Dehydrogenation of Hydrazones

Curtius discovered both the first synthetic route to aliphatic diazo compounds by nitrosation of amines (1883, see Sect. 2.3) and, in 1889, also their preparation by dehydrogenation of hydrazones, i.e., reaction (5) in Table 2-1. He treated the mono-and the bis-hydrazone of benzil (1,2-diphenylethanedione, 2.60) with yellow mercury (ii) oxide (2-23). With the monohydrazone 2.61, he obtained 2-diazo-l,2-diphenyl-ethan-l-one (azibenzil, 2.62). The corresponding bis-diazo compound (2.64) of 

Mechanism 2-24 is difficult to understand on the basis of observations made by Droescher and Jenny (1968). These authors mentioned that well crystallized, very pure HgO is not active for dehydrogenation of hydrazones. When a Guinier-Preston diagram of very pure HgO was compared with that of a sample that was activated 

Droescher and Jenny (1968) made their observations on the activity of HgO in the context of synthesizing (4-methoxybenzoyl)(4-methoxyphenyl)-diazomethane (2.69) from the corresponding hydrazone 2.68. They obtained 2.69 in 80% yield in tetrahydrofuran at 20°C. With inactive HgO but in the presence of potassium ethanolate they observed a dediazoniation. It is likely that desoxyanisoin (2.70) is formed in a Wolff-Kishner reaction (2-25). 

Klaerner et al. (1986) optimized the preparation of fresh and active HgO. It is important to work in the dark because light deactivates HgO. 

Stoichiometrically, one equivalent of HgO is necessary for the dehydrogenation of a hydrazone. Examples have been published in Organic Syntheses Smith and Howard (1955) described the procedure for diphenyldiazomethane, obtained from benzophenone hydrazone in petroleum ether in 89-96% yield. The necessity for the absence of moisture is emphasized, but no activation of the mercury(n) oxide seems to be required. Andrews et al. (1988) have reported on the dehydrogenation of acetone hydrazone to 2-diazopropane (70-90% yield) in ether in the presence of catalytic amounts of KOH in ethanol. There are also cases where two equivalents are used, e.g., the procedure for (benzoyl)(phenyl) diazomethane (2.62, yield 87-94%) published in Organic Syntheses by Nenitzescu and Solomonica (1943). Neither these nor other authors have explained, however, why two equivalents would be necessary. 

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Numerous methods to prepare individual classes of aliphatic diazo compounds have been extensively developed. The major strategies for their synthesis involve the alkaline cleavage of N-alkyl-N-nitroso-ureas, -carboxamides and -sulfonamides, dehydrogenation of hydrazones, as well as diazo group transfer from sulfonyl and related azides to active methylene compounds, and electrophilic diazoalkane substitution reactions. These synthetic methods have been comprehensively reviewed (15,16). Useful information on the preparation of selected diazo compounds can be found elsewhere (6,17). 

An interesting dehydrogenation of hydrazones (51) has been reported by Barton which relies on the available oxygen of aromatic nitro groups (equation 22). In a detailed study, quantitative yields were obtained using 4-nitrobenzoic acid as the oxidmt. Whilst this unusual reaction affords some advantages over earlier methods it is unlikely to be the method of choice in most instances. 

Cyclopentadimylidene (2). 2 was very easily obtained by photolysis or thermolysis of the corresponding diazo-cyclopentadienes (72). These were prepared by straightforward procedures (diazo-group transfer, dehydrogenation of hydrazones, or Bamford-Stevens reaction of tosyl-hydrazones) 26-80) from either cyclopentadienes (77) or substituted cyclopentadienones (73). 

The aliphatic diazo-compounds can also be prepared by careful dehydrogenation of the hydrazones (with HgO) (Curtius, Staudinger) and, conversely, they are converted into the latter by hydrogenation ... 

So far so good. But how can the fourth double bond be created There is a possibility of dehydrogenation of -CH-NH- group by hydrazine, similar to that of dehydrogenation of -CH-OH bond in saccharides by phenylhydrazine, which is hydrogenolyzed to ammonia and aniline. Here the molecule of cyclobutanetetronetetrakis(hydrazone), Z, is obtained, and hydrazine is split to ammonia [52]. 

Little woric has been carried out on sulfmylation reactions on those systems having thiocaibonyl and imino moieties. However, hydrazones are converted to a-sulfinyl derivatives on reaction of their anions (prepared from LDA in THF) at -78 C with sulrinate esters, although the full utility of this reaction remains to be explored. Furthermore, in an unusual reaction, p-toluenesulfmyl chloride has been shown to effect a facile one-step dehydrogenation of the thiolactam (17 equation 7) in good yield. These reactions contrast with the oxidative removal of thiocarbonyl, hydrazonyl and similar functionalities with Se species (see Section 2.2.4.2). 

The domain of oxidations with silver oxide includes the conversion of aldehydes into acids [63, 206, 362, 365, 366, 367 and of hydroxy aromatic compounds into quinones [171, 368, 369]. Less frequently, silver oxide is used for the oxidation of aldehyde and ketone hydrazones to diazo compounds [370, 371], of hydrazo compounds to azo compounds [372], and of hydroxylamines to nitroso compounds [373] or nitroxyls [374] and for the dehydrogenation of CH-NH bonds to -C=N- [375]. Similar results with silver carbonate are obtained in oxidations of alcohols to ketones [376] or acids [377] and of hydroxylamines to nitroso compounds [378]. 

Mercuric oxide, HgO (yellow modification or the less reactive red modification), resembles silver oxide in its oxidizing properties. This reagent transforms phenols and hydroquinones into quinones [383, 384] and is used especially for the conversion of hydrazones into diazo compounds [355, 386, 387, 388, 389, 390, 391, 392]. Dihydrazones of a-diketones furnish acetylenes [393, 394, 395, 396], A -Aminopiperidines are dehydrogenated to tetrazenes [397] or converted into hydrocarbons [395]. 

Nickel peroxide, an undefined black oxide of nickel, is prepared from nickel sulfate hexahydrate by oxidation in alkaline medium with an ozone-oxygen mixture [929] or with sodium hypochlorite [930, 931, 932, 933]. Its main applications are the oxidation of aromatic side chains to carboxyls [933], of allylic and benzylic alcohols to aldehydes in organic solvents [929, 932] or to acids in aqueous alkaline solutions [929, 930, 932], and of aldehydes to acids [934, the conversion of aldehyde or ketone hydrazones into diazo compounds [935] the dehydrogenative coupling of ketones in the a positions with respect to carbonyl groups [931] and the dehydrogenation of primary amines to nitriles or azo compounds [936]. 

Dehydrogenation of a-pyridinealdehyde hydrazone (251) yields not a-pyridyldiazomethane (252) but the cyclic isomer l,2,3-triazolo[3,4-a]pyridine (253).1 A similar ring closure is observed in diazo group transfers onto alkyl or aryl(2-pyridyl)methyl ketone (254) in MeOH/KOEt.1 The diazo intermediate could not be isolated but 3-acyl[l,2,3]triazolo[3,4-a]pyridine (255) is obtained.1... 

Dehydrogenation. Pyrazolines, available from the reaction of hydrazones and conjugated esters, undergo dehydrogenation readily on exposure to H2O2 in the presence of iron(II) chloride. 

An efficient CuS04/Cul-catalyzed aerobic intramolecular dehydrogenative cyclization reaction of A-methyl-Af-phenylhydrazones to cinnolines has been developed by Ge and coworkers through sequential C(sp )-H oxidation, cyclization, and aromatization processes (Scheme 8.107). This transformation is the first example of copper-catalyzed coupling reactions of hydrazones through a C(sp )-H bond functionalization pathway. This transformation starts with the oxidation ofiV-methyl-Af-phenylhydrazones into aldehyde intermediate through the activation of C(sp )-H under CuSO /O, catalytic system [181]. 

Reduction of dehydro-c-ascorbic acid phenylhydrazone (40) with LiAlH4 resulted in hydrogenation of the hydrazone residue and cyclization to bicyclic compound 41, which was dehydrogenated with boiling acetic anhydride during acetylation to give diacetate 43, then partly hydrolyzed to monoacetate 42 (Scheme 7) (72JOC3523). 

One of the common chemical methods for determining carbonyl compounds consists of converting them into hydrazones [7], This has been used for (1) oxycellulose [28], (2) nylon-6 and nylon-6,6 [29], (3) dehydrogenated poly (vinyl chloride) [30], (4) in irradiated polyethylene films [31], and (5) grafted polyethylene glycol [32],... 

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