Synthesis of 3,3-Di(ethoxycarbonyl)-1-vinylpyrrolidin-2-one and Determination of Its Reactivity Ratios with 1-Vinylpyrrolidin-2-one

Summary: Polyvinylpyrrolidone (PVP) is a synthetic, non‐toxic, water‐soluble polymer commonly used in a wide range of applications including several pharmaceutical applications. One example of an important application is the controlled release and delivery of therapeutic agents into sites of inflammation or tumours. However, PVP lacks reactive groups, which limits the possibility of adding new functions to the polymer in order to modify its physical and chemical properties. Furthermore, large differences in radical reactivity between 1‐vinylpyrrolidin‐2‐one (NVP) and most other monomers lead to compositional drift during copolymerization. This complicates the introduction of reactive groups into the polymer using this method. Monomers that are derivatives of NVP itself are expected to show smaller differences in radical reactivity and therefore provide a way of preparing PVP with adjustable properties. Here we present the synthesis of five NVP‐based monomers and their use in the preparation of functional PVP with adjustable properties in terms of solubility, loading of functional groups, and molar mass. The results show the possibility of tailoring PVP for different biomedical applications e.g. drug delivery systems.Copolymers from 1‐vinylpyrrolidin‐2‐one.magnified imageCopolymers from 1‐vinylpyrrolidin‐2‐one.

Section: Introductionmentioning

confidence: 99%

Synthesis of Novel Monomers and Copolymers from 1‐Vinylpyrrolidin‐2‐one: Attractive Materials for Drug Delivery Systems?

Engström

Lindgren

Helgee

2006

“…To test this hypothesis, we prepared four new derivatives of NVP The synthetic method is similar to earlier reported procedures in which the main purpose was to produce only monofunctional monomers. [28][29][30]37] Regardless of the starting ratio of NVP to the compound carrying the functional group, the crude product mixture in our experiments has always contained both monofunctional and difunctional monomers. Slow addition of the compound containing the functional group has also been tried in order to favor the formation of the monofunctional monomers, but such experiments also gave this mixture.…”

Section: Monomer Synthesesmentioning

confidence: 99%

“…[28,29] Functional groups affixed to the a-position of NVP will not significantly affect the reactivity of the double bond, and, hence, copolymerization of such a monomer and NVP would show little compositional drift. [30] We have previously reported the synthesis and use of two such monomers and one crosslinker for the preparation of a new type of hydrophilic polymer beads based on PVP. [31] In our continued work on these systems, we have prepared several other functional derivatives of NVP.…”

Section: Introductionmentioning

confidence: 99%

Functional Beads of Polyvinylpyrrolidone: Promising Support Materials for Solid‐Phase Synthesis

Engström¹,

Helgee²

2006

Summary: The solubility properties of polyvinylpyrrolidone (PVP) make it an attractive material for several different polymer‐assisted synthesis applications. However, PVP lacks reactive groups necessary for attaching compounds to the polymer. Furthermore, the radical reactivity of 1‐vinylpyrrolidin‐2‐one (NVP) is different from most other monomers, which results in compositional drift during copolymerization. Therefore, introducing reactive groups into the polymer using this method is intricate. Smaller differences in radical reactivity are expected from monomers that are derivatives of NVP itself. Hence, such monomers provide a way of preparing PVP with adjustable properties. Four new monomers containing pendant double bonds, all derivatives of NVP, were synthesized and used in the preparation of a new type of hydrophilic polymer bead by aqueous suspension polymerization. We also found that undec‐10‐en‐1‐ol can be used as a comonomer for the introduction of functional groups. The lightly crosslinked beads contain hydroxyl groups at a functional loading of 0.28 mmol/g and swell extensively in a broad range of solvents. Their potential as support materials has previously been demonstrated in a five‐step solid‐phase synthesis of 5‐(2,4,6‐trimethoxy‐phenyl)‐cyclohexa‐1,3‐dienecarboxylic acid.Scanning electron microscopy image of dry beads from PVP‐[B]2.magnified imageScanning electron microscopy image of dry beads from PVP‐[B]2.

“…The same problems have been encountered by other groups working with these kinds of systems. [28] Fortunately, for the intended applications, both monomer products are potentially useful and can be separated by column chromatography.…”

Section: Monomer Synthesesmentioning

confidence: 99%

Novel Densely Alkylated Hydroxyl‐Functional Polyvinylpyrrolidone Showing Phase‐Selective Solubility

Engström

Helgee

Sung

et al. 2006

Summary: Polyvinylpyrrolidone (PVP) is a commonly used polymer with many different applications in the pharmaceutical, cosmetic and food industries. However, the lack of reactive groups and the difficulty in copolymerizing the monomer, N‐vinylpyrrolidin‐2‐one (NVP) with most other monomers, limits the possibility of modifying the physical and chemical properties of the polymer. Monomers that are derivatives of NVP itself are expected to show small differences in radical reactivity as compared to the parent monomer and provide a way of adjusting the polymer properties without extensive compositional drift during copolymerization. Here we present the synthesis of two new functionalized NVP‐based monomers and their copolymerization with alkylated NVP‐monomers for the preparation of two functionalized PVPs with phase‐selective solubility in heptane. Both copolymers showed 99.99% selective solubility in heptane over DMF (thermomorphic system) and 99.99% in heptane over 90% EtOH‐H2O (latent biphasic system). These results suggest that the polymers could be used as soluble supports to facilitate recovery and recycling of catalysts or reagents from liquid/liquid systems after homogeneous reactions.Phase‐selectively soluble polyvinylpyrrolidone copolymer.magnified imagePhase‐selectively soluble polyvinylpyrrolidone copolymer.