Hydrazide pathway

The two reaction pathways studied involve a route from the carboxylic acid to the isocyanate via the acyl chloride and azide (Sodium Azide Pathway, Pathway A), Figure 4 and a route from the carboxylic acid to the isocyanate via the hydrazide (Hydrazide Pathway, Pathway B), Figure 5. The reactions were monitored by isolating the intermediate reaction products and characterizing them by melting points, elemental composition, or IR spectroscopy. 

Model Type A, vanillic acid and its acetylated or methylated derivative, generated the expected isocyanate without major problems either via the sodium azide or the hydrazide pathway. 

Figure 6. Infrared spectra of isocyanate formation of model Type A (R = CH,) via the sodium azide and the hydrazide pathways.

Hydrazide Pathway The unhydrolyzed copolymer (anhydride form) was methylated for 20 hrs by pressure-heating to 110°C its absolute methanol solution containing a small amount (ca. 0.5% of methanol) of N-N-4 dimethylaminopyridine followed by vacuum evaporation. The concentrated solution was precipitated from ether-pet ether 2 1 by dropwise addition, filtered and washed (ether-pet ether). 

Another pathway takes place upon cyclization of hydrazides of benzene carboxylic acids in the presence of CuCl in an inert atmosphere in DMF. However, only the cyclization of hydrazide 76 (R = H) in conditions of copper catalysis makes it possible to isolate compound 77 (yield 20%). Other hydrazides of acetylenylbenzoic acids react to give a complex mixture of products (Scheme 132) (85IZV1367 85MI2). 

As noted above, a convenient pathway to cinno-lines consists of intramolecular condensation of a diazonium group with a ketonic methyl group, or alternately with a double bond. The analogous reaction with an amide nitrogen leads to 1,2,3-benzotriazines, such as 198. Reaction of isatoic anhydride with N-aminomorpholine affords the hydrazide 196 then, treatment with nitrous acid yields initially the diazonium salt (197). Under the reaction conditions... 

Fluorescence is by far the most important emission in hydrazide chemiluminescence the possible involvement of triplet-singlet transfer in some cases is discussed below. The correct chemical pathway can be understood to mean in part that a hydrazide must be stable enough under the oxidative reaction conditions usually applied to ensure that only a small proportion of the hydrazide molecules are consumed in non-chemiluminescent oxidation reactions, 3.6-diamino-phthalic hydrazide 24, for example, should yield a highly fluorescent dicarboxylate dianion and therefore exhibit strong chemiluminescence. However, being a derivative... 

Hydrazides are formed by the acylation of hydrazines, and have a C-N bond of rather low chemical stability toward hydrolysis. It is, therefore, not surprising that the cleavage of this bond represents a major metabolic pathway for most hydrazides. The reaction is catalyzed by amidases since it can be inhibited by O-ethyl 0-(4-nitrophenyl) phenyl phosphothionate or bis(4-nitrophenyl) phosphate, which are classical inhibitors of this enzyme. 

B. J. van der Walt, J. M. van Zyl, A. Kriegler, Different Oxidative Pathways of Isonicotinic Acid Hydrazide and Its Meta-Isomer, Nicotinic Acid Hydrazide , hit. J. Biochem. 1994, 9, 1081-1093. 

The isocyanate reaction pathway seems to have no major advantage over the other methods with N-activation (vide supra), since it implies an additional reaction step and the isocyanates react directly with hydrazides giving azapeptides. Advantages may be the easier handling of the solid and stable TV-azolides in comparison to the liquid, toxic, and relatively unstable isocyanates. 

Thus far, three different routes have been established by which the N2 ligand is converted into the hydrazide state. In the top pathways of Figure 19, the hydron... 

Isonicotinyl hydrazide, an inhibitor of enzymes that are dependent on pyridoxal phosphate, also prevents the formation of pigment in illuminated, etiolated maize, but the inhibition is reversed by pyruvate or serine.9 This supports the previously held view that the C-2—C-3 fragment of serine can give rise to acetyl-CoA in young, greening tissue. However, the significance of this pathway in mature plants has yet to be ascertained. 

In solution, but not as a pure substance, 52 decomposes at room temperature additionally according to Thermolysis Pathway III into nitrogen and l,l-bis(trimethylsilyl)hydrazide, which, under thermolytic conditions. 

The biotransformation of hydrazine and hydrazide derivatives also proceeds by acetylation. The antihypertensive hydralazine (Apresoline) " ""and the MAO inhibitor phenelzine (Nardil) " are two representative hydrazine compounds that are metabolized by this pathway. The initially formed N-acetyl derivative of hydralazine is unstable and cyclizes intramolecularly to form 3-methyl-s-triazolo 3.4-a phtha-lazine as the major isolable hydralazine metabolite in humans. " The antituberculosis drug isoniazid or isonicoli-nic acid hydrazide (INH) is metabolized extensively to N-acetylisoniazid. " ... 

Acetylation of xenobiotic primary amine groups is a common metabolic pathway, whereas acetylation of xenobiotic hydroxyl and sulfhydryl groups is not. Primary aliphatic and aromatic amines, sulfonamides, hydrazines, and hydrazides are readily N-acetylated in vivo, and the reaction is catalyzed by various acetyl CoA N-acetyltransferases, commonly called N-acetyltransferases, as shown in Figure 16. 

Thermal fragmentation of maleic hydrazide in the range of 450°-800°C proceeds by two pathways (a) (2+2+2)-cycloreversion to give acetylene and isocyanic acid as primary products, and (b) a retro-Diels-Alder reaction to give initially diimide and a bisketene. ... 

Cyclization of 2-propenoic acid 2-(4-phenyl-2-thiazolyl)hydrazide (121), prepared from 2-hydra-zino-4-phenylthiazole and acryloyl chloride, with potassium carbonate yielded two kinds of thi-azolotriazepinones (122) (15% yield) and (123) (27% yield). The former, thiazolo[2,3-c]-1,2,4-triazepine (122), was the predicted product, but the production of the unexpected [3,2-6]-isomer (123) may have proceeded via the rearrangement pathway shown in Scheme 21 <82JHC747>. 

---