Pyruvaldehyde 2-Phenylhydrazone

[7013-79-8]  · C9H10N2O  · Pyruvaldehyde 2-Phenylhydrazone  · (MW 162.21)

(synthesis of a,b-unsaturated g-diketones,1 g-halo-a,b-unsaturated esters,4 pyrroles,1 1,4-diones,1 pyridazin-3-ones;5 aldol-type condensation with a pyruvaldehyde unit1)

Alternate Name: 2-(phenylhydrazono)propanal.

Physical Data: mp 125 °C,1 125.5-126 °C.2

Solubility: weakly sol benzene, ethanol, dioxane; can be used in suspension.

Form Supplied in: not commercially available.

Analysis of Reagent Purity: 1H NMR.

Preparative Methods: condensation of 1,1-dimethoxy-2-propanone with Phenylhydrazine in aqueous medium, followed by acidic hydrolysis (eq 1).1

Alternative methods, giving lower yields, involve condensation of 1-(N-piperidino)-1-propene with phenyldiazonium salts (eq 2),2,3 or oxidation of acetone phenylhydrazone with Selenium(IV) Oxide (eq 3).4

Handling, Storage, and Precautions: fairly stable pyruvaldehyde derivative; store in the refrigerator, well-protected from moisture; in acidic medium, isomerization takes place to the more stable 1-phenylhydrazone. Use in a fume hood.

Synthesis of Enediones.1

Condensation of equimolar amounts of pyruvaldehyde 2-phenylhydrazone with acetophenones, 2-acetylfuran, or 2-acetylpyridine, in the presence of potassium ethoxide in ethanol at rt gives aldol-type condensation products, i.e. g-(phenylhydrazono)-a,b-unsaturated ketones, which are converted into a,b-unsaturated g-diketones upon treatment with aqueous Hydrogen Chloride in the presence of Formaldehyde (eq 4).1 This aldol-type reaction with acetone gives various side products.1 However, the use of pyruvaldehyde 2-(4-nitrophenyl)hydrazone in condensations with aliphatic methyl ketones, e.g. Acetone and 3-methyl-2-butanone, does not show this disadvantage.1 The aldol reaction is not limited to methyl ketones as the title reagent condensed smoothly with indanone to afford the corresponding enedione monohydrazone and 1,4-dione (eq 5).1

As shown by the condensation reactions above, pyruvaldehyde 2-phenylhydrazone is a suitable building block in aldol-type reactions. This behavior contrasts with the reactivity of pyruvaldehyde, which is known to undergo predominantly self condensation under aldol-type reaction conditions.

Synthesis of g-Keto-a,b-unsaturated Esters.4

Pyruvaldehyde 2-phenylhydrazone condensed with (Ethoxycarbonylmethylene)triphenylphosphorane to yield the corresponding g-hydrazono-a,b-unsaturated ester, which is hydrolyzed to ethyl 4-oxo-2-pentenoate (eq 6).4

Synthesis of Pyridazin-3-ones.5

Active methylene compounds such as 2,2-Dimethyl-1,3-dioxane-4,6-dione (Meldrum's acid) condensed with pyruvaldehyde 2-phenylhydrazone under the catalytic influence of piperidine acetate at room temperature to afford the expected Knoevenagel condensation product (eq 7).5 However, if the reaction is performed at reflux, cyclization to 2,3-dihydro-6-methyl-2-phenyl-3-oxopyridazine-4-carboxylic acid takes place (eq 8).5

At 0 °C or below, pyruvaldehyde combines with phenylhydrazine to give the 2-phenylhydrazone in a kinetically controlled reaction.6 In acidic solution, isomerization to the more stable 1-phenylhydrazone occurs at room temperature, the latter compounds being suitable building blocks for the synthesis of 4-hydroxypyrazoles (eq 9).5

Synthesis of 1,4-Diones and Pyrroles.

Reduction of g-(phenylhydrazono)-a,b-unsaturated ketones with Tin(II) Chloride and concentrated aqueous hydrogen chloride in dioxane provides good yields of 1,4-diones (eq 10),1 while direct access to pyrroles is obtained via reaction of the same starting materials with Sodium Dithionite (eq 11).1

Related Reagents.

Acetone Cyclohexylimine; Acetone Hydrazone; 1-(N,N-Dimethylamino)-2-methyl-1-propene; Ethyl Pyruvate Diethyl Acetal; Propionaldehyde t-Butylimine; Pyruvaldehyde Diethyl Acetal.

1. Severin, T.; Adam, R. CB 1975, 108, 88.
2. Shvedov, V. I.; Altukhova, L. B.; Grinev, A. N. ZOR 1966, 2, 391 (CA 1966, 65, 8799c).
3. Shvedov, V. I.; Galstukhova, N. B.; Pankina, Z. A.; Zykova, T. N.; Lapaeva, N. B.; Pershin, G. N. Khim.-Farm. Zh. 1978, 12, 88 (CA 1979, 90, 103 336).
4. Severin, T.; Poehlmann, H. CB 1978, 111, 1564.
5. McNab, H.; Stobie, I. JCS(P1) 1982, 1845.
6. Begtrup, M.; Nytoft, H. P. JCS(P1) 1985, 81.

Norbert De Kimpe

University of Ghent, Belgium

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