Synthesis of β-Aminophosphonates and Study of Their Acid-Base Properties and Phase Distribution in Water-Organic Solvent Systems

Abstract

New and previously known -aminoethylphosphonates were synthesized by addition of primary and secondary amines to vinylphosphonates, and their IR and NMR spectra were examined. Diethyl 2-diethylaminoethylphosphonate and diethyl 2-morpholinoethylphosphonate were found to be stronger bases than the corresponding aminomethylphosphonates, but all these are weaker bases than their precursors, nonphosphorylated amines. Distribution constants of -aminophosphonates between water and some organic solvents were determined and compared with those of their -amino homologs.In the series of our preceding publications we described methods of synthesis and acid-base properties of a large number of -aminophosphoryl compounds [1] which can be regarded as phosphorus-containing analogs of natural amino acids. In the recent years, these compounds attract attention of researchers working in the fields of not only fine organic synthesis and chemistry of biologically active substances but also related sciences, such as biochemistry, pharmacology, medicine, agricultural chemistry, etc. [2, 3]. Apart from high efficiency as bioactive substances, -aminophosphoryl compounds were shown to be capable of forming complexes with various species, including metal ions, organic and inorganic acids, etc. [4,5]. In particular, we studied -aminophosphonates as extractants which ensured selective separation of noble metal ions from concomitant elements [6]. Variation of substituents at the phosphorus, -carbon, and nitrogen atoms over a wide range showed that the most selective extractants were those aminophosphoryl reagents which contained more than 20 carbon atoms; in this case, the optimal hydrophilic-lipophilic balance was achieved. It should be emphasized specially that the above information was deduced by analysis of correlations between the number of carbon atoms in the extractant molecules and their distribution constants in waterorganic solvent systems [7]. Therefore, the latter parameter is necessary to elucidate the structure-property relations with a view to effect subsequent purposeful synthesis of extractants, bioactive, and other potentially useful substances possessing an optimal combination of the desired characteristics.The present article opens a series of publications on the synthesis and study of extracting, membranetransfer, and ionophoric properties of a new class of phosphorus-and-nitrogen-containing complexing agents, -aminophosphoryl compounds. Here, we report on the synthesis, acid-base properties, and distribution constants in two-phase aqueous-organic systems of a series of previously described and new -aminophosphonates. When possible, the parameters under study were compared with the data for their analogs, -aminophosphonates, and precursors, the corresponding amines. We believe that such analysis is useful for estimation of factors responsible for physiological and complexing properties of the compounds under study.Properties of -phosphorylated amines have been studied to a considerably lesser extent, as compared to their ...

Investigations of the Chemistry of Alkyl Phosphites Toward Nitrogen-Containing Compounds: Efficient Approaches to α-Amino-, β-Amino-, and/or Enaminophosphonates

“…[47] However, the mechanism is more complicated than it appears in Scheme 15 since the nature of ketone, [47] the activator, [48] the solvent, [49] and the PK b of the amine [50] all have an effect. Several studies could prove that path A is the most convenient pathway.…”

Chemistry of Aminophosphonic Acids and Phosphonopeptides

“…Pudovik and Denisova first showed that ammonia adds to diethyl vinylphosphonate in the presence of EtONa in the normal manner (Scheme 5.34) [146]. The reaction with primary amines is usually activated by basic catalysts under heating [147]; secondary amines add to the vinylphosphonate easily without a catalyst, whereas aniline reacts only in the presence of MeONa and with only a fair yield [148].…”

N-Functionalization of β-aminophosphonates: cytotoxic effects of the new derivatives

“…9 Later on, different approaches were explored. [10][11][12][13] The most practical approach was developed by Odinets et al, 14 which was then followed by others. 15,16 According to this, primary or secondary amines may be added to the double bond of dialkyl vinylphosphonates in water as the medium in the absence of any catalyst.…”