Oxidation monoperphthalic acid

The most common method of epoxidation is the reaction of olefins with per-acids. For over twenty years, perbenzoic acid and monoperphthalic acid have been the most frequently used reagents. Recently, m-chloroperbenzoic acid has proved to be an equally efficient reagent which is commercially available (Aldrich Chemicals). The general electrophilic addition mechanism of the peracid-olefin reaction is currently believed to involve either an intra-molecularly bonded spiro species (1) or a 1,3-dipolar adduct of a carbonyl oxide, cf. (2). The electrophilic addition reaction is sensitive to steric effects. 

A solution of 10 g (0.023 mole) of cholesteryl acetate (mp 112-114°) in ether (50 ml) is mixed with a solution containing 8.4 g (0.046 mole) of monoperphthalic acid (Chapter 17, Section II) in 250 ml of ether. The solution is maintained at reflux for 6 hours, following which the solvent is removed by distillation (steam bath). The residue is dried under vacuum and digested with 250 ml of dry chloroform. Filtration of the mixture gives 6.7 g of phthalic acid (87% recovery). The solvent is evaporated from the filtrate under reduced pressure and the residue is crystallized from 30 ml of methanol, giving 6.0 g (58% yield) of -cholesteryl oxide acetate. Recrystallization affords the pure product, mp 111-112°. Concentration of the filtrate yields 1.55 g (15% yield) of a-cholesteryl oxide acetate which has a mp of 101-103° after crystallization from ethanol. 

The dried ether solution contains about 30 g (65%) of monoperphthalic acid and is approx. 0.26 to 0.28 M. It may be used directly for oxidation reactions (cf. Chapter 1, Section IV), or stored under refrigeration. Evaporation of the ether under reduced pressure (no heat) affords the crystalline product, mp 110° (dec). 

Bohme77 employed excess monoperphthalic acid in diethyl ether to oxidize dibenzyl and benzyl ethyl sulphoxides. Reaction time was 24 h at - 15 to + 10 °C, after which he added potassium iodide and water and titrated the iodine set free with thiosulphate. Dickenson78 oxidized dimethyl sulphoxide in malt, wort or beer with Na2S2Os. In... 

Pyridine-N-oxide has been prepared by oxidation of pyridine with perbenzoic acid,4 with monoperphthalic acid,6 with peracetic acid (hydrogen peroxide and acetic acid),6-7 and with hydrogen peroxide and other carboxylic acids.7... 

The oxidative cyclization of vinylallenes need not be directed by a pendant hydroxyl group in order to succeed. The higher reactivity of the allene compared with the exocyclic methylene group in 73 (Eq. 13.23) with monoperphthalic acid leads primarily to the allene oxide which rearranges to cydopentenone 74 [27]. Inevitably some epoxidation of the alkene also takes place during the reaction. When m-CPBA is used as the oxidant, another side reaction is associated with m-chlorobenzoic add-mediated decomposition of the intermediate epoxide. It is possible to overcome this problem by performing the epoxidation in dichloromethane in a two-phase system with aqueous bicarbonate so as to buffer the add [28]. 

If ether is not suitable for the oxidation reactions in which the peracid is to be used, the material can be dissolved in another solvent after removal of the ether. An excellent solvent for monoperphthalic acid oxidations is dioxane, and a solution of the peracid in dioxane is readily prepared by adding dioxane to the dried ether extract and then removing the ether under reduced pressure at 150. The dioxane must be peroxide-free.1... 

Convergine (101) and hippodamine (102) are an V-oxide/free base pair, since monoperphthalic acid oxidation of 102 gives convergine (101) and 101 can be reduced with lithium aluminum hydride to yield 102. The structure and absolute configuration of 101 and 102 have been established by X-ray diffraction analysis... 

The oxidation may be carried out by Caro s acid (per monosulphuric acid, H2S05) or with perbenzoic, peracetic or monoperphthalic acid. 

The sulfur in alkylthio groups of 1,2,4-thiadiazoles may be oxidized successively to the sulfoxide and sulfone stage. Thus, 5-amino(or anilino)-3-alkylthio- 1,2,4-thiadiazoles (321 R = NH2 or PhNH)85,133 and 3-alkylthio-1,2,4-thiadiazoles (321 R = H),90 on treatment with one or two moles of monoperphthalic acid, yield the appropriate oxidation products (322 and 323). Hydrogen peroxide or chlorine may replace the less convenient per-acid as the oxidizing reagent.86 By careful... 

Peracetic acid oxidation of 2-carbamoylquinoxaline (94) at 20°-25° gives the monoxides 95 and 96, and at higher temperatures the 1,4-dioxide (97) is isolated in 50% yield, together with a small amount of the 1,4-dioxide of 2-amino-3-quinoxalinone.m However, Hayashi and co-workers report the isolation of only 96 from 94 using monoperphthalic acid in ether <10°.109 In their attempt to correlate the nature of 2-substitution with the formation of 1- versus 4-oxides, they examined the behavior of some 2-alkyl substituted quinoxalines 113,114 2-ethylquin-oxaline gives the 1- and 4-oxides and the 1,4-dioxide, 2-isopropylquin-oxaline yields the 4-oxide and the 1,4-dioxide however, 2-f-butylquin-oxaline only furnishes the 4-oxide because of steric hindrance.114 The N-oxidation of 2-phenyl- and 2-alkyl-3-phenyl-quinoxalines with monoperphthalic acid furnishes the products shown in Table 1.114... 

Oxidation of the olefin 1 with an excess of monoperphthalic acid in ether/dichloromethane at 4°C in the dark gave a mixture of epimeric ketols 2 in 74% yield (trans cis 6 1). 

Pentafluorophenyl thioketones are available [115] from the reaction of the corresponding fluoroketones with B2S3 formed in situ. Oxidation with monoperphthalic acid generated the sulfine, the X-ray structure of which revealed a dimer in the crystal lattice. 

Enamines are susceptible to peracid oxidation, presumably through the epoxide, producing the a-hy-droxy ketone after hy lysis. Thus steroidal ketone (88) is converted via the pyrollidino enamine to the a-hydroxy derivative (89) in qiproximately 50% overall yield by treatment of the enamine with MCPBA followed by basic work up. Similar conversion of a steroidal enamide to the a>hydroxy ketone using monoperphthalic acid has been reported. 

Oxidation of 4-methoxypyridazine has been carried out with hydrogen peroxide in acetic acid and a mixture of 4-methoxypyridazine 1-oxide (11%), 2-oxide (8%), and 4(l T)-pyridazinone (2%) was isolated,the last compound resulting from hydrolysis. If the reaction temperature is raised to 100°, in addition to the foregoing three compounds l-methyl-4(l//)-p3Tidazinone is formed in very low yield. Of other alkoxypyridazines to be mentioned, 6-chloro-3,4-dimethoxypyridazine when oxidized with monoperphthalic acid yielded only the 1-oxide in 50% yield. 

Halopyridazines were likewise successfully iV -oxidized. 3-Chloro-pyridazine gives the corresponding 1-oxide with perbenzoic acid, whereas the isomeric 2-oxide is prepared indirectly by adding powdered copper to a diazotized solution of 3-aminopyridazine 2-oxide in hydrochloric acid-. " After earlier reported - failures to prepare 3,6-dichloropyridazine A-oxide from 3,6-dichloropyrid-azine and hydrogen peroxide in acetic acid [6-chloro-3(2/ )-p3nrid-azinone was isolated due to hydrolysis], the desired A-oxide was later obtained in low yield. " The yield of 3,6-dichloropyridazine A-oxide can be improved when using monoperphthalic acid in ethereal solution or perbenzoic acid in chloroform. ... 

Other, more complex halopyridazine A-oxides are known. 5-Amino-3,4- and 4-amino-3,5-dichloropyridazine form the corresponding 1-oxide, but 3,6-dichloro-4-methoxypyridazine is oxidized with monoperphthalic acid in ethereal solution to yield a mixture of the 1-oxide (12%), 2-oxide (5%), and 6-chloro-4-methoxy-3(2A)-pyrid-azinone and 6-chloro-4-methoxy-3(2A)-pyridazinone (up to 7%). Of aminopyridazines, the 3 isomer gives a resin with monoperphthalic acid, while the 2-oxide resulted from oxidation with... 

Oxidation of acetyltropenol with monoperphthalic acid led essentially to the A-oxide (LXIII) (65), while a great excess of the same reactant afforded the appropriate JV-oxide-epoxide (LXIV) (67b). The latter took up 2 moles of hydrogen giving rise to ( ) 3a-acetoxy-6j8-hydroxytropane (LXIa). Hence, the addition of the oxygen atom to the double bond at Cg,7 has taken an ea o-steric course (67b), as expected by virtue of previous experience with similar systems (74). 

Treatment of virosecurinine 108 with monoperphthalic acid gave two nonbasic isomeric products, 123 and 124, in a 1 5.5 ratio. The oxidative reaction may be envisaged to proceed via the A-oxide intermediate 122 which suffers rearrangement analogous to known transformations of A-allyl- and A-benzylamine oxides to 0-allyl and... 

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