Reductive alkylation of pentaphenylthiopyrylium perchlorate: An approach to regiospecific synthesis of hexasubstituted 2H-thiopyrans

Article abstract of DOI:10.1080/10426500802713275

Regiospecific synthesis of some new hexasubstituted 2H-thiopyrans was examined by reductive alkylation of pentaphenylthiopyrylium perchlorate and found to be in quantitative yields. Under our experimental conditions, the formation of unstable thiabenzene

Full text of DOI:10.1080/10426500802713275

Phosphorus, Sulfur, and Silicon, 185:84–87, 2010
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802713275
REDUCTIVE ALKYLATION OF
PENTAPHENYLTHIOPYRYLIUM PERCHLORATE:
AN APPROACH TO REGIOSPECIFIC SYNTHESIS
OF HEXASUBSTITUTED 2H-THIOPYRANS
Arash Mouradzadegun, Fatemeh Ghasem Hezave,
and Maryam Karimnia
Department of Chemistry, Faculty of Science, Shahid Chamran University,
Ahvaz, Iran
Regiospecific synthesis of some new hexasubstituted 2H-thiopyrans was examined by reduc-
tive alkylation of pentaphenylthiopyrylium perchlorate and found to be in quantitative yields.
Under our experimental conditions, the formation of unstable thiabenzene intermediates
could be observed through detectable color changing during the addition of C-nucleophiles
to thiopyrylium perchlorate. Moreover, the effect of phenyl groups on the 3,5-positions of
thiopyrylium perchlorate on the regioselectivity were compared with other analogs having
methyl groups on the same positions.
Keywords C-Nucleophile; pentaphenylthiopyrylium; reductive alkylation; 2H-thiopyrans
INTRODUCTION
Thiopyrylium salts with a large number of technological applications have been in-
vestigated extensively.1 These salts are, in general, capable of accepting nucleophiles by
addition at position 2, 4, or 6 giving the corresponding 2H- and 4H-thiopyran derivatives
in agreement with HMO reactivity indices.2 The earliest nucleophilic addition is the reac-
tion of thiopyrylium with organometallic reagents. Contrary to the reaction with Grignard
reagents, where no unambiguous evidence concerning the formation of thiabenzene in-
termediates is available, organolithium nucleophiles added selectively to thiopyrylium by
the attack at sulfur to give colored unstable thiabenzene intermediates,3 which undergo
rearrangement to 2H- and 4H-thiopyrans adducts with an apparently unpredictable regios-
electivity4–6 (Scheme 1).
The results of a mechanistic investigation of the rearrangement indicate an intramolec-
ular shift that involves a 1,2- or 1,4-migration of the sulfur substituents.7 According to
Scheme 1, if the R, R1, and R3 are all alkyl in structure I, the reaction proceeds rapidly
Received 1 September 2008; accepted 26 December 2008.
Thanks are due to Prof. H. Pirelahi for his help. Partial support of this investigation by the Research Council
at the University of Shahid Chamran is gratefully acknowledged.
Address correspondence to Arash Mouradzadegun, Department of Chemistry, Faculty of Science, Shahid
Chamran University, Ahvaz, Iran. E-mail: arash m@scu.ac.ir
84

HEXASUBSTITUTED 2H-THIOPYRANS
85
Scheme 1
at room temperature unselectively. 2,4,6-Triphenylthiopyrylium salt (R2 H) reacts less
rapidly with organometallic reagents, and the reaction time takes into account the rear-
rangement of the intermediate.8,9 Although the reaction shows good regioselectivity with
organolithiums8,9 (only 4H- or with more reactive reagents; only 2H-thiopyrans obtained),
it exhibits different regioselectivity toward Grignard reagents. The involvement of bulky
groups R2, e.g., the replacement of a hydrogen atom by methyl, also increases the rate of re-
arrangement and alters the regioselectivity depending on the nature of the C-nucleophiles.10
Following our studies on the chemistry and synthesis of thiopyrylium and thiopyrans deriva-
tives,11–15 and in order to obtain a better view on the competition of 2H- vs. 4H-thiopyran in
the reaction of organometallics with thiopyrylium salts, herein we undertake a systematic
examination of reductive alkylation of 2,3,4,5,6-pentaphenylthiopyrylium perchlorate in
the presence of various alkyl C-nucleophiles. Such a model should provide further insight
into the probable rearrangement and regioselectivity, and would also furnish an access to
new steric crowding of thiopyrans.
RESULTS AND DISCUSSION
Treatment of a molar equivalent of an ethereal MeMgBr solution with 0.001 mol
of pentaphenyl thiopyrylium perchlorate in dry ether under an argon atmosphere at room
temperature gave a red solution that faded when stirred. Workup of the reaction mix-
ture furnished 2-methyl-2,3,4,5,6-pentaphenyl-2H-thiopyran IIIa and 4-methyl-2,3,4,5,6-
penatphenyl-4H- thiopyran IVa in the ratio of 3:1 according to 1H NMR spectra. Based on
the theory that 2H-thiopyrans are thermodynamically more stable and the 4H-thiopyrans
are kinetic products, we decide to run this reaction under other temperature conditions.
At –20◦C, the same products were obtained in a new ratio of 2.5:1, while the reaction
under reflux showed high regioselectivity and gave 2H-thiopyran IIIa as the sole prod-
uct, though faster changing in color. Under identical experimental conditions, MeLi also
exhibited the same behaviors, and the only difference was a small relative increase of
the 4H-thiopyran. Addition of an equivalent ethereal solution of EtMgBr to 0.001 mol of
pentaphenyl thiopyrylium perchlorate under the same conditions afforded only 2-ethyl-
2,3,4,5,6-pentaphenyl-2H-thiopyan IIIb, though color changing from orange red to color-
less, where no evidence for formation of 4H-isomer could be observed. When an equivalent
of n-BuLi and t-BuMgCl ethereal solution was treated with 0.001 mol of pentaphenyl
thiopyrylium perchlorate under the above conditions, the same results, as EtMgBr had,
were obtained in which only 2-n-butyl-2,3,4,5,6-pentaphenyl-2H-thiopyran IIIc and 2-t-
butyl-2,3,4,5,6-pentaphenyl-2H-thiopyran IIId could be isolated according to spectral data.

86
A. MOURADZADEGUN ET AL.
The reaction clearly showed good regiospecificity, while in the latter case, no detectable
color changing could be observed as it has been expected from pervious report.3 Unusual
behavior of Grignards MeMgBr and EtMgBr by typical color changing for the formation
of thiabenzene, which could also be observed for analogous that having methyl groups in
3,5-positions,10bb may be expressed by the steric and electronic effect. Regiospecific for-
mation of hexasubstituted 2H-thiopyrans and the disappearance of 4H-isomers in the case
of pentaphenylthiopyrylium perchlorate, however, are contrast sharply with those analogs
that contain methyl groups on the 3,5-positions.
In conclusion, our experimental findings revealed that the thermodynamically more
stable hexasubstituted 2H-thiopyrans IIIa–d were easily prepared in high yields as the
sole products of reductive alkylation of pentaphenylthiopyrylium perchlorate, whereas for
other analogs having methyl groups on the 3,5-positions, the reaction did not show this
regiospecificity.10bb Although the isolation of thiabenzene intermediate was not successful
in any case, the characteristic color changing during the reaction showed that, with the
exception of using t-BuLi, in all other cases the formation of hexasubstituted 2H-thiopyrans
from the direct attack to 2- and 6-positions might be associated with a rearrangement of the
corresponding thiabenzene intermediates.
EXPERIMENTAL
Chemicals were purchased from Fluka, Merck, and Aldrich chemical companies.
All yields refer to isolated products. Monitoring of the reactions was accomplished by
TLC. Melting points were determined on a Gallenkamp melting point apparatus and are
1
uncorrected. HNMR spectra were recorded on 400 MHz Brucker using CDCl3 as the
solvent and TMS as the internal standard. Mass spectra were measured with a Varian
MAT-311A spectrometer.
Syntheses
Pentaphenylthiopyrylium perchlorate was synthesized from the corresponding
pyrylium perchlorate, which is prepared from benzaldehyde and desoxybenzoine by
the method previously described.16,17 The new hexasubstituted 2H-thiopyrans and 4H-
thiopyran were synthesized by the reaction of Grignard reagents (RMgX; R Me, Et, t-Bu;
X Br, Cl) and/or RLi (R Me, Bu) with equimolar pentaphenylthiopyrylium perchlorate
according to the reported method.7,10b The products were isolated by chromatography on
neutral alumina and recrystallized from alcohol.
General Procedure
Addition of an equivalent ethereal solution of different organometallic reagents to
0.001 mol of pentaphenyl thiopyrylium perchlorate in dry diethyl ether (50 mL) under an
argon atmosphere at the different temperature conditions (–20◦C, 25◦C, and reflux) was
monitored by the color changing in the reaction mixture and TLC. After completion, when
a red to orange solution faded upon stirring, the reaction was stopped by the addition of
a saturated solution of NH4Cl (20 mL). The ethereal phases were separated, dried over
CaCl2, and finally evaporated under vacuum. Then the residue was purified by PLC using
petroleum ether or/and recrystallized from suitable alcohols.

HEXASUBSTITUTED 2H-THIOPYRANS
87
2-Methyl-2,3,4,5,6-pentaphenyl-2H-thiopyran (IIIa). Yellow crystals, mp
205–206◦C (from amyl alcohol); m/z 492 (M.+ 100%), 477 (4.50), 445 (61.00), 166 (4.60);
UV, λ max (CHCl3) nm (log ε): 355.4 (3.98), 249.6 (4.65); 1H NMR (C6D6), δ: 1.51 (3H,
s, Me), 6.43–7.31 (25H, m, ArH), yield 83%.
2-Ethyl-2,3,4,5,6-pentaphenyl-2H-thiopyran (IIIb). Yellow crystals, mp
145–146◦C (from EtOH); m/z 506 (M.+ 100%), 477 (5.45), 445 (56.36), 352 (4.54), 166
1
(4.61); UV, λ max (EtOH) nm (log ε): 351 (4.21), 248.6 (4.96); H NMR (C6D6), δ:
1.13–1.32 (3H, t, Me), 2.36–2.60 (2H, q,CH2), 6.76–7.39 (25H, m, ArH), yield 75%.
2-n-Butyl-2,3,4,5,6-pentaphenyl-2H-thiopyran (IIIc). Yellow crystals, mp
81–82◦C (from EtOH); m/z 534 (M.+ 16.6%), 477 (41.90), 34 (100); UV, λ max (EtOH)
1
nm (log ε): 345 (3.98), 246.6 (4.22); H NMR (C6D6), δ: 0.84–1.47 (7H, m, n-Pr),
2.40–2.60 (2H, t, CH2), 6.66–7.39 (25H, m, ArH), yield 73%.
2-t-Butyl-2,3,4,5,6-pentaphenyl-2H-thiopyran (IIId). Yellow crystals, mp
92–93◦C (from EtOH); m/z 534 (M.+ <1%), 477 (100), 401 (14.76), 166 (5.71), 121
1
(6.95), 57 (10.47); UV, λ max (EtOH) nm (log ε): 332.2 (3.60), 263 (3.91); H NMR
(C6D6), δ: 1.13–1.19 (9H, s, Me), 6.26–8.31 (25H, m, ArH), yield 78%.
REFERENCES
1. G. Doddi and G. Ercloni, Advances in Heterocyclic Chemistry, Vol. 60 (Academic Press, New
York, 1994).
2. J. Koutecky, Collect. Czech. Chem. Commun., 24, 1608 (1959).
3. H. Pirelahi and C. C. Price. J. Org. Chem., 37, 1718 (1972).
4. G. Suld and C. C. Price, J. Am. Chem. Soc., 84, 2090 (1962).
5. F. Ogura, W. D. Hounshell, C. A. Maryanoff, W. J. Richter, and K. Mislow, J. Am. Chem. Soc.,
98, 3615 (1976).
6. C. A. Maryanoff, K. S. Hayes, and K. Mislow, J. Am. Chem. Soc., 99, 4412 (1977).
7. H. Pirelahi and H.Haghgooii, J. Heterocycl. Chem., 16, 917 (1979).
8. J. Follwieler, H. Pirelahi, and M.Siskia. J. Org. Chem., 36, 791 (1971).
9. H. Pirelahi, Y. Abdoh, and M. Tavassoli, J. Heterocycl. Chem., 14, 199 (1977).
10. (a) B. G. Maryanoff, J. Stackhouse, G. H. Senkler, and K. Mislow, J. Am. Chem. Soc., 97, 2718
(1975); (b) H. Rahmani and H. Pirelahi, Sulfur Lett., 20(4), 159 (1997).
11. (a) A. Mouradzadegun and N. Gheitasvand, Phosphorus, Sulfur, and Silicon, 180(5–6),
1385–1388 (2005); (b) A. Mouradzadegun and N. Gheitasvand, Iranian Chemistry and
Chemical Engineering Congress Abstracts (2004), p. 434.
12. A. Mouradzadegun and H. Pirelahi, J. Photochem., Photobiol. A: Chem., 138, 203–205 (2001).
13. A. Mouradzadegun and H. Pirelahi, Phosphorus, Sulfur, and Silicon, 165, 149–164 (2000).
14. A. Mouradzadegun and H. Pirelahi, Phosphorus, Sulfur, and Silicon, 157, 193–199 (2000).
15. H. Pirelahi, H. Rahmani, A. Mouradzadegun, A. Fathi, and A. Mooudjoodi, J. Photochem.,
Photobiol. A: Chem., 101, 33 (1996).
16. M. Simalty and J. Carretto, Bull. Soc. Chim. Fr., 2959 (1966).
17. P.-L. Desbene, J.-C. C. Cherton, J.-P. Le Roux, and J.-J. Basselier, Tetrahedron, 40, 2718 (1984).

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