Efficient synthesis of arylaldehyde oxime ethers functionalised with 3,4-dihydropyrimidinones and 2,5-quinazolinediones via a one-pot two-step method

Article abstract of DOI:10.3184/174751912X13546462577913

New arylahdehyde oxime ethers functionalised with N3-3,4- dihydropyrimidinone and 2,5-quinazolinedione groups were synthesised in moderate to good yields by the reaction of the corresponding 3,4-dihydropyrimidinones and quinazolinediones with paraformaldehyde and arylaldehyde oximes via a one-pot two-step strategy in the presence of chlorotrimethylsilane. The advantages of this method are the simple procedure, the high regioselectivity of the products and the mild reaction conditions.

Full text of DOI:10.3184/174751912X13546462577913

30 RESEARCH PAPER
JANUARY, 30–33
JOURNAL OF CHEMICAL RESEARCH 2013
Efficient synthesis of arylaldehyde oxime ethers functionalised with
3,4-dihydropyrimidinones and 2,5-quinazolinediones via a one-pot
two-step method
Zheng-Jun Quana,b, Xue-Hong Tanga,b, Yu-Xia Daa,b, Zhang Zhanga,b and Xi-Cun Wanga,b*
aKey Laboratory of Eco-Environment-Related Polymer Materials, Ministry of Education, China, Gansu 730070, P. R. China
bGansu Key Laboratory of Polymer Materials, College of Chemistry and Chemical Engineering, Northwest Normal University, Anning East
Road 967#, Lanzhou, Gansu 730070, P. R. China
New arylahdehyde oxime ethers functionalised with N3-3,4-dihydropyrimidinone and 2,5-quinazolinedione groups
were synthesised in moderate to good yields by the reaction of the corresponding 3,4-dihydropyrimidinones and
quinazolinediones with paraformaldehyde and arylaldehyde oximes via a one-pot two-step strategy in the presence
of chlorotrimethylsilane. The advantages of this method are the simple procedure, the high regioselectivity of the
products and the mild reaction conditions.
Keywords: arylaldehyde oximes, aldoxime ethers, 3,4-dihydropyrimidin-2-ones, 2,5-quinazolinedione derivatives, three-
component reaction
In continuation of our previous studies,1 the one-pot, two-step
reaction of simple nucleophiles (alcohols, amines) with para-
formaldehyde and 3,4-dihydropyrimidin-2-ones (DHPMs) in
the presence of chlorotrimethylsilane to produce N3-substi-
tuted 3,4-dihydropyrimidin-2-ones, we report the use of the
more complex aldoximes and ketoximes as the nucleophiles
in the synthesis of some oxime ether derivatives of N3-methyl-
3,4-dihydropyrimidin-2-ones and also of N3-methyl-2,5-
quinazolinediones.
Oxime ethers are important sub-structures of biologically
active compounds that are used extensively by the pharmaceu-
tical and agrochemical industries.2,3,4 Although some newer
methods of synthesis of oxime ethers have been reported
recently, the need for the development of a more general and
efficient method providing highly functionalised oxime ethers
remains.
3,4-Dihydropyrimidin-2-ones (DHPMs) have attracted con-
siderable interest due to their interesting pharmacological
properties, such as calcium channel modulators, antihyperten-
sives, α1a adrenergic agonists, mitotic kinesin inhibitors, and
hepatitis B virus replication suppressors.5 Among DHPM
derivatives, most of the pharmacologically attractive forms are
/N3/-substituted analogues.6 In the context of our interest in
the synthesis of functionalised DHPM derivatives,7 we here
report the synthesis of 14 N3-methyl-DHPMs modified with
oxime ethers by reaction of DHPMs with paraformaldehyde
and arylaldehydes oximes in the presence of trimethylsilyl
chloride (TMSCl). We have also accomplished the synthesis of
six N3-methyl-substituted 2,5-quinazolinediones by a similar
process starting from 2,5-quinazolinediones.
in Scheme 1, with the structure of the putative intermediate
shown in square brackets. Firstly, DHPM 1 was treated with
paraformaldehyde in the presence of TMSCl at 40 °C in dichlo-
romethane (DCM) for 24 h. Then arylaldehyde oxime 2 and
Et3N were added to the mixture which was refluxed for
12 h to give the N3-substituted-DHPM product 3. A variety of
DHPMs and arylaldehyde oximes as substrates were examined
and the corresponding oxime ethers were regioselectively
obtained (Table 1). In general, the electronics of the 4-aryl
substituents of the DHPMs did not appear to influence the
process, as substrates substituted with methyl methoxy or
chloro groups all gave the products in good yields (entries
2–6). Substitution on the phenyl ring of the oxime moiety is
not limited to a chloro group, but those with p-nitro and
p-methoxy groups were equally effective in giving the desired
products in good yields (entries 8 and 9). Use of ketone oximes
instead of aldehyde oximes also gave the corresponding oxime
ethers 3j–n in good yields (entries 10–14). 1H NMR spectra of
all products showed that the reaction occurred exclusively at
the N3 position of the DHPMs 1. The regioselectivity of the
reaction is consistent with our previous results1,7 and other
results of alkylation reactions.8
To further explore the scope of the one-pot reaction, we then
used 2,5-quinazolinedione derivatives 4a–e as substrates to
synthesise the oxime ethers functionalised with quinazolinone
(Table 2).As expected, the desired products 5a–f were obtained
smoothly when using ketone oximes as well as aldehyde
oximes, though this reaction had to be carried out in 1,4-dioxane
at 100 °C.
In conclusion, a variety of oxime ethers functionalised
DHPMs and 2,5-quinazolinediones with were regioselectively
prepared through a one-pot two step reaction between DHPM
and 2,5-quinazolinedione derivatives, paraformaldehyde,
chlorotrimethylsilane, and various arylaldehyde oximes. The
Results and discussion
The two-step synthesis of N3-methyl-substituted 4,5,6-trisub-
stituted 3,4-dihydropyrimidin-2-ones (DHPMs) 3 is summarised
Scheme 1 Synthesis of oxime ethers 3 from DHPMs 1, (CH2O)n and oximes 2.
* Correspondent. E-mail: wangxicun@nwnu.edu.cn

JOURNAL OF CHEMICAL RESEARCH 2013 31
Table 1 Synthesis of oxime ethers 3 from 3,4-dihydropyri-
midinones (DHPMs) 1 paraformaldehyde and aldehyde and
ketone oximes 2a
acetate and petroleum ether to afford the pure oxime ether 3 as the
unique product (no/cis/isomer was obtained).
For the analogous reaction of the 2,5-quinazolinediones (4, 1.0 mmol),
anhydrous CH2Cl2 (5 mL) was replaced by anhydrous 1,4-dioxane
(5 mL) (reflux temperature 100°C).
Entry
Ar
R1
R2
Product Yield/%b
Ethyl 3-[({[(E)-4-chlorobenzylidene]amino}oxy)methyl]-6-methyl-
2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate (3a): White
powder, m.p. 142–144 °C; H NMR: δ = 7.96 (s, 1H, =CH), 7.82
(br s, 1H, NH), 7.50 (d, J = 8.0 Hz, 2H, ArH), 7.51–7.23 (m, 7H, ArH),
5.78 (d, J = 11.2 Hz, 1H, NCH2), 5.75 (s, 1H, CH), 4.97 (d, J = 11.2
Hz, 1H, NCH2), 4.13–4.05 (m, 2H, CH2), 2.37 (s, 3H, CH3), 1.21 (m,
J = 7.2 Hz, 3H, CH3); 13C NMR: δ = 169.2, 166.9, 165.7, 160.1, 139.7,
129.2, 128.0, 113.1, 60.7, 44.6, 25.8, 24.8, 23.2, 13.5; MS: m/z = 427
(M+); Anal. Calcd for C22H22ClN3O4: C, 61.75; H, 5.18; N, 9.82.
Found: C, 61.80; H, 5.23; N, 9.78%.
1
2
C6H5
p-MeC6H4
p-MeOC6H4
p-Cl-C6H4
o-MeOC6H4
o-Cl-C6H4
C6H5
p-Cl-C6H4
p-Cl-C6H4
p-Cl-C6H4
p-Cl-C6H4
p-Cl-C6H4
p-Cl-C6H4
C6H5
H
H
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
71
74
73
76
72
75
73
75
74
70
74
72
75
71
1
3
H
4
H
5
H
6
H
7
H
8
C6H5
p-NO2-C6H4
p-OCH3-C6H4
C6H5
H
9
C6H5
C6H5
p-MeC6H4
p-MeOC6H4
o-Cl-C6H4
o-MeOC6H4
H
10
11
12
13
14
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
Ethyl 3-[({[(E)-4-chlorobenzylidene]amino}oxy)methyl]-6-methyl-
2-oxo-4-(p-tolyl)-1,2,3,4-tetrahydropyrimidine-5-carboxylate (3b):
C6H5
C6H5
1
White powder, m.p. 124–126 °C; H NMR: δ = 8.15 (s, 1H, =CH),
C6H5
7.96 (br s, 1H, NH), 7.50 (d, J = 8.0 Hz, 2H, ArH), 7.35–7.26 (m, 4H,
ArH), 7.09 (d, J = 8.0 Hz, 2H, ArH), 5.79 (d, J = 11.2 Hz, 1H, NCH2),
5.70 (s, 1H, CH), 4.96 (d, J = 11.2 Hz, 1H, NCH2), 4.12–4.06 (m, 2H,
CH2), 2.33 (s, 3H, CH3), 2.30 (s, 3H, CH3), 1.21 (t, J = 7.2 Hz, 3H,
CH3); 13C NMR: δ = 165.4, 152.9, 148.9, 145.6, 137.0, 137.7, 136.0,
130.3, 129.2, 128.9, 128.4, 127.3, 102.7, 77.8, 60.0, 59.2, 21.1, 18.6,
14.2; MS: m/z = 441 (M+); Anal. Calcd for C23H24ClN3O4: C, 62.51; H,
5.47; N, 9.51. Found: C, 62.46; H, 5.39; N, 9.39%.
Ethyl 3-[({[(E)-4-chlorobenzylidene]amino}oxy)methyl]-6-methyl-
2-oxo-4-(4-methoxyphenyl)-1,2,3,4-tetrahydropyrimidine-5-carbox-
ylate (3c): White powder, m.p. 112–114 °C; 1H NMR: δ = 8.47 (br s,
1H, NH), 7.97 (s, 1H, =CH), 7.50 (d, J = 8.0 Hz, 2H, ArH), 7.35–7.27
(m, 4H, ArH), 6.81 (d, J = 8.0 Hz, 2H, ArH), 5.79 (d, J = 11.2 Hz, 1H,
NCH2), 5.69 (s, 1H, CH), 4.98 (d, J = 11.2 Hz, 1H, NCH2), 4.08 (q,
J = 7.2 Hz, 2H, CH2), 3.76 (s, 3H, OCH3), 2.34 (s, 3H, CH3), 1.21 (t,
J = 7.2 Hz, 3H, CH3); 13C NMR: δ = 165.5, 159.2, 153.1, 148.8, 145.6,
136.0, 134.3, 130.3, 128.9, 128.6, 128.3, 113.8, 102.6, 77.6, 60.0,
58.9, 55.2, 18.5, 14.2; MS: m/z = 457 (M+); Anal. Calcd for
C23H24ClN3O5: C, 60.33; H, 5.28; N, 9.18. Found: C, 60.40; H, 5.25;
N, 9.29%.
Ethyl 3-[({[(E)-4-chlorobenzylidene]amino}oxy)methyl]-6-methyl-
2-oxo-4-(4-chlorophenyl)-1,2,3,4-tetrahydropyrimidine-5-carboxyl-
ate (3d): White powder, m.p. 115–116 °C; 1H NMR: δ = 7.90 (s, 1H,
=CH), 7.48 (d, J = 8.0 Hz 2H, ArH), 7.36–7.23 (m, 6H, ArH), 7.14
(br s, 1H, NH), 5.72 (d, J = 11.2 Hz, 1H, NCH2), 5.71 (s, 1H, CH),
5.03 (d, J = 11.2 Hz, 1H, NCH2), 4.10 (q, J = 7.2 Hz, 2H, CH2), 2.33
(s, 3H, CH3), 1.22 (t, J = 7.2 Hz, 3H, CH3); 13C NMR: δ = 165.2,
152.9, 149.0, 146.0, 140.6, 136.1, 133.7, 130.1, 129.0, 128.7, 128.7,
128.3, 102.3, 78.0, 60.2, 59.0, 18.7, 14.2; MS: m/z = 461 (M+); Anal.
Calcd for C22H21Cl2N3O4: C, 57.15; H, 4.58; N, 9.18. Found: C, 57.31;
H, 5.65; N, 9.31%.
a Reaction procedure of DHPM (1, 1.0 mmol), (CH2O)n (4.0 mmol),
TMS-Cl (2.5 mmol), CH2Cl2 (5 mL), 40 °C, 24 h; then oxime (2,
1 mmol), Et3N (2.5 mmol), 40 °C, 12 h.
b Isolated yield.
Table 2 Synthesis of ether oximes 5 from quinazolinones 4,
paraformaldehyde and aldehyde and ketone oximes 2a
Entry
Ar
R1
R2
Product Yield/%b
1
2
3
4
5
6
C6H5
C6H5
C6H5
C6H5
H
C6H5
C6H5
5a
5b
5c
5d
5e
5f
71
74
73
76
72
75
p-MeC6H4
p-Cl-C6H4
C6H5
C6H5
p-Cl-C6H4
p-Cl-C6H4
p-Cl-C6H4
p-Cl-C6H4
p-MeC6H4
H
H
a Reaction procedure: 2,5-quinazolinediones (4, 1.0 mmol),
(CH2O)n (4.0 mmol), TMSCl (2.5 mmol), 1,4-dioxane (5 mL),
100 °C, 24 h; then oxime (2, 1.0 mmol), Et3N (2.5 mmol), 100 °C,
12 h.
b Isolated yield.
Ethyl 3-[({[(E)-4-chlorobenzylidene]amino}oxy)methyl]-6-methyl-
2-oxo-4-(2-methoxyphenyl)-1,2,3,4-tetrahydropyrimidine-5-carbox-
ylate (3e): White powder, m.p. 243–245 °C; H NMR: δ = 8.15 (s,
method provides a highly efficient and convenient synthesis
oxime ethers. Synthesis and screening of compounds based
on DHPM scaffolds may lead to the discovery of interesting
biological activities.
1
1H, =CH), 8.13 (br s, 1H, NH), 7.38–7.32 (m, 4H, ArH), 7.25–7.23
(m, 2H, ArH), 6.95–6.84 (m, 2H, ArH), 6.11 (s, 1H, CH), 5.54 (d,
J = 9.6 Hz, 1H, NCH2), 4.89 (d, J = 9.6 Hz, 1H, NCH2), 4.02–4.98 (m,
2H, CH2), 4.03–3.97 (m, 2H, CH2), 3.83 (s, 3H, OCH3), 2.37 (s, 3H,
CH3), 1.10 (t, J = 7.2 Hz, 3H, CH3); 13C NMR: δ = 165.1, 157.1,
152.3, 145.4, 136.0, 132.1, 130.0, 129.9, 128.7, 128.4, 128.2, 120.9,
111.1, 101.2, 72.7, 60.0, 57.0, 55.6, 18.6, 14.0; MS: m/z = 457 (M+);
Anal. Calcd for C23H24ClN3O5: C, 60.33; H, 5.28; N, 9.18. Found: C,
60.45; H, 5.22; N, 9.10%.
Ethyl 3-[({[(E)-4-chlorobenzylidene]amino}oxy)methyl]-6-methyl-
2-oxo-4-(2-chlorophenyl)-1,2,3,4-tetrahydropyrimidine-5-carboxyl-
ate (3f): White powder, m.p. 210–212 °C; 1H NMR: δ = 7.90 (s, 1H,
=CH), 7.51–7.46 (m, 3H, ArH), 7.38 (br s, 1H, NH), 7.35–7.32
(m, 3H, ArH), 6.95–6.84 (m, 2H, ArH), 6.11 (s, 1H, CH), 5.54 (d,
J = 10.8 Hz, 1H, NCH2), 4.89 (d, J = 10.8 Hz 1H, NCH2), 4.04 (q,
J = 7.2 Hz, 2H, CH2), 2.39 (s, 3H, CH3), 1.16 (t, J = 7.2 Hz, 3H, CH3);
13C NMR: δ = 165.1, 152.0, 148.9, 146.2, 140.0, 136.0, 133.0, 130.4,
130.0, 129.5, 129.3, 128.9, 128.4, 127.7, 101.8, 77.6, 60.1, 56.2, 18.5,
14.1; MS: m/z = 461 (M+); Anal. Calcd for C22H21Cl2N3O4: C, 57.15;
H, 4.58; N, 9.09, Found: C, 57.30; H, 4.61; N, 9.25%.
Experimental
Melting points were determined on an XT-4 electrothermal micromelt-
ing point apparatus and are uncorrected. NMR spectra were recorded
at 400 (1H) and 100 (13C) MHz, respectively, on a Varian Mercury
plus-400 instrument using CDCl3 as solvent and TMS as an internal
standard. Elemental analyses were performed on a Carlo-Erba 1106
Elemental Analysis instrument. Mass spectra were obtained on a
Bruker Daltonics APEXII 47e FT-ICR spectrometer. Column chroma-
tography was performed on silica gel (300–400 mesh). Commercially
available reagents were used without further purification. Solvents
were purified prior to use according to the standard methods.
Synthesis of oxime ethers; general procedure
3,4-Dihydropyrimidinone (1, 1.0 mmol), paraformaldehyde (4.0 mmol),
and trimethylsilyl chloride (TMSCl) (2.5 mmol) were refluxed in
anhydrous CH2Cl2 (5 mL) for 24 h. To this mixture was added arylal-
dehyde oxime (2, 1.2 mmol) and Et3N (2.5 mmol). The combined
mixture was refluxed for 12 h. After completion of the reaction, which
was monitored by thin layer chromatography (TLC), any solid parti-
cles were filtered off and the filtrate evaporated. The crude product
was purified by column chromatography over silica gel with ethyl
Ethyl 3-[({(E)-benzylideneamino}oxy)methyl]-6-methyl-2-oxo-4-
phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate (3g): White powder,
1
m.p. 181–183 °C; H NMR: δ = 8.76 (br s, 1H, NH), 8.04 (s, 1H,
=CH), 7.50–7.22 (m, 10H, ArH), 5.84 (d, J = 11.2 Hz, 1H, NCH2),

32 JOURNAL OF CHEMICAL RESEARCH 2013
129.1, 128.9, 128.5, 128.2, 128.1, 128.0, 127.9, 127.4, 102.4, 77.4,
60.0, 58.7, 18.6, 14.2; MS: m/z = 469 (M+);Anal. Calcd for C28H27N3O4:
C, 71.62; H, 5.80; N, 8.95. Found: C, 71.50; H, 5.75; N, 8.88%.
Ethyl 3-[({[diphenylmethylene]amino}oxy)methyl]-6-methyl-2-oxo-
4-(p-tolyl)-1,2,3,4-tetrahydropyrimidine-5-carboxylate (3k): White
1
powder, m.p. 200–202 °C; H NMR: δ = 8.20 (br s, 1H, NH), 7.50–
7.06 (m, 14H, ArH), 5.88 (d, J = 11.2 Hz, 1H, NCH2), 5.74 (s, 1H,
CH), 4.87 (d, J = 11.2 Hz, 1H, NCH2), 4.12–4.07 (m, 2H, CH2), 2.31
(s, 3H, CH3), 2.30 (s, 3H, CH3), 1.21 (t, J = 6.8 Hz, 3H, CH3); 13C
NMR: δ = 165.5, 158.3, 152.9, 145.9, 138.9, 137.6, 136.1, 132.8,
129.5, 129.2, 129.1, 128.9, 128.2, 128.0, 127.9, 127.3, 102.6, 70.0,
59.9, 58.4, 21.1, 18.5, 14.2; MS: m/z = 483 (M+); Anal. Calcd for
C29H29N3O4: C, 72.03; H, 6.05; N, 8.69. Found: C, 72.15; H, 6.10; N,
8.79%.
Ethyl 3-[({[diphenylmethylene]amino}oxy)methyl]-6-methyl-2-oxo-
4-(4-methoxyphenyl)-1,2,3,4-tetrahydropyrimidine-5-carboxylate
1
(3l): White powder, m.p. 183–185 °C; H NMR: δ = 8.32 (br s, 1H,
NH), 7.5 (d, J = 8.0 Hz, 2H, ArH), 7.43–7.26 (m, 10H, ArH), 6.79 (d,
J = 8.0 Hz, 2H, ArH), 6.09 (s, 1H, CH), 5.87 (d, J = 10.8 Hz, 1H,
NCH2), 5.71 (s, 1H, CH), 4.88 (d, J = 11.2 Hz, 1H, NCH2), 4.14–4.08
(m, 2H, CH2), 3.76 (s, 3H, CH3), 2.31 (s, 3H, CH3), 1.20 (t, J = 7.2 Hz,
3H, CH3); 13C NMR: δ = 165.5, 159.2, 158.3, 153.0, 145.9, 136.1,
134.1, 132.8, 129.5, 129.1, 128.9, 128.6, 128.2, 128.0 and 128.0,
113.8, 102.6, 77.2, 59.9, 58.1, 55.2, 18.5, 14.2; MS: m/z = 499 (M+);
Anal. Calcd for C29H29N3O5: C, 69.72; H, 5.85; N, 8.41. Found: C,
69.89; H, 5.79; N, 8.32%.
Ethyl 3-[({[diphenylmethylene]amino}oxy)methyl]-6-methyl-2-oxo-
4-(2-chlorophenyl)-1,2,3,4-tetrahydropyrimidine-5-carboxylate(3m):
White powder, m.p. 174–176 °C; 1H NMR: δ = 8.14 (br s, 1H, NH),
7.47–7.20 (m, 14H, ArH), 5.82 (d, J = 11.2 Hz, 1H, NCH2), 5.73 (s,
1H, CH), 4.95 (d, J = 11.2 Hz, 1H, NCH2), 4.17–4.05 (m, 2H, CH2),
2.32 (s, 3H, CH3), 1.21 (t, J = 7.2 Hz, 3H, CH3); 13C NMR: δ = 165.3,
158.4, 152.9, 146.5, 140.4, 135.9, 133.6, 132.7, 129.6, 129.1, 128.9,
128.7, 128.6, 128.2, 128.0, 127.9, 102.1, 77.6, 77.2, 60.0, 58.2, 18.5,
14.2; MS: m/z = 503 (M+); Anal. Calcd for C28H26ClN3O4: C, 66.73; H,
5.20; N, 8.34. Found: C, 66.59; H, 5.12; N, 8.41%.
(E)-ethyl 3-[({[diphenylmethylene]amino}oxy)methyl]-6-methyl-2-
oxo-4-(2-methoxyphenyl)-1,2,3,4-tetrahydropyrimidine-5-carboxylate
(3n): White powder, m.p. 236–238 °C; 1H NMR: δ = 7.73 (br s, 1H,
NH), 7.53–7.20 (m, 12H, ArH), 6.88–6.81 (m, 2H, ArH), 6.09 (s, 1H,
CH), 5.89 (d, J = 10.8 Hz, 1H, NCH2), 4.89 (d, J = 10.8 Hz, 1H,
NCH2), 4.05 (q, J = 7.2 Hz, 2H, CH2), 3.73 (s, 3H, CH3), 2.32 (s, 3H,
CH3), 1.15 (t, J = 7.2 Hz, 3H, CH3); 13C NMR: δ = 165.7, 157.9,
157.3, 152.6, 146.1, 136.2, 132.9, 130.1, 129.4, 129.3, 129.2, 129.1,
128.8, 128.1, 128.0, 127.9, 120.4, 110.8, 100.6, 77.2, 59.7, 55.3, 54.4,
18.4, 14.1; MS: m/z = 499 (M+);Anal. Calcd for C29H29N3O5: C, 69.72;
H, 5.85; N, 8.41. Found: C, 69.79; H, 5.77; N, 8.50%.
3-({[(Diphenylmethylene)amino]oxy}methyl)-7,7-dimethyl-4-
phenyl-3,4,7,8-tetrahydroquinazoline-2,5(1H,6H)-dione (5a): White
powder; m.p. 199–201 °C. 1H NMR: δ = 9.15 (br s, 1H, NH), 7.96 (s,
1H, NCH), 7.96–7.21 (m, 9H, ArH), 5.84 (d, J = 10.4 Hz, 1H, NCH2),
5.80 (s, 1H, CH), 4.98 (d, J = 10.4 Hz, 1H, NCH2), 2.44–2.12 (m, 4H,
CH2), 1.07 (s, 3H, CH3), 0.93 (s, 3H, CH3); 13C NMR: δ = 193.6,
153.3, 149.5, 149.1, 141.4, 136.1, 130.1, 129.0, 128.6, 128.4, 127.9,
127.1, 110.2, 78.0, 57.3, 50.3, 39.9, 32.8, 29.3, 27.1. MS: m/z = 479
(M+); Anal. Calcd for C30H29N3O3: C, 75.13; H, 6.10; N, 8.76. Found:
C, 75.05; H, 6.19; N, 8.63%.
Fig. 1 The single crystal X-ray crystallography of product 3g.
5.81 (s, 1H, CH), 4.95 (d, J = 11.2 Hz, 1H, NCH2), 4.12–4.04 (m, 2H,
CH2), 2.36 (s, 3H, CH3), 1.20 (m, J = 7.2 Hz, 3H, CH3); 13C NMR:
δ = 165.5, 153.3, 150.1, 146.2, 142.1, 131.8, 130.1, 128.6, 128.5,
127.9, 127.4, 127.2, 102.3, 77.5, 59.9, 59.4, 18.5, 14.1; MS: m/z = 393
(M+); Anal. Calcd for C22H23N3O4: C, 67.16; H, 5.89; N, 10.68. Found:
C, 67.21; H, 5.85; N, 10.65%.
Ethyl 3-[({[(E)-4-nitrobenzylidene]amino}oxy)methyl]-6-methyl-
2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate (3h): White
powder, m.p. 168–169 °C; 1H NMR: δ = 8.70 (br s, 1H, NH), 8.23 (d,
J = 8.0 Hz, 2H, ArH), 8.03 (s, 1H, =CH), 7.72 (d, J = 8.0 Hz, 2H,
ArH), 7.41–7.22 (m, 5H, ArH), 5.82 (d, J = 12.4 Hz, 1H, NCH2), 5.73
(s, 1H, CH), 5.10 (d, J = 11.6 Hz, 1H, NCH2), 4.15–4.06 (m, 2H,
CH2), 2.36 (s, 3H, CH3), 1.22 (t, J = 7.2 Hz, 3H, CH3); 13C NMR:
δ = 165.4, 153.2, 153.1, 148.4, 147.9, 145.9, 145.8, 141.9, 137.8,
128.5, 128.0, 127.8, 127.3, 123.9, 102.5, 78.3, 60.1, 59.6, 18.5, 14.2;
MS: m/z = 438 (M+); Anal. Calcd for C22H22N4O6: C, 60.27; H, 5.06;
N, 12.78. Found: C, 60.42; H, 5.11; N, 12.71%.
Ethyl 3-[({[(E)-2-methoxybenzylidene]amino}oxy)methyl]-6-methyl-
3-({[(Diphenylmethylene)amino]oxy}methyl)-7,7-dimethyl-4-(p-
2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate (3i): White
tolyl)-3,4,7,8-tetrahydroquinazoline-2,5(1H,6H)-dione (5b): White
1
1
powder, m.p. 153–155 °C; H NMR: δ = 8.48 (s, 1H, =CH), 8.40
powder; m.p. 205–207°C. H NMR: δ = 8.92 (br s, 1H, NH), 7.47–
(br s, 1H, NH), 7.82 (dd, J = 1.6 Hz, 3.6 Hz, 1H, ArH), 7.43–7.24 (m,
6H, ArH), 6.97–6.89 (m, 2H, ArH), 5.85 (d, J = 11.2 Hz, 1H, NCH2),
5.82 (s, 1H, CH), 4.88 (d, J = 11.2 Hz, 1H, NCH2), 4.11–4.03 (m, 2H,
CH2), 3.84 (s, 3H, OCH3), 2.35 (s, 3H, CH3), 1.20 (m, J = 7.2 Hz, 3H,
CH3); 13C NMR: δ = 165.5, 157.7, 153.1, 146.2, 146.1, 142.1, 131.4,
128.5, 127.9, 127.5, 126.4, 120.7, 120.4, 111.1, 102.4, 77.3, 59.9,
59.2, 55.5, 18.5, 14.1; MS: m/z = 423 (M+);Anal. Calcd for C23H25N3O5:
C, 65.24; H, 5.95; N, 9.92. Found: C, 65.38; H, 6.01; N, 10.2%.
Ethyl 3-[({[diphenylmethylene]amino}oxy)methyl]-6-methyl-2-oxo-
4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate (3j): White
7.25 (m, 12H, ArH), 7.07 (d, J = 8.0 Hz, 2H, ArH), 5.92 (d, J =
10.8 Hz, 1H, NCH2), 5.76 (s, 1H, CH), 4.88 (d, J = 10.8 Hz, 1H,
NCH2), 2.40–2.05 (m, 4H, CH2), 1.05 (s, 3H, CH3), 0.93 (s, 3H, CH3);
13C NMR: δ = 193.6, 158.4, 153.2, 149.5, 138.3, 137.5, 136.0, 132.8,
129.6, 129.2, 129.1, 128.9, 128.2, 128.1, 128.0, 127.1, 77.5, 56.2,
50.3, 39.8, 32.8, 29.3, 27.2, 21.1. MS: m/z = 493 (M+); Anal. Calcd for
C31H31N3O3: C, 75.43; H, 6.33; N, 8.51. Found: C, 75.32; H, 6.27; N,
8.64%.
3-({[(Diphenylmethylene)amino]oxy}methyl)-7,7-dimethyl-4-(4-
chlorophenyl)-3,4,7,8-tetrahydroquinazoline-2,5(1H,6H)-dione (5c):
White powder; m.p. 215–217 °C. 1H NMR: δ = 8.60 (br s, 1H, NH),
7.45–7.19 (m, 14H, ArH), 5.83 (d, J = 11.2 Hz, 1H, NCH2), 5.77 (s,
1H, CH), 4.98 (s, J = 11.2 Hz, 1H, NCH2), 2.41–2.16 (m, 4H, CH2),
1.06 (s, 3H, CH3), 0.91 (s, 3H, CH3); 13C NMR: δ = 193.5, 158.5,
152.9, 149.6, 139.9, 135.9, 133.5, 132.7, 129.7, 129.1, 129.0, 128.7,
1
powder, m.p. 232–234 °C; H NMR: δ = 8.60 (br s, 1H, NH), 7.51–
7.22 (m, 14H, ArH), 5.89 (d, J = 10.4 Hz, 1H, NCH2), 5.78 (s, 1H,
CH), 4.89 (d, J = 10.4 Hz, 1H, NCH2), 4.14–4.06 (m, 2H, CH2), 2.32
(s, 3H, CH3), 2.30 (s, 3H, CH3), 1.20 (t, J = 7.2 Hz, 3H, CH3); 13C
NMR: δ = 165.5, 158.4, 148.5, 146.0, 141.8, 136.0, 132.8, 129.6,

JOURNAL OF CHEMICAL RESEARCH 2013 33
128.4, 128.3, 128.1, 128.0, 110.0, 77.9, 56.1, 50.3, 39.9, 32.8, 29.3,
27.1. MS: m/z = 513 (M+); Anal. Calcd for C30H28ClN3O3: C, 70.10; H,
5.49; N, 8.17. Found: C, 70.21; H, 5.53; N, 8.08%.
Crystallographic data for the structure analysis have been
deposited at the Cambridge Crystallographic Data Centre as
supplementary publication, CCDC No. 822849 for 3g. Copies
of these information can be obtained, free of charge on appli-
cation to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK
(fax: (44) 01223 336033 or E-mail: deposit@ccdc.cam.ac.uk).
4-Chlorobenzaldehyde-O-[((E)-7,7-dimethyl-2,5-dioxo-4-phenyl-
1,2,5,6,7,8-hexahydroquinazolin-3(4H)-yl)methyl)oxime (5d): White
powder; m.p. 199–201 °C. 1H NMR: δ = 9.15 (br s, 1H, NH), 7.96 (s,
1H, =CH), 7.96–7.21 (m, 9H, ArH), 5.84 (d, J = 11.2 Hz, 1H, NCH2),
5.80 (s, 1H, CH), 4.98 (d, J = 11.2 Hz, 1H, NCH2), 2.44–2.12 (m, 4H,
CH2), 1.07 (s, 3H, CH3), 0.93 (s, 3H, CH3); 13C NMR: δ = 193.6,
153.3, 149.5, 149.1, 141.4, 136.1, 130.1, 129.0, 128.6, 128.4, 127.9,
127.1, 110.2, 78.0, 57.3, 50.3, 39.9, 32.8, 29.3, 27.1. MS: m/z = 437
(M+); Anal. Calcd for C24H24ClN3O3: C, 65.82; H, 5.52; N, 9.60.
Found: C, 65.69; H, 5.46; N, 9.69%.
4-Chlorobenzaldehyde-O-{([(E)-4-(4-chlorophenyl)-7,7-dimethyl-
2,5-dioxo-1,2,5,6,7,8-hexahydroquinazolin-3(4H)-yl]methyl}oxime
(5e): White powder; m.p. 212–214 °C. 1H NMR: δ = 8.69 (br s, 1H,
NH), 7.91 (s, 1H, =CH), 7.46 (d, J = 4 Hz, 2H, ArH), 7.45–7.19 (m,
6H, ArH), 5.83 (d, J = 10.4 Hz, 1H, NCH2), 5.77 (s, 1H, CH), 4.98 (d,
J = 10.4 Hz, 1H, NCH2), 2.41–2.16 (m, 4H, CH2), 1.07 (s, 3H, CH3),
0.91 (s, 3H, CH3); 13C NMR: δ = 193.5, 158.5, 152.9, 149.6, 139.9,
135.9, 133.5, 132.7, 129.7, 129.1, 129.0, 128.7, 128.4, 128.3, 128.1,
128.0, 110.0, 77.9, 56.1, 50.3, 39.9, 32.8, 29.3, 27.1. MS: m/z = 471
(M+); Anal. Calcd for C24H23Cl2N3O3: C, 61.02; H, 4.91; N, 8.90.
Found: C, 60.91; H, 4.85; N, 8.83%.
4-Chlorobenzaldehyde-O-{[(E)-7,7-dimethyl-2,5-dioxo-4-(p-tolyl)-
1,2,5,6,7,8-hexahydroquinazolin-3(4H)-yl]methyl}oxime (5f): White
powder; m.p. 220–222 °C. 1H NMR: δ = 8.65 (br s, 1H, NH), 7.97 (s,
1H, =CH), 7.49 (d, J = 12 Hz, 2H, ArH), 7.36–7.26 (m, 4H, ArH), 7.10
(d, J = 8 Hz, 2H, ArH), 5.83 (d, J = 11.2 Hz, 1H, NCH2), 5.74 (s, 1H,
CH), 4.95 (d, J = 11.2 Hz, 1H, NCH2), 2.42–2.11 (m, 7H, CH2 and
CH3), 1.07 (s, 3H, CH3), 0.94 (s, 3H, CH3); 13C NMR: δ = 193.6,
152.2, 149.3, 149.1, 138.4, 137.6, 136.1, 130.2, 129.3, 129.0, 128.4,
127.1, 110.3, 77.86, 57.0, 50.3, 39.9, 32.8, 29.3, 27.2, 21.1. MS: m/z
= 451 (M+); Anal. Calcd for C25H26ClN3O3: C, 66.44; H, 5.80; N, 9.30.
Found: C, 66.53; H, 5.86; N, 9.21%.
We are thankful for the financial support from the National
Nature Science Foundation of China (No. 20902073 and
21062017), Ministry of Education of returned overseas students
to start research and fund projects, and Scientific and Techno-
logical Innovation Engineering programme of Northwest
Normal University (nwnu-kjcxgc-03-64, nwnu-lkqn-10-15).
Received 17 October 2012; accepted 7 November 2012
Paper 1201578 doi: 10.3184/174751912X13546462577913
Published online: 15 January 2013
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