Other Oxidation Methods

The epoxidation procedures described here are not general ones they are used in special cases to prepare stereoisomers that are difficult to obtain by other means. 2,4-Disubstituted-6-hydroxymethylphenols have been oxidized with good yields to spirooxirane derivatives with sodium periodate in the case of bulky substituents, for example, when R = R = ferf-butyl (Eq. 47).  

Periodate compounds have been used for the epoxidation of simple olefins too (MIO4, MH4O6, or M2H3IO6 M = Li, Na, K, Rb, Cs, etc.). In alkaline medium, xenon-trioxide epoxidizes alkenes stereoselectively there is no c/s-hydroxylation as when other inorganic oxides are employed.  

Olefins with hindered double bonds may be transformed stereospecifically to oxiranes by treatment with ozone. The epoxidation of propylene has been achieved with alkoxyalkyl-hydroperoxides obtained by the ozonization of olefins in the presence of alcohol.The yield depends on whether the alcohol is a primary, secondary, or tertiary one. The low-temperature (—70°) epoxidation of olefins with a yield of about 30% has been performed with electrophilic intermediates produced in the course of the ozonization of alkynes these intermediates are probably five-membered cyclic trioxides. This epoxidation is almost totally stereospecific. 

Chromic acid oxidation of olefins can rarely be used for the preparation of oxiranes because they occur as intermediates that rapidly undergo further transformation. From an investigation of the mechanism of oxidation of triaryl-substituted olefins, it was concluded that a carbonium ion or cyclic chromate ester is a possible intermediate. Selective epoxidation of compounds containing conjugated double bonds is attainable by means of chromic-acid oxidation (Eq. 48) 535 Exclusively cis product was obtained from a highly substituted octalin with Na2Cr04, KMn04, or ozone (Eq. 49).  

Oxiranes can be prepared by electrochemical oxidation. Regioselective w-epoxidation of polyisoprenoids will take place with excellent yields on sodium bromide-promoted electrochemical oxidation in neutral or basic medium. This has now been described as a general method. Hexafluoropropylene oxiranes have been produced by electrochemical means. The deoxygenation of dioxetane to oxirane with triphenylphosphine has been described (Eq, 50).  

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Nitric acid is also useful as an oxidant for the formation of sulphate from sulphones. Two such methods have been developed, firstly the established AOAC method which involves oxidation with a mixture of nitric acid and bromine221, and secondly the Carius method222. The latter is probably the oldest method used for the determination of sulphones as sulphate. This oxidation procedure involves heating the sulphone with concentrated nitric acid and sodium chloride at 280-300 °C in a sealed tube. The traditional method as described is prone to explosions. This problem may be alleviated by using less nitric acid whilst employing an oxygen atmosphere2 23,224. The Carius method is slower than the other oxidation methods described above but it usually yields the best results. 

Oxidation of the quinine C-9 hydroxy substituent to the ketone is best accomplished using the Woodward3 benzophenone/potassium t-butoxide method, now using toluene. The other oxidation methods investigated (Swern, Jones, ROCI variations) were less effective or limited because of the poor solubility of the substrate. Thermodynamic equilibration of these ketones has also been reported.3... 

Other oxidative methods have recently been reported whereby amines yield enamines either as intermediates [130] or as isolatable chloranil [131], 2,3-dichloronaphtha-l,4-quinone [131], or 2,5-dichloro-3,6-dimethoxybenzo-quinone [132, 133] adducts. Benzoyl peroxide [131] and active manganese dioxide [134] have been reported as effective oxidizing agents in the reactions above. (See Eqs. 49, 50.)... 

Chromic acid oxidation of a variety of indoles has been used as a synthetic route to isatins.117-124 A variety of other oxidative methods... 

Other - Oxidation Methods. Satisfactory titrimetric methods are based on the oxidation of arsenious acid to arsenic acid by means of potassium iodate,3 potassium dichromate,4 potassium permanganate5 and ceric sulphate.6 The last two methods are of importance. 

A very reactive ketone, obtained by Swern oxidation, is condensed in one-pot with MeMgBr. Other oxidation methods lead to the isolation of the ketone hydrate, which fails to react efficiently with Grignard reagents. 

An earlier procedure reported from this laboratory for the isolation of sulfides was based on the selective oxidation of the sulfides to the sulfoxides with photoexcited singlet oxygen followed by silica gel chromatographic separation of the sulfoxides (9). Reduction of the isolated sulfoxides back to the sulfides and a subsequent chromatographic purification resulted in the isolation of the sulfides as a pale yellow oil. However, when the sulfur is in a five-membered ring, the photooxidation may lead to side reactions (22). Therefore, other oxidation methods had to be explored. 

Because of the inertness of some nucleosides towards catalytic oxidation, other oxidative methods have also been examined. Thus, the synthesis of 9-(/3-D-ribofuranosyluronic acid)adenine, involving oxidation of 2, 3 -0-isopropylideneadenosine with potassium permanganate in aqueous alkaline solution, followed by acidic deprotection, has been reported from three laboratories.340-342 The product (ob-... 

Other oxidative methods have also been investigated. Thus, oxidation of the nucleosides at C-5 with chromium trioxide-pyridine,346 chromium trioxide-acetic acid,347 or periodate in aqueous acetone containing ruthenium trichloride,348 to give the corresponding uronic acid derivatives, has also been reported. 

The above discussion has concentrated upon the reagents used, but it is equally of value to comment on the substrate, particularly in reactions for which other oxidation methods have been reported to fail. A good example is the oxidation of the iron-carbonyl complex (31) to the ketone (32 equation 14). The use of dimethyl sulfoxide activated with sulfur trioxide-pyridine complex gave a 70% yield of the product, in contrast to the use of the Pfitzner-Moffatt procedure (dimethyl sulfoxide-DCC) or the chromium... 

MnOi oxidizes allylic and benzylic alcohols to the corresponding aldehydes. Oxidation of primary saturated alcohols wdth Mn02 is also possible but much slower. Therefore it is possible to oxidize an allylic or benzylic alcohol in the presence of an unprotected primary alcohol w ith MnO. The yields of this procedure. strongly depend on the activation grade of MnO. Other oxidation methods are Dess-Martin periodinane, IBX," TPAP or DMSO/QOiCB. ... 

Other oxidative methods have been mendoned, such as the transformation of enamides (63) to a-hydroxylated acyliminium salts (70), via the hemiaminals (69). ... 

An example of the construction of a 1,2-diketone from a 1,2-diol comes from the total synthesis of ( )-cephalotaxine (54) where the Corey-Kim conditions were used to convert diol 52 to diketone 53 in 89% yield while other oxidation methods were reported to have failed to affect this conversion.15 The more accessible ketone was then converted to the enol ether and LAH reduction afforded the racemic natural product 54. 

Oxidation of the above substrates were characterized by short reaction times and efficient conversion to expected products. Over-oxidation of substrates was not observed. Furthermore, the work up procedure was much easier and straightforward than other oxidation methods such as PCC, PDC, or Swem oxidation. The Dess-Martin reagent is also less toxic than the chromium-based oxidizing reagents. 

Another example where DMP reagent worked well while other oxidation methods proved unsuccessful was with the angucycline antibiotic framework.21 Oxidation of the secondary alcohol (46) to the desired ketone (47) adduct proceeded smoothly using DMP. However, compound 47 was found to be labile under other oxidation conditions (Swem, PCC, PDC) causing the epoxide to open and subsequent aromatization of the B ring to occur. 

Other oxidative methods for the preparation of sulphonamides, from sulphur(II)- or sulphur(IV)-containing compounds, have also been reported and these will now be discussed. 

Reaction of 6-methoxy-l-tetralone (30) with methylmagnesium iodide gave the dihydronaphthalene (31) in high yield (Scheme 4). However, the transformation of 31 to the tetralone 33, via perbenzoic acid epoxidation followed by acid workup, was capricious and resulted in low yields. A better route was developed, involving hydroboration (hydrogen peroxide oxidation) to the alcohol 32, followed by Pfitzner-Moffatt oxidation to the tetralone 33 in an overall yield of 61%. Other oxidation methods were tried but with varied and poor results. Alkylation of the tetralone 33 with 3-bromopropyne yielded 34, which underwent hydration [mercury (II) acetate in acetic acid-formic acid] to the diketone (35). The enone (36) obtained by base catalyzed cyclization was ster-eospecifically reduced with lithium aluminum hydride to the allylic alcohol... 

In 2013, AstraZeneca researchers reported an application of copper-catalyzed aerobic dehydrogenative aromatization in the 120 g scale synthesis of AZD8926, a drug candidate for the treatment of central nervous system disorders (Scheme 5.6) [29]. This aerobic dehydrogenation process was determined to be superior for large-scale implementation over other oxidation methods, such as a benzoquinone-mediated oxidation and various protocols using peroxide-based... 

This detection procedure is based on the oxidative dissolution of the Au-NPs bound to DNA into aqueous Au ions followed by their electrochemical sensing. Chemical dissolution of the Au-NP tags has been mainly carried out with a HBr/Br2 solution, this step being followed by accumulation and stripping analysis of the resulting Au[lll) ions. Due to the high toxicity of the HBr/Br2 solution, other oxidation methods have been also employed. 

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