Reactions of N-phthalylamino acid chlorides with trialkyl phosphites

Abstract

Reaction of commercially available trialkyl phosphites with N‐phthalylamino acids gave mixtures of seven products, whereas the same reaction carried out with pure triethyl phosphite yielded only the desired 2‐(N‐phthalylamino)‐1‐oxoalkanephosphonates. These compounds underwent rearrangement to the same types of products that were obtained with the commercial phosphites. This latter series of reactions was promoted by the presence of dialkyl phosphites. © 2000 John Wiley & Sons, Inc. Heteroatom Chem 11:232–239, 2000

Insight into the mechanism of three component condensation leading to aminomethylenebisphosphonates

“…= 0.56, 0.44 and 0.52, 0.48, respectively. This behavior of phosphonate ester group was reported earlier and thus is not surprising [11].…”

Synthetic Procedures Leading towards Aminobisphosphonates

“…Starting ketophosphonates are obtained by the Arbuzov reaction of acyl chlorides with trialkyl phosphites and used as substrates in the next step, namely, the addition of dialkyl phosphite to carbonyl double bonds (a representative example for preparation of tetramethyl pamidronate 22 is shown in Scheme 13). Since ketophosphonates are unstable species [58], the desired bisphosphonates are usually obtained via one-pot procedures applying mixtures of trialkyl-and dialkylphosphonates at elevated temperature [59]. Additionally, in situ generation of dialkyl-from trialkyl phosphites is possible by the addition of a protic solvent to the reaction mixture.…”

Synthesis of β-Aminophosphonates and -Phosphinates

“…Extension of the methodology used for alkyl halides to functionalized acyl halides allowed the preparation of β-amino-α-ketophosphonates. Treatment of N -protected amino acid 17 with thionyl chloride gave the corresponding acid chloride 18, which on reaction with trialkyl phosphite gave the corresponding α-ketophosphonate 19 (Scheme ) . Also, Arbuzov reaction of triethyl phosphite with optically active acid chlorides 18 afforded α-ketophosphonates 19 …”

“…Synthesis of 2-amino-1-hydroxy-substituted ethylene-1,1-bisphosphonic acids 60 has been developed by addition of dialkyl phosphite over α-ketophosphonates 58 , obtained from naturally occurring 1-amino acids, to afford N -protected 2-amino-1-hydroxyethylene-1,1-bisphosphonate 59 (Scheme ) . Acid hydrolysis enabled the protecting group and the phosphonate esters, yielding 2-amino-1-hydroxyethylene-1,1-bisphosphonic acid 60 21b. Treatment of this acid with sodium hydroxide gave the corresponding sodium salt 61 .…”

“…Several bisphosphonic acid derivatives 285 have been used for the synthesis of their N -methylated derivatives 286 (Scheme ). N -Methylation ( 286 , R = H) and N , N -dimethylation ( 286 , R = Me) of this system were achieved with a mixture of formic acid and formaldehyde 21b 79 …”