1.
General methods
1 13
H NMR, C NMR spectra were obtained utilizing a Bruker 600 and 400 MHz
instrument and reported in CDCl3 or DMSO(d6). 1H and 13CNMR chemical shifts are
reported in ppm relative to either TMS (1H) (δ = 0 ppm) as an internal standard or the
residual solvent peak as following: CDCl3 =7.26 (1H NMR), (CD3)2SO = 2.50 (1H
NMR), CDCl3 = 77.16 (13C NMR), (CD3)2SO = 40.00 (13C NMR). Commercially
available chemicals and solvents were purchased from Adamas-beta, Energy
Chemical, Chongqing Chuan dong Chemical and Chengdu Kelong Chemical. The
corresponding compounds were synthesized according to the reported literature
methods. Analytical thin-layer chromatography (TLC) was performed on silica gel
plates with F-254 indicator and compounds were visualized by irradiation with UV
light. Chromatography was carried out using silica gel 300-400 mesh. HRMs were
performed on Bruker Impact II 10200 instrument.
2. Experimental Procedures
2.1 General procedure for synthesis of p-QMs 2[1]
2.1.1 General procedure for synthesis of 2,6-di-tert-butyl-4-substituted
benzylidene cyclohexa-2,5-dien-1-one (2a-2v)
In a Dean-Stark apparatus, a solution of 2,6-di-tert-butylphenol (1.0 mmol) in 5 mL
toluene, the corresponding aromatic aldehyde (1.0 mmol) and piperidine (2.0 mmol)
were added. The reaction mixture was stirred at 150°C. The reaction was monitored
by TLC. After complete reaction, the mixture was cooled just below the boiling point
of the reaction mixture, and acetic anhydride (2.0 mmol) was added drop wisely in the
continuously stirring. The mixture was washed with water, extracted with ethyl acetic,
dried over anhydrous magnesium sulfate and concentrated in vacuo. The crude
produce was then purified by flash column chromatography on silica gel (gradient
eluent of EA/PE=1/200-1/100) to gain corresponding product.
2.1.2 General procedure for synthesis of
4-benzylidene-2,6-dimethylcyclohexa-2,5-dien-1-one (2w)[2]
2aw and 2ax was synthesized according to the following procedure:
benzoyl chloride (1.80 equiv.) was added dropwise to the corresponding benzaldehyd
e (1.0 equiv.) in toluene. Then aluminium chloride (0.40 equiv.) was slowly added and
the mixture was stirred at room temperature for 7 h. After completion, solvents were
evaporated and directly subjected to flash chromatography to obtain the pure product
S1. Palladium (10% by weight on carbon powder) (5% equiv.) was added in one
portion to a solution of S1 (1.0 equiv.) in ethanol under an atmosphere of H2 (balloon).
The reaction mixture was stirred vigorously for 3 h at room temperature and then
filtered through a pad of celite. The solvent was removed under reduced pressure and
the residue was purified by silica gel flash column chromatography to afford S2.
Potassium ferricyanide (4.0 equiv.) and potassium hydroxide (4.2 equiv.) in water
were added in one portion to a solution of S2 (1.0 equiv.) in hexane under argon. The
reaction mixture was stirred vigorously for 1 h at 23°C. The aqueous layer was
separated and extracted with hexanes. The combined organic layers were washed with
brine and dried over anhydrous sodium sulfate. The solids were removed by filtration
and the solution was concentrated by rotary evaporation. The residue was purified by
silica gel flash column chromatography to afford corresponding product 2w and 2x.
2.1.3 General procedure for synthesis of
2,6-di-tert-butyl-4-ethylidenecyclohexa-2,5-dien-1-one[2]
Potassium ferricyanide (4.0 equiv.) and potassium hydroxide (4.2 equiv.) in water
were added in one portion to a solution of 2,6-di-tert-butyl-4-ethylphenol (1.0 equiv.)
in hexane under argon. The reaction mixture was stirred vigorously for 1h at 23°C.
The aqueous layer was separated and extracted with hexanes. The combined organic
layers were washed with brine and dried over anhydrous sodium sulfate. The solids
were removed by filtration and the solution was concentrated by rotary evaporation.
The residue was purified by silica gel flash column chromatography to afford
corresponding product 2y
2.2 General procedure for synthesis of sulfonyl hydrazides[3]
Hydrazine hydrate (12.5 mmol) was added dropwise to a solution of sulfonyl chloride
(5.0 mmol) in dry THF (25 mL) at 0°C under N2. After vigorous stirring for 30 min at
0°C, ethyl acetate (60 mL) was added, and the mixture was washed repeatedly with
ice-cold 10% aqueous sodium chloride solution (3 × 20 mL). The organic layer was
dried over sodium sulfate, filtered, and added slowly to stirred hexane (40 mL) over 5
min. Sulfonyl hydrazide precipitated within 10 min as an off-white solid and was
collected by vacuum filtration. The filter cake was washed with hexanes (2 × 50 mL)
and then was dried in vacuum to give corresponding sulfonyl hydrazides in 60-80%
yields.
3. References
[1] Zhang, X. Z.; Du, J. Y.; Deng, Y. H.; Chu, W. D.; Yan, X.; Yu, K. Y.; Fan, C. A.
J. Org. Chem. 2016, 81, 2598
[2] Gao, S.; Xu, X.; Yuan, Z.; Zhou, H.; Yao, H.; Lin, A. Eur. J. Org. Chem. 2016,
3006.
[3] L. Liu, K. Sun, L. Su, J. Dong, L. Cheng, X. Zhu, C. T. Au, Y. Zhou, S. F. Yin,
Org. Lett 2018, 20, 4023-4027.
4. NMR spectra
5. HRMS of compounds
6. Crystal data and structure refinement for 4af
Empirical formula C27H31BrO3S
Formula weight 515.49
Temperature/K 290.36(10)
Crystal system orthorhombic
Space group P212121
a/Å 10.8798(2)
b/Å 10.9903(3)
c/Å 21.4683(6)
α/° 90.0
β/° 90.0
γ/° 90.0
Volume/Å3 2567.01(11)
Z 4
ρcalcg/cm 3
1.334
μ/mm‑1 3.137
F (000) 1072.0
3
Crystal size/mm 0.54 × 0.52 ×0.21
Radiation CuKα (λ = 1.54184)
2Θ range for data collection/° 8.236 to 134.136
Index ranges -12 ≤ h ≤ 12, -13 ≤ k ≤ 5, -18 ≤ l ≤ 25
Reflections collected 9789
Independent reflections 4538 [Rint = 0.0332, Rsigma = 0.0409]
Data/restraints/parameters 4538/1/296
Goodness-of-fit on F2 1.042
Final R indexes [I>=2σ (I)] R1 = 0.0417, wR2 = 0.1083
Final R indexes [all data] R1 = 0.0441, wR2 = 0.1114
Largest diff. peak/hole / e Å-3 0.16/-0.38
Flack parameter -0.006(16)
