Hydrolysis of cyclic acetals

With due consideration of the explanations just presented for the observed, relative stabilities of cyclic acetals derived from polyols, in terms of their constitution and conformation, nearly all of the following observations on the selective hydrolysis of cyclic acetals of alditols and dialkyl dithioacetals may be readily understood. 

An example of a simple catalyzed chemical reaction is the hydrolysis of cyclic acetal (4.1) to lactol (4.3) (Scheme 4.1).This reaction is reversible. To a rough approximation, AG... 

The generally accepted mechanism for the hydrolysis of cyclic acetals is the A-l mechanism, involving the rate-determining heterolysis of a protonated intermediate. At present, it is not known which one of the two possible protonated species, 29 or 30, is preponderant. 

Figure 6.38 Examination of the slower rates of hydrolysis of cyclic acetals compared with their acyclic counterparts (a) anti-ALPH nature of dioxolane hydrolysis p ° (b) two systems with identical structure-reactivity para-meters ° (c) recombination in a dioxolane hydrolysis (d) direct measurement of the relative rates of hydrolysis and recyclisation of the acyclic oxocarbenium ion intermediate in cyclic acetal hydrolysis.

Dioxolane cleavage. Hydrolysis of cyclic acetals is accomplished with thiourea in aqueous ethanol at reflux temperature. Some selectivity is shown in substrates such as l,2 5,6-di-0-isopropylidenefuranoses in which the terminal acetonide is cleaved. 

The acid-catalyzed hydrolysis of cyclic acetals of ketoses is best effected by use of 0.1 M aqueous oxalic acid or 50-80% aqueous acetic as the hydrolyst, because the use... 

It could be established that the hydrolysis of 1,3-dithianes derived from para-substituted acetophenones (4) is promoted by silver ions. Kinetic study using a 10% (vAf) diox-ane/water solvent shows that, when [Ag+] <0.2 mol L , the P-NO2, —Cl, —H and —Me derivatives hydrolyze via rapidly formed 1 Ag" " 1 dithiane complexes, but that the p-MeO derivative forms an unreactive 1 1 complex and hydrolyses via a 2 Ag+ 1 dithiane complex. Comparison of the kinetic parameters with those available for analogous open-chain SyS-acetals reveals that cycBzation leads to a substantial (>10 -fold) overall loss of reactivity and that this loss arises both from a lowering of acetal basicity toward Ag+ and from a slower rate of hydrolysis of the 1 1 complex. The implications for hydrogen ion-catalyzed hydrolysis of cyclic acetals have been discussed, as have the reasons for the lower reactivity of the cyclic acetals. ... 

Ceder O (1954) A kinetic study of the acid hydrolysis of cyclic acetals. Arkiv Kemi 6 523-535... 

Antibodies bound by sol-gel encapsulation are used in medicine, immunochro-matography, immunosensors, etc. Immimoglobulins that are trapped retain their ability to bind external antigens from solutions. Antibodie 14D9 catalyze hydrolysis of cyclic acetals, ketals, epoxides, etc. when incorporated in sol-gel matrices. The ability of a sol-gel matrix containing 10% PEG and antiatrazine antibodies to bind atrazine was studied. This matrix recogni2es and binds atrazine and widely distributed herbicides. In this case, neither leaching of antibodies nor nonspecific physical sorption of atrazine on the ceramic matrix occurs. The activity did not decrease... 

Fluoboric acid is also an efficacious promoter of cyclic oxo-carbenium ions (Scheme 4.24) bearing an activated double bond which, in the presence of open-chain and cyclic dienes, rapidly undergo a Diels-Alder reaction [91]. Chiral a, -unsaturated ketones bearing a -hydroxy substituents, protected as acetals, react with various dienes in the presence of HBF4, affording Diels-Alder adducts that were isolated as alcohols by hydrolysis of the acetal group by TsOH. Some examples of reactions with isoprene are reported in Table 4.23. The enantios-electivity of the reaction is dependent on the size of the substituent R on the of-carbon high levels of asymmetric induction were observed with R = z-Pr (90 1) and R = t-Bu (150 1) and low levels with R = Me (2.7 1) and R = Ph (3.0 1). Scheme 4.24 shows the postulated reaction mechanism. 

Intramolecular additions generally follow the same trends of stereoselectivity as observed in the bimolecular reactions. Eor example, allylic boronates ( )- and (Z)-118 provide the respective trans- and cis-fused products of intramolecular aUylation. As shown with allylboronate ( )-118, a Yb(OTf)3-catalyzed hydrolysis of the acetal triggers the intramolecular aUylboration and leads to isolation of the trans-fused product 119 in agreement with the usual cyclic transition structure (Eq. 96). 

In this Section, hydrolysis, acetolysis, and isomerization of acetals are considered. Selective deprotection of acetals may also be achieved through halogenation, hydrogenolysis, ozonolysis, and photolysis, but these topics, are covered in an accompanying article in this Series, on the reactivity of cyclic acetals of aldoses and aldosides,3 and will not be discussed here. 

Of all the selective, deprotection procedures that are available to carbohydrate chemists, the partial hydrolysis of polyacetals is probably the most familiar. Articles by de Beider4,5 and Brady6 contained examples of this type of reaction for aldose and ketose derivatives, respectively, and an article by Barker and Bourne7 gave useful information from the early literature on the graded, acid hydrolysis of acetal derivatives of polyols. A discussion of the stereochemistry of cyclic acetals of carbohydrates was included in an article by Mills 70 and in one by Ferrier and Overend,76 and a survey of the formation and migration of carbohydrate cyclic acetals was made by Clode.7c... 

It is intended that the present Chapter shall be complementary to Haines s article in this Volume8 that deals with the selective deprotection of protected sugars. The reader interested in all aspects of the hydrolysis, the alcoholysis, the acetolysis, and the isomerization of cyclic acetals pf sugars should refer to Haines s article. A review has also been published concerning the formation and migration of cyclic acetals of carbohydrates.80... 

Conformation of acetals Conformation of mono and dithioacetals Conformation of 1,3-oxazines and 1,3-diazines Formation and hydrolysis of the acetal function Hydride transfer to cyclic oxonium ion Oxidation of the C —H bond in acetals REFERENCES... 

A sirupy pentapropionate of L-sorbose was described by Hurd and Gordon.142 Crystalline esters of L-sorbose, such as the 1-benzoyl-,55 1-p-aminobenzoyl-148 and 1-tosyl-, 144,56 have also been synthesized. 1-p-Aminobenzoyl-L-sorbose was prepared as a possible substance for measuring the rate of glomerular filtration. It was synthesized by esterifying 2,3 4,6-diisopropylidene-L-sorbose with p-nitrobenzoyl chloride, with subsequent reduction of the nitrobenzoyl ester to 1-p-amino-benzoyl-2,3 4,6-diisopropylidene-L-sorbose. Removal of the isopropyli-dene groups by dilute acid hydrolysis furnished the desired product. 1-Tosyl-L-sorbose was independently prepared by two different methods. The first method,55 discussed on page 110, involves the oxidation of a properly substituted sorbitol derivative, while the latter method144 is similar to the one used for the preparation of the 1-p-aminobenzoyl derivative, namely esterification of 2,3 4,6-diisopropylidene-L-sorbose, followed by acid hydrolysis. This cyclic acetal has also been esterified to the crystalline l-mesyl-2,3 4,6-diisopropylidene-L-sorbofuranose by... 

Brown s crotylboration protocol was used effectively in the synthesis of azu-mamide A 28. Azumamides are unusual cyclic peptides that show potent inhibitory activity on histone deacetylase enzymes. A highly diastereo- and enan-tioselective (dr >99% 98% ee) crotylation of 3-benzyloxypropanal with the chiral reagent ( >crotyl-1Ipc2borane (l19E) afforded the homoallylic alcohol 29. Subsequent reductive ozonolysis and K2CO3-mediated hydrolysis of the acetate furnished the diol 3016 (Scheme 3.1m). 

A kinetics study has been performed on the formation of 1,3,6-trioxocane in the interaction of formaldehyde with diethylene glycol in the presence of 0-0.5moll-1 of sulfuric acid <1998ZFK1031>. The rate of the reaction was found to be determined by the equilibrium of cyclization of half-acetal into eight-membered ring and of reverse process of hydrolysis. Rate constants demonstrated linear dependence on Hammett acidity function. Activation energies were 20.9 and 14.0 kcal mol-1 for the formation of cyclic acetal and its hydrolysis, correspondingly. 

Other functional groups may be present in the molecule containing the double bond. Methallyl alcohol, H2C = C(CHjX HjOH, is hydrated by a mixture of 25% sulfuric acid in the presence of isobutyraldehyde to give the cyclic acetal of isobutylene glycol with the aldehyde. Hydrolysis of the acetal by dilute mineral acid gives isobutylene glycol (94%). Hydration of the double bond by aqueous sulfuric acid has been used to make chloro-i-butyl alcohol from methallyl chloride and /S-hydroxybutyric acid from crotonic acid. ... 

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