Traditional Synthetic Routes Research Articles

Synthesis of Anion Exchange Membranes with Side-Chain-Type Benzylic Cationic Groups Using Chloromethylbenzoylation

To circumvent the shortcomings of traditional synthetic routes relying on chloromethylation or bromination of benzylic methyl groups, a novel approach, chloromethylbenzoylation, has been proposed to synthesize commercially available poly(aryl ether)s (PAEs) with side-chain-type benzylic cationic groups for anion exchange membranes (AEMs). Previous works have demonstrated that adding alkyl side chain to PAE backbones can improve the alkaline stability of the AEMs. In this work, side-chain-type benzylchloride groups have been directly introduced onto poly resorcinol ketone (PRK) via an acylation reaction between 4-(chloromethyl)benzoic acid and PRK in P2O5/CH3SO3H at 60 oC. 1H NMR and GPC confirm that 100% substitution occurred, without side reactions such as crosslinking or degradation. Robust AEMs were then obtained through amination upon introduction of trimethylammonium (TMA+) groups. The chloride ionic conductivity of the AEM was 8.8 mS/cm at 30 °C, which is competitive with that of a commercial TokuyamaÒ A201 membrane at similar IEC values. In summary, this approach represents a simple and straightforward route capable of quantitative introduction of side-chain-type benzylchloride groups without using expensive or toxic reagents, with potential applications of the resultant AEMs in energy conversion and storage and other fields.

Increased availability of NADH in metabolically engineered baker's yeast improves transaminase-oxidoreductase coupled asymmetric whole-cell bioconversion.

BackgroundSaccharomyces cerevisiae can be engineered to perform a multitude of different chemical reactions that are not programmed in its original genetic code. It has a large potential to function as whole-cell biocatalyst for one-pot multistep synthesis of various organic molecules, and it may thus serve as a powerful alternative or complement to traditional organic synthetic routes for new chemical entities (NCEs). However, although the selectivity in many cases is high, the catalytic activity is often low which results in low space-time-yields. In the case for NADH-dependent heterologous reductive reactions, a possible constraint is the availability of cytosolic NADH, which may be limited due to competition with native oxidative enzymes that act to maintain redox homeostasis. In this study, the effect of increasing the availability of cytosolic NADH on the catalytic activity of engineered yeast for transamination-reduction coupled asymmetric one-pot conversion was investigated.ResultsA series of active whole-cell biocatalysts were constructed by over-expressing the (S)-selective ω-transaminase (VAMT) from Capsicum chinense together with the NADH-dependent (S)-selective alcohol dehydrogenase (SADH) originating from Rhodococcus erythropolis in strains with or without deletion of glycerol-3-phosphate dehydrogenases 1 and 2 (GPD1 and GPD2). The yeast strains were evaluated as catalysts for simultaneous: (a) kinetic resolution of the racemic mixture to (R)-1-phenylethylamine, and (b) reduction of the produced acetophenone to (S)-1-phenylethanol. For the gpd1Δgpd2Δ strain, cell metabolism was effectively used for the supply of both amine acceptors and the co-factor pyridoxal-5′-phosphate (PLP) for the ω-transaminase, as well as for regenerating NADH for the reduction. In contrast, there was nearly no formation of (S)-1-phenylethanol when using the control strain with intact GPDs and over-expressing the VAMT-SADH coupling. It was found that a gpd1Δgpd2Δ strain over-expressing SADH had a 3-fold higher reduction rate and a 3-fold lower glucose requirement than the strain with intact GPDs over-expressing SADH.ConclusionsOverall the results demonstrate that the deletion of the GPD1 and GPD2 genes significantly increases activity of the whole-cell biocatalyst, and at the same time reduces the co-substrate demand in a process configuration where only yeast and sugar is added to drive the reactions, i.e. without addition of external co-factors or prosthetic groups.Electronic supplementary materialThe online version of this article (doi:10.1186/s12934-016-0430-x) contains supplementary material, which is available to authorized users.

Techno-economic assessment of the production of phthalic anhydride from corn stover

Phthalic anhydride is used worldwide for an extremely broad range of applications spanning from the plastics industry to the synthesis of resins, agricultural fungicides and amines. This work proposes a conceptual design of a process for the production of phthalic anhydride from an agricultural residue (i.e. corn stover), energy integration alternatives as well as water consumption and life cycle greenhouse emissions assessment. The techno-economic and financial appraisal of the flowsheet proposed is performed. Results show how the valorization of all the carbohydrate-rich fractions present in the biomass as well as energy savings and integration is crucial to obtain an economically viable process and that it is in principle possible to produce renewable phthalic anhydride in a cost-competitive fashion with a lower impact on climate change compared to the traditional synthetic route.

Structural Evolution of Iron Antimonides from Amorphous Precursors to Crystalline Products Studied by Total Scattering Techniques.

Homogeneous reaction precursors may be used to form several solid-state compounds inaccessible by traditional synthetic routes, but there has been little development of techniques that allow for a priori prediction of what may crystallize in a given material system. Here, the local structures of FeSbx designed precursors are determined and compared with the structural motifs of their crystalline products. X-ray total scattering and atomic pair distribution function (PDF) analysis are used to show that precursors that first nucleate a metastable FeSb3 compound share similar local structure to the product. Interestingly, precursors that directly crystallize to thermodynamically stable FeSb2 products also contain local structural motifs of the metastable phase, despite their compositional disagreement. While both crystalline phases consist of distorted FeSb6 octahedra with Sb shared between either two or three octahedra as required for stoichiometry, a corner-sharing arrangement indicative of AX3-type structures is the only motif apparent in the PDF of either precursor. Prior speculation was that local composition controlled which compounds nucleate from amorphous intermediates, with different compositions favoring different local arrangements and hence different products. This data suggests that local environments in these amorphous intermediates may not be very sensitive to overall composition. This can provide insight into potential metastable phases which may form in a material system, even with a precursor that does not crystallize to the kinetically stabilized product. Determination of local structure in homogeneous amorphous reaction intermediates from techniques such as PDF can be a valuable asset in the development of systematic methods to prepare targeted solid-state compounds from designed precursors.

An Environmentally Friendly, Scalable and Highly Efficient Synthesis of (S,S)-Ethambutol, a First Line Drug against Tuberculosis

Two efficient synthetic routes to (S,S)-ethambutol, a first line drug used for tuberculosis treatment, based on the chiral pool approach viewing L-methionine as a starting material are reported. Several advantages over the traditional synthetic routes were observed: simple, safe, inexpensive reagents, and minimum byproduct formation. The key intermediate (S)-(+)-2-amino-1-butanol was obtained in its enantiomerically pure form from the corresponding aminobutyric acid. Keywords: Drugs, L-methionine, 1, 2-diamine, (S)-(+)-2-amino-1-butanol, (S, S)-ethambutol, tuberculosis.

Directly Synthesis of ZSM-22 Particles by Adding Polyurethane Foam in Ionic Liquid-directed Dry-gel-conversion

Pure-silica ZSM-22 particles with millimeter size were directly synthesized by adding polyurethane foam (PU foam) in ionic liquid-directed dry-gel-conversion process, where the dry gel was prepared under the unusual acidic condition for hydrolyzing the silica precursor with 1,3-alkylimidazolium ionic liquid as the structure direct- ing agent (SDA). Both the PU foam and the ionic liquid-directed dry-gel-conversion process played essential roles in the formation of macroscopic morphology, because only powder-like sample could be obtained in the absence of foam, and moreover, no such special morphology could be achieved on ZSM-22 zeolite prepared by the PU foam-added traditional hydrothermal synthetic route. Various synthetic parameters were systematically studied, in- cluding the influence of PU foam, adding time and adding amount of PU foam, as well as the crystallization time. Pure phase ZSM-22 particles with the highest crystallinity can be obtained by adding appropriate volume of PU foam after microwave aging. Finally, the directly synthesized ZSM-22 particles were modified by impregnating CuO, which exhibited superior N2O adsorption property to the CuO-impregnated post-molded ZSM-22 particles with binding materials. The results indicate that there is an important influence of the macro-morphology on the adsorption performance of zeolites.

A "schizophotonic" all-in-one nanoparticle coating for multiplexed SE(R)RS biomedical imaging.

SERS nanoprobes for in vivo biomedical applications require high quantum yield, long circulation times, and maximum colloidal stability. Traditional synthetic routes require high metal–dye affinities and are challenged by unfavorable electrostatic interactions and limited scalability. We report the synthesis of a new near-IR active poly(N-(2-hydroxypropyl) methacrylamide) (pHPMA). The integration of various SERS reporters into a biocompatible polymeric surface coating allows for controlled dye incorporation, high colloidal stability, and optimized in vivo circulation times. This technique allows the synthesis of very small (<20 nm) SERS probes, which is crucial for the design of excretable and thus highly translatable imaging agents. Depending on their size, the “schizophotonic” nanoparticles can emit both SERS and fluorescence. We demonstrate the capability of this all-in-one gold surface coating and SERS reporter for multiplexed lymph-node imaging.

A “Schizophotonic” All‐In‐One Nanoparticle Coating for Multiplexed SE(R)RS Biomedical Imaging

AbstractSERS nanoprobes for in vivo biomedical applications require high quantum yield, long circulation times, and maximum colloidal stability. Traditional synthetic routes require high metal–dye affinities and are challenged by unfavorable electrostatic interactions and limited scalability. We report the synthesis of a new near‐IR active poly(N‐(2‐hydroxypropyl) methacrylamide) (pHPMA). The integration of various SERS reporters into a biocompatible polymeric surface coating allows for controlled dye incorporation, high colloidal stability, and optimized in vivo circulation times. This technique allows the synthesis of very small (&lt;20 nm) SERS probes, which is crucial for the design of excretable and thus highly translatable imaging agents. Depending on their size, the “schizophotonic” nanoparticles can emit both SERS and fluorescence. We demonstrate the capability of this all‐in‐one gold surface coating and SERS reporter for multiplexed lymph‐node imaging.

Bright building blocks for chemical biology.

Small-molecule fluorophores manifest the ability of chemistry to solve problems in biology. As we noted in a previous review (Lavis, L. D.; Raines, R. T. ACS Chem. Biol.2008, 3, 142–155), the extant collection of fluorescent probes is built on a modest set of “core” scaffolds that evolved during a century of academic and industrial research. Here, we survey traditional and modern synthetic routes to small-molecule fluorophores and highlight recent biological insights attained with customized fluorescent probes. Our intent is to inspire the design and creation of new high-precision tools that empower chemical biologists.

Hydrogen-bond-supported dimeric boron complexes of potentially tetradentate β-diketiminate ligands

Two dimeric boron complexes of potentially tetradentate and trianionic β-diketiminate ligands bearing phenol substituents were prepared and characterized. The synthetic routes employed were designed to circumvent the undesirable formation of β-ketimines and 2-methylbenzoxazoles observed when traditional synthetic routes toward the target β-diketiminate ligands were attempted. The title complexes were isolated via demethylation of β-diketimine ligands and boron difluoride complexes bearing 2-anisole N-aryl substituents using boron tribromide. The resulting complexes were found to contain a unique hydrogen-bond-supported boron-oxygen-boron bridge, as confirmed by X-ray crystallography. The stability of the resulting dimeric structures relative to the corresponding monomeric, tetradentate boron complexes was studied computationally, and theory confirmed that the dimeric structures were strongly favored. The absorption spectra of the dimers were red-shifted relative to the parent β-diketimine ligands. The complexes were irreversibly oxidized and reduced electrochemically and were weakly emissive at low concentrations (Stokes shifts between 23 and 31 nm), showing little solvent dependence.

Interpenetration, Porosity, and High-Pressure Gas Adsorption in Zn4O(2,6-naphthalene dicarboxylate)3

Microporous coordination polymers (MCPs) have emerged as strong contenders for adsorption-based fuel storage and delivery in large part because of their high specific surface areas. The strategy of increasing surface area by increasing organic linker length has shown only sporadic success; as demonstrated by many members of the iconic Zn4O-based IRMOF series, for example, accessible porosity is often limited by interpenetration or pore collapse upon guest removal. In this work, we focus on Zn4O(ndc)3 (IRMOF-8, ndc = 2,6-naphthalene dicarboxylate), which exhibits typical surface areas of only 1000-2000 m(2)/g even though a surface area of more than 4000 m(2)/g is expected from geometric analysis of the originally reported crystal structure. We recently showed that a high surface area could be produced with zinc and ndc by room-temperature synthesis followed by activation with flowing supercritical CO2. In this work, we investigate in detail the porosity of both the low- and high-surface-area materials. Positron annihilation lifetime spectroscopy (PALS) is used to show that the low-surface-area material suffers from near-complete interpenetration, explaining why traditional synthetic routes have failed to yield materials with the expected porosity. Furthermore, the high-pressure hydrogen and methane sorption properties of noninterpenetrated Zn4O(ndc)3 are examined, and PALS is used to show that pore filling is not operative during room-temperature CH4 sorption even at pressures approaching 100 bar. These results provide insight into how gas adsorbs in high-surface-area materials at high pressure and reinforce previous contentions that increasing surface area alone is not sufficient for the simultaneous optimization of deliverable gravimetric and volumetric gas uptake in MCPs.

Synthesis of Benzo-15-crown-5 Under Ultrasonication

Using o-dihydroxybenzene and 1,11-dichloro-3,6,9-trioxaundecane as raw materials,sodium hydroxide as template,DMF as solvent and appropriate amount of 2,6-di-tert-butyl-4-methylphenol as antioxidant,benzo-15-crown-5 was successfully synthesized under ultrasonication at temperature 60~70 ℃.Compared with traditional synthetic routes,reaction time could be reduced to within 2 h,and the yield reached up to 30.7%.

Synthesis of Benzo-15-crown-5 Under Ultrasonication

Using o-dihydroxybenzene and 1,11-dichloro-3,6,9-trioxaundecane as raw materials,sodium hydroxide as template,DMF as solvent and appropriate amount of 2,6-di-tert-butyl-4-methylphenol as antioxidant,benzo-15-crown-5 was successfully synthesized under ultrasonication at temperature 60~70 ℃.Compared with traditional synthetic routes,reaction time could be reduced to within 2 h,and the yield reached up to 30.7%.

Spectroscopic and theoretical studies on the nucleophilic substitution of 2,3-dichloronaphthoquinone with para-substituted anilines in solid state via initial charge transfer complexation

Various spectroscopy techniques (UV–Vis, DRS, FT-IR, 1H NMR, LC–MS) and theoretical computations have been employed to investigate the mechanism of the nucleophilic substitution reaction of 2,3-dichloronaphthoquinone (DCNQ) with para-substituted anilines in solid state under base- and solvent-free conditions against traditional synthetic routes. The initial formations of electron donor acceptor (EDA) adduct between DCNQ and aniline was found to be the driving force for the substitution reaction to occur in solid phase.

Novel heterocyclic NO-donors as potential anti-cancer agents

A comparative study involving two sets of novel nitric oxide donating compounds was investigated. All target compounds were designed and prepared using traditional synthetic routes that were optimised to allow the efficient incorporation of either a furoxan core or a S-nitrosothiol group. In each synthetic sequence the NO was locked into a five-membered heterocyclic ring linked to an aromatic portion. This synthetic strategy provided the scope to generate a range of products with subtle substituent differences in order to help rationalise any variations seen, between individual compounds, in either the rate of NO release or biological profile. The chemical stability of all compounds was compared under a range of different conditions to ascertain the ease with which each heterocyclic ring breaks open, which is clearly a prerequisite for NO release. Having gained an appreciation of the stability and required handling conditions for each set of NO-donors, the compounds were evaluated for their ability to inhibit the proliferation of a panel of ovarian cancer cell lines. The results suggest that subtle chemical modifications to the structure of these NO-donors, in additional to changing the actual type of NO-donating species, can greatly influence their ability to release NO and act as cytotoxic agents.

Preparation and characterization of modified polyethersulfone hollow fiber membranes by blending poly (styrene-alt-maleic anhydride)

In this study, pH-sensitive polyethersulfone (PES) hollow fiber membrane was prepared by blending a copolymer of poly (styrene-alt-maleic anhydride) (PSMA). The PSMA alternating copolymer was synthesized by a traditional synthetic route, and was characterized by Fourier transform infrared spectroscopy (FTIR) analysis, nuclear magnetic resonance (1H NMR) and gel permeation chromatography technique (GPC). The PES/PSMA membrane was then transformed to carboxylic PES/PSMA-H carboxylic membrane using sodium hydroxide solution, by which the anhydride groups were transformed to carboxyl groups, and the modified membranes showed excellent pH-sensitivity and pH-reversibility. Furthermore, the alternating copolymer modified PES hollow fiber membranes showed evident hysteresis of water flux, for which it would take several hours to reach the equilibrium state.

A facile and efficient synthetic method for 4-phenylethynylphthalic anhydride

A novel approach to the synthesis of 4-phenylethynylphthalic anhydride has been described. The target compound was synthesized by Pd/Cu catalyzed Sonogashira coupling reaction between phenylacetylene and 4-bromophthalic acid which was for the first time employed as start material, followed by dehydration of 4-phenylethynylphthalic acid. Compared with traditional synthetic routes, this method provides several advantages such as readily available raw materials, convenient manipulation and high yield. The products were characterized by IR, 1H NMR, 13C NMR, MS and elemental analysis, respectively.

Divergent Synthesis of 2,3,5-Substituted Thiophenes by C-H Activation/Borylation/Suzuki Coupling

C―H activation/borylation has been married with Suzuki coupling to prepare DuP 697 (1) and analogs that would be otherwise difficult to obtain via the traditional synthetic route to 1.

‘On water’: unprecedented nucleophilic substitution and addition reactions with 1,4-quinones in aqueous suspension

Unique nucleophilic substitution and addition reactions of 1,4-quinones in aqueous suspension with aromatic amines, primary aliphatic amines, amino acid, ester of amino acid, heterocyclic amines, hydrazine, amide, and thioethers are described in absence of catalyst against the traditional synthetic routes of these reactions in non-aqueous medium in presence of catalyst.

Selective synthesis of chlorophosphoramidites using ionic liquids

A range of chlorophosphoramidites have been prepared in ionic liquids and compared with material synthesised in molecular solvents. Through the use of ionic liquids as reaction media the moisture sensitivity and impurity issues hampering existing traditional synthetic routes have been eased. Not only can stock chemicals be used without purification, but the reactions may be conducted at room temperature and at high concentrations. Furthermore, reaction times are reduced and rapid addition of reagents is possible whilst retaining tight control over product selectivity. Beyond their role as reaction media, ionic liquids also present a unique storage medium for these highly moisture sensitive chlorophosphoramidites.