Complexation oximes

Several structural modifications of the C-9 ketone of erythromycin have been explored oximes and hydrazones are less prone to intramolecular cydization, but they often have less antibiotic activity than erythromycin (140). Synthesis of more complex oxime derivatives resulted in the development of roxithromycin, the 9-[0-(2-methoxyethoxy)methyl]oxime (33) (141). Reduction of the oximes and hydrazones produced 9(S)-erythromycylamine (34) as the principal product, with minor amounts of the 9(R)-isomer (140) however, clinical studies showed that 9(5)-erythromycyclamine and its N-benzylidene derivative were poody absorbed in humans (142). Evaluation of more complex oxazine derivatives of erythromycylamine led to dirithromycin, the 2-(2-methoxyethoxy)ethylidene oxazine derivative (35) (143). A third route to modification of the ketone utilized a Beckmann rearrangement of the 9-oxime to expand the 14-membered ring to a 15-membered intermediate, which was subsequently reduced and AT-methylated to yield azithromycin (36) (144,145). The term azalide was proposed to denote these 15-membered azalactones (10,145). 

Et2Zn instead of 136 as a radical initiator was also effective for the radical reaction. In these tin-free reactions, the mechanism of propagation is proposed to be a process in which boron or zinc Lewis acids complex to the oxime, promoting addition. Once addition of a radical to the complexed oxime occurs, fragmentation of the EtsB or Et2Zn complex generates an ethyl radical that propagates the chain. 

II.I N-O Ligands 45.11.1.1 Schiff base complexes Oxime complexes... 

Synonyms Bis (8-oxyquinoline) copper Bis (8-quinolinato) copper Bis (quinolin-8-olato) copper Copper-8 Copper hydroxy quinolate Copper-8-hydroxyquinolinate Copper-8-hydroxyquinoline Copper oxinate Copper oxyquinolate Copper oxyquinoline Copper quinolate Copper-8-quinolate Cupric-8-hydroxyquinolate 8-Hydroxyquinoline copper complex Oxime copper Oxine copper... 

Oxidative cleavage of cyclic ketonitrones [158] is catalyzed by ferric chloride while the oxidation of some complex oximes in the presence of FeCla gav imidazo-line-N-oxides [159]. 

The use of oximes as nucleophiles can be quite perplexing in view of the fact that nitrogen or oxygen may react. Alkylation of hydroxylamines can therefore be a very complex process which is largely dependent on the steric factors associated with the educts. Reproducible and predictable results are obtained in intramolecular reactions between oximes and electrophilic carbon atoms. Amides, halides, nitriles, and ketones have been used as electrophiles, and various heterocycles such as quinazoline N-oxide, benzodiayepines, and isoxazoles have been obtained in excellent yields under appropriate reaction conditions. 

An unactivated methyl group can be functionalized by the cyclopalladation of oximes. The equatorial methyl of geminal methyls in steroids or hexapyr-anosides is selectively aceto.xylated by the reaction of the palladation complex 523 of the 3-oxime with lead tetraacetate[467,468]. 

The PdCli-catalyzed instantaneous rearrangement of A -carbethoxy-S-azabi-cyclo[5.1.0]oct-3-ene (60) takes place at room temperature to give A -car-bethoxy-8-azabicyclo[3.2.1]oct-2-ene (61)[50], The azepine 62 undergoes a smooth skeletal rearrangement to give 63, and the diazepine 64 is converted into the open-chain product[51]. Beckmann fission of the oxime 65 of ketones and aldehydes to give the nitrile 66 is induced by a Pd(0) complex and oxygen [52,53]. 

Synthesis from Aldehydes and Ketones. Treatment of aldehydes and ketones with potassium cyanide and ammonium carbonate gives hydantoias ia a oae-pot procedure (Bucherer-Bergs reactioa) that proceeds through a complex mechanism (69). Some derivatives, like oximes, semicarbazones, thiosemicarbazones, and others, are also suitable startiag materials. The Bucherer-Bergs and Read hydantoia syntheses give epimeric products when appHed to cycloalkanones, which is of importance ia the stereoselective syathesis of amino acids (69,70). 

The principle of solvent extraction in refining is as follows when a dilute aqueous metal solution is contacted with a suitable extractant, often an amine or oxime, dissolved in a water-immiscible organic solvent, the metal ion is complexed by the extractant and becomes preferentially soluble in the organic phase. The organic and aqueous phases are then separated. By adding another aqueous component, the metal ions can be stripped back into the aqueous phase and hence recovered. Upon the identification of suitable extractants, and using a multistage process, solvent extraction can be used to extract individual metals from a mixture. 

Note that the acetonitrile oxide cyclooligomers (e.g. 13) are not true oxime derivatives. Such derivatives have been prepared from biacetyl, however . Derivatives related to 14, below, were prepared and found not to be good complexing agents. They were, nevertheless, capable of phase transferring either sodium or potassium permanganate into dichloromethane. 

In the 19-nor series, the reaction with NOF is more complex and there is isolated in addition to the fluoro nitrimine corresponding to (31) a 20% yield of the nitroso dimer (34), which dissolves in methanol-methylene dichloride solution to give the pure blue color characteristic of the monomer (35). The latter then isomerizes to the oxime (36). 

Fluorination of NiCl2 -t- KCl produces red K2NiFe which is strongly oxidizing and will liberate O2 from water. Dark red complexes of the type [Ni (L)](C104)2 (H2L is a sexidentate oxime) have been obtained by the action of cone HNO3 on [Ni (H2L)](C104)2 and are stable indefinitely under vacuum but are reduced in moist air. 

The first drugs in this class to be introduced into clinical practice are simple derivatives of 5-nitrofurfural (18). Thus, the oxime is known as nitrofuroxime (19) while the semicarbazone is called nitrofurazone (20). In order to maintain better control over the distribution and metabolism of these antibacterial agents, increasingly complex side chains and rings have been grafted onto the hydrazone. 

Nitrosyl chloride reacts with aliphatic hydrocarbons at room temperature under the influence of light to give a complex mixture of substitution products. When the reaction is run on cyclohexane at —25°, however, the pure oxime hydrochloride crystallizes from the reaction mixture with virtually no side products. 

In 1965, Breslow and Chipman discovered that zinc or nickel ion complexes of (E)-2-pyridinecarbaldehyde oxime (5) are remarkably active catalyst for the hydrolysis of 8-acetoxyquinoline 5-sulfonate l2). Some years later, Sigman and Jorgensen showed that the zinc ion complex of N-(2-hydroxyethyl)ethylenediamine (3) is very active in the transesterification from p-nitrophenyl picolinate (7)13). In the latter case, noteworthy is a change of the reaction mode at the aminolysis in the absence of zinc ion to the alcoholysis in the presence of zinc ion. Thus, the zinc ion in the complex greatly enhances the nucleophilic activity of the hydroxy group of 3. In search for more powerful complexes for the release of p-nitrophenol from 7, we examined the activities of the metal ion complexes of ligand 2-72 14,15). 

An artificial metalloenzyme (26) was designed by Breslow et al. 24). It was the first example of a complete artificial enzyme, having a substrate binding cyclodextrin cavity and a Ni2+ ion-chelated nucleophilic group for catalysis. Metalloenzyme (26) behaves a real catalyst, exhibiting turnover, and enhances the rate of hydrolysis of p-nitrophenyl acetate more than 103 fold. The catalytic group of 26 is a -Ni2+ complex which itself is active toward the substrate 1, but not toward such a substrate having no metal ion affinity at a low catalyst concentration. It is appearent that the metal ion in 26 activates the oximate anion by chelation, but not the substrate directly as believed in carboxypeptidase. 

From strongly addic solutions benzoin-a-oxime precipitates molybdate and tungstate ions quantitatively chromate, vanadate, niobate, tantalate, and palladium) II) are partially predpitated. The molybdate complex is best ignited at 500-525 °C to Mo03 before weighing alternatively, the predpitate may be dissolved in ammonia solution and the molybdenum predpitated as lead molybdate, in which form it is conveniently weighed. 

The synthesis of alkoxy amines 2 by addition of organometallic reagents to the C-N double bond of oxime ethers 1 is plagued by the propensity for proton abstraction a. to the C-N double bond, the lability of the N-O bond and the poor electrophilicity of the oxime ethers. Therefore, frequently no products, undesired products or complex mixtures are obtained. The result depends on the substrate, organometallic reagent, solvent, temperature and additives1 6. 

Much better results are achieved in the addition of butyllithium to oxime ethers 4a, 4b and 4c activated by boron trifluoride-diethyl ether complex (BF3 OEt2) at — 78 °C (above a reaction temperature of — 30 °C complex mixtures of products are obtained) using toluene as the solvent. Furthermore, the stereoselectivity depends on the E/Z ratio of the starting oxime ethers. The reaction appears to be highly stereoselective, with the diastereoselectivity of the... 

Structural chemistrv of transition metal complexes of oximes. A. Chakravorty, Coord. Chem. Rev., 1974,13,1-46 (298). 

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