Zirconium(IV) compounds as efficient catalysts for synthesis of alpha-aminophosphonates

Zirconium(IV) compounds are reported as excellent catalysts for a three-component one-pot reaction of an amine, an aldehyde or a ketone, and a di/trialkyl/aryl phosphite to form alpha-aminophosphonates under solvent-free conditions at rt. Among the various zirconium compounds, ZrOCl2 x 8 H2O and ZrO(ClO4)2 x 6 H2O were most effective. The reactions were faster with dialkyl/diaryl phosphites than with trialkyl/triaryl phosphites. No O-Me cleavage occurs with aryl methyl ether and methyl ester groups. alpha,beta-Unsaturated carbonyl moiety does not undergo conjugate addition with the phorphorous moiety.     

Process intensification for synthesis of triglycerides of capric acid using green approaches

The present research focuses on intensified synthesis of tricaprin by esterification reaction between capric acid and glycerol catalysed by dry amberlyst-15 using ultrasonication approach. Effect of several reaction conditions like molar ratio, reaction temperature, and amberlyst-15 loading on the rate of conversion has been studied. Effect of ultrasonic conditions like duty cycle and irradiation time on the intensified synthesis is investigated. Recyclability of amberlyst-15 is studied to make process more economical. It is investigated that the optimum reaction conditions which gave maximum conversion of 95% were molar ratio of capric acid: glycerol as 3:5, reaction temperature 90 ​°C, 4% amberlyst −15 loading. It was further investigated that ultrasonic conditions which gave intensified synthesis were 70% duty cycle and irradiation time of 120 ​min. The ultrasonic assisted process was compared with conventional synthesis. Conventional synthesis gave 30% yield in 120 ​min and 82% in 18 ​h. Amberlyst-15 was successfully reused for 13 cycle without any change in the conversion (%) of reaction.     

New "green" approaches to the synthesis of pyrazole derivatives

A novel approach to the synthesis of pyrazole derivatives from tosylhydrazones of alpha,beta-unsaturated carbonyl compounds possessing a beta-hydrogen is proposed, exploiting microwave (MW) activation coupled with solvent free reaction conditions. The cycloaddition was studied on three ketones (trans-4-phenyl-3-buten-2-one, beta-ionone and trans-chalcone). The corresponding 3,5-disubstituted-1H-pyrazoles were obtained in high yields and after short reaction times. In order to simplify and point out the green chemistry features of the method, a further improvement was achieved under the same catalytic conditions with a "one pot" synthesis of these heterocyclic compounds, starting directly from their carbonyl precursors via tosylhydrazones generated in situ. For an exhaustive study, the dielectric properties of the solid reaction mixtures were also measured, in order to obtain input data for the numerical simulation of their heating behaviour in the single mode MW cavity which was used for experimental work. In order to supply a valid methodology and tool for measuring the environmental impact, a comparative study between the synthetic route proposed and the classical synthetic route has been carried out.     

One pot synthesis of alpha-aminophosphonates containing bromo and 3,4,5-trimethoxybenzyl groups under solvent-free conditions

New alpha-aminophosphonates were synthesized by the Kabachnik-Fields reaction of 3,4,5-trimethoxybenzaldehyde (TMB) with p- or m-bromoaniline and a dialkyl phosphite under solvent-free conditions. TMB was prepared from gallic acid via a four step synthetic sequence involving etherification, esterification, hydrazidation and potassium ferricyanide oxidation. The structures of all synthesized compounds were confirmed by elemental analysis, IR, 1H-, 13C- and 31P-NMR spectral data. Compound 7g was also characterized by X-ray crystallography. A half-leaf method was used to determine the in vivo curative efficacy of the eight title products against tobacco mosaic virus (TMV). It was found that compounds 7g and 7h possess good in vivo curative effects against TMV.     

Ring-expansion approaches for the total synthesis of salimabromide

We describe the evolution of a synthetic strategy for the construction of the marine polyketide salimabromide. Combining a bicyclo[3.1.0]hexan-2-one ring-expansion to build up a functionalized naphthalene and an unprecedented rearrangement/cyclization cascade, enabled synthesis of a dearomatized tricyclic subunit of the target compound. Alternatively, an intramolecular keteniminium [2 + 2]-cycloaddition and subsequent Baeyer–Villiger ring-expansion gave access to the sterically encumbered architecture of salimabromide. Sequential oxidation of the carbon framework finally enabled the total synthesis of this unusual natural product.     

Systems thinking approaches for international green chemistry education

1. Download : Download high-res image (133KB)
2. Download : Download full-size image

     

Green solvent-based approaches for synthesis of nanomaterials

The use of green solvents (including supercritical fluids and ionic liquids) in the synthesis of nanomaterials is highlighted. The methods described can not only reduce or eliminate the use or generation of substances hazardous to health and the environment, but can also be used to efficiently prepare nanomaterials with high performances. The unique characteristics of green solvents are responsible for the green features and unusual advantages of these approaches.     

2,3,5-三甲基氢醌的绿色合成工艺研究

以偏三甲苯(TMB)为原料,冰醋酸为溶剂,过氧化氢(50%)为氧化剂,通过直接氧化合成了2,3,5-三甲基氢醌(TMHQ);考察了反应温度、反应时间以及氧化剂和溶剂用量等对TMHQ收率的影响,确定了优化的氧化反应条件.结果表明,最优的氧化反应条件为:反应温度85℃,反应时间3h,TMB与冰醋酸的物质的量之比1∶12,TMB与过氧化氢的物质的量之比1∶11.     

Evaluation of alternative approaches for the synthesis of macrocyclic bisindolylmaleimides

Approaches for the synthesis of macrocyclic bisindolylmaleimides, in which the indole nitrogens are linked with a tether, are described. Two alternative approaches were investigated: macrocyclisation in either the 'southern' (by adding the tether to the bisindolylmaleimide ring system) or the 'northern' district. With two-, three- and four-atom tethers, both of these approaches were unsuccessful for a wide range of attempted macrocyclisation reactions (palladium-catalysed pi-allyl substitution, ring-closing metathesis, McMurry reaction, iodocyclisation, formation of a silylene derivative, substitution of an alpha,omega-disubstituted electrophile). The failure of all of these reactions was ascribed to the strained nature of the target ring system. However, with longer tethers (six to ten atoms), the macrocycles could prepared using either a ring-closing metathesis reaction or by substitution of an alpha,omega-dibromide). Fourteen successful macrocyclisation reactions are described; deprotection gave eleven macrocyclic bisindolylmaleimides in which an imide substituent had been removed.     

Novel approaches for the solid-phase synthesis of biheterocyclic dihydroimidazole analogues

The solid-phase syntheses of dihydroimidazolyl 2-alkylthiobenzimidazoles, dihydroimidazolyl 2-alkylsulfonylbenzimidazoles, dihydroimidazolyl dihydroquinoxalin-2,3-diones, and dihydroimidazolyl dihydrobenzimidazol-2-imines are described. Following reduction of a resin-bound amino acid amide, the primary amine of the resulting resin-bound diamine was N-acylated with 4-fluoro-3-nitrobenzoic acid. Treatment with POCl3 led to formation of a dihydroimidazole derivative via dehydrative cyclization. The resin-bound dihydroimidazole derivative was then used as the key starting material for the synthesis of the aforementioned biheterocycles. Following cleavage, the resulting compounds, obtained in moderate yield and good purity, were characterized by LC-MS and 1H NMR and 13C NMR spectroscopy.     

Stille coupling approaches for the synthesis of 8-aryl guanines

The reaction of 8-bromoguanines with aryl and hetaryl stannanes in the presence of a palladium catalyst leads to the formation of the corresponding 8-aryl(hetaryl)guanines. It was found that the addition of triphenylarsine or triphenylbismuth strongly reduces the reaction time and increases product yields.     

Ring-closing metathesis approaches for the solid-phase synthesis of cyclic peptoids

Cyclic peptoids were efficiently synthesized on a solid phase in high yields utilizing ring-closing metathesis (RCM). This method should be a valuable tool for easy access to cyclic peptoid libraries and various cyclic compounds.     

A green bromination method for the synthesis of benzylic dibromides

Reported herein is the identification of a new methodology for the dibromination of benzylic diols. This method proceeds in moderate to good yields for a wide variety of electron-deficient, electron-neutral, and electron-rich aromatic substrates. Moreover, the reagent, 1,3-dibromo-5,5-dimethylhydantoin, and the solvent, tetrahydrofuran, are substantially more environmentally benign than traditional solvents and reagents used for bromination. The utility of this methodology was demonstrated in the high-yielding synthesis of a key intermediate in the synthesis of omeprazole.     

A novel green template for the synthesis of mesoporous silica

Mesoporous pure silicas and functionalized silica with a narrow pore size distribution centered at 3.8 nm were prepared by a novel template, amphiphilic dendritic polyglycerol. The resulting silica materials were characterized by electron microscopy; nitrogen adsorption; (1)H, (13)C, and (29)Si solid-state cross-polarization magic-angle spinning NMR spectroscopy. It was shown that the template could be completely removed from the pure and functionalized silica in an environmentally friendly way by means of a simple water extraction procedure. Furthermore, it was shown that these materials could be easily functionalized, for example, by employing aminopropyl groups. Thus, a new environmentally friendly pathway to this fascinating class of silica material has been opened.     

A simple green procedure for the synthesis of 2H-azirines

An efficient and environmentally friendly method preparing 2H-azirines in good yield has been achieved by microwave irradiation of vinyl azides in solvent free conditions.     

New approaches to the synthesis of spiro-peroxylactones

Ozonolysis of (alkenyldioxy)cyclododecyl hydroperoxides in trifluoroethanol gave a separable mixture of the corresponding alpha-hydroperoxy- and alpha-hydroxy-substituted spiro-tetraoxacycloalkanes with ring sizes in the range 7-12. Dehydration of the hydroperoxides or oxidation of the hydroxy-compounds afforded the corresponding peroxylactones. The solid-state structure of 1,2,6,7-tetraoxaspiro[7.11]nonadecan-3-one was determined by X-ray crystallographic analysis.     

An extremely efficient three-component reaction of aldehydes/ketones, amines, and phosphites (Kabachnik-Fields reaction) for the synthesis of alpha-aminophosphonates catalyzed by magnesium perchlorate

Commercially available magnesium perchlorate is reported as an extremely efficient catalyst for the synthesis of alpha-aminophosphonates. A three-component reaction (3-CR) of an amine, an aldehyde or a ketone, and a di-/trialkyl phosphite (Kabachnik-Fields reaction) took place in one pot under solvent-free conditions to afford the corresponding alpha-aminophosphonates in high yields and short times. The use of solvent retards the rate of the reaction and requires a much longer reaction time than that for neat conditions. The reactions involving an aldehyde, an aromatic amine without any electron-withdrawing substituent, and a phosphite are carried out at rt. The reactions involving cyclic ketones, aromatic amines with an electron-withdrawing substituent, and aryl alkyl ketone (e.g., acetophenone) require longer reaction times at rt or heating. Magnesium perchlorate was found to be superior to other metal perchlorates and metal triflates during the reaction of 4-methoxybenzaldehyde, 2,4-dinitroaniline, and dimethyl phosphite. The catalytic activity of various magnesium compounds was influenced by the counteranion, and magnesium perchlorate was found to be the most effective. The reaction was found to be general with di-/trialkyl phosphites and diaryl phosphite. The Mg(ClO4)2-catalyzed alpha-aminophosphonate synthesis in the present study perhaps represents a true three-component reaction as no intermediate formation of either an imine or alpha-hydroxy phosphonate was observed that indicated the simultaneous involvement of the carbonyl compound, the amine, and the phosphite in the transition state.