Functional group activation hydrazines

Most reactive metabolites produced by CYP metabolic activation are electrophilic in nature, which means that they can react easily with the nucleophiles present in the protein side chains. Several functional groups are recurrent structural features in M Bis. These groups have been reviewed by Fontana et al. [26] and can be summarized as follows terminal (co or co — 1) acetylenes, olefins, furans and thiophenes, epoxides, dichloro- and trichloroethylenes, secondary amines, benzodioxoles (methylenediox-yphenyl, MDP), conjugated structures, hydrazines, isothiocyanates, thioamides, dithiocarbamates and, in general, Michael acceptors (Scheme 11.1). 

The hydrazide derivative can be used to modify aldehyde- or ketone-containing molecules, including cytosine residues using the bisulfite activation procedure described in Chapter 17, Section 2.1. The sulfonyl hydrazine group of Texas Red hydrazide reacts with aldehydes or ketones in target functional groups to form hy-drazone bonds (Fig. 218). Carbohydrates and glycoconjugates can be specifically labeled at the polysaccharide portion if the required aldehydes are first formed by periodate oxidation or another such method (Chapter 1, Section 4.4). 

The effect of ultrasonic irradiation on hydrazine reductions in the presence of iron powder and activated carbon in ethanol has also been evaluated. The studies include graphite-catalyzed reductions of aromatic nitro compounds to the corresponding arylamines. The notable features of these reactions are the low cost, high yields and the simplicity of the work-up procedure. Significantly, nitro groups can be reduced in the presence of a variety of functional groups. 

Hydrogenation is the most well studied area among immobilized palladium catalysis. While a great majority of the applications focused on the use of support such as alumina and activated carbon, a great diversity of novel support systems have been reported in recent years, aimed at finding a catalyst with a well-characterized coordination sphere and tailor-made activity. Pd(0) catalysts dispersed on crosslinked styrene-divinylbenzene copolymers have been prepared by impregnation of lipophilic complexes followed by reduction with hydrazine. It was found that the functional groups in the polymer as well as polymer particle sizes had a major effect on catalyst activity.t [i53]-[i95]... 

After two years, Inamoto developed an approach to the synthesis of 3-aryl/ alkylindazoles [20], by means of a Pd(OAc)2-catalyzed C-H amination reactions of hydrazine compounds. This method features the use of novel combinations of such Pd(OAc)2/Cu(OAc)2/AgOCOCF3, which successfully effect catalytic C-H activation followed by amination to give the cyclized products. The cyclization proceeded in milder reaction conditions (50 °C) and hence tolerated various functional groups such as alkoxycarbonyl and cyano groups and halogen atoms (Scheme 2.20). The data showed that the cyclization may be controlled by both steric and electronic factors on the arene. 

Inspired by the work of Burk and Feaster ) we attempted to use (2-pyridyl)hydrazine (4.36) as a coordinating auxiliary (Scheme 4.10). Hydrazines generally react effidently with ketones and aldehydes. Hence, if satisfactory activation of the dienophile can be achieved through coordination of a Lewis acid to the (2-pyridyl)hydrazone moiety in water. Lewis-add catalysis of a large class of ketone- and aldehyde-activated dienophiles is antidpated Subsequent conversion of the hydrazone group into an amine functionality has been reported previously by Burk and Feaster ... 

In the discussion of benzylamines, we have met medicinal agents that owe their activity to some particular functionality almost without reference to the structure of the rest of the molecule. The hydrazine group is one such function in that it frequently confers monamine oxidase-inhibiting activity to molecules containing that group. Such agents frequently find use as antidepressants. Thus, reduction of the hydrazone of phenyl-acetaldehyde (84) affords the antidepressant phenelzine (85). Similar treatment of the derivative of phenylacetone (86) gives pheniprazine (87). ... 

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