Comparison of the Thermal Stabilities of Diazonium Salts and Their Corresponding Triazenes

Article abstract of DOI:10.1021/acs.oprd.0c00162

A range of diazonium salts and their corresponding triazenes have been prepared in order to directly compare their relative thermal stabilities (via initial decomposition temperature) from differential scanning calorimetry (DSC) data. A structure-stability relationship has been explored to investigate trends in stability, depending on the aromatic substituent and the structure of the secondary amine component of the diazonium salts and triazenes. All of the triazenes investigated show significantly greater stability (many are stable above 200 °C) compared with the corresponding diazonium salts, which show varying stabilities.

Full text of DOI:10.1021/acs.oprd.0c00162

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Comparison of the Thermal Stabilities of Diazonium Salts and Their
Corresponding Triazenes
Christiane Schotten, Samy K. Leprevost, Low Ming Yong, Colan E. Hughes, Kenneth D. M. Harris,
and Duncan L. Browne*
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ABSTRACT: A range of diazonium salts and their corresponding triazenes have been prepared in order to directly compare their
relative thermal stabilities (via initial decomposition temperature) from differential scanning calorimetry (DSC) data. A structure−
stability relationship has been explored to investigate trends in stability, depending on the aromatic substituent and the structure of
the secondary amine component of the diazonium salts and triazenes. All of the triazenes investigated show significantly greater
stability (many are stable above 200 °C) compared with the corresponding diazonium salts, which show varying stabilities.
KEYWORDS: triazene, diazonium salt, thermal stability, DSC, continuous processing
INTRODUCTION
■
Diazonium salts are important intermediates in synthetic
chemistry, as they permit functionalization or transformation
at the attached aromatic carbon. Consequently, many trans-
formations utilizing diazonium salts have been developed.1−3
However, variability in the stability of diazonium salts renders
their use at large scale problematic.4,5 The stabilities of
diazonium salts range from excellent to explosive, though very
few are in the latter category. Nonetheless, the existence of some
explosive compounds raises caution and concern, which
provides motivation for the development of alternative synthetic
route design to avoid diazonium salt chemistry. The isolation of
some diazonium salts can be especially hazardous, as they are
shock-sensitive and decompose readily, while aryl diazonium
tetrafluoroborate, tosylate, disulfonimide or carboxylate salts are
often deemed stable for isolation, depending on the substituents
on the aromatic ring.6−10 The thermal instability of diazonium
salts and the evolution of large volumes of nitrogen gas upon
decomposition are particular issues for industrial-scale syn-
theses, and it is important to understand and control these
reactive intermediates.11 These issues have led to the develop-
ment of a number of continuous flow procedures in which
diazonium salts are made and consumed in situ.12,13 The
increased temperature control and presence of only small
amounts of reactive diazonium salt at any one time make this
way of processing inherently safer.
Another tactic for manipulating diazonium salts is to protect
them in the form of triazenes (Figure 1).14−20 Triazenes can be
prepared by protecting diazonium salts with secondary amines,
leading to products that exhibit very similar reactivity to
diazonium salts.21 Typically, under acidic conditions, triazenes
re-establish the reactivity exhibited by the parent diazonium salt
through an on−off equilibrium. While the diazonium compound
is still present in this situation, it is never isolated in dry form,
and thus, no shock sensitivity is encountered. Hence, triazenes
participate in much of the reactivity already established for
Figure 1. Overview of the reactivities of diazonium salts and triazenes
and the structure−stability relationship project design.
diazonium salts as long as a Lewis or Brønsted acid is present,
but with reduced risk and hence greater safety. Triazenes have
also been used as directing groups for metalation reactions and
as linkers in solid-phase synthesis, as they are usually stable
toward alkylating agents, strong bases, oxidation, and reduction.
Furthermore, most importantly, they are bench-sta-
ble.8,15,17,18,22−29
Special Issue: Flow Chemistry Enabling Efficient
Synthesis
Received: April 6, 2020
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© XXXX American Chemical Society
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While it is widely accepted that triazenes offer improved
thermal and shock sensitivity compared with the corresponding
diazonium salts, we have been unable to find any systematic
studies of structure−stability relationship (SSR) trends between
these two species. Herein we report a preliminary study toward
establishing such structure−stability relationships. Our project
design features the preparation of a set of tetrafluoroborate
diazonium salts bearing electron-rich, electron-poor and ortho,
meta, and para substituents, together with the corresponding
triazenes. In the triazene series, the secondary amine component
could also impact the stability of these materials, so a range of
secondary amines was designed, encompassing examples that
are cyclic (with different ring sizes), acyclic, and of different
symmetries. A few reports have measured decomposition
energies and decomposition temperatures of triazenes but
have not compared them directly to those of the corresponding
diazonium salts in a systematic manner. Lippert et al. showed
that the decomposition temperature of triazenes decreases with
the electron-withdrawing capacity of the substituents on the
aromatic ring, whereas the steric properties of the amine do not
must decrease in order to maintain the sample and the reference
at the same temperature. In the DSC data shown here and in the
Supporting Information, endothermic processes appear as
negative peaks (increased heat flow to the sample) while
exothermic processes appear as positive peaks (decreased heat
flow to the sample). In the present work, significant exothermic
events are assigned as compound degradation.30,42 For some of
the samples studied, the DSC data exhibit overlapping peaks
because of the occurrence of different thermal events, which
complicates the extraction of peak onset temperatures. For this
reason, our analysis of exothermic peaks assigned as
decomposition is focused on the initial decomposition temper-
ature rather than the onset temperature (see Figure 2). It is
have a strong influence.30 Dobele et al. used triazenes for the
̈
formation of aryl fluorides via the Wallach reaction and
measured DSC data for one of their triazene precursors to
demonstrate the high stability of triazenes.31 Although the
stability of triazenes compared with their diazonium salts is
mentioned in most publications, no direct comparison of their
relative stabilities has been established.
RESULTS AND DISCUSSION
■
The designed compounds were synthesized using known
methods. The diazonium salts (2a to 8a) were prepared on a
small scale in batch by first treating the corresponding anilines
with boron trifluoride diethyl etherate followed by addition of
isoamyl nitrite. Diazonium salt 1a, derived from anthranilic acid,
was not prepared because it is known to be a contact
explosive.32−38 The triazene compound series was prepared
using a telescoped continuous flow process optimized to
generate and consume the diazonium salt in situ while avoiding
precipitation of the intermediate diazonium salt (see Figure
3).39−41
Figure 2. DSC data for the anthranilic acid derived triazene 1b,
annotated to show the analysis and interpretation of different thermal
events.
important to note that, for a given sample, the initial
decomposition temperature will vary depending on the heating
rate used in the DSC measurement. However, as the DSC data
for all of the samples studied here were recorded at the same
heating rate (20 °C min−1), differences in the initial
decomposition temperatures of different samples provide a
reliable qualitative indication of their relative thermal stabilities.
Our 13C NMR data for the triazene series suggest that these
molecules undergo restricted rotation, as previously reported for
such materials (i.e., variable-temperature 13C NMR experiments
demonstrate temperature-dependent coalescence behav-
ior).30,43−50 There is inconsistency in the manner in which
this issue is reported in the literaturein some cases, the
observation of fewer 13C environments than expected is not even
addressed, while other cases simply note that the NMR data are
inconsistent with the proposed structure (with reference to the
restricted rotation phenomenon). To address this issue more
rigorously, the present paper reports 13C NMR data at three
different temperatures for each triazene studied (see the
Supporting Information), and we also demonstrate how these
temperature-dependent 13C NMR data can be used to calculate
the rotational energy barrier in the case of triazene 8b.
The degradation temperature of each compound was assessed
using differential scanning calorimetry (DSC). DSC is a
thermoanalytical technique in which a sample and a reference
(typically an empty sample holder) are heated or cooled at a
constant rate. The mode of operation differs for different types
of DSC instrument (e.g., power-compensated DSC or heat-flux
DSC), but the basic principle is that the instrument attempts to
maintain the sample and reference at the same temperature
throughout the heating/cooling process by varying the amounts
of heat that the instrument exchanges with the sample and with
the reference or by allowing heat exchange to occur between the
sample and the reference. As the present work is focused on
studying sample degradation at high temperature, the DSC
experiments involved heating the sample (and reference) from
20 °C to a temperature in the range of 160−250 °C at a rate of 20
°C min−1. If an endothermic or exothermic process occurs in the
sample, the amount of energy required to heat the sample differs
from the amount of energy required to heat the reference. For
example, during an endothermic process in the sample (e.g.,
melting), the energy supplied to the sample must increase in
order to maintain the sample and reference at the same
temperature; conversely, during an exothermic process in the
sample (e.g., decomposition), the energy supplied to the sample
The initial decomposition temperatures derived from the
DSC measurements are presented in Figure 3 (with further
analysis discussed in the Supporting Information), revealing
B
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Figure 3. Syntheses and initial decomposition temperatures (assigned from DSC data) for the diazonium salt (“a”) series and the triazene (“b”) series.
The estimated error in determining decomposition temperatures is 5 °C.
C
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some key observations both within and between the different
compound series. To aid interpretation, the results in Figure 3
are color-coded on a scale from red (low decomposition
temperature or explosive behavior) via blue (intermediate
decomposition temperature) to green (high decomposition
temperature). We note that instead of degradation, the
diazonium salts may undergo a Balz−Schiemann reaction with
the release of nitrogen gas and boron trifluoride and formation
of the corresponding aryl fluoride.51 In the present study, the
occurrence of the Balz−Schiemann transformation is regarded
as a decomposition pathway. Among the seven diazonium salts
studied by DSC analysis, the results in two cases (2a and 8a) are
considered as potentially indicative of Balz−Schiemann
processes; when these materials are heated, a melting endotherm
is followed by an exothermic or endothermic Balz−Schiemann
reaction, which is followed by an endothermic phase change
(boiling) of the product aryl fluoride at higher temperature (we
note that the boiling points of the corresponding aryl fluorides
are below the temperatures at which the Balz−Schiemann
process occurs, congruent with this interpretation). Three of the
other five diazonium salts (3a, 4a, and 6a) undergo a melting
endotherm, which is quickly followed by an exothermic
decomposition; this sequence of thermal events is consistent
with the melting behavior of those previously studied, which are
reported to exhibit “decomposition on melting”.52 Of the
remaining two diazonium salts, one (5a) does not decompose
below 200 °C, and the other (7a) decomposes in a manner
congruent with a “thermal runaway”.
(triazenes) highlights the greater stability of the triazene
molecules.
With regard to aromatic substituents, the sample set is too
small to draw firm conclusions, but comparison of the results for
the three monochloro anilines (para, ortho, and meta; 3a, 4a,
and 5a, respectively) points toward increased stability within the
diazonium series for meta substitution, with thermal stability
above 200 °C for 5a. The corresponding triazenes (3b, 4b, and
5b, respectively, with piperidine as the secondary amine) show
increased stabilities (decomposition above 200 °C). The same
trend in relative stability is observed for the p-bromo-substituted
diazonium salt 6a (initial decomposition temperature of 140
°C) versus the corresponding piperidine triazene 6b (decom-
position temperature above 200 °C). The electron-rich p-
methoxy-substituted diazonium salt 8a degrades at a lower
temperature (140 °C) than its triazene congener, although in
this case it appears that the para electron-donating group present
in 8b leads to increased instability, resulting in a broad
exothermic decomposition with an initial temperature of 150
°C. The electron-poor p-nitro-substituted diazonium salt 7a is
rendered significantly more thermally stable in its piperidine
triazene form 7b. In the case of 7a, the initial decomposition
temperature is 150 °C (Figure 4); however, the exothermic peak
in the DSC data in this case is sharp and leans toward higher
temperatures, indicative of an uncontrollable exothermic event
corresponding to thermal runaway during decomposition.
Although the use of a different DSC heating ramp might give
rise to a more well-defined exothermic behavior, for ease of
Some general observations can also be made with regard to
the triazene series. The triazenes that are solid at room
temperature all exhibit a melting endotherm below 100 °C,
and in most cases below 60 °C; in contrast, the triazenes that are
liquids at room temperature do not show this endothermic
transition in the DSC data. Typically, the triazenes do not
decompose below 200 °C. However, some of the triazenes
exhibit broad exotherms below 200 °C that are assigned as
degradation, including compound 1b (initial decomposition
temperature ca. 100 °C) and compounds 3c and 3f (initial
decomposition temperatures ca. 150 °C). The actual decom-
position pathways for these triazenes are not yet assigned;
however, the Balz−Schiemann reaction can be ruled out, as no
fluoride source is present in the preparation of these materials.
For five of the triazenes (2b, 4b, 5b, 6b, and 3e) a very broad
endothermic feature is observed, which is consistent with
evaporation of a liquid phase. In three of these cases (2b, 4b, and
6b), the material is a solid at room temperature; when the solid is
heated, a sharp endotherm due to melting is observed, followed
by the broad endotherm. In the other two cases (5b and 3e), the
material is already a liquid/oil at room temperature, and the
broad endotherm is the only feature observed below 200 °C in
the DSC data.
Comparison between the whole diazonium salt series and the
whole triazene series highlights that the triazenes are more stable
than the corresponding diazonium salts with respect to
thermally induced degradation (i.e., more compounds in the
triazene series are color-coded green). This difference is
particularly notable between 1a and 1b, for which the anthranilic
acid-derived triazene (1b) is isolable and not shock-sensitive
and degrades in a controlled exothermic process with initial
decomposition temperature of ca. 100 °C; in contrast, the
corresponding diazonium salt (1a) is explosive, as noted above.
Direct comparison between the set of “a” compounds
(diazonium salts) and the corresponding “b” compounds
Figure 4. DSC data for the p-nitrodiazonium salt (7a) and the p-
nitrotriazene (7b).
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comparison all of the compounds in this study were assessed
using an identical DSC ramp protocol (with heating at 20 °C/
min), and 7a was the only compound to show such behavior.
Notably, the corresponding triazene 7b exhibits two endother-
mic events (Figure 4), probably arising from residual solvent
evaporation followed by a phase transition (melting), with no
decomposition exotherm observed up to the highest temper-
ature studied (200 °C). For the triazene series bearing different
secondary amines (3b−g; Figure 3), pyrrolidines (3c and 3f)
appear to have reduced stability compared with other secondary
amines, including both acyclic and cyclic examples. Nonetheless,
compared with the parent diazonium salts, the triazenes have
greater stability. Clearly, a larger data set would allow the
dependence of the stability on the specific nature of the
substituents to be explored in greater depth.
Colan E. Hughes − School of Chemistry, Cardiff University,
Cardiff CF10 3AT, Wales, U.K.
Kenneth D. M. Harris − School of Chemistry, Cardiff University,
Cardiff CF10 3AT, Wales, U.K.; orcid.org/0000-0001-
7855-8598
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.oprd.0c00162
Author Contributions
The manuscript was written through contributions of all
authors. All of the authors approved the final version of the
manuscript.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
CONCLUSION
■
We thank Cardiff University and the Royal Society (D.L.B.,
Award RG150376) for financial support and the EPSRC UK
National Mass Spectrometry Facility at Swansea University for
MS measurements.
The structure−stability relationship study reported here has
compared the decomposition of a series of diazonium salts with
the decomposition of the corresponding triazenes. We have
demonstrated that triazenes derived from treatment of their
diazonium salt congeners with piperidine exhibit enhanced
stability, although preliminary studies suggest that this may not
be true for electron-rich systems. Moreover, the improved
stability appears to be applicable to a range of secondary amines,
with those based on a pyrrolidine motif exhibiting reduced
stability in comparison with other triazene systems. However,
the number of materials studied here is insufficient to allow more
precise conclusions on structure−stability relationships to be
derived. The continuous flow method used to prepare the
triazenes in this work obviates the requirement for large-scale
preparation of diazonium salts and thus delivers triazenes as
worthy candidates when planning synthetic routes requiring
functionalization at the carbon of an aromatic C−N bond.
Future work will investigate a larger matrix of compounds with
regard to both the aromatic substituents and the secondary
amine components.
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ASSOCIATED CONTENT
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* Supporting Information
The Supporting Information is available free of charge at
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(PDF)
AUTHOR INFORMATION
■
Corresponding Author
Duncan L. Browne − School of Chemistry, Cardiff University,
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College London, London WC1N 1AX, England, U.K.;
orcid.org/0000-0002-8604-229X;
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Email: duncan.browne@ucl.ac.uk
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Christiane Schotten − School of Chemistry, Cardiff University,
Cardiff CF10 3AT, Wales, U.K.; School of Chemistry, University
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Samy K. Leprevost − School of Chemistry, Cardiff University,
Cardiff CF10 3AT, Wales, U.K.
Low Ming Yong − School of Chemistry, Cardiff University,
Cardiff CF10 3AT, Wales, U.K.
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