Hydrazines substituted

This double condensation is prevented by the use of substituted hydrazines. 

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.)... 

Oximes, hydrazines and semicarbazones. The hydrolysis products of these compounds, t.e., aldehydes and ketones, may be sensitive to alkali (this is particularly so for aldehydes) it is best, therefore, to conduct the hydrolysis with strong mineral acid. After hydrolysis the aldehyde or ketone may be isolated by distillation with steam, extraction with ether or, if a solid, by filtration, and then identified. The acid solution may be examined for hydroxylamine or hydrazine or semicarbazide substituted hydrazines of the aromatic series are precipitated as oils or solids upon the addition of alkali. 

From Hydrazines and P-Bifunctional Compounds. One of the oldest examples in this class is the reaction of a p-diketone with a substituted hydrazine to give a pyrazole (eq. 1). 

Reaction of an acid chloride with trimethylsilylacetylene produces an a,P-ethynyl ketone, which on treatment with substituted hydrazines yields a mixture of 1,5- and 1,3-substituted pyrazoles (34). The ratio is dependent on the reaction conditions (eq. 3). 

Monochloramine is also used in organic synthesis for preparation of amines, substituted hydrazines, etc. For example, reaction of NH2CI with 3-azabicyclo [3.3.0]octane [5661-03-0] yields A/-amino-3-azabicyclo[3.3.0]octane [54528-00-6] a pharmaceutical intermediate (38). 

Pyridazinecarbohydrazides are prepared in the normal way from an ester or acid chloride and hydrazine or a substituted hydrazine, generally in good yields. Pyridazines with two ortho alkoxycarbonyl groups give cyclic hydrazides with hydrazine, which are pyridazinopyridazines. 

Phthalic anhydride and diethyl phthalate are easily converted with hydrazine into 4-hydroxyphthalazin-l(2/f)-one. Its substituted derivatives have been prepared using substituted hydrazines, substituted phthalic anhydrides, or diesters or disodium salts of substituted phthalic acids (Scheme 81). However, condensation of phenylhydrazine with phthalic anhydride gives only a small amount of the corresponding phthalazine, the main product being 2-anilinophthalimide. This can be rearranged in the presence of base into the phthalazine derivative. For the preparation of 2,3-disubstituted derivatives, 1,2-disub-stituted hydrazines are reacted with the appropriate phthalic anhydrides or phthaloyl chlorides. Derivatives of 4-amino- or 4-hydrazino-phthalazin-l(2iT)-one have been prepared either from the corresponding monothiophthalimide and 3-aminoisoindolin-3-one (1S4) or from ethyl 2-cyanobenzoate (155) and hydrazine hydrate (Scheme 82). Similarly,... 

AK(30)26l). 2-Acetoxyfuran-3(2i/)-ones react with hydrazine to give 3,6-disubstituted-4-ethoxycarbonylpyridazin-4(li/)-ones (184) as the main product, but with mono-substituted hydrazines in addition to these pyridazines anhydro-5-hydroxypyridazinium hydroxide (185) derivatives and some pyrazole derivatives are also formed (Scheme 102) (79JOC3053). The... 

The most common reaction of this type is the cyclization of various derivatives of hydrazine and substituted hydrazines with pyridine o-dicarboxylic acids and related compounds. Reactions in which the acid derivative reacts directly with the hydrazine are dealt with as [4 + 2] reactions in Section 2.15.10.6.1. 

Use of diaziridines in synthesis is assumed to be especially attractive for synthesis of substituted hydrazines large scale production of the parent compound, however, was not undertaken after an optimistic development (Section 5.08.3.2.2). 

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). 

Polyfluoroalkyl fluorosulfates react with substituted hydrazines to give the corresponding polyfluorocarboxylic hydrazides [90] (equation 78)... 

The reaction conditions (neutral, acidic or basic) do have an affect on the regioselectivity of the reaction. Acidic reaction conditions have also been shown to preferentially provide one regioisomer over basic conditions for reactions of aryl hydrazines. Extensive studies with 2-perfluoroacylcycloalkanones and mono-substituted hydrazines were studied to determine the selectivity of various alkyl-, aryl-, and heteroaryl-substituted hydrazines. Reactions of the aryl hydrazine 21 with the trifluoromethyl-substituted cycloalkanone 22 under neutral conditions (methanol, reflux) gave a mixture of isomers 23 and 24, whereas the reaction of the pyridyl hydrazine 25 was shown to give exclusively 26. 

The use of substituted hydrazines, phenylhydrazine, and 2,4-dinitrophenylhydra-zine (68T4285 74JOC843) can give both 5- and 3-acetylenylpyrazole (Table VT). In this case, the direction of cyclization depends both on the hydrazine structure and the experimental conditions. 

The interaction between l,5-diphenylpentadiyn-2,4-one-l and its aliphatic analog, 1,5-dimethylpentadiyn-2,4-one, with substituted hydrazines gives rise to a linear adduct, vinylacetylenylketone, which then cyclizes into 5-phenylethynylpyra-zoles and 5-methyl-3-propynylpyrazoles in 70-90% yields, respectively (73S47) (Scheme 21). 

TABLE VI. Alkynylpyrazoles Prepared by Cyclization of Diynones with Substituted Hydrazines [68T4285 74JOC843 74ZOR136 74ZOR730 75ZOR47 76T1293]. 

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). ... 

Without acid present, the major product is a substituted hydrazine. 

An analogous reaction of (2-acylphenyl)acetic acids with hydrazine or substituted hydrazines in refluxing benzene, xylene or butanol with azeotropic removal of water gives 3//-2,3-benzo-diazepin-4(5//)-ones 3.128,129... 

Uses It is one active ingredient present in water which has been purified by chlorination (Ref 6). It is used as an intermediate for.the prepn of hydrazine and substituted hydrazines. Recentiy there has been a renewed interest in chloramine as a possible intermediate for the prepn of UDMH (see Vol 7, H203-R) which avoids handling the highly carcinogenic dimethyl-nitrosamine (Refs 5 7)... 

Nearly all (extranuclear) hydrazonoquinoxalines are made by treatment of quinoxaline aldehydes, ketones, or their acetals with hydrazine or substituted hydrazine, but a few are produced by diazo coupling. These reactions are illustrated by the following examples. 

A similar strategy has been used to prepare pyrimidines, as well as pyra-zoles and isoxazoles by reacting the enamine intermediate with a variety of bidentate nucleophiles [78]. Microwave irradiation of a cyclic 1,3-diketone 49 and acetal 45 in water generated the corresponding enaminoketone 50 in situ which reacted with amidines, substituted hydrazines or hydroxylamine in only 2 min in a one-pot process to give 4-acylpyrimidines, pyrazoles or isoxazoles, respectively (Scheme 20). 

Different approaches towards pyrazoles have been described using microwave-accelerated cyclizations. A classical approach to pyrazoles is the cyclization of a j6-diketone with hydrazines. A series of 5-trichloromethyl-pyrazoles 58 and pyrazolium chlorides 59 were synthesized by reaction of a 4-methoxy-trihalo-3-alken-one 57 with differently substituted hydrazines (Scheme 19). The use of microwave and conventional heating for making pyrazoles gave... 

Disulfides can be reduced to thiols by mild reducing agents, such as zinc and dilute acid or Ph3P and H2O. The reaction can also be aceomplished simply by heating with alkali. Among other reagents used have been LiAlR, Mg/ MeOH, KBH(0—i-Pr)3, and hydrazine or substituted hydrazines. ... 

Removing the substituted hydrazine (58) leaves acetoacetic ester (57). Phenylhydrazine is available, so it is easier to make (59) and methylate afterwards. This removes the chemoselectivity problem as the more nucleophilic NH group attacks the more electrophilic ketone. 

Although nitrosamine and nitramine formation from UDMH (and similarly substituted hydrazines) will probably be the major reaction pathway as long as the atmosphere into which the hydrazines are emitted contains some ozone (as does the "natural" troposphere), our results indicate that different products would potentially be formed if these compounds are emitted into polluted atmospheres where O3 is suppressed by high levels of NO. 

The deoxygenation of aldehydes and ketones to the corresponding hydrocarbons via the hydrazones is known as the Wolff-Kishner reduction.28 Various modifications of the original protocols have been suggested. One of the most useful is the Huang-Minlon modification, which substituted hydrazine hydrate as a safer and less expensive replacement of anhydrous hydrazine. In addition, diethylene glycol together with sodium hydroxide was used to increase the reaction... 

Thiohydrazides can be prepared from alkyl- and aryl-substituted hydrazines and various 7V-thiobenzoylazoles,11651 as the following examples illustrate 11651,11661... 

A derivative of benzylhydrazine, procarbazine (8), exhibits antineoplastic activity. In an interesting insertion-type sequence, reaction of the p-toluamide (5) with ethyl azodicarboxylate leads directly to the substituted hydrazine (6). It is not unlikely that the first mole of the diazo compound... 

Hydroxymethylation (formaldehyde) of nitro-imidazole 76 affords 77, which is oxidized to aldehyde 78. To prepare the other fragment for this convergent synthesis, reaction of epichlorohydrin with morpholine leads to the aminoepoxide 79, which is reacted with hydrazine to afford 80. Reaction of this substituted hydrazine with dimethyl carbonate affords oxazolinone 81 by sequential ester interchange reactions. Condensation of 81 with aldehyde 78 affords the antitricho-... 

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