Hydrazones to nitriles

Pyrazolines. The synthesis involves oxidation of hydrazones to nitrile imines by Hg(OAc)j and in situ capture by alkenes. 

Oxidation of nitrogen and sulfur compounds. These oxidations serve to complete transformation of amines to hydroxylamines, hydrazones to nitriles, and p-amino esters to conjugated esters.- ... 

SCHEME 230 Proposed mechanism for die conversion of SAMP hydrazones to nitriles. 

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. 

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. 

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

Further applications can be mentioned briefly. SAMP was used in the resolution of 4-demethoxy-7-deoxydaunomycinone/ in ee determinations (Scheme 1), as a chelate for tetracarbonylmolybdenum complexes/ in intramolecular Heck reactions, as polysilylated hydrazine, in the enantioselective synthesis of isoquinuclidines, and in the conversion of hydrazones to aldehydes and nitriles. The structure of a chiral lithium SAMP hydrazone azaenolate has been determined. In cases where SAMP did not lead to satisfactory inductions, a modified auxiliary, (S)-l-amino-2-dimethylmethoxymethylpyrrolidine (SADP), enhanced the stereochemical control. 

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]. 

Addition of HaS to nitriles (73) represents an important method for the synthesis of primary thioamides (74 equation 33). The reaction is carried out under base or acid catalysis. The base-catalyzed process is particularly useful in the preparation of aromatic thioamides, i.e. for R = aryl, hetaryl in (73) triethylamine in molar proportion or pyridine, which at the same time also serves as solvent, are employed most commonly. The approach tolerates the presence of various other functionalities such as an amide, hydrazone, enamine, a-oxo, a-acetoxy ° or a-amino group. Moreover, the reaction has been applied to the synthesis of thioasparagine as such or incorporated into a dipeptide, as shown... 

In a number of instances (e.g., with steroids and sugars), oximes are formed prior to the silylation reaction [201, 202]. Muriatic o-pentafluorobenzylhydroxylamine has been used successfully to protect ketosteroids and increase the sensitivity of detection [203, 204]. It should be noted that oximes (under certain conditions) are converted quantitatively into the corresponding nitriles in a column [205]. In a number of instances it is expedient to use hydrazones to increase the stability of carbonyl compounds, including that of formaldehyde [206,207]... 

Formation of several pyrazolyl-pyrazolino[60]fullerene adducts (45a-c) from nitrile imines by use of this procedure has been described (Scheme 21.17) [53, 54]. The nitrile imines are generated in situ from the corresponding hydrazone 42a-c and NBS in the presence of EtsN and then reacted with Ceo (1) under the action of microwave irradiation, using a focused microwave oven. The route is simpler than the previously described method, which involved cycloaddition of Qo to nitrile imines prepared from the corresponding N-chlorobenzylidene derivatives [55]. 

Garanti and Zecchi have extended the range of their synthesis of 1,2-benzodiazepines via 1,7-electrocyclization of the nitrile imines (54). Earlier work used 1-chloro-hydrazones to produce diazepines bearing electron-withdrawing substituents, but now the use of 1-nitro-hydrazones (53) allows the preparation of unsubstituted and 3-alkyl-substituted diazepines (55) in moderate yield.The... 

Reagent for conversion of aldehydes to nitriles in good yield, via hydrazone formn. Mp 198-199° dec. 

Amines. Reaction of PCI3 with quaternary ammonium salts yields phosphaindolizines and thiazolodiazaphospholes. Imines produce phosphonates whereas hydrazones are converted to pyrazoles, indoles, and nitriles. Nitrones undergo rearrangement to secondary or tertiary amides and primary alkylnitro compounds are reduced to nitriles (eq 3). Diazonium salts are transformed to phosphonic acids. ... 

The imides, primaiy and secondary nitro compounds, oximes and sulphon amides of Solubility Group III are weakly acidic nitrogen compounds they cannot be titrated satisfactorily with a standard alkaU nor do they exhibit the reactions characteristic of phenols. The neutral nitrogen compounds of Solubility Group VII include tertiary nitro compounds amides (simple and substituted) derivatives of aldehydes and ketones (hydrazones, semlcarb-azones, ete.) nitriles nitroso, azo, hydrazo and other Intermediate reduction products of aromatic nitro compounds. All the above nitrogen compounds, and also the sulphonamides of Solubility Group VII, respond, with few exceptions, to the same classification reactions (reduction and hydrolysis) and hence will be considered together. 

Constitution. Pelletierine behaves as a secondary amine and the oxygen atom of the alkaloid is present in the form of an aldehyde group, since the base yields an oxime, convertible by the action of phosphorus pentachloride into a nitrile, b.p. 104-6°/13 mm., which is hydrolysed by caustic potash in alcohol to an acid, the ethyl ester of which is Loffler and Kaim s ethyl -2-piperidylpropionate. Pelletierine is not directly oxidisable to this acid. It also yields a liquid hydrazone, b.p. 130°/20 ram., which with sodium in alcohol at 136-70° reduces to dZ-eoniine. These reactions are explained by the following formulas, in which pelletierine is represented as -2-piperidylpropionaldehyde. 

Nickel peroxide is a solid, insoluble oxidant prepared by reaction of nickel (II) salts with hypochlorite or ozone in aqueous alkaline solution. This reagent when used in nonpolar medium is similar to, but more reactive than, activated manganese dioxide in selectively oxidizing allylic or acetylenic alcohols. It also reacts rapidly with amines, phenols, hydrazones and sulfides so that selective oxidation of allylic alcohols in the presence of these functionalities may not be possible. In basic media the oxidizing power of nickel peroxide is increased and saturated primary alcohols can be oxidized directly to carboxylic acids. In the presence of ammonia at —20°, primary allylic alcohols give amides while at elevated temperatures nitriles are formed. At elevated temperatures efficient cleavage of a-glycols, a-ketols... 

Reaction of 2,3-dichlorobenzoyl chloride with cyanide ion leads to the corresponding benzoyl cyanide (141). Condensation of that reactive intermediate with aminoguanidine 142 leads to the hydrazone-like product 143. Treatment with base results in addition of one of the guanidine amino groups to the nitrile function and formation of the 1,2,4-triazine ring. The product, lamo-trigine (144), is described as an anticonvulsant agent [31]. 

Hydrazones of the form ArCH=NNH2 react with HgO in solvents such as diglyme or ethanol to give nitriles (ArCN). Aromatic hydroxylamines (Ar—NH-—OH) are easily oxidized to nitroso compounds (Ar—N=0), most commonly by acid dichromate. ... 

Organocerium reagents also show excellent reactivity toward nitriles and imines,205 and organocerium compounds were found to be the preferred organometallic reagent for addition to hydrazones in an enantioselective synthesis of amines.206... 

Condensation of diazonium salts 1152 with activated nitriles provides hydrazones 1153. Treatment of hydrazones 1153 with hydroxylamine affords amidoximes 1154 in high yield. Upon heating with anhydrous sodium acetate in refluxing DMF, compounds 1154 undergo intramolecular cyclocondensation to provide 5-substituted 4-amino-2-aryl-277-1,2,3-triazoles 1155 in 75-85% yield (Scheme 190) <2006ARK(xv)53>. 

Nitrile oxides react in situ with formaldehyde dimethylhydrazone (129) to give oxime-hydrazones RC( NOH)CH NNMe2 (R = 4-O2NC6H4, MeCO, MeC ( NOH)). The reaction is performed on treatment of oximes with CH2 NNMe2 in the presence of Et3N without isolation of the intermediate nitrile oxides. 

---