Epoxidation conjugated acids

In general, one can use a variety of oxidation techniques to form derivatives of dienes and higher polyenes for their analysis however, the information obtained with conjugated systems is muddled by the complexity of products. Also, it is obvious that since the oxidized derivatives contain different functionalities, e.g. epoxides, alcohols, acids etc., the analytical techniques employed should also be variable (see also Scheme 2). 

Finally, HOH and ROH can leave protonated alcohols or ethers as leaving groups, hut neither the OH group (from alcohols) nor the OR group (from ethers, except for epoxides, see above) can leave. Remember, the conjugate acid of water is the hydronium ion, a strong acid (pKa = -1.7)... 

Anti-dihydroxylation Epoxides may be cleaved by an aqueous acid to give glycols. Proton transfer from the acid catalyst generates the conjugate acid of the epoxide, which is attacked by nucleophiles such as water. The result is anti-dihydroxylation of the double bond. 

Use of dimethyldioxirane obviates the problems associated with epoxidations of conjugated acids and esters with peroxy acids and of enones with alkaline hydrogen peroxide. The only by-product of the reaction is acetone, making this procedure an environmentally friendly one. 

Note that the leaving group in this case is the carboxylate anion, which then reacts further with the protonated epoxide to form the corresponding conjugate acid, i.e. the carboxylic acid, and the neutral epoxide. 

Trans hydroxylation of an alkene involves sequential conversion to an oxirane (epoxide), and its conjugate acid, followed by nucleophilic opening of the oxirane by water... 

If the leaving group of the substrate, like in allyl ethers, vinyl epoxides and vinyl cyclopropanes, is sufficiently basic to deprotonate the conjugate acid of the nucleophile then no additional base has to be added, thus broadening the scope and simplicity of this method. 

The reaction of oxiran with HF to yield CH2FCH2OH was chosen as the model for the ring-opening of epoxides that is caused by halogen acids, and theoretical ab initio calculations for the reaction were performed. For the gas-phase reaction, the preferred mechanism leads to retention of configuration at the carbon atoms of the ring. An alternative pathway via preliminary formation of the conjugate acid of the oxiran was found to fit a borderline A2 mechanism. 

The reaction of epoxides and nucleophiles was introduced in Chapter 11 (Section 11.8.2). Grignard reagents and organolithium reagents react with epoxides at the less sterically hindered carbon atom. The reaction of phenylmagnesium bromide and epoxide 33, for example, generates alkoxide 34. An aqueous acid workup converts the alkoxide to the conjugate acid and final product, alcohol 35. 

Step 1 The most abundant acid in the reaction mixture, the conjugate acid of the solvent methanol, transfers a proton to the oxygen of the epoxide. 

The test is based on chromophore modification resulting from the transformation of a 5,6-epoxide group to 5,8-epoxide in acid medium. This stmctural transformation means the loss of the conjugated double bond at positions 7 and 8 of the central polyene, causing a hypsochromic displacement of the absorption spectmm of 15-20 nm. Chromatographically, the 5,8-epoxide derivatives are more polar, so that chromatographic development by TLC using silica gel as support reveals bands with lower Rf values. 

Physical and Chemical Properties. The (F)- and (Z)-isomers of cinnamaldehyde are both known. (F)-Cinnamaldehyde [14371-10-9] is generally produced commercially and its properties are given in Table 2. Cinnamaldehyde undergoes reactions that are typical of an a,P-unsaturated aromatic aldehyde. Slow oxidation to cinnamic acid is observed upon exposure to air. This process can be accelerated in the presence of transition-metal catalysts such as cobalt acetate (28). Under more vigorous conditions with either nitric or chromic acid, cleavage at the double bond occurs to afford benzoic acid. Epoxidation of cinnamaldehyde via a conjugate addition mechanism is observed upon treatment with a salt of /-butyl hydroperoxide (29). 

Fenoldopam (76) is an antihypertensive renal vasodilator apparently operating through the dopamine system. It is conceptually similar to trepipam. Fenoldopam is superior to dopamine itself because of its oral activity and selectivity for dopamine D-1 receptors (D-2 receptors are as.sociated with emesis). It is synthesized by reduction of 3,4-dimethoxyphenylacetonitrile (70) to dimethoxyphenethylamine (71). Attack of diis last on 4-methoxystyrene oxide (72) leads to the product of attack on the epoxide on the less hindered side (73). Ring closure with strong acid leads to substituted benzazepine 74. O-Dealkylation is accomplished with boron tribromide and the catechol moiety is oxidized to the ortho-quinone 75. Treatment with 9NHC1 results in conjugate (1,6) chloride addition and the formation of fenoldopam (76) [20,21]. 

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