Ozonations secondary alcohols, ozone

Compounds containing susceptible C—H bonds can be oxidized to alcohols. " Nearly always, the C—H bond involved is tertiary, so the product is a tertiary alcohol. This is partly because tertiary C—H bonds are more susceptible to free-radical attack than primary and secondary bonds and partly because the reagents involved would oxidize primary and secondary alcohols further. In the best method, the reagent is ozone and the substrate is absorbed on silica gel. Yields as high as 99% have been... 

This dry ozonation procedure is a general method for hydrox-ylation of tertiary carbon atoms in saturated compounds (Table 1). The substitution reaction occurs with predominant retention of configuration. Thus cis-decalin gives the cis-l-decalol, whereas cis- and frans-l,4-dimethylcyclohexane afford cis- and trans-1,4-dimethylcyclohexanol, respectively. The amount of epimeric alcohol formed in these ozonation reactions is usually less than 1%. The tertiary alcohols may be further oxidized to diols by repeating the ozonation however, the yields in these reactions are poorer. For instance, 1-adamantanol is oxidized to 1,3-adamantane-diol in 43% yield. Secondary alcohols are converted to the corresponding ketone. This method has been employed for the hydroxylation of tertiary positions in saturated acetates and bromides. 

TS-1 is a material that perfectly fits the definition of single-site catalyst discussed in the previous Section. It is an active and selective catalyst in a number of low-temperature oxidation reactions with aqueous H2O2 as the oxidant. Such reactions include phenol hydroxylation [9,17], olefin epoxida-tion [9,10,14,17,40], alkane oxidation [11,17,20], oxidation of ammonia to hydroxylamine [14,17,18], cyclohexanone ammoximation [8,17,18,41], conversion of secondary amines to dialkylhydroxylamines [8,17], and conversion of secondary alcohols to ketones [9,17], (see Fig. 1). Few oxidation reactions with ozone and oxygen as oxidants have been investigated. 

Secondary alcohol 11 is first protected as a silyl ether with TBS chloride, after which the terminal double bond is ozonized. The resulting methyl ketone is subsequently converted stereoselectively with a Homer-Wadswonh-Emnions reaction21 into olefin 13. This reaction sequence leads to tram selectivity in the formation of the terminal double bond in 13. 

Few synthetically useful examples of the oxidation of ethers by oxygen or ozone have been publish-ed.7 96 Q0 In 1978, Ourisson and coworkers reported that ozonization of the natural product cedrane oxide (43) on silica gel at -78 °C led to the formation of the corresponding lactone (44) in 30% yield (equation 32).A small amount of the tertiary alcohol (45) was also produced. Later, in the course of a chiral total synthesis of compactin, Hirama examined the ozonolysis of the alkene (46 equation 33). ° Under carefully controlled conditions, selective ozonolysis of the double bond could be achieved in 88% yield. However, when excess ozone was employed, significant amounts of the benzoate (47) were obtained, even at -78 C. In subsequent studies, benzyl ethers of primary and secondary alcohols,and carbohydrates were oxidized to the corresponding benzoates in excellent yields. Surprisingly, no further synthetic rqrplications of this reaction have been reported. 

The only hydroxyl substitution product of ethene which is possible, and the only one known, has the constitution represented by the above formula and is plainly a secondary alcohol as it contains the secondary group ( = CH—OH). It may be produced by the oxidation of ethyl ether by means of chromic acid, CrOa, ozone, or even by air when in the sunlight. 

Hydroxylation of tertiary carbon atoms on silica gel. Israeli chemists have devised an experimental method for hydroxylation of saturated hydrocarbons at tertiary positions by ozone adsorbed on silica gel in this way concentrations of ozone of 4.5% by weight at -78 can be attained. First the hydrocarbon is impregnated on the silica gel and then ozone is passed through at -78° until the silica gel is saturated. After the silica gel has warmed to 20, the product is eluted. Tertiary alcohols can be obtained in this way in high yield with almost complete retention of configuration. The secondary alcohol adamantane-2-ol was oxidized to the ketone by this method. 

Miscellaneous Ozonations. Ozonation offers a simple neutral alternative for oxidation of secondary alcohols to ketones (eq 30). ... 

Several references have appeared on the use of solid-phase oxidants. Solid potassium permanganate-copper sulphate mixtures oxidize secondary alcohols to ketones in high yield, and pyridinium chromate or chromic acid on silica gel are described as convenient off-the-shelf reagents for oxidation of both primary and secondary alcohols. Anhydrous chromium trioxide-celite effects similar transformations only when ether is present as co-solvent. An excellent review, with over 400 references, on supported oxidants covers the use of silver carbonate-celite, chromium trioxide-pyridine-celite, ozone-silica, chromyl chloride-silica, chromium trioxide-graphite, manganese dioxide-carbon, and potassium permanganate-molecular sieve. 

Ozone reacts slowly with saturated hydrocarbons usually to give alcohols.92 93 The reactivity of alkanes toward ozone is several orders of magnitude less than that of alkenes. Oxidation of saturated hydrocarbons takes place preferentially at the tertiary carbon. In liquid-phase ozonation94 the order of reactivity of the primary, secondary and tertiary C—H bonds is 1 13 110. The formation of tertiary alcohols occurs with high degree (60-94%) of stereoselectivity.94-96... 

The results of dry ozonation, namely, regioselectivities and stereoselectivities, are very similar to those in superacidic liquid-phase ozonation. Tertiary C—H bonds in strained systems such as norbomane are inert to dry ozonation.93 Such compounds are oxidized at the secondary carbon to yield a mixture of alcohols and ketones.93 104 Similarly, substituted cyclopropanes exhibit a general preference for the oxidation of the secondary C—H bond in the a-position to the ring 104... 

The rate constants for oxidation of a series of cycloalkenes with ozone have been determined using a relative rate method. The effect of methyl substitution on the oxidation of cycloalkenes and formation of secondary organic aerosols has been analysed.155 Butadiene, styrene, cyclohexene, allyl acetate, methyl methacrylate, and allyl alcohol were epoxidized in a gas-phase reaction with ozone in the absence of a catalyst. With the exception of allyl alcohol, the yield of the corresponding epoxide ranged from 88 to 97%.156 Kinetic control of distereoselection in ozonolytic lactonization has been (g) reported in the reaction of prochiral alkenes.157... 

The alkylmercuric halides, on the other hand, reacted slowly enough with ozone to permit kinetic studies. While attempts were made to monitor ozone uptake during the first part of the reactions, it was clear that the primary and secondary alkylmercuric halides formed many ozone-reactive intermediates soon after the introduction of 03/02. Hence, in the case of isopropylmercuric chloride (Reaction 10, Table II), isopropyl alcohol was formed and had begun to react appreciably with ozone well before the mercurial had half reacted. By comparison, the reaction of tert-butylmercuric chloride was considerably faster than the primary and secondary alkylmercuric halides (Table III). In this case an excellent 1 1 correlation with ozone was noted throughout the majority of the reaction. Only at the end of this reaction, when other organic products began to appear (NMR), did the reaction mixture demand more than one equivalent of ozone. 

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. 

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