Thermal rearrangement of allyl substituted unsymmetric 4H-1,2,4-triazoles to the corresponding 1H-1,2,4-triazoles

Article abstract of DOI:10.3390/60500481

A series of neat 4-(2-alkenyl) substituted 5-methyl-3-phenyl-4H-1,2,4- triazoles were thermolyzed at 320°C producing a rearrangement products, of which the regioisomeric 1- and 2-substituted triazoles were the main products. The group migrations were rationalized in terms of consecutive S _N2-type reactions. This mechanism was supported by a study of the alkylations of the triazoles which gave similar product mixtures. 4-(2-alkenyl) substituted 3-phenyl-4H-1,2,4-triazoles, on the other hand, gave predominantly elimination products.

Full text of DOI:10.3390/60500481

Molecules 2001, 6, 481-495
molecules
ISSN 1420-3049
http://www.mdpi.org
Thermal Rearrangement of Allyl Substituted Unsymmetric
4H-1,2,4-Triazoles to the Corresponding 1H-1,2,4-triazoles.
Kåre B. Jørgensen, Ragnhild B. Olsen, Per H.J. Carlsen*
Department of Chemistry, Norwegian University of Science and Technology, N-7491 Trondheim,
Norway. Tel. +47 73 59 39 68, Fax +47 73 59 42 56.
* Author to whom correspondence should be addressed; e-mail: per.carlsen@chembio.ntnu.no
Received: 14 March 2000; in revised form 26 April 2001 / Accepted: 26 April 2001/ Published: 30
April 2001
Abstract: A series of neat 4-(2-alkenyl) substituted 5-methyl-3-phenyl-4H-1,2,4-triazoles were
thermolyzed at 320 oC producing a rearrangement products, of which the regioisomeric 1- and
2-substituted triazoles were the main products. The group migrations were rationalized in
terms of consecutive SN2-type reactions. This mechanism was supported by a study of the
alkylations of the triazoles which gave similar product mixtures. 4-(2-alkenyl) substituted 3-
phenyl-4H-1,2,4-triazoles, on the other hand, gave predominantly elimination products.
Keywords: Thermolysis, 1,2,4-triazole, rearrangement.
Introduction
The thermal rearrangement of 4-allyl substituted 3,5-diphenyl-4H-1,2,4-triazoles to the
corresponding 1-allyl-substituted compounds has been reported earlier [1]. The mechanistic pathway
for the group migration was rationalized in terms of successive SN2 / SN2' type reactivity, as has also
been observed before for the 4-alkyl substituted triazoles [2]. Small amounts of substituted pyridines
were also isolated, formation of which were believed to take place via an initial allyl shift reaction
from the 4-N position to one of the ring carbon atoms forming a sp3 hybridized carbon, thus
facilitating a subsequent ring cleavage, Scheme 1. To further investigate the generality of such a
mechanistic pathway substituent effects were studied. The rationale for this, was that as different
substituent exhibit different migratory aptitudes, either of the substituents in the sp3-intermediate may
migrate. Depending on the substitution this may therefore lead to different type of products and at the

Molecules 2001, 6
482
same time shed light onto the mechanisms involved. A series of new 4-allyl- and 4-benzyl-substituted
3-phenyl-4H-1,2,4-triazoles was therefore prepared, with either a proton or a methyl group as 5-
substituent, and their thermal behavior was investigated.
C
H
3
C
H
3
[2,3]-shift
N
N
N
N
Ph
Ph
Ph
- N2
N
Ph
N
Ph
N
Ph
Ph
Ph
N
Scheme 1
Results and Discussion
The 4-substituted 3-phenyl-4H-1,2,4-triazoles and 5-methyl-3-phenyl-4H-1,2,4-triazoles were best
prepared from the corresponding 1,3,4-oxadiazoles by reflux with the appropriate amine [3].
Thermolysis of 50 mg samples in evacuated, sealed glass tubes was carried out at 320 oC for exactly
20 min. This was accomplished by inserting the sample tubes into a closely fitting hole in a large metal
block, functioning as a heat reservoir, placed in an oven kept at the desired temperature. In addition, a
temperature probe was inserted in the hear reservoir. The compositions of the reaction mixtures were
determined by GLC analyses and the identity of the products were determined by comparison to
authentic samples or by their characteristic spectroscopic properties.
Table 1. Products formed by thermolysis at 320 oC of the neat allyl substituted triazoles.
Products (yield, %)
Triazole
2 (4%) + 3 (2%) + 4 (48%) + 5 (34%) + 6 (4%)
1
7 (40%) + 8 (24%) + 9 (20%) + 10 (5%) + 11(4%) + 6 (2%)
13 (56%) + 14 (41%) + 6 (1%)
7
12
15
23
30
16 (51%) + 17 (37%) + 18 (4%) + 19 (4%) + 20(2%)
18 (22-25%) + 24 (14-9%) + 25 (8-6%) + 26(5%)a) + 27 (4%) + 28 (5%) + 29(28-37%)
31 (75%) + 32 (22%) + 18 (1%)
The results from these thermolyses are compiled in Table 1. A seen in this table, rather complex
mixtures with a number of products were generally formed. The triazoles that were thermolyzed and
the reaction products formed are listed in Tables 2 and 3.

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483
Table 2. The structures of the 3-Phenyl-5-methyl-1H-1,2,4-triazoles
thermolyzed at 320 oC and the products formed.
N N
R
R'
N N
N
N
N
Ph
Substituent
CH3
N
R
CH3
Ph
CH3
Ph
N
R
CH2
CH2
1
2
3
7
4
5
H3C
CH3
CH3
CH2
8
10
13
6
9
CH
CH3
CH2
CH2
11
14
12
H
Thermolysis of the neat 4-allyl-5-methyl-3-phenyl-4H-1,2,4-triazole, 1, gave a 58:42 mixture of the
two regioisomers, the 1- and 2-allyl substituted triazoles 4 and 5, together with small amounts of the
cis and trans-4-(1-propenyl)-substituted triazoles 2 and 3 and the elimination product 6. Thermolysis of
pure 2 and 3 clearly showed that these triazoles remained unchanged under the reaction conditions. The
corresponding 4-(2-butenyl) substituted triazole 7 was found to react somewhat slower, as under the
standard conditions the degree of conversion was merely 60 %. The products formed was the two 1-
and 2- substituted triazoles 8 and 9 in an approximately 1:1 ratio. These products may well be formed
by the previously proposed SN2 type mechanism. Two other products, 10 and 11 were formed in a 5:4
ratio and may be formed by the corresponding SN2'-type mechanism. These results clearly indicated
that the pathways by which the 4-allyl-substituted triazoles rearranged presumably resemble the
mechanism previously observed for the corresponding 4-alkyl-3,5-diphenyl-4H-1,2,4-triazoles [1].

Molecules 2001, 6
484
Table 3. The structures of the 3-Phenyl-1H-1,2,4-triazoles thermolyzed
at 320 oC and the products formed.
R'
N N
R
N
N
N N
N
Substituent
R
Ph
H
N
R
H
Ph
H
Ph
N
CH2
CH2
15
21
19
20
24
25
26
27
31
18
22
H3C
16
17
23
CH3
CH
3
CH
2
CH2
CH3
CH
CH
CH
2
CH3
CH2
3
C
CH3
30
32
H
Support for this mechanism was also found in the alkylation reactions with triazole 6 under basic
conditions in DMF with the appropriate alkenyl halide. The only products formed in these reactions
were the 1- or 2-substituted triazoles.
The 4-allyl- and 4-(2-butenyl)-substituted 3-phenyl-4H-1,2,4-triazoles, 15 and 23 exhibited a
different reactivity under the standard reaction conditions. Thus, 15 did not yield the expected

Molecules 2001, 6
485
rearrangement product but gave as the main products the allyl isomerization products, cis- and trans-4-
(1-propenyl)-4H-1,2,4-triazoles, 16 and 17, which were merely the results of double bond migrations in
the allyl group. Only 6 % of the 1-substituted was formed and then also here as the corresponding
vinylic products 19 and 20. No traces of the allylic rearrangement products 21 and 22 were detected.
The corresponding 4-(2-butenyl)-substituted triazole 23 exhibited an unexpected behavior, and gave a
rather complex product mixture with the elimination product 18 as a major product (25 %) together
with minor amounts of SN2-type products 24 and 24 (20 %) and the SN2'-products 26 and 27 (9 %). In
addition was isolated small amounts of a product 28 (5 %) which structure was not identified but
appeared to be an isomer of the major product, 29 (28-37 %), which based on spectroscopic properties
was assigned the structure 1,3-di(3-phenyl-1H-1,2,4-triazol-1-yl)butane.
That the 4-(2-butenyl)- substituted triazole, 23, so readily undergo an elimination reaction may be
ascribed to reduced steric hindrance compared to triazole, 7, facilitating an elimination pathway which
may be rationalized as shown in Scheme 2.
N
N
H
N
N
N
N
Ph
H
H
H
N
Ph
Ph
N
H
N
H
2
CH
18
23
Scheme 2. Mechanism for the elimination of butadiene group upon
thermolysis of triazole, 23
The build-up of high concentrations of 18 may also be a prerequisite for the formation of product 29,
which may be formed by a simple addition of triazole 18 over the double bond in the unsaturated side
chain of the rearranged triazole 24 (or 25) as indicated in Scheme 3.
H C
3
N
H
PH
N
CH
2
N
N
N
N
N
N
N
+
Ph
Ph
R
R
R
N
N
Ph
R
N
R = H
18
29
24
Scheme 3. Formation of product 29
Support for this mechanism was established by a control experiment, where thermolysis under the
standard conditions of a mixture of the authentic triazoles 18 and 24 gave rise to formation of the same
product 29.
Thermolysis of the 4-benzyl substituted triazoles was straightforward as well, yielding exclusively
the corresponding 1- and 2-benzyl substituted products (Table 1). Contrary to what was observed for
3,5-diphenyl triazoles, formation of substituted pyridines was never observed.

Molecules 2001, 6
486
Triazoles 1, 7 and 12 showed a preference for group migration to the triazole N1-atom. In the
context of the proposed SN2-type mechanism, this was in reasonable agreement with the selectivities
observed for alkylation of triazoles 6 and 18 (Table 4). Uda et al. [4] in a study showed that the
selectivity in the N-alkylation of 1,2,4-triazoles was mainly controlled by steric factors. In our study
thermolysis of the benzyl substituted triazole 12 gave a 58 : 42 mixture of the 1- and 2-benzyl triazoles.
Table 4. Regioselectivities for thermolysis of the neat allyl substituted
triazoles at 320 oC and for alkylation of the 1H-triazoles.
R'
'R
N
N
N
N
R
Ph
R
Ph
N
N
b
a
Compound Thermolysis
Alkylation
a : b
a : b
58 : 42
55 : 45
58 : 42
100 : 0
100 : 0
77 : 33
93 : 7
1
80 : 20
90 : 10
89 : 11
96 : 4
7
12
15
23
30
64 : 36
The 3-phenyl group may stabilize a developing negative charge on the N-1 atom, in agreement with
reports by Gautun et al. [2] that electronic effects may control the regioselectivity. The regioselectivity
in the rearrangement was further compared to the selectivity observed for the alkylation reactions with
the anion of triazoles 6 and 18 in DMF. Conveniently, this study also supplied necessary reference
compounds.
Triazole 6 was obtained as described by Francis et al.[5] Synthesis of 18, using a procedure
described by Jacobs et al. [6] failed to give a satisfactory product. A viable alternative was deamination
of 4-amino-3-phenyl-4H-1,2,4-triazole using a modification of the procedure reported by Hoggarth [7].
In this case the crude product consisted of a 2:3 mixture of the desired 3-phenyl-1H-1,2,4-triazole, 18,
although obtained in merely 17 % after sublimation, together with 3,5-diphenyl-1H-1,2,4-triazole! The
mechanism for the formation of this product is not yet understood.
Allylations of 6 and 18 were carried out in DMF with the appropriate bromo-alkenes in the presence
of sodium hydride. The reactions with 6 readily gave the desired products in good yields. However,
alkylations of 18 were less successful, as all products were isolated in low yields only, 3-10 % after
preparative chromatography. An important competing reaction appeared to be decomposition of 18
under the reaction conditions. The nature of this decomposition is so far not clear. Triazoles 6 and 18
yielded mixtures of the 1- and 2- substituted products. Typically, benzylation of 6 yielded products 13

Molecules 2001, 6
487
and 14 in a 90:10 ratio. The regioisomers were all isolated by preparative TLC or flash
chromatography. The identities of the regioisomers were established by NMR and NOE-measurements.
E.g., the assignment of structure 13 was based on the increased of intensity of the CH3-NMR signal
upon irradiation of the benzylic CH2-signal. In addition, the 1H-NMR spectra of all the N-1-alkylation
products, the orto-protons of the 3-phenyl group were shifted 0.4-0.5 ppm downfield to approx. 8.0
ppm, relative to triazole substituted at the N-2 nitrogen. The regioselectivities were then determined by
GLC analysis. The results are summarized in Table 4.
o
The tendency in regioselectivity was the same for thermolysis at 320 C as for alkylation at room
temperature. Ratios were in better agreement for the less hindered 5-hydrogen-substituted systems than
for the more hindered 5-methyl substituted triazoles. These results therefore constitute an additional
support for the proposed nucleophilic displacement mechanism.
Other groups have studied thermal rearrangement reactions with triazoles. Thus Gilchrist and co-
workers[13] showed that 3,4,5-triphenyl-triazoles undergo a 1,5-shift reaction under vacuum flash
conditions. Similar observations were done by Habraken et al. [8] for 1-nitro-1,2,4-triazoles. In light of
these results, it may be surprising that in our study, no sign of products were isolated or could be
detected, that corresponded to migration of the allyl moiety from 4- to the 3- or 5-positions of the
triazoles. The possibility of intramolecular [2,3]-allyl shifts taking place was therefore ruled out.
Conclusions
The type of substituent in the 5-ring position of the triazole clearly had a major effect of the
outcome of the thermolyses. Changing the substituent from a hydrogen- into a methyl- or phenyl group
made rearrangements via a nucleophilic substitution mechanism to be dominant. Thus, 4-allyl-3-
phenyl-5-methyl-4H-1,2,4-triazole yielded only rearrangement products that can be derived from SN2
and SN2'-type mechanisms. The corresponding 4-allyl-3-phenyl-4H-1,2,4-triazole in addition formed
large amounts of elimination products. The reason for this difference in behavior is not clear, but can
best be rationalized by differences in stereoelectronic properties.
Acknowledgements
The authors wish to thank The Norwegian Research Council, NFR, for financial support.
Experimental
General
1
The H- and 13C-NMR spectra were recorded on a JEOL JNM-EX 400 FT NMR system using
tetramethylsilane (TMS) as internal standard. DEPT information is shown in the listings of the
13
o
individual C-NMR spectra. IR spectra were recorded in the gas phase at 270 C (GC-FTIR) with a
Nicolet 10-SXC FT-IR spectrometer equipped with a Carlo Erba HRGC 5160 Mega Series gas

Molecules 2001, 6
488
chromatograph equipped with a CP-Sil 5 CB capillary column (25 m). GLC analyses were performed
on a Perkin-Elmer Autosystem gas chromatograph equipped with a CP-Sil 5 CB capillary column (25
m).
Methyl-3-phenyl-1H-1,2,4-triazole (6)
This compound was prepared according to the procedure described by Francis et al. [5] The MS [9] and
13
1H-NMR [10] spectroscopic properties were in agreement with those described in the literature. C-
NMR (100 MHz, CDCl3): δ 12.3, 127.6, 130.1, 131.1, 157.3, 161.3 ppm; GC-FTIR: 3499, 3071, 2946,
1549, 1507, 1448, 1407, 1351, 1257, 1145, 1061, 1025, 1002, 775, 725 cm-1.
4-Amino-3-phenyl-1H-1,2,4-triazole (36).
2-Phenyl-1,3,4-oxatriazole [11], (96.71 g, 0.66 mol) was mixed with 260 mL of hydrazine hydrate (99
o
%) and the mixture heated at 140 C in a sealed tube over night. The precipitate was formed was
isolated by filtration to yield 63.3 g (79%) of 36 as white needle shaped crystals, (m.p. 86-88 oC).
3-Phenyl-1H-1,2,4-triazole (18).
To a solution of 4-Amino-3-phenyl-1H-1,2,4-triazole, 36, (30.0 g, 0.19 mol) in concentrated
hydrochloric acid (650 mL) was slowly added sodium nitrite (90 g) dissolved in 1.5 L of water. The
mixture was stirred over night, filtered and extracted with dichloromethane (2x750 mL). The aqueous
phase was concentrated under reduced pressure and the residue dissolved in ethanol and filtered in
order to remove sodium chloride. The crude product was a 3:2 mixture of 3,5-diphenyl-1,2,4-triazole
o
and 3-phenyl-1,2,4-triazole (18), which was obtained after repeated sublimation (140 C, 5 mmHg) in
o
o
4.71 g (17 %) yield as a white powder with melting point 115-117 C (Lit. 119 C [8]). The product
was unstable. 1H-NMR (400 MHz, CDCl3): δ 7.38-7.51 (m, 3H), 7.74-7.91 (m, 2H), 8.13 (s, 1H) ppm;
13C-NMR (100 MHz, CDCl3): δ 126.9, 128.6, 131.9, 132.7, 168.2 ppm; FT-IR: 3505, 3076, 3043,
1498, 1442, 1349, 1272, 1189, 1138, 1079, 1018, 978, 706 cm-1; MS [m/z (% rel. int.)]: 160 (100,
M+), 159(12), 145(8), 136(6), 105(38), 104(80), 103(14), 84(85), 77(48).
4-Allyl-5-methyl-3-phenyl-4H-1,2,4—triazole (1), 4-benzyl-5-methyl-3-phenyl-1,2,4-4H-triazole (12),
4-allyl-3-phenyl-4H-1,2,4-triazole (15), and 4-benzyl-3-phenyl-4H-1,2,4-triazole (30) were prepared as
described for similar systems in the literature [3] .
4-(Trans-2-butenyl)-5-methyl-3-phenyl-4H-1,2,4-triazole (7).
A solution containing 2-methyl-5-phenyl-1,3,5-oxadiazole (1.53 g, 9.58 mmol) and crotylamine (1.02
g, 14.4 mmol) in toluene (4 mL) was refluxed for 7 days. The crude product (2.05 g), gave after
o
1
crystallization from toluene gave 0.98 g (48%) of pure 7 as colorless crystals. Mp. 103-104 C. H-

Molecules 2001, 6
489
NMR (400 MHz, CDCl3): δ 1.71-1.73 (m, 3H), 2.47 (s, 3H), 4.44-4.47 (m, 2H), 5.41-5.56 (m, 2H),
13
7.46-7.49 (m, 3H), 7.59-7.62 (m, 2H) ppm; C-NMR (100 MHz, CDCl3): δ 11.1 (CH3), 17.6 (CH3),
45.7 (CH2), 124.5 (CH), 127.6 (C), 128.7 (CH), 128.8 (CH), 129.5 (CH), 129.9 (CH), 152.3 (C), 154.8
(C) ppm; GC-FTIR: 3072, 3035, 2935, 2874, 1525, 1476, 1411, 1352, 1292, 1236, 964, 766 cm-1; MS
[m/z (% rel. int.)]: 213(78, M+), 212(4), 198(14), 160(7), 159(59), 131(4), 130(3), 118(36), 104(30),
103(10), 77(24). Found M+: 213.1263 Calc. for C13H15N3: 213.1266; Analysis: Calc. for C13H15N3 ; C,
72.21; H, 7.09; N, 19.70 Found: C, 72.42; H, 7.35; N, 19.66.
4-(Trans-2-butenyl)-3-phenyl-4H-1,2,4-triazole (23).
Refluxing a solution containing 2-phenyl-1,3,4-oxadiazole (2.26 g, 15.5 mmol) and crotylamine (1.70
g, 23.9 mmol) in toluene (4 mL) for 3 days, gave a crude product which after flash column
1
chromatography (silica gel/acetone), yielded 1.50 g (49%) of the pure product as a colorless oil; H-
NMR (400 MHz, CDCl3): δ 1.72-1.74(m, 3H), 4.55-4.57(m, 2H), 5.53-5.70(m, 2H), 7.48-7.50(m, 3H),
7.61-7.64(m, 2H), 8.21(s, 1H) ppm; 13C-NMR(100 MHz, CDCl3): δ 17.6 (CH3), 46.9 (CH2), 124.6
(CH), 126.8 (C), 128.7 (CH), 128.8 (CH), 130.0 (CH), 131.2 (CH), 144.3 (CH), 153.8 (C) ppm; GC-
FTIR: 3073, 3037, 2933, 1494, 1471, 1377, 1361, 1188, 1066, 1023, 962, 815, 766 cm-1; MS [m/z (%
rel. int.)]: 199(86, M+), 198(6), 184(19), 170(3), 145(69), 118(15), 104(30), 89(14), 77(10). Found
M+: 199.1106 Calc. for C12H13N3: 199.1110; Analysis: Calc. for C12H13N3 ; C, 72.34; H, 6.58; N,
21.09 Found: C, 72.55; H, 6.69; N, 20.78.
Base catalyzed isomerization of allylic substituted triazoles. General procedure.
To solutions containing the appropriate triazole (0.15-0.20 g) in dry THF (5 mL) was added catalytic
amounts of potassium tert-butoxide (0.02 g). The reaction mixtures were stirred at room temperature
for 6 days, then quenched by addition of water and the solvent evaporated under reduced pressure. The
residues were dissolved in dichloromethane (20 mL) and the solutions dried over anhydrous
magnesium sulfate, filtered and concentrated under reduced pressure. The pure products were obtained
after flash chromatography or recrystallization.
5-Methyl-3-phenyl-4-(cis-vinyl)-4H-1,2,4-triazole (2).
Prepared from 1 (0.15 g) yielding an oil containing 95 % of 2 (together with 5 % of the trans-product).
1H-NMR (400 MHz, CDCl3): δ 1.35 (dd, J=1.9, 7.0 Hz, 3H), 2.32 (s, 3H), 5.92 (dq, J=7.5, 7.1 Hz,
13
1H), 6.40 (dq, J= 7.9, 1.9 Hz, 1H), 7.33-7.35 (m, 3H), 7.65-7.68 (m, 2H) ppm; C NMR (100 MHz,
CDCl3): δ 11.0, 12.3, 121.9, 127.5, 127.9, 128.6 (two peaks), 129.7, 130.9, 152.4, 153.6 ppm; GC-
FTIR: 3071, 3050, 2938, 1660, 1522, 1473, 1447, 1407, 1373, 1334, 979, 928, 762 cm-1; MS [m/z (%
rel. int.)]: 199(100, M+), 198(13), 185(8), 184(38), 131(15), 130(11), 104(19), 103(12), 82(17), 77(16),
76(5).

Molecules 2001, 6
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5-Methyl-3-phenyl-4-(trans-vinyl)-4H-1,2,4-triazole (3).
This compound was not be isolated from the mixture with 2. The yield in the isomerization reaction
was low. The identification of 3 was based on the GC-IR data. GC-FTIR: 3071, 2939, 1673, 1524,
1474, 1409, 1331, 1027, 980, 934, 765 cm-1.
3-Phenyl-4-(cis-1-propenyl)-4H-1,2,4-triazole (16).
Prepared by isomerization of 4-allyl-3-phenyl-4H-1,2,4-triazole (15). The crystalline product contained
1
96 % of 16 together with 4 % of the trans-compound 17; H-NMR (400 MHz, CDCl3): δ 1.73 (dd,
J=7.1, 1.9 Hz, 3H), 5.88 (dq, J=8.4, 7.1 Hz, 1H), 6.55 (dq, J=8.4, 1.9 Hz, 1H), 7.45-7.48 (m, 3H), 7.78-
7.80 (m, 2H), 8.22 (s, 1H) ppm; 13C-NMR (100 MHz, CDCl3): δ 12.3, 121.8, 126.2, 126.7, 128.4,
128.7, 130.1, 144.1, 153.1 ppm; GC-FTIR: 3070, 2932, 1662, 1484, 1404, 1379, 1187, 937, 819, 768,
741 cm-1; MS [m/z (% rel. int.)]: 185(100, M+), 184(24), 171(8), 170(63), 104(20), 103(11), 77(14);
Analysis: Calc. for C11H11N3 ; C, 71.33; H, 5.99; N, 22.69. Found: C, 71.21; H, 6.18; N, 22.88.
Phenyl-4-(trans-1-propenyl)-1H-1,2,4-triazole (17).
1H-NMR (400 MHz, CDCl3): δ 1.87 (dd, J=6.8, 1.5 Hz, 3H), 6.06 (dq, J=14.3, 6.8 Hz, 1H), 6.59 (dq,
13
J=14.3, 1.5 Hz, 1H), 7.49-7.51 (m, 3H), 7.70-7.72 (m, 2H), 8.35(s, 1H) ppm; C-NMR (100 MHz,
CDCl3): δ 15.1, 121.9, 122.7, 126.6, 128.8, 128.9, 130.2 ppm; GC-FTIR: 3073, 2933, 1487, 1385,
1308, 1198, 1068, 1025, 940, 817, 764 cm-1; GC-MS [m/z (% rel. int.)]: 185(100, M+), 184(37),
171(11), 170(87), 158(4), 143(5), 104(31), 103(16), 90(10), 89(11), 77(31).
Alkylation of 1,2,4-triazoles. General procedure.
To a solution of the appropriate triazole (6 or 18) in DMF (20 mL/g of triazole) under a nitrogen
atmosphere was added sodium hydride (1-2.5 eq). The mixture was stirred for 1 h at room temperature
and then added the alkenyl bromide (1.5 eq). The resulting reaction mixture was stirred overnight, and
then added water. The solution was concentrated under reduced pressure and dissolved in
dichloromethane. The solution was washed with 1 M HCl, 1M NaOH, water and brine, dried over
anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Reaction mixtures
from the alkylation of 18 were dissolved in ethanol and filtered before the solvent was evaporated
under reduced pressure. The products were separated by preparative TLC (silica / multi elution with
chloroform).
1-Allyl-5-methyl-3-phenyl-1H-1,2,4-triazole (4) and 1-allyl-3-methyl-5-phenyl-1H-1,2,4-triazole (5).
Prepared from 6 (1.31 g, 8.26 mmol), sodium hydride (0.20 g, 8.26 mmol) and allyl bromide (1.50 g,
12.4 mmol) and gave a 93:7 mixture of 4 and 5. The components were separated by preparative thin

Molecules 2001, 6
491
layer chromatography. Compound 4: 1H-NMR (400 MHz, CD3OD): δ 2.43 (s, 3H), 4.65 (dt, J=5.3, 0.6
Hz, 2H), 5.06 (dd, J=17.3, 0.6 Hz, 1H), 5.20 (dd, J=10.3, 0.6 Hz, 1H), 5.90 (ddt, J=15.6, 10.3, 5.2 Hz,
13
1H), 7.32-7.41 (m, 3H), 8.04-8.06 (m, 2H) ppm; C-NMR (100 MHz, CD3OD): δ 11.9, 50.9, 116.8,
126.1, 129.0, 131.0, 131.9, 132.3, 152.9, 160.7 ppm; GC-FTIR: 3072, 2996, 2943, 1521, 1475, 1445,
1348, 1298, 1128, 991, 927, 787, 725 cm-1; MS [m/z (% rel. int.)]: 199(100, M+), 198(31), 184(6),
129(12), 104(21), 103(15), 77(10), 76(5); Found M+: 199.1108. Calc. for C12H13N3: 199.1110;
Analysis: Calc. for C12H13N3; C, 72.34; H, 6.58; N, 21.09 Found: C, 72.18; H, 6.44; N, 21.35;
1
Compound 5: H-NMR (400 MHz, CD3OD): δ 2.44 (s, 3H), 4.76 (dt, J=6.7, 1.5 Hz, 2H), 5.16 (dd,
J=18.1, 0.9 Hz, 1H), 5.32 (dd, J=11.1, 0.8 Hz, 1H), 6.05 (ddt, J= 15.5, 10.3, 5.2 Hz, 1H), 7.47-7.49 (m,
3H), 7.63-7.64 (m, 2H) ppm; 13C-NMR (100 MHz, CD3OD): δ 13.9, 51.3, 118.3, 128.0, 128.6, 128.8,
130.1, 132.4, 160.3 ppm; GC-FTIR: 3075, 3040, 2995, 2945, 1506, 1456, 1413, 1381, 1338, 1288,
1248, 1182, 1016, 925, 805, 768 cm-1; MS [m/z (% rel. int.)]: 199(100, M+), 198(38), 184(6), 174(4),
159(4), 104(19), 77(10). Found M+: 199.1108 Calc. for C12H13N3: 199.1110
Trans 1-(2-Butenyl)-5-methyl-3-phenyl-1H-1,2,4-triazole (8) and trans-1-(2-butenyl)-3-methyl-5-
phenyl-1H-1,2,4-triazole (9).
Prepared from 6 (1.18 g, 7.40 mmol), sodium hydride (0.18 g, 7.40 mmol) and crotyl bromide (80 %
1
trans) (1.50 g, 11.10 mmol) in DMF (12 mL) yielding a 82:18 mixture of 8 and 9. Compound 8: H-
NMR (400 MHz, CDCl3): δ 1.70 (dd, J=6.4, 1.5 Hz, 3H), 2.46 (s, 3H), 4.66 (dd, J= 4.1, 1.5 Hz, 2H),
13
5.61-5.68 (m, 2H), 7.33-7.49 (m, 3H), 8.05-8.07 (m, 2H) ppm; C-NMR (100 MHz, CDCl3): δ 12.0,
13.1, 17.6, 45.6, 50.5, 123.9, 124.6, 126.1, 128.5, 128.6, 128.9, 129.9, 131.2, 152.4, 152.6, 160.6 ppm;
GC-FTIR: 3071, 3039, 2937, 2873, 1521, 1475, 1445, 1349, 1297, 1127, 965, 808, 782, 725 cm-1; MS
[m/z (% rel. int.)]: 213(100, M+), 212(4), 199(7), 198(36), 160(12), 159(100), 118(19), 104(27),
103(12), 77(12). Found M+: 213.1269 Calc. for C13H15N3: 213.1266; Analysis: Calc. for C13H15N3 ; C,
1
72.34; H, 6.58; N, 21.09 Found: C, 72.66; H, 6.87; N, 20.78. Compound 9: H-NMR (400 MHz,
CDCl3): δ 1.74 (d, J=4.9 Hz, 3H), 2.45 (s, 3H), 4.70 (d, J=3.4 Hz, 2H), 5.60-5.73 (m, 2H), 7.46-7.49
(m, 3H), 7.62-7.65 (m, 2H) ppm; 13C-NMR (100 MHz, CDCl3): δ 13.9, 17.8, 46.3, 50.8, 124.7, 125.2,
128.1, 128.5, 128.7, 130.0, 154.9, 160.1 ppm; GC-FTIR: 3073, 2945, 2872, 1504, 1458, 1412, 1380,
1340, 1242, 1017, 964, 811, 771, 725 cm-1; MS [m/z (% rel. int.)]: 213(73, M+), 212(9), 199(7),
198(54), 197(5), 172(5), 160(10), 159(100), 188(35), 104(26), 77(12). Found M+: 213.1269 Calc. for
C13H15N3: 213.1266; Analysis: Calc. for C13H15N3 ; C, 73.21; H, 7.09; N, 19.70. Found: C, 73.44; H,
6.78; N, 19.95.
1-Benzyl-5-methyl-3-phenyl-1H-1,2,4-triazole (13), and 1-benzyl-3-methyl-5-phenyl-1H-1,2,4-triazole,
(14).
Prepared from 6 (0.50 g, 3.14 mmol), sodium hydride (0.19 g, 7.85 mmol) and benzyl bromide (0.81 g,
1
3.14 mmol) in DMF (8 mL) yielding a 90:10 mixture of 13 and 14. Compound 13: H-NMR (400
MHz, CD3OD): δ 2.45 (s, 3H), 5.40 (s, 2H), 7.24-7.27 (m, 3H), 7.31-7.44 (m, 5H), 7.98-8.00 (m, 2H)

Molecules 2001, 6
492
ppm; 13C-NMR (100 MHz, CD3OD): δ 11.8, 53.1, 127.2, 128.3, 129.2, 129.7, 130.0, 130.4, 131.9,
137.0, 155.0, 161.6 ppm; GC-FTIR: 3073, 3038, 2945, 1521, 1475, 1445, 1348, 1301, 1175, 1108,
1028, 804, 725 cm-1; MS [m/z (% rel. int.)]: 249(92, M+), 248(22), 234(9), 172(5), 146(3), 104(13),
91(100), 77(8). Found M+: 249.1264 Calc. for C16H15N3: 249.1266; Analysis: Calc. for C16H15N3 ; C,
1
77.08; H, 6.06; N, 16.85. Found: C, 77.25; H, 6.17; N, 16.56; Compound 14: H-NMR (400 MHz,
CD3OD): δ 2.40 (s, 3H), 5.40 (s, 2H), 7.09-7.11 (m, 2H), 7.28-7.32 (m, 3H), 7.51-7.58 (m, 5H) ppm;
13C-NMR (100 MHz, CD3OD): δ 11.0, 52.0, 125.7, 126.3, 127.5, 128.3, 128.5, 128.7, 129.7, 135.6,
155.2, 160.0 ppm; GC-FTIR: 3073, 3038, 2946, 1503, 1455, 1412, 1379, 1338, 1243, 1019, 915, 815,
765, 727 cm-1; MS [m/z (% rel. int.)]: 249(58, M+), 248(24), 179(3), 177(5), 149(12), 137(8), 125(13),
123(14), 113(10), 111(19), 109(14), 105(13), 104(11), 99(13), 97(35), 96(13), 95(17), 91(85), 85(38),
84(13), 83(31), 82(11), 81(19), 77(13). Found M+: 249.1264 Calc. for C16H15N3: 249.1266
1-Allyl-3-phenyl-1H-1,2,4-triazole (21).
Prepared from 18 (0.50 g, 5.29 mmol), sodium hydride (0.10 g, 3.45 mmol) and allyl bromide (0.64 g,
5.29 mmol) in DMF (10 mL) yielding a 89:11 mixture of 21 with 1-allyl-5-phenyl-1H-1,2,4-triazole
(22). Compound 21: 1H-NMR (500 MHz, CDCl3): δ 4.83 (d, J= 5.8 Hz, 2H), 5.32-5.37 (m, 2H), 6.03-
6.08 (ddt, J= 17.5, 10.0, 5.0 Hz, 1H), 7.38-7.45 (m, 3H), 8.07-8.11 (m, 3H) ppm; 13C-NMR (100 MHz,
CDCl3): δ 50.9, 120.0, 126.3, 128.6, 128.8, 129.2, 131.3, 143.6 ppm; GC-FTIR: 3070, 3036, 2981,
2944, 1522, 1496, 1442, 1330, 1292, 1202, 979, 930, 775, 726 cm-1; MS [m/z (% rel. int.)]: 185(70,
M+), 184(23), 179(5), 159(19), 158(9), 145(18), 138(12), 118(10), 105(10), 104(47), 103(13), 91(18),
89(11), 84(12), 82(22), 81(12), 77(16). Found M+:185.0951 Calc. for C11H11N3: 185.0953; Analysis:
Calc. for C11H11N3 ; C, 71.33; H, 5.99; N, 22.69. Found: C, 71.54; H, 6.29; N, 22.48.
1-(Trans-2-butenyl)-3-phenyl-1H-1,2,4-triazole (24), and 1-(cis-2-butenyl)-3-phenyl-1H-1,2,4-triazole,
(25).
Prepared from 18 (0.50 g, 3.45 mmol), sodium hydride (0.10 g, 4.17 mmol) and crotyl bromide (0.70 g,
5.18 mmol) in DMF (10 mL) yielding a 66:28:6 mixture of 24, 25 and an unidentified product,
probably the 1-(2-butenyl)-5-phenyl-1H-1,2,4-triazole. The products were inseparable by thin layer
chromatography. Compound 24: 1H-NMR (500 MHz, CDCl3): δ 1.78 (dd, J=6.3, 1.5 Hz, 3H), 4.76 (d,
J=6.3 Hz, 2H), 5.68-5.78 (m, 1H), 5.80-5.87 (m, 1H), 7.39-7.68 (m, 3H), 8.07-8.11 (m, 3H) ppm.
1
Compound 25: H-NMR (500 MHz, CDCl3): δ 1.81 (dd, J= 1.0, 7.0 Hz, 3H), 4.86 (d, J=6.8 Hz, 2H),
5.68-5.78 (m, 1H), 5.87-5.94 (m, 1H), 7.39-7.68 (m, 3H), 8.07-8.11(m, 3H) ppm. The mixture of 24
13
and 25 exhibited the following spectroscopic properties: C-NMR (100 MHz, CDCl3): δ 17.8, 29.7,
46.5, 51.9, 122.8, 124.0, 126.3, 126.4, 128.6, 128.9, 129.2, 130.0, 130.9, 132.1, 143.1, 143.3 ppm;
GC-FTIR: 3069, 3040, 2936, 1521, 1496, 1443, 1324, 1293, 1200, 1026, 966, 842, 790, 725, 694 cm-1;
MS [m/z (% rel. int.)]: 199(49, M+), 184(6), 146(10), 145(100), 118(15), 104(32), 77(9). Found M+:
199,1108 Calc. for C12H13H3: 199.1110

Molecules 2001, 6
493
1-Benzyl-3-phenyl-1H-1,2,4-triazole (31), and 1-benzyl-5-phenyl-1H-1,2,4-triazole (32).
Prepared from 18 (0.50 g, 3.44 mmol), sodium hydride (0.10 g, 4.17 mmol) and benzyl bromide (0.88
g, 5.15 mmol) in DMF (10 mL) yielding a 64:36 mixture of 31 and 32 together with large amounts of
starting material. The products were unstable, and after work up only 7% of the products were isolated.
1
Compound 31: H-NMR (400 MHz, CDCl3): δ 5.38 (s, 2H), 7.30-7.35 (m, 3H), 7.37-7.46 (m, 5H),
8.04 (s, 1H), 8.10-8.12 (m, 2H) ppm; 13C-NMR (100 MHz, CDCl3): δ 53.7, 126.2, 126.4, 127.9, 128.5,
129.1, 129.2, 130.9, 143.7, 143.9 ppm; GC-FTIR: 3072, 3035, 2946, 1497, 1472, 1445, 1349, 1300,
-1
1176, 1106, 1028, 721 cm ; MS [m/z (% rel. int.)]: 235(73, M+), 234(11), 132(15), 91(100). Found
M+: 235.1108 Calc. for C15H13N3: 235.1110; Analysis: Calc. for C15H13N3 ; C, 76.57; H, 5.57; N,
1
17.86. Found: C, 76.22; H, 5.78; N, 17.59. Compound 32: H-NMR (400 MHz, CDCl3): δ 5.44 (s,
2H), 7.14-7.17 (m, 2H), 7.30-7.36 (m, 3H), 7.44-7.49 (m, 3H), 7.57-7.60 (m, 2H), 8.03 (s, 1H) ppm;
13C-NMR (100 MHz, CDCl3): δ 52.7, 126.9, 127.9, 128.1, 128.8, 128.9, 129.0, 130.2, 135.9, 151.3
ppm; GC-FTIR: 3073, 3037, 2951, 1483, 1457, 1378, 1278, 1239, 1177, 1121, 1015, 881, 767, 724
cm-1; MS [m/z (% rel. int.)]: 235(57, M+), 234(20), 220(3), 158(4), 132(12), 104(12), 91(100). Found
M+: 235.1106 Calc. for C15H13N3: 235.1110
1-(1-Methyl-2-propenyl)-5-methyl-3-phenyl-1H-1,2,4-triazole (10) and 1-(1-Methyl-2-propenyl)-3-
methyl-5-phenyl-1H-1,2,4-triazole (11).
Isolated from the thermolysis mixture of 7 and isolated by thin layer chromatography of the crude
reaction. The products could not be completely separated from 8. Compound 10: 1H-NMR (400 MHz,
CDCl3): δ 1.69 (d, J=6.8 Hz, 3H), 2.48 (s, 3H), 4.85-4.92 (m, 1H), 5.08 (d, J=17.3 Hz, 1H), 5.19 (d,
J=10.7 Hz, 1H), 6.06 (ddd, J=17.3, 10.7, 7.1 Hz), 7.34-7.40 (m, 3H), 8.07-8.09 (m, 2H) ppm; 13C-
NMR (100 MHz, CDCl3): δ 12.2(CH3), 20.0(CH3), 56.6(CH), 116.1(CH2). Further signals overlapped
with those of the main product 8. GC-FTIR: 3072, 2990, 2946, 1519, 1470, 1445, 1413, 1354, 1299,
1256, 1177, 1226, 1063, 1030, 988, 927, 784, 725 cm-1; GC-MS [m/z (% rel. int.)]: 213(57, M+),
199(12), 198(79), 160(12), 159(100), 157(11), 130(15), 128(11), 118(63), 105(10), 104(85), 103(34),
91(14), 89(15), 77(48). Compound 11: 1H-NMR (400 MHz, CDCl3): δ 1.61 (d, J=6.8 Hz, 3H), 2.45 (s,
3H), 4.97-5.05 (m, 1H), 5.07 (d, J=17.5 Hz, 1H), 5.22 (d, J=10.3 Hz, 1H), 6.11 (ddd, J=17.5, 10.3, 5.7
Hz, 1H), 7.46-7.50 (m, 3H), 7.57-7.61 (m, 2H) ppm; 13C-NMR (100 MHz, CDCl3): δ 14.6(CH ),
3
21.2(CH3), 56.9(CH), 116.8(CH2), Further signals coincide with those of the main product 9. GC-
FTIR: 3075, 2987, 2945, 1504, 1451, 1407, 1381, 1358, 1321, 1181, 1013, 926, 773, 729 cm-1; GC-
MS [m/z (% rel. int.)]: 213(28, M+), 212(6), 199(9), 198(66), 160(13), 159(100), 131(10), 130(11),
118(62), 104(56), 103(24), 95(22), 91(13), 89(11), 77(31).
Thermolysis of 15 gave two additional products which could not be separated by the available
1
chromatographic methods. H-NMR data, GLC-MS and GLC-FTIR spectra indicated the product to be
a mixture of 1-(cis-1-propenyl)-3-phenyl-1,2,4-1H-triazole (19) and 1-(trans-1-propenyl)-3-phenyl-
1,2,4-1H-triazole (20); Compound 19: GC-FTIR: 3070, 2936, 2874, 1676, 1523, 1495, 1446, 1321,

Molecules 2001, 6
494
1294, 1233, 1206, 1105, 1023, 934, 842, 794, 725, 693 cm-1; GC-MS[m/z (% rel. int.)]: 186(10),
185(70, M+), 184(11), 158(33), 132(5), 105(22), 104(100), 103(17), 89(4), 82(22), 81(19), 77(30),
76(17); Compound 20,: GC-FTIR: 3069, 2934, 1670, 1523, 1495, 1445, 1317, 1294, 1196, 1103, 1020,
783, 726 cm-1; GC-MS [m/z (% rel. int.)]: 185(79, M+), 184(11), 158(33), 132(5), 105(22), 104(100),
103(19), 82(21), 81(19), 77(27).
The main product after thermolysis of 23 was assigned the structure1,3-di(3-phenyl-1H-1,2,4-triazol-1-
yl)-butane (29): 1H-NMR (400 MHz, CDCl3): δ 1.62 (H-4, d, J= 6.8 Hz, 3H), 2.44-2.62 (H-2, m, 2H),
3.97-4.04 (H-1, m, 1H), 4.17-4.24 (H-1, m, 1H), 4.47-4.52 (H-3, m, 1H), 7.38-7.48 (m-, p- Ph, m, 6H),
8.08 (triazole-H, s, 1H), 8.09-8.15 (o-Ph, m, 4H), 8.20 (triazole-H, s, 1H) ppm; HH-COSY: The
methyl doublet at 1.62 ppm coupled with the H-3-proton at 4,47- 4.52 ppm. The H-2-protons at 2.44-
2.62 ppm coupled with each other as well as with the H-3-proton and the H-1-proton at 3.97-4.02 and
the H-1 proton at 4.17- 4.24 ppm respectively. The H-1 and the H-1?-protons also coupled. The meta
and para protons of the phenyl groups appeared between 7.4-7.5 ppm. The ortho protons appeared at
8.09-8.15 ppm. The 5-H-triazole protons were observed as singlets at 8.08 and 8.20 ppm, respectively;
13C-NMR (100 MHz, CDCl3): δ 21.2 (CH3), 36.3 (CH2), 46.0 (CH2), 53.2 (CH), 126.3 (CH, two
peeks), 128.5 (CH), 128.8 (CH), 129.3 (CH), 129.4 (CH), 130.8 (C), 131.0 (C), 143.3 (CH), 144.2
(CH), 162.9 (C), 163.0 (C) ppm; GC-FTIR: 3070, 2987, 2950, 1521, 1493, 1440, 1334, 1291, 1199,
1107, 1023, 968, 844, 726 cm-1; MS [m/z (% rel. int.)]: 344(57, M+), 200(4), 199(11), 198(4), 187(14),
186(92), 184(6), 174(11), 173(100), 172(85), 159(23), 158(61), 146(21), 145(36), 132(4), 131(9),
118(5), 105(14), 104(82), 89(10), 77(17). Found M+: 344.1751, Calc for C20H20N6: 345.1749;
Analysis: Calc. for C20H20N6 ; C, 69.75; H, 5.85; N, 24.40. Found: C, 69.51; H, 6.09; N, 24.18.
Minor amounts of a compound with very similar properties, which was assumed to be an isomer of 29,
was isolated together with minor impurities and exhibited the following spectroscopic properties: GC-
FTIR: 3128, 3069, 2985, 2947, 1522, 1494, 1439, 1279, 1202, 1026, 1010, 726, 696, 668 cm-1; GC-
MS [m/z (% rel. int.)]: 344(4, M+), 199(7), 198(4), 186(9), 184(8), 174(11), 173(99), 172(78), 159(13),
158(100), 146(14), 145(23), 132(4), 131(11), 118(4), 105(9), 104(81), 103(11), 89(13), 77(22), 76(5).
Found M+ 344.1751, Calc. for C20H20N6: 344.1742
References and Notes
1. Carlsen, P.H.J.; Jørgensen, K.B. J. Heterocycl. Chem., 1991, 34, 797
2. (a) Carlsen, P.H.J.; Gautun, O.R. Acta Chem. Scand., 1990, 44, 485; (b) Gautun, O.R.; Carlsen,
P.H.J. Acta Chem Scand., 1992, 46, 469; (c) Gautun, O.R.; Carlsen, P.H.J. Acta Chem Scand.,
1994, 48, 411
3. Carlsen, P.H.J.; Jørgensen, K.B. J. Heterocycl. Chem., 1994, 31, 805
4. Uda, M.; Hisazumi, Y.; Sato, K.; Kukota; S. Chem. Pharm. Bull., 1976, 24, 3103
5. Francis, J.E.; Gorczyca, L.A.; Mazzenga, G.C.; Meckler, H. Tetrahedron Lett. 1987, 28, 5133.
6. Jacobs, P.; Mangold, D.; Oeser, H.-G. Ger. Offen. DE 2935164, 1981.

Molecules 2001, 6
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7. Hoggarth, E. J. Chem Soc., 1952, 4811
8. Habraken, C.L.; Cohen-Fernandes, P. J. Chem. Soc., Chem. Commun., 1972, 37
9. Grichtel, H.; Töpper, B. Liebigs Ann. Chem., 1989, 1071
10. Pèrez, M.A.; Dorado, C.A.; Soto, J.L. Synthesis, 1983, 483
11. Ainworth, C. J. Am. Chem. Soc., 1955, 77, 1148
12. Atkinson, M.R.; Polya, J.B. J. Chem. Soc., 1954, 3319
13. Gilchrist, T.L.; Rees, C.W.; Thomas, C.J. J. Chem. Soc., Perkin Trans. I., 1975, 12
Sample Availability: Available from the authors.
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