Hydrazines cyano

The reaction of 5,6-diphenyl-3-cyano-l,2,4-triazine with hydrazine gives the amidrazone which, with 1,2-diketones, yields 3,3 -bistriazinyls 74 <95MI03 96CA(124)86945>. 

The synthetically versatile 6-amino-7-cyano-l,4-dihydro-3-methyl-l-phenyl-4-thioxothiopyrano[4,3-c]pyrazole 107 has been used for the synthesis of several bicyclic and tricyclic systems. For example, reaction with hydrazine gives 108, which can be used to generate tricycles 109-111 (Scheme 8) <2002H(57)1121>. 

Displacement of the methanethiol substituent in 224 by hydrazine, followed by cyclization onto the cyano-group led to efficient formation of the five-membered ring of 225 (Equation 60) <2003JHC547>. 

Cyclization of ethyl 3-cyano-3-methyl butyrate 201 with hydrazine hydrate gave the hydrazonopyridazine 202, which underwent ring closure with oxalyl chloride to give (85MIP1) pyridazinotriazine derivative 203. 

Iwakawa et al. studied the reaction of 3-acetonyl-5-cyano-l,2,4-thiadiazole 72 with a series of 4-substituted phenylhydrazine hydrochlorides. When electron-donating substituents were used (e.g., methyl and methoxy) in the phenyl ring of the hydrazine, the reaction proceeded via a Fischer-indole mechanism to give indoles 73 as the sole product. In contrast, reaction of 72 with phenylhydrazine and 4-chlorophenylhydrazine gave only small amounts of indole 72, but much higher yields of the pyrazole 74. The authors described in detail the respective reaction mechanisms... 

The reaction of 2-mercapto-4-(2, 4 -dichlorophenyl)-5-cyanopyrimidin-6(l//)one 421 (obtained by stirring ethyl cyanoacetate and thiourea with 2,4-dichlorobenzaldehyde in sodium ethylate at room temperature, in 70% yield), with a solution of monochloroacetic acid and />-cholorobenzaldehyde in glacial acetic acid, in the presence of sodium acetate, affords 2-[(/>-chlorophenyl)methylene]-6-cyano-7-(2, 4 -dichlorophenyl)thiazolo[3,2-tf]pyrimidin-3,5-dione 422. Finally, the reaction of compound 422 with hydrazine hydrate converts it into product 423 (Scheme 49) < 1996PS( 116)39>. 

More generally, electrolytically produced nucleophilic centers (amine, hy-droxylamine, hydrazine, alcohol) react with electrophilic centers (carbonyl group, cyano group, nitroso group) as illustrated in Scheme 9 for the synthesis of N-hydroxyindoles [13]. 

The method of choice for the synthesis of triazoles depends largely on the substitution pattern required. Acyclic compounds are usually the preferred substrates and the hydrazines are readily available and cheap. For 3-aminotriazoles, dimethyl A-cyanoisothiourea or diphenyl cyano-carbonimidates, although more expensive, are valuable precursors since the 5-substituent can be varied widely. 1,3-Dipolar addition using nitrilimines has been extensively used and again can be... 

Addition of nucleophiles to the cyano group of cyanothiadiazole under basic conditions takes place with unusual ease <88AG(E)434,94ACS372). Hydrolysis to the amide, for example, can be effected at 0°C in the presence of a catalytic amount of sodium hydroxide or basic ion-exchange resin. At reflux temperature, hydrazine and monosubstituted hydrazines convert 3,4-dicyano-l,2,5-thia-diazole into the l,2,5-thiadiazole[3,4-. The base-catalyzed addition of acetone to cyanothiadiazole forms an enamino ketone, used as a key intermediate for the synthesis of a number of heterocyclic ring systems, e.g. isothiazole, isoxazole, pyrazole, pyrimidine, and thiazole <77H(6)1985>. 

Having a cyano group and an amino group ortho to each other on a ring is another system that has led to the formation of fused pyrimidine ring systems. In this case, an aminopyrimidine is the result. Compound 42 in Scheme 5 is one such structure. Treatment of 42a with formamide leads to the amino derivative 43 <1999PS(155)175>. Alternatively 42b provides 44 after treatment with triethyl orthoformate followed by hydrazine <1999PS(155)175>. 

Condensation of 3-ethoxycarbonyl-, 3-acetyl-, or 3-cyano-l,2,3,4-tetrahydropyridine -carboxylic acid derivatives 275-277 with hydrazine hydrate in boiling ethanol afforded the pyrido[3,4-r/ pyridazine derivatives 278-280, respectively (Equation 20) <2002PS1359>. 

Pyrano[3,4- / pyridazine derivatives 733-735 were prepared by cyclocondensation reactions of 6-aryl-3-(ethoxy-carbonyl, acetyl, or cyano)-2-oxo-2/7,3/7,4/7-pyran-4-carboxylic acids 730-732, respectively, with hydrazine hydrate in boiling ethanol (Equation 61) <2002PS1359>. 

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