Guanidine Base Research Articles

Catalyst- and excess reagent recycling in aza-Michael additions.

16α-Azolyl-pregnenolone derivatives were prepared via 2-butyl-1,1,3,3-tetramethylguanidine (n-Bu-TMG) catalysed aza-Michael addition of 16-dehydropregnenolone (16-DHP) carried out in [bmim][BF4]. The application of the guanidine base and the imidazolium ionic liquid made it possible to recycle not only the catalyst/solvent mixture but also the excess of the N-heterocyclic reagent. By the introduction of CO2 at the end of the reaction, both the guanidine base and the unreacted (excess) reagent could be converted into ionic species that remained dissolved in the ionic liquid phase, while the steroid components were extracted with an apolar solvent. After the removal of CO2, the experiment could be repeated by the addition of the steroid substrate and only an equimolar amount of the N-heterocycle. The methodology was successfully applied to a number of N-heterocycles, such as imidazole, pyrazole, 1,2,3- and 1,2,4-triazoles, and benzimidazole. Indazole and indole could also be converted into the corresponding products, but a stronger base had to be used to obtain a recyclable system.

Bicyclic-ring base doping induces n-type conduction in carbon nanotubes with outstanding thermal stability in air

The preparation of air and thermally stable n-type carbon nanotubes is desirable for their further implementation in electronic and energy devices that rely on both p- and n-type material. Here, a series of guanidine and amidine bases with bicyclic-ring structures are used as n-doping reagents. Aided by their rigid alkyl functionality and stable conjugate acid structure, these organic superbases can easily reduce carbon nanotubes. n-Type nanotubes doped with guanidine bases show excellent thermal stability in air, lasting for more than 6 months at 100 °C. As an example of energy device, a thermoelectric p/n junction module is constructed with a power output of ca. 4.7 μW from a temperature difference of 40 °C.

Accelerated SuFEx Click Chemistry For Modular Synthesis.

SuFEx click chemistry is a powerful method designed for the selective, rapid, and modular synthesis of functional molecules. Classical SuFEx reactions form stable S-O linkages upon exchange of S-F bonds with aryl silyl-ether substrates, and while near-perfect in their outcome, are sometimes disadvantaged by relatively high catalyst loadings and prolonged reaction times. We herein report the development of accelerated SuFEx click chemistry (ASCC), an improved SuFEx method for the efficient and catalytic coupling of aryl and alkyl alcohols with a range of SuFExable hubs. We demonstrate Barton's hindered guanidine base (2-tert-butyl-1,1,3,3-tetramethylguanidine; BTMG) as a superb SuFEx catalyst that, when used in synergy with silicon additive hexamethyldisilazane (HMDS), yields stable S-O bond linkages in a single step; often within minutes. The powerful combination of BTMG and HMDS reagents allows for catalyst loadings as low as 1.0 mol % and, in congruence with click-principles, provides a scalable method that is safe, efficient, and practical for modular synthesis. ASSC expands the number of accessible SuFEx products and will find significant application in organic synthesis, medicinal chemistry, chemical biology, and materials science.

Accelerated SuFEx Click Chemistry For Modular Synthesis**

AbstractSuFEx click chemistry is a powerful method designed for the selective, rapid, and modular synthesis of functional molecules. Classical SuFEx reactions form stable S−O linkages upon exchange of S−F bonds with aryl silyl‐ether substrates, and while near‐perfect in their outcome, are sometimes disadvantaged by relatively high catalyst loadings and prolonged reaction times. We herein report the development of accelerated SuFEx click chemistry (ASCC), an improved SuFEx method for the efficient and catalytic coupling of aryl and alkyl alcohols with a range of SuFExable hubs. We demonstrate Barton's hindered guanidine base (2‐tert‐butyl‐1,1,3,3‐tetramethylguanidine; BTMG) as a superb SuFEx catalyst that, when used in synergy with silicon additive hexamethyldisilazane (HMDS), yields stable S−O bond linkages in a single step; often within minutes. The powerful combination of BTMG and HMDS reagents allows for catalyst loadings as low as 1.0 mol % and, in congruence with click‐principles, provides a scalable method that is safe, efficient, and practical for modular synthesis. ASSC expands the number of accessible SuFEx products and will find significant application in organic synthesis, medicinal chemistry, chemical biology, and materials science.

Enantioseparation and racemization of α-aryl-α-fluoroacetonitriles.

The 2-Aryl-2-fluoroacetonitriles have garnered increasing interest as versatile building blocks in asymmetric synthesis. However, the configurational stability of these organofluorines is poorly understood and analytical methods that can be used to differentiate between their enantiomers remain underdeveloped. In this study, baseline high performance liquid chromatography (HPLC) enantioseparation of ten 2-aryl-2-fluoroacetonitriles was achieved by screening frequently used chiral stationary phases. While Chiralcel OD, Chiralpak AD, and Chiralpak AS proved to be most broadly useful, preparative separation of the enantiomers of 2-(2-naphthyl)-2-fluoroacetonitrile was possible on Chiralcel OJ. This enabled racemization studies at various temperatures and in the presence of organic bases which showed that this compound is configurationally stable under neutral conditions upon heating to 130°C for 6 h but undergoes complete racemization within 10 h in the presence of stoichiometric amounts of a guanidine base at room temperature. The racemization is likely to proceed via formation of an achiral keteniminate intermediate and obeys reversible first-order reaction kinetics with a half-life time of 87.7 min in ethanolic hexanes at 23.2°C. Racemization is significantly slower and occurs with a half-life time of 23.1 h at 22.4°C when the guanidine is replaced with a weaker amidine base.

Structural and multi-functional properties of novel thorium complex bearing higher analogue of guanidine base

New-fangled water mediated and air stable thorium complex of molecular formula (AgunH)2[Th(dip)3].H2O have been prepared by reacting thorium(IV) nitrate, dipicolinic acid (H2dip) and aminoguanidine bicarbonate (AgunH.HCO3) at appropriate molar ratio via., template method. The complex has been systematically characterized by chemical analysis, elemental, spectral, thermal and single crystal studies including luminescence and antioxidant properties. The IR spectrum of the resulting complex infers that the carboxylate anion behaves as a monodentate and facilitates to form a monomeric rather than polymeric environment. This is further confirmed by single crystal X-ray diffraction studies. Thermal stability of the title compound undergoes step-wise decomposition to endure ThO(CO3) as the end residue. The single crystal X-ray study reveals that the thorium complex crystallizes in the triclinic crystal system with centric space group (P-1) of Z = 2. Each dipicolinate anion (dip2−) exhibits tridentate coordination modes through a nitrogen atom of pyridine ring and oxygen atoms of the carboxylate groups to form nine coordination with tri-capped trigonal prismatic geometry. Further, the anionic complex is neutralized by two aminoguanidinium (AgunH+) cations and stabilized along with a lattice water molecule. This material shows enhanced luminescent properties, this is due to the crucial role of dipicolinate anion not for aminoguanidinium moiety. Whereas, the aminoguanidinium species is promote to act as a secondary antioxidant.

Intermolecular domino Michael/aldol reactions of α,β-unsaturated esters, aromatic aldehydes, and various nucleophiles promoted with a catalytic amount of a guanidine base in DMSO

In DMSO, a catalytic amount of Barton's base (2-t-butyl-1,1,3,3-tetramethylguanidine, BTMG) effectively catalyzed intermolecular three-component reactions of α,β-unsaturated esters, aldehydes, and carbon-, sulfur-, or nitrogen-pronucleophiles to give three-component addition products with the formation of two new σ-bonds: pronucleophiles and aldehydes reacted with α,β-unsaturated esters at their β-positions and α-positions, respectively. Mechanism studies suggested that these reactions proceeded by the first intermolecular Michael addition of anionic nucleophiles that were formed from pronucleophiles with a catalytic amount of BTMG, followed by intermolecular aldol reactions of transient ester enolates even in the presence of more than stoichiometric amounts of acidic pronucleophiles. High nucleophilicity over Brønsted basicity of transient enolates in polar solvents was observed for transient ester enolates rather than ketone enolates.

Fe3O4-poly(AGE-DVB-GMA) composites immobilized with guanidine as a magnetically recyclable catalyst for enhanced biodiesel production

This present research aims at developing an efficient and reusable base catalyst to improve the biodiesel production for the need of green chemistry and sustainable development. To achieve this, the copolymer, namely poly(allylglycidyl ether-divinylbenzene-glycidyl methacrylate) (poly(AGE-DVB-GMA)), was firstly incorporated in the Fe3O4 nanoparticles forming magnetic Fe3O4-poly(AGE-DVB-GMA) composites, and then organic guanidine was bound on the magnetic matrices via covalent bonds with active epoxy groups. The characterization of the as-made magnetic copolymer support and solid base catalysts was performed by several techniques, and the results revealed that the guanidine base was successfully tethered on the magnetic copolymer support. This developed solid catalyst possessed large surface basicity of 2.45 mmol/g and highly magnetic responsiveness with saturation magnetization value of 18.13 emu/g, displaying good activity to the transesterification of soybean oil to biodiesel in a heterogeneous manner. Under the transesterification conditions of methanol/oil molar ratio of 20:1, catalyst dosage of 7 wt%, reaction temperature of 65 °C, reaction duration of 8 h, the biodiesel yield of 92.6% was attained over the guanidine-based solid catalyst. Moreover, the catalyst could be easily separated under an external magnetic field, and showed satisfactory catalytic activity even after four reuse cycles, thus posing considerable potential for the sustainable and clean production of biodiesel.

Photoredox-Mediated Hydrogen Isotope Exchange Reactions of Amino-Acids, Peptides, and Peptide-Derived Drugs.

Hydrogen isotopically labelled compounds are essential diagnostic tools in drug research and development, as they provide vital information about the biological metabolism of drug candidates and their metabolites. Herein we report a photoredox-initiated hydrogen atom transfer (HAT) protocol which efficiently and selectively introduces deuterium or tritium at C(sp3 )-H bonds, utilizing heavy water (D2 O or T2 O) as the hydrogen isotope source, and a guanidine base. This protocol has been successfully applied to the incorporation of deuterium in several amino acids (lysine, glycine and proline) and small peptides. Finally, the method has been applied to tritium, because tritium-labelled peptides are essential for application in biological experiments, such as ligand-binding assays, or absorption, distribution, metabolism, and excretion (ADME) studies.

Guanidine masked catechol initiator promoted ring-opening polymerization of sarcosine N-carboxyanhydride

The synthesis of catechol polymers often demands tedious protection and deprotection steps. In this work, the role of a guanidine base to subdue the catechol functions and promote the ring-opening polymerization (ROP) is suggested. Accordingly, guanidine, 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD), was employed to mediate ROP of N-carboxyanhydride (NCA) from a catechol initiator. MTBD played a dual-role in ROP of sarcosine-NCA (Sar-NCA) and masking the catechol initiator concurrently. Catechol-ended polysarcosine (PSar) was synthesized with a predicted molecular weight (Mn,SEC = 3.5 kg mol−1, Mn,NMR = 3.7 kg mol−1) and narrow dispersities (Đ < 1.11). This one base two-function strategy showed a new path for the synthesis of catechol functionalized polymers.

Photoinduced Proton-Transfer Polymerization: A Practical Synthetic Tool for Soft Lithography Applications.

Proton-transfer photopolymerization through the thiol-epoxy "click" reaction is shown to be a versatile new method for the fabrication of micro- and nanosized polymeric patterns. In this approach, complexation of a guanidine base, diazabicycloundecene (DBU), with benzoylphenylpropionic acid (ketoprofen) generates a photolabile salt. Under illumination at a wavelength of 365 nm, the salt undergoes a photodecarboxylation reaction to release DBU as a base. The base-catalyzed ring opening reaction then creates cross-linked poly(β-hydroxyl thio-ether) patterns. The surface chemistry of these patterns can be altered through alkylation of the thio-ether linkages. For example, a reaction with bromoacetic acid produces a hitherto unknown sulfonium/carboxylate-based zwitterionic motif that endows antibiofouling capacity to the micropatterns.

Sequential Reduction of Nitroalkanes Mediated by CS2 and Amidine/Guanidine Bases: A Controllable Nef Reaction.

In this letter, we describe a mild, functional group-tolerant reductive Nef reaction that utilizes CS2 and an amidine or guanidine base to sequentially cleave N-O bonds. These conditions transform secondary nitroalkanes to ketones via an isolable oxime with minimal erosion at labile stereogenic carbons, show excellent compatibility with groups sensitive to oxidizing or reducing conditions, display good scalability, and are well-suited for generating useful 3-pyrrolidinone motifs from readily accessible 1,3-dipolar cycloaddition products.

Extremely rapid postfunctionalization of maleate and fumarate main chain polyesters in the presence of TBD

Unsaturated polyester (UP) scaffold, poly (butylene maleate) (P1), possessing an electron-deficient double bond in the main chain was prepared and utilized as a precursor for thiol- and aza-Michael addition reactions. From a detailed catalyst search (amidine and guanidine bases), 1,5,7-triazabicyclo [4.4.0]dec-5-ene (TBD) proved to be the most efficient catalyst for thiol-Michael addition reactions since pendant thioether functional polyesters were achieved quantitatively within 1 min. Furthermore, P1 was allowed to react with primary and secondary amines through aza-Michael addition reactions, followed by thiol-Michael addition reaction thus affording the synthesis of pendant amine and thioether functional polyesters.

Investigating the Underappreciated Hydrolytic Instability of 1,8-Diazabicyclo[5.4.0]undec-7-ene and Related Unsaturated Nitrogenous Bases

The widespread use of amidine and guanidine bases in synthetic chemistry merits a thorough understanding of their chemical properties. The propensity of these reagents to hydrolyze under mild condi...

Organocatalysts for the Synthesis of Poly(ethylene terephthalate‐co‐isosorbide terephthalate): A Combined Experimental and DFT Study

AbstractOrganocatalysts are assessed for the insertion of isosorbide, a rigid, biobased diol monomer, into poly(ethylene terephthalate). A sulfonic acid (p‐toluenesulfonic acid—APTS), an amidine base (1,8‐diazabicyclo [5.4.0] undec‐7‐ene—DBU) and a guanidine base (1,5,7‐triazabicyclo[4.4.0]dec‐5‐ene—TBD) successfully catalyze the polymerization. The reaction mechanisms are studied by density functional theory. A bifunctional activation is observed in the presence of the sulfonic acid, the carbonyl moiety being activated via the acidic proton of APTS and the alcohol via the basic oxygen. Regarding DBU, a mechanism based on a basic activation of the alcohol rather than a nucleophilic attack of the catalyst is evidenced. The difference observed between TBD and DBU is attributed to a better H‐bonding ability of the former versus the latter.

A guanidine based bis Schiff base chemosensor for colorimetric detection of Hg(II) and fluorescent detection of Zn(II) ions

A novel guanidine base colorimetric and fluorescent bis Schiff base chemosensor L has been designed synthesized and characterized by elemental analyses, 1H NMR, FT-IR and ESI-MS spectral analysis. The chemosensor L could detect Hg2+ by “naked eye” colour change from yellow to red and Zn2+ through selective fluorescence enhancement in CH3OH-tris buffer (1/1, v/v) over other metal ions commonly obtained in physiological and environmental samples. The Job’s plot analysis revealed that 1:2 and 1:1 coordination patterns for L-Hg2+ and L-Zn2+ complexes respectively, which have further been confirmed by ESI-MS spectra. The DFT calculations are also in agreement with the experimental results. The limit of detection for Hg2+ and Zn2+ are found to be 9.89 × 10−7 M and 1.23 × 10−6 M respectively, which are far below than the guidelines provided by World Health Organization (WHO) for drinking water. Moreover the chemosensor L has applications in real sample analysis in environmental and biological samples and building molecular logical devices. To the best of our knowledge, this observation is the first case where a guanidine base bis Schiff base is being utilized for sensing of metal ions.

Synthesis of Biorenewable Starch–Farnesene Amphiphilic Conjugates via Transesterification of Terpene-Derived Diels–Alder Adducts

Herein we describe a new class of terpene-starch esters synthesized from biorenewable building blocks. Although our work is specific to starch, we believe the synthetic methodology can be extended to a wide range of polysaccharide substrates. In our approach, an ester functionality is first introduced to the farnesene backbone via high yielding, solvent-free Diels–Alder chemistry. The farnesene esters are subsequently transesterified with starch to produce a range of starch–farnesene amphiphilic biopolymers. The key transesterification reaction between farnesene and starch employs 1,5,6-triazabicyclo[4.4.0]dec-5-ene (TBD) as a guanidine base organocatalyst and is capable of producing materials with a high degree of substitution (DS). The DS can be modulated by altering the starch/farnesene feed ratio. Low DS starch–farnesene esters show surfactant-like properties while the higher DS materials were successfully solvent-cast into standalone films. Thermal and mechanical tests reveal starch–farnesene esters ...

Oxidative photopolymerization of thiol-terminated polysulfide resins. Application in antibacterial coatings

A UV photoinduced cross-linking of non-modified commercial poly(disulfide) resins (Thioplast) is reported via the air oxidative photocoupling of terminal thiol functions. Catalyzed by a photogenerated guanidine base (TBD), this step-growth photopolymerization is useful to maximize disulfide functions content. The mechanism proceeds through thiol deprotonation into thiolate anions, further oxidized into thiyl radicals, eventually dimerizing into disulfide cross-links. Starting with a detailed structural characterization of the thiol-terminated resin, photooxidative kinetics are studied under exposure to a polychromatic medium-pressure Hg arc using Raman and infrared spectroscopy. The effects of irradiance, film thickness, photobase concentration, resin molar mass, and content of an additional polythiol monomer (reactive diluent) have been investigated. In an effort of upscaling, irradiation under a 365 nm LED panel has enabled the fast preparation of 1.5 μm thick cross-linked poly(disulfide) coatings in a matter of minutes. Capitalizing on the ability of residual thiol groups to react with silver cations, a post-functionalization has been successfully performed, leading to films exhibiting at their surface stable thiolate-silver bonds as proved by X-ray photoelectron spectroscopy. Despite the well-established biocide action of silver ions, no antibacterial action has been evidenced by confocal fluorescence microscopy because of insufficient release.

Tuning properties of poly(ethylene glycol)-block-poly(simvastatin) copolymers synthesized via triazabicyclodecene

Simvastatin was polymerized into copolymers to better control drug loading and release for therapeutic delivery. When using the conventional stannous octoate catalyst in ring-opening polymerization (ROP), reaction temperatures ≥200°C were required, which promoted uncontrollable and undesirable side reactions. Triazabicyclodecene (TBD), a highly reactive guanidine base organocatalyst, was used as an alternative to polymerize simvastatin. Polymerization was achieved at 150°C using 5kDa methyl-terminated poly(ethylene glycol) (mPEG) as the initiator. ROP reactions with 2kDa or 550Da mPEG initiators were also successful using TBD at 150°C instead of stannous octoate, which required a higher reaction temperature. Biodegradability of the poly(simvastatin) copolymer in phosphate-buffered saline was also improved, losing twice as much mass than the copolymer synthesized via stannous octoate. The three copolymers exhibited modified rates of simvastatin release, demonstrating tunability for drug delivery applications.

Coupling Reactions of Alkynyl Indoles and CO2 by Bicyclic Guanidine: Origin of Catalytic Activity?

Density functional theory calculations were used to investigate the three possible modes of activation for the coupling of CO2 with alkynyl indoles in the presence of a guanidine base. The first of these mechanisms, involving electrophilic activation, was originally proposed by Skrydstrup et al. (Angew. Chem. Int. Ed. 2015, 54, 6682). The second mechanism involves the nucleophilic activation of CO2 . Both of these electrophilic and nucleophilic activation processes involve the formation of a guanidine-CO2 zwitterion adduct. We have proposed a third mechanism involving the bifunctional activation of the bicyclic guanidine catalyst, allowing for the simultaneous activation of the indole and CO2 by the catalyst. We demonstrated that a second molecule of catalyst is required to facilitate the final cyclization step. Based on the calculated turnover frequencies, our newly proposed bifunctional activation mechanism is the most plausible pathway for this reaction under these experimental conditions. Furthermore, we have shown that this bifunctional mode of activation is consistent with the experimental results. Thus, this guanidine-catalyzed reaction favors a specific-base catalyzed mechanism rather than the CO2 activation mechanism. We therefore believe that this bifunctional mechanism for the activation of bicyclic guanidine is typical of most CO2 coupling reactions.