One-pot Multistep Reaction Research Articles

New one-pot multistep process with multifunctional catalysts: decreasing the E factor in the synthesis of fine chemicals

The synthesis of a series of fine chemicals (4-(4-methoxyphenyl)-2-butanone, 4-(6,6-dimethylbicyclo[3,1,1]hept-2-en-2-yl)-2-butanone, and 2-cyclopentylcylopentanone) has been performed through a simple process that involves one-pot multi-step reactions (condensation–dehydration–reduction) using multifunctional base–acid-metal catalysts. The E factor for the specific process, as well as for the global process that includes the manufacturing of the reactants, has been calculated and compared with those obtained using conventional methods. In various cases, it is demonstrated that by means of process intensification with multifunctional solid catalysts, it is possible to decrease the E factor by one order of magnitude or more with respect to any of the manufacturing routes reported to date.

New route for the synthesis of benzimidazoles by a one-pot multistep process with mono and bifunctional solid catalysts

One-pot multistep reactions involving a new environmentally friendly catalytic procedure have been developed for the synthesis of benzimidazoles. Benzimidazole derivatives with biological and pharmaceutical interest have been prepared by a one-pot four step process with a solid catalyst containing basic and oxidation sites. The four steps refer to: (a) oxidation of the alcohol; (b) cyclocondensation of the aldehyde formed with ortho-phenylenediamines, (c) oxidation of the carbon–nitrogen bond, (d) N-alkylation reaction. The process is illustrated by the synthesis of 1,2-disubstituted benzimidazole derivative with antiviral activity.

Molecular Recognition of Redox-Switchable Bis-Crown Moieties Assembled on a Dicobalt Complex

A new dinuclear complex of cobalt(III) having double bis-crown moieties (1) was synthesized in a one-pot multistep reaction between the dinucleating ligand (H(2)L(1)), Co(OAc)(2) x 4 H(2)O, and 4'-aminomethylbenzo-15-crown 5-ether under aerobic conditions. The complex was characterized by UV-vis, IR, NMR, and CSI-mass spectroscopies, and the axial coordination of the 4'-aminomethylbenzo-15-crown 5-ether on both cobalt centers was confirmed. The bis-crown moieties of 1 acted as a potassium ion binding site with a large association constant (K) of 1.97 x 10(5) M(-1) (1:1) caused by the preorganized bis-crown structure. Solvent extraction of K(+) (potassium picrate) with 1 was investigated by UV-vis and NMR, and the extracted K(+) was quantified by an atomic absorption/flame emission spectrophotometer. The cyclic voltammogram of 1 showed irreversible redox waves at -0.57 V and +0.16 V versus Ag/AgCl in DMF, which are ascribed to the Co(III) and Co(II) redox couple. The large peak separation (Delta0.73 V) of this redox couple indicates the association and dissociation of the axial amine on the cobalt centers. The irreversible reduction peak of 1 at -0.57 V was shifted in the positive direction by 80 mV in the presence of the potassium ion, showing the complexation of 1 with the potassium ion. The reversible formation and decomposition of the double bis-crown moieties in 1 caused by the electrical stimulus were also investigated by thin-layer UV-vis spectroelectrochemistry. The switching of the double bis-crown structure of 1 was established over four trials with response to electrical energy.

Total diastereoselectivity in the one-pot multistep reaction of ( RS)-(+)-{[(4-methylphenyl)sulfinyl]methyl}-1-oxa-4-azaspiro[4.5]dec-3-ene and E-methyl cinnamate. An approach to (2 S,4 S,5 R,6 R)-2-(hydroxymethyl)-4,6-diphenyl-1-azabicycle[3.3.1]nonane

The base-mediated reaction of enantiomerically pure α-sulfinylketimine (+)- 1 with ( E)-methyl cinnamate afforded (+)- 5a in a one-pot procedure with complete diastereoselectivity. A sole diastereomer of the eight possible ones was isolated which revealed the stereocontrol of the chiral sulfinyl group in the construction of the three new stereogenic centres. The absolute configuration of stereocentres introduced in (+)- 5a was assigned on the basis of 1H NMR data and a single X-ray structure.

Positional Assembly of Enzymes in Polymersome Nanoreactors for Cascade Reactions

In a good position: Nanoreactors can be constructed by the controlled positioning of glucose oxidase (GOX) and horseradish peroxidase (HRP) within the central water pool and block-copolymer membrane of polymersomes. A one-pot multistep reaction sequence is performed with the nanoreactor in combination with free Candida antarctica lipase B (CALB) in the bulk solution (see picture; ABTS: 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)).

Synthesis of 3-O-Acylated Epicatechin Derivatives via Sequential One-Pot Multi-Step Reactions

An effective approach for the synthesis of epicatechin derivatives based on sequential one-pot multi-step reactions is described. Reductive etherification of the disulfanyl derivative was promoted with a catalytic amount of TfOH, providing the cis-substituted benzopyran derivative in a stereoselective manner.

Expanding the Utility of One-Pot Multistep Reaction Networks

Multistep sequential organic transformations were realized in a one-pot procedure by a combination of acid, base, and hydrogenation catalysts which were immobilized on polymer beads, ferrite nanoparticles, and a membrane, respectively. Thus, the combination of a resin-supported acidic catalyst (green), a nanoparticle-bound basic catalyst (blue) and a membrane-enclosed Pt/Al2O3 catalyst (yellow) promoted the tandem deacetalization-Knoevenagel hydrogenation reaction of benzaldehyde dimethylacetal (A) in the presence of water, malononitrile, and H2 at room temperature for 49 h (1 h at 1 atm, and 48 h at 1000 psi) to give D in 78% yield in a one-pot reaction. After the reaction, the three catalysts were readily separated and recovered. Pt/Al2O3 was recovered with a membrane, resin-supported acidic catalyst and the nanoparticle-bound basic catalyst were recovered by magnetic decantation and gravimetric decantation, respectively.

Transformation of a spirobarbituric acid via aminobarbituric acid‐hydantoin rearrangement

Abstractmagnified imageA successful application of the aminobarbituric acid‐hydantoin rearrangement to produce a bicyclic carbamoylhydantoin from an intermediate spirobarbituric acid is reported. 7a‐Phenylcarbamoyl‐tetrahydro‐1H‐pyrrolo[1,2‐c]imidazole‐1,3(2H)‐dione (8) was obtained in a one‐pot multistep reaction of 1‐acetyl‐2,2‐bis(ethoxycarbonyl)pyrrolidine (5) and phenylurea in the presence of sodium ethoxide. Under less severe conditions, 5 and phenylurea were reacted to afford 1‐acetyl‐7‐phenyl‐triaza[4,5]decane‐6,8,10‐trione (6). The structural elucidation of the bicyclic hydantoin 8 and the spirobarbituric acid 6 was based on relevant nmr signals in accordance with those of reference compounds, i.e. monocyclic hydantoins 4a,b and acetamidobarbituric acids 2a‐c. The latter compounds were newly prepared from diethyl acetamidomalonates 1 and phenylurea.

Epoxidation and hydroxlation of rubber seed oil: one‐pot multi‐step reactions

AbstractEpoxidized and hydroxylated rubber seed oils were prepared by peroxyformic acid generated in situ by reacting formic acid and hydrogen peroxide with RSO, a renewable resource. The structural and physico‐chemical properties of RSO have been determined. The fatty acid composition showed a high content of polyunsaturated fatty acids. The modified products were characterized with regard to their structure and properties. The findings of this study revealed that both hydroxylated and epoxidized RSO can be prepared by one‐pot multi‐step reactions.

Use of Thiazoles in the Halogen Dance Reaction: Application to the Total Synthesis of WS75624 B.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Total Synthesis of (+)‐Xyloketal D, a Secondary Metabolite from the Mangrove Fungus Xylaria sp.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Palladium on activated carbon: a valuable heterogeneous catalyst for one-pot multi-step synthesis

Pd on activated carbon (Pd/C) is demonstrated to be active and selective as one single catalyst in a series of one-pot multi-step reactions. The carefully chosen Pd/C catalysts were successfully applied in domino and tandem reactions involving (1) Heck reactions and hydrogenations for the synthesis of (a) dibenzyl and (b) 2-styryl-phenylamine, (2) Sonogashira coupling and intramolecular heteroannulation to form indole ring systems, and (3) Heck and Suzuki coupling reactions to produce 4-styryl-biphenyl. Total yields between 72 and 93% could be achieved. All reaction steps were performed with one and the same Pd/C catalyst, solvent, and additives. Temperature and pressure were adjusted as necessary. The order of the different reactions, the consecutive addition of educt(s) and optimization of reaction conditions was found to be crucial.

Use of thiazoles in the halogen dance reaction: application to the total synthesis of WS75624 B.

The total synthesis of the pyridine-thiazole-containing natural product WS75624 B (1) is described. This synthesis proceeds via the Stille coupling of appropriately functionalized pyridine and thiazole components, and this paper details our studies on the use of the halogen dance reaction to prepare the desired thiazole. Various halogen dance reactions on thizoles are described, including a novel one-pot multistep reaction in which 2-bromothiazole is treated with LDA in the presence of a silyl chloride at -78 degrees C and quenched with an electrophile to provide the highly functionalized thiazole derivatives 27.

Total synthesis of (+)-xyloketal D, a secondary metabolite from the mangrove fungus Xylaria sp.

(+)-Xyloketal D was prepared in a one-pot multistep domino reaction by heating optically active 5-hydroxy-4-methyl-3-methylenepentan-2-one (R) in toluene with 2,4-dihydroxyacetophenone. The absolute configuration of the natural product was confirmed by preparation of the starting enone from a lactone of established absolute configuration.

Lipopolymers for Surface Functionalizations. 1. Synthesis and Characterization of Terminal Functionalized Poly(N-propionylethylenimine)s

By a direct combination of the fast initiation technique and a selective quantitative termination reaction, terminally functionalized poly(N-propionylethylenimine)s (PPEIs) were prepared by cationic living ring-opening polymerization of 2-ethyl-2-oxazoline in a one-pot multistep reaction. The chain ends of the linear hydrophilic polymers were functionalized with different lipophilic moieties (methyl-, n-hexadecyl- (C16-), and 1,2-O-diooctadecyl-sn-glyceryl- ((C18)2-)) and a monofunctional silane coupling group. Varying the length of the double functionalized hydrophilic PPEI chain (n = 10, 20), surface active amphiphilic lipopolymers of controlled hydrophilic lipophilic balance could be obtained in high overall yields. The spectroscopic, chromatographic, and mass spectrometric characterization confirmed that each reaction step was nearly quantitative and narrow molecular weight distributions (Mw/Mn = 1.07−1.24) of all polymers.

Nanocomposites by Surface-Initiated Living Cationic Polymerization of 2-Oxazolines on Functionalized Gold Nanoparticles

End-functionalized 3D self-assembled monolayers (SAMs) on gold nanoparticles were used to initiate the living cationic ring-opening polymerization directly on gold nanoparticle surfaces (grafting-from technique). In this manner, dense polymer brushes were prepared in a one-pot multistep reaction. ER FTIR spectroscopy confirms the successful polymerization as well as the introduction of a terminal functional group. The resulting gold/polymer nanocomposite was very stable. The combination of a grafting-from reaction resulting in polymer brush-type shells of linear macromolecules and the introduction of a terminal mesogen by means of a quantitative termination resulted in an amphiphilic core-shell material with a well-defined hydrophilic/lipophilic balance (HLB). Ex-situ kinetic studies of the polymerization of 2-phenyl-2-oxazoline using FTIR spectroscopy and MALDI TOF mass spectrometry resulted in a linear relationship between the time and degree of polymerization of the grafted polymer. This as well as the successful end-functionalization by termination with secondary amines corroborates our view of a well-defined living polymerization mechanism.