Aryl esters, oxidation

Several aryl esters of 6-chloromethyl-2-oxo-2//-l -benzopyran-3-carboxylic acid act as human Lon protease inhibitors (alternate substrate inhibitors)46 without having any effect on the 20S proteasome. Proteasomes are the major agents of protein turnover and the breakdown of oxidized proteins in the cytosol and nucleus of eukaryotic cells,47 whereas Lon protease seems to play a major role in the elimination of oxidatively modified proteins in the mitochondrial matrix. The coumarin derivatives are potentially useful tools for investigating the various biological roles of Lon protease without interfering with the proteasome inhibition. 

Electrophilic substitution of the ring hydrogen atom in 1,3,4-oxadiazoles is uncommon. In contrast, several reactions of electrophiles with C-linked substituents of 1,3,4-oxadiazole have been reported. 2,5-Diaryl-l,3,4-oxadiazoles are bromi-nated and nitrated on aryl substituents. Oxidation of 2,5-ditolyl-l,3,4-oxadiazole afforded the corresponding dialdehydes or dicarboxylic acids. 2-Methyl-5-phenyl-l,3,4-oxadiazole treated with butyllithium and then with isoamyl nitrite yielded the oxime of 5-phenyl-l,3,4-oxadiazol-2-carbaldehyde. 2-Chloromethyl-5-phenyl-l,3,4-oxadiazole under the action of sulfur and methyl iodide followed by amines affords the respective thioamides. 2-Chloromethyl-5-methyl-l,3,4-oxadia-zole and triethyl phosphite gave a product, which underwent a Wittig reation with aromatic aldehydes to form alkenes. Alkyl l,3,4-oxadiazole-2-carboxylates undergo typical reactions with ammonia, amines, and hydrazines to afford amides or hydrazides. It has been shown that 5-amino-l,3,4-oxadiazole-2-carboxylic acids and their esters decarboxylate. 

A new synthesis of isoxazoles is by successive treatment of a ketoxime with butyllithi-um, the ester of a carboxylic acid and sulfuric acid, e.g. 1 -> 2 (94S989). Hitrovinyl oximes 3 (R1, R3 = alkyl or aryl) undergo oxidative cyclization to isoxazoles 4 by the action of DDQ or iodine/potassium iodide (94JHC861). Flash-vacuum pyrolysis of the 1,3-dipolar cycloadduct 5 of acrylonitrile oxide to norbornadiene results in a retro-Diels-Alder reaction to give cyclopentadiene and 3-vinylisoxazole 6 (94CC2661). 

The trisubstituted (Z)-olefin was introduced by Still-Gennari HWE olefination, as precedented by Schreiber [43, 44, 106], and following silyl protection provided 124. Conversion into the iodide 125 was followed by alkylation with the lithium enolate of aryl ester 126, to complete the C9-C16 subunit 121. The synthesis of the C17-C24 subunit 98 from 120 began with a four-step sequence involving protecting group manipulations and oxidation at C21 to provide aldehyde 127, converging with the earlier route to 98 [55-57],... 

A wide range of nitrile oxides is known (R3 = H, aryl, alkyl, ester, halide, etc). The method of choice for the preparation of simple nitrile oxides (R3 = alkyl, aryl) is oxidation of the corresponding oxime ... 

Two novel variations on remote oxidation involve radical relay mechanisms. Chlorine radicals generated by photolysis of iodobenzene dichloride are carried by the iodine atom of a suitable iodo-aryl ester of 5a-cholestan-3a-ol to permit hydrogen abstractions from C-9 or C-14, depending upon the ester employed.237 The m-iodobenzoate (293) afforded the 9a-chloro- and thence the cholest-9(ll)-ene derivative (294), whereas the p-iodophenylacetate similarly gave a 14-ene. 

In the case of the double NPS-protected lysine methyl ester, oxidation selectively takes place at the 6-sulfenamide function under spontaneous cyclization via the a-sulphe-namido group as nucleophile. Only one diastereoisomer of the A,A -bis(NPS)-protected methyl 6-amino-piperidine-2-yl-carboxylate seems to be formed. The transformation of a-amino alkanoates and diaryl or dialkyl disulfides to the aryl- or alkylsulfenimine derivatives can be performed electrochemically using MgBr2 as a mediator system. This reaction can either proceed in one step or starting from the corresponding sulfenamide [170]. 

The phosphoric acid triesters possess excellent anti-wear properties, see Chapters 3 and 6, and sufficient oxidative stability. Their disadvantage is their ability to hydrolyse, which depends significantly on the structure of the ester short chain alkyl esters and aryl esters hydrolyse more rapidly than the long-chain alkyl esters. The triaryl versions of phosphate esters are relatively unique among hydraulic fluids because of their self-extinguishing properties, the fluid does not create enough energy to support its own combustion in a fire [65]. 

Photorearrangements of aryl esters in zeolites (6.40) give different product distributions.210 Photosensitized oxidation of stilbene with oxygen (6.41) leads to different products in solution and in a zeolite.211... 

In addition to the industrial apphcations, in Scheme 8.1, other reactions have been the focus of extensive research and development. For example. Chapter 12 surveys the research efforts directed toward Pd-catalyzed oxidative carbonylation of phenol affords the important monomer, diphenyl carbonate (Scheme 8.2a). Other reactions of potential industrial significance highlighted in this chapter include the oxidation of alcohols to aldehydes and ketones (Scheme 8.2b), oxidative coupling of arenes and carboxylic acids to afford aryl esters (Scheme 8.2c), benzylic acetoxylation (Scheme 8.2d), and oxidative Heck reactions (Scheme 8.2e). The chapter concludes by highlighting a number of newer research developments, including ligand-modulated catalytic oxidations, Pd/NO cocatalysis, and alkane oxidation. 

Oxidative esterification of arenes with carboxylic acids produces aryl esters, which can be used as precursors to valuable phenol derivatives (Scheme 8.6). Commercial production of phenol involves the aerobic oxidation of cumene to cumene hydroperoxide, followed by conversion to acetone and phenol under acidic conditions (Hock process) [49]. Aerobic acetoxylation of benzene to phenyl acetate provides a potential alternative route to phenol, and Pd-catalyzed methods for this transformation have been the focus of considerable effort. None ofthese methods are yet commercially viable, however. 

Scheme 8.6 Pd-catalyzed oxidative esterification of arenes to aryl esters and phenol derivatives.

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