Butyrolactones hydrolysis

The effects of added salts are shown in Fig. 8. Sodium chloride has a small positive effect on the hydrolysis rate, and sodium chloride and sodium perchlorate have a similar, rather larger, effect on the rate of lactone formation. This is the expected result, for many salts increase the protonating power of the medium as measured by Hammett s acidity function116, and thus assist acid-catalyzed reactions. Sodium perchlorate, unusually, has a small negative effect on the hydrolysis rate. Qualitatively similar results have been found by Bunton et al,56, who studied the effects of added salts on the acid-catalyzed hydrolysis of ethyl acetate. Added lithium and sodium chloride assist the Aac2 hydrolysis of ethyl acetate, but the perchlorates have essentially no effect. In each case the effect is a little more positive than for y-butyrolactone hydrolysis, and, in particular, chloride anions appear to assist Aac2 hydrolysis more effectively than do the perchlorates. 

The lowest members of the series of perfluoroalkanedicarboxyhc acids have been prepared and are stable compounds. They have been synthesized by oxidation of the appropriate chlorofluoroolefin as well as by electrochemical fluorination and direct fluorination. Perfluoromalonic acid is an oxidation product of CH2=CHCE2CH=CH2 (21). Perfluorosuccinic acid has been produced by oxidation of the appropriate olefin (see eq. 7) (5) or by electrochemical fluorination of succinyl chloride or butyrolactone (41) and subsequent hydrolysis. 

Recently, it was found that the addition of benzylamine to 2-(5//)-furano-3-ylmethanesulfonate 280 (X = O—SOaMe) in methanol afforded a 7 1 mixture of the trans- and cw-methyl-A-benzyl-2-hydroxymethylaziridine-2-carboxylates 281 and 282, respectively (00TL3061). Treatment of 281 with benzyl alcohol in the presence of BF3 OEta furnished, after hydrolysis, rac-cw-amino-a-hydroxy-/3-butyrolactone 284 (Scheme 74). 

Hydrolysis, of 2 benzyl 2 carbometh oxycyclopentanone with lithium iodide m 2,4 6-colhdme, 46, 7 of 7 butyrolactone to ethyl y-bromo-butyrate with hydrogen bromide and ethanol, 46, 42 of 2,5 dicarbethoxy 1 4-cyclohexane-dione to 1,4 cyclohexanedione, 46, 25... 

The synthesis of 4-alkyl-y-butyrolactones 13 and 5-alkyl-<5-valerolactones 14 can be achieved in high enantiomeric excess by alkylation of ethyl 4-oxobutanoate and ethyl 5-oxopentanoate (11, n = 2, 3). The addition of diethylzinc, as well as dimethylzinc, leads to hydroxy esters 12 in high optical purity. When methyl esters instead of ethyl esters are used as substrates, the enantioselectivity of the addition reaction is somewhat lower. Alkaline hydrolysis of the hydroxy esters 12, followed by spontaneous cyclization upon acidification, leads to the corresponding y-butyro- and -valerolactones32. 

Hydrolysis of these polymers regenerates the diol and produces Y-butyrolactone, which rapidly hydrolyzes to w-hydroxybutyric acid. Because poly (ortho esters) are acid-sensitive, a base is used to neutralize the hydroxybutyric acid and to maintain the hydrolysis process under control. 

The original preparation of y-crotonolactone by Lespieau involved a five-step sequence from epichlorohydrin and sodium cyanide. A recent detailed study of this procedure reported an overall yield of 25% for the lactone. Glattfeld used a shorter route from glycerol chlorohydrin and sodium cyanide hydrolysis and distillation of the intermediate dihydroxy acid yielded y-cro-tonolactone in 23% yield and -hydroxy-y-butyrolactone in 28% yield. The formation of y-crotonolactone in 15% yield has also been reported from pyrolysis of 2,5-diacetoxy-2,5-dihydrofuran at 480-500 . ... 

Examples of catalysis involving concerted cyclic proton tremsfer in water have recently been reported in the hydrolysis of N-phenyl-iminotetrahydrofuran (Cunningham and Schmir, 1966, 1967). There is no effect of HjPO, HCO3, and CH3COOH on the rate of hydrolysis, but the type of product obtained, butyrolactone or 7-hydroxybutyranilide is dependent on their concentration. The following scheme was proposed [equation (8)]. 

The buffer species were suggested to increase the rate of formation of butyrolactone by the cyclic concerted mechanism [5]. Hydrolysis of 7-hydroxybutyranilide is also catalysed by H2 PO4 and HCOJ but not by imidazole. A similar mechanism has been postulated in the hydrolysis of trifluoroacetanilide [6] (Eriksson and Holst, 1966). 

Butyrolactones were also prepared from esters of N-protected AAs after being treated with lithium diisopropylamide (LD A) at -78°C and thereafter with ethylene oxide (93JOC6966), or by chlorination of an AA having at least two carbon atoms in a side chain and subsequent hydrolysis (73LA560). In the latter case products are formed as a mixture of diastereoi-somers in moderate yield. 

Both enantiomers of the bicyclic enone 78 and their derivatives have been proved to be useful chiral building blocks for the synthesis of natural products [29], among them y-butyrolactones. 78 is readily available in either enantiomeric form by a Diels-Alder reaction of furan with a-acetoxyacry-lonitrile and subsequent hydrolysis, followed by a resolution of the racemate... 

This cycloaddition-reduction-hydrolysis sequence was also used in an approach to butyrolactones related to ribonolactone (71). These compounds are inducing agents of hunger and satiety in mammalians. Here, a subsequent aldol 1,3-diol reduction was used, and the required carboxy function was established by oxidation of the aromatic ring with ruthenium tetroxide. Cycloaddition of benzonitrile oxide to allyl alcohol afforded an enantiomeric mixture of isoxazolines 55 and 56, which were treated with sodium hydride and methyl iodide to achieve separation by chromatography on cellulose triacetate (71). 0-Demethylation, followed by... 

As will be seen in the following section the most widespread use of the alkylation of lactones is that of y-lactones. Clearly the need for a-substitution of y-lactones was present before the advent of Creger s non-nucleophilic base. The most versatile method was the reaction of a-substitutcd malonic or acetoacetic esters with epoxyethane or 2-chloroethanol, followed by hydrolysis and decarboxylation or ketonic cleavage5. Another common approach was the condensation of butyrolactones (y-lactones) with aldehydes and subsequent hydrogenation5,s. It should be mentioned at this point that these older methods still have their merits, especially for large scale production. 

Two types of esterification reaction that can be studied with water as solvent are lactone formation, in which the alcohol is part of the same molecule as the acid, and the lsO-exchange reaction of carboxylic acids, which makes it possible to examine A-2 reactions of carboxylic acids under the conditions used for ester hydrolysis. Work in both these fields confirms the similarities between ester hydrolysis and formation. The hydrolysis and formation of y-butyrolactone have already been discussed (p. 109). We deal here with the lsO-exchange reactions of carboxylic acids. 

A more recent paper by Cunningham and Schmir242 on the hydrolysis of 4-hydroxybutyranilide XL in neutral and alkaline solution suggests that intramolecular nucleophilic attack by the neighbouring hydroxyl group is followed by bifunctional catalysis by phosphate or bicarbonate buffers of the conversion of the tetrahedral intermediate to products. A quantitative comparison was made between the effects of buffer on the hydrolysis of 4-hydroxybutyranilide and on the hydrolysis of 2-phenyliminotetrahydrofuran, since both reactions proceed via identical intermediates. The mechanism suggested243 states that the cyclisation of the hydroxyanilide ion yields an addition intermediate whose anionic form may either cleave to products or revert to reactant and whose neutral form invariably gives aniline and butyrolactone, viz. 

A simple synthesis of the novel hydroxylase inhibitor oudenone (76) has been reported which utilizes the furan ring as a masked hydroxybutyl unit (71JA1285). 2-Acetyl-l,3-cyclopentanedione was condensed with furfural in the presence of morpholine to yield (75). Hydrogenation of this product over platinum in the presence of sodium hydroxide followed by neutralization with hydrochloric acid yielded ( )-oudenone plus the side product (77 Scheme 18). It is interesting to note that hydrolysis of (76) at 150 °C in a sealed tube splits it into 1,3-cyclopentanedione and y-propyl-y-butyrolactone, a reaction which is the reversal of the foregoing synthetic process. 

Another type of chiral Michael acceptor, the oxazepine derivatives (47), is prepared by condensation of the (-)-ephedrine-derived malonic acid derivative (46) with aldehydes (Scheme 18).51 52 Treatment of (47) with a variety of Grignard reagents in the presence of NiCh affords, after hydrolysis and decarboxylation, the 3-substituted carboxylic acids (48), in most cases with more than 90% ee. Diastereoselective Michael additions to (47) were also used for the preparation of optically active cyclopropane derivatives (49)53 and P-substituted-y-butyrolactones (50 Scheme 18).54 A total synthesis of indolmycin is based on this methodology.55... 

Tulips contain preformed compounds known as tuliposides, (tuliposide A, 6.10, and tuliposide B, 6.11). Hydrolysis of the tuliposides results in formation of aglycones (6.12) and (6.13) which will form butyrolactones (6.14) and (6.15). These lactone forms are inhibitory to fungi. 

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