Epoxides with carboxylic acids

Jacobsen, E. N. Kakiuchi, F. Konsler, R. G. Larrow, J. F. Tokunaga, M. ( 1997) Enantioselective catalytic ring opening of epoxides with carboxylic acids., Tetrahedron Lett., 38 773-776. 

The reaction of epoxides with carboxylic acids in the presence of ammonium perchlorate can be very slow. The search for a catalyst to accelerate the cure rate for a particular formulation can be particularly rewarding. The slowness of the reaction can lead to a disadvantage of the system if not carefully investigated. If cure is stopped before all of the epoxide groups have been consumed, cure will continue at a rate which depends on storage temperature. The epoxide can continue to react with carboxyl groups rapidly at elevated temperatures, or very, very slowly at ambient temperature, to yield highly crosslinked propellant systems with low strain capability. 

Treatment of epoxides with concentrated formic acid or acetic acid, followed directly by alkaline hydrolysis of the resultant 1,2-diol monoeater, is sometimes regarded as a 4 hydration on the basis of the final product secured in this manner. Inasmuch as reactions of epoxides with carboxylic acids are accorded separate treatment in this chapter (Bee section IV.4.A), however, such two-step sequences will not be included among the hydration reactions of this section. 

Model system studies with these materials using N-phenyl-phthalamic acid 4, indicated that 3 was the most promising candidate. As in typical reactions of epoxides with carboxylic acids (3), reaction of 4 with 1 required temperatures in excess of 100°C. Extended time at 100°C, however, causes undesired imld-ization. Reaction of 4 with 2 was shown to be feasible, but was not further pursued. The anhydride linkage formed would likely... 

Oxidation is the first step for producing molecules with a very wide range of functional groups because oxygenated compounds are precursors to many other products. For example, alcohols may be converted to ethers, esters, alkenes, and, via nucleophilic substitution, to halogenated or amine products. Ketones and aldehydes may be used in condensation reactions to form new C-C double bonds, epoxides may be ring opened to form diols and polymers, and, finally, carboxylic acids are routinely converted to esters, amides, acid chlorides and acid anhydrides. Oxidation reactions are some of the largest scale industrial processes in synthetic chemistry, and the production of alcohols, ketones, aldehydes, epoxides and carboxylic acids is performed on a mammoth scale. For example, world production of ethylene oxide is estimated at 58 million tonnes, 2 million tonnes of adipic acid are made, mainly as a precursor in the synthesis of nylons, and 8 million tonnes of terephthalic acid are produced each year, mainly for the production of polyethylene terephthalate) [1]. 

The catalytic properties Co-POM/Si02 were assessed in oxidation of IBA to isobutyric acid [96] and a-pinene to verbenol/verbenone [97] with molecular oxygen as well as in a-pinene/lBA co-oxidation to produce the corresponding epoxide and carboxylic acid [97]. In turn, the catalytic performance of Ti-POM/Si02 was examined in a-pinene oxidation to... 

Epoxides. Epoxy compounds react with the carboxyl groups of CTPB to form polyesters. The reaction rates and extent of reaction of a number of epoxides have been determined with the model compound hexanoic acid (6). It was found that most epoxides undergo side reactions (as evidenced by the more rapid consumption of epoxide species) but that at least one difunctional epoxide, DER-332 (Dow Chemical Co.) (Table IV), exhibits a clean reaction with carboxylic acids, even in the presence of ammonium perchlorate. 

A nucleophile is an electron rich species that reacts with an electrophile. The term electrophile literally means electron-loving , and is an electron-deficient species that can accept an electron pair. A number of nucleophilic substitution reactions can occur with alkyl halides, alcohols and epoxides. However, it can also take place with carboxylic acid derivatives, and is called nucleophilic acyl substitution. 

Alkenes are also oxidized to epoxides hy peracid or peroxyacid (RCO3H), e.g. peroxyhenzoic acid (C6H5CO3H). A peroxyacid contains an extra oxygen atom compared with carboxylic acid, and this extra oxygen is added to the double bond of an alkene to give an epoxide. For example, cyclohexene reacts with peroxyhenzoic acid to produce cyclohexane oxide. 

It is well known that homogeneous compounds of Mo(VI) with carboxylic acids are powerful catalysts for the epoxidation of olefins. In order to heterogenize the Mo(VI) derivatives, a commercial carboxylated resins has been used by Ivanov et al. (ref. 1). A weak point of using a commercial resin is that it is not possible to control the number and distribution of carboxylic groups. This results in a poor flexibility of structure and properties of the final catalyst. 

Migration of the carbonyl during epoxide cleavage is used to produce hydroxy lactones from epoxides of carboxylic acids (Eq. 44) [84]. a-Acyl-2-indanones [85], furans [86], and A -oxazolines [87] (Eq. 45) can also be synthesized by cleavage and rearrangement of epoxides with BF3 Et20. 

Mechanistic studies of the opening of the epoxide point to catalyst activation of both nucleophile and electrophile in a bimetallic array [79]. The Cr complex results in moderate ee only when used with thiol nucleophiles but enhancement is feasible by using a dithiol in a two-step selection process [80]. Enantioselective epoxide opening with carboxylic acids is more efficient with (salen)Co(III) complexes (often obtained via in situ oxidation of the Co(II) complex) than with the Cr analogs (Table 6, entries 4 and 5) [81]. This methodology was successfully extended to intramolecular desym-metrization of meso epoxy alcohols [82]. 

Epoxides - The first indication of the synthetic utility of metalated carboxylic acids resulted from efforts to prepare steroidal aldosterone inhibitors from spiroepoxides.39 Model studies indicated that the reaction fails as a result of severe steric hindrance in either the epoxide or carboxylic acid and that monosubstitution occurs for the same reason.39 The reaction has been used in a key step of an elegant synthesis of vernolepin, 5. 40 Forcing conditions are required, and, in contrast to acid dianions, anions of unactivated esters fail to react with epoxides.39 41... 

Indium trichloride induces rearrangement of aryl-substituted epoxides to the respective aryl-substituted acetaldehydes via an exclusive hydride shift As phenyl group migration occurs more readily than hydride migration, stilbene oxide is converted to diphenylacetaldehyde (Scheme 8.140) [184]. N-Tosyl aziridines react smoothly with carboxylic acids in the presence of a catalytic amount of indium triflate to afford the corresponding -aminoacetates and benzoates (Scheme 8.141) [185]. Indium trichloride and indium bromide catalyze regio- and diastereoselective azidolysis, bromolysis, and iodolysis of a, -epoxycarboxylates in water (Scheme 8.142) [186]. 

Oxidative cleavage of epoxide to carboxylic acids with bismuth mandelate general procedure... 

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