Side reactions oxidative addition

Since it is important to control the thermally activated side reactions in addition to the temperature, the time of the PEB must also be controlled. It should be noted that excessive time at an elevated temperature can result in undesirable additional chemical changes in the polymer such as crosslinking or oxidation that result in solubility changes of both the exposed and unexposed regions. 

Side reactions. Oxidative cyclization of unsaturated y9-dicarbonyl compounds that have two a-hydrogens will give products that still have one a-hydrogen and can be oxidized further. If the product is oxidized at a rate competitive with that of the starting material, mixtures of products will be obtained. For instance, oxidative cyclization of 27 affords 36% of 28 and 10% of dienone 30 formed by further eno-lization and oxidation of 28 to radical 29 and then to dienone 30 (Scheme 8) [16]. Competitive oxidation of the product is usually not a problem in intermolecular addition reactions because a vast excess of the oxidizable substrate, such as acetone... 

In contrast to benzene, toluene has a much lower melting point (-93 °C) which allows the use of much lower reaction temperatures which should aid in the prevention of any unwanted side-reactions. In addition, the oxidation of toluene is expected to result in more favorable yields, due to the presence of the activating effect of the methyl group which should facilitate aromatic substitution. As shown in Fig. 2.2, toluene can be converted to the monohydroxylated product in decent yields with the ortho-isomer as the predominant product. 

In contrast to quinoline N-oxides, the amination of pyridine N-oxides with NHqOH/TsCl or 2-aminopyridine/TsQ was unsuccessful due to a variety of side reactions nucleophilic addition at positiOTi 4, dimerization, tosylation of the amination product, and nucleophile itself [111]. 

Furthermore, the catalytic allylation of malonate with optically active (S)-( )-3-acetoxy-l-phenyl-1-butene (4) yields the (S)-( )-malonates 7 and 8 in a ratio of 92 8. Thus overall retention is observed in the catalytic reaction[23]. The intermediate complex 6 is formed by inversion. Then in the catalytic reaction of (5 )-(Z)-3-acetoxy-l-phenyl-l-butene (9) with malonate, the oxidative addition generates the complex 10, which has the sterically disfavored anti form. Then the n-a ir rearrangement (rotation) of the complex 10 moves the Pd from front to the rear side to give the favored syn complex 6, which has the same configuration as that from the (5 )-( )-acetate 4. Finally the (S)-( )-mal-onates 7 and 8 are obtained in a ratio of 90 10. Thus the reaction of (Z)-acetate 9 proceeds by inversion, n-a-ir rearrangement and inversion of configuration accompanied by Z to isomerization[24]. 

The best procedures for 3-vinylation or 3-arylation of the indole ring involve palladium intermediates. Vinylations can be done by Heck reactions starting with 3-halo or 3-sulfonyloxyindoles. Under the standard conditions the active catalyst is a Pd(0) species which reacts with the indole by oxidative addition. A major con.sideration is the stability of the 3-halo or 3-sulfonyloxyindoles and usually an EW substituent is required on nitrogen. The range of alkenes which have been used successfully is quite broad and includes examples with both ER and EW substituents. Examples are given in Table 11.3. An alkene which has received special attention is methyl a-acetamidoacrylate which is useful for introduction of the tryptophan side-chain. This reaction will be discussed further in Chapter 13. 

In the reaction of ethylene with sulfuric acid, several side reactions can lead to yield losses. These involve oxidation, hydrolysis—dehydration, and polymerization, especially at sulfuric acid concentrations >98 wt % the sulfur thoxide can oxidize by cycHc addition processes (99). 

Nitrile A-oxides, under reaction conditions used for the synthesis of isoxazoles, display four types of reactivity 1,3-cycloaddition 1,3-addition nucleophilic addition and dimerization. The first can give isoxazolines and isoxazoles directly. The second involves the nucleophilic addition of substrates to nitrile A-oxides and can give isoxazolines and isoxazoles indirectly. The third is the nucleophilic addition of undesirable nucleophiles to nitrile A-oxides and can be minimized or even eliminated by the proper selection of substrates and reaction conditions. The fourth is an undesirable side reaction which can often be avoided by generating the nitrile A-oxide in situ and by keeping its concentration low and by using a reactive acceptor (70E1169). 

Isomerization of 3-cephems (27) to 2-cephems (28) takes place in the presence of organic bases (e.g. pyridine) and is most facile when the carboxyl is esterified. Normally an equilibrium mixture of 3 7 (3-cephem/2-cephem) is reached. Since the 2-cephem isomers are not active as antibacterial agents, the rearrangement proved to be an undesirable side reaction that complicated acylation of the C-7 amine under certain conditions. A method for converting such mixtures to the desired 3-cephem isomer involves oxidation with concomitant rearrangement to the 3-cephem sulfoxide followed by reduction. Additions... 

Chemical Oxidation This process has not been widely utihzed because of its high cost. Onlv wEere the concentration of the target compound is very low will tlie quantity of oxidant required be low enough to justify treatment by chemical oxidation. The efficiency of this process is also low, as many side reactions can occur that will consume the oxidant. In addition, complete oxidation of organics to carbon dioxide and water often will not occur unless a significant overdose is used. However, renewed interest has recently occurred for two reasons. 

Platinum, especially as platinum oxide, has been used by many investigators. If this catalyst contains residual alkali, it is apt to be ineffective for aromatic ring reduction unless an acidic solvent is used (1,3,19) or unless the compound also contains a carbonyl group, as in acetophenone, where 1,4-and 1,6-addition are possible (46). Nickel, unless especially active, requires vigorous conditions—conditions that may promote side reactions. 

Nitration vs side-chain oxidation of toluene in dilute MA was investigated by Namba et al (Ref 69). They found that addition of sulfuric acid accelerated both reactions but nitration more than oxidation. Addition of water to the MA favors oxidation as does an increase in reaction temp... 

There are examples in which base radicals undergo reaction with adjacent base residues. The 5-(2 -deoxyuridinyl)methyl radical (63, Scheme 8.30) can forge an intrastrand cross-link with adjacent purine residues. Cross-link formation is favored with a guanine residue on the 5 -side of the pyrimidine radical and occurs under low-oxygen conditions. A mechanism was not proposed for this process, but presumably the reaction involves addition of the nucleobase alkyl radical to the C8-position of the adjacent purine residue. Molecular oxygen likely inhibits crosslink formation by trapping the radical 63, as shown in Scheme 8.24. The radical intermediate 89 must undergo oxidation to yield the final cross-linked product 90,... 

Complex (92) has been obtained from the reaction of 1,2-disilylbenzene and [Ni(dmpe)2] at 80°C.315 The reaction is assumed to proceed via oxidative addition of Si—H bonds and subsequent elimination of H2, and some intermediates have been detected spectroscopically. (92) is described as a Nilv species, but care has to be taken, since a related hexasilylpalladium complex, initially formulated as PdVI,316 should better be viewed as Pd11 with two side-on bound Si—Si... 

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