Oxidation of Alcohols

12 Key excerpts on "Oxidation of Alcohols"

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  Experimental Organic Chemistry

  A Miniscale & Microscale Approach

  • John Gilbert, Stephen Martin(Authors)
  • 2015(Publication Date)
  • Cengage Learning EMEA

    (Publisher)

  585 C H A P T E R Oxidation of Alcohols and Carbonyl Compounds In this and the following chapter, we’ll explore oxidation and reduction reactions in organic chemistry. Such reactions are extremely important as they are commonly used to convert one functional group into another during the course of prepar-ing more complex materials from simpler ones. In the simplest sense, oxidation in organic chemistry involves increasing the number of carbon-oxygen bonds. For example, the complete combustion of hydrocarbons or other organic com-pounds to produce carbon dioxide, water, and heat is an oxidation, but because such oxidations destroy the organic molecule, they are not useful in synthesis. Hence, in the experiments that follow, we’ll explore the controlled oxidations of alcohols and aldehydes to give carbonyl compounds and carboxylic acids, respectively, as these transformations are widely used in contemporary synthetic organic chemistry. 16.1 I N T R O D U C T I O N Oxidation, often represented by the symbol [O], is a fundamental type of reaction in chemistry and is the opposite of reduction. The general concept of oxidation is typically introduced in beginning chemistry courses as an electron transfer pro-cess involving a loss of electrons from an ion or a neutral atom. Such definitions are difficult to apply to reactions in organic chemistry, however, as carbon forms covalent bonds and does not normally lose electrons. Nevertheless, oxidations of organic compounds usually do involve a loss of electron density at carbon as a con-sequence of forming a new bond between a carbon atom and a more electronega-tive atom such as nitrogen, oxygen, or a halogen. Reactions that result in breaking carbon-hydrogen bonds are also oxidations. Oxidations are frequently used in organic chemistry to effect functional group transformations.

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  Reaction Mechanisms in Organic Synthesis

  • Rakesh Kumar Parashar(Author)
  • 2013(Publication Date)
  • Wiley-Blackwell

    (Publisher)

  Chapter 7

  Oxidation

  7.1 Oxidation of Alcohols

  Oxidation of Alcohols to aldehydes or ketones is one of the most useful transformations in organic chemistry. Simple 1°- and 2°-alcohols in the gaseous state lose hydrogen (dehydrogenation reaction) when exposed to a hot copper surface. However, in solution phase alcohol oxidations are carried out using reactions in which the hydroxyl hydrogen is replaced by an atom or group that is readily eliminated together with the α-hydrogen. The decomposition of 1°- and 2°-alkyl hypochlorites is an example of such a reaction.

  In a similar manner, toluene-p -sulfonate derivative of alcohols on nucleophilic displacement with trimethylamine N -oxide followed by treatment with a base gives the carbonyl compound and trimethylamine.

  7.1.1 Chromium(VI)

  The most common reagent for the oxidation of 1°- and 2°-alcohols is chromic acid (H2 CrO4 ). It is difficult to stop the reaction at the aldehyde stage; thus, primary alcohols are oxidized to carboxylic acids. In some cases, good yield of an aldehyde can be obtained by removing the aldehyde from the reaction mixture.

  However, the secondary alcohols give ketones.

  In aqueous medium, chromium trioxide (CrO3 ) exists in equilibrium with several Cr(VI) species such as H2 CrO4 , Cr2 O7 2– , H2 Cr2 O7 , H2 Cr2 O7 − , CrO4 2− and HCrO4 − . The dominant form of Cr(VI) species formed in the aqueous solution depends on the pH value, solvent and concentration. At high dilution, dichromate anion (Cr2 O7 2− ) is the major species.

  At high concentration, (CrO3 )n and chromic acid (H2 CrO4 ) are the main species. As alcohol is oxidized to carbonyl compound, Cr(VI) is reduced to Cr(III). However, the detail mechanism shows that Cr(V) and Cr(IV) species are also involved in the Oxidation of Alcohols. The Cr(VI) species are usually HCrO4 − and CrO3 and the Cr(IV) is usually HCrO3 −

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  Liquid Phase Oxidation

  • C.H. Bamford, R.G. Compton, C.F.H. Tipper†(Authors)
  • 1980(Publication Date)
  • Elsevier Science

    (Publisher)

  Chapter 3 The Oxidation of Alcohols, Ketones, Ethers, Esters and Acids in Solution E.T. DENISOV 1. Introduction Alcohols, ketones, and acids are formed as intermediates in the liquid phase oxidation of hydrocarbons [l] and are subject to further conver- sions. Therefore, investigation of the mechanisms of such conversions is necessary for the correct understanding of hydrocarbon oxidation. More- over, the Oxidation of Alcohols and ketones is of scientific interest proper. The role of polar media and hydrogen bonding in chain oxidation is studied, particularly for alcohols and ketones. Alcohols are very con- venient for the investigation of ionic oxidation reactions. The oxidation of certain alcohols is of interest for technology. For example, acetic acid and ethyl acetate may be produced by the oxidation of ethanol, and acetone and hydrogen peroxide by the oxidation of 2-propanol. 2. Oxidation of Alcohols 2.1 THE KINETICS AND PRODUCTS OF ALCOHOL OXIDATION 2.1.1 Primary alcohols Oxidation of methanol in the liquid phase is slow. At 81-145°C with azodi-isobutyronitrile and t-butyl peroxide as initiators, the oxidation products are formaldehyde, formic acid, hydrogen peroxide, and methyl formate [ 21. The oxidation of ethanol was studied in detail by Zaikov et al. [3-71. The main products of the oxidation in a steel autoclave under a pressure of 50-95 atm at 145-230°C are acetic acid and ethyl acetate with hydrogen peroxide and acetaldehyde as intermediates. Formic acid and methyl formate are produced in small amounts. The oxidation of ethanol proceeds with autocatalysis. Acetaldehyde is oxidized not only to acetic acid but also to ethyl acetate by disproportionation [8] 2 CH3CHO = CH3COOCHZCH3 Addition of acetaldehyde to ethanol at the start of the oxidation acceler- ates the reaction, but, at a high degree of oxidation, it is retarded by the inhibiting action of resins formed from acetaldehyde. The sequence of References p p . 195-203

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  Science of Synthesis: Knowledge Updates 2021/3

  • P. A. Clarke, J. A. Joule, S. P. Marsden, P. A. Clarke, J. A. Joule, S. P. Marsden(Authors)
  • 2021(Publication Date)
  • Thieme

    (Publisher)

  [32–37] This approach, however, has so far not found widespread application. for references see p 452 434 Science of Synthesis 3.3 Oxidation of Alcohols, Aldehydes, and Carboxylic Acids 3.3. 4.3 Oxidation of Primary Alcohols Just like in preparative organic synthesis, the Oxidation of Alcohols is a central theme of biocatalysis. [38–40] Oxidation of simple primary alcohols represents a standard reaction during the characterization of novel or engineered alcohol dehydrogenases [41–43] or alco-hol oxidases. [44–52] A broad range of alcohol dehydrogenases and alcohol oxidases are now at hand (many of them commercially) for use in this transformation. This section first describes methods for the selective transformation of primary alcohols into alde-hydes. Subsequently, “through oxidation” into the corresponding carboxylate (deriva-tives) is discussed. 3.3. 4.3.1 Oxidation to Aldehydes As mentioned in the previous sections, alcohol dehydrogenases and alcohol oxidases rep-resent the preferred catalysts for the Oxidation of Alcohols. In both cases, the oxidation mechanism entails the abstraction of a hydride from the carbon atom to be oxidized. As the aldehyde proton is not abstractable as a hydride, alcohol dehydrogenase and alcohol oxidase catalyzed oxidations of primary alcohols are generally highly selective for the al-dehyde product; this is particularly true if (partially) purified enzymes are used. The situa-tion may change if whole-cell biocatalyst formulations are used, as in these cases endoge-nous aldehyde dehydrogenases (catalyzing the oxidation of aldehydes to acids) may be present. If “through oxidation” to the carboxylic acid is not desired, the application of a hydrophobic organic phase may solve the issue (and can avoid the need for tedious purifi-cation of the alcohol dehydrogenase or alcohol oxidase).

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  Biocatalysis in Organic Synthesis

  The Retrosynthesis Approach

  • Nicholas J Turner, Luke Humphreys(Authors)
  • 2018(Publication Date)
  • Royal Society of Chemistry

    (Publisher)

  Figure 6.26 .

  Figure 6.26 Selected methods for the chemical Oxidation of Alcohols to ketones.

  Despite many useful synthetic methods, the Oxidation of Alcohols often uses metal catalysts that need to be disposed of at the end of the reaction or conditions that may be unsuitable for more sensitive functional groups. This in turn may require the use of protecting groups, which adds extra steps to a synthesis. It can also be difficult to stop the oxidation at one level above the alcohol, with over-oxidation to give carboxylic acids or esters often observed. As a complementary technology, the Oxidation of Alcohols using enzymes offers the advantage of mild reaction conditions and high selectivity. This could be regioselective oxidation of a polyol substrate or selective oxidation of one enantiomer of a racemate. Each of the following sections details a family of enzymes that is capable of oxidising alcohols to aldehydes and ketones.

  6.4.1 Oxidation of Alcohols Using Ketoreductases

  As we saw in Chapter 5, ketoreductase enzymes are typically used to catalyse the reduction of ketones and aldehydes to the corresponding alcohols. We mentioned in Chapter 5 that these enzymes are also capable of catalysing the reverse process, the oxidation of an alcohol to the ketone or aldehyde. Due to this reactivity, these enzymes are also known as alcohol dehydrogenases (ADHs). These are the same enzymes and the names are used somewhat interchangeably, so remember that when you see ADH, it is the same as Kred and vice versa . The use of ketoreductases for the Oxidation of Alcohols has been less studied than the reduction of ketones, in part due to the fact that the oxidation of secondary alcohols removes a chiral centre rather than creating one in the reduction direction. As the ADH name suggests, the Oxidation of Alcohols using Kreds is a dehydrogenation reaction with the nicotinamide co-factor this time acting as a hydride acceptor rather than a hydride donor. As shown in Figure 6.27

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  Oxidation and Antioxidants in Organic Chemistry and Biology

  • Evgeny T. Denisov, Igor B. Afanas'ev(Authors)
  • 2005(Publication Date)
  • CRC Press

    (Publisher)

  7 Oxidation of Alcohols and Ethers 7.1 Oxidation of Alcohols 7.1.1 I NTRODUCTION The hydroxyl group of alcohol weakens the a -C H bond. Therefore, free radicals attack preferentially the a -C H bonds of the secondary and primary alcohols. The values of bond dissociation energy (BDE) of C H bonds in alcohols are presented in Table 7.1. The BDE values of C H bonds of the parent hydrocarbons are also presented. It is seen from comparison that the hydroxyl group weakens BDE of the C H bond by 23.4 kJ mol 1 for aliphatic alcohols and by 8.0 kJ mol 1 for allyl and benzyl alcohols. Alcohols are polar compounds. They have dipole moment and this influences their reactivity in reactions with polar peroxyl radicals (see later). The values of the dipole moments m for selected alcohols are given below [6]. Alcohol MeOH EtOH Me 2 CHOH PhCH 2 OH CH 2 ¼¼ CHCH 2 OH m (Debye) 1.70 1.69 1.58 1.71 1.60 Alcohols having a hydroxyl group form hydrogen bonds with polar compounds such as hydroperoxides, ketones, etc. This causes some peculiarities of the oxidation kinetics of alcohols. On the other hand, alcohols are weak acids and dissociate as acids in polar alcoholic media. Protonated alcohol molecules induce several heterolytic and homolytic reactions complicating the mechanism of oxidation and composition of the products. The hydroxyl group of the alkyl radical formed from alcohol complicates the mechanism of alcohol oxidation also. One of the peculiarities of alcohol oxidation is the production of hydrogen peroxide as a primary intermediate, and another is a high reducing activity of peroxyl radicals formed from oxidized alcohols. The chemistry and kinetics of alcohol oxidation are discussed in detail in monographs [7–10]. 7.1.2 C HAIN M ECHANISM OF A LCOHOL O XIDATION Alcohols, like hydrocarbons, are oxidized by the chain mechanism. The composition of the molecular products of oxidation indicates that oxidation involves first the alcohol group and the neighboring C H bond.

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  Organic Chemistry

  • T. W. Graham Solomons, Craig B. Fryhle, Scott A. Snyder(Authors)
  • 2022(Publication Date)
  • Wiley

    (Publisher)

  Thermophilic bacteria, growing in hot springs like these at Yellowstone National Park, produce heat-stable enzymes called extremozymes that have proven useful for a variety of chemical processes. Simon Terry/Science Source (R)-Alpine-Borane B Nicotinamide ring of NADH, showing the pro-R and pro-S hydrogens H S H R R—N H 2 N C O 12.4 Oxidation of Alcohols 553 12.4 Oxidation of Alcohols Primary alcohols can be oxidized to aldehydes, and aldehydes can be oxidized to carboxylic acids: H O [O] R OH O [O] R H OH R H 1° Alcohol Aldehyde Carboxylic acid Secondary alcohols can be oxidized to ketones: R′ O [O] R R′ OH R H 2° Alcohol Ketone Tertiary alcohols cannot be oxidized to carbonyl compounds. [O] X R″ OH R R′ 3° Alcohol These examples have one aspect in common: when an oxidation takes place, a hydrogen atom is lost from the alcohol or aldehyde carbon. A tertiary alcohol has no hydrogen on the alcohol carbon, and thus it cannot be oxidized in this way. 12.4A A Common Mechanistic Theme Oxidations of primary and secondary alcohols, like those above, follow a common mecha- nistic path when certain reagents are used. These reagents, some of which we will discuss below, temporarily install a leaving group on the hydroxyl oxygen during the reaction. Loss of a hydrogen from the hydroxyl carbon and departure of the leaving group from the oxygen result in an elimination that forms the C O π bond. Formation of the carbonyl double bond essentially occurs in a fashion analogous to formation of an alkene double bond by an elimi- nation reaction. The general pathway is shown here. Alcohol Oxidation by Elimination –HA A 1° or 2° alcohol reacts with a reagent that installs a leaving group (LG) on the alcohol oxygen atom. In an elimination step, a base removes a hydrogen from the alcohol carbon, the π bond forms, and the leaving group departs, resulting in the oxidized product.

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  General, Organic, and Biological Chemistry

  An Integrated Approach

  • Kenneth W. Raymond(Author)
  • 2012(Publication Date)
  • Wiley

    (Publisher)

  SAMPLE PROBLEM 9.4 Oxidizing alcohols Draw the product expected from each reaction. a. b. CH 3 CH 2 O ƒ C H HCH 2 CH 2 CH 3 K 2 Cr 2 O 7 CH 3 CH 2 CH 2 OH K 2 Cr 2 O 7 342 CHAPTER 9 Organic Reactions 2—Alcohols, Ethers, Aldehydes, and Ketones STRATEGY The place to begin is determining which type of alcohol (1°, 2°, or 3°) appears in each reaction. Primary alcohols are oxidized to aldehydes, which are immediately oxidized to carboxylic acids. Secondary alcohols are oxidized to ketones and tertiary alcohols are not oxidized. SOLUTION a. b. CH 3 CH 2 O ‘ CCH 2 CH 2 CH 3 CH 3 CH 2 O ‘ C ¬OH PRACTICE PROBLEM 9.4 In Chapter 14 we will study the citric acid cycle, a series of reactions involved in making compounds that can be used in a separate process to manufacture an energy-rich com- pound called ATP. A reaction early in the citric acid cycle involves the oxidation of an alcohol. Of the two reactants shown below (each appears somewhere in the cycle), which has an alcohol group that can be oxidized? Citrate HO¬ C ƒ ƒ ƒ C ƒ ƒ ƒ C H 2 ¬ H 2 O ‘ C O ‘ C O ‘ C ¬O - ¬O - ¬O - Isocitrate H¬ HO¬ C ƒ ƒ ƒ C ƒ ƒ ƒ C H 2 ¬ H O ‘ C O ‘ C O ‘ C ¬O - ¬O - ¬O - Nicotinamide adenine dinucleotide (NAD + ), an oxidizing agent used by living things, works in conjunction with certain enzymes that catalyze the oxidation of alco- hols. NAD + assists in the oxidation of an alcohol molecule by accepting one of its hydrogen atoms, becoming NADH in the process (Figure 9.5). The second hydrogen atom released from the alcohol becomes H + . For example, the first step in the metabo- lism of the ethanol present in beer, wine, and other alcoholic beverages takes place in the liver and is catalyzed by an NAD + -requiring enzyme (Health Link: Aldehyde Dehydrogenase).

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  Organic Chemistry

  • T. W. Graham Solomons, Craig B. Fryhle, Scott A. Snyder(Authors)
  • 2016(Publication Date)
  • Wiley

    (Publisher)

  A tertiary alcohol has no hydrogen on the alcohol carbon, and thus it cannot be oxidized in this way. 12.4A A Common Mechanistic Theme Oxidations of primary and secondary alcohols, like those above, follow a common mecha- nistic path when certain reagents are used. These reagents, some of which we will discuss below, temporarily install a leaving group on the hydroxyl oxygen during the reaction. Loss of a hydrogen from the hydroxyl carbon and departure of the leaving group from the oxygen result in an elimination that forms the C = O π bond. Formation of the carbonyl double bond essentially occurs in a fashion analogous to formation of an alkene double bond by an elimination reaction. The general pathway is shown here. Alcohol Oxidation by Elimination –HA A 1° or 2° alcohol reacts with a reagent that installs a leaving group (LG) on the alcohol oxygen atom. In an elimination step, a base removes a hydrogen from the alcohol carbon, the π bond forms, and the leaving group departs, resulting in the oxidized product. C O H LG A C O H H LG B: C O B H + LG + C O Primary and secondary alcohols have the required hydrogen atom at the alcohol carbon. They also have the hydroxyl hydrogen that is lost when the leaving group is installed, as shown above. 12.4 Oxidation of Alcohols 543 You might ask how an aldehyde can be oxidized by this mechanism, since an aldehyde does not contain a hydroxyl group to participate as shown above. The answer lies in whether the aldehyde reaction mixture includes water or not. In the presence of water, an aldehyde can form an aldehyde hydrate (by an addition reaction that we shall study in Chapter 16). [O] Aldehyde Aldehyde hydrate Carboxylic acid C O R H + H 2 O C O R HO C O HO H R H The carbon of an aldehyde hydrate has both a hydroxyl group and the hydrogen atom required for elimination; thus when water is present, an aldehyde can be oxidized by the mechanism shown above.

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  Modern Gold Catalyzed Synthesis

  • A. Stephen K. Hashmi, F. Dean Toste(Authors)
  • 2012(Publication Date)
  • Wiley-VCH

    (Publisher)

  Chapter 14 Oxidation of Alcohols and Carbohydrates Cristina Della Pina, Ermelinda Falletta, and Michele Rossi

  14.1 Introduction

  One of the most exciting and unforeseen developments in chemical research in recent decades has been the application of gold in catalysis. In fact, this metal has become an important tool in organic synthesis several years after the first reports on ethyne hydrochlorination and CO oxidation and it is now widely employed in many fundamental catalytic processes such as oxidation, hydrogenation, and coupling reactions [1–4]. New applications of gold have also been proposed for commercial syntheses by academic and industrial researchers [5–8]. An ultimate project concerns an inorganic reaction, that is, the direct synthesis of hydrogen peroxide, which has been developed by the impressive work of Hutchings' group [1–3].

  A strategic application of gold is the selective transformation of renewable biological resources, a task of key importance for balancing the CO2 cycle. In particular, valuable oxygenated compounds can be produced as new building blocks for further transformations.

  Although the selective oxidation of organic molecules by gold has been reviewed fairly recently [1–3], the continuing rapid progress makes an update of the state-of-the-art very desirable.

  Among the various challenging topics, the catalytic conversion of carbohydrates and alcohols to the corresponding carbonylic or carboxylic compounds still remains an powerful aim, as the products are employed as chemical intermediates and high-value components in, for example, the perfumery, food, and pharmaceutical industries [1–8]. Pressing environmental restrictions are pushing research towards the progressive shutdown of traditional methods, such as the use of heavy metal salts as oxidants, because of environmental problems related to the disposal of undesired and toxic by-products. In contrast, selective oxidations using the eco-friendly air or pure dioxygen as the oxidant, and supported metals as catalysts, are attracting general support. Gold catalysis has enjoyed important progress owing to the rapid advances in nanotechnology and nanoscience, resulting in new applications for commercial syntheses in both the academic and industrial research worlds [9–12]. The strong scientific appeal of gold can be easily understood considering its peculiar property to discriminate inside chemical groups and geometric positions [13–15], and its chemical stability, strictly related to the unique features of gold itself. First, the high electrode potential (E ° = +1.69 V), responsible for the well-known inertness of this metal, leads to the sought-after characteristics required in catalysis: resistance to oxygen and tolerance to chemical groups such as aliphatic and aromatic amines, which normally produce poisoning phenomena with other metals. Second, the kinetic aspects of gold catalysis reveal how the activity is highly dependent on the size of metallic gold particles. In particular, many investigations on the liquid-phase oxidation of polyols, alcohols, and carbohydrates indicate that only small gold particles are catalytically active [16, 17], this behavior being common to gold particles employed in the gas-phase oxidation of carbon monoxide [1]. An ultimate catalyst with a stable structure that is active without any support has recently been reported [18–23]: it consists of nanoporous Au, prepared by the dealloying of Au–Ag alloys, by leaching Ag from an Au–Ag alloy through a route similar to that for the preparation of Raney nickel. Gold in such a form is able to catalyze the selective oxidative coupling of methanol to methyl formate with selectivities above 97% and a high turnover frequency (TOF) at temperatures below 80 °C. As the overall catalytic characteristics of nanoporous Au are in agreement with studies on Au single crystals, Friend and co-workers [18] deduced that the selective surface chemistry of gold is unaltered but that O2 can be readily activated with this material. Surprisingly, gold not being in contact with an oxide support, nanoporous Au shows great activity for low-temperature CO oxidation with O2 as an oxidant at atmospheric pressure [20]. It is also active for the liquid-phase oxidation of glucose [21], electrochemical oxidation of methanol [22], and O2

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  Science of Synthesis: Catalytic Oxidation in Organic Synthesis

  • Kilian Muñiz(Author)
  • 2018(Publication Date)
  • Thieme

    (Publisher)

  Process Res. Dev. , (2010) 14 , 245. References 567 8.2 Enantioselective Oxidation of Alcohols B. M. Stoltz, A. C. Wright, D. C. Ebner, and N. Park General Introduction Enantioenriched secondary alcohols are valuable compounds in asymmetric synthesis, both for their presence in many pharmaceuticals, natural products, and other important products, and as important synthetic intermediates. In 2011, both classical and state-of-the-art methods for accessing enantioenriched secondary alcohols via the oxidative kinet-ic resolution of the corresponding racemates were reviewed in Science of Synthesis: Stereo-selective Synthesis (Section 2.4). [1] In this chapter, the intent is to provide the most synthet-ically useful methods presented in the previous review, as well as to report important ad-vances made in this field since that time. The Oxidation of Alcohols is a fundamental transformation in organic synthesis. How-ever, the asymmetric oxidation of racemic alcohols in a kinetic resolution process has only recently been developed. Whereas a more traditional approach to synthesize enan-tioenriched alcohols relies on the stereoselective reduction of a prochiral carbonyl, an ox-idative approach involves a reversed process, in which the stereocenter of an alcohol race-mate is enantioselectively destroyed, or ablated, by oxidation to the carbonyl, leaving the desired alcohol enantiomer intact (Scheme 1). [2] Scheme 1 General Oxidative Kinetic Resolution R 1 R 2 OH R 1 R 2 OH + R 1 R 2 OH R 1 R 2 O + enantioselective oxidant R 1 R 2 OH R 1 R 2 OH R 1 R 2 O k fast k slow Essential to a kinetic resolution is a substantial difference in the relative rates of oxidation of the two alcohol enantiomers in the racemate. The rate constants for the oxidation of the two enantiomers ( k fast and k slow ) dictate the overall efficiency of the resolution. The de-gree of efficiency may be described by a selectivity factor ( s = k fast / k slow ).

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  Metabolic Basis of Detoxication

  Metabolism of Functional Groups

  • William B. Jakoby(Author)
  • 2012(Publication Date)
  • Academic Press

    (Publisher)

  The two metabolically produced aldehydes, 6 and 7, mentioned earlier, also undergo in vivo conversion to acid as well as to alcohol. A common source of aldehyde is the hydroxylation of an aromatic methyl group followed by conversion to aldehyde and then to acid. Toluene, for exam-ple, appears to have only one fate in the body: oxidation to benzoic acid. Many examples of this route are known. The antiparasitic agent, 16, undergoes effi-cient stepwise oxidation in the body to 17, which was shown to be a more active compound than 16 (19). Mefenamic acid (18) is also metabolized in this fashion, being converted to 19 by what may be its only route of metabolism (20). Three mammalian enzymes are known to be able to oxidize aldehydes to acids: aldehyde dehydrogenase, aldehyde oxidase, and xanthine oxidase (2). Aldehyde dehydrogenase appears to be a typical soluble dehydrogenase requiring NAD+ as cofactor. It readily dehydrogenates typical short-chain aliphatic aldehydes as well as benzaldehyde and many substituted benzaldehydes. It is probably the principal enzyme responsible for oxidation of aldehydes to acids. Aldehyde oxidase and xanthine oxidase are complex metalloflavoproteins that in vitro possess the ability to oxidize aldehydes when oxygen is present as electron acceptor. However, their role in the in vivo oxidation of aldehydes has not been fully established. O H = C H y C H = C H 2 (16) R = CH 3 (17) R = COOH (18) R = CH 3 (19) R = COOH 96 Robert Ε. McMahon IV. INTERCONVERSION OF SECONDARY ALCOHOLS AND KETONES A large number of ketones are known to serve as substrates for mammalian alcohol dehydrogenases. These include the alicyclic ketones (18) (cyclo-hexanone, decalone, and their cogeners in particular) as well as aryl alkyl ketones and some short-chain aliphatic ketones. The equilibrium between ketones and their secondary carbinol analogs is shown in Eq. (2) for cy-clohexanone. This system differs in a very important way from that with al-dehydes.

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