Synthesis of New Imino Containing Tetrahydrochromeno[2,3-d]pyrimidines

Article abstract of DOI:10.1002/jhet.2729

Some new derivatives of 3,5-diaryl-4-imino-5,7,8,9-tetrahydro-3H-chromeno[2,3-d]pyrimidine have been prepared through a condensation reaction of 2-amino-4-aryl-3-cyano-5,6,7,8-tetrahydrobenzo[b]pyrans with triethyl orthoformate in boiling acetic anhydride followed by cyclization with primary aryl amines in the presence of a few drops triethylamine as catalyst in refluxing ethanol. The products were characterized on the basis of IR, ¹H-NMR, and ¹³C-NMR spectral and microanalytical data.

Full text of DOI:10.1002/jhet.2729

Month 2016
Synthesis of New Imino Containing Tetrahydrochromeno[2,3-d]
pyrimidines
*
Shohreh Ameli, Abolghasem Davoodnia, Mehdi Pordel, and Hossein Behmadi
Department of Chemistry, Mashhad Branch, Islamic Azad University, Mashhad, Iran
E-mail: adavoodnia@mshdiau.ac.ir; adavoodnia@yahoo.com
Received April 19, 2016
DOI 10.1002/jhet.2729
Published online 00 Month 2016 in Wiley Online Library (wileyonlinelibrary.com).
Some new derivatives of 3,5-diaryl-4-imino-5,7,8,9-tetrahydro-3H-chromeno[2,3-d]pyrimidine have been
prepared through a condensation reaction of 2-amino-4-aryl-3-cyano-5,6,7,8-tetrahydrobenzo[b]pyrans with
triethyl orthoformate in boiling acetic anhydride followed by cyclization with primary aryl amines in the
presence of a few drops triethylamine as catalyst in refluxing ethanol. The products were characterized on
1
the basis of IR, H-NMR, and 13C-NMR spectral and microanalytical data.
J. Heterocyclic Chem., 00, 00 (2016).
INTRODUCTION
of literature reveals that there are a number of methods
for the synthesis of chromeno[2,3-d]pyrimidines starting
from chromene or pyrimidine moiety [32–36]. However,
to the authors’ knowledge, the synthesis of 4-imino
tetrahydrochromeno[2,3-d]pyrimidine derivatives has been
largely overlooked, and there is only one reference in the
literature on the synthesis of these compounds [32].
These findings encouraged us to synthesize some new
4-imino tetrahydrochromeno[2,3-d]pyrimidine derivatives.
Therefore, in continuation of our previous works in the syn-
thesis of new heterocyclic compounds with potential
biological activities [37–48], in this paper, we report a
convenient synthesis of new 3,5-diaryl-4-imino-5,7,8,9-
tetrahydro-3H-chromeno[2,3-d]pyrimidines 5a–i through a
condensation reaction of 2-amino-4-aryl-3-cyano-5,6,7,8-
tetrahydrobenzo[b]pyrans 1a–d with triethyl orthoformate
2 in boiling acetic anhydride obtaining compounds 3a–d
followed by cyclization with primary aryl amines 4a–d
in the presence of a catalytic amount of triethylamine in
refluxing ethanol (Scheme 1).
The chromene moiety appears as an important struc-
tural component in both biologically active and natural
compounds and is widely employed as cosmetics, pig-
ments [1,2], and potential biodegradable agrochemicals
[3]. It is known that certain chromenes possess important
biological activities such as antioxidant [4], anticancer
[5,6], anti-HIV [7], antiviral [8], antihypertensive [9], an-
ticonvulsant [10], antileishmanial [11], TNF-α inhibitor
[12], and antifungal [13] activity. This motif widely found
in natural alkaloids, tocopherols, flavonoids, and anthocya-
nins [14], and several chromene derivatives have been
proven to be efficient DNA polymerase β inhibitors [15]
and apoptosis inducers [16]. On the other hand, a pyrimidine
scaffold is the base of many bioactive molecules such as an-
titubercular [17], antibacterial [18,19], antitumor [20],
antiinflammatory [21], antifungal [22], antiviral [23], and
antileishmanial [24] agent.
Chromeno[2,3-d]pyrimidines, which are constructed
from two fused chromene and pyrimidine rings, have also
generated great attention because of their interesting
biological properties such as antitumor [25,26], antituber-
cular [27], antibacterial [28], antifungal [29], and antimi-
crobial [27,30] activity. In addition, these compounds
exhibit excellent photophysical properties [31]. A perusal
RESULTS AND DISCUSSION
For our investigations, 2-amino-4-aryl-3-cyano-5,6,7,8-
tetrahydrobenzo[b]pyrans 1a-d were prepared according
© 2016 Wiley Periodicals, Inc.

S. Ameli, A. Davoodnia, M. Pordel, and H. Behmadi
Vol 000
Scheme 1. Synthesis of new 3,5-diaryl-4-imino-5,7,8,9-tetrahydro-3H-chromeno[2,3-d]pyrimidines.
to the literature procedure [49]. When these compounds
were allowed to interact with excess triethyl orthoformate
2 in acetic anhydride at reflux temperature, condensation
reaction occurred giving 3a–d. The latter compounds were
then reacted with primary aryl amines 4a–d in the various
catalyst-solvent systems at reflux temperature such as
t-BuOK in t-BuOH, pyridine as both catalyst and solvent,
Et3N in EtOH, and also in EtOH in the absence of a base
catalyst. Among them, the reactions were proceeded to
give the good yields of the products 3,5-diaryl-4-imino-
5,7,8,9-tetrahydro-3H-chromeno[2,3-d]pyrimidines 5a-i,
using triethylamine in refluxing ethanol.
The structural assignment of compounds 5a–i was based
upon spectral data and elemental analysis. For example, the
1H-NMR spectrum of compound 5a in DMSO-d6 did
not show the OEt signals of the precursor 3a at δ= 1.20
(t, J= 6.7Hz, 3H), δ =4.21 (q, J = 6.7 Hz, 2H) ppm, but
instead showed a signal at δ= 8.72 (s, 1H) for NH group
that is removed on deuteration, and other characteristic
signals in aromatic region for new phenyl group indicating
the formation of the tricyclic compound 5a. The IR
spectrum was devoid of the CN absorption band at
2209 cmÀ1 of the precursor but instead showed the NH
absorption band at 3349 cmÀ1, which shows the inclusion
of the nitrile moiety in the cyclisation process. Further
proof came from 13C-NMR spectrum that showed the
characteristic signals at δ 26.5, 28.7, 31.3, 32.0, and
50.1ppm for aliphatic carbons as well as the other signals
in the aromatic region and also carbonyl group. Also, this
compound gave satisfactory elemental analysis data
corresponding to the molecular formula C25H23N3O2
(Experimental).
good yields through the condensation reaction of 2-amino-4-
aryl-3-cyano-5,6,7,8-tetrahydrobenzo[b]pyrans with triethyl
orthoformate in boiling acetic in the presence of a few drops
triethylamine as catalyst in refluxing ethanol. The products
were characterized on the basis of spectral and microanalyt-
ical data.
EXPERIMENTAL
Melting points were recorded on a Stuart SMP3 melting
point apparatus. The IR spectra were obtained with KBr
disks using a Tensor 27 Bruker spectrophotometer. The
1H and 13C-NMR spectra were recorded with Bruker 300
and 400 MHz spectrometers, using TMS as internal
standard. Elemental analysis was performed on a Thermo
Finnigan Flash EA microanalyzer.
General procedure for the synthesis of compounds 3a–d.
A
mixture of the respective tetrahydrobenzo[b]pyran 1a–d
(2 mmol) and excess triethyl orthoformate 2 (2 mL) in
acetic anhydride (1 mL) was heated under reflux for
5–6 h. Upon completion, the mixture was poured onto
crushed ice. Then, the precipitate was collected and
recrystallized from ethanol (96%) to afford compounds
3a–d in high yields.
Ethyl
N-(3-cyano-7,7-dimethyl-5-oxo-4-phenyl-5,6,7,8-
tetrahydro-4H-chromen-2-yl)formimidate (3a).
Yield (88%);
mp 201–203°C; IR (KBr, cmÀ1): 2209 (CN), 1664
(C = O),À1H-NMR (400 MHz, DMSO-d6, δ ppm): 0.89
(s, 3H, CH3), 0.96 (s, 3H, CH3), 1.20 (t, J = 6.7 Hz, 3H,
CH3), 2.12 (ABq, Δν= 48.3 Hz, JAB = 16.0 Hz, 2H, CH2),
2.42 (s, 2H, CH2), 4.21 (q, J = 6.7 Hz, 2H, OCH2), 4.32
(s, 1H, CH), 7.10–7.30 (m, 5H, Ph), 8.46 (s, 1H,
N = CH); 13C-NMR (100 MHz, DMSO-d6, δ ppm): 13.8,
27.0, 28.3, 31.9, 37.1, 50.0, 64.1, 82.5, 111.6, 117.2,
127.2, 127.7, 128.6, 142.8, 156.0, 162.0, 163.0, 195.8;
Anal. Calcd for C21H22N2O3: C, 71.98; H, 6.33; N, 7.99,
Found: C, 72.12; H, 6.41; N, 7.81.
CONCLUSION
In brief, we have synthesized some new 3,5-diaryl-4-
imino-5,7,8,9-tetrahydro-3H-chromeno[2,3-d]pyrimidines in
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2016
Synthesis of Tetrahydrochromeno[2,3-d]pyrimidines
Ethyl N-(3-cyano-7,7-dimethyl-4-(3-nitrophenyl)-5-oxo-5,6,7,8-
4-imino-8,8-dimethyl-3,5-diphenyl-5,7,8,9-tetrahydro-3H-
chromeno[2,3-d]pyrimidin-6(4H)-one (5a). Yield (77%);
mp 272–275°C; IR (KBr cmÀ1): 3349 (NH), 1637 (C =O);
1H-NMR (400 MHz, DMSO-d6, δ ppm): 0.92 (s, 3H,
CH3), 1.06 (s, 3H, CH3), 2.13 (d, J = 16.0 Hz, 1H, one
proton of diastereotopic protons in CH2), 2.34 (d,
J = 16.0 Hz, 1H, one proton of diastereotopic protons in
CH2), 2.65 (ABq, Δν = 30.3 Hz, JAB = 17.6 Hz, 2H,
CH2), 5.46 (s, 1H, CH), 7.02 (t, J = 6.8 Hz, 1H, arom-
H), 7.14 (t, J = 6.7 Hz, 1H, arom-H), 7.20–7.30 (m, 4H,
arom-H), 7.39 (d, J = 7.0 Hz, 2H, arom-H), 7.55 (d,
J = 7.4 Hz, 2H, arom-H), 8.29 (s, 1H, N = CH), 8.72 (s,
1H, NH); 13C-NMR (100 MHz, DMSO-d6, δ ppm):
26.5, 28.7, 31.3, 32.0, 50.1, 99.8, 114.2, 121.7, 123.4,
126.9, 127.9, 128.3, 128.4, 139.2, 143.2, 156.0, 158.9,
161.3, 164.0, 195.9; Anal. Calcd for C25H23N3O2: C,
75.54; H, 5.83; N, 10.57, Found: C, 75.39; H, 5.75; N,
10.68.
4-imino-8,8-dimethyl-3-(2-methylphenyl)-5-phenyl-5,7,8,9-
tetrahydro-3H-chromeno[2,3-d]pyrimidin-6(4H)-one (5b).
Yield (74%); mp 240–241°C; IR (KBr cmÀ1) 3418 (NH),
1660 (C =O); 1H-NMR (400MHz, DMSO-d6, δ ppm): 0.91
(s, 3H, CH3), 1.06 (s, 3H, CH3), 1.58 (s, 3H, CH3), 2.11 (d,
J= 16.2Hz, 1H, one proton of diastereotopic protons in
CH2), 2.32 (d, J= 16.2Hz, 1H, one proton of diastereotopic
protons in CH2), 2.58 (ABq, Δν =33.2 Hz, JAB =15.4 Hz,
2H, CH2), 5.21 (s, 1H, CH), 7.05–7.20 (m, 5H, arom-H),
7.24 (t, J= 7.7Hz, 2H, arom-H), 7.30–7.40 (m, 2H, arom-
H), 8.07 (s, 1H, N=CH), 8.44 (s, 1H, NH); 13C-NMR
(100MHz, DMSO-d6, δ ppm): 17.5, 26.7, 28.8, 32.0, 32.2,
50.3, 98.9, 114.4, 126.3, 127.1, 127.2, 127.3, 128.3, 128.4,
130.5, 134.8, 137.3, 143.1, 156.4, 160.1, 161.3, 164.2,
196.3; Anal. Calcd for C26H25N3O2: C, 75.89; H, 6.12; N,
10.21, Found: C, 76.08; H, 6.06; N, 10.34.
5-(4-chlorophenyl)-4-imino-8,8-dimethyl-3-phenyl-5,7,8,9-
tetrahydro-3H-chromeno[2,3-d]pyrimidin-6(4H)-one (5c).
Yield (81%); mp 256–258°C; IR (KBr cmÀ1) 3435 (NH),
1657 (C=O); 1H-NMR (400MHz, DMSO-d6, δ ppm):
0.92 (s, 3H, CH3), 1.07 (s, 3H, CH3), 2.14 (d, J=16.0Hz,
1H, one proton of diastereotopic protons in CH2), 2.35 (d,
J=16.0Hz, 1H, one proton of diastereotopic protons in
CH2), 2.63 (ABq, Δν =32.9Hz, JAB =17.7Hz, 2H, CH2),
5.49 (s, 1H, CH), 7.03 (t, J=7.4Hz, 2H, arom-H),
7.25–7.35 (m, 3H, arom-H), 7.41 (d, J=8.4Hz, 2H, arom-
H), 7.55 (d, J=7.6Hz, 2H, arom-H), 8.31 (s, 1H, N=CH),
8.76 (s, 1H, NH); 13C-NMR (100MHz, DMSO-d6, δ
ppm): 26.5, 28.6, 30.8, 32.0, 50.0, 99.3, 113.9, 121.9,
123.5, 128.3, 128.4, 129.8, 131.5, 139.1, 142.1, 156.2,
158.9, 161.4, 164.2, 195.9; Anal. Calcd for
C25H22ClN3O2: C, 69.52; H, 5.13; N, 9.73, Found: C,
69.67; H, 5.19; N, 9.61.
tetrahydro-4H-chromen-2-yl)formimidate (3b).
Yield (85%);
mp 168–170°C; IR (KBr cmÀ1): 2208 (CN), 1668 (C= O),
1
1511 and 1364 (NO2), H-NMR (400 MHz, DMSO-d6,
δ ppm): 0.87 (s, 3H, CH3), 0.94 (s, 3H, CH3), 1.18 (t,
J= 6.9Hz, 3H, CH3), 2.10 (ABq, Δν= 51.7Hz, JAB = 16.1Hz,
2H, CH2), 2.39 (s, 2H, CH2), 4.19 (q, J = 6.9 Hz, 2H,
OCH2), 4.59 (s, 1H, CH), 7.55 (t, J=7.7Hz, 1H, arom-H),
7.66 (d, J= 7.4Hz, 1H, arom-H), 7.98 (s, 1H, arom-H), 8.01
(d, J = 8.1 Hz, 1H, arom-H), 8.47 (s, 1H, N = CH); 13C-
NMR (100 MHz, DMSO-d6, δ ppm): 13.8, 26.9, 28.2,
31.9, 36.7, 49.9, 64.2, 81.3, 110.7, 116.9, 122.3, 122.4,
130.2, 134.7, 145.0, 147.9, 156.6, 162.5, 163.6, 195.8;
Anal. Calcd for C21H21N3O5: C, 63.79; H, 5.35; N,
10.63, Found: C, 63.94; H, 5.28; N, 10.49.
Ethyl
N-(4-(4-chlorophenyl)-3-cyano-7,7-dimethyl-5-oxo-
5,6,7,8-tetrahydro-4H-chromen-2-yl)formimidate (3c).
Yield
(92%); mp 177-179°C; IR (KBr cmÀ1): 2212 (CN), 1675
1
(C=O), H-NMR (300MHz, DMSO-d6, δ ppm): 0.98 (s,
3H, CH3), 1.06 (s, 3H, CH3), 1.31 (t, J=7.2Hz, 3H, CH3),
2.21 (ABq, Δν =35.7Hz, JAB =15.9Hz, 2H, CH2), 2.59 (s,
2H, CH2), 4.31 (q, J=7.2Hz, 2H, OCH2), 4.47 (s, 1H,
CH), 7.29 (d, J=8.4Hz, 2H, arom-H), 7.41 (d, J=8.4Hz,
2H, arom-H), 8.57 (s, 1H, N=CH); 13C-NMR (75MHz,
DMSO-d6, δ ppm): 14.3, 27.5, 28.6, 32.4, 37.0, 50.4,
64.6, 82.4, 111.7, 117.5, 129.0, 130.1, 132.3, 142.3,
156.7, 162.6, 163.5, 196.2; Anal. Calcd for C21H21ClN2O3:
C, 65.54; H, 5.50; N, 7.28, Found: C, 65.41; H, 5.62;
N, 7.42.
Ethyl N-(3-cyano-4-(4-methoxyphenyl)-7,7-dimethyl-5-oxo-
5,6,7,8-tetrahydro-4H-chromen-2-yl)formimidate (3d).
Yield
(90%); mp 158–160°C; IR (KBr cmÀ1): 2207 (CN), 1669
1
(C = O), H-NMR (400 MHz, DMSO-d6, δ ppm): 0.97 (s,
3H, CH3), 1.04 (s, 3H, CH3), 1.29 (t, J=7.1Hz, 3H, CH3),
2.19 (ABq, Δν =50.1Hz, JAB =16.1 Hz, 2H, CH2), 2.56 (s,
2H, CH2), 3.72 (s, 3H, OCH3), 4.29 (q, J=7.1Hz, 2H,
OCH2), 4.35 (s, 1H, CH), 6.88 (d, J=8.5 Hz, 2H, arom-H),
7.14 (d, J= 8.5Hz, 2H, arom-H), 8.53 (s, 1H, N =CH); 13C-
NMR (100MHz, DMSO-d6, δ ppm): 13.8, 26.9, 28.3, 31.9,
36.2, 50.0, 55.0, 64.0, 82.7, 111.8, 113.9, 117.3, 117.4,
128.8, 155.8, 158.3, 161.8, 162.6, 195.7; Anal. Calcd for
C22H24N2O4: C, 69.46; H, 6.36; N, 7.36, Found: C, 69.29;
H, 6.49; N, 7.26.
General procedure for the synthesis of 3,5-diaryl-4-imino-
5,7,8,9-tetrahydro-3H-chromeno[2,3-d]pyrimidines 5a–i.
To
a solution of the primary aryl amine 4a–d (1mmol) in
ethanol (20mL) in the presence of three drops
triethylamine as catalyst, compounds 3a–d (1mmol) was
added. The reaction mixture was heated under reflux for
5–6h. After the completion of the reaction (monitored by
TLC), the mixture was cooled to room temperature. The
crude product was collected and recrystallized from ethyl
acetate/n-hexane (1:3) to afford compounds 5a–i in good
yields.
3-(3-chlorophenyl)-5-(4-chlorophenyl)-4-imino-8,8-dimethyl-
5,7,8,9-tetrahydro-3H-chromeno[2,3-d]pyrimidin-6(4H)-one
(5d). Yield (75%); mp 235–237°C; IR (KBr cmÀ1) 3376
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

S. Ameli, A. Davoodnia, M. Pordel, and H. Behmadi
Vol 000
(NH), 1656 (C=O); 1H-NMR (400MHz, DMSO-d6, δ
ppm): 0.92 (s, 3H, CH3), 1.07 (s, 3H, CH3), 2.15 (d,
J=16.1Hz, 1H, one proton of diastereotopic protons in
CH2), 2.35 (d, J=16.1Hz, 1H, one proton of
diastereotopic protons in CH2), 2.65 (ABq, Δν=31.6Hz,
DMSO-d6, δ ppm): 0.90 (s, 3H, CH3), 1.06 (s, 3H, CH3),
2.14 (d, J =16.1 Hz, 1H, one proton of diastereotopic
protons in CH2), 2.35 (d, J= 16.1 Hz, 1H, one proton of
diastereotopic protons in CH2), 2.66 (ABq, Δν= 26.3Hz,
JAB = 17.8Hz, 2H, CH2), 5.66 (s, 1H, CH), 7.02 (t,
J
AB =17.5Hz, 2H, CH2), 5.51 (s, 1H, CH), 7.08 (d,
J = 7.2 Hz, 1H, arom-H), 7.26 (t, J = 7.7 Hz, 2H, arom-H),
7.50-7.60 (m, 3H, arom-H), 7.75 (d, J =7.6 Hz, 1H,
arom-H), 8.02 (d, J = 7.7 Hz, 1H, arom-H), 8.33 (s, 1H,
arom-H), 8.45 (s, 1H, N= CH), 8.91 (s, 1H, NH);
13C-NMR (100MHz, DMSO-d6, δ ppm): 26.4, 28.6,
31.1, 32.1, 49.9, 98.6, 113.4, 122.0, 122.1, 123.0, 123.7,
128.4, 130.1, 134.4, 138.9, 145.1, 147.5, 156.5, 158.9,
161.5, 164.7, 196.0; Anal. Calcd for C25H22N4O4: C,
67.86; H, 5.01; N, 12.66, Found: C, 68.01; H, 5.12, N;
12.54.
J=7.7Hz, 1H, arom-H), 7.25–7.35 (m, 3H, arom-H), 7.39
(d, J=8.3Hz, 2H, arom-H), 7.55 (t, J=6.7Hz, 1H, arom-
H), 7.79 (d, J=6.4Hz, 1H, arom-H), 8.39 (s, 1H, N=CH),
8.92 (s, 1H, NH); 13C-NMR (100MHz, DMSO-d6, δ
ppm): 26.7, 28.7, 30.1, 32.1, 50.4, 114.5, 120.0, 120.9,
123.2, 127.3, 128.1, 128.7, 129.0, 130.4, 130.8, 131.9,
140.0, 143.3, 156.2, 159.0, 164.3, 196.4; Anal. Calcd for
C25H21Cl2N3O2: C, 64.39; H, 4.54; N, 9.01, Found: C,
64.20; H, 4.63; N, 9.12.
4-imino-5-(4-methoxyphenyl)-8,8-dimethyl-3-phenyl-5,7,8,9-
tetrahydro-3H-chromeno[2,3-d]pyrimidin-6(4H)-one (5e). Yield
(79%); mp 240–241°C; IR (KBr cmÀ1) 3435 (NH), 1656
4-imino-8,8-dimethyl-3-(2-methylphenyl)-5-(3-nitrophenyl)-
5,7,8,9-tetrahydro-3H-chromeno[2,3-d]pyrimidin-6(4H)-one
(5h). Yield (72%); mp 222–225°C; IR (KBr cmÀ1) 3313
(NH), 1638 (C=O), 1527 and 1333 (NO2); 1H-NMR
(400MHz, DMSO-d6, δ ppm): 0.91 (s, 3H, CH3), 1.08 (s,
3H, CH3), 1.59 (s, 3H, CH3), 2.15 (d, J=16.2Hz, 1H, one
proton of diastereotopic protons in CH2), 2.35 (d,
J=16.2Hz, 1H, one proton of diastereotopic protons in
CH2), 2.67 (ABq, Δν =23.7Hz, JAB =17.9Hz, 2H, CH2),
5.43 (s, 1H, CH), 7.05–7.20 (m, 4H, arom-H), 7.58 (t,
J=7.7Hz, 1H, arom-H), 7.73 (d, J=7.2Hz, 1H, arom-H),
8.07 (d, J=7.6Hz, 1H, arom-H), 8.13 (s, 1H, arom-H),
8.45 (s, 1H, N=CH), 8.67 (s, 1H, NH); 13C-NMR
(100MHz, DMSO-d6, δ ppm): 17.1, 26.5, 28.5, 31.6, 31.9,
49.9, 97.4, 113.3, 121.9, 123.4, 126.1, 126.2, 127.3,
128.6, 129.9, 130.2, 134.6, 137.0, 145.0, 147.3, 156.7,
159.9, 161.2, 164.5, 195.9; Anal. Calcd for C26H24N4O4:
C, 68.41; H, 5.30; N, 12.27, Found: C, 68.20; H, 5.37; N,
12.33.
4-imino-8,8-dimethyl-3-(3-methylphenyl)-5-(3-nitrophenyl)-
5,7,8,9-tetrahydro-3H-chromeno[2,3-d]pyrimidin-6(4H)-one
(5i). Yield (70%); mp 213–215°C; IR (KBr cmÀ1) 3363
(NH), 1641 (C = O), 1568 and 1350 (NO2); 1H-NMR
(400 MHz, DMSO-d6, δ ppm): 0.91 (s, 3H, CH3), 1.07 (s,
3H, CH3), 2.15 (d, J= 16.1 Hz, 1H, one proton of
diastereotopic protons in CH2), 2.24 (s, 3H, CH3), 2.36
(d, J =16.1 Hz, 1H, one proton of diastereotopic protons
in CH2), 2.67 (ABq, Δν = 27.1Hz, JAB = 17.7Hz, 2H,
CH2), 5.64 (s, 1H, CH), 7.15 (t, J = 7.9 Hz, 1H, arom-H),
7.25–7.35 (m, 3H, arom-H), 7.56 (t, J= 7.9Hz, 1H,
arom-H), 7.73 (d, J =7.7 Hz, 1H, arom-H), 8.02 (d,
J = 8.0 Hz, 1H, arom-H), 8.32 (s, 1H, arom-H), 8.43 (s,
1H, N= CH), 8.81 (s, 1H, NH); 13C-NMR (100MHz,
DMSO-d6, δ ppm): 21.1, 26.4, 28.6, 31.1, 32.0, 49.9,
98.5, 113.4, 119.3, 122.0, 122.6, 122.9, 124.4, 128.2,
130.1, 134.3, 137.6, 138.8, 145.1, 147.4, 156.5, 159.0,
161.4, 164.6, 195.9; Anal. Calcd for C26H24N4O4: C,
68.41; H, 5.30; N, 12.27, Found: C, 68.59; H, 5.39; N,
12.18.
1
(C = O); H-NMR (400MHz, DMSO-d6, δ ppm): 0.93 (s,
3H, CH3), 1.07 (s, 3H, CH3), 2.13 (d, J=16.1Hz, 1H, one
proton of diastereotopic protons in CH2), 2.33 (d,
J=16.1Hz, 1H, one proton of diastereotopic protons in
CH2), 2.64 (ABq, Δν =32.6Hz, JAB =17.5Hz, 2H, CH2),
3.65 (s, 3H, OCH3), 5.39 (s, 1H, CH), 6.79 (d, J=8.5Hz,
2H, arom-H), 7.02 (t, J=7.2Hz, 1H, arom-H), 7.25–7.35
(m, 4H, arom-H), 7.57 (d, J=8.0Hz, 2H, arom-H), 8.29 (s,
1H, N= CH), 8.68 (s, 1H, NH); 13C-NMR (100MHz,
DMSO-d6, δ ppm): 26.5, 28.6, 30.4, 31.9, 50.1, 54.9,
100.0, 113.6, 114.4, 121.6, 123.3, 128.4, 128.9, 135.2,
139.2, 155.8, 157.9, 158.8, 161.2, 163.6, 195.8; Anal. Calcd
for C26H25N3O3: C, 73.05; H, 5.89; N, 9.83, Found: C,
73.22; H, 5.81; N, 9.72.
4-imino-5-(4-methoxyphenyl)-8,8-dimethyl-3-(2-methylphenyl)-
5,7,8,9-tetrahydro-3H-chromeno[2,3-d]pyrimidin-6(4H)-one
(5f).
Yield (76%); mp 212–214°C; IR (KBr cmÀ1
)
1
3400 (NH), 1654 (C = O); H-NMR (400 MHz, DMSO-
d6, δ ppm): 0.93 (s, 3H, CH3), 1.07 (s, 3H, CH3), 1.66
(s, 3H, CH3), 2.13 (d, J = 16.1 Hz, 1H, one proton of
diastereotopic protons in CH2), 2.32 (d, J = 16.1 Hz,
1H, one proton of diastereotopic protons in CH2), 2.62
(ABq, Δν = 27.4 Hz, JAB = 16.5 Hz, 2H, CH2), 3.67 (s,
3H, OCH3), 5.18 (s, 1H, CH), 6.81 (d, J = 8.3 Hz, 2H,
arom-H), 7.10–7.20 (m, 4H, arom-H), 7.29 (d,
J = 8.3 Hz, 2H, arom-H), 8.09 (s, 1H, N = CH), 8.41 (s,
1H, NH); 13C-NMR (100 MHz, DMSO-d6, δ ppm):
17.4, 26.5, 28.6, 30.9, 31.9, 50.1, 55.0, 98.8, 113.4,
114.3, 125.9, 126.0, 127.0, 129.2, 130.2, 134.4, 134.9,
137.2, 156.0, 158.0, 159.8, 161.1, 163.5, 195.8; Anal.
Calcd for C27H27N3O3: C, 73.45; H, 6.16; N, 9.52,
Found: C, 73.31; H, 6.09; N, 9.63.
4-imino-8,8-dimethyl-5-(3-nitrophenyl)-3-phenyl-5,7,8,9-
tetrahydro-3H-chromeno[2,3-d]pyrimidin-6(4H)-one (5g).
Yield (75%); mp 259–261°C; IR (KBr cmÀ1) 3314 (NH),
1
1641 (C = O), 1529 and 1347 (NO2); H-NMR (400MHz,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2016
Synthesis of Tetrahydrochromeno[2,3-d]pyrimidines
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Acknowledgments. We gratefully acknowledge financial support
from the Islamic Azad University, Mashhad Branch, Iran.
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