Base-catalyzed reactions epoxidation

Base-catalyzed reactions, in which the nucleophile provides the driving force for ring opening, usually involve breaking the epoxide bond at the less substituted carbon, since this is the position most accessible to nucleophilic attack.86 87 The situation in acid-catalyzed reactions is more complex. The bonding of a proton to the oxygen weakens the C—O... 

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. 

A mechanism for the transformation of the benzodiazepine to the quinoline structure, which accounts for all data obtained from both cyclopenase- and acid- or base-catalyzed reactions, has been proposed by White and Dimsdale (79) (Fig. 8). The conversion is induced by attack of an electron acceptor (e.g., H" ) at the epoxide oxygen or by attack of an electron donor (e.g., OH ) on the N-1 atom. Bond formation between C-10 and C-5a of cyclopenin is facilitated by the close approach of these two atoms in the boat conformation. Therefore, the formation of a tricyclic intermediate appears likely, although a compound of this type has not been isolated so far. Another mechanism that would explain the enzymatic and acid-catalyzed conversions was proposed by Luckner and Never (42). 

The reactive intermediate in a base catalyzed reaction is the deproto-nated substrate. Deprotonation of an alcohol or phenol leads to the formation of an anion which is a stronger nucleophile than the substrate itself. This is of particular interest if the anion may undergo an intramolecular substitution. An example of such a mechanism is the base catalyzed formation of an epoxide... 

When an unsymmetrical secondary alcohol is formed, depending on which carbon-oxygen bond is cleaved. With propylene oxide, for example, a base-catalyzed reaction favors the formation of the secondary alcohol almost exclusively, whereas, a non-catalytic or acid-catalyzed alcoholysis yields a mixture of the isomeric ethers. However, the reactions of other a-epoxides, such as 3,4-epoxy-l-butene, 3,4-epoxy-l-chloropropane (epichlorohydrin), 3,4-epoxy-l-propanol (glycidol), and styrene oxide, are more complicated with respect to which isomer is favored. ... 

Epoxides. The reaction between epoxides and hydroxyl groups is an acid- or base-catalyzed reaction however, all work in the wood field has been with base-catalyzed reactions ... 

Let us look, for example, at the reaction of ethylene oxide with phenol. Acid catalyzes reaction by converting the epoxide into the highly reactive protonated epoxide. Base catalyzes reaction by converting the phenol into the more strongly nucleophilic phenoxide ion. 

Reactions with unsaturated compounds. /-Butyl hydroperoxide decomposes smoothly at 95-105° and hydroxylates double bonds, and even a,)3-unsaturated ketones the reactions are catalyzed by small amounts of osmium tetroxide and afford cir-glycols. In benzene solution in the presence of Triton B as catalyst it converts a ,/3-unsaturated ketones into the corresponding epoxides in yields of 50-90%. The steric requirement of the base-catalyzed reaction are indicated by the failure to react with isophorone or A -3-ketosteroids. Payne effected smooth preparation of /3-phenylglycidaldehyde by allowing cinnamaldehyde and /-butyl... 

Although much more selective than the uncatalyzed reaction, the base-catalyzed reaction has some dependence on stoichiometry. At a ratio of epoxide to acid of 1 1, essentially all the product is the hydroxy ester. However, when an excess of epoxide groups is present. Reaction 7 proceeds until all the acid is consumed, after which the epoxide-hydroxyl reaction (Reaction 9) starts. This is illustrated in Figure 4. 

Base-catalyzed anhydride-epoxide reactions have been found to have greater selectivity toward diester formation. Shechter and Wynstra (8) showed that equal molar amounts of acetic anhydride and phenyl glycidyl ether with either potassium acetate or tertiary amines as a catalyst reacted very selectively. They proposed the following reaction mechanism for the acetate ion catalyzed reaction ... 

The base-catalyzed reaction, however, proceeded readily at 100 C with 0.2% mol of potassium hydroxide and exhibited a high degree of selectivity. As can be seen from Figure 6, disappearance of phenol and epoxide proceeded at the same rate throughout the course of the reaction. This phenomenon indicates that epoxide reacted with phenol to the essential exclusion of any epoxide-alcohol reaction, Shechter and Wynstra (8) proposed a mechanism in which the phenol first is ionized to phenoxide ion as shown in Reaction 24 ... 

In a variation on this theme MgioAl2(OH)24C03 has been shown to catalyze the oxidation of a variety of olefins-linear and cyclic-and unsaturated alcohols and ketones with H2O2 in the presence of benzonitrile [60]. The reaction involves in situ formation of the Payne reagent [61], PhC(OOH)=NH, by base-catalyzed reaction of H2O2 with benzonitrile (Eq. 5). Reaction with the olefin then affords the epoxide and one equivalent of benzamide (Eq. 6). 

The conformationally biased cis- and trans-4-t- )vXy derivatives were examined. The stereochemistry of both acid- and base-catalyzed reactions was investigated in 85 15 DMSO-H2O. Under acidic conditions the epoxides give anti ring opening and the reaction is stereospecific. The base-catalyzed reactions involve tranx-diaxial ring opening. The acid-catalyzed reactions occur by preferential opening of the benzylic bond with inversion. ... 

The basic catalysis of the epoxide-phenol reaction has been studied by a variety of authors (12,13). In general, the conclusion has been that basic catalysis gives selectivity for the phenol-epoxide reaction over the secondary alcohol-epoxide reaction (the secondary alcohol being formed from the opening of an epoxide). Although the base catalyzed reaction has been studied, the specific mechanism for triphenylphosphine Catalysis has not been determined. We propose the mechanism shown in Reaction Scheme 3 which is consistent with our experimental results. 

There is a frequently noted incompatibility of organoiithiums with many chiral Lewis acids, which are often employed for asymmetric openings of epoxides [99]. Analogous Lewis base-catalyzed reactions are rare [100]. However, activation by Lewis acids, such as BFj OEt2, is necessary for the opening of less reactive epoxides [101]. While organoiithiums are rarely employed, applications of hetero-nucleophiles are well known in enantioselective desymmetrizations of meso-epoxides [102]. 

Epoxy resins are normally prepared by the base-catalyzed reaction between an epoxide sueh as epichloro-hydrin and a polyhydroxy compound such as bisphenol A ... 

In most articles relative to the study of the base-catalyzed reaction, a general mechanism is put forward unfortunately the contribution of the side reactions is very often disregarded. If the contribution of some of them (esterification or etherification of the hydroxy side groups, hydrolysis, etc.) can be avoided or at least reduced to a low extent, that of some others (especially those resulting from the amine/epoxide interaction) is more difficult to eliminate. Some studies provided information on the kinetic contribution of these side reaction. 

While participation resulting in a four-membered ring is generally rare, 0-4 participation is common in base-catalyzed reactions of appropriately substituted alcohols. For example, the epoxide (197) undergoes oxide migration to form the oxetane (198). ... 

Incidentally, our part in the discovery of the remarkable utility of DMSO as a solvent for base-catalyzed reactions (15.11, 5) was stimulated by our desire to find a solvent suitable for study of base-catalyzed epoxide polymerization under homogeneous conditions. DMSO has one drawback in that it can participate in chain-transfer. This decreases the molecular weight (as compared to comparable conditions in HMPT) and incorporates sulfoxide groups in the polymer from the following transfer process... 

Although acid-catalyzed and uncatalyzed alcohol-epoxide reactions are known to lead to a mixture of isomeric species, the base-catalyzed reactions give a product that is almost exclusively a primary ether and a secondary alcohol. If, then, a secondary alcohol is reacted with a glycidyl ether under conditions of base catalysis (to yield a new secondary alcohol), the almost exclusive reaction will be that of glycidyl ether with secondary alcohol. The reaction would still be complicated by the competition of the new hydroxyls with the starting alcohol for epoxide. 

The base-catalyzed reaction of epoxide with phenol, in equimolar amounts, is somewhat slower than that of the alcohol-epoxide with the same catalyst. The mechanism of reaction is given in the following reactions ... 

Thus in the aldol addition, just as in the case of epoxide-opening reactions, the chloride ion, formed as a necessary consequence of the mechanism of Lewis base catalysis with chlorosilanes, is not innocuous. In fact, it is a competent nucleophile that can attack an aldehyde or an epoxide activated by the Lewis base-coordinated silicenium cation in an intermolecular fashion. The desire to understand these two seemingly inconsistent results obtained in our study of the Lewis base-catalyzed reactions of trichlorosilanes presented an opportunity for the development of novel catalytic processes. For example, if a chloride ion can capture these activated electrophiles, could other exogenous nucleophiles be employed to intercept these reactive intermediates If so, a wide variety of bond-forming processes mediated by the phosphoramide-bound chiral Lewis acid [LB SiCls]" would be feasible. At this point it remained unclear if (1) an exogenous nucleophile could compete with the ion-paired chloride and (2) what kinds of nucleophiles could be compatible with the reaction conditions. 

Base-catalyzed reactions, in which the nucleophile provides the driving force for ring opening, usually involve breaking of the epoxide bond at the less substituted... 

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