Hydrazino groups

Oxidative cleavage of hydrazino substituents in pyridazines and phthalazines proceeds with thallium trinitrate in methanol, under mild conditions (Equation (24)) to give the corresponding methoxy derivatives in moderate yields 95JOCl466 . 

Hydrazone formation of pyridazine-3-hydrazines with aldoses, dialdofuranoses, and dialdopyranoses was studied by Stanovnik and co-workers. The respective hydrazones could be cyclized with Bt2 in MeOH or Pb(OAc)4 to j-triazolo[4,3-3]pyridazin-3-yl substituted polyols 1997JHC1115, 1998JHC513 . Similarly, 4-[(dimethylamino)-methylene]-l,8,8-trimethyl-2-oxabicyclo[3.2.1]octan-3-one was reacted with pyridazine-3-hydrazines and the resulting mixtures were subsequently treated with Pb(OAc)4. Besides j-triazolo[4,3-3]pyridazine formation also diazenes were obtained. This can be rationalized by the enehydrazine-hydrazone mixtures observed in the first reaction. For phthalazin-l-hydrazines only diazenes were obtained after oxidation 2005TA2927 . Also cyclizations of 

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Mechanistically, the reaction results from the mesomeric donor effect of the 2-hydrazino group. The coupling between the two molecules takes place in the 5-position (Scheme 48). 

On the other hand, elimination of the hydrazino group in 3-hydrazinopyridazines is possible with p-toluenesulfonamide under phase transfer reaction conditions (78TL3059). 

Hydrazino groups are also converted into H-compounds with mercury(II) oxide (74CR(C)-(278)427) in other reactions they have given hydrazones, or have been converted into pyrazoles and fused heterocyclic rings (77JAP(K)7785194), e.g. (72) -> (73). 

Amino groups are acetylated normally and are converted to hydroxy compounds with nitrous acid. Tlie 2,3-diamino [2,3-f>] derivative gives an imidazolo fused pyridopyrazine with acetic anhydride (75USP3898216). The oxidative removal of hydrazino groups has been used to give ring-unsubstituted derivatives (79JHC305). 

The reactions of 2- and 4-cyanoquinazolines are similar to those of the chloro compounds. Thus the cyano group can be replaced by alkoxide, phenoxide, substituted amino, and hydrazino groups substitution of the 4-cyano takes place more readily than that of the 2-cyano group.The nitrile substituent can also be hydrolyzed to an alkoxycarbonyl and amide group/ ... 

JMC1230), and hydrazino groups (65JCS3357) to give 184 and 185 respectively (Scheme 70). 

Condensation of hydrazino derivative 716 with formic acid gave triazolo[4,3-6]- and [3,4-c][l,2,4]triazines 718 and 719. The reaction proceeded through N-2 acylation of the hydrazino group to give intermediate... 

Note Removal of a hydrazino group is usually done oxidatively with loss of nitrogen. 

The following protocol describes a general method for modifying amines with SANH, SNHN, or SHTH and assaying for the incorporation of hydrazino groups in the final derivative. 

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). 

An empirical rule defining the minimum requirements for activity in this type of compound is illustrated by structure VI which shows that the -C=N-N C- moiety must be in a six membered heteroaromatic system with the hydrazino group (or its hydrazone) attached to one of the carbons. 

Another structurally simple modification involves replacement of a Lys residue with Lys(NH2) (6.83). Here, the amino group of lysine is replaced with a hydrazino group, which is less-basic by ca. 3 pKa units. This modification allows model peptides to be stabilized against endopeptidases such as trypsin and thrombin [207], Thus, the peptides Tyr-Gly-Xaa-Gly-Tyr-Ala-NH2 with Xaa = Lys or Arg were very rapidly hydrolyzed by trypsin (half-... 

Two noncatalytic methods have been used to remove amino or hydrazino groups. Diazotization and reduction of the diazonium salt by hypophos-phorous acid removes amino groups from aminotriazolopyridines 173,65 174,66 and 175,65 whereas silver oxide treatment removes hydrazino groups from compounds 176216 and 177.206... 

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