Organocatalytic synthesis of α-hydroxy and α-aminophosphonates

A new and highly flexible procedure is described for the synthesis of α-amino- and α-hydroxy phosphonates. In the presence of a catalytic amount of oxalic acid (10 mol %), trimethyl phosphite reacts with aldehydes or imines (generated in situ from an aldehyde and an amine) to yield the corresponding coupled products in good yield.     

Neat synthesis and antioxidant activity of α-aminophosphonates

A simple, efficient, and environmentally benign method for a three-component reaction of an amine, an aldehyde and diethyl phosphite catalyzed by Amberlyst-15 has been developed to afford α-amino phosphonates in high yields and short reaction times under solvent-free reaction conditions using microwave irradiation. The major advantages of the present method are inexpensive, ecofriendly and reusable catalyst and also studied their antioxidant activity of synthesized compounds.     

Convenient synthesis of fluoroalkyl α- and β-aminophosphonates

Addition of both alkyl phosphites and phosphonate α-carbanions to N-substituted aldimines derived from fluoroalkyl aldehydes presents a convenient method for synthesis of fluoroalkyl α- and β-aminophosphonates in good yield (55-86%) under mild conditions.     

Synthesis of new dialkyl α-aminophosphonates and dialkyl α-aminothiophosphonates

New dialkyl α-aminophosphonates and α-aminothiophosphonates were synthesized by reactions of dialkyl phosphites orO,O-dialkyl thiophosphites withN-benzylidene 2-(vinyloxy)ethylamine orN-(4-fluorobenzylidene)-2-(vinyloxy)ethylamine. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1815–1817, September, 1999.     

Antioxidant and anticancer activities of α-aminophosphonates containing thiadiazole moiety

In the current study, α-aminophosphonates containing thiadiazole moiety (1–4) was synthesized, characterized and their antioxidant and anticancer activities were carried out. The compounds (1–4) were synthesized from the reaction of 2-amino-5-methyl-1,3,4-thiadiazole with various aldehydes, triphenylphosphite and mixed valence Cu(I)/Cu(II) inorganic coordination polymer as a catalyst. The elucidation of compounds structures were carried out using different spectroscopic techniques. The antioxidant properties were carried out using radical scavenging methods (DPPH) which exhibited excellent scavenging activity particularly with compound 3. The cytotoxic effects of the five compounds on the human hepato cellular carcinoma (HepG2) and breast adeno carcinoma (MCF7) cell lines were evaluated using MTT assay which revealed the presence of cytotoxic effect with highest activity for compound 3 on HepG2 and compound 1 on MCF7. This suggests that these five compounds, particularly compounds 1 and 3, have antioxidant and anticancer effect and could be used as novel chemotherapeutic compounds but this needs further in vivo investigation to confirm our in vitro results.     

Microwave-assisted synthesis and anti-inflammatory activity evaluation of some novel α-aminophosphonates

An expeditious green synthetic approach was developed for the synthesis of α-aminophosphonates in good yields through one-pot three component reaction (Kabachnik-Fields reaction) of equimolar quantities of N-(4-amino-2-phenoxy phenyl)methanesulfonamide, diethylphosphite and various aldehydes under conventional as well as microwave irradiation methods. The newly synthesized compounds were characterized by NMR (³¹P, ¹H, and ¹³C), Mass, IR and C, H, N analyses. The synthesized compounds were screened for their anti-inflammatory activity using rat paw edema method. Most of the compounds from the series showed good anti-inflammatory activity when compared with standard drug. Especially the compounds 5d bearing 4-hydroxy-3-nitrophenyl moiety, 5e bearing 3-bromo-4-fluorophenyl moiety, 5g incorporated with 2,4-dichlorophenyl moiety and 5f containing 4-chlorophenyl moiety exhibiting edema inhibition of 91.01% to 85.39% after 4 h of carrageenan injection while the other compounds displayed inhibition ≥75%.     

Meglumine sulfate-catalyzed one-pot green synthesis and antioxidant activity of α-aminophosphonates

A green and efficient synthetic protocol has been developed for the synthesis of a new series of substituted diethyl(((2-methoxy-5-(trifluoromethyl)phenyl)amino)(phenyl)methyl)phosphonates via a one-pot three-component reaction of 2-methoxy-5-trifluoromethyl aniline with various aromatic-substituted aldehydes and diethyl phosphite using meglumine sulfate as an eco-friendly catalyst at room temperature under solvent-free conditions. The merits of this method are high product yield, short reaction time, easy workup, and purification. All the synthesized compounds were evaluated for the antioxidant activity by DPPH, NO, and H₂O₂ methods using ascorbic acid as a standard. The compounds 4a and 4g showed the highest antioxidant activity than that of the standard ascorbic acid.     

Synthesis,spectral characterization and bioactivity evaluation of novel α-aminophosphonates

A facile synthesis of novel α-aminophosphonates 5a-j was accomplished by condensation of imines (3a-j) with diethyl phosphite (4) in ethanol at 50–60°C using easily recoverable and reusable catalyst, tetramethyl guanidine (TMG) via pudovik reaction in high yields. All the title compounds were characterized by spectral and elemental analysis. They were further screened for their abilities towards in vitro antibacterial, antifungal and antioxidant activities. The compounds 5g, 5d, 5f exhibited good antibacterial and antifungal activities compared to the standard bactericide, Penicillin and fungicide, Griseofulvin, respectively. The compounds 5h, 5i, 5g, and 5c exhibited good antioxidant activity compared to the standard ascorbic acid.     

Click-chemistry approach to isoxazole-containing α-CF3-substituted α-aminocarboxylates and α-aminophosphonates

A convenient strategy for the synthesis of isoxazole-containing α-CF(3)-substituted α-aminocarboxylates and α-aminophosphonates have been developed. The method is based on copper-catalyzed 1,3-dipolar cycloaddition of different aromatic nitrile oxides to functionalized acetylenes.     

An efficient synthesis of α-hydroxyphosphonates and α-aminophosphonates in the presence of chlorotrimethylsilane

Abstract

Solvent free, and quantitative yielding synthesis of α-hydroxyphosphonates (2a–h) from 2-chloroquinolin-3-carbaldehyde (1a–h) and α-aminophosphonates (4a–p) from imines (3a–p), obtained from 2-chloroquinoline-3-carbaldehyde by using triethylphosphite in the presence of chlorotrimethylsilane at room temperature in short time.     

Nano Gd2O3 catalyzed synthesis and anti-oxidant activity of new α-aminophosphonates

A one pot three-component nano Gd₂O₃ catalyzed neat reaction of 2-morpholinoethanamine and dimethylphosphite with various salicylaldehydes under microwave irradiation afforded a series of new α-aminophosphonates in high yields. The synthesized compounds were characterized by FT-IR, (¹H, ¹³C, ³¹P)-NMR, and mass spectral methods. The antioxidant activity of these compounds was evaluated against DPPH, NO, and H₂O₂ methods and found that the compound Dimethyl (2-hydroxy-5-nitrophenyl) (2-morpholinoethylamino) methylphosphonate (4h) has higher antioxidant activity than the corresponding standards.     

Nano-Cuo–Au-catalyzed solvent-free synthesis of α-aminophosphonates and evaluation of their antioxidant and α-glucosidase enzyme inhibition activities

A new green and efficient method has been developed for the synthesis of α-aminophosphonates through one-pot three-component Kabachnik–Fields reaction. It involves the reaction of a 2-aminophenol with different substituted aromatic aldehydes and dimethyl phosphite in the presence of nanocopper oxide–gold (CuO–Au) catalyst under solvent-free conditions at 60?°C. Nano-CuO–Au catalyst was found to have many advantages like high activity, simple workup, and good (87%) to very high yields (96%). The products were characterized by IR, ¹H, ¹³C, and ³¹P NMR spectra and elemental analysis. All the synthesized compounds were screened for in vitro antioxidant and α-glucosidase inhibition activities. The compound 4b showed higher 2,2-diphenyl-1-picrylhydrazyl and H₂O₂ radical scavenging activity and compound 4e showed higher NO radical scavenging activity than the standard ascorbic acid. The compound 4j has much higher α-glucosidase enzyme inhibition activity than the standard acarbose.     

Synthesis and antitumor activity of α-aminophosphonates containing thiazole[5,4-b]pyridine moiety

A new procedure is developed for the synthesis of α-aminophosphonates containing thiazole[5,4-b]pyridine moiety from conveniently available starting materials. The target compounds were characterized by infrared, (1)H NMR, (13)C NMR, (31)P NMR, mass spectrometry and elemental analysis. The newly synthesized compounds were evaluated for their anticancer activities against PC-3, Bcap-37, H460 cells in vitro by the MTT method. Compounds 3b and 3f are highly effective against PC-3, Bcap-37 cells and good to H460 cells. Further study is necessary to find out the potential antitumor activities.     

Multicomponent reactions in a one-pot synthesis of α-aminophosphonates and α-aminophosphonic diamides with anti-inflammatory properties

Abstract  

Schiff-base Kabachnik–Fields intermediates generated in situ from substituted pyrazole-4-carbaldehyde and 2-aminothiophene derivatives were trapped by dialkyl phosphites to produce the corresponding α-aminophosphonates in moderate yields. The latter products could be also obtained in excellent yields (≥75%) by directly applying the phosphorus reagents to the Schiff bases. Next, dialkyl phosphites were applied to one of the parent aldehydes to give the expected α-hydroxyphosphonate derivatives. Applying hexaalkyl triamidophosphites to the Schiff base in ethanol afforded methylphosphonic diamide derivatives, whereas ring attack on the pyrazole ring occurred when the same amidophosphites were applied to the parent aldehyde to give the corresponding alkylidenephosphorane ylides in an open structure form in good yields. Some of the new compounds exhibited considerable anti-inflammatory properties.     

A catalyst-free synthesis of α-aminophosphonates in glycerol

A simple and efficient method is described using glycerol as a solvent in the catalyst-free synthesis of α-aminophosphonates in high purity. Products are prepared by the Kabachnik–Fields reaction from amines, phosphites, and carbonyl compounds. The method does not require a toxic catalyst.     

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.     

Microwave assisted synthesis and X-ray structure of a novel anthracene-derived aminophosphonate. Enantioseparation of two α-aminophosphonates and genotoxicity in vivo

A novel anthracene-derived α-aminophosphonate has been synthesized through a classical addition reaction of dimethyl phosphite to a Schiff base and via a microwave assisted Kabachnik–Fields reaction. The compound has been characterized by elemental analysis, TLC, IR, NMR, and fluorescent spectra. The X-ray analysis showed that the compound crystallizes in the orthorhombic space group Pbca (N° 61) with one molecule per asymmetric unit. The enantioseparation of two racemic aminophosphonates (5 and 6) into enantiomers (5a, 5b and 6a, 6b, respectively) has been performed. Data about genotoxicity and antiproliferative activity in vivo of the racemic compounds and their enantiomeric forms is also presented. The studied racemic α-aminophosphonates 5 and 6 and their enantiomers have weak genotoxic effect. Both pairs of enantiomers did not show a significant inhibition of cell dividing processes in the bone marrow cells compared to 5 and 6. The hematopoietic function of the bone marrow will not be discontinued after exposure of the tested compounds.