Synthesis of novel 1,2,3-triazole based polycarboxylic acid functionalised ligands for MOF systems

Article abstract of DOI:10.1016/j.tetlet.2019.01.014

Copper catalysed click reactions are excellent tools to generate various 1,2,3-triazole linked polytopic aromatic carboxylates. The general reaction route involves protection of the carboxylates before proceeding with the click reaction. These polycarboxylate azoles are conveniently prepared for potential utility as novel key building blocks for metal organic frameworks. In one case, the ligand crystallises into a solid structure containing 1D, 2D and 3D features, based on a zigzag 1D structure, a ‘chicken mesh’-like 2D structure and a 3D structure with very well-defined channels.

Full text of DOI:10.1016/j.tetlet.2019.01.014

Accepted Manuscript
Synthesis of novel 1,2,3-triazole based polycarboxylic acid functionalised li-
gands for MOF systems
Yonas Belay, Louis-Charl Coetzee, D. Bradley G. Williams, Alfred Muller
PII:
S0040-4039(19)30025-5
https://doi.org/10.1016/j.tetlet.2019.01.014
TETL 50547
DOI:
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
21 November 2018
4 January 2019
8 January 2019
Please cite this article as: Belay, Y., Coetzee, L-C., Bradley G. Williams, D., Muller, A., Synthesis of novel 1,2,3-
triazole based polycarboxylic acid functionalised ligands for MOF systems, Tetrahedron Letters (2019), doi: https://
doi.org/10.1016/j.tetlet.2019.01.014
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Tetrahedron Letters
journal homepage: www.elsevier.com
Synthesis of novel 1,2,3-triazole based polycarboxylic acid functionalised ligands for
MOF systems
Yonas Belaya, Louis-Charl Coetzeea, D. Bradley G. Williamsb and Alfred Mullera
a Department of Chemistry, University of Johannesburg, P.O. Box 524, Auckland Park, 2006, South Africa.
b University of Technology Sydney, School of Mathematical and Physical Sciences, P.O. Box 123, Broadway, Sydney, NSW 2007, Australia.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Copper catalysed click reactions are excellent tools to generate various 1,2,3-triazole linked
polytopic aromatic carboxylates. The general reaction route involves protection of the
carboxylates before proceeding with the click reaction. These polycarboxylate azoles are
conveniently prepared for potential utility as novel key building blocks for metal organic
frameworks. In one case, the ligand crystallises into a solid structure containing 1D, 2D and 3D
features, based on a zigzag 1D structure, a ‘chicken mesh’-like 2D structure and a 3D structure
with very well-defined channels.
Available online
Keywords
click reaction
azoles
2018 Elsevier Ltd. All rights reserved.
1,2,3-triazole
 Corresponding author. Tel.: +27 (0) 11 559 2359; e-mail: mullera@uj.ac.za
 Corresponding author. Tel.: +612-9514-2265; e-mail: bradley.williams@uts.edu.au

Introduction
Azoles are a class of five-membered heterocyclic compounds that contain at least one nitrogen atom and another heteroatom such as
nitrogen, oxygen, or sulphur in the ring. They are found in biologically active compounds1,2 and are good ligands for the synthesis of
coordination polymers3,4 and metal organic frameworks.5–7 1,2,3-Triazole is part of this family and can be conveniently synthesised by
the copper catalysed click reaction of azides with alkynes.8 Click chemistry proceeds under simple and mild reaction conditions,
affording high yields of products of a single isomer. The products obtained are stable to various chemical processes such as oxidation,
reduction and acid hydrolysis.9 The high utility of click chemistry has led to its adoption in many branches of chemistry, including
material science.10 That it can be used in convergent syntheses has allowed the rapid discovery of new functional materials.
Large-scale production of metal organic frameworks face several challenges, and one of these is the availability of inexpensive
organic linkers that can be readily manufactured. Such readily available organic linkers are highly sought after: most of the reported
linkers are products of multistep syntheses, have various levels of structural sophistication and would be difficult to produce on a large
scale. There remains a need for convenient synthesis methods using scalable reaction chemistry. Many of the synthesised metal organic
frameworks contain rigid aromatic carboxylates as an integral part of the ligand structure, and only in a few instances, have azoles been
employed either for their function, form, or as a strategic route in convergent syntheses.11,12 It is this less explored field of metal organic
frameworks using azole-based linkers that prompted us to synthesise such linkers of organic struts using the click reaction from readily
available starting materials. Herein, we report the synthesis of three polytopic carboxylic acid functionalised aromatic organic struts of
1,2,3-triazole based linkers, using the copper catalysed click reaction as a lynchpin approach. While triazoles have been useful for the
production of metal organic frameworks (MOFs) where hybrid inorganic and organic porous materials are synthesised by coordination
of appropriately functionalised organic ligands and metal ions,12,13 the present approach has not yet been demonstrated. In particular,
most reactions to date involving click chemistry in the context of MOFs has been for postsynthetic surface modification.12,14
Nevertheless, some MOFs have been produced from a limited number of triazole-containing ligands, and these have been mostly
applied for gas separation or absorption.15 In many cases in the present work, the materials produced crystals of suitable quality for
single crystal X-ray diffraction studies, and in one gave a solid structure with 1D, 2D and 3D characteristics, leading ultimately to the
production of well-defined channels in the higher order structure.
Results and Discussion
The general structure of the proposed polycarboxylate azole is shown in Figure 1. The 1,2,3-triazoles were synthesised16 from aromatic
azides and an alkyne, both bearing carboxylic acid groups. Details of their synthesis and characterisation are given below.
N
R
N
O
N
R
Figure 1. Generic structure of the polycarboxylate 1,2,3-triazoles; R = carboxylic acid.
O
O
O
OH
O
O
O
OH
iii
i
ii
OCH3
OCH3
OH
OCH3
OCH3
O
OH
1
OH
2
3
O
4
O
v
O
O
OH
OH
iv
O
OCH3
O
N
NH2
N3
7
N
N
HO
5
6
Scheme 1. (i) MeOH, H2SO4 (98%, 2.4 equiv.), reflux, 2 h, 98%; (ii) propargyl bromide (1.2 equiv.), K2CO3 (1.5 equiv.), acetone, reflux, 4 h,
90%; (iii) KOH (2 equiv.), MeOH, reflux, 1 h, 94%; (iv) H2O, H2SO4 (98%, 4 equiv.), NaNO2 (1.0 equiv.), NaN3 (1.2 equiv.), 0 ºC, 15 min.,
85%; (v) CuSO4•5H2O (0.3 M aqueous, 0.27 mol%), sodium ascorbate (1.1 M aqueous, 3.9 mol%), DMF/H2O (4:1), reflux, 24 h, 87%.
Commercially available 4-hydroxy-3-methoxy benzoic acid 1 was converted into its corresponding ester by reaction with methanol
in the presence of concentrated sulphuric acid, affording methyl 4-hydroxy-3-methoxy benzoate 2 in very high yield (Scheme 1).
Treatment of benzoate 2 with propargyl bromide in the presence of potassium carbonate in acetone gave alkyne 3 in excellent yield.
Methyl ester 3 was hydrolysed with potassium hydroxide in methanol to afford the free carboxylic acid 4 after work-up and
acidification. This process afforded one partner for the click reaction. The other, azide 6, was prepared in high yield by the diazotisation
of aniline 5 followed by reaction with sodium azide, affording 6 in 85% yield. Finally, the copper-catalysed click reaction of alkyne 4
with azide 6 provided the desired [1-(4-carboxy-phenyl)-1H-[1,2,3]triazol-4-ylmethoxy]-3-methoxy-benzoic acid (7) in 72% overall
yield from 1. The 1H NMR spectrum of 7 was characterised by disappearance of the signal for the terminal alkyne proton at 2.51 ppm
and appearance of the diagnostic low field singlet signal for the triazole ring proton at 9.07 ppm. The para-substituted aryl carboxylic
acid moiety presented a distinctive AB system at around 8.14 ppm and 8.06 ppm, while the trisubstituted aryl ring was characterised by
an anticipated higher field AB system around 7.57 ppm and 7.28 ppm accompanied by a singlet signal at 7.46 ppm demonstrating meta
coupling.
In a similar fashion, 5-hydroxyisophthalic acid 8 was esterified, converted into its propargyl ether and hydrolysed back to its
dicarboxylic acid derivative 11, in excellent yield (Scheme 2).This approach of protection, functionalisation and deprotection afforded

the optimal yield of the alkynyl product. Direct propargylation of the hydroxybenzoate presented difficulties including solubility issues
and lack of selectivity. Copper-catalysed reaction of 11 with 6 afforded triazole tricarboxylic acid 12 in a good overall yield of 65%
from 8.
O
O
O
O
RO
OR
i
RO
OR
iii
ii
OH
: R = H
O
8
10
11
: R = CH3
9
: R = CH3
: R = H
HO
O
iv
O
6
O
O
HO
HO
N
N
12
N
Scheme 2. (i) MeOH, H2SO4 (98%, 2.4 equiv.), reflux, 2 h, 94%; (ii) K2CO3 (1.5 equiv.), propargyl bromide (1.0 equiv.), acetone, 4 h, 92%;
(iii) KOH, MeOH, reflux, 1 h, 85%; (iv) CuSO4•5H2O (0.3 M aqueous, 1.4 mol%), sodium ascorbate (1.1 M aqueous, 3.9 mol%), DMF/H2O
(4:1), reflux, 24 h, 90%.
Similar general approaches were employed to synthesise tetracarboxylate 15 (Scheme 3) in good overall yield from commercially
available starting materials. This set of reactions demonstrates the convergent nature of the chemistry and the fact that it tolerates
various functional groups while providing excellent overall yields of the desired multifunctional carboxylic acids.
O
O
O
O
O
O
HO
OH
HO
OH
HO
OH
i
11
O
N3
14
NH2
13
ii
N
N N
HO
O
OH
15
O
Scheme 3. (i) H2SO4 (98%, 2.4 equiv.), H2O, NaNO2 (1.0 equiv.), NaN3 (1.2 equiv.), 0 °C, 15 min., 84%; (ii) CuSO4•5H2O (0.3 M aqueous,
1.43 mol%), sodium ascorbate (1.1 M aqueous, 3.95 mol%), DMF/H2O (4:1), reflux, 24 h, 83%.
Compounds 4, 7, 9, 10, and 14 could be recrystallised to generate good quality single crystals suitable for crystallography. Structural
data revealed hydrogen bonding and π-stacking as primary contributing factors for crystallinity. Carboxylates 4 (ESI, Fig. S1) and 7
(Fig. 2) show the head-to-head R22(8) ring motif. In 7, this primary interaction leads to an extended 1D zigzag polymeric ‘string’ (Fig.
2). Intramolecular H-bonding was also noted between the triazole nitrogen (N 2) and aromatic hydrogen as well as between the triazole
hydrogen with the methoxy oxygen (O 3) and the ether oxygen (O 4). Interactions between each ‘string’ formed by the primary H-
bonding, lead to a 2D chicken mesh-like structure (Fig. 2), and are shown in (Fig. 3), between the triazole nitrogen (N 1) and the
methylene hydrogen (H-C 9) along the b-axis. The primary 1D structure and secondary 2D structure eventuate in the formation of
repeating channels along the a-axis (Fig. 4). In substances bearing esters (9 and 10), non-classical hydrogen bonding at these moieties
prevails (Fig. 5 and 6). In 14 (Fig. 7), a larger R33(10) motif is realised due to the inclusion of water in the lattice (from the EtOH used
for the recrystallisation). Propargyl functionalities also partake in hydrogen bonding, whereas azides show no interactions. It is noted
that π-stacking is present in all except 4, where ring-slippage is prevalent.
Figure 2. Solid state structure of triazole 7.
Figure 3. Detail view of solid state H-bonding in triazole 7.

Figure 4. Solid state 3D channel structure in triazole 7.
Figure 5. Solid state H-bonding in diester 9.
Figure 6. Solid state H-bonding in diester 10.
Figure 7. Solid state H-bonding in azide diacid 14.
Conclusion
We have demonstrated that azole-based linkers of polytopic carboxylic acid functionalised aromatic products, as potential organic
struts for MOFs, can be conveniently synthesised in high yield using the copper-catalysed click reaction of azides with alkynes
functionalised aromatic carboxylic acids. Protection of the carboxylate functionalities was essential to obtain high yields. The specific
architecture of triazole 7 leads to an interesting solid state structure with channels.
Acknowledgments
We thank the National research foundation (NRF) of South Africa for generous funding.
References and notes
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16. Experimental procedures and characterisation techniques including single crystal X-ray diffraction spectroscopy of the crystalline compounds are
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O
OH
O
OH
'click'
+
OCH3
N3
O
Highlights




Click reactions produce polytopic triazole-carboxylic ligands
These ligands are potentially useful to produce MOFs
Most ligands are characterised by X-ray crystallography
One produces an interesting solid structure containing 1D, 2D and 3D features