Flavors and fragrances

Chloroacetate esters are usually made by removing water from a mixture of chloroacetic acid and the corresponding alcohol. Reaction of alcohol with chloroacetyl chloride is an anhydrous process which Hberates HCl. Chloroacetic acid will react with olefins in the presence of a catalyst to yield chloroacetate esters. Dichloroacetic and trichloroacetic acid esters are also known. These esters are usehil in synthesis. They are more reactive than the parent acids. Ethyl chloroacetate can be converted to sodium fluoroacetate by reaction with potassium fluoride (see Fluorine compounds, organic). Both methyl and ethyl chloroacetate are used as agricultural and pharmaceutical intermediates, specialty solvents, flavors, and fragrances. Methyl chloroacetate and P ionone undergo a Dar2ens reaction to form an intermediate in the synthesis of Vitamin A. Reaction of methyl chloroacetate with ammonia produces chloroacetamide [79-07-2] C2H ClNO (53). 

Many other acrolein derivatives produced via Diels-Alder reactions are classified as flavors and fragrances. Among those of commercial interest are lyral, (1) [31906-04-4] (91,92) andmyrac aldehyde, C 3H2oO, (2) [80450-04-0] (92,93). 

Eastman Goal Chemicals. In 1983 Eastman Chemical Co. became the first chemical producer in the United States to return to coal as a raw material for large-scale manufacture of industrial chemicals (35). In that year, Eastman started manufacturing acetic anhydride from coal. Acetic anhydride is a key intermediate for production of coatings, ceUulosic plastics, and cellulose acetate fibers. Acetic anhydride from other sources also is used in the manufacture of pharmaceuticals, starches and sweeteners, and flavors and fragrances. 

Specifications also appear in other pubHcations, including pubHcations of the Fragrance Materials Association (FMA) of the United States (53,57) (see also Fine chemicals). The FMA specifications include essential oils, natural flavor and fragrance materials, aromatic chemicals, isolates, general tests, spectra, suggested apparatus, and revisions adopted by the FMA. 

International Flavors and Fragrances, Quest International, Givaudan, Takasago, Haarmann Reimer... 

Formic acid is used as an intermediate in the production of a number of dmgs, dyes, flavors, and perfume components. It is used, for example, in the synthesis of aspartame and in the manufacture of formate esters for flavor and fragrance appHcations. 

The hydroxybenzaldehydes are used primarily as chemical intermediates for a variety of products. The largest single use of sahcylaldehyde is in the manufacture of coumarin. Coumarin is an important commercial chemical used in soaps, flavors and fragrances, and electroplating (see Coumarin). Other significant uses of both sahcylaldehyde and -hydroxybenzaldehyde are as follows. 

Flavors and Fragrances. SaUcylaldehyde is a starting material in the synthesis of coumatin, which finds extensive use in the soap (qv) and perfume (qv) industries and saUcylaldehyde can be used itself as a preservative in essential oils and perfumes (see Oils, essential). The antibacterial activity of sahcylaldehyde is strong enough to allow its use at very low concentrations (79). 

Diketones can be prepared by oxidation of the corresponding monoketone (287) or a-hydroxyketone (288). 1,2-Diketones are used extensively as intermediates in the preparation of pharmaceuticals, flavors, and fragrances. Toxicity data for selected diketones are shown in Table 11. 

Experimental procedures have been described in which the desired reactions have been carried out either by whole microbial cells or by enzymes (1—3). These involve carbohydrates (qv) (4,5) steroids (qv), sterols, and bile acids (6—11) nonsteroid cycHc compounds (12) ahcycHc and alkane hydroxylations (13—16) alkaloids (7,17,18) various pharmaceuticals (qv) (19—21), including antibiotics (19—24) and miscellaneous natural products (25—27). Reviews of the microbial oxidation of aUphatic and aromatic hydrocarbons (qv) (28), monoterpenes (29,30), pesticides (qv) (31,32), lignin (qv) (33,34), flavors and fragrances (35), and other organic molecules (8,12,36,37) have been pubflshed (see Enzyp applications, industrial Enzyt s in organic synthesis Elavors AND spices). 

Essential Oils. Essential oils are produced by distillation of flowers, leaves, stems, wood, herbs, roots, etc. Distillations can be done directly or with steam. The technique used depends mosdy on the desired constituents of the starting material. Particular care must be taken in such operations so that undesired odors are not introduced as a result of pyrolytic reactions. This is a unique aspect of distillation processing in the flavor and fragrance industry. In some cases, essential oils are obtained by direct expression of certain fmits, particular of the citms family. These materials maybe used as such or as distillation fractions from them (see Oils, essential). 

Other appHcations of amyl alcohols include their use as flavor and fragrance chemicals. Amyl isovalerate and amyl saHcylate consumed a maximum of 450 t of amyl alcohols (150). Isoamyl saHcylate is used to a large extent in soap and cosmetic fragrances because of its cost effectiveness (167). Isoamyl... 

Another analysis handled effectively by use of gc/ir/ms is essential oil characterization which is of interest to the foods, flavors, and fragrances industries (see Oils essential). Even very minor components in these complex mixtures can affect taste and aroma. Figure 4 shows the TRC and TIC for Russian corriander oil which is used extensively in seasonings and perfumes (15). The ir and ms are serially configured. Spectra can be obtained from even the very minor gc peaks representing nanogram quantities in the it flow cell. 

The main commercial apphcations for sahcylate esters are as uv sunscreen agents and as flavor and fragrance agents. Several have apphcation as topical analgesics. A number of sahcylate esters of commercial interest and their physical properties are hsted in Table 8. 

As a pharmaceutical, methyl salicylate is used in liniments and ointments for the relief of pain and for rheumatic conditions. As a flavor and fragrance agent, it is used in confectioneries, dentifrices, cosmetics, and perfumes. Other commercial applications for methyl salicylate are as a dye carrier, as a uv-light stabilizer in acrylic resins, and as a chemical intermediate. The May 1996 price was 5.50/kg (18). 

Isoamyl saUcylate is perhaps the most important ester of saUcyhc acid for perfumery purposes. Generally, it is manufactured by the transesterification of methyl saUcylate. It has a characteristic flowery aroma and is useful in soap fragrances. The May 1996 price was 5.30/kg (18). Other saUcylates of commercial interest as flavor and fragrance agents include isopropyl, isobutyl, phenethyl [87-22-9] and 2-ethyIhexyl saUcylates. 

Terpenes are found as constituents of essential oils and oleoresins of plants. Since antiquity they have been isolated and used in flavor and fragrance apphcations. Many important constituents of the essential oils have been identified and syntheses for them developed (see Oils, essential). 

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). 

Dimerization of Isoprene. Isoprene is becoming an increasingly important raw material for the production of terpenes. For example, myrcene (7) can be produced by the dimerization of isoprene (2-methyl-1,3-butadiene) (42—44) and myrcene is very useful for synthesizing a number of oxygenated terpenes important in the flavor and fragrance industry. 

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). 

Purified myrcene has minimal use in flavor and fragrance appHcations. Production and cost figures for cmde myrcene from P-pinene are not pubhshed to avoid disclosure of individual company operations, but the production volume is large (- SO, 000 t). 

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. 

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. 

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. 

The chemistry of organic sulfur compounds is very rich and organosulfur compounds are incorporated into many molecules. Thiols, or mercaptans as they were originally called, are essential as feedstocks in the manufacture of many types of mbber (qv) and plastics (qv). They are utilized as intermediates in agricultural chemicals, pharmaceuticals (qv), ia flavors and fragrances, and as animal feed supplements. Many reviews have been undertaken on the chemistry of the thiols, regarding both their preparation and their reactions (1 7). 

In the 1990s hplc has become widely used in the flavor and fragrance industry to measure vanillin and other phenoHc compounds. Routine methods have been developed that are particularly adapted to thermosensitive products, such as vanillin and its derivative products, with elution gradient and uv detection at given wavelengths. Certain critical impurities can thus routinely be traced to very low (10 ppm) concentrations. 

Cinnamaldehyde, [14371-10-9] CgH CH=CHCHO (bp, 253°C at 101.3 kPa), produced by the alkaline condensation of benzaldehyde and acetaldehyde is the main ingredient in cassia oil. It is used in soap perfumes and as an intermediate in the production of other flavor and fragrance compounds. 

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