Reaction of 1-benzoselenopyrylium salts with grignard reagents: Formation of 2,4-disubstituted selenochromenes and their conversion into the corresponding 1-benzoselenopyrylium salts [1]

Article abstract of DOI:10.1002/jhet.5570390226

Treatment of 2-tert-butyl-1-benzoselenopyrylium salts 1A and 2-phenyl-1-benzoselenopyrylium salts 1B with an alkyl(phenyl)magnesium halide resulted in nucleophilic addition at the C-4 position to give the corresponding 2,4-disubstituted 4H-selenochromenes 2A and 2B in good yields, respectively. The obtained selenochromenes 2 were then easily converted into the 4-substituted 2-tert-butyl-1-benzoselenopyrylium salts 6A by treatment with triphenylcarbenium tetrafluoroborate in high yields. The 4-substituted 2-phenyl derivatives 6B were also obtained in a similar manner. The reaction of the unsubstituted 1-benzoselenopyrylium salt 1C with an alkylmagnesium halide is also described.

Full text of DOI:10.1002/jhet.5570390226

Mar-Apr 2002
Reaction of 1-Benzoselenopyrylium Salts with Grignard Reagents:
Formation of 2,4-Disubstituted Selenochromenes and Their
405
Conversion into the Corresponding 1-Benzoselenopyrylium Salts [1]
Haruki Sashida,* Masahiro Yoshida, Hiroshi Minamida and Masanori Teranishi
Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa 920-1181, Japan
Received October 2, 2001
Treatment of 2-tert-butyl-1-benzoselenopyrylium salts 1A and 2-phenyl-1-benzoselenopyrylium salts 1B
with an alkyl(phenyl)magnesium halide resulted in nucleophilic addition at the C-4 position to give the cor-
responding 2,4-disubstituted 4H-selenochromenes 2A and 2B in good yields, respectively. The obtained
selenochromenes 2 were then easily converted into the 4-substituted 2-tert-butyl-1-benzoselenopyrylium
salts 6A by treatment with triphenylcarbenium tetrafluoroborate in high yields. The 4-substituted 2-phenyl
derivatives 6B were also obtained in a similar manner. The reaction of the unsubstituted 1-benzoselenopy-
rylium salt 1C with an alkylmagnesium halide is also described.
J. Heterocyclic Chem., 39, 405 (2002).
Research on thiopyrylium salts [2], six-membered het-
in good to excellent yields. Therefore, this report describes
the practical synthetic route for the 4H-selenochromenes
having carbon functional groups at the C-2 and C-4 posi-
tions by the reaction of the selenopyrylium salts with the
Grignard reagents, and the conversion of the obtained
selenochromenes into the corresponding 1-benzoselenopy-
rylium salts.
eroaromatic cations containing a sulfur, has attracted con-
siderable attention in recent years due to their difference
from pyrylium salts [3] in characteristic properties and
variegated reactivity. In spite of the impressive develop-
ment of both chemistries of the pyrylium salts and thiopy-
rylium salts, only a small effort on the synthesis of their
selenium analogues, the selenopyrylium salts, [4] have
been made. With regard to the 1-benzoselenopyrylium
salts, a few perchlorate derivatives [5,6,7] were known;
only one 2,4-diphenyl substituted selenopyrylium salt [6]
was prepared as the 1-benzoselenopyrylium salts having
two carbon functional groups. In addition, the reaction [7]
of the unsubstituted 1-benzoselenopyrylium salt with
phenylmagnesium bromide as the Grignard reagent to pro-
duce the 2-phenyl- or 4-phenyl-selenochromene has
scarcely been examined. To the best of our knowledge, no
2- and/or 4-(di)alkyl substituted derivatives have been
known until our study.
We have been deeply interested in the chemistry [8-13]
(syntheses, structure and physical properties and reactions)
of the telluropyrylium salts and selenopyrylium salts and
related compounds in recent years. Previously, we
described the facile preparation [12] of the 1-benzose-
lenopyrylium salts including the 2-alky-1-benzolselenopy-
rylium salts and their reactions [13] with several nucle-
ophiles to give the 4-functionalized 4H-selenochromenes
The reaction of the 2-tert-butyl-1-benzoselenopyrylium
tetrafluoborate 1A [12] and 2-phenyl-1-benzoselenopy-
rylium tetrafluoborate 1B [12] with 1.2 equivalents of
methylmagnesium iodide in diethyl ether at 0 °C resulted
in nucleophilic addition at the C-4 position to produce the
4-methyl-4H-selenochromenes 2Aa and 2Ba in 63 and
53% yields, respectively. 4-Ethyl-4H-selenochromenes
2Ab, 2Bb, 4-benzyl-4H-selenochromenes 2Ac, 2Bc and 4-
phenyl-4H-selenochromene 2Ad were similarly obtained
by treatment with the corresponding Grignard reagents in
good to high yields. Their regioisomers, the 4-substituted
2H-selenochromenes have never been produced. 2,4-
Diphenyl-4H-selenochromene 2Bd has already been syn-
thesized by the reaction of 2-phenylselenopyrylium per-
chlorate [5] with phenylmagnesium bromide, however,
there have been no reports on the successful synthesis of
selenochromenes carrying two general carbon functional
groups on the selenochromene ring until this study. The
results and the spectral data of the products are summa-
rized in Table 1.
On the other hand, the reaction of the parent selenopy-
rylium salt 1C with the alkylmagnesium bromide resulted
in a nucleophilic reaction at both the C-2 and C-4 positions
as shown in Scheme 2. The salt 1C was treated with
methylmagnesium iodide to afford 4-methyl-4H-
selenochromene 3a, 2-methyl-2H-selenochromene 4a and
2-methyl-4H-selenochromene 5 in 12, 6 and 5% yields,
respectively. When ethylmagnesium bromide was used as
the Grignard reagent, the salt 1C gave the 4-ethyl-4H-
chromene 3b (11% yield) and 2-ethyl-2H-chromene 3b
(24% yield); the isomeric product of the latter was not

406
H. Sashida, M. Yoshida, H. Minamida and M. Teranishi
Vol. 39
obtained in this case. A similar reaction of the salt 1C with
benzylmagnesium bromide proceeded to give the 4-benzyl
3c and 2-benzyl 4c derivatives in 18 and 14% yields,
respectively. The preparation of the 2-substituted
selenochromenes has been achieved by the reduction of the
corresponding selenochromon-4-ones [14] with diisobuty-
laluminum hydride or lithium aluminum hydride reduction
of 2-alkyl-1-benzoselenopyrylium salts, [13] however, the
4-substituted derivatives could not be prepared using the
method. All the selenochromenes 2A, 2B, 3 and 4 except
for 5 are hitherto unknown compounds except 2Bd.
Next, in order to obtain the 1-benzoselenopyrylium salts
having carbon functional groups at both the C-2 and C-4
positions, the reaction of the selenochromenes 2A with
+
-
triphenylcarbenium tetrafluoroborate (Ph C BF ) was
3
4
carried out. Treatment of 2-tert-butyl-4-methyl-
+
-
selenochromene 2Aa with 1.1 equivalents of Ph C BF
3
4
in nitromethane at room temperature afforded the desired
2-tert-butyl-4-methyl-1-benzoselenopyrylium tetrafluo-
roborate 6Aa in 80% yield as stable green prisms.
Application of the synthesis for the other 2,4-disubstituted
1-benzoselenopyrylium salt 6 was also successful. All salts
6a, 6b, 6c and 6d were isolated, quite stable and not sensi-
tive to air and light; but readily decomposed when in con-
tact with a protic solvent such as water and methanol. The

Mar-Apr 2002
Reaction of 1-Benzoselenopyrylium Salts with Grignard Reagents
407
results and the spectral data of the products 6 were listed in
have also observed that the 1-benzyl-2-benzotelluropy-
rylium salts 9 [8] could be isolated and exist in a solvent as
an equilibrium mixture of the salts 9 and the 1-benzylidene
compounds 10, which are the β–hydrogen eliminated com-
pounds of the salts 9. Thus, we suspect that the δ-hydrogen
elimination of the 4-benzyl-1-benzoselenopyrylium salts
Table 2. 2,4-Diphenyl-1-benzoselenopyrylium salt have
13
been obtained, but it is as the perchlorate, and no C nmr
spectral data for the known compound was given in the lit-
1
13
erature [5], so H nmr and C nmr spectral data of 6Bd
are included in Table 2.
-
It has been found that BF , the counter anion of the 1-
6c proceeds to form the 4-benzylideneselenochromenes
11. However, the 4-benzyl derivatives 6c could be isolated
as the stable crystalline products; the δ-hydrogen elimina-
tion did not occur.
In conclusion, the present results provide a facile synthetic
route for the preparation of the selenochromenes having gen-
4
benzotelluropyrylium salts 7A [11] and 1-benzoselenopy-
rylium salts 7B [12] having a primary alkyl group at the
C-2 position, abstracts the β–hydrogen of the methylene
carbon of the alkyl group forming the unstable exo-
methylidene compounds 8A and 8B. Furthermore, we

408
H. Sashida, M. Yoshida, H. Minamida and M. Teranishi
Vol. 39
The selenopyrylium salt 1 was treated with ethylmagnesium
bromide instead of methylmagnesium bromide and worked up as
described for the preparation of 2a to give 2b.
Reaction of 1-Benzoselenopyrylium Salts 1 with Benzyl-
magnesium Chloride.
The selenopyrylium salt 1 was treated with benzylmagnesium
chloride instead of methylmagnesium bromide and worked up as
described for the preparation of 2a to give 2c.
Reaction of 1-Benzoselenopyrylium Salts 1 with Phenyl-
magnesium Bromide.
The selenopyrylium salt 1 was treated with phenylmagnesium
bromide instead of methylmagnesium bromide and worked up as
described for the preparation of 2a to give 2d. Crystalline prod-
ucts 2Ad and 2Bd were recrystallized from acetone - n-hexane.
Reaction of 1-Benzoselenopyrylium Salts 1C with Methyl-
magnesium Bromide.
The selenopyrylium salt 1C was treated with methylmagne-
sium bromide and worked up as described for the preparation of
2a to give 3a, 4a and 5.
4-Methyl-4H-selenochromene (3a).
Compound 3a (25 mg) was obtained in 12% yield as a color-
less oil; H nmr (90 MHz, deuteriochloroform): 1.42 (3H, d, J = 7
Hz, 4-Me), 3.30 (1H, dq, J = 7, 6 Hz, 4-H), 6.27 (1H, dd, J = 6, 8
eral carbon functional groups at the C-2 and C-4 positions
and their conversion into the corresponding 1-benzose-
lenopyrylium salts. Further studies on not only the details
and utility of these selenopyrylium salts, but also the synthe-
sis of the other functionalized salts are now in progress.
1
Hz, 3-H), 6.87 (1H, d, J = 8 Hz, 2-H), 7.1-7.6 (4H, m, phenyl pro-
+
tons); high resolution mass m/z: M calcd for C
209.9948; found, 209.9947.
H Se,
10 10
2-Methyl-2H-selenochromene (4a).
EXPERIMENTAL
General Methods.
Compound 4a (13 mg) was obtained in 6% yield as a yellow
oil; H nmr (90 MHz, deuteriochloroform): 1.52 (3H, d, J = 7 Hz,
2-Me), 3.81 (1H, dq, J = 7, 5 Hz, 2-H), 5.72 (1H, dd, J = 5, 11 Hz,
1
3-H), 6.41 (1H, d, J = 11 Hz, 4-H), 6.9-7.5 (4H, m, phenyl pro-
Melting points were measured on a Yanagimoto micro melting
point hot stage apparatus and are uncorrected. The ir spectra were
recorded on a Hitachi 270-30 spectrometer. Mass and high reso-
lution mass spectra were recorded on a JEOL JMS-DX300
+
tons); high resolution mass m/z: M calcd for C
209.9948; found, 209.9951.
H Se,
10 10
2-Methyl-4H-selenochromene (5).
1
instrument. H nmr spectra were determined with a PMX-60SI
Compound 5 (11 mg) was obtained in 5% yield as a yellow oil.
This compound was identical with authentic sample [12].
(60 MHz), JEOL EX-90A (90 MHz) or JEOL JNM-GSX 400
(400 MHz) spectrometer in deuteriochloroform or deuterioace-
tonitrile using tetramethylsilane as an internal standard and J val-
ues are given in Hz. Microanalyses were performed in the
Microanalytical Laboratory of this Faculty.
Reaction of Selenopyrylium Salts 1C with Ethylmagnesium
Bromide.
The selenopyrylium salt 1C was treated with ethylmagnesium
bromide instead of methylmagnesium bromide and worked up as
described for the preparation of 2a to give 3b and 4b.
Reaction of 1-Benzoselenopyrylium Salts 1 with Methylmagne-
sium Bromide.
Methylmagnesium bromide (1.2 mmol) in ether solution (2
mL) was slowly added to a suspended mixture of the 1-benzose-
lenopyrylium salt 1 (1 mmol) in ether (5 mL) at 0 °C under an
argon atmosphere. The resulting mixture was stirred at room tem-
perature for 1 hour until the disappearance of the starting
selenopyrylium salt, and quenched by the addition of saturated
aqueous ammonium chloride solution (10 mL). The resulting
mixture was extracted with diethyl ether (30 mL x 3). The
organic extracts were washed with brine, dried over magnesium
sulfate and evaporated in vacuo. The residue was chro-
matographed on silica gel, with n-hexane as an eluent to give 2a.
4-Ethyl-4H-selenochromene (3b).
Compound 3b (25 mg) was obtained in 11% yield as a yellow
1
oil; H nmr (90 MHz, deuteriochloroform): 0.90 and 1.69 (3H, t,
J = 7 Hz, 2H, dq, J = 7, 7 Hz, 4-Et), 3.27 (1H, dt, J = 7, 7 Hz,
4-H), 6.30 (1H, dd, J = 6, 8 Hz, 3-H), 6.80 (1H, d, J = 8 Hz, 2-H),
6.9-7.5 (4H, m, phenyl protons); high resolution mass m/z: M
+
calcd for C H Se, 224.0104; found, 224.0097.
11 12
2-Ethyl-2H-selenochromene (4b).
Compound 4b (54 mg) was obtained in 24% yield as a yel-
1
low oil; H nmr (90 MHz, deuteriochloroform) 0.97 and 1.77
Reaction of 1-Benzoselenopyrylium salts 1 with Ethyl-
magnesium Bromide Salts.
(3H, t, J = 7 Hz, 2H, dq, J = 7, 7 Hz, 2-Et), 3.57 (1H, dt, J = 7,
6 Hz, 2-H), 5.75 (1H, dd, J = 6, 10 Hz, 3-H), 6.45 (1H, d, J = 10

Mar-Apr 2002
Reaction of 1-Benzoselenopyrylium Salts with Grignard Reagents
409
REFERENCES AND NOTES
E-mail: h-sashida@hokuriku-u.ac.jp Fax: +81(76)2292781.
Hz, 2-H), 6.9-7.5 (4H, m, phenyl protons); high resolution mass
+
m/z: M calcd for C H Se, 224.0104; found, 224.0099.
11 12
*
Reaction of Selenopyrylium Salts 1C with Benzylmagnesium
[1] This paper constitutes Part 17 in the series “Studies on
Tellurium-Containing Heterocycles” Part 16: ref. 13.
[2] G. Doddi and G. Ercolani, Advances in Heterocyclic
Chemistry: Thiopyrylium, Selenopyrylium and Telluropyrylium
Salts, Vol. 60. ed. A. R. Katritzky, Academic Press, Inc., London,
1994, pp. 65-195.
[3] A. T. Balaban, A. Dinculescu, G. N. Dorofeenko, G. W.
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Heterocyclic Chemistry: Pyrylium Salts: Synthesis, Reactions and
Physical Properties, Supplement 2, ed. A. R. Katrizky, Academic
Press, Inc., London, 1982.
Bromide.
The selenopyrylium salt 1C was treated with benzylmagne-
sium bromide instead of methylmagnesium bromide and worked
up as described for the preparation of 2a to give 3c and 4c.
4-Benzyl-4H-selenochromene (3c).
Compound 3c (52 mg) was obtained in 18% yield as a yellow
1
oil; H NMR (90 MHz, deuteriochloroform): 2.93 (2H, d, J = 8
Hz, CH Ph), 3.73 (1H, dt, J = 6, 8 Hz, 4-H), 6.24 (1H, dd, J = 6,
2
10 Hz, 3-H), 6.89 (1H, d, J = 10 Hz, 2-H), 6.9-7.5 (9H, m, phenyl
protons); high resolution mass m/z: M calcd for C
286.0261; found, 286.0240.
+
[4] I. D. Sadekov and V. Minkin, Advances in Heterocyclic
Chemistry: Developments in the Chemistry of Thiopyrans,
Selenopyrans and Telluropyrans, Vol. 59, Academic Press, 1994, pp.
179-244.
H Se,
16 14
2-Benzyl-2H-selenochromene (4c).
[5] I. Degani, R. Fochi, and C. Vincenzi, Gazz. Chim. Ital., 94,
451 (1964); Chem. Abstr., 61, 8275h (1964).
Compound 4c (40 mg) was obtained in 14% yield as a yellow
oil; H NMR (90 MHz, deuteriochloroform): 2.69 and 3.33 (each
1
[6] A. Tadino, L. Christiaens, and M. Renson, Bull. Soc. Roy.
Sci. Liege, 42, 129 (1973); Chem. Abstr., 79, 91965p (1973).
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[8] H. Sashida and K. Ohyanagi, J. Chem. Soc., Perkin Trans.
1, 2123 (1998).
1H, d, J = 8 Hz, CH Ph), 3.90 (1H, ddd, J = 6, 8, 8 Hz, 2-H), 5.67
2
(1H, dd, J = 6, 11 Hz, 3-H), 6.40 (1H, d, J = 11 Hz, 4-H), 7.0-7.5
+
(9H, m, phenyl protons); high resolution mass m/z: M calcd for
C H Se, 286.0261; found, 286.0236.
16 14
General Procedure for the Synthesis of the 2,4-Disubstituted 1-
[9] H. Sashida and K. Ohyanagi, Heterocycles, 51, 17 (1999).
[10] H. Sashida, Synthesis, 1866 (1999).
[11] H. Sashida and H. Minamida, J. Chem. Soc., Perkin Trans.
1, 1665 (1999).
[12] H. Sashida and H. Minamida, J. Chem. Res. (S), 569
(2000).
[13] H. Sashida, H. Minamida, and K. Yamamoto, J. Chem. Res.
(S), 572 (2000).
Benzoselenopyrylium Salts 6.
Triphenylcarbenium tetrafluoroborate (3.63 g, 11 mmol) was
added to a stirred solution of the selenochromene 2A, B (10
mmol) in dry nitromethane (20 mL) and the mixture was stirred
at room temperature for 30 minutes. To the reaction mixture was
added dry diethyl ether (ca. 200 mL) to precipitate the selenopy-
yrlium salt 6. All salts 6 were recrystallized from chloroform.
[14] H. Sashida, Synthesis, 745 (1998).
Acknowledgements.
[15] C. C. Price, M. Hori, T. Parasaran, and M. Polk, J. Am.
Chem. Soc., 85, 2278 (1963); H. Shimizu, S. Miyazaki, T. Kataoka,
M. Hori, and O. Muraoka, J. Chem. Soc., Perkin Trans. 1, 3129
(1994).
This work was supported by a Grant-in-Aid for Scientific
Reserch from Ministry of Education, Science, Sports and
Culture, Japan, and the Special Fund of Hokuriku University.