Bifunctional hydroxy acids

After their utilization as plastic items, PHAs can not only be composted, but can also be easily depolymerized to a valuable source of optically pure R-(-)-configured bifunctional hydroxy acids which are of interest as synthons for chiral high-value chemicals such as vitamins, antibiotics, pheromones and aromatics (Ren et al. 2005). Some of these acids also exhibit important biological properties such as antimicrobial and antiviral activity (Ruth et al. 2007). 

There are two main routes to synthesise aliphatic polyesters polycondensation of bifunctional hydroxy acids and ring-opening polymerisation (ROP) of cyclic ester monomers (Okada, 2002). 

The cyclization constant (7, which may be evaluated from the observed ratio of the two products at a given concentration c, affords a measure of the tendency for a given bifunctional compound to cyclize. A plot of log C vs. the ring size n for the lactonization of w-hydroxy acids... 

The principles set forth above account reasonably well for the course of bifunctional condensations under ordinary conditions and for the relative difficulty of ring formation with units of less than five or more than seven members. They do not explain the formation of cyclic monomers from five-atom units to the total exclusion of linear polymers. Thus 7-hydroxy acids condense exclusively to lactones such as I, 7-amino acids give the lactams II, succinic acid yields the cyclic anhydride III, and ethylene carbonate and ethylene formal occur only in the cyclic forms IV and V. 

Metal-deactivating antioxidants. Transition metal compounds decompose hydroperoxides with the formation of free radicals, thereby increasing the rate of oxidation. Such an enhanced oxidation can be slowed down by the addition of a compound that interacts with metal ions to form complexes that are inactive with respect to hydroperoxides. Diamines, hydroxy acids, and other bifunctional compounds exemplify this type of antioxidants. 

Ricinoleic acid is a bifunctional fatty acid containing a hydroxy group along the fatty chain. The presence of both carboxylic and hydroxyl groups allows incorporation of ricinoleic acid into a polymer backbone by formation of an ester bond. The synthesis of poly(ester-anhydride) contains two steps trans-... 

The diborylated cobaltocenium species [(CpBR2)2Co] + (R = t-Pr) is an interesting example that illustrates the different binding modes encountered for bifunctional Lewis acids.With hydroxy counterions, an oxygen-bridged complex (178), which represents an inverse chelate structure, was confirmed in the solid state and in solution (R = t-Pr, F). Salt-like structures on the other hand were observed with PFe as the counterion and a zwitterionic 1 1 complex (179) formed upon reaction of the diborylated cobaltocene with hexachloroethane. Low-temperature NMR studies show that the chloride rapidly exchanges position between the two Lewis-acidic boron centers. 

We observed earlier that polymer formation requires that the reacting monomer(s) must be at least bifunctional. It is pertinent to point out at this stage that polyfunctionaHty of reactants is a necessary but not sufficient condition for the formation of a polymer. Bifunctional monomers whether of the A-A/B-B or A-B types may react intramolecularly to produce cycHc products. For example, hydroxy acids when heated may yield lactams or linear polyamides. 

In addition to the oxidative scission of 1,2-diols, the reaction can be extended to related 1,2-bifunctional compounds such as oxiranes, 1,2-dicarbonyl compounds, 2-hydroxy aldehydes, ketones and acids, a-amino alcohols, 1,2-diamines and also to polyols. LTA cleaves a-hydroxy acids much more readily than do periodates and both reagents oxidize 2-hydroxy aldehydes and 1,2-dicarbonyl compounds relatively slowly. - Only periodic acid in water reacts with oxiranes via the corresponding diols. 

Alkyl-boronic acids, such as n-butylboronic acid, react with 1,2- or 1,3-diols or with a- or p-hydroxy acids to form 5- or 6-membered ring non-polar boronate derivatives (Figure 4.1(e)). They are prepared simply by adding n-butylboronic acid to a solution of the hydroxy-compound in dimethylformamide. The reaction is complete in 10-20 minutes at room temperature and the reaction mixture can be injected directly into a gas chromatographic column for analysis [55,133]. As alternatives, cyclic di-ferf-butylsilylene derivatives have been shown to be of value in the analysis of diols and hydroxy acids [132]. The preparation and use of cyclic derivatives for the analysis of bifunctional compounds have been reviewed [730]. 

The depsipeptides are formed from amino acids and other bifunctional acids (usually hydroxy acids). 

The effect of a carboxy group is illustrated by the reactivity of 2-bromopyridine-3- and 6-carboxylic acids (resonance and inductive activation, respectively) (cf. 166) to aqueous acid under conditions which do not give hydroxy-debromination of 2-bromopyridine and also by the hydroxy-dechlorination of 3-chloropyridine-4-car-boxylic acid. The intervention of intermolecular bifunctional autocatalysis by the carboxy group (cf. 237) is quite possible. In the amino-dechlorination (80°, 4 hr, petroleum ether) of 5-carbethoxy-4-chloropyrimidine there is opportunity for built-in solvation (167) in addition to electronic activation. This effect of the carboxylate ion, ester, and acid and its variation with charge on the nucleophile are discussed in Sections I,D,2,a, I,D,2,b, and II,B, 1. A 5-amidino group activates 2-methylsulfonylpyridine toward methanolic am-... 

Moreover, Kim and coworkers have shown that a-amino-butyrolactones can be synthesized by a related process employing the amino acid homoserine with an unprotected hydroxy functionality [31]. In a more recent publication by the same research group, morpholin-2-one derivatives of type 9-37 have been prepared (Scheme 9.6) [32]. Herein, glycolaldehyde dimer 9-32 acts as a bifunctional compound, which first reacts with the a-amino acids 9-33 to give the iminium ions 9-34,... 

Acid derivatives of saccharides constitute relevant bifunctional ligands, well suited for stabilization of five-membered oxo-Cr(V) chelates, since they provide both 2-hydroxy- 1-carboxylate and vic-diol sites for potential chelation.19,50,92... 

D-Gluconic acid (36) is another example of a bifunctional acyclic saccharide, and it presents two potential coordination groups 2-hydroxy-1-carboxylate and vic-OH groups. New results indicate that, at pH 3, coordination takes place through the 2-hydroxy-1-carboxylate group to yield three bis-chelate five-coordinated oxochro-mate(V) complexes. The experimental spectra and their simulations are shown in Fig. 9. Table V summarizes the spectroscopic parameters. 

Scheme 6.82 Proposed reactive complex of the Petasis reaction utilizing a-hydroxy aldehydes, amines, and organic boronic acids (A) and bifunctional mode of action of chelating thiourea catalyst 65 in the enantioselective Petasis-type 2-vinylation of N-acetylated quinolinium ions (B).

Scheme 6.141 Mechanistic proposal for the 121-catalyzed asymmetric intramolecular Michael addition exemplified for the model substrates ( )-4-hydroxy-l-phenyl-2-buten-l-one (n = 0) and ( )-5-hydroxy-l-phenyl-2-buten-l-one (n = 1) 121 functions as push/pull-type bifunctional catalyst inducing the cyclization of boronic acid hemiester (1) to form intermediate (2) release ofdiol product (3) by oxidation.

Although it is reported that the U-5C-4CR can work well with nucleophiles other than methanol, such as primary or secondary amines, the only examples reported in the literature are those where trifunctional a-aminoacids such as lysine [67] or homoserine [66] or bifunctional aldehydes such as glycolaldehyde [65] are employed. In these cases, the side-chain amino or hydroxy group acts as the nucleophile and opens the cyclic intermediate generating the corresponding lactams or lactones. A less nucleophilic solvent such as trifluoroethanol is usually employed, in order to maximize the intramolecular attack. The observed stereoselectivities are, apart from a few examples [66], usually not very high this could be due to different factors (a) the side chains of the a-amino acids are not very bulky (b) the intramolecular nucleophilic attack could be faster than the methanol attack and the cyclic intermediate could not equilibrate to the thermodynamically favored isomer (c) the intramolecular nucleophilic attack on the more stable diastereoiso-meric cyclic intermediate could be kinetically less favored. 

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