Azoles, metalation

Orientation in azole rings containing three or four heteroatoms Effect of azole ring structure and of substituents Proton acids on neutral azoles basicity of azoles Proton acids on azole anions acidity of azoles Metal ions... 

Many examples are known of complexes between metal cations and both neutral azoles and azole anions. Overlap between the cf-orbltals of the metal atom and the azole rr-orbitals is believed to increase the stability of many of these complexes. 

Azoles can form stable compounds in which metallic and metalloid atoms are linked to nitrogen. For example, pyrazoles and imidazoles Af-substituted by B, Si, P and Hg groups are made in this way. Imidazoles with a free NH group can be Af-trimethylsilylated and Af-cyanated (with cyanogen bromide). Imidazoles of low basicity can be Af-nitrated. 

Oxygen-containing azoles are readily reduced, usually with ring scission. Only acyclic products have been reported from the reductions with complex metal hydrides of oxazoles (e.g. 209 210), isoxazoles (e.g. 211 212), benzoxazoles (e.g. 213 214) and benzoxazolinones (e.g. 215, 216->214). Reductions of 1,2,4-oxadiazoles always involve ring scission. Lithium aluminum hydride breaks the C—O bond in the ring Scheme 19) 76AHC(20)65>. 

Neutral azoles are readily C-lithiated by K-butyllithium provided they do not contain a free NH group (Table 6). Derivatives with two heteroatoms in the 1,3-orientation undergo lithiation preferentially at the 2-position other compounds are lithiated at the 5-position. Attempted metallation of isoxazoles usually causes ring opening via proton loss at the 3-or 5-position (Section 4.02.2.1.7.5) however, if both of these positions are substituted, normal lithiation occurs at the 4-position (Scheme 21). 

For ring-opening reactions of C-metallated azoles, see Section 4.02.3.8. 

The azole ring can activate metallation at the ortho position of an Af-phenyl group, as in 1-phenyIpyrazoIes. 

Additional sections of this chapter cover (1) tautomeric reactions of azoles and their derivatives in electronically excited states and (2) stabilization of certain tautomers in their metal complexes. 

Tautomeric rearrangements of transition-metal complexes with azole ligands are relatively scarce. The fluxional behavior of the rhodium complex 43 with a neutral 3,5-dimethylpyrazole was explained as the result of rapid processes of metallotropy and prototropy occurring simultaneously (Scheme 24) [74JOM(C)51],... 

VI. Stabilization of Unusual Tautomeric Forms of Azoles and Their Derivatives in Metal Coordination Compounds... 

In contrast with aminoazole ligands, hydrazones of azoles adopt the imino form in their metal complexes 360 [X = O (93ZNK863), X = S (91MC110)]. 

Whereas vicinal hydroxy, mercapto, and hydroselenoaldimines of azoles strongly prefer the aminomethylene tautomeric form (Section II,E,2), their metal chelates 380 are characterized by.pronounced equalization of bond lengths within the chelate ring, which makes their structures similar to those expected for the aldimine tautomeric type. 

The mechanisms of the electrophilic substitutions in the isoxazole nucleus have not yet been studied. They should not differ fundamentally from those usually accepted for the substitution of aromatic systems but the structural specificity of the isoxazole ring might give rise to some peculiarities, as recently specially discussed.One important point is that isoxazole shows a clearcut tendency to form coordination compounds. Just as pyridine and other azoles, isoxazoles coordinate with halogens and the salts of heavy metals, for example of cadmium,mercury,zinc. Such coordination... 

Metalation of 4,5-dihydro-2-[(7 )-sulfinylmethyl]oxazoles (e.g., 2) with butyllithium at -90 C and reaction of the chiral azaenolates with aldehydes furnishes the hydroxyalkylated sulfinylox-azole derivatives 3 which are desulfurized to give the 4,5-dihydro-2-(2-hydroxyalkyl)oxazoles 4. The corresponding 3-hydroxy acids 5 are obtained by acidic hydrolysis in 60-85% overall yield and 26-53% ee31. 

Azoles provide effective corrosion inhibition primarily by chemisorption of the molecule on the metal substrate. Several different types of azoles are available for incorporation into formulations used for the corrosion inhibition of closed loop LPHW heating and low MU requirement, LP steam heating systems. 

Although azoles are commonly thought of as only yellow metal inhibitors, they are, in fact, used for corrosion inhibition in a wider range of metals such as steel and aluminum. They also are often incorporated in molybdate-based programs to both provide some synergism and reduce the level of molybdate required. Azoles also are employed in many types of organic-based formulations, where they improve the overall protection of steel and reduce the risk of corrosion of yellow metals due to the corrosive action of some common phosphonates. 

Pinacolone, o-(diphenylphosphino)benzoyl-coordination chemistry, 2, 401 Ping-pong reactions copper(II) complexes, 5, 717 Piperidine, /V-hydroxy-metal complexes, 2, 797 P a values azole ligands, 2, 77 Plant roots amino acids, 2, 962 carboxylic adds, 2,962 Plants... 

Minghetti, G., BanditeDi, G. and Bonati, E. (1979) Metal derivatives of azoles. 3. The pyrazolato anion (and homologs) as a mono- or bidentate ligand preparation and reactivity of tri-, hi-, and mononudear... 

The a-metalation of azoles (aromatic nitrogen-containing five-mem-bered rings) is a much more facile process than that for the analogous saturated systems, and a small number of heterocycles containing free NH groups can undergo some direct lithiation, despite the ionization of the... 

Direct metalation at the /8-carbon of azoles can also occur, although it is a much less facile process than that for the adjacent a-carbon, because of the greater charge density at what is normally a nucleophilic center in enamine-type reactions. Thus in order for reaction to occur, it is usually necessary to either block the a-position or activate the /3-site. If both factors are accommodated than /8-metalation occurs readily, and thus 3,4-disubstituted-2(3//)-thiazolethiones undergo direct lithiation with lithium diisopropylamide (LDA) at the 5-position, which is activated by the inductive effect of the adjacent sulfur (Scheme 4) (80S800). 

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