Pyrazole ring hydrazones

An analogous series of reactions is used to produce depyrimidinated DNA fragments. Hydrazine is used in these reactions, since both cytosine and thymine react with hydrazine. The bases are cleaved to yield urea and a pyrazole ring. The deoxyribose moiety is left as a hydrazone. Piperidine, which reacts with the hydrazone, is used to cleave the nucleotide chain. Cytosines react specifically with hydrazine in 5 mol/ L NaCl, but no specific reaction exists for thymines. Consequently, one aliquot yields labeled oligonu-cleotides 3 -terminated at cytosines, whereas a second aliquot contains nucleotides cleaved in the absence of NaCI at both cytosine and thymine residues. 

Thermolysis of diazides 23 occurs as a two-step process. Thus, at a temperature of 120-130°C, 2-aminoindazole hydrazone 24 is formed, and this compound can be isolated. At elevated temperatures, the second pyrazole ring is closed and 2,2 -biindazolyls 25 are formed (64JOC1150). 

Hydrazino groups are also converted into H-compounds with mercury(II) oxide (74CR(C)-(278)427) in other reactions they have given hydrazones, or have been converted into pyrazoles and fused heterocyclic rings (77JAP(K)7785194), e.g. (72) -> (73). 

In other cases, attempts to cyclize the hydrazone proved more difficult and resulted in mixtures of compounds. The products obtained along with pyrazol-3-ones were ring-opened compounds or other pyrazole derivatives. Pilgram, who obtained hydrazones 56a,b by standard methodology, reported one such example. 

Nitroquinoline 209 enters into a direct cyclocondensation with aromatic hydra-zones in NaOH/DMF giving pyrazolo[3,4-/]quinolines 210 and (or) triazino[6,5-/ quinolines 211 in low to moderate yield (Scheme 62) (OOOL413). Their ratio mainly depends on the structure of the starting hydrazone. For example, electron-donating substituents in its aryl moiety assist triazine ring closure. Evidently, pyrazoles 210 are products of two consecutive SNH and SN ipso reactions, whereas conversion of 209 into 211 looks rather complicated and better corresponds with cascade hetero-cyclizations considered in Section III.D.l. 

By contrast, 3-hydrazino-l,2,4-thiadiazoles (163), which are prepared by ring closure methods, are very sensitive to acids and undergo elimination of sulfur with formation of 5-arylamino-l,2,4-triazoles (164) as indicated in Scheme 61 (63JCS4566). The mechanism of this conversion is not known but presumably involves the attack of a hard nucleophile at the 5-position followed by ring opening, loss of sulfur and recyclization as has been observed with the quaternary salts (77JCS(P1)1791) (see Schemes 22, 23, and 24). Hydrazine (163) reacts with aldehydes to produce hydrazones (165) and with dimethyl malonate to yield pyrazoles (166). Diazonium salts of type (153) have been prepared by the methods... 

The fused pyrrole ring system (204) has been obtained by the reaction of 17/3-hydroxy-17-methylandrosta-l,4-dien-3-one with tosylmethyl isocyanide in the presence of sodium hydride in DMSO,92 and 17/3-hydroxy-17-methyl-7-oxa-5o -androstano-[3,2-c]- (205) or -[2,3-d]-isoxazoles (206 X = O) have been prepared by treating 7-oxa-2-(hydroxymethylene)-17/3 -hydroxy-17-methyl-5 a -androstan-3-one with hydroxylamine hydrochloride.93 In the presence of pyridine, the isox-azole (206 X = O) is formed, but when the reaction is catalysed by sodium acetate in acetic acid the isomeric steroid (205) results. Cycloaddition of hydrazine hydrate to the same 2-hydroxymethylene-7-oxa-steroid results in the [3,2-c]pyrazole (206 X = NH). A similar addition is encountered in the reactions between 3/3-hydroxy-16-(hydroxymethylene)-5a-androstan-17-one and the substituted hydrazines RNHNH2 (R = H, o-COC6H4NH2, or p-COQHUNH ,) when the corresponding [17,16-c]pyrazoles (207) are formed after cyclization of the intermediate hydrazones.94... 

Thermolysis of the sodium derivative of the tosylhydrazone (95.1) at 280-340 C gives the fused pyrazole it is possible that a diazo derivative is an intermediate [3292]. The monohydrazone of cyclohexane-1,3-dione is cyclized by heating with ethyl orthoacetate and an acidic catalyst [2565]. Annulation of a hydrazone [such as (95.2)] to a ring-carbon of the original hydrazine may be achieved by heating the compound in DMF with an aryl aldehyde [2912]. 

Hydrazine reacted normally with 52 leading to the corresponding hydrazone in a 74 % yield. With other trifluoroacetyl lactams and hydrazine or phenylhydrazine an interesting ring-opening of the lactame function, followed by ring-closure (RORC) occurred. This leads to unusual zwitterionic pyrazoles 55 (Scheme 57). 

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