Carboxylic hydrazides

This drug bears some formal chemical resemblance to the benzothiatriazines referred to above [327] in that a nitrogen atom occupies the position corresponding to C3 in the thiazide series. (XXVll, Figure 1.1) Clopamide (Aquex, Brinaldix) has obvious features in common with quinethazone and chlorexolone for example and can be regarded either as a piperidinocarboxamide or a substituted carboxylic hydrazide of the familiar o-chlorobenzenesulphonamide. 

Dynamic Mechanical Properties of Resins Cured with Carboxylic Hydrazides... 

The curing mechanism of epoxy resins with carboxylic hydrazides has not been sufficiently revealed so far. However, Kamon 36) has shown that one hydrazide group reacts with two epoxy groups. This result suggests that the structure of the epoxy resin cured with hydrazide is presumed to be nearly the same as that shown in Fig. 1 a, where the — NC segment is substituted by the -CONHN segment. 

Furan-2,3-diones 779 reacted with various hydrazines to yield pyrazole-3-carboxylic hydrazides 780 in moderate yields (Equation 168) <2005JHC117>. 4-Benzoyl-l-(4-nitrophenyl)-5-phenyl-l//-pyrazole-3-carboxylic acid 782 was obtained from the furan-2,3-dione 781 and A -benzylidene-A -(4-nitrophenyl)hydrazine (Equation 169) <2004CHE1039>. 

SMCCH Succinimidyl 4-(N-maleimidomethyl) cyclohexane-1 -carboxylate hydrazide 365.31 ... 

The ease of dehydration of pyridazine carboxamides, their hydrolysis, and Hofmann degradation to amines was outlined in CHEC-I <84CHEC-I(3B)1>. More recently, in the early 1990s, the Curtius rearrangement (Equation (19)) of the 4-carboxylic hydrazide of 6-(4-pyridyl)-3(2//)-pyridazinone to give an aza analogue of amrinone has been reported <90H(3i)2l63>. 

Oxadiazoles 8 [465] are obtained by acid-promoted cyclocondensation of carboxylic hydrazides (acylhydrazines) (a) with acid chlorides in the presence of P4O10 [466] and (b) with orthoesters catalyzed by alum (KA1(S04)2 12 H2O) [467] ... 

Thiazole carboxylic acid hydrazides were prepared in a similar way (444, 445). Thus by refluxing thioacetamide or thiobenzamide with y-bromoaceto acetic ester arylhydrazones (83) for several hours in alcohol the 4-carboxythiazole derivatives (84) listed in Table II-ll were obtained (Scheme 36) (656). This reaction is presumed to proceed via dehydration of the intermediate, thiazoline-S-oxide. 

A.ldehyde Syntheses. Aromatic (Ar) carboxylic acids are reduced to the corresponding aldehydes by a sequence of steps known as the McFadyen-Stevens reaction. The acid is converted to the hydrazide, derivatized with benzenesulfonylchloride, then decomposed to the aldehyde in hot glycol in the presence of a base ... 

Carboxylic acid hydiazides are prepared from aqueous hydrazine and tfie carboxylic acid, ester, amide, anhydride, or halide. The reaction usually goes poody with the free acid. Esters are generally satisfactory. Acyl halides are particularly reactive, even at room temperature, and form the diacyl derivatives (22), which easily undergo thermal dehydration to 1,3,4-oxadiazoles (23). Diesters give dihydtazides (24) and polyesters such as polyacrylates yield a polyhydrazide (25). The chemistry of carboxyhc hydrazides has been reviewed (83,84). 

The aminolysis of esters of pyrimidine occurs normally to yield amides. The reagent is commonly alcoholic ammonia or alcoholic amine, usually at room temperature for 20-24 hours, but occasionally under refiux aqueous amine or even undiluted amine are used sometimes. The process is exemplified in the conversion of methyl pyrimidine-5-carboxylate (193 R = Me) or its 4-isomer by methanolic ammonia at 25 °C into the amide (196) or pyrimidine-4-carboxamide, respectively (60MI21300), and in the butylaminolysis of butyl ttracil-6-carboxylate (butyl orotate) by ethanolic butylamine to give A-butyluracil-5-carboxamide (187) (60JOC1950). Hydrazides are made similarly from esters with ethanolic hydrazine hydrate. 

In most other reactions the azolecarboxylic acids and their derivatives behave as expected (cf. Scheme 52) (37CB2309), although some acid chlorides can be obtained only as hydrochlorides. Thus imidazolecarboxylic acids show the normal reactions they can be converted into hydrazides, acid halides, amides and esters, and reduced by lithium aluminum hydride to alcohols (70AHC(12)103). Again, thiazole- and isothiazole-carboxylic acid derivatives show the normal range of reactions. 

Properly substituted isoxazolecarboxylic acids can be converted into esters, acid halides, amides and hydrazides, and reduced by lithium aluminum hydride to alcohols. For example, 3-methoxyisoxazole-5-carboxylic acid (212) reacted with thionyl chloride in DMF to give the acid chloride (213) (74ACS(B)636). Ethyl 3-ethyl-5-methylisoxazole-4-carboxylate (214) was reduced with LAH to give 3-ethyl-4-hydroxymethyl-5-methylisoxazole (215) (7308(53)70). 

Claisen ester condensation, 6, 279 Thiazolecarboxylic acid chlorides reactions, 6, 279-280 Thiazolecarboxylic acid hydrazides synthesis, 6, 280 Thiazolecarboxylic acids acidity, 6, 279 decarboxylation, 6, 279 reactions, S, 92 6, 274 Thiazole-2-carboxylic acids decarboxylation, S, 92 Thiazole-4-carboxylic acids stability, S, 92 Thiazole-5-carboxylic acids decarboxylation, S, 92 Thiazole-4,5-dicarboxylic acid, 2-amino-diethyl ester reduction, 6, 279 Thiazole-4,5-dicarboxylic acids diethyl ester saponification, 6, 279 Thiazolediones diazo coupling, 5, 59 Thiazoles, 6, 235-331 ab initio calculations, 6, 236 acidity, S, 49 acylation, 6, 256 alkylation, S, 58, 73 6, 253, 256 analytical uses, 6, 328 antifogging agents... 

Some amides and hydrazides that have been prepared to protect carboxyl groups are included in Reactivity Chart 6. 

Simple isothiazole-4-carboxylic acids have been made from the corresponding nitriles, which are available in turn from the halogeno derivatives, or directly by the olefin route.5-Aminoiso-thiazole-4-esters and -nitriles are readily obtained by the thioamide route. The 4-acids behave normally and form acid chlorides, esters, amides, and hydrazides. In contrast to the 5-series... 

Hydrazides of vicinal acetylene-substituted derivatives of benzoic and azole carboxylic acids are important intermediate compounds because they can be used for cyclization via both a- and /3-carbon atoms of a multiple bond involving both amine and amide nitrogen atoms (Scheme 131). Besides, the hydrazides of aromatic and heteroaromatic acids are convenient substrates for testing the proposed easy formation of a five-membered ring condensed with a benzene nucleus and the six-membered one condensed with five-membered azoles. 

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). 

TABLE XXIX. l-Methyl-l,6-dihydropyrazolo[3,4-(i]pyridazm-7-ones Prepared by Cyclization of 4-(Alkyn-1 -yl)pyrazole-5-carboxylic Acid Hydrazides [85IZV1367 85MI2]. 

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