Oxidative dimerisation

In the presence of dehydrating agents, such as trialkyl orthoformates the PdCl2/ CUCI2 redox system catalyzes the reaction of CO, O2 and ROH to form dialkyl oxalates [221,222], equations (167) and (168). 

If the dehydrating agent is not present, then CO2 is formed and no oxalates are found. Ferric chloride can be used in place of copper(II) chloride as a cocatalyst, but the alcohol is oxidized to an acid in a competing reaction to some extent. 

Fenton and Steinwand suggest a catalyst regeneration scheme as shown in equation (170), which differs from the frequently described, equations (171) and (172) regeneration reaction for this system [221]. 

Gaenzler, Klaus and Schroeder report [222] that esters of oxalic acid can be produced in 90% selectivity at 60-70 C at 120 atmospheres pressure. In a typical reaction for dimethyl oxalate synthesis, an autoclave is charged with PdCl2 (1.5 g), DCl (0.75 g), anhydrous CuCU (10 g) and methanol (400g). The reactor (one-fourth filled) is pressurized with CO (100 atm.) and O2 (20 atm.) and warmed to 60 C. An exothermic reaction ensues and 37 g of dimethyl oxalate are distilled from the reaction mixture. The selectivity to the ester is 90% and the yield based on CO charged to the reactor is 9.65%. 

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A. P. Rauter, F. Piedade, T. Almeida, R. Ramalho, M. J. Ferreira, R. Resende, J. Amado, H. Pereira, J. Justino, A. Neves, F. V. M. Silva, and T. Canda, Sugar bislactones by one-step oxidative dimerisation with pyridinium chlorochromate versus regioselective oxidation of vicinal diols, Carbohydr. Res., 339 (2004) 1889-1897. 

Oxidative dimerization gives reasonable yields of vtc-dinitroalkanes for some substrates 2,3-dimethyl-2,3-dinitrobutane (48, 53 %) and 3,4-dimethyl-3,4-dinitrohexane (37 %) are obtained from 2-nitropropane (76) and 2-nitrobutane respectively.However, oxidative dimerization fails to convert 1,1-dinitroethane and trinitromethane into 2,2,3,3-tetranitrobutane and hexanitroethane respectively. Additionally, oxidative dimerisation is not a feasible route for the synthesis of v/c-dinitroalkanes from primary nitroalkanes. Although oxidative dimerization is limited in scope, and yields are often poor, the starting materials are usually inexpensive. 

Losartan, an ACE inhibitor, follows two oxidation-mediated degradation pathways [66]. The first is via the oxidation of the hydroxyl group to the aldehyde derivative. Second, via oxidative dimerisation forming two different degradation products (mediated by the condensation of two losartan molecules and the subsequent elimination of water). 

The copper catalyzed oxidative dimerisation of arylboronic acids was also used for the preparation of symmetrical bithiophene derivatives. 2-Formylhiophene-3-boronic acid and 5-boronic acid were both dimerised successfully giving the appropriate dithiophenes in 35% and 41% yield (6.98.). The optimised coupling conditions included running the reactions in DMF in the presence of 50 mol% copper(II) acetate.130... 

A final type of oxidation reaction associated with the loss of hydrogen atoms is seen in the oxidative dimerisation of phenols. In general, the oxidation of phenols, in either the presence or absence of metal ions, is not a clean process, and many products, derived from... 

The photostimulated reactions of thiolate anions with 2-halo-2 -nitropropane derivatives yield both oc-nitrosulphides via an S l pathway and disulphides (equation 71a)282 284. In contrast with the case of the oxidative dimerisation products of the mono-enolates, the disulphides are formed via an ionic mechanism nucleophilic attack by the thiolate anion on the a-halogen and subsequent reaction of a second thiolate with the sulphenyl halide. As expected for such a process, disulphide formation is favoured (and thus a-nitrosulphide formation is disfavoured) the more nucleophilic the thiolate (i.e. derived from a less acidic thiol) and the easier the abstraction of the halo-substituent (i.e. I > Br > Cl). Use of the protic solvent methanol instead of the usual dipolar aprotic solvents for the reaction of equation 71a is detrimental to the yield of the S l substitution products exclusively disulphides are formed285 (equation 71b). Methanol solvation probably retards the dissociation of the radical anion intermediate in the SRN reaction, into radical and anion, and hence retards the chain reaction relative to the ionic reaction. The non-nucleophilic methylsulphinate ion gives only an S l reaction product with 2-bromo-2-nitropropane286. 

Neither diferrocenyl ether ( Fc-O-Fc ) nor diferrocenyl peroxide ( Fc-OO-Fc ) are known so far. However, the corresponding compounds of sulfur, selenium and tellurium are well characterized (see Sect. 5.8). The dichalcogenides Fc-EE-Fc (E = S, Se, Te) are easily obtained by oxidative dimerisation of either the lithium ferrocenyl chalcogenate, Fc-ELi, or the chalcogenols, Fc-EH, for which they can be used as stable precursors (Sect. 5.3.3) [91, 95]. Reaction of the dichalcogenides Fc-EE-Fc with Fc-Li is a possible route to the monochalcogenides, Fc-E-Fc, but the yields are... 

In the case of 2,6-disubstituted phenols, the nature of the bismuth reagent, the nature of the alkyl substituents and the reaction conditions determined the outcome of the reactions. 2 Thus, in the reactions of 2,6-dimethylphenol (19) with pentaphenylbismuth (4) or with tetraphenylbismuthonium derivatives under basic conditions, ortho C-phenylation resulted in the formation of 6-phenylcyclo-hexadienone (20) in good yield. On the other hand, oxidative dimerisation took place in the reaction of 2,6-dimethylphenol with triphenylbismuth carbonate to afford the diphenoquinone (21) quantitatively 25... 

The similar oxidative dimerisation of 2-bromothiophene illustrates selectivity in the presence of halogen. The silver fluoride seems to be the oxidant as it is reduced to silver metal during the reaction. " ... 

Both sodium and nickel bring about oxidative dimerisations, despite the apparently reducing conditions, the former giving 4,4 -bipyridine and the latter 2,2 -bipyridine. Each reaction is considered to involve the same anion-radical resulting from transfer of an electron from metal to heterocycle, and the species has been observed by ESR spectroscopy, when generated by single electron transfer (SET) from lithium diiso-propylamide. In the case of nickel, the 2,2 -mode of dimerisation may be favoured by chelation to the metal surface. Bipyridyls are important for the preparation of Paraquat-type weedkillers. 

CA and actinocin, and the intercalating properties of the latter, prompted Nair [195] to hypothesise the existence of a regulatory mechanism for RNA synthesis, involving the oxidative dimerisation of HA. Following this suggestion, CA could specifically interact with DNA, preferably on guanine residues, such as actinomycin D does [196]. This was confirmed by the observation, that either preformed CA and HA (converted to CA by the nuclear fraction) were actually bound by DNA, in correspondence with guanine residues. However, no data exist about the actual formation and concentration of CA within the rat liver. 

Asymmetric oxidative dimerisation of S(+)-3,4,8-trimethyl-5,6.7,8-tetrahydro-2-naphthol in ether with potassium ferricyanide in aqueous 0.2M sodium hydroxide was effected by stirring at ambient temperature for 2 hours to afford the S,S-(+)-trans dimer in 62% yield (ref. 14). 

Oxidative dimerisation of 4-methoxyphenol has been mentioned in the previous chapter. 4-Methylphenol in bromobenzene containing caesium carbonate, the only effective base for the reaction, was mixed with 10mole% of a rhodium complex at ambient temperature. Heating of the mixture at 90X for 24 hours afforded a 51% yield of the coupled product, 2,2 -dihydroxy-5,5 -dimethylbiphenyl (ref. 73). The yield was improved by the addition of 2.2 moles of water. 

Loss of the tert-butyl groups occurred in the oxidative dimerisation of 2-methyl-6-tert-butylphenol in 54% yield finally to 3,3 -dimethyl-4,4 -dihydroxybiphenyl by heating with a catalytic quantity of ferric manganese naphthoate at 160°C during 6 hours in a stream of dry air to afford first a dimeric intermediate which after acidic washing in xylene solution was dealkylated by refluxing for 6 hours with 4-toluenesulphonic acid (ref.99). 

Oxidative dimerisation of a guaiacyl system, namely prestegane B, in dichloromethane containing boron trifluoride etherate was achieved in 80% yield by addition to a stirred suspension of ruthenium dioxide dihydrate in dichloromethane containing triflic acid/triflic anhydride (in the proportions 8 2 1) at 0°C followed by reaction for 3 hours (ref.73). 

In the area of oxidative dimerisation, a solution of 3,4-dimethoxytoluene in dichloromethane was added to silica gel impregnated with ferric chloride. After the solvent had been removed and the residue left for 1 hour, 2,2 -dimethyl-4,4, 5,5 -tetramethoxybiphenyl was formed in 95% yield (ref.74). 

Oxidative dimerisation at the side-chain has been described as relevant to the synthesis of lignans (ref.75). Methyl 3,4-dimethoxybenzoylacetate in refluxing aqueous acetonitrile treated with potassium persulphate and a small amount of copper sulphate in an inert atmosphere produced after several hours (monitored by TLC), the dimer shown (racemateimeso 3 1) in 58% yield. 

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