Cobalamins Cobaloximes

We shall report here the synthesis of cobalt-carbon bond involved in coenzyme B12 and cobalamine, cobaloxime, and Schiff base analog models, together with some aspects of their reactivity. 

One last point should be mentioned with respect to the 19F NMR results. Included in Table 6 is the chemical shift for CF 3-cobaloxime. The chemical shift for this species is at significantly lower field than that for CF3-cobalamin. It therefore, appears that the bis(dimethylglyoximato) ring system is considerably more electron withdrawing than the corrin system. As a result, the Co—C-bond is considerably more stable in these systems. These data once again lead one to question to what extent these inorganic systems should be considered useful models for B12. 

A special mention13 may be made of cobalt complexes the [Co(HDMG)2] (w = 0, 1) has been named cobaloxime by analogy with cobalamin , which is another name of vitamin B,2. 

Fig. 19. Direct-addition mechanism for addition of vinyl ethers to cobalamin and cobaloximes.

Cobalamine 7i-cations, applications, 7, 48 Cobalamines, Co-C homolysis, 7, 35 Cobalamins, characteristics and reactions, 1, 884 Cobaloximes... 

The types of model systems in which 5-coordinate species have been invoked range from the relatively electron-deficient cobaloximes to the relatively electron-rich Schiff base complexes, where the corrin ring in cobal-amins is replaced by two dioximato ligands or by a quadridentate N202 dinegative Schiff base ligand, respectively. These two classes of models, in fact, appear to bracket many characteristics of cobalamins since the cobaloximes are too electron-deficient and the Schiff base complexes are too electron-rich [136], As such, an understanding of the differences in properties between these two types... 

Bis[2,3-butanedione dioximato(l-)] cobalt derivatives (cobaloximes(I)) appear in most respects to be good model systems for the cobalamins of the vitamin B12 coenzyme.1 The central cobalt atom exhibits three stable oxidation states... 

Recrystallization from water/acetone (even at a basic pH) causes some hydrolysis of the acetal. (2,2-Diethoxyethyl)cobalamin, like all alkyl cobalamins, is light sensitive in solution in addition, and unlike most other alkylcobalamins, it is add sensitive, decomposing to both (formylmethyl)cobalamin and aqua-cobalamin.2 The formation of other alkylcobalamins and cobaloximes by reaction with enol ethers has been described.2... 

The active LCo complexes indicated above can be used to test this theory. Porphyrins and phthalocya-nines have an O-shaped system which has a more extended -system than that in cobalamins, but it does not provide a substantial increase in reactivity. It should be noted that the hydrogen bonds of the cobaloxime catalysts are essentially as effective as 7r-bonds in continuing the effects of delocalization around the macrocyclic ring. This effect has been noted elsewhere.142 Catalyst 11 comprises an O-shaped -system. Replacement of one jr-bond with a a-bond in the analogue 13 significantly affects the catalytic properties since both complexes retain their O-shape with -conjugation. Additional replacement of "T-bonds with o-bonds leads to a complete loss of catalytic properties as chelates 13, 20, or 21 indicate. Chelate 22, cannot be a CCT catalyst because of the absence of interaction between the two jr-systems. Chelate 34 is an exception its molecular structure is similar to 21 and 13, but it catalyzes chain transfer with a measurable rate. A possible explanation of this phenomenon will be provided in section 3.7. 

Strong bases (pKa > 11) also convert alkyl cobaloximes and alkyl cobalamins into -complexes such as 73. This is usually followed by further decomposition to olefins and alkanes. The stability of complexes such as 73 depends very much upon X and the nature of the axial ligand in the cobalt chelate.98-218-227 230 Strong nucleophiles such as RS or CN can cause decomposition of LCo—R as well.98-231 Under the normal conditions of radical polymerization, Markovnikov organocobaloxime should form whenever the hydride, LCoH, appears in the polymerization mixture. If 1,2-vinylidene monomers are being polymerized, then thermally unstable tert-alkyl-cobaloximes are obtained. These species are expected to undergo homolytic Co—C cleavage to yield tertiary radicals. 

Dicyanocobyrinic acid heptamethyl ester (Fig. 2) is useful because of its relative simplicity compared to cobalamins, and because of its high solubility in organic solvents. It is prepared by reaction of vitamin B12 with Me0H/H2S04 and then with KCN . Like Bi2 and cobaloximes , it is reduced to Co(I) with NaBH4 and alkylated by alkyl hdides . 

Attempts have been made to mimic the above reactions under nonenzymatic conditions. Methylcobalamin methylates homocysteine, but the reaction is a free radical process . Also, MeH4THF does not methylate cobaloxime(I) or Bj2s. AI-Methylamines are also unreactive toward Co(I) species. Tetraalkylammonium compounds alkylate Co(I) nucleophiles to form alkylcobalt compounds" it is possible that MeH4THF is protonated by the enzyme and Ais methylates the cobalamin. Methylation in low yield of cobalamin(I) by MeH4THF at low pH has been disputed. ... 

Finally, cobalt(III) cobaloximes and cobalamins have been found to react with vinyl ethers in nucleophilic solvents in the presence of a weak base to form )8-substituted ethylcobalt complexes [71] (e.g. Eqn. 29). 

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