One-pot Two-step Process Research Articles

One-pot route to β-adrenergic blockers via enantioselective organocatalysed epoxidation of terminal alkenes as a key step

A convenient and environmentally attractive one-pot two-step process for the synthesis of β-adrenergic blockers via Shi's organocatalytic epoxidation of terminal alkenes and subsequent aminolysis reaction of epoxides with isopropylamine under mild reaction conditions has been developed.

ChemInform Abstract: One‐Pot Multi‐Reaction Processes: Synthesis of Natural Products and Drug‐Like Scaffolds

AbstractReview: [50 refs.

Production of 2,5-Diformylfuran from Biomass-derived Glucose via One-Pot Two-Step Process

As a furan derivative from 5-hydroxymethylfurfural (HMF) or other biomass-based carbohydrates, 2,5-diformylfuran (DFF) is one of the most important platform molecules in the organic chemicals industry. Although it has many potential applications in the future, the production of DFF on a large scale is currently a challenge. As an alternative to the production of DFF from HMF, the target product DFF could be obtained from biomass-derived glucose with a complex catalytic system (AlCl3·6H2O/NaBr and a vanadium compound assisted with molecular oxygen) carried out in N,N-dimethylformamide (DMF). In this research, reactions were conducted in reactors with different capacities. The results showed that DFF yields based on glucose could reach 35 to 48% with almost complete transformation of glucose. This one-pot two-step reaction is characterized by the abundance and low cost of the starting materials and by the elimination of the separation and purification of HMF. This has great potential for applications in the future production of DFF on a large scale after further advancements and optimizations.

One-Pot Multi-Reaction Processes: Synthesis of Natural Products and Drug-Like Scaffolds

One-pot multi-reaction processes involving Overman rearrangements, metathesis cyclizations, and Diels–Alder reactions have been developed for the rapid and efficient synthesis of amino-substituted carbocyclic and heterocyclic compounds. This account describes the development and optimization of these processes, as well as their applications in the synthesis of natural products and drug-like scaffolds. 1 Introduction 2 A One-Pot Overman Rearrangement and Ring-Closing Metathesis Reaction 2.1 Scope and Limitations 2.2 Applications of the One-Pot Two-Step Process 2.3 A Directed Overman Rearrangement and Ring-Closing Metathesis Reaction Process 3 A One-Pot Three-Step Ruthenium(II) Tandem Catalytic Process 3.1 Development and Scope 3.2 A Microwave-Mediated One-Pot Three-Step Process 4 A One-Pot Three-Step Process Involving a Ring-Closing Enyne Metathesis and a Diels–Alder Reaction 4.1 Synthesis of Substrates 4.2 An Unexpected Hydrogen-Bonding-Directed Diels–Alder Reaction 4.3 Application of the Synthesis for C1-Amino-Substituted Indanes and Tetralins 4.4 Development of a Two-Pot Reaction Process 5 Conclusions

A one-pot two-step efficient metal-free process for the generation of PEO-b-PCL-b-PLA amphiphilic triblock copolymers

In an effort to reduce hazardous chemicals, a one-pot two-step process with active bases and inactive salts was developed for the synthesis of high molar mass PEO-block-PCL-block-P(L- or D,L-LA) amphiphilic triblock copolymers. A series of poly(e-caprolactone) (PCL)/poly(L- or D,L-lactide) (P(L- or D,L-LA)) di- and triblock copolymers have been prepared in bulk from metal-free catalytic systems and starting from either 1-pyrenemethanol or poly(ethylene oxide) (PEO) macroinitiator. The controlled generation of such structures was obtained after screening and comparing a wide variety of organic activators. Narrower dispersity characterizing each sample prepared from the PEO macroinitiator were elucidated by theoretical modeling. Finally, the ability of those triblock copolymers to self-associate in water was studied by dynamic light scattering and compared to PEO-b-P(CL-co-LA) copolymers.

One-pot sequential synthesis of isocyanates and urea derivatives via a microwave-assisted Staudinger–aza-Wittig reaction

A fast and efficient protocol for the synthesis of N,N'-disubstituted urea derivatives from alkyl halides and primary or secondary amines has been developed. The synthetic pathway combines nucleophilic substitutions and a Staudinger–aza-Wittig reaction in the presence of polymer-bound diphenylphosphine under 14 bar of CO2 pressure and has been performed in a one-pot two-step process. The protocol has been optimized under microwave irradiation and the scale-up experiment has been conducted under conventional conditions in a Parr reactor. The final compounds were isolated after simple filtration in almost quantitative overall yields which makes this procedure facile and rapid to execute.

Propylene epoxidation with in situ generated H2O2 in supercritical conditions

Several bi-functional materials based on palladium nanoparticles supported onto nanocrystalline titanium silicalite zeolite (Pd@TS-1) were prepared and used as active and reusable catalysts to direct PO production from hydrogen, oxygen and propylene through one-pot two-step combined process. This type of catalysts was able to carry out the consecutive process where palladium nanoparticles catalyzed the formation of H2O2 that was used as intermediate reagent for propylene epoxidation catalyzed by TS-1 nanocrystals, used as supporting active matrix. Influence of supercritical CO2 conditions in batch reactions was evaluated together with the associated effect due to the presence of platinum promoters (Pd(Pt)@TS-1). Other reaction parameters were also considered, such as palladium loading, use of acidity inhibitors and modification of H2/O2/C3 ratio. Reusability studies showed the high stability of the catalysts in consecutive catalytic cycles, their regeneration being possible.

Synthesis of 9‐Oxononanoic Acid, a Precursor for Biopolymers

Polymers based on renewable resources have become increasingly important. The natural functionalization of fats and oils enables an easy access to interesting monomeric building blocks, which in turn transform the derivative biopolymers into high-performance materials. Unfortunately, interesting building blocks of medium-chain length are difficult to obtain by traditional chemical means. Herein, a biotechnological pathway is established that could provide an environmentally suitable and sustainable alternative. A multiple enzyme two-step one-pot process efficiently catalyzed by a coupled 9S-lipoxygenase (St-LOX1, Solanum tuberosum) and 9/13-hydroperoxide lyase (Cm-9/13HPL, Cucumis melo) cascade reaction is proposed as a potential route for the conversion of linoleic acid into 9-oxononanoic acid, which is a precursor for biopolymers. Lipoxygenase catalyzes the insertion of oxygen into linoleic acid through a radical mechanism to give 9S-hydroperoxy-octadecadienoic acid (9S-HPODE) as a cascade intermediate, which is subsequently cleaved by the action of Cm-9/13HPL. This one-pot process afforded a yield of 73 % combined with high selectivity. The best reaction performance was achieved when lipoxygenase and hydroperoxide lyase were applied in a successive rather than a simultaneous manner. Green leaf volatiles, which are desired flavor and fragrance products, are formed as by-products in this reaction cascade. Furthermore, we have investigated the enantioselectivity of 9/13-HPLs, which exhibited a strong preference for 9S-HPODE over 9R-HPODE.

From Biomass to Chemicals: Synthesis of Precursors of Biodegradable Surfactants from 5‐Hydroxymethylfurfural

The selective acetalization of 5-hydroxymethylfurfural (HMF) with long-chain alkyl alcohols has been performed to obtain precursors of molecules with surfactant properties. If direct acetalization of HMF with n-octanol is performed in the presence of strong acids (homogeneous and heterogeneous catalysts), an increase in etherification versus acetalization occurs. Beta zeolite catalyzes both reactions. However, if the acidity of a zeolite (Beta) was controlled by partial exchange of H(+) with Na(+), the dioctyl acetal of HMF can be achieved in 95% yield by transacetalization. It is possible to achieve a high yield in a very short reaction time through a two-step one-pot process, which includes the synthesis of the dimethyl acetal of HMF followed by transacetalization with n-octanol. The one-pot process could be extended to other alcohols that contain 6-12 carbon atoms to afford 87-98% yield of the corresponding dialkyl acetal with a selectivity higher than 96%. The optimized catalyst with an adequate Na content (1.5NaBeta) could be recycled without loss of activity or selectivity.

One-pot synthesis of poly(l-lactide) multi-arm star copolymers based on a polyester polyol macroinitiator

Using a hyperbranched poly(glycolide) (hbPGA) macroinitiator the synthesis of poly(l-lactide) (PLLA) multi-arm star polyesters has been achieved via a core-first approach. The star-shaped copolymers were prepared in a one-pot two-step process via Sn(Oct)2-catalyzed ring-opening polymerization (ROP) conducted in the melt. Complete conversion of the end groups of the hbpolyglycolide polyester polyols is ensured by the reactive primary hydroxyl termini. By adjusting the monomer/initiator ratio a series of star copolymers with varying PLLA arm length has been obtained with molecular weights in the range of 1500 to 10,000 g/mol (SEC). The successful coupling of the PLLA arms to the hbPGA core has been confirmed via detailed 1D and 2D NMR spectroscopy. Because of the different hydrodynamic volume of the star polymers in contrast to their linear analogs, the weight-average molecular weight (Mw) was determined both by SEC and static light scattering (SLS). The star-shaped poly(lactide)s reveal different thermal properties in comparison to linear poly(lactide) homopolymers.

ChemInform Abstract: Rhodium(III)‐Catalyzed Intermolecular Direct Amination of Aromatic C—H Bonds with N‐Chloroamines.

AbstractThe one‐pot two‐step process without isolation of the chloroamines succeeds with comparable yields, cf.(XIX).

Straightforward assembly of phenylimidazoquinoxalines via a one-pot two-step MCR process.

An efficient multicomponent-based methodology providing a new entry into a medicinally important complex heterocyclic core is presented. The strategy is very general and able to endow target compounds with the highest possible number of diversity points. Notably, four new chemical bonds and two aromatic rings are formed in a one-pot fashion.

Glucose and temperature dual-responsive monodispersed hollow nanospheres via facile one-pot two-step process

Novel glucose and temperature dual-responsive monodispersed hollow nanospheres have been successfully fabricated via the one-pot two-step “self-removing” approach based on the consecutive radical (co)polymerization. Their diameter became smaller and their shells became porous with the increase of the feeding content of the glucose-responsive monomer (3-acrylamidophenylboronic acid (APBA)). The hollow nanospheres are glucose responsive at a pH value near the pKa (8.86) of the phenylboronic acid (PBA) derivative, with a swelling degree proportional to the concentration of glucose. Their volume phase transition temperature (VPTT) was obviously lower than that of the poly(N-isopropylacrylamide) (PNIPAM) hollow nanospheres and its transition temperature range also became wider.

Role of block copolymer surfactant on the pore formation in methylsilsesquioxane aerogel systems

Transparent and low-density methylsilsesquioxane (MSQ, CH3SiO1.5) aerogels can be obtained solely from methyltrimethoxysilane (MTMS) by a one-pot two-step process under the co-presence of surfactant. In the present study, we have systematically investigated the effects of the molecular structure of triblock copolymer-type nonionic surfactants PEO-b-PPO-b-PEO (PEO and PPO denote poly(ethylene oxide) and poly(propylene oxide) units, respectively) on the properties of the resultant MSQ aerogels. Macroscopic phase separation of hydrophobic MSQ networks from polar solvent occurs when no surfactant is employed, which results in macroporous opaque aerogels. In contrast, a co-presence of appropriate surfactant effectively suppresses the phase separation and yields transparent aerogels after supercritical drying. By employing various surfactants having different molecular weight and PO/EO ratio, the mechanism of suppression of phase separation or pore formation is discussed in detail. In situ1H NMR suggests that the PO units of surfactant interact with the hydrophobic MSQ network enriched with methyl groups and make the MSQ network hydrophilic by extending EO chains toward the aqueous solvent in the late phase of gelation, until which hydrogen bonding dominates between the Si-OH groups of polymerizing MSQ and the ether oxygens of the EO unit. Through the comprehensive understanding of the role of surfactant, the strategy for rational design of MSQ aerogels materials has become developable.

Novel one-pot process for the synthesis of 1,3-thiazoles via organocatalysed epoxidation of nitro-olefins

A facile one-pot two-step process for the synthesis of 1,3-thiazole heterocycles via organocatalytic epoxidation of nitro-olefins with the t-BuOOH/DBU system, and subsequent reaction of α-nitro-epoxides with thioamides under mild conditions has been developed.

Aromatic A-ring analogues of orobanchol, new germination stimulants for seeds of parasitic weeds

Strigolactones are signaling compounds in plants of increasing importance. In this paper the focus is on their activity as germinating agents for seeds of parasitic weeds. The syntheses of aromatic A-ring analogues of the germination stimulant orobanchol have been described. Starting substrate is the ABC unit of the stimulant GR24. Oxidation at the C-4 position gives a 4-oxo derivative which on subsequent reduction produces two C-4 epimeric alcohols, syn and anti in a ratio of 82 : 3. For practical access of the C-4 anti alcohol, the predominant syn epimer is inverted by a Mitsunobu procedure. The anti C-4 alcohol is then coupled with the D-ring in a one-pot two-step process involving a formylation and a reaction with bromobutenolide to give a mixture of the diastereomeric aromatic A-ring analogues of orobanchol. In contrast, the syn C-4 alcohol cannot be coupled directly with the D-ring. Protection of the C-4 syn OH is a prequisite. The best protecting function is the SEM group as deprotection after coupling with the D-ring can then readily be achieved. The structures of these new analogues have been ascertained by X-ray analyses. Both diastereomers of the C-4 syn as well as the C-4 anti orobanchol analogues have been tested as germination agents of seeds of Striga hermonthica and Orobanche ramosa. In addition, the acetates of both epimeric C-4 alcohols have been prepared and tested. Both diastereomers of the 4-oxo derivative have been prepared and bioassayed as well. The bioassays reveal that the diastereomers having the natural relative configuration are most active. The data also suggest that hydrogen bonding is not an important factor in the binding of the stimulant molecules in the receptor.

Bridging homogeneous and heterogeneous catalysis with MOFs: “Click” reactions with Cu-MOF catalysts

Various copper-containing MOF catalysts, i.e., [Cu(2-pymo) 2], [Cu(im) 2], [Cu 3(BTC) 2] and [Cu(BDC)] (2-pymo: 2-hydroxypyrimidinolate; im: imidazolate; BTC: benzene tricarboxylate; BDC: benzene dicarboxylate), have shown to be highly active and fully regioselective for “click” reactions (1,3-dipolar cycloaddition reactions). The activity of the best MOF catalyst is comparable to homogeneous Cu catalysts. It has been found that the activity of Cu changes with the organic linker in the MOF, being those containing CuN 4 more active than CuO 4 centers. The controlling step of the reaction is the formation of an adduct between Cu and phenylacetylene. When using MOF catalysts, the use of alcohol or alcohol–water solvents is not required, and the catalysts can be fully recovered and recycled. Finally, Cu-MOF catalysts allow to design a one-pot two-step process, where the azide is formed “in situ” and reacted immediately with phenylacetylene.

Practical One-Pot Two-Step Protocol for the Microwave-Assisted Synthesis of Highly Functionalized Rhodanine Derivatives

A fast and efficient protocol for the generation of substituted 5-arylidene rhodanines in a sequential one-pot two-step process combining the "Holmberg method" and the Knoevenagel condensation under microwave-assisted conditions has been developed. The final compounds 11a-k have been obtained in high yield and purity after a simple precipitation from methanol, making this procedure facile, practical, and rapid to execute.

(R)-1-Arylethanols from aryl iodides through a two-step one-pot enantioselective chemoenzymatic process

(R)-1-Arylethanols have been prepared in high to excellent overall yields through a two-step one-pot process that involves the palladium-catalyzed conversion of aryl iodides into the corresponding acetophenones, in the presence of acetic anhydride, EtN(i-Pr)2, LiCl, and Pd2(dba)3 followed by an enantioselective reduction step catalyzed by the alcohol dehydrogenase enzyme from Lactobacillus brevis.

Synthesis of Methacrylate-Based Functional Monomers via Boron Ester Acidolysis and Their Polymerization

A new method is presented for the synthesis of functional methacrylate ester monomers. In this method, boron esters of appropriate alcohols were reacted with methacrylic acid to give the corresponding methacrylic ester monomers. The monomers N,N-dimethylaminoethyl methacrylate (DAMA), 2-chloroethyl methacrylate (CEMA), 2-bromoethyl methacrylate (BEMA), 2-methoxyethyl methacrylate (MEMA) and butyl methacrylate (BMA) were prepared in a laboratory scale by a two-step one-pot process. In the first step, the corresponding boron esters were formed by azeotropic removal of water. Subsequently, addition of methacrylic acid and heating at 140–160°C in the presence of pyridine resulted in acidolysis of the boron esters, yielding the functional methacrylate ester monomers in acceptable yields (41–71%). The monomers obtained were characterized by 1H-NMR and FT-IR spectra after isolation and purification. Their polymerizability was also demonstrated.