Ketones from phenylhydrazones

Ketones from phenylhydrazones. Regeneration of ketones in refluxing aqueous (or... 

FISCHER - BORSCHE - DRECHSEL Indole synthesis Indole synlhesis from phenylhydrazones ol ketones (Fischer), in the case ol cyclohexanone phenylhydrazones letrahydrocarbazoies are obtained (Borsche-Drechsel). 

Benzeneseleninic anhydride, C5HjSe(0)0(0)SeC5Hs, which is prepared in situ from diphenyldiselenide and tert-hniyX hydroperoxide, is used for the oxidation of alcohols to aldehydes or ketones [525]. This reagent is a suitable dehydrogenating agent for the introduction of double bonds a to carbonyl groups [526] and the regeneration of ketones from their oximes, semicarbazones, and phenylhydrazones [527]. 

Hershberg developed an efficient method for the regeneration of ketones from their semicarbazones, phenylhydrazones, or oximes by exchange reaction. As applied to androstenolone acetate semicarbazone, the reaction is conducted in the presence of sodium acetate both to avoid deacetylation and to keep the exchanged semicarbazone in solution when the mixture is diluted with water. Thus 10 g. of pure... 

Kendall-Mattox reaction. Formation of a conjugated ketone from an a-bromoketone via a phenylhydrazone or semicarbozone. 

Indole synthesis from phenylhydrazones of ketones (Fischer) tetrahydrocarbazoles from cyclohexanone (Borsche-Drechsel) phenylhydrazones (see 1st edition). 

Fattee et al. ( ) isolated and identified the volatiles of "normal-flavored" raw peanuts. They found pentane, acetaldehyde, methanol, acetone, ethanol, and hexanal as major components and methyl formate, octane, 2-butanone, and pentanal as minor components. The characteristic aroma and flavor of raw peanuts were suggested to arise from a physical interaction of the components Isolated, with hexanal the most significant contributor to this aroma. Brown et al. (J ) isolated the aldehydes and ketones from raw peanuts as their 2,4-dinitro-phenylhydrazones. Concentrations of hexanal and octanal exceeded their flavor thresholds. The concentration data suggested that in addition to hexanal, octanal and possibly nonanal and 2-nonenal contribute to the "green or beany" flavor of raw peanuts. 

Oximes, Semicarbazones, Hydrazones, and Related Derivatives.—Lead tetraacetate was used to regenerate ketones from the semicarbazones and allowed a novel synthetic approach to 18-hydroxycorticosterone from 18-hydroxy-ll-oxoprogesterone. The use of benzeneseleninic anhydride as a deprotecting agent for phenylhydrazones, semicarbazones, oximes, and related derivatives has been described in full. ... 

Aldehydes and ketones may frequently be identified by their semicarbazones, obtained by direct condensation with semicarbazide (or amino-urea), NH,NHCONH a compound which is a monacidic base and usually available as its monohydrochloride, NHjCONHNH, HCl. Semicarbazones are particularly useful for identification of con jounds (such as acetophenone) of which the oxime is too soluble to be readily isolated and the phenylhydrazone is unstable moreover, the high nitrogen content of semicarbazones enables very small quantities to be accurately analysed and so identified. The general conditions for the formation of semicarbazones are very similar to those for oximes and phenylhydrazones (pp. 93, 229) the free base must of course be liberated from its salts by the addition of sodium acetate. 

Phenylhydrazones (compare Section III,74,C). Dissolve 0-5 g, of colourless phenylhydrazine hydrochloride and 0 8 g. of sodium acetate in 5 ml. of water, and add a solution of 0-2-0-4 g. of the aldehyde (or ketone) in a little alcohol (free from aldehydes and ketones). Shake the mixture until a clear solution is obtained and add a little more alcohol, if necessary. Warm on a water bath for 10-15 minutes and cool. Filter ofiF the crystalline derivative, and recrystalhse it from dilute alcohol or water sometimes benzene or light petroleum (b.p. 60-80°) may be used. 

In a more general approach toward pentacyclic heteroaromatics from tricyclic ketones, treatment of the N-methylated derivative of 112 with p-tolylhydrazine, followed by Fischer indolization of the resulting phenylhydrazone in a mixture of trifluoroacetic acid and acetic acid, produced only a low yield of 114, although this method proved to be considerably mrae efficient for synthesis of analogous systems containing other heteroatoms than nitrogen (98SC1239). 

Experiments.—Being a primary hydrazide (of carbamic acid), semicarbazide reduces ammoniacal silver solutions and Fehling s solution. It reacts readily with aldehydes and ketones with the elimination of water and formation of semicarbazones, which, since they are more easily hydrolysed than are phenylhydrazones and oximes, are to be preferred to the latter for purposes of separation and purification of carbonyl compounds. Shake an aqueous solution of the hydrochloride (prepared as described above) with a few drops of benzaldehyde, isolate the semicarbazone and purify it by recrystallisation from alcohol. Melting point 214° decomp. Benzaldehyde semicarbazone is decomposed into its constituents by gentle warming with concentrated hydrochloric acid. 

Alkyl- and aryl-hydrazones of aldehydes and ketones readily peroxidise in solution and rearrange to azo hydroperoxides [1], some of which are explosively unstable [2], Dry samples of the p-bromo- and p-fluoro-hydroperoxybenzylazobenzenes, prepared by oxygenation of benzene solutions of the phenylhydrazones, exploded while on filter paper in the dark, initiated by vibration of the table or tapping the paper. Samples were later stored moist with benzene at —60°C to prevent explosion [3], A series of a-phenylazo hydroperoxides derived from the phenyl-or p-bromophcnyl-hydrazones of acetone, acetophenone or cyclohexanone, and useful for epoxidation of alkenes, are all explosive [4], The stability of several substituted phenylazo hydroperoxides was found to be strongly controlled by novel substituent effects [5],... 

The most useful route to indoles is the Fischer indole synthesis, in which an aromatic phenylhydrazone is heated in acid. The phenylhydrazone is the condensation product from a phenylhydrazine and an aldehyde or ketone. Ring closure involves a cyclic rearrangement process. 

Diazaarsoles (R = Me, Et, Ph) result from the condensation of the phenylhydrazone of a methyl or benzyl ketone with arsenic trichloride in the presence of triethylamine (Scheme 8) <73TL4503, 74TL1977). Phenylhydrazones of cyclopentanone, cyclohexanone, norbornanone, nor-bornenone, and steroid ketones react as well. 

Only two classes appear to be known. The 1,2,5,6-system (599) is said to result from the treatment of the semicarbazide (598) with iron(III) chloride (28JIC439), and more recently it has been shown that benzoyl isothiocyanate adds to the phenylhydrazones of benzaldehyde and several ketones to give the l,3,4,6-oxatriazepine-5-thione system (600) (67JCS(C)952, 76JCS(P1)2243). The products rearrange to give (601) quantitatively on treatment with acid. 

Regeneration of carbonyl compounds from certain derivatives. Ketones can be recovered in satisfactory yield from the phenylhydrazones, p-nitrophenyl-hydrazones, tosylhydrazoncs, oximes, and semicarhazones by reaction with 1 equivalent of (C6H,Se0)20. 2,4-Dinilrophenylhydrazones and N,N-dimethyl-hydrazones arc inert under even rather vigorous conditions. The reagent can also be used to regenerate aldehydes from oximes or tosylhydrazones. 

Thus to permit cyclization, there must be at least one hydrogen a to the C=N bond. If there is only one, the product will be a 3,3-disubstituted-3H-indole. However, if both substituents at the hydrazone carbon have one or more a-hydrogens, product mixtures can result. Generally, it is expected that the more branched substituent is more likely to be involved in cyclization, so typically phenylhydrazones derived from methyl alkyl ketones give 2-methylindoles. However, the selectivity is subject to the reaction conditions and with certain reagents the selectivity can be reversed to favor the 2-alkylindole. 

The experimental procedure to be followed depends upon the products of hydrolysis. If the alcohol and aldehyde are both soluble in water, the reaction product is divided into two parts. One portion is used for the characterisation of the aldehyde by the preparation of a suitable derivative (e.g. the 2,4-dinitro-phenylhydrazone, semicarbazone or dimethone, see Aldehydes and ketones, Section 9.6.13, below). The other portion is employed for the preparation of a 3,5-dinitrobenzoate, etc. (see Alcohols and polyhydric alcohols, Section 9.6.4, p. 1241) it is advisable first to concentrate the alcohol by distillation or to attempt to salt out the alcohol by the addition of solid potassium carbonate. If one of the hydrolysis products is insoluble in the reaction mixture, it is separated and characterised. If both the aldehyde and the alcohol are insoluble, they are removed from the aqueous layer separation is generally most simply effected with sodium metabisulphite solution (compare Expt 5.82), but fractional distillation may sometimes be employed. 

You should already be familiar with approximately half of the reactions listed in Table 9.2 from your introductory class. Moreover, you have probably tried to prepare an oxime, a phenylhydrazone, a 2,4-dinitrophenylhydrazone, or a semicarbazone. These compounds serve as crystalline derivatives with sharp and characteristic melting points for identifying aldehydes and ketones and for distinguishing them. When spectroscopic methods for structure elucidation were not available, such a means of identification was very important. 

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