Tetramethylguanidine Research Articles

Palladium Catalyst Recycling for Heck-Cassar-Sonogashira Cross-Coupling Reactions in Green Solvent/Base Blend.

The identification of a green, versatile, user‐friendly, and efficient methodology is necessary to facilitate the use of Heck‐Cassar‐Sonogashira (HCS) cross‐coupling reaction in drug discovery and industrial production in the pharmaceutical segment. The Heck‐Cassar and Sonogashira protocols, using N‐hydroxyethylpyrrolidone (HEP)/water/N,N,N′,N′‐tetramethyl guanidine (TMG) as green solvent/base mixture and sulfonated phosphine ligands, allowed to recycle the catalyst, always guaranteeing high yields and fast conversion under mild conditions, with aryl iodides, bromides, and triflates. No catalyst leakage or metal contamination of the final product were observed during the HCS recycling. To our knowledge, a turnover number (TON) up to 2375, a turnover frequency (TOF) of 158 h−1, and a process mass intensity (PMI) around 7 that decreased around 3 after solvent, base, and palladium recovery, represent one of the best results to date using a sustainable protocol. The Heck‐Cassar protocol using sSPhos was successfully applied to the telescoped synthesis of Erlotinib (TON: 1380; TOF: 46 h−1).

Structure and Noncovalent Interactions of Molybdenum Disulfide Monolayers in the Layered Organo-inorganic Compound with Tetramethylguanidine

A layered compound with regularly alternating monolayers of MoS2 and N,N,N',N'-tetramethylguanidine (TMG) is synthesized by the reaction of monolayer dispersions of molybdenum disulfide containing anionic particles (MoS2)x– with protonated TMG molecules. It is found by a combination of methods (X‑ray diffraction analysis adapted for turbostrate-disordered systems, high-resolution transmission electron microscopy, FT-IR spectroscopy, and quantum-chemical calculations by the density functional theory) that the structure of MoS2 layers with octahedrally coordinated molybdenum atoms forming chains of Mo–Mo bonds is stabilized in the compound. Noncovalent binding interactions occur between the MoS2 monolayers and TMG molecules including CH…S, NH…S, and N…S contacts with the predominant contribution of contacts of the first type to the binding energy (СIF file CCDC no. 1 990439).

Charge-based separation of synthetic macromolecules by non-aqueous ion exchange chromatography

Traditional polymer-separation methods, such as size-exclusion chromatography and (gradient) liquid adsorption chromatography, cannot provide separations exclusively based on the number of deprotonated carboxylic-acid groups along the backbone chain of polymers. A novel separation method, based on non-aqueous ion-exchange chromatography (NAIEX), was developed, which allows such a separation of acid-functional polymers that are soluble in organic solvents. The polar, aprotic N-methyl-2-pyrrolidone was found to be a suitable solvent. It features a high relative permittivity (favouring dissociation of ion pairs into free ions) and it is a good solvent for polymers and organic salts, such as triethyl-ammonium formate. A negative charge is established on these polymers by deprotonation of the carboxylic-acid groups in the presence of an organic superbase (tetramethyl guanidine). Traditional potent organic bases, such as triethylamine, do not possess the base strength to compensate for the increase in pKa of polymeric carboxylic acid groups in non-aqueous conditions. Triethyl-ammonium formate is proposed as an alternative to traditional salts used for elution in aqueous ion-exchange chromatography. Separation was performed on an industry-standard strong-anion-exchange column and (near-)universal detection of the polymers was performed by high-temperature evaporative-light-scattering detection. The NAIEX method yielded a separation based on the acid-functionality distribution of the polymer. NAIEX was compared with traditional normal- and reversed-phase liquid-chromatography approaches for the separation of acid-functional copolymers.

Proton-transfer in 1,1,3,3 tetramethyl guanidine by means of ultrasonic relaxation and Raman spectroscopies and molecular orbital calculations.

In this work, we report on the structure and dynamics of the 1,1,3,3 tetramethyl guanidine (TMG) aqueous solutions in a wide concentration and temperature range by combining vibrational and ultrasonic spectroscopies. The experimental Raman spectra have been compared with the corresponding spectra obtained by ab initio quantum mechanical and density functional theory electronic structure calculations. This comparison indicated that only a single mechanism occurs when dissolving TMG in water and this is the proton transfer reaction, while the formation of byproducts during hydrolysis of TMG is dubious. This observation is further supported by the concentration dependence of the Raman spectra. The analysis of the ultrasonic relaxation data also revealed that the system exhibits a single relaxation process associated with this proton transfer reaction. It has been also observed that both relaxation amplitude and frequency exhibit a clear monotonous increase with increasing amine concentration in the solutions supporting the concept of the proton transfer reaction. The corresponding activation enthalpy was estimated directly from the temperature dependence of the acoustic data and found equal to ΔH*=5.56±0.34kcal/mol, which seems to be reasonable for hydrogen-bond formation. Furthermore, the concentration dependence of the acoustic parameters and kinematic viscosity data has been used as a probe for the molecular association in these solutions. The results have been discussed in relation to the ability or inability of water molecules to form stable clathrates after the addition of amine molecules in the solutions.

Reversible covalent chemistry of carbon dioxide unlocks the recalcitrance of cellulose for its enzymatic saccharification

To overcoming the natural recalcitrance of cellulose for glucose production via enzymatic hydrolysis, a new strategy of destroying hydrogen bond donor to reconstruct cellulose’s hydrogen bonding network was developed via a mild reversible reaction of cellulose with CO2 catalyzed by organic bases. The reaction dynamics of cellulose with CO2 in the presence of organic bases was studied by using in situ IR. Investigation also included how the organic bases in pretreatment media and pretreatment parameters including CO2 pressure, pretreatment temperature and time affected the physical-chemical structure of cellulose by Fourier Transform Infrared Spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM) and Atomic force microscopy (AFM) and subsequent enzymatic scarification of cellulose. The findings showed that dissolution activation efficiency significantly correlated to various parameters, that can be optimized to be the tetramethyl guanidine (TMG)/CO2/DMSO solvent system at 50 °C, 2 MPa of CO2 for 2 h, by which a complete transformation the cellulose crystalline structure from I to II, and 100% glucose yield were achieved. The recyclability and usability are also investigated.

Tetramethylguanidine (TMG)-catalyzed reductive spirocyclization of tryptamine derivatives with formic acid as a C1 synthon

A reductive spirocyclization of tryptamine derivatives with formic acid as a C1 building block has been achieved via dearomatization. The reaction was catalyzed by a commercially available and cost-effective organic base, tetramethylguanidine (TMG). A variety of spiroindolenines were obtained in high yields under mild conditions.

Doxycycline hyclate mediated silver\u2013silver chloride nanoparticles and their antibacterial activity

In the present work, we used doxycycline hyclate (DX) and tetramethylguanidine (TMG) for the synthesis of silver–silver chloride nanoparticles (DX-Ag–AgCl NPs) as a simple method for the production of nanoparticles (NPs). A new synthesis method for DX-Ag–AgCl NPs in aqueous medium, using the DX and TMG as a reducing and stabilizing agent, is reported. DX-Ag–AgCl NPs were characterized by transmission electron microscopy. The elemental composition and the crystalline nature of synthesized nanoparticles were determined by energy-dispersive X-ray (EDX) spectroscopy and X-ray diffraction (XRD) analysis, respectively. From EDX, it is confirmed that synthesized NPs contain elemental silver and chloride, and their crystalline nature was confirmed by XRD. The Fourier transform infra-red spectra showed the DX present in surface of DX-Ag–AgCl NPs. Synthesized NPs analyzed for antibacterial activity by agar well method against Gram-positive and Gram-negative pathogens. Synthesized DX-Ag–AgCl NPs were spherical shaped and in the range of 10–40 nm of size was observed from TEM images. In the crystalline nature, XRD peaks indicate the presence of silver and silver chloride in produced NPs. Synthesized NPs show potential antibacterial activity on Bacillus cereus KCCM 11773, Bacillus subtilis KCCM 11316, Staphylococcus aureus KCCM 40050, Escherichia coli KCCM 11234, Klebsiella pneumoniae KCCM 11418, and Proteus vulgaris KCCM 40211.

Guanidine as inexpensive dual function ligand and reducing agent for ATRP of methacrylates

N,N,N′,N′-Tetramethyl guanidine, an inexpensive and commercially available organic base, is used for the first time as ligand without any chemical modification for the supplemental activator and reducing agent atom transfer radical polymerization.

The Guanidine-Promoted Direct Synthesis of Open-Chained Carbonates

In order to reduce CO2 accumulation in the atmosphere, chemical fixation methodologies were developed and proved to be promising. In general, CO2 was turned into cyclic carbonates by cycloaddition with epoxides. However, the cyclic carbonates need to be converted into open-chained carbonates by transesterification for industrial usage, which results in wasted energy and materials. Herein, we report a process catalyzed by tetramethylguanidine (TMG) to afford linear carbonates directly. This process is greener and shows potential for industrial applications.

Capturing CO2 to reversible ionic liquids for dissolution pretreatment of cellulose towards enhanced enzymatic hydrolysis

To overcome the natural recalcitrance of cellulose for glucose production in aqueous media catalyzed by enzyme, in this study, a dissolution pretreatment strategy was developed by using in situ formed CO2-based reversible ionic compounds (RICs)/DMSO mixed organic electrolytes under mild conditions. The influences of the constitution of RICs, CO2 pressure, dissolution pretreatment time on the physic-chemical structure of cellulose were investigated systematically by FTIR, XRD, SEM, AFM towards in-depth understanding of the correlations between the pretreatment conditions, micro-scale structure and enzymatic saccharification of cellulose. The results showed that the tetramethyl guanidine (TMG) based RICs solvent system [TMGH]2+[O2COCH2CH2OCO2]2−/DMSO (XRICs = 0.1, XRICs: the mole fraction of the formed RICs in the mixture) presented the best performance, which was evidenced by 100% glucose yield after the dissolution-regeneration pretreatment strategy under mild conditions (T = 60 °C, Pco2 = 2.0 MPa, t = 2 h). Furthermore, the solvent system have good recyclability and usability.

Toward the total synthesis of citreamicin η: Synthesis of the pentacyclic core and GAB-ring annelation model studies

A short 11-step synthesis of the pentacyclic core of the polycyclic xanthone antibiotic citreamicin η has been completed. Although the basic approach was inspired by our previous explorations of polycyclic xanthone chemistry, the present report features some new insights into the Moore rearrangement and offers some improvements to our original methodology that include additions of aryllithiums to squarate esters, additions of cerium acetylides to hindered ketones utilizing PDA as an internal indicator, and the use of cyclic di-tert-butylsilyl (DTBS) ethers to protect electron-rich benzyl alcohols toward ionization under acidic conditions. We also developed an improved protocol for selective o-bromination of phenols utilizing N-bromosuccinimide (NBS) and tetramethylguanidine (TMG) that promises to be generally useful. Finally, we developed a modular approach for the synthesis of isoquinolones and dihydro-5H-oxazolo[3,2-b]isoquinoline-2,5(3H)-diones that features a novel sequence of alkoxycarbonylation, acetone arylation, transamidation.

Efficient cycloaddition of CO2 to epoxides using novel heterogeneous organocatalysts based on tetramethylguanidine-functionalized porous polyphenylenes

The conversion of CO2 into cyclic carbonates by cycloaddition to epoxides is achieved under relatively mild reaction conditions (without solvent, 7 bar of CO2, 100 °C) using easily available heterogeneous tetramethylguanidine(TMG)-polyphenylene organocatalysts. These new highly stable catalysts were easily prepared by reaction of tetramethylurea in the presence of oxalyl chloride with aminomethyl polyphenylenes. The TMG-functionalized polyphenylene (2PhCH2TMG) prepared from a pre-functionalized network was efficient and competitive compared with other reported catalysts achieving high epoxides conversion (>90%) and 100% selectivity towards the corresponding cyclic carbonates. The catalyst was easily separated from the reaction media and reused after basic regeneration without loss of activity.

Guanidine-Catalyzed Reductive Amination of Carbon Dioxide with Silanes: Switching between Pathways and Suppressing Catalyst Deactivation

A mechanistic investigation into the guanidine-catalyzed reductive amination of CO2, using a combination of 1H, 29Si NMR, FT-IR, MS, and GC profiling, is reported. Inexpensive and readily available N,N,N′,N′-tetramethylguanidine (TMG) was found to be an equally effective catalyst compared to more elaborate cyclic guanidines. Different catalytic pathways to formamide 2, aminal 4, and N-methylamine 3 were identified. A pathway to formamide product 2 dominates at 23 °C. Increasing the reaction temperature to 60 °C enables a competitive, higher-energy pathway to 4 and 3, which requires direct reduction of CO2 with PhSiH3 to formoxysilane E. Reduction of aminal 4, in the presence of CO2 and the catalyst, led to formation of a 1:1 ratio of 2 and 3. The catalyst itself can be formylated under the reaction conditions, resulting in its deactivation. Thus, alkylated TMGs were found to be more stable and more active catalysts than TMG, leading to a successful organocatalyzed reductive functionalization of CO2 with s...

Copper-Catalyzed Vinylogous Aerobic Oxidation of Unsaturated Compounds with Air.

A mild and operationally simple copper-catalyzed vinylogous aerobic oxidation of β,γ- and α,β-unsaturated esters is described. This method features good yields, broad substrate scope, excellent chemo- and regioselectivity, and good functional group tolerance. This method is additionally capable of oxidizing β,γ- and α,β-unsaturated aldehydes, ketones, amides, nitriles, and sulfones. Furthermore, the present catalytic system is suitable for bisvinylogous and trisvinylogous oxidation. Tetramethylguanidine (TMG) was found to be crucial in its role as a base, but we also speculate that it serves as a ligand to copper(II) triflate to produce the active copper(II) catalyst. Mechanistic experiments conducted suggest a plausible reaction pathway via an allylcopper(II) species. Finally, the breadth of scope and power of this methodology are demonstrated through its application to complex natural product substrates.

Organocatalyzed Anionic Ring-Opening Polymerizations of N-Sulfonyl Aziridines with Organic Superbases.

The anionic ring-opening polymerizations (AROPs) of N-sulfonyl aziridines, in the presence of organic superbases including phosphazene (t-Bu-P4), Verkade's base (P(i-PrNCH2CH2)3N, TiPP), DBU, MTBD, and N,N,N',N'-tetramethylguanidine (TMG), using N-benzyl-p-toluenesulfonamide (BnN(H)Ts) as initiator were explored to produce metal-free poly(sulfonylaziridine)s. Among the superbases used, the catalytic activity was found directly proportional to their basicity. Remarkably, t-Bu-P4 and TiPP gave a living/controlled AROP of 2-methyl-N-tosylaziridine (TsMAz), where t-Bu-P4 performed better, affording the metal-free and well-defined poly(sulfonylaziridine)s with high molar masses (Mn(SEC) > 30 kg mol-1) and low dispersities (Đ < 1.10) in 3.5 h. For the less reactive monomers of 2-methyl-N-ethylsulfonyl aziridine (EsMAz) and 2-phenyl-N-tosylaziridine (TsPhAz), t-Bu-P4 showed the same excellent catalytic efficiency (30 equiv, conv. > 95%, 5 h). The organocatalyzed AROP allowed the use of lower catalyst (t-Bu-P4) loading than the amount of initiator (BnN(H)Ts), but the propagating polymer chains were as many as the number of equivalents of the introduced initiators, which could lower the loading of catalyst used to amounts as low as 0.05 mol %.

A new synthetic strategy towards 2,4,5-trisubstituted 1H-imidazoles and highly substituted pyrrolo[1,2-c]imidazoles by use of α-azidochalcones via Michael addition-cyclization followed by Wittig reaction

Efficient and facile protocols for the preparation of highly functionalized 1H-imidazoles and 5H-pyrrolo[1,2-c]imidazoles are described. Heating a mixture of an α-azidochalcones and N,N,N′,N′-tetramethyl guanidine under neat conditions gave the corresponding 2,4,5-trisubstituted 1H-imidazole via Michael addition-cyclization in excellent yields. Subsequently, the prepared 1H-imidazoles undergo addition-Wittig reaction with acetylenic esters in presence of triphenylphosphine in dichloromethane to afford 5H-pyrrolo[1,2-c]imidazoles in high yields.

Asymmetric sequential double Michael reactions of γ,δ-unsaturated β-ketoesters to nitroolefins catalyzed by Ni (II)-diamine complex

The asymmetric sequential double Michael reactions of γ,δ-unsaturated β-ketoesters and nitroolefins catalyzed by 2mol% of readily prepared Ni(II)-bis[(R,R)-N,N′-dibenzylcyclohexane-1,2-diamine] complex and then with 1 equivalent of tetramethylguanidine (TMG) for cyclization have been developed. The reaction gave the corresponding Michael adducts of multifunctional cyclohexenol derivatives with three chiral stereocenters in good yields, moderate diastereoselectivities, and high enantioselectivities under mild reaction conditions.

Spectroscopic studies of the intramolecular hydrogen bonding in o-hydroxy Schiff bases, derived from diaminomaleonitrile, and their deprotonation reaction products

The structural study of five Schiff bases derived from diaminomaleonitrile (DAMN) and 2-hydroxy carbonyl compounds was performed using 1H, 13C and 15N NMR methods in solution and in the solid state as well. ATR-FTIR and X-Ray spectroscopies were used for confirmation of the results obtained by NMR method. The imine obtained from DAMN and benzaldehyde was synthesized as a model compound which lacks intramolecular hydrogen bond. Deprotonation of all synthesized compounds was done by treating with tetramethylguanidine (TMG). NMR data revealed that salicylidene Schiff bases in DMSO solution exist as OH forms without intramolecular hydrogen bonds and independent on the substituents in aromatic ring. In the case of 2-hydroxy naphthyl derivative, the OH proton is engaged into weak intramolecular hydrogen bond. Two of imines (salDAMN and 5-BrsalDAMN) exist in DMSO solution as equilibrium mixtures of two isomers (A and B). The structures of equilibrium mixture in the solid state have been studied by NMR, ATR-FTIR and X-Ray methods.The deprotonation of three studied compounds (salDAMN, 5-BrsalDAMN, and 5-CH3salDAMN) proceeded in two different ways: deprotonation of oxygen atom (X form) or of nitrogen atom of free primary amine group of DAMN moiety (Y form). For 5-NO2salDAMN and naphDAMN only one form (X) was observed.

Synthesis, Characterization and Biological Activity of Novel Zirconium, Zinc and Cadmium Complexes Derived from Substituted Tetramethyl Guanidine

A novel series of metal complexes of guanidine ligand derived from condensation of 1,1,3,3-tetramethylurea and 2-aminopyridine in present of POCl3 have been synthesized. The complexes are characterized using FTIR, UV-Vis and also molar conductance was measured. These spectroscopic studies confirmed that the ligand bonded to the metals through the nitrogen atoms. The suggested structures of the metal complexes are square planner. The ligand and its metal complexes were tested against Gram-negative bacteria; Escherichia coli, Serratia marcescens and Gram-positive bacteria; Bacillus sabtilis and Staphylococcus aureus by applying disc diffusion method. The most antibacterial activity of synthesized compounds belongs to CdL2 complex. The results of this study showed that the metal complexes have more antibacterial activity against species when compared to the parent ligand.

Tetramethylguanidine-based gels and colloids of cellulose

Novel and stable gels of cellulose were produced. These gels are prepared at room temperature by combination of cellulose and tetramethylguanidine (TMG) in different ratios (1:1, 1:2, 1:3 in equivalents of alcohol groups of cellulose per number of molecules of TMG). Detailed NMR, SEM, rheological and XRD studies of these gels were carried out. The concentration of cellulose in the gel, temperature, frequency of oscillation and shear rate were used as variables in order to understand the fundamentals and optimize operational conditions, considering their possible use as matrices for CO2 capture. Cellulose recovery from a specific gel was performed using ethanol as precipitating agent, leading to a lower crystallinity, which permits to consider this polymer in further studies associated to physical/chemical modification of cellulose.