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(14) Trapping of Transient Thienyllithium 4 in a Flow Microreac-
tor; General Procedure The flow reactor system consisted of
two micromixers [Mixer 1 (T-shaped micromixer; = 500 m)
and Mixer 2 (T-shaped micromixer; = 250 m)], two micro-
tube reactors [Microtube 1 ( = 1000 m, L = 25 cm) and Micro-
tube 2 ( = 1000 m, L = 200 cm)], and three tube precooling
units [Precooling Unit 1 ( =1000 m, L = 100 cm), Precooling
Unit 2 ( = 1000 m, L = 50 cm), and Precooling Unit 3 ( = 1000
m, L = 50 cm)]. A 0.075 M solution of 2,3-dibromothiophene
(1) in THF (flow rate: 6.00 mL min–1) and a 0.60 M solution of
LDA in THF (flow rate: 1.50 mL min–1) were introduced into
Mixer 1 by syringe pumps. The resulting mixture passed
through Microtube 1 and was mixed with a 0.30 M solution of
the appropriate electrophile in THF (flow rate: 3.00 mL min–1) in
Mixer 2. The resulting solution then passed through Microtube
2. Once a steady state was reached (60 s), the product solution
was collected for 240 s, while being quenched with sat. aq
NH4Cl. The layers were separated, and the aqueous layer was
extracted with Et2O. The combined organic extracts were
washed with H2O and brine, dried (Na2SO4), and filtered. The
filtrate was concentrated under reduced pressure to provide a
crude product that was purified by column chromatography
(silica gel).
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(15) An NOE enhancement was observed between the aromatic
proton on the thiophene ring and the methine proton.
(16) 1-(4,5-Dibromo-2-thienyl)cyclohexanol (8c)
Colorless prisms; yield: 475.6 mg (78%); mp 80–81 °C (hexane);
Rf = 0.31 (hexane–CH2Cl2, 1:1). IR (ATR): 3348, 2927, 2854, 1445,
1305, 1158, 1131, 1000, 970, 814, 796 cm–1. 1H NMR (400 MHz,
CDCl3): = 6.76 (s, 1 H), 2.03 (s, 1 H), 1.91–1.55 (m, 9 H), 1.36–
1.23 (m, 1 H). 13C{1H} NMR (100 MHz, CDCl3): = 156.1, 124.8,
113.0, 109.5, 72.7, 39.6, 25.3, 22.2. Anal. calcd for C10H12Br2OS:
C, 35.32; H, 3.50. Found: C, 35.29; H, 3.39.
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(17) CCDC 2020290 contains the supplementary crystallographic
data for compound 8c. The data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via
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sized 8d were not consistent with those reported by Knochel
(ref. 10).
(19) For details, see the Supporting Information.
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© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–F