Flow Equipment
The technical drawings for the prototype development of the static mixer were created using the AutoCAD software from Autodesk. The static mixer was 3D printed in stainless steel 1.4404 (316L/V4A) at the d3d Manufacturing GmbH (Baindt, Germany) using the selective laser melting (slm) process. Threads and sealing surfaces were machined afterwards. Steel capillaries with an outer diameter of 1/16″ and an inner diameter of 1.0 mm consisting of stainless steel 1.4404 (316L/V4A) were used, which were purchased from TECHLAB. PTFE tubing with an AD (1/4″) and ID (1/8″) was purchased from Bohlender and PEEK capillaries AD (1/16″) and ID (1.0 mm) from BGB and cut to the required lengths. All solutions were pumped with Fusion 4000 pumps from CHEMYX and high-pressure glass syringes from CETONI in volumes of 10, 25, 50 mL. Flow microreactor systems were dipped in individual bath to control the temperature. The syringe holders for the syringe pump were designed according to the requirements and 3D printed at JOMANTIK in Alumide.
General procedure A:
Continuous flow synthesis for the preparation of single homologated boronic esters All single homologations was carried out with the setup shown in scheme 3. The developed static mixer also represents the reactor with a volume of 60 µL. Stainless steel capillaries 1/16” (ID = 1 mm) were used for all connections. All solutions were pumped using Fusion 4000 pumps from CHEMYX. A precooled stream (coiled cooling loop VR = 1.00 mL, l = 127.4 cm) containing the boronate (0.1 M in THF, 14.72 mL/min, 1.00 eq.) and ClBrCH2 (1.50 eq.) was combined with a precooled stream (coiled cooling loop VR = 1.00 mL, l = 127.4 cm) containing Table 2: Residence time optimization of 1,2-aniotropic rearrangement. Yields determined via GC using internal standard. S-18 nBuLi (1.5 M in hexane, 1.28 mL/min, 1.30 eq.) in a static mixer. The mixture was reacted at – 40 °C for 225 ms (VR = 60 µL, V̇ total = 15.98 mL/min) before the stream was directed to an electrically heated water bath at 40 °C for 9 s (VR = 2.40 mL, l = 305.7 cm). To ensure that the system was in a steady state mode, the system was flushed for 30 s (approx. 6 reactor volumes) before sampling was started. The resulting stream was dropped into a saturated aqueous solution of NH4Cl and extracted with Et2O. The combined organic phases were washed with brine, dried over MgSO4, filtered and the solvents were removed under reduced pressure. The crude residue was purified by column chromatography (silica gel; pentane:Et2O 100:1) to yield the homologated boronates 5a-h.
Read the full article here: The Matteson reaction under flow conditions – iterative homologations of terpenes
Authors: Conrad Kuhwald and Andreas Kirschning* Institute of Organic Chemistry, Leibniz University Hannover, Schneiderberg 1B, 30167 Hannover, Germany