β-Carbonyl Phenyltetrazolesulfones
ganic phase was dried with Na2SO4. Removal of the solvent gave
product 4 of high purity (Ͻ5% impurities). Recrystallisation was
effected by dissolving the crude product in hot toluene or CH2Cl2
(1–2 mL), filtering the solution through glass wool and layering
the solution with iPr2O (ca. 2 mL) and hexane (ca. 10 mL). After
standing overnight, the mother liquor could be decanted and the
pure product dried under high vacuum.
rated aldehydes. Since the reaction mechanism seems to re-
quire acid-catalysed enol formation, lone-pair-donating R1
substituents, such as the 2-MeOC6H4 and 4-MeOC6H4
groups, can explain a slower reaction, due to less enol for-
mation. Electron-withdrawing substituents on the other
hand may decrease the nucleophilicity of the formed enol,
again resulting in a slower reaction, as observed in the small
decrease in reactivity of 4c vs. 4a.
Interestingly, the benzothiazole derivatives 4k,l have sim-
ilar dihedral angles and NMR and IR spectroscopic data
as the most reactive phenyltetrazole compounds, but show
only minimal reactivity. We attribute this discrepancy to
stereoelectronic differences of phenyltetrazole and benzo-
thiazole moieties, apparently not evident in any of these ex-
1-Phenyl-2-(1-phenyl-1H-tetrazol-5-ylsulfonyl)ethanone (4a): Ac-
cording to the general procedure, compound 4a was obtained in
91% yield (70% yield after recrystallisation from toluene and
iPr2O) as a colorless crystalline solid (m.p. 86–89 °C). 1H NMR
(CDCl3): δ = 7.88 (d, J = 7.8 Hz, 2 H, ar-H), 7.80–7.56 (m, 6 H,
ar-H), 7.51 (t, J = 7.8 Hz, 2 H, ar-H), 5.32 (s, 2 H, 8-H) ppm. 13C
NMR (CDCl3): δ = 186.8, 153.6, 135.0, 134.8, 132.9, 131.5, 129.5
(2 C), 129.1 (2 C), 128.6 (2 C), 125.7 (2 C), 62.1 (1 C, C-8) ppm.
perimental data. Whereas these compounds are not suitable IR (Nujol): ν˜ = 3065, 2961, 2915, 1687 (s), 1595, 1580, 1497, 1449,
1356 (s), 1301, 1212, 1158, 1015, 982, 885, 823, 754, 686 cm–1.
for the β-alkynylation and β-alkenylation of α,β-unsatu-
HRMS: calcd. for C15H12N4NaO3S [M + Na] 351.0528; found
rated aldehydes, they are successfully employed in a range
of analogous reactions.[6]
351.0536.
Supporting Information (see footnote on the first page of this arti-
cle) Additional experimental details and full characterization of all
new compounds.
Conclusions
A practical synthesis of β-carbonyl phenyltetrazolesul-
Acknowledgments
fones has been devised. In general, high yields were ob-
tained (up to 99%), and the products were isolated with
high purity after a single recrystallization. Furthermore, X-
ray crystallography, kinetic studies and NMR and IR spec-
tral investigations have provided a number of insights of
the internal properties of these compounds. Besides the α-
methylated compound 4g, all other β-carbonyl phenyl-
tetrazoles 4a–j were found to be reactive in the organocata-
lytic addition to pentenal, demonstrating again the broad
applicability of this reaction.[3h] Correlation between reac-
tivity and analytical data has been observed and provides
insight into both the steric and electronic effects governing
the reactivity of these compounds.
This work was made possible by grants from Carlsberg Founda-
tion, and OChemSchool. T. Z. thanks the Swiss National Science
Foundation for a fellowship.
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Experimental Section
General Procedure for the Formation of β-Carbonyl Phenyltetraz-
[2] See, e.g.: a) K. Chen, P. S. Baran, Nature 2009, 459, 824; b) M.
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olesulfones 4a–j: The respective α-halocarbonyl compound
2
(1.0 mmol) was dissolved in CH2Cl2 (5 mL), and 1-phenyl-1H-
tetrazole-5-thiol (1.1 mmol, 1.1 equiv.) was added. Then Et3N
(1.1 mmol, 1.1 equiv.) was added slowly. The reaction mixture was
stirred for 10–60 min and monitored by TLC. Upon consumption
of 2, the organic phase was washed with 2 m HCl and satd. aq.
Na2CO3. The organic phase was concentrated, and the crude sul-
fide 3 used without further purification in the next step. Finely
crushed periodic acid (3.0 mmol, 3 equiv.) was suspended in MeCN
(5 mL) and the mixture stirred for 30 min until a clear solution was
obtained. CrO3 (0.1 mmol, 0.1 equiv.) was added. Then the sulfide
3 was added as a solid. Immediate formation of a precipitate was
observed. Alternatively, periodic acid and 3 were premixed and
stirred for 30 min before addition of CrO3. The reaction was moni-
tored by 1H NMR spectroscopy and/or TLC and was complete
after 10–45 min. A pad of Celite (8 cm in diameter and 5 cm in
height) was wetted with pentane. Then water (25 mL) was added
to the MeCN solution and the mixture adsorbed to the Celite. The
adsorbed product was washed with pentane (75 mL), and then the
product was washed off the Celite with CH2Cl2 (250 mL). The or-
Eur. J. Org. Chem. 2011, 47–52
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