One-Pot Synthesis of Aryl Selenonic Acids and Some Unexpected Byproducts

Article abstract of DOI:10.1021/acs.joc.1c01369

The synthesis of aryl selenonic acids was achieved from diverse aryl bromides via a one-pot method involving metalation, selenation, and oxidation with hydrogen peroxide followed by ion exchange to afford the pure products in 77-90% yield. An o-hydroxymethyl derivative was found to dehydrate readily, affording the first example of a cyclic selenonic ester, while two minor byproducts were isolated and shown by X-ray crystallography to be mixed salts of aryl selenonic acids with either the corresponding aryl seleninic or selenious acid.

Full text of DOI:10.1021/acs.joc.1c01369

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One-Pot Synthesis of Aryl Selenonic Acids and Some Unexpected
Byproducts
Kai N. Sands, Benjamin S. Gelfand, and Thomas G. Back*
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ABSTRACT: The synthesis of aryl selenonic acids was achieved from diverse aryl
bromides via a one-pot method involving metalation, selenation, and oxidation with
hydrogen peroxide followed by ion exchange to afford the pure products in 77−90%
yield. An o-hydroxymethyl derivative was found to dehydrate readily, affording the
first example of a cyclic selenonic ester, while two minor byproducts were isolated
and shown by X-ray crystallography to be mixed salts of aryl selenonic acids with
either the corresponding aryl seleninic or selenious acid.
typically either isolated as their metal salts or were obtained
from the latter by treatment with strong acids such as
perchloric acid.13−15 Purification and characterization were
often minimal with the methods available at the time. In more
recent examples, Abdo and Knapp16 prepared sodium and
triethylammonium salts of selenonic acid derivatives of
carbohydrates, while Singh et al.17 obtained the selenonic
acid analogue of selenocysteine and confirmed its structure by
X-ray diffraction. Perfluoro analogues18 and p-chlorobenzene-
selenonic acid19 have also been reported. In general, the
preparation of selenonic acids is hampered by their strong
acidity and water solubility, the difficulty in separating the free
acids from byproduct metal salts, their high polarity that
generally precludes chromatographic purification on common
adsorbents like silica gel, and their hygroscopic nature.
Moreover, diselenide and seleninic acid precursors of selenonic
acids are not always readily available, resulting in the need for
alternative procedures based on more common starting
materials.
INTRODUCTION
■
Benzeneseleninic acid (1a) and its anhydride 2a, as well as
various analogues, have been widely studied and used in a
diverse range of synthetically useful oxidations.1 Some of these
processes employ catalytic amounts of the selenium compound
in the presence of inexpensive and environmentally friendly
stoichiometric co-oxidants such as hydrogen peroxide.2
Examples include the conversion of alcohols to aldehydes or
ketones,3 phenols to quinones,4 dehydrogenation of steroidal
ketones,5 lactones,6 and lactams3b to α,β-unsaturated com-
pounds, epoxidations7 and dihydroxylations8 of alkenes, and
Baeyer−Villiger oxidations.9 In the latter three cases, the
corresponding peroxyseleninic acid 3a was proposed as the
active oxidant.
In contrast, although the corresponding selenonic acids 4
were first reported more than a century ago, they have been
studied less frequently and have found little application as
synthetic reagents. This is in large measure due to difficulties in
their preparation and characterization, which led to errors and
uncertainties in their structure identification in earlier work.
For example, in 1909, Doughty10 reported the preparation of
4a by heating selenic acid (H2SeO4) in benzene in a sealed
tube for 100 h at 110 °C. Subsequently, a more efficient
variation of this process employed selenium trioxide and
benzene in liquid sulfur dioxide to obtain the same product.11
However, in 1964, Paetzold and Lienig12 repeated the earlier
work of Doughty and demonstrated the presence of both
Se(IV) and Se(VI) in the product by means of a Bunsen test.
On this basis, they suggested that the product was actually the
selenonium selenonate salt 5a, produced by protonation of 1a
by 4a. Several other early reports of selenonic acids were based
on the oxidation of diselenides or seleninic acids with oxidants
like nitric acid or potassium permanganate. The products were
Very recently, we reported that, contrary to previous
reports,7 the epoxidation of cyclooctene with benzeneseleninic
acid (1a) and hydrogen peroxide proceeds chiefly via stepwise
formation of selenonium selenonate salt 5a, followed by 4a and
finally the proposed peroxyselenonic acid 6a, as shown in
Scheme 1. Epoxidation with 6a generated in this manner
proved significantly faster than with the peroxyseleninic acid
Received: June 9, 2021
Published: July 16, 2021
https://doi.org/10.1021/acs.joc.1c01369
© 2021 American Chemical Society
J. Org. Chem. 2021, 86, 9938−9944
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Scheme 1. Oxidation Pathways for the Reaction of
Benzeneseleninic Acid (1a) with Hydrogen Peroxide
3a.20 Furthermore, Syper and Młochowski21 isolated perox-
yseleninic acid 3a and indicated that it isomerized to selenonic
acid 4a upon heating in acetonitrile. However, we found that
this reaction, which proceeded even at room temperature in
solution and was accompanied by oxygen evolution, actually
produced the salt 5a and not 4a, as confirmed by an X-ray
structure of the product.20 This also confirmed the earlier
structure proposed by Paetzold and Lienig on the basis of their
Bunsen test of the product obtained by the method of
Doughty. Since 4a alone failed to effect epoxidation, its further
conversion to the postulated peroxyselenonic acid 6a with
hydrogen peroxide is a requirement for epoxidation. Thus, 6a
appears to be the most active oxidant species in this redox
manifold, but proved too unstable to isolate. Given the
difficulties in the preparation of selenonic acids and their
incomplete characterization in much of the earlier work, along
with the newly discovered and unexpected role that 4a and 6a
play in the epoxidation of a typical alkene, we now report a
new protocol for the preparation of a series of diverse
selenonic acids.
Figure 1. Structures and yields of aryl selenonic acids.
room temperature in the presence of formic acid. The lithium
selenonates were then extracted into water and passed through
a short column of Rexyn 101(H) ion-exchange resin to
generate the free selenonic acids 4. The aqueous solutions of 4
were freeze-dried under vacuum to afford the final products in
a high state of purity. Although some selenonic acids have been
prepared by the further oxidation of seleninic acids or
diselenides,13 usually with harsh oxidants, the advantage of
the present method is that it starts with more widely available
aryl bromides for products where the corresponding
diselenides and seleninic acids are not readily available.
During optimization studies of the preparation of 4b, we
observed that tert-butyllithium was more effective than n-
butyllithium in the metalation−selenation sequence, as the
latter resulted in the formation of significant amounts of the
corresponding aryl n-butyl selenides. Low temperatures also
proved necessary to avoid decomposition of the products (vide
infra) as well as to avoid reaction of tert-butyllithium with the
solvent THF. Although the overall stoichiometry of the process
requires only 3 equiv of hydrogen peroxide to convert the
lithium selenolates (ArSeLi) to selenonic acids 4, a total of 4 or
5 equiv of hydrogen peroxide was typically added in two
portions to achieve complete oxidation. Attempts were made
to catalyze the formation of the selenonic acids with several
acids. Acetic acid had little effect and proved difficult to
remove from the product, while trifluoroacetic acid resulted in
considerable decomposition. However, formic acid enhanced
the rate ca. 3-fold, afforded products of high purity, and was
easily removed from the product. While the precise reason for
the beneficial effects of formic acid is unclear, one possibility is
that it protonates an intermediate seleninic acid, thereby
activating it toward further attack by hydrogen peroxide.22,23
Alternatively, it is conceivable that formation of the
corresponding peroxyformic acid (HC(O)OOH) in situ24
enhances the oxidation of the selenium species in Scheme 2 en
route to products 4. Since the selenonic acids are hygroscopic,
removal of water from their aqueous solutions by rotary
evaporation required elevated temperatures that led to
extensive decomposition. This was easily avoided by freeze-
drying the solutions under high vacuum. All of the products
were then characterized by 1H, 13C, and 77Se NMR
spectroscopy as well as by high-resolution mass spectrometry.
RESULTS AND DISCUSSION
■
The synthesis of arylselenonic acids 4a−4l (Scheme 2 and
Figure 1) was achieved in one pot from a series of aryl
bromides by metalation with tert-butyllithium in THF solution
at −78 °C, addition of powdered selenium, and oxidation of
the resulting selenolates (ArSeLi) with hydrogen peroxide at
Scheme 2. Preparation of Aryl Selenonic Acids 4 from Aryl
Bromides
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The results shown in Figure 1 indicate that good to high
(77−90%) yields of diverse aryl selenonic acids can be
produced, including products containing electron-donating
(4b, 4c, 4d, 4e, 4f, and 4g) and -withdrawing substituents (4h,
4i), located at either the ortho-, meta-, or para-positions. The
naphthalene (4j) and biphenyl (4k) derivatives were also
obtained without difficulty. The attempted preparation of 2-
(hydroxymethyl)benzeneselenonic acid (4l) by the usual
method resulted instead in the formation of the cyclic
selenonate ester 4m through dehydration of 4l. The 77Se
NMR spectrum of 4m in CDCl3 revealed a signal at 1116.5
ppm, which is considerably further downfield than the
resonances of selenonic acids 4a−4k (1020−1031 ppm in
D2O). Crystallization of 4m by slow evaporation from water
produced crystals suitable for X-ray crystallography, which
confirmed its structure unequivocally (Figure 2). When 4m
selenious acid (H2SeO3) by the more strongly acidic selenonic
acid 4b.27 The formation of 7b in this instance was attributed
to a small amount of excess unreacted elemental selenium that
remained after the selenation step and was subsequently
converted to selenious acid by oxidation with hydrogen
peroxide, followed by protonation by the principal product,
the selenonic acid 4b. Alternatively, it is conceivable that
selenious acid was produced by oxidative C−Se bond cleavage
of an arylseleno intermediate during the process. While the
compounds prepared by the typical procedure in the
Experimental Section and listed in Figure 1 were free of
selenious acid, on the basis of the 77Se NMR and HRMS
spectra of the final products, this result indicates that care must
be taken to ensure that the selenation step is allowed to go to
completion and that the use of excess selenium is avoided in
the preparation of the products 4.
When a sample of 2,6-dimethylbenzeneselenonic acid (4g)
was heated in dioxane at 70 °C, followed by cooling to room
temperature, a small amount of the salt 8g crystallized and its
structure was determined by X-ray crystallography (see Figure
4). Interestingly, the structure consists of a dimeric hydrogen-
Figure 2. ORTEP diagram of cyclic selenonate ester 4m. For details,
see the Supporting Information, Figure S54 and Table S1.
was dissolved in D2O, the NMR spectra were quite different
from those in CDCl3, including a 77Se signal at 1021.9 ppm,
consistent with the selenonic acid structure 4l and indicating
that the dehydration is reversible. While cyclic seleninate esters
containing Se(IV) are well known,25 to our knowledge, cyclic
selenonate esters have not been previously reported.
The above selenonic acids proved stable at or below room
temperature and could be stored for at least several weeks
when refrigerated. However, during optimization studies,
several unexpected byproducts were also discovered. Attemp-
ted recrystallization of a sample of crude 4b from dichloro-
methane delivered a small amount of the salt 7b instead of 4b.
Its 77Se NMR spectrum revealed signals at 1299.726 and 1024.5
ppm, typical of selenious and selenonic acid species,
respectively, and an X-ray crystal structure (Figure 3)
confirmed that it was the salt derived from protonation of
Figure 4. ORTEP diagram of salt 8g. For details, see the Supporting
Information, Figure S56 and Table S3.
bridged selenonate anion and a protonated seleninic acid
cation. While this resembles the 1:1 salt 5a in Scheme 1, the
2:1 stoichiometry in 8g was unexpected. However, evaporation
of the mother liquor and examination of the residue by NMR
spectroscopy in CDCl3 revealed the presence of the
corresponding 1:1 salt 5g as the main product. This
experiment thus demonstrates that heating selenonic acids 4
can result in the facile loss of oxygen to generate the
corresponding seleninic acid 1 followed by its protonation by 4
to afford the more stable mixed Se(IV)−Se(VI) salts such as
8g and 5g (Scheme 3).
Attempts to extend the procedure shown in Scheme 2 to the
preparation of free alkyl selenonic acids proved more difficult
because of their decomposition upon treatment with Rexyn
101(H), which was required to liberate the free acids from
their lithium salts. However, crude lithium methane- and n-
butaneselenonates (9 and 10, respectively) could be prepared
by a modification of the general procedure (see the
Experimental Section). Similarly, endo-3-camphorselenonic
acid (11) was obtained in solution from the hydrogen
peroxide oxidation of the corresponding diselenide28 in the
presence of HCl−diethyl ether but decomposed upon
attempted isolation.
Figure 3. ORTEP diagram of salt 7b. For details, see the Supporting
Information, Figure S55 and Table S2.
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An additional portion of hydrogen peroxide (50%, 60 μL, 1.0 mmol)
was added, and stirring at room temperature was continued for 3 h.
The reaction mixture was then diluted with water (5 mL), and the
aqueous layer was collected. The organic layer was extracted with
H2O (1 mL), and the combined aqueous layers were washed with
diethyl ether (5 mL). The aqueous layer was then passed through a
short column of Rexyn 101(H) ion-exchange resin (2.0 g/mmol), and
the resin was washed with an additional 2 mL of H2O. Removal of the
water by freezing the solution in an acetone−dry ice bath and
sublimation under high vacuum afforded 163 mg (80%) of residual
product 4a as an off-white solid. Mp: 57−59 °C (lit. mp 64 °C,12 63−
64 °C;11b 58−60 °C;20 the mp of 142 °C10 or 144 °C21 reported in
the older literature was incorrectly assigned to 4a and is due to the salt
5a).12,20 1H NMR (400 MHz, D2O): δ 7.77−7.75 (m, 2 H), 7.61
(crude tt, J = 7.4, 1.7 Hz, 1 H), 7.54 (crude tt, J = 7.4, 1.5 Hz, 2 H).
13C{1H} NMR (101 MHz, D2O): δ 143.0, 134.0, 130.3, 125.7.
77Se{1H} NMR (76 MHz, D2O): δ 1024.3. HRMS (ESI) m/z calcd
for C6H5O380Se [M − H]−: 204.9409; found: 204.9405.
Scheme 3. Thermal Decomposition of Selenonic Acid 4g to
Produce Mixed Se(IV)−Se(VI) Salts
Preparation of 4-Methoxybenzeneselenonic Acid (4b).15a
The product was isolated (205 mg, 87%) as a waxy off-white solid.
1
Mp: dec from 86 °C. H NMR (400 MHz, D2O): δ 7.70 (d, J = 7.9
Hz, 2 H), 7.11 (d, J = 8.0 Hz, 2 H), 3.74 (s, 3 H). 13C{1H} (101
MHz, D2O): δ 163.2, 134.6, 127.8, 115.5, 55.8. 77Se{1H} (76 MHz,
D2O): δ 1024.4. HRMS (ESI) m/z calcd for C7H7O480Se [M − H]−:
234.9515; found: 234.9510.
In summary, the process described here provides a one-pot
method for the preparation and characterization of diverse aryl
selenonic acids from the corresponding readily available aryl
bromides. The cyclic selenonic ester 4m appears to be the first
example of its class. Several unexpected salts 7b, 4g, and 5g
were formed by protonation of Se(IV) oxyacids by the stronger
Se(VI) acids 4 during initial attempts to prepare selenonic
acids 4b and 4g.
When the above process was scaled up to 1.87 g (10.0 mmol) of 4-
bromoanisole and 0.790 g (10.0 mmol) of selenium powder, 2.12 g
(90%) of product 4b were obtained.
In a separate experiment, where a small excess (<5%) of selenium
was present, recrystallization of the crude product from dichloro-
methane resulted in the formation of a crystalline precipitate of salt
7b, the structure of which was determined by X-ray crystrallography
(see Figure 3).
The following products were prepared similarly, starting with 1.00
mmol of the corresponding aryl bromide. In the case of compounds
4e, 4h, and 4m, a second portion of 2 mmol of hydrogen peroxide was
added instead of the usual 1 mmol in order for the reaction to go to
completion.
EXPERIMENTAL SECTION
■
General Experimental. All reactions were performed using oven-
dried glassware under a nitrogen atmosphere. Tetrahydrofuran was
dried over LiAlH4 and was freshly distilled before use. Hydrogen
peroxide was titrated before use29 and had a concentration of 50
1%. Yields reported are isolated yields. Rexyn 101(H) ion-exchange
resin was washed with water, methanol, and water before use. 1H, 13C,
19F, and 77Se NMR spectra were recorded in D2O or CDCl3 at 400,
3-Methoxybenzeneselenonic Acid (4c). The product was isolated
(205 mg, 87%) as a clear oil. 1H NMR (400 MHz, D2O): δ 7.51 (t, J
= 8.1 Hz, 1 H), 7.38 (dt, J = 7.8, 1.3 Hz, 1 H), 7.34 (dd, J = 2.6, 1.6
Hz, 1 H), 7.19 (ddd, J = 8.4, 2.6, 1.0 Hz, 1 H), 3.79 (s, 3 H). 13C{1H}
NMR (101 MHz, D2O): δ 159.9, 143.9, 131.4, 120.1, 118.1, 110.8,
55.9. 77Se{1H} NMR (76 MHz, D2O): δ 1024.0. HRMS (ESI) m/z
calcd for C7H7O480Se [M − H]−: 234.9515; found: 234.9510.
4-Tolueneselenonic Acid (4d).11a,15a,b The product was isolated
(189 mg, 86%) as an off-white solid. Mp: 64−70 °C (dec) (lit.11a mp
66−73 °C). 1H NMR (400 MHz, D2O): δ 7.67 (d, J = 8.4 Hz, 2 H),
7.39 (d, J = 8.0 Hz, 2 H), 2.32 (s, 3 H). 13C{1H} NMR (101 MHz,
D2O): δ 145.5, 139.9.0, 130.8, 125.6, 20.7; 77Se{1H} NMR (76 MHz,
D2O): δ 1025.3. HRMS (ESI) m/z calcd for C7H7O380Se [M − H]−:
218.9566; found: 218.9565.
101, 377, and 76 MHz, respectively. External references of C6F6 in
C6D6 (δ −164.9 ppm relative to CFCl3)30 or PhSeSePh (δ 463
relative to Me2Se),26 respectively, were used. 13C and 19F NMR
spectra were recorded with broadband proton decoupling. 77Se NMR
were recorded using the UDEFT pulse program.31 Multiplicities are
reported as s = singlet, d = doublet, t = triplet, q = quartet, dd =
doublet of doublets, m = multiplet. Exact mass determinations were
performed with a Q-TOF LC/MS instrument, using electrospray
ionization (ESI) in either positive or negative mode, as indicated.
CAUTION! While no explosive behavior was observed during the
preparation of any of the selenonic acids in Figure 1 by the following
procedure, peroxyseleninic and peroxyselenonic acids are potentially
explosive materials that should be handled with appropriate
precautions. On a few occasions during the optimization of the
process, we did note that the reaction mixture foamed and effervesced
from the sudden release of oxygen, presumably from the
decomposition of peroxy species formed during the reaction.
Furthermore, elevated temperatures should be avoided to prevent
decomposition of the selenonic acid products.
Typical Procedure: Preparation of Benzeneselenonic Acid
(4a). 4-Bromobenzene (0.11 mL, 164 mg, 1.0 mmol) was diluted with
10 mL of dry THF and cooled to −78 °C. tert-Butyllithium (1.6 M,
1.25 mL, 2.0 mmol)32 was added dropwise, and the reaction mixture
was stirred for 10 min. Selenium (79 mg, 1.0 mmol) was added, and
stirring was continued at −78 °C for 15 min. The cold bath was
removed, and the reaction mixture was stirred at room temperature
for an additional 15 min. Hydrogen peroxide (50%, 0.17 mL, 3.0
mmol) was added, followed immediately by formic acid (75 μL, 2.0
mmol), and the mixture was stirred at room temperature for 30 min.
2-Tolueneselenonic Acid (4e).15a The product was isolated (184
mg, 84%) as colorless, hygroscopic crystals. Mp: 54−58 °C. 1H NMR
(400 MHz, D2O): δ 7.81 (d, J = 8.1 Hz, 1 H), 7.48 (t, J = 7.5 Hz, 1
H), 7.37−7.31 (m, 2 H), 2.55 (s, 3 H). 13C{1H} NMR (101 MHz,
D2O): δ 141.5, 136.5, 133.4, 132.4, 126.5, 126.1, 18.6. 77Se{1H} NMR
(76 MHz, D2O): δ 1023.2. HRMS (ESI) m/z calcd for C7H7O380Se
[M − H]−: 218.9566; found: 218.9564.
3-Tolueneselenonic Acid (4f).15a The product was isolated (172
mg, 79%) as a clear oil. 1H NMR (400 MHz, D2O): δ 7.58−7.54 (m,
2 H), 7.42−7.41 (m, 2 H), 2.28 (s, 3 H). 13C{1H} NMR (101 MHz,
D2O): δ 142.8, 141.2, 134.6, 130.0, 125.8, 122.6, 20.5. 77Se{1H} NMR
(76 MHz, D2O): δ 1025.2. HRMS (ESI) m/z calcd for C7H7O380Se
[M − H]−: 218.9566; found: 218.9562.
2,6-Dimethylbenzeneselenonic Acid (4g). The product was
isolated (179 mg, 77%) as an off-white solid. Mp dec from 109 °C.
1H NMR (400 MHz, D2O): δ 7.33 (t, J = 7.5 Hz, 1 H), 7.18 (d, J =
7.5 Hz, 2 H), 2.63 (s, 6 H). 13C{1H} NMR (101 MHz, D2O): δ
142.6, 138.0, 132.7, 131.0, 21.2. 77Se{1H} NMR (76 MHz, D2O): δ
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1030.9. HRMS (ESI) m/z calcd for C8H9O380Se [M − H]−:
232.9722; found: 232.9721.
cold bath was removed, and the mixture was stirred at room
temperature for an additional 15 min. Hydrogen peroxide (50%, 0.57
mL, 10 mmol) was added, and the reaction was stirred at room
temperature for 4 h. The solvent was removed in vacuo with no
In a separate experiment, a solution of 111 mg (0.476 mmol) of 4g
in dioxane was heated at 70 °C in an oil bath for 3.5 h. When cooled
to room temperature, a small amount of salt 8g crystallized and was
collected and subjected to X-ray crystallography (Figure 4). The
supernatant liquid was evaporated in vacuo, and the residue was
triturated with D2O to afford mainly unreacted 4g in the D2O
solution, while the remaining off-white solid was identified as the 1:1
1
heating to give crude 9 as a white solid. Mp: dec from 103 °C; H
NMR (400 MHz, D2O): δ 3.28; 13C{1H} NMR δ 42.6; 77Se{1H}
NMR (76 MHz, D2O): δ 1044.9. The crude product can be stored for
at least several days at −5 °C, but it decomposed upon treatment with
Rexyn 101(H) resin, resulting in a mixture of selenious acid and
unreacted methaneselenonic acid as the major and minor products,
respectively. 77Se{1H} NMR (76 MHz, D2O): δ 1300.3 (H2SeO3,
major), 1040.0 (CH3SeO3H, minor).
1
salt 5g (49.8 mg, 46%). Mp: dec from 121 °C. H NMR (400 MHz,
CDCl3): δ 11.77 (s, 2 H), 7.37−7.29 (m, 2 H), 7.14 (m, 4 H), 2.77
(s, 12 H). 13C{1H} NMR (101 MHz, CDCl3): δ 142.7, 140.4, 138.8,
137.8, 133.5, 132.7, 131.0, 130.4, 21.9, 19.9. 77Se{1H} NMR (76
MHz, CDCl3): δ 1176.1, 1036.9.
Lithium Butaneselenonate (10). The crude lithium salt 10 was
prepared in the same manner as 9 to afford a white solid, which could
be stored at −5 °C for several days, but decomposed upon treatment
with Rexyn 101(H) resin. Mp: dec from 106 °C. 1H NMR (400 MHz,
D2O): δ 3.55 (t, J = 7.7 Hz, 2 H), 1.94 (pentet, J = 7.7 Hz, 2 H), 1.54
(pentet, J = 7.4 Hz, 2 H), 0.96 (t, J = 7.4 Hz, 3 H). 13C{1H} NMR
(101 MHz, D2O): δ 59.1, 24.8, 21.2, 12.6. 77Se{1H} NMR (76 MHz,
D2O): δ 1061.6.
endo-3-Camphorselenonic Acid (11). endo-3-Camphor disele-
nide28 (230 mg, 0.50 mmol) was dissolved in 10 mL of
dichloromethane, and hydrogen peroxide (50%, 0.17 mL, 3.0
mmol) was added, followed by HCl·OEt2 (2.0 M, 0.5 mL, 1
mmol). The reaction was allowed to stir at room temperature for 15
min, during which time the yellow color of the diselenide was
discharged. The product selenonic acid was found to be stable in
solution for several hours but rapidly decomposed upon attempted
isolation. A freshly prepared product obtained by evaporation of
volatile material in vacuo at room temperature had the following
properties. 1H NMR (400 MHz, CDCl3): δ 7.56 (br s, 1 H), 4.75 (s, 1
H), 2.71 (s, 1 H), 2.10−2.00 (m, 1 H), 2.00−1.88 (m, 1 H), 1.83−
1.70 (m, 1 H), 1.70−1.57 (m, 1 H), 0.98 (s, 3 H), 0.90 (s, 3 H), 0.87
(s, 3 H). 13C{1H} NMR (101 MHz, CDCl3): δ 205.4, 82.9, 59.4, 47.4,
46.6, 30.1, 23.3, 19.9, 18.9, 9.6. 77Se{1H} NMR (76 MHz, CDCl3): δ
1052.1. HRMS (ESI) m/z calcd for C10H15O480Se [M − H]−:
279.0141; found: 279.0140.
4-Fluorobenzeneselenonic Acid (4h).15e The product was isolated
(178 mg, 80%) as a clear colorless oil. 1H NMR (400 MHz, D2O): δ
7.82 (dd, J = 8.9, 5.0 Hz, 2 H), 7.28 (dd, J = 8.8, 8.9 Hz, 2 H).
13C{1H} NMR (101 MHz, D2O): δ 165.3 (d, J = 253.1 Hz), 138.6,
128.6 (d, J = 9.7 Hz), 117.4 (d, J = 23.2 Hz). 19F{1H} NMR (377
MHz, D2O): δ −104.3. 77Se{1H} NMR (76 MHz, D2O): δ 1021.4.
HRMS (ESI) m/z calcd for C6H4FO380Se [M − H]−: 222.9315;
found: 222.9315.
4-(Trifluoromethyl)benzeneselenonic Acid (4i). The product was
1
isolated (228 mg, 83%) as a white solid. Mp: dec from 46 °C. H
NMR (400 MHz, D2O): δ 7.98 (d, J = 8.4 Hz, 2 H), 7.90 (d, J = 8.4
Hz, 2 H). 13C{1H} NMR (101 MHz, D2O): δ 145.8, 134.0 (q, J =
33.0 Hz), 126.9 (q, J = 3.8 Hz), 126.1, 122.6 (q, J = 272.4 Hz).
19F{1H} NMR (377 MHz, D2O): δ −63.2. 77Se{1H} NMR (76 MHz,
D2O): δ 1020.4. HRMS (ESI) m/z calcd for C7H4F3O380Se [M −
H]−: 272.9283; found: 272.9289.
Naphthalene-1-selenonic Acid (4j).15d The product was isolated
1
(206 mg, 81%) as an orange-brown solid. Mp: dec from 94 °C. H
NMR (400 MHz, D2O): δ 8.45 (d, J = 8.5 Hz, 1 H), 8.12 (d, J = 7.4
Hz, 1 H), 8.05 (d, J = 8.3 Hz, 1 H), 7.90 (d, J = 8.2 Hz, 1 H), 7.66 (t,
J = 7.7 Hz, 1 H), 7.56 (t, J = 7.6 Hz, 1 H), 7.51 (t, J = 7.8 Hz, 1 H).
13C{1H} NMR (101 MHz, D2O): δ 138.7, 134.2, 133.8, 128.6, 128.2,
127.1, 127.0, 126.5, 124.3, 123.2. 77Se{1H} NMR (76 MHz, D2O): δ
1020.9. HRMS (ESI) m/z calcd for C10H7O380Se [M − H]−:
254.9566; found: 254.9565.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c01369.
■
sı
1,1′-Biphenyl-3-selenonic Acid (4k). The product was isolated
(220 mg, 78%) as a viscous orange oil. 1H NMR (400 MHz, D2O): δ
8.02 (s, 1 H), 7.86 (d, J = 7.8 Hz, 1 H), 7.79 (d, J = 8.5 Hz, 1 H), 7.65
(t, J = 7.9 Hz, 1 H), 7.60 (d, J = 7.0 Hz, 2 H), 7.44 (t, J = 7.3 Hz, 2
H), 7.38 (t, J = 7.3 Hz, 1 H). 13C{1H} NMR (101 MHz, D2O): δ
143.7, 142.7, 138.6, 132.3, 130.8, 129.3, 128.6, 127.1, 124.5, 123.9.
77Se{1H} NMR (76 MHz, D2O): δ 1024.3. HRMS (ESI) m/z calcd
1H, 13C, 77Se, and 19F NMR spectra of compounds 4a−
4m, 5g, and 9−11 (Figures S1−S53), along with X-ray
crystallographic data for compounds 4m, 7b, and 8g
(Figures S54−S56 and Tables S1−S3) (PDF)
for C12H9O380Se [M − H]−: 280.9722; found: 280.9720.
2-(Hydroxymethyl)benzeneselenonic Acid (4l) and Cyclic Selen-
onate Ester 4m. The cyclic selenonate ester 4m was isolated (177
mg, 82%) by the usual method as a white solid. Crystallization by slow
evaporation from water gave colorless needles. Mp: 65−67 °C. The
structure was confirmed by single crystal X-ray diffraction (Figure 2).
NMR spectra were recorded in CDCl3 (dried over 3 Å molecular
Accession Codes
CCDC 2088126−2088128 contain the supplementary crys-
tallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by
emailing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
1
sieves). H NMR (400 MHz, CDCl3): δ 8.01 (d, J = 8.0 Hz, 1 H),
7.86 (td, J = 7.6, 1.1, Hz, 1 H), 7.74 (td, J = 7.7, 1.1 Hz, 1 H), 7.59 (d,
J = 7.8 Hz, 1 H), 5.62 (s, 2 H). 13C{1H} NMR (101 MHz, CDCl3): δ
137.2, 135.1, 133.6, 131.0, 125.0, 124.0, 70.2. 77Se{1H} NMR (76
MHz, CDCl3): δ 1116.5. HRMS (ESI) m/z calcd for C7H7O380Se [M
+ H]+: 218.9555; found: 218.9555.
When 4m was dissolved in D2O, it afforded the hydrated form 4l.
1H NMR (400 MHz, D2O): δ 7.83 (d, J = 7.2 Hz, 1 H), 7.61−7.56
(m, 2 H), 7.44−7.40 (m, 1 H), 4.89 (s, 2 H). 13C{1H} NMR (101
MHz, D2O): δ 140.4, 138.5, 133.7, 129.5, 128.4, 126.4, 60.0. 77Se{1H}
NMR (76 MHz, D2O): δ 1021.9. HRMS (ESI) m/z calcd for
C7H7O480Se [M − H]−: 234.9515; found: 234.9513.
AUTHOR INFORMATION
Corresponding Author
■
Thomas G. Back − Department of Chemistry, University of
Calgary, Calgary, Alberta, Canada T2N 1N4; orcid.org/
0000-0002-3790-1422; Email: tgback@ucalgary.ca
Authors
Kai N. Sands − Department of Chemistry, University of
Calgary, Calgary, Alberta, Canada T2N 1N4
Benjamin S. Gelfand − Department of Chemistry, University
of Calgary, Calgary, Alberta, Canada T2N 1N4
Lithium Methaneselenonate (9). Selenium (79 mg, 1.0 mmol)
was suspended in 10 mL of dry THF and cooled to −78 °C.
Methyllithium (1.6 M, 0.66 mL, 1.05 mmol) was added dropwise, and
the reaction mixture was stirred at −78 °C for 10 min, after which the
Complete contact information is available at:
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Featured Article
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https://pubs.acs.org/10.1021/acs.joc.1c01369
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the Natural Sciences and Engineering Research
Council of Canada (NSERC) for funding (Grant No. RGPIN
2019-04373). K.N.S. thanks the following for financial support:
a Walpole Island First Nation Scholarship, an ii’taa’poh’to’p
Graduate Scholarship, and an Alberta Graduate Excellence
Scholarship (AGES). We thank Mr. Wade White for assistance
in recording NMR and mass spectra.
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