Efficient synthesis of 2-oxazolidinones and quinazoline-2,4(1H,3H)-diones from CO2 catalyzed by tetrabutylammonium fluoride

Article abstract of DOI:10.1016/j.tet.2018.04.059

By employing tetrabutylammonium fluoride (TBAF) as a catalyst, the various carboxylative cyclizations of the propargylic amines having internal alkynes with CO₂ proceeded to afford the corresponding 2-oxazolidinones. In this case, it was also found that the generated 2-oxazolidinones were tautomerized into the corresponding 2-oxazolones due to the basicity of TBAF. In addition, we performed the synthesis of quinazoline-2,4(1H,3H)-dione from 2-aminobenzonitrile and CO₂ by using TBAF as a catalyst.

Full text of DOI:10.1016/j.tet.2018.04.059

Accepted Manuscript
Efficient synthesis of 2-oxazolidinones and quinazoline-2,4(1H,3H)-diones from CO
catalyzed by tetrabutylammonium fluoride
2
Akira Fujii, Hideaki Matsuo, Jun-Chul Choi, Tadahiro Fujitani, Ken-ichi Fujita
PII:
S0040-4020(18)30448-4
10.1016/j.tet.2018.04.059
TET 29474
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 15 March 2018
Revised Date: 16 April 2018
Accepted Date: 18 April 2018
Please cite this article as: Fujii A, Matsuo H, Choi J-C, Fujitani T, Fujita K-i, Efficient synthesis of 2-
oxazolidinones and quinazoline-2,4(1H,3H)-diones from CO catalyzed by tetrabutylammonium fluoride,
2
Tetrahedron (2018), doi: 10.1016/j.tet.2018.04.059.
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Efficient synthesis of 2-oxazolidinones and
quinazoline-2,4(1H,3H)-diones from CO2 catalyzed
by tetrabutylammonium fluoride
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Akira Fujii, Hideaki Matsuo, Jun-Chul Choi, Tadahiro Fujitani, Ken-ichi Fujita*

ACCEPTED MANUSCRIPT
Efficient synthesis of 2-oxazolidinones and quinazoline-2,4(1H,3H)-diones from CO2
catalyzed by tetrabutylammonium fluoride
Akira Fujii, Hideaki Matsuo, Jun-Chul Choi, Tadahiro Fujitani, and Ken-ichi Fujita*
National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba Central 5, 1-1-1
Higashi, Tsukuba, Ibaraki 305-8565, Japan
Fax +81(29)8614577; E-mail: k.fujita@aist.go.jp
Abstract: By employing tetrabutylammonium fluoride (TBAF) as a catalyst, the various
carboxylative cyclizations of the propargylic amines having internal alkynes with CO2 proceeded to
afford the corresponding 2-oxazolidinones. In this case, it was also found that the generated
2-oxazolidinones were tautomerized into the corresponding 2-oxazolones due to the basicity of
TBAF. In addition, we performed the synthesis of quinazoline-2,4(1H,3H)-dione from
2-aminobenzonitrile and CO2 by using TBAF as a catalyst.
Keywords: Carbon dioxide; Catalysis; Tetrabutylammonium fluoride
1

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1. Introduction
The chemistry of carbon dioxide (CO2) has drawn much attention in the last two decades because
CO2 is abundant, nontoxic, non-flammable, and easily available. Moreover, CO2 is one of the most
attractive C1 building blocks to displace toxic reagents such as phosgene and carbon monoxide.1
CO2 also has great potential as a renewable resource for the production of value-added chemicals,
and thus much effort has been expended to incorporate CO2 in fine chemical synthesis.2 However,
because CO2 is thermodynamically stable and kinetically inert due to its high oxidation state,
organometallic complexes of noble metals must often be used as catalysts for the chemical fixations
of CO2.3 Recently, transformations of CO2 have also been achieved by metal-free organocatalysts
through the activation of CO2 or substrates.4
Previously, as an example of organocatalysts, tetrabutylammonium fluoride (TBAF) was reported
to catalyze the cyclization reaction of β-alkynyl hydrazines to give the corresponding azaproline
derivatives.5 This transformation appeared to be caused by a quaternary ammonium cation–π
interaction with the triple bond of alkynes.6 In addition, several other TBAF-catalyzed cyclization
reactions of alkynyl compounds have been reported.7 Recently, we discovered that the carboxylative
cyclization of a propargylic amine having a terminal alkyne with CO2 is catalyzed by the quaternary
ammonium salts to provide the corresponding 2-oxazolidinone.8 Among the quaternary ammonium
salts applied to the carboxylative cyclization, TBAF was found to be the most effective. We report
herein the TBAF-catalyzed carboxylative cyclization of various propargylic amines with CO2 to
provide 2-oxazolidinones, and the quaternary ammonium salt-catalyzed tautomerization of a
2-oxazolidinone into the corresponding 2-oxazolone. Moreover, we found that TBAF was the most
effective quaternary ammonium salt for the synthesis of quinazoline-2,4(1H,3H)-diones from
2-aminobenzonitriles and CO2.9
2. Results and discussion
2.1. Synthesis of 2-oxazolidinones from propargylic amines and CO2
2-Oxazolidinones are important heterocyclic compounds in many applications in organic
synthesis and pharmaceutical chemistry. For example, they can be used as cholesteryl ester transfer
protein inhibitors and monoamine oxidase inhibitors.10 Syntheses of 2-oxazolidinones by the
carboxylative cyclization of propargylic amines with CO2 have been reported to be catalyzed by
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organometallic complexes of noble metals11 such as silver12 and gold.13 Recently, a number of
metal-free catalysts, such as superbases,14 N-heterocyclic carbenes,15 triethanolamine,16 and
cyanuric acid,17 which are less expensive and environmentally benign, have been used for the
carboxylative cyclization of propargylic amines with CO2 as alternatives to organometallic catalysts.
Very recently, we found that 1 mol% of TBAF catalyzes the carboxylative cyclization of
propargylic amine 1a, which has a terminal alkyne, to provide the corresponding 2-oxazolidinone
2a under CO2 pressure of 0.5 MPa at 110 ºC, as shown in Scheme 1. This reaction was considered
that the propargylic amine 1a reacted with CO2 to form the corresponding carbamic acid, then the
carbamic acid was dually activated by a quaternary ammonium cation–π interaction with the triple
bond and a fluoride ion–hydrogen interaction with OH of the carbamic acid.8
Scheme 1. Carboxylative cyclization of a propargylic amine 1a with CO2.
First, we performed the TBAF–catalyzed carboxylative cyclization of propargylic amine 1b,
which has an internal alkyne, with CO2 as shown in Table 1. A t-butanol solution of propargylic
amine 1b and 1 mol% of TBAF as a catalyst were stirred for 12–24 h in a sealed autoclave under a
CO2 atmosphere of 0.5 MPa at 90–110 ºC. By carrying out the carboxylative cyclization of 1b at
110 ºC for 12 h, the corresponding 2-oxazolidinone 2b was obtained in an 83% chemical yield
along with a small amount of a 2-oxazolone 3b (3%; Table 1, entry 1). Similarly, in our previous
report using an N-heterocyclic carbene as a catalyst, a small amount of 2-oxazolidinone was
obtained in the carboxylative cyclization of a propargylic amine.15a Then, by carrying out the
carboxylative cyclization of 1b at 90 ºC for 24 h, the corresponding 2-oxazolidinone 2b was
obtained in an 85% chemical yield and the formation of 2-oxazolone 3b was suppressed, probably
due to the low reaction temperature (1%; Table 1, entry 3).
Table 1. Carboxylative cyclization of propargylic amine 1b with CO2.a
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Entry Temp (ºC) Time (h) Yield of Yield of Recovery of
2b (%)b
3b (%)b
1b (%)b
1
2
3
110
90
12
12
24
83
3
1
1
0
44
9
55
90
85
a Reaction conditions: 1b (1 equiv.), TBAF (1 mol%), t-BuOH (1 M based on 1b), carried out at 90–
110 ºC for 12–24 h in a sealed autoclave under a CO2 atmosphere of 0.5 MPa.
b Determined by the integration of 1H NMR with reference to an internal standard.
We subsequently examined the time-course of the carboxylative cyclization of propargylic amine
1b at 90 ºC (Figure 1). The results showed that the chemical yield of 2-oxazolidinone 2b increased
till 48 h, then mildly decreased thereafter. On the other hand, the formation of 2-oxazolone 3b was
observed with a decrease in the yield of 2-oxazolidinone 2b. Figure 1 suggests that the
carboxylative cyclization of propargylic amine 1b with CO2 proceeds to initially provide
2-oxazolidinone 2b, and that the generated 2-oxazolidinone 2b is tautomerized into the
corresponding 2-oxazolone 3b, the tautomerization into which was also reported in a case using an
N-heterocyclic carbene as a catalyst.15a
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100
80
60
40
20
0
1b
2b
3b
0
10 20 30 40 50 60 70 80 90 100
Time (h)
Figure 1. Time-course curves of the carboxylative cyclization of propargylic amine 1b.
Next, we examined the tautomerization of 2-oxazolidinone 2b into 2-oxazolone 3b through the
use of various tetrabutylammonium salts as catalysts, as shown in Table 2.18 First, by the stirring of
a t-butanol solution of 2-oxazolidinone 2b at 80 ºC for 6 h under an argon atmosphere through the
use of 5 mol% of TBAF, 2b was tautomerized to afford 2-oxazolone 3b in a 55% chemical yield
(Table 2, entry 1). In contrast, when tetrabutylammonium chloride, bromide, or acetate was used as
a catalyst, no 2-oxazolone 3b was obtained (Table 2, entries 2–4). On the other hand, when
tetrabutylammonium hydroxide was employed as a catalyst, 2-oxazolone 3b was obtained in a 67%
chemical yield (Table 2, entry 5), which was higher than the yield in the case using TBAF. From
these results, it is assumed that the tautomerization of 2-oxazolidinone 2b into 2-oxazolone 3b was
caused by the deprotonation of CH2N in 2b due to the basicity of the catalyst.
Table 2 Tautomerization of 2-oxazolidinone 2b using various tetrabutylammonium salts as
catalysts.a
Entry
Catalyst
Bu4NF
Yield of 3b (%)b
1
2
55
0
Bu4NCl
5

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3
4
5
Bu4NBr
0
Bu4NOAc
Bu4NOH
0
67
a Reaction conditions: catalyst (5 mol%), 2b (1 equiv.), t-BuOH (0.2 M based on 2b), carried out at
80 ºC for 6 h in glassware.
b Determined by the integration of 1H NMR with reference to an internal standard.
In order to prevent the tautomerization of 2-oxazolidinone 2b into 2-oxazolone 3b under the
carboxylative cyclization of propargylic amine 1b with CO2, we carried out the carboxylative
cyclization of 1b catalyzed by tetrabutylammonium acetate (Table 3). However, the formation of
2-oxazolone 3b was detected under the reaction conditions for the carboxylative cyclization of 1b
(1%; Table 3, entry 4). In addition, for the purpose of catalyzing the carboxylative cyclization of 1b,
TBAF was more effective than tetrabutylammonium acetate (Table 3, entries 1 and 2).
Table 3. Carboxylative cyclization of propargylic amine 1b with CO2.a
Entry
Catalyst
Time
(h)
12
Yield of Yield of
2b (%)b
3b (%)b
1c
2
Bu4NF
Bu4NOAc
Bu4NF
55
1
0
2
1
12
36
3c
48
89
4
Bu4NOAc
48
86
a The reaction conditions were identical to those in Table 1.
b Determined by the integration of 1H NMR with reference to an internal standard.
c Cited from Figure 1.
Finally, we performed the carboxylative cyclizations of various propargylic amines 1 to provide
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the corresponding 2-oxazolidinone 2 by employing TBAF as a catalyst under controlled reaction
conditions, as shown in Table 4. The introduction of a methoxy or a methyl group at the phenyl
group in R1 decreased the reactivity of the triple bond, as in our previous report.15 In these cases, by
carrying out the reaction for 48 h, the corresponding 2-oxazolidinone 2 was mainly obtained (Table
4, entries 2 and 4). In contrast, when a trifluoromethyl or a cyano group was introduced at the
phenyl group in R1, the initial carboxylative cyclization of 1 appeared to proceed smoothly due to
the high reactivity of the triple bond, and the generated 2-oxazolidinone 2 appeared to be
tautomerized into the corresponding 2-oxazolone 3 at 110 ºC. As a result, 2-oxazolone 3 was mainly
obtained by carrying out the reaction at 110 ºC for 24 h (Table 4, entries 5 and 7). In these cases, by
carrying out the reaction at 70 ºC, the corresponding 2-oxazolidinone 2 was mainly obtained (Table
4, entries 6 and 8). In the case of the methyl group in R1, even by employing 5 mol% of TBAF as a
catalyst, the corresponding 2-oxazolidinone 2h was obtained in an only 8% chemical yield (Table 4,
entry 12).19
Table 4. Carboxylative cyclizations of various propargylic amines 1 for the synthesis of
2-oxazolidinones 2.a
Bu4NF
Temp. Time
(ºC) (h)
110 24
110 48
110 24
110 48
110 24
Yield (%)
1
Entry
R1
R2
(mol%)
2c-h 3c-h
1
2
3
4
5
6
7
1
2
1
1
1
1
1
22
78
77
89
12
84
2
0
5
4-CH3OC6H4
4-CH3C6H4
CH3
1c
1
CH3
1d
3
57
6
4-CF3C6H4
4-CNC6H4
CH3
CH3
1e
1f
70
24
110 24
64
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8
9
1
1
1
1
5
70
3
88
84
91
1
12
9
110 24
110 18
110 24
110 24
C6H5
CH3
CH2C6H5
CH2C6H5
1g
10
11
12
3
0
1h
8
0
a The reaction conditions were identical to those in Table 1.
b Determined by the integration of 1H NMR with reference to an internal standard.
2.2. Synthesis of quinazoline-2,4(1H,3H)-diones from 2-aminobenzonitriles and CO2
Quinazoline-2,4(1H,3H)-diones and their derivatives have attracted much attention due to their
wide range of biological and pharmacological activities.20 The reaction of CO2 with
2-aminobenzonitriles is an environmentally benign process with 100% atom efficiency, and it has
been widely investigated by use of various catalysts21 including DBU,22 imidazolium salt,23 and
guanidine.24 Very recently, Dyson et al. reported that 10 mol% of TBAF or tetramethylphosphonium
salts catalyzed the formation of quinazoline-2,4(1H,3H)-dione from 2-aminobenzonitrile under
atmospheric pressure of CO2 at 90 ºC and proposed its catalytic cycle.9 On the other hand, in this
paper, by employing 1 mol% of various quaternary ammonium salts, which is similar to the amount
of catalysts used for the synthesis of 2-oxazolidinones 2, we examined the synthesis of
quinazoline-2,4(1H,3H)-diones from 2-aminobenzonitriles under a pressurized CO2 atmosphere.
In order to optimize the catalyst, we examined the synthesis of quinazoline-2,4(1H,3H)-dione 5a
from 2-aminobenzonitrile 4a with CO2 through the use of 1 mol% of various catalysts, such as
quaternary ammonium salts and organic bases, as shown in Table 5. First, we confirmed that stirring
of a DMSO solution of 2-aminobenzonitrile 4a at 110 ºC for 3 h under a CO2 atmosphere of 2 MPa
in the absence of catalysts yielded none of the corresponding quinazoline-2,4(1H,3H)-dione 5a
(Table 5, entry 1). Next, by a screening of the catalytic activity of various tetraalkylammonium
halides (Table 5, entries 2–7), TBAF was found to afford the highest chemical yield among them
(55%; Table 5, entry 4). This result suggests that the higher basicity of the counter anion of the
tetraalkylammonium salt facilitates the carboxylative cyclization of 4a with CO2. It was also found
that a tetraalkylammonium fluoride with longer alkyl groups afforded a higher chemical yield
(Table 5, entries 2–4). In addition, tetrabutylammonium acetate afforded a 40% chemical yield
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(Table 5, entry 8). On the other hand, by employing quaternary ammonium hydroxides with various
structures, the chemical yields of 5a were low in all cases (1–6%; Table 5, entries 9–12). This may
have been due to the formation of bicarbonate ion from the hydroxide ion in the presence of CO2.25
Although cesium fluoride moderately catalyzed the reaction to afford 5a in a 45% chemical yield
(Table 5, entry 13), organic bases such as 1,1,3,3-tetramethylguanidine (TMG) and triethanolamine
did not catalyze the reaction effectively (11% and 0%; Table 5, entries 14 and 15, respectively).
Table 5. Optimization of the catalyst for the synthesis of quinazoline-2,4(1H,3H)-dione 5a.a
Entry
1
Catalyst
none
Yield of 5 (%)b
Recovery of 4 (%)b
0
38
41
55
0
99
61
2
Me4NF
3
Et4NF
59
4
Bu4NF
45
5
Bu4NCl
>99
>99
99
6
Bu4NBr
0
7
Bu4NI
0
8
Bu4NOAc
Me4NOH
Bu4NOH
(C6H13)4NOH
(C16H33)Me3NOH
CsF
40
3
60
9
90
10
11
12
13
14
15
5
91
6
93
1
98
45
11
0
54
TMG
88
triethanolamine
>99
a Reaction conditions: 4a (1 equiv.), catalyst (1 mol%), DMSO (1 M based on 4a), carried out at
110 ºC for 3 h in a sealed autoclave under a CO2 atmosphere of 2 MPa.
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b Determined by the integration of 1H NMR with reference to an internal standard.
Finally, we performed the synthesis of various quinazoline-2,4(1H,3H)-diones 5 at 110 ºC for 24
h under a CO2 atmosphere of 2 MPa by employing 1 mol% of TBAF as a catalyst, as shown in
Table 6. 2-Aminobenzonitrile derivatives with electron-withdrawing or electron-donating groups at
benzene 4b-f could react with CO2 to provide the corresponding quinazoline-2,4(1H,3H)-diones
5b-f in excellent chemical yields in all cases (96–99%; Table 6, entries 2–6). On the other hand,
2-amino-3-cyanopyridine 4g with CO2 provided 5g in a moderate chemical yield under the present
reaction conditions (59%; Table 6, entry 7).
Table 6. Syntheses of various quinazoline-2,4(1H,3H)-diones 5.a
Entry
1
Substrate
Product
Yield (%)b
97
4a
4b
4c
4d
5a
5b
5c
5d
2
3
4
98
96
>99
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5
6
7
>99
98
4e
5e
4f
5f
59
4g
5g
a The reaction conditions were identical to those in Table 5.
b Isolated yield.
3. Conclusion
In the case of the TBAF–catalyzed carboxylative cyclization of a propargylic amine having an
internal alkyne with CO2, it was found that a 2-oxazolone is obtained by the tautomerization of the
generated 2-oxazolidinone, which was similar to the result obtained using an N-heterocyclic
carbene as a catalyst. By optimization of the reaction conditions, including the reaction temperature
and the reaction time, we could perform the TBAF–catalyzed carboxylative cyclization of a
propargylic amine to provide the corresponding 2-oxazolidinone selectively. Further, it was found
that TBAF is the most effective quaternary ammonium salt for catalyzing the carboxylative
cyclization of 2-aminobenzonitriles when using a catalyst concentration of 1 mol% under a
pressurized CO2 atmosphere.
4. Experimental
4.1. General
Kieselgel 60 F254 (Merck) was used for TLC, and Wakogel C-300 (Wako) was used for silica gel
column chromatography. Degassed solvent was prepared by freeze-pump-thaw cycling of
commercially available dry solvents for the carboxylative cyclization of propargylic amines 1, the
tautomerization of 2-oxazolidinone 2b, and the synthesis of quinazoline-2,4(1H,3H)-diones 5.
Propargylic amines 1b-h and 2-oxazolidinone 2b were prepared by the methods reported in the
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literature (1b,13e 1c, e,26 1d,13a 1f,15b 1g,27 1h,12e 2b15b). The other reagents, and the dry solvents
were commercially available and were used as received. Carbon dioxide (Showa Denko Gas
Products Co., Ltd., purity > 99.99%) was used without further purification.
13
1H and C NMR spectra were measured with a Bruker Avance III 400 spectrometer (1H: 400
13
MHz; C: 100 MHz). Chemical shifts were reported as ppm downfield from TMS as an internal
standard in δ units. Coupling constants (J) were given in hertz (Hz).
4.2. Carboxylative cyclization of a propargylic amine 1 with CO2: General procedure
To a t-butanol solution (0.6 mL) of a propargylic amine 1 (0.6 mmol) in a stainless steel autoclave
was added a quaternary ammonium salt (0.006–0.03 mmol) under an argon atmosphere. The
autoclave was sealed, heated at 70–110 ºC and then pressurized with CO2 of 0.5 MPa. The
carboxylative cyclization of 1 proceeded by the magnetic stirring of the resulting mixture at 70–110
ºC for the indicated time. After the reaction the autoclave was cooled in an ice bath and
depressurized. The chemical yields of the 2-oxazolidinone 2 and the 2-oxazolone 3 were determined
1
by integrating H NMR with reference to an internal standard (3-hydroxybenzyl alcohol except in
the case of 1b, when benzoin methyl ether was used instead), a dichloromethane solution (2 mL) of
which was added to the reaction mixture.
2-Oxazolidinones 2b-h are known compounds, and their NMR spectra were found to agree with
the values reported in the literature (2b-d, f, g,15b 2e,28 2h,14).
2-Oxazolones 3b-g are known compounds, and their NMR spectra also agreed with the values
reported in the literature.18a
4.3. Tautomerization of 2-oxazolidinone 2b into 2-oxazolone 3b: General procedure
To a t-butanol solution (0.8 mL) of 2-oxazolidinone 2b (0.16 mmol) in glassware was added
tetrabutylammonium salt (0.008 mmol) under an argon atmosphere. Tautomerization of 2b
proceeded by the stirring of the resulting mixture at 80 ºC for 6 h. After the filtration of the reaction
mixture through a silica gel pad, the chemical yield of 2-oxazolone 3b was determined by
1
integrating H NMR with reference to an internal standard (3-hydroxybenzyl alcohol), a
dichloromethane solution (2 mL) of which was added to the filtrate.
4.4. Synthesis of quinazoline-2,4(1H,3H)-diones 5 from 2-aminobenzonitriles 4 and CO2:
General procedure
Table 5: To a DMSO-d6 solution (1 mL) of 2-aminobenzonitrile 4a (1 mmol) in a stainless steel
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autoclave was added a catalyst (0.01 mmol) under an argon atmosphere. The autoclave was sealed,
heated at 110 ºC and then pressurized with CO2 of 2 MPa. The cyclization reaction of 4a proceeded
by the magnetic stirring of the resulting mixture at 110 ºC for 3 h. After the reaction the autoclave
was cooled in an ice bath and depressurized. The chemical yield of quinazoline-2,4(1H,3H)-dione
5a was determined by integrating 1H NMR with reference to an internal standard
(3,5-dimethoxybenzyl alcohol), which was added to the reaction mixture.
Table 6: DMSO solution (6 mL) of 4 (6 mmol) was treated for the carboxylative cyclization of 4
with CO2 according to the procedure of Table 5. After the reaction, the autoclave was cooled in an
ice bath and depressurized, and the reaction mixture was added to water (60 mL). The precipitation
was collected by filtration, washed with water and diethyl ether, and then dried in vacuo at 35 ºC for
15 h to give the pure product 5.
Quinazoline-2,4(1H,3H)-diones 5a-g are known compounds, and their NMR spectra were found
to agree with the values reported in the literature.
1
4.4.1. Quinazoline-2,4(1H,3H)-dione (5a).29 White solid; H NMR (400 MHz; DMSO-d6) δ 11.28
(s, 1H, NH), 11.14 (s, 1H, NH), 7.89 (d, J = 7.4 Hz, 1 H, ArH), 7.64 (t, J = 7.6 Hz, 1 H, ArH), 7.20–
7.16 (m, 2H, ArH); 13C NMR (100 MHz; DMSO-d6) δ 162.9, 150.4, 140.9, 135.0, 127.0, 122.3,
115.4, 114.4.
1
4.4.2. 6,7-Dimethoxyquinazoline-2,4(1H,3H)-dione (5b).29 White solid; H NMR (400 MHz;
DMSO-d6) δ 11.09 (s, 1H, NH), 10.91 (s, 1H, NH), 7.26 (s, 1H, ArH), 6.68 (s, 1H, ArH), 3.83 (s,
13
3H, CH3), 3.79 (s, 3H, CH3); C NMR (100 MHz; DMSO-d6) δ 162.4, 154.9, 150.4, 145.0, 136.5,
107.2, 106.2, 97.8. 55.8, 55.7.
4.4.3. 6-Methylquinazoline-2,4(1H,3H)-dione (5c).24 White solid; 1H NMR (400 MHz; DMSO-d6) δ
11.20 (s, 1H, NH), 11.04 (s, 1H, NH), 7.69 (s, 1H, ArH), 7.46 (dd, J = 1.7, 8.3 Hz, 1H, ArH), 7.07
(d, J = 8.3 Hz, 1H, ArH) 2.32 (s, 3H, CH3); 13C NMR (100 MHz; DMSO-d6) δ 162.8, 150.3, 138.7,
135.9, 131.5, 126.5, 115.3, 114.2, 20.2.
1
4.4.4. 6-Fluoroquinazoline-2,4(1H,3H)-dione (5d).24 Pale yellow solid; H NMR (400 MHz;
DMSO-d6) δ 11.43 (s, 1H, NH), 11.21 (s, 1H, NH), 7.61–7.53 (m, 2H, ArH), 7.22–7.19 (m, 1H,
13
ArH); C NMR (100 MHz; DMSO-d6) δ 162.2 (4JC-F = 2.8 Hz), 157.3 (1JC-F = 238.2 Hz), 150.1,
137.6, 122.9 (2JC-F = 24.1 Hz), 117.6 (3JC-F = 7.8 Hz), 115.4 (3JC-F = 7.5 Hz), 112.0 (2JC-F = 23.7
Hz).
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4.4.5. 6-Chloroquinazoline-2,4(1H,3H)-dione (5e).24 Pale yellow solid; H NMR (400 MHz;
DMSO-d6) δ 11.36 (brs, 2H, NH), 7.82 (d, J = 2.3 Hz, 1H, ArH), 7.69 (dd, J = 2.5, 8.7 Hz, 1H,
ArH), 7.18 (d, J = 8.8 Hz, 1H, ArH); 13C NMR (100 MHz; DMSO-d6) δ 161.8, 150.1, 139.7, 134.8,
126.3, 125.9, 117.5, 115.8.
1
4.4.6. 6-Bromoquinazoline-2,4(1H,3H)-dione (5f).24 Pale yellow solid; H NMR (400 MHz;
DMSO-d6) δ 11.44 (s, 1H, NH), 11.27 (s, 1H, NH), 7.94 (d, J = 2.3 Hz, 1H, ArH), 7.80 (dd, J = 2.4,
13
8.7 Hz, 1H, ArH), 7.13 (d, J = 8.7 Hz, 1H, ArH); C NMR (100 MHz; DMSO-d6) δ 161.7, 150.0,
140.1, 137.5, 128.9, 117.8, 116.2, 113.8.
1
4.4.7. Pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (5g).30 Pale yellow solid; H NMR (400 MHz;
DMSO-d6) δ 11.68 (s, 1H, NH), 11.47 (s, 1H, NH), 8.60 (dd, J = 1.8, 4.8 Hz, 1H, ArH), 8.26 (dd, J
= 1.8, 7.8 Hz, 1H, ArH), 7.25 (dd, J = 4.8, 7.7 Hz, 1H, ArH); 13C NMR (100 MHz; DMSO-d6)
δ 162.4, 154.6, 152.4, 150.4, 136.4, 118.9, 109.9.
Acknowledgment
This work was based on results obtained from a project (P16010) commissioned by the New Energy
and Industrial Technology Development Organization (NEDO).
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