Veratric acid

CgHjoO,. A compound of largely historical interest for its role in establishing the structure of many natural products. Methylation of vanillin gives veratraldehyde which may be oxidized to veratric acid. Veratric acid was identified as a degradation product of the alkaloid papaverine. 

Convolamine, Ci,H2304N. This alkaloid is hydrolysed by boiling alcoholic potash into tropine and veratric acid, and is, therefore, veratroyl-tropine. It has m.p. 114-5° and yields a picrate, m.p. 263-4° (dec.) aurichloride, m.p. 201-2° platinichloride, m.p. 216-7°, and methiodide, m.p. 273-5°. 

In a similar attempt, Decker and Eichler reduced A -methylnor-papaverinium phenolbetaine (VIII) with tin and hydrochloric acid and obtained i/i-laudanine, m.p. 112°, pierate, m.p. 162-3°, which was subsequently investigated by Spath and Epstein, who showed that on methylation it furnished dMaudanosine and that the ethyl ether on energetic oxidation yielded veratric acid (3 4-dimethoxybenzoic acid) and the methyl ethyl ether of nor-m-hemipinic acid. This clearly indicated that the free hydroxyl group was in the woquinoline nucleus, and its position was determined by the fact that on mild oxidation 7-methoxy-6-ethoxy-l-keto-2-methyl-l 2 3 4-tetrahydrowoquinoline, m.p. 95-6°, was produced, and on this basis these authors assigned formula (IX R = H R = CH3) to -laudanine. 

By methylation with dimethyl sulphate and potash, it yields methyl-eugenol, boiling at 248° to 249° and which on oxidation yields veratric acid, melting at 179° to 180°. 

The principal derivative for identification purposes is veratric acid, C H.,(C00H)(0CH3)2, which is obtained by oxidising 6 grams of methyl-eugenol with a solution of 18 grams of potassium permanganate in 400 c.c. of water. When recrystallised from alcohol, veratric acid melts at 179° to 180°. 

On oxidation it yields veratric acid melting at 179° to 180°, and by the action of bromine on the phenol-ether dissolved in absolute ether, a dibromide is obtained, which melts at 101° to 102°. It has the constitution—... 

Valeraldehyde, p28 Valeric acid, p38 Valeronitrile, p35 Valeryl chloride, p45 Vanillic acid, hi43 Vanillin, hl42 Vanillyl alcohol, hl45 Veratraldehyde, d492 Veratric acid, d496 Veratrole, d493 Veronal, d330... 

Tertiary benzamides whose N-atom is part of a cyclic system can also be hydrolyzed metabolically as shown in the following examples. The hydrolysis of the amide group in 6-[4-(3,4-dimethoxybenzoyl)piperazin-l-yl]-3,4-di-hydro-1 //-quinolin-2-one (OPC-8212, 4.85), an inotropic agent, occurred in rats, mice, dogs, monkeys, and humans [54], After oral administration to rats, both products of hydrolysis, namely 3,4-dimethoxybenzoic acid (veratric acid, 4.86) and piperazine-l//-quinolin-2-one (4.87) were detected in the plasma, urine, and feces. 

Reduction. The reductive capacity of P. chrysosporium has been known for a long time. For example, veratraldehyde, veratric acid, vanillin, vanillic acid and analogous structures were converted into the corresponding... 

In our studies on the lignin peroxidase catalyzed oxidation of veratraldehyde and veratric acid no degradation was observed under the reaction conditions used. However, ligninolytic cultures of P. chrysosporium degraded veratraldehyde and veratric acid via reduction to veratryl alcohol... 

In some of the reductions of veratric acid or vanillic acid 250 /iM ATP was added to the reaction mixture. 

Previously, the quantitative reduction of veratraldehyde and veratric acid to veratryl alcohol by active ligninolytic cultures of P. chrysosporium had been described by Leisola and Fiechter (21). 

In this scheme veratryl alcohol was viewed to be metabolized by the combined action of oxidative systems (the lignin peroxidase and possibly other active oxygen species) and reductive conversions (aldehyde and quinone reductions). A possible route via veratric acid was discounted because both veratraldehyde and veratric acid were not substrates for the lignin peroxidase under the condition studied. However, both veratraldehyde and veratric acid were rapidly and quantitatively reduced by ligninolytic cultures of P. chrysosporium (21). 

Veratraldehyde [ 120-14-9] M 166.2, m 42-43°. Crystd from ethyl ether, pet ether, CCI34 or toluene. Veratric acid see 3,4-dimethyoxybenzoic acid. 

The halogens in o-bromo- or o-iodo-veratric acids are replaced by ketone enolates to give primary products which on lactonization or lactamization lead to benzazepines or benzoxepines respectively.126 There would appear to be no reason why this reaction could not be extended to reactions of o-halo-phenylacetic acids in general. 

Vanillic acid, hi32 Vanillin, hi 31 o-Vanillin, hi 30 Vanillyl alcohol, hi 35 Veratraldehyde, d430 Veratric acid, d434 Veratrole, d431 Veronal, d280 Vinylacetic acid, b403 Vinyl bromide, b284... 

Fig. 4-1. Examples of classical methods indicating a phenylpropanoid structure of lignin. (A) Permanganate oxidation (methylated spruce lignin) affords veratric acid (3,4-dimethoxybenzoic acid) (1) in a yield of 8% and minor amounts of isohemipinic (4,5-dimethoxyisophtalic acid) (2) and dehydrodiveratric (3) acids. The formation of isohemipinic acid supports the occurrence of condensed structures (e.g., /3-5 or y-5). (B) Nitrobenzene oxidation of softwoods in alkali results in the formation of vanillin (4-hydroxy-3-methoxybenzaldehyde) (4) (about 25% of lignin). Oxidation of hardwoods and grasses results, respectively, in syringaldehyde (3,5-dimethoxy-4-hydroxybenzaldehyde) (5) and p-hydroxybenzaldehyde (6). (C) Hydrogenolysis yields pro-pylcyclohexane derivatives (7). (D) Ethanolysis yields so-called Hibbert ketones (8,9,10, and 11).

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