Hydrazines monoalkyl

The 1-alkyl-diaziridines can easily be hydrolyzed to alkyl hydrazines. Hence alkyl hydrazines are easily available from Grignard reagents and thus from alkyl halides. The three last examples of Table XII show the yield of alkyl hydrazine calculated on the diazirine used. The reaction has preparative interest because the alkylation of hydrazine with alkyl halides only gives monoalkyl hydrazines in exceptional cases. ... 

Reaction of aldehydes with hydrazine, or mono- or 1,2-disubstituted hydrazines is the method used almost exclusively for the preparation of hexahydro-l,2,4,5-tetrazines (377). All types of hydrazines have been used hydrazine itself, monoalkyl-, monoaryl-, dialkyl-, diaryl-, alkylaryl-, alkylacyl- or arylacyl-hydrazines. The aldehydes used were mainly aliphatic aldehydes. An excellent review by Wiley of the literature on this reaction up to 1974 is available (78HC(33)1075, p. 1190). 

Platinum oxide has also been used for the preparation of monoalkyl- or monoaralkyl-hydrazines from the corresponding hydrazones.84,85 It is noted that the yields of hydrazines appear to have been improved considerably with use of ethanol-acetic acid as solvent,85 compared to the use of methanol.84... 

Khalil et al. (05PS479) reacted hydrazine hydrate with ethyl acetoacetate, ethyl benzoylacetate or ethyl nicotinoylacetate in boiling ethanol and obtained 5-substituted pyrazol-3-ols la-c (Scheme 75). The existence of pyrazoles 325a-c predominantly in their enol tautomeric form was confirmed by spectroscopic data as well as by phase-transfer catalysis (PTC) alkylations, affording O-monoalkylated or O- and... 

Auch Acyl-hydrazone einfacher Carbonsauren werden ohne Nebenreaktionen mit verschiedenen Katalysatoren zu den Acyl-hydrazinen hydriert, die in der Regel durch saure Verseifung in Monoalkyl-hydrazine iiberfuhrbar sind. Zahlreiche aliphatische und aromatische Aldehyd- und Keton-acetylhydrazone lassen sich so zu den entsprechenden Hydraziden umsetzen z.B.12 ... 

Figure 10.25 Twenty-nine specific toxicophores for mutagenicity as identified by Kazius el al. (Kazius, J-, et al. Derivation and validation of toxicophores for mutagenicity prediction. J. Med. Chem. 2005, 48, 312-320.) (A) Specific aromatic nitro, (B) specific aromatic amine, (C) aromatic nitroso, (D) alkyl nitrite, (E) nitrosamine, (F) epoxide, (G) aziridine, (H) azide, (I) diazo, (J) triazene, (K) aromatic azo, (L) unsubstituted heteroatom-bonded heteroatom, (M) aryl hydroxylamine, (N) alkyl halide, (O) acyl halide, (P) N- or 5-mustard, (Q) polycyclic aromatics, (R) bay-region, (S) K-region, (T) sulphonate-bonded C, (U) unsaturated aldehyde, (V) alkyl A-nitro, (W) diazonium, (X) p-propiolactone, (Y) unsubstituted a,p unsaturated alkoxy, (Z) l-aryl-2-monoalkyl hydrazine, (AA) aromatic methylamine, (AB) aryl hydroxylamine ester, and (AC) polycyclic planar system.

Metabolism studies on 1,2-dimethylhydrazine in vivo led to the mechanism of metabolic activation outlined in Fig. 18 (725). Unlike monoalkylated hydrazines, 1,2-disubstituted hydrazines appear to form azo and azoxy compounds which act as proximate carcinogens. In the case of 1,2-dimethylhydrazine, azoxymethane and methylazoxymethanol were detected in the urine of treated rats 126). Studies on the metabolic fate of procarbazine in vivo have also shown that dealkylation occurs 108, 109). 

An alternative method for preparing the dialkyl triazole sulfonyluieas 20 involved alkylation of monoalkyl-substituted triazole sulfonyluieas which were prepared as shown. In this case, reaction of hydrazine with the cyanoimidate 16 gave rise to only one aminotriazole product 19. Subsequent alkylation of the derived sulfonylurea afforded the dialkyltriazole sulfonylureas 20. 

A new synthesis of monoalkyl hydrazines has been reported which overcomes many problems associated with previous methodology. In a modified procedure analytically pure monoalkylhydrazine hydrochlorides are available from aldehydes or ketones by reaction with t-butyl carbazate. The use of the t-butyl group greatly facilitates hydrolysis of the intermediate carbazate, giving direct in situ formation of the hydrazine hydrochloride salts (Scheme 39). 

Toth lists 9 symmetrical and 10 unsymmetrical hydrazines as tumori-genic compounds. From their studies with acetylhydrazine and isopropylhydra-zine. Nelson el have proposed that monoacyl and monoalkyl hydrazines... 

Lam et al. synthesized isoxazolines 469 and pyrazolines 470 via monoalkylation with dimsyl anion and styrene oxide 480 and following an oxidation/ elimination strategy [292]. Oxidation of secondary alcohols 481 is performed via Jones oxidation and cyclization with cleavage from the resin follows in a separate step. Diverse elements can be introduced to the heterocycle using either hydroxylamine 483 or hydrazine derivatives 484 (Scheme 72). Corresponding six-membered heterocycles like pyridazine derivatives 471 can be obtained when the linked molecule 482 bears a benzoyl substituent instead of the phenyl substituent at the a-C-atom [293]. 

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