Arylhydrazines

Arylhydrazines may be prepared by reducing diazonium salts with excess warm sodium sulphite solution, followed by acidification with hydrochloric acid. The hydrochloride usually crystallises out on cooling and treatment of the latter with excess sodium hydroxide solution liberates the free base. The preparation of p-nitrophenylhydrazine by this method is illustrated in Expt 6.92. 

The mechanism of this reduction probably involves the initial addition of a sulphite ion to the diazonium group to give an azosulphonate which undergoes further conjugate (1,4-) addition of the nucleophilic sulphite ion. The resulting intermediate is protonolytically cleaved on heating under acidic conditions  

This method cannot be applied to polynitro amines, since these are so weakly basic that they can be diazotised only under special conditions in strongly acidic media (Section 6.7.1, p. 922). In such cases use may be made of the susceptibility to nucleophilic displacement of halogen when activated by ortho and para nitro groups. Thus the valuable reagent 2,4-dinitrophenylhydrazine (Expt 6.93) is readily prepared by reacting l-chloro-2,4-dinitrobenzene with hydrazine. Reaction with ammonia similarly gives 2,4-dinitroaniline (cognate preparation in Expt 6.93). 

A further example is provided by the reaction of l-chloro-2,4,6-trinitrobenzene (picryl chloride) with jV,jV-diphenylhydrazine to give N,N-diphenylpicrylhydrazine (Expt 6.94). This compound is of interest in that 

Suspend 35 g (0.27 mol) of finely powdered hydrazine sulphate in 125 ml of hot water contained in a 400-ml beaker, and add, with stirring, 118g (0.87 mol) of sodium acetate hydrate or 85 g of potassium acetate. Boil the mixture for 5 minutes, cool to about 70 °C, add 80 ml of rectified spirit, filter at the pump and wash with 80 ml of hot rectified spirit. Keep the filtered hydrazine solution for the next stage in the preparation. 

Should this last strategy require the synthesis of functional aryl hydrazines, it would have the advantage of producing strongly adhering monolayers at low anodic potential and in a wide range of arylhydrazine concentrations and pH values that would make it quite promising for further applications. 

The covalent bonding of functional aryl groups to a wide variety of (semi)conductive surfaces can be achieved cathodically via the electrochemical reduction of diazo-nium salts. This method is currently one of the most described and used since a large number of functionalities can be efficiently imparted to a broad range of inorganic substrates. 

The pioneering work of Delamar et al. [14] demonstrated the coating of glassy carbon by an organic layer of 4-nitrophenyl by the electrochemical reduction of (4-nitrophenyl)diazonium tetrafluoroborate (typical concentration 1-10 mM) from an ACN solution. Cyclic voltammetry shows two reduction phenomena in the first scan. The first peak centered at —0.04 V versus SCE is irreversible and corresponds to the diazonium reduction, whereas the second one is reversible and appears at a more cathodic potential (—1.20 V vs SCE) that is related to the electroactivity of the nitro group. A second voltammogram recorded on the same electrode shows 

Owing to the easy electroreduction of such species, the electrografting of aryl diazonium salts has been quite easily achieved in aqueous media [15]. For this purpose, the pH of the solution has to be kept below 2 (e.g., by the addition of H2SO4) in order to avoid degradation of the diazonium salt by its reaction with water. This advantage is of importance for both ecologic and economic impacts of the method. 

In addition, if the cathodic electrografting of diazonium compounds onto carbon substrates (glassy carbon, HOPG, carbon fibers, carbon nanotubes [16], carbon felts 

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They are formed by treatinga-diketones, a-hyd-roxyaldehydes, hydroxyketones, aminoalde-hydes or aminoketones with arylhydrazines. Sugars can be identified by their osazones which have characteristic melting-points, formation times or crystal appearance. 

HC(22)l). Other azopyrazoles (318) and (319) have been described in Section 4.04.2.1.4(viii). These compounds can be reduced to amines (zinc and acetic acid) or to arylhydrazines (zinc in alkaline medium) (67HC(22)l). 

Owing to their particular interest two individual reactions will now be discussed separately. The reaction of methoxycarbonylhydrazine and 3-bromo-2,4-pentanedione affords, in addition to the expected pyrazole (608), a pyrazolium salt (609), the structure of which was established by X-ray crystallography (74TL1987). Aryldiazonium salts have been used instead of arylhydrazines in the synthesis of pyrazolines (610) and pyrazoles (611) (82JOC81). These compounds are formed by free radical decomposition of diazonium salts by titanium(n) chloride in the presence of a,/3-ethylenic ketones. 

Aniline 77 was converted into its diazonium salt with nitrous acid and this was followed by reduction with stannous chloride to afford the corresponding arylhydrazine 78. Condensation of 78 with 3-cyanopropanal dimethylacetal 79 gave the arylhydrazone 80. Treatment of 80 with PPE resulted in cyclization to indole 81. The nitrile group was then reduced to the primary amine by catalytic hydrogenation. Reaction of the amine with excess formalin and sodium borohydride resulted in Imitrex (82). 

The mechanism of the decarboxylation of isoxazole-3-car boxy lie acids has not yet been specially studied, but the available experimental evidence allows some suggestions to be made. It seems that on heating isoxazole carboxylic acids in solution, or in the presence of arylhydrazines, it is the acid anion (158) formed which is being de-... 

In order to allow further transformation to an indole, the carbonyl compound 8 must contain an a-methylene group. The hydrazone 1 needs not to be isolated. An equimolar mixture of arylhydrazine 7 and aldehyde or ketone 8 may be treated directly under the reaction conditions for the Fischer indole synthesis. ... 

In the hydrogenation, 200 g of acetophenone azine, 1000 ml of EtOAc and 5 g of 10% Pd-on-C was shaken at 30-50 psig for 10 h. Hydrogen absorption had ceased. About 7.6 g of phenylethylamine, formed by cleavage of the N—N bond, was obtained as a by-product. Oxidation of hydrazines can be done catalytically. Ethyl 2-arylhydrazine carboxylates were oxidized easily by bubbling air at 25 "C through a toluene or dioxane solution in the presence of Pd or Pt (5d). 

Hydrazino compounds can react with one or two equivalents of arenediazonium ions. In reactions of arylhydrazines without substituents at the P-nitrogen in mineral acid media the initial product, the 1,4-diaryltetraz-1-ene (6.24), disproportionates rapidly into aryl azide and amine (Scheme 6-17). As shown by 15N labeling experiments (Clusius and Craubner, 1955), equal amounts of all the products shown in Scheme 6-17 are obtained. In acetate buffer the reaction is regiospecifically different. The diazonium ion attacks the a-, not the P-nitrogen, and a 1,3-diaryltetraz-l-ene is formed (6.25). 

Dihydroxybenzene (hydroquinone), and probably also the 1,2-isomer, act as reducing agents for arenediazonium ions arylhydrazines are formed, but not in good yields. The azo coupling of 2-hydroxy-l,4-benzoquinone is discussed in Section 10.10 (Scheme 10-71). 

The vicinal dihydrazones formed from monosaccharides with arylhydrazines have been called arylosazones, but are preferably named as ketoaldose bisfphenylhydra-zone)s... 

Fig. 17 Rapid preparation of imidazoles and thiazoles on solid-phase. Reagents a RNH2, (CH30CH2)2, MW 220°C, 15min, closed vessel b TFA in CH2CI2, rt, 60min. R = aliphatic, benzyl, or arylamines or arylhydrazine...

However, in some cases azines can be converted to hydrazones by treatment with excess hydrazine and NaOH. Arylhydrazines, especially phenyl, p-nitrophenyl, and 2,4-dinitrophenyl, are used much more often and give the corresponding hydrazones with most aldehydes and ketones.Since these are usually solids, they make excellent derivatives and are commonly employed for this purpose. Cyclic hydrazones are also known, ° as are conjugated hydrazones. a-Hydroxy aldehydes and ketones and ot-dicarbonyl compounds give osazones, in which two adjacent carbons have carbon-nitrogen double bonds ... 

Reaction of 6-phenacylimidazo[l,2- ][l,2,4]triazin-7-one, 164, with arylhydrazines gives the corresponding hydra-zones, which are cyclized to imidazopyridazinotriazines 165 upon treatment with phosphorus oxychloride... 

Other non-traditional preparations of 1,2,3-triazoles have been reported. The rearrangement in dioxane/water of (Z)-arylhydrazones of 5-amino-3-benzoyl-l,2,4-oxadiazole into (2-aryl-5-phenyl-27/-l,2,3-triazol-4-yl)ureas was investigated mechanistically in terms of substituents on different pathways <06JOC5616>. A general and efficient method for the preparation of 2,4-diary 1-1,2,3-triazoles 140 from a-hydroxyacetophenones 139 and arylhydrazines is reported <06SC2461>. 5-Alkylamino-] //-], 2,3-triazoles were obtained by base-mediated cleavage of cycloadducts of azides to cyclic ketene acetals <06S1943>. Oxidation of N-... 

JOC8210>. Condensation of succinaldehyde with arylhydrazines and benzotriazole gives 1-aminopyrrolidines 646 that upon treatment with organomagnesium reagents rearrange to 1,4,5,6-tetrahydropyridazines 647 <1998S1627>. 

NHNH2-------- —A, .2 This salt converts arylhydrazines at low temperatures... 

Aryl chlorothioformates, 23 628 Aryl complexes, zirconium, 26 655 Aryl ethers, uses for, 70 581 2-Arylglycine esters, 72 166 Aryl halide amination, 9 278 Aryl halides, reaction with carbon monoxide, 5 11 Arylhydrazines, 9 270 Arylmethane dyes, 9 503... 

The l-arylpyrazol-5-ones (4.9), prepared by the two-step condensation of an arylhydrazine with ethyl acetoacetate, are the most commonly used coupling components for the synthesis of greenish yellow azo dyes. Coupling occurs at the 4-position of the pyrazolone ring which, as in the case of the acetoacetarylamides discussed above, is activated towards electrophilic attack by the two flanking unsaturated carbon atoms (Scheme 4.14). 

Closely related to the pyrazolones, but less commonly used, are the 5-aminopyrazoles (4.10). Again, these compounds give greenish yellow dyes when coupled at the activated 4-position indicated by the arrow in Scheme 4.15. The aminopyrazoles are prepared by condensation of an arylhydrazine with 3-aminobut-2-enenitrile (diacetonitrile), which is itself produced by dimerisation of ethanenitrile (acetonitrile) over a nickel catalyst. 

The method of Y. Meyer, reduction of the diazonium chlorides to arylhydrazines with strongly acid stannous chloride solution, is less elegant. The difference in the actions of stannous salt in acid and in alkaline solution should be noted. 

Arylhydrazines were reacted with EMME at ambient temperature for 24 hr to give hydrazinomethylenemalonates (87GEP33617554). 

TosN, (0.37 g, 2 mmol), the arylhydrazine (2 mmol), and TEA-Br (0.1 g, 0.5 mmol) in xylene (10 ml) are added to aqueous NaOH (50%, 10 ml) and the mixture is refluxed until the azide has been fully consumed (2-10 h). The organic phase is separated and the aqueous phase is extracted with PhH (3 x 10 ml). The combined organic solutions are dried (MgS04) and evaporated to yield the arene [e.g. PhH 40% (6 h) pyridine 98% (6 h) from 2-hydrazino derivative pyridazine 79% (8 h) from 3-hydrazino derivative)]. 

The electrochemical oxidation of A, Ai-dibenzyl, Ai -arylhydrazines gives carbocations that react with alkenes affording five-membered heterocycles (Scheme 48) [70]. 

Photo-oxidation of l,l-dialkyl-2-arylhydrazines by single-electron transfer with trimethylsilyl cyanide (TMSCN) as cyanide ion source leads to regio- and stereoselective a-hydrazino nitriles. This stereoselective cyanation of hydrazines takes place on the more substituted carbon atom compared with the results obtained with tertiary amines (Scheme 5). 

In the reflux procedure, minor amounts of the corresponding arylhydrazines are formed as by-products. 

The oxidation of arylhydrazines with An2TeO is unsuitable for synthetic purposes, since it furnishes a complex mixture of products. 

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