Methylhydrazine treatment

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)... 

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. 

It appears that treatment of phenacyl bromides 1239 with methylhydrazine in refluxing acetic acid leads also to 1,4-disubstituted triazoles 1244. Fivefold excess of methylhydrazine is used in these reactions. According to the proposed mechanism, structures 1240-1243, methylhydrazine has a double role, as a condensing agent and an oxidant. In the final account, three molecules of methylhydrazine have to be used to produce one molecule of triazole 1244, two molecules of methylamine and one molecule of ammonia. The basic triazole 1244 (X = Y = H) is separated in 59% yield. The reactions go well with electron-donating substituents (for X = OH, the yield is 81%), but electron-withdrawing substituents can lower the yield dramatically (11% for X = N02) (Scheme 206) <2003JCM96>. 

In the simplest example, 2-chloropyrazine can be treated with methylhydrazine to afford 244a Commencing with 244a, treatment with 3-methyl-2-butanone gives an enamine, which, after thermal Fischer-type cyclization, leads to 245 (Equation 88) <1994MI17>. 

Molinate (27) (65USP3198786) is simply made from perhydroazepine and 5-ethyl chlorothioformate, while the recently introduced pyrazolate (28) (75GEP2513750) is synthesized from l,3-dimethylpyrazol-5-one, itself easily made from methylhydrazine and ethyl acetoacetate. Reaction of the pyrazolone with 2,4-dichlorobenzoyl chloride takes place on carbon at the 4-position, and then treatment with toluene-p-sulfonyl chloride gives pyrazolate. Difenzoquat (29) (75USP3922161) is readily available from 3,5-diphenylpyrazole by methylation. Ethofumesate (30) (69GEP1926139) is synthesized from p-benzoquinone (Scheme 8). 

Chloro derivative 291 was obtained from dioxo derivative 70 by treatment of phosphoryl chloride in dimethylformamide at 100°C for 2 hours (80CPB3537). The treatment of chloro derivative 291 with methylhydra-zine in a mixture of ethanol and chloroform under reflux gave 2H-pyrido[ 1,2-a]pyrimidin-2-one 295 and rearranged pyridazino[3,4-6]-quinoxaline 296 in 4.8% and 78% yields, respectively (Scheme 21) (80CPB3537). 3,4-Dihydroquinoxalinone 70 could not be rearranged into pyridazino[3,4-6]quinoxaline 296 by treatment with methylhydrazine. When hydrazine hydrate was employed instead of methylhydrazine, tricyclic ethyl ester 297 (R1 = Et) was obtained. The latter reaction gave methyl ester 297 (R1 = Me) when carried out in a mixture of methanol and chloroform (80CPB3537). 

The radical reaction of hydrazine and methylhydrazine with some a,(3-unsaturated ketones 54 initiated by 2,2-dipenyl-l-picrylhydrazyl (DPPH) is described in [60]. At — 78°C the treatment is practically regioselective and yields pyrazoles 55, while regioisomeric heterocycles 56 are observed in trace amounts (Scheme 2.13). 

Mixtures of the isomers (243) and (244) react with hydrazine hydrate to give the products (245) and (246) (Equation (34)) <84EUP108382> and the aza derivatives (247). Methylhydrazine gave the amines (248) (Equation (35)) <84JHC965>. Alkaline cleavage of compound (249) followed by treatment with hydrazine gave compounds (250) and (251) (Equation (36)) <81ACH167>. 

PyrazoUne-5-ones. Treatment of 2-bromo-l,3-diphenyl-l,3-propanedione (1) with methylhydrazine in ethanol at room temperature gives l-methyl-3,4-diphenyl-A -pyrazoline-5-one (2) in 56% yield. It is probably formed by a halohydrin rearrangement as indicated. 

The acid catalysed conversion of the nitroso derivative of benzyl-methylhydrazine (278) into its isomer (279) is significant in the context of the above mechanism. In addition, the formation of aryl azides from nitrosohydrazides such as 280 by treatment with 20% sodium hydroxide solution (equation 144) is consistent with the results of Clusius and co-workers. 

From 1-tert-butyl 2-ethyl S-acetyl-6-oxopiperidine-l,2-dicarboxy-late. Treatment of Boc-protected 5-acetyl-6-oxopiperidine-2-carboxylic acid ethyl ester 218 with a 64% aqueous solution of hydrazine in acetonitrile gave (R,S)-2-ferf-butoxycarbonylamino-4-(3-oxopyrazol-4-yl)butyric acid 219, in 67% yield. The corresponding 1-methyl derivative 220 was obtained in only 17% yield by treating 218 with methylhydrazine under similar conditions (99EJMC967) (Scheme 49). 

Hydrazinoquinoxalines are generally prepared from the corresponding chloroquinoxalines by treatment with hydrazine hydrate in refluxing ethanol. It has been found that displacement reactions with hydrazine can be carried out under milder conditions than the parallel reactions with ammonia or amines, and that when methylhydrazine is reacted with chloroquinoxalines, a 1 1 disubstituted hydrazine is formed, rather than a 1 2 disubstituted product. ... 

Tetrahydroindazolones (408) have been converted to the angular dihydrobenzo[l,2-c 4,3-c ]di-pyrazoles (410) and the corresponding fully unsaturated compounds (411) as shown in Scheme 20 <9lH(32)4i>. Treatment of (408) with ethyl formate or acetyl chloride in the presence of base gave the ) -dicarbonyl derivatives (409) which by further treatment with hydrazine or methylhydrazine led to dihydrobenzo[l,2-c 3,4-c ]dipyrazoles, e.g., (410), and to dehydrobenzo[l, 2-c 4,3-c ]dipyrazoles, e.g., (411), by subsequent dehydrogenation. 

Esters 59 react with methylhydrazine to give the hydrazides 60 which, in the presence of one equivalent of acetic acid, condense with cyclohexane-1,3-dione under Dean-Stark conditions to give the enaminones 61. Treatment of 61 with sodium hydride in tetrahydrofuran affords the diazetidi-nones 62 in moderate to good yields. Scheme 19 (91H2417). 

Treatment of benzonitrile oxide with 1-ethoxycarbonyl-l-methylhydrazine affords the hydroxamoylhydrazinecar-boxylate 195 which can be cyclized with sodium hydride to the oxatriazinone 52 (Scheme 33) <1998ASJ180>. 

The -isothiocyanatoketone (25) was reacted with hydrazine or methylhydrazine via an intramolecular cyclization affording the 3-thioxo-l,2,4-triazepines (26), which can be converted to the 2//-5,7-diphenyl-3-methylthio-5,6-dihydro-l,2,4-triazepines (27) upon treatment with methyl iodide (Scheme 3) <84Ml 9i4-oi>. 

The Claisen ester condensation gives the right product just by treatment with base. The reasons for this are discussed in Chapter 26. We had then planned to treat the keto-diester with methylhydrazine but there is a doubt about the regioselectivity of this reaction—the ketones are more electrophilic than the ester all right, but which ketone will be attacked by which nitrogen atom ... 

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