Methyl salicylate synthetic

Methyl salicylate is produced synthetically for commercial purposes by the esterification of salicylic acid with methanol or by extraction by steam distillation of wintergreen leaves or sweet birch bark. The source, natural or synthetic, is declared on the label. The methyl salicylate NF must assay not less than 98.0% and not more than 100.5% and be processed by Good Manufacturing Practice described in USP (20). 

Coum rinic Acid Compounds. These synthetic phyUoquinone derivatives and congeners have been employed as anticoagulants since the isolation of 3,3 -methylenebis(4-hydroxy-2H-l-benzopyran-2-one) [66-76-2] (bis-4-hydroxycoumarin or dicoumarol) (1) from spoiled sweet clover in 1939. The ingestion of the latter was responsible for widespread and extensive death of bovine animals at that time. The parent compound for the synthesis of many congeners is 4-hydrocoumarin, which is synthesized from methyl salicylate by acetylation and internal cyclization. The basic stmctures of these compounds are shown in Figure 2, and their properties Hsted in Table 6 (see Coumarin). 

Hydroxycoumarin [1076-38-6] can be synthesized by cyclization of acetyl methyl salicylate. It is a coumatin metaboHte occurring in spoiled hay. Derivatives of 4-hydroxycoumarin such as dicoumarol [66-76-2] warfarin [81-81-2] cyclocoumarol [518-20-7] ethylbis—coumaracetate [548-00-5] and bis-4-hydroxycoumarin [25892-93-7] are synthetic blood anticoagulants (see Blood, coagulants and anticoagulants). 

Hydroxybenzoic acid is obtained as white crystals, fine needles, or fluffy white crystalline powder. It is stable in air and may discolor gradually in sunlight. The synthetic form is white and odorless. When prepared from natural methyl salicylate, it may have a light yellow or pink tint and a faint, wintergreen-like odor. w-Hydroxybenzoic acid crystallizes from water in the form of white needles and from alcohol as platelets or rhombic prisms. -Hydroxybenzoic acid crystallizes in the form of monoclinic prisms. Various physical properties of hydroxybenzoic acids are listed in Tables 1—4. 

Early Synthesis. Reported by Kolbe in 1859, the synthetic route for preparing the acid was by treating phenol with carbon dioxide in the presence of metallic sodium (6). During this early period, the only practical route for large quantities of salicylic acid was the saponification of methyl salicylate obtained from the leaves of wintergreen or the bark of sweet birch. The first suitable commercial synthetic process was introduced by Kolbe 15 years later in 1874 and is the route most commonly used in the 1990s. In this process, dry sodium phenate reacts with carbon dioxide under pressure at elevated (180—200°C) temperature (7). There were limitations, however not only was the reaction reversible, but the best possible yield of salicylic acid was 50%. An improvement by Schmitt was the control of temperature, and the separation of the reaction into two parts. At lower (120—140°C) temperatures and under pressures of 500—700 kPa (5—7 atm), the absorption of carbon dioxide forms the intermediate phenyl carbonate almost quantitatively (8,9). The sodium phenyl carbonate rearranges predominately to the 07 0-isomer, sodium salicylate (eq. 8). 

Methyl 2-hydroxybenzoate (methyl salicylate, oil of wintergreen) occurs in many plants, but it also is readily prepared synthetically by esterification of... 

Essential oils are obtained from fruits and dowers (61,62). Volatile esters of short- and medium-chain carboxylic acids or aromatic carboxylic acids with short- and medium-chain alcohols are primary constituents of essential oils, eg, ethyl acetate in wines, brandy, and in fruits such as pineapple benzyl acetate in jasmine and gardenia methyl salicylate in oils of wintergreen and sweet birch. Most of these naturally occurring esters in essential oils have pleasant odors, and either they or their synthetic counterparts are used in the confectionery, beverage, perfume, cosmetic, and soap industries (see Oils,... 

Wintergreen Gaultheria procumbens (Ericacae) or Betula lenta (Betulaceae) leaves bark 0.7-1.5 0.2-0.6 methyl salicylate (98%) flavour, antiseptic, antirheumatic prior to distillation, plant material is macerated with water to allow enzymic hydrolysis of glycosides methyl salicylate is now produced synthetically... 

Methylis Salicylas, Methyl Salicylate, is an ester, produced synthetically, and is the principal constituent of Oil of Gaultheria and Oil of Betula. It is soluble in all proportions in alcohol or glacial acetic acid. 

Oxidative cyclization of unsaturated /3-dicarbonyl compounds with two a-hydro-gen atoms will give products that still have one a-hydrogen and can be oxidized further. If the product is oxidized at a rate competitive with that of the starting material, mixtures of products will be obtained. For instance, oxidative cyclization of 26 affords 36 % of 27 and 10 % of dienone 28 formed by further oxidation of 27, as shown in Scheme 6 [7]. The product is occasionally oxidized much more readily than the starting material so that none of the initial product is isolated. These reactions may still be synthetically useful if the products of further oxidation are monomeric. For example, oxidative cyclization of methyl 3-oxo-6-heptenoate provides 78% of methyl salicylate [29]. The overall reaction consumes 4equiv. Mn(OAc)3. Competitive oxidation of the product is not usually a problem in inter-molecular addition reactions, because a vast excess of the oxidizable substrate, for example acetone or acetic acid, is usually used as solvent. Use of excess substrate is not possible in oxidative cyclizations. 

The onset of the industrial production of essential oils can be dated back to the first half of the 19 century. After the importance of single aroma chemicals was recognised in the middle of the century, efforts were started to isolate such compounds from corresponding natural resources for the first time. This was soon followed by the synthesis of aroma chemicals. In this context, the most important pioneers of synthetic aroma chemicals have to be mentioned, such as methyl salicylate [1843], cinnamon aldehyde [1856], benzyl aldehyde [1863] and vanillin [1872], as they constitute the precursors of a rapidly growing number of synthetically produced (nature-identical) aroma chemicals in the ensuing years. 

In some cases, the product is oxidized much more readily than the starting material so that none of the initial product is isolated. These reactions may still be synthetically useful if the products of further oxidation are monomeric. For instance, oxidative cyclization of 31 provides 78% of methyl salicylate (34) (Scheme 9) [24-... 

Methyl-1-propanethiol Methyl propionate 3-Methyl-5-propyl-2-cyclohexen-1 -one Methyl propyl ketone 2-Methylpyrazine flavoring agent, synthetic food Methyl salicylate Methyl sorbate 5-Methyl-2-thiophenecarboxyaldehyde 3-Methylthiopropionaldehyde 2-Methyl-3-tolylpropionaldehyde, mixed o-, m-, p-Methyl 9-undecenoate Methyl 2-undecynoate Methyl valerate MSG Musk ambrette Myrcene Myristaldehyde Myristyl alcohol Myrtenol 2-Naphthalenethiol P-Naphthyl ethyl ether P-Naphthyl isobutyl ether d-Neomenthol Nerol Neryl acetate Neryl butyrate Neryl formate Neryl isobutyrate Neryl isovalerate Neryl propionate... 

The taste of a toothpaste is critical for the consumer. Apart from very specific exceptions, such as flavors for children, the range of flavors is very limited. Eighty percent of tastes are based on mint, peppermint, or a mixture of the two. Most of the remainder is methyl salicylate from the gaultheria plant. In some countries, there are variations from these norms for example fruity notes in Japan, aniseed in the Mediterranean, and spicy notes in South America. Flavors must be pleasant and associated with a clean feeling. This is the reason mint/peppermint oils together with menthol account for 60-80% of flavor bases for toothpastes. The flavor sources are either natural or synthetic. 

Methyl salicylate is derived from oil of wintergreen—Gaultheria procumbens (Ericaceae). It is an aromatic ester derived from salicylic acid and methanol, though it can now be produced synthetically. Methyl salicylate is mainly used in topical applications and liniments as a counter-irritant and antirheumatic. Internal administration is not recommended since it is quite toxic in large doses. 

Both of these oils have a specific gravity ranging usually from 1 180 to 1187 at 15 C. Both of them, as well as the synthetic methyl salicylate, form a perfectly clear solution with five (5) times their volume of 70 per cent, alcohol at about 20 C., which, in connection with other distinctive characters, is an excellent practical test for their purity. 

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