Hydrazine groups

Functionalized hydrazine groups can be replaced by fluonne. The first example is the replacement ot tnalkylhydrazine groups in bis(l,2,2-trimethylhydrazmo)meth-ane, a hydrazine acetal, by tnchloroacetyl fluonde to fotm 1,1,2- trimethyl-2-fluoromethylhydrazine in 87% yield [5J]... 

AKZ640). Although some data (00UK642) support a ready hydration of the activated triple bond in a weakly basic medium, the latter route seems less probable, since the cyclization of hydrazine 22 is a monomolecular process (70AKZ640) and the hydrazine group is much more nucleophilic than water. 

The reaction mechanism (12) was interpreted as the —E-effect of the hydrazine group in the 2-position of the selenazole ring being the primary cause of the oxidation. An irreversible attachment of two... 

As a further typical reaction of the hydrazine group of the 2-hydrazinoselenazoles (cf. Section I,C,2), pyrazolone formation was investigated. By condensation of the hydrazines with -ketoesters in acetic acid, it was possible to synthesize a series of l-(selenazol-2-yl)-3-alkylpyrazol-5-ones (16). ... 

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). ... 

Blocking the conversion to DA would appear stupid unless this could be restricted to the periphery. More dopa would then be preserved for entry into the brain, where it could be decarboxylated to DA as usual. Drugs like carbidopa and benserazide do precisely that and are used successfully with levodopa. They are known as extracerebral dopa decarboxylase inhibitors (ExCDDIs). Carbidopa (a-methyldopa hydrazine) is structurally similar to dopa but its hydrazine group (NHNH2) reduces lipid solubility and CNS penetration (Fig. 15.4). 

Figure 1.110 The reaction of SANH with an amine-containing molecule results in an amide bond derivative that terminates in a protected hydrazine group. Reaction with an aldehyde-containing molecule results in release of the acetone-protecting group and formation of a stable hydrazone bond.

For most applications, molar ratios in the range of 5 1 to 20 1 will work best to generate a number of hydrazine groups on the protein. Maintain the final percentage of DMF in the reaction mixture at less than 10 percent to avoid precipitation of protein. 

The number of hydrazine groups per protein molecule can be determined by reacting a small portion of the hydrazine-modified protein with p-nitrobenzaldehyde, which forms a chromogenic product upon formation of the hydrazone derivative (Figure 1.111). 

Texas Red hydrazide is a derivative of Texas Red sulfonyl chloride made by reaction with hydrazine (Invitrogen). The result is a sulfonyl hydrazine group on the No. 5 carbon position of the lower-ring structure of sulforhodamine 101. The intense Texas Red fluorophore has a QY that is inherently higher than either the tetramethylrhodamine or Lissamine rhodamine B derivatives of the basic rhodamine molecule. Texas Red s luminescence is shifted maximally into the red region of the spectrum, and its emission peak only minimally overlaps with that of fluorescein. This makes derivatives of this fluorescent probe among the best choices of labels for use in double-staining techniques. 

Hydrazide groups react with aldehyde and ketone groups to form hydrazone linkages (Chapter 2, Section 5.1). Three BODIPY derivatives are available that contain a hydrazine group modification of carboxylate side chains. Biomolecules such as proteins that don t normally possess aldehyde residues can be modified to contain them by a number of chemical means (Chapter 1, Section 4.4). 

Figure 17.6 The reaction of SANH with amine-containing proteins or other molecules results in amide bond modifications containing terminal hydrazine groups. The reaction of SFB with amine-containing proteins or other molecules results in amide bond modifications containing terminal aldehyde groups. Subsequently, the two modified molecules can be reacted together to create a conjugate via hydrazone bond formation.

Thus, the 2-hydrazinopyridone compound 89 was transformed to the corresponding fused tetrazolo[l,5- ]pyridine 90 in 61% yield <2000J(P1)3686>, and the partially saturated 1-hydrazinoisoquinoline compound 91 when reacted with nitric acid gave the appropriate tetrazole 92 in 64% yield <1994KGS511>. In the case of the acylhydrazino isoquinoline derivative 93, a deprotection of the hydrazine group was carried out first followed by treatment with... 

Kocevar et al. investigated the reactivity of 3-hydrazinopyridazines 386 in the presence of the oxazolone compound 387 <2001H(54)1011 >. In some special cases (mostly when R8 = Me), formation of 388 in high yields was observed, while in other cases an entirely different transformation (formation of a pyrazolone ring as a substituent instead of the hydrazine group) was experienced. 

Figure 7.83 Possible routes for the metabolic activation of hydralazine. The oxidation of the hydrazine group may also involve the formation of a nitrogen-centered radical, which could also give rise to phthalazine with loss of nitrogen.

According to Dr Henry(Ref 3), "Direct nitration of 1-amino-2-methylguanidine is not possible because the hydrazine group would be... 

The treatment of a N-substituted hydrazine hydrobromide successively with the a,a-dicyano-epoxide 91 and with TV-methyl hydrazine results in the racemic a-hydrazino hydrazide 92 (Scheme 29)/111 Repeating the above two reactions allows the elongation of 92 into the racemic (hydrazide) peptide 93/1121 A derived procedure, with ClCH2COCl instead of 91, is applied to the synthesis of the first (hydrazide) cyclotripeptide 94 (R1 = 4-C1C6H4 or 4-MeQlLi) (Scheme 30), by coupling of the N-terminal chloroacetyl and C-terminal hydrazine groups/113 It has been later extended to the synthesis of linear (hydrazide) polypeptides/114 It is noteworthy that the a-carbon is racemic in all of the above cases. 

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 synthesis of 207 is based on an intramolecular aminolysis of the (3-lactam ring in 206. This latter compound was prepared by stereoselective alkylation of 203 with l-bromo-3-butene and subsequent oxidative cleavage of the double bond to give the carboxylic acid 204, which next was coupled with 205. The resulting peptide product 206 rapidly cyclized to a ten-membered ring compound, on reductive deprotection of the hydrazine group, and then coupled with /V-carbo-benzoxytyrosine to give 207. 

The hydrazines usually are converted to hydrocarbons by treatment with hot, aqueous cupric sulfate, ferric chloride, or potassium chromate.7- uo 1Ui 116 113 Although hydrazines often are isolated from reduction mixtures as hydrochlorides, it is advisable to convert them to the free bases before carrying out the oxidation if this is not done, a chlorine atom may replace the hydrazine group.117 118< 119 Phenylhydrazine hydrochloride is converted to chlorobenzene in 86% yield when treated with a solution of cupric sulfate containing hydrochloric add.118... 

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