Hydroxycarboxylic acids, lactonization

With some hydroxycarboxylic acids lactone formation is observed in the reaction with carbodiimides.Sometimes N-acylureas are formed as byproducts. For example, in the reaction of -hydroxycarboxylic acids 468 with DCC, y-butyrolactones 469 are produced." ... 

An example of an exo-trig process would be lactonization of a m-hydroxycarboxylic acid ... 

CO-Hydroxycarboxylic acids give, after silylation to bis(trimethylsilylated) intermediates and subsequent treatment with mild Lewis acdds, small- and large-ring lactones in high yields. Thus co-hydroxytridecanoic acid 332 (n= 12) affords, via 333 n= 12), at room temperature, the macrolide 334 in 89% yield [115]. The medium-sized 8- and 9-membered lactones are, however, not formed, only diolides. Likewise, trimethylsilyl 6-trimethylsilyloxyhexanoate 333 is readily lactonized in the presence of 4-trifluoro-... 

In their pioneering work on the lactonisation of an extensive series of co-hydroxycarboxylic acids, Stoll et al. (1934) proposed a procedure for determining the specific rate for cyclisation from the yield of the monomeric lactone at the end of the reaction. To this end they considered the simplified... 

Oxidation of cyclic ketones by H2O2 in the presence of an acid zeolite was used for the preparation of lactones and u-hydroxycarboxylic acids [124]. Thus, for c-pentanone oxidation in the presence of H-ZSM-5, -valerolactone is obtained with 62.3% selectivity at 40% conversion, whereas 5-hydroxy-pentoic acid is obtained with 34% yield in the presence of Zeolon M. 

In lipase-catalyzed ROP, it is generally accepted that the monomer activation proceeds via the formation of an acyl-enzyme intermediate by reaction of the Ser residue with the lactone, rendering the carbonyl more prone to nucleophilic attack (Fig. 3) [60-64, 94]. Initiation of the polymerization occurs by deacylation of the acyl-enzyme intermediate by an appropriate nucleophile such as water or an alcohol to produce the corresponding co-hydroxycarboxylic acid or ester. Propagation, on the other hand, occurs by deacylation of the acyl-enzyme intermediate by the terminal hydroxyl group of the growing polymer chain to produce a polymer chain that is elongated by one monomer unit. 

Reactions of hydroxycarboxylic acids, HO(CHj) COOH, also depend on value of n. In acid solutions, y-hydroxycarboxylic acid (n = 3) and 8-hydroxycarboxylic acid (n = 4) form cyclic esters (lactones) with, respectively, five-membered and six-membered rings. 

Most of the carbonyl compounds discussed in this section are either pyran-2- or -4-ones but a small number of pyran-3-ones and chroman-3-ones are known <77HC(31)193>. Tetrahy-dropyran-2-ones are lactones of 5- (or S-) hydroxycarboxylic acids and are not discussed in detail. 

When the formation of the lactone is purposefully looked at, DMF that promotes the oxidation of primary alcohols in carboxylic acids can be used as solvent in PDC oxidations. The resulting hydroxycarboxylic acid would cyclize to a lactone if favoured.173... 

The /3-lactone was formed by the cyclization of a 3-hydroxycarboxylic acid with sulfonyl chloride. An alternative synthesis attempted to control all stereochemical relationships in the molecule using the properties of silyl moieties attached to substrates and reagents <20040BC1051>. Stereoselective reactions of this type included the use of silyl groups in enolate alkylations, hydroboration of allylsilanes, and an anti Se2 reaction of an allenyl silane with an aldehyde and ry -silylcupration of an acetylene. The /3-lactone was again formed by the standard sulfonyl chloride cyclization method. 

If the Mitsunobu inversion is carried out intramolecularly (i.e., in a hydroxycarboxylic acid), a lactone is produced with inversion of the configuration at the OH-bearing stereocenter (Figure 2.35). This lactonization is stereochemically complementary to the paths via activated hydroxycarboxylic acids, which lead to lactones with retention of the configuration at the OH-bearing C atom (Section 6.4.2). 

For work on a 1 -mole scale one would thus have to use a 1.000-liter flask to activate and then lactonize the entire ft)-hydroxycarboxylic acid. Of course, it is much more practical to work in a smaller reaction vessel. However, one must also not exceed the mentioned concentration limit of < 1 pmol/L. Therefore, one can introduce only as much of the carboxylic acid in this smaller reaction vessel at a time so that its concentration does not exceed 1 pmoEL. Subsequently, one would have to activate this amount of acid and would then have to wait until it is lactonized. After that additional acid would have to be added and then activated, and so on. A more practical alternative is shown in Side Note 6.3. 

Fig. 17.32. Oxidative cleavage of an asymmetric ketone with complementary regiose-lectivities. Lactone A is obtained by Baeyer-Villiger oxidation of menthone [2-methyl-5-(l- methylethyl)cyclo-hexanone]. Alternatively, one may first convert menthone into the silylenol ether B and cleave its C=C double bond with ozone to obtain a silyl ester containing an a-methoxyhydroperoxide group as a second functional group (which resembles the unstable structural element of the so-called ether peroxides cf. Figure 1.38). The latter is reduced with NaBH4tothe hydroxylated silyl ester C. The hydroxycarboxylic acid is obtained by acid-catalyzed hydrolysis. It cyclizes spontaneously to give lactone D.

Reaction with Lactones, Hydroxycarboxylic acid ester complexes of titanium are formed by reaction of a tetraalkyl titanate with a lactone, such as p-propiolactone, y-butyrolactone, or valerolactone (35). For example,... 

Intramolecular condensation of co-hydroxycarboxylic acids is a standard method to prepare lactones. Acid catalysts or more elaborate mediators are usually required as well as continuous removal of water. Transition-metal-catalyzed cyclocarbonylation of unsaturated alcohols is a fascinating alternative, which proceeds under neutral conditions [26]. Intramolecular hydroesterification of... 

The discontinuous process for preparing macrolactones described in the text is impractical. Instead of this process one uses a continuous method with a syringe pump one adds a solution of the hydroxycarboxylic acid very slowly—that is, in the course of hours or days—into a small flask, which contains >1 equivalent of the activator and, if necessary, just enough triethylamine to neutralize any released HCl.The rate at which the acid is added is regulated such that it is equal to or smaller than the lactonization rate. This procedure is called working under pseudo-high dilution. At the end of the... 

L-ascorbic acid (Figure 9-9) is a lactone (internal ester of a hydroxycarboxylic acid) and is characterized by the enediol group, which makes it a strongly reducing compound. The D form has no biological activity. One of the isomers, D-isoascorbic acid, or erythorbic acid, is produced commercially for use as a food additive. L-ascorbic acid is readily and reversibly oxidized to dehydro-L-ascorbic acid (Figure 9-10), which retains vitamin C activity. This compound can be further oxidized to diketo-L-gulonic acid, in a... 

Whilst the majority of the discussion thus far has been concerned with metallo-substituted redox molecular sieves, it is important to note that proto-nated zeolite forms can also be employed for selective oxidation with aqueous hydrogen peroxide. An excellent example of this is the study conducted by the Mobil Oil Corporation.52 Their work has shown that a number of protonated zeolites such as H-ZSM-5 or zeolite-/ can be used with hydrogen peroxide to catalyse the oxidation of cyclic ketones to lactones or the co-hydroxycarboxylic acids (Figure 4.12). 

Under Fischer esterification conditions, many hydroxycarboxylic acids i intramolecular esters (lactones). ... 

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