A flow chemistry
process for the generation and use of acylketene
precursors through extrusion of nitrogen gas is reported. Key to the
development of a suitable continuous protocol is the balance of reaction
concentration against pressure in the flow reactor. The resulting
process enables access to intercepted acylketene scaffolds using volatile
amine nucleophiles and has been demonstrated on the gram scale. Thermal
gravimetric analysis was used to guide the temperature set point of
the reactor coils for a variety of acyl ketene precursors. The simultaneous
generation and reaction of two reactive intermediates (both derived
from nitrogen extrusion) is demonstrated.