Cyclocondensation of Arylhydrazines with 1,3-Bis(het)arylmonothio-1,3-diketones and 1,3-Bis(het)aryl-3-(methylthio)-2-propenones: Synthesis of 1‑Aryl-3,5-bis(het)arylpyrazoles with Complementary Regioselectivity

Two
efficient highly regioselective routes for the synthesis of unsymmetrically
substituted 1-aryl-3,5-bis­(het)­arylpyrazoles with complementary regioselectivity
starting from active methylene ketones have been reported. In the
first protocol, the newly synthesized 1,3-bis­(het)­aryl-monothio-1,3-diketone
precursors (prepared by condensation of active methylene ketones with
het­(aryl) dithioesters in the presence of sodium hydride) were reacted
with arylhydrazines in refluxing ethanol under neutral conditions,
furnishing 1-aryl-3,5-bis­(het)­arylpyrazoles 7, in which
the het­(aryl) moiety attached to the thiocarbonyl group of monothio-1,3-diketones
is installed at the 3-position. In the second method, the corresponding
3-(methylthio)-1,3-bis­(het)­aryl-2-propenones (prepared in situ by
base-induced alkylation of 1,3-monothiodiketones) were condensed with
arylhydrazines in the presence of potassium tert-butoxide
in refluxing tert-butyl alcohol, yielding 1-aryl-3,5-bis­(het)­arylpyrazoles 9 with complementary regioselectivity (method A). The efficiency
of this protocol was further improved by developing a one-pot, three-component
procedure for the synthesis of pyrazoles 9, directly
from active methylene ketones, by reacting in situ generated 3-(methylthio)-1,3-bis­(het)­aryl-2-propenones
with arylhydrazines in the presence of sodium hydride (instead of
potassium tert-butoxide as base). The structures
and regiochemistry of newly synthesized pyrazoles were confirmed from
their spectral and analytical data along with X-ray crystallographic
data of three pairs of regioisomers.