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doi.org/10.1002/cctc.202100152
ChemCatChem
also scrutinized the equivalency of CO source and other CO
surrogates. However, we have found that on decreasing the
equivalency of oxalic acid to 4 equiv., the yield of 2a decreased
to 30% (Table 1, entry 18). Furthermore, on substituting oxalic
acid with formic acid and paraformaldehyde, the desired
quinazolinone 2a was formed in traces (Table 1, entries 19–20).
However, we didn’t observe formation of 2a in absence of
oxalic acid (Table 1, entry 21). Interestingly, other homogeneous
and heterogeneous catalysts were also examined, and we
noticed that Pd@PS also resulted the product 2a in 82% yield
and found to be in harmonious with developed reaction
conditions (Table 1, entries 22–24). Hence, 1a (1 equiv.), Pd/C
(5 mol%), K3PO4 (2.5 equiv.), KI (1.5 equiv.) in DMSO (inner vial)
and oxalic acid (6 equiv.) in DMF (outer vial) were found to be
most suitable conditions for the synthesis of targeted 2-
arylquinazolinones.
Intriguingly, other ammonium surrogates or nitrogen
components and their equivalency were also searched to get
maximum yield of desired 2-arylquinazolinone 2a. In order to
check the effect of various ammonia sources on synthesis of 2a,
we have tested various ammonia components such as
(NH4)2CO3, NH4HCO3, CH3COONH4, HCOONH4, urea and aq. NH3,
results summarized in Table 2. Fortunately, we obtained 81%
yield of desired quinazolinone 2a on employing ammonium
carbonate as ammonia source (Table 2, entry 1). Furthermore,
other ammonia sources also furnished the product in moderate
to good yields of 2a i.e. 35–63% (Table 2, entries 2–6). Further,
we have also checked the equivalency of ammonium carbamate
compatible for synthesis of desired product in maximum yield.
On decreasing the equivalency of ammonia source to 2 equiv.,
the yield of 2a reduced to 42% (Table 2, entry 8). We have
observed that 3 equiv. of ammonium carbamate was sufficient
to obtain 2a in maximum yield. Hence, ammonium carbamate
or ammonium carbonate was found to be the best suitable
ammonia source for the synthesis of 2-aryl quinazolinones.
With intend to examine the generality and applicability of
the developed strategy, we scrutinized diversely substituted N-
(2-iodophenyl)benzamide or 2-iodoacetanilides for the synthesis
of corresponding quinazolinones under optimal reaction con-
ditions, results tabulated in Table 3. Initially, we have selected
electron donating substrates e.g. N-(2-iodophenyl)-4-meth-
ylbenzamide (1b) and N-(2-iodophenyl)-4-propylbenzamide
(1c) for cascade aminocarbonylation and cyclization under set
reaction conditions and obtained respective substituted quina-
zolinone, 2b and 2c in good yields i.e. 73–75% respectively.
However, on applying ammonium carbonate as ammonia
component not much deviation in yield was observed. In the
similar lines, in order to check the electronic and steric effect,
we have also attempted 4-OMe, 3-OMe (1d and 1e) and 2-OMe
substituted substrates to get respective quinazolinones. We
obtained 65% yield of 4-OMe (2d) product and 71% yield of
product in case of 3-OMe (2e), while we ended up with
complex reaction mixture in case of ortho-substituted com-
pound. This difference in the yield of products might be due to
electronic and steric factors respectively. Interestingly, reaction
of 1d in presence of ammonium carbonate as ammonia
component resulted in slightly higher yield i.e., 68% yield.
However, in case of di-methoxy substitution (1f), we got
moderate yield of the product 2f. Thereafter, we have
attempted 4-F and 4-Cl halogen substrates (1g and 1h) and
obtained corresponding products 2g and 2h in good yields i.e.
70–72%. However, we have not noticed any change in the yield
of product 2g in case of ammonium carbonate. Then, we
shifted our focus towards thiophene substituted compound 1i
and the reaction also ended with desired quinazolinone
product 2i in 69% yield. In pursuit to expand more substrate
scope, N-(2-iodo-4-methylphenyl)benzamide (1j) delivered 2j in
74% yield. Encouraged by these results, halogen substituted
compounds (1k–n) were also targeted for synthesis of sub-
stituted 2-arylquinazolinones. We obtained moderate to good
yields of products 2k–m in case of 4-F, 4-Cl and 4-Br
substituents. However, in case of 5-Cl substituted compound,
we obtained excellent yield of product 2n in 77% yield and
75% yield with ammonium carbonate.
Furthermore, electron withdrawing substrate i.e., methyl 4-
benzamido-3-iodobenzoate (1o) resulted the desired 2-arylqui-
nazolinone in appreciable yield but somewhat lower yield in
case of ammonium carbonate as ammonium component. To
further check the effect of developed strategy on di-substituted
compounds, we checked N-(2-iodo-4-methylphenyl)-4-meth-
ylbenzamide (1p) and N-(4-fluoro-2-iodophenyl)-4-meth-
ylbenzamide (1q) under set reaction conditions. Fortunately,
the respective substrates procured the desired products in 60
and 68% yields respectively. Intriguingly, N-(2-iodophenyl)-2-
phenylacetamide (1r) was also subjected for the synthesis of
quinazolinones, but we obtained the product in 42% yield.
Although, application of ammonium carbonate didn’t change in
the yield of desired product. Furthermore, substrate with longer
carbon chain length i.e., N-(2-iodophenyl)-3-phenylpropana-
mide was also attempted but delivered the anticipated
quinazolinone in very low yield.
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Table 2. Optimization of NH3 sources for 2-arylquinazolinones synthesis.
Reaction conditions: 1 (1 equiv.), ammonia source (3 equiv.), 5 wt% Pd/C
(5 mol%), K3PO4 (2.5 equiv.), KI (1.5 equiv.), DMSO (1.5 mL); Outer Vial:
°
Oxalic acid (6 equiv.) in DMF (0.5 mL) stirred at 130 C for 24 h; [a] Isolated
yield; [b] 30% aq. solution of NH3
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