Facile Ring-Opening Reactions of Phthalimides as a New Strategy to Synthesize Amide-Functionalized Phosphonates, Primary Phosphines, and Bisphosphines

Abstract

The nucleophile-assisted ring-opening reaction of phthalimides 1 has been studied. The reaction of phthalimides 1 with 0.5 equiv of hydrazine produced the novel bisphosphonates 2 in near quantitative yields whereas with 10-fold excess of hydrazine, diethyl aminoalkylphosphonates 3 was formed in 75% yields. The reaction of phthalimide 1b with 3-(aminopropyl)phosphine resulted in a novel compound 4a containing a PIII hydride and a PV phosphonate within the same molecule. In addition, the reaction of 1b with 2-aminoethanol and 2-aminoethanethiol resulted in the formation of new phosphonates 4b,c. The reaction of bisphosphonates 2 with LiAlH4 in THF at 0 °C selectively reduced the phosphonate groups producing corresponding air-stable primary bisphosphines 6 in 80% yields. Further, the formylation of bisphosphines 6 under very mild conditions using 37% aqueous formaldehyde produced the corresponding novel water-soluble bisphosphine chelating agents 7 in near quantitative yields. All the new compounds have been characterized by 1H, 13C, 31P NMR, IR spectroscopy and mass spectrometry.

Syntheses of Phosphonic Esters of Alendronate, Pamidronate and Neridronate

“…Griffiths [25] proposed the same methodology in the course of a tetramethylester bisphosphonate preparation, but deprotection of the phthalimides in refluxing HBr also cleaved all the phosphonic esters. Nevertheless, Gali et al [26] showed that on diethyl alkylphthalimide phosphonates, the use of excess hydrazine can selectively deprotect the amine function without any ester cleavage.…”

New Vistas in Chemistry and Applications of Primary Phosphines

“…The nucleophile assisted ring-opening reactions of phosphonate bearing phthalimide 13 has been utilized in the synthesis of mixed primary phosphinephosphonate and aromatic amide functionalized primary bisphosphines as outlined in Scheme 6 [50].…”

“…For example, the interaction of aminopropyl phosphine (3) with the phthalimide 13 produced rare example of a phosphonate functionalized primary phosphine 14 in excellent yields (Scheme 6) [50]. The corresponding reaction of the phthalimide phosphonate 13 with 0.5 equivalent of hydrazine resulted in the bisphosphonate species 15 which upon further reduction with LiAlH 4 produced the primary bisphosphine 16 functionalized with aromatic amides.…”

“…It is interesting to note that the reduction of the bisphosphine 15 with LiAlH 4 in dry THF at 0°C was selective in terms of reducing only the phosphonate groups in 15, although amide groups are susceptible for reduction under these conditions. The novel bisphosphine 16 was obtained in 80% yields, as an air stable, pale yellow solid [50].…”

From Racemic Primary Aminoalkyl(phosphanyl)ferrocene Complexes to a Lithium–Phosphorus closo Cluster

“…Reactions with carbonyl groups, alkyl and aryl halides, halogens, alkali metals, and Lewis acids are well known and provide many possibilities to produce functionalized, even chiral-phosphorus containing secondary or tertiary phosphines. [9] However, one of the most convenient methods is deprotonation of the primary phosphine by using organometallic compounds of the alkali metals as strong bases. Twofold deprotonations are also possible by this method.…”