Properties of polyethylene modified with phosphonate side groups. I. Thermal and mechanical properties

Low-density polyethylene was modified by the inclusion of phosphonate ester pendent groups by using an oxidative chlorophosphonylation reaction followed by esterification of the polyethylene poly(phosphonyl chloride) with an alcohol. Two different types of phosphonate esters were prepared: dimethyl phosphonate from the reaction with methanol and a phosphonate graft copolymer from the reaction with hydroxy-terminated poly(ethylene oxide) (PEO). For the latter, oligomers with molecular weights of 350 and 750 were used. For each type of phosphonate, a series of polymers were prepared with pendent group concentrations ranging from 0 to 9.1 substituents per 100 carbon atoms. The modified polymers were characterized by infrared spectroscopy, differential scanning calorimetry, and by measurement of the tensile modulus. Infrared spectroscopy proved to be useful for determining if the polymer modification reaction resulted in entirely phosphonate ester pendent group substitutions or if unesterified phosphonic acid groups were also present. The polymers prepared in this investigation exhibited no infrared absorbances arising from phosphonic acid groups. The presence of phosphonate ester groups resulted in a decrease of crystallinity with increasing phosphonate concentration and with the exception of the polymers containing 9.1 PEO–phosphonate grafts per 100 carbon atoms, the effect of phosphonylation on the melting temperature of the polymers was consistent with Flory's theory for the melting point depression of random copolymers. The tensile modulus measured from a constant uniaxial elongation experiment decreased with increasing phosphonylation. The behavior of all three phosphonate series was identical and could be attributed to the effect of decreasing polymer crystallinity.     

Synthesis of four enantiomers of 2-acetamido-1-hydroxypropylphosphonates

Enantiomerically pure diethyl 2-acetamido-1-hydroxypropylphosphonates were synthesised from N-[(R)-(1-phenylethyl)]aziridine-(2S)- and N-[(S)-(1-phenylethyl)]aziridine-(2R)-carboxaldehydes via phosphonylation followed by acetylation of the hydroxy groups and the simultaneous hydrogenolytic cleavage of the aziridine rings and the removal of the chiral auxiliaries. In addition, enantiomerically pure diethyl (1S,2R)- and (1R,2S)-2-amino-1-hydroxypropylphosphonates (the phosphonate analogues of isothreonine) were separated.     

顺[1-溴-2-羟基-2-(对-甲氧基苯基)乙基]膦酸二异丙酯的羟基反应性能的研究

研究了顺[1-溴-2-羟基-2-(对-甲氧基苯基)乙基]膦酸二异丙酯羟基的反应性能。由于膦酸酯基和电负性的溴原子的吸电子作用,羟基氧原子周围的电子云密度降低．从而增强了羟基上质子的酸性并减弱了碱性条件下相应的烷氧基负离子的亲核能力,因而得到了有关羟基与酚进行Mitsunobu脱水反应和酯化反应的特殊反应性能。同时,由于氢键的作用和膦酸酯基团的空问障碍作用,羟基与酰氯的反应活性较低。     

Organocatalytic asymmetric direct phosphonylation of alpha,beta-unsaturated aldehydes: mechanism, scope, and application in synthesis

The first direct organocatalytic enantioselective phosphonylation of alpha,beta-unsaturated aldehydes with phosphite, in combination with a Br?nsted acid and a nucleophile, is presented. Mechanistic investigations have revealed that the first step in the catalytic process, after the formation of the iminium intermediate, is the addition of phosphite to the beta-carbon atom, leading to the phosphonium ion-enamine intermediate. The rate-determining step for the reaction is the transformation of P(III) to P(V), which occurs via a nucleophilic SN2-type dealkylation, and a screening of various nucleophiles shows that soft nucleophiles in combination with a Br?nsted acid improve the reaction rate and enantioselectivity. The reaction conditions developed show that the use of 2-[bis(3,5-bistrifluoromethylphenyl)trimethylsilanoxymethyl]pyrrolidine as the catalyst and tri-iso-propyl phosphite as the phosphonylation reagent, in the presence of stoichiometric amount of benzoic acid and sodium iodide, gave the beta-phosphonylation of aromatic and aliphatic alpha,beta-unsaturated aldehydes in good yields and enantioselectivities. The products formed by this new reaction have been used for the synthesis of a number of biologically important compounds, such as optically active hydroxyl phosphonate esters, phosphonic acids, and especially glutamic acid and fosmidomycin precursors, of which the two latter are showing important properties for the treatment of central nervous system diseases and as anti-malarial compounds, respectively. DFT calculations have been applied to explain the approach of the phosphite to the reactive carbon atom in the iminium intermediate in order to account for the observed absolute enantioselectivity in the reaction.     

Glycosylphosphonates of 2-Amino-2-deoxy-aldoses. Synthesis of a Phosphonate Analogue of Lipid X

A preparation of glycosylphosphonates ( 27 , 28 , 36 , 38 , and 39 ) from 2-azido-2-deoxy-glycoses ( 26 , 35 , and 37 ) and the synthesis of the non-isosteric phosphonate analogue 3a of lipid X( 2 ) are described. The 2-azido group was introduced by azidonitration. Treatment of the 1-O-acetyl-2-azido-2-deoxy-β-D-galactopyranose 22 with 1.5-3 equiv. of P(OMe)₃ and 1.2-2.5 equiv. of TfOSiMe₃ gave mainly recovered starting material. In P(OMe)₃ as the solvent, the dimethyl phosphoramidate 24 was obtained by way of a Staudinger reaction, even in the presence of TfOSiMe₃. Treatment of the benzylated α-D-galacto-trichloroacetimidate 26 , however, with P(OMe)₃ and TfOSiMe₃ gave a 1:1 mixture of the α- and β-D-galacto-phosphonates 27 and 28 , while the acetylated α-D-gluco- imidate 35 led to the α-D-gluco-configurated phosphonate 36 . The stereoselectivity of the phosphonate formation is related to the relative ease of formation of oxonium-ion intermediates from 26 and 35 . Starting from the phosphonate 36 , deacetylation, benzylidenation, reduction of the azido group, acylation with (R)-3-(benzyloxy)tetradecanoic acid and deprotection yielded the desired compound 3a which was crystallized in the presence of 2 equiv. of (aminomethylidyne)trimethanol (Tris.). The structure of the phosphonates was deduced from their ¹H-, ¹³C-, and ³¹P-NMR spectra.     

Synthesis of α-hydroxy(polyprenyl) bisphosphonates

Bisphosphonates derived from natural terpenes were synthesized by phosphonylation of corresponding aldehydes. The general strategy of introduction of the phosphonate groups into the polyprenol molecule involves successive treatment of a hydroxyl compound by Swern reagent to oxidize the C-OH group into C=O and a (EtO)₃P/[PyH]⁺ClO _? ⁴ mixture to phosphylate the resulting carbonyl compound.     

Cyclic Elimination and Intramolecular Insertion Reactions of Thermally-Generated Monomeric Metaphosphoric Esters (Metaphosphates)

Abstract

2-Aryl-1,3,2-dioxaphospholanes (aryloxyphosphites) decompose thermally in the gas phase with loss of ethylene to generate aryl metaphosphates which cyclise by intramolecular insertion (phosphonylation) or abstract a β-hydrogen to form a terminal alkene by loss of HPO₃.     

Cyclisation reactions of 2-substituted benzoylphosphonates with trialkyl phosphites via nucleophilic attack on a carbonyl-containing ortho substituent

Dimethyl 2-acetoxy- and dimethyl 2-benzoyloxy-benzoylphosphonate undergo cyclisation and deoxygenation in the presence of excess trimethyl phosphite to give dimethyl (3-methyl-1-benzofuran-2-yl)phosphonate and dimethyl (3-phenyl-1-benzofuran-2-yl)phosphonate, respectively. The reaction pathway has been shown to involve phosphite attack on initially formed tricyclic dioxaphospholane intermediates with the subsequent loss of two molecules of trimethyl phosphate. In the absence of additional trimethyl phosphite the initially formed tricyclic dioxaphospholane intermediates lose one molecule of trimethyl phosphate and then undergo a novel rearrangement to give β-ketophosphonates. The mechanism for this reaction helps explain some previously reported epoxide rearrangements. In contrast, the initially formed anionic intermediate from the reaction of dimethyl 2-benzoyloxymethylbenzoylphosphonate with trimethyl phosphite undergoes decomposition to give a carbene intermediate which is trapped by the trimethyl phosphite to give an ylidic phosphonate.     

PHOSPHONYLATION BY A SPIROPHOSPHORANE: APPLICATION OF THE RIBOZYME CHEMISTRY IN THE BIOORGANIC SYNTHESIS

The phosphonylation by oxirane/phosphorous acid is characterized by formation of spirophosphorane, which provides the active intermediate in the reaction, β-hydroxyalkyl alkylene phosphite. Here, we demonstrate that a well-known and readily accessible spirophosphorane, 2λ⁵-2,2′spirobi[1,3,2-benzodioxaphosphole] can be used as convenient and effective phosphonylating agent in similar reaction. The easily detectable primary 3-phenylpropyl H-phosphonate, as well as 5′-O-tritylthymidyl, 4-N-benzoyl-5′-O-trityl-deoxycytidyl, 5′-O-trityl-deoxycytidyl, 6-N-benzoyl-5′-O-trityl- deoxyadenosyl 5′-O-trityluridyl, and 2′,3′-isopropylidene-uridyl H-phosphonates were prepared using a simple and straightforward procedure. Our results provide an interesting example of the potential and the limitations of a synthetic approach utilising reaction of leaving of diol system.     

Synthesis and Transformations of 5-Substituted 2-Furoyl Phosphonates

5-Chloromethyl-2-furoyl chloride when treated with triethyl phosphite has given 5-chloromethyl-2-furoyl phosphonate. This compound has reacted with sodium azide in the presence of potassium iodide to give 5-azidomethyl-2-furoyl phosphonate. Treatment of 5-chloromethyl-2-furoyl phosphonate with secondary amines even under mild conditions has caused cleavage of P–C bond with liberation of diethyl hydrogen phosphite and formation of 5-chloromethyl-2-furancarboxamide. Butanthiol in the presence of potassium carbonate in acetonitrile has converted the chloromethyl group into the butylthiomethyl one and simultaneously split the P–C bond with the formation of the corresponding thioester. Under the action of S-methylthiuronium iodide and triethylamine, 5-chloromethyl-2-furoyl phosphonate has been unexpectedly reduced into the 5-methyl derivative. 5-Butylthiomethyl- and 4-(N-morpholinomethyl)-2-furoul chlorides have been phosphorylated with triethyl phosphite into the corresponding 5-functionalized 2-furoyl phosphonates. The prepared furoyl phosphonates have reacted with resonance-stabilized phosphoranes to give phosphorylated derivatives of 3-(furyl)acrylates and 4-(furyl)but-3-en-2-one with trans-location of phosphoryl and carbonyl groups with respect to the double bond.

     

Synthesis of β-Amino Phosphonates in One-Pot Procedure

Abstract: β-amino phosphonate derivatives are synthesized in one-pot procedure via reduction of β-enamino phosphonate intermediates with NaBH₄/acetic acid or trifluoroacetic acid.     

One-pot synthesis of 2-amino-4H-chromen-4-yl phosphonate derivatives using β-cyclodextrin as reusable catalyst in water

Various 2-amino-4H-chromen-4-yl phosphonate derivatives were synthesized in good yields by condensation of salicylaldehyde, malononitrile or ethylcyanoacetate, and triethyl phosphite using β-cyclodextrin as a reusable catalyst under neutral conditions, in water.     

Cyclopropanation of 1,2-dibromoethylphosphonate: a synthesis of β-aminocyclopropylphosphonic acid and derivatives

Diethyl (1,2-dibromoethyl)phosphonate was found to undergo cyclopropanation with nitromethane in good yield. The resulting trans β-nitrocyclopropylphosphonate was converted to the trans N-protected aminocyclopropylphosphonate through a reduction–protection sequence. Subsequent hydrolysis gave the free β-aminocyclopropylphosphonic acid without any formation of ring-opening byproduct. Cyclopropanation of 1,2-dibromoethylphosphonates with nitroalkanes and their reduction are also discussed.     

Highly Stereoselective Synthesis of E-α,β-Uksaturated Nitriles from Diphenyl Cyanomethyl Phcsphine Oxide.

The Wittig-Horner reaction from diethyl cyanomethyl phosphonate 1a and aldehydes is seldom highly stereoselective¹. The use of diiscpropyl cyanomethyl phosphonate 1b has been recently proposed to improve the stereoselectivity of the reaction towards the E-α, β- unsatured nitriles 2E².     

Zn6[MeN(CH2CO2)(CH2PO3)](6)(Zn)]4- anion: the first example of the oxo-bridged Zn6 octahedron with a centered Zn(II) cation

Hydrothermal reactions of N-(phosphonomethyl)-N-methylglycine, MeN(CH(2)CO(2)H)(CH(2)PO(3)H(2)) (H(3)L), with zinc(II) acetate resulted in the formation of a novel zinc carboxylate-phosphonate, [Zn(6)L(6)(Zn)][Zn(H(2)O)(6)](2) x 22H(2)O (1). The structure of 1 contains a heptanuclear zinc phosphonate cluster anion, [Zn(6)L(6)(Zn)](4-), in which seven zinc(II) cations form an unusual Zn(6)(Zn) centered octahedron with six of its Zn(3) triangle faces each further capped by a phosphonate group. The Zn(II) cations of the Zn(6) octahedron are five-coordinated whereas the centered Zn(II) cation is octahedrally coordinated. Packing of these cluster anions creates micropores occupied by the hydrated zinc(II) cations as well as lattice water molecules. The structural skeleton of 1 is retained after the removal of the lattice water molecules.     

Properties of polyethylene modified with phosphonate side groups. II. Dynamic mechanical behavior

The viscoelastic behavior of phosphonate derivatives of phosphonylated low-density polyethylene (LDPE) was studied by dynamic mechanical techniques. The polymers investigated contained from 0.2 to 9.1 phosphonate groups per 100 carbon atoms and included the dimethyl phosphonate derivative and two derivatives for which the phosphonate ester group was an oligomer of poly(ethylene oxide) (PEO). The temperature dependences of the storage and loss moduli of the dimethyl phosphonate derivatives were qualitatively similar to those of LDPE. At low phosphonate concentrations, the α, β, and γ dispersion regions characteristic of PE were observed, while at concentrations greater than 0.5 pendent groups per 100 carbons atoms, only the β and α relaxations could be discerned. At low degrees of substitution, the temperature of the β relaxation T_β decreased from that of PE, but above a degree of substitution of 0.1, T_β increased. This behavior was attributed to the competing influences of steric effects which tend to decrease T_β and dipolar interactions between the phosphonate groups which increase T_β. For the phosphonate containing PEO, a new dispersion region designated as the β′ relaxation was observed as a low-temperature shoulder of the β relaxation. The temperature of the β′ loss was consistent with T_g(U) of the PEO oligomers as determined by differential scanning calorimetry, and it is suggested that the β′-loss process results from the relaxation of PEO domains which constitute a discrete phase within the PE matrix.     

Regioselective synthesis of pyridines and dihydropyridines derived from β-amino acids and aminophosphonates by reaction of N-vinylic phosphazenes with α,β-unsaturated ketones

Reaction of N-vinylic phosphazenes with α,β-unsaturated ketones leads to the formation of pyridines derived from β-amino acids in a regioselective fashion. The use of functionalized enones derived from α-acylstyryl-carboxylates or -phosphonates affords biologically active asymmetrical and symmetrical dihydropyridines substituted with carboxylate or phosphonate groups including nitrendipine, felodipine, MRS 1097, and efonidipine analogs.     

Synthesis and Enzymatic Evaluation of Substrates and Inhibitors of β-Glucuronidases

The phosphono and the tetrazolyl analogues 4 and 5 of 4-methylumbelliferyl β-D -glucuronide (=(4-methyl-2-oxo-2H-1-benzopyran-7-yl β-D -glucopyranosid)uronic acid; 6 ) were synthesized and evaluated as substrates of β-glucuronidases. Similarly, the phenylcarbamate 7 and its phosphono analogue 8 were prepared and evaluated as inhibitors. To examine the diastereoselectivity of the phosphorylation, we also synthesized the protected L -ido-D -gluco-, and D -galacto-configurated phospha-glycopyranuronates 12, 13, 21, 22, 34 and 35 . Two strategies were followed. In the first one, the glucuronic acid 19 was decarboxylated to 11 and further transformed, via 20 , into the trichloroacetimidate 10 (Scheme 2). Phosphorylation of 10 with (MeO)₃P yielded the diastereoisomers 12 and 13 , the diastereoselectivity depending on the solvent. In MeCN, 12 and 13 were obtained in a ratio of 1:1, while in non-participating solvents the L -ido 12 was by far the major diastereoisomer. The acetate 11 was inert to (MeO)₃P, but reacted with (PhO)₃P to the anomeric mixture 21/22 , in keeping with a stabilizing 1,3-interaction in the intermediate phosphonium salt. Similarly, the phospha-galacturonates 34 and 35 were prepared from the galactoside 23 via the enol ether 26 , the lactone 27 , and the acetates 28/29 that were also transformed into the trichloroacetimidate 33 (Scheme 3). In the second, higher-yielding strategy, phosphorylation of the pentodialdehyde 39 to 40/41 was followed by hydrolysis and acetylation to the phospha-glucuronates 43/44 (Scheme 4). Transesterification to 45/46 , selective deacetylation to 48/49 , and formation of the trichloroacetimidates 50/51 were followed by glycosidation and deprotection to 4 . The tetrazole 5 was prepared from the lactones 54/55 via the N-benzylamides 57/58 that were treated with TfN₃ to give the N-benzyltetrazoles 59/60 (Scheme 4). These were transformed into the trichloroacetimidates 63/64 , glycosylated to 65 , and deprotected. The O-carbamoylhydroximo-lactone 7 derived from the glucuronate 67/68 , and the phosphonate analogue 8 were prepared by established methods. The phosphonate 4 is slowly hydrolyzed by the E. coli β-glucuronidase, but neither 4 nor the tetrazole 5 are affected by the bovine liver β-glucuronidase (Table 4). The phenylcarbamate 7 of D -glucarhydroximo-1,5-lactone, but not its phosphonate analogue 8 , is an inhibitor (K_I = 8 m?M ) of the E. coli β-glucuronidase. The bovine liver β-glucuronidase is inhibited strongly by 7 (IC₅₀ = 0.2 m?M ) and weakly by 8 (IC₅₀ = 2mM ).     

Mass spectrometry and molecular modeling studies on the inclusion complexes between alendronate and β-cyclodextrin

Complexation of alendronate sodium (AlnNa) with β-cyclodextrin (β-CD) was studied by means of ESI-mass spectrometry. The experimental results show that stable 1:1 inclusion complexes between selected bisphosphonates and β-CD were formed. In addition, complexes with different stoichiometry were observed. DFT/B3LYP calculations were performed to elucidate the different inclusion behavior between alendronate and β-CD. Molecular modeling showed that the inclusion complex of Aln-β-CD where the two phosphonate groups bound to the central carbon atom of bisphosphonate were inserted into the cavity of β-CD from its “top” side was thermodynamically more favorable than when they were inserted from its “bottom” side; the complexation energy was ?74.05 versus ?60.85 kcal/mol. The calculations indicated that the formation of conventional hydrogen bonds was the main factor for non-covalent β-CD:Aln complex formation and stabilization in the gas phase.