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Microwave-assisted synthesis of (aminomethylene)bisphosphine oxides and (aminomethylene)bisphosphonates by a three-component condensation

“…One of the most convenient and widespread methods is the three-component condensation involving an amine, an orthoformate and a dialkyl phosphite. Usually, primary or secondary amines were reacted with an equivalent, or a small excess of triethyl orthoformate and 2–7 equivalents of diethyl phosphite [ 6 – 21 ]. In most cases, the corresponding acids were the target molecules that were obtained by hydrolysis of the esters [ 15 – 21 ].…”

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

“…29,84 An important variation, with the utilization of trialkyl phosphites [85][86][87] was also reported. Moreover, the biological importance of 1-aminomethylene-1,1-bisphosphonates has prompted the developments of improved methodologies including synthesis under solvent-free conditions, 88 catalytic synthesis, 89 and activation with microwave irradiation. 88,90 …”

“…In spite of complex reaction pathway, the method appears to be fairly general and can be applied for the construction of various N-monosubstituted and N,N-disubstituted 1-aminomethylenebisphosphonates bearing alkyl, cycloalkyl and aryl substituents at the nitrogen atom. 11,84,89 Of recent studies, should be mentioned synthesis of non-carrier-added (nca) 131 Ilabeled bisphosphonic acid 57 by the reaction of the amine 55 with triethyl ortoformate and diethyl phosphite followed by iododesilylation (Scheme 21). 92 Another recent example is threecomponent reaction between aminoadamantanes 58, triethyl ortoformate and diethyl phosphite which was used to obtain bisphosphonates 59.…”

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

“…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].…”

“…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].…”