Synthesis of new potential UV-ﬁlters

Three new silylated 2-(2’-hydroxyphenyl)benzotriazole derivatives were prepared. Starting with the easily available simple 2-(2’-hydroxyphenyl)benzotriazole, the target compounds were synthesized by a stepwise synthetic protocol, namely alkylation, thermal rearrangement and silylation.


Introduction
As a result of the thinning of the protective ozone layer, the exposure to ultraviolet light (UV) is increasing worldwide. UV light, which is approximately 90% of this radiation, can pass through window glass, penetrates into the dermis, and may cause tanning, wrinkling, and skin cancer. Malignant melanoma is the most harmful of all skin cancers. It has been increasing faster than any other cancer and regarding the number of cases it has more than doubled in the last 5 years. Therefore, protection against the UV light has been growing and is of crucial significance [1]- [7].
A number of molecules are employed as UV light protecting agents. Among them compounds having intramolecular H-bond are strong UV absorbers and show proper photostability. 2-(2'-Hydroxyphenyl)benzotriazole derivatives (e.g. Mexoryl XL) are widely used as UV stabilizers. In these molecules the photoinduced excited state returns to the ground state by a proton transfer and rapid non-radiative dissipation of the harmful UV energy (S 1 →S ' 1 →S ' 0 →S 0 ) [8]- [13]. Recently, we have described papers about the synthesis of new silylated hydroxyphenyl-benzotriazole derivatives. Some of them had excellent UVA-filter activity and high photostability [14]. Following this research, we have prepared three new hydroxyphenyl-benzotriazole derivatives with substituents on the benzotriazole moiety and/or on the phenyl group. The synthesis followed is shown in the Fig. 1.

Results and discussion
Earlier we had elaborated a new and economical method for the synthesis of 2-(2'-hydroxyphenyl)benzotriazole derivatives ( Fig. 1) and here we used its potential for the preparation of these starting materials [15,16]. Compound 1a was then treated with 2-(chloromethyl)prop-1-ene in the presence of KI and K 2 CO 3 to afford ether 2a, in good yield. The 1 H and 13 C NMR spectra of 2a showed the typical pattern of a benzo[d] [1,2,3]triazole skeleton where two pairs of orthocoupled aromatic protons at (δ 7.42 and δ 7.96 ) were assignable to C 4 -H and C 5 -H, (or C 6 -H and C 7 -H), respectively. Furthermore, the 1 H NMR spectrum revealed the presence of a 2-

Results and discussion
Earlier we had elaborated a new and economical method for the synthesis of 2-(2'-hydroxyphenyl)benzotriazole derivatives (1, Scheme 1) and here we used its potential for the preparation of these starting materials [15,16]. Compound 1a was then treated with 2-(chloromethyl)prop-1-ene in the presence of KI and K 2 CO 3 to afford ether 2a, in good yield. The 1 H and 13 C NMR spectra of 2a showed the typical pattern of a benzo[d] [1,2,3]triazole skeleton where two pair of ortho-coupled aromatic protons at (δ 7.42 and δ 7.96 ) assignable to C 4 -H and C 5 -H, (or C 6 -H and C 7 -H), respectively. Furthermore, the 1 H NMR spectrum revealed the presence of a 2-methyl-2-propenyloxy group (δ 4.47, δ 4.86 , and δ 4.95 ), and a cyclohexylphenyl moiety. Thermal rearrangement of compounds 2a in boiling N,N-diethylbenzeneamine afforded the wanted intermediate 3a, in excellent yield. In the 1 H spectrum the signal at (δ 11.42 , OH) together with the other part of spectra justified the structure of 3a. This compound was then silylated with heptamethyltrisiloxane in the presence of Karlstedt catalyst [17] to furnish the target compounds 4a, in good yield. The structure of compound 4a was also justified by its spectra. For instance, both 1 H and 13 C NMR spectra showed the characteristic signals of the benzotriazole and cyclohexylphenyl skeleton, the hydroxyl group (δ 11.34 ), and the heptamethyl-disiloxanyl moiety [δ 0.08 (Si-CH 3 ) and δ 0,11 (18 H, 6 CH 3 )].
The reaction of the chloro compound 1b with 2-(chloromethyl)prop-1-ene gave the ether 2b, which was thermally rearranged . The product 3b was then silylated with heptamethyltrisiloxane in the presence of Karlstedt catalyst to afford compound 4b, in an overall yield 44.3%.
Likewise, the methoxy analog 4c was prepared with the alkylation of 1c followed by rearrangement and silylation. Here, the overall yield of the three steps was lower (15.6%). methyl-2-propenyloxy group (δ 4.47, δ 4.86 , and δ 4.95 ), and a cyclohexylphenyl moiety. Thermal rearrangement of compounds 2a in boiling N ,N -diethylbenzeneamine afforded the wanted intermediate 3a, in excellent yield. In the 1 H spectrum the signal at (δ 11.42 , OH) together with the other part of spectra justified the structure of 3a. This compound was then silylated with heptamethyltrisiloxane in the presence of Karlstedt catalyst [17] to furnish the target compounds 4a, in good yield. The structure of compound 4a was also justified by its spectra. For instance, both 1 H and 13 C NMR spectra showed the characteristic signals of the benzotriazole and cyclohexylphenyl skeleton, the hydroxyl group (δ 11.34 ), and the heptamethyl-disiloxanyl moiety [δ 0.08 (Si-CH 3 ) and δ 0,11 (18 H, 6 CH 3 )].
The reaction of the chloro compound 1b with 2-(chloromethyl)prop-1-ene gave the ether 2b, which was thermally rearranged. The product 3b was then silylated with heptamethyltrisiloxane in the presence of Karlstedt catalyst to afford compound 4b, in an overall yield 44.3%.
Likewise, the methoxy analog 4c was prepared with the alkylation of 1c followed by rearrangement and silylation. Here, the overall yield of the three steps was lower (15.6%).

Conclusion
We have elaborated a straightforward method for the preparation of three potential UV-filters. The synthesis of these compounds 4a-c was achieved in three steps starting with the easily available benzotriazole derivatives 1a-c, in good or acceptable overall yield. The UV absorption and photostability of these new compounds will be published in due course.

Experimental
All solvents were used as received from commercial vendors and no further attempts were made to purify or dry them. Melting points were determined on a Büchi apparatus and are uncorrected. IR spectra were recorded on a Bruker Alpha FT Spectrophotometer. 1 H NMR and 13 C NMR were recorded on a Bruker DRX-500 spectrometer operating at 500 MHz and 125 MHz, respectively. All NMR spectra are reported in ppm relative to TMS, used as an internal standard. The 1 H and 13 C NMR signals were assigned on the bases of ATP, COSY, HMQC, and HMBC experiences. Merck precoated silica gel 60 F 254 plates were used for TLC and Kieselgel 60 for column chromatography using a solution of hexane-EtOAc (5:0.2) as eluent. Elemental analyses for C, H, N agreed favorably with calculated values.

General procedure for the preparation of compounds 2a-c
Compound 1 (23.6 mmol), KI (3.9 g, 23.6 mmol), and K 2 CO 3 (3.2 g, 23.6 mmol) were mixed in butan-2-one (100 ml) and after adding 2-(chloromethyl)prop-1-ene (5.0 g, 5.6 ml, 23.8 mmol) the resulting mixture was heated under reflux for 4 h. After cooling, the precipitate was filtered off and the solvent was evaporated in vacuo. The residue was purified by column chromatography.
The following products were thus prepared:

General procedure for the synthesis of 3a-c by thermal rearrangement
A solution of compound 3 (30 mmol) in N ,Ndiethylbenzeneamine (50 ml) was heated under reflux for 4 h. After cooling, the mixture was treated with aqueous HCl (15 %, 50 ml) and then extracted three times with CH 2 Cl 2 (50 ml each). The combined organic extracts were dried (MgSO 4 ), and concentrated to give a solid residue which was crystallized from hexane.
Yield To a stirred solution of compound 3 (3 mmol) in xylene (20 ml) were added 1,1,1,3.5,5,5-heptamethyltrisiloxane (1 g, 4.5 mmol) and Karlstedt catalyst (10 drops), and the resulting mixture was heated at 100 o C for 8 h. After cooling, the solvent was evaporated in vacuo and the residue was purified by column chromatography.