Describe The Concept Of Oxidation Levels And Discuss The Use Of Oxidising And Reducing Agents For The Modification Of Functional Groups In Organic Chemistry.
Describe The Concept Of Oxidation Levels And Discuss The Use Of Oxidising And Reducing Agents For The Modification Of Functional Groups In Organic Chemistry.
The majority of the reactions of organic compounds, which involve conversion of one type to another, can be classified as oxidation or reduction. This conclusion can be justified on the basis of the definitions of the terms, oxidation and reduction. Oxidation is defined as a loss of electrons and reduction as a gain of electrons. Other definitions have been formulated which deal with such concepts as oxidation involving removal of hydrogen to form multiple bonds or to make new bonds between carbon and a more electronegative element, and reduction involving reactions in which carbon forms new bonds to hydrogen.
It is harder to define oxidation as a loss of electrons in organic compounds compared with metals. In oxidation and reduction of metals, the electronic changes involve transfer, and thus a true net loss or gain of electrons. In covalently bonded compounds, such as the compounds of carbon, such electron transfers do not usually occur. Instead, the carbon atom, even though it retains a covalency of four, changed markedly in the degree of control it exerts over the covalently bound electrons. Thus, it may be that when the electron density about a carbon atom decreases, it has undergone oxidation, and conversely an increase in electron density can be interpreted as a reduction.
Also the oxidation level or the oxidation number of a compound tells us whether an oxidation or reduction reaction has happened. There are a variety of methods of calculating oxidation numbers. In compounds such as methane, CH4, we know that hydrogen has an oxidation number of +1. Assuming that the algebraic sum of all the oxidation numbers must equal zero, the oxidation state of carbon in methane is therefore
-4. When the oxidation number of an atom increases, that atom is said to be oxidised and when the oxidation number decreases, reduction has taken place. Therefore when methane undergoes combustion, carbon dioxide and water are the products. The carbon has been oxidised because its oxidation state has increased from -4 in methane to +4. On the other hand, oxygen has been reduced because its oxidation state has decreased from 0 in its elemental state to -2 in water.
The various oxidising reagents available to the organic chemist have widely different oxidation potentials. Since the various functional groups in organic compounds also have widely different reduction potentials, certain oxidising agents have been found to be specific for converting certain organic functional groups to other functional groups because the respective oxidation and reduction potentials are of the right order of magnitude. Other organic compounds may be too difficult to oxidise (have too low a reduction potential) for one oxidising agent whereas another reagent of higher potential is capable of accomplishing the oxidation.
Oxidation of Hydrocarbons at Sigma Bond.
Since the bond dissociation energies of single bond of alkanes are quite similar, few oxidation procedures permit selective cleavage of specific C-C or C-H bonds without complete oxidation of the entire molecule. Allylic, benzylic and tertiary C-H bonds are weaker than other types and can occasionally oxidised successfully without affecting the remainder of the molecule. For example, cumene, propene, toluene, cyclohexene and similar compounds can be oxidised to useful products.
Cyclic hydrocarbons containing six-membered rings are dehydrogenated when heated in the presence of hydrogenation catalysts such as palladium or platinum.
An indirect route to oxidation products of alkanes is via halogenation followed by hydrolysis of the alkyl halide to the alcohol. The alcohols may be further oxidised under controlled conditions as will be discussed later.
Oxidation of Hydrocarbons at pi (?) Bonds.
Oxidation may result from attack of the oxidising on pi (?) bonds as well as on sigma (?) bonds. Although the pi bonds of alkenes are more reactive with ionic reagents than are the sigma bonds, certain oxidising agents can quite selectively oxidise sigma bonds. Other reagents selectively attack the pi bond. A reagent for accomplishing a cis addition to alkenes is osmium tetroxide; the method, however is both expensive and hazardous since the reagent is very toxic.
A particularly useful group of oxidising agents for converting alkenes to epoxides and glycol derivatives are the peroxy acids. Peroxy acids are compounds characterised by having the peroxide link present and may be considered as derivatives of hydrogen peroxide. They are usually prepared by the addition of hydrogen peroxide to an excess of the acid, or by the reaction of the anhydride of the acid with hydrogen peroxide. They are subject to loss of oxygen on standing. For this reason peroxyformic acid must be used immediately after preparation.
Alkenes react with peroxy acids under mild conditions to produce epoxides or their derivatives. Since the epoxides initially formed are susceptible to attack to form the monoesters of the 1,2-diols, it is not always possible to isolate the epoxides.
Peroxy esters are also useful oxidising agents in the presence of metal salts. These compounds are capable of converting allylic C-H bonds (as in cyclohexene) to C-O bonds and this reaction constitutes perhaps the most convenient route to allyl alcohol derivatives.
An important use of terminal alkynes is synthesising conjugated alkynes and in general extending the length of a carbon chain involves oxidative coupling. It is well known that terminal alkynes form metal acetylides as the result of the relative acidic alkyne proton.
These metal acetylides may be converted to the corresponding conjugated diynes and may ...
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Peroxy esters are also useful oxidising agents in the presence of metal salts. These compounds are capable of converting allylic C-H bonds (as in cyclohexene) to C-O bonds and this reaction constitutes perhaps the most convenient route to allyl alcohol derivatives.
An important use of terminal alkynes is synthesising conjugated alkynes and in general extending the length of a carbon chain involves oxidative coupling. It is well known that terminal alkynes form metal acetylides as the result of the relative acidic alkyne proton.
These metal acetylides may be converted to the corresponding conjugated diynes and may be used in a variety of syntheses requiring a longer carbon chain.
Oxidation of Alcohols.
Alcohols may be considered to be the first oxidation products of the alkanes even though they are seldom prepared by direct oxidation. Primary and secondary alcohols are oxidised to aldehydes and ketones respectively. However isolating aldehydes is not easy as they are further oxidised. Numerous procedures have been developed to permit isolation of aldehydes from oxidation of primary alcohols. By far the most widely used reagents for oxidation of alcohols are derivatives of hexavalent chromium and heptavalent manganese. Chromium trioxide (CrO3) and sodium dichromate (NaCr2O7) are reduced to trivalent chromic ion (Cr3+) during the course of such oxidations, which involve a net transfer of three electrons to each chromium atom. Use of potassium permanganate (KmnO4), for the oxidation of organic compounds in acid media, results in the reduction of heptavalent manganese to Mn2+ for a net transfer of five electrons to the manganese atom. When KMnO4 is used in neutral or basic media, manganese dioxide (MnO2) is the reduction product for a net transfer of three electrons per manganese atom.
Since ketones are not readily oxidised by these reagents the reaction does not usually proceed beyond this stage. Therefore the problem of converting secondary alcohols to the corresponding ketone, by use of oxidising agents, is a simple one when compared with primary alcohols. However since the boiling point of the aldehyde is lower than the corresponding alcohol, it is often possible to remove it by distillation in good yield, before the aldehyde is oxidised to the corresponding carboxylic acid.
In contrast tertiary alcohols undergo oxidation only after an acid catalysed dehydration has occurred, and the resulting alkene is attacked in the predicted manner.
Other oxidising agents commonly used for conversion of alcohol functions to other functions are Br2 and HNO3.
Oxidation of Carbonyl Compounds.
The structural difference between aldehydes and ketones results in a tremendous differential in the reduction potential of these two groups of compounds. This is evident from the fact that many qualitative tests for distinguishing between these two groups of compounds are based on this fact, for example tollens reagent.
The oxidation of aldehydes with chromic acid is acid-catalysed and accelerated by electron withdrawing groups, and is postulated to proceed through the formation and decomposition of a chromic ester of the hydrated aldehyde.
The rate of oxidation of p-nitrobenzaldehyde is considerably enhanced over that of the unsubstituted benzaldehyde.
The mechanism for oxidation by permanganate solutions appears to vary, depending on whether neutral or acidic media are used or on whether basic media are used. The former is acid-catalysed and appears to proceed though the formation and decomposition of a permanganic ester.
The latter seems to proceed by a free-radical chain process. Electron-withdrawing groups accelerate both processes. Alicyclic ketones are not readily oxidised by permanganate and chromate solutions under mild conditions. In fact, acetone is sometimes used as a solvent in such oxidations. However, cyclic ketones are oxidised by nitric acid to open the ring, resulting in the formation of a dicarboxylic acid.
The reaction of ketones with peroxy acids permits the formation of esters; this reaction is known as the Baever-Villiger oxidation. Very reactive peroxy acids such as peroxytrifluoroacetic acid are preferred, since reaction of peroxy acids in general with ketones is much slower than with alkenes. Less reactive peroxy acids with strong acids as catalysts and long reaction times also permit the conversion of ketones to esters in good yields. The rate is accelerated by electron-donating groups in the ketone and by electron-withdrawing groups in the peroxy acid.
Oxidation of Nitrogen Compounds.
Organic nitrogen-containing compounds are known in which the nitrogen atom varies in oxidation states between the fully reduced amines and the fully oxidised nitro group. Many reagents possessing oxidising power convert primary and secondary amines to a variety of products such as hydroxylamines, oximes, nitroso, and nitro compounds, and aldehydes and ketones. However, these reactions are usually of little preparative value. t-Alkyl primary amines may be converted to tertiary nitroalkanes by use of KMnO4, peroxyacetic acid or hydrogen peroxide.
If an ortho or para position is unoccupied, primary aromatic amines are oxidised to quinones rather than to the oxidised nitrogen derivative.
This behaviour can be accounted for on basis of the marked electron-donor character of nitrogen, and the resulting high electron density at the ortho and para positions. Tertiary amines are generally converted smoothly to amine oxides by hydrogen peroxide.
Oxidation of Sulphur Compounds.
The sulphur analogues of the alcohols are known as mercaptans or thiols. They differ in chemical properties, predominantly as the result of the difference between oxygen and sulphur. For example, they are not oxidised to thioaldehydes and ketones as are primary and secondary alcohols, but are converted instead to disulfides upon oxidation.
The reaction is believed to proceed by a free radical initiated chain reaction. Thiols do form thioethers by a reaction analogous to the Williamson synthesis of ethers.
Thioethers are oxidised at the sulphur atom to sulfoxides and sulfones.
Sulphoxides function as specific oxidants for conversion of alkyl halides and sulphonates to carbonyl compounds. Thiols may be oxidised to sulphonic acids by the action of nitric acid on their lead salts.
Antioxidants.
Quite often it becomes desirable to protect readily oxidizable compounds from being oxidised. Compounds known as antioxidants are available which accomplish this purpose when added in small quantities. Such compounds are usually aromatic amines or phenols; structures which themselves are subject to attack by oxygen and which result in the formation of resonance-stabilised free radicals. These resonance-stabilised free radicals are usually considered to be quite inefficient in propagating a chain reaction, thus functioning as "chain stoppers". Examples of useful antioxidants are hydroquinone, phenyl-?-naphthylamine, quinones, and 4-t-butylcatechol.
Antioxidants are important in protecting many commercial products from deterioration by oxidation, among which are foods, gasoline, lubricating oils and rubber. Hydroquinone, which is easily oxidised to quinone, inhibits oxidation of benzaldehyde at a concentration of only 0.001% and is commonly added to benzaldehyde for protection in storage.
Reduction of Organic Compounds.
Many procedures containing a wide range of reagents have been developed for the reduction of organic compounds. The term reduction is often used alongside hydrogenation in organic chemistry. Many reductions involve addition of hydrogen to the species being reduced, often by substitution.
The major factors affecting method of reduction for an organic compound are as follows:
(1) The method should be selective for the functional group to be reduced, and should not affect other reducible functional groups in the molecule.
(2) Good conversion to the desired product should be possible
(3) The method should be the most convenient one available from the standpoint of the reagents available, equipment available, time required and on occasions the economic factors must be considered. The latter factor is essential from a manufacturing point of view.
Reduction of Unsaturated Hydrocarbons.
The most generally applicable method for reducing alkenes and alkynes is by catalytic hydrogenation. The catalysts used are predominantly active metals such as finely divided nickel (prepared by dissolving aluminium from a nickel-aluminium alloy with sodium hydroxide (Raney nickel)). All are used in conjunction with hydrogen gas under various pressures.
Most C=C double bonds are subject to reduction by one or more of the hydrogenation methods. The problem of reduction of carbon to carbon double bonds in the presence of other reducible functional groups is important. Study of reaction of functional groups in catalytic hydrogenation created the following approximate (decreasing) order of reactivity.
Thus multifunctional compounds containing functional groups of greater reactivity than the double bond cannot be practically reduced catalytically to the saturated compound. As a result other methods have been developed.
Copper chromite will affect the selective hydrogenation of carbonyl groups in the presence of carbon-carbon double bonds.
Alkenes are hydrogenated in the presence of this catalyst but at a low rate. Terminal alkenes readily with aluminium hydride and can be reduced in this manner.
Particularly effective reagent for reduction of alkenes is diimide, NH=NH. The intermediate is highly unstable and can not be isolated, but can be generated by abase catalysed elimination reaction of certain of hydrazine.
Alkynes can be reduced to cis alkenes by use of diborane:
Sodium in liquid ammonia reduces alkynes to trans alkenes in a steriospecific manner:
The Trans arrangement is preferred since the charges in the intermediate charged species would repel each other and are farther apart in the trans structure than in the cis structure.
Reduction of Aromatic Hydrocarbons.
Because of the resonance stabilisation, aromatic hydrocarbons are more difficult to reduce than alkynes. As expected functional groups present on the ring alter the reactivity toward reduction. In general, however, benzene derivatives are easily reduced catalytically over platinum and rhodium catalysts over Raney nickel at high Hydrogen pressure.
Aromatic compounds may also be reduced using solutions of sodium or Lithium in liquid ammonia. This method is known as the Birch reduction. Birch reduction of aromatic compounds leads to 1,4 - cyclohexadiene.
Electron- donor groups (-OCH3) direct the negative charges away from the carbon bearing high electron density. Electron- acceptor groups stabilise the charge at the carbon bearing the acceptor group and thus control the structure of the product.
Reduction of Alkyl and Aryl Halides.
Catalytic reduction is often effective for reduction of halides, particularly allylic and benzylic halides. Removal of groups such as halogens by catalytic hydrogenation is usually referred to as hydrogenolysis.
However, halogens quite often " poison " or inactivate hydrogenation catalysts. Lithium aluminium hydride can also be used to displace Br with hydride ion. Alkyl iodides are reduced with hydriodic acid. A recently developed method for reducing both alkyl and aryl halides involves the use of trialkyltin hydrides.
The reaction has been shown to proceed by a free radical chain process, and their force will not be restricted to halides that will readily undergo nucleophilic displacement.
Although the organotin hydrides also undergo addition to alkenes and alkynes by free-radical mechanism and reduce carbonyl compounds to alcohols, allylic halides and alpha-halo ketones are by preference reduced at the carbon halogen bond rather than undergoing addition to the double bond or reduction of the carbonyl group.
Reduction of Alcohols and Phenols.
Reduction of alcohols to the corresponding hydrocarbon is usually difficult to accomplish. Only benzyl and allyl alcohols have been reduced directly. Certain alpha-hydroxy ketones are also susceptible to reduction leading to alpha-methylene ketones.
Rhodium and ruthenium catalysts are most effective for decreasing the extent of hydrogenolysis during reduction of an aromatic ring.
An indirect method of reducing alcohols to the corresponding hydrocarbon is through the intermediate tosylate by use of LiAlH4.
An amino group can replace the hydroxyl group of phenols by heating the phenol with a mixture of ammonia and zinc chloride.
Reduction of Carbonyl Compounds.
In general, carbonyl compounds are readily reduced to the corresponding alcohols. Sodium in moist alcohol reduces aldehydes and ketones to primary and secondary ketones respectively. Lithium aluminium hydride (LiAlH4) and Sodium borohydride (NaBH4) has become extremely important for reducing carbonyl compounds. These metal hydrides do not usually attack alkene linkages, which permits their use for selective reduction of carbonyl groups in the presence of alkene groups.
The advantage of using NaBH4 is that it is a milder reducing agent and will reduce aldehydes and ketones but not acids and esters. Also , it reacts very slowly with water so that reasonably rapid reductions can be conducted in water solution without serious loss of reagent by hydrolysis.
The copper chromite catalyst is also selective for reduction of unsaturated polar groups. The selectivity may arise from the stronger adsorption of the polar carbonyl groups on the metal oxide surface rather than of the relatively non-polar group.
Carbonyl compounds can be reduced to the hydrocarbon by three principal methods:
(1) Clemmenson reduction, limited to mixed aromatic aliphatic ketones or diaryl ketones.
(2) The Wolf-Kishner reduction.
(3) Reduction of the thioketal or thioacetal and Raney nickel.
The mechanism of the Clemmenson reduction is not fully understood but it is known that the intermediate secondary alcohol is not an intermediate in this reaction, since it is not reduced to the hydrocarbon under these conditions.
Reduction of Carboxylic Acids and Derivatives.
The classical method for converting carboxylic acids to the reduction product , the primary alcohol, has been to esterify and reduce the ester by either by sodium in boiling alcohol or by catalytic hydrogenation under high hydrogen pressure using copper chromite as the catalyst. It is also possible to reduce the ester by use of Lithium Aluminium Hydride or diborane. Sodium borohydride does not reduce the ester , making it possible to reduce carbonyl functions of aldehydes and ketones in the presence of esters ( and carboxylic acids ) (see over page)
Metal hydrides are also used as reducing agents for organic compounds. The method of reduction of carboxylic acids directly to the primary alcohol is shown below.
Any excess LiAlH4 is destroyed by adding ethyl acetate, then water to hydrolyse the alkoxide followed by isolation and purification of the alcohol in the usual manner.
Acid halides are reduced by the Rosemmund method to give aldehydes. Since aldehydes are readily reduced, methods have been developed to inactivate the catalyst so that it is not sufficiently active to reduce the aldehyde. The classical Rosemmund catalyst is Pd on BaSO4.
Acid chlorides can also be reduced with LiAlH4 in the same manner as the carboxylic acids except that hydrogen gas is not evolved. Acid anhydrides are also reduced in the same manner. The product in each case is a primary alcohol.
Reduction of Ethers
The Ether link in general is not subject to reduction. However, benzyl and allyl ethers, as well as epoxides, are susceptible to certain reduction methods, and as such are as extreme importance to the syntheses. For example the benzyl group can be used as a protecting group of alcohols, permitting oxidation of other groups under conditions that would also oxidise the alcohol. One can then remove the benzyl group by catalytic hydrogenation.
As you can see oxidation and reduction are important reactions in organic chemistry. Many compounds are only viable through these processes.
LiAlH4 also reduces epoxides (oxiranes) to the corresponding monoalcohols (i.e. after hydrolysis). Epoxides are also reduced in a similar manner by B2H6.
Reduction of Organic Nitrogen Compounds.
Organic nitrogen compounds which are subject to reduction with retention of the nitrogen atom are nitro, nitroso, azo, hydroxylamine, azoxy, hydrazo, hydrazino derivatives, nitriles, imines, oximes, amides, imides and hydrazones. The final products of reduction of all these derivatives are the amines (unless the C-N bond is cleaved during the process). Because of the ease of introduction of the nitro group into aromatic systems, this group serves as a starting point for most aromatic nitrogen derivatives. Consequently, its reduction has been studied quite extensively. Although the amount of quantitative information available on oxidation and reduction potentials of organic compounds is limited, some data are available on nitrobenzene. It has been shown that nitrosobenzene, the first reduction product of nitrobenzene, can not be isolated as it is readily reduced to phenylhydroxylamine.
Because of the marked ability of the aromatic structure to exert a stabilising influence on intermediate structure through resonance, a wide variety of compounds can be isolated, intermediate between the fully oxidised nitrobenzene and the fully reduced aniline. Although some of these intermediates are also observed in the aliphatic series as well, they are relatively less stable and relatively less important. The following table shows the reduction reaction of some functional groups.
Functional Group
Name
Preferred Reducing Agent and Conditions
Product
Alternative Reagent
-NO2
Nitro
Zn/NH4Cl
Zn /NaOH
Zn/NaOH/CH3OH
--NHOH
--NHNH-
--N=N--
-NO
Nitroso
Na3AsO3/NaOCH3
Sn/HCl
Sn/HCl
Zn/NH4Cl
--N=N-->O
--NH2
--NH2
--NHOH
Ni/H2, Fe/HCl
Ni/H2,Fe/HCl
-NHOH
Hydroxylamino
Zn/CH3COOH
--NH2
Ni/H2
-N=N-
Azo
Zn/NaOH
Sn/HCl
--NHNH-
--NH2
Fe/HCl
-N=N-->O
Azoxy
Fe
Sn/HCl
--N=N-
--NH2
Fe/HCl
-NHNH-
Hydrazo
Sn/HCl
--NH2
Fe/HCl
There are many other nitrogen containing functional groups which under go reduction reactions. For example amides, nitriles, imines, hydrazones, oximes and diazonium salts all undergo reduction with retention of nitrogen. LiAlH4 is the main reducing agent used. The remarkable versatility of the metal hydrides as reducing agents has made it possible to accomplish most reductions by one or another of these reagents. Also, because these reducing agents react at different rates with different functional groups it is possible to selectively reduce certain multifunctional compounds i.e. sodium borohydride reacts moderately fast with aldehydes and ketones, but very slow with esters, amides, nitriles, nitro groups and alkyl halides.
Certain nitrogen compounds are susceptible to reduction to other products by the cleavage of the C-N bond. These reductions have remarkable synthetic value and a few of them are summarised in the following table.
Functional Group
Name
Preferred Reducing Agent & Conditions
Product
Alternative Reagents
-C=N
Nitrile
LiAlH(OC2H5)3
[--CH=NH]-->C=O
H
-C=O
NR2
Dialkylamide
LiAlH2(OC2H5)2
[--CH-NR2]
OH -->
--C=O
H
LiAlH4; low temperature Pd/H2
C=NNHCNH2
O
Semi-carbazone
KOH, H2O, 200?
CH2
The use of the less reactive reducing agent LiAlH2(OC2H5)2 makes it possible to stop the reduction of an amide at an intermediate stage, which when followed by hydrolysis, yields the aldehyde. Yields up to 70% are obtainable.
The reductive cleavage of N-benzyldialkylamines affords an excellent synthesis for symmetrical and unsymmetrical secondary amines. The starting materials are readily available by dialkylation of benzylamine or by monoalkylation of alkylbenzylamines, which in turn are prepared by the reduction of Schiff bases.
As you can see oxidation and reduction are very important reactions in organic chemistry. Many organic compounds are only viable through these processes.