Abstract:Traube's dianion, 4-methylcarboxysydnone-3-hydroxylate (2), and its monomethyl ester (1) are readily isolated as their di- and mono-potassium salts from the reaction of nitric oxide with dimethylmalonate and potassium methoxide in methanol. Metathesis reactions of 1 with silver nitrate and tetra(n-butyl)ammonium bromide yield the silver and tetra(n-butyl)ammonium salts of 4-methylcarboxysydnone-3-hydroxylate. In contrast to other known sydnone derivatives, the present sydnones are stable in both acidic and bas… Show more
“…Considering the negative charge of 1 , it should react readily with electrophiles, although the site of the electrophilic attack is not obvious and at least four different products could result (Figure ). We examined the reaction of the tetra- n -butylammonium salt, 1 , prepared from its potassium salt by metathesis, with methyl iodide, dimethyl sulfate, and trifluoromethanemethylsulfonate, and observed the formation of two alkylated products, 3 ( A ) and 4 ( B ), in ratios depending on the reagent and reaction conditions (Scheme ). 1 Possible methylation products of 1 . 1 Products from the Methylation of 1 …”
Section: Resultsmentioning
confidence: 99%
“…To avoid complicating the reaction mixture with these possible side products we sought to determine the conditions for transesterification of the anion 1 to give its ethyl ester 5 , eq 5. An acid catalyst is used in these reactions; clearly the stability of these sydnones in strong acid is an important reason why these conditions can be employed …”
Section: Resultsmentioning
confidence: 99%
“…We have examined the trends in these bands by using a range of methods for both 3 and 4 , Tables and , and a range of basis sets from ζ to triple ζ in quality, Table . MP2 vibrational energies are often scaled to compare these values with experiment, but in our experience the DFT vibrational energies seldomn require this manipulation . Apart from VWN correlation functional and the Perdew gradient corrected function P86 all of the DFT methods give significantly higher energies for the ν 42 band than is found for experiment.…”
Section: Crystallographic Resultsmentioning
confidence: 99%
“…The potassium and tetra- n -butylammonium salts of 3-carboxymethylsydnone- N -oxide, 1 , were prepared by reaction of nitric oxide with dimethyl malonate, as previously reported, followed by cation methathesis …”
Methylation of the anionic 4-methylcarboxy 1,2,3-oxadiazolate 3-oxide occurs at either the disubstituted ring nitrogen or the oxygen of the N-oxide depending upon the conditions and reagents employed. Alkylation with methyl iodide leads to N-alkylation, while dimethyl sulfate gives O-alkylation and trifluoromethanemethylsulfonate gives a mixture of the two products. The regioselectivity of these methylations has been confirmed by X-ray diffraction of the two products, and these are in turn correlated with their theoretically predicted (B3LYP//6-311++G**) relative energies and vibrational spectra. Theoretically, N-alkylation is expected to give an isomer that is over 10 kcal mol-1 more stable than the O-alkylated product. As a neat melt the kinetic O-alkylation product cleanly isomerizes in 2 h when heated to 140 degrees C to give the thermodynamic N-methylated isomer. Taken together the results illustrate the remarkable new sydnone N-oxide derivatives which are readily accessed in this chemistry, with the N-alkylation of the sydnone N-oxide, corresponding to the first case of such an N-alkylation for a diazenium diolate.
“…Considering the negative charge of 1 , it should react readily with electrophiles, although the site of the electrophilic attack is not obvious and at least four different products could result (Figure ). We examined the reaction of the tetra- n -butylammonium salt, 1 , prepared from its potassium salt by metathesis, with methyl iodide, dimethyl sulfate, and trifluoromethanemethylsulfonate, and observed the formation of two alkylated products, 3 ( A ) and 4 ( B ), in ratios depending on the reagent and reaction conditions (Scheme ). 1 Possible methylation products of 1 . 1 Products from the Methylation of 1 …”
Section: Resultsmentioning
confidence: 99%
“…To avoid complicating the reaction mixture with these possible side products we sought to determine the conditions for transesterification of the anion 1 to give its ethyl ester 5 , eq 5. An acid catalyst is used in these reactions; clearly the stability of these sydnones in strong acid is an important reason why these conditions can be employed …”
Section: Resultsmentioning
confidence: 99%
“…We have examined the trends in these bands by using a range of methods for both 3 and 4 , Tables and , and a range of basis sets from ζ to triple ζ in quality, Table . MP2 vibrational energies are often scaled to compare these values with experiment, but in our experience the DFT vibrational energies seldomn require this manipulation . Apart from VWN correlation functional and the Perdew gradient corrected function P86 all of the DFT methods give significantly higher energies for the ν 42 band than is found for experiment.…”
Section: Crystallographic Resultsmentioning
confidence: 99%
“…The potassium and tetra- n -butylammonium salts of 3-carboxymethylsydnone- N -oxide, 1 , were prepared by reaction of nitric oxide with dimethyl malonate, as previously reported, followed by cation methathesis …”
Methylation of the anionic 4-methylcarboxy 1,2,3-oxadiazolate 3-oxide occurs at either the disubstituted ring nitrogen or the oxygen of the N-oxide depending upon the conditions and reagents employed. Alkylation with methyl iodide leads to N-alkylation, while dimethyl sulfate gives O-alkylation and trifluoromethanemethylsulfonate gives a mixture of the two products. The regioselectivity of these methylations has been confirmed by X-ray diffraction of the two products, and these are in turn correlated with their theoretically predicted (B3LYP//6-311++G**) relative energies and vibrational spectra. Theoretically, N-alkylation is expected to give an isomer that is over 10 kcal mol-1 more stable than the O-alkylated product. As a neat melt the kinetic O-alkylation product cleanly isomerizes in 2 h when heated to 140 degrees C to give the thermodynamic N-methylated isomer. Taken together the results illustrate the remarkable new sydnone N-oxide derivatives which are readily accessed in this chemistry, with the N-alkylation of the sydnone N-oxide, corresponding to the first case of such an N-alkylation for a diazenium diolate.
“…4 One aspect that to date has been difficult to elucidate fully concerns the factors that control the cis/trans stereochemistry of the oxygens in the −N(O)NOR 3 group. Arulsamy and co-workers very recently addressed this issue as it relates to compounds in which the diazeniumdiolate nitrogen is attached to carbon, 5,6 but to date we know of only one report in which an E configuration has been confirmed in a nitrogenbound diazeniumdiolate; this special case (R 1 = isopropyl, R 2 = H, R 3 = 2-bromoethyl) 7 in which base-induced removal of the N−H proton led to an anion whose E isomer was trapped by an intramolecular alkylation process to form cyclic product 2 8 (see Scheme 1). In an effort to obtain a macroscopically observable pair of acyclic Z and E isomers in sufficient equilibrium concentrations that the E form's properties can be directly characterized and compared with those of the Z isomer, we hypothesized that minimizing steric interactions among the R groups might achieve that objective.…”
Diazeniumdiolates that have the structure RHN-N(O)═NOR' are of interest as prodrug (caged) forms of the bioeffectors nitric oxide (NO) and nitroxyl (HNO). Previous work has focused on examples possessing α-branched R groups, with isopropylamine (IPA)/NO (R = isopropyl) being the smallest examined to date. To probe the effect of minimizing the alkyl-group size on the chemistry of IPA/NO, we prepared the corresponding methylamine derivative as a sodium salt that was highly unstable but could be trapped in very low overall yield as the stable O(2)-benzyl derivative. To prepare enough for efficient characterization, we devised an alternate synthesis involving a novel N-dealkylation route. CH(3)HN-N(O)═NOBn, synthesized in high yield and crystallized as the Z isomer as determined by X-ray crystallography, was observed to exist as a 11:1 mixture of two isomeric forms in dynamic equilibrium in solution. Similar results were seen for the O(2)-ethyl derivative, whose two equilibrium constituents were partially separated by HPLC to reveal essentially identical UV and mass spectra, indicating them to be Z and E isomers of CH(3)HN-N(O)═NOEt. The results could lead the way to a fuller understanding of the chemistry of the acyclic (E)-diazeniumdiolates.
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