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Synthesis and Crystal Structure of Diethyl Tosyloxybenzylphosphonate
Abstract
Diethyl tosyloxybenzylphosphonate was synthesized by the reaction of hydroxybenzylphosphonate with p-toluenesulfonyl chloride characterized by NMR spectroscopy, elemental analyses and X-ray single-crystal diffraction. The possessing parameters: m.f. C18H23O6PS, monoclinic, P2(1)/n, a = 8.1087(9) Å, b = 20.215(2) Å, c = 12.5201(12)Å, α= 90°, β= 98.7380(10)°, γ= 90°, V = 2028.5(4) Å3, Z = 4, Mr = 398.39, Dc = 1.305 g/cm3, μ = 0.268 mm-1, F(000) = 840, T = 298(2) K, R1 = 0.0462, wR2 = 0.1076 for 3579 observed reflections with I >2σ;(I).
... Besides carboxylic chlorides, anhydrides and acids, sulfonic acid derivatives may also function as the acylating agents. By analogy with the reaction of α-hydroxyphosphonates (1B) with carboxylic chlorides, the acylation was also attempted with sulfonyl chlorides [95][96][97]. Methanesulfonyl chloride (Scheme 14, Route "a") [96] and p-toluenesulfonyl chloride (Scheme 14, Route "b") [97] worked well as sulfonylating agents in the presence of triethylamine. of the article emphasize the need for mild reaction conditions (25 °C, 0.5-3.5 h), as heating of the reaction mixture resulted in the formation of a by-product through the trimerization of the starting isothiocyanate. The α-thiocarbamoyl-oxyphosphonates 30 obtained in this way expressed plant growth regulating activity. ...
... By analogy with the reaction of α-hydroxyphosphonates (1B) with carboxylic chlorides, the acylation was also attempted with sulfonyl chlorides [95][96][97]. Methanesulfonyl chloride (Scheme 14, Route "a") [96] and p-toluenesulfonyl chloride (Scheme 14, Route "b") [97] worked well as sulfonylating agents in the presence of triethylamine. of the article emphasize the need for mild reaction conditions (25 °C, 0.5-3.5 h), as heating of the reaction mixture resulted in the formation of a by-product through the trimerization of the starting isothiocyanate. The α-thiocarbamoyl-oxyphosphonates 30 obtained in this way expressed plant growth regulating activity. ...
... Besides carboxylic chlorides, anhydrides and acids, sulfonic acid derivatives may also function as the acylating agents. By analogy with the reaction of αhydroxyphosphonates (1B) with carboxylic chlorides, the acylation was also attempted with sulfonyl chlorides [95][96][97]. Methanesulfonyl chloride (Scheme 14, Route "a") [96] and p-toluenesulfonyl chloride (Scheme 14, Route "b") [97] worked well as sulfonylating agents in the presence of triethylamine. ...
This review summarizes the main synthetic routes towards α-hydroxyphosphonates that are known as enzyme inhibitors, herbicides and antioxidants, moreover, a number of representatives express antibacterial or antifungal effect. Special attention is devoted to green chemical aspects. α-Hydroxyphosphonates are also versatile intermediates for other valuable derivatives. O-Alkylation and O-acylation are typical reactions to afford α-alkoxy-, or α-acyloxyphosphonates, respectively. The oxidation of hydroxyphosphonates leads to ketophosphonates. The hydroxy function at the α carbon atom of hydroxyphosphonates may be replaced by a halogen atom. α-Aminophosphonates formed in the nucleophilic substitution reaction of α-hydroxyphosphonates with primary or secondary amines are also potentially bioactive compounds. Another typical reaction is the base-catalyzed rearrangement of α-hydroxy-phosphonates to phosphates. Hydrolysis of the ester function of hydroxyphosphonates leads to the corresponding phosphonic acids.
... Beyond their potential bioactivity, the α-hydroxyphosphonates may be important intermediates in a series of syntheses [1]. The most important reactions are alkylations [1], acylations [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27], phosphorylations [28], substitutions [1], rearrangements [1], and dealkylations [1]. As regards acylations, a series of α-(aryloxyacetoxy)-alkylphosphonate derivatives [12][13][14][15] was prepared mainly by acylation of different α-hydroxyphosphonates with α-hydroxyphosphonates with carboxylic acid chlorides, including aryloxy-butyryloxy or -valeroxy [16] and heterocyclic derivatives [17,18]. ...
... Obviously, this is an elegant way of acylation. It is noteworthy that a tosyloxybenzylphosphonate was also described [27]. The phosphorylation of α-hydroxyphosphonates [28] was elaborated by us. ...
An efficient method applying acyl chlorides as reagents was developed for the acylation of the hindered hydroxy group of dialkyl α-hydroxy-benzylphosphonates. The procedure did not require any catalyst. A few acylations were also performed with the SC-enantiomer of dimethyl α-hydroxy-benzylphosphonate, and the optical purity was retained. A part of the acyloxyphosphonates was tested against eight tumor cell lines of different tissue origin at c = 50 μM concentration. The compounds elicited moderate cytostatic effect against breast, skin, prostate, colon, and lung carcinomas; a melanoma cell line; and against Kaposi’s sarcoma cell lines. Then, dose-dependent cytotoxicity was assayed, and benzoylation of the α-hydroxy group was identified as a moiety that increases anticancer cytotoxicity across all cell lines. Surprisingly, a few analogues were more toxic to multidrug resistant cancer cell lines, thus evading P-glycoprotein mediated drug extrusion.
The reaction of dimethyl (1-aryl-1-hydroxymethyl)phosphonates with 1-chloro-3-phospholene 1-oxides, diphenylphosphinic chloride or diphenyl chloridophosphonate affords the corresponding (1-phosphoryloxymethyl)phosphonates. The products with two different >P(O)– moieties exhibit characteristic δ P shifts and ³ J P,P couplings in the ³¹ P NMR spectra.
Abstract Straightforward and one-pot strategy to synthesize the bifunctional phosphorus Betti bases under solvent-free conditions via the condensation of 2-naphthol, aryl aldehydes and the diphenylphosphine oxide has been developed in the presence of p-toluenesulfonic acid for the first time. The entitled compounds are obtained in good yields and fully characterized by NMR, MS, IR and elemental analysis.
The three-component reaction of aldehydes, amines and triethyl or diphenyl phosphite was efficiently catalyzed by magnesium dodecyl sulfate at room temperature in water to give various α-amino phosphonates in high yields. The catalyst is easily available from inexpensive sodium dodecyl sulfate and magnesium bromide. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 22:358–362, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.20689
A conformational study of the title compound has been carried out in solution and solid states. The molecules are packed in the crystal forming a charge-transfer complex, where two different molecular pairs are found. Visible spectra data show two weak absorption bands.
The structures of 1-phenylsulphonylpyrrole, 1-phenylsulphonylindole, 4,5,6,7-tetrahydro-1-phenylsulphonylindole, and 1,2,3,4-tetrahydro-9-phenylsulphonylcarbazole have been determined by X-ray crystallography. The heterocyclic nitrogen is planar in some and pyramidal in others. A preferred geometry for the PhSO2N unit emerged from the structures; it is compared with available data for sulphonamides.
Phosphonamidate-containing peptidic substrate analogues of the HIV-1 gag-pol proteinase-reverse transcriptase junction {-Phe-psi[PO2-N]-(S)-Pro- and -Phe-psi[P(OMe)O-N]-(S)-Pro-}, mimicks for the transition states for proteolysis, have been synthesised. The absolute stereochemistry at C-1 of the phosphonophenylalanine residue was determined by X-ray crystallography. Boc-(S)-Asn-Phe-psi[PO2-N]-(S)-Pro-(S)-Ile-NH-i-Bu and Boc-(S)-Asn-(R)-Phe-psi[P(OMe)O-N]-(S)-Pro-(S)-Ile-NH-i-Bu inhibit the HIV-1 proteinase.
IN the course of experiments on the amino-acid composition of rumen Protozoa, an unknown ninhydrin-positive substance was found by paper chromatography to be present in acid hydrolysates of the ether-ethanol soluble fraction of Protozoa. The substance was isolated in crystalline form and identified as 2-amino-ethane phosphonic acid, H2N.CH2.CH2.PO(OH)2, (synthesized by Finkelstein1, Kosolapoff2, Hackspill3 and Chavane4).
Commercially available titania (TiO2) is reported as an extremely efficient catalyst for the synthesis of α-aminophosphonates. A three-component reaction of an amine, an aldehyde or a ketone and a dialkyl phosphite (Kabachnik–Fields reaction) took place in one-pot, under solvent-free conditions to afford the corresponding α-aminophosphonates in high yields and short times. The TiO2 catalyzed α-aminophosphonate synthesis in the present study perhaps represents a true three-component reaction as no intermediate formation of either an imine or α-hydroxyphosphonate was observed that indicated the simultaneous involvement of the carbonyl compound, the amine and the phosphite in the transition state. Furthermore, the catalyst can be reused for several times without any significant loss of catalytic activity.
The preparation, physical and spectroscopic properties of l-amino-2-arylethylphosphonic, and -phosphinic acids as well as -phosphine oxides, the phosphorus analogues of phenylalanine are described, and the reactions of l-amino-2-(4-fluorophenyl) ethylphosphonates with acetals, isocyanides, esters, acid anhydrides, activated aromatic nitro- and halogen compounds, and with N-protected alanine are reported. It is shown that several of the 1-amino-2-arylethylphosphonic acids are strong inhibitors of PAL and anthocyanin synthesis and also are quite active botryticides. Among the active compounds were l-amino-2-(4-fluorophenyl)ethylphosphonic acid, 3f, and the methyl-substituted compounds 3k, 31, and 3m. The fluoroderivative 3f was also effective as a seed-dressing agent in barley showing a 100% protection against the fungus Fusarium nivale at 600 ppm.
Considerations of substrate structural variability for the enzyme glutamine synthetase (GS) have led to the design of α- and γ-substituted analogues of the naturally occurring GS inhibitor phosphinothricin (PPT). The novel cyclic inhibitor D,L-cyclohexanephosphinothricin (CHPPT) was prepared via conjugate addition of diethyl methylphosphonite to 2-cyclohexenone, followed by stereospecific Bucherer-Bergs amino acid synthesis. CHPPT stereochemistry was determined by COSY and NOESY 2D NMR techniques. The substituted phosphinothricins function as active site probes useful for elucidating the mechanism of GS inhibition by PPT.
The synthesis of five amino phosphorus derivatives, 1a-e, is described. The derivatives were incorporated into a series (18) of analogues of the 5-14 portion of angiotensinogen, in most cases at the scissile Leu-Val bond. The resultant compounds were tested in vitro for their ability to inhibit human plasma renin. Replacement of the scissile bond with the phosphinic analogue of Leu10-Val11 (1b) gave the most potent inhibitors, having IC50 = 7.5 x 10(-8) M for H-Pro-His-Pro-Phe-His-(1b)-Ile-His-Lys-OH and IC50 = 1.0 x 10(-7) M for Z-Arg-Arg-Pro-Phe-His-(1b)-Ile-His-NH2. The shorter phosphonic acid sequence Z-Pro-Phe-His-(1d) retained biological activity with an IC50 = 6.4 x 10(-6) M.
Phosphonodipeptides and phosphonooligopeptides based on L- and D-(1-aminoethyl)phosphonic acids L-Ala(P) and D-Ala(P) and (aminomethyl)phosphonic acid Gly(P) at the acid terminus have been synthesized and investigated as antibacterial agents, which owe their activity to the inhibition of bacterial cell-wall biosynthesis. A method for large-scale synthesis of the potent antibacterial agent L-Ala-L-Ala(P) (1, Alafosfalin) is described. Structure-activity relationships in the dipeptide series have been studied by systematic variation of structure 1. L stereochemistry is generally required for both components. Changes in the L-Ala(P) moiety mostly lead to loss of antibacterial activity, but the phosphonate analogues of L-phenylalanine, L-Phe(P), and L-serine, L-Ser(P), give rise to weakly active L-Ala-L-Phe(P) and L-Ala-L-Ser(P). Replacement of L-Ala in 1 by common and rare amino acids can give rise to more potent in vitro antibacterials such as L-Nva-L-Ala(P) (45). Synthetic variation of these more potent dipeptides leads to decreased activity. Phosphonooligopeptides such as (L-Ala)2-L-Ala(P) have a broader in vitro antibacterial spectrum than their phosphonodipeptide precursor, but this is not expressed in vivo, presumably due to rapid metabolism to 1. Stabilized compounds such as Sar-L-Nva-L-Nva-L-Ala(P) (46) have been developed that are more potent in vivo and have a broader in vivo antibacterial spectrum than the parent phosphonodipeptide.
A variety of phosphorus amino acid and dipeptide analogues have been synthesized and evaluated as inhibitors of the metalloenzyme leucine aminopeptidase from porcine kidney. Two phosphonate dipeptides were found to be modest inhibitors of the enzyme (8e, Ki = 58 microM; 8h, Ki = 340 microM). The phosphinic acid (17-OH) and phosphinamide (17-NH2) analogues related to bestatin were prepared by condensation of the phosphinate amino acid derivative 11, via a trivalent phosphonite ester 12, with leucine isocyanate derivatives 13. These compounds also proved to be unexceptional in their inhibition of LAP (17-O-, Ki = 56 microM; 17-NH2, Ki = 40 microM). A series of simple (alpha-aminoalkyl)phosphonic acid and -phosphinic acids were also evaluated, and the most potent inhibitors were found to be the phosphonic acid analogues of L-Leu and L-Phe [R)-3e, Ki = 0.23 microM; (R)-3h, Ki = 0.42 microM). Slow-binding behavior was observed for (R)-3e (kon = 400 +/- 55 M-1 s-1) and (R)-3h (kon = 445 +/- 50 M-1 s-1). The phosphinic acid analogues of Leu and Phe are 100-fold less potent than the phosphonate derivatives. The fact that tetrahedral phosphorus analogues are less potent inhibitors of LAP than they are of other zinc peptidases suggests that the mechanism of LAP may be fundamentally different than that of the latter enzymes.
Monoclonal antibodies, induced with a phosphonate diester hapten, catalyzed the coupling of p-nitrophenyl esters of N-acetyl
valine, leucine, and phenylalanine with tryptophan amide to form the corresponding dipeptides. All possible stereoisomeric
combinations of the ester and amide substrates were coupled at comparable rates. The antibodies did not catalyze the hydrolysis
of the dipeptide product nor hydrolysis or racemization of the activated esters. The yields of the dipeptides ranged from
44 to 94 percent. The antibodies were capable of multiple turnovers at rates that exceeded the rate of spontaneous ester hydrolysis.
This achievement suggests routes toward creating a small number of antibody catalysts for polypeptide syntheses.
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.