10.1002/ejoc.201900604
European Journal of Organic Chemistry
FULL PAPER
(Z)-N,4-dimethyl-N-(1-(5-methyl-1H-tetrazol-1-yl)-2-
phenylvinyl)benzenesulfonamide (4aa): White solid, m.p. 111.1-112.5 ˚C,
yield 21.0 mg, 19%; Rf = 0.17 (hexanes/EtOAc = 3/1); 1H NMR (CDCl3,
500 MHz): δ 7.71 (dd, J = 8.1, 1.1 Hz, 2H), 7.51-7.42 (m, 3H), 7.20 (d, J
= 8.2 Hz, 2H), 7.13 (d, J = 8.3 Hz, 2H), 6.45 (s, 1H), 3.19 (s, 3H), 2.77 (s,
3H), 2.39 (s, 3H); 13C NMR (CDCl3, 125.8 MHz): δ 153.1, 146.9, 144.7,
134.3, 130.6, 130.4, 129.9, 129.22, 129.19, 127.6, 126.8, 37.0, 21.6, 9.4.
HRMS (ESI) m/z calcd for C18H20N5O2S (M+H)+ 370.1332, found
370.1336.
Acknowledgments
Scheme 3. The Proposed Reaction Mechanism for the Formation of 3aa and
4aa.
We are grateful to the foundations from NSFC (21402106) and
the Project-sponsored by SRF for ROCS, SEM (20141685). We
also acknowledge the support provided by Shandong Natural
Science Foundation (ZR2018JL013 and ZR2018MB014) and
Higher Educational Science and Technology Program
(J15LA02). X. Meng acknowledges the support from Qufu
Normal University for Research Start-up Foundation.
Conclusions
In summary, a novel metal-free hydroheteroarylation reaction of
ynamides with tetrazoles has been developed to achieve the
direct synthesis of a variety of functionalized (Z)-α-tetrazol
enamide products. The reaction could proceed efficiently with
Keywords: Metal-free • Hydroheteroarylation • Ynamide •
Tetrazole • Enamide
complete
regio-
and
stereo-selectivities,
and
good
chemoseletivities. It should be noted that 2H-tetrazoles play two
key roles as the Brönsted acids and nucleophiles. The possible
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mechanism was proposed to be going through
a key
keteniminium intermediate under the acidic conditions. The
features of the present transformations contain metal-free
conditions, easily handled operations and high yields for the
synthesis of (Z)-α-tetrazol enamides. This extra catalyst-free
condition makes current reaction very advantageous for the
modifications and screening of pharmaceutical products. Next
works will focus on the investigations of potentially bioactive
molecules and expansions of the reaction strategy.
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Experimental Section
Typical procedure for the direct synthesis of (Z)-α-tetrazol enamides 3aa
and 4aa: to a stirred solution of ynamide 1a (85.6 mg, 0.3 mmol) in DCE
(3 mL) was added 2H-tetrazole 2a (37.8 mg, 0.45 mmol, 1.5 equiv) in air.
The resulting mixture was placed into preheated oil bath of 80 ˚C,
monitored by thin layer chromatography (TLC) analysis, generally for 2
hours. Upon the completion of reaction, the mixture was cooled to room
temperature, followed by the solvent was removed by a rotary evaporator
under reduced pressure. The residue was subjected to column
chromatography (eluent: ethyl acetate/petrol ether = 1/10~1/3) to afford
the pure N-2 and N-1 adducts (3aa and 4aa), respectively.
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(Z)-N,4-dimethyl-N-(1-(5-methyl-2H-tetrazol-2-yl)-2-
phenylvinyl)benzenesulfonamide (3aa): White solid, m.p. 110.9-111.8 ˚C,
yield 89.7 mg, 81%; Rf = 0.37 (hexanes/EtOAc = 3/1); 1H NMR (CDCl3,
500 MHz): δ 7.71 (dd, J = 7.9, 2.3 Hz, 2H), 7.49 (d, J = 8.3 Hz, 2H), 7.43-
7.38 (m, 3H), 7.37 (s, 1H), 7.19 (d, J = 8.0 Hz, 2H), 3.31 (s, 3H), 2.23 (s,
3H), 2.21 (s, 3H); 13C NMR (CDCl3, 125.8 MHz): δ 162.5, 144.1, 135.3,
131.3, 130.6, 130.0, 129.7, 129.3, 128.9, 127.3, 126.4, 37.1, 21.6, 10.8.
HRMS (ESI) m/z calcd for C18H20N5O2S (M+H)+ 370.1332, found
370.1335.
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