Oxidation Of Alcohols To Aldehydes And Ketones Pdf
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Oxidation of Alcohols to Aldehydes and Ketones
Platinum Metals Rev. The oxidations of alcohols to aldehydes and ketones are vital reactions in synthetic organic chemistry, and high selectivity and mild conditions are important prerequisites for ease of product work-up and lower cost.
Currently, many of the best oxidants for these conversions contain high valent ruthenium, with ruthenium acting as a catalyst for these reactions. It is important to have detailed knowledge and understanding of the mechanisms of the oxidation reactions and the factors that influence them, as only by completely understanding how these processes work will it be possible to design better or optimal catalysts.
In this paper, the more viable oxidants currently available are reported and some investigations into the mechanisms of the reactions and factors affecting them are discussed. As the catalytic conversions of primary alcohols into aldehydes and of secondary alcohols into ketones are essential for the preparation of many key synthetic intermediates in organic chemistry, there is currently much activity being undertaken in the search for catalytic systems which can perform these operations.
In particular, the reaction shown in Equation i does not usually stop at the formation of the aldehyde and over-oxidation to the carboxylic acid often occurs. However, there are various drawbacks to using these reagents; for instance, they are either rather aggressive, need relatively high or low temperatures, give unwanted and difficult to remove by-products, are difficult to separate from the product after the reaction is over, require acidic conditions which limit the choice of substrate, or, they do not give complete conversions in all applications.
Thus, there is clearly a need to prepare milder and more selective oxidants with higher rates of conversion. Several oxidative systems which at least partially fit the above criteria have recently been reported, and many of these contain or are based on ruthenium. The chemistry of high-oxidation-state ruthenium is less well developed than that of, for example, osmium 4 or rhenium 5.
Specifically, reaction mechanisms and the factors which influence the performance of various oxidants are poorly understood. It is clear, however, that several of the high valent oxo ruthenium compounds made so far are active in transforming both primary alcohols into aldehydes and secondary alcohols into ketones.
Many of the known ruthenium-containing oxidants are also tolerant of other sensitive functional groups in organic molecules. It would be desirable to have a very selective catalytic oxidant, which would not attack other potentially reactive groups, such as double bonds, halides, epoxides, esters, amides, or protecting groups, such as silyl or benzoate, amongst many others.
This ideal catalytic oxidant should also be easy to recycle. Designing such systems remains a challenge, although significant progress is being made.
Other factors which influence the acceptance of new catalysts include the ease of operation and the ease of synthetically or commercially producing the catalyst. The only known well-defined stable ruthenium VIII compound is ruthenium tetroxide, RuO 4 , which is frequently far too vigorous an oxidant, as it attacks many functional groups, such as double bonds, and often forms carboxylic acids. Consequently, research has focused on ruthenium compounds in slightly lower oxidation states.
These compounds are obtained in moderate yield, and the first two are made by utilising RuO 4 as a gas, and require appropriate manipulative and experimental skills. The cis -oxo arrangement is unusual because of the considerable electronic stabilisation associated with the trans -dioxo, d 2 , configuration The acetic acid derivative was shown to be a good catalytic oxidant with MNO as co-oxidant. No effects were observed on varying the length of the alkyl chain R.
Fluorinated compounds often display very different properties to their protonated analogues, probably because fluorine and hydrogen, although being of similar size, have very different electronegativities. However, we found that apart from significantly affecting the synthetic yields of the oxidants, no effect on the oxidations was observed.
The most well-known ruthenium oxide catalyst, tetrapropylammonium perruthenate TPAP and its sister tetrabutylammonium perruthenate TBAP are effective in many selective organic transformations of the type summarised in Equations i and ii using MNO as the co-oxidant.
A comprehensive review has recently been published TPAP is also almost the only ruthenium oxidation catalyst to have been studied kinetically. TPAP is a three-electron oxidant overall, but it is believed that the alcohol oxidation step is of the two-electron type.
The fact that TPAP will oxidise cyclobutanol to cyclobutanone suggests that a one-electron oxidation process is not involved, since a one-electron oxidant would cleave cyclobutanol to acyclic products Other reported ruthenium VI oxidants will usually convert primary alcohols into acids, although internal alcohols will still be converted into ketones.
The yields range from moderate to good, depending on the substrate. Conversions are carried out in basic aqueous media, as ruthenate and per-ruthenate are unstable at lower pH.
This limits the reagents to substrates which are stable at high pH. Even ruthenium tetroxide, RuO 4 , has been reported as oxidising secondary alcohols to ketones 1 , However, both RuO 4 and sodium ruthenate are known to attack double bonds, although sodium ruthenate will do so only if high temperatures or longer reaction times are employed 18 , The compound [RuO 2 tetramesitylporphyrinato ] has been reported to oxidise alkyl alcohols to ketones, although its primary application is as an alkane oxidant A catalyst should be unchanged after a reaction.
Instead, the ruthenium oxo compounds are really primary oxidants, that is, they directly oxidise the substrate. The co-oxidant is the secondary oxidant — which regenerates the primary oxidant. A few of the commonly used secondary oxidants do react directly with alcohols for example, MNO with primary alcohols , but the conversions are generally low. Alcohol oxidations with transition metal oxo reagents probably mainly involve the same basic transformation as shown in Figure 1 , involving an ester intermediate.
For all of the catalytic oxidants mentioned above, primary alcohols react more rapidly than secondary alcohols, probably due to steric hindrance of secondary alcohols. It is generally thought that the reagents, reported above, which effectively catalyse the reaction in Equation i , do so because of the presence of molecular sieves in the reaction medium.
The molecular sieves efficiently remove water formed in the reaction and present as water of crystallisation of MNO. It is known that an aldehyde hydrate is necessary for the reaction in Equation iii to occur. The mechanism for the oxidation by chromic acid of an aldehyde is shown in Figure 2 22 and ruthenium oxide oxidations are presumed to be similar.
Some preliminary results from our laboratory, however, imply that the presence of water in the reaction medium does not necessarily mean that the reaction in Equation iii will proceed. The mechanism for the chromic acid catalysed oxidation of an aldehyde. This is similar to oxidations using ruthenium oxide. The stoichiometric oxidations of propanol with the sodium salts of ruthenate and perruthenate have been investigated kinetically and mechanistically Both reactions are believed to proceed via free radical-like transition states, although the subsequent steps differ.
The proposed mechanism is shown in Figure 3. For the stoichiometric oxidation of propanol with perruthenate, as shown in Figure 3 , it is thought likely that because the HRuO 4 ion is less reactive, the product would move out of the solvent cage before further reaction. These proposed mechanisms fit theoretical predictions For the co-oxidants hexacyanoferrate III , diperiodatocuprate III and periodate, the data imply that a complex is formed, as for the stoichiometric oxidation, Figure 3.
The role of the co-oxidant is only to regenerate Ru VI. The exception is when the co-oxidant is chloramine-T. In this case, the co-oxidant appears to react directly with the Ru VI ion, see Figure 5.
This active complex then reacts rapidly with propanol to form acetone It seems very likely, however, that these mechanisms are only valid in aqueous base and the mechanisms are probably different in non-aqueous media, as shown, for example, by the different reaction products obtained in the oxidation of cyclobutanol with TPAP and basic perruthenate.
Proposed mechanism for the activation of ruthenate by chloramine-T, prior to the oxidation of propanol. However, the MNO co-oxidant is expensive, an irritant to the eyes, the respiratory system and the skin, and its final product, 4-methyl morpholine, is corrosive and causes burns to the skin, the eyes and mucous layers in the nasal tract.
Apart from this, even the best known catalysts do not give quantitative or almost-quantitative transformations in all apparently suitable systems and, as such, there is a great need to develop more effective and more selective catalysts with higher turnovers. In general, the activity of catalysts is affected by the steric bulk for instance, cone angles of the attached groups and the electron density on the metal.
The significant effect of the groups attached to the Ru VI centre is demonstrated by the examples of Ru VI O 2 moieties bonded to porphyrins or to other bulky tetradentate ligands: many of these compounds are effective catalysts for the epoxidation of olefins None of the other ruthenium VI oxo catalysts, referred to above, can perform this reaction.
However, even Ru VI O 2 compounds, with bulky bidentate ligands, can catalyse epoxidation reactions As part of a project to develop commercially viable catalysts for the oxidation of alcohols, we are interested in determining how various substituents affect the chemistry of ruthenium VI oxo compounds. One potential route would involve the synthesis of organometallic ruthenium VI oxo compounds. The possibility of being able to vary and fine-tune a wide range of alkyl or aryl substituents should offer much information on these systems and facilitate the design of highly specific catalysts.
However, only a few mono-oxo ruthenium VI organometallic compounds are known 29 and ruthenium VI organometallic di-oxo compounds have so far proved to be totally elusive. Alternatively, one can study the effects of substituents in inorganic ruthenium oxo compounds. This latter approach has the advantage that routes to discreet, fully characterisable compounds of this type are already available. This series was chosen because we thought that substituents on a flat aromatic ring, for which Hammett substituent constants were available, should show easily quantifiable electronic effects on the ruthenium centre.
As can be seen from Figure 6 , substitution at either the 3- or 4-position of the pyridine ring should have a significant effect on the charge on the pyridine nitrogen and consequently on the net charge on the ruthenium centre.
Localised relative charges on a 3-Br-pyridine and b 4-Br-pyridine and the resulting relative charge distribution in the complexes they constitute c and d , respectively. Similarly, the nature of the substituent Y either electron pushing or electron withdrawing should affect the charge on the pyridine nitrogen and hence on the ruthenium centre.
This is confirmed by examining the IR spectra of these compounds. Since these values are due to an inductive effect, one would expect the inductive effect to increase with decreasing distance between the substituent, Y, and the ruthenium centre. This is observed, with the slope of the graph for the 3-substituted compounds being much steeper than for the 4-substituted compounds. All runs were repeated at least three times and are reproducible m — medium.
The Table shows values for stoichiometric oxidations of 1-hexanol to hexanal by Y O 2 Cl 2 Ru with a range of co-catalysts. This implies that electron density on the metal has no significant effect on these compounds as oxidants. While most of the above compounds are mediocre oxidants, the performance of [RuO 2 Cl 2 4-Br-py 2 ] is exceptional and so is that of [RuO 2 Cl 2 3-Br-py 2 ], to a lesser extent.
Both of these are far superior oxidants to any of the other compounds in this series. The 4-Br-pyridine derivative gives especially high rates of conversion with reasonable turnovers. We are at present investigating this clear ligand effect.
One of the great disadvantages of many homogeneous catalytic systems is the problem of separating the product from the catalyst.
For this reason heterogeneous catalysts remain very popular, as the catalyst can simply be filtered off and reused. One way of attempting to combine the advantages of homogeneous and heterogeneous catalysts is by bonding soluble catalysts to insoluble supports, although these have yet to attain a large scale industrial breakthrough We have supported ruthenate on poly- 4-vinylpyridine and on zeolite-Y.
Both these supported catalysts appear to be very selective in the oxidations referred to in Equations i and ii , with a wide range of co-oxidants at room temperature The catalysts can be filtered off and reused. We are currently investigating both the structures and the versatility of these catalysts. A ruthenium hydrotalcite heterogeneous competitor has recently been reported This catalyst is reported to oxidise primary and secondary alcohols into aldehydes and ketones, respectively, in high yields with high selectivity.
The use of oxygen as co-oxidant, as in the system mentioned above, is very advantageous from an environmental point of view.
The outcome of the oxidation of an alcohol depends on the type of oxidizing agent used and on the substituents at the carbon atom bearing the OH group. Selective oxidation of primary alcohols to aldehydes is the most difficult preparation to be carried out. In most cases, further oxidation to carboxylic acid is being observed even under mild conditions and the use of only one equivalent of oxidizing agent. Since the oxidation of primary alcohols to aldehydes is a synthetically important reaction, many attemps have been made to develop reagents for just this purpose. Unfortunately, no generally applicable method is available; however many different ones have been used.
Platinum Metals Rev. The oxidations of alcohols to aldehydes and ketones are vital reactions in synthetic organic chemistry, and high selectivity and mild conditions are important prerequisites for ease of product work-up and lower cost. Currently, many of the best oxidants for these conversions contain high valent ruthenium, with ruthenium acting as a catalyst for these reactions.
Intramolecular Reactions of Alcohols and Ethers. Many oxidants work by attaching a good leaving group to oxygen, which is followed by elimination. When I was learning organic chemistry I remember the reagents for oxidation reactions completely coming out of left field. Hold on. Where did these reagents come from?
The present invention provides a continuous process for the oxidation of alcohols with the aid of nitroxyl compounds as catalysts in multiphase systems. The oxidation of alcohols to aldehydes or ketones is an important transformation in organic chemistry, since compounds having a high reaction potential are formed from readily available alcohols. Such transformations are therefore of great importance in industrial processes. Catalytic processes are particularly advantageous. A process frequently employed in industry is the gas-phase dehydrogenation of alcohols. However, only volatile compounds can be used in this process.