Diazomethane phosphonic acid

Seyferth s diazomethane phosphonic acid dimethyl ester, which enables the aldehyde —> alkyne elongation shown in Figure 14.30, is unstable. This is why Bestmann replaced it by a less sensitive synthetic equivalent, namely diazo acetone phosphonic acid dimethyl ester (Formula C in Figure 14.31), since with potassium methoxide—which is proportionately present in a solution/suspension of solid potassium carbonate in dry methanol—the dia-... 

Isolable pyrazolines (183) are obtained from the (1,3-butadiene)phosphonic acid esters (182 X=S02Me, COOalkyl R "=H or Me R2=Me or Ph) (products from (182 X=CN) are thermo-labile) and diazomethane. Pyrolysis of the phosphorylated pyrazolines affords phosphonopentadienes rather than phosphono-cyclopropanes (contrast (184)) and with NaH give pyrazoles or pyrazolephbsphonic acid esters. 

New developments in the synthesis of a-hydroxy phosphonic acids and their derivatives have concentrated on their asymmetric formation. The chiral phosphonic diamides (629) (in which R = isopropyl, 2,2-dimethylpropyl, or benzyl or a derivative thereof) in either racemic or optically active forms were converted into their anions and allowed to react with aldehydes to give the products (630) the diastereoisomeric composition of the latter could be ascertained by the use of P NMR spectroscopy, and after acidic hydrolysis and subsequent methylation (diazomethane) it was possible to isolate optically active forms of the dimethyl esters of (l-hydroxyalkyl)phos-phonic acids, the (/ ,R)-diamide giving rise to the (5)-acids as their esters. The best results were achieved when R = Bu CFl2, and enantiomeric excesses were generally above 85% . 

Other acidic functional groups will also undergo reaction with diazomethane. Thus phosphonic acids (eq 5) and phenols (eq 6) are methylated in high yields, as are hydroxytropolones (eq 7) and vinylogous carboxylic acids (eq 8). The origin of the selectivity in eq 6 is due to the greater acidity of the A-ring phenol. 

Further studies on 1,3-dipolar addition reactions of diazophosphonates have been recorded,122 and work on 2-diazo-l-hydroxyalkylphosphonates also continues.123 The ester (155 R = H) reacts with esters of acetylenedicarboxylic acid without liberation of nitrogen to give stereoisomeric C-phosphorylated pyrazolines, which can be decomposed with both phosphorus-carbon and carbon-carbon bond fission, affording mixtures containing dimethyl acetylphosphonate, dimethyl hydrogen phosphonate, and tri(alkoxycarbonyl)pyrazolines. In the reaction between the same diazophosphonate and diazomethane, the latter conceivably acts as a basic catalyst for proton transfer in a series of steps which includes phosphonate-phosphate isomerization. The importance of a labile proton is demonstrated by the fact that the ester (155 R = Me) does not react in the manner described above. 

Insertions into Aldehyde C-H Bonds. The a-diazo ketones (and esters) derived from diazomethane and an acid chloride (or chloroformate) will also insert into the C-H bond of aldehydes to give 1,3-dicarbonyl derivatives. The reaction is catalyzed by SnCL, but some simple Lewis acids, such as BF3 etherate, also work. The reaction works well for ahphatic aldehydes, but gives variable results with aromatic aldehydes, at times giving none of the desired diketone (eq 32). StericaUy hindered aldehydes will also participate in this reaction, as illustratedin eq 33 with the reaction of ethyl a-diazoacetate and pivaldehyde. In a related reaction, a-diazo phosphonates and sulfonates will react with aldehydes in the presence of SnCL to give the corresponding -keto phosphonates and sulfonates. This reaction is a practical alternative to the Arbuzov reaction for the synthesis of these species. 

Trifluoromethanesulfonic acid catalyzes the reaction of phenyl diazomethane with dimethyl H-phosphonate. Diazoacetate and diethyl H-phosphonate react less effectively under similar conditions [76]. 

Sample of VX stored for a long time in glass container was investigated using GC/MS system. A variety of age decomposition products including O-alkyl and N,N-diisopropylamino- substituted thiophosphonic esters and acids as well as phosphonic anhydrides were identified. Diazomethane methylation was used to obtain derivatives convenient to GC process. Retention parameters and EI-MS spectra were obtained and presented in the paper. 

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