Henry Condensation Research Articles

Active Base Hybrid Organosilica Materials based on Pyrrolidine Builder Units for Fine Chemicals Production

AbstractThe catalytic activity of “pyrrolidine type” fragments included or anchored in the mesoporous silica supports or polymeric frameworks have been fully reported for enantioselective transformation. Nevertheless, low attention was focused on their catalytic abilities to perform base‐catalyzed reaction. Accordingly, hybrid materials including pyrrolidine fragments in the mesoporous silica supports were prepared following different synthesis methods, such as micellar and fluoride sol‐gel routes in absence of structural directing agents. Their great catalytic performance was explored for various base‐catalyzed reactions to the formation of C−C bond through Knoevenagel, Claisen‐Schmidt and Henry condensations under microwave irradiation. The benefits of microwave irradiation combined with suitable catalytic properties of pyrrolidine hybrid materials with strong base sites and high accessibility to active centers, allowed carrying out successfully base‐catalyzed condensation reactions for the production of fine chemicals. Moreover, the hybrid catalyst exhibited high selectivity and good stability over different catalytic cycles contributing to environmental sustainability.

High performance of ultrasonic-assisted synthesis of two spherical polymers for enantioselective catalysis

Chiral polymers have aroused great attention in among chiral supramolecular materials based on their features. Herein, for the first time, the synthesis of chiral polymeric composites (CMNPs/1,4-Zbtb & 1,3-Zbtb) have been reported with entrapment through three strategies: ultrasonic irradiation, solvothermal, and mechanical stirring. According to the obtained results, it is found that ultrasound-assisted synthesis can be considered as an inexpensive and efficient method than the others, from the point ofviewof energy and time consuming. In this strategy, encapsulation of chiral magnetic nanoparticles (CMNPs) by using tetrazole-based polymers (Zbtbs) happens, in-situly. These chiral sphere-like inorganic–organic polymers can be considered as core and shell composites with catalytic activity due to their acidic (semi unsaturated Zn: open metal sites) and basic (abundant basic nitrogens) centers. In these structures, the unprecedented chirality induction can happen from the core to shell by non-covalent interaction, easily. They could catalyze symmetric oxidation and asymmetric henry condensation to give chiral β-nitroalkanol. Circular dichroism and chiral gas chromatography were used to characterize the produced enantiomers. These chiral polymeric materials can be considered as unique acid-base bifunctional catalysts with efficient properties such as high stability, enantiomeric excess, enantioselectivity to the main product, and protecting from CMNPs leaching.

Exploring the copper binding ability of Mets7 hCtr-1 protein domain and His7 derivative: An insight in Michael addition catalysis.

Mets7 is a methionine-rich motif present in hCtr-1 transporter that is involved in copper cellular trafficking. Its ability to bind Cu(I) was recently exploited to develop metallopeptide catalysts for Henry condensation. Here, the catalytic activity of Mets7-Cu(I) complex in Michael addition reactions has been evaluated. Furthermore, His7 peptide, in which Met residues have been substituted with His ones, was also prepared. This substitution allowed His7 to coordinate Cu (II), with the obtainment of a stable turn conformation as evicted by CD experiments. His7-Cu (II) proved also to be a better catalyst than Mets7-Cu(I) in the addition reaction. In particular, when the substrate was the (E)-1-phenyl-3-(pyridin-2-yl)prop-2-en-1-one, a conversion of 71% and a significative 58% of e.e. was observed.

Nanometer-thick films of antimony oxide nanoparticles grafted on defective graphenes as heterogeneous base catalysts for coupling reactions

Films of few-layers defective N-doped or undoped graphene (10–15 nm) containing antimony oxide nanoparticles (15–30 nm) have been prepared on quartz by pyrolysis of alginate or chitosan adsorbing Sb(OAc)3. XPS shows that the prevalent Sb oxidation state is +III, while thermoprogrammed CO2 desorption shows that these films exhibit basic sites. These thin films have used as basic catalysts to promote the Michael addition of active methylene compounds and the Henry condensation. These results have been rationalized by DFT calculations that have shown that undercoordinated or two-fold coordinated oxygen atoms on SbOx clusters can act as basic sites, providing a wide range of basic strength.

Ultrasonic-Assisted Linker Exchange (USALE): A Novel Post-Synthesis Method for Controlling the Functionality, Porosity, and Morphology of MOFs.

The introduction of organic ligands into metal-organic frameworks (MOFs) with a specific topology and that cannot be attained by direct synthesis is a big challenge. To meet this challenge, different ligand exchange/incorporation methods have been employed. Here, a new method, called ultrasonic-assisted linker exchange (USALE), has been developed to overcome the above-mentioned problems. USALE is a novel method for ligand exchange based on the use of ultrasonic waves. The temperature and pressure caused by the USALE method in microscopic zones are so intense that the linker exchange process is much faster than with other methods. In addition to saving time during synthesis, the use of the USALE method leads to a higher surface area and pore volume compared with other methods such as solvent-assisted linker exchange (SALE). In this way, improved gas adsorption capacity has been achieved for daughter frameworks synthesized by the USALE method. By using the USALE method, we have transformed a nonporous and easy-to-synthesize TMU framework ([Zn(OBA)(BPDB)0.5]n⋅2DMF (TMU-4), in which H2OBA=4,4'-oxybis(benzoic acid) and BPDB=1,4-di(4-pyridyl)-2,3-diaza-1,3-butadiene) into another porous framework ([Zn(OBA)(H2DPT)0.5]n⋅DMF (TMU-34), in which H2DPT=3,6-di(4-pyridyl)-1,4-dihydro-1,2,4,5-tetrazine) that otherwise requires a relatively long time to synthesize. In addition to reducing the synthesis time for TMU-34 (in comparison with both direct sonochemical synthesis and the indirect SALE method), the data obtained revealed that the daughter TMU-34 framework synthesized by the USALE method has a higher surface area and accessible pore volume than TMU-34 frameworks synthesized by SALE and direct methods. The application of SALE-TMU-34 and USALE-TMU-34 in a catalytic Henry condensation reaction and Congo Red adsorption experiments showed that the higher porosity of USALE-TMU-34 leads to a higher turn-over frequency and saturation capacity compared with SALE-TMU-34.

Efficient synthesis of (−)-(R)- and (+)-(S)-rolipram

A novel, efficient and protecting group free enantioselective synthetic approach of (−)-(R)-1 and (+)-(S)-rolipram 2 is described employing the organocatalyzed asymmetric Michael addition, Henry condensation, Wittig olefination and reductive lactamization reactions as key steps.

Direct synthesis and application of bridged diamino-functionalized periodic mesoporous organosilicas with high nitrogen contents

Bridged diamino-functionalized periodic mesoporous organosilicas [BD-PMO(Et), Et = ethyl] materials were synthesized directly by co-condensation of 2-bis (triethoxysilyl)ethane (BTEE) and 1,4-bis[3-(tirmethoxysilyl)-propyl]ethylenediamino (BTMSEN) under acidic conditions with pluronic triblock copolymer P123 as a template. The nitrogen content in BD-PMO(Et) could be adjusted up to 40% without disturbing the ordered mesoporous structure. These materials were proved to be effective heterogeneous catalysts for the liquid-phase reactions such as Knoevenagel and Henry condensations as well as in the intermolecular cross-double-Michael addition reaction between α-methyl-β-nitrostyrene and α, β-unsaturated ketone. They exhibited comparable catalytic activities with homogeneous catalyst piperazine and can be reused for several times without any negative environmental impact.

Chemoselective Henry Condensations Catalyzed by Artificial Carboligases.

The promiscuity of de novo designed enzymes provides a privileged platform for diverse abiological reactions. In this work, we report the first example of a nitroolefin synthase that catalyzes the Henry condensation between aromatic aldehydes and nitromethane. Significant catalytic activity was discovered in the computationally designed and evolved carboligase RA95.5-8, and mutations around the active site were shown to improve the reaction rate, demonstrating the potential to optimize the enzyme by directed evolution. This novel nitroolefin synthase could participate in complex biological cascades, whereby the highly tunable chemoselectivity could afford useful synthetic building blocks.

Cis-2,5-Diaminobicyclo[2.2.2]octane, a New Chiral Scaffold for Asymmetric Catalysis.

Catalysis of widely used chemical transformations in which the goal is to obtain the product as a pure enantiomer has become a major preoccupation of synthetic organic chemistry over the past three decades. A large number of chiral entities has been deployed to this end, many with considerable success, but one of the simplest and most effective catalytic systems to have emerged from this effort is that based on a chiral diamine, specifically trans-1,2-diaminocyclohexane. While there have been attempts to improve upon this scaffold in asymmetric synthesis, few have gained the recognition needed to take their place alongside this classic diamine. The challenge is to design a scaffold that retains the assets of trans-1,2-diaminocyclohexane while enhancing its intrinsic chirality and maximizing the scope of its applications. It occurred to us that cis-2,5-diaminobicyclo[2.2.2]octane could be such a scaffold. Synthesis of this diamine in enantiopure form was completed from benzoic acid, and the (1R,2R,4R,5R) enantiomer was used in all subsequent experiments in this laboratory. Condensation of the diamine with various salicyl aldehydes generated imine derivatives which proved to be excellent "salen" ligands for encapsulation of transition and other metals. In total, 12 salen-metal complexes were prepared from this ligand, many of which were crystalline and three of which, along with the ligand itself, yielded to X-ray crystallography. An advantage of this ligand is that it can be tuned sterically or electronically to confer specific catalytic properties on the salen-metal complex, and this feature was used in several applications of our salen-metal complexes in asymmetric synthesis. Thus, replacement of one of the tert-butyl groups in each benzenoid ring of the salen ligand by a methoxy substituent enhanced the catalytic efficiency of a cobalt(II)-salen complex used in asymmetric cyclopropanation of 1,1-disubstituted alkenes; the catalyst was employed in an improved synthesis of the cyclopropane-containing drug candidate Synosutine. Reduction of the pair of imine functions of the ligand to secondary amines permitted formation of a copper(I)-salen complex that catalyzed asymmetric Henry ("nitroaldol") condensation with excellent efficiency; this catalyst was applied in an economical synthesis of three drugs of the "beta-blocker" family including (S)-Propanolol. Chromium(II) and chromium(III) complexes were prepared from our bicyclooctane-salen ligand bearing a pair of tert-butyl groups in each benzenoid ring. These complexes were found to catalyze, respectively, enantioselective formation of homoallylic alcohols from Nozaki-Hiyama-Kishi allylation of aromatic aldehydes and dihydropyranones from hetero-Diels-Alder cycloaddition. Plausible reaction models emerging from knowledge of the absolute configuration of products from each of these reactions place the metal-coordinated substrate in a quadrant beneath the bicyclooctane scaffold so that one face of the substrate is blocked by an aryl ring of the salen ligand while the opposite face is left open to attack. The consistent and predictable stereochemical outcome from reactions catalyzed by salen-metal complexes derived from our diaminobicyclo[2.2.2]octane scaffold adds a valuable new dimension to asymmetric synthesis.

Tunable acid–base bifunctional catalytic activity of FeOOH in an orthogonal tandem reaction

In this report, we have explored the acid–base bifunctional catalytic activity of iron oxohydroxides (FeOOH) by catalyzing deacetalization and Henry condensation reactions successively in a single pot.

ChemInform Abstract: Domino Reactions for the Synthesis of Various α‐Substituted Nitro Alkenes.

AbstractThe synthesis of a variety of 2‐nitroallylic alcohols (VI), α‐nitro‐α,β‐unsaturated carbonyl compounds (III)/(IV) and (VIII)/(IX) is presented, involving a domino Henry condensation—dehydration—MBH reaction of β‐nitroethanol as well as α‐nitrocarbonyl compounds with aromatic and aliphatic aldehydes.

Straightforward synthesis of nitroolefins by microwave- or ultrasound-assisted Henry reaction

β-Nitroalcohol or nitroethylene derivatives can be obtained from aryl aldehydes and nitromethane under Henry condensation conditions. We present a new modification using microwave irradiation or ultrasound as the energy source. Microwave irradiation allowed a novel one-pot synthesis of nitroolefins from aryl aldehydes using ammonium acetate as a catalyst without solvent. Different reaction conditions, such as base, solvent, and reaction time were studied. Only small amounts of β-hydroxyl nitro compounds were isolated, using microwave irradiation for less than 25 min. In contrast, the use of ultrasound increased the yield of the nitroalcohols.

ChemInform Abstract: A Practical Route for the Preparation of Aromatic trans‐β‐Nitroolefins

Abstractvia an effective variation of the Henry condensation

ChemInform Abstract: The Henry Condensation Under High Pressures. Part 2. Influence of the Nature of the Aromatic Aldehyde and the Pressure on the Yield of the . omega.-Nitrostyrenes and Side Reactions.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Decoration of chitosan microspheres with inorganic oxide clusters: Rational design of hierarchically porous, stable and cooperative acid–base nanoreactors

One of the fundamental enzymatic catalyst assets, which is the most difficult to engineer in synthetic systems, is the coexistence of multifunctional sites and their synergetic cooperation. In this work, an efficient approach toward cooperative acid–base materials using natural matrices is proposed. Taking advantages from chitosan polysaccharide as nano-assembling system and on the supercritical drying technique to preserve their porosity, the mutual interactions between different glucosamine units and the Lewis acidic precursors (Ti, Zr, Al, Sn) allowed the preparation of hierarchically porous microspheres in which well-separated amino groups from chitosan are replicated with highly dispersed acidic inorganic oxides. This decoration at the nano-scale entails a notable improvement on the hydrothermal stability of the resulting organic–inorganic hybrid materials. The resulting acid–base hybrid materials are assessed for three carbon–carbon forming reactions (Henry condensation, Michael addition and jasminaldehyde synthesis) and systematically compared to the pure acidic inorganic oxide and basic chitosan microspheres. The bifunctional materials displayed interesting catalytic activity and selectivity, with respect to monofunctional ones, witnessing thus on the cooperative effect attainable in chitosan@inorganic oxide microspheres.

Improving Catalytic Activity by Synergic Effect between Base and Acid Pairs in Hierarchically Porous Chitosan@Titania Nanoreactors

The beneficial effect of the bifunctional character of the chitosan@titania hybrid in heterogeneous catalysis was elucidated: considering a prototypical Henry condensation, Michael addition, and Jasminaldehyde synthesis, the cohabitation of a basic site (NH(2)) and an acidic site (Ti) in the same reactor provided clear activity and selectivity enhancements, with respect to the monofunctional acidic titania and basic chitosan counterparts.

Regio- and Stereospecific Syntheses and Nitric Oxide Donor Properties of (E)-9- and (E)-10-Nitrooctadec-9-enoic Acids

[reaction: see text] Nitrated fatty acids act as endogenous peroxisome proliferator-activated receptor gamma (PPARgamma) ligands and nitric oxide (NO) donors. We describe the first specific preparation of the two regioisomers of nitrooleic acid, (E)-9-nitrooctadec-9-enoic acid (1) and (E)-10-nitrooctadec-9-enoic acid (2), from cis-cyclooctene and monomethyl azelate, respectively. These syntheses rely upon a Henry condensation between a nine-carbon nitro component and a nine-carbon aldehyde. Preliminary chemiluminescence NO detection studies reveal the ability of these nitrated fatty acids to release NO.

Henry condensations with 4,6- O-benzylidenylated and non-protected d-glucose and l-fucose via DBU-catalysis

Mechanistic intermediates, and thermodynamically favored side products, in the Henry condensations of partially protected and non-protected pyranoses with a free anomeric hemiacetal function with nitromethane in various solvents for the kinetically controlled syntheses of C-glycopyranosides in the presence of DBU/molecular sieve catalyst system were identified.

Synthesis of the bisbenzannelated spiroketal core of the γ‐rubromycins. The use of a novel Nef‐type reaction mediated by Pearlman’s catalyst

The synthesis of the bisbenzannelated spiroketal core 6 of γ-rubromycin 1 from the substituted nitrostyrene 20 was achieved by using a novel Nef-type reaction mediated by Pearlman’s catalyst. The precursor 28 was synthesised from readily prepared starting materials using Henry condensation chemistry. The product 6 was found to exist in two conformations in solution as shown by NMR spectroscopy.

New synthetic pathways to C-glycosides

C-glycopyranosyl compounds exhibit antimicrobial, antifungal, and antitumor activities, most probably based on enzyme inhibition or interference with cell surface recognition phenomena. Recent developments in glycobiology have shown the importance of the glycoside component of glycoproteins for cell recognition and differentiation processes. C-glycosidic analogues of that component would be metabolically stable, and thus offer enhanced therapeutic value. Synthesis of a configurational variety of e.g. amino (glycopyranosyl) methanes is thus an important synthetic goal. The amino group would allow linking the C-glycoside to a variety of scaffolds. Our first approach has been to C-link a C–N synthon (HCN or CH 3NO 2) to the anomeric carbon of a natural carbohydrate. We have realized this with cyanide on glycal, on per- O-acetyl sugars and on cyclic acetal protected glycosyl fluorides, prepared by a novel method. The catalytic hydrogenation of glycosyl cyanides presented challenges and new synthetic possibilities. With CH 3NO 2, and 4,6- O-alkylidene protected d-glucose or d-mannose derivatives, we obtained very good yields of cyclic Henry condensation products in THF with a novel catalytic procedure. The novel reduction of the resulting nitro (4,6- O-benzylidene- β- d-glycopyranosyl) methane with Fe 0/Ni 0 in THF/H 2O/CO 2 readily supplied amino (4,6- O-benzylidene- β- d-glucopyranosyl) methane, derivatives of which were diastereodiversified into d-allo, d-manno, and d-altro C-glycosides. These approaches fail, however, if prerequisite natural carbohydrate precursors are not available in a given case. Thus, a total synthesis scheme was also initiated. Phthalimido acetaldehyde diethylacetal and 4-penten-2-ol, with TiCl 4, form 2-methyl-4-chloro-6-phthalimido-methyl tetrahydropyran, which was functionalized into phthalimido (6-deoxy- β- d, l-hexopyranosyl) methanes. Chiral extensions of this method are possible. C-`disaccharides' became available from the Ferrier `dimerisation' of glycals, and from the hydrogenation of glycosyl cyanides.