Epoxide-alcohol reaction

Using model systems, they found that without a catalyst no reaction occurred at 100 °C. At 200 °C epoxide disappeared at a much faster rate than phenol did (Figure 5) about 60% of the reaction was epoxide-phenol and the other 40% was epoxide-formed alcohol. Because alcohol was absent at the beginning of the reaction and only appeared when phenol reacted with epoxide, it was concluded that the phenol preferred to catalyze the epoxide-alcohol reaction rather than react itself. 

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 ... 

The epoxide-mercaptan reaction is highly selective, and there appears to be no concomitant epoxide-alcohol reaction. Thus, to obtain a cross-linked network with a diepoxide, the functionality of the mercaptan must be greater than two. 

The uncatalyzed epoxide-alcohol reaction was shown by Shechter and Wynstra (8) to be "rather sluggish" a temperature of 200 C is necessary to realize a conveniently rapid rate. The reaction can be catalyzed by either acid or base to yield primary and secondary alcohols that will further react with the free epoxide to form polyethers (Reaction 33). 

Acid catalysis of the epoxide-alcohol reaction is no more selective than base catalysis. The ratio of alcohols formed and the amount of polyether obtained vary with the type and amount of catalyst, epoxide-to-alcohol ratio, solvent, and reaction temperature. 

The methods are at hand to distinguish which mechanism is responsible for the increase in EEW during isothermal aging. The epoxide homopolymerization should have a second order dependence on epoxide concentration and no dependence on secondary alcohol concentration, whereas the epoxide-alcohol reaction should display a first order dependence on both epoxide and secondary alcohol concentration. Therefore, a study of isothermal aging kinetics versus EEW of the epoxy resin will distinguish these mechanisms. 

Epoxide - alcohol reaction pseudo first order kinetics (k units of s k units of g eq s ). 

Base-catalyzed reactions are very specific and take place readily at 100 °C. In the presence of about 0.2 mol % potassium hydroxide, the consumption rate of phenols exactly corresponds to the disappearance of epoxides. This suggests that, in this case, the epoxide-alcohol reaction according to reaction (77) is absent. A reaction mechanism according to Scheme 26 has been proposed to explain this behaviour. 

In some cases products of rearrangement are obtained either partially or exclusively on treatment of Grignard reagents with epoxides. Thus, reaction of the 2/ ,3/ -epoxide (14) with methyl Grignard reagent affords a mixture of two epimeric secondary A-nor alcohols (15) in 80% yield and the tertiary hydroxy compound, 2a-methyl-5a-cholestan-2/f-ol (16) in 15 % yield. ... 

It is appropriate at this juncture to address some of the more useful transformations of 2,3-epoxy alcohols.913 A 2,3-epoxy alcohol such as compound 14 possesses two obvious electrophilic sites one at C-2, and the other at C-3. But in addition, C-l of a 2,3-epoxy alcohol also has latent electrophilic reactivity. For example, exposure of 14 to aqueous sodium hydroxide solution results in the formation of triol 19 in 79% yield (see Scheme 5). In this interesting transformation, hydroxide ion induces the establishment of an equilibrium between 2,3-epoxy-l-ol 14 and the isomeric 1,2-epoxy-3-ol 18. This reversible, base-induced epoxide migration reaction is a process known as the Payne rearrangement.14... 

REACTIONS WITH ALCOHOLS, PHENOLS AND EPOXIDES Alcohols... 

The synthesis of the Y zeolite-encapsulated manganese complex of the salen ligand has been reported recently [51]. It was found to have catalytic activity in the oxidation of cyclohexene, styrene, and stilbene with PhlO. Typically, 1 Mn(salen) is present per 15 supercages, resulting in catalytic turn-overs in the order of 60. The reactions investigated with the respective product yields are given in Scheme 5. Typical oxidation products are epoxides, alcohols and aldehydes. In comparison to the homogeneous case encapsulation seems to lower the reaction rate. From cyclohexene the expected oxidation product cyclohexene oxide is present in excess and is formed on the Mn(salen) site. 2-cyclohexene-l-ol is probably formed on residual Mn cations via a radical mechanism. 

The molybdenum-hydroperoxide complex (Step 3) reacts with the olefin in the rate-determining step to give the epoxide, alcohol, and molybdenum catalyst. This mechanism explains the first-order kinetic dependence on olefin, hydroperoxide, and catalyst, the enhanced reaction rate with increasing substitution of electron-donating groups around the double bond, and the stereochemistry of the reaction. 

The reaction accommodates halides, esters, ethers, nitriles, cyclopropanes, epoxides, alcohols and nitio groups. Even carbohydrates can be used.492-494 However, vinylic halides afford aldehydes and ketones... 

Alkenes can be transformed into epoxides by reaction with Ac-IBX (44), generated by reaction of Dess-Martin periodinane with water.506 As the oxidation of alcohols is quicker, it is normally possible to oxidize alcohols with no interference from alkenes. 

Dunach, Inesi and others also investigated the electrochemical synthesis of cyclic carbonates from C02 with epoxides, alcohols and glycols [66]. In this regard, Yang et al. [67] reported the use of pure room temperature ionic liquids (ILs) as reaction media in the electrochemical activation of C02 for the synthesis of cyclic carbonate from epoxide, under mild conditions. C02-saturated IL (BMIMBF4) solutions were also used for the electrochemical carboxylation of activated olefins [68]. Monocarboxylic acids were obtained in moderate yield (35-55%), and the IL was recycled five times. 

Cyclization of unsaturated epoxides.1 Reaction of the epoxy alcohol (2) derived from linalool with cobaloxime(I), (1), forms the P-hydroxycobaloxime 3. 

The reactions of Grignard reagents with aldehydes and ketones give alcohols, reaction with acid chlorides and esters give tertiary alcohols, reaction with carbon dioxide to give carboxylic acids, reaction with nitriles give ketones, and reaction with epoxides give alcohols. 

The synthesis of darunavir (1) is shown in Scheme 12. Optically active bis-THF alcohol (-)-ll was converted to activated mixed carbonate 46 by treatment with N,N-disuccinimidyl carbonate (DSC) in the presence of triethylamine.30 For the synthesis of the hydroxyethylsulfonamide isostere, epoxide 38 was treated with isobutyl amine (47) in 2-propanol at reflux to provide the corresponding amino alcohol. Reaction of the resulting amino alcohol with p-nitrophenylsulfonyl chloride in the presence of aqueous NaHC03 afforded the sulfonamide derivative 48 in 95% yield for the two steps. This was converted to darunavir in a three-step process, involving (1) catalytic hydrogenation of nitro to an amine, (2) removal of the Boc group by exposure to trifluoroacetic acid in... 

Sharpless epoxidation of alkenylsilanols.1 Allylic silanols also undergo highly enantioselective Sharpless epoxidation. This reaction furnishes simple epoxides such as styrene oxide in high optical purity. Thus reaction of fram-(3-lithiostyrene il) with ClSi(CH,)2H gives 2, which can be oxidized to the alkenylsilanol 3. ShaTp-less epoxidation of 3 gives the epoxide 4, which is converted to styrene epoxide 5 by cleavage with fluoride ion. The stereochemistry of epoxidation of 3 is similar to that of the corresponding allylic alcohol. 

---