8 research outputs found
Replication Data for: Asymmetric Evaluations: Government Popularity and Economic Performance in the United Kingdom
Replication data and code for: "Asymmetric Evaluations: Government Popularity and Economic Performance in the United Kingdom
Continuous Flow Synthesis of a Key 1,4-Benzoxazinone Intermediate via a Nitration/Hydrogenation/Cyclization Sequence
The
preparation of a functionalized 4H-benzo-[1,4]-oxazin-3-one
was completed via a three-step nitration/hydrogenation/cyclization
sequence. The unstable nature of the nitro and amino intermediates,
in addition to the hazards associated with the nitration of organic
compounds in general, makes this procedure exceedingly difficult to
perform on industrial scale. To overcome these limitations, we have
developed a fully integrated continuous protocol in which the aromatic
starting material (2,2-difluoro-2-(3-fluorophenoxy)-<i>N</i>,<i>N</i>-dimethylacetamide) is subjected to an initial
continuous flow dinitration using 20% oleum in combination with 100%
HNO<sub>3</sub> (2.5 equiv) using a microstructured device heated
to 60 °C. This was followed directly by continuous flow hydrogenation
of the dinitrointermediate over a Pd/C fixed bed catalyst at 45 °C.
The resulting air-sensitive diamino derivative was then directly cyclized
to the desired 6-amino-2,2,7-trifluoro-4H-benzo-[1,4]-oxazin-3-one
target compound via an acid-catalyzed cyclization step at 80 °C
using a tubular reactor. Uninterrupted continuous flow processing
was achieved by integrating liquid–liquid membrane separation
technology and the inline removal of excess of hydrogen gas using
gas permeable tubing into the process. The overall product yield for
the continuous flow process was 83%, a significant increase compared
to yield reported for the batch process (67%)