Syntheses of hydrazines

In this Section only those hydrazine syntheses are discussed that occur with formation of an N-N bond (TV-amination). For syntheses of substituted hydrazines by reduction of hydrazones, azines, iV-nitroso compounds, and diazonium salts the Sections relevant thereto should be consulted. 

The synthesis of substituted hydrazines has been extensively studied in recent years, with emphasis on alkylhydrazines, and the voluminous literature has been the subject of several reviews.273,274 

Hydroxylamine-O-sulfonic acid (aminyl hydrogen sulfate) has often proved superior to chloramine for amination the former is a stable crystalline substance that can be easily handled and weighed. It aminates primary279,280 and secondary amines280 to hydrazines, and tertiary amines to hydrazinium salts.28 It is a stronger animating agent than chloramine as it converts pyridine into the 1-aminopyridinium salt, a reaction that cannot be carried out by chloramine.281 Other heterocycles, e.g., uracil,282 can also be converted into hydrazines by hydroxylamine-O-sulfonic acid. 

1-Diethylhydrazine can be usefully prepared by animating triethylamine with hydroxylamine-O-sulfonic acid and decomposing the resulting 1,1,1-tri-ethylhydrazinium salt by alkali to ethylene and the diethylhydrazine this method is better than amination of diethylamine.280 

Hydrazine, Mathieson Chem. Corp., Baltimore, Maryland, 1953 R. F. Evans, Rev. Pure Appl. Chem., 12, 146 (1962) A. N. Kost and R. S. Sagitulin, Usp. Khim., 33, 361 (1964) C. G. Overberger, I. P. Anselme, and I. J. Lombardino, Organic Compounds with Nitrogen-Nitrogen Bonds, The Ronald Press Company, New York, 1966. 

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Nucleophiles react with /V-H and Al-acyl oxaziridines with transfer of NH and /V-acyl, respectively. Much of this chemistry (91S327) has been carried out with cyclohexanespiro-3 -oxaziridine (26) attack at the NH group gives intermediate (27) which gives cyclohexanone and animation of the nucleophile. Transfers of NH to N-, 0-, S-, and C-nucleophiles, enable the syntheses of hydrazines, /V-amino-peptides, hydroxyamines, sulfenamides, thiooximes, sulfonamides, aziridines, and a-amino acids. 

Two new syntheses of hydrazines from secondary amines have been reported. In one 1,1-diarylhydrazines are the products of the Hofmann rearrangement of the corresponding ureas (Scheme 33), and in the other ... 

The most useful syntheses of pyridazines and their alkyl and other derivatives begins with the reaction between maleic anhydride and hydrazine to give maleic hydrazide. This is further transformed into 3,6-dichloropyridazine which is amenable to nucleophilic substitution of one or both halogen atoms alternatively, the halogen(s) can be replaced by hydrogen as shown in Scheme 110. In this manner a great number of pyridazine derivatives are prepared. 

The vast majority of syntheses of pyrido[2,3-t/]- and pyrido[3,4-t/]-pyridazines fall into this category, resulting from the cyclization of various o-substituted pyridine derivatives (2,3- or 3,4-, respectively) with hydrazine or its congeners. 

In a 2-1. three-necked round-bottomed flask, equipped with a mechanical stirrer (Note 1), reflux condenser, and dropping funnel, are placed 30 g. of pure 2-nitrofluorene, m.p. 157° [Org. Syntheses, Coll. Vol. 2, 447 (1943)], and 250 ml. of 95% ethanol. After warming to 50° on a steam bath, 0.1 g. of palladized charcoal catalyst (previously moistened with alcohol) is added (Note 2) and the stirrer is started. About 15 ml. of hydrazine hydrate is added from the dropping funnel during 30 minutes (Note 3). At this point an additional 0.1 g. of catalyst (previously moistened with alcohol) is added and the mixture is heated until the alcohol refluxes gently. After 1 hour the nitrofluorene has dissolved completely and the supernatant liquor is almost colorless. 

Preparation of thiadiazoles via the Hurd-Mori cyclization has led to the synthesis of a variety of biologically active and functionally useful compounds. Discussion of reactions prior to 1998 on the preparation of thiadiazoles have been compiled in a review by Stanetty et al Recent syntheses of thiadiazoles as intermediates for useful transformations to other heterocycles have appeared. For example, the thiadiazole intermediate 36 was prepared from the hydrazone 35 and converted to benzofuran upon treatment with base. Similarly, the thiadiazole acid chloride 38 was converted to the hydrazine 39 which, upon base treatment, provided the pyrazolone, which can be sequentially alkylated in situ to provide the product 40. ... 

The 1,2,4-triazine 4-oxides 55 were synthesized by the reaction of nitrones 158 (generated from a-hydroxylamino ketones and aldehydes) with an excess of hydrazine, followed by the oxidation of the intermediate 4-hydroxy-2,3,4,5-tetrahydro-l,2,4-triazines 159 with lead(TV) oxide (73KGS134). 

Hydrazides (RCONHNH2) are highly useful starting materials and intermediates in the synthesis of heterocyclic molecules.2 They can be synthesized by hydrazinolysis of amides, esters and thioesters.3 The reaction of hydrazine with acyl chlorides or anhydrides is also well known,4 but it is complicated by the formation of 1,2-diacylhydrazines, and often requires the use of anhydrous hydrazine which presents a high thermal hazard. Diacylation products predominate when hydrazine reacts with low molecular weight aliphatic acyl chlorides, which makes the reaction impractical for preparatory purposes.5... 

Syntheses of fluoro-substituted pyrazoles continue to be of interest. Both 3- and 5-fluoropyrazoles (44 and 45, respectively) can be prepared from 43 <96JOC2763>. Treatment of 43 with hydrazine followed by N-alkylation provides 44, whereas reactions with monosubstituted hydrazines afford 45. The 4-(trifluoromcthyl)pyrazoles 47 are obtained from J-trifluoromethyl vinamidinium salt 46 <96TL1829>. The 5-trifluoromethyl-3-carboethoxypyrazoles 49 are obtained from the 1,3-dipolar cycloadditions of trifluoromethyl alkenes 48 with ethyl diazoacetate <96T4383>. 

Suhtnicion nickel powders luive been synthesized successfully from aqueous NiCh at various tempmatuTKi and times with ethanol-water solvent by using the conventional and ultrasonic chemical reduction method. The reductive condition was prepared by flie dissolution of hydrazine hydrate into basic solution. The samples synthesized in various conditions weae claractsiz by the m ins of an X-ray diffractometry (XRD), a scanning electron microscopy (SEM), a thermo-gravimetry (TG) and an X-ray photoelectron spectroscopy (XPS). It was found that the samples obtained by the ultrasonic method were more smoothly spherical in shape, smaller in size and narrower in particle size distribution, compared to the conventional one. 

SL901>. Reductive cleavage of 5-silyl, 3-, 4- and 5-silylmethylisoxazoles gave their corresponding silyl P-enaminones, which on reaction with hydrazines, provided regioselective syntheses of 3- or 5-silylpyrazoles and 3-, 4- or 5-silylmethylpyrazoles, respectively <06T611>. 

Disubstituted 1,2,3-triazoles are usually minor components in the product mixtures obtained from reactions of triazole with electrophiles (see Section 5.01.5). The few regioselective syntheses of such compounds include a reaction of aminoacetophenones 1235 with hydrazines. The reaction with methylhydrazine proceeds well without any catalysis, but that with phenylhydrazine requires cupric chloride as a catalyst. It is assumed that hydrazone 1236 that forms in the first step is in a tautomeric equilibrium with its azo form 1237. However, it is not clear how bond formation between the nitrogen atoms and oxidation to the triazole system occurs. 4-Aryltriazoles 1238 are obtained in 50-66% yield (Scheme 205) <2003SC3513>. 

The ring in oxadiazolinones 54 (R1 = 3-benzyloxyphenyl, CbzNH-L-leucine, R2 = H, Y = 0) in a reaction with hydrazine hydrate cleaved to afford product 55, which was then used in the syntheses of peptide mimetics <1998JME3923, 1999BMC599>. The reaction of oxadiazolinone 54 (R Fmoc, R2 = H, Y = 0) with primary... 

Acid- and base-promoted methods have also been used in the syntheses of pyrazoles. Hydrogenation of methyl 2-Cbz(hydrazine)-3-hydroxy-4,4-dimethoxybutanoate 11 followed by cyclization in the presence of trifluoroacetic acid afforded the first asymmetric synthesis of the (4S,5.R)-5-carbomethoxy-4-hydroxy-A2-pyrazoline 12 <00TL8795>. Reaction of 2-nitrobenzyl triphenylphosphonium ylide (13) with aiyl isocyanates afforded 2-aryl-2H-indazoles 14 <00TL9893>. Base-promoted reaction of nitrobenzenes 15 with aryl imines 16 afforded aryl pyrazoles 17 . 

A diastereoselective synthesis of bis(3,5)pyrazolophanes was accomplished by sequential inter- and intramolecular cycloadditions of homochiral nitrilimine intermediates . A-Alkyl pyrazolidine-3,5-diones were synthesized in a three-step sequence from dialkyl malonates <00JHC1209>. Methyl acetoacetate was employed as the initial substrate to 3-carboxamido-4-pyrazolecatboxylic acid derivatives <00JHC175>. Vilsmeier type reagent 33 reacted with imines 34 to afford enaminoimine hydrochlorides 35, which were transformed to pyrazoles 36 upon addition of hydrazine <0OJHC13O9>. 

The aim of this study is to synthesize of binuclear octaphthalocyanine and dimeric phthalocyanines. For this purpose, nitro-substituted dimeric phthalocyanine 3 using 1 and 2. In the second step, using hydrazine hydrate as a reductant, amine-substituted dimeric phthalocyanine 4 was synthesized from nitro-substituted dimeric phthalocyanine 3. 

Hexanitroazobenzene (HNAB) (90), an explosive exhibiting thermal stability (m.p. 220 °C, VOD 7250 m/s, d = 1.77 g/cm ), is formed from the reaction of hydrazine with picryl chloride (87) followed by oxidation of the resulting hydrazide (89) with fuming nitric acid. The commercial availability of picryl chloride limits such reactions. However, 2,4-dinitrochlorobenzene is widely available and can be used to synthesize many of the above products (Section 4.8.1.3). 

Tranylcypromine Tranylcypromine, ( )-lran5-2-phenylcyclopropylamine (7.2.10), differs from the drugs described above in that it is not a derivative of hydrazine. It is synthesized from the ethyl ester of 2-phenylcyclopropan carboxylic acid (7.2.7), which... 

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