Topics in Current Chemistry (2019) 377:1
1 3
3.2.2 N‑Heterocycles
The pyridine scaffold is encountered in numerous biologically active compounds,
and pyridine (41) is thus a useful synthon for the elaboration of pharmaceuticals
and agrochemicals [90]. Pyridine (41) and methylpyridines (42) were prepared
from glycerol (3) in a two‑step continuous flow process involving fixed‑bed reac‑
tors (Fig. 24). The catalytic dehydration of glycerol to acrolein (26) was conducted
over HZSM‑22 zeolite at 400 °C in a first packed bed reactor. Gaseous ammonia
was mixed with the reactor effluents containing 26, and the mixture was redirected
toward a second bed consisting of zinc oxide supported on HZSM‑5 zeolite oper‑
ated at 425 °C. Pyridine (41) and methylpyridines (42) were obtained in a steady
combined yield of 61–65% over 9 h of operation, but the yield dropped as the time‑
on‑stream increased [91].
A related strategy for the synthesis of quinoline (44) consisted of reacting aniline
(43) and glycerol (3) in a fixed‑bed reactor operated at 470 °C (Fig. 25). There is,
however, an important difference from the abovementioned sequential process for
the synthesis of pyridines. In the present example, the dehydration of 3 to 26 was
followed by condensation with 43 to give 44 in a cascade using a single nickel‑mod‑
ified mesoporous β‑zeolite catalyst. The catalyst initially gave a good yield for qui‑
noline (up to 71% after 2 h), but it decreased to 15% after 6 h. Catalyst regeneration
by calcination was possible [92].
Like pyridine, the indole moiety is frequently found in biologically active mol‑
ecules. There are many synthetic methodologies for the functionalization of this het‑
erocycle, and many drugs and agrochemicals bear an indole scaffold [93]. Fu and
coworkers reported a direct synthesis of indole and methylindoles (45) based on the
pyrolysis of furfural (6) in the presence of ammonia (Fig. 26). The reaction took
place in a fixed‑bed reactor packed with HZSM‑5 zeolite and operated at 600 °C
under atmospheric pressure. A combined yield of up to 33% was obtained with fur‑
fural as feedstock, while the use of HMF (7) resulted in a combined yield of only 7%
[94].
2‑Methylpyrazine (47) is the starting material for the synthesis of pyrazinamide,
an antituberculosis drug included in the World Health Organization’s Model List of
Fig. 24 Two‑step continuous‑flow synthesis of (methyl)pyridines (41, 42) from glycerol (3)
130
Reprinted from the journal
1 3
3.2.2 N‑Heterocycles
The pyridine scaffold is encountered in numerous biologically active compounds,
and pyridine (41) is thus a useful synthon for the elaboration of pharmaceuticals
and agrochemicals [90]. Pyridine (41) and methylpyridines (42) were prepared
from glycerol (3) in a two‑step continuous flow process involving fixed‑bed reac‑
tors (Fig. 24). The catalytic dehydration of glycerol to acrolein (26) was conducted
over HZSM‑22 zeolite at 400 °C in a first packed bed reactor. Gaseous ammonia
was mixed with the reactor effluents containing 26, and the mixture was redirected
toward a second bed consisting of zinc oxide supported on HZSM‑5 zeolite oper‑
ated at 425 °C. Pyridine (41) and methylpyridines (42) were obtained in a steady
combined yield of 61–65% over 9 h of operation, but the yield dropped as the time‑
on‑stream increased [91].
A related strategy for the synthesis of quinoline (44) consisted of reacting aniline
(43) and glycerol (3) in a fixed‑bed reactor operated at 470 °C (Fig. 25). There is,
however, an important difference from the abovementioned sequential process for
the synthesis of pyridines. In the present example, the dehydration of 3 to 26 was
followed by condensation with 43 to give 44 in a cascade using a single nickel‑mod‑
ified mesoporous β‑zeolite catalyst. The catalyst initially gave a good yield for qui‑
noline (up to 71% after 2 h), but it decreased to 15% after 6 h. Catalyst regeneration
by calcination was possible [92].
Like pyridine, the indole moiety is frequently found in biologically active mol‑
ecules. There are many synthetic methodologies for the functionalization of this het‑
erocycle, and many drugs and agrochemicals bear an indole scaffold [93]. Fu and
coworkers reported a direct synthesis of indole and methylindoles (45) based on the
pyrolysis of furfural (6) in the presence of ammonia (Fig. 26). The reaction took
place in a fixed‑bed reactor packed with HZSM‑5 zeolite and operated at 600 °C
under atmospheric pressure. A combined yield of up to 33% was obtained with fur‑
fural as feedstock, while the use of HMF (7) resulted in a combined yield of only 7%
[94].
2‑Methylpyrazine (47) is the starting material for the synthesis of pyrazinamide,
an antituberculosis drug included in the World Health Organization’s Model List of
Fig. 24 Two‑step continuous‑flow synthesis of (methyl)pyridines (41, 42) from glycerol (3)
130
Reprinted from the journal