Hantzsch-type Reaction Research Articles

Immobilization of Bacillus amyloliquefaciens protease “Neutrase” as hybrid enzyme inorganic nanoflower particles: A new biocatalyst for aldol-type and multicomponent reactions

Organic–inorganic hybrid nanoflowers (hNFs) with commercial protease “Neutrase” is proposed and characterized as efficient and green biocatalysts for promiscuous catalysis in aldol-type and multicomponent reactions. Neutrase hNFs [Neutrase-(Cu/Ca/Co/Mn)3(PO4)2] are straightforwardly prepared through mixing metal ion (Cu2+, Ca2+, Co2+ or Mn2+) aqueous solutions with Neutrase in phosphate buffer (pH 7.4, 10 mM) resulting in precipitation (3 days). The hNFs were characterized by various techniques including scanning electron microscopy (SEM), energy dispersive X-ray (EDX), element mapping, X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). In SEM images, the metal-Neutrase complexes revealed flower-like or granular structures after hybridization. The effect of metal ions and enzyme concentrations on the morphology and enzyme activity of the Neutrase-hNFs was examined. The synthesized Neutrase-Mn hNFs showed superior activity and stability compared to free Neutrase. Traditional organic CC coupling reactions such as aldol condensation, decarboxylative aldol, Knoevenagel, Hantzsch-type reactions and synthesis of 4H-pyran derivatives were used to test the generality and scope of Neutrase promiscuity, while optimizing conditions for the Neutrase-Mn hNF biocatalyst. Briefly, Neutrase-Mn3(PO4)2 hNFs showed excellent enzyme activity, stability and reusability, qualifying as effective reusable catalysts for coupling reactions under mild conditions.

Synthesis, molecular docking and modeling of new acenaphthenequinones clubbed of anticancer

The acenaphthenequinone-thiosemicarbazone (1) was utilized as a precursor for the synthesis of 2-(2-(5-acetyl-4-methylthiazol-2-yl)hydrazono)acenaphthylen-1(2H)-one (3) by applying Hantzsch-type reaction 3‑chloro-2,4-pentanedione (2). Claisen–Schmidt reaction of 3 with 4-chlorobenzaldehyde furnished the corresponding thiazolyl-chalcone 4, which underwent cyclization upon treatment with hydrazine hydrate or phenyl hydrazine to produce the corresponding thiazolyl-pyrazoles 5 and 6, respectively. All of the structures of these synthesized compounds were elucidated by elemental analysis and the spectral analysis such as IR, 1HNMR and mass spectroscopy. The DFT calculated Mulliken's atomic charge was used to represent the activity of the synthesized derivatives. While, the theoretical study of molecular docking was applied to expect their reactivity towards 5ORO protein. In addition, the synthesized analogues were examined against different cancer cell lines. All of theoretical and experimental studies were represented a good correlation with the anticancer activities for the synthesized derivatives.

Urease: a highly efficient biocatalyst for synthesis of polyhydroquinolines and polyhydroacridines from the ammonia formed in situ.

Urease, a nickel-dependent enzyme, has a powerful catalytic activity to decompose urea into ammonia via hydrolysis reaction under mild condition. In the present work, urease was employed for the synthesis of two series of polyhydroquinoline and polyhydroacridine derivatives via one-pot condensation of the ammonia generated in situ from urea, aryl aldehydes, and dimedone or ethyl acetoacetate (i.e., Hantzsch-type reaction) in water under mild green condition. The valuable features of this enzymatic method are mild reaction conditions, short reaction times, wide substrate toleration, and high yield of products. The present work provides a novel enzymatic catalysis to synthesize polyhydroquinolines and polyhydroacridines and expands the application of urease in organic synthesis.

Cytotoxic and renoprotective diterpenoids from Clerodendranthus spicatus

Three new diterpenoids, spicatusenes A–C (1–3), and eleven known ones (4–14) were isolated from the aerial parts of Clerodendranthus spicatus. Their structures were identified by spectroscopic methods. The cytotoxic activities of all the compounds against human cancer cells (HL-60, SMMC-7721, A-549, MCF-7, and SW-480) were examined and found that compounds 2, 3, 6, 8, 10, and 13 were active against one or more cancer cell lines. Besides, the renoprotective effects of all the isolates in TGF-β1-induced rat kidney fibroblasts revealed that compounds 3–7, 9, 13, and 14 were beneficial for renal fibrosis. Finally, a plausible biosynthetic pathway for 1 via a Hantzsch-type reaction was proposed.

Choline Chloride Catalyzed Eco-Friend and Effective One-Pot Synthesis of 9-Arylacridine-1,8-dione and Hexahydroquinoline via Hantzsch Type Reaction

Choline Chloride Catalyzed Eco-Friend and Effective One-Pot Synthesis of 9-Arylacridine-1,8-dione and Hexahydroquinoline via Hantzsch Type Reaction

Green and efficient synthesis of acridine-1,8-diones and hexahydroquinolines via a KH2PO4 catalyzed Hantzsch-type reaction in aqueous ethanol

A simple, clean, and economical methodology for the synthesis of acridine-1,8-dione and hexahydroquinoline derivatives via Hantzsch-type condensation has been described. This study highlights the development of a new green pathway for the preparation of substituted 1,4-dihydropyridines derivatives. The mild, cheap, and nontoxic potassium dihydrogen phosphate (KH2PO4) is proved to be an efficient catalyst for the above multi-component reaction to get excellent yields. Widely available and mostly benign catalyst, eco-friendly solvent, and easy purification are among the several attractive features.

One-pot, three-component synthesis of spiro[indeno[1,2-b]quinoline-10,3′-pyrroles] via the Hantzsch-type reaction of 1H-pyrrole-2,3-diones

A new methodology for the synthesis of spiro[indeno[1,2-b]quinoline-10,3′-pyrrole] derivatives via a Hantzsch-type reaction has been developed. This process involves the one-pot, three-component reaction of a 1H-pyrrole-2,3-dione, an aminocyclohexenone and 1,3-indanedione in acetic acid at reflux. Operationally simple, metal-free reaction conditions, simplicity of product isolation and good yields are key advantages of this methodology.

ChemInform Abstract: Three‐Component Synthesis of Pyrrole‐Related Nitrogen Heterocycles by a Hantzsch‐Type Process: Comparison Between Conventional and High‐Speed Vibration Milling Conditions.

The use of solvent-free, high-speed vibration milling conditions has allowed the development of a one-pot telescoped process for the synthesis of pyrroles starting from ketones, primary amines, and β-dicarbonyl compounds and comprising an initial α-iodination followed by an in situ three-component Hantzsch-type reaction. This method was compared with a solution-based protocol from α-iodoketones, primary amines, and β-dicarbonyl compounds. Although both protocols were far more general than previous Hantzsch-type pyrrole syntheses, the mechanochemical method was superior in that it afforded considerably higher yields in spite of comprising an additional step. The stereochemical integrity of the pyrroles obtained from chiral α-aminoesters was maintained. This solvent-free method was also used for the efficient preparation of ter- and quater-aryl/heteroaryl frameworks containing two pyrrole units and a variety of fused pyrrole systems, including benzo[g]indoles, indeno[1,2-b]pyrroles, indoles, and homoindoles.

Facile entry to an efficient and practical enantioselective synthesis of a polycyclic cholesteryl ester transfer protein inhibitor.

An efficient enantioselective synthesis of the chiral polycyclic cholesteryl ester transfer protein (CETP) inhibitor 1 has been developed. The synthesis was rendered practical for large scale via the development of a modified Hantzsch-type reaction to prepare the sterically hindered pyridine ring, enantioselective hydrogenation of hindered ketone 6 utilizing novel BIBOP-amino-pyridine derived Ru complex, efficient ICl promoted lactone formation, and a BF3 mediated hydrogenation process for diastereoselective lactol reduction. This efficient route was successfully scaled to produce multikilogram quantities of challenging CETP drug candidate 1.

ChemInform Abstract: Azo‐Coupling of Pyrazole‐3(5)‐diazonium Chlorides with Cyanothioacetamide: A Convenient Synthesis of Pyrazolo[5,1‐c][1,2,4]triazine‐3‐carbothioamides.

AbstractThe corresponding products (III) can be further converted with α‐bromo ketones to the products (V) or oxidized with H2O2 to give compounds (VI) and (VII).

Azo-coupling of pyrazole-3(5)-diazonium chlorides with cyanothioacetamide: a convenient synthesis of pyrazolo[5,1-c][1,2,4]triazine-3-carbothioamides

Cyanothioacetamide reacts with pyrazole-3(5)-diazonium chlorides to afford pyrazolo[5,1-c][1,2,4]triazine-3-carbothioamides 5. The latter can be oxidized with H2O2 to give either pyrazolo[5,1-c][1,2,4]triazine-3-carboxamides or 1,2,4-thiadiazole derivatives, depending on the reaction conditions. The Hantzsch-type reaction of thioamides 5 with α-bromo ketones leads to 3-(thiazol-2-yl)pyrazolo[5,1-c][1,2,4]triazines.

Diketene-based neat four-component synthesis of the dihydropyrimidinones and dihydropyridine backbones using silica sulfuric acid (SSA)

Abstract Heterocyclic skeleton building blocks to afford dihydropyrimidinones and dihydropyridines based on neat adducts of diketene, alcohols and aldehydes via silica sulfuric acid (SSA) catalyzed ring opening of diketene in four-component Biginelli-type and Hantzsch-type reactions are presented.

A facile protocol for the synthesis of 4-aryl-1,4,7,8-tetrahydro-3,5-dimethyldipyrazolo[3,4-b:4′,3′-e]pyridine derivatives by a Hantzsch-type reaction

A facile and efficient protocol is described for the synthesis of 4-aryl-1,4,7,8-tetrahydro-3,5-dimethyldipyrazolo[3,4-b:4′,3′-e]pyridine derivatives in good yields by the condensation of 3-methyl-1H-pyrazol-5(4H)-one, aromatic aldehydes, and ammonium acetate under catalyst-free conditions. The advantages of this protocol are operational simplicity, mild reaction conditions, high yields, and little environmental impact.

Candida antarctica lipase B-catalyzed the unprecedented three-component Hantzsch-type reaction of aldehyde with acetamide and 1,3-dicarbonyl compounds in non-aqueous solvent

A direct approach to 1,4-dihydropyridines by lipase-catalyzed unprecedented three-component Hantzsch-type reaction of aldehyde with 1,3-dicarbonyl compounds and acetamide in non-aqueous solvent has been developed. Some control experiments have been performed to demonstrate the specific catalytic effect of CAL-B. Acetamide was utilized as a novel ammonia source in the Hantzsch-type reaction for the first time. An array of 1,4-dihydropyridines was successfully synthesized through this methodology.

Biginelli and Hantzsch-Type Reactions Leading to Highly Functionalized Dihydropyrimidinone, Thiocoumarin, and Pyridopyrimidinone Frameworks via Ring Annulation with β-Oxodithioesters

An efficient and highly convergent route to dihydropyrimidinones (DHPMs) and hitherto unreported dihydropyridopyrimidinones has been developed by one-pot, three-component cyclocondensation of aromatic aldehydes, β-oxodithioesters, and urea/6-amino-1,3-dimethyluracil in the presence of recyclable SiO2-H2SO4. On the other hand, salicylaldehyde, β-oxodithioester, and urea reacted under similar conditions to afford the 3-aroyl/heteroaroyl-2H-chromen-2-thiones in high yields instead of Biginelli product. The attractive feature of this approach is the synthesis of three important bioactive heterocyclic frameworks from the same β-oxodithioester under the similar reaction conditions, making this new strategy highly useful in diversity-oriented synthesis (DOS).

ChemInform Abstract: Asymmetric Tandem Reactions: New Synthetic Strategies

AbstractReview: 23 refs.

Asymmetric tandem reactions: New synthetic strategies

The use of domino and multicomponent reactions in asymmetric synthesis is constantly increasing nowadays. This allows for the synthesis of complex molecules in a single synthetic sequence, usually with high atom economy. Herein, we report three examples of new asymmetric tandem reactions recently developed in our laboratories, giving rise to new families of enantiomerically enriched fluorinated and nonfluorinated heterocycles. Thus, 1,4-dihydropyridines (1,4-DHPs) bearing fluorinated substituents at C6 were assembled by means of a Hantzsch-type reaction; cyclic β-amino carbonyl derivatives were prepared using a cross-metathesis (CM)–intramolecular aza-Michael sequence; while fluorinated indolines were obtained, for the first time, in a tandem nucleophilic addition–intramolecular aromatic substitution.

Synthesis of methyl 6-aryl-5-(1H-benzimidazol-2-yl)-2-methylnicotinates

A three-component cyclocondensation of 4-(dimethylamino)benzaldehyde, 2-phenacyl-1H-benz-imidazoles, and methyl 3-aminobut-2-enoate in refluxing acetic acid occurs via a Hantzsch type reaction and is accompanied by the loss of N,N-dimethylaniline to give the previously unknown methyl 6-aryl-5-(1H-benzimidazol-2-yl)-2-methylnicotinates.

Studies on peroxidized lipids. II. Fluorescent products relevant to aging pigments derived from malondialdehyde and methylamine.

Malondialdehyde (MDA) is a secondary product of in vitro and in vivo lipid peroxidation. Reactions of MDA, prepared by acid hydrolysis of malonaldehyde bis (dimethylacetal), with methylamine were performed at 37°under various pH conditions (pH 1-8). Two major fluorescent compounds, 1, 4-dimethyl-1, 4-dihydropyridine-3, 5-dialdehyde (1) and 1-methyl-4-(dimethoxyethyl)-1, 4-dihydropyridine-3, 5-dialdehyde (2), and two nonfluorescent UV-absorbing by-products, β-methylaminoacrolein (3) and 2, 6-dimethyl-2, 6-diazabicyclo [3.3.1] 3, 7-nonadiene-4, 8-dialdehyde (4), were isolated. The structures of these products were elucidated by analysis of their 13C and 1H NMR spectra, mass spectra and UV absorption spectra. Compounds 1 and 2 were produced in the best yields at pH 6-8, 3 was produced at every pH, and 4 was produced at pH 2-5. The 1, 4-dihydropyridine-3, 5-dialdehyde fluorophore in 1 and 2 may have been formed via a Hantzsch-type reaction of MDA and methylamine. The fluorescence spectrum of 1 with a maximum at 460 nm was the same as that of a conjugated Schiff base of MDA and amino acid or those of aging or lipofuscin pigments accumulated in the cells.