Heliotropine

Pyruvic Acid Compounds.—Lubrzynska and Smedley have recently shown that a number of aldehydes such as heliotropin, anisic aldehyde, benzaldehyde, and cinnamic aldehyde, condense with pyruvic acid in slightly alkaline solution, with the formation of )8-unsaturated-a-ketonic acids. For example, if heliotropin and pyruvic acid in alkaline solution be left standing for about eight days at ordinary temperature, dihydroxy-methylene-benzal-pyruvic acid is formed. This body forms yellow needles, melting at 163° Similarly, anisic aldehyde yields methoxy-benzal-pyruvic acid, melting at 130° and cinnamic aldehyde yields cinnamal-pyruvic acid, melting at 73°. 

To prepare heliotropin from isosafrol (which results from the isomerisation of safrol with alkalis), 5 parts of isosafrol are treated with a solution of 25 parts of potassium bichromate, 38 parts of cioncentrated sulphuric acid, and 80 parts of water. The reaction product is steam distilled and the distillate is extracted with ether, and the heliotropin obtained is purihed by means of alkaline bisulphite in the usual manner. 

Heliotropin melts at 37°, but its perfume is injured by exposure to a temperature several degrees below this, and it should always be stored in cool dark places. In very hot weather the stock may with advantage be kept dissolved in alcohol, ready for use. Its perfume is a powerful heliotrope odour, and is improved by blending it with a little coumarin or vanillin, or with bergamot, lemon, or neroli oil. Attention should be drawn to the fact that the fancy perfumes whose names resemble heliotrope are usually mixtures of heliotropin—the cheaper ones being chiefly acetanilide, the more expensive ones containing vanillin or coumarin. 

Heliotropine forms a number of well-defined crystalline compounds, which are suitable for its identification. Bromopiperonal... 

It is easily converted into isosafrol (containing the propenyl group) by the action of alcoholic potash. Safrol is used to an enormous extent for perfuming cheap soaps, and is also of great commercial value on account of the fact that on oxidation it yields heliotropin, an artificial perfume which is now largely employed (q.v.). 

The liquid is filtered, and on extraction with ether yields some pipe-ronal (heliotropin), melting at 37°. The residual liquid is boiled with magnesium carbonate-, resinous matter extracted with ether, the liquid filtered and the acid set free by means of dilute sulphuric acid. Homopiperonylic acid crystallises out on evaporation, and forms fine needles melting at 127° to 128°. 

Isosafrol results from the isomerisation of safrol by heating with alcoholic potash, and this conversion is the preliminary step in the manufacture of heliotropine since isosafrol yields considerably more heliotropine on oxidation than safrol does. Isosafrol has the following constitution —... 

Isosafrol yields piperonal (heliotropine) melting at 37° as the principal product of oxidation when potassium permanganate is used as the oxidising agent. If the oxidation be very energetic piperonylic acid, melting at 228°, is the principal reaction product. 

In comparison with the araliphatic alcohols discussed in Section 2.5.2, very few phenol alcohols are used as fragrance and flavor materials. Neither the alcohols corresponding to vanillin, ethylvanillin, and heliotropin nor their esters have special organoleptic properties. Anise alcohol and its acetate are the only products that are used to some extent in perfume and aroma compositions. 

Phenol aldehydes are generally pleasant-smelling products. Some of them are particularly important as fragrance and flavor materials. Anisaldehyde and certain derivatives of protocatechu aldehyde (3,4-dihydroxybenzaldehyde) are well-known representatives. The monomethyl ether of protocatechu aldehyde, vanillin, is perhaps the most widely used flavor material. Other important derivatives of this aldehyde are veratraldehyde (dimethyl ether) and heliotropin (formaldehyde acetal derivative) they are not only used as fragrance and flavor substances, but also are intermediates in many industrial processes. 

From Isosafrole. For many years, oxidative cleavage of isosafrole was the only route applicable on an industrial scale. Examples of oxidants that give good yields of heliotropin are chromium(VI) salts, oxygen, and ozone. 

From Catechol. Several routes have recently been developed for the synthesis of heliotropin from catechol. In one such route, catechol is converted into 3,4-dihydroxymandelic acid with glyoxylic acid in an alkaline medium in the presence of aluminum oxide. 3,4-Dihydroxymandelic acid is oxidized to the corresponding keto acid (e.g. with copper-(II) oxide), which is decarboxylated to 3,4-dihydroxybenzaldehyde [176]. The latter product is converted into heliotropin, for example, by reaction with methylene chloride in the presence of quaternary ammonium salts [177]. 

In another route, catechol is first reacted with methylene chloride and converted into 1,2-methylenedioxybenzene [177]. Reaction with glyoxylic acid in strongly acidic media yields 3,4-methylenedioxymandelic acid [178]. Subsequent oxidation and decarboxylation with nitric acid affords heliotropin. 

Uses. Heliotropin is used in many flowery-spicy flne fragrances and is also an important ingredient of flavor compositions. 

The oil contains more than 80% safrole and, like Brasilian sassafras oil is therefore used as a raw material for the production of heliotropin (piperonal, see p. 137) via isosafrole. 

Sassafras oil is used as a generic term for commercial essential oils containing high quantities of safrole. They originate from different botanical species. The main use of these oils is the isolation of safrole as the starting material for the production of heliotropin (see p. 136)... 

Safrole is used for the preparation of heliotropine, which is mainly used in vanilla flavours. Safrole has to be converted into isosafrole by alkali treatment or ruthenium or rhodium catalysis analogous to the eugenol to isoeugenol conversion before it can be oxidised to heliotropine using chromic acid as a catalyst [13] (Scheme 13.12). 

N.A. Spiraea ulmaria L. Salicylates, flavonol glycosides, heliotropin, vanillin, tannins.99 100 118 Laxative, treat headache. 

Glyoxahne, 14 Guaiacol, m87 Heliotropin, m239 Heliotropyl alcohol, m242 Hemimellitene, t333 Hemimellitic acid, b28 Heptaldehyde, h5... 

One of the earliest perfumery materials to be produced industrially was benzaldehyde, prepared from toluene in 1866. In 1868 coumarin was first synthesized, soon to be followed by heliotropin, ionone, and vanillin. The first nitro musks appeared in 1888, and amyl salicylate in 1898. Since then, for the last hundred years, the history of perfumery has been dominated by the creation of new aromatic chemicals. 

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