Aryl phosphonates

Alkyl or aryl phosphonates, which contain a carbon—phosphoms bond, are comparatively more stable. They are of interest as antiscaling additives and corrosion inhibitors for cooling towers and heat exchangers (see Dispersants Water, industrial water treatment), surfactants (qv), sequestrants, and textile-treating agents. Trialkyl phosphites are usehil as esterification (qv) reagents. 

Examples of cyclic aliphatic or aryl phosphonate triesters, such as 36 or 37 have also been prepared by this HHT method from their cyclic phosphite precursors (2). 

In contrast, when excess amounts of the HHTs derived from simple aliphatic glycinate esters, such as 25, were used in excess in reactions with diaryl phosphites (SO), the related glyphosate aminals containing aryl phosphonate esters 46 were isolated in low yield (5-15%). Like many aminals, these triesters 46 were acid-sensitive and were quantitatively converted to the corresponding triester strong acid salts 47 upon treatment with either HCl or methanesulf onic acid (27). 

Thel, 2-oxaphosphole derivatives were also obtained from the reaction of alkyl(aryl) phosphonic acids with a /3-unsaturated ketones or aldehydes (Scheme 5) [34, 35],... 

Treatment of (-)-ephedrine (42) with a variety of aIkyl(aryl)phosphonic dichlorides 106a-d afforded the isomeric pairs of the corresponding 2-alkyl(aryl)-2-oxo-l,3,2 oxazaphospholidines (Scheme 31 and Table 1) [32, 62-65],... 

Equation 11.35 Conversion of aryl iodides into aryl phosphonates. 

The conversion of aryl iodides into aryl phosphonates, a useful precursor to aryl phosphonic acids, was performed in a Teflon autoclave by Villemin [51]. A domestic microwave oven was used for these experiments and the reaction times for classic heating were effectively reduced from 10 h to 4-22 min. The reactivity of iodides was good whereas the use of bromides resulted in lower yields and reactions with tri-flates were very slow (Eq. 11.35). It is notable that the reactions were brought to completion with short reaction times in a non-polar solvent. 

Aryloxytitanium halides, 25 83 2-Arylpyridines, 27 111 Aryl phosphate esters, 79 51 Aryl phosphates, 7 7 493 Aryl phosphonates, 79 37 Arylphosphorus compounds, 79 28 Aryls, palladium, 79 652 Aryl-silicon compounds, 22 553, 554 Arylsulfinic acids, 27 248-249 Arylsulfonylated gelatin, 72 444 Aryltin trihalides, 24 810-811 Arylyl amines, 70 396-399 Asahi Chemical Industries EHD processes, 9 676-677 sebacic acid production, 9 679-680 ASAM (alkaline-sulfite-AQ-methanol) process, 27 30... 

Palladium-catalyzed cross-coupling reactions of diaryliodonium tetrafluo-roborates have recently been employed for conversions of mercaptans to aryl-and diaryl sulfides, sodium arenesulfinates to diaryl sulfones, and dialkyl phosphites to aryl phosphonates (Scheme 43) [120-122]. 

A Teflon autoclave was used in the transformation of aryl iodides to aryl phosphonates, useful precursors to aryl phosphonic acids, in a study made by Villemin [105]. With a domestic microwave oven, the reaction times were successfully shortened compared to those from classic heating from 10 hours to 4-22 minutes. Aryl iodides exhibited good reactivity while bromides gave lower yields and triflates very slow reactions (Scheme 36). It is interesting to note that the reactions were implemented with short reaction times in the nonpolar solvent toluene, which is essentially microwave-transparent [5]. 

Scheme 37 Palladium- and nickel-catalyzed synthesis of aryl phosphonates...

The arylation of phosphite anions using several iodonium salts is the most important reaction of this Section. Although aryl phosphonates have been prepared by numerous methods, this approach has the advantages of easy availability of starting materials, mild reaction conditions, simple workup, and better yields. 

Scheme 4.1 Hydrolysis of activated aryl esters 2a and carbonates 2b proceeds via an anionic, tetrahedral intermediate (in square brackets). Hydrolytic antibody 48C7 was elicited with an aryl phosphonate derivative 1 that mimics this high energy species and its flanking transition states.

The surface modification of LDHs with organic molecules has recently been investigated [42,143]. It has been reported, for example, that the product of the reaction of a ZnAl(OH) LDH with an organic oxychloride is an esterified LDH, with the organic molecules attached directly to the matrix cations (i.e. not through the surface OH groups) [144-146]. Similarly, the preparation of modified MgAl- and ZnAl-LDHs, in which alkyl and aryl phosphonate anions... 

An optimised solid-phase method for the generation of diverse a-amino-alkyl or -aryl phosphonates derived from peptides and polymer-assisted solution-phase parallel synthesis of dipeptide p-nitroanilides and dipeptide diphenyl phosphonates have been reported. A modular method for the construction of polypeptides containing the Phe-Arg phosphinic acid isostere has been described. A novel methodology for the solid-phase synthesis of phosphinic peptides has been developed in which the phosphorus-carbon bond was formed... 

Phosphonates have also been prepared from alcohols and (Ar0)2P(=0)Cl, NEts and a TiCl4 catalyst. ° The reaction of (R0)2P(=0)H and aryl iodides with a Cul catalyst leads to aryl phosphonates. " Polymer-bound phosphonate esters have been used for olefination. Dienes are produced when allylic phosphonate esters react with aldehydes. 

Figure 9 Serine hydrolases as targets of ABPP. (a) Catalytic mechanism of peptide substrate cleavage via the action of a catalytic triad, (b) Aryl phosphonate and fluorophosphonate probe scaffolds.

In a comparative study of the rates of alkaline hydrolysis of the heteroaryl and heteroarylmethyl phosphonates (105) and (106), respectively, with those of aryl phosphonic analogues (107), mesomeric interactions between phosphorus and the... 

In order to choose the best carboxyhc acid bioisoster pXa and log P are important parameters to look at before proceeding with one surrogate or another. An interesting study comparing p Ta and log P values of some aryl phosphonic acids, aryl tetrazoles, and aryl sulfonamides has been published by Franz. The values of pA and log P are very important parameters in drug design. Several pubhshed examples show that the interchange of carboxylic acid for tetrazole and... 

Hanessian, S., Bennani, Y.L., and Herve, Y, A novel asymmetric synthesis of a- and P-amino aryl phosphonic acids, Synlett, 35, 1993. 

Guzman, A., Alfaro, R., and Diaz, E., Synthesis of aryl phosphonates by reaction of Grignard reagents with diethyl cyanophosphonate, Synth. Commun., 29, 3021, 1999. 

Yuan, C., Chen, S., Zhou, H., and Maier. L.. Studies on organophosphorus compounds. Part 75. A facile synthesis of l-(hydroxyamino)alkyl(or aryl)phosphonic acids. Synthesis, 955, 1993. 

Aryl phosphonates. Phosphite anioo DMF. Arylphosphonate esters are obtained... 

V. THE FORMATION OF P C(AROMATIC) BONDS. SYNTHESES OF ARYL PHOSPHONIC AND PHOSPHINIC ACIDS... 

Alkene-,alkyne-,aryl-phosphonic and phosphinic acids.-(of-Stannylalkyl)phosphonic acid diesters have been employed to prepare alkenylphosphonic diesters. Treatment of the tin compounds (251) (generated in situ) with an aldehyde R CHO at -70 yielded a mixture of ( ) and (Z) isomers of (252), the proportions being controlled essentially by... 

Scheme 15.67. Palladium and nickel-catalyzed preparation of aryl phosphonates.

The first Pd -catalyzed P-arylation of dialkyl phosphites with arylboro-nic acids or aryl trifluoroborates has been carried out by using palladium acetate, the rigid bidentate ligand dmphen (dmphen = 2,9-dimethyl-1,10-phenanthroline), and without addition of a base or acid. The arylated phosphonates (512) were isolated in 44-90% yields (Scheme 132). 

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