Octocrilen

Structural formula
Structure without complete stereochemistry
General
Non-proprietary name	Octocrilen
other names	OCTOCRYLENE ( INCI ) ( RS ) -2-cyano-3,3-diphenylacrylic acid-2-ethylhexyl ester ( IUPAC ) 2-ethylhexyl-2-cyano-3,3-diphenyl acrylate
Molecular formula	C 24 H 27 NO 2
Brief description	viscous colorless or light yellow or yellow liquid
External identifiers / databases
CAS number 6197-30-4 EC number 228-250-8 ECHA InfoCard 100.025.683 PubChem 22571 Wikidata Q424805
properties
Molar mass	361.48 g · mol -1
density	1.051 g cm −3
Melting point	−10 ° C
boiling point	218 ° C (2 hPa)
solubility	practically insoluble in water (1.3 mg / l at 20 ° C) completely soluble in propylene carbonate , dipropylene glycol and other propylene glycol monoalkyl ethers
Refractive index	1.567 (20 ° C)
safety instructions
GHS labeling of hazardous substances no GHS pictograms H and P phrases H: no H-phrases P: no P-phrases
Toxicological data	> 5000 mg kg −1 ( LD 50 ,  rat ,  oral )
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . Refractive index: Na-D line , 20 ° C

Octocrilen , also known as octocrylene , is an active ingredient that is used as a sun protection filter in cosmetics . It is a 1: 1 mixture of two isomeric chemical compounds that have structural elements of cyanoacrylates and cinnamic acid esters . The extensive π-electron system and the rigid molecular structure cause the UV- absorbing effect. Octocrilen is an oily, clear, yellow liquid that cannot be mixed with water.

Manufacturing

The Knoevenagel reaction of benzophenone ( 1 ) with 2-ethylhexylcyanoacetate ( 2 ) (from cyanoacetic acid and 2-ethylhexanol in the presence of p -toluenesulfonic acid in 92% yield) in the presence of propionic acid and ammonium acetate produced at 100 ° C within 5 to 6 hours after distillation Octocrilen ( 3 ) with yields between 79 and 94%.

Under the chosen conditions (temperature, time) there is no complete conversion of the starting materials, but the formation of undesired by-products, such as. B. 2-cyano-3,3-diphenylacrylamide and colored impurities. Because of the photosensitizing properties of benzophenone, even minor impurities thereof should be avoided in the end product.

In reverse of the reaction sequence , ethyl cyanoacetate ( ethyl cyanoacetate ) can also be reacted first with benzophenone

The Knoevenagel reaction with the addition of glacial acetic acid and gaseous ammonia requires long reaction times (> 48 hours) for high conversion (> 95%) in order to achieve industrially useful end product yields of 90%. The ethyl 2-cyano-3,3-diphenyl acrylate obtained is then transesterified in the presence of sodium carbonate with 2-ethylhexanol in 97% yield to give octocrilene .

A reaction variant using benzophenone imine is intended to avoid the problems of low reaction conversion and benzophenone contamination. Benzophenone imine (obtained from benzophenone with ammonia in the presence of titanium dioxide within 5 hours at 130 ° C. and 200 bar pressure with selectivities of up to 99% and conversions of up to 98%) is reacted with 2-ethylhexylcyanarylate at room temperature. After vacuum distillation in a thin-film evaporator , octocrilene is obtained as a pale yellow oil in 94% yield and a purity of 99.5%.

properties

Octocrilen absorbs light with an absorption maximum at 303 nm mainly in the UV -B and little in the short-wave UV-A range. The filter effect is not very strong. Octocrilen is always used in combination with other filter substances, while at the same time reducing the photostability of certain UV-A filters, such as. B. Avobenzone increased and consequently their protective effect stabilized.

If such combinations also nanoparticulate titanium dioxide contained as an inorganic UV absorber, must because of the high photoreactivity uncoated TiO ₂ nanoparticles with the formation of reactive oxygen species ( reactive oxygen species are calculated, ROS) that promote the photo-decomposition of the organic UV absorber and cancel their protective effect.

After being applied to the skin, Octocrilen suppresses possible recrystallization of dissolved UV filter substances. Octocrilen itself is photostable and low in irritation when used.

In recent years, an increase in contact allergies has been reported when using Octocrilen in sunscreen products, which appears to be mainly due to prior photosensitization in adults due to the topical use of ketoprofen preparations. Overall, primary sensitizations to octocrilene appear to be rare.

The pronounced lipophilicity of organic UV absorbers leads to a high bioaccumulation potential , and traces of octocrils have therefore been found for years in lakes and rivers, as well as in tap water. Recent studies of the effects of octocrylene at the molecular level in zebrafish (Engl. Zebrafish ) indicate "a low potential for reproductive effects".

Risk assessment

Octocrilen was included by the EU in 2012 in accordance with Regulation (EC) No. 1907/2006 (REACH) as part of substance evaluation in the Community's rolling action plan ( CoRAP ). The effects of the substance on human health and the environment are re-evaluated and, if necessary, follow-up measures are initiated. The reasons for the inclusion of Octocrilen were concerns regarding high (aggregated) tonnage and widespread use as well as the dangers arising from a possible assignment to the group of PBT / vPvB substances. The re-evaluation took place from 2012 and was carried out by France .

In the South Sea state of Palau , octocrilen has been banned in sunscreens to protect coral reefs since January 2020. The ban is based on the results of a study published in 2017 on the pollution of the underwater world at Jellyfish Lake .

Trade names

• Uvinul N 539 T, Parsol 340, Eusolex OCR

Web links

• Koninklijke DSM : Parsol 340

Individual evidence

1. ↑ Entry on OCTOCRYLENE in the CosIng database of the EU Commission, accessed on December 18, 2019.
2. ↑ ^{a b} Patent WO2008089920A1 : Process for the manufacture of substituted 2-cyano cinnamic esters. Filed January 18, 2008 , published July 31, 2008 , Applicant: DSM IP Assets BV, Inventors: J. Huang, S. Jing, R. Karge, R. Proplesch. ‌
3. ↑ Patent US5917080 : Preparation of 2-cyano-3,3-diarylacrylic esters. Registered on May 24, 1996 , published on June 29, 1999 , Applicant: BASF AG, Inventors: M. Holderbaum, K. Beck, A. Aumüller, T. Witzel, G. Voit. ‌
4. ↑ ^{a b c d e f g h i} data sheet Octocrylene at Sigma-Aldrich , accessed on May 14, 2017 ( PDF ).
5. ^ LyondellBasell: Application Data, Solubility Screen, Ultraviolet Light Absorbers .
6. ↑ Patent US5451694 : Process for preparing substituted 2-cyanocinnamic esters. Applied on April 22, 1994 , published on September 19, 1995 , applicant: Haarmann & Reimer GmbH, inventors: W. Kuhn, W. Marks, T. Thielmann, E. Dilk. ‌
7. ↑ Patent US3149148 : Process for condensation reactions. Filed January 2, 1962 , published September 15, 1964 , Applicant: General Aniline & Film Corp., Inventor: M. Kladko, MM Lee. ‌
8. ↑ Patent US5047571 : Process for the preparation of 2-cyano-3,3-diarylacrylates. Applied on April 13, 1990 , published on September 10, 1991 , applicant: BASF AG, inventor: P. Spang, P. Neumann. ‌
9. ↑ Patent US5679855 : Preparation of benzophenone imines. Applied on November 21, 1995 , published on October 21, 1997 , Applicant: BASF AG, Inventor: G. Voit, M. Holderbaum, T. Witzel, A. Aumüller. ‌
10. ↑ Patent US5917080 : Preparation of 2-cyano-3,3-diarylacrylic esters. Registered on May 24, 1996 , published on June 29, 1999 , Applicant: BASF AG, Inventors: M. Holderbaum, K. Beck, A. Aumüller, T. Witzel, G. Voit. ‌
11. ↑ NA Shaath, SPF Boosters & Photostability of Ultraviolet Filters , HAPPI, October 2007, http://www.happi.com/contents/view_features/2007-10-01/spf-boosters--photostability-of-ultraviolet-f/
12. ↑ Federal Institute for Risk Assessment (BfR): UV filter substances in sunscreens (PDF; 112 kB). BfR opinion of 6 August 2003.
13. ↑ S. Mourning: Sun protection - Sometimes appearances are deceptive. In: Pharmazeutische Zeitung, issue 22, 2006. Available online .
14. ↑ J. Kockler, M. Oelgemüller, S. Robertson, BD Glass: Influence of Titanium Dioxide Particle Size on the Photostability of the Chemical UV Filters Butyl Methoxy Dibenzoylmethane and Octocrylene in a Microemulsion . In: Cosmetics . tape 1 , 2014, p. 128-139 , doi : 10.3390 / cosmetics1020128 .
15. ^ A. Bennàssar et al .: Two cases of photocontact allergy to the new sun filter octocrylene Dermatology Online Journal 15 (12): 14.
16. ^ AC de Groot, DW Roberts: Contact and photocontact allergy to octocrylene: a review . In: Contact Dermatitis . tape 70 , no. 4 , 2014, p. 193-204 , doi : 10.1111 / cod.12205 .
17. ↑ N. Blüthgen, N. Meili, G. Chew, A. Odermatt, K. Fent: Accumulation and effects of the UV-filter octocrylene in adult and embryonic zebrafish (Danio rerio) . In: Sci. Total Environ. tape 476–477 , 2014, pp. 208–217 , doi : 10.1016 / j.scitotenv.2014.01.015 .
18. ↑ Community rolling action plan ( CoRAP ) of the European Chemicals Agency (ECHA): Octocrilene , accessed on May 20, 2019.
19. ^ The Republic of Palau Bans Sunscreen Chemicals to Protect its Coral Reefs and UNESCO World Heritage site - International Coral Reef Initiative. In: icriforum.org. November 4, 2018, accessed February 20, 2020 . 
20. ^ Coral Reef Research Foundation: Final Report - Sunscreen Pollution Analysis in Jellyfisch Lake , Palau, January 2017 ( PDF ).