An ionic liquid catalyzed reusable protocol for one-pot synthesis of 2,3-dihydroquinazolin-4(1H)-one under mild conditions

Article abstract of DOI:10.1039/c5nj01545f

An efficient protocol has been developed for the synthesis of 2,3-dihydroquinazolinone compounds from anthranilamide and aldehydes or ketones via ionic liquid catalyzed cyclization reaction. The reaction features high efficiency, shorter reaction duration, mild reaction conditions and inexpensive reagents. The catalyst was recovered and reused. The recyclability of ionic liquid resulted in excellent yields of products without loss of any catalytic activity.

Full text of DOI:10.1039/c5nj01545f

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PAPER (or FOCUS or PERSPECTIVE)
Ionic liquid catalyzed reusable protocol for
one-pot synthesis of 2,3-dihydroquinazolin-
Cite this: DOI: 10.1039/c3nj00000x
4(1H)-one under mild conditions
S. Nagarajan,a Tanveer M. Shaikh*,a Elango Kandasamy*a
Received 00th XXXXX 2013,
Accepted 00th XXXXX 2013
An efficient protocol has been developed for the synthesis of 2,3-
dihydroquinazolinone compounds from anthranilamide and aldehydes or ketones
via ionic liquid catalyzed cyclization reaction. The reaction features high efficiency,
shorter reaction duration, mild reaction conditions and inexpensive reagents. The
catalyst was recovered and reused. The recyclability of ionic liquid resulted
DOI: 10.1039/c3nj00000x
www.rsc.org/njc
excellent yields of product without loss of any catalytic activity
.
The synthetic transformations employing nonꢀtoxic,
ecoꢀfriendly catalyst have been received much attention in recent
years. Particularly, utilizing organocatalyst and green catalyst,
ionic liquids37 are beneficial compared with the metal catalysts.
aDepartment of Chemistry, Vel Tech University, Avadi, Chennai 610062,
Introduction
Quinazolinones are important class of Nꢀheterocycles, and
often present in natural products, drug molecules and
pharmaceutical compounds.1 Initially, Bischler and Lang
reported the first synthesis of quinazolinone in 1895. Later, in
1903, Gabriel prepared alternate approach via oxidation of 3,4ꢀ
hydroxyquinazole to quinazolinone.2 Moreover, 2,3ꢀ
dihyroquinazolinones are associated with several important
biological activities such as, antiꢀcancer,3 antiꢀinflammation,4
antiꢀbacterial,5 antiꢀvirus,6 antiꢀtuberculosis,7 antiꢀmalarial,8
antiꢀhypertensive,9 antiꢀobesity, antiꢀpsychotic, antiꢀdiabetes,10
etc. In this context, several synthetic methodologies have been
developed employing metalꢀsalts such as SmI2,11 Ruꢀsalt,12
CuCl2,13 SnCl2,14 Sc(OTf)3,15 ZnCl2,16 [CpIrCl2]2,17 Pd(OAc)2,18
CuO,19 [Zr(DS)4],20 Ga(OTf)3,21 TiCl4,22 KAl(SO4)2.12H2O,23a
Al(H2PO4)3,23b [Ce(NH4)2.(NO3)6],24 and metal nanoꢀparticles,25
of Co, Cu, Ag, In, La and Fe. Transition metals are expensive,
unstable and often produce considerable amount of metal
wastes. Therefore series of nonꢀmetal catalysts has been
developed for the preparation of molecules containing this
Tamilnadu, India. Email: elangoomc@gmail.com
The other reported green procedures for the synthesis of 2,3ꢀ
dihydroquinazolinones have been employed using ionic
liquids,37aꢀg and organocatalysts such as phosphoric acid,38
T3P,39 tBuOK,40
K3PO4,43
β
ꢀcyclodextrine,41 polyethylene glycolꢀ400,42
p
ꢀsulfonic acid (calyx[4]arene)44 and are known.
Despite these synthetic protocols a practical, mild and green
catalysts are still in great demand. In continuation of our efforts
to develop ecoꢀfriendly protocols for multicomponent
reaction,45 here in, we wish to report a new efficient method
employing ionic liquid catalyzed 1a-c (Figure 1) oneꢀpot
synthesis of 2,3ꢀdihydroquinazolinones under mild conditions
(Scheme 1).
motif,
HCl,26
pꢀTSA,27
I2,28
TMSCl,29
NH4Cl,30
trifluoroethanol,31 acidic silica,32 cyanuric chloride,33
heteropoly acid,34 Amberlystꢀ15,35 montmorillonite Kꢀ10.36
Figure 1. The structures of ILs examined in this paper
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3
4
5
6
7
5
H2O
H2O
H2O
25
4
2
120
2
10
5
1
1
5
2
70
10
10
5
5
5
10
15
20
100
10
5
85
95c (85, 80)d
neat
10 (25)e
40
MeOH
EtOH
EtOH
EtOH
EtOH
nil
EtOH:H2O
THF
CH2Cl2
CH3CN
DMF
8
9
88
92
91
91
80
96
90
94
81
88
80
82
Scheme 1. ILꢀcatalyzed synthesis of 2,3ꢀdihydroquinazolinones
10
11
12
13
14
15
16
17
18
19
Results and discussion
The ionic liquids 1a-c was prepared in large scale using our
synthetic procedure.45d Our initial efforts focused on developing
general, suitable and green reaction conditions and the results
5
5
5
5
5
10
10
10
10
20
are summarized in Table 1. When anthranilamide
was allowed to react with benzaldehyde (1 equiv.) in the
presence of ionic liquid 1a as catalyst (2 mol%) in H2O at 25
°C, the traces of
was formed. The yield improved dramatically
upon addition of 5 mol% of catalyst, resulted 70% yield of
(Table 1, entry 3). While increasing the amount of catalyst to
10 mol% 2,3ꢀ dihydroquinazolinone ( ) was obtained in 85%
2 (1 equiv.)
Toluene
EtOAc
3
5
4
a
aReaction conditions: anthranilamide (3.0 mmol), benzaldehyde
(3.0 mmol), ionic liquid 1a, solvent; bisolated yield; creaction was
carried out in mortar pestle; d catalyst 1b and 1c were employed,
respectively; estirred for overnight; solvent mixture of 2:1.
4
4
yield (entry 4). Surprisingly, when the reaction was subjected to
grinding using mortar for 2 minutes, quinazolinone was isolated
as sole product in >95% yield. The product conversion
proceeded slowly and in low yield (25%) under solventꢀfree
condition (entry 6). A number of experiments were performed
in an effort to extent the general/largeꢀscale procedure to the
preparation of 2,3ꢀdihydroquinazolinone. The reaction proceeds
The versatility of this protocol was investigated by
examining the reaction of anthranilamide (2) and scope of
various aldehydes (3) to this cyclization using the optimized
conditions, and the results are presented in Table 2. When we
treated 4ꢀmethyl benzaldehyde (Table 2, entry 2) with
in polar solvents (MeOH, EtOH) and afforded the product
40% and 88% yields, respectively (entries 7ꢀ8). To address, the
need for enhanced yield, we added 10 mol% of catalyst 1a
4 in
anthranilamide, a desired product
4 was observed in 93% yield
after a short reaction time of three minutes. Interestingly, high
yield (93ꢀ95%) and selective cyclization were observed with all
the electronꢀdonating substrates (entries 3ꢀ8). Similarly, the
consistency was observed in case of electronꢀwithdrawing
substrates (such as, NO2, CN, CO2H), which were smoothly
,
which resulted 92% of 2,3ꢀdihydroquinazolinone in 10 minutes
(entry 9). It was found that the use of 15ꢀ20 mol% 1a, the
reaction was faster and completed within a minute. However,
the stoichiometric amount of catalyst 1a (in absence of solvent)
was resulted low yield of product (entry 12). The reaction
improved efficiently, upon addition of a mixture of EtOH:H2O
(1:2) to the reaction (entry 13). Other screened solvents such as,
THF, CH2Cl2, CH3CN, DMF, toluene, EtOAc, led to a 80ꢀ94%
afforded
the
corresponding
2,3ꢀdihydroquinazolinone
compounds (entries 9ꢀ12). The sterically encumbered aldehyde
afforded the excellent yield of the corresponding
quinazolinones (entries 13ꢀ14). The reaction with thiopheneꢀ2ꢀ
carboxaldehyde resulted with 93% yield. However, the other
heteroꢀcarboxaldehyde such as 2ꢀfuraldehyde and indoleꢀ3ꢀ
carboxaldehyde were resulted with low yield of the desired
product (entries 15ꢀ17). These heterocycles are sensitive
towards air and acid catalyst.46 The reaction with
propionaldeyde displayed a slightly slower reaction rate,
reaching poor conversion at 6 hours (entry 18).
yields of product
screened ionic liquids 1b and 1c were resulted product
4
(entries 14ꢀ19). It was found that the other
in
4
85% and 80% yields, respectively. The reaction proceeds most
efficiently with ionic liquid 1a, probably due to strong CꢀF
bonding enhance the rate of reaction. The excellent results were
°
obtained with 10 mol% of ionic liquid 1a at 30 C, H2O in
°
mortar grinding (Table 1, entry 5) or at 30 C, EtOH:H2O
stirring in sample vial (Table 1, entry 13).
Table 2 Reaction of anthranilamide and aldehydes for the
preparation of 2,3-dihydroquinazolinonea
Table 1 Evaluation of reaction parametersa
Entry
Substrate
Product
Time
(min)
Yield
(%)b,c
3
4
Entry Catalyst
(mol%)
Solvent
(mL)
Time
(min)
Yieldb
(%)
1
2
96
1
2
2
5
H2O
H2O
10
10
traces
35
2 | J. Name., 2012, 00, 1-3
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2
3
93
16
24
24
10
10
17
18
3
4
5
3
1
5
93
95
90
6
10
aReaction conditions: anthranilamide (3.0 mmol), aldehyde
°
(3.0 mmol), catalyst 1a (10 mol%), H2O, 30 C, mortar pestle;
bproducts were characterized by m.p., FTIR, 1Hꢀ and 13Cꢀ
NMR; cisolated yields.
6
3
89
We next explored the effect of ketones to this cyclization
reaction. Initially, the treatment of acetophenone (
anthranilamide ( ) and 10 mol% of ionic liquid 1a in H2O at
room temperature resulted in the formation of low yield of 2,3ꢀ
dihydroquinazolinone . Therefore, the same reaction was
performed in ethanol solvent; the product was obtained in
93% yield in 3 hours stirring. Encouraged by these results, we
evaluated other substituted acetophenones for example methyl,
fluoro, bromo and methoxy, which smoothly transformed to the
corresponding product in 88ꢀ92% yields, respectively (entries
2ꢀ5). Unfortunately, the sterically hindered benzophenone have
shown poor reactivity and low yield of product under these
conditions (entry 6). It is noteworthy that the reaction of cyclic
and aliphatic ketones such as cyclohexanone, cyclopentanone,
acetone and others were successfully yielded the corresponding
quinazolinonone in excellent yield (89ꢀ93%) within 3ꢀ10
5) with
2
7
8
4
2
91
92
6
CHO
Cl
6
Cl
9
3
3
90
89
O
NH NO2
N
H
10
minutes (entries 7ꢀ12). However, in the case of
(entry 13) no desired product was obtained.
βꢀketo ester
11
12
2
5
91
91
Table 3 Reaction of anthranilamide and ketones for the
preparation of 2,3-dihydroquinazolinonea
Entry
Substrate
Product
Time
(min)
Yield
(%)b,c
5
6
13
14
15
15
2
92
90
93
1
2
3
4
93
90
7
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We then studied the recyclability of the catalyst 1a to this
cyclization reaction. The ionic liquid 1a was recovered after
completion of the reaction and directly subjected to the
cyclization reaction. To our surprise the reaction of recovered
3
12
12
90
92
catalyst 1a (10 mol%) with anthranilamide
benzaldehyde ( ) was resulted in the formation of 95% yield of
quinazolinone ( ). These results were consistent for the next
four cycles without loss of efficiency of the catalyst 1a (Figure
2). Similarly, when we subjected ketones ( ) to our reusability
(
2
)
and
3
4
4
5
5
studies, the results are excellent and afforded the corresponding
2,3ꢀdihydroquinozolinone in >95% yield.
8
88
20
Yield of quinazolinone
100
80
60
6
24
40
20
0
Yield of
quinazolinone
7
8
24
3d
18
91
Cycle Cycle Cycle Cycle
1
2
3
4
.
Figure 2. Catalyst 1a reusability study
Conclusions
9
3d
90
89
In conclusion, we have described an efficient ionic liquid 1a
catalyzed multicomponent cyclization that allows the
transformation of anthranilamide with aldehydes or ketones
into their corresponding 2,3ꢀdihyroquinazolinones in excellent
yields. The CꢀN bond formation of aldehydes was achieved by
two different conditions. It is important to note that the catalyst
ionic liquid has been recycled after completion of the reaction.
A novel feature of this catalytic reaction is that short reaction
time, mild conditions and recoverable catalyst.
10
10d
11
12
13
10d
94
93
nr
2d
Experimental
General
Solvents were freshly distilled prior to use and glassware was dried
in oven at 120 °C for 5 h. All the reagents were purchased from
Merck and Sigma Aldrich. H NMR spectra were recorded at 400
24
nil
1
MHz and 13C NMR spectra at 100 MHz on a Bruker AVANCE FT
NMR instrument using CDCl3 and DMSOꢀd6 as standard solvents.
Electrospray ionization mass spectrometry (ESIꢀMS) spectra were
recorded on a Waters QꢀTOF Premier mass spectrometer. LC/MS
data were performed on a Agilent MSD mass spectrometer. Method
info: A: 0.05 % HCOOH in H2O, B: 0.04 % HCOOH in CH3CN;
flow rate: 2.0 ml/min; Column: Chromolith RPꢀ18e, 100ꢀ3 mm, +ve
aReaction conditions: anthranilamide (3.0 mmol), ketone (3.0
°
mmol), catalyst 1a (10 mol%), EtOH, 30 C, stirred in glass
vial; bproducts were characterized by m.p., FTIR, 1Hꢀ and 13Cꢀ
NMR; cisolated yields; dreaction time in minutes
4 | J. Name., 2012, 00, 1-3
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DOI: 10.1039/C5NJ01545F
mode. Elemental analyses of the compounds were obtained from Colorless liquid; yield 94%; elemental analysis: calcd. for C,
thermoquest CE instrument CHNSꢀO, EA/110 model. IR spectra 27.48; H, 4.23; N, 16.02, found: C, 27.24, H, 4.11, N, 16.01;
were recorded using KBr pellets on a Bruker Vector 22 FTꢀIR 1HꢀNMR (CDCl3, 400 MHz) δ 12.9 (s, 1
H
H
, N
H), 9.6 (s, 1H, 5ꢀ
spectrometer operating at 400ꢀ4000 cmꢀ1. Melting points were
measured in DALAL melting point apparatus, India and corrected.
C
H
), 8.6 (s, 1
8Hz, 6
5), 139.5 (
H(CH3)2), 21.4 CH(CH3)2) ESꢀMS m/z 112.1580; 19FꢀNMR
H
, 3ꢀC
H
), 4.9 (m, 1
H
, C
(CH3)2), 1.6 (d, J =
H
, CH(CH3)2), 13CꢀNMR (CDCl3, 100 MHz) δ 143.1 (
Cꢀ
C
ꢀ3), 124.8, 121.6, 118.5 115.3, (CF3SO3), 55.7
Synthesis of 1-isopropyl-1,2,4-triazolium triflate 1a.
C
78.9378.
To a solution of 1ꢀ isopropylꢀ1,2,4ꢀtriazoles (10 mmole) in
toluene (10 ml) was added drop wise trifluromethanesulfonic
acid (10 mmole). This reaction mixture was then heated to 80
°C for 12 h. After completion of the reaction, flask was cooled
to room temperature (25 °C) and excess of toluene was removed
under reduced pressure. The resulting residue was thoroughly
washed with hexane (20 mL x 2) and further dried over vacuum
1-Isopropyl 1, 2, 4-triazolium methanesulfonate (1b)
Colorless liquid; yield 91%; elemental analysis: calcd. for, C,
34.60; H, 6.78; N, 20.18; found, C, 34.54, H, 6.56, N, 20.10;
1HꢀNMR (CDCl3, 300 MHz): δ 12.4 (s, 1
H
, N
H
), 10.1 (s, 1
H
H
,
,
5ꢀCH), 8.6 (s, 1H, 3ꢀCH), 4.9 (m, 1H, CH(CH3)2), 2.8 (s, 3
H3SO3), 1.6 (d, 6H, CH(CH3)2); 13CꢀNMR (CDCl3, 75 MHz):
to afford pure catalyst 1a
.
C
δ 143.3 (
21.8 (CH(
C
C
ꢀ5), 140.3 (
H3)2).
Cꢀ3), 55.4 (CH(CH3)2 ), 39.6 (CH3SO3),
Note:
methanesulfonate
Syntheses
of
1ꢀisopropylꢀ1,2,4ꢀtriazolum
and 1ꢀbutylꢀ1,2,4ꢀtriazolium
(
1b)
phenylsulfonate (1c) ionic liquids has been prepared similar to
1a
1-Isopropyl 1, 2, 4-triazolium phenylsulfonate (1c)
White solid; yield 89%; elemental analysis: calcd. for, C, 48.87;
H, 5.97; N, 15.54; found : C, 48.64, H, 5.85, N, 15.34; 1H NMR
.
Syntheses of 2,3-dihydroquinazolinone (4)
(CDCl3, 300 MHz): δ 12.8 (brs, 1H, N
8.6 (s, 1 , 3ꢀC ), 7.8 (m, 2 , C ), 7.3 (m, 3
1H, C (CH3)2), 1.5 (d,
= 6.6 Hz, 6H, CH(CH3)2); 13CꢀNMR
(CDCl3, 75 MHz): δ 143.0 ( ꢀ5), 140.2 ( ꢀ3), 130.3, 128.3,
125.8 ( C6H5SO3), 55.5 ( H(CH3)2 ), 21.4 (CH( H3)2).
H
), 10.1 (s, 1
H
, 5ꢀC
H),
H
H
H
H
H
, C
H) 4.8 (m,
Catalyst 1a (10 mol %) was added to a solution of
anthranilamide (3.0 mmole) and the corresponding aldehyde
(3.0 mmole) in water (1 mL). The reaction mixture was mixed
in a mortar and pestle at room temperature for designated time.
The progress of the reaction was monitored by TLC. After
completion of the reaction, the reaction mixture was quenched
with mixture of water:ethanol (5:0.5 mL). The corresponding
H
J
C
C
C
C
2-phenyl-2, 3-dihydroquinazolin-4(1H)-one (Table 2, entry 1)
°
°
1
White solid; yield 96%; mp 217ꢀ219 C (Lit.33: 218ꢀ220 C); Hꢀ
NMR (400 MHz, DMSOꢀd6): δ 8.2 (s, 1H), 7.6 (m, 1H), 7.5 ( m,
2H), 7.3 (m, 3H), 7.2 (m, 1H), 7.1 (s, 1H), 6.7 ( m, 2H), 5.7 (s, 1H);
13CꢀNMR (100 MHz, DMSOꢀd6); δ 163.5, 147.8, 141.6, 133.2,
128.4, 128.3, 127.3, 126.8, 117.0, 114.9, 114.3, 66.5; IR (KBr):
3305, 3180, 3059, 1665, 1615, 1535, 1450 cmꢀ1; LC/MS [M+H]+
(m/z) 235.
solid product was filtered, and washed with nꢀhexane (5 mL x
2), which afforded pure 2,3ꢀdihydroquinazolinone.
Syntheses of 2,3-dihydroquinazolinone (6)
Catalyst 1a (10 mol%) was added to
a solution of
anthranilamide (3.0 mmole) and the corresponding ketone (3.0
mmole) in ethanol (1 mL). The reaction mixture was stirred in 5
mL glass vial at room temperature. The progress of the reaction
was monitored by TLC. After completion of the reaction, the
reaction mixture was quenched with mixture of water:ethanol
2-(3,5-dimethoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one (Table
2, entry 4)
White solid; yield 95 %; mp 139ꢀ140 °C; 1HꢀNMR (400 MHz,
DMSOꢀd6): δ 8.2 (s, 1H), 7.5 (d, J = 12 Hz, 1H), 7.2 (m, 1H), 7.1 (s,
1H), 6.7 ( d, J = 8 Hz, 1H), 6.6 (m, 3H), 6.4 (m, 1H), 5.6 (s, 1H), 3.7
(s, 6H); 13CꢀNMR (100 MHz, DMSOꢀd6): δ 163.5, 160.3, 147.7,
144.1, 133.2, 127.3, 117.1, 114.9, 114.3, 104.9, 99.7, 66.1, 55.2;
FTIR (KBr): 3302, 3186, 3061, 2936, 2806, 1908, 1655, 1613, 1510,
1440, 1388, 1300, 1250, 1152, 1029 cmꢀ1; LC/MS [M+H]+ (m/z)
285.
(5:0.5 mL). The solid was filtered, and washed with nꢀhexane
(5 mL x 2), which afforded pure 2,3ꢀdihydroquinazolinone.
Procedure for the reusability of new triazolium based ionic
liquids 1a
The catalyst was separated from the reaction mixture by simple
filtration technique and the filtrate was concentrated to remove
excess of water and small amount of ethanol. Then the crude
residue was thoroughly washed with mixture of hexane: ethyl
acetate (4:1) 5 mL and dried at 45 °C over vacuum for 1 h. This
residue was subjected directly to catalyst reusable study.
4-(4-oxo-1,2,3,4-tetrahydroquinazolin-2-yl) benzoic acid (Table 2,
entry 12)
White solid; yield 91%; mp 271ꢀ273 °C; 1HꢀNMR (400 MHz,
DMSOꢀd6): δ 12.9 (s, 1H), 8.3 (s, 1H), 7.9 (d, J = 8 Hz, 2H), 7.6 ( m,
3H), 7.2 (m, 2H), 6.7 (m, 2H), 5.8 (s, 1H); 13CꢀNMR (100 MHz,
Spectral data for selected compounds
1-Isopropyl 1, 2, 4-triazolium trifluoromethanesulfonate (1a)
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DMSOꢀd6): δ 167.0, 163.4, 147.5, 146.4, 133.4, 130.8, 129.3, 127.3, DMSOꢀd6): 163.5, 147.5, 133.6, 127.6, 116.9, 114.7, 114.3, 67.3,
127.0, 117.2, 114.9, 114.4, 66.0; FTIR (KBr): 3300, 3179, 3127, 29.4; IR (KBr): 3330, 3261, 3033, 2991, 2969, 1655, 1620, 1515,
3063, 2934, 2865, 2677, 2551, 1698, 1656, 1610, 1584, 1509, 1431, 1484, 1388, 1361, 1335, 1278, 1197, 1180, 1140 cmꢀ1.
1385, 1291, 1155, 1015 cmꢀ1; LC/MS [M+H]+ (m/z) 269.
2-isobutyl-2-methyl-2,3-dihydroquinazolin-4(1H)-one (Table 3,
2-(naphthalen-2-yl)-2, 3-dihydroquinazolin-4(1H)-one (Table 2,
entry 11)
entry 13)
°
°
1
White solid; yield 94%; mp 172ꢀ174 C (Lit.28b: 171ꢀ173 C); Hꢀ
°
1
Colorless solid; yield 92%; mp 167ꢀ169 C; HꢀNMR (400 MHz, NMR (400 MHz, DMSOꢀd6): δ 7.8 (s, 1H), 7.5 (d, J = 8Hz 1H), 7.2
DMSOꢀd6): δ 8.5 (m, 1H), 8.2 (s, 1H), 7.9 (t, J = 8 Hz, 2H), 7.7 (m, (m, 1H), 6.6 (m, 3H), 1.9 (m, 1H), 1.8 (m, 1H), 1.5 (m, 3H), 0.9 (m,
2H), 7.5 (m, 3H), 7.2 (m, 1H), 7.1 (s, 1H), 6.7 (m, 1H), 6.5 (s, 1H); 6H); 13CꢀNMR (100 MHz, DMSOꢀd6): δ 163.5, 147.5, 133.6, 127.5,
13CꢀNMR (100 MHz, DMSOꢀd6): δ 164.0, 148.4, 135.1, 133.7, 116.4, 114.4, 113.8, 69.8, 49.8, 29.1, 24.8, 24.6, 23.8; IR (KBr):
133.2, 130.5, 129.3, 128.5,127.5, 126.0, 125.8, 125.1, 124.5, 117.2, 3324, 3170, 2950, 2865, 1657, 1612, 1580, 1511, 1484, 1432, 1390,
114.9,114.5, 65.9; IR (KBr): 3381, 3306, 3227, 3053, 2921, 1935, 1362, 1320, 1285, 1189, 1150, 1060, 825, 745 cmꢀ1.
1655, 1610, 1503, 1424, 1373, 1299, 1152 cmꢀ1; LC/MS [M+H]+
2, 2-diethyl-2,3-dihydroquinazolin-4(1H)-one (Table 3, entry 12)
(m/z) 275.
White solid; yield 93%; mp 189ꢀ190 °C; 1HꢀNMR (400 MHz,
DMSOꢀd6): δ 7.7 (s, 1H), 7.5 (m, 1H), 7.1 (m, 1H), 6.6 (d, J = 8Hz,
1H), 6.6 (m, 1H), 6.4 (s, 1H), 1.6 (m, 4H), 0.9 (m, 6H); 13CꢀNMR
(100 MHz, DMSOꢀd6): δ 163.8, 148.1, 133.5, 127.4, 115.9, 114.0,
113.4, 72.4, 33.2, 8.3; IR (KBr): 3320, 3167, 2870, 1665, 1600,
1570, 1521, 1479, 1428, 1385, 1323, 1285, 1178, 1090, 1050, 840,
739 cmꢀ1; LC/MS [M+H]+ (m/z) 205.
2-methyl-2-phenyl-2, 3-dihydroquinazolin-4(1H)-one (Table 3,
entry 1)
Colorless solid; yield 93%; mp 225ꢀ226 °C (Lit.28b: 224ꢀ225 °C); 1Hꢀ
NMR (400 MHz, DMSOꢀd6): δ 8.7 (s, 1H), 7.6 (s, 1H), 7.5 (m, 3H),
7.2 (m, 2H), 7.1 (m, 2H), 6.7 (m, 1H), 6.5 (m,1H), 1.6 (s, 3H);13Cꢀ
NMR (100 MHz, DMSOꢀd6) δ: 163.7, 147.6, 147.1, 133.2, 127.9,
127.2, 126.9, 125.1, 116.7, 115.0, 114.2, 70.1, 30.7; IR (KBr): 3400,
3045, 1667, 1618, 1510, 1599, 14420, 1395, 1330, 1275, 1220,
1191, 1153, 1120, 1082, 1030 cmꢀ1; LC/MS [M+H]+ (m/z) 239.
Acknowledgements
1'H-spiro [cyclohexane-1,2'-quinazolin]-4'(3'H)-one ( Table 3,
EK thank the Department of Science and Technology, Science
and Engineering Research Board (DSTꢀSERB, SR/FT/CSꢀ
60/2011), India for providing research fund. Also the authors
thank Dr. G. Anantharaman Department of Chemistry, India
Institute of Technology Kanpur for NMR and ESIꢀMS
measurement.
entry 8)
°
°
1
White solid; yield 91%; mp 223ꢀ225 C (Lit.28b: 224ꢀ225 C); Hꢀ
NMR (400 MHz, DMSOꢀd6): δ 7.9 (s, 1H), 7.5 (m, 1H), 7.2 (m, 1H),
6.8 (s, 1H), 6.6 (m, 2H), 1.7 (m, 2H), 1.6 (m, 6H), 1.4 (m, 1H), 1.2
(m, 1H); 13CꢀNMR (100 MHz, DMSOꢀd6): δ 163.1, 146.7, 133.0,
127.0, 116.4, 114.5, 114.4, 67.7, 37.1, 24.6, 20.8; IR (KBr): 3280,
3184, 3030, 2980, 2932, 2858, 1660, 1620, 1520, 1484, 1420, 1390,
1276, 1185, 1150 cmꢀ1; LC/MS [M+H]+ (m/z) 217.
Notes and references
aDepartment of Chemistry, Vel Tech University, Avadi, Chennai 610062,
Tamilnadu, India. Email: elangoomc@gmail.com
1'H-spiro[cyclopentane-1,2'-quinazolin]-4'(3'H)-one (Table 3,
Electronic Supplementary Information (ESI): scanned spectral data is
available with this journal. See DOI: 10.1039/b000000x/
entry 9)
°
°
1
White solid; yield 90%; mp 258ꢀ260 C (Lit.30: 257ꢀ260 C); Hꢀ
NMR (400 MHz, DMSOꢀd6): δ 8.0 (s, 1H), 7.5 (d, J = 8 Hz, 1H), 7.2
(t, J = 12 Hz, 1H), 6.7 (s, 1H), 6.7 (m, 1H), 6.6 (m, 1H); 13CꢀNMR
(100 MHz, DMSOꢀd6): δ 163.9, 148.0, 133.4, 127.7, 117.0, 115.0,
114.8, 77.5, 22.4; IR (KBr): 3283, 3186, 3035, 2982, 2929, 2940,
2855, 1666, 1620, 1519, 1483, 1431, 1390, 1325, 1270, 1177, 1150
cmꢀ1; LC/MS [M+H]+ (m/z) 203.
1
a) J. F. Wolfe, T. L. Rathman, M. C. Sleevi, J. A. Campbell, T. D.
Greenwood, J. Med. Chem., 1990, 33, 161; b) Y. Xia, Z. Y. Yang, M.
J. Hour, S. C. Kuo, P. Xia, K. F. Bastow, Y. Nakanishi, P.
Nampoothiri, T. Hackl, E. Hamel and K. H. Lee, Biorg. Med. Chem.
Lett., 2001, 11, 1193; c) R. P. Maskey, M. Shaaban, I. Grun and H.
Laatsch, J. Nat. Prod., 2004, 67, 1131; d) D. Wang, F. Gao, Chem.
Central J., 2013, 7, 95 e) M. Rahman, A. K. Bagdi, S. Mishra and A.
Hajra, Chem. Commun., 2014, 50, 2951.
2, 2-dimethyl-2,3-dihydroquinazolin-4(1H)-one (Table 3, entry 10)
2
3
Gabriel, Chem. Ber., 1903, 36, 800.
a) V. Chandregowda, A. K. Kush, G. C. Reddy, Eur. J. Med. Chem.,
2009, 44, 3046; b) A. E. Wakeling, S. P. Guy, J. R. Woodburn, S. E.
Ashton, B. J. Curry, A. J. Barker, K. H. Gibson, Cancer. Res., 2002,
62, 5749.
°
°
1
White solid; yield 89%; mp 183ꢀ184 C (Lit.28b: 182ꢀ183 C); Hꢀ
NMR (400 MHz, DMSOꢀd6): δ 7.9 (s, 1H), 7.6 (d, J = 8 Hz 1H), 7.2
(t, J = 8 Hz, 1H), 6.6 (m, 3H), 1.3 (s, 6H); 13CꢀNMR (100 MHz,
6 | J. Name., 2012, 00, 1-3
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4
5
a) V. Alagarsamy, V. R. Solomon, K. Dhanabal, Bioorg. Med. 26 L. H. Klemm, T. J. R. Weakley, R. D. Gilbertson, J. Heterocycl.
Chem., 2007,15, 235; b) A. Baba, N. Kawamura, H. Makino, Y.
Ohta, S. Taketomi, T. Sohda, J. Med. Chem., 1996, 39, 5176.
Chem.,1998, 35, 1269.
27 M.ꢀJ. Hour, L.ꢀJ. Huang, S.ꢀC. Kuo, Y. Xia, K. Bastow, Y.
Nakanishi, E. Hamel, K.ꢀH. Lee, M. J. Hour, L. J. Huang, J. Med.
Chem., 2000, 43, 4479.
a) R. Rohini, P. M. Reddy, K. Shanker, A. Hu, V. Ravinder, Eur. J.
Med. Chem., 2010, 45, 1200; b) L. Antipenko, A. Karpenko, S.
Kovalenko, A. Katsev, E. K. Porokhnyavets, V. Novikov, 28 a) S. Rostamizadeh, A. M. Amani, R. Aryan, H. R. Ghaieni, N.
A.Chekotilo, Chem. Pharm. Bull., 2009, 57, 580; c) V. Jatav, S.
Kashaw, P. Mishra, Med. Chem. Res., 2008, 17, 205.
Shadjou, Synth. Commun., 2008, 38, 3567; b) X. S. Wang, K. Yang,
J. Zhou, S. J. Tu, J. Comb. Chem., 2010, 12, 417.
6
7
8
9
H. Li, R. Huang, D. Qiu, Z. Yang, X. Liu, J. Ma, Z. Ma, Prog. Nat. 29 J.ꢀP. Wan, S.ꢀF. Gan, J.ꢀM. Wu, Y. Pan, Green. Chem., 2009, 11,
Sci., 1998, 8, 359. 1633.
P. Nandy, T. M. Vishalakshi, A. R. Bhat, Indian. J. Heterocycl. 30 A. Shaabani, A. Maleki, H. Mofakham, Synth. Commun., 2008, 38
,
Chem., 2006, 15, 293.
3751.
R. Lakhan, O. P. Singh, R. L. Singh, J. Indian. Chem. Soc, 1987, 64
,
31 R. Z. Qiao, B. L. Xu, Y. H. Wang, Chin. Chem. Lett., 2007, 18, 656.
316.
32 a) M. Dabiri, P. Salehi, M. Baghbanzadeh, M. A. Zolfigol, M. Agheb,
S. Heydari, Catal. Comm., 2008, , 785; b) S. E. Lopez, M. E.
Rosales, N. Urdaneta, M. V. Gody, J. E. Charris, J. Chem. Res., 2000,
, 258; c) P. Salehi, M. Dabiri, M. A. Zolfigol, M. Baghbanzadeh,
Synlett, 2005, , 1155.
H. J. Hess, T. H. Cronin, A. Scriabine J. Med. Chem., 1968, 11,130.
9
10 M. S. Malamas, J. Millen J. Med. Chem, 1991, 34, 1492.
11 G.ꢀP. Cai, X.ꢀL. Xu, Z.ꢀF. Li, P. Willam, P. Weber, J. Lu, J.
Heterocycl. Chem., 2002, 39, 1271.
6
7
12 A. J. A. Watson, A. C. Maxwell, J. M. J. Williams, Org. Biomol. 33 M. Sharma, S. Pandey, K. Chauhan, D. Sharma, B. Kumar, P. M.
Chem. 2012, 10, 240.
Chauhan J. Org .Chem., 2012, 77, 929.
13 R. J. Abdel, W. Voelter, M. A. Saeed, Tetrahedron. Lett., 2004, 45
,
,
34 Y.ꢀX. Zong, Y. Zhao, W.ꢀC. Luo, X. H. Yu, J.ꢀK. Wang, Y. Pan,
Chin. Chem. Lett., 2010, 21, 778.
3475.
14 C. L. Yoo, J. C. Fettinger, M. J. Kurth, J. Org. Chem., 2005, 70
35 P. V. Murthy, D. Rambabu, G. RamaKrishna, C. M. Reddy, K. R.
Prasad, M. V. B. Rao, M. Pal, Tetrahedron. Lett., 2012, 53, 863.
6941.
15 a) J. X. Chen, H. Y. Wu, W. K. Su, Chin. Chem. Lett., 2007, 18, 536; 36 P. Salehi, M. Dabiri, M. A. Zolfigol, M. Baghbanzadeh, Synth.
b) M. Prakesh, V. Kesavan, Org. Lett., 2012, , 1896. Commun., 2006, 36, 2287.
16 J.ꢀH. Tang, D.ꢀX. Shi, L.ꢀJ. Zhang, Q. Zhang, J.ꢀR. Li, Synth. 37 a) J. Chen, W. Su, H` Wu, M. Liu, C. Jin, Green. Chem., 2007, 9,
7
Commun., 2010, 40, 632.
972; b) M. Dabiri, P. Salehi, M. Baghbanzadeh, Monatsh. Chem.,
2007, 138, 1191; c) B. N. Darvatkar, S. V. Bhilare, A. R.
Deorukhkar, D. G. Raut, M. M. Salunkhe, Green Chem. Lett. Rev.,
17 J. Zhou, J. Fang, J. Org. Chem., 2011, 76, 7730.
18 a) H. Li, L. He, H. Neumann, M. Beller, X.ꢀF. Wu, Green Chem.,
2014, 16, 1336; b) H. Hikawa, Y. Ino, H. Suzuki,Y. Yokoyama, J.
Org. Chem.,2012, 77, 7046; c) X. Jiang, T. Tang, J.ꢀM. Wang, Z.
Chen, Y.ꢀM. Zhu, S.ꢀJ. Ji, J. Org. Chem., 2014, 79, 5082.
19 a) D. Zhan, T. Li, H. Wei, W. Weng, K. Ghandi, Q. Zeng, RSC
2010, 4, 301; d) X.ꢀS. Wang, K. Yang, J. Zhou, S.ꢀJ. Tu, J. Comb.
Chem., 2010, 12, 417; e) X.ꢀS. Wang, K.ꢀY. Zhang, C.ꢀS. Yao, Synth.
Commun., 2010, 40, 2633; f) M. Ali, B. Fard, A. Mobinikhaledi, M.
Hamidinasab, Synth. React. Inorg. Metal-Organic Nano-metal
Chemistry., 2014, 44, 567; g) J. Chen, W. Su, H. Wu, M. Liu and C.
Adv.,2013,
3
, 9325; b) S. Santra, A. K. Bagdi, A. Majee, A. Hajra ,
, 24931.
RSC. Adv., 2013,
3
Jin, Green Chem., 2007, 9, 972; h) J. Dupont, R. F. De Souza, P. A.
20 H. R. Safaei, M. Shekouhy, S. Khademi, V. Rahmanian, M. Safaei, J.
Ind. Eng. Chem., 2014, 20, 3019.
Z. Suarez, Chem. Rev. 2002, 102, 3667; i) M. G. Freire, A. F. M.
Claudio, J. M. M. Araujo, J. A. P. Coutinho, I. M. Marrucho, J. N. C.
Lopes, L. P. N. Rebelo, Chem Soc. Rev. 2012, 41, 4966.
21 J. X. Chen, D. Z. Wu, F. He, M. C. Liu, H. Y. Wu, J. C. Ding, W. K.
Su, Tetrahedron Lett., 2008, 49, 3814.
38 a) M. Rueping, A. P. Antonchick, E. Sugiono, K. Grenader, Angew.
Chem.,Int. Ed., 2009, 48, 908; b) D.ꢀJ. Cheng, Y. Tian, S.ꢀK. Tian,
Adv. Synth. Catal., 2012, 354, 995.
22 D. Shi, L. Rong, J. Wang, Q. Zhuang, X. Wang and H. Hu,
Tetrahedron Lett., 2003, 44, 3199.
23 a) M. Dabiri, P. Salehi, S. Otokesh, M. Baghbanzadeh, G. 39 M. Desroses, M. Scobie and T. Helleday, New J. Chem., 2013, 37
Kozehgary, A. A. Mohammadi, Tetrahedron Lett., 2005, 46, 6123; b) 3595.
H. R. Shaterian, A. R. Oveisi, M. Baghbanzadeh, Synth. Commun., 40 K. H. Narasimhamurthy, S. Chandrappa, K. S. Sharath Kumar, K. B.
,
2010, 40, 1231.
Harsha, H. Ananda, K. S. Rangappa, RSC Adv., 2014, 4, 34479.
24 M. Wang, J. J. Gao, Z. G. Song, L. Wang, Chem. Heterocycl. Compd
.
41 a) K. Ramesh, K. Karnakar, G. Satish, B. S. P. Anil Kumar, Y. V. D.
Nageswar, Tetrahedron Lett., 2012, 53, 6936; b) J. Wu, X. Du, J. Ma,
Y. Zhang, Q. Shi, L. Luo, B. Song, S. Yang, D. Hu, Green Chem.,
2014, 16, 3210.
2011, 47, 851.
25 a) J. Safari, S. G. Ravandi, C. R. Chimie.,2013, 16, 1158; b) A. G.
Choghamarani, M. Norouzi, J. Mol. Catal. A., 2014, 395, 172; c) J.
Safari, S. Gandomiꢀ Ravandi, J. Mol. Catal. A: Chem., 2013, 371
135; d) J. Safari, S. G. Ravandi , RSC. Adv., 2014, 4, 11654; e) S.
Santra, M. Rahman, A. Roy, A. Majee, A. Hajra, Catal. Commun., 43 X.ꢀF. Wu, S. Oschatz, A. Block, A. Spannenberg, P. Langer, Org.
2014, 49, 52; f) S. Tarannum, N. Ahmed, Z. N. Siddiqui, Catal. Biomol. Chem., 2014, 12, 1865.
Commun., 2015, 66, 66; g) A. G. Choghamarani, G. Azadi, RSC. 44 M. Rahman, I. Ling, N. Abdullah, R. Hashim , A. Hajra, RSC. Adv
Adv., 2015, , 9752. 2015, , 7755.
,
42 P. Yerram, R. Chowrasia, S. Seeka, S. J. Tangenda, Eur. J. Chem.,
2013, 4, 462.
.
5
5
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45 a) K. Elango, R. Srirambalaji, G. Anantharaman, Tetrahedron Lett.,
2007, 48, 9059; b) S. Nagarajan, K. Elango Catal. Lett., 2014, 144
,
.
1507; c) S. Nagarajan, T. M. Shaikh, K. Elango J. Chem. Sci
(accepted 2015); d) large scale preparation of 1a: for details, see
Supporting Information.
46 a) T. L. Gilchrist, Heterocyclic Chemistry, 3rd Ed. Pearson, 2010,
241; b) B. H. Lipshutz, Chem. Rev., 1986, 86, 795.
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Graphical abstract
Ionic liquid catalyzed reusable protocol for one-pot synthesis of 2,3-
dihydroquinazolin-4(1H)-one under mild conditions
S. Nagarajan, Tanveer M. Shaikh, Elango Kandasamy*
Department of Chemistry, Vel Tech. University,
Avadi, Chennai 600062, Tamilnadu, India
E-mail: elangoomc@gmail.com
This article described an efficient protocol for the syntheses of 2,3-dihydroquinazolinones. The synthetic
utility of this methodology has been demonstrated with 30 different substrates. The reaction showed good
functional group tolerance and high levels of catalytic activity.