Oxidation of terminal acetylene

Catalyst for tht coupling of terminal acetylenes. Cuprous chloride catalyzes the oxidation of terminal acetylenes in methanol-pyridine by air or oxygen in amounts of only 0.012 mole per mole of the acetylene, and the diacetylene is obtained in... 

Figure 7.8. The oxidation of terminal acetylenes, and even some internal acetylenes, results in the formation of ketene intermediates that react with water to give the carboxylic acids (see Chapter 6). It appears that the ketenes also react with active-site residues, inactivating the P450 enzyme that forms them. The hydrogen that undergoes a 1,2-migration during the oxidation reaction is indicated by a star. The structures of 2-ethynylnaphthalene and 10-undecynoic acid, both of which inactivate P450 enzymes, at least in part by this mechanism, are shown.

P450-catalyzed oxidation of terminal acetylenes to substituted acetic acids (Chapter 6) is more prone to result in heme alkylation than the oxidation of terminal olefins. The structure-activity relationships for the acetylene reaction are similar to those for terminal olefins, except that there are fewer instances in which the reaction does not result in errzyme inactivation. For example, P450 is inactivated by phenylacetylene but not delectably by styrene ", and P450 is inactivated by internal acetylenes, albeit without heme adduct formation, but not by internal olefins 22 , Catalytic oxidation of the acetylenic function is required for enzyme inactivation and terminal acetylenes give heme adducts analogous to those obtained with terminal olefins - 259 jhe salient difference in the adducts obtained with acetylenes and olefins... 

The phase-transfer-assisted permanganate oxidation of alkynes and alkenes has been reviewed. Terminal and internal alkynes are oxidized to 1,2-dicarbonyl compounds by the combined action of diphenyl disulphide, ammonium peroxidisulphate and water or by sodium periodate in the presence of ruthenium dioxide (equation 34). Other reagents for the conversion of acetylenes into 1,2-dicarbonyl compounds are hydrogen peroxide in the presence of (2,6-dicarboxylatopyridine)iron(II), the complex oxo(A, A -ethylenebissalicylideneiminato)chromium(V) trifluoromethanesulphonate (216)and ruthenium tetroxide as a mediator in electrooxidation. l-Acetoxyalkan-2-ones 217 are obtained by the oxidation of terminal acetylenes with sodium perborate and mercury(II) acetate in acetic acid ". Terminal alkynes give a-ketoaldehydes 218 on treatment with dilute hydrogen peroxide, combined with mercury(II) acetate and sodium molybdate or sodium tungstate under phase-transfer conditions. ... 

Acetylenes, which have shorter and stronger 7t-bonds than olefins, can also be oxidized by cytochrome P450 enzymes. The oxidation of terminal acetylenes gives ketenes in which the terminal hydrogen has quantitatively migrated to the internal carbon of the triple bond (Fig. 4.31) [191, 192]. The ketene is then hydrolyzed to yield the carboxylic acid as the observed metabolite. By analogy to the oxidation of olefins, the immediate product shotrld be the unsaturated epoxide (oxirene), but oxirenes are extremely un-... 

Fig. 4.31 The oxidation of terminal acetylenes in which the oxygen is added to the terminal carbon produces ketene metabolites in which the acetylenic hydrogen (ff )...

The oxidation of terminal acetylenes, like that of monosubstituted olefins, often results in inactivation of the P450 enzyme involved in the oxidation. In some instances, this inactivation involves reaction of the ketene metabolite with nucleophilic residues on the protein [196, 197], but in other instances it involves alkylation of the prosthetic heme group (Fig. 4.31). Again, as found for heme alkylation in the oxidation of olefins, the terminal carbon of the acetylene binds to a pyrrole nitrogen of the heme and a hydroxyl is attached to the internal carbon of the triple bond. Of course, as one of the two m-bonds of the acetylene remains in the adduct, keto-enol equilibration yields a final adduct structure with a carbonyl on the original internal carbon of the triple bond [182, 198]. It is to be noted that the oxidation of terminal triple bonds that produces ketene metabohtes requires addition of the ferryl oxygen to the imsubstituted, terminal carbon, whereas the oxidation that results in heme alkylation requires its addition to the internal carbon. As a rale, the ratios of metabolite formation to heme alkylation are much smaller for terminal acetylenes than for olefins. 

Methyl ketones are important intermediates for the synthesis of methyl alkyl carbinols, annulation reagents, and cyclic compounds. A common synthetic method for the preparation of methyl ketones is the alkylation of acetone derivatives, but the method suffers limitations such as low yields and lack of regioselectivity. Preparation of methyl ketones from olefins and acetylenes using mercury compounds is a better method. For example, hydration of terminal acetylenes using HgSO gives methyl ketones cleanly. Oxymercuration of 1-olefins and subsequent oxidation with chromic oxide is... 

A similar phenomenon was observed for 3-amino- and5-amino-4-iodopyrazoles. The anomalous reaction in which the products of oxidative coupling of terminal acetylenes (up to 90%) are present along with the products of deiodination (up to 90%) has been described for the first time [99JCS(P1 )3713] and will be considered below in the part related to cross-coupling of 4-iodopyrazoles. 

The efficient formation of diaryliodo-nium salts during the electrolysis of arylio-dides has been reported by Peacock and Fletcher [166]. The electroiodination of a 3D-aromatic molecule, dodecahydro-7,8-dicarba-nido-undecaborate has also been reported [167]. The iodination (and bromi-nation) of dimedone has been reported to yield 2-iododimedone, which formally is an electrophilic substitution reaction [123]. In a similar process, the indirect electrochemical oxidation of aliphatic ketones in an alkaline Nal/NaOH solution environment has been shown to yield a,a-diiodoketones, which rapidly rearrange to give unsaturated conjugated esters [168]. Dibenzoylmethane has been converted into dibenzoyliodomethane [169]. Terminal acetylenes have been iodinated in the presence of Nal. However, this process was proposed to proceed via oxidation of the acetylene [170]. 

Oxidative carbonyiation. Terminal acetylenes are converted into acetylene-carboxylales by CO (1 atm.) and an alcohol in the presence of a catalytic amount of PdCl2 and 1 equivalent of CuCl2. In addition a base such as sodium acetate is necessary. The reaction is an oxidative carbonyiation with PdCl2, which is reduced to Pd(0). PdCl2 can be used in catalytic amounts if CuCl2 is available for oxidation of Pd(0) to PdCl2. The base is needed to neutralize the HCI formed (equation I). The yields of the carboxylate are 60-75%. ... 

Oxidative coupling of terminal acetylenes in the presence of copper(I) catalysts is the best method of preparing symmetrically substituted butadiyne derivatives,5 and has been applied to the coupling of trimethylsilyl-acetylene. Better yields are obtained using the Hay procedure in which the catalyst is the TMEDA complex of copper(I) chloride.7 The procedure submitted here is an improved version of Walton and Waugh s synthesis of BTMSBD by the Hay coupling of trimethylsilylacetylene.2 BTMSBD has also been prepared by... 

Oxidations by oxygen and catalysts are used for the conversion of alkanes into alcohols, ketones, or acids [54]-, for the epoxidation of alkenes [43, for the formation of alkenyl hydroperoxides [22] for the conversion of terminal alkenes into methyl ketones [60, 65] for the coupling of terminal acetylenes [2, 59, 66] for the oxidation of aromatic compounds to quinones [3] or carboxylic acids [65] for the dehydrogenation of alcohols to aldehydes [4, 55, 56] or ketones [56, 57, 62, 70] for the conversion of alcohols [56, 69], aldehydes [5, 6, 63], and ketones [52, 67] into carboxylic acids and for the oxidation of primary amines to nitriles [64], of thiols to disulfides [9] or sulfonic acids [53], of sulfoxides to sulfones [70], and of alkyl dichloroboranes to alkyl hydroperoxides [57]. 

Copper sulfate, CuS04 5H20, is used for the oxidative coupling of terminal acetylenes [5S] for the conversion of a-hydroxy ketones (acyloins) into a-diketones [351, 352] and, in cooperation with potassium peroxy-disulfate, for the selective oxidation of methyl groups on benzene rings to aldehyde groups [355],... 

Copper acetate, Cu(OCOCHj)2 or Cu(0C0CH3)2 H20, resembles copper sulfate in its oxidizing properties and is used for the oxidative coupling of terminal acetylenes [53, 357] and for the conversion of acyloins into a-diketones [353, 359]. Its presence favorably affects the acetoxylation of toluenes to benzyl acetates by sodium persulfate [360]. 

Scheme 5-3 Pd-catalyzed cross-coupling reaction of terminal acetylenes with sp- halides i, oxidative addition ii, transmetallation iii, reductive elimination.

Oxidative coupling of terminal acetylenes (1, 168169).3 Yamamoto and Sond-heimer have reported the synthesis of a tetraalkylated tetradehydro[18]annulenedione (5), of interest as a possible quinone, from (1). The acetylene (1) is oxidatively coupled... 

This amine is used to advantage instead of ammonia in the Glaser oxidative coupling of terminal acetylenes. ... 

Anhydrous material, prepared by refluxing the hydrate with acetic anhydride and washing the insoluble product with dry ether, is used in methanol-pyridine for the oxidative coupling of terminal acetylenes to diynes. Mechanism. Review. ... 

Cuprous ammonium chloride. The combination of cuprous chloride and ammonium chloride in a slightly acidic aqueous solution catalyzes oxidative (air) coupling of terminal acetylenes to diacetyienes. - The groups NHa, OH, COjH, and COjR do not interfere, in the synthesis formulated, cross coupling was accomplished in a mixture of ethanol and 0.08 A hydrochloric acid containing the catalyst. 

Coupling of terminal acetylenes with 3-chloropyridazines has been performed, using the Pd -Cu -EtjNH system, giving 3-(alkynyl)pyridazines in yields of up to 78% phenylacetylene gives (90) with 3-chloropyridazine 1-oxide but only gives tars with the isomeric 2-oxide/ 3-(Alkynyl)cinnolines have been similarly prepared from 3-iodo- and 3-bromo-cinnolines, and attempts to couple alkenes have been reported it is not unusual, in this type of reaction, to obtain small amounts of homo-coupling products i.e. biaryls), but an excellent yield of 3,3 -bicinnolinyl (81%) was obtained from 3-bromo-cinnoline and styrene. 

The mer-(CO)3(dppe)W(C=CHPh), 3, prepared as described below, contains a vinylidene ligand, a ligand that occupies a central role in the chemistry of monohapto carbon ligands in organometallic chemistry. Chemical transformations relate the vinylidene ligand to acetylides, -vinyls, acyls, and carbynes. Low oxidation state monohapto vinylidenes of tungsten have recently been implicated as catalysts in the polymerization of terminal acetylenes. ... 

The major metabolic pathway of terminal acetylenic derivatives is via oxidation to the corresponding acetic acid derivatives. Thus, Sullivan and coworkers and Wade and coworkers showed in 1979 that the major metabolites of ethynylbiphenyls in the rat were biphenyl-4-yl acetic acids. These metabolites are further oxidized to 4 -hydroxybiphenyl-4-yl acetic acids before being excreted in the urine (Scheme 4). Because the in vitro metabolism of biphenylacetylenes by rat liver microsomes requires nicotine-adenine-dinucleotide phosphate (NADPH) and molecular oxygen and is inhibited by carbon monoxide, it was concluded that the oxidative metabolism of the acetylenes to the corresponding acetic acid derivatives is mediated by cytochrome P450 . Acetic acid... 

Parallel chemical oxidation of deuterium labeled biphenylacetylene with metachloro-perbenzoic acid yielded the same product as was obtained in the enzymatic reaction. These observations exclude the possible oxidation of the acetylenic terminal C—H bond, because such a reaction would not be compatible with complete conservation of the deuterium atom. Thus, the formation of a ketene derivative was postulated (Scheme 5). However, the nature of the intermediate from which the ketene derivative is formed remains to be elucidated. An oxirene structure was suggested in parallel to alkene epoxidation however, oxirenes are very unstable species due to electronic and steric factors It is currently believed that a complex between the acetylenic n electrons and cytochrome P450 iron-oxene moiety is formed, leading to the formation of the ketene. ... 

Another well-known transformation of terminal acetylenes is an oxidative dimerization leading to butadiynes. Recently Pericas and coauthors have found that alkoxyacetylenes also can be oxidatively dimerized in the presence of a copper(I) catalyst yielding relatively stable 1,4-dialkoxy-1,3-butadienes 73 (equation 44). 

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