N-vinyl Amides Research Articles

N-Vinylation of lactams with calcium carbide water system

Direct N-vinylation of lactams with calcium carbide water system was performed under super-basic conditions. The vinylation occurred exclusively at NH group leaving CO function intact to afford cyclic N-vinyl amides in yields up to 97%. The obtained products are prospective monomers for the preparation of synthetic peptides.

Three-Component Gold(I)-Catalyzed Alkoxyvinylation.

Acetylene has been underexploited despite being a highly valuable feedstock for chemical synthesis. We have developed the first true gold(I)-catalyzed intermolecular three-component reaction between acetylene, alkenes, and alcohols to afford β-vinyl hemiaminal scaffolds from N-vinyl amides. Unusual biscyclopropyl and 3-vinyl N-heterocyclic scaffolds were obtained through the incorporation of a second N-vinyl unit or tethered alkene into the starting material.

Diversely substituted poly(N-vinyl amide) derivatives towards non-toxic, stealth and pH-responsive lipid nanocapsules

Surface modification of lipid nanocapsules (LNC) is necessary to impart stealth properties to these drug carriers and enhance their accumulation into the tumor microenvironment. While pegylation is commonly used to prolong the circulation time of LNC, the increased presence of anti‐PEG antibodies in the human population and the internalization issues associated to the PEG shell are strong incentives to search alternatives. This work describes the development of amphiphilic poly(N-vinyl amide)-based (co)polymers, including pH-responsive ones, and their use as LNC modifiers towards improved drug delivery systems. RAFT polymerization gave access to a series of LNC modifiers composed of poly(N-methyl-N-vinyl acetamide), poly(N-vinyl pyrrolidone) or pH-responsive vinylimidazole-based sequence bearing a variety of lipophilic end-groups, namely octadecyl, dioctadecyl or phospholipid groups, for anchoring to the LNC. Decoration of the LNC with these families of poly(N-vinyl amide) derivatives was achieved via both post-insertion and per-formulation methods. This offered valuable and non-toxic LNC protection from opsonization by complement activation, emphasized the benefit of dioctadecyl in the per-formulation approach and highlighted the great potential of poly(N-methyl-N-vinyl acetamide) as PEG alternative. Moreover, incorporation of imidazole moieties in the shell of the carrier imparted pH-responsiveness to the LNC likely to increase the cellular uptake in the acidic tumor microenvironment, opening up new possibilities in the field of active targeting.

СИНТЕЗ И ХАРАКТЕРИСТИКА ЭКОЛОГИЧЕСКИ БЕЗОПАСНЫХ ВОДОРАСТВОРИМЫХ ПОЛИМЕРОВ НА ОСНОВЕ N-ВИНИЛАМИДА

The article provides a rationale for the synthesis of environmentally friendly water-soluble polymers based on N-vinyl amide, used in various technological processes. The relevance of the work is associated with solving environmental problems of creating biodegradable materials and minimizing the negative impact of polymer materials on the environment. The aim of the work was to synthesize and characterize polymers based on N-vinylamide. The conditions for the synthesis of poly-N-vinylpyrrolidone, poly-N-vinylcaprolactam, poly-N-vinylformamide and polyacrylamide, including the temperature and time of synthesis, have been developed. Alcohols of various structures, hexane and distilled water were used as solvents; thermal initiation was carried out using dinitrile azo-bis-isobutyric acid. The viscosity average molecular weight and intrinsic viscosity of the obtained polymers were calculated. Polymers with molecular weights from 10,000 to 94,000 were obtained by radical polymerization. Polymers of the poly-N-vinylamide series are characterized by the presence of a hydration shell consisting of several layers. The structure of the hydration shell of poly-N-vinylcaprolactam, in which water molecules form hydrogen bonds with the carbonyl group of the polymer, is presented. To characterize the polymers, the IR spectra of their aqueous solutions were obtained, and the assignment of absorption bands in the obtained spectra was given. The synthesized polymers have good complexing ability, which expands the possibilities of their application for the extraction of inorganic and organic substances.

Visible light-induced synthesis of (Z)-β-iodoenamides from N-vinyl amides mediated by the ion pair charge transfer state

A facile and novel approach for the highly chemo- and stereoselective synthesis of (Z)-β-iodoenamides from N-vinyl amides has been developed based on a visible-light-induced ion pair charge transfer state derived from pyridinium iodides.

Visible-Light-Induced Oxazoline Formations from N-Vinyl Amides Catalyzed by an Ion-Pair Charge-Transfer Complex

Visible-light photoredox catalysis plays an important role in various reactions which are inaccessible under typical thermal conditions. Distinctly different from common visible-light photoredox catalysis which often involves transition-metal complexes, conjugated organic dyes, or electron donor–acceptor complexes, herein, the use of ion-pair charge-transfer (IPCT) complex-induced visible-light photoredox catalytic reactions are described, wherein the cyclization–methoxylation of N-vinyl amides in methanol was achieved under irradiation with blue LEDs. The reaction employs a heteroarenium iodide as the photocatalyst and can be extended to cyclization–alkoxylation, −acyloxylation, and −hydroxylation. This protocol provides an eco-friendly synthetic route to a wide range of oxazoline derivatives. Mechanistic investigations with UV–visible spectroscopy and control experiments confirm the existence of the IPCT absorption band in the visible region for the heteroarenium iodide, which is responsible for the observed reactivity.

Synthetic Studies Towards Spirocyclic Imine Marine Toxins Using N-Acyl Iminium Ions as Dienophiles in Diels–Alder Reactions

Cyclic imine marine toxins have attracted considerable attention from the synthetic community in the past two decades due to their unique chemical structures and clinically relevant biological activities. This review presents recent efforts of our group in the development of various strategies to efficiently construct the common spirocyclic imine fragments of the cyclic imine toxins. In particular, the use of α,β-unsaturated N-acyl iminium ion dienophiles in Diels–Alder reactions are highlighted, whereby direct access to spirocyclic imine motifs was obtained and important mechanistic details were discovered. Alternative approaches to spirocyclic imine systems involving hydroamination of amino alkynes are also summarized. One such approach led to serendipitous access to N-vinyl amide products, while our most recently ­reported approach involving an intermolecular Diels–Alder/cross-­coupling sequence using novel 2-bromo-1,3-butadienes to access 5,6-spirocyclic imines is also discussed. Additionally, the development of a novel method to construct another challenging motif present in the portimines is also introduced.1 Introduction2 Strategies towards the Spirocyclic Imine Fragment of Cyclic Imine Toxins2.1 Diels–Alder Cycloadditions of α,β-Unsaturated N-Acyl Iminium Dienophiles2.2 Early Studies Using in situ-Generated Iminium Ion Dienophiles2.3 Use of More Stable Iminium Ion Dienophiles for Diels–Alder Reactions2.4 Other Notable Strategies towards Spirocyclic Imines2.5 Recent Efforts towards the 5,6-Spirocyclic Imine Marine Toxin Portimine A2.6 Construction of Another Challenging Motif of Portimine A3 Conclusion and Future Perspectives

Unexpected Direct Synthesis of N-Vinyl Amides through Vinyl Azide-Enolate [3+2] Cycloaddition.

The unexpected synthesis of industrially important N-vinyl amides directly from aldehydes and α,β-unsaturated N-vinyl amides from esters is reported. This reaction probably proceeds through an initial [3+2] azide-enolate cycloaddition involving a vinyl azide generated in situ. A survey of the reaction scope and preliminary mechanistic findings supported by quantum computational analysis are reported, with implications for the future development of atom-efficient amide synthesis. Intriguingly, this study suggests that (cautious) reevaluation of azidoethene as a synthetic reagent may be warranted.

XtalFluor-E® mediated proto-functionalization of N-vinyl amides: access to N-acetyl N,O-acetals.

XtalFluor-E® has been extensively used in a broad range of reactions in the past few years. Here we report its use with protic nucleophiles in a catalytic manner for the in situ generation of protons that lead to the proto-functionalization of activated olefins. Utilizing the latter protocol, proto etherification of enamides gives rise to N,O-acetals in nearly quantitative yields.

Kinetic Hydrate Inhibition with N-Alkyl-N-vinylformamide Polymers: Comparison of Polymers to n-Propyl and Isopropyl Groups

Gas hydrates in the upstream oil and gas industry often cause problems during production, such as plugged pipelines causing down time and loss of revenue. Kinetic hydrate inhibitors (KHIs) have successfully been used in the field for about 2 decades. KHIs work to delay hydrate nucleation and/or crystal growth in the hydrate-stable operating region. KHIs, such as polymers containing N-vinyl amide units, for example, methacrylamide-based KHI polymers with isopropyl groups, have been commercialized and are now used in field operations. However, there are no reports of polymers with n-propyl groups that have been commercialized as a KHI. Using a structure-II-forming natural gas, we have now investigated the KHI performance of homopolymers with n-propyl and isopropyl groups based on the N-vinylformamide (NVF) monomer. A range of copolymers with NVF with higher cloud points were also synthesized and tested because the cloud points of these homopolymers were found to be lower than preferred for most field operations. The polymer series containing nPr-NVF monomer was found to perform better as KHIs than the iPr-NVF series as KHIs at 2500 ppm concentration in deionized water at all copolymer ratios with a similar molecular weight. Two of the best polymers from each of the nPr-NVF and iPr-NVF series were tested at varying concentrations from 1500 to 5000 ppm. A similar trend was found as with the tests of the complete series, in which the nPr-NVF polymer performed better than the iPr-NVF polymer. Poly(N-(n-propyl)-N-vinylformamide) homopolymer gave a similar KHI performance as a commercial sample of polyvinylcaprolactam (PVCap).

Influence of the microwave irradiation on the enzymatic activity of trypsin in the presence of poly(N-vinyl amides)

The features of the microwave irradiation effect on trypsin state and changes jn its enzymatic activity in the presence of poly(N-vinyl amides) at various temperatures have been studied. Comparison of the denaturizing effect of the irradiation and of convective heating has revealed, along with the thermal factors, the specific effects of microwave radiation. These effects have been found to affect both protein and polymer molecules, to change their interaction parameters, and thus, to modulate trypsin enzymatic function.

Key Role of Intramolecular Metal Chelation and Hydrogen Bonding in the Cobalt‐Mediated Radical Polymerization of N‐Vinyl Amides

This work reveals the preponderance of an intramolecular metal chelation phenomenon in a controlled radical polymerization system involving the reversible trapping of the radical chains by a cobalt complex bis(acetylacetonato)cobalt(II). The cobalt-mediated radical polymerization (CMRP) of a series of N-vinyl amides was considered with the aim of studying the effect of the cobalt chelation by the amide moiety of the last monomer unit of the chain. The latter reinforces the cobalt-polymer bond in the order N-vinylpyrrolidone<N-vinyl caprolactam<N-methyl-N-vinyl acetamide, and is responsible for the optimal control of the polymerizations observed for the last two monomers. Such a double linkage between the controlling agent and the polymer, through a covalent bond and a dative bond, is unique in the field of controlled radical polymerization and represents a powerful opportunity to fine tune the equilibrium between latent and free radicals. Possible hydrogen bond formation is also taken into account in the case of N-vinyl acetamide and N-vinyl formamide. These results are essential for understanding the factors influencing Co-C bond strength in general, and the CMRP mechanism in particular, but also for developing a powerful platform for the synthesis of new precision poly(N-vinyl amide) materials, which are an important class of polymers that sustain numerous applications today.

New N-vinylamide-based polymers for the preconcetration of nitrophenols from aqueous media

New cross-linked copolymer with molecular imprints of 4-nitrophenol have been synthesized by the radical polymerization of cyclic N-vinyl amides and ethylene glycol dimethacrylate. Sorption characteristics of the obtained polymers depend on the nature of the functional monomer, ratio of components in the prepolymerization mixture, pH of solution, and temperature. It has been established that N-vinylpyrrolidone-based copolymers provide higher selectivity of 4-nitrophenol extraction than N-vinylcaprolactam-based products.

Simple entry to new 2-alkyl-1,2,3,4-tetrahydroquinoline and 2,3-dialkylquinoline derivatives using BiCl3-catalyzed three component reactions of anilines and aliphatic aldehydes in the presence (or lack) of N-vinyl amides

A general protocol for the simple and efficient synthesis of 2-alkyl-1,2,3,4-tetrahydroquinolines and 2,3-dialkylquinolines was reported. Synthetic protocol describes the one-pot preparation of these tetrahydroquinoline and quinoline products using the same reagents (aliphatic aldehydes and anilines) in the BiCl3-catalyzed multicomponent condensation process where the third component, N-vinyl amide is present.

Radical cation salt induced tandem cyclization between anilines and N-vinyl amides: synthesis of 2-methyl-4-anilino-1,2,3,4-tetrahydroquinoline derivatives

A tandem cyclization of imines with N-vinyllactams induced by TBPA + was investigated, and a series of 2-methyl-4-anilino-1,2,3,4-tetrahydroquinolines were synthesized based on a domino process in which N-vinyllactams serve as an acetaldehyde surrogate. A single electron transfer mechanism was proposed and radical cation salt acts as both a Lewis acid and one electron oxidant to induce such transformation.

A Versatile Cyclodehydration Reaction for the Synthesis of Isoquinoline and β-Carboline Derivatives

The direct conversion of various amides to isoquinoline and beta-carboline derivatives via mild electrophilic amide activation, with trifluoromethanesulfonic anhydride in the presence of 2-chloropyridine, is described. Low-temperature amide activation followed by cyclodehydration upon warming provides the desired products with short overall reaction times. The successful use of nonactivated and halogenated phenethylene derived amides, N-vinyl amides, and optically active substrates is noteworthy.

Direct N-vinylation of aryl and hetaryl carboxamides with trimethoxyvinylsilane

A general method for direct N-vinylation of aryl and hetaryl carboxamides with trimethoxyvinylsilane using a copper(II) acetate–TBAF system as catalyst is elaborated. The yield of N-vinyl amides depends strongly on the initial amide and nature of the solvent.

Akresol: A new polymer quenchant

The cooling capacity of aqueous solutions of polymer compositions based on polycarboxylic acids and copolymers of N-vinyl amides is studied. Tests of a new quenchant based on interpolymer complexes of anion-active components are performed and the process possibilities and the reproducibility of properties of different batches of this quenchant are estimated.

SINGLE-STEP SYNTHESIS OF ALKYNYL IMINES FROM N-VINYL AND N-ARYL AMIDES

SINGLE-STEP SYNTHESIS OF ALKYNYL IMINES FROM N-VINYL AND N-ARYL AMIDES

Direct Synthesis of Pyridine Derivatives

We describe a single-step conversion of various N-vinyl and N-aryl amides to the corresponding pyridine and quinoline derivatives, respectively. The process involves amide activation with trifluoromethanesulfonic anhydride in the presence of 2-chloropyridine followed by π-nucleophile addition to the activated intermediate and annulation. Compatibility of this chemistry with sensitive N-vinyl amides, epimerizable substrates, and a variety of functional groups is noteworthy.