Hydrazone metalated

Enders et al.173) transformed open chain and cyclic P-ketoesters into the corresponding SAMP-hydrazones. Metalation with n-butyllithium, followed by trapping of the intermediate anions with alkyhalides generates esterhydrazones which upon cleavage by ozonolysis finally leads to optically active p-ketoesters. While the overall chemical yields are good, the enantiomeric excesses of 18-60% are relatively low. 

The concentration of aluminum in serum can be determined by adding 2-hydroxy-1-naphthaldehyde p-methoxybenzoyl-hydrazone and measuring the initial rate of the resulting complexation reaction under pseudo-first-order conditions.The rate of reaction is monitored by the fluorescence of the metal-ligand complex. Initial rates, with units of emission intensity per second, were measured for a set of standard solutions, yielding the following results... 

According to a detailed mechanistic study, the first step is the abstraction of the relatively acidic hydrazone proton (93- 97). This is followed by hydride attack on the trigonal carbon of the C=N bond, mainly from the a-side at C-3, together with the concomitant loss of the tosylate anion (97 -> 98). Expulsion of nitrogen from the resulting intermediate (98) yields a fairly insoluble anion-metal complex (99) which upon decomposition with water provides the methylene derivative (100). 

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

S)- and (+ )-(7 )-l-Amino-2-(methoxymethyl)pyrrolidine- (SAMP and RAMP)-hydrazones derived from methyl ketones and chiral hydrazines are metalated regioselectively at the methyl... 

Metalated SAMP- or RAMP-hydrazones derived from alkyl- or arylethyl ketones 3 add to arylaldehydes both diastereo- and enantioselectively. Substituted / -hydroxy ketones with relative syn configuration of the major diastereomer are obtained with de 51-80% and 70-80% ee. However, recrystallization of the aldol adducts, followed by ozonolysis, furnishes diastereo- and enantiomerically pure (lS, S )-. yn-a-mcthyl-/3-hydroxy ketones 5 in 36-51% overall yield. The absolute configuration of the aldol adducts was established by X-ray crystallographic analysis. Starting from the SAMP- or RAMP-hydrazone either enantiomer, (S,S) or (R,R), is available using this methodology16. 

Low valent transition metal centers preferentially coordinate to the phosphorus in diazaphospholes. Accordingly, P-coordinated complexes of [l,2,3]diazapho-spholes with Cr, W, Fe, and Mn carbonyls were obtained as early as 1980 [1, 2,4], Later, Kraaijkamp et al. observed [108] both P- or -coordination modes in complexes of [l,2,3]diazaphospholes with MX2(PEt3) (M = Pt, Pd X = C1, Br). Methanolysis of these complexes led to the diazaphosphole ring opening and formation of five membered metallacyclic P,/V-chelates (103), incorporating P-bonded phosphonite and /V-coordinated hydrazone functionalities (Scheme 32) [109],... 

There are two main factors to consider in order to understand the bonding and structures of metal complex azo colorants, namely (i) azo/hydrazone tautomerism and (ii) the nature of the azo-to-metal bonding. 

Dyes based on 4-phenylazo-l-naphthol (6) have been used extensively to study azo/hydrazone tautomerism since they exist as an equilibrium mixture of both the azo and hydrazone tautomers.8 However, they are of little use commercially and of no use whatsoever for metal complex azo dyes since the hydroxy group is not ortho to the azo group so these cannot act as chelating ligands. 

The l-phenylazo-2-naphthol (7) and particularly the 2-phenylazo-l-naphthol (8) systems are used extensively, providing many of the commercial metal complex azo colorants. Azo pigments are derived from (7) whilst azo dyes are obtained from (8). Both these types of colorant exist predominantly, if not exclusively, in the hydrazone tautomeric form.8,9... 

Dyes (11) from azophenols exist totally in the azo form8 whereas dyes (12) from heterocyclic couplers such as pyrazolones8,11 and acyclic couplers such as acetoacetanilides8 12 (13) exist totally in the hydrazone form. Dyes (14) derived from amino couplers exist in the azo form.8 However, as described above, all these dyes will exist predominantly in the azo form in the derived metal complexes. 

Transition Metal Complexes with Bis(Hydrazone) Ligands of 2, 6-Diacetylpyridine. Hepta-Coordination of 3d Metals... 

In earlier studies the in vitro transition metal-catalyzed oxidation of proteins and the interaction of proteins with free radicals have been studied. In 1983, Levine [1] showed that the oxidative inactivation of enzymes and the oxidative modification of proteins resulted in the formation of protein carbonyl derivatives. These derivatives easily react with dinitrophenyl-hydrazine (DNPH) to form protein hydrazones, which were used for the detection of protein carbonyl content. Using this method and spin-trapping with PBN, it has been demonstrated [2,3] that protein oxidation and inactivation of glutamine synthetase (a key enzyme in the regulation of amino acid metabolism and the brain L-glutamate and y-aminobutyric acid levels) were sharply enhanced during ischemia- and reperfusion-induced injury in gerbil brain. 

The hydrazino group is highly reactive, forming hydrazones with aldehydes and ketones. It is also a reducing agent, and it forms complexes with many metal ions (34). 

Chiral Hydrazone Systems. In 1976, Corey and Enders34 demonstrated the great synthetic potential of metalated dimethylhydrazones as highly reactive intermediates in regio- and diastereoselective C C bond formation reactions. The procedure for carrying out the electrophilic substitution reaction... 

Figure 2-2. Electrophilic substitution to the carbonyl group of aldehydes and ketones via metalated (chiral) hydrazones. 

The reason for the rate increase in the presence of phenylhydrazine remains unclear. The authors note that phenylhydrazone also accelerates the reaction and that the formation of the hydrazone from the solvent (acetone) cannot be ignored. Phenylhydrazine is known to reduce Cu(II) to Cu(I) (115), and the authors observed that the hydrazone is also capable of this reduction. It is interesting that the same rate acceleration could not be induced by other amine bases such as pyridine, l,5-diazabicyclo[4.3.0]non-5-ene (DBN), or DBU. While it is likely that phenyl-hydrazine-phenylhydrazone accelerates the slow step of the catalytic cycle through some sort of interaction with the metal, the exact nature of this involvement remains unclear. Elucidation of its role in the reaction may greatly aid the development of this transformation, and it is expected that it will impact the ultimate solution to this problem. 

Phase-transfer catalytic conditions provide an extremely powerful alternative to the use of alkali metal hydrides for the synthesis of cyclopropanes via the reaction of dimethyloxosulphonium methylides with electron-deficient alkenes [e.g. 54-56] reaction rates are increased ca. 20-fold, while retaining high yields (86-95%). Dimethylphenacylsulphonium bromide reacts in an analogous manner with vinyl-sulphones [57] and with chalcones [58] and trimethylsulphonium iodide reacts with Schiff bases and hydrazones producing aziridines [59]. 

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