Carboxylic acid hydrazides hydrazones

Isocarboxazid Isocarboxazid, 2-benzylhydrazid-5-methyl-3-isoxazolecarboxylate (7.2.6), can be synthesized from acetylacetone, which on nitrosation with nitrous acid gives 5-methyl-isoxazol-3-carboxyhc acid (7.2.2). Esterification of this product gives the ethyl ester of 5-methyl-isoxazol-3-carboxyhc acid (7.2.3). The synthesized ester (7.2.3) is further reacted with benzylhydrazine, to give isocarboxazide (7.2.6), or with hydrazine, which forms 5-methyl-isoxazol-3-carboxylic acid hydrazide (7.2.4). Reacting the latter with benzaldehyde gives hydrazone (7.2.5), which is further reduced to the isocarboxazide (7.2.6) [46,47]. 

Carbonyl compounds Azobenzene-4-carboxylic acid hydrazide. l,2-Dimethyl-4,3-di(mercaptomethyl)benzene. N,N-Dimethylglycinehydrazide hydrochloride. 2,4-Dinitro-phenylhydrazine. 2-Diphenyiacetyl-l,3-indanedione-l-hydrazone. Ethoxycarbonylhydrazine. 

Sarhan (01M753) (Scheme 28) condensed lH-indole-3-carboxylic acid hydrazide 120 with ethyl 3-oxobutanoate 5 without solvent and isolated hydrazone 121 in 70% yield. Compound 121 could be cyclized to l-(lH-indole-2-carbonyl)pyrazol-3-one 122 in 67% yield by heating in a mixture of ethanol and acetic acid (10 2 ratio). Using this solvent, mixture pyrazol-3-one 681 was obtained independently in 34% yield by heating hydrazide 120 with ethyl 3-oxobutanoate 5. 

Treatment of salicylic hydrazide in toluene with a single carbon insertion unit, such as carboxylic acid anhydride, acid chlorides, and orthoesters in the presence of an equimolecular amount of methanesulfonic acid, gave the l,3,4-benzoxadiazepin-5-ones (141) (43-68% yield), via the O-acylation intermediates (140) (Scheme 25) <928929). In the second example, 2,3-dihydro-1,3,4-benzoxadiazepines (143) were prepared by the condensation of salicylic aldehyde hydrazones (142) with an appropriate aldehyde in 50-60% yields <82KGS1319>. 

Within the last two decades, a number of chemical structures have been proposed as metal deactivators for polyolefins. These include carboxylic acid amides of aromatic mono- and di-carboxylic acids and N-substituted derivatives such as N,N -diphenyloxamide, cyclic amides such as barbituric acid, hydrazones and bishydrazones of aromatic aldehydes such as benzaldehyde and salicylaldehyde or of o-hydroxy-arylketones, hydrazides of aliphatic and aromatic mono- and di-carboxylic acids as well as N-acylated derivatives thereof, bisacylated hydrazine derivatives, polyhydrazides, and phosphorus acid ester of a thiobisphenol. An index of trade names and suppliers of a few commercial metal deactivators is given in Appendix A4. 

An exception to the expected ester formation of a phenol and a carboxylic acid is found in the case of salicylaldehydes. Girard et al. found that salicylaldehydes (91) preferentially form hydrazones like 92 when DEAD or related azadicarboxylates are employed in the Mitsunobu reaction. The hydrazone formation occurs with or without a carboxylic acid coupling partner. If DEAD is used during the reaction, the neighboring alcohol is protected as the boc ester during the reaction. This presiunably occurs through Boc transfer from DEAD via a tetrahedral intermediate. The subsequent hydrazone formation can then proceed via a concerted or nonconcerted reaetion with the reactive triphenylphosphonium boc hydrazide species that is formed after the collapse of the tetrahedral intermediate. 

Hexokinase, 287 Homoarginine, 552, 553 Homobiotinyl p-nitrophenyl ester, 615 Homoserino, 156, 414 Hydrazides as inhibitors, 38 test for, 211 Hydrazines, 210 synthesis of, 210 Hydrazones, test for, 211 Hydrocinnamaldehyde, 125 Hydrocinnamic acid, 123 Hydrofluoric acid, 201 Hydrogenation, 200 Hydrogen peroxide, 49-51, 315 Hydrophobic probes, 191 3/S-Hydroxy-5-androstene-17/S-carboxylic acid, 477... 

Hydrazide groups can react with carbonyl groups to form stable hydrazone linkages. Derivatives of proteins formed from the reaction of their carboxylate side chains with adipic acid dihydrazide (Chapter 4, Section 8.1) and the water-soluble carbodiimide EDC (Chapter 3, Section 1.1) create activated proteins that can covalently bind to formyl residues. Hydrazide-modified enzymes prepared in this manner can bind specifically to aldehyde groups formed by mild periodate oxidation of carbohydrates (Chapter 1, Section 4.4). These reagents can be used in assay systems to detect or measure glycoproteins in cells, tissue sections, or blots (Gershoni et al., 1985). 

---