Approaches to the Synthesis of Dicarboxylic Derivatives of Bis(pyrazol-1-yl)alkanes

Abstract

Carboxylation of bis(pyrazol-1-yl)alkanes by oxalyl chloride was studied. It was found that 4,4′-dicarboxylic derivatives of substrates with electron-donating methyl groups and short linkers (from one to three methylene groups) can be prepared using this method. Longer linkers lead to significantly lower product yields, which is probably due to instability of the intermediate acid chlorides that are initially formed in the reaction with oxalyl chloride. Thus, bis(pyrazol-1-yl)methane gave only monocarboxylic derivative even with a large excess of oxalyl chloride and prolonged reaction duration. An alternative approach involves the reaction of ethyl 4-pyrazolecarboxylates with dibromoalkanes in a superbasic medium (potassium hydroxide–dimethyl sulfoxide) and is suitable for the preparation of bis(4-carboxypyrazol-1-yl)alkanes with both short and long linkers independent of substitution in positions 3 and 5 of pyrazole rings. The obtained dicarboxylic acids are interesting as potential building blocks for metal-organic frameworks.

Bis(4-carboxylpyrazol-1-yl)acetic acid: a scorpionate ligand for complexes with improved water solubility

“…The NMR data agree well with the data of very recently published dicarboxylic derivatives of bis ( pyrazol-1-yl)alkanes including a bis(4-carboxylpyrazol-1-yl) methane by A. S. Potapov and coworker. 17 The presence of non equivalent carboxylic acid functionalities was also supported by IR spectroscopy, as they give rise to vibrational bands at 1753 and 1676 cm −1 , respectively. Due to H 3 bcpza holding these two different types of carboxylic groups, two different pK a values are to be expected.…”

Bis(pyrazol-1-yl)methane-4,4′-dicarboxylic Acid

“…Bis(pyrazol-1-yl)methane-4,4 -dicarboxylic acid (H 2 bpmdc) was synthesized as described previously [15] and recrystallized from water to give single crystals suitable for X-ray crystal structure determination.…”

“…Recently, we have developed a universal approach for the synthesis of a new series of bis(pyrazol-1-yl)alkane-4,4 -dicarboxylic acids starting from the commercially available pyrazole-4-carboxylic acid [15]. Taking into account the potential of these compounds as supramolecular building block, biologically active substances, monomers for polyesters and polyamides, we have studied the crystal structure and supramolecular analysis of Nheterocyclic compound titled bis(pyrazol-1-yl)methane-4,4 -dicarboxylic acid (H 2 bpmdc).…”

“…Taking into account the potential of these compounds as supramolecular building block, biologically active substances, monomers for polyesters and polyamides, we have studied the crystal structure and supramolecular analysis of Nheterocyclic compound titled bis(pyrazol-1-yl)methane-4,4 -dicarboxylic acid (H 2 bpmdc). This dicarboxylic acid was synthesized recently in our group and was characterized by NMR and IR spectroscopy, thermal and elemental analyses [15]; however, its crystal structure determination has not been performed yet.…”

Special Issue “Recent Advances in the Synthesis, Functionalization and Applications of Pyrazole-Type Compounds”

“…The highest activity in 1 µg/mL and 2 µg/mL on drug sensitive (DS) and multidrug-resistant (MDR) Mycobacterium tuberculosis strains, equal to the activity of the basic antitubercular drug rifampicin, was recorded for 2-amino-8-oxa-1,5-diazaspiro[4.5]dec-1-en-5-ium chloride [ 4 ]. Potapov et al described different approaches to the synthesis of dicarboxylic derivatives of bis(pyrazol-1-yl)alkanes which are interesting building blocks for metal-organic frameworks [ 5 ]. Svete et al reported on the synthesis of a series of 12 silica gel-bound enaminones and their Cu(II) complexes, which were used as suitable heterogeneous catalysts in [3+2] cycloadditions of 3-pyrazolidinone-derived azomethine imines to terminal ynones, for the regioselective synthesis of 6,7-dihydro-1 H ,5 H -pyrazolo[1,2- a ]pyrazoles [ 6 ].…”