Molecules 2019, 24, 2116
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but both were titrated (acid-base and iodometric), since the exact concentration can differ from the
labeled one, especially for NaOCl. This concentration also diminishes over time, even when refrigerated.
Anhydrous Na SO was bought from Fisher Scientific and a stock solution was made in water (200 g/L).
2
3
3
.2. 2,4,6-Tribromophenol (Table 1, Entry 1)
Phenol was purchased from Acros Organics and used without any purification. The reactor was
built as depicted in Figure 1. Both reactor 1 and 3 had an ID of 1 mm and a volume of 3 mL, but reactor
◦
2
had an ID of 2.4 mm and a volume of 50 mL. Reactor 2 was placed in a 50 C water bath. The HBr
and NaOCl were titrated to find a concentration of 8.89 M for HBr and 1.45 M for NaOCl. A phenol
solution of 0.194 M in CHCl was made, as well as a solution of 200 g/L Na SO in H O. The latter
3
2
3
2
three solutions were pumped by the peristaltic pumps of the Vapourtec E-series (VapourTec Ltd, Bury
Saint Edmunds, UK), while the HBr was loaded in a syringe and placed on a Chemyx Fusion 100
syringe pump (Chemyx Inc, Stafford, TX, USA). The flow rates were 0.196 mL/min for HBr (9 eq.),
0
.804 mL/min for NaOCl (6 eq.), 1 mL/min for phenol (1 eq.), and 1.468 mL/min for Na SO (12 eq.).
2 3
This resulted in a residence time of 25 min in reactor 2, the bromination reactor. After running the
reaction for three complete residence times, the outlet was collected for 30 min.
The two phases were separated, and the water phase was extracted with 3
×
50 mL CHCl3.
All organic phases were combined, dried with MgSO , filtrated, and evaporated in vacuo. Drying
4
under a high vacuum yielded 1.83 g of pure 2,4,6-tribromophenol (yield = 95%). Purity was confirmed
by liquid chromatography-mass spectrometry (LC–MS) (Agilent Technologies, Santa Clara, CA, USA)
1
13
and nuclear magnetic resonance spectroscopy (NMR), both H-NMR and C-NMR (Bruker, Billerica,
MA, USA). These spectra can be found in the Supporting Information.
0
0
3
.3. 2,2 ,6,6 -Tetrabromobisphenol A (Table 1, Entry 2)
Bisphenol A was purchased from Sigma-Aldrich (St. Louis, MO, USA) and used without any
purification. The reactor was built as depicted in Figure 1. All tubing had an internal diameter of 1 mm,
and the three reactors had volumes of 2, 10, and 3 mL respectively. The HBr and NaOCl were titrated
to find a concentration of 8.89 M for HBr and 1.45 M for NaOCl. A bisphenol A solution of 0.233 M
in Et O was made, as well as a solution of 200 g/L Na SO in H O. The latter three solutions were
2
2
3
2
pumped by the peristaltic pumps of the Vapourtec E-series, while the HBr was loaded in a syringe and
placed on a Chemyx Fusion 100 syringe pump. The flow rates were 0.393 mL/min for HBr (7.5 eq.),
1
.61 mL/min for NaOCl (5 eq.), 2 mL/min for bisphenol A (1 eq.), and 2.94 mL/min for Na SO (10 eq.).
2 3
This resulted in a residence time of 2 min and 30 s in reactor 2, the bromination reactor. After running
the reaction for three complete residence times, the outlet was collected for 10 min.
The two phases were separated, and the water phase was extracted with 3
×
50 mL Et O. All organic
2
phases were combined, dried with MgSO , filtrated, and evaporated in vacuo. Drying under a high
4
0
0
vacuum yielded 2.10 g of pure 2,2 ,6,6 -tetrabromobisphenol A (yield = 83%). A perfect selectivity was
obtained, while incorrect parameters resulted in the degradation of the carbon skeleton and production
1
13
of tribromophenol (
δ = 7.64). Purity was confirmed by LC–MS, H-NMR.and C-NMR. These spectra
can be found in the Supporting Information.
3
.4. 1,2,5,6,9,10-Hexabromocyclododecane (Table 1, Entry 3)
E,E,Z)-1,5,9-cyclododecatriene was bought from Fisher Scientific and used without any
(
purification. The reactor was built as depicted in Figure 1. All tubing had an internal diameter
of 1 mm, and the three reactors had volumes of 0.4, 1, and 1 mL respectively. Reactor 2 was cooled
by an ice/water bath to prevent overbromination forming hepta- and octabromocyclododecane.
The HBr and NaOCl were titrated to find a concentration of 9.16 M for HBr and 1.31 M for
NaOCl. An (E,E,Z)-1,5,9-cyclododecatriene solution of 0.107 M in a 1/2 mixture of cyclohexane
and dichloromethane was made, as well as a solution of 200 g/L Na SO in H O. All reagents were
2
3
2
loaded in syringes, but while the HBr, NaOCl and Na SO were pumped by Chemyx Fusion 100
2
3