pH-dependent isomerism of (Iso)thioureidomethylenebisphosphonates

Chuiko, A. A.; Filonenko, L. P.; Borisevich, A. N.; Lozinskii, M. O.

doi:10.1134/s1070363209010113

Cited by 3 publications

(4 citation statements)

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“…Triethylammonium Salt of (Thioureidomethylene)bisphosphonic Acid (4) [8]. t-BuNCS (3 ml, 25 mmol) was added to a solution of (aminomethylene)bisphosphonic acid (3) (3.82 g, 20 mmol) in a mixture of methanol (50 ml), water (10 ml), and triethylamine (15 ml, 108 mmol) and left for 24 h at 60°C (heating the mixture to reflux leads to decomposition of the product).…”

Section: Methodsmentioning

confidence: 99%

“…(Thioureidomethylene)bisphosphonic acid 1 required for this reaction was synthesized by the acid-catalyzed decomposition of [(tertbutylthioureido)methylene]bisphosphonic acid 2, which we obtained previously as the disodium salt from (aminomethylene)bisphosphonic acid 3 [8]. Since acid 2 is unstable in the free state, it was used in situ without separation from the reaction mixture.…”

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confidence: 99%

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Synthesis of [(thiazol-2-ylamino)-methylene]bisphosphonic acids

Chuiko

Filonenko

Lozinskii

2011

Chem Heterocycl Comp

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Among bisphosphonate derivatives containing heterocycles biologically active compounds are found [1][2][3]. We have synthesized a series of 3-substituted (thiazol-2-ylaminomethylene)bisphosphonates [4,5] with phytotoxic activity by the condensation of (thioureidomethylene)bisphosphonic acids with halo ketones. Biological activity has also been found for tetraesters of [(thiazol-2-yl)aminomethylene]bisphosphonic acids unsubstituted at the position N-3 synthesized by the condensation of aminothiazoles with triethyl orthoformate [7].In the present work, we attempted to extend our method for the Hantzsch condensation to the synthesis of [(thiazolylamino)methylene]bisphosphonic acids unsubstituted at position N-3. (Thioureidomethylene)bisphosphonic acid 1 required for this reaction was synthesized by the acid-catalyzed decomposition of [(tertbutylthioureido)methylene]bisphosphonic acid 2, which we obtained previously as the disodium salt from (aminomethylene)bisphosphonic acid 3 [8]. Since acid 2 is unstable in the free state, it was used in situ without separation from the reaction mixture. Acid 2 decomposes in hydrochloric acid with loss of the tert-butyl residue to give (thioureidomethylene)bisphosphonic acid 1. This reaction proceeds under milder conditions than the decomposition described for tert-butylthiourea [9], which was carried out by heating in concentrated hydrochloric acid at reflux. However, the decomposition of acid 2 proceeds with formation of (aminomethylene)bisphosphonic acid 3 as a side product. The optimal conditions for the formation of desired acid 1 according to the 31 P NMR spectrum of the reaction mixture are obtained using 10% hydrochloric acid at 90°C. Under these conditions, the decomposition of acid 2 requires 10 min and leads to a mixture consisting of 83% of the desired acid 1 and 17% of the by-product acid 3. An attempt to use concentrated hydrochloric acid led to a mixture of not readily identifiable side products. Acid 1 precipitated from the mixture as fine-crystalline mono-(triethylammonium) salt 4, which is stable and can be stored under ordinary conditions without decomposition.

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

Synthesis of [(thiazol-2-ylamino)-methylene]bisphosphonic acids

Chuiko

Filonenko

Lozinskii

2011

Chem Heterocycl Comp

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“…It is worst mentioning that due to the partial double bond character of the SC-N bond thioureidobisphosphonates exist in solutions as mixtures of the E and Z isomers whose ratio is strongly pH-dependent. 111 Substituted thioureidomethylenebisphosphonic acids react with haloketones to form thiazoles. Isocyanatomethylenebisphosphonate 107 was demonstrated to be an interesting starting building block giving access to drugs for the treatment of metastatic bone cancer.…”

Section: Scheme 34mentioning

confidence: 99%

1-Amino-1,1-bisphosphonates. Fundamental syntheses and new developments

Romanenko¹,

Kukhar²

2012

Arkivoc

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1-Amino-1,1-bisphosphonates have become increasingly important in different fields of chemistry, medicine and agriculture. The combination of the unique physical, chemical and biological properties of methylenebisphosphonate and aminophosphonate fragments opens wide possibilities for the design of biologically active compounds including therapeutic agents to treat bone disorders related to calcium metabolism, immunomodulators, anti-infectives and plant growth regulators. The scope of this review is to summarize the existing strategies for the preparation of diversely functionalized 1-amino-1,1-bisphosphonates and to illustrate their utility as synthetic building blocks.

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“…Classical ones include the formation of Schiff bases, which are then alkylated [150] or reduced [126], and synthesis of thioureido derivatives as intermediates in the preparation of heterocyclic compounds [151][152][153].…”

Section: Miscellaneousmentioning

confidence: 99%

Synthetic Procedures Leading towards Aminobisphosphonates

Chmielewska

Kafarski

2016

Molecules

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Abstract:Growing interest in the biological activity of aminobisphosphonates has stimulated the development of methods for their synthesis. Although several general procedures were previously elaborated to reach this goal, aminobisphosphonate chemistry is still developing quite substantially. Thus, innovative modifications of the existing commonly used reactions, as well as development of new procedures, are presented in this review, concentrating on recent achievements. Additionally, selected examples of aminobisphosphonate derivatization illustrate their usefulness for obtaining new diagnostic and therapeutic agents.

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pH-dependent isomerism of (Iso)thioureidomethylenebisphosphonates

Cited by 3 publications

References 3 publications

Synthesis of [(thiazol-2-ylamino)-methylene]bisphosphonic acids

Synthesis of [(thiazol-2-ylamino)-methylene]bisphosphonic acids

1-Amino-1,1-bisphosphonates. Fundamental syntheses and new developments

Synthetic Procedures Leading towards Aminobisphosphonates

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