Hydrazones heterocycle synthesis

Hetero-substituted dienes as precursors of heterocycles 81S753. Hydrazones in synthesis of heterocycles 77MI2 74MI1. 

Preparation of thiadiazoles via the Hurd-Mori cyclization has led to the synthesis of a variety of biologically active and functionally useful compounds. Discussion of reactions prior to 1998 on the preparation of thiadiazoles have been compiled in a review by Stanetty et al Recent syntheses of thiadiazoles as intermediates for useful transformations to other heterocycles have appeared. For example, the thiadiazole intermediate 36 was prepared from the hydrazone 35 and converted to benzofuran upon treatment with base. Similarly, the thiadiazole acid chloride 38 was converted to the hydrazine 39 which, upon base treatment, provided the pyrazolone, which can be sequentially alkylated in situ to provide the product 40. ... 

Six-membered heterocycles with one tellurium and two nitrogen atoms in the ring are represented by 2-aroyl derivatives of 1,2,3-telluradiazine and 5,6-benzo-1,2,3-telluradiazine 89. For the synthesis of these compounds, IV-aroylhydrazones of 2-bromotellurenylcyclohexenealdehyde and 2-bromotellurenylbenzaldehyde 90 were used as the starting materials (98ZOK959). Dehydrobromination of the hydrazones 90 occurs on treatment with triethylamine and gives the heterocycles 89 in about 80% yields. 

Recent studies have been directed towards the synthesis of heterocyclic hydrazones which have lower toxicities than thiosemicarbazones [44], It has been proposed that the hydrazinic N-H group is essential for activity since it might be involved in a crucial radical formation step important in the mechanism of RDR. This is supported by the loss of antileprotic activity for this series of compounds when the hydrazinic hydrogen is replaced by a methyl group [44]. The heterocyclic hydrazones, like thiosemicarbazones, behave as tridentate ligands. 

A new method for the synthesis of 1,2,3-thiadiazoles has been reported. The method starts with the thioanilide derivative 72, which is converted into the hydrazone 73. Oxidative heterocyclization by treatment with hydrogen peroxide gave exclusively the 1,2,3-thiadiazoline 74 (Scheme 8) <2003S2559>. 

Considerable difficulties are often experienced in the preparation of basic dyes from quaternised heterocyclic diazo components. An alternative technique is to use an oxidative coupling procedure, in which a mixture of a hydrazone and a coupling component is treated with a mild oxidising agent, such as a hexacyanoferrate(III) [102] an azo compound is then produced as shown in Scheme 4.36 for the synthesis of Cl Basic Red 30 (4.100) [103]. Quaternisation of heterocyclic derivatives can lead to the formation of mixtures of isomers, as in the case of Cl Basic Red 22 (4.101). As well as the 2,4-dimethyl derivative shown, the product contains about 15% of the 1,4-dimethyl isomer [104]. 

In 1981 we published the first paper [22] on the synthesis of s-triazolo[4,3-a]pyridinium salts, 4, by the anodic oxidation of hydrazones 3 in the presence of pyridine (Scheme 5). In our working mechanistic scheme we proposed nitrilimine as the possible intermediate and pointed out that this reaction opens the door to a wide range of heterocyclic systems via anodic oxidation of aldehyde hydrazones through 1,3-dipolar cycloaddition reactions of the nitrilimine involved. 

Ethylenimines or aziridines [lb] can be considered cyclic imines and are only briefly covered in Section 5. The preparation of heterocyclic imine systems, semicarbazones, hydrazones, azines, and oximes, is omitted from this chapter. The synthesis of carbodiimides is presented in Chapter 9. 

In 1997, the first truly catalytic enantioselective Mannich reactions of imines with silicon enolates using a novel zirconium catalyst was reported [9, 10]. To solve the above problems, various metal salts were first screened in achiral reactions of imines with silylated nucleophiles, and then, a chiral Lewis acid based on Zr(IV) was designed. On the other hand, as for the problem of the conformation of the imine-Lewis acid complex, utilization of a bidentate chelation was planned imines prepared from 2-aminophenol were used [(Eq. (1)]. This moiety was readily removed after reactions under oxidative conditions. Imines derived from heterocyclic aldehydes worked well in this reaction, and good to high yields and enantiomeric excesses were attained. As for aliphatic aldehydes, similarly high levels of enantiomeric excesses were also obtained by using the imines prepared from the aldehydes and 2-amino-3-methylphenol. The present Mannich reactions were applied to the synthesis of chiral (3-amino alcohols from a-alkoxy enolates and imines [11], and anti-cc-methyl-p-amino acid derivatives from propionate enolates and imines [12] via diastereo- and enantioselective processes [(Eq. (2)]. Moreover, this catalyst system can be utilized in Mannich reactions using hydrazone derivatives [13] [(Eq. (3)] as well as the aza-Diels-Alder reaction [14-16], Strecker reaction [17-19], allylation of imines [20], etc. 

Azoles can be produced from the products of palladium-catalyzed hydrazone arylation and can themselves serve as substrates for arylation reactions to produce N-aryl azoles by the Fischer indole synthesis. N-Aryl pyrazoles and related heterocycles can also be prepared after obtaining N-aryl hydrazines by palladium-catalyzed procedures. Benzophenone hydrazone was first found by both the Yale and MIT groups to be a particularly effective substrate for palladium-catalyzed reactions, as summarized in Eq. (25) [183, 184]. Reactions of benzophenone hydrazone with either aryl bromides or iodides occur in high yields in the presence of either DPPF- or BINAP-ligated palladium. These reactions are general and proceed with electron-rich, electron-poor, hindered, or unhindered aryl halides. The products of these re-... 

Hydrazino nitrogen heterocycles are readily converted into 1,2,4-triazolo[/ ]-fused systems, as exemplified by Scheme 54 <1971JOC10>. A similar approach has been used for the synthesis of triazoloindole derivative 91 (Scheme 55) <2005BMC1847, CHEC-III(11.03.9.1)117>. Oxidation of the 2-pyrazolyl hydrazones 92 with lead tetraacetate gives, via azines 93, the 3//-pyrazolo [5,12,-4-triazoles 94 (Scheme 56) <1979TL1567>. 

Arrieta et al. (1998) illustrated the synthesis of (4,3 )-bipyrazole (3) by utilizing the mixture of dimethylhydrazone and ethyl phenylpropiolate under microwave irradiation. They also described the microwave-assisted 1,3-dipolar cycloadditions with electron-dehcient dipolarophiles to afford the corresponding cycloadducts. The use of pyrazolyl hydrazones led to valuable compounds, such as bipyrazoles (4), in good yields, providing a new approach to the preparation of these heterocyclic derivatives. 

Hydrazones and oximes are oi value in itie synthesis of heterocycles. For example, the acid-catalysed cydization of phenylhydrazones gives indoles. 

The utility of the SAMP/RAMP hydrazone method in diastereo- and enantioselective Michael additions was demonstrated in the synthesis of 5-oxo esters " (eq 9), -lactones (eq 10), 0x0 diesters and dinitriles, heterocyclic compounds (eq 11), MIRC (Michael initiated ring closure) reactions, and 2-substituted 4-oxo sulfones. ... 

A versatile synthesis of pyrazoles from benzophenone hydrazones was demonstrated with a variety of 1,3-bifunctional substrates under acidic conditions <2002TL2171>. Hydrazones 668 and 671, prepared from palladium-catalyzed heteroaryl halides with benzophenone hydrazone, reacted with 1,3-bifunctional substrates 669 and 672 under acidic conditions to yield pyrazoles 670 and 673, respectively (Equations 139 and 140) <2004TL5935>. Enolates of a-chloro-/3-oxoaldehydes react with arylhydrazines in the presence of acetic acid or / -oxo-a-chlorenamines react with arylhydrazines to produce osazones of carbonyl-substituted glyoxals, which under conditions of acid catalysis undergo intramolecular heterocyclization to the corresponding functionalized pyrazoles <1998CHE167>. 

Zimmermann, T. Afacile synthesis of 3H-indolium perchlorates by one-pot hydrazone formation/Fischer indolization. J. Heterocycl. Chem. 2000, 37, 1571-1574. 

The synthesis of this type of compound was achieved by nucleophilic attack of the nitrogen of the C-3 hydrazone residue on C-6 of 65c when it carries a leaving substituent such as a sulfonyloxy group or a bromine atom. This intramolecular heterocyclization process was achieved by the action of sodium iodide in acetone or by the action of acetic anhydride on the mono-O-p-toluene sulfonate to give 111 and 114, respectively (82MI5) (Scheme 28). The spectral data confirmed the assigned structure. 

An environmentally benign aqueous protocol for the synthesis of heterocyclic hydrazones using PSSA as a catalyst has been developed (Scheme 8.27). The simple reaction proceeds efficiently in water in the absence of any organic solvent under MW irradiation and involves basic filtration as the product isolation step. ... 

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