Thought I would add this reference to a similar epoxidation.
Patent EP1140788
The epoxidation of an optionally substituted trans-cinnamic alcohol of formula:
to give an epoxide of formula la can conveniently be carried out using a suitable epoxidizing agent, for example, vanadic anhydride and hydrogen peroxide, vanadium (acetylacetonate) 2 and tert-butyl hydroperoxide, or a peroxy acid such as perbenzoic acid, m-chloroperbenzoic, peracetic acid, pertrifluoroacetic acid or mono-or di-peroxy-phthalic acid. The reaction can be carried out in any suitable solvent or combination of solvents, for example, in a hydrocarbon, a halogenated hydrocarbon, a linear or branched ether, a carboxylic acid, or an ester. Specific solvents include benzene, toluene, chloroform, methylene chloride, diethyl ether, dioxane, acetic acid, and ethyl acetate. Preferably the reaction is carried out in methylene chloride or ethyl acetate. More preferably in methylene chloride. The reaction can be carried out at any suitable temperature from the freezing point to the reflux temperature of the reaction mixture. Preferably the reaction is carried out at a temperature in the range of about 0 C to about 50 C. More preferably at a temperature in the range of about 5 C to about 25 C.
United States patent 5,068,433 and related United States patent 5,391,735 disclose that an epoxide of formula Ib can be prepared from trans-cinnamic alcohol using a suitable oxidizing agent, for instance vanadic anhydride and hydrogen peroxide, or a peroxy acid such as, e. g., perbenzoic acid, m-chloroperbenzoic, peracetic, mono-or di-peroxyphthalic, or peroxy-trifluoroacetic acid. At Example 1, these patents specifically exemplify the preparation of an epoxide of formula Ib by the oxidation of trans-cinnamic alcohol with m-chloroperbenzoic acid. The oxidation of trans-cinnamic alcohol with m-chloroperbenzoic acid was also reported by P. Melloni et al. Tetrahedron, 1985,41, no. 7,1393-1399.
m-Chloroperbenzoic acid is expensive to use on a commercial scale. Thus, a different epoxidation reagent would be preferred for the commercial scale production of a compound of formula (A). Studies with mono-peroxy-phthalic acid have shown that this reagent can be used to prepare epoxide Ib on a commercial scale. However, the preparation of mono-peroxy-phthalic acid from phthalic anhydride and hydrogen peroxide is time consuming. Additionally, the epoxidation reaction with mono-peroxy-phthalic acid generates a large amount of solid phthalic acid by-product that must be filtered from the product mixture. This filtration step is time consuming and generates a large amount of aqueous and solid wastes. Thus, m-chloroperbenzoic acid and mono-peroxy-phthalic acid are not ideally suited for the commercial scale epoxidation of trans-cinnamic alcohol.
It has been discovered that the epoxidation of cinnamyl alcohol can conveniently be carried out on a commercially scale using peracetic acid. Peracetic acid is less expensive and, as a liquid, is easier to handle on a large scale than m-chloroperbenzoic acid, which is a solid. Additionally, the use of peracetic acid reduces the time required for preparing epoxide Ib, by eliminating the need to prepare mono-peroxy-phthalic acid; peracetic acid also substantially reduces the amount of aqueous and solid waste generated by the epoxidation reaction compared to the reaction with mono-peroxy-phthalic acid.
Accordingly, the invention provides a method for preparing an epoxide of formulala:
comprising oxidizing a corresponding optionally substituted trans-cinnamic alcohol with peracetic acid. The epoxide la is highly sensitive to decomposition by strong acids.
Commercial peracetic acid is stabalized with sulfuric acid. Accordingly, the peracetic acid should be treated with a suitable base (e. g. sodium or potassiun acetate) prior to use; or the reaction can conveniently be run in the presence of a suitable solid base (e. g. sodium or potassium carbonate). Preferably, the reaction is carried out on a commercial scale.
Preferably, the reaction is carried out in methylene chloride and at a temperature below about 30 C.
Example 1. (2RS, 3RS)-2,3-Epoxy-3-phenylpropanol (I).
Sodium carbonate (224 g) and trans-cinnamyl alcohol (200.0 g) were mixed with 2L of methylene chloride. a slow nitrogen sweep was maintained through the vapor space of the flask and the mixture was cooled to 15-20 C with a cold water bath. Peracetic acid solution (35%, 381.2mL) was added over a 3 hour period, maintaining the internal temperature below 25 C. After the peracetic acid addition was complete, the mixture was stirred for 2-3 hours until complete, as shown by HPLC analysis. The mixture was cooled to 10 C with an ice bath, and a solution of sodium sulfite (160g) in 1200 ml water was added slowly over 90 minutes, keeping the temperature below 30 C. The phases were separated and the aqueous phase was extracted with methylene chloride (200 mL) to give a solution of the title compound.
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