Synthesis, X-ray Crystallographic Analysis and Bioactivities of α-Aminophosphonates Featuring Pyrazole and Fluorine Moieties

A series of novel -aminophosphonates containing pyrazole and fluorine moieties was designed and synthesized through ultrasonic-assisted condensation and solvent-free addition reactions. Their structures were verified by IR, ^1H NMR, ^13C NMR and elemental analysis. The crystal structure of diethyl[（4-cyano-1H-pyrazol-3-ylamino）（3,5-difluorophenyl）methyl]phosphonate（4a, C15H17F2N4O3P） was determined by single-crystal X-ray diffraction. Compound 4a crystallizes in the triclinic system, space group P1 with a = 8.381（3）, b = 10.103（5）, c = 11.268（3） A, α= 83.772（19）, β= 74.726（19）, γ= 70.964（18）, V = 869.9（6） 3, Mr = 370.30, Dc = 1.414 g/cm^3, Z = 2, F（000） = 384, = 0.200 mm^-1, MoKa radiation（ = 0.71073 ）, the final R = 0.0487 and w R = 0.0823 for 1582 observed reflections with I 〉 2（I）. X-ray diffraction analysis reveals that there are two planes in 4a, and the dihedral angle is 71.51°. Two intermolecular hydrogen bonds and a face-to-face … stacking interaction are observed in the crystal structure. The compounds were evaluated for their antifungal, antiviral and antitumor activities, respectively. Among them, 4b, 4c, 4g and 4h exhibit good activities on Sclerotium rolfsii Sacc at 200 μg/m L, while 4b, 4c, 4f and 4g possess good anti-TMV activities at 500 μg/m L. Unfortunately, all of the compounds showed weak antitumor activities.

Solvent-and Catalyst-free Synthesis and Antifungal Activities of α-Aminophosphonate Containing Cyclopropane Moiety

Nine new a-aminophosphonate derivatives containing cyclopropane moiety have been synthesized via conventional and microwave irradiation methods under solvent- and catalyst-free condition. The structures of the title compounds have been confirmed by ^1H NMR, ^31p NMR FTIR, EI-MS and FTICR-MS. Their antifungal activities were evaluated in vivo and some of the compounds were found to exhibit excellent antifungal activities against Corynespora cassiicola, Pseudomonas syringae pv. Lachrymans, Pseudoperonospora cubensis and Sclerotinia sclerotiorum.

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

Alum （KAl（SOa）E.12H2O） is an inexpensive, efficient, non-toxic and mild catalyst for the one-pot synthesis of α-aminopho- sphonates. A three component reaction of an aldehyde/ketone, an amine and triethyl phosphite was carried out under solvent-free conditions to afford the corresponding α-aminophosphonates in short reaction times and high yields with the green aspects by avoiding toxic catalysts and solvents. 2009 Murlidhar S. Shingare. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

Synthesis and antitumor activity of α-aminophosphonate derivatives containing thieno[2,3-d]pyrimidines

Two series of thieno[2,3-d]pyrimidine derivatives were designed and synthesized, in which bioactive α-aminophosphonate subunits were introduced at the N3 position through an N-N bond connection. The in vitro cytotoxic activity of the novel compounds was tested against human esophageal carcinoma cells （EC109）, human hepatocarcinoma cells （HepG2）, human gastric carcinoma cells （MGC-803）, respectively, by the MTT method. The evaluation results revealed that compounds fimb, 6mf, 6mg, 6rid and 6nh exerted the most potent inhibition against HepG2, MGC-803 and EC109 cells, respectively. In particular, compound 6rag presented excellent inhibitory effect against HepG2 （91.2%） and MGC-803 （94.4%） cells.

Extraction and recovery of cerium(Ⅳ) and thorium(Ⅳ) from sulphate medium by an α-aminophosphonate extractant

In the present work, a novel α-aminophosphonate extractant（Cextrant 230） was synthesized for the extraction and recovery of cerium and thorium from sulphate medium. The introduction of amine group into the phosphate molecule would enhance the extraction of Ce（Ⅳ） and Th（Ⅳ）. The effects of extractant concentration, H2SO4 concentration and temperature on the metal extraction were investigated in detail. It was found that the extraction of Ce（Ⅳ）, Th（Ⅳ） and REs（La, Gd, Yb） in sulphate medium decreased in the following order： Ce（Ⅳ）〉Th（Ⅳ）〉REs（Ⅲ）. A solvent extraction process to extract and recover cerium and thorium from bastnasite leaching was proposed, in which the purities of cerium and thorium products reached 99.9% and 99% with yield of 92% and 98%, respectively.

Thiamine hydrochloride(VB1):An efficient catalyst for one-pot synthesis of α-aminophosphonates under ultrasonic irradiation

An efficient synthesis of novelα-aminophosphonates by the reaction of aldehydes and amines with triethyl phosphite in the presence of the easily available,inexpensive,and nontoxic catalyst thiamine hydrochloride（VB1）.This method affords theα-aminopho-sphonates under the influence of ultrasound irradiation in aqueous medium,in short reaction times（4-6 min）,high yields（85-95%）, with improved purity.The process is green,mild,inexpensive and excellent yields are the main compensation of this procedure.

Cobalt(Ⅱ) chloride accelerated one-pot three-component synthesis of α-aminophosphonates at room temperature

A simple,efficient,and general method has been developed for the one-pot,three-component synthesis ofα-aminophosphonates from condensation reaction of trimethyl phosphite,aryl aldehydes and aryl amines in the presence of CoCl_2-6H_2O under solvent-free conditions.Thusα-aminophosphonates were synthesized relatively quickly in good yields at room temperature.

The design and synthesis of a novel organophosphorus compound containing the structure of both β-amino acid and β-aminophosphonate

A novel organophosphorus compound containing the structure of bothβ-amino acid andβ-aminophosphonate is designed and synthesized.Arbuzov reaction with P（OEt）_3,the N-Boc protected iodide 3 cannot provide the desired product but 2-oxazolidinone 4 because of the neighboring-group participation of the Boc moiety.To avoid the intramolecular participation of the carbamates,the Ts protecting group is employed and the Ts-protected iodide 5 affords the target product successfully.

A Facile Synthesis of N-Substituted Spirocyclic Diester of α-Aminophosphonic Acid

A simple and direct method for preparation of N-substituted spirocyclic dieSter of □-amino phosphonic acid (4) in high yield is introduced. The reaction consists of the threecomponent reachon of phenylurea (1), an aromatic aldehyde (2), and 3,9-dichloro-2,4,8,10-tetraoxa- 3, 9 -diphosphaspiro [5,5] undecane (3) in anhydrous benzene.

Synthesis,Bioactivity and Crystal Structure Analysis of Diisopropyl[(4-cyanopyrazol-3-ylamino)(2-hydroxyl-phenyl) methyl]phosphonate

The title compound,diisopropyl[（4-cyanopyrazol-3-ylamino）（2-hydroxylphenyl） -methyl] phosphonate was synthesized by the addition reaction of diisopropyl phosphite and N-（4-cyanopyrazole-3-yl） -2-hydroxylphenyl-imine. Its structure was characterized by IR,1H NMR,elemental analysis and single-crystal X-ray diffraction. The crystal belongs to the triclinic system,space group P1^- with a = 9.1840（13） ,b = 9.2278（13）,c = 12.1952（17） A,α = 93.846（2） ,β = 90.947（2） ,γ = 111.289（2） °,V = 959.9（3） A^3,Dc = 1.309 g/cm^3,Z = 2,μ（MoKa） = 0.173,F（000） = 400,the final R = 0.0414 and wR = 0.1196 for 2985 observed reflections（I 〉 2σ（I）） . The pyrazole and benzene moieties are approximately coplanar in each case. The dihedral angle between planes 1 and 2 is 82.99°. The crystal structure is stabilized by three intermolecular hydrogen bonds of O（1） -H（1） …O（2） ,N（2） -H（2） …N（3） and N（2） -H（2） …O（1） . Preliminary bioassay indicated that the title compound possessed antiviral activity to some extent.

An Aminopyrrolidinyl Phosphonates—A New Class of Antibiotics: Facile Synthesis and Predicted Biological Activity

A novel class of aminopyrrolidinyl phosphonates was synthesized in 74% - 80% isolated yield by the addition of three-fold excess of primary amines to diethyl 4-chloro-1-butynylphosphonates. The reaction was carried out at room temperature and in the absence of solvent or catalyst to give solely compounds which showed predicted biological activity based on PASS program. Some of the synthesized derivatives of antibiotics exhibit properties for the treatment of stroke, the treatment of acute neurological disorders, and can also be acetyl esterase inhibitors.

Synergistic extraction of heavy rare earths by mixture of α-aminophosphonic acid HEHAMP and HEHEHP

Synergistic extraction of heavy rare earths(REs) were investigated in chloride media by the mixture of(2-ethylhexylamino)methyl phosphonic acid mono-2-ethylhexyl ester(HEHAMP) and 2-ethylhexyl phosphoric acid mono-2-ethylhexyl ester(HEHEHP). The maximum synergistic enhancement coefficients(R) of Lu, Yb, Tm, Er, Y and Ho are 2.89, 2.76, 2.54, 2.14, 2.14 and 2.06, respectively, when the mole fraction X_(HEHAMP) is 0.5. The synergistic separation factors of the heavy REs are obtained(β_(Y/Ho)=1.31,β_(Er/Y)= 1.61,β_(Tm/Er)= 1.78, β_(Yb/Tm)= 1.76, β_(Lu/Yb) = 1.20). The extracted complex is determined to be RE[H(EHAMP)_2][H(EHEHP)_2]_2 by the slope analysis method. The loading capacities of the mixtures consisting of 15% HEHAMP and 15% HEHEHP for Y and Lu are about 26.59 g/L(Yb_2 O_3) and 27.25 g/L(Lu_2 O_3),respectively.

Extraction and separation of heavy rare earths from chloride medium byα-aminophosphonic acid HEHAPP

The extraction and separation of heavy rare earths（REs） using newly synthesized a-aminophosphonic acid extractant 2-ethylhexyl-3-（2-ethylhexylamino）pentan-3-yl phosphonic acid（HEHAPP, HA） in nheptane were investigated from chloride medium. The extraction stoichiometries of lanthanum, gadolinium, yttrium and lutetium are determined to be REA3 by the slope analysis method. The favorable separation factors of adjacent heavy REs（Ⅲ）,i.e. β（Y/Ho）, β（Er/Y）,β（Tm/Er）,β（Yb/Tm） and β（Lu/Yb）, are determined to be1.87,1.36, 3.21,3.22 and 1.93, respectively, when extracted from a binary system at proper condition. The loading capacities of HA for Ho, Er, Yb and Lu increase in the order Ho 〈 Er 〈 Yb 〈 Lu with the values being 0.201, 0.205, 0.216 and 0.229 mol/L, respectively. So HA would be a potential extractant for the separation of heavy REs（Ⅲ）. Among inorganic acids such as H2 SO4, HNO3 and HCl, HCl is tested to be the most effective stripping agent.

Separation of trivalent rare earths from nitrate medium using solvent extraction with a novel extractant 2-ethylhexyl((2-ethylhexylamino)methyl)phosphonic acid

By introducing the amine group into the structure of P227,a novel extractant 2-ethylhexyl((2-ethylhexylamino)methyl)phosphonic acid(EEAMPA,abbreviated as HA)was synthesized for the extraction and separation of trivalent rare earths(REs)from nitrate medium.The influence factors including extractant concentration,equilibrium time,HNO_(3)concentration,separation factors,cycle regeneration,stripping acidity,and actual leach liquor of metal ions,were studied systematically.The results show that the extraction ability of EEAMPA for REs decreases with increasing acidity.A possible extraction mechanism is proposed and the extracted species as REHA_(3)(NO_(3))are confirmed by the slope analysis method.The extraction equilibrium can reach faster than P227.It shows good chemical stability and cycling regeneration.Stripping studies show that HCl is an excellent stripping agent and REs can be effectively stripped from the organic phase.