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| Names | |
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| IUPAC name 3-phenylprop-2-enyl acetate | |
| Other names | |
| Identifiers | |
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3D model (JSmol) | |
| ChEBI | |
| ChemSpider |
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| ECHA InfoCard | 100.002.838 |
| EC Number |
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| KEGG |
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| RTECS number |
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| UNII | |
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| Properties | |
| C11H12O2 | |
| Molar mass | 176.215 g·mol−1 |
| Appearance | Colorless liquid |
| Odor | Sweet, floral, balsamic odor[3] |
| Density | 1.057 g/mL[4] |
| Boiling point | 265 °C (509 °F; 538 K)[3] |
| 212.3 mg/L[1] | |
| logP | 2.85[5][6] |
| Vapor pressure | 0.008 mm Hg (20°C)[1] |
Refractive index (nD) | 1.539 - 1.543[3] |
| Hazards | |
| Occupational safety and health (OHS/OSH): | |
Main hazards | Causes eye irritation, may cause an allergic skin reaction[7] |
| GHS labelling: | |
 [7] | |
| Warning[7] | |
| H317,H319[7] | |
| P261,P264,P272,P280,P302+P352,P305+P351+P338,P321,P333+P313,P337+P313,P363,P501[7] | |
| NFPA 704 (fire diamond) | |
| Flash point | 103–113 °C (217–235 °F; 376–386 K)[3][8] |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
Cinnamyl acetate (3-phenylprop-2-enyl acetate) is a chemical compound of the cinnamyl ester family, in which the variable R group is substituted by amethyl group. As a result of the non-aromatic carbon-carbon double bond, cinnamyl acetate can exist in aZ and anE configuration:[9]
Cinnamyl acetate naturally occurs in fresh bark ofcinnamon (Cinnamomum zeylanicum Blume and other Cinnamomum species), with concentrations of 2,800–51,000 ppm.[10][5]
Cinnamyl acetate is used as a flavour ester in for example bread and animal feed and has a sweet floral-fruity fragrance.[6][11][12] Moreover, it is used in several cosmetics, some toiletries but also in non-cosmetic products, for example detergents.[9]
Cinnamyl acetate, used in fragrances and as flavour ingredient, has been discussed by several institutions. In 1965, the compound was annotated as 'Generally Recognized as Safe as a flavor ingredient’ by the Flavor and Extract Manufacturers" Association (FEMA). The association determined the average maximum use levels in several products that were considered to be safe:[13]
| Beverages | Ice cream, ices, etc. | Candy | Baked goods | Chewing gum |
|---|---|---|---|---|
| 2.7 ppm | 6.5 ppm | 16 ppm | 11 ppm | 8.7 ppm |
TheEuropean Parliament registered cinnamyl acetate as both a flavouring substance and a cosmetic compound in 1996.[14][15] The Joint (FAO/WHO) Expert Committee on Food Additives (JECFA) described in 2000 that “the substance does not present a safety concern at current levels of intake when used as a flavouring agent”.[1] In 2009, theEFSA Panel on Food Contact Materials, Enzyme, Flavourings and Processing Aids (CEF) concluded that cinnamyl acetate does not give rise to safety concerns when used as flavour ingredient in food.[6] Cinnamyl acetate is also permitted by theU.S. Food & Drug administration for use as flavouring agent in food if the minimum quantity needed for its effect is used.[16]
Estimates of the average annual production and daily intake of cinnamyl acetate as flavouring agent are reported by theWHO. According to this report, the annual volume of production in Europe is 1498 kg, and in the USA 2255 kg. The daily intake per person in Europe is estimated to be 210 μg, and in the USA 300 μg. Per kg body weight the daily intake is estimated for Europeans to be 4 μg/kg and for Americans to be 5 μg/kg.[17]
Since cinnamyl acetate is naturally occurring in plants, it can be extracted and purified to obtain the compound. However, this has a low yield and therefore the production costs are high. The use of chemical methods can offer more efficient strategies to produce cinnamyl acetate.[10]
There are multiple ways to synthesize cinnamyl acetate2. One way is the synthesis fromcinnamyl alcohol1 andvinyl acetate. This reaction is catalyzed by the enzymetriacylglycerol ester hydrolase, which is alipase that is very specific towards the ester bond. The byproduct of this reaction isacetaldehyde. The reaction equation for this reaction is:[18]
-Cinnamyl_acetate_Bio_Synthesis_C_V1.svg)
Since acetaldehyde has an unfavourable deactivating effect on the lipase used in the synthesis,ethyl acetate can be used as reactant instead of vinyl acetate. In thistransesterification reaction cinnamyl alcohol1 reacts with ethyl acetate to form cinnamyl acetate2 andethanol. This synthesis requires the lipase Novozym 435, and is performed in a solvent-free system. The reaction is as follows:[12]
-Cinnamyl_acetate_Bio_Synthesis_B_V1.svg)
Cinnamyl acetate2 can also be synthesized via a non-enzymatic reaction. An example of such a reaction is one with the use of cinnamyl bromide3 andsodium acetate as reactants. Since these compounds are immiscible substrates, solid-liquid phase transfer catalysis (PTC) can be used, using quaternary ammonium bromide as aphase transfer catalyst. This is shown in the following reaction:[19]
-Cinnamyl_acetate_PTC_Synthesis_V1.svg)
Besides these three examples, there are many more ways to synthesize cinnamyl acetate.
Theaddition reaction ofdinitrogen trioxide to cinnamyl acetate produces an intermediate in the synthesis ofchloramphenicol.[20]
Cinnamyl acetate belongs to the group of cinnamyl derivatives. In general, these cinnamyl derivatives are absorbed from the gut very quickly, after which they are metabolized and excreted as polar metabolites in the urine or feces within 24 hours.[5][21]
Within the cinnamyl derivatives, cinnamyl acetate belongs to the group of cinnamyl esters. After absorption from the gut, this group of compounds is firsthydrolyzed to cinnamyl alcohol bycarboxylesterases. Carboxylesterases are a group of enzymes. The most important enzymes within this group are the A-esterases. These are present in most body tissues, but they are prevalent in thehepatocytes. Subsequently, thecinnamyl alcohol isoxidized which leads to the formation ofcinnamaldehyde. This reaction is catalyzed by humanNAD+-dependentalcohol dehydrogenase. Now, there are two routes for the furtherbiotransformation of cinnamaldehyde. The minor route of biotransformation is theS-glutathionylation. The major route, however, is the conversion of cinnamaldehyde intocinnamic acid by the enzymealdehyde dehydrogenase. Next, the cinnamic acid is transformed intocinnamoyl CoA which is again converted to either cinnamoylglycine by N-acyl transferase or tobenzoyl CoA throughβ-oxidation, the latter being the major route. Intermediate metabolites in the β-oxidation pathway can be converted to 3-hydroxy-3-phenylpropionic acid andacetophenone, which can be excreted via the urine. However, the conversions of these intermediate metabolites are minor routes. Finally, the benzoyl CoA is conjugated withglycine under formation ofhippuric acid or it is hydrolyzed generating freebenzoic acid. This can be excreted via the urine directly or afterglucuronidation. Hippuric acid, which is the major metabolite, is also excreted via the urine.[5][21][6]
Since cinnamyl acetate is used as both a fragrance material and a food flavouring ingredient, dermal and oral exposure are considered to be the major routes of absorption. The dermal systematic exposure of cinnamyl acetate via cosmetic products is estimated to be 0.0115 mg/kg body weight/day.[5]
Several experiments using animals were conducted in the past to assess the toxicity of cinnamyl acetate. In one experiment, the oral toxicity was tested in rats. The rats received oral doses of cinnamyl acetate and theLD50 was found to be 3.3 g/kg. During the experiment, symptoms as slow respiration and coarse tremors were observed for high doses.[1] Other experiments showed LD50 values of 4.750 g/kg for oral administration in mice and guinea pigs. Also, the LD50 value forintraperitoneal administration was investigated and found to be 1.200 g/kg.[22]
Furthermore, studies on the dermal toxicity were performed. Experiments on rabbits resulted in an LD50 of more than 5.0 g/kg, but no clinical effects were observed. Moreover, the level of skin irritation in swines was tested via a48-h patch test. In this study, 0.05 g of cinnamyl acetate was applied and no irritation was observed. Another two experiments examined the skin irritation caused by 0.1 mL cinnamyl acetate on guinea pigs and rabbits via a direct application on the skin (open application). Mild to moderate irritation was observed in these experiments.[1]
ANOAEL for oral administration of 275 mg/kg body weight/day was determined from toxicological data by theEFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP).[6]
Besides these experiments on animals, some human studies were executed. A 48-h closed patch test on five healthy, male volunteers was performed using 5% cinnamyl acetate inpetrolatum. In this study, no irritation was observed. Mild irritation was observed in another 48-h patch test on fifty male volunteers using 32% cinnamyl acetate inacetone. Finally, a human study on skin sensitization was executed on 25 healthy, male volunteers. In this experiment a maximization test (48-h patch) was done using 5% cinnamyl acetate in petrolatum. Skin sensitization reactions were not observed.[1]
Moreover,standard Draize tests were used to assess the dermal toxicity in humans, guinea pigs and rabbits. This resulted in mild skin irritation for doses of 16 mg per 48 hours for humans and for doses of 100 mg per 24 hours for guinea pigs. Moderate skin irritation was observed for rabbits exposed to doses of 100 mg per 24 hours.[22]
Lastly, the potential of cinnamyl acetate to causesister chromatid exchanges was tested usingChinese Hamster Ovary Cells. This was done because it was found that another component of plant essence and cinnamyl derivative,cinnamaldehyde, increased the frequency of sister chromatid exchanges induced bymitomycin C. However, the result of this test proved that cinnamyl acetate does not cause sister chromatid exchange due to the absence of an alpha-beta unsaturatedcarbonyl group.[23]
Cinnamyl acetate is found in the leaf oils of theCinnamomum osmophloeum tree, which grows in central and northern Taiwan. It is found that these oils have antibacterial, antimildew, antitermite, antimite, antifungal and anti-inflammatory activities. Furthermore, the oils show mosquito larvicidal activity againstAedes aegypti andAedes albopictus larvae. However, cinnamyl acetate serves only a minor role in these activities.[24][25][26][27]
Moreover, cinnamyl acetate has a repellent effect onAnopheles gambiae, and is therefore useful to protect against these insects.[28]
