Citral

Citral occurs in many essential oils such as those of hops, rose, ginger, orange and basil. Its importance stems from its occurrence in lemon and lemongrass, the oils of which both depend heavily on citral for their characteristic odours. It can comprise as much as 85% of lemongrass oil. 

Having deduced the structure of a compound from degradation experiments, the next task for the natural products chemist is to confirm 

The French team started with the available compound, 2,4-dibromo- 

2-methylbutane (3.6). They reacted this with acetylacetone (pentan-2,4-dione) in the presence of base. There is no ambiguity in this reaction. The most acidic proton is that between the carbonyl groups of acetylacetone 

Citral is the key odoriferous principle of lemon and lemongrass oils and is therefore potentially useful in perfumes and flavours. More importantly, citral is a key intermediate in many synthetic routes to the ionones (a group of perfumery ingredients which will be described more fully in Chapter 8) and vitamins A, E and K. The synthesis of Barbier, Bouveault and Tiemann served its purpose as confirmation of the structure of citral. However, in terms of preparing large amounts of material for commercial use or even for use as an intermediate in further laboratory syntheses, it is somewhat lacking. This will be discussed in detail in Chapter 9 for the present suffice it to say that the need for an efficient synthesis of citral stimulated much synthetic effort over the years. 

By hydration to terpin and subsequent dehydration, pinenes can be converted into terpineols the main representative is a-terpineol, which is used in lime, among many other flavours. 

By isomerisation, a-pinene can be converted into camphene, and this can then be esterified to obtain an ester of isoborneate, which can be saponified to isoborneol. Isoborneol can be dehydrogenated to camphor, which can be reduced again to borneol, which is used in many fruit flavours. 

Pyrolysis of -pinene results in the triene myrcene, which leads to menthol and its derivatives, on one hand, and the rose alcohols and citral-related chemicals, on the other hand. 

The choice by a company for a sustainable or a petrochemical source of an ingredient will depend on various aspects, but cost will be the primary driving force. Availability of a low-cost feedstock is crucial, but also the available and appropriate technology in the company will have a large influence on this decision. 

Terpenes important for both fragrances and flavours can be prepared from citral, such as citronellol, linalool, nerolidol, geraniol, farnesol and bisabolol. Citral is also an important starting material for the synthesis of vitamins A and E, carotenoids and other flavour and fragrance compounds like ionones. Most of the /3-ionone synthesised is probably used for vitamin A synthesis. 

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With dilute sulphuric acid citral forms p-cymene. Citral can be condensed with propa-none to form a ketone, pseudoionone, C13H20O, which is technically important, as it is readily convertible into a and -ionone. 

Addition of dihydrosilane to a, /J-unsaturated carbonyl compounds such as citral (49), followed by hydrolysis, affords saturated citroneJlal (50) directly. The reaction is used for the selective reduction of conjugated double bonds[45,46]. In addition to Pd catalyst, the use of a catalytic amount of... 

Triethylammonium formate is another reducing agent for q, /3-unsaturated carbonyl compounds. Pd on carbon is better catalyst than Pd-phosphine complex, and citral (49) is reduced to citronellal (50) smoothly[55]. However, the trisubstituted butenolide 60 is reduced to the saturated lactone with potassium formate using Pd(OAc)2. Triethylammonium formate is not effective. Enones are also reduced with potassium formate[56]. Sodium hypophosphite (61) is used for the reduction of double bonds catalyzed by Pd on charcoal[57]. 

These trivial names may be retained citral (3,7-dimethyl-2,6-octadienal), vanillin (4-hydroxy-3-methoxybenzaldehyde), and piperonal (3,4-methylenedioxybenzaldehyde). 

Materials for flavoring may be divided into several groups. The most common groupings are either natural or artificial flavorings. Natural materials include spices and herbs essential oils and thek extracts, concentrates, and isolates fmit, fmit juices, and fmit essence animal and vegetable materials and thek extracts and aromatic chemicals isolated by physical means from natural products, eg, citral from lemongrass and linalool from hois de rose. 

A flavor is tried at several different levels and in different mediums until the most characteristic one is selected. This is important because the character of a material is known to change quaUty with concentration and environment. For example, anethole, ben2aldehyde, and citral taste different with and without acid. Gamma-decalactone has different characters at different levels of use. -/ fZ-Butyl phenylacetate with acid is strawberry or fmity without acid it is creamy milk chocolate. 2,5-Dimethyl-4-hydroxy-3-(2Fi)-furanone with acid is strawberry without acid it is caramel or meat. 

Nature Identical Flavor Matenal A flavor ingredient obtained by synthesis, or isolated from natural products through chemical processes, chemically identical to the substance present in a natural product and intended for human consumption either processed or not eg, citral obtained by chemical synthesis or from oil of lemongrass through a bisulfite addition compound. 

From West Indian lime oil, a trace low Foiling constituent, 1-methyl-1,3-(or 1,5 /74< 5 -3 7- -cyclohexadiene has been characterized (27). This compound, which possesses an intense and characteristic lime aroma, was later confirmed to be the 1,3-isomer [1489-56-1] (11). This compound can easily be made in a biomimetic way through the reaction of citral [5392-40-5] (3,7-dimethyl-2,6-octadienal) with citric acid (28,29). 

Some of the other eucalyptus oils of commercial importance iaclude the Chinese eucalyptus, a camphor/ciaeole-type oil E. citriodora Hook, a citroaeUal-type oil E. staigeriana F.v. Muel., a citral-type oil and E. macarthuri H. Deane Maiden, a geranyl acetate-type oil. 

Bergamot. Bergamot oil is produced by cold expression from peels of fmits from the small citms tree. Citrus bergamia. The fmits are inedible and of httle value. Bergamot is grown mainly in southern Italy and northern and western Africa. The oil is used to impart a sweet freshness to perfumes. Its largest chemical constituent, to the extent of 35—40%, is linalyl acetate [115-95-7] (1), with a much smaller amount of citral [5392-40-5] (2) as an important odor contributor. 

Rearrangement of dehydrolinalool (4) using vanadate catalysts produces citral (5), an intermediate for Vitamin A synthesis as well as an important flavor and fragrance material (37). Isomerization of the dehydrolinalyl acetate (6) in the presence of copper salts in acetic acid followed by saponification of the acetate also gives citral (38,39). Further improvement in the catalyst system has greatly improved the yield to 85—90% (40,41). 

The production of myrcene (7) from P-pinene is important commercially for the synthesis of a wide variety of flavor and fragrance materials. Some of those include nerol and geraniol, citroneUol (27) and citral (5). 

Uses ndReactions. The largest use of myrcene is for the production of the terpene alcohols nerol, geraniol, and linalool. The nerol and geraniol are further used as intermediates for the production of other large-volume flavor and fragrance chemicals such as citroneUol, dimethyloctanol, citroneUal, hydroxycitroneUal, racemic menthol, citral, and the ionones and methylionones. 

Gitral Manufacture. Natural sources of citral are lemongrass oil and l itsea cuheha. Both oils contain 70—80 wt % citral. Synthetic citral is made from terpene sources such as nerol and geraniol and in multitonnage quantities from petrochemical sources. 

The price of natural citral from Utsea cubeba in 1995 was 17.60—18.70/kg and the price of terpene-based synthetic citral was for 6.60—8.80/kg (69). Higher grades of synthetic citral are available for flavor and fragrance uses and price largely depends on the quaUty and quantity purchased. Shipment of citral is usually made in lined dmms, pails, or aluminum cans. 

Most terpene-based citral (5) produced is based on the catalytic oxidative dehydrogenation of nerol (47) and geraniol (48), or by the Oppenauer oxidation of nerol and geraniol (123—125). 

Petrochemical-based methods of citral manufacture are very important for the large-scale manufacture of Vitamin A and carotenoids. Dehydrolinalool and its acetate are both made from the important intermediate, P-methyUieptenone. 

Citral readily forms acetals by acid-catalyzed addition of alcohols or by the use of trialkoxyorthoformates. Citral dimethyl acetal [7549-37-3] is stable under alkaline conditions, whereas citral is not. Neryl and geranyl nitriles can be made by oximation of citral and dehydration of the intermediate oxime. For instance, geranonitrile [31983-27-4] is made as follows ... 

The products have the characteristic lemon odor of citral and also have greater odor strength and chemical stabiUty than citral. As the need for more stable citms-like fragrances for use in bleach developed, other nitrile compounds have been made available commercially. CitroneUyl nitrile is made from citroneUal dimethyloctanenitrile is produced from dimethyloctanal by the oximation method. 

Citral reacts in an aldol condensation using excess acetone and a basic catalyst, usually sodium hydroxide. The excess acetone can be recovered for recycle. The resulting intermediate pseudoionone [141-10-6] (83) after cyclization with phosphoric acid gives predominantly a-ionone [127-41 -3] (84), which is the isomer commercially important in flavors and fragrances. A hydrocarbon solvent is generally necessary in order to get high yields. P-Ionone [14901-07-6] (85) is the predominant isomer if sulfuric acid is used as the catalyst but lower temperature than that for cyclization to a-ionone is required. y-Ionone [79-6-5] (86) is also produced. 

Fig. 7. Methyl pseudoionones formed from reaction of citral with 2-butanone. Reaction at the 3-position of 2-butanone yields isomethylpseudoionone [111 7-41-5] whereas reaction at the 1-position gives normal-methylpseudoionone [26651-96-7].

In the condensation of 2-butanone with citral, if the reaction temperature is kept at 0—10°C, higher yields of the isomethyl pseudoionones, which are the more thermodynamically stable isomers, are obtained. The aldol iatermediates have more time to equilibrate to the more stable isomers at the lower temperature. The type of base used and a cosolvent such as methanol are also very important ia getting a high yield of the isomethyl pseudoionones (168). 

In addition to differences in thek methodology to extend the carbon chain, these manufacturers differ in thek syntheses of P ionone. P Ionone is commercially prepared via an acid-cataly2ed rearrangement of pseudoionone (26). This intermediate is manufactured on an industrial scale from either citral (27) or dehydro-hnalool (28) (21) (Fig. 5). 

Citral is prepared starting from isobutene and formaldehyde to yield the important C intermediate 3-methylbut-3-enol (29). Pd-cataly2ed isomeri2ation affords 3-methylbut-2-enol (30). The second C unit of citral is derived from oxidation of (30) to yield 3-methylbut-2-enal (31). Coupling of these two fragments produces the dienol ether (32) and this is followed by an elegant double Cope rearrangement (21) (Fig. 6). 

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