Tetramethylguanidino Naphthalene Research Articles

Synergetic binary organocatalyzed ring opening polymerization for the precision synthesis of polysiloxanes

Organocatalytic ring-opening polymerization (ROP) is a versatile method for synthesizing well-defined polymers with controlled molecular weights, dispersities, and nonlinear macromolecular architectures. Despite spectacular advances in organocatalytic ROP, precision synthesis of polysiloxanes remains challenging due to the mismatch in polarity between highly polar initiators and nonpolar monomers and polymers and the difficulty in suppressing the formation of scrambling products via transetherification reactions during ROP of cyclic siloxanes. Here, we describe a binary organocatalytic ROP (BOROP) of hexamethylcyclotrisiloxane (D3) employing organic bases as catalysts and (thio)ureas as cocatalysts. The BOROP of D3 using triazabicyclodecene (TBD) and (thio)ureas generates polydimethylsiloxanes (PDMSs) with narrow dispersity (Mw/Mn < 1.1). Despite the similar basicities of TBD and 1,8-bis(tetramethylguanidino)naphthalene (TMGN), which is known as a proton sponge, a unitary organocatalytic system using TMGN was inactive for the ROP of D3. When the TMGN was paired with acidic urea, the BOROP of D3 yielded PDMSs with narrow dispersity (Mw/Mn < 1.1). Data suggest that the synergetic effect of TMGN and urea is results in an unprecedented activation–deactivation equilibrium between dormant and propagating species. The benefits of the present BOROP system are demonstrated by the formation of PDMS elastomers with more uniform network structures that are highly stretchy and have excellent mechanical properties.

A Successful Application of Phosphazene Base P2‐tBu to [11C]ABP688 Radiosynthesis in Fully Automated Synthesis Module

[11C]ABP688 is the radioligand widely used for metabotropic glutamate subtype 5 (mGluR5) imaging in positron emission tomography (PET). The successful production of [11C]ABP688 in commercial automated synthesis module with hindered strong organic base was achieved. I compared 1,8‐bis(tetramethylguanidino)naphthalene (TMGN), tert‐butylimino‐tri(pyrrolidino)phosphorane (BTPP), P2‐tBu, P4‐tBu, and NaH as a base for C‐11 methylation of oxime and found P2‐tBu would be a suitable alternative for the conventional inorganic bases (NaH or NaOH). Considering the GMP application, P2‐tBu can provide compatibility with automated synthesizer and the resulting reliable synthesis. Three batches of the optimized condition for [11C]ABP688 synthesis were examined for quality assurance.

Characterization of bioactive and nutraceutical compounds occurring in olive oil processing wastes.

Several bioactive compounds, including phenolic acids and secoiridoids, are transferred from olive drupes to olive oil during the first stage of production. Here, the characterization of these low molecular weight (LMW) compounds in olive oil and in closely related processing materials, like olive leaves (OL) and olive mill wastewaters (OMW), was faced up, for the first time, by matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF MS). A novel binary matrix composed of 1,8-bis(tetramethylguanidino)naphthalene (TMGN) and 9-aminoacridine (9AA) (1:1 molar ratio), displaying excellent ionization properties at low levels of laser energy, was employed in reflectron negative ion mode by a MALDI TOF/TOF system equipped with a neodymium-doped yttrium lithium fluoride (Nd:YLF) laser (345 nm). MS/MS experiments were performed by using ambient air as the collision gas. Four major secoiridoids typically present in olive oil, i.e., the aglycones of oleuropein and ligstroside, and oleacein and olecanthal at m/z 377.1, 361.1, 319.1 and 303.1, respectively, were detected in virgin olive oil (VOO) extracts, along with some of their chemical/enzymatic hydrolysis by-products, such as elenolic (m/z 241.1), decarboxymethyl-elenolic acids (m/z 183.1) and hydroxytyrosol (m/z 153.1). Besides oleuropein aglycone and oleacein, hydroxylated derivatives of decarboxymethyl-elenolic acid and hydroxytyrosol were evidenced in OMW. While oleuropein was confirmed in OL extracts, several interesting phenolic compounds, including hydroxytyrosol, were recognized in OMW. The proposed approach based on the use of a novel binary matrix for MALDI MS/MS analyses of LMW bioactive compounds can be considered a promising analytical tool for a rapid screening of the phenolic fraction in olive oils and related processing wastes.

Using aromatic polyamines with high proton affinity as "proton sponge" dopants for electrospray ionisation mass spectrometry.

Proton sponges are polyamines with high proton affinity that enable gentle deprotonation of even mildly acidic compounds. In this study, the concept of proton sponges as signal enhancing dopants for electrospray ionisation is presented for the first time. 1,8-Bis(dimethylamino)naphthalene (DMAN) and 1,8-bis(tetramethylguanidino)naphthalene (TMGN) were chosen as dopants, using methanol and acetonitrile/methanol as solvents. Individual standard compounds, compound mixtures and a diesel fuel as a complex sample matrix were investigated. Both proton sponges enhanced signal intensities in electrospray ionisation negative mode, but TMGN decomposed rapidly in methanolic solution. Significantly higher signals were only achieved using the acetonitrile/methanol mixture. On average a more than 10-fold higher signal intensity was measured with 10-3 mol l-1 DMAN concentration. A stronger signal increase of alcohol functionalities was observed compared to acid functionalities. All compound classes which were detected in the diesel fuel (CH- and CHOx-class) received roughly 100-fold higher signal intensities when using DMAN as a dopant. Furthermore, the number of detected compounds as well as the double bond equivalent of the detected compounds increased. The compound class distribution shifted when adding DMAN and the formerly dominant CHO2-, CHO3-, and CHO4- classes received similar relative intensities as formerly less accessible classes. The findings depict DMAN as a promising additive for electrospray ionisation negative analysis of at least mildly acidic compounds, even within complex sample material.

Successful application of a neutral organic base, 1,8-bis(tetramethylguanidino)naphthalene (TMGN), for the radiosynthesis of [11C]raclopride

[11C]Raclopride is one of the most popular PET tracers used in Parkinson's disease studies. We previously prepared [11C]raclopride with reasonable yields using NaOH as an inorganic base, but the reaction patterns fluctuated. In this study, we describe the successful application of a commercially available ‘super basic’ proton sponge, TMGN, as a base for the [11C]methylation step using [11C]CH3OTf. This novel TMGN method produced better radiochemical yields, as well as enhanced reproducibility and a reduction in side products. Under optimal conditions (1.2 equiv. of TMGN), the radiochemical yield was 14.4±0.2% (ndc, EOS, n=5) and the specific activity was 66.6±13.3 GBq/mmol (n=5).

Strong Organic Bases as Building Blocks of Mesoporous Hybrid Catalysts for C–C Forming Bond Reactions

Abstract1,8‐Bis(tetramethylguanidino)naphthalene (TMGN), a neutral organic base that combines the properties of guanidine and the properties of proton sponges, was used as a building block to produce organic–inorganic silica‐based mesoporous hybrids with strong basic properties. The TMGN‐based mesoporous hybrids (TMGN/SiO2) were prepared by a sol–gel route working at a neutral pH and low temperatures, which avoided the use of SDAs. TMGN has been modified in order to have two terminal reactive silyl groups able to perform co‐condensation with a conventional organosilane (TMOS) used as a silicon source. This synthesis has allowed us to directly introduce the unmodified, functionalized TMGN as part of the walls of the mesoporous silica by a one‐pot synthesis. TMGN/SiO2 hybrid materials present excellent catalytic properties for C–C bond forming reactions: Knoevenagel, Henry (nitroaldol), and Claisen–Schmidt condensations. The activity of the hybrid materials is higher than that of the counterpart homogeneous catalyst.

Alkylation of Substituted Benzoic Acids in a Continuous Flow Microfluidic Microreactor: Kinetics and Linear Free Energy Relationships

Alkylation of para-substituted benzoic acids by iodomethane using an organic superbase, 1,8-bis(tetramethylguanidino)naphthalene (TMGN) in DMF was chosen as a model reaction to test the quality of the control of experimental parameters in a continuous flow microfluidic reactor as it is expected to follow a perfect second order kinetics with a large dynamics by varying the substituents. These conditions may be directly used for the synthesis of natural product esters. Because TMGN reacts slowly with iodomethane, the three different mixing strategies between substrate, base and alkylating reagent were compared. The rate constants were determined for the reaction with a set of alkylating agents and in different solvents. In order to test the quality of the obtained data, temperature effect and free energy relationships, which are expected to follow predictable laws, were investigated. The kinetics vary over 6 orders of magnitude and follows a perfect Arrhenius law, allowing the determination of the energies, enthalpies, and entropies of activation. Finally, we established a Hammett linear relationship for a series of 16 substituted benzoic acids, leading to a reaction constant ρ of −0.65 for this reaction. The quality of the obtained kinetics allowed us to discuss the outliers. All kinetics were obtained with less than 0.5 mmol of substrate.

Proton sponge-functionalized silica as high performance adsorbents for solid-phase extraction of trace perfluoroalkyl sulfonates in the environmental water samples and their direct analysis by MALDI-TOF-MS

1,8-Bis(dimethylamino)naphthalene (DMAN), a classical 'proton sponge', was functionalized on silica particles as a novel solid-phase extraction (SPE) adsorbent (DMAN@silica) for extracting perfluoroalkyl sulfonates (PFSs). High reproducibility and excellent extraction capability for PFSs were obtained in a wide pH range (3.0~8.5). The adsorbed PFSs on DMAN@silica sorbents could be efficiently eluted by 1,8-bis(tetramethylguanidino)naphthalene (TMGN) solution which is a proton sponge with higher proton affinity than DMAN. The elution could be directly analyzed by MALDI-TOF-MS using TMGN as matrix. Clear mass spectra for the PFSs were obtained due to no matrix ions interference observed. Furthermore, a novel strategy based on the DMAN@silica-SPE enrichment, followed by MALDI-TOF-MS analysis, was proposed and applied for PFSs quantification in environmental water samples. The calibration curves of each of the target analytes showed a wide linear dynamic range of response (0.1-10 ng L(-1) for perfluorooctane sulfonate (PFOS), perfluorohexyl sulfonate (PFHxS) and perfluorobutylsulfonate (PFBS)), which were over 2 orders of magnitude. The detection limits for PFOS, PFHxS, and PFBS were 0.021, 0.016, and 0.013 ng L(-1), respectively (S/N = 3). Recoveries of PFOS, PFHxS, and PFBS are in the ranges of 92-104%, 95-102%, and 98-109% for spiked river water samples. These results indicated that the prepared DMAN@silica adsorbents could efficiently enrich PFSs and that the proposed method is reliable.

Quantitative detection of trace perfluorinated compounds in environmental water samples by Matrix-assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry with 1,8-bis(tetramethylguanidino)-naphthalene as matrix

Determination of perfluorinated compounds (PFCs) is very important because of their potential hazards to the environment and human health. In present work, 1,8-bis (tetramethylguanidino)-naphthalene (TMGN), a superbasic proton sponge, was firstly employed as the matrix for quantitative detection of acidic PFCs in environmental water samples by Matrix-assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry (MALDI-TOF-MS). Several acidic PFCs, such as perfluorooctanesulfonate (PFOS) and perfluorooctanoic acid (PFOA), were selected as model analytes for demonstrating the feasibility of the detection method. The results showed that deprotonated ions of these PFCs were detected without any other matrix ions interference. The achieved sensitivity with TMGN for PFOS detection was ten-fold higher than that with 1,8-bis (dimethyl-amino)-naphthalene (DMAN) which was used for the detection of fatty acid by MALDI-TOF-MS. The high sensitivity of this method made it feasible to monitor and quantify acidic PFCs in complicated environmental water samples. Furthermore, a novel combined strategy of solid phase extraction (SPE) followed by MALDI-TOF-MS detection was developed for quantifying PFCs in environmental water samples. The calibration curves with a wide linear dynamic range (0.1–10ngL−1 for PFOS, PFHxS, and PFBS, and 0.5–50ngL−1 for PFOA, PFNA, and PFDA.) were obtained. The limit of detection (LOD) for PFOS of this method was 0.015ngL−1 (a signal-to-noise ratio of 3), which was lower than the LOD (0.036ngL−1) obtained by high-pressure liquid chromatography/tandem mass spectrometry (LC–MS/MS) method. Moreover, the strategy was used to detect the selected PFCs in water samples collected from Xiaoqinghe river and Gaobeidian wastewater. The achieved concentrations of PFCs were closed to those obtained by LC–MS/MS method. It is indicated that the proposed MALDI-TOF-MS method with TMGN as the matrix is much reliable and can be used as an alternative method to detect trace PFCs in environmental water samples.

Deprotonation of hydrogen bonded Schiff bases by three strong nitrogen bases

Three Schiff bases obtained from substituted salicylaldehydes and 2-hydroxy-1-naphthaldehyde and aliphatic amines were investigated in terms of possible withdrawal of tautomeric proton from intramolecular hydrogen bridge. Three strong nitrogen bases: 1,8-bis(dimethylamino)naphtalene (DMAN), 1,1,3,3-tetramethylguanidine (TMG) and 1,8-bis(tetramethylguanidino)naphthalene (TMGN) were used as deprotonating agents in acetonitrile solution at room temperature. In the specified conditions it was found that only in the case of 5-nitrosalicylaldehyde and isopropyl amine derivative this process could be performed using TMG and TMGN as a base. The other derivatives, where bridged proton is shifted to oxygen or nitrogen atom, do not undergo such reaction. The deprotonation process was monitored by nitrogen and proton NMR measurements.

Spectroscopic and PM5 semiempirical studies of the proton accepting properties of 1,8-bis(tetramethylguanidino)naphthalene

The strongly basic 1,8-bis(tetramethylguanidino)naphthalene (TMGN) has been mono- and di-protonated by pentachlorophenol (PCP) and HClO 4 acid. Formation of hydrogen bonds in the 1:1 and 1:2 mixtures in acetonitrile has been studied by FT-IR, 1H NMR; 13C NMR spectroscopy as well as in the gas phase by ESI MS and PM5 semiempirical methods. The spectroscopic data show that in the 1:1 mixtures of TMGN with PCP or perchloric acid the base becomes protonated forming an intramolecular [N–H⋯N] + hydrogen bond. This hydrogen bond is strongly asymmetrical and is at most of medium strength. In the 1:2 mixtures, the intramolecular [N–H⋯N] + hydrogen bond is conserved irrespective of the kind of the acid and, in the case of the TMGN complex with PCP, additionally an intermolecular [O⋯H⋯O] − hydrogen bond is formed whereas in the TMGN complex with HClO 4 another N atom of the guanidine groups is protonated. The ESI MS measurements indicate the formation of protonated TMGN and deprotonated carboxylic acids and phenols as separated ions instead of a complex in the gas phase. The ClO 4 - anion forms, however, complexes with the protonated TMGN molecules. We show that the anion has a strong influence on the fragmentation pathway. The structures of TMGN and its selected protonated species are visualized using the semiempirical PM5 method. The calculated hydrogen bond parameters are in good agreement with the X-ray data.

The proton affinity of the superbase 1,8-bis(tetramethylguanidino)naphthalene (TMGN) and some related compounds: a theoretical study.

The spatial and electronic structure of the very strong neutral organic bases bis(tetramethylguanidino)naphthalene (TMGN), 4,5-bis(tetramethylguanidino)fluorene (TMGF) and some related compounds are explored by ab initio computational methods. Their affinity towards the proton is scrutinized both in the gas phase and in solution in acetonitrile. The protonation at the most basic center (the imine nitrogen) yields asymmetric and relatively strong intramolecular hydrogen bonds (IHB). It is found that the angular strain effect and steric repulsion practically vanish in TMGN which implies that its high absolute proton affinity (APA) has its origin in the inherent basicity of the guanidine fragment and a relatively strong IHB in [TMGN]H(+). The nonbonded repulsions in TMGF are higher than in TMGN, which in conjunction with a slightly stronger IHB in the corresponding conjugate acid makes it more basic: APA(TMGF)>APA(TMGN). An interesting new phenomenon is observed in both TMGN and TMGF: the proton triggers the resonance stabilization not only in the directly bonded guanidine moiety, but also in the other guanidine fragment which is more distant from the proton, albeit in a less pronounced manner. The latter feature is termed a partial protonation. This supports the hydrogen bonding and contributes to the IHB stabilization. Convincing evidence is presented that the solvent effect in acetonitrile is determined by two antagonistic factors: 1) the intrinsic (gas phase) proton affinity and 2) the size effect which is given by the ratio between the positive charge in molecular cation (conjugate acid) and the magnitude of the molecular surface. The resulting pK(a) values are given by an interplay of these factors.