Epoxides hydrolysis with hydroxide

The reaction of an epoxide with hydroxide ion leads to the same product as the acid-catalyzed opening of the epoxide a 1,2-diol (glycol), with anti stereochemistry. In fact, either the acid-catalyzed or base-catalyzed reaction may be used to open an epoxide, but the acid-catalyzed reaction takes place under milder conditions. Unless there is an acid-sensitive functional group present, the acid-catalyzed hydrolysis is preferred. 

There are two possible types of mechanism for the uncatalyzed hydrolysis of epoxides, a simple SN2 reaction of the substrate with water and a reaction of the protonated substrate with hydroxide ion. Another question to be answered concerns the position of attack of the nucleophile in substituted ethylene oxides. Experiments by Long and Pritchard [150] with H2180 indicate that in the uncatalyzed hydrolysis of propylene oxide two-thirds of the overall reaction occur via attack at the primary carbon. The corresponding percentage for the reaction of isobutylene oxide has not been determined precisely, but it is 20 % at least, probably much more. Attack at the primary carbon predominates also in the uncatalyzed reaction of propylene oxide with chloride ion [152]. 

Attempted hydrolysis of the acetate function of the 10a-8jS,9j5-epoxide (303) with dilute methanolic potassium hydroxide afforded, via retro-aldol type cleavage, the 8,9-seco-steroid (304). 

The most studied example of 0 -3 participation is probably the base-catalyzed hydrolysis of 2-chloroethanol to produce ethylene oxide. As mentioned above, the reaction is catalyzed by hydroxide but not by water. Studies of the solvent isotope effect along with spectroscopic and conductivity measurements have confirmed the postulated two-step process. The reaction is often used as a stereospecific route to the more hindered epoxide derived from an olefin (via initial halohydrin addition). The carbohydrate field serves as a rich field for the application of epoxide opening and closing reactions. In this respect, Cerny and co-workers have observed that (193), (194), and (195) undergo hydroxide-catalyzed epoxide formation with relative rates of 1 23.3 180, respectively. 

Reaction of olefin oxides (epoxides) to produce poly(oxyalkylene) ether derivatives is the etherification of polyols of greatest commercial importance. Epoxides used include ethylene oxide, propylene oxide, and epichl orohydrin. The products of oxyalkylation have the same number of hydroxyl groups per mole as the starting polyol. Examples include the poly(oxypropylene) ethers of sorbitol (130) and lactitol (131), usually formed in the presence of an alkaline catalyst such as potassium hydroxide. Reaction of epichl orohydrin and isosorbide leads to the bisglycidyl ether (132). A polysubstituted carboxyethyl ether of mannitol has been obtained by the interaction of mannitol with acrylonitrile followed by hydrolysis of the intermediate cyanoethyl ether (133). 

With a-chloro ketones, lithiated (2S)-2,5-dihydro-2-isopropyl-3,6-dimethoxypyrazincs react at the carbonyl group to give the aldol adducts which, upon subsequent treatment with sodium hydroxide, give the epoxides 413. Hydrolysis leads to fi.y-epoxy amino acids, or further functionalized amino acids when the epoxide is opened with nucleophiles13. 

A rather complex microwave-assisted ring-opening of chiral difluorinated epoxy-cyclooctenones has been studied by Percy and coworkers (Scheme 6.131) [265]. The epoxide resisted conventional hydrolysis, but reacted smoothly in basic aqueous media (ammonia or N-methylimidazole) under microwave irradiation at 100 °C for 10 min to afford unique hemiacetals and hemiaminals in good yields. Other nitrogen nucleophiles, such as sodium azide or imidazole, failed to trigger the reaction. The reaction with sodium hydroxide led to much poorer conversion of the starting material. 

The reaction actually involves the sodium salt of bisphenol A since polymerization is carried out in the presence of an equivalent of sodium hydroxide. Reaction temperatures are in the range 50-95°C. Side reactions (hydrolysis of epichlorohydrin, reaction of epichlorohydrin with hydroxyl groups of polymer or impurities) as well as the stoichiometric ratio need to be controlled to produce a prepolymer with two epoxide end groups. Either liquid or solid prepolymers are produced by control of molecular weight typical values of n are less than 1 for liquid prepolymers and in the range 2-30 for solid prepolymers. 

The substituent effect of a methyl group on the rate coefficient of the basic hydrolysis of ethylene oxide is small. The kOH values for ethylene oxide, propylene oxide, and isobutylene oxide are almost the same (Table 9). It has been demonstrated by Long and Pritchard [150] with the aid of experiments in oxygen-18 labeled water that hydroxide ion attacks propylene oxide and isobutylene oxide predominantly at the primary carbon. Consequently, the base catalyzed hydrolysis of epoxides is a simple bimolecular nucleophilic substitution. 

On a laboratory scale, alkaline hydrolysis is carried out with only a slight excess of alkali, typically IM potassium hydroxide in 95% ethanol, refluxing for one hour, and the fatty acids recovered after acidification of the reaction mixture. This is a sufficiently mild procedure that most fatty acids, including polyunsaturates, epoxides, and cyclopropenes, are unaltered (19). 

A more complicated pH-rate profile is also observed for the hydrolysis reactions of benzo[a]pyrene diol epoxide epoxide 80, and is shown in Fig. 5.102 This profile shows Regions A-D that are similar to those for reaction of precocene I oxide 76 (Fig. 4), except that Region B reaches a full plateau that extends from pH 5 to 9 in water. The interpretation of this pH-rate profile is essentially the same as the interpretation of the profile for hydrolysis of precocene I oxide (Fig. 4). The pH-independent reaction of 80 in Region B (discussed in detail in Section Benzylic epoxides and arene oxides ) yields 60% tetrols in a stepwise mechanism involving a carbocation intermediate and 40% ketone from a completely separate pathway (Scheme 31). The negative inflection of the profile at pH 10-11.5 indicates that hydroxide ion reacts as a base with the intermediate carbocation to reform diol epoxide 80 and thus slow the reaction rate. There is a corresponding increase in the yield of ketone 107 at pH >11. 

The aziridine ring is more stable than the oxirane ring in alkaline solution, as demonstrated by the low reactivity in attempts to accomplish isomerization of the hydroxyepimines to amino epoxides in alkaline media at room temperature, which contrasts with the rapid epoxide migration (see Sect. V,2). Isomerization of hydroxyepimines occurs only at high temperatures, and leads finally to the formation of amino derivatives of 1,6-anhydrohexoses.379,740 For example, when 166 is heated in 5% potassium hydroxide, 2-amino-l,6-anhydro-2-deoxy-/3-D-mannopyranose (168) is formed as the main product this can be explained by transient formation of 2-amino-l,6 3,4-dianhydro-2-deoxy-/3-D-altropyranose (167), and its subsequent, diaxial hydrolysis.379 Compound 167 is probably in equilibrium with epimine 166. Acid hydrolysis of the aziridine ring in 153 also follows a diaxial mechanism, without scission of the 1,6-anhydride bond, to give 4-amino-l,6-anhydro-4-deoxy-)8-D-mannopyranose756 (177). 

The bromo epoxide 402 used in these syntheses is prepared from 371 by initial conversion to (iS)-l,4-dibromo-2-butanol (401) [16] followed by cyclization with potassium hydroxide [18]. Alkylation of 1,3-dithiane first with EE-protected co-chloroalcohols to give 403 and then with the ( S)-epoxide 402 affords 404. Opening the oxirane with either Super-Hydride or methyl cuprate creates the requisite carbon skeletons 405 with the appropriate fimctionality patterns. Removal of the EE protecting group and mercury-mediated hydrolysis of the thioacetal directly furnishes the spiroacetals 407 as a 3 2 mixture of diastereomers [16]. 

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