H3PW12O40: An efficient and recyclable heterogeneous catalyst for the selective synthesis of 2-Aryl-5,6-dihydro-4H-1,3- oxazines and 2-Aryl-1,4,5,6-tetrahydropyrimidines

Article abstract of DOI:10.1515/znb-2010-0404

An environmentally friendly and highly efficient procedure has been developed for the selective synthesis of 2-aryl-5,6-dihydro-4H-1,3-oxazines and 2-aryl-1,4,5,6-tetrahydropyrimidines by cyclocondensation of arylnitriles with 3-amino-1-propanol and 1,3-diaminopropane in the presence of catalytic amounts of H₃PW₁₂O₄₀ under thermal conditions and MW irradiation. Under the same reaction conditions, dicyanobenzenes are transformed to their corresponding mono-oxazines and monotetrahydropyrimidines with excellent chemoselectivity. These reactions are simple and clean, giving the products in high yields and high purity. The catalyst can be easily recovered after the reaction and reused efficiently in subsequent runs.

Full text of DOI:10.1515/znb-2010-0404

H3PW O40: An Efficient and Recyclable Heterogeneous Catalyst for
12
the Selective Synthesis of 2-Aryl-5,6-dihydro-4H-1,3-oxazines and
2-Aryl-1,4,5,6-tetrahydropyrimidines
Iraj Mohammadpoor-Baltork, Majid Moghadam, Shahram Tangestaninejad,
Valiollah Mirkhani, and Zohre Eskandari
Department of Chemistry, Catalysis Division, University of Isfahan, Isfahan 81746-73441, Iran
Reprint requests to Prof. I. Mohammadpoor-Baltork. Fax: +98-311-668-9732.
E-mail: imbaltork@sci.ui.ac.ir
Z. Naturforsch. 2010, 65b, 461 – 469; received December 17, 2009
An environmentally friendly and highly efficient procedure has been developed for the selective
synthesis of 2-aryl-5,6-dihydro-4H-1,3-oxazines and 2-aryl-1,4,5,6-tetrahydropyrimidines by cyclo-
condensation of arylnitriles with 3-amino-1-propanol and 1,3-diaminopropane in the presence of cat-
alytic amounts of H3PW12O40 under thermal conditions and MW irradiation. Under the same reac-
tion conditions, dicyanobenzenes are transformed to their corresponding mono-oxazines and mono-
tetrahydropyrimidines with excellent chemoselectivity. These reactions are simple and clean, giving
the products in high yields and high purity. The catalyst can be easily recovered after the reaction and
reused efficiently in subsequent runs.
Key words: Oxazines, Tetrahydropyrimidines, Microwave Irradiation, Solid Acid Catalyst,
Tungstophosphoric Acid
Introduction
tive synthetic methods for 1,3-oxazines and tetrahy-
dropyrimidines (without using organic solvents) in
terms of economic benefit, environmental impact and
The development of efficient and selective syn-
thetic transformations in one operation is a major chal- safety.
lenge in modern organic synthesis. 5,6-Dihydro-4H-
Microwave-assisted organic synthesis (MAOS) is a
1,3-oxazine and 1,4,5,6 tetrahydropyrimidine deriva- powerful technique that is being used more and more
tives are of importance because of the broad spectrum to accelerate thermal organic reactions. This is a con-
of their biological and physiological properties such as sequence of the selective absorption of microwave en-
choline acetyl transfer inhibitory [1], muscarinic ag- ergy by polar molecules or polar transition state in-
onist [2], antihypertensive [3], antidepressant [4], an- termediates formed in the course of the reaction. The
tiviral [5], and antibacterial [6] activities. These hete- notable features of the microwave approach are en-
rocyclic compounds have also been used as protecting hanced reaction rates, formation of purer products in
groups [7], as monomers for polymer synthesis [8], and high yields and easier manipulation [25, 26]. The use
as precursors for the synthesis of a variety of functional of solid acid catalysts with microwave irradiation pro-
groups in organic chemistry [9, 10]. Thus, the synthesis vides even more benign processes.
of 1,3-oxazine and tetrahydropyrimidine derivatives is
in considerable demand.
In recent years, the use of Keggin-type heteropoly
acids (HPAs) as heterogeneous and homogeneous cat-
Several methods for the preparation of 2-substituted alysts has received considerable attention in synthetic
5,6-dihydro-4H-1,3-oxazines and 1,4,5,6-tetrahydro- organic chemistry [27– 30]. Heteropoly acid cata-
pyrimidines have previously been reported [11– 24]. lysts have many advantages such as reusability, non-
However, some of these methods are associated with corrosive properties, easy handling, non-toxicity, easy
certain drawbacks such as harsh reaction conditions, work-up, and high stability toward air and moisture,
the use of complex or toxic reagents, low yields of which make them economically and environmentally
the products and long reaction times. Therefore, there attractive. Among heteropoly acids, tungstophospho-
is still a need to develop convenient and chemoselec- ric acid (H3PW12O40) is the most widely used catalyst
c
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I. Mohammadpoor-Baltork et al. · H3PW12O40: An Efficient and Recyclable Heterogeneous Catalyst
Table 1. Reaction of 4-cyanopyridine (1 mmol) with 3-
amino-1-propanol in the presence of H3PW12O40 under dif-
ferent conditions.
Entry
3-Amino-1-propanol
(mmol)
H3PW12O40
(mmol)
T
Yield
Scheme 1.
(◦C)
(%)a
1
2
3
4
5
6
2
3
4
4
4
4
4
4
4
0.012
0.012
0.005
0.009
0.012
0.012
0.012
0.012
0.012
–
125
125
125
125
125
70
100
125
125
125
40
60
55
80
98
45
65
60
52
15
because of its high acid strength, low reducibility and
selective action [31 – 33].
Recently, we have reported the synthesis of ox-
azolines, imidazolines and thiazolines in the pres-
ence of bulk and supported H3PW12O40 under sol-
vent free conditions [34, 35]. In continuation of our
efforts to develop new synthetic methods for impor-
tant organic compounds [36, 37], we now report a
novel, efficient and environmentally benign method for
the selective synthesis of 2-aryl-5,6-dihydro-4H-1,3-
oxazines and 2-aryl-1,4,5,6-tetrahydropyrimidines us-
ing H3PW12O40 as a reusable heterogeneous catalyst
under thermal conditions and under microwave under
irradiation (Scheme 1).
7
8b
9c
10
4
b
a
Isolated yields;
reaction was performed in the presence of
c
H3PMo12O40
12O40
;
reaction was performed in the presence of H4Si-
W
.
(Table 1, entry 10). In the reaction of 4-cyanopyridine
with 1,3-diaminopropane, the best yield of the corre-
sponding tetrahydropyrimidine was also obtained un-
der the same reaction conditions.
Under the optimized conditions, the H3PW12O40-
catalyzed cyclocondensations of various aromatic and
heteroaromatic nitriles with 3-amino-1-propanol and
1,3-diaminopropane were investigated. All the reac-
tions proceeded smoothly to give the corresponding 2-
aryl-5,6-dihydro-4H-1,3-oxazines (Table 2, entries 1 –
9) and 2-aryl-1,4,5,6-tetrahydropyrimidines (Table 3,
entries 1 – 8) in high yields.
In order to expand the scope of this method further,
the reactions of dinitriles with 3-amino-1-propanol
and 1,3-diaminopropane were also examined. The ex-
perimental results show that dinitriles were converted
to their mono-oxazines (Table 2, entries 10 and 11)
and mono-tetrahydropyrimidines (Table 3, entries 9
and 10) with excellent selectivity even in the presence
of a large excess of 3-amino-1-propanol and 1,3-di-
aminopropane or upon elongation of reaction times
Results and Discussion
Initially, the reaction of 4-cyanopyridine with 3-
amino-1-propanol in the presence of H3PW12O40 was
chosen as a model to optimize the reaction condi-
tions. Different reaction temperatures and molar ra-
tios of reagents and catalyst were examined (Ta-
ble 1, entries 1 – 7). The best result was obtained
by carrying out the reaction with 1 : 4 : 0.012 mo-
lar ratios of 4-cyanopyridine, 3-amino-1-propanol and
◦
H3PW12O40 at 125 C (Table 1, entry 5). We then
screened other heteropoly acids such as H3PMo12O40
and H4SiW12O40 for their ability to catalyze this reac-
tion (Table 1, entries 8 and 9). H3PW12O40 was found
to be the most efficient catalyst for this purpose. It is
noteworthy that in the absence of the catalyst, the cor-
responding oxazine was produced in only 15 % yield
Conditions
G
X = O
Yield (%)
X = NH
Yield (%)
Time
1 h
2 min
1.5 h
Time
2 h
7 min
1.5 h
8 min
125 ◦C
MW
3-CN
3-CN
4-CN
4-CN
95
98
94
95
90
96
86
85
125 ◦C
MW
3.5 min
Scheme 2.
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I. Mohammadpoor-Baltork et al. · H3PW12O40: An Efficient and Recyclable Heterogeneous Catalyst
463
Table 2. Synthesis of 1,3-
oxazines from nitriles cat-
alyzed by H3PW12O40 under
thermal conditions and mi-
crowave irradiation.
Entry
Nitrile
Product
Thermal
MW
Yield (%)a
(Time, h)
Yield (%)a
(Time, min)
1
2
88 (2)
97 (3)
90 (1.5)
93 (5)
3
4
90 (1)
90 (7.3)
88 (7)
96 (2.08)
5
92 (1.1)
95 (8)
6
7
80 (1.2)
98 (1.08)
90 (2)
70 (4)
97 (3)
90 (4)
85 (8)
95 (3.5)
8
9
92 (1.8)
94 (1.5)
10
11
95 (1)
98 (2)
a
Isolated yields.
Conditions
X = O
Yield (%)
X = NH
Yield (%)
Time
1.1 h
8 min
Time
2.3 h
5 min
Thermal
MW
92
95
98
92
Scheme 3.
(Scheme 2). Chemoselective transformation of dini- tetrahydropyrimidines under the same reaction con-
triles to mono-oxazines and mono-tetrahydropyr- ditions. These results indicate that the present pro-
imidines is of practical importance because the remain- tocol is potentially applicable for the chemoselec-
ing nitrile group can be converted into other important tive conversion of arylnitriles to their 1,3-oxazines
functional groups.
and tetrahydropyrimidines in the presence of alkylni-
It is also noteworthy that alkylnitriles did not af- triles. To explore the selectivity of this method fur-
ford the corresponding 2-substituted oxazines and ther, we have also investigated the competitive reac-
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I. Mohammadpoor-Baltork et al. · H3PW12O40: An Efficient and Recyclable Heterogeneous Catalyst
Table 3. Synthesis of tetrahy-
dropyrimidines from nitriles
catalyzed by H3PW12O40 un-
der thermal conditions and mi-
crowave irradiation.
Entry
Nitrile
Product
Thermal
MW
Yield (%)a
(Time, h)
Yield (%)a
(Time, min)
1
2
94 (4.25)
90 (4)
90 (3.5)
93 (4)
3
4
94 (4)
95 (6)
95 (4)
85 (10)
5
98 (2.3)
92 (5)
6
7
8
9
98 (2.3)
90 (10)
90 (3.3)
86 (1.5)
92 (4)
93 (5)
88 (4.5)
85 (8)
10
90 (2)
96 (7)
a
Isolated yields.
tion of 3-bromobenzonitrile and cyclohexanecarboni- ter 3 min, giving the corresponding 1,3-oxazine in
trile with 3-amino-1-propanoland 1,3-diaminopropane 97 % yield. When the amount of the catalyst was de-
in the presence of the catalyst. The results showed that creased (0.005 and 0.009 mmol), the reaction pro-
only 3-bromobenzonitrile reacted, whereas cyclohex- ceeded more slowly, and the yields of the 1,3-oxazine
anecarbonitrile remained intact in the reaction mixture were reduced to 56 and 79%, respectively, even when
(Scheme 3). Such a selectivity can be considered as the reaction was carried out for 4 min at 85 ◦C.
a useful practical achievement in the synthesis of 1,3- Reaction temperature played a crucial role in this
oxazines and tetrahydropyrimidines.
microwave-assisted reaction. We found ◦that the in-
crease of the temperature from 40 to 85 C increased
the yield from 32 to 97 %. The effect of the reaction
time was also examined. It was found that as the re-
action time was extended from 1 to 3 min, the yield
of the desired product improved from 45 to 97 %.
However, the yield was not affected when the reac-
tion time exceeded 3 min. We also examined the mo-
lar ratio of 4-cyanopyridine to 3-amino-1-propanol. It
was found that increasing the molar ratio from 1 : 2 to
1 : 4 increased the yield of the expected 1,3-oxazine
from 50 to 97 %. Finally, we investigated the effect of
In order to decrease the reaction time, microwave
irradiation was used in these reactions. The reac-
tion of 4-cyanopyridine with 3-amino-1-propanol was
selected as a model optimize the reaction condi-
tions. First, we performed this reaction in the ab-
sence of the catalyst, and 4-cyanopyridine (1 mmol)
was reacted with 3-amino-1-propanol (4 mmol) di-
rectly under microwave irradiation with the power
set at 800 W. Only 17◦% of the product was ob-
tained after 4 min at 85 C. The reaction in the pres-
ence of 0.012 mmol of H3PW12O40 was complete af-
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I. Mohammadpoor-Baltork et al. · H3PW12O40: An Efficient and Recyclable Heterogeneous Catalyst
465
Table 4. Recovery and reuse of H3PW12O40 in the reaction
of 4-cyanopyridine with 3-amino-1-propanola.
geneous catalyst under thermal conditions and un-
der microwave irradiation. The commercial availablity,
non-toxicity and reusability of the catalyst, a sim-
ple experimental procedure, excellent chemoselectiv-
ity, short reaction times and high yields are the main
advantages of the present method.
Run
1
3
5
7
Time (h)
1.08
1.08
1.08
1.08
Yield (%)b
Run
2
4
6
8
Time (h)
1.08
1.08
1.08
1.08
Yield (%)b
98
98
98
98
98
98
98
98
98
95
9
1.08
10
1.08
a
Reaction conditions: 4-cyanopyridine (1 mmol), 3-amino-1-
propanol (4 mmol), H3PW12O40 (0.012 mmol) at 125 ◦C; b isolated
yields.
Experimental Section
Melting points were obtained with a Stuart Scientific ap-
paratus and are uncorrected. Yields refer to isolated prod-
ucts. 1H- and 13C-NMR (500 and 125 MHz) spectra were
recorded on a Bruker-Avance AQS 500 spectrometer in
CDCl3 using TMS as internal standard. IR spectra were
recorded on a Shimadzu IR-435 spectrophotometer. Mass
spectra were obtained on a platform II spectrometer from
Micromass; EI mode at 70 eV. The microwave system used
in the experiments includes the following items: Micro-
SYNTH labstation, complete with glass door, dual mag-
netron system with pyramid-shaped diffuser, 1000 W deliv-
ered power, exhaust system, magnetic stirrer, “quality pres-
sure” sensor for flammable organic solvents, ATCFO fiber
optic system for automatic temperature control.
the microwave irradiation power in this reaction. It was
found that the yield of the desired product increased
from 60 to 97 % when the microwave power was in-
creased from 600 to 800 W. Therefore, 1 : 4 : 0.012
molar ratios of 4-cyanopyridine, 3-amino-1-propanol
◦
and H3PW12O40 and a power of 800 W at 85 C
were found to be the optimal conditions. In the reac-
tion of 4-cyanopyridine with 1,3-diaminopropane, the
best yield of the corresponding tetrahydropyrimidine
was obtained with an irradiation power of 1000 W
at 100 ◦C.
Similarly, various aromatic and heteroaromatic
nitriles reacted with 3-amino-1-propanol and 1,3-
diaminopropane in the presence of catalytic amounts
of H3PW12O40, and the corresponding 1,3-oxazines
(Table 2, entries 1 – 9) and tetrahydropyrimidines (Ta-
ble 3, entries 1 – 8) were obtained in high yields. In-
spection of the data in Tables 2 and 3 shows that
the yields of the reactions under thermal conditions
and microwave irradiation are comparable, but under
microwave irradiation, the reaction times are consid-
erably shorter. Chemoselective transformation of di-
cyanobenzenes to their mono-oxazines (Table 2, en-
tries 10 and 11) and mono-tetrahydropyrimidines (Ta-
ble 3, entries 9 and 10) (Scheme 2) and selective con-
General experimental procedure for the synthesis of 1,3-
oxazines and tetrahydropyrimidines under thermal condi-
tions
A mixture of arylnitrile (1 mmol), 3-amino-1-propanol
or 1,3-diaminopropane (4 mmol) and H3PW12O40
◦
(0.012 mmol) was stirred at 125 C for the appropriate time
according to Tables 2 and 3. The progress of the reaction was
monitored by TLC (eluent: ethyl acetate/n-hexane, 4 : 1).
After completion of the reaction, the mixture was cooled
to room temperature, and cold EtOH (15 mL) was added.
The catalyst was separated by filtration. The filtrate was
evaporated, and the crude product was purified by column
version of arylnitriles to their 1,3-oxazines and tetrahy- chromatography on neutral alumina to afford pure products.
dropyrimidines in the presence of aliphatic nitriles
(Scheme 3) were also achieved under microwave irra-
diation.
General experimental procedure for the synthesis of 1,3-
oxazines and tetrahydropyrimidines under microwave irra-
diation
Finally, the possibility of recovering and reusing of
the catalysts, which is very important from practical
and economical points of view, was examined for the
reaction of 4-cyanopyridine with 3- amino-1-propanol.
After completion of the reaction, cold EtOH (15 mL)
was added, and the catalyst was separated by filtra-
tion. The recovered catalyst could be reused nine times
without any loss of catalytic activity (Table 4).
In conclusion, we have developed a novel and highly
efficient method for the synthesis of 1,3-oxazines and
A mixture of arylnitrile (1 mmol), 3-amino-1-propanol
or 1,3-diaminopropane (4 mmol) and H3PW12O40
(0.012 mmol) was subjected to microwave irradiation at the
required power level according to the optimized conditions
for the appropriate time (Tables 2 and 3). After completion
of the reaction (TLC), the mixture was cooled to r. t., and
cold EtOH (15 mL) was added. The catalyst was separated
by filtration. The solvent was evaporated, and the residue
was purified by column chromatography on neutral alumina
tetrahydropyrimidines using H3PW12O40 as a hetero- to give pure product.
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I. Mohammadpoor-Baltork et al. · H3PW12O40: An Efficient and Recyclable Heterogeneous Catalyst
5,6-Dihydro-2-phenyl-4H-1,3-oxazine (Table 2, entry 1)
CH2CH2CH2), 3.61 (t, J = 5.9 Hz, 2 H, CH2N), 4.36 (t,
J = 5.4 Hz, 2 H, CH2O), 7.21 – 7.26 (m, 1 H, ArH), 7.53
(d, J = 9.9 Hz, 1 H, ArH), 7.83 (d, J = 8.9 Hz, 1 H, ArH),
8.05 (s, 1 H, ArH). – 13C NMR (125 MHz, CDCl3): δ =
24.8 (CH2CH2CH2), 42.7 (CH2N), 65.3 (CH2O), 122.2 (C),
125.5 (CH), 129.5 (CH), 130.1 (CH), 133.2 (CH), 134.9
(C), 153.5 (OCN). – MS (EI, 70 eV): m/z (%) = 241.06
(5.99) [M+2]+, 239.08 (7.63) [M]+, 238.09 (8.74), 183.05
(48.09), 155.03 (31.14), 102.08 (29.66), 76.11 (92.37), 57.17
(50.21). – C10H10BrNO: calcd. C 50.03, H 4.20, N 5.83;
found C 50.10, H 4.12, N 5.76.
Pale-yellow oil [21]. – IR (neat): v = 3040, 2852, 1646
(C=N), 1600, 1344, 1262, 1125, 810, 750 cm−1. – 1H NMR
(500 MHz, CDCl3): δ = 1.99 (quin, J = 5.6 Hz, 2 H,
CH2CH2CH2), 3.62 (t, J = 5.9 Hz, 2 H, CH2N), 4.37 (t, J =
5.5 Hz, 2 H, CH2O), 7.34 – 7.43 (m, 3 H, ArH), 7.88 – 7.90
(m, 2 H, ArH).
2-(4-Chlorophenyl)-5,6-dihydro-4H-1,3-oxazine (Table 2,
entry 2)
Colorless oil [38]. – IR (neat): v = 3060, 2855, 1648
(C=N), 1562, 1453, 1350, 1220, 1085, 840 cm−1. – 1H
NMR (500 MHz, CDCl3): δ = 1.97 (quin, J = 5.6 Hz, 2 H,
CH2CH2CH2), 3.60 (t, J = 5.9 Hz, 2 H, CH2N), 4.35 (t, J =
5.5 Hz, 2 H, CH2O), 7.30 – 7.35 (m, 2 H, ArH), 7.80 – 7.84
(m, 2 H, ArH). – 13C NMR (125 MHz, CDCl3): δ = 21.8
(CH2CH2CH2), 42.6 (CH2N), 65.2 (CH2O), 128.2 (2 CH),
128.3 (2 CH), 132.6 (C), 136.3 (C), 154.7 (OCN).
5,6-Dihydro-2-(3-nitrophenyl)-4H-1,3-oxazine (Table 2,
entry 6)
◦
M. p. 94 – 95 C [39]. – IR (KBr): v = 3085, 2920, 1652
(C=N), 1612, 1521, 1465, 1350, 1259, 1130, 1105, 840, 800,
1
692 cm−1. – H NMR (500 MHz, CDCl3): δ = 2.02 (quin,
J = 5.6 Hz, 2 H, CH2CH2CH2), 3.65 (t, J = 5.9 Hz, 2 H,
CH2N), 4.44 (t, J = 5.5 Hz, 2 H, CH2O), 7.54 (t, J = 8 Hz,
1 H, ArH), 8.24 – 8.28 (m, 2 H, ArH), 8.74 (s, 1 H, ArH).
2-(3-Chlorophenyl)-5,6-dihydro-4H-1,3-oxazine (Table 2,
entry 3)
5,6-Dihydro-2-(pyridin-4-yl)-4H-1,3-oxazine (Table 2,
entry 7)
Colorless oil. – IR (neat): v = 3052, 2950, 1660 (C=N),
1
1602, 1560, 1348, 1230, 1085, 808, 720 cm−1. – H NMR
M. p. 53 – 55 ◦C [40]. – IR (KBr): v = 3052, 2905, 2850,
(500 MHz, CDCl3): δ = 1.98 (quin, J = 5.6 Hz, 2 H,
CH2CH2CH2), 3.60 (t, J = 5.9 Hz, 2 H, CH2N), 4.36
(t, J = 5.4 Hz, 2 H, CH2O), 7.26 – 7.30 (m, 1 H, ArH),
7.30 (d, J = 8 Hz, 1 H, ArH), 7.77 (d, J = 7.8 Hz, 1 H,
ArH), 7.89 (s, 1 H, ArH). – 13C NMR (125 MHz, CDCl3):
δ = 21.9 (CH2CH2CH2), 42.7 (CH2N), 65.3 (CH2O), 125.1
(CH), 127.2 (CH), 129.2 (CH), 130.3 (CH), 134.2 (C),
135.9 (C), 154.4 (OCN). – MS (EI, 70 eV): m/z (%) =
197.09 (3.59) [M+2]+, 195.10 (10.68) [M]+, 149.08 (83.31),
139.04 (100), 111.05 (73.13), 75.05 (43.10), 61.06 (29.48). –
C10H10ClNO: calcd. C 61.39, H 5.15, N 7.16; found C 61.28,
H 5.12, N 7.20.
1640 (C=N), 1600, 1541, 1453, 1340, 1220, 1152, 1060,
1
844 cm−1. – H NMR (500 MHz, CDCl3): δ = 2.00 (quin,
J = 5.6 Hz, 2 H, CH2CH2CH2), 3.63 (t, J = 5.9 Hz, 2 H,
CH2N), 4.38 (t, J = 5.4 Hz, 2 H, CH2O), 7.73 (d, J = 6 Hz,
2 H, ArH), 8.65 (d, J = 6 Hz, 2 H, ArH).
5,6-Dihydro-2-(pyridin-3-yl)-4H-1,3-oxazine (Table 2,
entry 8)
Yellow oil. – IR (neat): v = 3047, 2995, 1655 (C=N),
1593, 1470, 1342, 1280, 1130, 1115, 1023, 810, 705 cm−1. –
1H NMR (500 MHz, CDCl3): δ = 1.98 (quin, J = 5.6 Hz,
2 H, CH2CH2CH2), 3.59 (t, J = 6.6 Hz, 2 H, CH2N), 4.36
(t, J = 5.4 Hz, 2 H, CH2O), 7.25 – 7.28 (m, 1 H, ArH),
8.14 (d, J = 9.6 Hz, 1 H, ArH), 8.61 (d, J = 5.6 Hz, 1 H,
ArH), 9.07 (s, 1 H, ArH). – 13C NMR (125 MHz, CDCl3):
δ = 21.9 (CH2CH2CH2), 42.7 (CH2N), 65.3 (CH2O), 122.8
(CH), 129.8 (C), 134.4 (CH), 148.6 (CH), 151.1 (CH),
153.9 (OCN). – MS (EI, 70 eV): m/z (%) = 162.15 (48.05)
[M]+, 161.14 (28.08) [M–1]+, 122 (17.69), 106.12 (100),
78 (53.25). – C9H10N2O: calcd. C 66.65, H 6.22, N 17.27;
found C 66.54, H 6.25, N 17.17.
2-(4-Bromophenyl)-5,6-dihydro-4H-1,3-oxazine (Table 2,
entry 4)
◦
M. p. 73 – 75 C [24]. – IR (KBr): v = 3050, 2900, 1665
(C=N), 1605, 1480, 1340, 1265, 1115, 830 cm−1. – 1H
NMR (500 MHz, CDCl3): δ = 1.99 (quin, J = 5.6 Hz, 2 H,
CH2CH2CH2), 3.60 (t, J = 5.9 Hz, 2 H, CH2N), 4.36 (t, J =
5.5 Hz, 2H, CH2O), 7.49 (d, J = 10.9 Hz, 2 H, ArH), 7.78 (d,
J = 10.9 Hz, 2 H, ArH).
2-(3-Bromophenyl)-5,6-dihydro-4H-1,3-oxazine (Table 2,
entry 5)
5,6-Dihydro-2-(thiophen-2-yl)-4H-1,3-oxazine (Table 2,
entry 9)
◦
Yellow oil. – IR (neat): v = 3072, 2905, 1651 (C=N),
M. p. 51 – 53 C [41]. – IR (KBr): v = 3090, 2884, 1644
1570, 1460, 1353, 1250, 1120, 860, 795, 710 cm−1. – 1H (C=N), 1522, 1425, 1350, 1120, 1088, 850, 830, 718 cm−1. –
NMR (500 MHz, CDCl3): δ = 1.98 (quin, J = 5.6 Hz, 2 H, 1H NMR (500 MHz, CDCl3): δ = 1.98 (quin, J = 5.6 Hz, 2 H,
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I. Mohammadpoor-Baltork et al. · H3PW12O40: An Efficient and Recyclable Heterogeneous Catalyst
467
CH2CH2CH2), 3.57 (t, J = 5.9 Hz, 2 H, CH2N), 4.34 (t, J = CH2N), 4.9 (br s, 1 H, NH), 7.33 (d, J = 11 Hz, 2 H, ArH),
5.4 Hz, 2 H, CH2O), 7.00 – 7.02 (m, 1 H, ArH), 7.33 (d, J = 7.37 (d, J = 11 Hz, 2 H, ArH).
5 Hz, 1 H, ArH), 7.46 (d, J = 3.6 Hz, 1 H, ArH).
2-(3-Chlorophenyl)-1,4,5,6-tetrahydropyrimidine (Table 3,
4-(5,6-Dihydro-4H-1,3-oxazine-2-yl)benzonitrile (Table 2,
entry 10)
entry 3)
◦
M. p. 131 – 132 C. – IR (KBr): v = 3300 (NH), 2922,
◦
M. p. 162 – 163 C. – IR (KBr): v = 3045, 2920, 2210 2800, 1620 (C=N), 1571, 1550, 1373, 1330, 1220, 1110, 840,
(CN), 1644 (C=N), 1503, 1420, 1343, 1260, 1133, 1090, 715 cm−1. – H NMR (500 MHz, CDCl3): δ = 1.87 (quin,
1
1
842 cm−1. – H NMR (500 MHz, CDCl3): δ = 2.00 (quin, J = 5.8 Hz, 2 H, CH2CH2CH2), 3.48 (t, J = 5.7 Hz, 4 H,
J = 5.6 Hz, 2 H, CH2CH2CH2), 3.63 (t, J = 5.8 Hz, 2 H, 2 CH2N), 4.9 (br s, 1 H, NH), 7.26 – 7.30 (m, 1 H, ArH),
CH2N), 4.38 (t, J = 5.4 Hz, 2 H, CH2O), 7.65 (d, J = 8.4 Hz, 7.37 (d, J = 10.9 Hz, 1 H, ArH), 7.56 (d, J = 10.2 Hz, 1 H,
2 H, ArH), 8.00 (d, J = 8.4 Hz, 2 H, ArH). – 13C NMR ArH), 7.66 (s, 1 H, ArH). – 13C NMR (125 MHz, CDCl3):
(125 MHz, CDCl3): δ = 21.8 (CH2CH2CH2), 42.8 (CH2N), δ = 20.6 (CH2CH2CH2), 42.2 (2 CH2N), 124.2 (CH), 126.6
65.4 (CH2O), 113.7 (C), 118.6 (C), 127.5 (2 CH), 131.8 (CH), 129.6 (CH), 129.8 (CH), 134.4 (C), 138.7 (C), 153.7
(2 CH), 138.3 (C), 154.1 (OCN). – MS (EI, 70 eV): m/z (NCN). – C10H11ClN2: calcd. C 61.70, H 5.70, N 14.39;
(%) = 186.33 (38.30) [M]+, 160.13 (3.19), 130.23 (47.87), found C 61.54, H 5.75, N 14.32.
102.07 (9.57), 76.28 (31.91), 52.18 (100). – C11H10N2O:
calcd. C 70.96, H 5.41, N 15.04; found C 70.83, H 5.37,
N 15.15.
2-(4-Bromophenyl)-1,4,5,6-tetrahydropyrimidine (Table 3,
entry 4)
155 – 156 ◦C [44]. – IR (KBr): v = 3420 (NH), 2905,
1610 (C=N), 1540, 1460, 1250, 1170, 1110, 820 cm−1. –
1H NMR (500 MHz, CDCl3): δ = 1.84 (quin, J = 5.8 Hz,
3-(5,6-Dihydro-4H-1,3-oxazine-2-yl)benzonitrile (Table 2,
entry 11)
◦
M. p. 153 – 155 C. – IR (KBr): v = 3062, 2920, 2222 2 H, CH2CH2CH2), 3.47 (t, J = 6.6 Hz, 4 H, 2 CH2N), 4.9
(CN), 1660 (C=N), 1580, 1478, 1375, 1170, 1090, 800, (br s, 1 H, NH), 7.47 (d, J = 8.6 Hz, 2 H, ArH), 7.52 (d,
740 cm−1. – H NMR (500 MHz, CDCl3): δ = 1.99 (quin, J = 8.6 Hz, 2 H, ArH). – MS (EI, 70 eV): m/z (%) = 239.99
1
J = 5.6 Hz, 2 H, CH2CH2CH2), 3.61 (t, J = 5.8 Hz, 2 H, (32.58) [M+2]+, 237.99 (34.84) [M]+, 236.98 (59.28) [M–
CH2N), 4.37 (t, J = 5.3 Hz, 2 H, CH2O), 7.46 (t, J = 1]+, 181.90 (35.75), 159.01 (10.41), 102.91 (32.13), 74.94
7.9 Hz, 1 H, ArH), 7.67 (d, J = 8.6 Hz, 1 H, ArH), 8.13 (64.25), 60.93 (100).
(d, J = 9 Hz, 1 H, ArH), 8.19 (s, 1 H, ArH). – 13C NMR
(125 MHz, CDCl3): δ = 21.8 (CH2CH2CH2), 42.7 (CH2N),
65.5 (CH2O), 112.4 (C), 118.5 (C), 128.9 (CH), 130.8 (CH),
131.1 (CH), 133.4 (CH), 135.4 (C), 153.6 (OCN). – MS (EI,
70 eV): m/z (%) = 186.09 (5.06) [M]+, 185.08 (6.47) [M–
1]+, 149.03 (100), 130.04 (30.65), 102.04 (34.85), 76.03
(55.11). – C11H10N2O: calcd. C 70.96, H 5.41, N 15.04;
found C 70.85, H 5.35, N 15.13.
2-(3-Bromophenyl)-1,4,5,6-tetrahydropyrimidine (Table 3,
entry 5)
◦
M. p. 138 – 139 C. – IR (KBr): v = 3192 (NH), 3059,
2933, 1607 (C=N), 1547, 1512, 1362, 1302, 1194, 862, 798,
1
713 cm−1. – H NMR (500 MHz, CDCl3): δ = 1.86 (quin,
J = 5.8 Hz, 2 H, CH2CH2CH2), 3.51 (t, J = 5.7 Hz, 4 H,
2 CH2N), 5.2 (br s, 1 H, NH), 7.23 (t, J = 7.6 Hz, 1 H,
ArH), 7.51 (d, J = 10.8 Hz, 1 H, ArH), 7.57 (d, J = 10.2 Hz,
1 H, ArH), 7.82 (s, 1 H, ArH). – 13C NMR (125 MHz,
2-Phenyl-1,4,5,6-tetrahydropyrimidine (Table 3, entry 1)
◦
M. p. 86 – 87 C [42]. – IR (KBr): v = 3350 (NH), 2805, CDCl3): δ = 22.7 (CH2CH2CH2), 42.0 (2 CH2N), 122.5
1641 (C=N), 1620, 1400, 1315, 1245, 850, 730 cm−1. – 1H (C), 124.8 (CH), 129.5 (CH), 129.9 (CH), 132.9 (CH),
NMR (500 MHz, CDCl3): δ = 1.88 (quin, J = 5.8 Hz, 2 H, 138.5 (C), 153.8 (NCN). – MS (EI, 70 eV): m/z (%) =
CH2CH2CH2), 3.40 (t, J = 5.8 Hz, 4H, 2 CH2N), 4.6 (br 240.03 (37.91) [M+2]+, 238.04 (40.11) [M]+, 237.04 (100)
s,1 H, NH), 7.36 (t, J = 7.8 Hz, 2 H, ArH), 7.49 (t, J = 7.4 Hz, [M–1]+, 182.02 (57.14), 159.15 (47.25), 102.10 (94.51),
1 H, ArH), 7.87 (d, J = 7.4 Hz, 2 H, ArH).
76.12 (91.21). – C10H11BrN2: calcd. C 50.23, H 4.64,
N 11.72; found C 50.37, H 4.69, N 11.64.
2-(4-Chlorophenyl)-1,4,5,6-tetrahydropyrimidine (Table 3,
entry 2)
2-(4-Pyridyl)-1,4,5,6-tetrahydropyrimidine (Table 3,
entry 6)
M. p. 144 – 145 ◦C [43]. – IR (KBr): v = 3250 (NH), 3040,
2904, 1620 (C=N), 1540, 1410, 1360, 1282, 1180, 1060,
M. p. 97 – 99 ◦C. – IR (KBr): v = 3200 (NH), 2921, 2854,
1
830 cm−1. – H NMR (500 MHz, CDCl3): δ = 1.86 (quin, 1622 (C=N), 1596, 1533, 1362, 1305, 1280, 826 cm−1. –
J = 5.8 Hz, 2 H, CH2CH2CH2), 3.49 (t, J = 5.8 Hz, 4 H, 2 1H NMR (500 MHz, CDCl3): δ = 1.87 (quin, J = 5.8 Hz,
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468
I. Mohammadpoor-Baltork et al. · H3PW12O40: An Efficient and Recyclable Heterogeneous Catalyst
2 H, CH2CH2CH2), 2.8 (br s, 1 H, NH), 3.53 (t, J = 5.8 Hz, 2-(4-Cyanophenyl)-1,4,5,6-tetrahydropyrimidine (Table 3,
4 H, 2 CH2N), 7.54 (d, J = 6.1 Hz, 2 H, ArH), 8.63 (d, J = entry 9)
6.1 Hz, 2 H, ArH). – 13C NMR (125 MHz, CDCl3): δ = 20.4
M. p. 69 – 71 ◦C. – IR (KBr): v = 3213 (NH), 3020, 2922,
(CH2CH2CH2), 42.2 (2 CH2N), 120.4 (2 CH), 144.3 (C),
2240 (CN), 1626 (C=N), 1537, 1492, 1367, 1308, 1186,
150.1 (2 CH), 152.7 (NCN). – MS (EI, 70 eV): m/z (%) =
161.15 (61.69) [M]+, 160.15 (100) [M–1]+, 105.10 (94.81),
131.11 (16.54), 78.11 (44.81). – C9H11N3: calcd. C 67.06,
H 6.88, N 26.07; found C 66.89, H 6.93, N 25.93.
1
835 cm−1. – H NMR (500 MHz, CDCl3): δ = 1.84 (quin,
J = 5.7 Hz, 2 H, CH2CH2CH2), 3.49 (t, J = 6.3 Hz, 4 H,
2 CH2N), 4.1 (br s, 1 H, NH), 7.63 (d, J = 8.3 Hz, 2 H, ArH),
7.75 (d, J = 8.3, Hz, 2 H, ArH). – 13C NMR (125 MHz,
CDCl3): δ = 19.7 (CH2CH2CH2), 41.4 (2 CH2N), 112.5 (C),
117.9 (C), 126.7 (2 CH), 131.3 (2 CH), 140.1 (C), 153.1
(NCN). – C11H11N3: calcd. C 71.33, H 5.99, N 22.69; found
C 71.18, H 5.90, N 22.77.
2-(3-Pyridyl)-1,4,5,6-tetrahydropyrimidine (Table 3,
entry 7)
Yellow oil. – IR (neat): v = 3300 (NH), 2805, 1617 (C=N),
1593, 1421, 1394, 1200, 1019, 817, 770, 700 cm−1. – 1H 2-(3-Cyanophenyl)-1,4,5,6-tetrahydropyrimidine (Table 3,
NMR (500 MHz, CDCl3): δ = 1.90 (quin, J = 5.8 Hz, 2 H,
CH2CH2CH2), 2.6 (br s, 1 H, NH), 3.54 (t, J = 5.7 Hz, 4 H,
2 CH2N), 7.26 – 7.32 (m, 1 H, ArH), 8.02 (d, J = 9.5 Hz, 1 H,
ArH), 8.64 (d, J = 4.8 Hz, 1 H, ArH), 8.87 (s, 1 H, ArH). –
13C NMR (125 MHz, CDCl3): δ = 22.7 (CH2CH2CH2),
42.3 (2 CH2N), 123.2 (CH), 132.7 (C), 134.1 (CH), 147.2
(CH), 150.8 (CH), 152.6 (NCN). – C9H11N3: calcd. C 67.06,
H 6.88, N 26.07; found C 67.19, H 6.81, N 26.13.
entry 10)
◦
M. p. 136 – 139 C. – IR (KBr): v = 3177 (NH), 3025,
2959, 2220 (CN), 1622 (C=N), 1541, 1475, 1367, 1194,
806 cm−1. – H NMR (500 MHz, CDCl3): δ = 1.87 (quin,
1
J = 5.7 Hz, 2 H, CH2CH2CH2), 3.51 (t, J = 5.8 Hz, 4 H, 2
CH2N), 4.2 (br s, 1 H, NH), 7.47 (t, J = 7.8 Hz, 1 H, ArH),
7.66 (d, J = 5.1 Hz, 1 H, ArH), 7.90 (d, J = 5.3 Hz, 1 H, ArH),
7.96 (s, 1 H, ArH). – 13C NMR (125 MHz, CDCl3): δ = 20.6
(CH2CH2CH2), 42.4 (2 CH2N), 112.5 (C), 118.4 (C), 129.2
(CH), 129.9 (CH), 130.4 (CH), 132.9 (CH), 138.5 (C), 152.7
(NCN). – MS (EI, 70 eV): m/z (%) = 185.13 (52.98) [M]+,
184.13 (100) [M–1]+, 129.08 (91.39), 102.07 (47.68), 75.06
(22.02). – C11H11N3: calcd. C 71.33, H 5.99, N 22.69; found
C 71.21, H 5.94, N 22.75.
2-(2-Thienyl)-1,4,5,6-tetrahydropyrimidine (Table 3,
entry 8)
M. p. 183 – 185 ◦C [24]. – IR (KBr): v = 3192 (NH),
3061, 2934, 2852, 1607 (C=N), 1549, 1525, 1514, 1431,
1362, 1325, 1302, 1194, 1166, 862, 798, 712 cm−1. – 1H
NMR (500 MHz, CDCl3): δ = 2.87 (quin, J = 5.8 Hz, 2 H,
CH2CH2CH2), 3.50 (t, J = 5.6 Hz, 4 H, 2 CH2N), 5.1 (br
s, 1 H, NH), 6.90 – 7.01 (m, 1 H, ArH), 7.20 (dd, J = 3.7,
0.9 Hz, 1 H, ArH), 7.31 (dd, J = 5.0, 0.9 Hz, 1 H, ArH).
Acknowledgement
Financial support of this work by the Center of Excellence
of Chemistry and the Research Council of the University of
Isfahan is gratefully appreciated.
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