Reaction of 2,6-di-tert-butyl-4-hydroxymethylphenol with dodecaneselenolate and sodium selenide

Article abstract of DOI:10.1007/s11172-021-3077-7

Synthesis of 2,6-di-tert-butyl-4-(dodecylselanylmethyl)phenol and bis(3,5-di-tert-butyl-4-hydroxybenzyl) selenide by the reaction of 2,6-di-tert-butyl-4-hydroxymethylphenol with dodecaneselenolate and sodium selenide was developed.

Full text of DOI:10.1007/s11172-021-3077-7

Russian Chemical Bulletin, International Edition, Vol. 70, No. 1, pp. 195—196, January, 2021
195
Reaction of 2,6-di-tert-butyl-4-hydroxymethylphenol with
dodecaneselenolate and sodium selenide
S. E. Yagunov,a S. V. Kholshin,a N. V. Kandalintseva,a,b and O. I. Prosenkoa,b
aNovosibirsk State Pedagogical University,
28 ul. Vilyuiskaya, 630126 Novosibirsk, Russian Federation.
Fax: +7 (383) 244 1856. E-mail: syagunov@yandex.ru
bNovosibirsk Research Institute of Antioxidants,
54a ul. Krasnyi Prospekt, 630091 Novosibirsk, Russian Federation.
Fax: +7 (383) 217 0781
Synthesis of 2,6-di-tert-butyl-4-(dodecylselanylmethyl)phenol and bis(3,5-di-tert-butyl-4-
hydroxybenzyl) selenide by the reaction of 2,6-di-tert-butyl-4-hydroxymethylphenol with
dodecaneselenolate and sodium selenide was developed.
Key words: selenides, benzylic selenides, 4-hydroxybenzyl selenides, 2,6-di-tert-butyl-4-
hydroxymethylphenol.
Previously, we have described the tandem reaction
involving 2,6-dimethylphenol, formaldehyde, and do-
decaneselenol that resulted in 4-dodecylselanylmethyl-
2,6-dimethylphenol. A key intermediate of this reaction
was 4-hydroxymethyl-2,6-dimethylphenol.1 In conti-
nuation of this research, we were interested in a more
in-depth study of this type of the reaction. The known
one-pot synthetic procedures to access benzylic selenides
from benzylic alcohols do not mention the use of hydr-
oxymethylphenols as the starting materials.2,3 In the
present work, we studied the reaction of 2,6-di-tert-butyl-
4-hydroxymethylphenol (1) with two selenium-con-
taining reagents, viz., dodecaneselenolate and sodium
selenide.
The reaction of compound 1 with sodium selenide
generated in situ by the reduction of elemental selenium
with NaBH44 was also first attempted in refluxing EtOH.
However, these conditions were ineffective for the syn-
thesis of selenide 3 since the reaction was slow (complete
conversion of 1 was achieved only within 20 h) and pro-
duced large amount of side product, 2,6-di-tert-butyl-4-
ethoxymethylphenol. The transformation was dramatically
accelerated by using aqueous EtOH (1 : 1) as a solvent and
3 h after the process onset the reaction mixture contained
98.8% of bis(3,5-di-tert-butyl-4-hydroxybenzyl) selenide (3),
0.6% of 2,6-di-tert-butyl-4-ethoxymethylphenol, and 0.6%
of bis(3,5-di-tert-butyl-4-hydroxybenzyl) diselenide. Com-
pound 3 was isolated in the yield of 92%.
In summary, we demonstrated that the reaction of
hydroxymethylphenols with selenium nucleophiles is a ver-
satile approach towards (selanylmethyl)phenols. The
synthesized compounds are of interest as selenium-con-
taining analogs of known sulfur-containing antioxidants,
(alkylsulfanyl)methyl-substituted phenols5,6 and bis(4-
hydroxybenzyl) sulfides.7,8 Bis(4-hydroxybenzyl) selenides
were synthesized for the first time.
The reaction of compound 1 with dodecaneselenolate
generated in situ by the reduction of didodecyl diselenide
1
with NaBH4 was carried out in refluxing EtOH for 3 h.
According to GC/MS analysis, the reaction mixture con-
tained 96.7% of 2,6-di-tert-butyl-4-(dodecylselanylmeth-
yl)phenol (2), 2.2% of 2,6-di-tert-butyl-4-ethoxymethyl-
phenol, and 1.2% of didodecyl diselenide. Compound 2
was obtained in the isolated yield of 84%.
Scheme 1
Reagents and conditions: i. C12H25SeSeC12H25, NaBH4, EtOH, Δ; ii. Se, NaBH4, H2O, EtOH, Δ.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 195—196, January, 2021.
1066-5285/21/7001-0195 © 2021 Springer Science+Business Media LLC

Yagunov et al.
196
Russ. Chem. Bull., Int. Ed., Vol. 70, No. 1, January, 2021
ous EtOH (25 mL), NaBH4 (0.22 g, 5.88 mmol) was added
portionwise, followed by addition of compound 1 (0.95 g,
4.0 mmol) after dissolution of selenium. The mixture was refluxed
for 3 h, transferred into a separatory funnel, diluted with a NaCl
solution (50 mL), and extracted with EtOAc (3×20 mL). The
combined organic extracts were washed with a NaCl solution,
dried with Na2SO4, and concentrated in vacuo. The crystalline
residue (1.04 g) containing 98.8% of the target product (HPLC
data) was recrystallized from EtOH (30 mL) to give 0.95 g (92%)
of the title product with purity of >99.9% (HPLC data) as color-
less needles. M.p. 134.5—135.6 °C. Found (%): C, 69.54; H, 9.01.
C30H46O2Se. Calculated (%): C, 69.61; H, 8.96. UV (EtOH),
λmax/nm (lgε): 237 (4.25), 278 (3.60). IR (CCl4), ν/cm–1: 3646
(OH). 1H NMR, δ: 1.43 (s, 36 H, But); 3.74 (s, 4 H, CH2); 5.12
(s, 2 H, OH); 7.10 (s, 4 H, H(2), H(6), H(2´), H(6´)). 13C NMR,
δ: 28.43 (CH2), 30.20 (CH3), 34.18 (C(CH3)3), 125.32 (C(2),
C(6), C(2´), C(6´)), 129.71 (C(1), C(1´)), 135.78 (C(3), C(5),
C(3´), C(5´)), 152.42 (C(4), C(4´)). 77Se NMR, δ: 313.30. MS
(EI, 70 eV), m/z (Irel (%)): 518 [M]+ (1), 219 [M – C15H23OSe]+
(100).
Experimental
NMR spectra were recorded on a Bruker Avance 600 spectro-
meter (600.13 (1H), 150.90 (13C—{1H}), and 114.51 MHz
(
77Se—{1H})) in CDCl3. IR spectra were recorded on an Agilent
Cary 600 Series FTIR instrument for the solutions in CCl4
(c = 2•10–2 mol L–1) using a KBr cuvette (l = 0.5 mm). UV
spectra were recorded with a Shimadzu UV-1800 instrument for
the solutions in EtOH (c = 4•10–5 mol L–1). The GC/MS
analysis was performed with an Agilent 7890B chromatograph
(HP-5MS UI column, 30 m×0.25 mm, helium as a carrier gas)
coupled with an Agilent 5977A mass detector (EI, 70 eV).
Melting points were measured by a capillary method (heat-
ing rate of 0.5 deg min–1) using a MP 50 Mettler Toledo appa-
ratus. All reactions were carried out under the inert atmo-
sphere. Compounds 2 and 3 were handled under red light.
Solvents were purified and dried by the standard procedures9
prior to use.
2,6-Di-tert-butyl-4-(dodecylselanylmethyl)phenol (2). To
a solution of didodecyl diselenide (497 mg, 1.0 mmol) in EtOH
(5 mL), NaBH4 (151 mg, 4.0 mmol) was added. The mixture was
refluxed for 1 h, then a solution of compound 1 (473 mg,
2.0 mmol) in EtOH (2 mL) was added, and the mixture was
refluxed for 3 h. The mixture was transferred into a separatory
funnel, diluted with a NaCl solution (50 mL), and extracted with
hexane. The organic extracts were washed with NaCl, dried with
Na2SO4, and concentrated in vacuo. Purification of the residue
(0.95 g) by silica gel column chromatography (elution with 4%
EtOAc in hexane) afforded 785 mg (84%) of yellowish resin that
crystallized on cooling. Rf 0.30 (4% EtOAc in hexane). M.p.
23.0—23.4 °C. Found (%): C, 68.92; H, 10.41. C27H48OSe.
Calculated (%): C, 69.35; H, 10.35. UV (EtOH), λmax/nm (lgε):
204 (4.48), 278 (3.19). IR (CCl4), ν/cm–1: 3646 (OH). 1H NMR,
δ: 0.87 (t, 3 H, Se(CH2)11CH3, J = 7.2 Hz); 1.24 (m, 18 H,
Se(CH2)2(CH2)9CH3); 1.42 (s, 18 H, But); 1.61 (pent, 2 H,
SeCH2CH2, J = 7.5 Hz); 2.49 (t, 2 H, SeCH2CH2, J = 7.5 Hz);
3.73 (s, 2 H, ArCH2); 5.10 (s, 1 H, ArOH); 7.06 (s, 2 H, H(3),
H(5)). 13C NMR, δ: 13.99 (CH3), 22.57 (CH2), 24.16 (CH2), 27.47
(CH2), 29.10 (CH2), 29.23 (CH2), 29.44 (CH2), 29.50 (CH2),
29.52 (CH2), 29.54 (CH2), 30.02 (CH2), 30.20 (C(CH3)3), 30.46
(CH2), 31.80 (CH2), 34.17 (C(CH3)3), 125.31 (C(3), C(5)),
129.78 (C(4)), 135.75 (C(2), C(6)), 152.38 (C(1)). 77Se NMR,
δ: 245.50. MS (EI, 70 eV), m/z (Irel (%)): 468 [M]+ (0.4), 219
[M – C12H25Se]+ (100).
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Received June, 15 2020;
in revised form September 4, 2020;
accepted September 30, 2020
Bis(3,5-di-tert-butyl-4-hydroxybenzyl) selenide (3). To a sus-
pension of elemental selenium (0.16 g, 2.0 mmol) in 50% aque-