Synthesis, spectroscopic and thermal characterization of azido-1,2,4-triazoles: A class of heteroarenes with a high nitrogen content

Article abstract of DOI:10.1002/ejoc.201101450

The syntheses of azido-1,2,4-triazoles 1-5 were carried out from triaminoguanidine hydrochloride and a carboxylic acid (formic, acetic, 2,2,2-trifluoroacetic, 2-benzylacetic, monochloroacetic acid) by a three-step synthetic route and were analyzed by accelerating rate calorimetry (ARC). The thermal decomposition of 1-5 was studied theoretically by using CHETAH and T1 software, and experimentally by using DSC to obtain kinetic data. Numerical modelling and mass spectrometry were also performed to estimate the nature of the intrinsic molecular reactivity of 1-5 and the possible early stages of a self-heating process. Complete optimization by using HF, B3LYP and MP2(full) methods at the 6-31G* level were performed on significant tautomeric forms of the azido-triazoles to confirm the electronic structures that were obtained by EI-MS. We have synthesized azido-1,2,4-triazoles 1-5 from triaminoguanidine hydrochloride and a carboxylic acid by a three-step route. The procedure has been optimized from a "green agreeability" point of view. The thermal decomposition of 1-5 has been investigated theoretically by using predictive software, and experimentally by using differential scanning calorimetry. Copyright

Full text of DOI:10.1002/ejoc.201101450

FULL PAPER
DOI: 10.1002/ejoc.201101450
Synthesis, Spectroscopic and Thermal Characterization of Azido-1,2,4-
triazoles: A Class of Heteroarenes with a High Nitrogen Content
Paolo Cardillo,[a] Marco Dellavedova,[a] Lucia Gigante,*[a] Angelo Lunghi,[a]
Christian Pasturenzi,[a] Elisabetta Salatelli,[b] and Paolo Zanirato*[c]
Keywords: Azido-heteroaryls / DSC analysis / Density functional calculations / Ab initio calculations / Electronic
structure / ARC test
The syntheses of azido-1,2,4-triazoles 1–5 were carried out
from triaminoguanidine hydrochloride and a carboxylic acid
(formic, acetic, 2,2,2-trifluoroacetic, 2-benzylacetic, mono-
chloroacetic acid) by a three-step synthetic route and were
analyzed by accelerating rate calorimetry (ARC). The ther-
mal decomposition of 1–5 was studied theoretically by using
CHETAH and T1 software, and experimentally by using DSC
to obtain kinetic data. Numerical modelling and mass spec-
trometry were also performed to estimate the nature of the
intrinsic molecular reactivity of 1–5 and the possible early
stages of a self-heating process. Complete optimization by
using HF, B3LYP and MP2(full) methods at the 6-31G* level
were performed on significant tautomeric forms of the azido-
triazoles to confirm the electronic structures that were ob-
tained by EI-MS.
equivalent 3- and 5-substituents crystallize as tautomers
that bear substituents with more pronounced electron-do-
nor properties at the 5-position.[8] Additional impetus was
given to this work by the fact that, to the best of our knowl-
edge, only two azido-triazoles (1,2,4-triazolyl azide 1 and
methyl-1,2,4-triazolyl azide 2, Scheme 1) have been pre-
pared to date, but their isomeric structures have not been
ascertained.[9]
Introduction
Azides derived from five-membered heteroarenes play an
increasing role in chemistry,[1] and their synthesis has stimu-
lated overwhelming interest.[2] To date, the great majority
of heteroaryl azides have been obtained by the aromatic
nucleophilic displacement of various nucleofuge groups
with an azido ion, by diazotization of heteroarylamines fol-
lowed by the addition of sodium azide or the conversion of
hydrazines to azides by diazotization.[3] A number of five-
membered azido heteroarenes with one or two heteroatoms
have been successfully produced in our laboratory by the
azido transfer reaction with regioselectively lithiated het-
eroaryls and tosyl azide.[4]
Our long-term interest in the field of the heteroaryl
azides prompted us to study an extension to azido-1,2,4-
triazoles, some of which are virtually unknown. This study
was carried out in view of the chemical, thermal, theoretical
and biological importance of the 1,2,4-triazole system,
which has been shown to be a tunable aryl/alkyl ionic li-
quid.[5] The 1,2,4-triazole substructure has been incorpo-
rated into a wide variety of therapeutically important
agents, which mainly display antimicrobial[6] and anti-in-
flammatory activities.[7] Normally, 1,2,4-triazoles with non-
Scheme 1. Three-step synthesis of 1–5; R = H, CH3, CF3, CH2Ph,
CH2Cl.
The synthetic route to azido-1,2,4-triazoles 1–5 described
here is a combination of two reactions: a cyclocondensation
by heating triaminoguanidine hydrochloride (TAG·HCl)
with an excess of the appropriate carboxylic acid (Scheme 1,
Step 2) followed by diazotization of the (aminotriazolyl)-
hydrazine intermediate I with 2 equiv. of sodium nitrite
(Step 3). TAG·HCl was prepared from guanidine hydro-
chloride and 3 equiv. of hydrazine hydrate at room tempera-
ture in water (Step 1).
[a] Stazione Sperimentale per i Combustibili SSC,
Viale A. De Gasperi 3, 20097 San Donato Milanese (MI), Italy
[b] Dip.to di Chimica Industriale e dei Materiali,
Viale Risorgimento 4, 40136 Bologna, Italy
[c] Dip.to di Chimica Organica “A. Mangini”,
Viale Risorgimento 4, 40136 Bologna, Italy
E-mail: paolo.zanirato@unibo.it
gigante@ssc.it
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201101450.
Eur. J. Org. Chem. 2012, 1195–1201
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We were also interested in the conversion of the pre- groups on I (Step 3). The risk of Steps 1 and 3 was analyzed
viously reported routes to 1,2,4-triazoles for 1 and 2 into a by accelerating rate calorimetry (ARC, see Exp. Sect.).[19]
three-step “green” route. Green chemistry and chemical
safety are linked concepts that should be applied when po- in static nitrogen (Φ = 5 °C min–1) showed less dangerous
tentially hazardous compounds are involved.[10]
exothermic decomposition at Tp 225 °C (ΔdH
Differential scanning calorimetry (DSC)[20] of TAG·HCl
=
=
The thermochemical properties of nitrogen-rich covalent 1166 Jg–1) compared to other TAG salts.[21] To maintain
azides and their potential use as high-energy-density mate- a parallel between the experimental results and electronic-
rials are under continuous investigation.[11] Attention has structure calculations, various isomeric structures of TAG
been recently paid to the energetic content of compounds have been reported by using ab initio molecular orbital
as triazolium-based ionic salts,[12] which contribute to high (MO) and density functional methods.[22]
heats of formation and high energetic densities, but no ther-
mal behaviour has been reported on this class of neutral Theory
species. The only exception is a study on the gas-phase
Structural characterization of 1–5 was made by IR and
1H and 13C NMR spectroscopy and MS in combination
with electronic methods. Complete optimization was per-
formed on various isomers of each triazole to determine the
energy and geometrical parameters by using HF, B3LYP[23]
and MP2(Full)[24] methods at the 6-31G* level of calcula-
tions (Table 1).
flash-pyrolysis of 3-azido-1,2,4-triazole, which results in the
elimination of nitrogen and formation of N-cyanomethan-
imine (CH2=N–CN) presumably via a nitrene intermedi-
ate.[13] Compounds 1–5 were selected as significant exam-
ples of a series of nitrogen-rich covalent azides whose dan-
gerous threshold values, given by the molecular composi-
tion ratio (C + O + S)/N, are Յ 3, and to shed light on the
role of both the substituent and the azido group on thermal
decomposition (TD) phenomena. The hazardous properties
of this class of oxygen-free compounds are attributed to the
easy polarization of the –N3 π-bond, which facilitates N2
extrusion.[14] Many organic compounds that contain one
(or more) azido group(s) are thermally (or mechanical
shock) sensitive.[15]
Interest in these potentially explosive molecules has
grown as researchers have overcome their awe of the hazard
posed by handling azides.[16] In spite of the fact that organic
azides are generally stable towards common oxidants and
acidic aqueous solutions, azides with large positive heats
of formation (ΔfH) are inherently unstable. The underlying
reasons for the reactivity or lack of stability of a molecule
can be elucidated by examining its thermodynamic param-
eters and by scrutinizing its (a) kinetic variables,[11b,11c] (b)
critical temperatures,[17] (c) numerical protocols based on
its symmetry and geometry, (d) spatial distributions and en-
ergies of a few dominant orbitals and (e) electric polariz-
abilities and hyperpolarizabilities.
Table 1. Calculated absolute energies [a.u., zero-point energy (ZPE)
corrected values], density [ρ, g/mL] and heat of formation [ΔfH,
kJmol–1] (T1) for the favoured isomeric structures of 1–5.
B3LYP/6-31+G* MP2(FC)/6-31G*
ρ
ΔfH
1a
1b
1c
2a
2b
2c
3a
3b
3c
4a
4b
4c
5a
5b
5c
–405.760266
–405.772144
–405.770004
–445.053855
–445.065423
–445.057823
–742.794577
–742.794832
–742.799141
–676.030034
–676.028236
–676.040001
–904.656129
–904.658682
–904.664538
–404.654038
–404.664637
–404.662583
–443.800346
–443.810762
–443.803633
–740.223598
–740.227316
–740.232491
–673.521779
–673.519257
–673.532333
–902.830695
–902.831700
–902.840035
0.7464
–
–
–
0.9290
–
–
–
0.8850
–
–
0.6290
–
566.67
537.17
537.40
523.71
495.03
505.48
–92.09
–110.30
–117.12
621.88
609.51
592.70
475.74
488.39
503.73
–
0.7861
The azido group is involved in π-electron interaction with
the 1,2,4-triazole nucleus, which is dependent on the nature
of the substituent. As an example, Figures 1 and 2 depict
the prototropic electronic structures (1a, 1b, 1c and 3a, 3b,
Results and Discussion
According to the synthetic route described above 3c, respectively) and their significant geometric parameters
(Scheme 1), TAG·HCl was prepared from guanidine hydro- (the absolute energies of the more stable prototropic iso-
chloride (1 equiv.) and hydrazine hydrate (3 equiv.) in boil- mers are in bold in Table 1). In all cases, the azido group is
ing water or at room temperature (Step 1).[18] 1H-1,2,4-Tri- oriented in the same plane as the heteroaryl triazole ring,
azol-5-yl azide (1), 3-methyl-1H-1,2,4-triazol-5-yl azide (2), similar to 3,6-diazido-1,2,4,5-tetrazine,[11d] triazidotrinitro-
5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl azide (3), 5-benzyl- benzene and azidothymidine.[25]
1H-1,2,4-triazol-3-yl azide (4) and 3-(chloromethyl)-1H-
Most work on simple 2-azido-azole molecules (thiazole
1,2,4-triazol-3-yl azide (5) were prepared from an excess of and imidazole) has focussed on azido–tetrazole isomerism,
the corresponding carboxylic acid (formic, acetic, 2,2,2-tri- which has been extensively studied experimentally[26] and
fluoroacetic, 2-phenylacetic and monochloroacetic acid, theoretically.[27] Figure 3 depicts the triazolo–tetrazoles Tet-
respectively) and TAG·HCl by cyclocondensation to hy- 1–5 hypothesized at the MP2(FC)/6-31G* level, and Table 2
drazinyl-1,2,4-triazolylamino intermediates (I, Step 2) and reports the energetic values of the most stable isomer (T1)
converted into the corresponding target azido-1,2,4-tri- for each substituent calculated by ab initio MO and density
azoles by the diazotization of the amino and hydrazino functional methods.
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Azido-1,2,4-triazoles
Figure 1. Molecular modelled tautomeric structures (a, b, c) and some geometric parameters [° and Å] for 1 calculated at the MP2(FC)/
6-31G* level.
Figure 2. Molecular modelled tautomeric structures (a, b, c) and some geometric parameters [° and Å] for 3 calculated at the MP2(FC)/
6-31G* level.
Figure 3. The most stable tautomeric structures for Tet-1–5 calculated at the MP2(FC)/6-31G* level.
In order to predict and detect the early-stage processes
Table 2. Calculated absolute energies [a.u., ZPE-corrected values],
ρ [g/mL] and ΔfH [kJmol–1] (T1) for the most stable isomers of
Tet-1–5.
involved in the TD of 1–5, theoretical calculations by using
CHETAH (chemical thermodynamic and hazard evalu-
ation)[28] and T1[29] software packages and EI-MS (70 eV)
were performed. The data calculated with CHETAH for the
azido–triazoles are listed in Table 3.
ΔdH values for 1–4 were predicted to be over the threshold
of –2930 Jg–1, above which compounds are considered dan-
gerous, whereas that of 5 was undetermined due to the ab-
sence of a Benson group.[30] Moreover, comparison of the
CHETAH-predicted heats of formation (ΔfH) with those ob-
B3LYP/6-31+G* MP2(FC)/6-31G*
ρ
ΔfH
Tet-1
Tet-2
Tet-3
Tet-4
Tet-5
–405.737313
–445.033189
–742.765759
–676.001630
–904.641010
–404.631496
–443.768791
–740.866486
–676.031632
–902.833857
0.7706 701.69
0.7162 590.04
0.9067 –18.03
0.6391 701.50
0.8071 628.38
By comparison, calculations for the possible isomers Tet- tained by using the computationally less intensive thermo-
1–5 are summarized in Table 2, which confirm the linear chemical recipe T1, revealed that the values obtained by using
azido preference shown by azido–diazoles.[2a,4a]
the two approaches are comparable (cf. Tables 1 and 3).
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Table 3. Calculated (CHETAH) heats of combustion [ΔcH, Jg–1], spectra, which show different fundamental fragmentation
decomposition (ΔdH, Jg–1), formation (ΔfH, kJmol–1) and N–N2
by the pathways A and B (Scheme 2). Unexpectedly,
attempts to record the EI mass spectra of 5 under the same
bond energies (B3LYP/6-31G*) [kJmol–1] of 1–5.
ΔcH
ΔdH
ΔfH
EN–N2
conditions failed.
The calculated prototropic forms (Table 1, a–c) show an
energy gap of 10–40 kJmol–1, which might be too low to
markedly affect the thermal behaviour of structures that
have a heat of formation tenfold larger.
1
2
3
4
5
–1569.6
–2172,0
–1310.6
–5123.9
–
–5250.9
–5365.9
–3345.2
–3815.8
–
540.57
507.64
–141.37
614.71
–
111.0
104.0
118.8
135.5
209.2
DSC enabled us to characterize the thermal stability of
1–5. The experimental heats of decomposition obtained by
The calculated absolute energies (Table 1) of 1–5 indicate DSC and the related initial exothermal onset temperature
that the nature of the substituent on the triazole ring sub- (TEOT) are shown in Table 4.
stantially affects the prototropy of these compounds, where
Table 4. DSC-determined heat of decomposition [Jg–1], tempera-
1b and 2b of the type 3-R-5-azido-1H-1,2,4-triazole (R =
ture [°C] and kinetic parameter [Ea, kJmol–1] for the TD of 1–5
H, CH3) are favoured with respect to 3c, 4c and 5c of the
type 3-azido-5-R-1H-1,2,4-triazole (R = CF3, CH2Ph and
CH2Cl). Accordingly, the nature of R affects the EI mass
under various conditions.[a]
Compd. ΔdH[b] ΔdH[c] TEOT
Tp
TEET
Ea
lnA°[h]
[d]
[e]
[f]
[g]
1
2
3
4
5
2245
2025
1355
790
2270
1725
1190
790
160
186
186
193
187
179
209
215
213
206
197
126.18
123.99
129.39
126.07
122.79
27.97
27.34
28.30
27.26
27.59
160
160
155
130
1675
1681
[a] TD data refer to a scan rate (Φ) of 5 °Cmin–1. [b] In static
air. [c] Under nitrogen. [d] Exothermic onset temperature. [e] Peak
decomposition temperature. [f] Exothermic endset temperature. [g]
From thermoanalytical data obtained by using the ASTM E698
method. [h] Frequency factor [min–1].
The DSC profiles, the example of 2 is shown in Figure 4,
measured at different heating rates from 90 to 200 °C, were
analyzed by using the ASTM E698 method. From a plot of
logb (b = heating rate in °Cmin–1) against 1/T (T = peak
temperature in °C), the activation energies (Ea), the preex-
ponential factor (A0) and the kinetic constant (k) for each
Scheme 2. Structural dependence of the main EI mass spectra frag-
mentation of 1–5.
Figure 4. DSC experiments performed under nitrogen at scanning rates (Φ) of 2, 5 and 10 °Cmin–1 of 2 (top) and DSC kinetic evaluation
results of 2, conversion [%] vs. time [t, min] at various temperatures (bottom).
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Azido-1,2,4-triazoles
Table 5. Kinetic parameters and activation energies for the TD of 1–5 calculated from thermoanalytical data obtained by using the ASTM
E698 method.[a]
1
2
3
4
5
k / min–1
1.403ϫ1012
126.8
7.475ϫ1011
124.0
1.952ϫ1012
129.4
1.389ϫ1012
126.1
9.598ϫ1011
122.8
Ea / kJmol–1
ΔrH / kJmol–1
123.7
–0.17
121.5
–0.18
126.9
–0.19
123.6
–0.19
120.3
–0.18
Sa / K–1 mol–1
[b]
[a] DSC data refer to four runs at heating rates of 2, 5, 10 and 15 °Cmin–1 in static nitrogen. [b] Calculated at 298 K.
to a reference sample with DSC 820 and DSC 823 Mettler Toledo
instruments with the following accuracy standards: (i) 5 °Cmin–1
for the evaluation of decomposition enthalpy under both oxidative
and closed steel vessel nonoxidative conditions from 30 to 280 °C,
(ii) 2, 5 and 10 °Cmin–1 for the evaluation of kinetic data from
dynamic heating under nitrogen in a closed steel vessel from 30
to 280 °C, unless otherwise stated.[31] Thermogravimetric analysis,
which measured weight loss under both oxidative and nonoxidative
heating conditions in an open vessel, allowed the IR and mass spec-
tra of the released gases to be recorded (TGA-DSC 1LF/164 from
absolute temperature can be calculated. The data obtained
for 1–5 are reported in Table 4.
The TD reactions of 1–5 were treated as having first-
order kinetics as plots of lnk vs. T show a linear trend with
correlation coefficients R = 0.999. The Ea values of 1–5
were calculated with corresponding lnA0 values. Assuming
a unimolecular processes, we calculated the activation en-
thalpies (ΔH‡) and entropies (ΔSa) from the data (Table 5).
The ASTM-calculated half-lives and the corresponding
Ea values for the TD of 1–5 at 25 °C were comparable. This Mettler Toledo, Nexus FTIR from Thermo Fischer Scientific,
Pfeiffer Vacuum Thermostar MS spectrometer). The melting points
of 1, 2, 4 and 5, were 120.3, 132.5, 143.2 and 69.3 °C, respectively,
obtained from DSC and were in agreement with previously mea-
sured values.
implies substantially comparable thermal behaviour, which
can be ascribed to the extrusion of nitrogen and formation
of a nitrene without the assistance of the R substituents.
This was also confirmed by the slightly negative Sa values.
Materials: The synthetic route, which was slightly modified with
respect to those previously described, is a “green” processes. The
basic reaction steps that allow the access to 1–5, the formation of
TAG·HCl and the nitrosation of the hydrazinyl-1,2,4-triazolylam-
ino intermediates, were studied by ARC in a process hazard assess-
ment. Guanidine hydrochloride, hydrazine hydrate, sodium nitrite
and the carboxylic acids (formic, acetic, 2,2,2-trifluoroacetic, 2-
benzylacetic, monochloroacetic acid) were purchased at high purity
from Aldrich Chemical Italy.
Conclusions
The three-step synthetic route to asymmetric azido-1,2,4-
triazoles 1–5 appears to be applicable to different low-melt-
ing aliphatic acids in a closed procedure. The chemical effi-
ciency at low temperature for Steps 1 and 3, the low cost of
reagents, the generally high product yields and the use of
water as the medium make this process ecofriendly. The risk
of Steps 1 and 3 (Scheme 1) at room temperature was ascer-
tained by ARC. An ARC test on Step 2 was unsuccessful.
The potentially hazardous properties and thermochemi-
cal behaviour of 1–5 were investigated by DSC, NMR and
FTIR spectroscopy and EI-MS. The TD of 2–3 and 5 dis-
play medium to high exothermicity, higher for 1 and lower
for less nitrogen-containing 4. TD generally occurs without
the assistance of oxygen, and both the ring and the azido
group fragmentation result in the loss of 2 equiv. of nitrogen
and cyanogen.
ARC Tests: The ARC (TIAX) tests were carried out according to
ASTM specifications (E1981-98 Standard Guide for Assessing the
Thermal Stability of Materials by Methods of Accelerating Rate
Calorimetry).
Step 1. Triaminoguanidine Synthesis: Total sample amount: 2.96 g.
Test cell type: Hastelloy C. Test cell weight: 13.95 g. Test cell vol-
ume: 8 ml. Φ factor: 1.61. A mixture of guanidine hydrochloride
(0.4 g), hydrazine hydrate (0.6 g) and water (2.0 g) was loaded in the
sample holder at room temperature. A standard Heat Wait Search
(HWS) test was set up in the 30–300 °C range with magnetic stir-
ring (50 rpm). Initial decomposition temperature, To = 170 °C. Ini-
tial pressure (at To) = 14.7 bar. Maximum self-heating rate (SHR,
Φ-corrected) = 0.2 °Cmin–1. Temperature at maximum SHR, Tmax
= 188 °C. pressure at Tend = 40.6 bar. Φ-corrected adiabatic tem-
perature rise = 46 °C. Φ-corrected final temperature = 216 °C. De-
composition enthalpy = –193 kJkg–1. At the end of the test at room
temperature, a residual pressure of 14.5 bar and a sample weight
loss of 33.4% were observed, which means that the sample gener-
ated noncondensable decomposition products.
On the whole, the molecular modelling performances
agree with the respective tautomeric structures observed by
EI-MS and support their thermal properties, which show
relatively more energetic decomposition for azido–triazoles
that contain no substituent or the methyl-releasing group
(1 and 2, respectively).
Step 2. Nitrosation of the Hydrazinyl-1,2,4-triazolamine: Total sam-
ple amount: 4.78 g. Test cell type: Hastelloy C. Test cell weight:
14.12 g. Test cell volume: 8 mL. Φ factor: 1.55. Hydrazinyl-1,2,4-
triazolamine solution (2.85 g) was loaded in the sample holder at
room temperature. A standard HWS test was set up in the 30–
300 °C range and with magnetic stirring (50 rpm). During the se-
arch period at 30 °C, NaNO2 (0.7 g) in water (1.23 g) was added
through a syringe. The instrument detected an exothermic effect as
soon as the NaNO2 solution was added, which resulted in a large
Experimental Section
Physical Measurements and Calculations: The initial thermochemi-
cal data were calculated by the ASTM program for chemical
thermodynamic and energy release evaluation (CHETAH, ver. 8.0,
2005).[28] The heats of formation obtained by this method were
compared with those calculated by using a recently released Spar-
tan 06 code, T1.[29] Thermal performances were measured relative
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L. Gigante, P. Zanirato et al.
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amount of gas. Some of the gas was vented during the addition
through the open charge tube of the instrument. After the first
exothermic effect, other two exothermic consecutive effects were
detected and monitored in adiabatic mode by the instrument. The
main results of the first exothermic effect are: starting temperature,
To = 30 °C. Initial pressure at To = 1.2 bar. Maximum SHR (Φ-
(75 MHz, [D6]acetone): δ = 144.2, 140.8 ppm. MS: m/z (%) = 110
(32.8) [M+], 82 (7.9) [M–N2]+, 53 (100) [M – 57]+.
3-Methyl-1H-1,2,4-triazol-5-yl Azide (2): Yield: 88%. M.p. 128–
30 °C. C3H4N6 (124.10): calcd. C 29.03, H 3.25, N 67.72; found C
28.92, H 3.23, N 67.67. IR: ν
= 2147 (N3) cm–1. 1H NMR
˜
max
(300 MHz, CDCl3): δ = 10.5 (N–H), 2.52 (3 H, Me) ppm. 13C
NMR (75 MHz, CDCl3): δ = 157.4, 155.3, 12.2 (t) ppm. MS: m/z
(%) = 124 (3.8) [M]+, 67 (100) [M – 57]+.
corrected) = 136 °Cmin–1. temperature at maximum SHR, Tmax
=
36 °C. Pressure at Tend = 1.5 bar. Observed adiabatic temperature
rise = 34 °C. Φ-corrected temperature rise = 52 °C. Φ-corrected
final temperature = 82 °C. Reaction enthalpy = –152 kJkg–1. The
main results of the second exothermic effect are: To = 64 °C. Initial
5-Trifluoromethyl-1H-1,2,4-triazol-3-yl Azide (3): Yield: 67%, oil.
C3HF3N6 (178.07): calcd. C 20.23, H 0.57, N 47.19; found C 20.18,
H 0.57, N 47.18. IR: νmax = 2156 (N3), 1187 (CF3) cm–1. 13C NMR
˜
pressure at To
= 1.5 bar. Maximum SHR (Φ-corrected) =
1 °Cmin–1. Temperature at maximum SHR, Tmax = 101 °C. Pres-
sure at Tend = 16.0 bar. Φ-corrected adiabatic temperature rise =
110 °C. Φ-corrected final temperature = 174 °C. Decomposition
enthalpy = –322 kJkg–1. At the end of the test at room temperature,
a residual pressure of 21 bar was observed, which means that the
sample generated noncondensable decomposition products.
(75 MHz, CDCl3): δ = 153.5, 152.5 (q, J = 0.8 Hz), 118.8 (q, J =
5.4 Hz) ppm. MS: m/z (%) = 178 (8.1) [M]+, 159 (3.0) [M – F]+,
137 (7.1), 121 (13.4) [M – 57]+, 69 (100).
5-Benzyl-1H-1,2,4-triazol-3-yl Azide (4): Yield: 77%. M.p. 146–
48 °C. C9H8N6 (200.20): calcd. C 53.99, H 4.03, N 41.96; found C
53.95, H 4.02, N 41.88. IR: ν
= 2140 (N3) cm–1. 1H NMR
˜
max
(300 MHz, CDCl3): δ = 10.5 (N–H), 7.28 (br. m, 5 H, Ph), 4.07 (2
H, CH2) ppm. 13C NMR (75 MHz, CDCl3): δ = 158.5, 157.7,
135.2, 129.5, 129.3, 128.0, 33.7 ppm. MS: m/z (%) = 200 (3.8)
[M]+, 143 (16.4) [M – 57]+, 121 (16.0), 92 (100).
Caution: Organic azides are potentially explosive! This category of
compounds has been subjected to risk evaluation.[15,16] Explosions
may occur in the preparation and handling of organic azides, al-
though we experienced no problems in handling our aryl or het-
eroaryl organic azides, which can be stored indefinitely at low tem-
perature (4 °C).
3-(Chloromethyl)-1H-1,2,4-triazol-3-yl Azide (5): Yield: 76%. M.p.
69–73 °C. C3H3ClN6 (158.59): calcd. C 22.73, H 1.91, N 53.01;
found C 22.68, H 1.90, N 52.98. IR: ν
= 2143 (N3), 728 (Cl)
˜
Instrumentation: Melting points were determined with a Kofler hot-
max
cm–1. ESI: m/z = 159 [M + 1]+, 181 [M + 23]+. 1H NMR (300 MHz,
CDCl3): δ = 8.80 (N–H), 4.67 (2 H, CH2) ppm. 13C NMR
(75 MHz, CDCl3): δ = 156.7, 155.6, 35.9 ppm.
stage apparatus. IR spectra were measured from films with a Per-
1
kin–Elmer Spectrum 2000 FTIR spectrometer. H and 13C NMR
spectra were recorded with a Varian Gemini 300 (300 and
75.4 MHz, respectively) from solutions in (CD3)2CO or CDCl3.
Mass spectra were recorded with VG7070E instruments by using
an electron impact ionization method (70 eV) at the same pressure
(10–7 atm) and temperature (27 °C). Calculations were performed
by using the program Spartan 06 (Windows), DFT and MP2 meth-
ods at B3LYP/6-31G* and MP2/6-31G* levels, running on an
AMD K7 processor at 1333 MHz by which optimized structures
and energetics of the N–N2 bond dissociation were obtained.
Supporting Information (see footnote on the first page of this arti-
cle): ARC tests main results for steps 1 and 2, including figures
showing the heat rate and pressure rate plots vs. test cell tempera-
ture under adiabatic conditions related to the exothermic effect.
Temperature and pressure plots vs. time and pressure plot vs. tem-
perature related to the whole test. Heat rate and pressure rate plots
vs. test cell temperature under adiabatic conditions for the three
exothermic effects. Temperature and pressure plots vs. time related
to the exothermic effect and pressure plot vs. temperature related
to the whole experiment. DSC profiles of the TD and plot of the
kinetic evaluation for azides 1–5.
Synthesis 1–5. General Procedure: A suspension of TAG·HCl (2.1 g,
0.015 mol) in liquid carboxylic acid (35 mL; formic acid: b.p.
100.8 °C; acetic acid: b.p. 118–119 °C; 2,2,2-trifluoroacetic acid:
b.p. 72.4 °C) was heated at 70–100 °C for 4–16 h. The resulting mix-
ture that contained the hydrazinyl-1,2,4-triazolamine intermediate
I (approximate yield: ca. 90–95%) was combined with concentrated
HCl (25 mL), and the resulting solution heated. In the instance of
solid carboxylic acids (2-phenylacetic acid: m.p. 76–77 °C; mono-
chloroacetic acid: m.p. 63 °C), TAG·HCl was added to the melted
acid and the route carried out as described. The excess volatile
carboxylic acid was removed under partial vacuum and recovered.
With 2-phenylacetic and monochloroacetic acids, a few extractions
with diethyl ether were required. The residual acidic solution was
combined with water (25 mL) and added dropwise at 0–5 °C to a
saturated aqueous solution of NaNO2 (0.033 mol, 2.3 g) over
30 min until gas evolution ceased. The solution was warmed to
room temperature and stirred for 30 min, neutralized (pH = 6.5)
with solid NaHCO3 and extracted with diethyl ether (3ϫ20 mL).
Upon concentration of the ethereal solution under vacuum, the
resulting solid residues (oily in the case of 3) were stored overnight
in a refrigerator and characterized by IR and 1H and 13C NMR
spectroscopy, elemental analysis and MS.
Acknowledgments
This work was supported by the Ministero Università e Ricerca
and the Alma Mater Progetto di Finanziamento Triennale, Ateneo
di Bologna.
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Received: October 4, 2011
Published Online: December 28, 2011
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Eur. J. Org. Chem. 2012, 1195–1201
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