Hydrazones diazo ketones

Non-functionalized aliphatic diazo compounds are fairly rare, and so are their reductions. Good examples of the reduction of diazo compounds to either amines or hydrazones are found with a-diazo ketones and a-diazo esters (pp. 124, 125, 160). 

Benzaimulated products are obtained via thermolysis of a-diazo ester-substituted complexes. For example, formation of diazo ketone complex (103) via a tosyl hydrazone followed by thermolysis gave (104) (Scheme 167). ... 

Diazo group transfer to 1,2-diketones via ketoxime Mid sulfonyl hydrazone is generally carried out in the presence of organic bases, and affords high yields of diazo compounds. Dichlorotricyclo[2.2.1.0w]heptan-2,3-dione (94) is converted into its monotosylhydrazone 95 which is passed over basic alumina to afford yellow crystalline diazo ketone 96.34 The monohydrazone of 4,5-diketo-[9]paracyclophane (97) is prepared from the diketone Mid further oxidized with MnC>2 to give diazoketone 98. 

Methods 3-5 are considered if the corresponding carbonyl compounds are available for the synthesis of the oximes, hydrazones, or 4-toluenesulfonyl-hydra-zones. As discussed in Section 2.5, reaction type 5 can also be applied to obtain a-diazo ketones, starting from a ketone in which a CH2 group adjacent to the carbonyl group is oximated. 

Heteroatom-Heteroatom Cleavage. N=N double bonds can be cleaved by Zn/AcOH less frequently, hydrazines may be obtained from the reduction (eqs 5 and 6). Hydrazones may also be reduced to amines, as used in a variant of the classical Knorr pyrrole synthesis. Diazo ketone (2) has been successfully reduced, despite the apparent potential for adverse side reactions (eq 7). ... 

The methoxymethyl ether protecting groups of 33 were then cleaved using triphenylphosphine and carbon tetrabromide. The resulting hydroquinone function was oxidized by palladium on carbon under an atmosphere of air to afford the quinone 52 (70 %). A two-step procedure was implemented to install the diazo function. First, the ketone function of 52 was condensed with N,N -bis( tert-butyldimethylsilyl)hydrazine in the presence of scandium triflate, which formed the Af-tert-butyldimethylsilyl hydrazone 53. The hydrazone (53) was then oxidized using difluoroiodobenzene to afford kinamycin C (3) in 35 % yield. 

This silyl hydrazone formation-oxidation sequence was originally developed as a practical alternative to the synthesis and oxidation of unsubstituted hydrazones by Myers and Furrow [31]. The formation of hydrazones directly from hydrazine and ketones is invariably complicated by azine formation. In contrast, silyl hydrazones can be formed cleanly from /V,/V -bis(7< rt-butyldimethylsilyl)hydrazine and aldehydes and ketones with nearly complete exclusion of azine formation. The resulting silylhydrazones undergo many of the reactions of conventional hydrazones (Wolff-Kishner reduction, oxidation to diazo intermediate, formation of geminal and vinyl iodides) with equal or greater efficiency. It is also noteworthy that application of hydrazine in this setting may also have led to cleavage of the acetate substituents. 

Ketone hydrazones can be converted into aliphatic diazo compounds which are, in contrast to nonfluorinated analogs, quite stable at room temperature. 2-Diazo-l,l,1-trifluoropropane is obtained as a solution in diethyl ether or pentane by the oxidation of l,l,l-trifluoropropan-2-one hydrazone using silver oxide.243 Analogously, phenyl trifluoromethyl ketone hydrazone is oxidized to the diazo compound 6 by mercury(II) oxide in alkaline media.362 Bis(per-fluoromethyl)- 7 and bis(perfluoroethyl)diazomethane are prepared by lead(IV) acetate oxidation of the corresponding hydrazones in benzonitrile solution at 0-25 c.244,245... 

Acylation of 2- -octylthiochroman by AczO is quantitative at the 6-position (Equation 23) <2003PS(178)993> and benzoylation of thioxanthene occurs at the 2- and 7-positions and both ketone functions have been converted into the hydrazones and thence the diazo compound 277. The bis-carbene derived from 277 by cryogenic photolysis has been used to study magnetic coupling interactions through the sulfur atom (Scheme 32) <1997JA8058>. 

Functional groups containing the C = N bond, such as hydrazones, oximes and diazo compounds, can also be used in the synthesis of fluorinated derivatives and these reactions are the subject of this section. The reaction products in these procedures are usually the corresponding g cw-difluoromethylene compounds. Since oximes and hydrazones arc obtained from aldehydes and ketones, these reactions can be considered as an alternative to the direct transformation of a carbonyl group into the difluoromethylene group. As indicated in Section... 

Many substituted carbenes have been prepared in situ by heating the tolyl hydrazones of aldehydes and ketones with alkali in aprotic solvents. Intermediates are diazo compounds which then decompose thermally to give nitrogen and a carbene. In the carbene, a-H or a-R migration readily occurs to give an olefin product and some intramolecular cyclization is observed. If no a-H or a-R are available, possible fates of the carbene include dimerization, insertion, and addition to the substrate. Some examples are... 

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]. 

In addition, manganese oxide oxidizes benzylic methyl or methylene to carbonyl [814] and cleaves the carbon bonds of vicinal diols [577, 522]. It converts amines into imines [577, 525] tertiary amines into secondary amines [572], formamides [526, 527, 525], or ketones aromatic primary amines [575, 525] and hydrazo compounds [525] into azo compounds hy-droxylamines into nitroso [576] or nitro compounds [525] hydrazones into diazo compounds [520] phosphines into phosphine oxides [575] thiols into disulfides [576] and sulfides into sulfoxides [541]. 

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]. 

Ketone derivatives whose oxidations have wide applications in synthesis are hydrazones and vicinal dihydrazones. Hydrazones are transformed into diazo compounds, and vicinal dihydrazones are converted into acetylenes. By far the most widely used oxidant is yellow mercuric oxide... 

Because of the difficulties of purification and handling, many of the results for diazoalkanes have been obtained from reactions in which the diazo compound is not the starting material but in which it may reasonably be supposed to be an intermediate. Most popular in this respect has been the base-catalysed decomposition of arylsulphonyl-hydrazones of aliphatic aldehydes and ketones, a reaction which was first investigated by Bamford and Stevens (1952). Because the reaction... 

Solvents are commonly dimethylformamide, a chloroalkane or chloroalkene (methylene chloride, chloroform, 1,2-dichloroethane, etc.) or phosphoryl chloride. Temperatures used are generally in the range CM00 C.la Substrates include activated aromatic or heteroaromatic compounds, alkenes (including enamines and enol derivatives), methyl or methylene ketones and "active methyl or methylene groups in general, and hydrazones, azines and aliphatic diazo compounds. 

A suspension of 4-benzyloxyphenyl phenyl ketone hydrazone (26.22 g, 0.0867 mol) in CH Clj (250 mL) was stirred over MnOj (52.4 g, 0.50 mol) for 3 h and filtered, washing with CHjClj (100 mL). The filtrate was added over 30 min to a refluxing solution of acrylonitrile (6.6 mL, 5.3 g, 0.10 mol) in heptane (200 mL). After completion of the addition, the mixture was held at reflux for 3 h until the purple color of the diazo compound was discharged. The CHjClj was removed by distillation until the internal temperature of the mixture reached 80 0. The mixture was held at this temperature for 3 h and was diluted with EtOAc to obtain a homogeneous solution. After cooling, 21.97 g (78%) of the product separated mp 105-115°C. Concentration of the mother liquors afforded an additional 2.20 g (8%) mp 101-109°C. An analytical sample consisting of a 4 1 mixture of diastereomers was obtained from EtjO/hexane mp 115-121 °C. 

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