A-Methylhydrazine derivation

The oral agent procarbazine is a methylhydrazine derivative, and it is commonly used in combination regimens for Hodgkin s and non-Hodgkin s lymphoma and brain tumors. 

Brunner KW, Young CW. A methylhydrazine derivative in Hodgkin s disease and other malignant neopksms Aerapeutic and toxic effects studied in 51 patients. Ann Intern Med (1965) 63,69-86. 

The NH2 groups in the A-methylhydrazine derivatives (153-157) have been reacted with ferrocene-2-carboxaldehyde (FcCHO, Fc=ferrocenyl) to yield the corresponding hydrazones (158-162). Electrochemical studies of these compounds reveal only a single reversible oxidation pattern, pointing to an electrochemical equivalence of the ferrocenyl groups. 

Meso-ionic 3-alkyl-l,2,3,4-oxatriazol-5-ones (271) are obtained by the nitrosation of 1-alkyl semicarbazides, RNHNHCONHj. At low temperatures, the intermediate A-nitroso derivatives (272) can be isolated, which cyclize on heating. An alternative synthetic route is illustrated by the formation of meso-ionic 3-methyl-l,2,3,4-oxatriazol-5-one (271, R = Me) from A-nitroso-iV-methylhydrazine (273) and phosgene. ... 

Miscellaneous Synthetic compounds - Procarbazine, (N-isopropyl-Of-(2 methylhydrazino)-g -toluamide hydrochloride), one of several derivatives of methylhydrazine which have antineoplastic activity against transplanted tumors, has proven clinically useful in the management of Hodgkin s disease. A second derivative, N-allophanoyl-a-(2 methylhydrazine)- -toluam-ide, appeared to have activity comparable to that of procarbazine in a preliminary clinical trial. 47 The mechanism by which procarbazine and related compounds produce cytotoxicity is not established. Procarbazine produced a short-lived inhibition of synthesis of DNA, RNA and protein when studied in a mouse lymphoma 48 the methyl group enters the 1-carbon pool and participates in transmethylation reactions. 49 Pertinence of these observations, as well as those previously described of molecular autoxidation to the drug s antitumor effects, awaits demonstration. 

Gyromitrin is a volatile derivative of hydrazine (see Figure 4) with the chemical formula of acetaldehyde methyl formylhydrazone and is readily converted to N-methyl-N-formyl hydrazine and N-methylhydrazine. It is primarily a liver toxin although the red blood cells and central nervous system are also involved. The... 

The difunctionality of NH2 moiety in the methylhydrazine derivatives has also been underlined by the reaction of (156) with trimethylorthobenzoate to afford the l-phospha-2,3,5,6-tetrazine derivative (163), which on oxidation with benzoquinone can be transformed to the radical species (164). EPR and ENDOR spectroscopic experiments clearly point to a spin polarization through the spirocyclic phosphorus atom to the other phosphorus and nitrogen nuclei in the phosphazene ring of (164). ... 

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. 

Palladium-catalyzed cyclization reactions with aryl halides have been used to synthesize pyrazole derivatives. V-Aryl-lV-(c>-bromobenzyl)hydrazines 26 participated in a palladium-catalyzed intramolecular amination reaction to give 2-aryl-2W-indazoles 27 . Palladium-catalyzed cascade intermolecular queuing-cyclocondensation reaction of o-iodophenol (28) with dimethylallene and aryl hydrazines provided pyrazolyl chromanones 29 <00TL7129>. A novel one-pot synthesis of 3,5-disubstituted-2-pyrazolines 32 has been achieved with an unexpected coupling-isomerization sequence of haloarene 30, propargyl alcohol 31, and methylhydrazine <00ACIE1253>. 

The reaction of 5-aryl-3-(chloromethyl)[l,3,4]oxadiazole-2(3//)-thiones 100 with hydrazine or methylhydrazine yields the corresponding 2,3-dihydro[l,2,4]triazolo[3,4-A][l,3,4]oxadiazole derivatives 102 <1984JCED477>. By analogy, hydrazine and phenylhydrazine convert the [l,2,4]triazole-2(3//)-thiones 101 into 3,7-dihydro-2//-[l,2,4 tria-zolo[4,3-r][ 1,2,4] triazoles 103 <1992PS99, 2002JCCS1035>. Finally, the azole-2(3//)-thiones 101 react with hydroxylamine to form the 3,7-dihydro[l,2,4]triazolo[5,l-d[l,2,4]oxadiazoles 104 (Scheme 8) <1992PS99>. 

Fortunately, of the vast number of mushroom species that exists, only a few produce secondary metabolites that cause fatal poisonings. If toxins causing benign symptoms, such as abdominal pain and diarrhea, hallucinations, or alcohol incompatibility, are disregarded, the most significant mushroom toxins are the extremely hazardous compounds of amatoxins, orellanine, and, to a lesser extent, methylhydrazine and its derivatives. Consequently, there is only a... 

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 reaction of 2-thiovioluric acid (69) with hydrazine hydrate in boiling ethanol afforded triazolopyrimidine derivative 70, but in boiling acetic acid yielded N-acetyltriazolo[4,5-d]pyrimidine derivative 71. In the same manner, the N-phenyl and A-methyl-l, 2,3-triazolo derivatives 72 and 73 were obtained through the condensation of 69 with phenylhydrazine and with methylhydrazine, respectively (91MI1) (Scheme 13). 

Oxidative processes using mild oxidants (e.g., HgO or Mn02) leading to NN bond formation convert /k-hydrazones 538 into the 1-amino-l,2,3-triazole derivatives 539 (Scheme 242) <1967TL3295, 1971JPR882>. A regioselective synthesis of 2,4-disubstituted 1,2,3-triazoles is based on a reaction of aminoacetophenones 540 with hydrazines (Scheme 243) . The reaction with methylhydrazine proceeds well without any catalysis, but that with phenylhydrazine requires cupric chloride as a catalyst. It is assumed that hydrazone 541 that forms in the first step is in a tautomeric equilibrium with its azo form 542 <2003SC3513>. 

The ene hydrazine 100, prepared from dimedone and methylhydrazine, forms the Michael adduct 101 with dimethyl acetylenedicarboxylate. The adduct is converted into a mixture of pyrrole and pyridone derivatives, 103 and 104, in boiling tetralin. These products arise by a [3.3]sigmatropic shift in the adduct with cleavage of the nitrogen-nitrogen bond to give 102, followed by cyclization and elimination of ammonia and methanol, respectively (equation 42)63. 

Dimozine. A code name for unsym-Dimethyl-hydrazine, described in this Vol under Di-methylhydrazine and Derivatives... 

Dimethylhydrazine and Derivatives uns-Dimethylhydrazine (UDMH) (1,1-Di-methylhydrazine), code name Dimazine, (H3O2N.NH2 mw 60.10, N 46.62% col flammable liq with ammonia-like odor hygroscopic sp gt 0.791 at 22° ft p minus 58° bp 63° v sol in w, ale, eth in hydrocarbons. Following methods of prepn are listed in Refs 1 11 a) reaction of dimethylamine (DMA) chloramine ... 

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