Nitriles from hydrazones

Mercuric oxide/potassium hydroxide Nitriles from hydrazones... 

Several attractive methods, leading to syn-5,7 or anti-6,8-adducts, with excellent diaslereoselec-tivities have been developed using azaallyl-type Michael donors derived from hydrazones, imines, nitriles and laclim ethers. 

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. 

Oxidation of aldehyde hydrazones. The reaction produces nitriles, including chiral nitriles from SAMP-hydrazones in methanol at pH 7 and 0°C. 

Nitrile imines Hydrazones undergo a thermal 1,2-hydrogen shift to afford azome-thine imine intermediates which in turn can undergo 1,3-dipolar cycloaddition [51] bipyrazoles were obtained from pyrazolylhydrazones under the action of microwave irradiation. The synthesis involved [3+2] cydoaddition with alkenes after... 

An alternative route to the pyrazolino[60]fullerenes involves use of nitrile imines as dipoles - these are prepared in a one-pot procedure starting from hydrazones. 

Homologated nitriles from aldehydes or ketones. This reaction can be carried out in two steps conversion to the 2,4,6-triisopropylbenzenesuIfonylhydrazone (5, 706) followed by reaction of the hydrazone with KCN (equation I). The method is applicable to unsaturated ketones and to substrates containing a hydroxyl group. 

Once again, new reagents for the direct conversion of aldehydes into nitriles have been reported,probably the most useful of which is the modified reductive cyanation procedure which now allows the preparation of nitriles from aldehydes with the addition of one C-atom (Scheme 20). An analogous procedure involves the reaction of potassium cyanide with the 2,4,6-tri-isopropylbenzenesulphonyl (trisyl) hydrazones of both aliphatic aldehydes and ketones (Scheme 21). 

DipolarCycloaddition Reactions. The 1,3-dipolar cyclization of nitrile oxide with dipolarophiles generates structurally important heterocycles. As shown by Lee,139 the reaction can be carried out in an aqueous-organic biphasic system in which the nitrile oxide substrates can be generated from oximes or hydrazones in situ. The method provides a convenient one-pot procedure for generating a variety of heterocyclic products. 

The formation of several pyrazolylpyrazolino[60]fullerene adducts (208a-c) from nitrile imines have been described (Scheme 9.64) [111]. The nitrile imines are generated in situ from the corresponding hydrazone 205 and NBS in the presence of Et3N... 

The oxidation of hydrazones 143 provides, in principle, a very convenient route to nitrile imines from easily accessible starting materials. However, the earliest reagent used, lead tetraacetate, was of limited effectiveness as yields were low and the reaction often gave high yields of diacyUiydrazides as byproducts. Work has been done on the apphcation of several other oxidants to this process to produce a more effective general route. The one that has proved most popular is chloramine T (A(-chloro-A(-sodio-p-toluenesulfonamide, CAT) which is used under mild conditions and has been shown to work well for both cycloaddition (79) (e.g., in the preparation of 146 from 145) and electrocychzation (80) reactions. 

Dihydrooxadiazoles 106 have been syntheised in moderate to high diastereomeric excess by the addition of aromatic nitrile oxides across the C=N bond of the hydrazones 105. The N-N bond can subsequently be cleaved with formic acid, and the chiral auxiliary recycled <99H(50)995>. The oxadiazolone 108 was produced (56%) from the oxime 107 by heating it with phenyl isocyanate <99SC3889>. ... 

Under mildly basic conditions, methoiodides prepared from aldehyde-derived SAMP-hydrazones are converted to nitriles 28. 

In our group the diastereoselective 1,2-addition of organometallic reagents to aldehyde SAMP hydrazones was employed in the synthesis of several alkaloids and we have now extended our method to the efficient asymmetric synthesis of the poison-dart-frog indolizidine alkaloids 2091 and 223J and their enantiomers via a common late-stage intermediate amino nitrile (5R,8R,8aS)-63 [45]. This amino nitrile chemistry had previously been used by Polniaszek and Belmont in the first enantioselective total syntheses of 5,8-disubstituted indolizidine alkaloids [46]. They were able to prepare the indolizidines 205A (65) from 64 in one or two steps (Scheme 1.2.15). 

Most solid-phase syntheses of pyrazoles are based on the cyclocondensation of hydrazines with suitable 1,3-dielectrophiles. The reported examples include the reaction of hydrazines with support-bound a,(3-unsaturated ketones, 1,3-diketones, 3-keto esters, a-(cyano)carbonyl compounds, and a, 3-unsaturated nitriles (Table 15.19). Pyrazoles have also been prepared from polystyrene-bound 3-(hydrazino)esters, which are generated by the addition of ester enolates to hydrazones (Entry 7, Table 15.19 see also Section 10.3). Benzopyrazoles can be prepared from support-bound hydra-zones using the reaction sequence outlined in Figure 15.11. Oxidation of a polystyrene-bound benzophenone hydrazone yields an a-(acyloxy)azo compound. Upon treatment with a Lewis acid, this intermediate is converted into a 1,2-diazaallyl cation,... 

A 2-Dehydroquinuclidinyl-2- and 3-carboxamides were formed from the corresponding esters by the action of alcoholic ammonia.47,49 Quinuclidinecarboxylic esters were also used in the preparation of hydrazides and their hydrazones,95,132 and the amides in the synthesis of nitriles.47,49,90... 

Benzylidenehydrazinouracils (514), derived from 6-hydrazinouracils (513) and aldehydes, are cyclized upon UV irradiation and treatment with thionyl chloride or NBS, to afford pyrazolo[3,4-rf]pyrimidines (516), depending on the presence of protons at R2 and/or R3 (Scheme 51) fully methylated hydrazones are decomposed into 6-methylaminouracils (515) and nitriles <73S300, 74H(2)153, 75BCJ1484, 84JHC969, 92AHC(55)129>. 

Unsolvated potassium cyanide and hydrazone dissolve as the reactants are converted to the thermodynamically favored trans-nitrile. Shortly after all of the solid dissolves, a second solid precipitates from solution. This solid is presumed to be potassium mesitylenesulfinate and is usually accompanied by some foaming. An oversize flask used with efficient stirring keeps the reaction mixture from foaming into the condenser. 

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