Aqueous Sulfate Separation by Sequestration of [(SO4)2(H2O)4]4− Clusters within Highly Insoluble Imine‐Linked Bis‐Guanidinium Crystals

Selective crystallization of sulfate with a simple bis‐guanidinium ligand, self‐assembled in situ from terephthalaldehyde and aminoguanidinium chloride, was employed as an effective way to separate the highly hydrophilic sulfate anion from aqueous solutions. The resulting bis‐iminoguanidinium sulfate salt has exceptionally low aqueous solubility (K_sp=2.4×10^?10), comparable to that of BaSO₄. Single‐crystal X‐ray diffraction analysis showed the sulfate anions are sequestered as [(SO₄)₂(H₂O)₄]^4? clusters within the crystals. Variable‐temperature solubility measurements indicated the sulfate crystallization is slightly endothermic (ΔH_cryst=3.7 kJ mol^?1), thus entropy driven. The real‐world utility of this crystallization‐based approach for sulfate separation was demonstrated by removing up to 99 % of sulfate from seawater in a single step.     

Organic Superbases in Recent Synthetic Methodology Research

Organic superbases are a distinct and increasingly utilized class of Brønsted base that possess properties complementary to common inorganic bases. This Concept article discusses recent applications of commercial organic superbases in modern synthetic methodologies. Examples of the advantages of organic superbases in three areas are highlighted, including the discovery of new base-catalyzed reactions, the optimization of reactions that require stoichiometric Brønsted base, and in high-throughput experimentation technology.     

A Photoresponsive Receptor with a 105 Magnitude of Reversible Anion-Binding Switching

In a leap toward anion separation that uses only energy input for binding and release cycles, we report herein a new class of photoswitchable anion receptors featuring a diiminoguanidinium functionality that displays a change of more than five orders of magnitude in switched-off binding strength towards sulfate, a representative oxyanion, upon photoirradiation with UV light. The (E,E)-2-pyridyl-diiminoguanidinium cation, synthesized as the triflate salt, binds sulfate with extraordinary strength in [D₆]DMSO owing to its bidentate guanidinium hydrogen bonding, which can chelate the O−S−O edge of sulfate. Upon photoisomerization to the Z,Z isomer, the anion-binding site is essentially shut off by intramolecular hydrogen bonds to the 2-pyridyl substituents, as shown by anion-binding titrations, theoretical calculations, and X-ray structural analysis. This approach will allow the development of advanced anion-separation cycles that use only energy input and generate no chemical waste, and thus address challenging chemical separation problems in a more sustainable way.     

Intramolecular guanidine epoxide ring opening reactions

The synthesis of a range of cyclic guanidines via intramolecular ring opening of epoxides or iodocyclisation is reported. A preliminary investigation of the glycosidase inhibitory activity of these substances is also discussed.     

Metal‐Free and Alkali‐Metal‐Catalyzed Synthesis of Isoureas from Alcohols and Carbodiimides

The first addition of alcohols to carbodiimides catalyzed by transition‐metal‐free compounds employs 1,5,7‐triazabicyclo[4.4.0]dec‐5‐ene (TBD) and its alkali metal salts. Isoureas are obtained in short reaction times and high yields when TBDK is used as the catalyst. Control of the coordination sphere of potassium with exogenous chelating ligands, in combination with mechanistic DFT calculations, demonstrated the role and positive influence of the alkali‐metal cation on the kinetics.     

Microwave-assisted synthesis of highly functionalized guanidines on soluble polymer support

An efficient method for the N,N′-di(Boc)-protected guanidines containing piperazine and homopiperazine scaffolds has been developed under multi-step microwave irradiation. Followed by alkylation of carbamate-protected guanidines with various alkyl halides is also explored. This protocol proceeds via deprotonation of the acidic N-carbamate hydrogen of the guanidine by sodium hydride on soluble polymer support. In this manner, highly functionalized guanidines were obtained after cleavage from the support. The reaction is tolerant of a wide range of functional groups on both the alkyl halide and guanidine components. In addition, the reaction is sufficiently simple workup by precipitation in each step to yield the substituted guanidines in high purity. In conjunction with microwave irradiation and soluble polymer support, this method provides an efficient route to access highly functionalized guanidines.     

Solid-phase synthesis of N-acyl-N′-carbamoylguanidines

Amino acids immobilized on polystyrene-Wang or Rink amide resin were reacted with p-nitrophenyl chloroformate to give an activated urethane that was displaced by S-methylisothiourea. Following N-acylation with an acid chloride, the thiomethyl group was displaced by primary or secondary amines with the aid of mercury (II) chloride to yield the unsymmetrically substituted title compounds after resin cleavage.     

Mono- and diprotonation of the superbasic bisguanidine 1,2-Bis(N,N,N',N'-tetramethylguanidino)benzene (btmgb) and Pt II and Pt IV complexes of chelating bisguanidines and guanidinates

New Pt complexes of chelating bisguanidines and guanidinate ligands were synthesized and characterized. 1,2-Bis(N,N,N',N'-tetramethylguanidino)benzene (btmgb) was used as a neutral chelating bisguanidine ligand, and 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidinate (hpp(-)) as a guanidinate ligand. The salts [btmgbH](+)[HOB(C(6)F(5))(3)](-) and [btmgbH(2)]Cl(2) and the complexes [(btmgb)PtCl(2)], [(btmgb)PtCl(dmso)](+)[PtCl(3)(dmso)](-), and [(btmgb)PtCl(dmso)](+)[Cl(-)] were synthesized and characterized. In the [btmgbH](+) cation the proton is bound to only one N atom. In the other complexes, both imine N atoms are coordinated to the Pt(II), thus adopting a eta(2)-coordinational mode. The hpp(-) anion, which usually prefers a bridging binding mode in dinuclear complexes, is eta(2)-coordinated in the Pt(IV) complex [(eta(2)-hpp)(hppH)PtCl(2){N(H)C(O)CH(3)}], which is formed (in low yield) by reaction between cis-[(hppH)(2)PtCl(2)] and H(2)O(2) in CH(3)CN.     

Catalytic Aerobic Phenol Homo- and Cross-Coupling Reactions with Copper Complexes Bearing Redox-Active Guanidine Ligands

Due to their large importance in synthetic chemistry, catalytic C−C coupling reactions of phenols are currently intensively studied. Herein, new copper catalysts for the C−C coupling reaction of phenols using dioxygen as a green oxidizing reagent are reported. By using redox-active guanidine ligands, the activity as well as chemoselectivity in the cross-coupling reaction of non-complementary phenols (between an electron-rich phenol and a less nucleophilic second phenol) is significantly improved. Based on the collected data for several test reactions, a reaction mechanism is proposed.     

1,2,5,6-Tetrakis(guanidino)-Naphthalenes: Electron Donors,Fluorescent Probes and Redox-Active Ligands

New redox-active 1,2,5,6-tetrakis(guanidino)-naphthalene compounds, isolable and storable in the neutral and deep-green dicationic redox states and oxidisable further in two one-electron steps to the tetracations, are reported. Protonation switches on blue fluorescence, with the fluorescence intensity (quantum yield) increasing with the degree of protonation. Reactions with N-halogenosuccinimides or N-halogenophthalimides led to a series of new redox-active halogeno- and succinimido-/phthalimido-substituted derivatives. These highly selective reactions are proposed to proceed via the tri- or tetracationic state as the intermediate. The derivatives are oxidised reversibly at slightly higher potentials than that of the unsubstituted compounds to dications and further to tri- and tetracations. The integration of redox-active ligands in the transition-metal complexes shifts the redox potentials to higher values and also allows reversible oxidation in two potentially separated one-electron steps.     

On the Electronic Structure of NiII Complexes That Feature Chelating Bisguanidine Ligands

In this work we report on the syntheses and properties of several new Ni complexes featuring the chelating bisguanidines bis(tetramethylguanidino)benzene (btmgb), bis(tetramethylguanidino)naphthalene (btmgn), and bis(tetramethylguanidino)biphenyl (btmgbp) as ligands. All complexes were structurally characterized by single‐crystal X‐ray diffraction and quantum chemical calculations. A detailed inspection of the magnetic susceptibility of [(btmgb)NiX₂] and [(btmgbp)NiX₂] (X=Cl, Br) revealed a linear temperature dependence of χ^?1(T) above 50 K, which was in agreement with a Curie–Weiss‐type behavior and a triplet ground state. Below approximately 25 K, however, magnetic susceptibility studies of the paramagnetic d⁸ Ni complexes revealed the presence of a significant zero‐field splitting (ZFS) that results from spin–orbit mixing of excited states into the triplet ground state. The electronic consequences that might arise from the mixing of states as well as from a possible non‐innocent behavior of the ligand have been explored by an experimental charge density study of [(btmgb)NiCl₂] at low temperatures (7 K). Here, the presence of ZFS was identified as one potential reason for the flat ?Cl‐Ni‐Cl deformation potential and the distinct differences between the ?X‐Ni‐X valence angles observed by experiment and predicted by DFT. An analysis of the topology of the experimentally and theoretically derived electron‐density distributions of [(btmgb)NiCl₂] confirmed the strong donor character of the bisguanidine ligand but clearly ruled out any significant non‐innocent ligand (NIL) behavior. Hence, [(btmgb)NiCl₂] provides an experimental reference system to study the mixing of certain excited states into the ground state unbiased from any competing NIL behavior.     

Structural and Mechanistic Insights into s‐Block Bimetallic Catalysis: Sodium Magnesiate‐Catalyzed Guanylation of Amines

To advance the catalytic applications of s‐block mixed‐metal complexes, sodium magnesiate [NaMg(CH₂SiMe₃)₃] ( 1 ) is reported as an efficient precatalyst for the guanylation of a variety of anilines and secondary amines with carbodiimides. First examples of hydrophosphination of carbodiimides by using a Mg catalyst are also described. The catalytic ability of the mixed‐metal system is much greater than that of its homometallic components [NaCH₂SiMe₃] and [Mg(CH₂SiMe₃)₂]. Stoichiometric studies suggest that magnesiate amido and guanidinate complexes are intermediates in these catalytic routes. Reactivity and kinetic studies imply that these guanylation reactions occur via (tris)amide intermediates that react with carbodiiimides in insertion steps. The rate law for the guanylation of N,N′‐diisopropylcarbodiimide with 4‐tert‐butylaniline catalyzed by 1 is first order with respect to [amine], [carbodiimide], and [catalyst], and the reaction shows a large kinetic isotopic effect, which is consistent with an amine‐assisted rate‐determining carbodiimide insertion transition state. Studies to assess the effect of sodium in these transformations denote a secondary role with little involvement in the catalytic cycle.     

Exceptional Substrate Diversity in Oxygenation Reactions Catalyzed by a Bis(μ-oxo) Copper Complex

The enzyme tyrosinase contains a reactive side-on peroxo dicopper(II) center as catalytically active species in C−H oxygenation reactions. The tyrosinase activity of the isomeric bis(μ-oxo) dicopper(III) form has been discussed controversially. The synthesis of bis(μ-oxo) dicopper(III) species [Cu₂(μ-O)₂( L1 )₂](X)₂ ([ O1 ](X)₂, X=PF₆⁻_, BF₄⁻, OTf⁻, ClO₄⁻), stabilized by the new hybrid guanidine ligand 2-{2-((dimethylamino)methyl)phenyl}-1,1,3,3-tetramethylguanidine ( L1 ), and its characterization by UV/Vis, Raman, and XAS spectroscopy, as well as cryo-UHR-ESI mass spectrometry, is described. We highlight selective oxygenation of a plethora of phenolic substrates mediated by [ O1 ](PF₆)₂, which results in mono- and bicyclic quinones and provides an attractive strategy for designing new phenazines. The selectivity is predicted by using the Fukui function, which is hereby introduced into tyrosinase model chemistry. Our bioinspired catalysis harnesses molecular dioxygen for organic transformations and achieves a substrate diversity reaching far beyond the scope of the enzyme.     

Enantioselective Protonation of Itaconimides with Thiols and the Rotational Kinetics of the Axially Chiral C?N Bond

Bicyclic guanidines are able to catalyze the protonation reactions of 2‐phthalimidoacrylates with thiols in excellent yields and enantioselectivities. The protonation reaction of itaconimides with secondary phosphine oxides is also known. Herein, the tandem conjugate addition–enantioselective protonation of N‐substituted itaconimides with thiols catalyzed by chiral bicyclic guanidine is investigated. The rotational barrier of the C? N axis of N‐2‐tert‐butyl phenylitaconimide is also studied, both experimentally and computationally.     

Wrapping an Organic Reducing Reagent in a Cationic Boron Complex and Its Use in the Synthesis of Polyhalide Monoanionic Networks

The reaction between BF₃ ? OEt₂ and one of two guanidines, 1,8‐bis(tetramethylguanidinyl)naphthalene (btmgn) and 1,2,4,5‐tetrakis(tetramethylguanidinyl)naphthalene (ttmgn), yields the salts [(btmgn)(BF₂)]BF₄ and [(ttmgn)(BF₂)₂](BF₄)₂. NMR spectroscopic data show that the boron atoms in the cation and anion exchange in the case of [(ttmgn)(BF₂)₂](BF₄)₂, but not in the case of [(btmgn)(BF₂)]BF₄. The rate constant for this exchange was estimated to be 4 s^?1 at 80 °C for solutions in CH₃CN. These salts were subsequently used for the reduction of dihalides Br₂ or I₂ to give polyhalide salts. We report the synthesis and first complete characterization (including structural analysis) of salts that contain pentabromide monoanions. In these salts, the Br₅^? anions interact to give dimeric units or polymeric chains. Our results are compared to previous quantum chemical calculations on the gas‐phase structure of the Br₅^? anion. The possible pathways that lead to the polyhalides are evaluated. In the case of [(ttmgn)(BF₂)₂](BF₄)₂, reduction is accompanied by ttmgn oxidation, whereas in the case of [(btmgn)(BF₂)]BF₄ reduction is initiated by aromatic substitution.