Intramolecular esterification lactonization

Hydroxy acids compounds that contain both a hydroxyl and a carboxylic acid function have the capacity to form cyclic esters called lactones This intramolecular esterification takes place spontaneously when the ring that is formed is five or six membered Lac tones that contain a five membered cyclic ester are referred to as 7 lactones, their six membered analogs are known as 8 lactones... 

Section 19 15 An intramolecular esterification can occur when a molecule contains both a hydroxyl and a carboxyl group Cyclic esters are called lactones and are most stable when the nng is five or six membered... 

Various aldehydes 184 and alcohols have been shown to be competent in the redox esterification of unsaturated aldehydes in the presence of the achiral mesityl triazo-lium pre-catalyst 186. Both aromatic and aliphatic enals participate in yields up to 99% (Table 13). Tri-substituted enals work well (entry 3), as do enals with additional olefins present in the substrate (entries 4 and 7). The nucleophile scope includes primary and secondary alcohols as well as phenols and allylic alcohols. Intramolecular esterification may also occur with the formation of a bicyclic lactone (entry 8). 

The preparation of lactones via intramolecular catalytic esterification can be carried out by the Tishchenko reaction of dialdehydes. Alkaline earth metal oxides have been shown to be active not only for the intermolecular Tishchenko reaction, but also for the intramolecular Tishchenko lactonization. Thus, these solid catalysts have been applied for the Tishchenko reaction of o-phthalaldehyde to phthalide 182) (Scheme 34). 

Saturated and unsaturated y-lactones and 5-lactones which are synthesised from the corresponding acyclic hydroxy fatty acids by intramolecular esterification are important flavour compounds found ubiquitously in fruits and also in milk and fermentation products in parts-per-million concentrations. The natural lac-... 

Hydrogenation of the starting material is expected to result in reduction of the ketone carbonyl while leaving the carboxyl group unaffected. Because the isolated product lacks a carboxyl group, however, that group must react in some way. The most reasonable reaction is intramolecular esterification to form a y-lactone. 

Lactones are cyclic compounds formed through the intramolecular esterification of a hydroxy fatty acid. 7-Lactones and 8-lactones, with fivesided and six-sided rings, respectively have been found in cheese (Jolly and Kosikowski, 1975 Wong et al., 1975 Collins et al., 2004). The origin of the precursor hydroxy fatty acids has been ascribed to a 8-oxidation system in the mammary gland of ruminants (see Fox et al., 2000), the reduction of keto acids (Wong et al., 1975) and/or the action of lipoxygenases and other enzymes present in members of the rumen microflora (Dufosse et al., 1994). Lactones have low flavor thresholds and while their aromas are not specifically cheese-like (their aromas have been described variously as peach, apricot and coconut ), they may contribute to the overall flavor of cheese (see Collins et al., 2004). 

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

To make intramolecular esterification feasible it is always necessary to activate one or both interacting sites of a hydroxy acid precursor. All the methods of macrocyclic ring closure involving lactonization come from this principal idea. 

Intramolecular esterification of y- and 5-hydroxy carboxylic acids forms five- and six-membered lactones. 

A hydroxy acid is both alcohol and acid. In those cases where a five- or six-membered ring can be formed, intramolecular esterification occurs. Thus, a y- or 5-hydroxy acid loses water spontaneously to yield a cyclic ester known as a lactone. Treatment with base (actually hydrolysis of an ester) rapidly opens the... 

Formation of 2-Ethyl-2(5H) Furanone. The presence of artifacts with increased retention times suggests the formation of components of increased polarity and/or the formation of higher molecular weight constituents from condensation or addition reactions. The acids, aldehydes and alcohols present can undergo oxidation to form y- and 6-lactones (14, 15). The formation of the lactone, 5-ethyl-2(5H)-furanone, probably occurs by the steps outlined in Figure 4. A plausible sequence would be reaction of 2-hexenoic acid to form a peroxy radical at the y-position followed by production of the hydroperoxide. Cleavage of the 0-0 bond with the subsequent addition of H could lead to 4-hydroxy-2-hexenoic acid. Intramolecular esterification would then produce the identified lactone. 

Lactones are cyclic esters resulting from the intramolecular esterification of a hydroxyacid through the loss of water to form a ring structure, a- and )8-Lactones are highly reactive and are used or occur as intermediates in organic synthesis y- and 5-lactones are stable and have been found in cheese. Lactones possess a strong aroma, which although not specifically cheese-like, may be important in the overall cheese fiavor impact. 

Lactone A cyclic ester, the product of intramolecular esterification. 

Intramolecular esterification 1 he production of lactones from liydroxy acids on treatment with mineral acid catalyst. 

In order to overcome unfavourable entropy effects which lead to the formation of polyethers from o)-hydroxy-carboxylic acids, rather than lactonization, a rapid intramolecular esterification process, under mild conditions, has been developed... 

The intramolecular esterification of simple m-hydroxy-acids (for example, those containing only a saturated hydrocarbon chain) or of its co-halogeno derivative can be realized easily (Fig. 5), but the harsh reaction conditions are not compatible with the numerous sensitive functions present in the seco co-hydroxyacids of natural origin. The necessity to perform the lactonization in a smoother way has been an efficient motor for progress. The same considerations apply for the macrolactamization or the formation of macrocarbocycles of natural origins. 

A microemulsion of low water content has been found to be an excellent medium for synthesis of long-chain lactones [97]. These compounds, which are important perfume ingredients, are not easily made by conventional organic synthesis because intermolecular esterification dominates over intramolecular esterification. In the microemulsion, the molecular arrangement at the oil/water interface seems to favor the cyclization reaction (Fig. 15). 

Carboxylic acids whose molecules have a hydroxyl group on a 7 or S carbon undergo an intramolecular esterification to give cyclic esters known as y- or 8-lactones. The reaction is acid catalyzed ... 

---