Thermolysis of triazoles as melts - Is the 3,5-diphenyl-1,2,4-triazole group a good leaving group?

Article abstract of DOI:10.1002/1099-0690(200011)2000:22<3749::AID-EJOC3749>3.0.CO;2-X

The mechanism of the rearrangement of 4-alkyltriazoles to the corresponding 1-alkyltriazoles on thermolysis at 330 °C is shown to involve initial formation of an intermediate 1,4-dialkyltriazolium triazolate salt. The triazolate ion subsequently attacks at the alkyl group bearing 1- and 4-positions of the dialkyltriazolium ion, yielding the observed products. No evidence for unimolecular reaction steps has been found. The triazole moiety in these compounds is only a weak leaving group, which requires activation by alkylation. Unimolecular reaction steps never take place, neither from neutral triazole species nor from activated dialkyl-substituted triazolium species.

Full text of DOI:10.1002/1099-0690(200011)2000:22<3749::AID-EJOC3749>3.0.CO;2-X

FULL PAPER
Thermolysis of Triazoles as Melts ؊ Is the 3,5-Diphenyl-1,2,4-triazole Group
a Good Leaving Group?
Odd R. Gautun[a] and Per H. J. Carlsen*[b]
Keywords: Triazole / Thermochemistry / Rearrangements / Reaction mechanisms
The mechanism of the rearrangement of 4-alkyltriazoles to
the corresponding 1-alkyltriazoles on thermolysis at 330 °C
is shown to involve initial formation of an intermediate 1,4-
dialkyltriazolium triazolate salt. The triazolate ion sub-
ucts. No evidence for unimolecular reaction steps has been
found. The triazole moiety in these compounds is only a
weak leaving group, which requires activation by alkylation.
Unimolecular reaction steps never take place, neither from
sequently attacks at the alkyl group bearing 1- and 4-posi- neutral triazole species nor from activated dialkyl-substituted
tions of the dialkyltriazolium ion, yielding the observed prod-
triazolium species.
Introduction
general, this reactivity resembles that of quaternary ammo-
nium ions, which may undergo substitution as well as elim-
ination reactions. Nucleophilic substitution and elimination
are closely related.
The rearrangement of optically active 4-(2-butyl)-substi-
tuted triazoles appeared to be in agreement with this mech-
anism, except that approximately 15% racemization oc-
curred.[4] This was rationalized in terms of the nucleophilic
attack taking place at both the 1- and 4-alkylated positions
of the triazolium ion, but an alternative explanation may
be that partial racemization takes place during the alkyl
Studies of the thermal rearrangement of neat 4-alkyl-sub-
stituted 4H-1,2,4-triazoles, 1, to the corresponding 1-alkyl-
1H-1,2,4-triazoles, 2, have been reported previously.[1] It
was shown that the triazole moiety in such systems behaves
as a leaving group, giving rise to products corresponding to
both substitution and elimination reaction pathways.[2] The
question now arises as to whether alkyl-substituted triazoles
behave like alkyl halides or sulfonates or like, e.g., trialkyl-
amines, which require activation by alkylation in order to
function as leaving groups. We report herein on our efforts
to further elucidate the mechanism of this rearrangement.
This study is also of interest in view of the synthetic utility
of N-substituted benzotriazoles.[3]
group transfer through
triazolate anion ion pair.
a new 2-butyl carbocationϪ
However, unimolecular pathways may also account for
the racemization. There is a good deal of evidence to sug-
gest that in most SN1 reactions the carbenium ions are
never removed far from their leaving groups. Instead, the
nucleophile attacks an ion pair.[5] For triazoles bearing alkyl
substituents that may form stable carbenium ions, cleavage
of the alkylϪtriazole bond may lead to ion-pair formation,
which may facilitate racemization of the optically active
group. This parallels the dual uni- and bimolecular reactiv-
ity of 2-bromobutane.[6] In previous work, we have also
noted that all attempts to prepare 4-substituted triazoles
where the substituent was capable of forming a stabilized
carbenium ion, e.g. with tert-butyl and 1-adamantyl groups,
met with failure and only the elimination products were
isolated.[7]
Results and Discussion
Previous work excluded a concerted, unimolecular mech-
anism, but gave evidence for a mechanism involving an ini-
tial bimolecular nucleophilic displacement reaction leading
to formation of a triazolium triazolate ‘‘salt’’, 3. As a con-
sequence, the triazole ring was activated as a leaving group.
Subsequent nucleophilic attack by the triazole anion at the
alkyl group bearing positions of the triazolium ion of the
ionic intermediate 3 led to formation of the products. This
reaction scheme is bimolecular in nature (Scheme 1). In
Scheme 1
[a]
Faculty of Science, Department of Chemistry, University of
Tromsø,
9037 Tromsø, Norway
[b]
Department of Chemistry, Norwegian University of Science
and Technology,
7491 Trondheim, Norway
Fax: (internat.) ϩ47Ϫ73/59 42 56
E-mail: per.carlsen@chembio.ntnu.no
Scheme 2
Eur. J. Org. Chem. 2000, 3749Ϫ3753
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2000
1434Ϫ193X/00/1122Ϫ3749 $ 17.50ϩ.50/0
3749

O. R. Gautun, P. H. J. Carlsen
FULL PAPER
Scheme 3
Potentially borderline cases are the (2-butyl)triazoles, rise to product mixtures consisting of homoallyl-, cyclobu-
which may react along both uni- and bimolecular pathways. tyl-, and cyclopropylmethyl products.[10] In many cases,
However, thermolysis of a melt containing 1-(2-butyl)-3,5- such systems are known to undergo solvolysis much more
diphenyl-1H-1,2,4-triazole (4),[7] and 4-propyl-3,5-ditolyl- rapidly than the corresponding alkyl compounds.[11] These
4H-1,2,4-triazole (5), led only to the products correspond- reactions have been proposed to proceed through the
ing to the thermal rearrangement of 5, without any signs of formation of a non-classical cation, C4H7ϩ, the structure
cross-over products (Scheme 2). These results indicated that of which has been discussed by several groups.[12] The 4-
ion-pair formation by heterolytic cleavage did not take cyclopropylmethyl-3,5-diphenyl-4H-1,2,4-triazole (10), was
place with the 2-butyl group in the 1-position, thus exclud- prepared according to established methods.[7] Thermolysis
ing unimolecular ion-pair formation by heterolytic cleavage of 10 at 330 °C for 33 min yielded a product mixture con-
of the non-activated triazole.
sisting of 1-cyclopropylmethyl-3,5-diphenyl-1H-1,2,4-tri-
Alternatively, cleavage may take place from the dialkyltri- azole (11), 1-cyclobutyl-3,5-diphenyl-1H-1,2,4-triazole (12),
azolium ion. Thus, the partial racemization observed[4] for and 1-(3-butenyl)-3,5-diphenyl-1H-1,2,4-triazole (13), in a
(S)-8 may occur via the activated triazole, i.e. the dialkyltri- 7.7:1.3:1.0 ratio, together with 33% of the unchanged start-
azolium ion, by cleavage of one of the triazoleϪalkyl bonds ing material and traces of cis- and trans-crotyl-3,5-diphenyl-
resulting in the formation of a free 2-butyl cation together 1H-1,2,4-triazole and 3,5-diphenyl-1H-triazole (7). These
with the neutral triazole, followed by recombination to give are the types of products generally obtained upon solvolysis
the triazolium ion. A driving force for this pathway would of cyclopropylmethyl and cyclobutyl derivatives,[13] or by
be the stability of the sec-butyl cation (Scheme 3).
diazotization of cyclobutylamine or cyclopropylmethyl-
In a quest for other substituents that may form more amine.[14] With these results in mind, thermolysis of 4-cyclo-
stable carbenium ions and which can also function as butyl-3,5-diphenyl-4H-1,2,4-triazole (14), could therefore
probes allowing assessment of full or partial unimolecular be expected to lead to similar products. Indeed, thermolysis
reaction steps, we investigated 4-cyclopropyl-substituted tri- of 14 at 330 °C for 30 min resulted in complete conversion
azoles. Cyclopropyl halides are known to be resistant to with the generation of the same products 11, 12, and 13 in
nucleophilic attack and undergo unimolecular solvolysis re- a 4.3:1.0:1.0 ratio, together with 30% of 3,5-diphenyltri-
actions with concomitant ring-opening of the cyclopropane azole, 7 (Scheme 5). It is noteworthy that 10 was not formed
ring to give the corresponding allyl carbenium ion.[8] Cyclo- upon thermolysis of 14 or vice versa.
propyl-substituted triazoles may therefore represent probes
for unimolecular mechanisms. Thus, 4-cyclopropyl-3,5-di-
phenyl-4H-1,2,4-triazole (9), was prepared according to
standard literature methods.[7] Neat 9 (Scheme 4) was then
subjected to thermolysis at 330 °C for 30 min, but none of
the anticipated products were produced. This was also the
case when the experiment was repeated at 350 °C for
120 min. Some carbonation took place and 87% of the un-
changed starting material was recovered after the thermo-
lysis. Thus, in the neutral cyclopropyltriazole system, the
triazole ring does not function as a leaving group. The re-
sistance of 9 to reaction rules out a low-energy dissociative
ion-pair mechanism.
Scheme 5
The cyclopropylmethyl group, on the other hand, could
be expected to promote formation of ion pairs as cyclopro-
pylmethyl cations are known to be highly stabilized.[9] Ionic
reactions, e.g. solvolyses of cyclopropylmethyl halides, give
The products were isolated by preparative TLC and iden-
tified by comparison of their spectroscopic and chromatog-
raphic properties with those of authentic samples. The re-
sults are presented in Table 1.
The triazoleϪalkyl group CϪN bond is activated to-
wards cleavage in the triazolium salt. To elucidate this pos-
sible pathway, 4-cyclopropylmethyl-1-methyl-3,5-diphenyl-
1,2,4-triazolium tetrafluoroborate (15), was subjected to
thermolysis in solution. This salt was readily prepared by
treating triazole 10 with trimethyloxonium tetrafluorobo-
Scheme 4
3750
Eur. J. Org. Chem. 2000, 3749Ϫ3753

Thermolysis of Triazoles
FULL PAPER
Table 1. Product distributions on thermolysis of the neat triazoles furthermore confirms the previous hypothesis that the tri-
9, 10, and 14 at 330 °C for 30 min; ratios were determined by GC
analysis
azole moiety in these compounds functions as a weak leav-
ing group, requiring activation by alkylation. Unimolecular
reaction steps never take place, neither from the neutral tri-
azole species nor from the activated dialkyl-substituted tri-
azolium species. Among the systems we have studied, the
course of the reaction has been found to be independent of
the nature of the alkyl substituents. The 3,5-diphenyl-1,2,4-
triazole ring can therefore be classified as a poor leaving
group.
Triazole Product 7 Conversion Product distribution
%
%
Relative ratios of compounds:
11
12
13
10
14
9
trace
30
0
77
100
0
7.7
4.3
Ϫ
1.3
1.0
Ϫ
1.0
1.0
Ϫ
rate in 1,2-dichloroethane at 60 °C for 3 h.[15] The NMR
spectra of the crude thermolysate showed no sign of prod-
ucts in which the cyclopropylmethyl group had rearranged.
When thermolysis was attempted in the more polar solvents
acetonitrile and DMF (CD3CN and [D7]DMF) in sealed
NMR tubes at 150 °C for 12 h, again no detectable
amounts of rearrangement products were found. These re-
sults give the general impression that unimolecular reaction
steps do not take place. When the triazolium salt was
heated in acetonitrile at 200 °C for 3 h, however, 1-methyl-
3,5-diphenyl-1H-1,2,4-triazole (16), was formed as the sole
product (Scheme 6), presumably due to attack at the cyclo-
propylmethyl group by the solvent functioning as a weak
nucleophile.
Experimental Section
General: 1H and 13C NMR spectra were recorded on a JEOL JNM-
EX400 FT NMR spectrometer using CDCl3 as solvent and tetra-
methylsilane (TMS) as an internal standard. Ϫ IR and GC-IR
spectra were obtained on a Nicolet 20-SXC FT-IR (GC Carlo Erba
5160, 25 m, CP-Sil-5 CB). Ϫ Mass spectra were recorded on an
AEI MS-902 spectrometer at 70 eV (IP) with an inlet temperature
of 200 °C. Ϫ GC measurements were performed on a Varian 3700
gas chromatograph equipped with a BP-1 capillary column (24 m).
All products were found to be stable under the GC conditions. Ϫ
Melting points are uncorrected.
Thermolysis of 4-Alkyl-3,5-diphenyl-4H-1,2,4-triazoles. ؊ General
Procedure: The triazole (0.06Ϫ0.15 mmol) was placed in a thick-
walled glass tube, which was evacuated and sealed. The sample tube
was then placed in an oven at ca. 330 °C for 30 min. After cooling
to room temperature, the tube was broken, the contents were dis-
solved in dichloromethane, and the composition of the crude prod-
uct was determined by GC analysis. The components of the mix-
ture were subsequently isolated by preparative TLC and their iden-
tities were confirmed by comparison of their spectroscopic and
chromatographic properties with those of authentic samples. The
identities of the products were similarly established by GC-FTIR
analysis.
Scheme 6
The above results are consistent with mechanisms where
no cleavageϪrecombination of the triazoleϪalkyl group
CϪN bonds takes place. This is further supported by the
fact that 10 and 14 do not interconvert (Scheme 5). Elim-
ination products were absent in the thermolysates derived
from the cyclopropylmethyltriazole, whereas the cyclobu-
tyltriazole formed appreciable amounts of elimination
products. Substituted cyclobutanes are known to undergo
elimination reactions, which rarely occur with cyclopro-
pylmethyl compounds.[16] The results with cyclopro-
pylmethyltriazole also excluded possible radical rearrange-
ment mechanisms, as the cyclopropylcarbinyl radical un-
dergoes rapid rearrangement to the homoallylcarbinyl rad-
ical. The use of the radical clock has been discussed.[17] Rate
constants for this reaction have been determined to be of
the order of 2·107 sϪ1 by Castellino and co-workers.[18]
Synthesis of 4-Alkyl-3,5-diphenyl-4H-1,2,4-triazoles. ؊ General
Procedure: A solution of bis(α-chlorobenzylidene)hydrazone[19]
(0.20 g, 0.72 mmol) and the appropriate amine (3.3 mmol) in dry
benzene (10 mL) was placed in a glass ampoule, which was sealed
and then heated in an oil bath at 140 °C for 40 h. After cooling,
the ampoule was opened, the contents were taken up in dichloro-
methane (20 mL), and the resulting solution was washed sequen-
tially with 1  aq. HCl, 2  aq. NaOH, and water. After drying
with anhydrous magnesium sulfate, the solvent was evaporated and
the crude product was recrystallized as detailed below.
4-Cyclopropyl-3,5-diphenyl-4H-1,2,4-triazole (9): After recrystal-
lization from 75% ethanol, the yield of the pure product was
100 mg (53%) (Ͼ 99% pure by GC); m.p. 223.5Ϫ224.0 °C. Ϫ 1H
NMR (400 MHz, CDCl3): δ ϭ 0.39Ϫ0.44 (m, 2 H), 0.92 (q, J ϭ
6.8 Hz, 2 H), 3.54 (sextet, J ϭ 3.6 Hz, 1 H), 7.50Ϫ7.55 (m, 6 H),
7.87Ϫ7.90 (m, 4 H). Ϫ 13C NMR (100 MHz, CDCl3): δ ϭ 10.4,
27.6, 127.4, 128.4, 128.5, 129.6, 156.6. Ϫ IR (KBr): ν˜ ϭ 3068, 3061,
3049, 3041, 3017, 1472, 1467, 1442, 1415, 1287, 1076, 1062, 1030,
1023, 974, 929, 886, 848, 789, 773, 721 cmϪ1. Ϫ MS: m/z (%) ϭ
Conclusion
This study confirms the previously proposed mechanism
for the thermolysis of 4-alkyltriazoles to the corresponding 261 (100) [Mϩ], 260 (32), 144 (26), 131 (12), 130 (25), 104 (23), 103
(49), 89 (33), 77 (30), 63 (13). Ϫ Calcd. for C17H15N3: Mϩ
261.1266; found 261.1262. Ϫ C17H15N3 (261.3): calcd. C 78.14, H
5.79, N 16.08; found C 78.01, H 6.03, N 15.87.
1-alkyltriazoles. This mechanism involves initial formation
of an intermediate salt, a 1,4-dialkyltriazolium triazolate,
from which the product is formed through attack of a nucleo-
phile at the alkylated 4- and 1-positions. Thus, there is no
evidence for unimolecular reaction steps. The present work recrystallization from toluene, the yield of the pure product was
4-Cyclopropylmethyl-3,5-diphenyl-4H-1,2,4-triazole (10): After
Eur. J. Org. Chem. 2000, 3749Ϫ3753
3751

O. R. Gautun, P. H. J. Carlsen
FULL PAPER
120 mg (60%) (97.5% pure by GC). It was obtained as a white
(5 mmol) in dry DMF (5 mL) under nitrogen was added NaH
crystalline material, m.p. 194.0Ϫ195.5 °C. Ϫ H NMR (100 MHz, (0.2 g) and the mixture was stirred for 30 min. Then, the appropri-
CDCl3): δ ϭ (Ϫ0.39)Ϫ(Ϫ0.18) (m, 2 H), 0.16Ϫ0.35 (m, 2 H), ate alkyl halide or sulfonate (5Ϫ7 mmol) was added. The resulting
1
0.52Ϫ0.85 (m, 1 H), 3.97 (d, J ϭ 6.8 Hz, 2 H), 7.49Ϫ7.78 (m, 10
H).[20] 13C NMR (25 MHz, CDCl3): δ ϭ 3.9, 11.4, 49.4, 127.8, added and this solution was washed with 1  aq. HCl, 1  aq.
128.8, 129.1, 129.9, 155.5. Ϫ IR (KBr): ν˜ ϭ 3079, 3031, 3006, 2962, NaOH, and water. After drying over anhydrous magnesium sulfate,
mixture was stirred overnight. Dichloromethane (20 mL) was then
Ϫ
2926, 1471, 1406, 1384, 1328, 1033, 830, 778, 744, 729, 707 cmϪ1
.
evaporation of the solvent gave the product.
Ϫ MS: m/z (%) ϭ 275 (100) [Mϩ], 274 (19), 221 (45), 144 (17), 131
(72), 118 (29), 104 (29), 89 (42), 77 (20), 55 (77). Ϫ Calcd. for
C18H17N3: Mϩ 275.1423; found 275.1418. Ϫ C18H17N3 (275.4):
calcd. C 78.52, H 6.22, N 15.26; found C 78.45, H 6.13, N 15.34.
1-Cyclopropylmethyl-3,5-diphenyl-1H-1,2,4-triazole (11): From 3,5-
diphenyl-1H-1,2,4-triazole and cyclopropylmethyl tosylate, 11 was
obtained in 64% yield as white crystals (97% pure by GC). Ϫ H
1
NMR (400 MHz, CDCl3): δ ϭ 0.24 (q, J ϭ 5.2 Hz, 2 H), 0.50 (q,
J ϭ 6.3 Hz, 2 H), 1.21Ϫ1.30 (m, 1 H), 4.05 (d, J ϭ 6.8 Hz, 2 H),
7.30Ϫ7.40 (m, 3 H), 7.43Ϫ7.47 (m, 3 H), 7.59Ϫ7.63 (m, 2 H), 8.10
(d, J ϭ 6.8 Hz, 2 H). Ϫ 13C NMR (100 MHz, CDCl3): δ ϭ 3.9,
11.5, 53.6, 126.3, 127.7, 128.5, 128.9, 129.5, 130.0, 131.1, 155.3,
161.1. Ϫ IR (KBr): ν˜ ϭ 3082, 3065, 3046, 3033, 3011, 2978, 2947,
1479, 1457, 1443, 1426, 1410, 1394, 1356, 1296, 1284, 1179, 1133,
1115, 1073, 1051, 1027, 1018, 983, 936, 926, 837, 791, 770, 763,
731, 704, 700 cmϪ1. Ϫ MS: m/z (%) ϭ 275 (100) [Mϩ], 274 (25),
248 (3), 221 (50), 144 (17), 131 (58), 118 (33), 104 (44), 103 (14),
91 (12), 89 (35), 77 (21), 63 (13). Ϫ Calcd. for C18H17N3: Mϩ
275.1423; found 275.1418.
4-Cyclobutyl-3,5-diphenyl-4H-1,2,4-triazole (14): After recrystal-
lization from toluene, the yield of the pure product was 88 mg
(44%) (Ͼ 99% pure by GC); m.p. 184.0Ϫ185.5 °C. Ϫ 1H NMR
(400 MHz, CDCl3): δ ϭ 1.45Ϫ1.62 (m, 2 H), 1.81 (dq, J ϭ 9.7 and
2.5 Hz, 2 H), 1.96Ϫ2.03 (m, 2 H), 4.90 (p, J ϭ 8.2 Hz, 1 H),
7.48Ϫ7.51 (m, 6 H), 7.65Ϫ7.69 (m, 4 H). Ϫ 13C NMR (100 MHz,
CDCl3): δ ϭ 15.3, 31.2, 51.0, 128.4, 129.0, 129.8, 155.2. Ϫ IR
(KBr): ν˜ ϭ 3060, 3043, 3009, 2997, 2977, 2947, 1471, 1444, 1413,
1342, 783, 774, 728, 716, 704 cmϪ1. Ϫ MS: m/z (%) ϭ 275 (100)
[Mϩ], 274 (12), 248 (10), 247 (55), 246 (45), 245 (6), 222 (7), 221
(37), 144 (20), 143 (7), 132 (5), 131 (50), 130 (15), 118 (32), 117
(35), 116 (10), 115 (8), 104 (56), 103 (28), 91 (14), 90 (12), 89 (88),
77 (56), 63 (30). Ϫ Calcd. for C18H17N3: Mϩ 275.1423; found
275.1421. Ϫ C18H17N3 (275.4): calcd. C 78.52, H 6.22, N 15.26;
found C 78.64, H 6.39, N 15.04.
1-(3-Butenyl)-3,5-diphenyl-1H-1,2,4-triazole (13): From 3,5-di-
phenyl-1H-1,2,4-triazole and 1-bromo-3-butene, 13 was obtained
1
in 74% yield as an oily product (Ͼ 99% pure by GC). Ϫ H NMR
(400 MHz, CDCl3): δ ϭ 2.70 (q, J ϭ 7.2 Hz, 2 H), 4.29 (t, J ϭ
7.6 Hz, 2 H), 5.04Ϫ5.09 (m, 2 H), 5.67Ϫ5.76 (m, 1 H), 7.38Ϫ7.47
(m, 3 H), 7.50Ϫ7.54 (m, 3 H), 7.64Ϫ7.68 (m, 2 H), 8.16 (d, J ϭ
6.8 Hz, 2 H). Ϫ 13C NMR (100 MHz, CDCl3): δ ϭ 34.2, 48.5,
117.9, 126.3, 128.5, 128.9, 129.0, 130.0, 131.1, 133.4, 155.7, 161.2.
Ϫ IR (neat): ν˜ ϭ 3070, 3033, 3003, 2980, 2948, 1519, 1477, 1464,
1443, 1411, 1354, 1302, 1284, 1174, 1132, 1071, 1027, 1018, 996,
982, 922, 790, 773, 731 cmϪ1. Ϫ MS: m/z (%) ϭ 275 (62) [Mϩ], 274
(45), 221 (42), 131 (100), 118 (21), 104 (71), 103 (25), 91 (11), 89
(16), 77 (35). Ϫ Calcd. for C18H17N3: Mϩ 275.1423; found
275.1418.
3,5-Bis(4-methylphenyl)-4-propyl-4H-1,2,4-triazole (5): From bis(α-
chloro-4-methylbenzylidene)hydrazine (9.7 g, 0.032 mol) in pro-
pylamine (200 mL), 6.84 g (69%) of 5 was obtained after recrystal-
lization from toluene (Ͼ 99% purity by GC); m.p. 202Ϫ203.5 °C.
Ϫ 1H NMR (100 MHz): δ ϭ 0.60 (t, J ϭ 7.3 Hz, 3 H), 1.39 (sextet,
J ϭ 7.3 Hz, 2 H), 2.43 (s, 6 H), 4.03 (t, J ϭ 7.3 Hz, 2 H), 7.31 (d,
J ϭ 7.8 Hz, 4 H), 7.55 (d, J ϭ 8.3 Hz, 4 H). Ϫ 13C NMR (25 MHz):
δ ϭ 10.6, 21.4, 23.2, 46.3, 125.0, 128.7, 129.5, 140.0, 155.5. Ϫ IR
(KBr): ν˜ ϭ 3068, 2976, 2958, 2944, 2921, 2876, 1479, 1474, 1465,
1449, 1417, 1383, 1347, 1339, 1021, 849, 822, 753 cmϪ1. Ϫ MS:
m/z (%) ϭ 292 (23), 291 (100) [Mϩ], 290 (12), 276 (19), 249 (26),
132 (21), 118 (35), 103 (26), 91 (18), 77 (17). Ϫ Calcd. for
C19H21N3: Mϩ 291.1735; found 291.1737. Ϫ C19H21N3 (291.4):
calcd. C 78.32, H 7.26, N 14.42; found C 78.23, H 7.38, N 14.38.
1-Cyclobutyl-3,5-diphenyl-1H-1,2,4-triazole (12): As expected, reac-
tion of 3,5-diphenyl-1H-1,2,4-triazole with cyclobutyl bromide gave
a mixture of products, from which 1-cyclopropylmethyl-3,5-di-
phenyl-1H-1,2,4-triazole (11) (67%), 1-(3-butenyl)-3,5-diphenyl-
1H-1,2,4-triazole (13) (8%), and the desired product 1-cyclobutyl-
3,5-diphenyl-1H-1,2,4-triazole (12) (25%) were isolated by prepar-
ative TLC. The overall yield was merely 15%. Spectroscopic details
4-Cyclopropylmethyl-1-methyl-3,5-diphenyl-4H-1,2,4-triazolium
Tetrafluoroborate (15): A solution of 4-cyclopropylmethyl-3,5-di-
phenyl-4H-1,2,4-triazole, 10, (1.0 g, 3.7 mmol) and trimethyloxon-
ium tetrafluoroborate (0.77 g, 4 mmol) in 1,2-dichloroethane
(25 mL) was stirred at 60 °C for 3 h. The reaction mixture was then
concentrated under reduced pressure and the residue was repeat-
edly washed with dry diethyl ether to yield 1.55 g of 15 (quantita-
1
for 12: H NMR (400 MHz): δ ϭ 1.75Ϫ1.87 (m, 1 H), 1.94Ϫ2.02
(m, 1 H), 2.39Ϫ2.46 (m, 2 H), 2.89 (dp, J ϭ 9.6, J ϭ 2.4 Hz, 2 H),
4.90 (p, J ϭ 8.3 Hz, 1 H), 7.37Ϫ7.47 (m, 3 H), 7.50Ϫ7.55 (m, 3
H), 7.60Ϫ7.69 (m, 2 H), 8.15Ϫ8.21 (m, 2 H).
1
tive). Ϫ H NMR (100 MHz, CD3CN): δ ϭ (Ϫ0.39)Ϫ(Ϫ0.44) (m,
3,5-Bis(4-methylphenyl)-1-propyl-1H-1,2,4-triazole (6): After recrys-
tallization from toluene, 90 mg (79%) of 6 was obtained; m.p.
101Ϫ102.5 °C (Ͼ 99% purity by GC). Ϫ 1H NMR (100 MHz): δ ϭ
0.91 (t, J ϭ 7.3 Hz, 3 H), 1.93 (sextet, J ϭ 7.3 Hz, 2 H), 2.38 (s, 3
H), 2.43 (s, 3 H), 4.16 (t, J ϭ 7.3 Hz, 3 H), 7.28 (m, 4 H), 7.55 (d,
J ϭ 7.8 Hz, 2 H), 8.04 (d, J ϭ 8.3 Hz, 2 H). Ϫ 13C NMR (25 MHz):
δ ϭ 11.0, 21.4, 23.5, 50.7, 125.5, 126.2, 128.4, 128.7, 129.2, 129.5,
138.8, 140.0, 155.5, 161.1. Ϫ IR (KBr): ν˜ ϭ 2962, 2947, 2934, 2917,
2 H), 0.16Ϫ0.35 (m, 2 H), 0.52Ϫ0.90 (m, 1 H), 3.97 (d, J ϭ 6.8 Hz,
2 H), 4.05 (s, 3 H), 7.49Ϫ7.78 (m, 10 H).
Thermolysis of 4-Cyclopropylmethyl-1-methyl-3,5-diphenyl-4H-
1,2,4-triazolium Tetrafluoroborate (15): A solution of 15 (50 mg) in
dry acetonitrile (2 mL) was placed in a glass tube, which was sealed
and then heated at 205 °C for 3 h. After cooling, GC analysis of the
contents of the tube showed that 1-methyl-3,5-diphenyl-1H-1,2,4-
triazole, 16, was the only product formed. The product was isolated
by preparative TLC and its identity was confirmed by comparison
of its spectroscopic properties with those of an authentic sample.[21]
2877, 1472, 1468, 1425, 1352, 1182, 1129, 1018, 840, 826, 759 cmϪ1
.
Ϫ MS: m/z (%) ϭ 292 (24), 291 (100) [Mϩ], 263 (12), 262 (58), 249
(48), 145 (48), 132 (13), 119 (21), 118 (76), 117 (28), 116 (17), 103
(28), 91 (21), 77 (21). Ϫ Calcd. for C19H21N3: Mϩ 291.1736; found
Synthesis of 1-Alkyl-3,5-diphenyl-1H-1,2,4-triazoles. ؊ General 291.1731. Ϫ C19H21N3 (291.4): C 78.32, H 7.26, N 14.42; found C
Procedure: To
a
solution of 3,5-diphenyl-1H-1,2,4-triazole[18]
78.47, H 7.41, N 14.67.
3752
Eur. J. Org. Chem. 2000, 3749Ϫ3753

Thermolysis of Triazoles
FULL PAPER
Lui, D. J. DeFrees, J. Am. Chem. Soc. 1988, 110, 7325; R. F.
W. Bader, K. E. Laidig, J. Mol. Struct. (Theo.) 1992, 261, 1;
G. A. Olah, V. P. Reddy, G. K. S. Prakash, Chem. Rev. 1992,
92, 69.
J. S. Staral, J. D. Roberts, J. Am. Chem. Soc. 1978, 100, 8018.
J. D. Roberts, R. H. Mazur, J. Am. Chem. Soc. 1951, 73, 2509;
R. H. Mazur, W. N. White, D. A. Semenov, C. C. Lee, M. S.
Silver, J. D. Roberts, J. Am. Chem. Soc. 1959, 81, 4390.
L. A. Lee, R. Evans, J. W. Wheeler, J. Org. Chem. 1972, 37,
343; H. Meerwein, Org. Synth. 1966, 46, 113.
S. Halazy, A. Krief, Tetrahedron Lett. 1980, 21, 1997.
V. W. Bowry, J. Lusztyk, K. U. Ingold, J. Chem. Soc. Chem
Commun. 1990, 923; V. W. Bowry, J. Lusztyk, K. U. Ingold, J.
Am. Chem. Soc. 1991, 113, 5687; V. W. Bowry, K. U. Ingold,
J. Am. Chem. Soc. 1991, 113, 5699; P. S. Engel, J. T. He, K. U.
Banks, K. U. Ingold, J. Lusztyk, J. Org. Chem. 1997, 62, 7211.
A. J. Castellino, T. C. Bruice, J. Am. Chem. Soc. 1988, 110,
1313; A. J. Castellino, T. C. Bruice, J. Am. Chem. Soc. 1988,
110, 7511.
[1]
O. R. Gautun, P. H. J. Carlsen, Acta Chem. Scand. 1992, 46,
469; P. H. J. Carlsen, K. B. Jørgensen, O. R. Gautun, S. Jagner,
˚
M. Hakansson, Acta Chem. Scand. 1995, 49, 676.
[13]
[14]
[2]
[3]
[4]
[5]
O. R. Gautun, P. H. J. Carlsen, Acta Chem. Scand. 1994, 48,
411.
A. R. Katritzky, X. Lan, J. Z. Yang, O. V. Denisko, Chem. Rev.
1998, 98, 409Ϫ548.
P. H. J. Carlsen, O. R. Gautun, Acta Chem. Scand. 1990, 44,
485.
D. J. Raber, J. M. Harris, P. v. R. Schleyer, Ions and Ion Pairs
in Organic Reactions, vol. 2 (Ed.: M. Szwarc), Wiley, New
York, 1974.
C. K. Ingold, Structure and Mechanism in Organic Chemistry,
Cornell University Press, Ithaca, N.Y., 1953, p. 318.
[15]
[16]
[17]
[6]
[7]
[8]
O. R. Gautun, P. H. J. Carlsen, Acta Chem. Scand. 1991, 45,
609.
[18]
P. v. R. Schleyer, T. Su, M. Saunders, J. C. Rosenfeld, J. Am.
Chem. Soc. 1969, 91, 5174; L. Radom, P. C. Hariharan, J. A.
People, P. v. R. Schleyer, J. Am. Chem. Soc. 1973, 95, 6531.
S. Sarel, J. Yovell, M. Sarel-Imber, Angew. Chem. 1968, 80,
592; H. G. Richey, in: Carbonium Ions (Eds.: G. A. Olah, P. v.
R. Schleyer), Wiley, New York, 1972, p. 1243.
K. B. Wiberg, B. A. Hess, A. J. Ashe, H. G. Richey, in: Car-
bonium Ions, vol. 3 (Eds.: G. A. Olah, P. v. R. Schleyer), Wiley,
New York, 1972, p. 1295.
J. D. Robert, J. Org. Chem. 1964, 29, 294; J. D. Robert, J. Org.
Chem. 1965, 30, 23; M. C. Caserio, W. H. Graham, J. D. Ro-
berts, Tetrahedron 1960, 11, 171.
[19]
[20]
J. Lange, H. Tondys, Dissert. Pharm. Pharmacol. XXII, 1980,
217.
[9]
The extreme high-field NMR shifts observed for the cyclopro-
pyl protons are due to two of the protons being forced into the
shielding region of the phenyl rings. Molecular modeling stud-
ies indicated that the phenyl rings lie approximately 56° out of
the plane of the triazole ring and that the cyclopropylmethyl
substituent is essentially perpendicular to this plane. The mo-
lecular modeling studies were performed using PCModel, Ver-
sion 7, from Serena Software, Box 3076, Bloomington, IN
47402Ϫ3076, USA; E-mail: gilbert@serenasoft.com.
P. H. J. Carlsen, Acta Chem. Scand. 1987, B41, 302.
Received April 7, 2000
[10]
[11]
[12]
[21]
P. C. Myhre, G. G. Webb, C. S. Yannoni, J. Am. Chem. Soc.
1990, 112, 8992; M. Saunders, K. E. Laidig, K. B. Wiberg, P.
v. R. Schleyer, J. Am. Chem. Soc. 1988, 110, 7652; W. Koch, B.
[O00180]
Eur. J. Org. Chem. 2000, 3749Ϫ3753
3753