No abstract

A number ofa-ketophosphonates have been prepared and their enol-keto tautomerism has been studied by means ofproton and phosphorus NMR and infrared spectroscopy and the ferric chloride test. Aliphatic ketophosphonates exist largely in the keto tautomeric forms, with only a small amount of enol forms present. All the aromatic acylphosphonates studied, however, enolize extensively. An x-ray analysis confirmed enolization and E configuration as the only stereochemical isomer. Reaction of diazomethane with diethyl p-methoxyphenylacetyl phosphonate gave a mixture of 0-methylation and carbene insertion products, whereas the same reaction with diethyl isobutyryl phosphonate gave only carbene insertion products.Recent publications have indicated that a number of amino phosphonic acids, as such or in small peptides, possess biological activities (1-4) and therefore can be considered as bioisosteres of the amino carboxylic acids. In a program designed to synthesize some specific peptides containing a phosphonic acid residue, we have had occasion to prepare some a-amino phosphonic acids by the reported procedures involving the conversion of the appropriate alkyl a-ketophosphonate into its oxime followed by reduction of the latter (5-7). In this work, we noticed that some ofthe ketophosphonates we prepared produced pronounced color changes with ferric chloride, suggesting that these compounds exist as enols. Inasmuch as we found no literature reports on the enol-keto tautomerism of a-ketophosphonates, it was of interest to investigate this phenomenon by comparing it to the situation with substituted pyruvic acids (8) and esters (9). RESULTS AND DISCUSSIONThe diethyl ketophosphonates la-li (Scheme 1) were prepared Qualitative and quantitative studies of the keto-enol tautomerism ofthese a-ketophosphonates were based on results offerric chloride color test, proton and phosphorus NMR, and infrared spectroscopy. We chose to investigate the tautomerism by using NMR rather than the classical Kurt Meyer bromine titrations (12) because of convenience. For this, we established the enol-keto tautomerism of methyl phenylpyruvate by NMR and found it to approximate the results obtained by Stock et al. (9) using bromine titrations.The proton NMR characteristics of the a-ketophosphonates shown in Scheme 1 were examined in chloroform-dl (Table 1).Each of the aliphatic diethyl ketophosphonates la-ic exhibited a signal around 3 ppm with appropriate splitting, indicating the presence of the methylene protons (in la and ic) or methine proton (in lb) attached to a carbon atom adjacent to a carbonyl function. No vinylic proton was observed in the downfield region. This strongly suggested that these aliphatic diethyl ketophosphonates exist predominantly in the keto tautomeric form, although the presence ofa small singlet at 1.14 ppm (about 5%) in addition to the large singlet at 1.04 ppm (95%) for the t-butyl group in Ic suggested the presence of about 5% enol form in this case (this was supported by evidence of 31P NMR, see below). One ...

3‐Alkylthiopropanale (I) reagieren mit Triphenylphosphit (II) und Thioharnstoffen (III) zu Aminoalkanphosphonaten (IV), die sauer zu Phosphonsäuren (V) verseift werden.