Piperic acid

Piperic acid [tra/ts,tra/ts-5-(3,4-methyienedioxyphenyl)-2,4-pentadieneoic acid] [136-72-1] M 218.2, m 217 , pKe i 4.7. Crystd from EtOH. Turns yellow in light. Sublimes with partial dec. 

Anderson first hydrolysed piperine by alkalis into a base and an acid, which were named by Babo and Keller piperidine and piperic acid respectively. The chemistry of these products is so well known that it need not be discussed here. The alkaloid was synthesised by Rugheimer by the action of piperoyl chloride on pijieridine. 

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. 

Piperic acid [136-72-1] M 218.2, m 217°. Crystd from EtOH. Protect from light. 

The piperic acid portion is derived from a cinnamoyl-CoA precursor, with chain extension using acetate/malonate (compare flavonoids, page 149), and combines as its CoA ester with piperidine. 

Sylvatine (C24H3303N mp 112° [a]D +0°) isolated from this plant was shown to be an amide of piperic acid. Mass and other spectra indicated structure 148 and confirmation was achieved by reduction, hydrolysis, and/or oxidation, the product of the latter process being 5-methylhexanoic acid (136). 

The chemistry of the pungent compounds of pepper has been under study since the isolation of piperine in 1820. Piperine was shown to be a piperidide of piperic acid, and had the trans. trans configuration. The three other possible isomers were soon postulated, and they were named isopiperine (cis.trans). isochavicine (trans. cis) and chavicine (cis.cis) even before they were synthesized. The assignment of the isomeric configuration starts from the amide end. 

Heliotropin, Piperonal.— Heliotropin receives its other name of piperonal from its relation to compounds occurring in pepper. In black pepper, Piperus nigra there is present an alkaloid known as piperine (p. 888). From this alkaloid an acid, piperic acid, is obtained. This acid is a methylene di-ether containing an alpha unsaturated side chain as in iso-eugenole, etc. On oxidation the side chain breaks at the double bond, as has been explained, and yields an aldehyde which is piperonal. 

Protocatechuic Acid.—One of the di-hydroxy benzoic acids is related to vanillin, which we have already studied. The acid is known as protocatechuic acid, and derives its name from the fact that it may be obtained from a gum or resin, known as gum catechin by fusion with potash, i.e. by heat and oxidation in presence of an alkali. A large variety of plant products including alkaloids essential oils, gums, resins and tannins yield this acid. The following may be mentioned gum catechin, gum benzoin, guaiac resin, myrrh, piperine or piperic acid, vanillin, cafe-tannic acid. These natural sources at once suggest a relationship to vanillin (p. 661) and heliotropin (p. 662). It is the acid corresponding to protocatechuic aldehyde, 3-4-di-hydroxy benzal-dehyde (p. 661), which explains the relationship just mentioned. Its constitution, is then ... 

This compound, the hexa-hydro pyridine has just been referred to, and also previously, in connection with penta-methylene di-amine (p. 194). In both these connections its constitution has been established. As its name indicates, it is obtained from pepper in which it is present in amide combination with an acid known as piperic acid. The compound thus formed is the alkaloid of black pepper and is called pipeline. 

The fruit of the plant Piper nigrum is the common black pepper of the household. This fruit yields an alkaloid known as pipeline present to about 4 to 9 per cent in commercial pepper. On hydrolysis the alkaloid yields piperidine or hexa-hydro pyridine and an acid known as piperic acid. Piperine is thus considered as a piperidine amide of piperic acid. Physiologically this alkaloid acts like quinine but is less active and is uncertain. It is only rarely used in medicine. 

Pipen fie, C17H19O3N, is an alkaloid found in black pepper. It is insoluble in water, dilute acid, and dilute base. When heated with aqueous alkali, it yields piperic acid, C12H10O4, and the cyclic secondary amine piperidine (see Sec. 31.12), CsF N. 

Pipcric acid is insoluble in water, but soluble in aqueous NaOH and aqueous NaHC03. Titration gives an equivalent weight of 215 6. It reacts readily with Br2/CCl4, without evolution of HBr, to yield a compound of formula Ci2Hio04Br4. Careful oxidation of piperic acid yields piperonylic acid, C8H6O4, and tartaric acid, HOOCCHOHCHOHCOOH. 

II + acetic anhydride + sodium acetate — piperic acid (Ci2H]o04) piperic add + PCI5 — JJ (Ci2H903Cl)... 

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... 

Plants of the Compositae, Piperaceae and Rutaceae families [2] have been used as ingredients in many medicinal preparations and as food spices and many of them are used as insecticides [6]. Several long-chain unsaturated amides have been isolated from these plants, and they can be classified into two main structural types (a) (2 , 4 )-dienamides derived from straight-chain fatty acids and isobutylamine, pyrrolidine or piperidine units (1-22) (Chart 1), and (b) amides with the piperonal unit derived mainly from piperic acid in combination with the above mentioned amines (23-34) (Chart 2). 

The structure of piperic acid was deduced from oxidative experiments. Piperic acid when oxidized with potassium permanganate gave oxalic acid and two new products, piperonal and piperonylic acid (26) (the structures of which were subsequently established (31) ) according to the following equation ... 

From this, piperic acid was considered to be represented by II (29) a structure accommodated by the subsequent observation that the acid is converted by careful oxidation (KMn04 in basic solution) to piperonal, piperonylic acid, and tartaric acid (32). The acid of structure II, obtained by condensing piperonal with acetaldehyde followed by the action of sodium acetate and acetic anhydride on the resulting aldehyde I, was identical with piperic acid (38). 

After the structure of piperidine had been established (30), it was possible to confirm the early assumption that pipeline is the piperidine amide of piperic acid (29). Piperine resulted when the acid chloride of II (PCI5) was treated with piperidine (37). Hence, piperine must be represented by III. Methyl, ethyl and phenyl analogs of piperine have been prepared by similar syntheses (39). 

Hydrolysis of chavicine with alcoholic potassium hydroxide yielded piperidine and isochavicinic acid (43), m.p. 200-202° (earlier workers (42) reported the isolation of an isomer, chavicinic acid). Isochavicinic acid is isomeric with piperic acid and the catalytic hydrogenation of both acids... 

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