Glyoxylic hydrazone

Entry 21 involves addition to a glyoxylic hydrazone and the cis ring junction is dictated by strain effects. The primary phenylselenyl group is reductively removed under the reaction conditions. Entry 22 involves generation of a stannyloxy radical by addition of the stannyl radical at the carbonyl oxygen. Cyclization then ensues, with the cis-trans ratio being determined by the conformation of the cyclization TS. 

Intermolecular alkyl radical addition to imine derivatives was studied in aqueous media using indium as a single electron transfer radical initiator. The one-pot reaction based on radical addition to glyoxylic hydrazone provided a convenient method for preparing the a-amino acids. Indium-mediated radical addition to an electron-deficient C=C bond also proceeded effectively to provide a new carbon-carbon bond-forming method in aqueous media (Scheme 7.11).15... 

This mechanism is supported by the fact that a secondary hydrazone such as (8) yields the azohydrazone (9) rather than the formazan.8 Ketone hydrazones also yield azohydrazones. The coupling of hydrazones of glyoxylic acid (10) with diazonium salts is accompanied by decarboxylation to yield 3-unsubstituted formazans (11). Similarly, hydrazones of mesoxalic acid (12) yield formazans with a carboxyl group in position 3, e.g., 13 (Scheme 2).910 Both 11 and 13 can react with diazonium salts to yield the... 

Ethyl hydraziacetate produced by the hydrogenation of ethyl diazoacetate is likewise hydrolysed by acid yielding hydrazine, glyoxylic acid, and alcohol. The hydraziacetate is the hydrazone of ethyl glyoxy-late ROOC.O=N.NH2. 

Although the present procedure illustrates the formation of the diazoacetic ester without isolation of the intermediate ester of glyoxylic acid />-toluenesulfonylhydrazone, the two geometric isomers of this hydrazone can be isolated if only one molar equivalent of triethylamine is used in the reaction of the acid chloride with the alcohol. The extremely mild conditions required for the further conversion of these hydrazones to the diazo esters should be noted. Other methods for decomposing arylsulfonyl-hydrazones to form diazocarbonyl compounds have included aqueous sodium hydroxide, sodium hydride in dimethoxyethane at 60°, and aluminum oxide in methylene chloride or ethyl acetate." Although the latter method competes in mildness and convenience with the procedure described here, it was found not to be applicable to the preparation of aliphatic diazoesters such as ethyl 2-diazopropionate. Hence the conditions used in the present procedure may offer a useful complement to the last-mentioned method when the appropriate arylsulfonylhydrazone is available. 

Since this postsynthetic, chemoselective lipidation procedure bypasses all the difficulties encountered during preparative HPLC purification of lipopeptides, the a-hydrazinoacetyl peptides were further developed into a strategy of lipidation by chemoselective hydrazone formation between lipophilic glyoxaldehyde vectors and prepurified hydrazino peptides (Scheme 10).11241 The hydrazino handle can be located at the N-termini or even at preselected lysine side-chain positions. Various lipophilic vectors were proposed containing one or more fatty acids coupled via amides to spacers which in turn are linked to glyoxylic acid via an amide bond.1124-1271... 

Almotriptan has also been synthesized via decarboxylation of the carboxylic acid intermediate 65, but a detailed preparation of 65 was not provided in the patent literature (Scheme 22)." The patent indicates that the carboxy indole 65 was prepared according to the method of Gonzalez.°° Thus, (2-oxo-tetrahydro-3-furanyl)-glyoxylic acid ethyl ester (62) was heated in aqueous H2SO4 to give 2-oxo-5-hydroxypentanoic acid in situ, which was treated with hydrazine 59 to produce hydrazone 63. Fischer cyclization of 63 using HCl gas in DMF gave the lactone 64, which was converted to carboxylic acid 65. Decarboxylation of 65 was catalyzed by cuprous oxide in quinoline at 190 °C to afford almotriptan (5)." ... 

B. The p-toluenesulfonylhydrazone of glyoxylic acid chloride. Caution Since hydrogen chloride and sulfur dioxide are liberated during this reaction, it should be conducted in a hood. To a suspension of 50.2 g. (0.21 mole) of glyoxylic acid / -toluenesulfonyl-hydrazone in 250 ml. of benzene is added 30 ml. (49 g. or 0.42 mole) of thionyl chloride (Note 5). The reaction mixture is heated under reflux with stirring until vigorous gas evolution has ceased and most of the suspended solid has dissolved (about... 

Arylthiophens and Di- and Poly-heterocycles. - The reaction of (201) with sulphur gave (202) in 45% yield. Treatment of the hydrazone (203) with PPA at 110°C gave (204), the structure of which was proven by desulphurization of a degradation product with Raney nickel. From the simple phenyl-hydrazone of ethyl 2-thienyl glyoxylate, (205) and (206) were obtained in a 7 3 ratio. Authentic (206) was prepared via the Friedel-Crafts reaction of... 

The complex 1-pyrazoline (334) is one of the products of the thermolysis of the diazocyclohexadienone (333) in diphenylacetylene. The sodium tosyl-hydrazone (335) decomposes, on heating, to the strained 3//-pyrazole (336) on further heating, this yields the benzodiazepine (337). The yellow isomer of (l,5-diphenylformazanyl)glyoxylic acid has been identified as the pyrazolin-one (338). ° Epichlorhydrin forms the pyrazolidin-4-ols (339) when treated with AW -dialkyl-hydrazines. ... 

In the presence of a catalytic amount of Sc(OTf)3, benzoylhy-drazones react with ketene silyl acetals to afford the corresponding adducts, 8-lV-benzoylhydrazino esters, in high yield (eq 10). Several benzoylhydrazones including those derived from aromatic, aliphatic, a,/3-unsaturated aldehydes, and glyoxylate work well. The reactions of polymer-supported hydrazones with silyl enolates are also catalyzed by Sc(OTf)3 to produce pyrazolone derivatives after base treatment. ... 

Glyoxalines s. Imidazoles Glyoxalyl chloride tosyl-hydrazone as reactant 26,201 Glyoxylic acids... 

O-" naphthoquinone imine 1 benzalaniline, phenyl-glyoxylic acid imine, sali-cylaldoxime, benzo-phenone hydrazone, benz-hydrazidine... 

The FDP-aldolase catalyzed DHAP-addition to glyoxylic acid, examined in detail by Wandrey and Bossow-Berke under continuous flow reaction conditions [18], required the determination of the relative and absolute configuration. Employing the SAMP-/RAMP-hydrazone method, the aldol reaction of 1 with benzyl glyoxylate afforded a doubly protected adduct, which was deprotected with trifluoroacetic acid anhydride (TFAA) and subsequent debenzylation with H2/ Pd-C to give the final product, identical with the enzyme product. The independent chemical synthesis and the enzymatic route are compared in scheme 4. It... 

In the course of our work, we became interested in the development of an NHC-catalyzed synthesis of y-lactams from a formal [3+2] cycloaddition reaction between enals and imines. While this reaction had been first reported by Bode [143], its enantioselective version remained elusive at the onset of our studies. We identified aminoindanol-derived azolium salt 10 as an efficient precatalyst to afford y-lactams with excellent enantioselectivity level when cinnamaldehyde reacts with A -acyl hydrazones derived from ethyl glyoxylate (Scheme 21) [144], Unfortunately, this reaction proved to be sluggish, affording a low yield of the target product after 24 h of reaction time. 

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