Piperonal preparation

Protocatechualdehyde has been made by a variety of methods, but is usually prepared from catechol by the Reimer-Tiemann method 1 by demethylation of vanillin,2 or veratric aldehyde 3 or from piperonal by the action of phosphorus pentachloride followed by hydrolysis.4... 

Piperonylic acid has been made by the oxidation of piperic acid,1 piperonal,1 safrole2 and isosafrole2 with potassium permanganate. It has also been prepared by the action of methylene iodide on protocatechuic acid 3 in the presence of alkali. 

Partially methylated derivatives of D-glucosone have been prepared by decomposition of the corresponding partially methylated phenylosazones with p-nitrobenzaldehyde osones have been obtained from 5-0-methyl-D-glucose phenylosazone and from 3,4,5-tri-O-methyl-D-glucose phenylosazone in this way.22 Although 6-0-methyl-D-glucose phenylosazone is not altered by heating with benzaldehyde or piperonal in aqueous ethanolic... 

In a multistep transformation between Gly and piperonal, the tetracyclic system ISO was prepared [92H(33)537]. During the studies of Securinenga alkaloids, ethyl 2-thienylacetoacetate was subjected to reductive amination with L-Pro-OMe after cyclization, two tetracyclic diastereoisomers 151 and 152 were formed (83JOC3428). 

Four isobutylamide analogs of the natural products were synthesized in order to compare their insecticidal efficacy with that of the natural products. The synthetic scheme for the preparation of cis-fagaramide ( ) is shown in Figure 1. The syntheses of the cis (9) and trans (8) isomers of N -isobutyl-cinnamamide were accomplished by procedures similar to those utilized in the preparation of the cis (7) and trans (1 ) isomers of fagaramide, with the exception that benzaldehyde was used as starting material in the former case, piperonal in the latter. Isobutylbenzamide (10) was synthesized from benzoyl chloride and isobutylamine. 

The cis-fagaramide (J) was synthesized as outlined below. The required acetylenic acid (c) was prepared from piperonal (a) by the Corey s procedure.Treatment of piperonal with carbon tetrabromide, triphenylphosphine and zinc gave the bromo olefin (b) as an oil in 71% yield. The bromo olefin (b) was treated with 2 equivalents of n-butyl lithium followed by quenching with dry ice to give acetylenic acid (c) in 54% yield. Treatment of (c) with excess thionyl chloride without solvent at 50 followed by addition of isobutyl amine in benzene gave the acetylenic amide (d) as a viscous oil in 96% yield. Partial reduction of (d) gave cis-fagarmide (7 ) in 89% yield. 

An alternate synthesis of 3,4-methylenedioxyphenylacetone starts originally from piperonal. A suspension of 32 g electrolytic iron in 140 mL glacial acetic acid was gradually warmed on the steam bath. When quite hot but not yet with any white salts apparent, there was added, a bit at a time, a solution of 10.0 g of l-(3,4-methylenedioxyphenyl)-2-nitropropene in 75 mL acetic acid (see the synthesis of MDA for the preparation of this nitrostyrene intermediate from piperonal and nitroethane). This addition was conducted at a rate that permitted a vigorous reaction free from excessive frothing. The orange color of the reaction mixture... 

EXTENSIONS AND COMMENTARY There are about twenty different synthetic routes in the literature for the preparation of MDA. Many start with piperonal, and employ it to make methylenedioxyphenylacetone or a mcthylcnedioxydihydro-cinnamic acid amide instead of the nitrostyrene. The phenylacetone can be reduced in several ways other than the cyanoborohydride method mentioned here, and the amide can be rearranged directly to MDA. And there are additional methods for the reduction of the nitrostyrene that use no lithium aluminum hydride. Also there are procedures that have safrole or isosafrole as starting points. There is even one in the underground literature that starts with sassafras root bark. In fact, it is because safrole is one of the ten essential oils that MDA can humorously be referred to as one of the Ten Essential Amphetamines. See the comments under TMA. 

Cognate preparations. 3,4-Methylenedioxy-co-nitrostyrene. In a 250-ml round-bottomed flask mix 30 g (0.20 mol) of 3,4-methylenedioxybenzalde-hyde (piperonal), 13.4g (0.22mol) of nitromethane, 7.8g (0.1 mol) of ammonium acetate and 50 ml of glacial acid. Attach a reflux condenser, and boil the mixture under gentle reflux for 1 hour. Pour the reaction mixture with stirring into a large excess of ice-water (about 1 litre). When all the ice has... 

The norbelladine derivative 408, which served as the starting material for the synthesis of ( )-oxocrinine (415) (Scheme 35), may be readily prepared from the reductive animation of piperonal with tyramine followed by acylation with trifluoroacetic anhydride (191,192). When the N-acylated monophenol 408 was treated with excess thallium tris(trifluoroacetate) in methylene chloride, the di-enone 412 was obtained in 19% yield (191), whereas use of the oxidant vanadium oxyfluoride in trifluoroacetic acid/trifluoroacetic anhydride afforded 412 in 88% yield (192). Base-induced N-deacylation of 412 was accompanied by spontaneous cyclization to furnish racemic oxocrinine (415). Attempts to oxidize the free amine derived from 408 led to the formation of a number of products, some of which resulted from oxidation at nitrogen. 

A corresponding aldehyde [1.1 mmol, piperonal (a), ferrocene carboxaldehyde (b)] and ketone [1.0 mmol, acetylferrocene (a), 2-methylcyclohexanone (b)] were stirred in an Ehrlenmeyer flask, 2 mmol of powdered KOH added, and the mixture stirred after addition of one drop of Aliquat 336 [see (3.279) and (3.280)]. The Ehrlenmeyer flask was irradiated with microwaves [(a) 3 min, MOW (b) 2 min, MOW] and the final product dissolved in dichloromethane. After filtration on Celite, the solvent was removed and the residue chromatographed on a preparative chromatographic layer of silica (AcOEt/cyclohexane 20/80). The condensation product was further purified by crystallization in ether. Yield (a) 73% (lit. 37%), red solid (b) 63%, red solid. 

Prepartion of Piperonal Chapter 16 Process for Preparing Piperonal... 

Piperonal is a base material for preparing a heliotrope type perfume and has widely been used as a perfume for general cosmetics, and in addition, it is a useful compound as a starting material for synthesis of medical and agricultural chemicals and a brightener for metal plating. 

In the method of producing piperonal through 3,4-methylenedioxymandelic acid as mentioned above, the 3,4-methylenedioxymandelic acid formed by the initial reaction (hereinafter referred to as addition reaction) of 1,2-methylenedioxybenzene and glyoxylic acid is insoluble in the reaction system and precipitates as crystals. Thus, after separating the crystals of the 3,4-methylenedioxy-mandelic acid by an operation such as filtration, a subsequent reaction (hereinafter referred to as oxidation reaction) of 3,4-methylenedioxymandelic acid and nitric acid has been carried out. However, operations such as filtration, etc. are complicated, and this method is disadvantageous as an industrial preparation process. 

In the laboratory of P.G. Steel, a five-step synthesis of ( )-epiasarinin from piperonal was developed. The key steps in the sequence involved the Darzens condensation, aikenyi epoxide-dihydrofuran rearrangement and a Lewis acid mediated cyclization. The desired vinyl epoxide intermediate was prepared by treating the solution of ( )-methyl-4-bromocrotonate and piperonal with LDA, then quenching the reaction mixture with mild acid (NH4CI). 

Protocatechualdehyde (3,4-dihydroxybenzfildehyde). The preparation of this aldehyde from piperonal was accomplished for the first time in 1871 at Tiibingen by Rudolf Fittig, age 36, and his American co-worker Ira Remsen, age 25. In earlier work on the alkaloid piperine and its cleavage products piperic acid and piperidine, Fittig had isolated two products of oxidation of piperic acid, piperonal and piperonylic acid, now known to be constituted as formulated. The aldehyde bore... 

The second synthesis of cephalotaxine was reported by Semmelhack and co-workers (24), also in 1972. Their convergent strategy involved the alkylation of spirocycle 49, prepared in several steps from p)nTolidone 45, with p-nitrobenzenesulfonate ester 50, prepared from piperonal in 45-55% overall yield as shown in Scheme 2. The resulting key intermediate, 51a (X = Cl), was converted to ( )-cephalotaxinone (22), initially through an aryne intermediate. Route I, Scheme 3, in 15% yield. Cephalotaxinone was then converted to ( )-cephalotaxine (1) upon reduction with diisobutyl-aluminum hydride. The Semmelhack group expended considerable effort studying the conditions of the nucleophilic aromatic substitution (i.e., 51a-c... 

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