Hydrazones Tosylhydrazones

Regeneration of carbonyl compounds from certain derivatives.1 Ketones can be recovered in satisfactory yield from the phenylhydrazones, p-nitrophenyl-hydrazones, tosylhydrazones, oximes, and semicarbazones by reaction with 1 equivalent of (C6H5SeO)20. 2,4-Dinitrophenylhydrazones and N,N-dimethyl-hydrazones are inert under even rather vigorous conditions. The reagent can also be used to regenerate aldehydes from oximes or tosylhydrazones. 

Thus, the reduction of tosylhydrazones with sodium borodeuteride in dioxane provides only monodeuterated analogs. For the insertion of two deuteriums it is necessary to first exchange the hydrazone proton and to carry out the reduction in aprotic or deuterated solvents. Under these conditions the reduction of the tosylhydrazone derivatives of 7- and 20-keto... 

Zr(03PCH3), 2(03PC6H4S03H)o8, acetone, water, reflux 30 min-24 h, 70-95% yield. Semicarbazones, tosylhydrazones, and hydrazones are also cleaved."... 

The same type of reaction occurs in the work of Hauptman (76T1293), who, studying the chemistry of diethynylcarbenes, found that the pyrolysis of the lithium salts of diethynylketone tosylhydrazones 5 (140-150°C) in the presence of olefins leads to cyclopropanes. This process results in the formation of the corresponding 3-ethynylpyrazoles. The formation of l-p-tolylsulfonyl-3-alkynylpyrazoles from hydrazone runs in milder conditions (50°C, 14 h) (Scheme 24). 

Cyclic a,p-unsaturated ketones can be cleaved by treatment with base of their epoxy tosylhydrazone derivatives to give acetylenic ketones. The reaction can be applied to the formation of acetylenic aldehydes (R=H) by using the corresponding, 2,4-dinitrotosylhydrazone derivatives.Hydrazones (e.g., 47) prepared from... 

Other possibilities of converting the aldehyde group to a methyl group are desulfurization of the mercaptal (p. 104) and reduction of azines, hydrazones and tosylhydrazones (p. 106). 

Bicyclo[2.2.1]hept-7-yl cations, formed via the corresponding diazonium ions by diazotization of bicyclo[2.2.1]heptan-7-amine derivatives, rearrange partially to give bicyclo[3.2.0]heptanes (Houben-Weyl, Vol. 4/4, pp 106-107). Related diazonium ions can also be formed by irradiation of bicyclo[2.2.1]heptan-7-one tosylhydrazones in diluted sodium hydroxide and rearrange to form predominantly bicyclo[3.2.0]heptan-e. o-2-ols. On photolysis, the hydrazone 17 in 0.2 M sodium hydroxide gave t> <7o-2-methylbicyclo[3.2.0]heptan-exo-2-ol (18) with 77% selectivity and in 72-78% overall yield (GC).68... 

Both tosylhydrazones95-287-288 and oximes289 292- 336 were formed in good yields from the corresponding cyclobutanones under standard conditions. The tosylhydrazone of 4-isopropyli-dene-7,7-dimethylbicyclo[3.2.0]hept-2-en-6-one was reported288 to first crystallize at — 20 °C as a thermally labile stereoisomer which isomerized to a 1 5 mixture of the two possible stereoisomeric hydrazones 1 at room temperature. In deuteriochloroform at room temperature, the half life of the least stable isomer was approximately 8 hours. The exact configuration of each stereoisomer was not stated. 

The reduction of tosylhydrazones by complex metal hydrides has been used very effectively to prepare saturated steroid hydrocarbons in high yields.317 In certain cases this reduction (with lithium aluminum hydride) takes a different course, and olefins are formed.318 The effect is dependent on both the reagent concentration and the steric environment of the hydrazone.319 Dilute reagent and hindered hydrazone favor olefins borohydride gives the saturated hydrocarbon. The hydrogen picked up in olefin formation comes from solvent, and in full reduction one comes from hydride and the other from solvent. This was shown by deuteriation experiments with the hydrazone (150) 319... 

A 2-cyclohexenone derivative can be transformed into the corresponding epoxy tosyl-hydrazone by sequential treatment with peracid and tosylhydrazine. The elimination of nitrogen and p-toluenesulfinate and fragmentation after rearrangement to the 3-tosylazo allylic alcohol may occur under mild conditions. Carbonyl compounds with 5,6-triple bonds are formed in high yields (J. Schreiber, 1967 M. Tanabe, 1967). If one applies this reaction to a 9,10-epoxy-1-decalone, a ten-membered 5-cyclodecyn-l-one ring is formed (D. Felix, 1971). This product is an important intermediate in the perfume industry and has been used on a large scale. For this purpose Eschenmoser developed a synthesis in which the readily removed styrene was split off instead of a sulfmic acid. Thus a l-amino-2-phenylaziridine hydrazone was used instead of a tosylhydrazone (D. Felix, 1968). ... 

Figure 10.2 illustrates selected examples of these epoxide products. Aromatic and heteroaromatic aldehydes proved to be excellent substrates, regardless of steric or electronic effects, with the exception of pyridine carboxaldehydes. Yields of aliphatic and a,/ -unsaturated aldehydes were more varied, though the enantio-selectivities were always excellent. The scope of tosylhydrazone salts that could be reacted with benzaldehyde was also tested (Fig. 10.3) [29]. Electron-rich aromatic tosylhydrazones gave epoxides in excellent selectivity and good yield, except for the mesitaldehyde-derived hydrazone. Heteroaromatic, electron-poor aromatic and a,/ -unsaturated-derived hydrazones gave more varied results, and some substrates were not compatible with the catalytic conditions described. The use of stoichiometric amounts of preformed sulfonium salt derived from 4 has been shown to be suitable for a wider range of substrates, including those that are incompatible with the catalytic cycle, and the sulfide can be recovered quantitatively afterwards [31]. Overall, the demonstrated scope of this in situ protocol is wider than that of the alkylation/deprotonation protocol, and the extensive substrate...

Tosylhydrazones can be silylated with (fert-bufyldimethylsilyl)trifluoromethanesulfonate (Me2teriBuSi03SCF3) on the sulfonamide nitrogen. This is how the starting material for a broadly applicable alkane synthesis is produced ( Figure 1.49). Due to their ability to undergo reductive cyanization (Figure 17.69) mesitylene sulfonyl hydrazones allow for a two-step synthesis of nitriles from ketones. 

Tosylhydrazones can be reduced to the corresponding alkanes under milder conditions compared to the reduction of carbonyl compounds by the Wolff-Kishner method. This is illustrated in Figure 14.60 by the reduction of the aldhydrazone A (for a possible preparation, see Table 7.2) to the alkane C. The reduction is carried out with NaBH4 in MeOH.The effective reducing agent, formed in situ, is NaBH(OMe)3. This reductant delivers a hydride ion for addition to the C=N double bond of the tosyl-hydrazone A. Thereby the hydrazide anion B is formed. Much as in the second step... 

Semicarbazones (Table 1, R = CONH2) also react with iodine monofluoride. The gem-difluoro compounds are generally obtained in lower yields than with unsubstituted hydrazones, but the corresponding aldehyde derivatives (entry 16) arc reactive in this case. Finally, in the reaction of tosylhydrazones, gew-difluorides are obtained in only low to moderate yields (entries 4 and 23). 

Halogenated pyridazinones have been thus prepared from muco-chloric acid (35) 286,312-316 mucobromic acid, or the related chlorobromo acid. Instead of hydrazine semicarbazide can be used and the intermediate semicarbazone cyclized in hot acetic acid, loss of the carbamide group taking place simultaneously. Acid hydrazides likewise form hydrazones first, which cyclize with the aid of phosphorus oxychloride. Tosylhydrazones are reported to cyclize easily. ... 

Lead tetraacetate converts hydrazones to carbonyl compounds plus the corresponding alcohols. For example, benzophenone hydr ne is converted into benzophenone in 36-67% yields plus lesser amounts of benzhydrol. Substituted ketone hydrazones give a-acetoxyazo compounds with 1 equiv. of lead tetraacetate, although 2 equiv. of lead tetraacetate results in ketones. This also has been observed with tosylhydrazones. Arylhydrazones of aldehydes give diacylhydrazines (equation... 

Oxidative cleavage of hydrazones. Carbonyl compounds can be regenerated from 2,4-dinitrophenylhydrazones, tosylhydrazones, or N-methyl-N-tosylhydra-zones in 80-95% yield by oxidation with sodium nitrite in TFA or HOAc (0-5°, 1-2 hours). In the case of tosylhydrazones, the other product of cleavage has been identified as tosyl azide, the product of reaction of tosylhydrazine with nitrous acid. 

N,N-Methyltosylhydrazones. Ketones react only slowly with N,N-methyl-tosylhydrazine (1) but hydrazones of this type can be prepared by N-alkylation of tosylhydrazones with phase-transfer catalysis. The more reactive thioketones also react sluggishly with 1, but in this case, the reaction can be catalyzed by soft Lewis acids. Thus the reaction of 2 with 1 proceeds in high yield at room temperature in the presence of 1 equiv. of silver nitrate. Mercuric acetate also promotes this reaction, but the yield of 3 is only 50% because of formation also of 4 in 44% yield. 

Oxidation. Triphenylbismuth carbonate suspended in CH2CI2 is a heterogeneous oxidant for a variety of functional groups. Allylic alcohols are efficiently oxidized to the corresponding unsaturated aldehydes or ketones, even in the presence of a thiol, which is itself oxidized by this reagent to a disulfide, cis- and Irani-1,2-Glycols are cleaved to dialdehydes hydrazones are oxidized to diazocompounds oximes are cleaved to ketones and 1,2-dialkylhydrazines are oxidized to azo compounds. Phenylhydrazones, semicarbazones, tosylhydrazones, aromatic and aliphatic amines, enamines, and enol ethers are inert to 1. 

Direct transition from level 2 to level 0 can be achieved by way of the Wolff-Kishner reaction (treatment of the respective hydrazones with alkali), a classical pathway for the reduction of carbonyl compounds. At the same time, a direct conversion of aldehydes and ketones into alkenes is also feasible via reductive cleavage of their tosylhydrazones under the action of MeLi, the Shapiro reaction (Scheme 2.63). "... 

Most steroid ketones react readily with tolnene- Siilphonyl hydrazide -CH3 C6H4 S03 NH NH2) to form crystalline derivatives ( tosylhydrazones ) which are valuable intermediates for the preparation of olefins and fully-saturated unsubstituted products. Three modes of reaction of tosyl-hydrazones have become important. 

C(6) [14] and C(7) tosylhydrazones [2y] in contrast gave the A - and A -olefins respectively. A i4a-hydroxy-i7-tosyl-hydrazone (5) reacted with C(i8>"methyl migration and participation by the hydroxyl group to form the i3a,i4a-epoxy derivative (6) [28]. All these reactions can be accommodated by a carbonium-ion mechanism (see below). 

Pyridazines were obtained also by photolysis of 1-phenyl-l-vinyl azide in the presence of iron pentacarbonyl (3,6-di-phenylpyridazine was obtained in 1.1% yield) (78HCA589) or by thermal decomposition of an allenic hydrazonate (81JA7011). Acetylenic hydrazides can be transformed into pyridazines [84BSF(2)129], and thermal cyclization of dialkali metal salts of cu-hydroxyketone tosylhydrazones afforded pyridazines in moderate yield (85TL655). Propionyl phenylhydrazine, after reaction with 4-bromobutyronitrile, converts into a pyridazine (87SC1253). 

Ketones - Nitriles/ Ketones can be converted into nitriles by way of the tosyl-hydrazones. Thus the tosylhydrazone of cyclohexanone (I) on treatment with potassium cyanide in methanol acetic acid at room temperature followed by addition o( 2N... 

Eschenmoser and his coworkers then went on to introduce other diazo precursors. Two of them were 2-phenylaminoaziridine and // a/w-2,3-diphenylaminoaziridine . The aminoaziridine hydrazones (48) of a-epoxyketones decompose thermally and afford acetylenes in higher yields than the tosylhydrazones . Furthermore, only inert and volatile by-products are formed and the reaction takes place purely... 

As is the case with Wolff-Kishner reactions, the application of tosylhydrazone reductions relies on the successful conversion of carbonyls to the requisite hydrazone derivatives (58). This usually presents no problem except with relatively hindered or deactivated ketones and, in fact, several failures of the methodology are traced to unsuccessful tosylhydrazone formation (i.e. for examples with 62, 63, -- diketone (9) in equation 4, and the substrate of entry 3, Table 2). 

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