| As an effective ingredient of sunscreen cosmetics,ultraviolet absorbents occupies a very important position in the field of traditional sunscreen because of its high efficiency,stability and excellent safety.Among them,triazines and benzotriazoles ultraviolet absorbers involve many kinds of sunscreen products and have a high market share,but there are still some problems in the synthesis of related compounds,such as insufficient production capacity,high consumption and low efficiency and low purity of the final products.Therefore,in this study,three representative triazine ultraviolet absorbers bis-ethylhexoxyphenol methoxyphenyl triazine(UV-627),diethylhexyl butamido triazinone(HEB),ethylhexy triazone(UV T-150)and a representative benzotriazole ultraviolet absorber methylene bis-benzotriazolyl tetramethyl butylphenol(UV-360)were synthesized.The reaction conditions and final product purification conditions were screened and optimized in order to obtain the synthesis process of ultraviolet absorbers to meet the market demand.At the same time,the synthesis process was enlarged to better adapt to industrial production.Among them,the magnification scale of UV-360 has reached the kilogram level.In addition,this study selected benzotriazole UV sunscreen octrizole(UV-329)as the lead compound for the design and synthesis of new UV absorbers,and analyzed and compared the UV absorption spectra of the new compounds,in order to provide basic theoretical reference for the follow-up research and development of new efficient UV absorbers through the study of structure-activity relationship of related types of UV absorbers.In the part of synthesis process research.In this study,the synthetic processes of UV-627,HEB,UVT-150 and UV-360 were designed and constructed.The reaction conditions such as time,temperature,catalyst and the refining conditions of the target compound were screened and optimized.The pilot scale-up processes of the compounds were studied on the basis of small-scale test.Among them,the UV T-150 is magnified at the hundred grams level and the UV-360 is magnified at the kilogram level.The specific results of the study are as follows.(1)The synthetic route of UV-627 was constructed by a three-step reaction of Grignard coupling,Friedel-Crafts alkylation and Etherification.The Grignard reaction maintained a yield of 67.20% on a scale of ten grams.Grignard reagent was added at 5℃,the amount of solvent was less than 30 m L,and the reaction time was reduced to 3 h,which greatly increased the safety and controllability of the reaction.The Friedel-Crafts alkylation reaction maintained a yield of 87.72% at the scale of five grams.Anhydrous aluminum chloride with high catalytic activity and lower economic cost was prefeered as the catalyst,and the strategy of batch addition of the catalyst 15 min interval was adopted to reduce the production cost on the premise that a stable yield was guaranteed.60℃was selected as the reaction temperature and the reaction time was reduced to 5 h,which ensured the stable yield and reduced the energy consumption.The yield of the Etherification was 85.00% at the gram scale.The refining conditions of the final product were optimized,and the content of the product was increased from 89.90 % to more than 99.60 %,which provided the possibility for safe and reliable industrial production of high purity bis-ethylhexoxyphenol methoxyphenyl triazine.(2)The synthetic route of HEB was constructed by amidation,reduction,esterification and aromatic nucleophilic substitution.The yield of amidation reaction was more than 85.00% in gram scale.The refining scheme of petroleum ether beating and ethanol recrystallization is adopted,and the amidation products can be directly used in the next reaction,which greatly improves the synthesis efficiency.The yield of nitro reduction reaction can be more than 82.00% when the scale of nitro reduction was less than 10 g.The iron powder / ammonium chloride catalytic system was used,which greatly improved the universal applicability and safety of the reaction.The purification scheme of recrystallization of petroleum ether was adopted to improve the purity of the reduction product.The aromatic nucleophilic substitution reaction selected 120℃ as the reaction temperature and 5 h as the reaction time,which reduced the energy consumption on the basis of ensuring 90.48% yield,which made it possible for the industrial production of diethylhexyl butamido triazinone with high efficiency and low consumption.(3)The synthetic route of UV T-150 was constructed by esterification,reduction and nucleophilic substitution.The esterification reaction can keep the yield of about 95.00% at the scale of five grams.The esterification product can be directly applied to the next reaction and the synthesis efficiency was improved.The nucleophilic substitution reaction adopted the stage heating strategy of interval 30 min,which ensured that the yield was more than 89.30%.The pilot-scale scale-up study on the synthesis process was carried out on the basis of the small-scale test,the esterification reaction and nucleophilic reaction were both magnified more than 50 times,and the feed quantity reached 100 grams scale.The yield of esterification reaction could be maintained at about 83.20%,while the yield of nucleophilic substitution reaction can be kept at about 88.10%.By used the post-treatment scheme of decolorization of activated carbon and recrystallization of ethanol,the content of the product can be increased to more than 99.00%.The synthesis route has the advantages of few steps,high safety and economic benefits.The pilot scale experiment from gram to hundred grams has been completed,which provides the possibility for large-scale industrial production of ethylhexy triazone.(4)The synthetic route of UV-360 was constructed by diazo coupling reaction,reduction cyclization reaction and methylene splicing.The diazo coupling reaction could reach a yield of 66.20% on the gram scale.The reduction reaction can reach a yield of 96.70% on the gram scale.The reduction reaction was carried out in the zinc powder/ethyl acetate/water system,which greatly reduced the economic cost of the reaction and improved the universal applicability and safety of the reaction method.The post-treatment of methylene splicing link adopts the refining scheme of methanol slurry and isopropanol single solvent recrystallization,which was able to increase the content of the target product to more than 99.10%.The scale-up experiment from gram scale to two kilogram scale has been completed,and the yield of the compound could be kept above 72.00%.In the experimental process,the solvent was recycled,which reduced the industrial synthesis cost as much as possible on the basis of meeting the purpose of process synthesis,and reduced the impact of waste liquid on the environment.The synthesis process is economical,efficient,safe and environmentally friendly,and can meet the requirements of large-scale industrial production of target compounds.In the part of the study of structure-activity relationship.In this study,8 ester derivatives and 7 amide derivatives were synthesized by esterification and amidation with acyl chloride,a total of 15 new UV absorbers were synthesized.The UV-visible light absorption properties of the new compounds were measured,and the relationship between their structure and UV absorption properties was studied and analyzed.The results show that both hydroxyl position esterification derivation and hydroxyl ortho-amidation derivation can lead to the blue shift of ultraviolet absorption and decrease the absorption intensity.The structure-activity relationship analysis showed that the acyl substituents introduced in the experiment reduce the electron cloud density in the core structure of the compound,and restrict the formation of six-membered chelating rings,resulting in the limitation of the mutual change of phenols and ketones,and then the intensity of n-π conjugation is reduced,then the π-π * transition is mainly carried out after the electron absorbs energy.In addition,the effects of the types of substituents on the UV absorption properties of the compounds are different.With the increase of substituent carbon chain and branched chain,the UV absorption intensity of the compound decreases gradually.The light absorption intensity of aryl substituted derivatives is lower than that of alkyl substituted derivatives.Compared with ester derivatives,the UV absorption wavelength range of amide derivatives is larger,and the blue shift of these derivatives is smaller,and the characteristic absorption peak wavelength is in the range of 300-350 nm wavelength.To sum up,the synthesis processes of four representative ultraviolet absorbents were studied in this paper.Through the screening and optimization of reaction conditions,four efficient and stable synthetic processes of ultraviolet absorbers were determined.In addition,the synthesis process was enlarged and studied,and the synthesis process of ultraviolet absorber which met the requirements of industrial production was obtained.In addition,a total of 15 new ultraviolet absorbers in two series were designed and synthesized.Through the performance test,analysis and comparison of the synthesized new UV absorbers,the structure-activity relationship of the corresponding types of UV absorbers was verified to a certain extent,which can provide basic theoretical reference for the follow-up research and development of new high-efficiency UV absorbers. |
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