A New Route to Some Novel Phosphole Derivatives

Abstract

Previous work has shown that the unstable five co-ordinate phospholes (1; R=alkoxy, R′=alkyl) produced in the reaction of trialkyl phosphites with a two molar equivalent of dimethyl acetylenedicarboxylate can be converted into the novel phospholes (2; R=alkoxy) by treatment with hydrogen bromide at low temperature. We have now shown that a similar approach can be used to generate the phospholes (2; R=alkyl, aryl) by using dialkyl alkylphosphonites or dialkyl arylphosphonites rather than trialkyl phosphites. However, the reduced stability of the phosphorane intermediates (1; R=alkyl, aryl, R′=alkyl) relative to those produced in the trialkyl phosphite reactions means that these trapping reactions are difficult to carry out successfully.     

Reactions of N‐phthalylamino acid chlorides with trialkyl phosphites

Reaction of commercially available trialkyl phosphites with N‐phthalylamino acids gave mixtures of seven products, whereas the same reaction carried out with pure triethyl phosphite yielded only the desired 2‐(N‐phthalylamino)‐1‐oxoalkanephosphonates. These compounds underwent rearrangement to the same types of products that were obtained with the commercial phosphites. This latter series of reactions was promoted by the presence of dialkyl phosphites. © 2000 John Wiley & Sons, Inc. Heteroatom Chem 11:232–239, 2000     

Comparative Studies on the Amidoalkylating Properties of N-(1-Methoxyalkyl)Amides and 1-(N-Acylamino)Alkyltriphenylphosphonium Salts in the Michaelis–Arbuzov-Like Reaction: A New One-Pot Transformation of N-(1-Methoxyalkyl)Amides into Phosphonic or Phosphinic Analogs of N-Acyl-α-Amino Acids

Abstract

It was demonstrated that N-(1-methoxyalkyl)amides do not react with trimethyl phosphite under neutral or basic conditions. The treatment of N-(1-methoxyalkyl)amides with trialkyl phosphites or dialkyl phosphonites, triphenylphosphonium tetrafluoroborate, and Hünig's base caused immediate formation of the corresponding 1-(N-acylamino)-alkyltriphenylphosphonium tetrafluoroborates, followed by the slow Michaelis–Arbuzov-like reaction of phosphonium salt with phosphites or phosphonites to α-(N-acylamino)-alkanephosphonic or α-(N-acylamino)alkanephosphinic acid esters, respectively. A plausible mechanism of the considered transformations, assuming an equilibrium between N-(1-alkoxyalkyl)amide, triphenylphosphonium tetrafluoroborate, 1-(N-acylamino)alkyltriphenyl-phosphonium salt, N-acylimine, and N-acyliminium salts, is discussed.     

ZERO VALENT METAL COMPLEXES OF 5,5-DIMETHYL-2-R-1,3,2-DIOXAPHOSPHORINANES

Abstract

The preparation and characterization of some Ni(0) and Pt(0) complexes of 5,5-dimethyl-2-phenoxy-1,3,2-dioxaphosphorinane is reported. This phosphite, which contains a single six-membered ring, displays donor-acceptor properties intermediate to P(OCH₂)₃CR and trialkyl or triaryl phosphites. The conformation of the ligand in the complexed form is proposed to be a chair ring with an axial phenoxy group.     

Scope and Limitation of the Reactions of 3-Imino Derivatives of Pentane-2,4-Diones with Organophosphorus Reagents

Abstract

3-(Hydroxyimino)pentane-2,4-dione reacts with phosphonium ylides, Wittig–Horner reagents, trialkyl phosphites, and Lawesson's reagents to give the olefinic and cyclic products, the phosphonate adducts, the dialkyl phosphate products, the phosphinodithioic acid, and 2,4-dithione products, respectively. Furthermore, the reaction of 3-(phenylimino)pentane-2,4-dione with Wittig, Wittig–Horner reagents and trialkyl phosphite resulted in the formation of 2,5-diendioate, diethoxy phosphoryl hexanoate and the phosphate products. Possible reaction mechanisms are considered and the structural assignments are based on analytical and spectroscopic results. The antibacterial and antifungal activities for some of the new compounds are also reported.     

Halide Exchange at Vinylic Position Catalyzed by Copper (1)halide Complexes of Trivalent Phosphorus

In the course of our recent studies of the direct synthesis of vinylic phosphonates from vinylic halides with copper(I) halide complexes of trialkyl phosphites,¹ there was uncovered an accompanying facile halogen exchange reaction. This prompted a further examination of this exchange reaction employing a series of copper(I) halide complexes of triphenyl phosphite and triphenylphosphine.     

First asymmetric Abramov-type phosphonylation of aldehydes with trialkyl phosphites catalyzed by chiral Lewis bases

Chiral phosphine oxides (Lewis bases) catalyze silicon tetrachloride-mediated, enantioselective phosphonylation of aldehydes with trialkyl phosphites (Abramov-type reaction), which leads to optically active α-hydroxyphosphonates with moderate enantioselectivities. ³¹P NMR analysis of the phosphonylation of benzaldehyde with triethyl phosphite supports the assumed reaction mechanism.     

Studies on reactions of the N-phosphonium salts of pyridines. XIII. Direct polycondensation reaction of carbon dioxide or disulfide with diamines under mild conditions

Polyureas of high molecular weight were obtained by the direct polycondensation reaction of carbon dioxide with diamines at 40°C for several hours under a pressure of carbon dioxide (below 30 atm) by use of diphenyl phosphite in pyridine. Optimal temperature and pressure were 40°C and 20 atm of carbon dioxide. The polycondensation reaction was also affected by solvents and type and amounts of tertiary amines. Pyridine was most effective as tertiary amine and solvent as well. Of the phosphorous compounds used, triaryl phosphites and diphenyl phosphite were most effective, but trialkyl phosphites failed to give polymer. The reaction was assumed to proceed via a carbamyl N-phosphonium salt of pyridine formed by dephenoxylation of phosphites. Similarly, polythioureas were prepared by heating a mixture of carbon disulfide, diamines, and diphenyl phosphite in pyridine at 40°C for 6 hr under nitrogen.     

Stereochemistry of the Three-Component Reaction Between the Ley′S Aldehyde,Benzyl Amines,and Trialkyl Phosphites. A New Approach to the Protected Enantiomerically Pure 1-Amino-2,3-Dihydroxypropylphosphonates

Abstract

Enantiomerically pure orthogonally protected dimethyl 1-aminophosphonates (2R,5R,6R,1′R)- and (2R,5R,6R,1′S)-10, phosphonate analogs of 4-hydroxythreonine, were prepared employing the three-component reaction between trimethyl phosphite, (2R,5R,6R)-5,6-dimethoxy-5,6-dimethyl-1,4-dioxane-2-carbaldehyde (Ley’s aldehyde), and benzhydrylamine. Since both aminophosphonates 10 exist in a chloroform solution as single rotamers, the absolute configurations at C1′ were unequivocally established based on ¹H and ¹³C NMR spectral data. Studies on stereochemistry of the addition of trialkyl phosphites showed that in chloroform in all cases the nucleophile preferentially attacks the si-face of the C?N bond, while in alcohols the 1,2-stereoinduction is negligible, and sense of chirality of phenylethylamines is solely responsible for a π-facial discrimination in the 1,3-asymmetric inductions.     

Reaction of N-(Trichloroacetyl)trichloroacetimidoyl Chloride with Phosphites

N-(Trichloroacetyl)trichloroacetylimidoyl chloride reacts with trialkyl phosphites with substitution of the imidoyl chlorine atom and formation of C-phosphorylated heterodienes. The reaction with triphenyl phosphite or o-phenylene diethylphosphoroamidite proceeds as [4+1]-cycloaddition to give mono- or spirocyclic oxazaphospholines with the five-coordinate phosphorus atom. Dialkyl or diphenyl hydrogen phosphites add across the C = N bond of imidoyl chloride to give labile N-(-phosphorylated) trichloroacetamides.     

The Reactivity of Mn(II) and Ti(IV) Dialkylamides with Organophosphorus Esters

Abstract

Treatment of dialkyl (or diaryl) phosphites with titanium tetrakis-(diethylamide) at room temperature resulted in a smooth displacement of both ester functions by the diethylamino groups to give bis(diethylamino) phosphorus acid (58–65%). The same results are obtained at ?40° and no evidence of an intermediate product was detected using ¹H n.m.r. techniques. Treatment of dimethyl phosphite with titanium tetrakis(n-dibutylamide) resulted in isolation of two products which were identified as bis-(n-dibylamino) phosphorus acid (52%) and methyl-(n-dibutylamino) phosphorus acid (21%). On the other hand, trialkyl (triaryl) phosphates are inert to the titanium reagents.     

A Critical Overview of the Kabachnik–Fields Reactions Utilizing Trialkyl Phosphites in Water as the Reaction Medium: A Study of the Benzaldehyde‐Benzylamine Triethyl Phosphite/Diethyl Phosphite Models

α‐Aminophosphonates may be synthesized by the three‐component condensation of oxo‐compounds, amines, and dialkyl phosphites or trialkyl phosphites. In the latter case, mostly water is the reaction medium and a catalyst is also needed. This approach has been studied critically by us, exploring the background of this version of the Kabachnik–Fields condensation. The possibilities for the Kabachnik–Fields condensation of benzaldehyde, benzylamine, and triethyl phosphite or diethyl phosphite including the accomplishment in water were studied in detail.     

Zirconium(IV) compounds as efficient catalysts for synthesis of alpha-aminophosphonates

Zirconium(IV) compounds are reported as excellent catalysts for a three-component one-pot reaction of an amine, an aldehyde or a ketone, and a di/trialkyl/aryl phosphite to form alpha-aminophosphonates under solvent-free conditions at rt. Among the various zirconium compounds, ZrOCl2 x 8 H2O and ZrO(ClO4)2 x 6 H2O were most effective. The reactions were faster with dialkyl/diaryl phosphites than with trialkyl/triaryl phosphites. No O-Me cleavage occurs with aryl methyl ether and methyl ester groups. alpha,beta-Unsaturated carbonyl moiety does not undergo conjugate addition with the phorphorous moiety.     

Imidazole as an efficient catalyst for the synthesis of 2-amino-3-cyano-4H-chromen-4yl-phosphonates

An efficient procedure for the preparation of 2-amino-3-cyano-4H-chromen-4-yl phosphonate derivatives via a three-component reaction of salicylaldehyde, malononitrile and trialkyl phosphites or diethyl phosphite using inexpensive and environmentally friendly imidazole as organocatalyst has been reported. Beside excellent yields and easy workup, the reaction is done in an almost neutral medium.     

Synthesis of Some Mixed Dialkyl Phosphites and their Use as Forerunners for Potential Chiral Phosphates

Abstract

Organophosphorus compounds containing a c h i d ccntrc at the P atom are of considerable interest fiom a stcreochemical point of view. Accordingly, trialkyl phosphates (RO)(RIO)(R20)P(0) (4) were synthesized starting from dialkyl phosphites. Thus: direct hydrolysis of dialkyl phosphites (ROhP(0)H (1) with tetraethylammonium hydroxide (20% aqueous solution), followed by extraction with dichloromethane affords the corresponding tetraethylammonium alkyl hydrogen phosphitcs (2). Good yields (q) of mixed dialkyl phosphites (3) were obtained on heating stoichiometric amounts of (2) and alkyl iodides in acetonitrile solution at 6O°C, for 6 hrs. Mixed dialkyl phosphites (3) were used in synthesis of some trialkyl phosphates (4) by PTC (see scheme).     

Dual Stereochemical Control in Reaction of Di- and Trialkyl Phosphites with Aldimines

Stereochemistry of addition of di- and trialkyl phosphites to C=N compounds was investigated. Reactions of achiral dialkyl phosphites with chiral aldimines as well as that of chiral di-(1R,2S,5R)-menthyl phosphite with achiral aldimines result in low diastereomeric enrichment of the addition compound. Reaction stereoselectivity increased when supplementary chiral inductor was introduced to the reaction system. Reaction of di-(1R,2S, 5R)-menthyl phosphite with (S)-α-methylbenzylbenzaldimine proceeds as concerted asymmetric induction to form practically one diastereomer of N-substituted aminophosphonic acid. However, reaction of di-(1R,2S, 5R)-menthyl phosphite with (R)-α-methylbenzylbenzaldimine proceeded as not concerted asymmetric induction, and diastereomeric enrichment of the product was low. By chemical extrapolation, absolute configuration of compounds formed was established. Tri-(1R,2S,5R)-menthyl phosphite reacts with C=N compounds in the presence of boron trifluoride etherate to form aminophosphonic acid derivatives with the absolute configuration opposite to that appearing in the reaction of di-(1R,2S,5R)-menthyl phosphite with the same C=N compounds.     

Synthesis of Pharmacologically Active 2-Substituted-1,3-Diphosphonates

Abstract

A new series of diphosphonates (I) was synthesized and investigated for their pharmacological activity. 2-Substituted-1,3-propylidene diphosphonates (I) were prepared by reaction of sodium dialkyl phosphite or trialkyl phosphite with ditosylates of 2-substituted-1,3-propanediol or 2-substituted-1,3-dibromopropane. Pharmacological screenings of these 1,3-propylidenediphosphonates have shown that these compounds have potent cardiovascular activity and are potentially useful in the treatment of hypertension.     

Novel Ylidic Phosphoryl Compounds from Halogenated Furan-2,5-Diones with Trivalent Phosphorus Esters: Application of this Approach to New Trisphosphonates Containing a Geminal Bisphosphonate Unit

Abstract

The reactions of trivalent phosphorus esters, including trialkyl phosphites, dialkyl phosphonites, and alkyl phosphinites, with 3-halo- and 3,4-dihalo-furan-2,5-diones has been shown to lead to the formation of novel phosphorus ylides possessing additional phosphoryl-containing groups. For the reaction of 3,4-dihalo-furan-2,5-diones with trialkyl phosphites, the products are trialkoxyphosphonium ylides containing an adjacent geminal bisphosphonate unit. These can be used to provide a convenient route to novel 2,3,3-tris(dialkoxyphosphoryl)-substituted propionate esters which can be hydrolyzed to give the corresponding novel trisphosphonic monocarboxylic acid.     

Reactions with aziridines XXI The (Michaelis-)arbusov reaction with N-acyl aziridines and other amidoethylations at phosphorus.

Heating trialkyl phosphites with N-acyl aziridines produces dialkyl 2-amidoethyl-phosphonates bearing one of the phosphite alkyl groups on nitrogen. Other alkoxy phosphines behave analogously. Dialkyl phosphites furnish the same type of products devoid of the N-alkyl group.     

Organophosphorus antioxidants—VIII. Kinetics and mechanism of the reaction of organic phosphites with peroxyl radicals

Trialkyl phosphites react with cyanoisopropylperoxyl radicals, generated by thermolysis of azobis(isobutyronitrile) in the presence of oxygen, to give the corresponding phosphates with rate constants of the order of 10³ M⁻¹ sec⁻¹ at 65°C. Phenyl phosphites are oxidized also. A small amount of cyanoisopropyl phosphite is formed by substitution of the phosphite by alkyloxyl radicals leading to phenoxyl radicals. Sterically hindered aryl phosphites react with cyanoisopropylperoxyl radicals to yield the corresponding phosphates and alkoxyl radicals which in a second step react with phosphite by substitution releasing a sterically hindered phenoxyl radical. Therefore, sterically hindered phosphites are capable of acting as chain-terminating primary antioxidants. Because the rate constants of reaction of these phosphites with peroxyl radicals are only in the range of 10² M⁻¹ sec⁻¹ and 100 times smaller than those of phenols, phosphites should be less active as primary antioxidants than phenols.