2-ethylhexyl methoxycinnamate | 83834-59-7

• 物质功能分类: 香精与香料 - 合成香料 - 羧酸及酯类香料
• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: 2-ethylhexyl methoxycinnamate
• 英文别名: 2'-ethylhexyl 4-methoxycinnamate；octinoxate；octyl methoxycinnamate；2-ethylhexyl (E)-3-(4-methoxyphenyl)acrylate；ethylhexyl methoxycinnamate；2-ethylhexyl (E)-3-(4-methoxyphenyl)prop-2-enoate
• CAS: 83834-59-7
• 化学式: C₁₈H₂₆O₃
• 分子量: 290.403
• InChiKey: YBGZDTIWKVFICR-JLHYYAGUSA-N

物化性质

• 沸点：
  198-200 °C/3 mmHg(lit.)
• 密度：
  1.009
• 闪点：
  193 °C
• 溶解度：
  溶于氯仿、二氯甲烷、乙酸乙酯、DMSO、丙酮等。
• LogP：
  6 at 23℃
• 物理描述：
  2-ethylhexyl p-methoxycinnamate is a colorless to pale yellow viscous liquid. (NTP, 1992)
• 颜色/状态：
  Pale yellow liquid
• 气味：
  Practically odorless
• 熔点：
  -25°C
• 蒸汽压力：
  2.3X10-5 mm Hg at 25 °C (est)
• 稳定性/保质期：

  常温常压下稳定

• 保留指数：
  2339

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  21
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

ADMET

代谢

当系统吸收时，可以经历肝脏代谢。在角质层中，可以通过脂肪酶的酶降解，其中酯类发生水解。暴露在阳光下时会降解成光产物，这导致紫外线吸收效率降低。

Can undergo hepatic metabolism when systematically absorbed. Can be enzymatically degraded by lipases in the stratum corneum where esters undergo hydrolysis. Degrade into photoproducts when exposed to sunlight, which leads to a decrease in UV absorption efficiency.

来源:DrugBank

代谢

作为亲脂性物质，活性成分很可能被代谢；在任何情况下，它至少被认为是被血浆酯酶水解的，尽管速度很慢。

As a lipophilic substance, the a.i. is very likely to be metabolized; it is known in any case to be hydrolyzed by plasma esterases, although slowly.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 副作用

Dermatotoxin - PACD (photoallergic contact dermatitis). 皮肤毒素 - 光变态性接触性皮炎。

Dermatotoxin - PACD (photoallergic contact dermatitis).

来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases

毒理性

• 相互作用

农业工作者被鼓励使用防晒霜以降低紫外线相关皮肤癌的风险。... 以前的研究已经表明某些商业防晒霜能够增强渗透。这个项目的重点是确定防晒霜配方中的活性成分（即UV吸收成分和防晒/驱虫组合的驱虫剂）是否也作为除草剂的经皮渗透增强剂。在没有防晒霜对照组的24小时内，2,4-二氯苯氧乙酸（2,4-D）通过无毛小鼠皮肤的渗透百分比从54.9 ± 4.7变化到padimate-O的86.9 ± 2.5。在测试的活性成分中（7.5%的甲氧基肉桂酸辛酯，7%的奥克立林，0.6%的对苯二酚，5%的水杨酸辛酯，5%的辛酸酯，8%的padimate-O，10%的磺酸酯，9.5%和19%的N,N-二乙基-m-甲苯酰胺（DEET）），除了奥克立林之外，所有成分与对照组相比都显著增加了2,4-D的总渗透（P < 0.05），只有奥克立林和对苯二酚没有显著减少相应的时间延迟。水杨酸辛酯（P < 0.01）和甲氧基肉桂酸辛酯（P < 0.05）显著增加了3H2O通过小鼠皮肤的渗透，表明角质层的物理损伤。进一步的研究表明，无毛小鼠皮肤上观察到的渗透增强也发生在人类皮肤上。因此，防晒霜配方中的活性成分增强了中等亲脂性除草剂2,4-D的经皮渗透。

Agricultural workers are encouraged to use sunscreen to decrease the risk of UV-related skin cancer. ... Previous studies have shown certain commercial sunscreens to be penetration enhancers. The focus of this project is to determine whether active ingredients in sunscreen formulations (i.e., the UV absorbing components and insect repellants for the sunscreen/bug repellant combinations) also act as dermal penetration enhancers for herbicides in vitro. The total percentages of 2,4-dichlorophenoxyacetic acid (2,4-D) penetrating through hairless mouse skin in 24 hr ranged from 54.9 +/- 4.7 for the no sunscreen control to 86.9 +/- 2.5 for padimate-O. Of the active ingredients tested (7.5% octyl methoxycinnamate, 7% octocrylene, 0.6% oxybenzone, 5% homosalate, 5% octyl salicylate, 8% padimate-o, 10% sulisobenzone, and 9.5% and 19% N,N-diethyl-m-toluamide (DEET)), all but octocrylene led to a significant increase in total 2,4-D penetration as compared to the control (P < 0.05), and only octocrylene and oxybenzone did not significantly decrease the corresponding lag time. Octyl salicylate (P < 0.01) and octyl methoxycinnimate (P < 0.05) significantly increased the 3H2O penetration across mouse skin, indicating physical damage to the stratum corneum. Additional studies demonstrated that the penetration enhancement seen across hairless mouse skin also occurred with human skin. Thus, the active ingredients of sunscreen formulations enhance dermal penetration of the moderately lipophilic herbicide 2,4-D.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

作者们试图确定在使用含有辛基甲氧基肉桂酸酯、氧苯酮和辛基水杨酸盐的SPF 29防晒霜后，是否可以预防局部紫外线B（UVB）诱导的二硝基氯苯（DNCB）接触过敏反应的抑制。十九名受试者连续三天每天接受三剂最小红斑剂量的UVB照射（UVB组），或者先涂抹防晒霜然后接受相同剂量的UVB照射（防晒霜加UVB组），照射面积为16平方厘米的臀部。照射完成后的一天，将DNCB应用于这个臀部位置，两周后，在前臂进行四种不同浓度DNCB的挑战测试。一个由10名受试者组成的对照组按照上述方式进行了DNCB测试，但没有预先暴露于UVB（无UVB组）... UVB组对所有挑战剂量的DNCB（3.125、6.25和8.8微克）的反应率降低，除了最高剂量（12.5微克）与无UVB对照组相比（费舍尔精确检验，P <或= 0.008），并且与防晒霜加UVB组相比（P <或= 0.02）。无UVB组和防晒霜加UVB组在测试的任何DNCB剂量上的反应率没有显著差异（P >或= 0.53）... 这些结果表明，在使用比预防红斑所需保护高出九倍的防晒霜后，局部UVB辐射不会导致局部UVB诱导的接触过敏反应抑制...

/The authors/sought to determine whether the effect of preapplication of a sun protection factor (SPF) 29 sunscreen (containing octyl methoxycinnamate, oxybenzone, and octyl salicylate) could prevent local UVB-induced suppression of contact hypersensitivity to dinitrochlorobenzene (DNCB). Nineteen subjects received either three minimal erythema doses of UVB daily on three consecutive days (UVB group) or sunscreen followed by this same dose of UVB irradiation (sunscreen plus UVB group) to a 16-sq cm area of the buttock. One day after completion of irradiation, DNCB was applied to this buttock site, and 2 weeks later, forearm challenge with four different concentrations of DNCB was performed. A control group of 10 subjects underwent DNCB testing as above, but with no prior exposure to UVB (no-UVB group). ... The UVB group had a reduced response rate to all challenge doses of DNCB (3.125, 6.25, and 8.8 ug), except for the highest dose (12.5 ug) compared with the no-UVB control group (Fisher's Exact test, P < or = 0.008), and compared with the sunscreen plus UVB group (P < or = 0.02). The no-UVB and sunscreen plus UVB groups showed no significant differences in response rates to any of the doses of DNCB tested (P > or = 0.53). ... These results indicate that application of a sunscreen with over ninefold greater protection than that needed to prevent erythema prior to localized UVB radiation prevents localized UVB-induced suppression of contact hypersensitivity...

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

糖酯和蔗糖油酸酯对辛甲氧肉桂酸（OMC）在i）胶体悬浮液（纳米乳液和纳米胶囊）和ii）传统的水包油乳液中的体内经皮渗透的影响进行了评估。结果显示，与其它配方相比，由糖酯配制的纳米乳液在角质层的渗透性最高。与对照相比，含有糖酯的纳米乳液使OMC的皮肤沉积量增加了两倍。获得的数据表明，角质层中检测到的OMC总量和渗透深度强烈依赖于配方的性质、粒子大小和增强剂的类型。

The influence of sucrose laureate and sucrose oleate on the in vivo percutaneous penetration of octyl methoxycinnamate (OMC) formulated in i) colloidal suspensions (nano-emulsions and nanocapsules), and ii) conventional o/w emulsions was evaluated. The results showed that nano-emulsions formulated with sucrose laureate exhibited the highest penetration in the stratum corneum compared to the other formulations. A two-fold increase in OMC skin deposition was observed with the nano-emulsion containing sucrose laureate when compared to the control. The data obtained suggest that the total amount of OMC detected in the stratum corneum and the penetration depth are strongly dependent upon the formulation's nature, the particle size, and the type of enhancer.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

无毛小鼠暴露于模拟太阳能量光谱的紫外线重复剂量下。在休息期之后，每周三次将12-O-四癸酰佛波-13-醋酸酯（TPA）应用到皮肤区域……使用了适当的对照。测试组通过含50%活性成分的产品得到了完全保护，而含7.5%活性成分的产品产生了一种效果，相当于将日照量减少了四倍。有人建议活性成分本身可能是一种促进剂，但没有证据支持这一点。

Hairless mice were exposed to repeated doses of UV simulating the solar energy spectrum. After a rest period, 3 applications a week were made to an area of skin of 12-o-tetradecanoyl phorbol-13-acetate ... Suitable controls were used. The test group was completely protected by 50 % a.i., and 7.5 % gave an effect equivalent to reducing the insolation four-fold. It had been suggested that the a.i. could itself have been a promoter, but there was no evidence of this.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

• 吸收

涂抹在皮肤上后可以系统吸收，在角质层较深的层面以及尿液中、血浆中和母乳中均有发现。应用2mg/cm2防晒霜后检测到的平均最大血浆浓度为女性7ng/mL，男性16ng/mL。

Can be systemically absorbed after skin application, being found in the deeper layers of the stratum corneum as well as urine, plasma, and breast milk. The mean maximum plasma concentration detected after application of 2mg/cm2 sunscreen was 7ng/mL in women and 16ng/mL in men.

来源:DrugBank

吸收、分配和排泄

• 消除途径

可以在尿液中以未改变的形式检测到。

Can be detected in urine in unchanged form.

来源:DrugBank

吸收、分配和排泄

裸鼠皮肤。这项研究是在一个实验室内进行的。大部分物质存在于剥落的皮肤中；在角质层中较少，而在实验室内最少。实验室内的大致含量为：6小时后1.13%，16小时后11.4%，24小时后17.9%。角质层和剥落物的数据分别为31.4%、44.4%和45.7%（应用剂量的百分比）。3%和20%的活性成分溶液给出了相似的结果。

Naked rat skin. This was studied in a chamber experiment. Most of the material was found in the stripped skin; there was less in the stratum corneum, and least in the chamber. The approximate amounts found in the chamber were: after 6 hrs, 1.13 %; after 16 hrs, 11.4 %; and at 24 hrs 17,9 %. The figures for the horny layer and the strippings combined were, respectively, 31.4 %, 44.4 % and 45.7 % (percentages of applied doses). Solutions of 3% and 20 % of a.i. gave similar results.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

八名健康志愿者在肩胛间区涂抹了少量放射性活性物质。其中一组4人在手表玻璃下涂抹；另外4人将其涂抹在纱布上，其中一例有封闭。除了尿液中大约0.2%的吸收外，对活性物质的吸收测试均为阴性。所使用的浓度未予说明。

Eight healthy volunteers had small amounts of radioactive a.i. applied to the interscapular region. One group of 4 had the material applied under a watch glass; the other 4 had it applied on gauze, with occlusion in one case. Tests for absorption of a.i. were negative except for about 0.2 % in urine. The concentrations used were not stated.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在初步实验中，口服含有100毫克活性成分的胶囊。通过气相色谱/质谱法（GC/MS）研究了尿液在24小时内对甲基酯衍生物的累积排泄量，从而得知4-甲氧基肉桂酸的含量。（这种方法也能检测到4-羟基肉桂酸）。在24小时内，回收了摄入量的13.2%，相当于如果活性成分完全吸收，预期回收量的21.5%。在实验的主要部分，使用了一种含有10%活性成分的O/W乳膏。将2克这种物质（= 200毫克活性成分）涂抹在5名年龄在29至46岁之间的男性受试者的肩胛间区域。覆盖的皮肤面积为25x30厘米。涂抹后，该区域被3层纱布覆盖，保持12小时。在0、0.5、1、2、3、5、7和24小时时采集血液。在0、1、2、3、4、5、6、7、12、24、48、72和96小时时收集尿液。对照组的血浆样本在未涂抹任何物质前，水平相当于大约10纳克/毫升。实验期间没有发现血浆水平有任何上升的迹象。尿液显示“生理”水平为100至300纳克/毫升。在任何样本中都没有发现这种量的显著增加。作者得出结论，在实验条件下，几乎没有任何化合物被吸收。

In a preliminary experiment, a capsule containing 100 mg of a.i. was taken orally. ... The cumulative excretion of 4methoxycinnamate in the urine over 24 hours was studied by GC/MS of the methyl ester derivative. (This method would also detect 4-hydroxycinnamic acid). Over 24 hours, 13.2 % of the amount ingested was recovered, equivalent to 21.5 % of the amount that would be expected if the a.i. were completely absorbed. In the main part of the experiment, an o/w cream containing 10 % a.i. was used. Applications of 2 grams of this material (= 200 mg a.i.) were made to the interscapular area of each of 5 male subjects, aged 29 to 46. The area of skin covered was 25x30 cm. After application, the area was covered with 3 layers of gauze, left in place for 12 hours. Blood was taken at times 0, 0.5, 1, 2, 3, 5, 7, and 24 hours. Urine was collected at 0, 1, 2, 3, 4, 5, 6, 7, 12, 24, 48, 72 and 96 hours. The control plasma samples showed a level equivalent to about 10 ng/ml before any application had been made. There was no evidence of any rise in plasma levels during the experiment. The urine showed a "physiological" level of 100 to 300 ng/ml. No significant increase in this amount was found in any sample. The authors conclude that very little, if any, of the compound was absorbed under the conditions of the experiment.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S24/25,S26,S36
• 危险类别码：
  R36/37/38
• WGK Germany：
  3
• 海关编码：
  29189090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  请将贮藏器密封，并将其存放在阴凉、干燥处。确保工作环境具备良好的通风或排气设施。

制备方法与用途

防晒剂——对甲氧基肉桂酸异辛酯属于油溶性UV-B吸收剂，是一种无色或浅黄色液体，具有轻微的特征性气味。目前，它是最常用的防晒剂之一。对甲氧基肉桂酸异辛酯具有极好的紫外光280~310nm吸收曲线，并且吸收率高、安全性良好、毒性极小，同时还具备良好的油溶性。因此，广泛应用于日用化工、塑料、橡胶和涂料等领域，也可作为油溶性液体UV-B吸收剂与其他防晒剂复配。

对甲氧基肉桂酸异辛酯可用于配制防晒霜（膏、乳、液）等护肤化妆品，能有效防止阳光中的紫外线导致的皮肤晒红、晒伤、晒黑。此外，它也是光感皮炎治疗药物之一。在工业上，对甲氧基肉桂酸异辛酯还可以用作塑料和油墨的抗老剂及紫外线吸收剂。

反应信息

• 作为反应物：
  描述：

  2-ethylhexyl methoxycinnamate 在 aluminum oxide 、 重铬酸吡啶 、 二异丁基氢化铝 作用下， 以 正己烷 、 二氯甲烷 为溶剂， 反应 26.0h， 生成 4-甲氧基肉桂醛
  参考文献：
  名称：

  脯氨酸催化邻喹二甲烷的不对称Diels-Alder反应

  摘要：

  在l-脯氨酸存在下，具有高非对映选择性和对映选择性的α-氨基-邻-喹二甲烷与α，β-不饱和醛的催化不对称Diels-Alder反应，该促进剂起促进剂的作用，从相应的前体生成喹二甲烷以及对映选择性Diels-Alder反应的手性催化剂。

  DOI：

  10.1016/j.tetlet.2014.05.107
• 作为产物：
  描述：

  4-烯丙基苯甲醚 在 Hoveyda-Grubbs catalyst second generation 、 [CpRu(PN)(MeCN)]PF₆ 作用下， 以 甲苯 为溶剂， 反应 6.5h， 生成