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The NaBH4 reduction of nitrosobenzene to hydrazobenzene/aniline≈3 : 1, phenylhydroxylamine to aniline, azoxybenzene to hydrazobenzene, azobenzene to hydrazobenzene, and hydrazobenzene to aniline is catalysed by bis(dimethylglyoximato)cobalt compounds (“cobaloximes”), CoCl2, and some other salts of transition metals. The NaBH4−CoCl2 system is a convenient and mild reducing agent which effects the reduction of e.g.trans-azobenzene to hydrazobenzene even at −60°C. The diazene configuration has no effect on the reduction of the N=N group;cis-fixed benzo[c]cinnoline is smoothly converted into 2.2′-diaminobiphenyl. Aliphatic diazeneslike 2.3-diazanorbornene andtrans-di-1-adamantyldiazene do not react.

Reduction of nitrobenzene with sodium or lithium naphthalenide results in formation of azobenzene and azoxybenzene in modest yields. With sodium naphthalenide, azoxybenzene formation is favored; use of lithium naphthalenide results in enhanced azobenzene yields. Reduction of azoxybenzene with naphthalenide results in azobenzene and a variety of fragmentation products. Hydrazobenzene was the only product formed upon azobenzene formation.

En presence de substrats organiques comme cyclohexadiene-1,4 diphenyl-1,2hydrazine, catechols, thiols le systeme Fe(II)-H 2 O 2 -CH 3 CN conduit a des produits de deshydrogenation. Avec des substrats tels que alcools, aldehydes, methylstyrene, sulfures sulfoxydes et phosphines le compose d'addition Fe(II)(H 2 O 2 ) 2+ favorise leur monooxygenation en aldehydes, acides carboxyliques, epoxydes, sulfoxydes, sulfones et phosphine oxydes respectivement

Erhitzt man Phenylbutazon mit Essigsaure und Salzsaure zum Sieden, so entsteht intermediar Hydrazobenzol, das sich weitgehend in Benzidin umlagert. Die auftretende Blau- bzw. Violettfarbung ist auf das in einer Nebenreaktion durch Oxidation von Hydrazobenzol sich bildende 5 zuruckzufuhren. Giest man das Reaktionsgemisch nach Zugabe von Natriumnitritlosung in eine sodaalkalische β-Naphthollosung, so bildet sich ein roter Farbstoff, der hauptsachlich aus 4,4′-Bis-(2-hydroxy-1-azonaphthyl)biphenyl (1) besteht, aber in groseren Mengen auch 2-Hydroxy-naphthyl-1-azobenzol (4) enthalt. The Identification of Phenylbutazone By heating phenylbutazone with glacial acetic acid and hydrochloric acid hydrazobenzene is formed intermediately which rearranges to benzidine. The blue or violet colour yielded is due to oxidation of hydrazobenzene to 5. After addition of sodium nitrite and pouring into a solution of sodium carbonate and β-naphthol a red product was formed, which mainly consists of 4,4′-bis(2-hydroxy-1-azonaphthyl)biphenyl (1) and 2-hydroxy-naphthyl-1-azobenzene (4).

[4−14C] phenylbutazone (4-butyl-1,2-diphenyl-3,5-[4−14C] pyrazolidinedione) has been synthesised on the 5 mmole scale. [2−14C] Diethyl malonate was reacted with n-butyl bromide and the product condensed with hydrazobenzene in the same reaction vessel. The radiochemical yield of highly purified product was 48%. It is proposed that care should be taken in analyses for metabolic products, particularly by TLC, since 4-hydroxyphenylbutazone was shown to be an oxidation product of phenylbutazone in solution and on TLC plates under quite mild conditions. A pure sample of 4-hydroxy [4−14C] phenylbutazone was isolated.

2,3-Dicarbomethoxy-7,7-dimethyl-7-silabicyclo[2.2.1]hepta-2,5-diene (III) on photolysis gave dimethyl tetraphenylphthalate whereas the photolysis of 7,7-dimethyl-7-silabicyclo[2.2.1]hep-5-ene-2,3-dicarboxylic anhydride (XIa) resulted in the formation of 1,1-dimethyl-2,3,4,5-tetraphenyl-1-silacyclopentadiene (XIIIa). The thermolysis of XIa also gave rise to XIIIa. Similarly, the photolysis as well as thermolysis of 1,4,5,6,7,7-hexaphenyl-7-silabicyclo[2.2.1]hept-5-ene-2,3-dicarboxylic anhydride (XIb) led to hexaphenylsilacyclopentadiene (XIIIb). Attempts to detect radical intermediates in these thermal and photochemical transformations by carrying out the reaction in the presence of hydroquinone, hydrazobenzene, 3,6-diphenyl-1,2-dihydro-1,2,4,5-tetrazine, cumene and tolan were unsuccessful. An attempted preparation of 7-silabicyclo[2.2.1]hepta2,5-dienes by the reaction of silacyclopentadienes such as 1-methyl-1-vinyl2,3,4,5-tetraphenyl-1-silacyclopentadiene (XV) and 1-methyl-1,2,3,4,5-pentaphenyl-1-silacyclopentadiene (XVI) with dimethyl acetylenedicarboxylate resulted in the isolation of dimethyl tetraphenylphthalate indicating that the corresponding 7-silabicyclo[2.2.1]hepta-2,5-dienes are thermally unstable.

Hydrazobenzene was irradiated with an ultraviolet light in n-hexane under a nitrogen atmosphere. The products were azobenzene, aniline, and a trace of semidines. The yield of azobenzene was usually larger than that calculated on the basis of the disproportionation of hydrazobenzene, while the yield of aniline was less. The reactions were followed by the determination of the disappearance of hydrazobenzene and that of the formation of azobenzene. On the basis of the available data, in the photochemical reaction of hydrazobenzene it was assumed that the formation of azobenzene was not due to the disproportionation, but to the oxidation of hydrazobenzene, and that no fission of the N–N bond of hydrazobenzene occurred to give azobenzene.

In a given experiment, second order kinetics were displayed during the greater part of the reaction over a considerable range of initial concentrations of reactants. In general, the second order behavior was maintained to greater extent of reaction when hydrazobenzene was in excess. The calculated second order rate constant, k, decreased with increase in initial hydrazobenzene concentration and increased with increase in initial concentration of ammonium persulphate. For different equimolar concentrations of reactants, k was virtually independent of initial concentrations. The value of k was proportional to the square root of the ratio of the initial concentrations of persulphate and hydrazobenzene. The activation energy of the over-all reaction was 16 kcal. per mole. A free radical mechanism appears to account reasonably well for the major experimental observations.

In order to explain the lack of agreement observed in the spectrochemical literature, the spectrum of hydrazobenzene in 95% ethanol has been carefully measured in the spectral range 210–330 nm. It presents two absorption bands, at 246 and 290 nm respectively: the assignment of the former to a charge transfer and of the latter to a benzenoid transition is proposed. The graphical resolution of the spectrum into component bands reveals the existence of a third band, underlying the other two, which is attributed to a (n → π*) transition.

Summary Azobenzene (HAzb) reacts with [RhCl(C 2 H 4 ) 2 ] 2 to give [RhCI(Azb) 2 ] 2 (I). The latter reacts with [RhCI(PF 3 ) 2 ] 2 yielding [RhCI(Azb)(PF 3 )] 2 (1I) which contains both Rh III and Rh I . Both PF 3 groups are attached to the same rhodium atom. (II), which is also readily formed from PF 3 and [RhCI(Azb)(CO)] 2 , (III), reacts with CO to reform (III). There is ready intermolecular phosphine exchange in (II) and the mixed carbonyl-trifluorophosphine complex [Rh 2 Cl 2 (Azb) 2 (PF 3 )(CO)] (IV) is obtained by mixing solutions of (II) and (III). Bridge cleavage occurs when (II) or (IV) are treated with Ph 3 P. Me 2 NPF 2 reacts with (III) to yield RhCI(Me 2 NPF 2 ) 3 . (I) is the other product of these latter reactions. [RhCI(PF 3 ) 2 ] 2 acts as a catalyst for the reduction of azobenzene to hydrazobenzene.

It was found that in solutions of all compounds investigated containing the hydrazo group (hydrazobenzene, diphenylcarbazone, diphenylcarbazide and dithizone), hydrogen peroxide is formed in the presence of dissolved oxygen. The rate of the formation of hydrogen peroxide in alkaline solutions decreases in the following order : carbazone, hydrazobenzene, carbazide, dithizone, and increases from acidic to alkaline solutions. In acidic solution the formation of hydrogen peroxide occurs mainly with hydrazobenzene.

Dianions derived from 3,3′-dimethylazobenzene, 3,3′-dimethoxyazobenzene, 4-methylazobenzene, 4-methoxyazobenzene, 4,4′dimethylazobenzene, 4,4′-dimethoxyazobenzene, 4,4′-diisopropylazobenzene, 4,4′-ditert-butylazobenzene, 4,4′diphenylazobenzene and dibenzopyridazine were prepared by treatment with excess of lithium in tetrahydrofuran. Reaction of these dianions with chlorodiphenylmethylsilane gave disilylsubstituted hydrazines. The ultraviolet spectra of these silylhydrazines resemble that of hydrazobenzene.

Die Synthese von 1,4-Dioxo-2,3-diazachinolizidin (1) gelang a) durch Erhitzen von Piperidyl-1,2-dicarbonsaurediathylester (3) mit wasserfreiem Hydrazin in Gegenwart von Natriumathylat und b) durch Umsetzung von Picolinsaurehydrazid mit Chlorameisensaureathylester zum Athylester des Picolinsaurehydrazid (4) der zum Pipecolinsaurehydrazidathylester (7) hydriert und anschliesend in Gegenwart von Natriumathylat zu 1 kondensiert wurde. Aus Piperidyl-1,2-dicarbonsaureester (3) und Hydrazobenzol erhielt man 1,4-Dioxo-2,3-diaza-(2′,3′-diphenyl)-chinolizidin (9). Aus 3 und Hydrazinhydrat entstand 1,3-Dioxo-2-aza-(2′-amino)-indolizidin (12). 1,4-Dioxo-2,3-diazaquinolizidine and 1,3-Dioxo-2-aza-(2′-amino)-indolizidine The synthesis of 1,4-dioxo-2,3-diazaquinolizidine (1) was successful a) by heating of diethyl piperidyl-1,2-dicarboxylate (3) with anhydrous hydrazine in presence of sodium ethoxide and b) by reaction of picolinic acid hydrazide with ethyl chloroformate to 4, which was hydrogenated to 7 and condensed in presence of sodium ethoxide to 1. 1,4-Dioxo-2,3-diaza-(2′,3′-diphenyl)-quinolizidine (9) was obtained from diethyl piperidyl-1,2-dicarboxylate (3) and hydrazobenzene. 3 and hydrazine gave 1,3-dioxo-2-aza-(2′-amino)-indolizidine (12).

Mit dem Ziel, bessere Methoden zur Cyclisierung von Peptiden zu finden, wird die Carboxylgruppe von N-geschutzten Aminosauren und Peptiden mit Hydrazobenzol zu den Diphenylhydraziden 1 oder mit cyclischem Phthalsaurehydrazid zu den O-Acyl-3-hydroxy-phthalazonen 4 verknupft. Die Verbindungen 1 und 4 lassen sich durch Oxydation mit N-Brom-succinimid in aktivierte Derivate verwandeln, die zur Ubertragung des Acyl-Rests auf Aminogruppen geeignet sind, was durch Synthese von Z-Glycinbenzylamid (2) und Z-Phenylalanylglycinathylester (3) gepruft wurde**. Die Ubertragung dieses Prinzips auf die feste Phase gelingt mit den Aminoacyl-Verbindungen 6 der 4-Hydrazino-benzoesaure, die an Chlormethylpolystyrol Ester-artig verankert werden. - Eine zweite Methode der nachtraglichen Aktivierung besteht in der Eliminierung von Wasser aus 2,2-Diphenyl-athylenglykolestern 7 zu reaktiven Enolestern, wie an der Sythese der Peptide 2 und 3 sowie an der Cyclisierung von Phe-(Pro)2-(Phe)2-Val-(Pro)2-D-Ala-PheOH zum D-Ala-antamanid (9) gezeigt wird. Peptide Syntheses, XLIV1). Subsequent Activation of Carboxylic Derivatives by Oxidation or Elimination of Water; Application for Cyclizing Peptides In order to find out better methods for cyclization of peptides the carboxylic groups of N-protected amino acids and peptides are linked with hydrazobenzene to give the diphenylhydrazides 1, or with cyclic phthalhydrazide to the O-acyl-3-hydroxy-phthalazones 4. The compounds 1 and 4 are activated by oxidation with N-bromosuccinimide and then used for peptide synthesis as shown by formation of Z-glycinebenzylamide (2) and Boc-phenylalanylglycine ethyl ester (3). The same principle has been applied in a solid phase technique by using 4-carboxyphenylhydrazides 6 whose carboxyl end was bound as an ester to chloromethylated polystyrene. - A second possibility of consecutive activation consists in elimination of water from 2,2-diphenylglycolesters 7. The reactivity as peptide forming agents of the enol esters thus formed, is demonstrated by the synthesis of the peptides 2 and 3, and by cyclization of the decapeptide Phe-(Pro)2-(Phe)2-Val-(Pro)2-D-Ala-PheOH yielding D-Ala-antamanide (9).

ヒドラゾベンゼンの無触媒熱反応を種々の条件下で定量的に検討した。反応主生成物はいずれの条件下でもアゾベンゼンとアニリンであった。無溶媒下の熱反応を速度論的に検討した結果,アニリンとアゾベンゼンの生成速度はおのおのヒドラゾベンゼンの濃度に関して2次で与えられ,その生成速度比は常に2:1であった。また,活性化エネルギーはともに37.7kcal・mol-1であった。不対称ヒドラゾベンゼンを同様に熱反応させた結果,交錯化合物はまったく確認されなかった。これらの結果より,ヒドラゾベンゼンの熱反応では主反応は不同変化であり,かつアゾベンゼンの生成にさいしてはN-N結合の開裂は起こっていないことが判明した。

10%ホルムアミド-アセトン溶液で処理したロ紙をもちい,シクロヘキサンを展開剤とするペーパークロマトグラフィーによってヒドラゾベンゼンの全ベンジジン転位反応生成物が同定された。塩酸触媒によるヒドラゾベンゼンのベンジジン転位反応を種々の条件下でおこなった。おのおのの場合,すべての転位生成物と不同変化による生成物がみとめられた。ベンジジンとジフェニリンの生成量は,溶媒のエタノール水濃度90vol%付近の点で最少値をしめした。しかしベンジジンとジフェニリンの生成比率は溶媒組成,酸濃度,転位温度などにほとんど関係なく,常に一定(約60:40)であった。

The polymorphism of severalsubstituted azoxybenzenes and azopyridines has been examined, and the eutectic points of these substances with reference compounds determined. Of special interest are o:o′-dichloroazoxybenzene and p:p′-azoxytoluene, the latter of which provides the simplest example of monotropic liquid crystal formation. No evidence was found forHodgson's suggestion thatcis-azobenzene is a compound of azoxybenzene and hydrazobenzene.

In Conjunction with an attempt to prepare hydrazobenzene by alkaline sulfide reduction of nitrobenzene, the reduction of azoxybenzene, a reduction intermediate, has been studied kinetically under the synthetic conditions. The rates of reduction are markedly affected by the solubility or the dispersibility of azoxybenzene in the solution of reducing agent. During the course of reaction, the product hydra-zobenzene is again oxidized to azobenzene by the disulfide formed through autoxidation of hydrosulfide.

The products obtained when α-(o-nitrophenylthio) acids are reduced by means of sodium borohydride and palladium–charcoal depend on (a) the reaction temperature, (b) the solvent, (c) the length of time in which the α-(o-nitrophenylthio) acid is in contact with the reducing agent, and (d) the nature of the substituents on the α-(o-nitrophenylthio) acid. By varying these conditions, benzothiazine hydroxamic acids (i.e. substituted 3,4-dihydro-4-hydroxy-3-oxo-2H-1,4-benzothiazines), the corresponding lactams (3,4-dihydro-3-oxo-2H-1,4-benzothiazines), and derivatives of 2-carboxymethylthioazobenzene can be prepared.In two cases, additional products were obtained. When (o-nitrophenylthio)acetic acid was catalytically reduced for 30 min in dioxane, 3,4-dihydro-3-oxo-2H-1,4-benzothiazine-1,1-dioxide (VIc) was an unexpected product, and when α-(4-trifluoromethyl-2-nitrophenylthio)-isobutyric acid was left for a prolonged time in contact with sodium borohydride and palladium–charcoal, a derivative of hydrazobenzene, namely, 2-carboxy(α,α-dimethyl)methylthio-5-trifluoromethylhydrazobenzene (V), was one of the three identified products.

The oxidation of hydrazobenzene (AH2) to azobenzene by iodine in aqueous ethanol solution was found to be very rapid and in order to render the kinetics measurable it proved necessary to reduce the concentration of free iodine by complexing with iodide. This revealed a parallel oxidation path, much slower than for iodine, involving the triiodide ion. The overall rate law thus is: −d[AH2]/dt = k1[AH2][I2] + k2[AH2][I3−] where the rate constants, in 60 volume% ethanol, are given by, k1 = 4.2 × 1011 exp [−10,000/RT] M−1 sec−1and k2 = 2.5 × 1011 exp [−16,400/RT] M−1 sec−1. These and other features of the kinetics, including the inverse dependence of the rate constants on the ethanol concentration and the absence of effects due to added quinone and various metal ions, are interpreted in terms of a simple bimolecular mechanism for each path. Some measurements of the thermodynamics of triiodide formation in aqueous ethanol also are reported.

The interaction of nitroaromatic radical-anions electrolytically produced in dimethylformamide with methyl vinyl ketone monomer has been studied polarographically and amperometrically. It has been found that the decay rate of radical-anions is first order with respect to their concentration and to monomer concentration. The interaction between the nitroaromatic radical-anions and methyl vinyl ketone monomer leads to restoring approximatively 3/4 of initial nitrocompound and to the methyl vinyl ketone polymerization. Phenylhydroxylamine and hydrazobenzene are also present as reaction products. The reaction between the nitroaromatic radical-anions and methyl vinyl ketone is interpreted on the basis of a proton abstraction from the monomer by the radical-anions. Die Wechselwirkung von Methylvinylketon mit elektrolytisch in DMF-Losung erzeugten Radikalanionen von aromatischen Nitroverbindungen wurde polarographisch und amperometrisch untersucht. Die Geschwindigkeit der Abnahme der Radikalanionen ist von der 1. Ordnung sowohl in bezug auf ihre Konzentration als auch auf die des Monomeren. Bei diesem Prozes werden etwa 3/4 der urspruunglichen Nitroverbindung wieder zuruckgebildet; auserdem polymerisiert das Methylvinylketon. Phenylhydroxylamin und Hydrazobenzol sind ebenfalls im Reaktionsgemisch nachweisbar. Diese Reaktionen lassen sich deuten, wenn angenommen wird, das ein Radikalanion primar ein Proton aus dem Monomeren abspaltet.

Over the range of concentration of perchloric acid in which the acid conversion of 2,2′-dichlorohydrazobenzene is strictly of second order in hydrogen ions, that of 2,2′-dibromohydrazobenzene shows transitional kinetics. It has an order which rises from about 1·2 to 1·9 as the acid concentration is raised from 0·2 to 2·0N. Analysis of the rate curves shows that the rate is additively composed from rates of concurrent independent reactions, one of first order, and one of second, in hydrogen ion. The two-proton rate constant is smaller by a factor of 50,000 than that for hydrazobenzene. The one-proton constant is smaller by a factor of several thousands than the smallest comparable one-proton rate constant of rearrangement, that of 2,2′-dimethylhydrazobenzene. This is the first demonstration of the promotion of the one-proton mechanism of rearrangement by deactivating aromatic substituents. The phenomenon apparently depends on the 2,2′-orientation of the substituents, for the acid-conversion of 4,4′-dibromohydrazobenzene in similar conditions is strictly of second order in hydrogen ions. The compositions of the products of the acid conversions of 2,2′- and 4,4′-dibromohydrazobenzene are closely similar to those of the 2,2′- and 4,4′-dichloro-analogues respectively.

Condensation of appropriate β-keto esters with phenylhydrazine gave 5-oxo-1-phenyl-2-pyrazoline-3-and 4-alkanoic esters 1 and 3 which were saponified to the corresponding alkanoic acids 2 and 4. Analogous condensation of the same β-keto esters with hydrazobenzene gave 5-oxo-1,2-diphenyl-3-pyrazoline-3-and 4-alkanoic esters 5 and 7 which were similarly converted to acids 6 and 8. The structures of the oxopyrazolines as revealed by their infrared absorption are discussed, and results of their antiinflammatory screening are reported.

The benzidine rearrangement of hydrazobenzene is retarded by the addition of α-, β-, and γ-cyclodextrins. The effects on the rate of the cyclodextrins are decreased by the addition of cyclohexanol. The deceleration of the reaction by the cyclodextrins was attributed to the equilibrium complexation of the substrate in the cavities of the cyclodextrins, which may either restrict the large conformational change of the substrate necessary for reaching a sandwich-type transition state or lower the concentration of the diprotonated hydrazobenzene by means of the space alkalinity of cyclodextrins.

1. The complexes RhCl(PPh3)3 and RuCl2(PPh3)3 catalyze the reduction of nitrobenzene by 2-propanol to aniline at temperatures above 120°. This process is promoted by KOH. 2. In the absence of the indicated complexes, KOH catalyzes the reduction of nitrobenzene to azoxy-, azo-, and hydrazobenzene.

1. The complexes RhCl(PPh3)3 and RuCl2(PPh3)3 catalyze the transfer of hydrogen from 2-propanol to azoxybenzene with the formation of aniline. KOH promotes the process without changing its direction. 2. KOH also catalyzes the reduction of azoxybenzene in the absence of the Rh and Ru complexes, with the predominant formation of azobenzene and hydrazobenzene, but not of aniline.

第7報の実験により,ケイ素鉄還元方法の際に加えるCa(OH)2はFe(OH)3,Na2SiO3などと結合して3CaO・Fe2O3・6H2Oと3CaO・Fe2O3・3SiO2間の固溶体となり,立方晶形に結晶することが明らかになった。このことから,鉄粉を還元剤として使用してヒドラゾベンゼンを合成する際にも, Ca(OH)2とケイ酸ソーダを加えればゲル状Fe(OH)3を結晶化し, Fe(OH)3 皮膜による還元反応の妨害を除くことができると推定してこの実験を行い, つぎの結果をえた。1)ニトロベンゼン過剰な状態でカセイソーダ水溶液中での鉄粉の反応率を測定したところCa(OH)2とケイ酸ソーダを加えることにより, カセイソーダの濃度が20～30%では鉄粉の反応率が約4 倍に増大することがわかった。2)反応温度95～100℃,カセイソーダの濃度15～20%の比較的緩和な条件でも,Ca(OH)2とケイ酸ソーダを加えることにより, 鉄粉を還元剤としてヒドラゾベンゼンをよい収率でえられることがわかった。

Feprazone is a recently synthesised non-steroidal anti-inflammatory drug (1). It is structurally closely related to phenylbutazone, the difference lying in the side chain which is dimethylallyl in feprazone (see formula in Fig. 1) and butyl in phenylbutazone. For the purposes of the study the drug was labelled with 14C (Fig. 1) starting with [ 14C] i-diethylmalonate which was condensed with dimethylallyl chloride to give diethyldimethylallyl [2–14C] Amalonate. This was further condensed with hydrazobenzene to yield [ 14c] feprazone (2).

Reduction of nitrobenzene with sodium or lithium naphthalenide results in formation of azobenzene and azoxybenzene in modest yields. With sodium naphthalenide, azoxybenzene formation is favored; use of lithium naphthalenide results in enhanced azobenzene yields. Reduction of azoxybenzene with naphthalenide results in azobenzene and a variety of fragmentation products. Hydrazobenzene was the only product formed upon azobenzene formation.

The benzidine rearrangement of hydrazobenzene is retarded by the addition of α-, β-, and γ-cyclodextrins. The effects on the rate of the cyclodextrins are decreased by the addition of cyclohexanol. The deceleration of the reaction by the cyclodextrins was attributed to the equilibrium complexation of the substrate in the cavities of the cyclodextrins, which may either restrict the large conformational change of the substrate necessary for reaching a sandwich-type transition state or lower the concentration of the diprotonated hydrazobenzene by means of the space alkalinity of cyclodextrins.