The synthesis and reactivity of alkyl-aminosubstitutedmethylenediphosphonates

Optimization, Continuation and Lack of the One-Step Diphosphorylation Reaction. Assay of Modification of the Tetraethyl(pyrrolidine-2,2-diyl)bisphosphonate

“…28 In 1997 and 1999, Qian et al detailed a one pot but intricate two steps procedure involving Vilsmeier reagents and organophophorus compounds with P-H bounds (SCHEME 1-Equation (2)). 23,34 At the same time, we have designed an easy one step method also employing Vilsmeier reagents (amide or lactam/POCl 3 ) with trialkylphosphite. 28,35 INSERT SCHEME 1…”

“…15 Linear compounds: the results for the acyclic series are displayed on The yield of 4, the simplest bisphosphonate in the series, is higher than the one reported by Qian. 23 If a second methyl group is added on the nitrogen (tertiary amine), the 7 corresponding return is almost divided by a factor of two, being reduced from 68 % to 30 %.…”

“…1 They are known for their various uses: dental (tooth pastes and mouthwashes) [2][3][4] and medical applications (against rheumatoid arthritis, 5,6 for the inhibition of bone resorptive processes such osteoporosis and Paget's disease, 2,[7][8][9] skeletal scintigraphy when combined with 99 Tc, [10][11][12] breast cancer therapy, 13 antiviral, 14,15 anti-inflammatory 16,17 and anti-rheumatismal agents, 18 pain-easing activities, 16 antimoebic 15 ), antibacterial agents, 19 plant growth regulators, 20 herbicides, [21][22][23] pesticides, 19 in the nuclear industry, [24][25][26] flame retardants 21 and 2 chelators in water treatment, 21 etc… Gem-bisphosphonates and gem-bisphosphonic acids can readily form complexes with calcium and magnesium and this behavior is one of the principles sustaining their use as drugs. 3,15 Recently, amino-gem-bisphosphonates have been involved in the conformational study of pyrrolinoxyl radicals 27 and they also work as spin trapping agents relevant to biology.…”

The development of bisphosphonates for therapeutic uses, and bisphosphonate structure-activity consideration

“…[58][59][60][61] Unfortunately, when the longer chain amide 47b was treated under the same reaction conditions, only the mono-phosphonate 48b was obtained. …”

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

“…68 The addition into the reaction mixture of triethylamine initiates a different reaction pattern and gives rise to E-vinylphosphonates 28 (Scheme 9). 69 Should also be noted that hydridophosphorane 29 reacts with the Vilsmeier reagents similar to dialkyl phosphites forming methylenebisphosphoranes 30 (Scheme 10).…”