Condensation Reagent Research Articles

Preparation and application of aramid nanofiber via carbodiimide assisted polymerization

Poly (p-phenylene terephthalamide) (PPTA), is well known as a material with excellent properties, but its application is greatly limited due to the harsh methods required for its preparation. This study proposes an innovative carbodiimide-assisted polymerization (CAP) method to simplify the synthesis process of PPTA. The ηinh of the prepared PPTA is 4.97 dl/g. Achieving amidation condensation at normal temperature and pressure, this method is suitable for synthesizing PPTA and allows for the recycling of the condensation reagent, offering a novel approach to green synthesis. Compared to the commercial fiber Kevlar 29, PPTA exhibits similar thermal stability, with negligible decomposition before 500°C. Using the deprotonation method to prepare aramid nanofiber (ANF) resulted in various shapes of bulk materials. The ANF bulk exhibits excellent mechanical properties, with tensile and compressive strengths of 36.9 MPa and 60.68 MPa, respectively, on par with standard engineering materials. Additionally, ANF and PPTA share similar thermal stability. Furthermore, the study prepared aramid nanofiber/partially hydrolyzed polyacrylamide (ANF/HPAM) composite paper, which demonstrated outstanding mechanical performance and thermal stability. The ANF/HPAM composite paper (2% concentration of HPAM) exhibited a tensile strength of 63.32 MPa. These findings offer new insights into developing high-performance fiber materials.

Oxidative Synthesis of α‐Nitroketones from α‐Substituted Malononitrile and Nitromethane Using Molecular Oxygen without Condensation Reagents

AbstractWe developed an oxidative synthetic method for α‐nitroketones from α‐substituted malononitriles and nitromethane under molecular oxygen. Only base and molecular oxygen are necessary without condensation reagents; this is an environmentally benign synthesis.

Recent advances in asymmetric synthesis of chiral amides and peptides: racemization-free coupling reagents.

Over past decades, chiral amides and peptides have emerged as powerful and versatile compounds due to their various biological activities and interesting molecular architectures. Although some chiral condensation reagents have been applied successfully for their synthesis, the introduction of racemization-free methods of amino acid activation have shown lots of advantages in terms of their low cost and low toxicity. In this review, advancements in amide and peptide synthesis using racemization-free coupling reagents over the last 10 years are summarized. Various racemization-free coupling reagents have been applied in the synthesis of enantioselective amides and peptides, including ynamides, allenones, HSi[OCH(CF3)2]3, Ta(OMe)5, Nb(OEt)5, Ta(OEt)5, TCFH-NMI, water-removable ynamides, DBAA, DATB, o-NosylOXY, TCBOXY, Boc-Oxyma, NDTP, 9-silafluorenyl dichlorides, the Mukaiyama reagent, EDC and T3P. The racemization-free reagents described in this review provide an alternative greener option for the asymmetric synthesis of chiral amides and peptides. We hope that this review will inspire further studies and developments in this field.

Synthesis of BODIPY FL-tethered ridaifen-B, RID-B-BODIPY, and its localization in cancer cells.

We synthesized ridaifen-B boron dipyrromethene (RID-B-BODIPY) using 2-methyl-6-nitro benzoic anhydride (MNBA)-mediated dehydration condensation reaction between amino alkyl-tethered RID and BODIPY FL. Comparative experiments between dicyclohexylcarbodiimide (DCC) and MNBA for their coupling reactions demonstrated that MNBA is an effective condensation reagent for amines and BODIPY FL. A cell staining study with RID-B-BODIPY showed intracellular localization of BODIPY FL fluorescence, attributed to the RID-B structure, indicating the successful development of a tool for analyzing intracellular molecular behavior efficiently.

Preparation of Alginic Acid/Poly(2‐Oxazoline) Hybrid Gels and Their Use in Cell Preservation

AbstractA hybrid gel is developed aiming to extend the storage period for cell preservation compared with an alginate gel. The introduction of poly(2‐oxazoline)s into alginic acid promises to improve functional materials by changing their functional groups (e.g., poly(2‐isopropyl‐2‐oxazoline) has the lower critical solution temperature behavior). This study demonstrates chemical modification of a carboxylate of sodium alginate by 1,3‐diaminopropane‐terminated poly(2‐oxazoline)s using 3‐ethylcarbodiimide hydrochloride (EDC) and N‐hydroxy succinimide (NHS) as the condensation reagents for the aminations. The incorporated ratio of poly(2‐oxazoline)s side chains into the carboxylates estimated by 1H NMR is ca. 5–12% and the remaining pendent carboxylates are used for gelation by adding calcium salts (CaCl2). Gelation is observed within 30 min producing 93–99% gel fractions that swell in water. Similar gelation occurs in the cultivation medium of green‐fluorescence protein (GFP)‐encoded and COVID‐19 spike protein‐encoded DNA recombinant E.coli in both the absence and presence of isopropyl β‐D‐1‐thiogalactopyranoside (IPTG). Even in the presence of IPTG, fluorescence ascribed to GFP is not observed while the cells are kept at 25 °C for 3 weeks. After solvation by ethylenediaminetetraacetic acid (EDTA), fluorescence intensity at 508 nm is clearly observed and cell preservation at room temperature is thereby demonstrated.

Effect of solvent-free membranes-forming processes on HT-PEM properties of highly soluble polybenzimidazole

The cost-effective sol-gel process for the preparation of phosphoric acid (PA) doped P-PBI membranes using PPA as both condensation reagent and solvent could avoid the use of hazardous organic solvents. However, optimizing the trade-off effect between mechanical properties and proton conductivity of sol-gel membranes by increasing polymer content is ineffective due to the limited solubility of P-PBI in PPA. Herein, we successfully fabricated a series of sol-gel membranes with tunable properties using a highly soluble polybenzimidazole (N-PBI). In addition, the sol-gel (5 wt%) N-PBI membrane was further specially dried and post-doped with PA to obtain a re-doped sol-gel N-PBI membrane. Therefore, the properties of PA-doped N-PBI membranes fabricated using three different processes-conv, sol-gel, and re-doped sol-gel-were thoroughly characterized. The sol-gel N-PBI membranes demonstrated a dependence of mechanical properties and proton conductivity on polymer content, with a maximum tensile strength of 7.0 MPa at 7 wt% polymer content and a maximum proton conductivity of 205 mS/cm (200 °C) at 2 wt% polymer content. The ADL-controlled re-doped sol-gel N-PBI membrane achieved higher saturated ADL than the sol-gel N-PBI membrane, resulting in higher proton conductivity and fuel cell performance. The sol-gel (2 wt%) N-PBI membrane exhibited an ultra-high H2/O2 peak power density of 1058 mW/cm2 under an optimized operating condition, and the sol-gel (7 wt%) N-PBI membrane achieved stable operation without apparent degradation for over 2000 h at 160 °C with 0.3 A/cm2 current density.

Practical N-to-C peptide synthesis with minimal protecting groups

Accessible drug modalities have continued to increase in number in recent years. Peptides play a central role as pharmaceuticals and biomaterials in these new drug modalities. Although traditional peptide synthesis using chain-elongation from C- to N-terminus is reliable, it produces large quantities of chemical waste derived from protecting groups and condensation reagents, which place a heavy burden on the environment. Here we report an alternative N-to-C elongation strategy utilizing catalytic peptide thioacid formation and oxidative peptide bond formation with main chain-unprotected amino acids under aerobic conditions. This method is applicable to both iterative peptide couplings and convergent fragment couplings without requiring elaborate condensation reagents and protecting group manipulations. A recyclable N-hydroxy pyridone additive effectively suppresses epimerization at the elongating chain. We demonstrate the practicality of this method by showcasing a straightforward synthesis of the nonapeptide DSIP. This method further opens the door to clean and atom-efficient peptide synthesis.

Improved Synthetic Process of Baloxavir Marboxil Intermediate 3-Benzyloxy-4-oxo-4H-pyran-2-carboxylic Acid

The article presents a process research study of 3-benzyloxy-4-oxo-4H-pyran-2-carboxylic acid (1), a crucial intermediate in the synthesis of baloxavir marboxil. The original four-step sequence exhibited various limitations, such as low yield (43%), the use of problematic solvents, a large excess of costly reagents, safety concerns, and impurity control difficulties. To address these challenges, process optimization was carried out to achieve the desired goals for large-scale industrial production. Optimization of the enamine 4b synthesis was performed, resulting in the development of an azeotropic removal method for the byproduct methanol. This improvement led to minimized ring-opening impurity 15 and a significant reduction in the consumption of the condensation reagent. Furthermore, a simplified one-pot two-step oxidation sequence was devised to streamline the process for the synthesis of compound 1. This optimization involved controlling the formation of hydrolytic impurity 16 and its downstream aldol condensation form 17. The optimized process was successfully demonstrated on a 600 g scale with a product purity of 99.9%, and the overall yield was substantially improved, rising from 43 to 66%.

Revealing the sources and sinks of negative cluster ions in an urban environment through quantitative analysis

Abstract. Atmospheric cluster ions are important constituents in the atmosphere, and their concentrations and compositions govern their role in atmospheric chemistry. However, there is currently limited quantitative research on atmospheric ion compositions, sources, and sinks, especially in the urban atmosphere where pollution levels and human populations are intense. In this study, we measured the compositions of negative cluster ions and neutral molecules using an atmospheric pressure interface high-resolution time-of-flight mass spectrometer (APi-TOF) and a chemical ionization mass spectrometer in urban Beijing. Quantitative analysis of cluster ions was performed by their comparison with condensation sink (CS), reagent ions, and neutral molecules. We demonstrate the feasibility of quantifying cluster ions with different compositions using in situ-measured ion mobility distributions from a neutral cluster and air ion spectrometer (NAIS). The median concentration of negative cluster ions was 85 (61–112 for 25 %–75 %) cm−3 during the measurement period, which was negatively correlated with CS. The negative cluster ions mainly consisted of inorganic nitrogen-containing ions, inorganic sulfur-containing ions, and organic ions in the form of adducts with NO3- or HSO4-. The CHON-related organic ions accounted for over 70 % of the total organic ions. Although the molecules clustered with NO3- and HSO4- had similar compositions, we found that HSO4- clustered more efficiently with CHO and CHONnonNPs species (CHON excluding nitrated phenols), while NO3- clustered more efficiently with nitrated phenols (CHONNPs). Additionally, most organic ions were positively correlated with neutral molecules, resulting in similar diurnal cycles of organic ions and neutral molecules. However, an exception was found for CHONNPs, the concentration of which is also significantly influenced by the reagent ions NO3-. The charge fractions are generally higher for molecules with higher molecular weight and a higher oxidation state, and the opposite diurnal variations in charging fractions between H2SO4 and organic species indicate a charging competition between them. Finally, we choose HSO4- and C3H3O4- as representatives to calculate the contribution of different formation and loss pathways. We found their losses are condensational loss onto aerosol particles (73 %–75 %), ion–molecule reaction losses (19 %), and ion–ion recombination losses (6 %–8 %).

Total Synthesis of Pargamicin A.

We report the total synthesis and configurational assignment of pargamicin A, a highly oxidized nonribosomal peptide that potently inhibits the growth of drug-resistant bacteria. Our synthetic approach relies on late-stage piperazine ring formation and careful selection of condensation reagents to assemble the densely substituted hexapeptide backbone. This work enables the synthesis of pargamicin congeners for the development of structure-activity relationships and informs strategies for accessing other sterically congested piperazic acid-containing natural products.

New molecular hybrids containing benzimidazole, thiazolidine-2,4-dione and 1,2,4-oxadiazole as EGFR directing cytotoxic agents

Herein, we, synthesized some new molecular hybrids (7a-o) having benzimidazole, thiazolidine-2,4-dione and 1,2,4-oxadiazole scaffolds from the commercially available 1-methyl-1H-benzo [d]imidazole-2-carbaldehyde (1) using two key methodologies such as Knoevenagel condensation and Vilsmeier reagent mediated one-pot synthesis. Further, all the compounds in their μM concentration were screened for their in vitro cytotoxic activity against three human cancer cell lines which includes MCF-7, A-549 and HepG2. Among all, the compound 7n exhibited superior activity against all the cell lines as compared to standard drug erlotinib. Besides, the compounds 7d, 7e and 7f showed superior activity against MCF-7 and most promising activity against A-549 and HepG2 when compared with the positive control. As well, the tyrosine kinase EGFR inhibitory activity for the potent compounds 7d, 7e, 7f and 7n, revealed that the compounds 7e and 7n displayed nearly double potency as compared to the erlotinib drug. The molecular docking studies of active compounds 7d, 7e, 7f and 7n on EGFR target were also conducted and the results were found to be covenant with the corresponding IC50 values.

A novel sustainable luminescent ABS composite material for 3D printing

The development of 3D printing composites with good photoluminescence and mechanical properties is a necessary condition for its practical application. Here, the long persistent phosphors Sr2MgSi2O7: Eu2+, Dy3+ were modified with 3-aminopropyltriethoxysilane(KH550), and the phosphors were grafted with ABS with peptide condensation reagent 0-(7-Azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate(HATU). The effects of phosphors on their photoluminescence and mechanical properties were evaluated. The structure and morphology of the phosphor were determined by X-ray diffraction and scanning electron microscopy, and the successful grafting of the phosphor with ABS was verified by Fourier transform infrared spectroscopy. The optical properties of the composites were evaluated by fluorescence spectroscopy and afterglow decay curve, and the mechanical properties were determined by tensile test. The results show that the luminescence properties and tensile strength of ABS are greatly enhanced with the increase of phosphor content. When 3 wt% grafted phosphor is doped, the luminescence strength, tensile load and tensile strength reach the maximum.

Synthesis of 5-Trifluoromethyl-Substituted (Z)-N,N-Dimethyl-N′-(pyrazin-2-yl)formimidamides from 2-Aminopyrazines, LiI/Selectfluor, FSO2CF2CO2Me and DMF under Cu Catalysis

AbstractThe synthesis of 5-trifluoromethyl-substituted (Z)-N,N-dimethyl-N′-(pyrazin-2-yl)formimidamides via the iodination of 2-aminopyrazines with Selectfluor/LiI followed by a domino trifluoromethylation with FSO2CF2CO2Me and a condensation with DMF in the presence of CuI is realized under mild conditions. This three-step method offers CF3-substituted (Z)-N,N-dimethyl-N′-(pyrazin-2-yl)formimidamides in yields of 55–70% and with high regioselectivities. LiI serves as an iodine source, whilst DMF functions as both a solvent and a condensation reagent. The regioselectivity of these trifluoromethylation reactions is strongly dependent upon the substituent pattern on the 2-aminopyrazines. A possible mechanism for this method is also discussed.

Asymmetric Synthesis of Imidazo[2,1‐a]isoquinolin‐3‐ones with Dihydroisoquinolines and N‐substituted Amino Acids

AbstractA mild direct synthesis of chiral imidazo[2,1‐a]isoquinolin‐3‐one derivatives with dihydroisoquinolines and N‐substituted amino acids have been developed. By the use of easily accessible DCC as condensation reagent at ambient temperature, a series of imidazo[2,1‐a]isoquinolin‐3‐ones can be assembled readily in low to good yields with low to excellent dr values. Interestingly, the use of N‐substituted L‐Threonine and L‐Serine afforded oxazino[2,3‐a]isoquinolin‐4‐one derivatives with good diastereoselectivities.

An Improved and Plant Viable Synthesis of Vitamin K1

An improved and simplified process of vitamin K1 preparation. The article confers the new reagent BF3. Acetic acid complex as a condensation reagent for phytol with compound III in vitamin K1 synthesis, which eludes the use of ethereal reagent and make the process hazard free. Further innovation presents base catalyzed synthesis of vitamin K1 which is an oxidative product of compound IV. Sodium methoxide base is used in synthesis which eliminates use of metal oxidant, costly and hazardous reagent. The new approach ensures the non-generation of epoxide impurity (V) which tends to form during Ag2O catalyzed synthesis. Finally, article also focused on formation and conformation of 7R and 11R diastereomeric centers and ensure the formation of vitamin k1 with desired stereochemistry also article submit proof of concept and supporting literature survey for desired stereochemistry.

Algal carbons hydrothermally produced from Spirulina and Chlorella with the assistance of phthalaldehyde: An effective precursor for nitrogen-containing porous carbon

A microalgal suspension of Spirulina and Chlorella in water was hydrothermally reacted at 220 °C for 14 h in an autoclave; this efficiently obtained hydrothermal carbons as an aggregate of non-porous spheres several microns in diameter when phthalaldehyde was added as an auxiliary condensation reagent. The algal hydrothermal carbons contained considerable quantities of nitrogen; approximately 6 wt% originated from the protein component in microalga, which could be converted to microporous carbons with a ca. 2 wt% nitrogen-content and a specific surface area of approximately 700 m2/g, via heating from room temperature to 900 °C under an argon atmosphere. The algal porous carbons containing pyridinic-nitrogen derived from Chlorella exhibited high activity for electrical double-layer capacitors, with capacitances of approximately 250 F/g and 200 F/g, respectively, at current densities of 0.2 A/g and 1.0 A/g in 1 M H2SO4 in a three-electrode system under galvanostatic conditions.

Direct 3-Acylation of Indolizines by Carboxylic Acids for the Practical Synthesis of Red Light-Releasable Caged Carboxylic Acids.

To enhance the practicality of photouncaging system using 3-acyl-2-methoxyindolizines, direct acylation of indolizines with carboxylic acids was developed using condensation reagents, generally used for peptide coupling. This method allowed for caging a broad range of carboxylic acids with indolizines. The method enabled a facile synthesis of water-soluble caged bioactive carboxylic acids having an intramolecular photosensitizer. The efficient release of carboxylic acids from the synthesized caged compounds upon red light irradiation was confirmed in neutral buffered solutions.

Applications of Yamaguchi Method to Esterification and Macrolactonization in Total Synthesis of Bioactive Natural Products

AbstractYamaguchi protocol provides functionalized esters regioselectively from carboxylic acids and alcohols employing 2,4,6‐trichlorobenzoyl chloride as the condensation reagent in the presence of a stoichiometric amount of 4‐N,N‐dimethylaminopyridine. The key features of this method comprise a high yield of esters, short reaction time, mild conditions, macrocyclic lactone ring formation, and regioselective preparation of highly functionalized esters. Such beneficial quality of this method as a whole have motivated the organic chemist and biological community to explore the application of Yamaguchi protocol in more heights and as a result, the present overview is aimed to cover the application of this method as a key step in the area of the total synthesis of bioactive natural products. The present review tries to focus on the natural sources, structures, and biological activities of the promising natural products elegantly.

Synthesis of A2+B3 type hyperbranched poly(amide-ether) block copolymer and its shape memory function

High-molecular-weight hyperbranched polyether-b-amides (hb-PEBA; number average molecular weight (Mn) = 29.2–96.2 kDa) were successfully prepared by polycondensation of NH2-terminated poly(ethylene oxide) (PEO; Mn = 3.35, 4.6, 8.0, and 10.0 kDa) as A2-type and COOH-terminated three-armed N-methylbenzamide pentamers (TMA-3MAB5) as B3-type macromonomers in N-methylpyrrolidone (NMP) at 35–60 °C for 6 h. TMA-3MAB5 was prepared by stepwise condensation of 4-N-methylaminobenzoic acid (MAB), trimesic acid (TMA), and thionyl chloride/NMP as the building block, core molecule, and condensation reagent, respectively. Transparent to opaque films were prepared from all polymer samples through the solvent casting method using CHCl3, and the crystallization of PEO segments (crystallization degree Xc 15%–66%) was confirmed using differential scanning calorimetry (DSC). The hb-PEBA films showed tensile strengths of 0.71–16.8 MPa, with breaking elongation of 40–350%, and tensile elastic moduli of 0.10–1.43 GPa, depending on Mn and polymer composition. The superior shape memory properties of hb-PEBA polymers compared with their linear counterparts were confirmed by deformation at 80 °C, shape retention (memory) at room temperature, and shape recovery by reheating. Overall, the well-controlled TMA-3MAB5 was undoubtedly effective for the synthesis of high Mnhb-PEBA, resulting in improved mechanical and shape memory properties.

Amide bond formation: beyond the dilemma between activation and racemisation.

The development of methods for amide bond formation without recourse to typical condensation reagents has become an emerging research area and has been actively explored in the past quarter century. Inspired by the structure of vitamin B12, we have developed a metal-templated macrolactamisation that generates a new wave towards classical macrolactam synthesis. Further, distinct from the extensively used methods with condensation reagents or catalysts based on catalyst/reagent control our metal-catalysed methods based on substrate control can effectively address long-standing challenges such as racemisation in the field of peptide chemistry. In addition, the substrate-controlled strategy demonstrates the feasibility of "remote" peptide bond-forming reaction catalysed by a metal-ligand complex. Moreover, an originally designed hydrosilane/aminosilane system can avoid not only racemisation but also unnecessary waste production. This feature article documents our discovery and application of our original approaches in amide bond formation.