Azole complexes

Example 5 Hayakawa and Noyori group in their studies on new activators for phosphoroamidite coupling reactions have applied the most effective member of the group of acid/azole complexes AT-(phenyl)imidazolium tri-flate (N-PhIMT) in the efficient synthesis of biologically important compounds [20j]. A noteworthy example is synthesis of cytidine-5 -monophos-pho-AT-acetylneuraminic acid. This compound is a source of sialic acid in the sialyltransferase-catalysed biosynthesis of sialyl oligosaccharides [25]. 

Hartree-Fock calculations with the 3-21G and 6-31G basis sets have been performed to study the structure and energetics of Na+, K+ and Al+ -azole complexes. Structures have been fully optimized at the 3-21G level. Calculated X+ (X = H, Li, Na, K, Al) binding energies of 1,2,3-triazole show that cation association energies follow the sequence Li+ > Al+ > Na+ > K+, and all of them are much smaller than the corresponding protonation energies (92JPC3022). 

Azoles are different from the fundamental five-membered heterocycles and azines. They form mainly complexes with coordination via the pyridinic N atom (1). Azoles may be monodentate (128) or bridging (129) ligands. Because only the cr- (N) coordination has so far been proven structurally, it is possible to subdivide the azole complexes according to the type of the en-docyclic heteroatoms. 

The structure of complex compound 687 (R = Ph, M=W) was proved by x-ray diffraction. These data testify that for the first time (compare with Refs. 5, 263, and 264) azole complexes were obtained in which the metal coordinates with an endocyclic donor center of nonpyridine type. Evidently, the interaction (3.95) of... 

The first n-complexes of azole series 711 were isolated recently (3.147) [75], However, the perspectives of Scheme (4.15) for obtaining other r 5-complexes of azole ligands are unclear because of the absence of reported data on the gas-phase syntheses of azole complexes. 

Structurally characterized trivalent manganese imidazole or imid-azolate complexes are also extremely rare. Current examples are limited to Mn(III) porphyrins (61), Mn(III) thiolates (Section III,B)> a Mn(III) salicylate complex (Section IV,B) and Mn(III) and Mn(IV) carboxylate complexes (Section VI,B) (62). None of these complexes contains a Mn-to-imidazole ratio greater than two consequently, no structural model for Mn SOD exists presently in Mn coordination chemistry. However, a five-coordinate Mn(II) monomer with three imidazole ligands, Mn(2-Me-ImH)3Cl2 (ImH = imidazole), has been characterized by X-ray diffraction techniques (63). 

Acid salts of imidazole- and benzimidazole-related compounds have been evaluated as alternative promoters to the various activators developed for the condensation of a nucleoside phosphoramidite and a nucleoside. The acid/azole complexes were developed to circumvent some of the disadvantages most commonly encountered in both solution- and solid-phases. Azolium promoters were shown to achieve high yielding coupling reactions even with nucleosides of low reactivity. Hayakawa has also reviewed and broadened the recent phosphoramidite methodologies by describing the versatility of allyl and allyloxycar-... 

Azoles, complexes with halogens and halides 80MI29. 

Metal chelates are preser t in the complexes of Schiff bases of amino-(X = NR2), hydroxy- (X = O), and mercapto- (X = S) derivatives of monoheteroaromatic five-membered systems, azoles, and azines. A few publications on the complexes of azomethines of the monoheteroaromatic five-membered systems have appeared only recently. The X-ray structural study of copper(II) bis(2-N-n-octyliminomethyl)benzo[ 7]thio-phene-3-olate) 199 (04ZNK1696) is interesting in the sense that its square-planar structure is complemented by an extended octahedral one due to the intermolecular contacts of the thiophene sulfur with the copper site. Among the azole complexes, azomethine derivatives of p3Tazole (Equation (32)) prevail (05RCR193). There are several types of coordination units (N,N-, N,0-, N,S-, N,Se-) created by variation of the donor sites X in position 5 of the pyrazole ring. When X = O, S, Se, tautomer b is realized, whereas when X = NR, tautomer a predominates (Equation (32)). However, irrespective of the type of tautomer, in the chelates the coordination units have practically equalized bonds. 

Complex tautomerism for azoles with heteroatoms in the 1,2-positions occurs for pyrazoles which are not substituted on nitrogen. Scheme 10 shows the four important tautomeric structures (148)-(151) for 3-methylpyrazolin-5-one, and (152) and (153) as examples of other possible structures. A detailed investigation of this system disclosed that in aqueous solution (polar medium) the importance of the tautomers is (149) > (151) (150) or (148), whereas in cyclohexane solution (non-polar medium) (151) > (148) (149) or (150). 

In this initial section the reactivities of the major types of azole aromatic rings are briefly considered in comparison with those which would be expected on the basis of electronic theory, and the reactions of these heteroaromatic systems are compared among themselves and with similar reactions of aliphatic and benzenoid compounds. Later in this chapter all the reactions are reconsidered in more detail. It is postulated that the reactions of azoles can only be rationalized and understood with reference to the complex tautomeric and acid-base equilibria shown by these systems. Tautomeric equilibria are discussed in Chapter 4.01. Acid-base equilibria are considered in Section 4.02.1.3 of the present chapter. 

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. 

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>. 

Alkyl radicals produced by oxidative decarboxylation of carboxylic acids are nucleophilic and attack protonated azoles at the most electron-deficient sites. Thus imidazole and 1-alkylimidazoles are alkylated exclusively at the 2-position (80AHC(27)241). Similarly, thiazoles are attacked in acidic media by methyl and propyl radicals to give 2-substituted derivatives in moderate yields, with smaller amounts of 5-substitution. These reactions have been reviewed (74AHC(i6)123) the mechanism involves an intermediate cr-complex. 

H-Benzo[a]carbazole, 4,4a,5,l 1,1 la,l Ib-hexahydro-synthesis, 4, 283 Benzo[b]carbazole, N-acetyl-photochemical rearrangements, 4, 204 Benzo[/]chroman-4-one, 9-hydroxy-2,2-dimethyl-synthesis, 3, 851 Benzochromanones synthesis, 3, 850, 851, 855 Benzochromones synthesis, 3, 821 Benzocinnoline-N-imide ring expansion, 7, 255 Benzocinnolines synthesis, 2, 69, 75 UV, 2, 127 Benzocoumarins synthesis, 3, 810 Benzo[15]crown-5 potassium complex crystal stmcture, 7, 735 sodium complex crystal stmcture, 7, 735 Benzo[ 18]cr own-6 membrane transport and, 7, 756 Benzo[b]cyclohepta[d]furans synthesis, 4, 106 Benzocycloheptathi azoles synthesis, 5, 120... 

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],... 

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

Dimethyl-, 3,5-diphenyl-, and 3,5-di-tert-butylpyrazolato potassium salts with [Cp RuCl]4 give the first structurally proven -coordinated complexes 48 (R = Me, t-Bu, Ph) in the azole series (99JA4536). 

Reaction of [Rh(rj -Cp )2(/r-0H)3]2C104 with excess pyrazole or 4-bromopyr-azole and potassium hydroxide forms the neutral complexes 163 (R = H, Br)... 

Organometallic Complexes of Polyheteroatom Azoles Other than Pyrazole... 

Triazole (HL) with Me SAuCl, the gold(I) species, in the presence of potassium hydroxide gives the polymeric complexes [AuL] with exobidentate coordination mode of the azolate ligand (79IC658). 

The third chapter of Volume 83 of Advances in Heterocyclic Chemistry is Part 5 in the series by Alexander Sadimenko (Fort Hare, Republic of South Africa) and covers organometallic complexes of azoles other than pyrazoles. This chapter continues the series of which parts 1-4 were published in volumes 78, 79, 80, and 8l of Advances in Heterocyclic Chemistry, respectively. 

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