Propargyl Unit Research Articles

Solvent-free thiol-Ene/-Yne click reactions for the synthesis of alkoxysilyl telechelic poly(propylene oxide)s

Thiol-ene/−yne click reactions can be a versatile toolbox for the design and modification of polymers, enhancing functionality and providing opportunities for the development of innovative materials and applications. Here, we report a simple strategy to synthesize alkoxysilyl telechelic poly(propylene oxide)s (PPO)s: a) through a post-polymerization functionalization via Williamson reactions, commercial PPO is modified at the chain-end secondary alcohols with allyl or propargyl units, achieving >99% conversion; b) subsequent click reactions of (3-mercaptopropyl)trimethoxysilane (MPTMS), triggered by thermal and photochemical radical initiators, result in the incorporation of alkoxysilane groups on the polyether chain. Both thermal and photochemical thiol-ene/−yne click pathways are robust methodologies for preparing alkoxysilyl-modified PPOs in excellent yields (> 99%). Optimal conditions were identified as solvent-free, at 65 °C with 2,2′-azobis(2-methylpropionitrile) (AIBN) as the radical source. Detailed NMR analyses confirm the quantitative transformation of vinyl/propargyl functionalities in the resulting alkoxysilyl telechelic PPOs. Preliminary studies on the stability of alkoxysilyl end-groups are reported using 29Si NMR spectroscopy.

Base-promoted Conia-ene cyclization of propargyl amides.

We report a tBuOK-promoted synthesis of 1,3-dihydro-2H-pyrrol-2-one and 4-methylenepyrrolidin-2-one systems via Conia-ene like intramolecular cyclization. The method features extremely short reaction times (5 min) and mild reaction conditions (rt), enabling the trapping of a propargyl unit by an amide enolate. An intriguing anionic chain mechanism is at work, which can trigger the isomerization of an exo-alkene giving access to the otherwise elusive endo-product.

4-Propargyl-substituted 1H-pyrroles induce apoptosis and autophagy via extracellular signal-regulated signaling pathway in breast cancer.

Novel pyrrole derivatives (PDs) with propargyl units (1-7) were investigated for their anticancer activity on breast cancer cells. The MTT assay was used to assess the cell viability. Morphological changes in human breast cancer cells were visualized under a phase-contrast microscope. Apoptosis and autophagy were detected using the DNA fragmentation assay and staining by autophagic vacuoles, respectively. The levels of apoptosis- and autophagy-related proteins such as cytochrome c, Bcl-2, LC3-I/II were investigated by Western blot analysis. The effect of PDs on the ERK1/2 signaling pathway was investigated using specific inhibitors. All the tested PDs were found to be active in the range of 36.7 ± 0.2 to 459.7 ± 4.2 µM. Compounds 3 and 4 showed cytotoxic activity in breast cancer cells, but were found to be safer with lower cytotoxicity on human nontumorigenic epithelial breast cells. Compound 4 induced apoptosis, whereas compound 3 induced autophagy. Both compounds inhibited the ERK signaling pathway in breast cancer cells. The present study revealed that both synthesized PDs induced different programmed cell death types by inhibiting the ERK signaling pathway in two genotypically different breast cancer cells. Therefore, novel PDs might be promising anticancer agents for breast cancer therapy and further structural modifications of PDs may yield promising anticancer agents.

Nickel-Catalyzed α-1,3-Dienylation of 1,3-Dicarbonyl Compounds with Propargylic Carbonates

AbstractHerein reported is a nickel-catalyzed α-1,3-dienylation reaction of 1,3-dicarbonyl compounds with substituted propargylic (e.g., but-2-ynyl) carbonates. The propargyl unit changes into a 1,3-dienyl unit, which is incorporated at the α-position of the 1,3-dicarbonyl compounds.

Design, synthesis, antimicrobial evaluation and docking studies of urea-triazole-amide hybrids

A series of urea-1,2,3-triazole-amide hybrids was designed and synthesized via click reaction of urea derivatives containing a propargyl unit with 2-bromo-N-phenylacetamide derivatives and characterized by FTIR, NMR and HRMS data. The antimicrobial evaluation of these synthesized compounds towards three bacteria (Bacillus subtilis, Escherichia coli and Staphylococcus aureus) and two fungi (Aspergillus niger and Candida albicans) was carried out. The activity results revealed that all these hybrids 4(a-r) exhibited better activity than their precursors i.e. alkynes 2(a-c). Moreover, almost all the synthesized triazoles were found to be more potent than the reference drug Fluconazole against C. albicans. Further, docking studies of compound 4j in the active sites of S. aureus DNA gyrase complexed with DNA and antifungal target Lanosterol 14-α demethylase were also carried out.

Heterobimetallic propargyl gold complexes with π-bound copper or silver with enhanced anticancer activity.

Several propargyl functionalised substrates with different heteroatoms (N, O or S) have been used for the preparation of propargyl gold(i) phosphine complexes. The complexes were prepared in high yields either by reaction of the substrate with [Au(acac)PPh3] or by reaction of [AuCl(PPh3)] with potassium hydroxide and the substrate in methanol. Several of the complexes have been characterised by X-ray diffraction showing the presence of secondary bonds such as π-stacking and aurophilic interactions. The reaction of the propargyl gold(i) phosphine complexes with [Cu(NO3)(PPh3)2] or [Ag(OTf)(PPh3)2] afforded heterobimetallic complexes with π-coordination of {Cu(PPh3)2} or {Ag(PPh3)2} to the alkyne bond. When the substituent of the propargyl unit contained more strongly coordinating pyridine moieties, [(PyCH2)2NCH2C[triple bond, length as m-dash]CAuPPh3], coordination of the heterometal to the pyridine units occurred, displacing the phosphine groups and giving rise to a dimeric structure. The antiproliferative activity of the complexes against cisplatin resistant lung cancer cell line A549 was determined by MTT assay. The mononuclear gold complexes showed excellent activities with IC50 values < 14 μM. Coordination of copper of silver to the alkynyl fragment resulted in a significant increase in activity suggesting a synergistic effect between the two metal centres.

A New Strategy for the Synthesis of 4‐Propargyl‐Substituted 1H‐Pyrroles from N‐(5‐phenyl‐2,4‐pentadiynyl) β‐Enaminones

AbstractA new method for the synthesis of 4‐propargyl‐substituted 1H‐pyrroles is described. When treated with sodium hydride in refluxing dichloromethane, N‐(5‐phenyl‐2,4‐pentadiynyl) β‐enaminones, synthesized by the coupling of N‐propargylic β‐enaminones with phenylacetylene, afforded 4‐propargyl‐substituted pyrrole derivatives. This conversion was general for a variety of N‐(5‐phenyl‐2,4‐pentadiynyl) β‐enaminones and displayed broad functional group tolerance. During the reaction, not only cyclization of linear precursors to pyrrole ring takes place, but also propargyl group is introduced to pyrrole core in one‐pot. The enrichment of pyrrole compounds with a propargyl unit might exhibit potential for the synthesis of heterocyclic molecules of pharmacological interest.

Synthesis of Propargyl-Functionalized NHC Gold Complexes

A series of propargyl functionalized N-heterocyclic carbene gold(I) complexes have been synthesized from the corresponding imidazolium salts with tetrabutylammonium acetylacetonate in the presence of a gold(I) precursor in a one-pot reaction. Several complexes of different stoichiometries are described: [AuBr(NHC)], [Au(NHC)2]Br and [Au(C6F5) (NHC)], and many of these have been characterized by X-ray diffraction studies. Aurophilic interactions are present in the compounds bearing less sterically hindered carbenes, and secondary interactions such as hydrogen bonds, π–π stacking, or weak contacts of the gold center with the carbon of the propargyl unit have also been found. These complexes possess a high degree of water solubility, which makes them potentially useful for the synthesis of biologically active compounds or as gold catalysts in water. Activation of the propargyl unit in [AuBr(NHC)] complexes leads to the formation of interesting trimers with bridging bidentate C∧C alkynyl-carbene ligands.

S-Triazine-based functional monomers with thermocrosslinkable propargyl units: Synthesis and conversion to the heat-resistant polymers

Three s-triazine-based functional monomers with thermo-polymerizable propargyl-ether units were synthesized by a facile procedure. These monomers can be thermally cured to form the crosslinked networks, which showed 5-wt% loss temperature of up to 400 °C and the char yields of more than 50% at 1000 °C. Moreover, the crosslinked networks exhibited the coefficients of thermal expansion (CTE) of below 43 ppm °C−1 varying from 30 to 300 °C and glass transition temperatures (Tg) of up to 290 °C, respectively. These monomers were also used to improve the thermostability of a commercial bismaleimide (4,4′-bismaleimidodiphenylmethane). The results indicated that blending the bismaleimide and the triazine monomers gave the new resins, which showed higher Tg and lower CTE than the bismaleimide, suggesting the triazine monomers can be considered as the modifiers for enhancement of the thermostability of the commercial bismaleimides.

Catalytic enantioselective 1,6-conjugate additions of propargyl and allyl groups.

Conjugate (or 1,4-) additions of carbanionic species to α,β-unsaturated carbonyl compounds are vital to research in organic and medicinal chemistry, and there are several known chiral catalysts that facilitate the catalytic enantioselective additions of nucleophiles to enoates1. However, catalytic enantioselective 1,6-conjugate additions are uncommon, and ones that are able to incorporate readily functionalizable moieties, such as propargyl or allyl groups, into acyclic α,β,γ,δ-doubly unsaturated acceptors are unknown2. Chemical transformations that could generate a new bond at the C6 position of a dienoate are particularly desirable, as the resulting products would be subjected to further modifications; such reactions, especially when dienoates contain two equally substituted olefins, are scarce3 and are confined to reactions promoted by a phosphine–copper (with alkyl Grignard4,5, dialkylzinc or trialkylaluminum compounds6,7), a diene–iridium (with arylboroxines)8,9, and a bisphosphine–cobalt catalyst (with monosilyl-acetylenes)10. 1,6-conjugate additions are otherwise limited to substrates where there is full substitution at C411. It is not clear why certain catalysts favor bond formation at C6, and – while there are a small number of catalytic enantioselective conjugate allyl additions12,13,14,15 – related 1,6-additions and processes involving a propargyl unit are non-existent. In this manuscript, we show that an easily accessible organocopper catalyst can promote 1,6-conjugate additions of propargyl and 2-boryl-substituted allyl groups to acyclic dienoates with high selectivity. A commercially available allenylboron compound or a monosubstituted allene may be used. Products can be obtained in up to 83 percent yield, >98 percent diastereo- (for allyl additions) and 99:1 enantiomeric ratio. Mechanistic details, including the origins of high site- (1,6- versus 1,4-) and enantioselectivity as a function of the catalyst structure and reaction type, have been elucidated by means of density functional theory (DFT) calculations.

Palladium-Catalyzed Modular Synthesis of Substituted Piperazines and Related Nitrogen Heterocycles.

We report here a novel method for the modular synthesis of highly substituted piperazines and related bis-nitrogen heterocycles via a palladium-catalyzed cyclization reaction. The process couples two of the carbons of a propargyl unit with various diamine components to provide nitrogen heterocycles in generally good to excellent yields and high regio- and stereochemical control.

Magnetite nanoparticles coated with alkyne-containing polyacrylates for click chemistry

New magnetic core shell nanoparticles were synthesized consisting of magnetite cores and poly-(O-propargyl acrylate) shells. Strong fixing of the shells was achieved by primary anchoring phosphates or α-dihydroxydiphosphonates containing acrylate or methacrylate functionalities. The magnetic nanoparticles are attractive as supports for a variety of function which can be easily introduced by Cu-catalyzed alkyne azide cycloaddition (CuAAC, a click reaction). In this way, also the loading of the magnetic nanoparticles with propargyl units was determined by reaction with 4-azidoacetophenone and analysis of the supernatant. In order to demonstrate the attractiveness of the magnetic nanoparticles a novel azido-containing conjugate with biotin as recognition function and dansyl as fluorescence marker was introduced by CuAAC reaction. All NP show superparamagnetic behavior with high-saturation magnetization values and were further characterized by FTIR, photoelectron spectroscopy and TEM.

Palladium-Catalyzed Medium-Ring Formation for Construction of the Core Structure of Laurencia Oxacycles: Synthetic Study of Laurendecumallene B

Palladium-catalyzed medium-ring formation from a cyclic propargyl carbonate via a ring-opening and -closing cascade proceeded at the central carbon atom of the propargyl unit to provide a tetrahydro-2H-oxocine derivative bearing the core structure of laurencia oxacycle. The synthetic application of this reaction to a possible laurendecumallene B precursor is also presented.

A Simple Metal-Promoted Three-Step Access to n/5/m Angular Carbocyclic Systems

A simple three-step access to n/5/m angular tricyclic skeleta from terminal cycloalkenylacetylenes, Cr(CO)(6), and propargylmalonate esters is described. The process involves a cyclopentannulation of propargylmalonates and enynyl Fischer carbenes, followed by a metal-promoted Cope-type fragmentation of the propargyl unit. The resulting 4-allenyl-carbonyl derivatives can undergo either a 5-exo annulation via a tin enolate or an unprecedented gold catalyzed 6-endo cyclization.

Photochemical thiol–yne functionalization of polypeptide scaffolds

Copolypeptides with propargyl side chains were functionalized with different thiols (1-thio-β-D-glucose tetraacetate, 7-mercapto-4-methylcoumarin, and methyl-3-mercaptopropionate) by initiator/catalyst-free thiol–yne photochemistry. No more than 1.5 instead of ideally 2 equivalents of thiol could be added to the propargyl units even when the thiol was used in excess, attributable to steric constraints (close proximity of the reaction site to the copolypeptide backbone) or conjugation (extended aromatic system). Nevertheless, this procedure enables a facile and modular synthesis of highly functionalized homo- and hetero-functional copolypeptides.

Cyclopolymers from N,N-diallyl-N-propargyl-(12-N′-formylamino)-1-dodecylammonium chloride and their use as inhibitors for mild steel corrosion

A dodecanediamine (DDA)-based new monomer, N,N-diallyl-N-propargyl-(12-N'-formylamino)-1-dodecylammonium chloride, on homo- and co-cyclopolymerization (with SO2) afforded cationic polyelectrolytes, which on acidic hydrolysis of the formyl group gave water-soluble polyelctrolytes. One of the allyl groups undergoes cyclopolymerization with either the propargyl or the other allyl group in competing pathways; the incorporation of the allyl group is found to be faster than the propargyl unit by a ratio of 4:1. Both the monomer and its precursor as well as the polymers were used to study the corrosion inhibition of mild steel by gravimetric and electrochemical methods in acidic and saline media at 60 A degrees C. The inhibitor molecules (at a concentration of 200 ppm) exhibited inhibition efficiencies (%IE) in the ranges 81-99 % in 1 M HCl, 97-98 % in 4 M HCl, 87-93 % in 7.7 M HCl, 68-91 % in 0.5 M H2SO4, and 84-92 % in 3.5 % NaCl. There is a considerable increase in the IEs by the monomers and polymers in comparison to the parent 1,12-DDA.

Ferrocenes Containing a Pendant Propargylic Chain Obtained via Addition of Propargyl Alcohol to μ-Vinyliminium Ligands in Diiron Complexes

The diiron bridging vinyliminium complexes [Fe2{μ-η1:η3-C═N(Me)2C(R′)═C(R″)}(μ-CO)(CO)(Cp)2][SO3CF3] (R′ = H, R″ = SiMe3, 3a; R′ = H, R″ = Tol =4-MeC6H4, 3b; R′ = Me, R″ = Me, 3c; R′ = SPh, R″ = Me, 3d; R′ = H, R″ = Fc = [Fe(C5H4)(Cp)], 6e) react with propargyl alcohol (HC≡CCH2OH), in refluxing toluene, affording the polysubstituted ferrocenes as mixtures of two isomeric forms: [1-NMe2-2-R′-3-R″-5-CH2OCH2C≡CH-Fc] (R′ = H, R″ = SiMe3, 6a; R′ = H, R″ = Tol, 6b; R′ = Me, R″ = Me, 6c; R′ = SPh, R″ = Me, 6d, R′ = H, R″ = Fc, 6e) and [1-NMe2-2-R′-3-R″-4-CH2OCH2C≡CH-Fc] (R′ = H, R″ = SiMe3, 7a; R′ = H, R″ = Tol, 7b; R′ = Me, R″ = Me, 7c; R′ = SPh, R″ = Me, 7d) in overall yields of about 55–65%. Formation of the functionalized cyclopentadienyl in the ferrocene products takes place through the assembly of two propargyl units with the bridging vinyliminium ligand: one alkynol is incorporated by a [3 + 2] cycloaddition with the bridging C3 ligand; a second alkynol unit gives rise to a pendant chain through −OH substitution. Investigations show that the substitution step is catalyzed by the parent diiron complex itself or by a mononuclear iron fragment (likely the Fp+ complex). The pendant propargyl chain has been exploited to connect the ferrocene to other molecular fragments: in particular, the reaction of 6a with 4-biphenyl azide, by copper-catalyzed azide–alkyne cycloaddition (CuAAC), leads to the formation of the triazole-functionalized ferrocene [1-NMe2-2-CH2OCH2-N3(C6H4Ph)C2H-4-SiMe3-Fc] (12). Moreover, 6a reacts with Co2(CO)8, affording the complex [Co2{μ-η2-HC≡CR}(CO)6] (13), (HC≡CR = 6a), where the alkyne adopts a η2 coordination to a dicobalt hexacarbonyl fragment. The molecular structure of 7a has been determined by X-ray diffraction studies.

Photoinduced energy transfer across non-covalent bonds in the nanoscale: cyclodextrin hosts with enhanced luminescent properties for guest communication

Two photoactive cyclodextrin hosts have been prepared and studied in participation on photophysical processes, one with a ruthenium tris(bipyridyl) core which forms a trimeric host and the other with an appended anthracene unit. An acetylide functionalized bipyridyl cyclodextrin, , was prepared by palladium coupling of mono-6-propargyl permethylated beta-CD and 4-bromo-2,2'-bipyridine. The ruthenium complex, [Ru(3)]Cl(2), shows luminescence from the (3)MLCT centered at 650 nm with a quantum yield of 0.044 and a lifetime at room temperature of 1.1 micros in aerated aqueous solution. The enhanced luminescence properties have been attributed to extra delocalisation afforded by the three propargyl units appended to the complex and the stabilization of the MLCT state. An anthracene functionalised cyclodextrin was prepared from mono-6-O-p-toluenesulfonyl permethylated beta-cyclodextrin and 9-anthracene methanol. It shows fluorescence at room temperature with a maximum at 400 nm with a lifetime of 7 ns. Transient absorption spectroscopy has been used to elucidate the excited state properties of [Ru(3)]Cl(2) and hosts. A broad band centered around 600 nm in the [Ru(3)]Cl(2) transient spectrum corresponds to the absorption of the pi-radical anion of the ethynyl fragment of ligand and in a signal at 595 nm was observed, corresponding to the absorption of the anthracene excited singlet state. We used a bisadamantyl guest to assemble the two hosts and studied the energy transfer from the ruthenium core to the anthracene unit by steady state emission spectroscopy. The photoinduced energy transfer process in assemblies of host with ruthenium or osmium metalloguests, [Ru(biptpy)(tpy)](NO(3))(2) and [Os(biptpy)(tpy)](NO(3))(2), was studied by femtosecond transient spectroscopy and steady state emission spectroscopy. The singlet state of the anthracene pendant unit acted as a donor to the MLCT of the Ru(II) or Os(II) metalloguests. An energy transfer rate from the singlet anthracene excited state to the (1)MLCT of the ruthenium centre of 4.8 x 10(8) s(-1) was estimated in the case of the ruthenium guest. The photoinduced triplet energy transfer ( approximately 6 x 10(6) s(-1)) from a longer lived luminescent guest Rubph to the anthracene unit was studied by transient absorption spectroscopy.

Participation of propargyl moiety in Butler's cyclopolymerization process

In order to investigate the possible participation of propargyl group in Butler's cyclopolymerization process, a number of quaternary ammonium chlorides containing allyl and propargyl units are prepared in excellent yields. While the monomer containing two propargyl units as the only unsaturated groups did not undergo cyclopolymerization or cyclocopolymerization with sulfur dioxide, the monomer having one allyl and one propargyl groups afforded water-soluble homo- and co-polymers. The monomer diallylmethylpropargylammonium chloride gave cross-linked homopolymers, whereas its copolymer with sulfur dioxide was found to be linear and water-soluble. Careful analysis of the 1H and 13C NMR spectra revealed for the first time the participation of the propargyl units in Butler's cyclopolymerization process to yield polymers having five-membered cyclic structure embedded in the polymer chain.

‘Safety-Catch’ Propargyl-Based Linker Strategy for the Immobilization of Amines and Carboxylic Acids in SPOS

Integral propargyl alcohol and propargyl chloroformate linkers were developed for a 'safety-catch' acid-sensitive linker strategy. The syntheses of the integral propargyl linkers were achieved by direct conversion of the solid support starting from Merrifield resin, hydroxymethylpolystyrene or 4-bromopolystyrene. Amines and carboxylic acids have been coupled and released to demonstrate that transformation of the propargyl units to cobalt carbonyl complexes facilitates the cleavage under mild acidic conditions in high purity.