Hydrazones, substituted, preparation

Other multi-heteroatom systems. Triheterocycles with a tetrazine as the central ring can be prepared by a base-induced intramolecular condensation reaction of the hydrazone-substituted pyrimidone shown in Equation (79) C1997JCM154, 1997JRM1041>. 

The hydrazones (136), prepared from 2-hydroxy-2-methyl-4-oxopentane (135) and substituted hydrazines, react with aldehydes to give the corresponding tetrahydro-l,3,4-oxadiazepines (137) in 60-70% yields (Scheme 24) <82KGS1319>. 

Anomalous Fischer cyclizations are observed with certain c-substituted aryl-hydrazones, especially 2-alkoxy derivatives[l]. The products which are formed can generally be accounted for by an intermediate which w ould be formed by (ip50-substitution during the sigmatropic rearrangement step. Nucleophiles from the reaction medium, e.g. Cl or the solvent, are introduced at the 5-and/or 6-position of the indole ring. Even carbon nucleophiles, e.g. ethyl acetoacelate, can be incorporated if added to the reaction solution[2]. The use of 2-tosyloxy or 2-trifluoromethanesulfonyloxy derivatives has been found to avoid this complication and has proved useful in the preparation of 7-oxygen-ated indoles[3]. 

A considerable number of examples will be found in the text in which halo-genated and other substituted olefins are produced. Their modes of fonnation do not usually differ in principle from the corresponding unsubstituted case. However, some special methods have been used, for example, the direct preparation of halo olefins from ketones with phosphorous hahdes, or via hydrazones. 

Ethynyl derivatives of 2-aryl-4,5,6,7-tetrahydroindazole were prepared from the p-chlorophenyl hydrazone of cyclohexanone. The hydrazone was treated with two equivalents of -butyllithium at —78°C to generate the dianion, which was then quenched with the appropriate substituted ethyl ester (94MT29). 

Excellent simple (90-100%) and induced diastereoselectivities (92-100%) were observed in the syntheses of 3,4-disubstituted 5-oxoalkanoates using, instead, various substituted aldehydes and ketones to prepare the chiral hydrazones. 

Another sequence involving an anionic and a Pd-catalyzed step was described by the groups of Rossi and Arcadi [477]. These authors prepared substituted tetrahy-dro-2H-pyrrolo[3,2-c]pyrazolones 2-934 starting from hydrazones 2-932 and aryl-halides or alkenyl triflates 2-933 (Scheme 2.208). The first step is the formation of a pyrazolone. There follows cleavage of the urea moiety with piperidine and an inter-as well as an intramolecular Heck-type reaction with 2-933. 

The enamine 141 can be cyclized to the [l,2,4]triazolopyridopyrimidine 142 upon treatment with sodium ethoxide (Scheme 40) <2002M1297>. This fused tricyclic system may also be obtained, like the pteridine analogue (cf. Scheme 38), from the reaction of hydrazonoyl halides and pyridopyrimidines such as 143, and also by treatment of the triazolopyrimidine 144 with dimethylformamide dimethylacetal (DMF-DMA) dimethylacetal and subsequent ring closure <2003MOL333, 2003HAC491> (Scheme 41). Another series of triazolopyridopyrimidines, for example, 146, can be prepared from a hydrazine-substituted pyridopyrimidine 145, in two ways either directly by reaction with an acid chloride, or via a derived hydrazone (Scheme 42) <1996MI585>. 

Hydrazones are also useful substrates in the preparation of pyrazoles. Reaction of N-monosubstituted hydrazones with nitroolefins led to a regioselective synthesis of substituted pyrazoles <060L3505>. lf/-3-Ferrocenyl-l-phenylpyrazole-4-carboxaldehyde was achieved by condensation of acetylferrocene with phenylhydrazine followed by intramolecular cyclization of the hydrazone obtained under Vilsmeier-Haack conditions <06SL2581>. A one-pot synthesis of oxime derivatives of l-phenyl-3-arylpyrazole-4-carboxaldehydes has been accomplished by the Vilsmeier-Haack reaction of acetophenone phenylhydrazones <06SC3479>. 

Several approaches to the 1,2,3-triazole core have been published in 2000. Iodobenzene diacetate-mediated oxidation of hydrazones 152 led to fused 1,2,3-triazoloheterocycles 153 <00SC417>. Treatment of oxazolone 154 with iso-pentyl nitrite in the presence of acetic acid gave 1,2,3-triazole 155, a precursor to 3-(W-l,2,3-triazolyl)-substituted a,P-unsaturated a amino acid derivatives <00SC2863>. Aroyl-substituted ketene aminals 156 reacted with aryl azides to provide polysubstituted 1,23-triazoles 157 <00HC387>. 2-Aryl-2T/,4/f-imidazo[43-d][l,2,3]triazoles 159 were prepared from the reaction of triethyl AM-ethyl-2-methyl-4-nitro-l//-imidazol-5-yl phosphoramidate (158) with aryl isocyanates <00TL9889>. 

H(53)323> and 1,2,4-triazinoquinolines have been reported. The preparation of a novel heterocyclic ring system, the indazolotriazinopurine 107, by the condensation of 8-hydrazinotheophylline (103) with 5-substituted isatins 104, via the hemiaminal 105 and hydrazone 106 intermediates, has been described <00JHC373>. 

Hydrazine hydrate, 50, 3 Hydrazoic acid, safe substitute for, 50, 107 HYDRAZONES, PREPARATION, 50,... 

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],... 

Aminotriazoles and their derivatives can be prepared from bis hydrazones and from substituted bis hydrazones of a-diketones. The bis hydrazones may in some cases be prepared more conveniently from -bromoketones than from a-diketones. Oxidation with mercuric oxide or with manganese dioxide gives the 1-aminotriazoles directly (Scheme m-ns Although two isomeric triazoles would be ex-... 

Substituted 1,2,4-oxadiazoles were prepared by addition of nitrile oxides to imines or hydrazones. It has been reported that interaction of hydroximoyl chlorides 262 with chiral hydrazones 263 in the presence of EtsN leads to intermediates 264 with diastereoselectivity up to 97%. A subsequent N-N bond cleavage to remove chiral auxiliary by formic acid leads to 1,2,4-oxadiazolines 265 with ee up to 91% (equation 113). ... 

Numerous methods to prepare individual classes of aliphatic diazo compounds have been extensively developed. The major strategies for their synthesis involve the alkaline cleavage of N-alkyl-N-nitroso-ureas, -carboxamides and -sulfonamides, dehydrogenation of hydrazones, as well as diazo group transfer from sulfonyl and related azides to active methylene compounds, and electrophilic diazoalkane substitution reactions. These synthetic methods have been comprehensively reviewed (15,16). Useful information on the preparation of selected diazo compounds can be found elsewhere (6,17). 

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