Methylhydrazines

Scheme 4 shows in a general manner cyclocondensations considered to involve reaction mechanisms in which nucleophilic heteroatoms condense with electrophilic carbonyl groups in a 1,3-relationship to each other. The standard method of preparation of pyrazoles involves such condensations (see Chapter 4.04). With hydrazine itself the question of regiospecificity in the condensation does not occur. However, with a monosubstituted hydrazine such as methylhydrazine and 4,4-dimethoxybutan-2-one (105) two products were obtained the 1,3-dimethylpyrazole (106) and the 1,5-dimethylpyrazole (107). Although Scheme 4 represents this type of reaction as a relatively straightforward process, it is considerably more complex and an appreciable effort has been expended on its study (77BSF1163). Details of these reactions and the possible variations of the procedure may be found in Chapter 4.04. 

An interesting illustration of a bielectrophile contributing two heteroatoms to the resultant five-membered ring is the 2-alkyl-2-chloro- (or fluoro-) sulfonylcarbamoyl chlorides (212). With methylhydrazine initial attack by the more basic nitrogen occurred on the carbamoyl chloride, and this was followed by base-induced cyclization to 1,2,3,5-thiatriazolidine derivative (213) (77JCR(S)238, 77JCR(M)2813). Other reactions of this type are discussed in Chapter 4.28. 

Phenyl-l,2-dithiolylium salt (483) with hydrazine, methylhydrazine or phenylhydrazine yielded the corresponding pyrazole (485) via the intermediates (484a-c). The ring-fused system (486) is a convenient source of the ring-fused pyrazole (487) when treated with hydrazine (see Chapter 4.31). 

Methyl-3-heptanone Methylhydrazine Metolachlor Methyl mercaptan Methyl parathion Methyl phenol N-Methyl-2-pyrrolidinone Methyl tert-butyl ether Mevinphos ... 

There are two methods for the introduction of a hydroxyalkyl group at position 5 of the pyrazol-3-one ring. Schmidt and Zimmer converted furanediones 258a-k into arylmethylenepyrazol-3-reaction with hydrazine hydrate or methylhydrazine (83Jmechanism proposed for the reaction involves nucleophilic attack of the hydrazine on the ketone carbonyl, followed by attack on the ester carbonyl and ring opening of the... 

To shed light on the reaction pathway, a cyclization with methylhydrazine was carried out (70ZOR439 73ZOR832), since pyrazoles with nonequivalent positions 3 and 5 are obtained in this case. From l-methoxybut-l-en-3-yne and methylhydrazine sulfate a 4 5 mixture of 1,3- (110) and 1,5-dimethylpyrazoles (111) was formed (GLC) (70ZOR439). In the reaction of methoxybutenyne homologs (R = Ft, -Pr) with methylhydrazine (72°C, H", H2O, 2 h), lengthening of the alkyl radical leads to an increase in the content of 1,5-isomer (111), with yields of 50-60%. Thus, when R = Ft, the ratio is 2 3 (73ZOR832). 

A comparative evaluation of the reactivity of nonsymmetric hydrazines with 1-heteroalk- l-en-3-ynes has been performed (8 lUKl 252). Methylhydrazine reacts with these compounds mainly via the unsubstituted amino group (69ZOR1179). The same is observed for dialkylhydrazines (with X = R2N, RO, RS) (81UK1252). 

The reaction of 4-dialkylaminobut-3-yn-2-ones with monosubstituted alkylhy-drazines, e.g., methylhydrazine, leads to a mixture of isomeric pyrazoles 365,366 and 367, 368. 

Triarylthiapyrylium salts react with methylhydrazine to give 3,5,7-triaryI-l-methyI-l/f-... 

Triarylthiapyrylium tetrafluoroborate (10 mmol) was added over a few minutes to methylhydrazine (10 mL. large excess), cooled in a liquid N2 bath. The mixture was left at 0CC for 13 h and the red product was collected. 

Treatment of isatoic anhydrides with thionyl chloride furnishes the isocyanates 22, which react with methylhydrazine to yield Ihe benzotriazepinediones 23.362... 

Chemical Reactions. It burns with a luminous flame and is readily expld (Ref 2). It is reduced with Zn dust and Na hydroxide to dimethyl hydrazine (Ref 2). Action of coned HC1 forms methylhydrazine and formaldehyde (Ref 2). Treatment in anhyd eth with Na metal forms a solid adduct which gives dimethylhydrazine on addn of w (Ref 4). For a review of thermal and photochem reactions see Ref 8 Explosive Limits. In mixts with air the crit press at which exp] occurs varies inversely with temp betw 350 and 380° (Ref 6)... 

Simultaneous Differential Thermal-Mass Spectrometer Analysis of Nitrate Salts of Mono-methylhydrazine and Methylamine , SAMSO TR-70-117(1970) 54) Anon, Propellants,... 

Treatment of the acylproline esters 72 with methylhydrazine results in the cyclisation with inversion to form the l,3,5-triazepin-3,5-diones 73 <96CC85>. 4,5-Dihydro-1//-1,3,4-benzotriazepines have been prepared by the cyclisation of amidrazones with carbonyl compounds <95AP505, 96H(43)2549> and a route to 3,4-dihydro-l//-l,3,4-benzotriazepine-2,5-diones is reported <96JHC1131>. 

Treatment of 4-methoxy-3-nitrocoumarin 23 with hydrazine hydrate and methylhydrazine in ethanol at room temperature for 3 h gave 1,2-dihydro-5-(2-hydroxyphenyl)-4-nitro-3H-pyrazol-3-one 24a and l,2-dihydro-5-(2-hydroxyphenyl)-2-methyl-4-nitro-3H-pyrazol-3-one 24b in 70 and 51% yields, respectively. 

Compound 24a was also obtained in 17% yield by heating of 4-hydroxy-3-nitrocoumarin 27 [12] with hydrazine hydrate in ethanol. A similar reaction of 27 with methylhydraine in boiling ethanol did not afford 24b because of the decomposition of the starting coumarin. However, when 27 was treated with methylhydrazine at room temperature for 24 h without solvent, the ring-opened methylhydrazine adduct 28 (36% yield) and 1,2-dihydro-5-(2-hydroxyphenyl)-l-methyl-4-nitro-3H-pyrazol-3-one 26 (ll%yield) were... 

Methylhydrazine can combust spontaneousiy in the presence of air when in the form of a film at the surface of a porous substance. All oxidants give rise to dangerous reactions with this compound. 

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