Hydrazines nucleophilic cleavage with

Figure 1.43 indicates major sites of reactivity within the ring structures for nucleophilic displacement reactions. Cytosine, thymine, and uracil all react toward nucleophilic attack at the same two sites, the C-4 and C-6 positions. The presence of powerful nucleophiles, even at neutral pH, can lead to significant base modification or cleavage with pyrimidine residues (Debye, 1947). For instance, hydrazine spontaneously adds to the 5,6-double bond, initiating further ring reactions,... 

Hydrazine as a A -nucleophile reacted with alkyl- and phenyl-substituted 1-acetoxy-2,2-dich-lorocyclopropanes 1 to give substituted pyrazoles 3, 4 and 5. The preferred cleavage site was the carbon-carbon bond between the donor-substituted carbon atom and the halogen-free carbon atom. When the 1-methyl derivative 1 (R = Me) was treated with phenylhydrazine the corresponding 3-methyl-l-phenylpyrazole 2 was obtained in 43% yield. 

Polymer-bound chiral hydrazines have been synthesized to furnish a-branched amides (Scheme 12.17) [13, 23], Enantiopure (i-methoxyamines 37 and 38, derived from readily available hydroxyproline and N,N-dibenzylleucinol, respectively, have been attached to solid support and transformed into the corresponding hydrazine auxiliaries 39 and 40 via several steps. The synthesis of a series of enantiomerically enriched a-branched amides required the coupling of aliphatic and aromatic aldehydes to form hydrazones 41 and 42 followed by the addition of different nucleophiles. Cleavage of the N-N bond of the resulting hydrazines 43 and 44 led to a-branched amines 45. Further conversion with benzoyl chloride or acetyl chloride furnished amides 46 in yields of 24—51% and 50-83% ee. 

It can be seen that the formation of N20 through the cleavage of the N N bond, as occurring for other hydrazines, is avoided. The nucleophile is able to form a very stable product, azomethane, by transferring two electrons and protons. Thus, the nitroxyl species, [Fen(CN)5 H15NO]3 ", can be formed in Eq. (17) and survive enough to react with... 

The Gabriel method of making primary amines (Scheme 2.33) rests on the fact that the imide hydrogen of phthalimide is rendered acidic by the two carbonyl groups. It therefore forms a potassium salt, which is a powerful nucleophile and may be alkylated. Hydrolysis of the amide generates the primary amine. The cleavage of the phthalimide may be carried out with hydrazine (H NNHj). 

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