Carboxamides hydrazines

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. 

Semicarbazide hydrochloride (hydrazine carboxamide hydrochloride) [563-41-7] M 111.5, m 173 (dec), 175 (dec), pK " 3.66. Crystd from aqueous 75% EtOH and dried under vacuum over CaS04. Also crystd from a mixture of 3.6 mole % MeOH and 6.4 mole % of water. [Kovach et al. J Am Chem Soc 107 7360 1985.] IR v 700, 3500 cm" [Org Synth Coll Vol I 485 I94I-, Davison and Christie J Chem Soc 3389 I955 -, Thiele and Stange Chem Ber 27 33 I894 pK Bartlett J Am Chem Soc 54 2853 1923]. The free base crystd as prisms from abs EtOH, m 96° [ Curtius and Heidenreich Chem Ber 21 55 1894]. TOXIC ORALLY, possible CARCINOGEN and TERATOGEN. 

The reactivity of 4-phenylimidazo[5,l-c][l,2,4]triazin-8-carboxamide 485 toward hydrazine has been studied [82JCS(P 1) 1811], whereby pyrazol-4-ylidenehydrazino)imidazole-4-carboxamide 486 was formed (Scheme 102). 

DOPA decarboxylase, should permit more efficient utilization of DOPA. A compound very closely related structurally to the substrate for the enzyme fulfills this function. Carbidopa 168 was designed for this purpose. Carbidopa s synthesis begins with a modified Strecker reaction using hydrazine and potassium cyanide on arylacetone 165 to give 166. This is then hydrolyzed with cold HC1 to give carboxamide 167. 

In the pyrazolo [ 1,5-a]pyridine series, the reaction of hydrazine with the 2,3-dimethoxycarbonyl derivative afforded the corresponding 2-hydrazide, whereas saponification and decarboxylation gave the 3-carboxylic acid.169 Further, several 2-substituted 3-carboxamides, -hydrazides, and -carboxylic acids were obtained,169,239 using standard methods. Decarboxylation was also reported.169 A number of transformations of py razolo [3,4-h]pyridine... 

Treatment of ethyl l-oxo-l//-pyrimido[l,2-a]quinoline-2-carboxylates with ammonia in methanol and hydrazine hydrate in ethanol at ambient temperature afforded 2-carboxamides and 2-carbohydrazides, respectively (74MIP1 79MIP2). Reaction of l-oxo-l//-pyrimido[l,2,-a]quinoline-2-carboxylic acids (169) with A-. /V-carbonyldiimidazole in dimethyl-formamide, then with 5-aminotetrazole gave 7V-(5-tetrazolyl)-1 -oxo-1H-pyrimido[l,2-a]quinoline-2-carboxamides (170) (77GEP2630469 77USP 4017625). 

The majority of pyrimido[4,5-c]pyridazines have been prepared from pyrimidine precursors. The chloropyrimidines (176) give the desired heterocyclic ring (177) on reaction with hydrazine (72BSF1483). Hydrazine also reacts with ethyl a-diazo-/3-oxo-5-(4-chloro-2-methylthiopyrimidine)propionate (178) to give the pyrimido[4,5-c]pyridazine-3-carboxamide (78). A mechanism for this interesting reaction has been proposed as shown, on the basis of the detection of hydrogen azide in the reaction mixture. There is no precedent for the reaction of the a-carbon of a-diazo-/3-oxopropionates with nucleophiles under basic conditions (76CPB2637). 

Meszaros, Hermecz et al. transformed the quaternary 6,7.8,9-tetrahydro-pyrido[1.2-u]pyrimidinium salts (204) with acid to the carboxylic acids (205 R1 = H)257 and with sodium hydrogen carbonate solution to the l,6,7,8-tetrahydropyrido[l,2- ]pyrimidines (205 R = alkyl).7x2 8 From the alkaline hydrolysis reaction mixture, compounds 206 and 207 were also isolated.133 The quaternary salt (204 R = Me) was transformed with hydrazine hydrate to 6-methylpiperidone and with ammonia to 6-methyl-4-oxo-6.7,8,9-tetrahydro-4//-pyrido[1.2- ]pyrimidine-3-carboxamide and its A-methyl derivative.133... 

Semicarbazide (Aminourea, Carbamylhydrazine or Hydrazine carboxamide). NHi.NH.CO.NHj mw 75.07 colorl prisms mp 96° d l,484g/cc at 4°. V sol in w sol in ethanol. Prepn is by electrolytic redn of nitrourea in sulfuric acid. The base Is then obtd by reaction of the semicarbazide sulfate with liq ammonia. CA Registry No [57-56-7]. See also in Vol 2, C45-L, under Carbazide for a definition of semicarbazide Semicarbazide forms salts which are either expl or, as in the case of the hydrochloride, are used in propint compns... 

Ethyl 3-ethyl-2-methyl-4-oxo-4//-pyrido[ 1,2-a]pyrimidine-7-carboxyl-ate 486 reacted with ammonia, methylamine, and dimethylamine in methanol at ambient temperature for 3 days, with benzylamine at 175°C for 1 hour, and with hydrazine in boiling ethanol for 1 hour to afford the appropriate 7-carboxamides 487 and 7-carbohydrazide (83PHA218). The treatment of 7-carboxamide 487 (R = R1 = H) with boiling phosphoryl chloride for 1 hour afforded 7-nitrile 488. 7-Carboxylic acid chloride 490 was... 

Many of the iV-alkyl and iV-aryl derivatives of urazine have been synthesized and characterized, but the parent substance is not well known. In the past, urazine has been prepared by thermal deammonation of carbohydrazide-iV-carboxamide [eq. (I)],1 fusion of hydrazidicarbamide with hydrazinium hydrogen sulfate [eq. (2)],2 fusion of earbohy-drazide with urea [eq. (3)],3 action of sodium hypobromite on semicarbazide [eq. (4)],4 reaction of dichlorourea with concentrated ammonia [eq. (5)],5 and the reaction between 1,2 hydrazine carboxylic ester and hydrazine hydrate... 

Many hydrazine derivatives condense readily with potassium cyanate to give AT-substituted semicarbazides. Car-bohydrazide reacts with 1 or 2 mols of potassium cyanate to form carbohydrazide-iV-carboxamide or carbohydrazide-iVjiV -dicarboxamide. 

Thiazolecarboxylic acids, esters or acid chlorides react readily with ammonia or various amines, affording the corresponding carboxamides. Dehydration of the amides with phosphorus pentoxide or phosphoryl chloride occurs readily and gives the corresponding nitriles (Scheme 99). Thiazolecarboxylic acid hydrazides are obtained in a similar way, using hydrazine or substituted hydrazines instead of ammonia or amines. The Raney nickel reduction of cyanothiazoles leads to the corresponding amino compounds, the 4-cyano derivative being the isomer most readily reduced. 

HYDRAZINE CARBOXAMIDE see HGUOOO HYDRAZINECARBOXAMIDE MONOHYDROCHLORIDE see SBW500 HYDRAZINE, COMPD. WITH BORANE (1 1) see HGU025... 

An alternative, new approach for the synthesis of co-carboxamide-containing amino acid derivatives is based on the oxidation of suitably protected a,a-diamino acids (2,4-diamino-butyric acid, ornithine, lysine) with permanganatet or ruthenium(lV) oxide,as shown in Scheme 6. The co-Boc-carboxamide group is stable toward catalytic hydrogenation, acetic acid, and 10% TEA/CH2CI2, is unstable in the presence of 1M NaOH/MeOH, and is cleaved with methanolic hydrazine hydrate, 25% TFA/CH2CI2, 25% HBr/AcOH, or HF.P l... 

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