Oxidation aromatic side chain

Fig. 4.48 Classical versus green aromatic side-chain oxidation.

Aromatic side chain, oxidation of, 65. Azo-compounds, formation of, 56, 59, 60. 

A process akin to the allylic oxidation in activation is aromatic side chain oxidation to produce acids or anhydrides. Phthalic anhydride, an important intermediate in production of polyesters, plasticizers, and fine chemicals synthesis, can be produced via selective oxidation of -xylenes using vanadium oxide catalysts (Eqn. 3). This process today accounts for over 85% of the phthalic anhydride produced worldwide, and has largely displaced the partially wasteful and more expensive naphthalene-based route (Eqn. 4), by which nearly all PA was produced in 1960 (Figure 4). Nearly all of the phthalic anhydride produced today is used for manufacturing vinyl plasticizers, with a much smaller application in the fine chemicals industry. 

The subject of this chapter is the hydroxylation of all kinds of aromatic rings, either substituted or unsubstituted. The ring(s) may be in an external substrate added to a metal complex - dioxygen system, or may be part of a ligand coordinated to the metal ion within the catalyst complex. Aromatic side-chain oxidations are treated in the sections for alkane, alkene or alkyne oxidation, depending on the substituent. 

The mechanism of side-chain oxidation is complex and involves reaction of C-J-l bonds at the position next to the aromatic ring to form intermediate ben-zylic radicals, tert- Butyl benzene has no benzylic hydrogens, however, and is therefore inert. 

Titov claims that the free radical mechanism applies for nitration of aliphatic hydrocarbons, of aromatic side chains, of olefins, and of aromatic ring carbons, if irf the latter case the nitrating agent is ca 60—70% nitric acid that is free of nitrous acid, or even more dil acid if oxides of nitrogen are present... 

Scheme 12.22. Side Chain Oxidation of Aromatic Compounds... 

Scheme 38 Side-chain oxidation of aromatic compounds mediated by Fe(ll).

Nature utilizes the shikimate pathway for the biosynthesis of amino acids with aryl side chains. These nonprotein amino acids are often synthesized through intermediates found in the shikimate pathway. In many cases, L-a-amino acids are functionalized at different sites to yield nonprotein amino acids. These modifications include oxidation, hydroxylation, halogenation, methylation, and thiolation. In addition to these modifications, nature also utilizes modified biosynthetic pathways to produce compounds that are structurally more complex. When analyzing the structures of these nonprotein amino acids, one can generally identify the structural similarities to one of the L-a-amino acids with aromatic side chains. 

Etard reagents (chromyl chloride and some derivatives) suffer from the problem that occasionally they can exhibit a lack of selectivity and low yields. They are useful in the selective oxidation of aromatic side-chains to a carbonyl group, aldehyde or ketone but in many instances, the formation of the initial complex is slow and yields are low because of difficulties in the work-up which lead to undesired over-reaction. Attempts have been made to solve the problems by the use of sonication [134]. A simple preparation of the liquid reagent was proposed and the Etard reaction itself together with the hydrolytic step were conducted under sonication, with some success (Scheme 3.25). 

Scheme 4. Side chain oxidation of aromatics on THPc faujasites [65-66].

Tremendous effects have been made in studying the possibilities for the electrochemical generation and regeneration of inorganic redox agents like Cr(VI) V(V), Mn(III) Ce(IV) , and Co(in) and their application in the oxidation of aromatics. These studies are mainly performed by means of three types of reactions side-chain oxidations to form benzaldehydes, side-chain oxidations to generate benzoic acids, and nuclear oxidations for the synthesis of quinones (Scheme 1). 

Side-chain oxidations of alkyl aromatic compounds to aromatic carboxylic acids by electrogenerated and regenerated chromic acid have been studied extensively in the case of saccharin formation from o-toluene sulfonamide This... 

In addition to the synthesis of saccharin, also a number of other side-chain oxidations have been studied leading to aromatic carboxylic acids by indirect electrochemical oxidation using chromic acid as oxidizing agent. They include the oxidation of p-nitrotoluene 2,4-dinitrotoluene toluene, p-xylene, and p-tolualdehyde... 

A principally different approach for the indirect electrochemical oxidation of aromatic compounds goes via the formation of hydroxyl radicals from cathodically generated hydrogen peroxide and from reductively formed iron(II) ions. The thus in situ formed Fenton reagent can lead to side-chain as well as nuclear oxidations of aromatic compounds. Side-chain oxidations to form benzaldehydes according to Eqs. (18)—(24) can also be initiated by the redox pairs and Cu instead of... 

Oxidative cleavage of olefins, terminal alkynes, or aromatic rings 9-11 Oxidation of aromatic side chains 9-21 Oxidation of amines 9-22 Oxidation of primary alcohols or ethers... 

Permanganate ion is a strong oxidant and tends to cleave aromatic side chains. However, when used under phase-transfer conditions,109,849 it converts benzylic methine groups into alcohols, and benzylic methylene compounds to ketones. Convenient oxidations can be carried out when KMn04 is applied in Et3N, an organic solvent (CHC13), and traces of water at room temperature.850... 

Thus oxidation of the nucleus may be activated and may form a possible explanation of the relative low initial selectivity generally observed [345, 347]. As to side chain oxidation, introduction of oxygen and dissociation of a second hydrogen atom yields the aldehyde as the first desorb-able aromatic product. On V2Os -based catalysts the aldehyde is easily converted into the acid. The transition of an adsorbed aldehyde into a sym-... 

Reaction 1 has been postulated both in oxidations of alkanes in the vapor phase (29) and in the anti-Markovnikov addition of hydrogen bromide to olefins in the liquid phase (14). Reaction 2 involves the established mechanism for free-radical bromination of aromatic side chains (2). Reaction 4 as part of the propagation step, established in earlier work without bromine radicals (26), was not invoked by Ravens, because of the absence of [RCH3] in the rate equation. Equations 4 to 6, in which Reaction 6 was rate-determining, were replaced by Ravens by the reaction of peroxy radical with Co2+ ... 

Potassium nitrosodisulfonate, 258 Trimethylsilyl chlorochromate, 327 By hydrolysis of acetals or thioacetals Amberlyst ion-exchange resin, 152 Methylthiomethyl p-tolyl sulfone, 192 By isomerization of allylic alcohols N-Lithioethylenediamine, 157 By oxidation of aromatic side chains Trimethylsilyl chlorochromate, 327 From oxidative cleavage of alkenes [Bis(salicylidene-7-iminopropyl)-methylamine]cobalt(II)... 

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