The Synthesis and Bioactivity of Dimethyl (2,3- Dihydrobenzo[b][1,4]Dioxin-6-Yl)(Aryl Amino)Methylphosphonates

Abstract

A new series of α-aminophosphonates have been synthesized by a one-pot three-component reaction of 2,3-dihydrobenzo[b][1,4]dioxine-6-carbaldehyde, various amines, and dimethyl phosphite by using nano-TiO₂ as a catalyst under solvent-free conditions at 50°C. The major advantages of the present method are high yields, short reaction times, recyclable catalyst, and solvent-free reaction conditions. Among these new structurally diversified set of α-aminophosphonates, dimethyl (2,3-dihydrobenzo[b][1,4]dioxin-6-yl)(3-nitrophenylamino) methylphosphonate and dimethyl (2,3-dihydrobenzo[b][1,4]dioxin-6-yl)(4-fluoro-3-nitro-phenyl-amino) methylphosphonate have shown higher antioxidant activity in diphenyl picryl hydrazyl (DPPH) scavenging, reducing power assay, and lipid peroxidation methods.     

Nano ceria catalyzed synthesis of α-aminophosphonates under ultrasonication

A simple, efficient and general method has been developed for the one-pot three component syntheses of α-aminophosphonates. The condensation of aldehyde, amine and triethyl phosphite by employing CeO₂ nanoparticles as catalyst gave α-aminophosphonates. The catalyst showed good recyclability. Nano CeO₂ has been found to be an excellent catalyst for the green synthesis of α-aminophosphonates under ultrasound irradiation and solvent-free condition. The α-aminophosphonates are obtained in good to excellent yield. This catalyst provides cleaner conversion, short reaction time and high selectivity which makes the protocol feasible and economical attractive.     

Zirconium-catalyzed asymmetric Kabachnik–Fields reactions of aromatic and aliphatic aldehydes

An effective catalyst has been developed for the three-component reaction of aldehydes, anilines and phosphites in an asymmetric catalytic Kabachnik–Fields reaction to give α-aminophosphonates. A catalyst was sought that would give high asymmetric inductions for aromatic and, and more particularly, for aliphatic aldehydes since there has not previously been an effective catalyst developed for this class of aldehydes. The optimal catalyst is prepared from three equivalents of the 7,7′-di-t-butylVANOL ligand, one equivalent of N-methylimidazole and one equivalent of zirconium tetraisopropoxide. This catalyst was most efficient in the presence of 10 mol% benzoic acid. Optimal conditions for aryl aldehydes required the use of 3,5-diisopropyl-2-hydroxyaniline and gave the aryl α-aminophosphonates in up to 96% yield and 98% ee over 11 different aryl aldehydes. The best aniline for aliphatic aldehydes was found to be 3-t-butyl-2-hydroxyaniline and gave the corresponding phosphonates in up to 83% yield and 97% ee over 18 examples. The asymmetric inductions for aliphatic aldehydes were comparable with those for aromatic aldehydes with a mean induction of 90% ee for the former and 91% ee for the latter. The best method for the liberation of the free amine from the aniline substituted α-aminophosphonates involved oxidation with N-iodosuccinimide.

An effective catalyst has been developed for the three-component reaction of aldehydes, anilines and phosphites in an asymmetric catalytic Kabachnik–Fields reaction to give α-aminophosphonates.     

One-pot three-component Kabachnik-Fields synthesis of α-aminophosphonates using H-beta zeolite catalyst

One-pot three-component Kabachnik-Fields synthesis of α-aminophosphonates with high yields from the reaction between carbonyl compound, primary amine, and substituted phosphite can be carried out in a short period, using H-beta zeolite as a reusable catalyst.     

A green one-pot three-component synthesis of α-aminophosphonates under solvent-free conditions and ultrasonic irradiation using Fe3O4@SiO2-imid-PMAn as magnetic catalyst

An efficient and environment friendly process for the synthesis of α-aminophosphonates has been devised. Through a one-pot three-component condensation of various aldehydes, amines, and triethyl phosphite in the presence of Fe₃O₄@SiO₂-imid-PMAⁿ nanoparticles as magnetic catalysts under solvent-free conditions and ultrasonic irradiation, α-aminophosphonates were obtained with excellent yields. The reactions under solvent-free conditions at room temperature are compared with the ultrasonic-assisted reactions. This new procedure has notable advantages such as short reaction time, excellent yields, easy purification, and the absence of any tedious workup or purification. The aforementioned catalyst could be easily recovered by an external magnetic field and can be reused for six consecutive reaction cycles without significant loss of activity. In addition, SEM and DLS of the catalyst after the reaction cycle were investigated.     

Solvent-free sonochemical kabachnic-fields reaction to synthesize some new α-aminophosphonates catalyzed by nano-BF3•SiO2

To obtain a rapid, efficient synthesis of some new α-aminophosphonates, ultrasonic irradiation has been applied to the reaction mixtures containing amine, aromatic or heteroaromatic aldehydes and triethyl phosphite. The Kabachnik-Fields reaction was performed by using nano-BF₃?SiO₂ as a recyclable catalyst under solvent free conditions. Key advantages of this procedure consist in the eco-friendly and highly efficient reaction conditions, high yields, an easy work-up procedure, short reaction times and solvent free conditions. All title compounds were characterized by spectral and elemental analysis. They were further screened for their in vitro antioxidant activity by the DPPH, O^2? and NO methods. The majority of the title compounds showed good antioxidant activity when compared with the standard antioxidants.     

Efficient Bakers’ Yeast-Catalyzed Multicomponent Synthesis of α-Aminophosphonates in One Pot

Utilizing bakers’ yeast (Saccharomyces cerevisiae) as a biocatalyst, synthesis of α-aminophosphonates in one pot has been accomplished by the three-component reaction of an aldehyde, an amine, and diethyl phosphite in moderate to good yields under solvent-free reaction conditions.

Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.     

TfOH/C-catalyzed one-pot three-component synthesis of α-amino phosphonates under solvent-free conditions

The TfOH/C was readily prepared via simple absorption of triflic acid onto activated charcoal. This solid acid was used as an efficient catalyst for the synthesis of α-aminophosphonates through the Kabachnik–Fields reaction of carbonyl compound, amine and diethyl phosphite under solvent-free conditions.     

Design,green synthesis,anti-microbial,and anti-oxidant activities of novel α-aminophosphonates via Kabachnik-Fields reaction

An efficient and environmentally friendly protocol has been developed for the synthesis of novel α-aminophosphonates in good to excellent yields (76–92%) by a one-pot, three-component reaction of an amine, an aldehyde, and diphenyl phosphite using polyethylene glycol (PEG-400) as a green solvent at 80°C via Kabachnik-Fields reaction. Their chemical structures were elucidated by IR, ¹H, ¹³C, and ³¹P NMR spectroscopy, mass spectrometry, and elemental analysis. The titled compounds displayed moderate to high anti-microbial and anti-oxidant activities.     

Tween-20: An Efficient Catalyst for One-Pot Synthesis of α-Aminophosphonates in Aqueous Media

Abstract

A green one-pot three-component synthesis has been developed for α-aminophosphonates by condensation of aldehydes, amines, and diethylphosphite by using nonionic surfactant Tween-20 as catalyst in aqueous media. The results showed that this synthetic route for α-aminophosphonates takes just 25–60 min for completion at 60 °C and affords 64%–91% yields depending on the nature of the amine substrates. The major advantages of this novel method are green reaction conditions with water as solvent, simple workup, less reaction times, and high to moderate yields.     

Clean Procedure for the Synthesis of α-Aminophosphonates Catalyzed by Biodegradable Ionic Liquid

Abstract

A biodegradable SO₃H-functionalized ionic liquid (IL) was prepared and used as the catalyst for a one-pot, three-component condensation synthesis of α-aminophosphonates from aldehydes, amines, and triethylphosphite/diethylphosphite at room temperature under solvent-free conditions or in aqueous media. The products could be simply separated from the reaction mixture and the catalyst could be recycled and reused for several times without noticeably reducing catalytic activity.     

Mesoporous aluminosilicate nanocage-catalyzed three-component coupling reaction: an expedient synthesis of α-aminophosphonates

Here we demonstrate for the first time the synthesis of α-aminophosphonates through the three-component coupling reaction of aldehydes, amines, and diethyl phosphite by using highly acidic 3D mesoporous aluminosilicate nanocage catalyst, which gave excellent yield with a high selectivity in a short reaction time due to its high acidity, 3D pores, and a huge space in the nanocages.     

Microwave assisted synthesis and Anti-microbial activity of new Diethyl ((dialkoxyphosphoryl) (2-hydroxyphenyl) methyl) phosphoramidates

The synthesis of new α-aminophosphonates 4a-j (diethyl((dialkoxyphosphoryl)(phenyl)methyl)phosphoramidates) were achieved through a one pot simple and efficient method from the three-component condensation reaction (Kabachnik-Fields reaction) of diethyl phosphoramidate, aryl salicylaldehydes, and dialkyl phosphite by using microwave irradiation under solvent-free and catalyst-free conditions in good to excellent yields and short reaction times. The structures of the novel products were established by IR, ¹H, ¹³C & ³¹P-NMR and Mass spectroscopy. All the synthesized compounds were screened their antimicrobial activity.     

Alum： An efficient catalyst for one-pot synthesis of α-aminophosphonates

Alum (KAl(SO ₄) ₂·12H ₂O) is an inexpensive, efficient, non-toxic and mild catalyst for the one-pot synthesis of α-aminophosphonates.A three component reaction of an aldehyde/ketone, an amine and triethyl phosphite was carried out under solvent-free conditions to afford the corresponding a-aminophosphonates in short reaction times and high yields with the green aspects by avoiding toxic catalysts and solvents.     

Sodium Dihydrogen Phosphate as an Efficient Catalyst for One-Pot,Three-Component Synthesis of α-Aminophosphonates Under Solvent-Free Conditions at Room Temperature

A simple, efficient, and general method has been developed for the one-pot, three-component synthesis of α-aminophosphonates from a condensation reaction of trimethyl phosphite, aldehydes, and amines in the presence of sodium dihydrogen phosphate under solvent-free conditions. Thus, α-aminophosphonates were synthesized relatively quickly in good yields at room temperature.     

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.     

A mild and highly efficient protocol for the one-pot synthesis of primary α-amino phosphonates under solvent-free conditions

Under solvent-free reaction conditions and in the presence of solid LiClO₄ a novel and mild protocol for the one-pot, three-component synthesis of primary α-amino phosphonates from an aldehyde, hexamethyldisilazane and a trialkyl phosphite is described giving high yields and having short reaction times. The same products are obtained in very low yields, when the three-component reaction is carried out under microwave irradiation and in the absence of solid LiClO₄. Examples of some prepared 1-aryl-N,N′-bis(arylidene)methanediamines are also described.     

Nano indium oxide catalyzed efficient synthesis of propargylamines via C-H and C-Cl bond activations

A simple, and efficient nano In₂O₃ catalyzed one-pot three-component coupling of terminal alkyne, dichloromethane, and secondary amine has been developed for the synthesis of propargylamines under mild reaction conditions. The catalyst was recovered and reused for three times without significant loss of catalytic activity.     

Highly efficient metal-free one-pot synthesis of α-aminophosphonates through reduction followed by Kabachnik–fields reaction using three-component system

One-pot synthesis of α-aminophosphonates directly from aryl nitro compounds, aldehydes/ketones, and diethyl phosphite using sodium dithionite through reduction and followed by Kabachnik–Fields reaction under metal-free conditions is reported. The major advantages are excellent yield, high chemoselectivity, neutral reaction medium, and simple experimental procedure. This methodology consists of the following steps: 1) amine formation from nitro compound, 2) imine formation from amine and aldehyde/ketone, 3) phosphate addition to imine.     

BF3·SiO2-catalyzed one-pot synthesis of α-aminophosphonates in ionic liquid and neat conditions

α-Aminophosphonates were synthesized in a simple and efficient method from the three-component condensation reaction of 5-amino 2,2-difluoro-1,3-benzodioxole, aromatic aldehydes, and diethyl phosphite by silica-supported boron trifluoride (BF₃·SiO₂) in ionic liquid ([bmim][HCl]) under solvent-free conditions at room temperature in good to excellent yields and short reaction times. The catalyst can be recovered and reused for several times without any significant loss of activity. It was observed that a homogeneous reaction medium proved beneficial for the yield of the reaction.