Carboxylation, selective oxidation

Nickel peroxide is a solid, insoluble oxidant prepared by reaction of nickel (II) salts with hypochlorite or ozone in aqueous alkaline solution. This reagent when used in nonpolar medium is similar to, but more reactive than, activated manganese dioxide in selectively oxidizing allylic or acetylenic alcohols. It also reacts rapidly with amines, phenols, hydrazones and sulfides so that selective oxidation of allylic alcohols in the presence of these functionalities may not be possible. In basic media the oxidizing power of nickel peroxide is increased and saturated primary alcohols can be oxidized directly to carboxylic acids. In the presence of ammonia at —20°, primary allylic alcohols give amides while at elevated temperatures nitriles are formed. At elevated temperatures efficient cleavage of a-glycols, a-ketols... 

Selective oxidation of methyl pyrroles 65 possessing an a-carboxylic ester and sensitive p-substituents can be accomplished using cerium triflate in methanol <96TL315>. Moreover, the resultant a-methoxymethylpyrroles 66 may be converted to dipyrrylmethanes 67 in a "one-pot" sequence by treatment with 48% HBr. The dipyrrylmethanes, in turn, can be further oxidized to dipyrryl ketones by ceric ammonium nitrate <96JHC221>. 

Reversed micelles have also shown to be useful not only in bioconversions, but also in organic synthesis. Shield et al. (1986) have reviewed this subject and brought out its advantages in peptide synthesis, oxidation or reduction of steroids, selective oxidation of isomeric mixtures of aromatics, etc. In the oxidation of aromatic aldehydes to carboxylic acids with enzymes hosted in reverse micelles, the ortho substituted substrates react much more slowly than other isomers. 

One feature of this oxidation system is that it can selectively oxidize primary alcohols in preference to secondary alcohols, as illustrated by Entry 2 in Scheme 12.5. The reagent can also be used to oxidize primary alcohols to carboxylic acids by a subsequent oxidation with sodium chlorite.34 Entry 3 shows the selective oxidation of a primary alcohol in a carbohydrate to a carboxylic acid without affecting the secondary alcohol group. Entry 5 is a large-scale preparation that uses NaC102 in conjunction with bleach as the stoichiometric oxidant. 

Attempts to achieve selective oxidations of hydrocarbons or other compounds when the desired site of attack is remote from an activating functional group are faced with several difficulties. With powerful transition-metal oxidants, the initial oxidation products are almost always more susceptible to oxidation than the starting material. When a hydrocarbon is oxidized, it is likely to be oxidized to a carboxylic acid, with chain cleavage by successive oxidation of alcohol and carbonyl intermediates. There are a few circumstances under which oxidations of hydrocarbons can be synthetically useful processes. One group involves catalytic industrial processes. Much effort has been expended on the development of selective catalytic oxidation processes and several have economic importance. We focus on several reactions that are used on a laboratory scale. 

Table 3 indicates that 5%Pt,l%Bi/C is active for three reaction cycles in the selective oxidation of the chosen alcohols. For primary alcohols the use of water as solvent can promote the aldehyde to carboxylic acid reaction (3). This effect is observed in the selective oxidation of 1-octanol where octanoic acid is formed with 97% selectivity in the first cycle dropping to 81% in the third. In the selective oxidation of geraniol only citral is observed as the oxidation product. The presence of the double bond stabilises the aldehyde even in the presence of... 

Early observations by Heyns established that selective oxidation of carbohydrates is possible for example, the hydroxymethyl group involving C-l in L-sorbopyranose could be converted into a carboxyl... 

Chromium trioxide in pyridine selectively oxidizes the hydroxymethyl groups in thymidine, 2 -deoxyadenosine, 2 -deoxyguano-sine, and 2 -deoxycytidine to carboxyl groups,525 but the partial liberation of the free, heterocyclic bases in the reactions suggested that oxidation at C-3 also occurs to some extent. 

Selective oxidation of dimethylanisoles (11,441). An o- or a p-methyl group in a dimethylanisole that bears an m-methyl group is selectively oxidized by K2S208 catalyzed by CuS04 to an aldehyde group, which can be oxidized further to a carboxyl group by sodium chlorite.1... 

Scheme 9.1 shows a generalized sequence of reactions for the oxidation of an alkane, via alcohol, ketone and carboxylic acid, to the completely oxidized products, water and carbon dioxide. The latter are often referred to as combustion products as they are the same as those formed by burning hydrocarbons. These are not normally desirable chemical products unless it is necessary to destroy a toxic, hazardous or otherwise unwanted waste material. Oxidation itself is not difficult to achieve, and is a highly exothermic or even explosive process. Selective oxidation, however, is a much greater challenge, as it is important to stop the sequence at the desired product without proceeding further down the oxidation pathway. 

Recently, Choudary et al. reported the first example of catalytic N-oxidation of tertiary amines by tungstate-exchanged Mg/Al LDHs in water [113], and the halodecarboxylation of Q ,/l-unsaturated aromatic carboxylic acids to /1-bromostyrenes has also been achieved for the first time, using a molybdate-exchanged Mg/Al LDH catalyst [114] this latter catalyst was active for selective oxidation [ 115,116]. 

The resulting butene molecule under2 oes selective oxidation where the two terminal metbyl groups are converted to carboxylic acid groups... 

Spent 2,2,6,6-tetramethyl-l-oxopiperidinium can be regenerated directly at a platinum anode in aqueous acetonitrile and aldehyde products do not undergo further oxidation to the carboxylic acid [37]. Either of the two racemic quinolyl-l-oxyls 4 functions better as catalyst for the oxidation of primaiy and secondary al-kanols, but the chiral forms do not achieve selective oxidation of one enantiomer of... 

The effects of solvents were also reported (24). Lower aliphatic carboxylic acids, such as butyric and valeric, gave the best results with respect to the selective oxidation of acrolein. For butyric acid, the conversion of acrolein and the selectivity of acrylic acid were 45.1 and 86.0%, respectively, with 5 X 10 4 mole of Co(acac)3 per liter of solution for 4 hours at 35°C. 

Selective oxidation of N-1 of adenine derivatives is typically carried out with peracids <1998JOC3213>, but has also been achieved with hydrogen peroxide and catalytic methyltrioxorhenium (Scheme 10) <2000T10031>. The inclusion of pyridazine-2-carboxylic acid as a stabilizer for reactive rhenium peroxides led to increased yields. Caffeine did not react under these conditions. 

Beginning with the enantiomer of 27, the reaction sequence outlined in Fig. 4 was repeated, leading to compound 14 (63). Selective oxidation of 14 afforded the carboxylic acid 23(63). The arsenic-containing nucleoside 25 was obtained by treating 5 -chloro-5 -deoxyadenosine with excess dimethylarsinosodium and oxidation of the resultant arsine (63). 

The catalysis of the selective oxidation of alkanes is a commercially important process that utilizes cobalt carboxylate catalysts at elevated (165°C, 10 atm air) temperatures and pressures (98). Recently, it has been demonstrated that [Co(NCCH3)4][(PF6)2], prepared in situ from CoCl2 and AgPF6 in acetonitrile, was active in the selective oxidation of alkanes (adamantane and cyclohexane) under somewhat milder conditions (75°C, 3 atm air) (99). Further, under these milder conditions, the commercial catalyst system exhibited no measurable activity. Experiments were reported that indicated that the mechanism of the reaction involves a free radical chain mechanism in which the cobalt complex acts both as a chain initiator and as a hydroperoxide decomposition catalyst. 

Table 1. Selected oxidations of saturated primary alcohols to carboxylic acids at the nickel hydroxide electrode...

Selective oxidation of polymethylpyrimidines. 2,4-Di- and 2,4,6-trimethyl-pyrimidines are selectively oxidized to 4-carboxylic acids by a slight excess of Se02 in pyridine. Yields are about 40-65%. This increased reactivity of a 4-methyl group of polymethylpyrimidines is also observed in reaction with ethyl nitrite in liquid ammonia to form 4-aldoximcs and with ethyl benzoate in the presence of KOC2H to form phenacyl derivatives. 

Terminal alkynes are prone to undergo facile oxidative cleavage to yield carboxylic acids with loss of the terminal carbon atom. In fact, most of the oxidizing agents that can be used in the selective oxidation of internal alkenes to 1,2-diketones [Ru04,711 PhIO with Ru catalysts,712 KMn04,713 T1(N03)3,716 0s04718] convert terminal alkynes to carboxylic acids. 

Optically pure piperazine-2-carboxylic acid (22) and related derivatives, substituted at position 5, are synthesized from piperazine-2,5-diones 50 derived from Xaa-Ser dipeptides as educts, where the substitution R1 at position 5 depends on the side group of the aminoacyl moiety (Scheme 10). After reduction of the piperazine-2,5-diones 50 to 5-alkyl-2-(hy-droxymethyl)piperazines 51 and urethane-type protection of both the imino groups, the desired A,A -bis-protected piperazine-2-carboxylic acid or related 5-alkyl derivatives 52 are obtained by selective oxidation of the hydroxymethyl group. 240 ... 

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