Substituent-controlled domino-Knoevenagel-hetero Diels-Alder reaction—a one-pot synthesis of polycyclic heterocycles

The reaction of 2-(N-alkenyl-N-aryl)amino-4-oxo-4H-1-benzopyran-3-carbaldehyde with dimedone/Meldrum’s acid/4-hydroxycoumarin by heating in ethanol in the presence of pyridine produces polycyclic heterocycles bearing pyridine and pyran rings in a one-pot reaction. The effect of substituents on N-atom of the amino function controls the mode of reaction. Terminal alkenes prefer intramolecular Michael type reaction, but non-terminal alkenes favour Diels-Alder reaction, whereas, under similar condition, 2-(N-alkyl-N-allyl)amino-4-oxo-4H-1-benzopyran-3-carbaldehyde undergoes domino-Knoevenagel-hetero Diels-Alder reaction.     

Isothermal cure kinetics of uncatalyzed and catalyzed diglycidyl ether of bisphenol-A/carboxylated polyester hybrid powder coating

The thermal cure behavior of diglycidyl ether bisphenol-A/carboxylated polyester hybrid powder coating system in the absence and presence of catalyst was monitored using differential scanning calorimetry. Curing temperatures were between 160 and 200?°C. The experimental results showed an autocatalytic behavior of the reaction, which could be described by the model proposed by Kamal. This model includes two rate constants k ₁ and k ₂ and two reaction orders m and n. The activation energies E _a1 and E _a2 of these rate constants were 51.7 and 42.3?kJ/mol for uncatalyzed cure reaction and 40.6 and 35.0?kJ/mol for externally catalyzed reaction. The average order of the overall reaction was found to be 2.45 and 2.72 for uncatalyzed and catalyzed system, respectively. Except for the late stage of cure reaction, the model agreed well with the experimental data, especially at high temperatures and in externally catalyzed cure reaction. A diffusion factor was introduced into the model to account for the effect of diffusion on the cure rate. The modified model greatly improved the predicated data at the late stage of cure reaction.     

Selective hydroisomerization of n-dodecane over platinum supported on zeolites

In this study, in order to develop catalysts for the selective isomerization of higher paraffin, the hydroisomerization reaction of n-dodecane was performed as a model reaction. Pt/ZSM-48, Pt/HZSM-5, Pt/HY, and Pt/SAPO-11 were examined for the selective hydroisomerization of n-dodecane. The catalysts were characterized via X-ray powder diffraction, N₂ adsorption, and the temperature-programmed desorption of ammonia. Among the catalysts studied, the Pt/HZSM-48 catalyst exhibited the best isomerization selectivity in the hydroisomerization reaction of n-dodecane, which is attributed to the moderate acid sites and medium-sized pores present in the HZSM-48. The highest iso-dodecane yield was obtained at a reaction temperature of 280 °C in the Pt/HZSM-48 catalyst. The optimal selectivity of the n-dodecane hydroisomerization over the Pt/SAPO-11 catalyst was obtained at approximately 300 °C, which was slightly higher than that of the Pt/HZSM-48 catalyst.     

New Grafted Copolymers Carrying Betaine Units Based on Gellan and N-Vinylimidazole as Precursors for Design of Drug Delivery Systems

New grafted copolymers possessing structural units of 1-vinyl-3-(1-carboxymethyl) imidazolium betaine were obtained by graft copolymerization of N-vinylimidazole onto gellan gum followed by the polymer-analogous reactions on grafted polymer with the highest grafting percentage using sodium chloroacetate as the betainization agent. The grafted copolymers were prepared using ammonium persulfate/N,N,N′,N′ tetramethylethylenediamine in a nitrogen atmosphere. The grafting reaction conditions were optimized by changing one of the following reaction parameters: initiator concentration, monomer concentration, polymer concentration, reaction time or temperature, while the other parameters remained constant. The highest grafting yield was obtained under the following reaction conditions: c_i = 0.08 mol/L, c_m = 0.8 mol/L, c_p = 8 g/L, t_r = 4 h and T = 50 °C. The kinetics of the graft copolymerization of N-vinylimidazole onto gellan was discussed and a suitable reaction mechanism was proposed. The evidence of the grafting reaction was confirmed through FTIR spectroscopy, X-ray diffraction, ¹H-NMR spectroscopy and scanning electron microscopy. The grafted copolymer with betaine structure was obtained by a nucleophilic substitution reaction where the betainization agent was sodium chloroacetate. Preliminary results prove the ability of the grafted copolymers to bind amphoteric drugs (cefotaxime) and, therefore, the possibility of developing the new sustained drug release systems.     

Nickel-catalyzed C–O/N–H,C–S/N–H,and C–CN/N–H annulation of aromatic amides with alkynes: C–O,C–S,and C–CN activation

The Ni-catalyzed reaction of ortho-phenoxy-substituted aromatic amides with alkynes in the presence of LiO^tBu as a base results in C–O/N–H annulation with the formation of 1(2H)-isoquinolinones. The use of a base is essential for the reaction to proceed. The reaction proceeds, even in the absence of a ligand, and under mild reaction conditions (40 °C). An electron-donating group on the aromatic ring facilitates the reaction. The reaction was also applicable to carbamate (C–O bond activation), methylthio (C–S bond activation), and cyano (C–CN bond activation) groups as leaving groups.

The Ni-catalyzed reaction of ortho-phenoxy-substituted aromatic amides with alkynes in the presence of LiO^tBu as a base results in C–O/N–H annulation with the formation of 1(2H)-isoquinolinones.     

Synthesis of 8-aryl substituted benzo[a]phenanthridine derivatives by consecutive three component tandem reaction and 6-endo carbocyclization

A concise construction of benzo[a]phenanthridines involving multicomponent tandem reaction/carbocyclization in a sequential format is described. The reaction proceeds initially via formation of a 4-aryl-3-arylethynyl-isoquinoline from 2-bromobenzaldehyde/tert-butylamine/1,3-diyne in a three component format followed by a second ring closure either via gold/silver catalyzed intramolecular hydroarylation or via iodo-catalyzed regioselective 6-endo-dig electrophilic cyclization. The salient feature of the strategy involves a three component reaction followed by transformation of the resulting product in to polyheterocycles with increased structural complexity in two steps.     

Visible-light-mediated selective thiocyanation/ipso-cyclization/oxidation cascade for the synthesis of thiocyanato-containing azaspirotrienediones

A visible-light-mediated metal-free thiocyanate radical addition/ipso-cyclization/oxidation cascade reaction for the synthesis of thiocyanato-containing azaspirotrienediones from N-phenylpropynamides is described. Cheap and readily available ammonium thiocyanate was used as a precursor to the thiocyanate free radical, which undergoes a radical addition reaction with the alkyne, followed by selective ipso-cyclization and oxidation to afford the dearomatized products. No product of ortho-cyclization was detected. The reaction completes the synthesis of C–S, C–C, and CO bonds in one pot, with abundant and renewable air oxygen as the sole sacrificial reagent and oxygen source.     

A visible-light-promoted cross-dehydrogenative-coupling reaction of N-arylglycine esters with imidazo[1,2-a]pyridines

A mild and convenient visible-light-promoted cross-dehydrogenative-coupling reaction between N-arylglycine esters and imidazo[1,2-a]pyridines for the construction of CC bond was developed. A range of N-arylglycine esters and imidazo[1,2-a]pyridines were able to undergo the CDC reaction readily to afford α-heteroaryl substituted α-amino acid derivatives in good to excellent yields. A tentative mechanism for the photoredox reaction was also proposed. Importantly, the use of copper(II) salt as the sole catalyst in this visible-light-promoted transformation makes this reaction sustainable and practical.     

Preparation of optically pure cross-conjugated cyclopentadienones

The synthesis of optically pure cross-conjugated cyclopentadienones is readily achieved in two steps via a one-pot alkylcuprate addition/aldol condensation/dehydration sequence using racemic or enantioenriched endo-3a,4,7,7a-tetrahydro-1H-4,7-methano-inden-1-ones followed by microwave-mediated Lewis acid-catalysed retro Diels-Alder reaction. An alternative route involving a modified Baylis-Hillman protocol followed by conjugate addition with alkylcuprates and a retro Diels-Alder reaction was also investigated.     

Inorganic base-mediated stereoselective hydroamination of arylalkynes with imidazole: An efficient access to N-vinylimidazoles

A metal-free inorganic base-mediated highly stereoselective hydroamination of arylalkynes with imidazoles has been developed, and the corresponding N-vinylimidazoles were obtained in good yields and with moderate to excellent stereoselectivities (up to 99:1). For the electron rich alkynes, the reaction system of CsOH·H₂O/NMP/140?°C led to the predominant formation of E-addition products, while the reaction system of KOH/NMP/90?°C afforded the Z-isomers as the major product. The electron deficient alkynes furnished predominantly the E-addition products in both reaction systems. This study essentially provides a general and an efficient protocol for the synthesis of E-isomer of the N-vinylimidazoles.     

Synthesis of oxetane/azetidine containing spirocycles

Oxetane-benzopyran spirocycles were synthesised via a palladium catalysed cyclisation-cross coupling cascade reaction whilst oxetane/azetidine-pyrrolidino isoindolone spirocycles were synthesised via a silver catalysed 1,3-dipolar cycloaddition reaction followed by a palladium catalysed carbonylation-amination process.     

Domino Michael/aza-Wittig reaction in the diastereoselective construction of spiro[azepane-4,3′-oxindoles]

A convenient synthetic strategy for the diastereoselective assembly of spiro[azepane-4,3′-oxindoles] was developed via a Staudinger/Michael/aza-Wittig/reduction/N-deprotection reaction sequence starting from PMB-protected oxindole-substituted ethylazides. The key step of the method is a domino self-catalytic Michael/aza-Wittig reaction wherein the phosphazene moiety acts first as the catalyst and then as the reactant, resulting in the formation of a seven-membered N-heterocycle.     

Synthesis of a novel pyrrolo-[3,2-c]quinoline N-oxide by aza-Baylis-Hillman adduct of o-nitrobenzaldehyde

A new and high yielding approach for the synthesis of a novel pyrrolo-[3,2-c]quinoline N-oxide is described. The key step consisted in the palladium-catalyzed reductive cyclization of an uncommon 3-ketopyrrole derivative of o-nitrobenzaldehyde, obtained in a straightforward manner through an aza-Baylis-Hillman/ring closing metathesis/aromatization reaction. A deoxygenation reaction of this novel pyrrolo-[3,2-c]quinoline N-oxide afforded a new substituted pyrrolo-[3,2-c]quinoline analogue.     

N-Allyl-1,3-oxazines via a facile keto-ene/cyclization tandem reaction

The intramolecular keto-ene/cyclization tandem reaction of γ-N-allylamino ketones is an effective means of producing 1,3-oxazines. The reaction usually requires high temperatures and/or pressures. We discovered that N,N-diallyl amines undergo the reaction at lower temperatures than their monoallyl analogs. An extreme example, 1-N,N-diallylamino-9,10-anthraquinone, undergoes the keto-ene reaction near ambient temperature. In the case of 1-N,N′-dialkylaminoanthraquinones, electron deficient ene components can even be used, allowing the preparation of a broad spectrum of oxazines. Furthermore, the N-allyl-1,3-oxazine can be easily deallylated to produce a 1,3-oxazine that contains a secondary amine.     

Expanding spherical shell kinetic model for diffusion-controlled solid-state reactions

A reaction kinetic model has been derived for a solid-state diffusion-controlled reaction in a system of spherical particles of A isolated in a matrix of B. This model is analogous to the Ginstling-Brounsthein model except that the diffusion of A is the rate-controlling step. The model, therefore, resulting in an expanding spherical shell of product AB, is

where t = time, x = fraction reaction, K = reaction rate constant.     

RhodiumIII-catalyzed remote difunctionalization of arenes assisted by a relay directing group

Rhodium-catalyzed diverse tandem twofold C–H bond activation reactions of para-olefin-tethered arenes have been realized, with unsaturated reagents such as internal alkynes, dioxazolones, and isocyanates being the coupling partner as well as a relay directing group which triggers cyclization of the para-olefin group under oxidative or redox-neutral conditions. The reaction proceeded via initial ortho-C–H activation assisted by a built-in directing group in the arene, and the ortho-incorporation of the unsaturated coupling partner simultaneously generated a relay directing group that allows sequential C–H activation at the meta-position and subsequent cyclization of the para-olefins. The overall reaction represents C–C or N–C difunctionalization of the arene with the generation of diverse 2,3-dihydrobenzofuran platforms. The catalytic system proceeded with good efficiency, simple reaction conditions, and broad substrate scope. The diverse transformations of the products demonstrated the synthetic utility of this tandem reaction.

Rhodium-catalyzed twofold C–H bond activation of para-olefin-tethered arenes has been realized using diverse unsaturated reagents. The overall reaction represents C–C or N–C difunctionalization of arenes with the generation of diverse 2,3-dihydrobenzofurans.     

Assessment of the regioselectivity in the condensation reaction of unsymmetrical o-phthaldialdehydes with alanine

One approach for the synthesis of isoindolinones, a privileged bioactive heterocyclic core structure, involves a condensation reaction of o-phthaldialdehydes with a suitable nitrogen-containing nucleophile. This fascinating reaction is revisited here in the context of the use of o-phthaldialdehydes that contain additional substituents in the aromatic ring leading to a detailed analysis of the regioselectivity of the reaction. Eleven monosubstituted o-phthaldialdehydes were synthesised and reacted with alanine. The regioselectivity observed across the eleven substrates led to the design of a disubstituted substrate that reacted with very high control. A gram-scale reaction followed by esterification gave one major regioisomer in high yield. In addition, the regioselectivity observed on reaction of two novel monodeuterated substrates led to an increased mechanistic understanding.     

A quantum chemical study on the mechanism of chiral N-oxides-catalyzed Strecker reaction

The mechanism for the Strecker reaction of silyl cyanide (H₃SiCN) and benzaldehyde N-methylimine (PhCHNCH₃) catalyzed by chiral 3,3′-dimethyl-2,2′-bipyridine N,N′-dioxide was investigated using the density functional theory (DFT) at the B3LYP/6-31G* level. The calculations revealed that the non-catalyzed reaction proceeded in a concerted way via a five-membered ring transition state, while the catalytic one occurred stepwisely via a hexacoordinate hypervalent silicate intermediate. It was predicted that both non-catalyzed and catalytic Strecker reactions involved two competitive reaction pathways, that is, addition followed by isomerization or isomerization followed by addition. The calculations indicated that two reaction pathways were comparable for both non-catalyzed and catalytic Strecker reactions. In the catalytic reaction, the strong electron donor (N-O) of chiral N-oxide played an important role in enhancing the reactivity and nucleophilicity of H₃SiCN by coordinating O atom to the Si atom of H₃SiCN. Chiral N-oxide could be used as a good catalyst for the reaction, which was in agreement with the experimental observations.     

Bromophilic substitution/carbophilic substitution cascade reactions of α,α-dibromo-2-methoxyacetophenone with C-, N- and O-nucleophiles

α,α-Dibromo-2-methoxyacetophenone reacts, under mild reaction conditions, with C-, N- and O-nucleophiles via a bromophilic substitution/protonation/carbophilic substitution cascade process to afford α-monosubstituted-2-methoxyacetophenones in moderate to good yield. The only exception from this reaction pathway is the reaction with the anion derived from malononitrile in which 2-aroyl-1,1,3,3-tetracyanopropene is obtained.     

Rapid access to the synthesis of polysubstituted δ-lactones via tandem stereoselective conjugate addition/α-alkylation of unsaturated 7,3-lactone-α-d-xylofuranose derivative

α-d-xylo-7,3-Unsaturated lactone, a versatile chiral building block, undergoes Cu-catalyzed conjugated addition with high yield and stereoselectivity. When the conjugated reaction is quenched with a suitable alkyl halide, a tandem stereoselective conjugated/α-alkylation reaction is achieved. Further, selective hydrolysis of the 1,2-O-isopropylidene moiety followed by oxidative cleavage and reduction reaction, afforded the title compounds.