Hollie K. Jacobs

Synthesis and metal ion complexation properties of a novel polyethyleneimine N-methylhydroxamic acid water soluble polymer

A major goal of our research program is to develop water soluble chelating polymers for the selective separation of trivalent cations such as iron(III) and tetravalent actinide ions such as Th(IV) or Pu(IV) from aqueous, radioactive waste streams. As part of this effort, we have synthesized a new water soluble polyethyleneimine polymer that incorporates N-methylhydroxamic acid chelating groups. Both the synthesis of this chelating polymer, PEI-NMH, and its ability to achieve selective separation of target metal ions using ultrafiltration will be discussed. It is interesting to note that the PEI-NMH polymer selectively binds iron(III) over thorium(IV) at pH 1 in contrast to its primary hydroxamate analog PEI-H. The binding properties of these polymers have been evaluated using both potentiometric and spectrophotometric methods. A comparison of the binding properties of PEI-NMH and PEI-H reveals the importance of the nature of the ligand in the complexation process.

Chiral γ and δ Hydroxysulfones via lipase catalyzed resolutions - synthesis of (R)(+)-4-hexanolide and (2R,5S)-2-methyl-5-hexanolide using intramolecular acylation

Abstract Lipas PS-30 (Amano) was found to be an effective catalyst for enantioselective transesterification of a number of racemic γ and δ hydroxysulfones with isopropenyl acetate in ether. The intramolecular acylation of the ethyl carbonate derivatives obtained from the chiral hydroxysulfones 1d and 1b has been used for the preparation of R (+)-4-hexanolide, sex pheromone of the female dermestid beetle Trogoderma glabrum and (2 R , 5 S )-2-methyl-5-hexanolide, the sex pheromone of the carpenter bee.

Convenient method for the preparation of some polyhydroxamic acids : Michael addition of amines to acrylohydroxamic acid derivatives

Reagents 1, 2, and 3 are readily prepared by the reaction of the appropriate hydroxylamine derivatives with acryloyl chloride. They undergo Michael addition with a variety of amines to give the corresponding O-protected hydroxamate derivatives in moderate to good yields. Subsequent removal of the protecting group provides a convenient method for the preparation of a number of mono, di, tri and tetrahydroxamic acids.

Synthesis of Symmetrical Methylenebis(Alkyl Hydrogen Phosphonates) by Selective Cleavage of Methylenebis(Dialkyl Phosphonates) with Morpholine

Abstract The preparation of partial esters of methylenebisphosphonic acids has been of recent interest due to their potential therapeutic applications. This paper describes a convenient method to prepare symmetrical methylenebis(alkyl hydrogen phosphonates) by the selective cleavage of the corresponding methylenebis(dialkyl phosphonate) with refluxing morpholine. The effects of structural variations on the amine as well as the substrate have been investigated to understand the scope and limitations of this reaction. A superior approach to hindered bisphosphonic acid esters involves the cleavage of their dimethyl esters, 4, using morpholine. This method is also useful to access a number of C-alkyl dialkyl methylenebisphosphonic acids such as 6. This study clearly shows that cleavage with morpholine is convenient, inexpensive, and allows for the preparation of a variety of P,P′-disubstituted partial esters in good yields and high purity.

Reactions of N-Benzyloxycarbamate Derivatives with Stabilized Carbon Nucleophiles: A New Synthetic Approach to Polyhydroxamic Acids and Other Hydroxamate-Containing Mixed Ligand Systems†

Hydroxamic acids are an important class of chelators of hard metal ions such as Fe(III), which have found applications in therapeutic, diagnostic, and separation chemistry. Hence, methods for their preparation and incorporation into various matrices are important. A new strategy for the preparation of hydroxamic acids that uses readily available N-benzyloxy carbamic acid ethyl ester, 1, has been developed. N-Alkylation of 1 occurs readily to give N-alkyl-N-benzyloxy carbamates, 2, which react with a variety of stabilized carbon nucleophiles to give functionalized protected hydroxamic acids, 3, in good to excellent yields. The O-protected hydroxamate intermediates 3 can be further alkylated with halides to access a variety of potential metal binding hosts. The usefulness of this methodology has been demonstrated by the synthesis of a novel trihydroxamic acid 6, mixed ligand systems 9 and 12, and the macrocyclic dihydroxamic acid 16.

Bakers' Yeast Reduction of γ and δ Ketonitriles: Intermediates for the Synthesis of (S)-5-Hexanolide and Other Chiral Lactones

Abstract A number of γ and δ ketonitriles have been synthesized and their reduction with bakers yeast carefully studied. Both 4-oxopentanenitrile and 5-oxohexanenitrile are reduced in moderate yields to the corresponding (S) alcohols of high ee while other substrates gave products of varying optical purities. These alcohols are useful intermediates for the preparation of chiral lactones, including the synthetically important (S)(−)-4-methylbutyrolactone and (S)-(−)-5-hexanolide.

CONVENIENT SYNTHETIC METHODS FOR THE PREPARATION OF N-FLUOROALKYLHYDROXAMIC ACIDS

ABSTRACT Polyhydroxamate chelators containing fluoro substituents are of interest as potential extractants for actinides in separations involving supercritical carbon dioxide. In this context, we have developed three new reagents 1, 2, and 3, that allow the efficient incorporation of an N-fluoroalkyl hydroxamate moiety onto a variety of substrates using acylation, alkylation, and Michael addition strategies.

New methodology for the preparation of 3-hydroxy-2-pyridinone (3,2-HOPO) chelators - Reaction of amines with a novel electrophilic 3,2-HOPO precursor.

The preparation of the new electrophilic iminium ester mesylate salt 5 and its reaction with primary and secondary amines have been investigated. Aniline, t-butylamine, and secondary amines react with 5 via ring opening to give the corresponding HOPO derivatives in high yields. The usefulness of this methodology has been demonstrated by the preparation of two new di-HOPO derivatives 19 and 21. This method allows the introduction of the HOPO ligand onto a variety of amine platforms without the concomitant formation of an amide bond and provides access to HOPO chelators of increased water solubility.

New intramolecular alkylation and Michael addition reactions of hydroxysulfone derivatives—stereoselective preparation of functionalized cyclic ethers

Abstract A number of bromoacetal derivatives of γ and δ hydroxysulfones have been prepared and shown to undergo intramolecular alkylation reactions in good yields to give highly functionalized oxacyclic ring systems. Tetrahydrofuranyl and tetrahydropyranyl ring systems have also been prepared using the Michael addition reactions of the acrylate derivatives of hydroxysulfones.

A study of the intramolecular cyclization reactions of some derivatives of 3-arylsulfonyl cycloalkanols☆

Abstract Carbonate and acyl derivatives of 3-arylsulfonylcyclohexanols and heptanols, upon deprotonation with LHMDS in THF at −78°C, undergo an intramolecular cyclization reaction to give bicyclic lactones or the corresponding acyl transfer products in synthetically useful yields. In contrast, the corresponding cyclopentyl derivatives show different reactivity.