Tetrazoles: A new class of compound for crystallization modification

Article abstract of DOI:10.1039/c0ce00263a

Tetrazoles are a class of organic compound often used as carboxylic acid analogues. This analogous behaviour is shown to extend to crystallization modification, that is, tetrazoles are also able to influence crystal growth and morphology although in a dif

Full text of DOI:10.1039/c0ce00263a

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Tetrazoles: a new class of compound for crystallization modification†
Massimiliano Massi, Mark I. Ogden, Tomoko Radomirovic and Franca Jones*
Received 19th April 2010, Accepted 30th June 2010
DOI: 10.1039/c0ce00263a
Tetrazoles are a class of organic compound often used as carboxylic acid analogues. This analogous
behaviour is shown to extend to crystallization modification, that is, tetrazoles are also able to influence
crystal growth and morphology although in a different manner to their carboxylate counterparts. All
the tetrazoles investigated thus far are shown to impact on barium sulfate and calcium carbonate
crystallization to varying degrees. Thus, the tetrazoles represent a new class of crystal modifier.
The investigation of crystallization is an active field, with much
literature focussed on the impact that impurities or additives
have on that process (for further reading see ref. 1–3). Crystal-
lization control is desirable for many reasons, including
controlling physical properties such as size and shape, complete
inhibition (scale control), or growth acceleration for more effi-
1,2
cient processing. Thus, additives or impurities are a means of
enforcing some control over the crystallization processes occur-
ring. To this end, many additives or impurities have been
3
investigated to date, ranging from small molecules to polymeric
4
species and even to biological species. It is an area that we too
Fig. 1 The tetrazole derivatives investigated in this work: (1H-tetrazol-
-yl)benzene (phtetH), methyl 4-(1H-tetrazol-5-yl)benzoate (mbtetH),
4-(1H-tetrazol-5-yl)benzaldehyde (bztetH), and 1,4-bis(1H-tetrazol-5-
yl)benzene (phtet ).
5
5
have been interested in, looking at factors such as the impact of
6
7
stereochemistry and functional groups, amongst others. Phos-
phonates are considered the most potent inhibitors, followed by
sulfonates and carboxylates though this is tempered by other
2 2
H
the presence of triethylammonium chloride. The tetrazoles were
À1
8
factors such as stereochemistry, etc. In this manuscript we
investigated at a concentration range of 0–1 g L . The crystal
7
growth experiments were carried out as described previously. In
present a new class of crystal growth modifier that to the authors’
knowledge has never before been used to modify crystallization,
the tetrazoles.
the case of barium sulfate, the crystallization process involved
the standard addition of barium chloride to sodium sulfate, while
for calcium carbonate the diffusion method (carbon dioxide
diffusing into a calcium chloride solution) was employed (further
details can be obtained from the ESI†).
Over the past decades, methodologies to prepare tetrazole
rings as well as the synthesis of tetrazole-containing compounds
9–11
have been extensively investigated.
The wide interest in this
particular heterocycle stems from its many applications. The
peculiar coordination chemistry of the tetrazolate anion has been
Fig. 2 shows the impact of the various tetrazole additives on
the crystallization of barium sulfate at the 500 ppm level.
1
2–14
exploited for the preparation of coordination complexes
and
15,16
metal–organic frameworks
recently, lanthanoid elements.
of transition metals and, more
Tetrazoles have been exploited
17–19
as analogues of carboxylic acids in medicinal chemistry formu-
lations with antifungal, antibacterial, anticancer, as well as anti-
20
a
neurodegenerative activities. In fact, the similar pK of these
21
two functional groups means the tetrazole ring can be utilised
as a more metabolically stable (hence more biocompatible)
surrogate of a carboxylic acid group. Fig. 1 shows the structures
of the tetrazole derivatives investigated in this work.
All of these tetrazoles were prepared according to published
10
3
procedures, by addition of NaN to the corresponding nitrile in
Curtin University of Technology, Department of Chemistry, GPO Box
U1987, Perth, WA, Australia 6845. E-mail: F.Jones@curtin.edu.au;
Fax: +61 618 9266 4699; Tel: +61 618 9266 7677
†
details, SEM images of barium sulfate formed in the presence of mbtet
Electronic supplementary information (ESI) available: Experimental
À
À
(
close up) and bztet , calcium carbonate formed in the presence of
À
Fig. 2 SEM images of barium sulfate formed in the presence of (a) 0 mM
À
mbtet , Raman spectrum of hexagonal calcium carbonate particles and
SEM images of calcium carbonate and barium sulfate formed in the
presence of sodium chloride. DOI: 10.1039/c0ce00263a
À
tetrazole, (b) 3.42 mM phtet , (c) 2.45 mM mbtet and (d) 2.47 mM
2
À
phtet
2
.
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À
It can be seen that the presence of phtet during barium sulfate
appears to specifically inhibit calcite formation and/or stabilize
vaterite formation.
crystallization results in particles with a larger aspect ratio
(
Fig. 2b) but interestingly a rough, seemingly porous (100) face is
It can be conclusively stated that the tetrazole functionality has
À
2À
also observed (see Fig. S1†). This was found to a much lesser
À
an effect on crystallization since in phtet and phtet
2
no other
extent when bztet was present (see Fig. S2†), the particles almost
À
functional moieties are present. In addition, the increase in the
number of tetrazole groups from one to two shows an increased
impact on morphology as would be expected based on the typical
behaviour of more established carboxylate and phosphonate-
being equivalent to the control particles. The presence of mbtet
also resulted in barium sulfate with a larger aspect ratio (Fig. 2c).
2À
The addition of phtet
greatest impact with thick rhombohedral rods being formed
Fig. 2d). These results show that tetrazole derivatives do have an
2
to growing barium sulfate showed the
1
based systems. Finally, morphology experiments in the presence
(
of sodium chloride at concentrations in excess of those used in
2À
impact on crystal growth, and that the chemical functionality of
the additive does influence the nature of that impact.
this study (even accounting for the 2 tetrazole groups in phtet2 )
show that these effects are not due to the presence of sodium or
chloride ions (see Fig. S5†). We hypothesise that the action of the
tetrazole involves the nitrogen atoms as well as an electrostatic
interaction and we are pursuing this with further experimental
and modelling investigations.
The larger aspect ratio observed for barium sulfate formed in
the presence of all of the tetrazole molecules investigated here
suggests a promotion of growth on the (001) face relative to the
1
other faces, thus the tetrazoles appear to be promoting barium
sulfate crystallization (at least on the (001) face relative to the
other morphological faces present). The results obtained with
In conclusion, a new class of crystal modifiers, the tetrazoles,
has been presented in this manuscript. This broadens the ‘toolkit’
of the scientist aiming to design additives to control crystalliza-
tion, adding a new functional group to the more widely used
anionic moieties such as carboxylates and phosphonates.
Furthermore, while the tetrazoles are often used as analogues of
carboxylates in various fields, tetrazole-based crystal growth
modifiers appear to have the potential to be significantly more
potent than comparable carboxylates.
2À
phtet
2
can be contrasted with our previous work with the
3
analogous carboxylate, terephthalic acid, which produced no
elongation of the barite crystals, but instead a mixture of crystals
comparable to those found in the blank, along with clusters of
smaller platelets, albeit at lower additive concentrations.
The presence of the various tetrazoles also has a significant
impact on calcium carbonate crystallization (Fig. 3). The pres-
À
À
2À
2
ence of phtet , bztet and phtet
(see ESI† for calcium
À
carbonate crystallized in the presence of mbtet , Fig. S3) results
in an impact typical of many calcite inhibitors with rounding of
the corners, compared to the typical rhombohedra observed
Acknowledgements
22
À
MM would like to thank the Australian Research Council for
funding (DP0985481).
in the blank (Fig. 3a). The presence of bztet , however, results
in the stabilisation of hexagonal vaterite (confirmed with Raman
spectroscopy, see Fig. S4†). Normally, vaterite is observed as
a transient species before the thermodynamic product (calcite)
crystallizes. Some additives, however, are known to stabilise
Notes and references
23
vaterite. Finally, the tetrazoles appear to be more potent
inhibitors of calcium carbonate crystallization than the simple
carboxylate-containing amino acids, which require ꢀ10 mM for
1
2
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Fig. 3 Calcium carbonate crystallized in the presence of (a) 0 mM tet-
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