Hydrazones from

From Hydrazones. The synthesis of l,2,3-thiadiazole-4-carboxylic acids by the action of thionyl chloride on ethoxycarbonylhydrazones of a-keto-acids has been applied to j3-phenylpyruvic acid. The reaction produces a mixture of 5-phenyl-l,2,3-thiadiazole-4-carboxylic acid (6 X = OH), its acid chloride, and the oxadiazine (7), which is converted into (6 X = Cl) in boiling thionyl chloride.  

Tosylhydrazones of cycloalkanones (8) undergo cyclization with thionyl chloride to give cycloalkeno-1,2,3-thiadiazoles (9), probably by way of the stages shown. Further action of peroxy-acids successively furnishes the 2-oxides and 1,1,2-trioxides.  

From Hydrazones.—Raap and Micetich s synthesis of 1,2,3-thiadiazoles [from (12)] has been applied to the production of further examples (13). The use of the readily accessible hydrazone (14) provides the desired compounds directly in one step. The condensation of diazoacetate with 0-ethyl thionoacetate affords the substituted 1,2,3-thiadiazole (15).  

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BARTON KELLOGG Olefinalion Olefin synthesis (letrasubsirtuted) from hydrazones and thiokelones via A -f,3,4-Ihiadiazollnes. 

Halogen-substituted olefins may be obtained from hydrazones by the action ofN-halocompounds. 327, /. 328.372 (Chloro compounds of this type may also be made by the direct action of phosphorous pentachloride on the ketone, e.g. ref. 329, 330.)... 

Several thiadiazolo-triazoles 43 have been synthesized that show antifungal and cytotoxic properties. hiadiazoles 45 were prepared from hydrazones 44 by treating them neat with thionyl chloride at room temperatures. The thiadiazoles were formed regio-selectively on the methyl group of the hydrazone. 

A thiophene-annelated thiadiazole has been prepared from hydrazone 47, which was obtained from the thiolactone 46. Reaction of the hydrazone at room temperature with thionyl chloride resulted in an 8 1 mixture of 48 and 49. Heating the reaction to 80°C in dichloroethane provided 48 exclusively. ... 

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). 

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. 

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. 

Scheme 6/2.10. Synthesis of aldehydes and "Prins-products" from hydrazones.

A similar reaction sequence allows the preparation of symmetrical and unsymmetri-cal ketazines 318 from hydrazones and diazodiphenylmethane or 2-diazo-l,2-diphenyl- 1-ethanone 293). 

From Hydrazones and Thionyl Chloride [4+1] Atom Fragments 479... 

Similar chemistry is possible starting from hydrazones bearing acidic a protons an initial diastereoselective enolization and electrophilic functionalization of the hydrazone can be followed by derivatization which is stereoselective in the planar sense . ... 

From Hydrazones and Thionyl Chloride Four Atoms Plus One Atom... 

Stable representatives of telluroketones were not available until recently. 2,5-Dihydro-1,3,4-telluradiazole 172 can be prepared from hydrazones 171 and tellurium tetrachloride or tetrabromide in yields of 19-48 and 42-55%, respectively (Scheme 8.39) (237). Ketazines 173 were obtained as byproducts of this reaction in 32 5% yield. It was proposed that XeX4 is hrst reduced to TeX2 in the reaction medium. The latter species probably generates both the diazo compound and the telluroketone derived from hydrazone 3 and then a [3+2] cycloaddition occurs. In fact, both 172 and 173 were obtained when hydrazones 3a-c were treated with the difhcult-to-handle tellurium dichloride in the presence of triethylamine. 

As shown in equation 53, when the zincated hydrazone, prepared from hydrazone by treatment with 2 equivalents of f-butyllithium and zinc(II) bromide, is treated with alkenylborane, the a-borylorganozinc is obtained with high diastereoselectivity. This pseudo-gem-dimetal species reacts with allyl halide stereospecifically. Through the transformation, three stereogenic centers are constructed diastereoselectively77. 

Application of this methodology to vinylstannane285 led to the discovery of a one-pot preparation of pyrroles. Indeed, the aza-enolate derived from hydrazone 435 smoothly reacted with vinyltrimethylstannane at 30 °C to afford exclusively the gewz-Zn/Sn dimetal-lated adduct 444, which upon hydrolysis delivered the corresponding y-stannylhydrazone 445. Alternatively, exposure of 444 to oxygen afforded the 2,3-disubstituted-l-(dimethyl-amino)-l -pyrrole 446 (equation 190). 

Michael-type condensation of cyanoacetohydrazide (NCCH2CONHNH2, CAH) with 1,3-dicarbonyl compounds gave pyrazolo[3,4-b]pyridines under certain conditions. With l,l,l-trifluoropentane-2,4-dione in the presence of piperidine a 1 3 mixture of pyrazolone 92a and the expected aminopyridone 91a was obtained.15 The bicycle was also obtained from hydrazone (90) or by thermal reaction between its two precursors.32 Reaction of CAH and / -keto aldehydes gave good yields of only bicyclic products 92b,20 whereas ethyl benzoylacetate in the presence of piperidine gave bicycle 92c (Ar = Ph)... 

When tozylhydrazone 368 is stirred in benzene at room temperature, within 2 h pyrazoline 369 is formed, while its subsequent refluxing in the same solvent converts the five-membered ring to cyclopropane (compound 370) [380] (Scheme 3.120). Heterocycle 370 can be obtained directly from hydrazone 368 by heating in benzene for 2 h. 

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