Hydrazine derivative

Derivatives of hydrazine, especially the hydrazide compounds formed from carboxylate groups, can react specifically with aldehyde or ketone functional groups in target molecules. Reaction with either group creates a hydrazone linkage (Reaction 44)—a type of Schiff base. This bond is relatively stable if it is formed with a ketone, but somewhat labile if the reaction is with an aldehyde group. However, the reaction rate of hydrazine derivatives with aldehydes typically is faster than the rate with ketones. Hydrazone formation with aldehydes, however, results in much more stable bonds than the easily reversible Schiff base interaction of an amine with an aldehyde. To further stabilize the bond between a hydrazide and an aldehyde, the hydrazone may be reacted with sodium cyanoborohydride to reduce the double bond and form a secure covalent linkage. 

H Hydrazide Compound H Aldehyde Compound H Hydrazone Linkage  

The treatment of acyl hydrazine derivatives with phosgene gives 1,3,4-oxadiazole-5-ones 

Similarly, a related cyclization of PhNHC(0)NHNH with phosgene occurs [2254]  

The related dihydrazides of the dicarboxylic acid series also react with phosgene [1252]  

Treatment of semicarbazides with phosgene results in the formation of 1,2,4-triazoles 

A related compound is derived from the reaction of oxamic acid hydrazide with phosgene [1686]  

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Low-valent nitrogen and phosphorus compounds are used to remove hetero atoms from organic compounds. Important examples are the Wolff-Kishner type reduction of ketones to hydrocarbons (R.L. Augustine, 1968 D. Todd, 1948 R.O. Hutchins, 1973B) and Barton s olefin synthesis (p. 35) both using hydrazine derivatives. 

AMINES - AMINES,AROMATIC - PffiTHYLENEDIANILINE] (Vol2) -hydrazine derivative fiYDRAZINE AND ITS DERIVATIVES] (Vol 13)... 

Agricultural Uses. Pesticides represent the second largest commercial market for hydrazine. Hundreds of hydrazine derivatives have been patented for a wide range of agricultural appHcations. Table 13 presents a sampling of the 50—60 that are commercially available or developmental products. These compounds are made from hydrazine, MMH, and UDMH and are for the most part heterocycHc nitrogen compounds (see Insect control technology). 

Many hydrazones and azines are colored and useful as dyestuffs. Examples are 2-hydroxynaphthazine, a yellow fluorescent dye (Lumogen LT Bright Yellow), and the pyridon—azino—quinone class of red-violet dyes. Numerous hydrazine derivatives are antioxidants and stabilizers by virtue of their reducing and chelating powers. 

Another example is a claim of possible industrial appHcation for preparing l-cyclohexyl-3,5-dimethylpyrazole [79580-49-7] (75) and similar compounds from 1,2,6-thiadiazine-l,1-dioxide (74) by extmsion of SO2 (eq. 20) (48). This process has the added advantage of not requiring hydrazine derivatives as reactants. 

Miscellaneous Reactions. Aromatic sulfonic acid derivatives can be nitrated using nitric acid [52583-42-3] HNO, ia H2SO4 (19). Sultones may be treated with hydrazine derivatives to give the corresponding ring-opened sulfonic acid (20). 

Other methods of generating a-aminoketones in situ are common, if somewhat less general than the methods already described. 2-Nitrovinylpyrrolidine, which is readily available, yields 2,3-bis(3-aminopropyl)pyrazine on reduction and this almost certainly involves ring opening of the intermediate enamine to an a-aminoketone which then dimerizes under the reaction conditions (Scheme 59) (78TL2217). Nitroethylene derivatives have also served as a-aminoketone precursors via ammonolysis of the derived epoxides at elevated temperatures (Scheme 60) (76S53). Condensation of 1,1-disubstituted hydrazine derivatives with a-nitro-/3-ethoxyethylene derivatives has been used in the synthesis of l,4-dialkylamino-l,4-dihydropyrazines (Scheme 61) (77S136). 

The pyrazole ring is particularly difficult to cleave and, amongst the azoles, pyrazoles together with the 1,2,4-triazoles are the most stable and easiest to work with. This qualitative description of pyrazole stability covers the neutral, anionic and cationic aromatic species. On the other hand, the saturated or partially saturated derivatives can be considered as hydrazine derivatives their ring opening reactions usually involve cleavage of the N—C bond and seldom cleavage of the N—N bond. It should be noted, however, that upon irradiation or electron impact the N—N bond of pyrazoles can be broken. 

Practically all diaziridines (151) can be hydrolyzed by acids to a carbonyl compound and a hydrazine derivative. The only exceptions are diaziridines derived from formaldehyde, in which acid catalyzed N—N cleavage successfully competes with slow hydrolysis. Monoalkylhydrazines are formed in 80-95% yield, A/,A/ -dialkylhydrazines in 65-85% yield (B-67MI50800). 

While the use of substituted hydrazine derivatives is generally recognized to be the most reliable method for dehydrobromination of bromo ketones without rearrangement, this side reaction can be important in some cases. Both the 2-bromo-A" -3-ketone and its 4-bromo isomer give the same A" -diene hydrazone (33), °° which is cleaved to the ketone in very poor yield (however, see ref. 65 for a successful use of the semicarbazide method). 

The wide applicability of the PK reaction is apparent in the synthesis of pyrroles, for example, 45, en route to novel chiral guanidine bases, levuglandin-derived pyrrole 46, lipoxygenase inhibitor precursors such as 47, pyrrole-containing zirconium complexesand iV-aminopyrroles 48 from 1,4-dicarbonyl compounds and hydrazine derivatives. The latter study also utilized Yb(OTf)3 and acetic acid as pyrrole-forming catalysts, in addition to pyridinium p-toluenesulfonate (PPTS). 

Evidence in favor of the amino-thionic tautomeric form of 2-amino-l,3,4-thiazoline-5-thione 239 (A = X = S R = H) was obtained from X-ray structural determinations [72AX(B)1584]. A NMR-spectroscopic study (77JOC3725) of compounds 239 (A = Se X = S R = Me) demonstrated their amino-thionic structure. A similar tautomeric form 240 is also dominant for the hydrazine derivative (R = NHNHCOPh) [73JCS(P2)4]. 

It should be noted that furoxan amides and hydrazides could only be prepared in aqueous solution. In ether solution, reaction of diethyl furoxandicarboxylate with amines and hydrazine derivatives have been shown to give isoxazolones 93 (Scheme 45) (08CB3512, 09LA52, 09LA80). 

In an initial step triphenylphosphine adds to diethyl azodicarboxylate 5 to give the zwitterionic adduct 6, which is protonated by the carboxylic acid 2 to give intermediate salt 7. The alcohol reacts with 7 to the alkoxyphosphonium salt 8 and the hydrazine derivative 9, and is thus activated for a SN2-reaction ... 

In summary the Mitsunobu reaction can be described as a condensation of an alcohol 1 and a nucleophile—NuH—11, where the reagent triphenylphosphine is oxidized to triphenylphosphine oxide and the azodicarboxylate reagent 12 is reduced to a hydrazine derivative 13 ... 

The piperidide 30 a of o-aminohippuric acid cyclizes to the benzodiazepinedionc 31 a in refluxing acetic acid.209 Similarly, the free acids 30b-e210 and their ethyl esters 30f—I211 undergo ring closure on heating. The reaction has been extended to hydrazine derivatives 30m-q.212... 

Triazinopurinyl derivative 612 was prepared (91S625) by hydrazinolysis of 610, followed by cyclization of the presumably formed hydrazine derivative 611 (Scheme 125). 

In many instances, however, the intermediate triazoline can be isolated and separately converted into the aziridine, often with poor stereoselectivity. The first practical modification to the original reaction conditions generated the (presumed) nitrenes by in situ oxidation of hydrazine derivatives. Thus, Atkinson and Rees prepared a range of N-amino aziridine derivatives by treatment of N-aminophthali-mides (and other N-aminoheterocydes) with alkenes in the presence of lead tetraacetate (Scheme 4.10) [7]. 

It has since transpired that the active aziridinating species in these reactions are the N-acetoxylated hydrazine derivatives, rather than nitrenes exposure of ethyl-quinazolinone ( Q1-NH2 ) to lead tetraacetate at low temperature generates N-(acetoxyamino)-quinazolinone ( Q -NHOAc ), which is a relatively stable sub-... 

The hydrazines of quinoxaline aldehydes and ketones are so closely akin to regular hydrazinoquinoxalines that all are included in this section. The NMR properties of such hydrazine derivatives have been studied. ... 

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