Acid-promoted hydrolysis

If only the monocarboxybc acid is required, the ester after hydrolysis with potash may be strongly acidified with sulphuric acid and the mixture heated under reflux the mineral acid promotes decarboxylation at a temperature just above 100°. The net result is the replacement of the halogen atom of the alkyl halide by —CH COOH thus in the above example ... 

The carbonyl group can be deprotected by acid-catalyzed hydrolysis by the general mechanism for acetal hydrolysis (see Part A, Section 7.1). A number of Lewis acids have also been used to remove acetal protective groups. Hydrolysis is promoted by LiBF4 in acetonitrile.249 Bismuth triflate promotes hydrolysis of dimethoxy, diethoxy, and dioxolane acetals.250 The dimethyl and diethyl acetals are cleaved by 0.1-1.0 mol % of catalyst in aqueous THF at room temperature, whereas dioxolanes require reflux. Bismuth nitrate also catalyzes acetal hydrolysis.251... 

Considerable attention has been devoted to the preparation and chemistry of a,/3-unsaturated carbonyl compounds, which are valuable intermediates in organic synthesis [125]. Acid-promoted hydrolysis of alkoxyallenes has therefore frequently been employed to prepare a variety of functionalized a,/8-unsaturated carbonyl compounds [12b, 41, 44, 60, 126]. A recent example is illustrated in Scheme 8.54with C-l-silylated alkoxyallene 218 as a convenient starting material for the synthesis of bicyclo[5.4.0]undec-4-en-2-one 221. Sequential deprotonation and silylation at the terminal C=C bond efficiently transformed 218 into a 1,3-disilylated allene which was converted into the acryloylsilane 219 under acidic conditions. A [3 + 4] annula-tion of intermediate 219 with lithium dienolate 220 furnished bicydic compound 221 in good yield [127]. 

Hydrolysis Reactions. Hydrolysis reactions involve cleavage of a single bond by reaction with water, a hydronium, or a hydroxide ion (78). The bond is typically polarized between an electron-deficient atom (C in carbonyl, P in organophosphates) and an electron-rich atom (0, Cl, Br). The reaction may be neutral, base-, or acid-promoted, depending on the substrate properties and the reaction conditions, such as pH, temperature, and ionic strength (78, 79). 

The acceleration of a reaction by a substance that is also consumed during the process. An example of such a phenomenon is the acceleration of a reaction by a Brpnsted acid present in large excess or maintained by a nearly constant concentration by a buffer. The acceleration of the hydrolysis of an amide by a certain Brpnsted acid is actually general acid promotion rather than general acid catalysis. The term promotion has been used as a synonym for pseudo catalysis. 

Asymmetric transformations of ot-amino acids promoted by optically active metal complexes have been reported by several groups 269). The control of the stereoselective hydrolysis reactions of racemic esters by chiral micellar compounds prepared from amino acids has been intensively investigated 270). 

An alternative focus based on known antitumor activity of adriamycin-type systems stimulated the synthesis of the aza-anthraquinones 599 and 600 (Scheme 177) (84CC897). Thus, synergistic chloro-oxazoline directed metalation of 597 with methyllithium followed by treatment with 2,5-dimethoxybenzaldehyde and acid-promoted cyclization provided the lactone 598. Radical bromination and base-induced hydrolysis gave an intermediate keto acid which, upon Friedel-Crafts cyclization with methanesulfonic acid, led to the aza-anthraquinone 599 in modest yield. The azanaphthacene dione 600 was prepared by an analogous series of reactions starting with 597. 

It was observed that the presence of sulphuric acid promotes the hydrolysis of esters (e.g. [104,107,109]). The rate of hydrolysis is for the most part significantly lower than the esterification rate. Moreover, as already discussed above, in addition to the main reaction producing alcohol and nitrating acid, the hydrolysis process is generally accompanied by side reactions. Acids other than sulphuric, or perchloric [104], e.g. acetic [106] or phosphoric, if present in the esterifying mixture, hydrolyse esters to a markedly smaller extent than sulphuric acid. The acid make up of an esterification mixture in industry is established experimentally. Economic factors also plays a part here. 

Thiazolidin-4-ones have been prepared by condensation of support-bound imines with a-mercapto carboxylic acids (Entry 11, Table 15.18). These thioaminals are quite stable and tolerate, for example, treatment with TFA [228,229]. Thiazolidines, which can be prepared from resin-bound cysteine and aldehydes (Entry 12, Table 15.18), are also remarkably stable towards acid-promoted hydrolysis. Libraries of thiazolidinones have been used to identify new cyclooxygenase-1 inhibitors [230]. 

Gibberellic acid promoted abscission at all concentrations, possibly by acceleration of protein hydrolysis and polysaccharide hydrolysis kinetin... 

Cyclization to a morpholinolactone (59) occurs in the hydrolysis reaction of the di-A-hydroxylethylated compound (60). Compound (59) is rapidly hydrolysed by water to (61) but in file presence of equimolar amounts of amines (RNH2) or ammo acid derivatives (62) forms.56 A novel reaction of cyclic 2-diazo-l,3-dicarbonyl compounds (63) with lactones (64) affords the products (65) in the presence of rhodium acetate, Rh2(OAc)4.57 Lewis acid-promoted intramolecular additions of allylsilanes to lilac tones gave substituted cyclopentanes.58 A proposed transition state guided efforts to improve the stereoselectivity of the reaction. The reaction of a series of /1-lactone derivatives, such as (66)-(68), has been studied and they have been ling cleaved the reaction outcome is both Lewis acid and structure dependent.59... 

Alkali-treated proteinoids containing the 18 common amino acids promote the hydrolysis of the ester bond of p-nitrophenylphosphate 9). In general, the higher the proportion of neutral and basic amino acids proteinoid has, the higher the activity is9>. 

An acid-mediated Prins type cyclization of enol ether 328 followed by basic hydrolysis of the intermediate trifluoro-acetate provides a key step during synthetic studies toward leucascandrolide A (Equation 139) <20010L755>. The acid-promoted Prins cyclization of enol ethers attracts much attention <20030L1499, 2004HCA2750, 2005OL2683>. 

The first of these reactions is a hydrolysis process, the second is a carbonic acid-promoted dissolution, and the third is a proton-promoted dissolution. Equations 3.59b and 3.59c are the forward reactions in Eqs. 3.17 and 3.15, respectively. They provide a mechanistic underpinning for the dependence of kd in Eq. 3.14 on pH or pc0, as discussed in Section 3.1. Indeed, if Eq. 3.7 is applied to the forward reaction in Eq. 3.14 and rate laws for Eq. 3.59 are developed consistently with the hypothesis leading to Eq. 3.7, the result is7,33,34... 

It may be concluded that hydrochloric acid promotes the peroxide-induced monoethylation of -dioxane. However, this selective alkylation reaction is accompanied by hydrolysis of the dioxane. 

The Lewis acid promoted addition of allylsilane (48) to nitroalkene (47) gave the unsaturated ketone (49) after hydrolysis of the nitro group. The palladium-catalyzed oxidation affords the 1,4-diketone (50 Scheme 13). °... 

Enantioselective protonation of prochiral allyl anion derivatives is a very simple and attractive route for the preparation of optically active olefins. The acid-promoted hydrolysis of allyltins or allylsilanes is an interesting alternative the enantioselectivity of which has not yet been investigated. Allyltrialkyltin, a synthetic equivalent of allyl anion, is more reactive than the corresponding allylsilane and can be isolated. The... 

Aluminum chloride and its derivatives are the most familiar Lewis acids and are routinely employed in many Lewis acid-promoted synthetic transformations. The first polymer-supported metal Lewis acids to be studied were polymers attached by weak chemical or physical interactions to a Lewis acid. In the 1970s Neckers and coworkers reported the use of styrene-divinylbenzene copolymer-supported AlCl,- or BF3 as catalyst in condensations, esterifications, and acetalization of alcohols [11,12]. This type of polymer-supported AICI3 (1) is readily prepared by impregnation of a polystyrene resin with AICI3 in a suitable solvent. Subsequent removal of the solvent leaves a tightly bound complex of the resin and AICI3. The hydrophobic nature of polystyrene protects the moisture-sensitive Lewis acid from hydrolysis, and in this form the Lewis acid is considerably less sensitive to deactivation by hydrolysis. This polymer complex could be used as a mild Lewis acid catalyst for condensation of relatively acid-sensitive dicyclopropylcarbinol to an ether (Eq. 1) [13],... 

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