: C, 72.1; H, 5.3; N, 10.5. Found: C, 71.8; H, 5.5; N,
10.7.
1
estimated by H NMR in residue (A) prior to column chromatog-
raphy. These products were also isolated from the column but in
lesser quantities than in residue (A) because of losses on the column.
Similar results were obtained for a reaction under nitrogen
atmosphere. Compound 7 was obtained in a similar fashion.
5-Methoxycarbonyl-5-H-2,4,6-triphenyl-2,5-dihydro-1,2,3-tri-
azine 7. Compound 7 was isolated as a yellow fluorescent solid
6-Methoxycarbonyl-3a,6a-diphenyl-2,4-bis(p-bromophenyl)-
3,3a,4,6a-tetrahydropyrrolo[2,3-d][1,2,3]triazol-2-ium-3-ide 5c.
Compound 5c was isolated as a yellow solid (35%): mp 169-170
1
(92%): mp 193-196 °C (CH2Cl2: hexane). H NMR (400 MHz
CDCl3): δ 3.65 (s, 3H, OCH3), 5.32 (s, 1H, 5-CH), 7.43-7.48
(m, 9H, aromatic), 7.96-8.04 (m, 6H, aromatic). 13C NMR
(CDCl3): δ 38.4 (C-5), 53.2 (-OCH3), 134.7, 134.8 (C-6 and C-4),
145.7, 116.2, 128.9, 123.5 (C-1′, C-2′, C-3′, C-4′, respectively, 2-N-
phenylring), 126.6, 128.7, 129.8, 133.3 (remaining aromatics), 167.8
1
°C (from ethanol). H NMR (400 MHz CDCl3): δ 3.6 (s, 1H,
OCH3,), 6.88-6.96 (m, 10H, aromatic), 7.07-7.09 (d), 7.25-7.27
(d), (4-N-C6H4-Br-p, AA′BB′ JAB 9.1 Hz), 7.65-7.67 (d), 8.30-
8.33 (d), (2-N-C6H4-Br-p, AA′BB′ JAB 8.7 Hz), 8.32 (s, 1H,
5-CH). 13C NMR (CDCl3): δ 51.2 (OCH3), 93.0 (C-6a), 105.6 (C-
3a), 108.1 (C-6), 135.4 (C-1′, 6a-Ph), 137.1 (C-1′, 3a-Ph), 139.3,
124.7, 132.3, 126.4 (C-1′, C-2′, C-3′, C-4′, respectively, 2-N-
C6H4-Br-p), 138.3, 119.5, 132.2, 115.5 (4-N-C6H4-Br-p), 127.9,
127.7, 127.5, 127.2 (remaining aromatics), 148.4, (C-5), 165.2 (Cd
O). Anal. Calcd for C30H22Br2N4O2: C, 57.2; H, 3.5; N, 8.9.
Found: C, 57.3; H, 3.4; N, 8.5.
(CdO). IR (NaCl) V cm-1
: 1742 (CdO). Anal. Calcd for
C23H19N3O2: C, 74.8; H, 5.2; N, 11.4. Found: C, 74.3; H, 5.1; N,
11.2.
Reactions in Water and under Solvent Free Conditions. (i)
A suspension of 2,4,5-triphenyl-1,2,3-triazolium-1-phenylaminide
1a (0.3 g, 0.77 mmol) in water (7 cm3) was treated with an excess
of methyl propiolate (0.14 cm3, 1.57 mmol), stirred at 90 °C for
24 h, and extracted into methylene chloride (4 × 10 cm3). The
combined extracts were dried over MgSO4 and evaporated under
reduced pressure, and the residue, in methylene chloride (2 cm3),
was placed on a silica gel column (230-400 mesh ASTM). The
column was eluted with a gradient mixture (1:0 to 2:1 v/v) of
petroleum spirit (bp 40-60 °C)/methylene chloride using a 2.5%
(v/v) changing gradient. The first eluant was 7 (7%). The major
product 3a was subsequently obtained in a high yield of 81%.
(ii) 2,4,5-triphenyl-1,2,3-triazolium-1-phenylaminide 1a (0.1 g,
0.26 mmol) in a test tube was treated dropwise with methyl
propiolate (0.023 cm3, 0.26 mmol), and the stoppered test tube was
heated at 60 °C for 1 h. The residue in methylene chloride (2 cm3)
was placed on a silica gel column (230-400 mesh ASTM). Elution
with a gradient mixture (1:0 to 1:1 v/v) of petroleum spirit (bp
40-60 °C)/methylene chloride gave 3a (73%).
Cyclooctano-1,2,3-triazolium-1-p-nitrophenylaminide-1,3-
dipole 8. A solution of d,L-trans-1,2-cyclooctanediol (12.5 g, 86.8
mmol) and dibutyl tin oxide (21.6 g, 86.8 mmol) in 250 cm3 of
toluene was heated under reflux until 2 cm3 of water had been
collected in the Dean Stark trap (ca. 4 h). Evaporation of the solvent
under reduced pressure gave a syrup which was crystallized from
petroleum spirit (bp 90-100 °C) to give a white crystalline solid
cyclooctane-1,2-di-((n-butyl)tin (1V) ether (15 g, 71%): mp 160-
162 °C (from petroleum spirit (bp 90-100 °C). Anal. Calcd
C16H32O2Sn: C, 51.3; H, 8.5. Found: C, 51.0; H, 8.4.
6-Methoxycarbonyl-3a,6a-diphenyl-2,4-bis(p-chlorophenyl)-
3,3a,4,6a-tetrahydropyrrolo[2,3-d][1,2,3]triazo-2-ium-3-ide 5d.
Compound 5d was isolated as a yellow solid (25%): mp 163-
1
164 °C (from ethanol). H NMR (400 MHz CDCl3): δ 3.66 (t,
3H, CO2CH2CH3), 6.92-6.94 (m, 10H, aromatic), 7.13-7.16 (m,
4H, aromatic), 7.50-7.52 (d), 8.38-8.41 (d), (2-N-C6H4-Cl-p,
AA′BB′ JAB 9 Hz), 8.34 (s, 1H, 5-CH). 13C NMR (CDCl3): δ 51.2
(OCH3), 93.0 (C-6a), 105.7 (C-3a), 107.9 (C-6), 135.3 (C-1′, 6a-
Ph), 137.1 (C-1′, 3a-Ph), 138.8, 124.5, 127.7, 137.8 (C-1′, C-2′,
C-3′, C-4′, respectively, 2-N-C6H4-Cl-p), 138.2, 119.2, 127.8,
127.2 (C-1′, C-2′, C-3′, C-4′, respectively, 4-N-C6H4-Cl-p), 128.0,
129.2, 127.5, 127.6 (overlapping aromatics), 148.5 (C-5), 165.2 (Cd
O). Anal. Calcd for C30H22Cl2N4O2: C, 66.5; H, 4.0; N, 10.3.
Found: C, 66.8; H, 3.80, N, 10.0.
6-Methoxycarbonyl-3a,6a-diphenyl-2,4-bis(p-nitrophenyl)-
3,3a,4,6a-tetrahydropyrrolo[2,3-d][1,2,3]triazo-2-ium-3-ide 5e.
Compound 5e was isolated as a yellow solid (25%): mp 143-144
1
°C (from ethanol). H NMR (400 MHz CDCl3): δ 3.69 (s, 3H,
OCH3), 6.92-7.01 (m, 10H, aromatic), 7.23-7.25 (d), 8.04-8.05
(d), (4-N-C6H4-NO2-p, AA′BB′ JAB 7.7 Hz), 8.40-8.42 (d),
8.65-8.67 (d), (2-N-C6H4-NO2-p, AA′BB′ JAB 8.3 Hz), 8.46 (s,
1H, 5-CH). 13C NMR (CDCl3): δ 51.6 (OCH3), 93.2 (C-6a), 105.6
(C-3a), 134.5 (C-1′, 6a-Ph), 136.1 (C-1′, 3a-Ph), 111.5 (C-6), 144.0,
124.4, 125.4, 146.5 (C-1′, C-2′, C-3′, C-4′, respectively, 2-N-
C6H4-NO2-p), 144.4, 117.0, 124.6, 142.0 (C-1′, C-2′, C-3′, C-4′,
respectively, 4-N-C6H4-NO2-p), 127.9, 124.5 (remaining overlap-
ping aromatic signals), 149.8 (C-5), 164.5 (CdO). Anal. Calcd for
C30H22N6O6: C, 64.0; H, 3.9; N, 14.9. Found: C, 64.1; H, 4.0; N,
15.1.
A solution of the crude white solid (15 g, 0.04 mol) in
dichloromethane (50 cm3) was treated dropwise with bromine (2.06
g, 0.04 mol) in dichloromethane (16 cm3) while stirring over a 30
min period, after which the solvent was allowed to evaporate to
the open air in a fumehood. The crude 2-hydroxy cyclooctanone
oily product (5.7 g, 0.04 mol) was immediately treated with
p-nitrophenylhydrazine (12.2 g, 0.08 mol) in acetic acid (200 cm3),
and the mixture was heated under reflux for 40 min during which
time 1,2-bis(p-nitrophenyl)hydrazone of cyclooctan-1,2-dione pre-
Hydrolytic Degradation of 2 and 3 to 6 and 7. Synthesis of
5-Ethoxycarbonyl-5-H-2,4,6-triphenyl-2,5-dihydro-1,2,3-triaz-
ine 6. A solution of 2a (0.15 g, 0.30 mmol) in a (1:1 v/v) mixture
of aqueous ethanol (40 cm3) was stirred under reflux for 7 days,
cooled, extracted with methylene chloride (4 × 10 cm3), and the
combined extract was dried over MgSO4 and evaporated under
reduced pressure. The residue (A) in CH2Cl2 (2.0 cm3) was placed
1
cipitated (8.70 g, 53%): mp 240-242 °C (from 1,4-dioxane). H
NMR (250 MHz DMSO-d6) 1.47-1.90 (m, 8H, cyclooctyl), 2.67-
5686 J. Org. Chem., Vol. 71, No. 15, 2006

Synthesis of 2,5-Dihydro-1,2,3-triazine DeriVatiVes
2.78 (m, 4H, cyclooctyl), 7.21-7.23 (d), (Hortho of AA′BB′ of NH-
C6H4-NO2-p, JAB 8.8 Hz,), 7.3-7.32 (d), (Hortho of AA′BB′ of
NH-C6H4-NO2-p, JAB 9.3 Hz), 8.14-8.16 (d), (Hmeta of AA′BB′
of NH-C6H4-NO2-p), 8.23-8.26 (d), (Hmeta of AA′BB′ of NH-
C6H4-NO2-p), 10.5 (bs, 1H, NH), 12.42 (bs, 1H, NH, intramo-
lecular H-bonded of ZE form). 13C NMR (DMSO-d6) 25.0, 25.5,
25.4, 26.8, 29.4, 35.3 (methylene chain), 150.2, 112.2, 126.1, 139.1
(C-1′, C-2′, C-3′, C-4′ of NH-C6H4-NO2-p), 145.2 (>CdN-),
149.2 (>CdN-), 151.4, 112.4, 139.5 (C-1′, C-2′, C-3′, C-4′ of
NH-C6H4-NO2-p, one overlapping signal). Anal. Calcd for
C20H22N6O4: C, 58.5; H, 5.4; N, 20.5. Found: C, 58.4; H, 5.3; N,
20.6.
X-ray Structure Determinations. X-ray quality single crystals
of 3a (CCDC 286736), 7 (CCDC 286737), and 9 (CCDC 601382)
were obtained by recrystallization from hexane. Intensity data were
collected at 298 K on a four circle diffractometer with Mo KR
radiation (λ ) 0.71069Å) and a graphite monochromator. The
structures were solved by direct methods, SHELXS-97,22 and
refined by full matrix least squares using SHELXL-97.23 SHELX
operations were automated using ORTEX which was also used to
obtain the drawings.24 All non-hydrogen atoms were refined
anisotropically.
X-ray Crystal Data for Compound 3a. C30H24N4O2, Mr )
472.53 amu; monocyclic, space group P21/n with unit cell a )
10.2928(19) Å, b ) 16.430(4) Å, c ) 14.593(3) Å, and V ) 2466.9-
(8) Å3. Dcalcd ) 1.272 Mg/m3, Z ) 4, T ) 298(2) K, and µ(Mo
KR) ) 0.082 mm-1. The refinement converged to R1 ) 0.0475,
wR2 ) 0.1133 (I > 2σ(I)).
X-ray Crystal Data for Compound 7. C23H19N3O2, Mr )
369.41 amu; orthorhombic, space group P212121 with unit cell a
) 9.9253(13), b ) 10.973(7), c ) 17.458(4) Å, and V ) 1901.4-
(14) Å3. Dcalcd ) 1.290 Mg/m3, Z ) 4, T ) 292(2) K, and µ(Mo
KR) ) 0.084 mm-1. The refinement converged to R1 ) 0.0535,
wR2 ) 0.1362 (I > 2σ(I)).
X-ray Crystal Data for Compound 9. C24H24N606, Mr ) 492.49
amu; triclinic, space group Ph1 with unit cell a ) 11.2071(14) Å, b
) 14.295(2) Å, c ) 15.583 (2) Å, R ) 76.913(12)°, â ) 88.719-
(10)°, γ ) 68.613(12)°, and V ) 2259.3 (5) Å3. Dcalcd ) 1.448
Mg/m3, Z ) 4, T ) 298(2) K, and µ(Mo KR) ) 0.107 mm-1. The
refinement converged to R1 ) 0.0485, wR2 ) 0.1307 (I > 2σ(I)).
Further information on the structure determinations (excluding
structure factors) has been deposited with the Cambridge Crystal-
lographic Data Centre as supplementary publication numbers.
Copies of the data can be obtained, free of charge, on application
to CCDC, 12 Union Road, Cambridge CB2 1EZ, U.K. [fax: +44-
(0)-1223-336033 or e-mail: deposit@ccdc.cam.ac.uk].
A suspension of 1,2-bis(p-nitrophenyl)hydrazone of cyclooc-
tanone-1,2-dione (2 g, 4.88 mmol) in dry methylene chloride (60
cm3) was treated with lead dioxide (5 g, 20.9 mmol) and stirred at
ambient temperature for 48 h. The lead salts were removed by
filtration through Celite after which the filtrate was evaporated under
reduced pressure to give 8, a red crystalline solid (0.92 g, 46%);
1
mp 173-174 °C (from acetone). H NMR (400 MHz CDCl3): δ
1.65 (m, 4H, cyclooctyl CH2), 1.93 (m, 4H, cyclooctyl CH2), 2.94
(m, 4H, cyclooctyl CH2), 6.13 (2H, Hortho of 1-aminide-p-NO2-
C6H4, broad collapsed doublet due to an aryl ring exchange21 in
the 1,2-bisazo form), 8.01 (6H, Hortho of 2-p-NO2-C6H4 and Hmeta
of -aminide-p-NO2-C6H4, broad collapsed multiplet due to aryl
ring exchange21). 13C NMR (CDCl3): 26.3 (broad), 30.4, 112.1
(broad), 126.1 (exchange21 broadened), 142.8 (CdN). Anal. Calcd
for C20H20N6O4: C, 58.8; H, 4.9; N, 20.4. Found: C, 58.6; H, 5.1;
N, 20.4.
2,4-bis-p-Nitrophenyl-6-methoxycarbonyl-3a,6a-hexamethyl-
ene-3,3a,4,6a-tetrahydropyrrolo-[2,3-d]-1,2,3-triazol-2-ium-3-
ide 9. A solution of 8 (0.5 g, 1.22 mmol) in dry acetone (6 cm3)
was treated with methyl propiolate (0.19 cm3, 2.14 mmol), stirred
under reflux for 3 h during which time the product 9 precipitated
as a yellow powder (0.51 g, 85%): mp 159-161 °C (from EtOH).
1H NMR (250 MHz CDCl3): 1.11-1.78 (m, 8H, cyclooctyl), 2.02-
2.04 (m, 1H, cyclooctyl), 2.18-2.24 (m, 1H, cyclooctyl), 2.69-
2.73 (m, 1H, cyclooctyl), 2.92-2.94 (m, 1H, cyclooctyl), 3.81 (s,
3H, OCH3), 7.53-7.55(d), 8.24-8.27 (d), (4-N-C6H4-NO2-p,
AA′BB′ JAB 9.3 Hz), 7.90 (s, 1H, 5-CH), 8.31-8.32 (d), 8.37-
8.40 (d), (2-N-C6H4-NO2-p, AA′BB′ JAB 9.3 Hz). 13C NMR
(CDCl3): δ 24.2, 25.1, 25.8, 28.9, 30.0 (methylene chain, one
overlapping signal), 51.2 (OCH3), 88.6 (C-6a), 101.6 (C-3a), 110.5
(C-6), 144.1, 124.1, 125.6, 149.3 (C-1′, C-2′, C-3′, C-4′, respec-
tively, 2-N-C6H4-NO2-p), 145.4, 116.9, 114.0, 142.6 (C-1′, C-2′,
C-3′, C-4′, respectively, 4-N-C6H4-NO2-p), 146.6 (C-5), 164.8
Acknowledgment. Aoife M. Fahy acknowledges the finan-
cial support of the Irish Research Council for Science Engineer-
ing and Technology (IRCSET). Alan G. Ryder acknowledges
the support of Science Foundation Ireland (Grant No. 02/IN.1/
M231).
Supporting Information Available: Cystallographic informa-
tion files for compounds 3a, 7, and 9 are available in pdf format.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(CdO). IR (NaCl) ν cm-1
: 1705 (CdO). Anal. Calcd for
JO060752X
C24H24N6O6: C, 58.5; H, 4.9; N, 17.1. Found: C, 58.5; H, 4.6; N,
17.1.
(22) Sheldrick, G. M. Acta Crystallogr., Sect. A: Found. Crystallogr.
1990, 46, 467-473.
(21) Butler, R. N.; Cunningham, M. G. J. Chem. Soc., Perkin Trans. 1
1980, 744-749. Butler, R. N.; Evans, A. M.; Gillan, A. M.; James, J. P.;
McNeela, E. M.; Cunningham, D.; McArdle, P. J. Chem. Soc., Perkin Trans.
1 1990, 2537-2544.
(23) Sheldrick, G. M. SHELXL-97, Program for Solution of Crystal
Structures; University of Go¨ttingen: Go¨ttingen, Germany, 1997.
(24) McArdle, P.; Daly, P.; Cunningham, D. J. Appl. Crystallogr. 2002,
35, 378.
J. Org. Chem, Vol. 71, No. 15, 2006 5687