"Greener" Synthesis of Zoledronic Acid from Imidazol-1-yl-acetic Acid and P-Reagents Using Diethyl Carbonate as the Solvent Component

2020 ◽  
Vol 17 ◽  
Author(s):  
Alajos Grün ◽  
Zsuzsanna Szalai ◽  
György Keglevich
Keyword(s):  
Acetic Acid ◽  
Zoledronic Acid ◽  
Methanesulfonic Acid ◽  
Phosphorous Acid ◽  
Phosphorus Trichloride ◽  
Solvent Mixtures ◽  
Diethyl Carbonate ◽  
Green Solvent ◽  
Solvent Component ◽  
Greener Synthesis

Abstract: The synthesis of a third generation dronic acid, zoledronic acid by the reaction of imidazol-1-yl-acetic acid with phosphorus trichloride/phosphorous acid in diethyl carbonate (DEC) as a "green" solvent, and in DEC – methanesulfonic acid (MSA) solvent mixtures is described. The earlier not "green" and expensive MSA and sulfolane solvents may be re-placed by DEC

“Greener” synthesis of bisphosphonic/dronic acid derivatives

2014 ◽  
Vol 3 (2) ◽  
pp. 111-116 ◽  
Author(s):  
Rita Kovács ◽  
Alajos Grün ◽  
Sándor Garadnay ◽  
István Greiner ◽  
György Keglevich
Keyword(s):  
Zoledronic Acid ◽  
Carboxylic Acids ◽  
Methanesulfonic Acid ◽  
Phosphorous Acid ◽  
Phosphorus Trichloride ◽  
Risedronic Acid ◽  
Molar Ratios ◽  
Wide Range ◽  
Greener Synthesis

Abstract According to literature, the synthesis of dronic acid derivatives from the corresponding carboxylic acids using phosphorus trichloride and phosphorous acid as the P-reactants is controversial, due to the wide range of molar ratios and diverse conditions. In this minireview, we summarize our results on the clarification of these problems. For example, with zoledronic acid and risedronic acid, we found that, using methanesulfonic acid (MSA) as the solvent, 3.2 equivalents of phosphorus trichloride was enough. Generalizing this optimized method, etidronate, fenidronate, ibandronate and alendronate were obtained in yields of 38%–57%, which is reasonable for valuable dronates, and in most cases, with high purities. Mechanistic aspects are also discussed.

scholarly journals A Mechanistic Study on the Formation of Dronic Acids

Molecules ◽  
2021 ◽  
Vol 26 (24) ◽  
pp. 7587
Author(s):  
Péter Ábrányi-Balogh ◽  
István Greiner ◽  
György Keglevich
Keyword(s):  
Acetic Acid ◽  
Quantum Chemical ◽  
Methanesulfonic Acid ◽  
Phosphorous Acid ◽  
Bone Diseases ◽  
Phosphorus Trichloride ◽  
Mechanistic Study ◽  
First Variation ◽  
The First Variation ◽  
High Level

Dronic acid derivatives, important drugs against bone diseases, may be synthesized from the corresponding substituted acetic acid either by reaction with phosphorus trichloride in methanesulfonic acid as the solvent or by using also phosphorous acid as the P-reactant if sulfolane is applied as the medium. The energetics of the two protocols were evaluated by high-level quantum chemical calculations on the formation of fenidronic acid and benzidronic acid. The second option, involving (HO)2P‑O‑PCl2 as the nucleophile, was found to be more favorable over the first variation, comprising Cl2P‑O‑SO2Me as the real reagent, especially for the case of benzidronate.

The Synthesis of 3-Phenylpropidronate Applying Phosphorus Trichloride and Phosphorous Acid in Methanesulfonic Acid

2016 ◽  
Vol 20 (16) ◽  
pp. 1745-1752 ◽  
Author(s):  
Alajos Grun ◽  
David I. Nagy ◽  
Orsolya Nemeth ◽  
Zoltan Mucsi ◽  
Sandor Garadnay ◽  
...  
Keyword(s):  
Methanesulfonic Acid ◽  
Phosphorous Acid ◽  
Phosphorus Trichloride

A Study on the Synthesis of Risedronic Acid: The Role of an Ionic Liquid Additive

2019 ◽  
Vol 16 (3) ◽  
pp. 238-244 ◽  
Author(s):  
Dávid Illés Nagy ◽  
Alajos Grün ◽  
Júlia Sinkovicz ◽  
Sándor Garadnay ◽  
István Greiner ◽  
...  
Keyword(s):  
Ionic Liquid ◽  
Good Yield ◽  
Methanesulfonic Acid ◽  
Phosphorous Acid ◽  
Phosphorus Trichloride ◽  
Pure Form ◽  
Risedronic Acid

Background: The synthesis of high value risedronic acid is not fully resolved, as, for the time being, the best method based on the preparation from 3-pyridylcarboxylic acid by reaction with phosphorus trichloride in methanesulfonic acid gives risedronic acid in a good yield, but in an unpure form. Methods: Alternative protocols realizing the synthesis in sulfolane as the solvent and/or in the presence of suitable IL additive were developed to obtain the target dronic acid in a pure form. Results & Conclusion: Using phosphorus trichloride and phosphorous acid in two equivalents quantities together with 0.6 equivalents of [bmim][BF4] without any solvent, the method afforded the target dronic acid in a yield of 66% in a pure form.

Hydrohalogenation of Unactivated Alkenes Using a Methanesulfonic Acid/Halide Salt Combination

Synthesis ◽  
2021 ◽  
Author(s):  
Jean-François Paquin ◽  
Xavier Bertrand ◽  
Pascal Paquin ◽  
Laurent Chabaud
Keyword(s):  
Acetic Acid ◽  
Methanesulfonic Acid ◽  
Alkyl Halides ◽  
Halide Salt ◽  
Acid Halide ◽  
Halide Salts

AbstractThe hydrochlorination, hydrobromination, and hydroiodination of unactivated alkenes using methanesulfonic acid and inorganic halide salts (CaCl2, LiBr, LiI) in acetic acid are reported. This approach uses readily available and inexpensive reagents to provide the alkyl halides in up to 99% yield. An example of deuteriochlorination using deuterated acetic acid as the solvent is also demonstrated.

Green Synthesis, Molecular Docking Studies and Anticancer Effects of 3-Methyl-2-(((1-Methyl-1H-Benzo[d]imidazol-2-yl) thio) Methyl) Quinazolin-4(3H)-One

2021 ◽  
Vol 25 (7) ◽  
pp. 138-146
Author(s):  
E. Laxminarayana ◽  
P. Bhasker ◽  
D. Ramesh ◽  
Md. Rafeeq ◽  
B. Srinivasa Reddy
Keyword(s):  
Acetic Acid ◽  
Molecular Docking ◽  
Green Synthesis ◽  
Docking Studies ◽  
Chemotherapeutic Agents ◽  
Green Solvent ◽  
Anticancer Effects ◽  
Best Fit ◽  
Green Conditions ◽  
Peg 600

compound 2-((1H-benzo[d]imidazol-2-yl)thio)acetic acid (1) with o-aminobenzamide (2) gave compound (2-[1-(1H-benzimidazol-2-yl)-ethylsulfanyl]-3H-quinazolin-4-one (3). 3 could also be syntehsized by an alternative two routes scheme 2 and scheme 3. It appears from scheme 3 that it is giving good yields under green and eco-friendly conditions using PEG-600 (polyethylent glycol). Compound 10 was synthesized in two routes scheme4 and scheme 5. It appears from Route B (Scheme 4) that it is giving good yields: alkylation followed by oxidation in route A followed by alkylation in PEG-600 used as a green solvent. The total sequence of reactions has been carried out using eco-friendly and green conditions. Further, anticancer activity was carried out by using docking studies and binding conformation of active compounds of 3, 8, 9 and 10. The results show that 3 and 9 have potential to be developed as chemotherapeutic agents and compounds 3, 9 molecule showed best fit, potent dock score when compared with doxorubicin.

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