Hydrolysis, acidic conditions

Under acidic conditions, furfuryl alcohol polymerizes to black polymers, which eventually become crosslinked and insoluble in the reaction medium. The reaction can be very violent and extreme care must be taken when furfuryl alcohol is mixed with any strong Lewis acid or Brn nstad acid. Copolymer resins are formed with phenoHc compounds, formaldehyde and/or other aldehydes. In dilute aqueous acid, the predominant reaction is a ring opening hydrolysis to form levulinic acid [123-76-2] (52). In acidic alcohoHc media, levulinic esters are formed. The mechanism for this unusual reaction in which the hydroxymethyl group of furfuryl alcohol is converted to the terminal methyl group of levulinic acid has recendy been elucidated (53). 

Fig. 22. Mechanism for the hydrolysis of tert-huty acetate under strongly acidic conditions.

Hydrolysis in neutral aqueous solutions proceeds slowly at room temperature and more rapidly at acidic conditions and elevated temperatures. The hydrolysis—esterification reaction is reversible. Under alkaline conditions hydrolysis is rapid and irreversible. Heating the alkaline hydrolysis product at 200—250°C gives 4,4 -oxydibutyric acid [7423-25-8] after acidification (148). 

Hydrolysis. Although hydantoins can be hydroly2ed under strongly acidic conditions, the most common method consists of heating ia an alkaline medium to give iatermediate ureido acids (the so-called hydantoic acids), which are finally hydroly2ed to a-amino acids. 

The recovery of fiber from broke (off-specification paper or trim produced in the paper mill) is compHcated by high levels of urea—formaldehyde and melamine—formaldehyde wet-strength resin. The urea resins present a lesser problem than the melamine resins because they cure slower and are not as resistant to hydrolysis. Broke from either resin treatment may be reclaimed by hot acidic repulping. Even the melamine resin is hydrolyzed rapidly under acidic conditions at high temperature. The cellulose is far more resistant and is not harmed if the acid is neutralized as soon as repulping is complete. 

Another synthesis of the cortisol side chain from a C17-keto-steroid is shown in Figure 20. Treatment of a C3-protected steroid 3,3-ethanedyidimercapto-androst-4-ene-ll,17-dione [112743-82-5] (144) with a tnhaloacetate, 2inc, and a Lewis acid produces (145). Addition of a phenol and potassium carbonate to (145) in refluxing butanone yields the aryl vinyl ether (146). Concomitant reduction of the C20-ester and the Cll-ketone of (146) with lithium aluminum hydride forms (147). Deprotection of the C3-thioketal, followed by treatment of (148) with y /(7-chlotopetben2oic acid, produces epoxide (149). Hydrolysis of (149) under acidic conditions yields cortisol (29) (181). 

In acid solution, the double bond of (203) is hydrogenated to the trans-fused sulfone (204). Presumably, this hydrogenation goes through a cis-fused intermediate that is rapidly epimerized to (204) under the acidic conditions of the reaction. Condensation of the sodium salt of 7,7-ethylenedioxy-3-oxooctanoate (205) with (204) produces (206). Cmde (206) is cyclized, hydroly2ed, and decarboxylated, producing the tricycHc compound (207). Hydrogenation of (207) followed by ketal hydrolysis and cyclization affords (208) in an overall yield of 35% from hydrindandione (203). 

Studies of reaction mechanisms ia O-enriched water show the foUowiag cleavage of dialkyl sulfates is primarily at the C—O bond under alkaline and acid conditions, and monoalkyl sulfates cleave at the C—O bond under alkaline conditions and at the S—O bond under acid conditions (45,54). An optically active half ester (j -butyl sulfate [3004-76-0]) hydroly2es at 100°C with iaversion under alkaline conditions and with retention plus some racemization under acid conditions (55). Effects of solvent and substituted stmcture have been studied, with moist dioxane giving marked rate enhancement (44,56,57). Hydrolysis of monophenyl sulfate [4074-56-0] has been similarly examined (58). 

Although a C—CN bond is normally strong, one or two cyano groups in TCNE can be replaced easily, about as easily as the one in an acyl cyanide. The replacing group can be hydroxyl, alkoxyl, amino, or a nucleophilic aryl group. Thus hydrolysis of TCNE under neutral or mildly acidic conditions leads to tricyanoethenol [27062-39-17, a strong acid isolated only in the form of salts (18). 

Selective substitutions have been most studied in the pyrido[3,4-tf]pyridazine field. The 1,4-dichloro derivative (334) was more reactive than 1,4-dichlorophthalazine, and was expected from MO calculations to show a more reactive 4-chlorine group. In practice, however, almost equal amounts of monosubstitution products were observed on hydrolysis, although slight differences in the use of alkaline and acid conditions, or on hydrazination, have been reported (69CPB2266). Reaction of this 1,4-dichloro compound, or substituted... 

Aminoisoxazole has been synthesized in- high yield by the hydrolysis and ring closure reaction of cyclohexylideneaminoacrylonitrile under acidic conditions (equation 45) (69GEP1814116). 

Severe concentration cell corrosion involves segregation of aggressive anions beneath deposits. Concentrations of sulfate and chloride, in particular, are deleterious. Acid conditions may be established beneath deposits as aggressive anions segregate to these shielded regions. Mineral acids, such as hydrochloric and sulfuric, form by hydrolysis. The mechanism of acid formation is discussed in Chap. 2. 

Acetonides are quite stable to base, and to oxidation, dehydration and acylation reactions carried out in pyridine. They are cleaved by acid hydrolysis. The 17,21-acetonides of 17a,21-dihydroxy-20-keto steroids and related acetals are split by very mild acid conditions. ... 

Nitriles are classified as carboxylic acid derivatives because they are converted to carboxylic acids on hydrolysis. The conditions required are similar- to those for the hydrolysis of amides, namely, heating in aqueous acid or base for several hours. Like the hydrolysis of amides, nitrile hydrolysis is ineversible in the presence of acids or bases. Acid hydrolysis yields fflnmonium ion and a carboxylic acid. 

Methylene acetals are the most stable acetals to acid hydrolysis. Difficulty in their removal is probably the reason that these compounds have not seen much use. Cleavage usually occurs under strongly acidic or Lewis acid conditions. 

Cyclization of the two pendant alkyl side chains on barbiturates to form a spiran is consistent with sedative-hypnotic activity. The synthesis of this most complex barbiturate starts by alkylation of ethyl acetoacetate with 2-chloropentan-3-one to give 152. Hydrolysis and decarboxylation under acidic conditions gives the diketone, 153. This intermediate is then reduced to the diol (154), and that is converted to the dibromide (155) by means of hydrogen bromide. Double Internal alkylation of ethyl... 

In a similar vein, acylation of the corticoid 50 with furoyl chloride gives the diacyl derivative 51. Reduction with sodium borohydride serves to convert the 11-ketone to the alcohol 52. Hydrolysis under mild acid conditions preferentially removes the acyl group at the less hindered 21 position. The hydroxyl group in that derivative (53) is then converted to the mesylate 54. Replacement by chlorine affords mometasone (55) [12]. 

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