4-Ethynylbenzyl alcohol 97

Uses

• 4-Ethynylbenzyl alcohol can be used in the synthesis of platinum-acetylide dendrimers, rotaxanes and arylacetylenes.
• It was employed in the preparation of arylalkyne-tagged sugars for the photoinduced glycosylation of cysteine-containing peptides.
• It can also act as a precursor to synthesize fluorescent probes via Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click reaction.

Synthesis

275386-60-2

10602-04-7

General steps: 1. To an anhydrous triethylamine (TEA) solution of (4-bromophenyl)methanol (935 mg, 5 mmol), Pd(PPh3)2Cl2 (175 mg, 0.25 mmol), CuI (48 mg, 0.25 mmol), and P(t-Bu)3 (51 mg, 0.25 mmol) were sequentially added under nitrogen protection. 2. After stirring the reaction mixture for 5 minutes, ethynyltrimethylsilane (980 mg, 10 mmol) was added dropwise. 3. The reaction mixture was microwaved at 130 °C for 4 hours and subsequently cooled to room temperature. 4. The reaction mixture was filtered through diatomaceous earth and the filtrate was concentrated under reduced pressure. 5. The residue was extracted three times with a mixture of ethyl acetate (EtOAc) and water and the organic layers were combined. 6. The organic layer was washed with brine, dried over anhydrous sodium sulfate (Na2SO4), filtered and purified by silica gel column chromatography (petroleum ether/ethyl acetate=4/1) to afford (4-((trimethylmethylsilyl)ethynyl)phenyl)methanol as a brown oil (670 mg, 66% yield). [0633] 1. To a solution of (4-((trimethylmethylsilyl)ethynyl)phenyl)methanol (250 mg, 1.23 mmol) in tetrahydrofuran (THF) was added tetrabutylammonium fluoride (TBAF, 500 mg, 2.45 mmol) in one portion at 0 °C. 2. The reaction mixture was stirred from 0 °C to room temperature for 3 hours. 3. The reaction mixture was concentrated under reduced pressure and the residue was extracted three times with a mixture of ethyl acetate (EtOAc) and water and the organic layers were combined. 4. The organic layer was washed with brine, dried over anhydrous sodium sulfate (Na2SO4), filtered and purified by silica gel column chromatography (petroleum ether/ethyl acetate=4/1) to afford (4-ethynylphenyl)methanol as a brown oil (170 mg, 100% yield). 1H NMR (400 MHz, CDCl3) δ 7.45-7.49 (m, 2H), 7.21-7.26 (m, 2H), 4.69 (s, 1H), 4.65 (s, 2H).

References

[1] Angewandte Chemie - International Edition, 2004, vol. 43, # 29, p. 3814 - 3818
[2] Patent: WO2018/14802, 2018, A1. Location in patent: Paragraph 0364
[3] Patent: WO2008/31157, 2008, A1. Location in patent: Page/Page column 65
[4] Chemistry - A European Journal, 2013, vol. 19, # 29, p. 9452 - 9456
[5] Synthesis (Germany), 2014, vol. 46, # 3, p. 348 - 356