Hydrazine compounds with

Atazanavir 141 is a HTV-l protease inhibitor that is used as a treatment for AIDS. It is a t3 pical peptide mimetic that contains an unusual hydrazine compound with a pyridyl-phenyl side chain [89]. An intermediate for this side chain is 4-pyrid-2-yl-benzaldehyde 140, which was made via a nickel-catalysed Kumada reaction (Scheme 32). DIB ALH is added to the reaction to reduce Ni(ll) to Ni(0). Only 0.6 mol% of catalyst was needed and the product was isolated in 90% yield. 

Preliminary indication of the presence of a phenol ester may be obtained by heating the compound with soda-lime esters of phenols and also aromatic hydroxy-acids usually give the phenol. (Likewise amides, Imides, nitriles, substituted hydrazines, uretheines, etc. eifiord ammonia.)... 

Ureas. Chlorination of aqueous urea yields unstable A/-chloro compounds. With excess C10 decomposition yields CO2, N2O, and NCl the latter decomposes further to NO (96). Only two soHd derivatives have been isolated A/-chlorourea [3135-74-8] mp 74—76°C, and N,lSf-dichlorourea [2959-01-5] which decomposes at its mp of 83°C with evolution of NCl. As an amide, urea also undergoes the Hofmann reaction yielding hydrazine. This route to hydrazine was once employed commercially. 

It is customary to perform the condensation of 1,4-dicarbonyl compounds with hydrazines in the presence of mineral acid to avoid the formation of A-aminopyrroles. Contrary to early claims that 4,5-dihydropyridazines are formed <07CB4598), these compounds are now regarded as 1,4-dihydro derivatives 81CB564). 

Treatment of cotarnine and similar compounds with hydrogen cyanide, alkoxides, mercaptides, hydroxylamine, hydrazine, and amines has been reported to give 1-substituted derivatives of 1,2,3-tetrahydroisoquinoline (171, R = CN, OR, SP, NHOH, NHNH, NHR) (262-265). 

Nitrogen forms more than 20 binaiy compounds with hydrogen of which ammonia (NH3, p. 420), hydrazine (N2H4, p. 427) and hydrogen azide (N3H, p. 432) are by far the most important. Hydroxylamine, NH2(OH), is closely related in structure and properties to both ammonia, NH2(H), and hydrazine, NH2(NH2) and it will be convenient to discuss this compound in the present section also (p. 431). Several protonated cationic species such as NH4+, N2H5+, etc, and deprotonated anionic species such as NH2 , N2H3 , etc. also exist but ammonium hydride, NH5, is unknown. Among... 

Aryl-6-carboethoxy(and 6-carboxy)-4-oxo-2-thioxo-l,3,8-triaza-naphthalenes are converted (100°, 3 hr) 7 7 7b to 2-oxo compounds with chloroacetic acid (cf. 136 and 237). The 4-oxo group is replaced (96°, 1 hr) by hydrazine along with ring-closure involving the 6-carboethoxy group in the 2-thioxo compounds, this substituent is simultaneously converted to an oxo group. 

Condensation of ethyl acetoacetate with phenyl hydrazine gives the pyrazolone, 58. Methylation by means of methyl iodide affords the prototype of this series, antipyrine (59). Reaction of that compound with nitrous acid gives the product of substitution at the only available position, the nitroso derivative (60) reduction affords another antiinflammatory agent, aminopyrine (61). Reductive alkylation of 61 with acetone in the presence of hydrogen and platinum gives isopyrine (62). Acylation of 61 with the acid chloride from nicotinic acid affords nifenazone (63). Acylation of 61 with 2-chloropropionyl chloride gives the amide, 64 displacement of the halogen with dimethylamine leads to aminopropylon (65). ... 

Reaction of substituted hydrazine analogue with protected 3-dicarbonyl compound 67 leads to a ring-forming two-site reaction and formation of the pyrazoline diuretic agent, muzolimine (68). ... 

Hydrazine reacts with biphenyl-2,2 -dicarbaldehyde (3, R = H). under elimination of nitrogen, to give phenanthrene,17 most probably not via the intermediate formation of a diazocine system. With other 2,2 -diacylbiphenyl compounds the expected dibenzo[[Pg.520]

Reaction of hydrazine 165 with a number of monosaccharides give hydrazones 166 (92BCJ546). Their acetylations gave peracetyl derivatives 167. The same reactions were extended to the /V-methyl and the 7-methyl derivatives of 165 (93 JPROO). That compounds 166 exist as open-chain structures was based on a 2D NMR study (93MI1) (Scheme 35). 

Tetrahydroimidazo[5,l-c][l,2,4]triazine 474 was prepared (79KGS1540) by treating imidazole derivatives 472 or 473 with hydrazine. Compound 473 was obtained by reaction of the respective imidazole with 1,2-dibromoethane or by the reaction of the alcohol derivative 471 with phosphorus tribromide. On the other hand, chlorination of471 with thionyl chloride gave 472 (Scheme 100). 

A variety of aromatic diamines have been used for the synthesis of polyimides. It would be too time consuming to report all the pathways described in literature, so here only the most common ones are considered. The biggest part of these different methods leads to nitro compounds generally reduced using H2 or hydrazine monohydrate with catalytic amounts of Pd-C in refluxed ethanol or dioxane. The numbers in parentheses refer to Fig. 5.28 ... 

Regarding the series of hetero aromatic pentacyclic compounds with three heteroatoms, an accelerated synthesis of 3,5-disubstituted 4-amino-1,2,4-triazoles 66 under microwave irradiation has been reported by thermic rearrangement of dihydro-1,2,4,5 tetrazine 65 (Scheme 22). This product was obtained by reaction of aromatic nitriles with hydrazine under microwave irradiation [53]. The main limitation of the method is that exclusively symmetrically 3,5-disubstituted (aromatic) triazoles can be obtained. 

Monosubstituted hydrazines treated with nitrous acid give azides in a reaction exactly analogous to the formation of aliphatic diazo compounds mentioned in 12-47. Among other reagents used for this conversion have been N204 ° and nitrosyl tetrafluoroborate (NOBp4). ... 

Nitro compounds can be further reduced to hydrazo compounds with zinc and sodium hydroxide, with hydrazine hydrate and Raney nickel,or with LiAlH4 mixed with a metal chloride such as TiCU or VCl3. The reduction has also been accomplished electrochemically. 

In addition, several addition reactions have been reported for the iron complex [Fe(CNCH3)j] with hydrazine and with methylamine (99) the products (XVI) and (XVII), respectively, are described. A crystal structure study on the latter compound was carried out. 

Hydrazine is an endothermic compound and the vapour is exceptionally hazardous in that once it is ignited, it will continue to bum by exothermic decomposition in complete absence of air or other oxidant [1]. Distillation of anhydrous hydrazine (prepared by dehydrating hydrazine hydrate with solid sodium... 

Summary Fluorosilylamines and -hydrazines react with organolithium compounds to yield stable lithium derivatives. Perfluoro (Si-N) four- and six-membered ring systems are obtained with SiF4. The synthesis and crystal structures of the compounds are discussed. 

Treatment of the hydrazine derivative 303 with triethyl orthoformate gives the cyclized compound 304 <1987AP765> (Equation 53). Similarly, treatment of hydrazine 305 with formic acid gives the tricycle 306 the formamide intermediate was not isolated <2001CHE1150> (Equation 54). 

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. 

Condensation of aromatic acyl compounds with N,N-dimethylformamide diethyl acetal in a pressure tube under the action of microwave irradiation affords easy access to l-aryl-3-dimethylaminoprop-2-enones in almost quantitative yield after 6 min. These intermediates can then be reacted with hydrazine hydrate under conventional reflux in ethanol to form the corresponding 3-substituted pyrazoles [95] (Scheme 8.69). 

Hydrazines react with thiocarbonyl compounds, such as dithioesters, to afford directly symmetrical 1,3,4-thiadiazoles via a dithioacylhydrazine intermediate, which can be isolated and converted to the thiadiazole upon treatment with an electrophilic reagent or under thermal conditions (see Section 5.10.9.1.1). Examples of the direct formation of thiadiazoles from hydrazines and thiocarbonyls can be found in CHEC-II(1996) <1996CHEC-II(4)379>. 

The pyrazolone ring system is accessible through ring closure by the condensation of 1,3-diketo compounds with hydrazine derivatives. 

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