Phosphonic-carboxylic anhydrides

Scheme 10. Reagents and conditions (a) KHMDS, THF (b) LiOH, THF/H2O (c) CICO2/BU, EtsN, NaNs 20-65 °C (d) quinolone-4-carboxylic acid, propane phosphonic acid anhydride, EtsN.

Recent developments in this area include the use of poly[hydroxy(tosyloxy)-iodo]styrenes [80], chiral 2-(a-alkoxyalkyl) analogs of [hydroxy(tosyloxy)-iodo]benzene [81 - 83], and iodine(III)-phosphonate and -phosphinate reagents [84] for C-oxygen bond formation at a-carbon. Oxysulfonylations at the a-carbon atoms of carboxylic anhydrides with [hydroxy(sulfonyloxy)iodo]arenes have also been documented [85]. 

Mixed polymeric sulfonic carboxylic anhydrides prepared by Ang and Harwood (1973) were slow to react with alcohols larger than ethanol. Similsu ly, amines did not react quantitatively with these anhydrides. It was thought that this reaction was slowed due to the protonation of the amino groups by the free sulfonic acid groups present on the polymer. Hence the reaction, when repeated in the presence of an excess of a tertiary amine such as pyridine or triethylamine, was found to proceed smoothly (Jain, 1977). The formation of AT-acylpyridinium compounds as intermediates in these reactions may also account for the enhanced reactivity and lack of steric hindrance. The reactions of acetylpolystyrene sul-phonates and phosphonates with aniline have also been investigated (Laird and Spence, 1977). 

A dispersant that can be used in drilling fluids, spacer fluids, cement slurries, completion fluids, and mixtures of drilling fluids and cement slurries controls the rheologic properties of and enhances the filtrate control in these fluids. The dispersant consists of polymers derived from monomeric residues, including low-molecular-weight olefins that may be sulfonated or phosphonated, unsaturated dicarboxylic acids, ethylenically unsaturated anhydrides, unsaturated aliphatic monocarboxylic acids, vinyl alcohols and diols, and sulfonated or phosphonated styrene. The sulfonic acid, phosphonic acid, and carboxylic acid groups on the polymers may be present in neutralized form as alkali metal or ammonium salts [192,193]. 

Mixed anhydrides between phosphoric, phosphonic, and phosphinic acids on one side and sulfonic or carboxylic acids on the other are conveniently prepared via phosphor-azolides.[150]... 

Synthesis of isomeric chiral protected (63 )-6-amino-hexahydro-2,7-dioxopyrazolo[l,2- ]pyrazole-l-carboxylic acid 280 is shown in Scheme 36. Crude vinyl phosphonate 275, obtained by treatment of diethyl allyloxycarbonylmethyl-phosphonate with acetic anhydride and tetramethyl diaminomethane as a formaldehyde equivalent, was used in the Michael addition to chiral 4-(f-butoxycarbonylamino)pyrazolidin-3-one 272. The Michael addition is run in dichloro-methane followed by addition of f-butyl oxalyl chloride and 2 equiv of Huning s base in the same pot to provide 276 in 58% yield. The allyl ester is deprotected using palladium catalysis to give the corresponding acid 277, which is... 

Despite continnons progress in amide bond formation, the acylation of hydroxylamine nnder carbodiimide promotion is often contaminated by Af,0-diacylation even with sub-stoichiometric amounts of acids. Appendino and colleagues have developed a practical solution to the problem by combining the in situ activation of carboxylic acids 102 with the cyclic phosphonic anhydride PPAA (103), and the generation of hydroxylamine from its corresponding hydrochloride to form 104 (Scheme 54). 

There have been efforts to form aromatic polyamides directly from diacids at moderate temperatures by using various phosphorus compounds for in situ activation of the carboxyl groups [Arai et al., 1985 Higashi and Kohayashi, 1989 Krigbaum et al., 1985]. A useful agent is diphenyl(2,3-dihydro-2-thioxo-3-benzoxazolyl)phosphonate, which probably activates the carboxyl group by forming a mixed carboxylic-phosphoric anhydride [Ueda, 1999 Ueda et al., 1991]. 

Coppola, G.M., Hardtmann, G.E., and Pfister, O.R., Chemistry of 2//-3,l-bcn/.oxazinc-2,4(l//)-dione (isatoic anhydride). Part 2. Reactions with thiopseudoureas and carbanions, J. Org. Chem., 41, 825,1976. Kabachnik, M.L, Rossiiskaya, P.A., and Shepeleva, E.S., Esters of a-keto phosphonic acids. Part 3. Two types of carboxylic acid derivatives, Izv. Akad. Nauk SSSR, Ser. Khim., 163, 1947 Chem. Abstr, 42, 4132i, 1948. 

In principle, the reactions employed to bring about peptide formation between an (aminoalkyl)phosphonic acid and an aminocarboxylic acid are similar to those used in conventional peptide chemistry. Thus, a diester of the (aminoalkyl)phosphonic acid is brought into contact with the A-protected aminocarboxylic acid in the presence of dicy-clohexylcarbodiimide (Scheme 60) or the carboxylic acid may be activated by preliminary reaction (mixed anhydride formation) with an appropriate reagent, e.g. Bu COCl , ClCOOEt or ClCOOCHMeEt , or by the use of A-hydroxysuccinimide The... 

A further displacement of practical utility is that of halogen in phosphonic and phos-phinic chlorides by carboxylate ions (with silver or thallium salts, for example) to give mixed anhydrides, e.g. 581 and 582. Such anhydride formation provides a system particularly reactive at the carbonyl group towards nucleophiles, and thus preliminary activation of the carboxyl group by the diphenylphosphinoyl group becomes useful in amide or peptide formation ... 

Mixed anhydrides represent original attempts for preparing prodrugs of carboxylic or phosphonic acid. Clodronic acid dianhydrides (Fig. 33.7), for example, were shown to be novel bioreversible prodrugs of clodronate. They are more lipophilic than the parent clodronate, stable against chemical hydrolysis, and hydrolyse enzymatically to clodronate in human serum. ... 

Another approach employs treatment of H-phosphonic acid or its monoalkyl ester with a carboxylic acid anhydride and an alcohol at 20-50 C. Dimethyl H-phosphonate is obtained according to this procedure in quantitative yield based on the starting phospho-nic acid (See Appendix) [38]. 

General procedure for the preparation of dialkyl H-phosphonates by direct esterification of H-phosphonic acid in the presence of carboxylic acid anhydride (ref DE4,121,696,1991). 

Dialkyl H-phosphonates are used not only for the preparation of N-protected amino acids, but also as active coupling agents in the peptide synthesis [89,115,116], Among a wide variety of methods for the synthesis of peptides, the procedure via mixed carboxylic-phosphoric anhydride-type intermediate has so far attracted attention because this compound plays an important role in the biosynthesis of proteins and peptides [117]. Zhao et al. [89] offer the following reaction scheme for the synthesis of peptides. Phenylalanine and tryptophane are nsed as amino acids. 

Trialkyl phosphites also react with anhydrides in an analogous reaction. Thus, as shown in Scheme 10.52, triethylphosphite [(CH3CH20)3P] apparently reacts with ethanoic anhydride [acetic anhydride (CH3C0)20)] by attack at the carbonyl group by the phosphorus. The resulting carboxylate anion is then available for attack at an ethoxy carbon atom to produce the corresponding acyl phosphonate. On the other hand, a similar reaction, when attempted with the corresponding acyl chloride results in decomposition of the reactants. 

Common comonomers are those that place carboxylic, sulfonate, phosphite, polyethylene glycol, or hydrophobic groups along the backbone. They include maleic anhydride (subsequently hydrolyzed), sodium 2-acrylamido tert-butylsulfonic acid (Na-ATBS), sodium styrene sulfonate, l-allyloxy-2-hydroxypropyl sulfonate, l-allyloxy-2-hydroxypropyl phosphite, vinyl phosphonic acid, vinyl acrylate, polyethoxy acrylate, ethyl acrylate, methyl vinyl ether, and hydroxyl propyl acrylate [2,47-50]. 

Strong pyridine anhydrides sulfoxides tertiary amines aliphatic or aromatic hydroxyl carboxylic acid urea urethane sulfonic acids primary and secondary amines amide phosphonic acids... 

A simple and efficient method for the synthesis of alcohols from the corresponding carboj lic acids has been described by Sureshbabu and co-workers. Activation of atyl and allg l carboxylic acids with 1-propane-phosphonic acid cyclic anhydride (440) and subsequent reduction in the presence of NaBH4 yielded the alcohol in good yields (83-93%) and with good purity. The reduction of JV -protected amino acids (441) has been also successfully carried out to obtain corresponding alcohols (442) (Scheme 151). ... 

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