Synthesis of quinazolinones from anthranilamides and aldehydes via metal-free aerobic oxidation in DMSO

Article abstract of DOI:10.1016/j.tetlet.2014.02.065

A highly environmentally benign protocol for the synthesis of quinazolinones from anthranilamides and aldehydes via aerobic oxidation was developed in wet DMSO. This protocol is operationally simple, exhibits broad substrate scope, and does not need toxic metal catalysts and bases. In addition, the utility of this transformation was further demonstrated by converting the resulting quinazolinones into other useful products in the same-pot without their isolation.

Full text of DOI:10.1016/j.tetlet.2014.02.065

Tetrahedron Letters 55 (2014) 2340–2344
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis of quinazolinones from anthranilamides and aldehydes via
metal-free aerobic oxidation in DMSO
⇑
Na Yeun Kim, Cheol-Hong Cheon
Department of Chemistry, Korea University, Anam-ro, Seongbuk-gu, Seoul 136701, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
A highly environmentally benign protocol for the synthesis of quinazolinones from anthranilamides and
aldehydes via aerobic oxidation was developed in wet DMSO. This protocol is operationally simple,
exhibits broad substrate scope, and does not need toxic metal catalysts and bases. In addition, the utility
of this transformation was further demonstrated by converting the resulting quinazolinones into other
useful products in the same-pot without their isolation.
Received 2 January 2014
Revised 10 February 2014
Accepted 18 February 2014
Available online 6 March 2014
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Quinazolinones
Aerobic oxidation
DMSO
Anthranilamide
One-pot synthesis
Quinazolinones are very important building blocks found in
biologically and pharmacologically active compounds, natural
products, and functional materials.1 Consequently, the develop-
ment of efficient methods for the synthesis of quinazolinones is
of great importance. One conventional method for the preparation
of quinazolinones is oxidative cyclization of Schiff bases derived
from o-anthranilamides and aldehydes in the presence of oxi-
dants.2 However, this method generally requires the use of excess
amounts of oxidants and generates a large amount of waste, thus
requiring tedious purification processes.3,4
Aerobic oxidations employing oxygen as the ultimate oxidant
have attracted much attention from the synthetic community as
green protocols.5 In this regard, the synthesis of quinazolinones
via aerobic oxidation provides an attractive alternative to tradi-
tional oxidative cyclization methods. Rather surprisingly, although
there have been a few reports of the synthesis of quinazolinones
via aerobic oxidative cyclization, the most aerobic oxidative cycli-
zation protocols reported were generally performed in the pres-
ence of metal co-catalysts;6 there has been only one report for
the synthesis of quinazolinones via aerobic oxidative cyclization
under microwave radiation without any assistance with metal
co-catalysts.7 Thus, it is highly desired to develop a more general
and environmentally benign protocol for the synthesis of quinaz-
olinones under mild conditions.
Recently, we developed metal-free aerobic oxidation protocols
for the synthesis of benzofused heteroaromatic compounds in the
presence of a nucleophile which acts as a catalyst for the cycliza-
tion of imines. For example, cyanide turned out to be a highly effi-
cient catalyst for the synthesis of benzoxazoles and benzothiazoles
under aerobic oxidation conditions without any aid of metal co-
catalyst and bases by converting disfavored 5-endo-trig cyclization
into favored 5-exo-tet cyclization.8 As a part of our continuing
studies for the development of new protocols for the synthesis of
biologically important heterocyclic compounds through aerobic
oxidation, we attempted to extend this nucleophile-catalyzed aer-
obic oxidative cyclization protocol to the synthesis of quinazoli-
nones from anthranilamide and aldehydes.
Herein we present a highly environmentally benign protocol for
the synthesis of 2-substituted quinazolinones from anthranila-
mides and aldehydes via aerobic oxidative cyclization in an open
flask without the use of metal co-catalysts and bases. Furthermore,
the same protocol was applied to the synthesis of 2,3-disubstituted
quinazolinones from N-substituted anthranilamides and aldehd-
yes. Since this protocol does not use any other additives and gen-
erates few by-products other than water, the usefulness of this
protocol was further demonstrated by the direct transformation
of the resulting quinazolinones into other useful products in the
same pot without their isolations.
It is generally believed that the formation of quinazolinone 5
from Schiff base 3 proceeds in a two-step sequence under oxidative
cyclization conditions: the first step is cyclization of 3 to afford 2,3-
dihydroquinazolinone 4 and subsequent oxidation of 4 yields the
⇑
Corresponding author. Tel.: +82 2 3290 3147; fax: +82 2 3290 3121.
E-mail address: cheon@korea.ac.kr (C.-H. Cheon).
http://dx.doi.org/10.1016/j.tetlet.2014.02.065
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.

N. Y. Kim, C.-H. Cheon / Tetrahedron Letters 55 (2014) 2340–2344
2341
desired product 5 (Scheme 1).2 We hypothesized that under the
Table 2
Optimization of reaction conditions
aerobic oxidative cyclization conditions, the first step (the conver-
sion of 3 into 4) might be the rate-determining step for the overall
process. Under such a scenario, it was expected that if the rate of
the first step were accelerated, the overall reaction rate could be
increased. Similar to our previous working hypothesis for the syn-
thesis of benzoxazoles,8 it was expected that a nucleophile might
enable the cyclization of 3 through intermediate 6 formed by the
reaction of 3 with a nucleophile via a 6-exo-tet cyclization. In par-
ticular, if the 6-exo-tet cyclization of 6 (pathway b) were faster than
the 6-endo-trig cyclization of 3 (pathway a),9 a nucleophile could
significantly accelerate the cyclization of 3, which eventually facil-
itates the formation of 5.
In order to test our working hypothesis, we first explored a
nucleophile as a catalyst on the aerobic oxidative cyclization of
3a derived from anthranilamide 1 and benzaldehyde 2a under sim-
ilar conditions used for the synthesis of benzoxazoles (Table 2). At
first glance, a nucleophile appeared to be effective for this transfor-
mation; quinazolinone 5a was obtained in 56% at 100 °C after 16 h
in the presence of a stoichiometric amount of cyanide (entry 1).
With this encouraging result in hand, several other nucleophiles
were investigated as catalysts for this protocol. Rather disappoint-
ingly, all the nucleophiles tested provided 5a in low to moderate
yields (entries 2–5). Despite numerous efforts to improve the yield
of this transformation, we could not further improve the yield of
5a. Under these conditions, we decided to investigate the back-
ground reaction for this transformation. When the reaction was
performed in the absence of cyanide, the aerobic oxidative
O
O
Solvent
O
100 oC, time (h)
NH2
+
NH
Ph
H
Ph
NH2
1
N
5a
open flask
2a
Entry
Solvent
Time (h)
Yielda (%)
c
1b
2
3
4
5
DMSO
DMSO
DMF
16
16
16
16
16
16
16
16
3.5
16
—
100 (91)d
44
12
1,4-Dioxane
H2O
Toluene
EtOH
c
—
—
—
c
6
7
c
8e
9f
10g
DMSO
DMSO
DMSO
Trace
100
Trace
Yields were determined by 1H NMR analysis of the crude reaction mixture.
Reaction was performed in the presence of 4 Å molecular sieves.
Imine 3a was obtained as the major product.
Isolated yield.
a
b
c
d
e
f
At 80 °C.
At 120 °C.
Under argon atmosphere.
g
cyclization still proceeded, but 5a was obtained in much lower
yields (entry 6). However, the reaction performed in the absence
of molecular sieves provided 5a in slight better yields than the
reaction under standard conditions (entry 7). When the reaction
was performed in the absence of both a nucleophilic catalyst and
molecular sieves, rather unexpectedly, the aerobic oxidative cycli-
zation reaction more rapidly progressed than did that with both a
nucleophile and molecular sieves and the desired quinazolinone 5a
was obtained in excellent yield (entry 8).
O
N
O
O
Nu-
NH2
R
NH2
NH2
2
R
3
1
O
6-endo-trig
NH2
cyclization
With these rather unexpected results in hand, we investigated
the possibility of the direct synthesis of 5a from anthranilamide
1 and benzaldehyde 2a without the isolation of intermediate 3a
(Table 2). Initially, this reaction was performed in the presence of
molecular sieves to facilitate the formation of the corresponding
imine 3a. However, under these conditions, 5a was not observed
even after 16 h; instead, 3a was formed as a minor product along
with unreacted starting compounds (entry 1). When the same
reaction was carried out in the absence of molecular sieves, rather
unexpectedly the reaction proceeded to completion to afford 5a in
excellent yields after 16 h (entry 2). Under these conditions, the ef-
fect of solvent was investigated on the formation of quinazolinone
(entries 2–7). It was found that the choice of solvent had a signif-
icant influence on this transformation. Quinazolinone 5a was
formed in quantitative yields in DMSO, while the reaction pro-
ceeded with very poor efficiency in other solvents. The reaction
temperature was also found to have a strong influence on this
transformation (entries 2, 8 and 9). The formation of quinazolinone
proceeded very slowly at 80 °C (entry 8); an increase to 100 °C re-
sulted in a more rapid reaction (entry 2), and further temperature
increase to 120 °C promoted complete transformation within 3.5 h
(entry 9). When the same reaction was performed under argon
atmosphere, no formation of quinazolinone was observed, which
supported that the air would be responsible for the terminal oxid-
nant in this transformation (entry 10).10
R
(pathway a)
N
H
6
Nu
O
O
- Nu-
[O]
NH
NH
R
6-exo-tet
N
R
N
H
4
cyclization
5
(pathway b)
Scheme 1. Working hypothesis.
Table 1
Investigation of nucleophiles
O
O
Nucleophile (100 mol%)
DMSO, 4A MS
NH2
NH
100 oC, time (h)
N
Ph
N
5a
Ph
3a
open flask
Entry
Nucleophile
Time (h)
Yielda (%)
1
2
3
4
NaCN
NaI
KI
NaOPh
NaOAc
—
NaCN
—
16
16
16
16
16
16
16
12
56
37
43
31
19
30
5
6
7b
8b
66
Under the optimized reaction conditions, the substrate scope
was investigated for this transformation (Table 3). Various aro-
matic aldehydes were readily applied to this protocol and the de-
100 (94)c
a
b
c
Yields were determined by 1H NMR analysis of the crude reaction mixture.
Reaction was performed in the absence of molecular sieves.
Isolated yield.
sired products
5 were obtained in high to excellent yields
(entries 1–11). Stereoelectronic effects of the aromatic aldehydes

2342
N. Y. Kim, C.-H. Cheon / Tetrahedron Letters 55 (2014) 2340–2344
Table 3
Table 4
Substrate scope for 2-substituted quinazolinones 5
Substrate scope for 2,3-disubstituted quinazolinones 8
O
O
N
O
O
O
O
R'
R'
R
DMSO, 100 oC, time (h)
open flask
NH2
NH
N
H
DMSO, 120 oC, 48 h
N
+
+
H
R
H
R
open flask
NH2
1
R
NH2
7
N
8
2
5
2
Entry
Quinazolinone 5
Time (h)
Yielda (%)
Entry
Quinazolinone 8
Yielda (%)
1
2
3
4
5
6
7
8
5a: R = C6H5
12
12
12
18
12
30
30
18
18
36
18
18
36
36
12
36
18
36
36
12
91
84
89
88
98
95
76
85
86
79
82
95
93
96
71
92
97
42
67
93
8
R
R0
5b: R = 4-MeOC6H4
5c: R = 4-MeC6H4
5d: R = 4-ClC6H4
5e: R = 4-(MeO2C)C6H4
5f: R = 4-NCC6H4
5g: R = C6F5
5h: R = 2-MeC6H4
5i: R = 2-ClC6H4
5j: R = 1-naphthyl
5k: R = 2-naphthyl
5l: R = 2-furyl
5m: R = 2-thienyl
5n: R = 2-pyridyl
5o: R = CH@CHPh
5p: R = n-hexyl
5q: R = c-hexyl
5r: R = t-butyl
1
2
3
4
5
6
7
8
8a
8b
8c
8d
8e
8f
8g
8h
8i
C6H5
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
CH2Ph
CH3
80
77
72
72
84
72
68
65
73
38
42
86
80
4-MeOC6H4
4-MeC6H4
4-ClC6H4
4-(MeO2C)C6H4
2-MeC6H4
2-ClC6H4
2-Furyl
2-Thienyl
H
n-Hexyl
C6H5
9
10
11
12
13
14
15
16
17
18b
19b
20c
9
10
11
12
13
8j
8k
8l
8m
C6H5
a
Isolated yields.
5s: R = H
5a: R = C6H5
anthranilamides were also applied to this protocol to afford the de-
sired products 8 in high yields (entries 12 and 13).
a
b
c
Isolated yields.
After the successful development of the protocol for the synthe-
sis of 2-substituted- and 2,3-disubstituted quinazolinone deriva-
tives, we attempted to further demonstrate the usefulness of this
protocol. Particularly, since this protocol was performed in the ab-
sence of any oxidants and metal catalysts, and water might be the
only by-product from this transformation,5 we expected that a
resulting quinazolinone could be further transformed into other
useful products in the same pot without its isolation.
Based on this idea, we first attempted to develop a novel one-
pot method for the preparation of 4-aminoquinazoline 10 from 1
and 2a through the direct conversion of resulting quinazolinone
5a into 4-chloroquinazoline 9, followed by the displacement of
an amine nucleophile without the isolation of 5a (Scheme 2).13
When POCl3 was added to the solution of 5a prepared under stan-
dard conditions, no chlorinated compound 9 was observed (Eq. 1).
We suspected that the high reactivity of DMSO toward POCl3 might
interfere in the formation of 9. Thus, we decided to carry out the
same reaction in DMF, which is commonly used in the Vilsmeier
reaction.14 However, under such conditions the aerobic oxidation
2.5 equiv of aldehyde were used.
20 mmol scale.
had a little effect on the formation of 5; quinazolinones 5 were ob-
tained in high yields regardless of the stereoelectronic nature of
the aromatic aldehydes. Heteroaromatic aldehydes were also ap-
plied to this aerobic oxidation protocol without any sacrifice of
its efficiency (entries 12–14). In addition, this protocol could be ex-
tended to a,b-unsaturated aldehydes, such as cinnamaldehyde (en-
try 15). Aliphatic aldehydes including formaldehyde11 were also
applied to this protocol and the desired products were obtained
in good to high yields (entries 16–19). This method could be em-
ployed on a gram scale without any loss of efficiency demonstrat-
ing the practicality of this method (entry 20).
With the successful development of a new protocol for the syn-
thesis of 2-substituted quinazolinones 5, we attempted to extend
this protocol to the synthesis of 2,3-disubstituted quinazolinones
8
from N-substituted anthranilamides 7 and aldehydes 2
(Table 4).12 Under similar conditions for the synthesis of 5, we ex-
plored the possibility of the direct synthesis of 2,3-disubstituted
quinazolinone 8a from N-phenyl anthranilamide 7a with 2a. To
our delight, 8a was obtained in high yield without any further opti-
mization of the reaction conditions (entry 1). Under these condi-
tions, the substrate scope of aldehydes for this transformation
was investigated (entries 1–7). The stereoelectronic effect of the
aromatic aldehydes had little effect on the formation of 8. In addi-
tion, the protocol could be extended to heteroaromatic aldehydes
and the desired quinazolinones were obtained in good yields (en-
tries 8 and 9). However, the extension of this protocol to aliphatic
aldehydes turned out to be challenging. In particular, the struc-
tures of aliphatic aldehydes had strong influence on the synthesis
of quinazolinones. Formaldehyde and 1-heptanal provided 8j and
8k, respectively, in synthetically useful yields (entries 10 and 11).
However, aliphatic aldehydes bearing more than two alkyl groups
O
O
Cl
2a
POCl3
DMSO, 100 oC
NH2
NH
Ph
N
(1)
24 h
open flask
NH2
O
N
5a
N
9
Ph
1
1
Not Isolated
No Reaction
O
O
2a
DMF, 100 oC
NH2
NH
Ph
NH2
+
(2)
(3)
24 h
open flask
NH2
O
N
N
3a
Ph
5a
~30 %
Major
O
NHPh
N
2a
1) POCl3, 50 o
C
NH2
DMSO (3 equiv)
DMF, 100 o
NH
Ph
C
2) NH2Ph
NH2
N
5a
N
Ph
48 h
10
1
open flask
at the a-carbon, such as c-hexyl and t-butyl aldehydes, did not pro-
vide the expected quinazolinone products and a complex mixture
Not Isolated
37 % over three-step
was obtained with these substrates. Other N-substituted
Scheme 2. One-pot synthesis of 4-aminoquinazoline 10.

N. Y. Kim, C.-H. Cheon / Tetrahedron Letters 55 (2014) 2340–2344
2343
O
N
did not proceed to completion and 5a was obtained as the minor
O
O
O
product along with 3a (Eq. 2). Because DMSO is often used in oxi-
dation reactions,15 we assumed that DMSO might have some ben-
eficial effect on the above aerobic oxidative cyclization reaction.
When the reaction was carried out in the presence of 3 equiv of
DMSO in DMF solution, delightfully, the aerobic oxidative cycliza-
tion went smoothly to afford 5a in quantitative yields. Further-
more, the resulting 5a was directly converted into 9 with POCl3
in the same pot and the subsequent addition of aniline afforded
4-aminoquinazoline 10 in synthetically useful yield over three
steps, even without complete optimization of the one-pot reaction
conditions (Eq. 3).16
NH2
NH2
NH2
NH2
H2O
2
R
R
R
N
H
OH
1
3
6'
6-exo-tet
cyclization
(pathway b)
6-endo-trig
cyclization
(pathway a)
O
O
[O]
NH
NH
N
R
N
H
4
R
5
Aldehyde equivalents could be also subjected to this protocol
(Scheme 3).17 For example, when 3,3-dihydro-2H-pyrone 11, com-
monly used as a 5-hydroxypentanal equivalent, was used in this
transformation in the presence of 10 mol % of para-toluenesulfonic
acid (PTSA), the reaction smoothly proceeded to afford the corre-
sponding quinazolinone 12 in good yield under the standard con-
ditions with aldehydes (Eq. 4). Moreover, the resulting
quinazolinone 12 was directly employed in the Mitsunobu reac-
tion18 to yield mackinazolinone 1319 in synthetically useful yields
in the same pot although all the reaction conditions were not opti-
mized (Eq. 5).
With these results in hand, we attempted to gain information
about the reaction mechanism for this transformation. During opti-
mization, the quinazolinone was found to be formed in the pres-
ence of molecular sieves without any assistance of a nucleophile
(Table 1, entry 6). This result suggested that under these condi-
tions, quinazolinone 5 could be formed by the direct cyclization
of 3 via 6-endo-trig cyclization (pathway a in Scheme 1) although
the yield was low. In addition, it was observed that the choice of
a nucleophile had an influence on the efficiency of this transforma-
tion (Table 1, entries 1–5). These results also supported our work-
ing hypothesis where a nucleophile might be involved in the
cyclization of imine 3 via the 6-exo-tet cyclization of intermediate
6 formed from 3 with the nucleophile (pathway b). Particularly,
since it was observed that the formation of 5 was significantly
accelerated in the absence of molecular sieves and a nucleophile
(Table 1, entry 8), we expected that water could be the nucleophilic
catalyst for the cyclization of 3 into 4, which eventually accelerates
the formation of quinazolinone 5.
Scheme 4. Proposed reaction pathway.
formed from the reaction of 3 with water and the 6-exo-tet cycliza-
tion of intermediate 60 occured along with uncatalyzed 6-endo-trig
cyclization of 3. Since the 6-exo-tet cyclization from 60 was much
faster than the 6-endo-trig cyclization from 3, the yield of quinaz-
olinone was significantly increased under such conditions. This
proposed mechanism also rationalized the significant increase in
the yield of quinazolinone from anthranilamide 1 and aldehyde
2. In the presence of molecular sieves (in the absence of water), ini-
tially formed intermediate 60 was rapidly converted into imine 3,
which could undergo cyclization via only 6-endo-trig cyclization.
However, in the absence of molecular sieves (in the presence of
water), the intermediate 60 readily underwent cyclization through
6-exo-tet cyclization, leading to the desired product in comparable
yields with those from imine 3.
In conclusion, we have developed a highly environmentally be-
nign protocol for the synthesis of 2-substituted and 2,3-disubsti-
tuted quinazolinones from anthranilamides and aldehydes via
aerobic oxidative cyclization in wet DMSO without any additives.
This new protocol features operational simplicity, high atom econ-
omy, and broad substrate scope. The usefulness of this new proto-
col was further demonstrated by the direct application of the
resulting quinazolinones to Vilsmeier and Mitsunobu reactions in
the same pot without their isolations. Further application of this
protocol to total synthesis of biologically important natural prod-
ucts and more detailed mechanistic studies for this transformation
are currently underway in our laboratory.
Based on these results, we proposed a possible reaction mecha-
nism where water would act as a nucleophilic catalyst for this pro-
tocol (Scheme 4). The quinazolinone 5 could be obtained from
imine 3 via either the direct 6-endo-trig cyclization (pathway a)
of 3 or the 6-exo-tet cyclization (pathway b) of intermediate 60
formed by the reaction of 3 with water. Since the formation of
intermediate 60 was intrinsically impossible in the absence of
water, 5 was obtained in low yields through 6-endo-trig cyclization
of 3. However, in the presence of water, intermediate 60 could be
Acknowledgments
This work was partly supported by Basic Science Research Pro-
gram through the National Research Foundation of Korea (NRF)
funded by the Ministry of Science, ICT and Future Planning
(2013R1A1A1008434). C.-H.C. also thanks the Ministry of Educa-
tion (NRF20100020209) for financial support from the NRF fund.
Supplementary data
O
O
OH
NH
PTSA (10 mol%)
open flask
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet. 2014.
02.065.
NH2
NH2
(4)
(5)
+
O
11
DMSO, 100 o
24 h
C
N
12
51 %
1a
References and notes
11
O
O
OH
NH
O
1. For reviews, see: (a) Mhaske, S. B.; Argade, N. P. Tetrahedron 2006, 62, 9787–
9826; (b) Connolly, D. J.; Cusack, D.; O’Sullivan, T. P.; Guiry, P. J. Tetrahedron
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DIAD
NH2
open flask
N
DMSO, 100 o
24 h
C
PPh3
rt, 12 h
NH2
1a
N
12
N
13
56 % over two-step
not isolated
Scheme 3. Application of aldehyde equivalent 11 and direct further
functionalization.

2344
N. Y. Kim, C.-H. Cheon / Tetrahedron Letters 55 (2014) 2340–2344
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3. There are a few reports of the oxidative synthesis of 5 from benzylic alcohols as
aldehyde precursors with anthranilamides in the presence of transition metal
catalysts. For examples, see: (a) Hikawa, H.; Ino, Y.; Suzuki, H.; Yokoyama, Y. J.
Org. Chem. 2012, 77, 7046–7051; (b) Watson, A. J. A.; Maxwell, A. C.; Williams, J.
M. J. Org. Biomol. Chem. 2012, 10, 240–243; (c) Zhou, J.; Fang, J. J. Org. Chem.
2011, 76, 7730–7736.
4. Alternatively, 5 are synthesized via the condensation of anthranilamides and
carboxylic acids and their derivatives and subsequent dehydrative cyclization
of the resulting amides. For recent examples, see: (a) Gellibert, F.; Fouchet, M.
H.; Nguyen, V. L.; Wang, R.; Krysa, G.; Gouville, A. C.; Huet, S.; Dodic, N. Bioorg.
Med. Chem. Lett. 2009, 19, 2277–2281; (b) Purandare, A. V.; Gao, A.; Wan, H.;
Somerville, J.; Burke, C.; Seachord, C.; Vaccaro, W.; Wityak, J.; Poss, M. A. Bioorg.
Med. Chem. Lett. 2005, 15, 2669–2672.
15. Steinhoff, B. A.; Stahl, S. S. J. Am. Chem. Soc. 2006, 128, 4348–4355.
16. During the amination, the significant amount of 9 was hydrolyzed to form the
original quinazolinone 5a.
17. Reddy, B. V. S.; Venkateswarlu, A.; Madan, C.; Vinu, A. Tetrahedron Lett. 2011,
52, 1891–1894.
5. Modern Oxidation Methods; Bäckvall, J.-E., Ed., 2nd ed.; Wiley-VCH: Weinheim,
Germany, 2004.
6. (a) Minisci, F.; Recupero, F.; Cecchetto, A.; Punta, C.; Gambarotti, C. J. Heterocycl.
Chem. 2003, 40, 325–328; (b) Xu, W.; Fu, H. J. Org. Chem. 2011, 76, 3846–3852;
(c) Xu, W.; Jin, Y.; Liu, H.; Jiang, Y. Y.; Fu, H. Org. Lett. 2011, 13, 1274–1277.
7. Deligeorgiev, T. G.; Kaloyanova, S.; Vasilev, A.; Vaquero, J. J.; Alvarez-Buillab, J.;
Cuadro, A. M. Color. Technol. 2010, 126, 24–30.
8. (a) Cho, Y.-H.; Lee, C.-Y.; Ha, D.-C.; Cheon, C.-H. Adv. Synth. Catal. 2012, 354,
2992–2996; (b) Cho, Y.-H.; Lee, C.-Y.; Cheon, C.-H. Tetrahedron 2013, 69, 6565–
6573.
18. For an example of Mitsunobu reaction in DMSO, see: Devdutt, C.; Suprabhat, R.
Indian Pat. Appl. (2006), IN 2004DE00394 A 20060526.
19. For the previous synthesis of mackinazolinone 13, see: (a) Bowman, W. R.;
Elsegood, M. R.; Stein, T.; Weaver, G. W. Org. Biomol. Chem. 2007, 5, 103–113;
(b) Mhaske, S. B.; Argade, N. P. Tetrahedron 2004, 60, 3417–3420; (c) Kamal, A.;
Ramana, A. V.; Reddy, K. S.; Ramana, K. V.; Babu, A. H.; Prasad, B. R. Tetrahedron
Lett. 2004, 45, 8187–8190.