Iodine-catalyzed three-component reaction of quinazoline-2,5-diones with aldehydes and styrenes for the synthesis of allylamine derivatives

Article abstract of DOI:10.1016/j.tet.2014.10.006

Iodine-catalyzed three component reaction of quinazoline-2,5-diones, aldehydes, and styrenes provides allylamine derivatives was described. Both paraformaldehyde and ethyl glyoxalate can be applied in this reaction with simple styrenes with high regiosele

Full text of DOI:10.1016/j.tet.2014.10.006

Tetrahedron xxx (2014) 1e6
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Tetrahedron
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Iodine-catalyzed three-component reaction of quinazoline-2,5-
diones with aldehydes and styrenes for the synthesis of allylamine
derivatives
,
b
,
a
,
,
,b
Zhang Zhang a , Yu-Shan Zhang b, Zheng-Jun Quan a b, Yu-Xia Da a
,
*
,b,
Xi-Cun Wang a
*
a Key Laboratory of Eco-Environment-Related Polymer Materials, Ministry of Education, China, Gansu 730070, PR China
b Gansu Key Laboratory of Polymer Materials, College of Chemistry and Chemical Engineering, Northwest Normal University, Anning East Road 967#,
Lanzhou, Gansu 730070, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 9 July 2014
Received in revised form 27 September 2014
Accepted 4 October 2014
Available online xxx
Iodine-catalyzed three component reaction of quinazoline-2,5-diones, aldehydes, and styrenes provides
allylamine derivatives was described. Both paraformaldehyde and ethyl glyoxalate can be applied in this
reaction with simple styrenes with high regioselectivity.
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Iodine
Allyamines
Three-component reaction
CeC formation
CeN formation
1. Introduction
vinylation reaction that enables the catalytic functionalization of
alkenes with aminals.15 As compared to analogous reactions, the
Allylamines represent an important structural motif frequently
found in a wide variety of natural products, pharmaceuticals,1
bioactive and antimycotic activity products.2,3 They are one of the
most valuable chemical intermediates for a wide range of organic
compounds.4 Among the different types of allylic substitution re-
actions, the synthesis of allylamines is of special interest. The
transition-metal-catalyzed allylic aminations of allylalcohols5 and
their derivatives6e9 have become a powerful tool for the con-
struction of allylamines. Alternatively, the Lewis acid-promoted
reductive amination of cinnamaldehyde giving allylamines has
also been reported.10e12 The sequential hydrozirconation trans-
metalation imine addition of alkynes establishes an efficient new
route for the preparation of synthetically useful allylic amine
building blocks.13 However, such a reaction is a synthetic challenge
due to the intrinsic poor nucleophilicity of simple alkenes. Recently,
some groups have reported the palladium-catalyzed Heck arylation
of allylamine derivatives employing aryl iodide or arenediazonium
salts.14 Huang et al. have developed a novel palladium-catalyzed
selective N-allylation of electron-deficient N-heterocycles and
amides with olefins has limitedly been investigated. In this respect,
notable progress was made respectively by Beller and Shibasaki
groups via the allylic substitution of allylic alcohols with amides to
afford allylic amines (Scheme 1).16 More recently, Beller et al. de-
scribed a general and regioselective 1,4-addition of electron de-
ficient amides into 1,3-dienes catalyzed by [{Pd(p-cinnamyl)Cl}2] in
* Corresponding authors. Tel./fax: þ86 931 7972626; e-mail addresses: zhangz@
Scheme 1. Synthesis of allylamine derivatives.
nwnu.edu.cn (Z. Zhang), wangxicun@nwnu.edu.cn (X.-C. Wang).
http://dx.doi.org/10.1016/j.tet.2014.10.006
0040-4020/Ó 2014 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Zhang, Z.; et al., Tetrahedron (2014), http://dx.doi.org/10.1016/j.tet.2014.10.006

2
Z. Zhang et al. / Tetrahedron xxx (2014) 1e6
the presence of 1,3-bis(diphenylphosphino)propane to deliver
allylamines.17
increased to 40 mol %, a considerably higher yield was observed
(entry 14). Reducing the I2 loading to 30 mol % leaded to a low yield
of 57% (entry 15), and increasing the I2 loading to 50 mol %, the yield
have no obvious change (entry 16). It is worth mentioning that the
reaction proceeds with highly selective, delivering exclusively the
linear E isomer of the allylic amine product 4a in all cases.
We haverecently reportedthe synthesis of allylamine derivatives
via I2-catalyzed one-pot multi-component reaction of 3,4-
dihydropyrimidinones (or amides), paraformaldehyde, and sty-
renes.18 This direct method from unactivated styrenes does not need
any additives and proceeds with high regioselectivity, which forms
water as the sole by-product.
Herein, we became interested in the formation of more chal-
lenging allylic amines. Glycinate are fascinating precursors for the
synthesis of multifunctionalized heterocycles.19 Therefore, we
present the iodine-catalyzed direct N-allylation of quinazoline-2,5-
dione with aldehydes (including ethyl glyoxalate, and para-
formaldehyde) and non-activated alkenes (Scheme 1).
With the optimized conditions in hand, a wide variety of
substituted quinazoline-2,5-diones (1), 2a, and styrenes (3) were
submitted to investigate its substrate scope and generality
(Scheme 2). A series of allylamine derivatives 4aeh were obtained
with moderate yield and high regioselectivity. No significant dif-
ference in yield was observed with electron-donating or electron-
withdrawing substituents on the phenyl group of substrates 1.
However, steric effects has a negative effect on the reaction. When
introducing steric hindrance ortho to the aromatic ring, trace de-
sired product 4f with a mixture was detected. The reaction of 4-NO2
or 3-NO2 substituted quinazoline-2,5-diones 1geh with 2a and 3a
resulted in the formation of 4geh in 39e42% yield, respectively,
whereas a minor amount of by-products as 5a and 5b were also
isolated. Notably, in all reactions in which we observed lower yields
of 4, starting materials were recovered. In some experiments, we
also observed the formation of trace amount of by-products.
2. Results and discussion
Initially, the model reaction of octahydroquinazoline-2,5-dione
(1a), ethyl glyoxalate (2a, 50 wt % solution in toluene), and sty-
rene (3a) was used to optimize the reaction conditions (Table 1).
Only trace amount of product 4a was obtained when sulfuric
acid-modified polyethylene glycol (PEG-OSO3H) or trimethylsilyl
chloride (TMSCl) was utilized as catalyst (entries 1 and 2). The ap-
plication of trifluoroacetic acid (TFA) resulted in no conversion
(entry 3). When trifluoromethanesulfonic acid (TfOH), the desired
product 4a was isolated in 17% yield (entry 4). Also, some typical
Lewis acids such as ZnCl2, FeCl3 were tested in this reaction, and
only FeCl3 promoted the reaction in 32% yield of 4a (entries 5 and 6).
Notably, good result was obtained using 0.2 equiv of molecular io-
dine as the catalyst in 1,4-dioxane at 110 ꢀC for 24 h, and the desired
product 4a was isolated in 60% yield (entry 7). Good reaction yield
and activity were also observed using I2 or FeCl3 combing with TfOH
(entries 8 and 9), which provided the desired product 4a 48% and
58% yield, respectively. Then, the effects of solvent and temperature
in this reaction were also investigated. Among the solvents exam-
ined, dioxane, which was used in an earlier study gave good result,
in contrast to the unsatisfactory result obtained with DMF and
DMSO as solvent (entries 12 and 13). Other nonpolar solvents, such
as xylene and toluene (entries 10 and 11) only gave a low yield even
at higher temperature. When the catalyst loading of I2 was
Table 1
Optimization of the three-component reaction conditionsa
Scheme 2. Three-component reaction of quinazoline-2,5-diones, ethyl glyoxylate, and
styrenes.
Next, we tried to extend the scope of the methodology to the use
of methylglyoxal instead of ethyl glyoxylate in the three-
component reaction (Scheme 3). To our surprise, the reaction
only provide product (6a) with recovered 1a. Similarly, 4-Me, 4-Cl
or 3-NO2 substituted quinazoline-2,5-diones reacted well to de-
liver the corresponding products 6ced.20 The mechanism studies
on the deacylation are underway.
Entry
Catalysis (mol/%)
Solvent
Temp (ꢀC)
Time (h)
Yield (%)b
1
2
3
4
5
6
7
8
PEG-OSO3H (20)
TMSCl (20)
TFA (20)
TfOH (20)
ZnCl2 (20)
FeCl3 (20)
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Xylene
Toluene
DMF
DMSO
Dioxane
Dioxane
Dioxane
110
110
110
110
110
110
110
110
110
120
110
150
150
110
110
110
24
24
24
24
24
24
24
24
24
24
24
24
24
36
36
36
Trace
Trace
ndc
17
Trace
32
60
48
58
35
I
2 (20)
FeCl3 (20)/TfOH (2)
9
I
I
I
I
2 (20)/TfOH (2)
2 (20)
2 (20)
10
11
12
13
14
15
16
42
2 (20)
ndc
Trace
64
I2 (20)
I
I
I
2 (40)
2 (30)
2 (50)
57
65
a
Reaction conditions: quinazoline-2,5-dione (1a, 0.5 mmol), ethyl glyoxylate (2a,
1.5 mmol), styrene (3a, 0.75 mmol), catalyst, solvent (3 mL), 110 ꢀC.
b
Isolated yield of 4a after purification by flash chromatography.
Not detected in the reaction mixture.
c
Scheme 3. Reaction between quinazoline-2,5-dione, methylglyoxal, and styrene.
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Z. Zhang et al. / Tetrahedron xxx (2014) 1e6
3
To further expand the scope of substrates, we examined para-
formaldehyde (2c) as the aldehyde partner in the three-component
reaction (Table 2). When decreasing the catalyst of I2 loading to
20 mol % in dioxane at 110 ꢀC within 12 h, the three-component
reaction proceeded to deliver the allylamine derivatives 6aep in
good yields. We found that quinazoline-2,5-diones bearing
electron-withdrawing groups (4-NO2, 4-Cl, 4-F, and 4-Br) provided
higher yields than those containing electron-donating groups (4-
Me) on the phenyl ring. Styrenes bearing electron-withdrawing
groups provided higher yields than those containing electron-
donating groups (entries 1-15). Steric effects due to the in-
stallation of ortho-substituents (2-Cl) were negligible (entry 16).
When the styrene was replaced with 2-vinylnaphthalene, the re-
action also resulted in the formation of allylamine derivatives
6qe6r in 60e64% yield (entries 17 and 18). However, some limi-
tations were noted in case of alkyl olefin (1-octene) or hetero-
aromatic olefin (4-vinyl pyridine or 2-vinyl pyridine); they were
unreactive in this reaction.
1,2,3,4,5,6,7, 8-octahydroquinazoline-2,5-dione. After the reaction
was completed (monitored by TLC), pure product was obtained
from the crude product by filtration and recrystallization to
afford.21
4.2. General procedure for three-component reactions
The mixture of quinazoline-2,5-dione (1a, 0.5 mmol, 135.0 mg),
ethyl glyoxylate (2a, 3.0 equiv, 1.5 mmol, 306 mg), styrene (3a,
1.5 equiv, 0.75 mmol, 78.0 mg), I2 (0.2 equiv, 0.1 mmol, 25.4 mg) and
1,4-dioxane (3 mL) was stirred at 110 ꢀC. After the starting material
1a had been consumed (monitored by TLC), 15 mL water were
added and the mixture was extracted with EtOAc (3ꢁ15 mL). The
extract was washed with 10% Na2S2O3 solution (w/w), dried over
anhydrous Na2SO4 and evaporation. The product was purified by
flash chromatography on silica gel using ethyl acetate/petroleum
ether as eluent to provide the corresponding allylamine.
4.2.1. (E)-Ethyl-2-(7,7-dimethyl-2,5-dioxo-4-phenyl-1,2,5,6,7,8-
hexahydroquinazolin-3(4H)-yl)-4-phenyl-3-butenoate (4a). White
solid, mp 95e96 ꢀC; yield: 64% (ethyl acetate/petroleum ether: 1/
Table 2
Three-component reaction of quinazoline-2,5-diones, paraformaldehyde, and
styrenesa
2.5); 1H NMR (400 MHz, CDCl3)
d
¼8.75 (br, 1H, NH), 7.40 (d,
J¼8.0 Hz, 2H, ArH), 7.30e7.22 (m, 8H, ArH), 6.48 (d, J¼16.0 Hz, 1H,
CH), 6.24e6.18 (q, 1H, CH), 5.56 (s, 1H, CH), 4.80 (d, J¼8.0 Hz, 1H,
CH), 4.16e4.11 (q, 2H, CH2), 2.41e2.11 (m, 4H, 2CH2), 2.20 (t,
J¼8.0 Hz,3H, CH3), 1.08 (s, 3H, CH3), 0.90 (s, 3H, CH3); 13C NMR
(100 MHz, CDCl3)
d
¼193.4, 169.2, 153.1, 149.5, 141.5, 135.8, 135.7,
Entry
R1
R2
Product
Yieldb (%)
128.5, 128.4, 128.2, 127.8, 127.4, 126.7, 121.7, 110.1, 61.7, 61.3, 58.0,
50.3, 39.8, 32.8, 29.2, 27.1, 14.1; HRMS [MþH]þ calcd for C28H30N2O4
459.2278, found 459.2287.
1
2
3
4
5
6
7
8
H
C6H5
C6H5
C6H5
C6H5
4-ClC6H5
4-BrC6H5
4-CH3C6H5
4-CH3C6H5
4-ClC6H5
C6H5
C6H5
C6H5
4-CH3C6H5
4-ClC6H5
4-BrC6H5
C6H5
6a
6b
6c
6d
6e
6f
6g
6h
6i
6j
6k
6l
6m
6n
6o
6p
6q
6r
70
52
61
62
53
56
41
39
51
64
63
60
42
53
61
65
64
60
4-CH3
4-Cl
3-NO2
H
H
H
4-CH3
4-CH3
4-F
4-Br
4-NO2
4-NO2
4-NO2
3-NO2
2-Cl
H
4.2.2. (E)-Ethyl-2-(7,7-dimethyl-2,5-dioxo-4-(p-tolyl)-1,2,5,6,7,8-
hexahydroquinazolin-3(4H)-yl)-4-phenyl-3-butenoate (4b). White
solid, mp 196e197 ꢀC; yield: 55% (ethyl acetate/petroleum ether: 1/
3); 1H NMR (400 MHz, CDCl3)
d
¼9.36 (br, 1H, NH), 7.24e7.17 (m, 7H,
9
ArH), 7.02 (d, J¼8.0 Hz, 2H, ArH), 6.42 (d, J¼16.0 Hz, 1H, CH),
6.20e6.13 (q, 1H, CH), 5.45 (s, 1H, CH), 4.70 (d, J¼8.0 Hz, 1H, CH),
4.10e4.04 (q, 2H, CH2), 2.34e2.03 (m, 7H, CH3, 2CH2), 1.14 (t,
J¼8.0 Hz, 3H, CH3), 1.01 (s, 3H, CH3), 0.85 (s, 3H, CH3); 13C NMR
10
11
12
13
14
15
16
17
18
(100 MHz, CDCl3)
d
¼193.4, 169.2, 153.1, 149.3, 138.5, 137.4, 135.9,
135.4, 129.0, 128.4, 128.2, 127.4, 126.7, 121.8, 110.1, 61.6, 61.3, 57.9,
50.3, 39.7, 32.7, 29.2, 27.2, 21.1, 14.1; HRMS [MþH]þ calcd for
C
C
12H10
12H10
4-Cl
C29H32N2O4 473.2435, found 473.2444.
a
Reaction conditions: quinazoline-2,5-dione (0.5 mmol), paraformaldehyde
(3.0 mmol), styrene (0.75 mmol), I2 (20% mmol), dioxane (3 mL), 110 ꢀC, 12 h.
4.2.3. (E)-Ethyl-2-(4-(4-chlorophenyl)-7,7-dimethyl-2,5-dioxo-
1,2,5,6,7,8-hexahydroquinazolin-3(4H)-yl)-4-phenyl-3-butenoate
(4c). White solid, mp 197e199 ꢀC; yield: 54% (ethyl acetate/pe-
b
Isolated yield of 4a after purification by flash chromatography.
3. Conclusions
troleum ether: 1/3); 1H NMR (400 MHz, CDCl3)
d
¼8.78 (br, 1H, NH),
7.36e7.22 (m, 9H, ArH), 6.48 (d, J¼16.0 Hz, 1H, CH), 6.22e6.15 (q,
1H, CH), 5.55 (s, 1H, CH), 4.78 (d, J¼8.0 Hz, 1H, CH), 4.18e4.13 (q, 1H,
CH2), 2.41e2.11 (m, 4H, 2CH2), 1.22 (t, J¼8.0 Hz,1H, CH3), 1.09 (s, 3H,
In summary, we have documented the I2-catalyzed three-
component reaction of octahydroquinazoline-2,5-diones with
ethyl glyoxylate or paraformaldehyde and styrenes. The reaction
proceeds with high regioselectivity to deliver allylic amine de-
rivatives and shows good tolerance towards wide substrate scope,
as demonstrated by the application of paraformaldehyde, and ethyl
glyoxylate.
CH3), 0.90 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3)
d¼193.3, 169.0,
153.0, 149.6, 140.1, 135.9, 135.7, 133.6, 128.8, 128.6, 128.4, 126.7,
121.4, 109.7, 61.6, 61.4, 57.5, 50.3, 39.8, 32.8, 29.3, 27.1, 14.1; HRMS
[MþH]þ calcd for C28H29ClN2O4 493.1889, found 493.1898.
4.2.4. (E)-Ethyl-4-(4-chlorophenyl)-2-(4-(4-chlorophenyl)-7,7-
dimethyl-2,5-dioxo-1,2,5,6,7,8-hexahydroquinazolin-3(4H)-yl)-3-
butenoate (4d). White solid, mp 203e204 ꢀC; yield: 53% (ethyl
4. Experimental section
4.1. General procedure
acetate/petroleum ether: 1/3); 1H NMR (400 MHz, CDCl3)
d¼9.17
(br, 1H, NH), 7.27 (d, J¼8.0 Hz, 2H, ArH), 7.19 (t, J¼8.0 Hz, 4H, ArH),
7.07 (d, J¼8.0 Hz, 1H, ArH), 6.36 (d, J¼16.0 Hz, 1H, CH), 6.11e6.05 (q,
1H, CH), 5.46 (s, 1H, CH), 4.74 (d, 8.0 Hz, 1H, CH), 4.11e4.06 (q, 2H,
CH2), 2.34e2.04 (m, 4H, 2CH2), 1.15 (t, J¼8.0 Hz, 1H, CH3), 1.02 (s,
4.1.1. Preparation of 4-phenyl-7,7-dimethyl-1,2,3,4,5,6,7,8-octahy-
droquinazoline-2,5-dione. The reaction of benzaldehyde (10 mmol)
with urea (12 mmol), and 5,5-dimethylcyclohexane-1,3-dione
(10 mmol) in the presence of H2SO4 (10% mmol) as catalyst in
ethanol (15 mL) at 80 ꢀC for 8 h produced 4-phenyl-7,7-dimethyl-
3H, CH3), 0.83 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3)
168.9, 152.9, 149.5, 140.1, 134.5, 134.1, 133.7, 128.8, 128.7, 128.6,
d
¼193.3,
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4
Z. Zhang et al. / Tetrahedron xxx (2014) 1e6
127.9, 122.2, 109.7, 61.6, 61.4, 57.5, 50.2, 39.8, 32.8, 29.2, 27.1, 14.1;
14.1; HRMS [MþH]þ calcd for C20H23N3O6 402.1660, found
HRMS [MþH]þ calcd for C28H28Cl2N2O4 527.1499, found 527.1510.
402.1666.
4.2.5. (E)-Ethyl-2-(4-(4-bromophenyl)-7,7-dimethyl-2,5-dioxo-
1,2,5,6,7,8,-hexahydroquinazolin-3(4H)-yl)-4-(p-tolyl)-3-buteno-ate
(4e). White solid, mp 213e214 ꢀC; yield: 47% (ethyl acetate/pe-
4.2.10. (E)-3-Cinnamyl-7,7-dimethyl-4-phenyl-3,4,7,8-tetrahydr-
oquinazoline-2,5(1H,6H)-dione (6a). White solid, mp 176e178 ꢀC;
yield: 70% (ethyl acetate/petroleum ether: 1/3); 1H NMR (400 MHz,
troleum ether: 1/3); 1H NMR (400 MHz, CDCl3)
d¼9.03 (br, 1H, NH),
CDCl3)
d
¼9.32 (br, 1H, NH), 7.41 (t, J¼4.0 Hz, 2H, ArH), 7.34e7.23 (m,
7.39 (d, J¼8.0 Hz, 2H, ArH), 7.27 (d, J¼8.0 Hz, 2H, ArH), 7.11 (s, 5H,
ArH), 6.43 (d, J¼16.0 Hz, 1H, CH), 6.13e6.07 (q, 1H, CH), 5.54 (s, 1H,
CH), 4.79 (d, J¼8.0 Hz, 1H), 4.18e4.12 (q, 2H, CH2), 2.41e2.10 (m, 7H,
CH3, 2CH2), 1.22 (t, J¼7.0 Hz, 3H, CH3), 1.08 (s, 3H, CH3), 0.89 (s, 3H,
8H, ArH), 6.48 (d, J¼16.0 Hz, 1H, CH), 6.11e6.05 (m, 1H, CH), 5.46 (s,
1H, CH), 4.67 (dd, J¼15.0 Hz, 5.0 Hz, 1H, CH2), 3.49 (dd, J¼16.0 Hz,
8.0 Hz, 1H, CH2), 2.43e2.10 (m, 4H, 2CH2), 1.08 (s, 3H, CH3), 0.92 (s,
3H, CH3); 13C NMR (100 MHz, CDCl3)
d
¼193.6, 153.1, 150.0, 141.3,
CH3); 13C NMR (100 MHz, CDCl3)
138.3, 135.9, 132.8, 131.4, 129.2, 129.1, 126.6, 121.6, 120.2, 109.7, 61.6,
61.4, 57.2, 50.2, 39.8, 32.7, 29.2, 27.0, 21.2, 14.1; HRMS [MþH]þ calcd
for C29H31BrN2O4 551.1540, found 551.1546.
d
¼193.2, 169.1, 152.9, 149.5, 140.6,
136.4, 133.8, 128.6, 128.5, 127.9, 127.8, 127.2, 126.4, 123.5, 109.3, 57.4,
50.4, 46.9, 39.8, 32.8, 29.2, 27.2; HRMS [MþH]þ calcd for
C25H26N2O2 387.2067, found 387.2072.
4.2.11. (E)-3-Cinnamyl-7,7-dimethyl-4-p-tolyl-3,4,7,8-tetrahydro-
quinazoline-2,5(1H,6H)-dione (6b). White solid, mp 204e205 ꢀC;
yield: 52% (ethyl acetate/petroleum ether: 1/4); 1H NMR (400 MHz,
4.2.6. (E)-Ethyl-2-(7,7-dimethyl-4-(4-nitrophenyl)-2,5-dioxo-
1,2,5,6,7,8-hexahydroquinazolin-3(4H)-yl)-4-phenyl-3-butenoate
(4g). White solid, mp 207e209 ꢀC; yield: 42% (ethyl acetate/pe-
CDCl3)
d
¼9.43 (br, 1H, NH), 7.36e7.24 (m, 7H, ArH), 7.14 (d,
troleum ether: 1/2.5); 1H NMR (400 MHz, CDCl3)
d¼9.17 (br, 1H,
J¼8.0 Hz, 2H, ArH), 6.50 (d, J¼16.0 Hz, 1H, CH), 6.13e6.06 (m, 1H,
CH), 5.44 (s, 1H, CH), 4.68 (dd, J¼14.6 Hz, 4.0 Hz, 1H, CH2), 3.50 (dd,
J¼16.0 Hz, 8.0 Hz, 1H, CH2), 2.45e2.11 (m, 7H, CH3, 2CH2), 1.09 (s,
NH), 8.05 (d, J¼8.0 Hz, 2H, ArH), 7.53 (d, J¼8.0 Hz, 2H, ArH),
7.22e7.11 (m, 5H, ArH), 6.41 (d, J¼16.0 Hz,1H, CH), 6.10e6.04 (q,1H,
CH), 5.66 (s, 1H, CH), 4.82 (d, J¼8.0 Hz,1H, CH), 4.13e4.08 (q, J¼16.0,
2H, CH2), 2.38e2.04 (m, 4H, 2CH2), 1.17 (t, J¼8.0 Hz, 3H, CH3), 1.03
3H, CH3), 0.95 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3)
d¼193.7,
153.1, 149.9, 138.3, 137.6, 136.4, 133.7, 129.3, 128.5, 127.8, 127.2,
126.4, 123.5, 109.4, 57.1, 50.4, 46.7, 39.8, 32.8, 29.2, 27.2, 21.1; HRMS
[MþH]þ calcd for C26H28N2O2 401.2224, found 401.2229.
(s, 3H, CH3), 0.80 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3)
d¼193.2,
168.9, 152.9, 150.2, 148.7, 147.3, 136.6, 135.3, 128.7, 128.6, 128.2,
126.6, 123.7, 120.9, 109.1, 61.7, 61.6, 57.3, 50.2, 39.9, 32.8, 29.2, 27.0,
14.2; HRMS [MþH]þ calcd for C28H29N3O6 504.2129, found
504.2138.
4.2.12. (E)-3-Cinnamyl-7,7-dimethyl-4-(4-chlorophenyl)-3,4,7,8-
tetrahydroquinazoline-2,5(1H,6H)-dione (6c). White solid, mp
216e218 ꢀC; yield: 61% (ethyl acetate/petroleum ether: 1/3); 1H
4.2.7. (E)-Ethyl-2-(7,7-dimethyl-4-(3-nitrophenyl)-2,5-dioxo-1,2,5,
6,7,8-hexahydroquinazolin-3(4H)-yl)-4-phenyl-3-butenoate
(4h). White solid, mp 174e176 ꢀC; yield: 39% (ethyl acetate/pe-
NMR (400 MHz, CDCl3)
d
¼9.38 (br, 1H, NH), 7.35e7.23 (m, 9H, ArH),
6.46 (d, J¼16.0 Hz, 1H, CH), 6.09e6.03 (m, 1H, CH), 5.45 (s, 1H, CH),
4.66 (dd, J¼16.0 Hz, 4.0 Hz, 1H, CH2), 3.47 (dd, J¼16.0 Hz, 8.0 Hz, 1H,
CH2), 2.43e2.01 (m, 4H, 2CH2), 1.08 (s, 3H, CH3), 0.92 (s, 3H, CH3);
troleum ether: 1/2.5); 1H NMR (400 MHz, CDCl3)
d
¼8.63 (br, 1H,
NH), 8.28 (s, 1H, ArH), 8.07 (d, J¼8.0 Hz, 1H, ArH), 7.79 (d, J¼8.0 Hz,
1H, ArH), 7.45 (t, J¼8.0 Hz, 1H, ArH), 7.29e7.22 (m, 5H, ArH), 6.50 (d,
J¼16.0 Hz, 1H, CH), 6.24e6.18 (q, 1H, CH), 5.69 (s, 1H, CH), 4.79 (d,
J¼8.0 Hz, 1H, CH), 4.18e4.12 (q, J¼16.0, 1H, CH2), 2.45e2.11 (m, 4H,
2CH2), 1.20 (t, J¼8.0 Hz, 3H, CH3), 1.10 (s, 3H, CH3), 0.90 (s, 3H, CH3);
13C NMR (100 MHz, CDCl3)
d
¼193.5, 153.0, 150.1, 139.8, 136.2, 134.0,
133.7, 128.8, 128.6, 128.5, 127.9, 126.4, 123.2, 109.0, 56.8, 50.3, 47.0,
39.8, 32.8, 29.2, 27.1; HRMS [MþH]þ calcd for C25H25ClN2O2
421.1677, found 421.1684.
13C NMR (100 MHz, CDCl3)
d
¼193.3, 168.8, 152.4, 150.1, 148.3, 143.7,
4.2.13. (E)-3-Cinnamyl-7,7-dimethyl-4-(3-nitrophenyl)-3,4,7,8-
tetrahydroquinazoline-2,5(1H,6H)-dione (6d). White solid, mp
233e235 ꢀC; yield: 62% (ethyl acetate/petroleum ether: 1/3); 1H
136.2, 135.4, 133.8, 129.3, 128.5, 126.6, 122.8, 122.4, 121.1, 109.1, 61.6,
61.5, 57.8, 50.1, 39.8, 32.8, 29.1, 27.1, 14.0; HRMS [MþH]þ calcd for
C
28H29N3O6 504.2129, found 504.2137.
NMR (400 MHz, CDCl3)
d¼9.55 (br,1H, NH), 8.25 (s,1H, ArH), 8.12 (t,
J¼4.0 Hz, 1H, ArH), 7.79 (d, J¼8.0 Hz, 1H, ArH), 7.54e7.49 (m, 1H,
ArH), 7.32e7.25 (m, 5H, ArH), 6.48 (d, J¼12.0 Hz, 1H, CH), 6.10e6.08
(m, 1H, CH), 5.60 (s, 1H, CH), 4.69 (dd, J¼16.0 Hz, 8.0 Hz, 1H, CH2),
3.51 (dd, J¼16.0 Hz, 8.0 Hz, 1H, CH2), 2.49e2.11 (m, 4H, 2CH2), 1.11
4.2.8. Ethyl 2-(7,7-dimethyl-4-(4-nitrophenyl)-2,5-dioxo-1,2,5,6, 7,8-
hexahydroquinazolin-3 (4H)-yl)acetate (5a). White solid, mp
221e222 ꢀC; yield: 15% (ethyl acetate/petroleum ether: 1/2); 1H
NMR (400 MHz, CDCl3)
d
¼9.53 (br, 1H, NH), 8.20 (d, J¼8.0 Hz, 2H,
(s, 3H, CH3), 0.93 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3)
d¼193.5,
ArH), 7.59 (d, J¼8.0 Hz, 2H, ArH), 5.52 (s, 1H, CH), 4.49 (d, J¼16.0 Hz,
1H, CH), 4.21e4.16 (q, 2H, CH2), 3.51 (d, J¼16.0 Hz, 1H, CH),
2.47e2.11 (m, 4H, 2CH2), 1.26 (t, J¼8.0 Hz, 3H, CH3), 1.12 (s, 3H, CH3),
152.7, 150.8, 148.5, 143.5, 136.0, 134.4, 133.6, 129.6, 128.6, 128.0,
126.4, 123.0, 122.8, 122.0, 108.3, 57.1, 50.2, 47.3, 39.8, 32.8, 29.1, 27.2;
HRMS [MþH]þ calcd for C25H25N3O4 432.1918, found 432.1924.
0.92 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3)
d¼193.4, 168.1, 152.9,
150.5, 147.6, 147.5, 128.2, 123.9, 108.3, 61.5, 59.3, 50.1, 47.0, 39.8,
32.7, 29.2, 27.1, 14.1; HRMS [MþH]þ calcd for C20H23N3O6 402.1660,
found 402.1665.
4.2.14. (E)-7,7-Dimethyl-4-phenyl-3-(3-(p-chlorophenyl)allyl)-3,4,
7,8-tetrahydroquinazoline-2,5(1H,6H)-dione (6e). White solid, mp
206e208 ꢀC; yield: 53% (ethyl acetate/petroleum ether: 1/3); 1H
NMR (400 MHz, CDCl3)
d
¼9.28 (br, 1H, NH), 7.41 (d, J¼8.0 Hz, 2H,
4.2.9. Ethyl 2-(7,7-dimethyl-4-(3-nitrophenyl)-2,5-dioxo-1,2,5,6, 7,8-
hexahydroquinazolin-3 (4H)-yl)acetate (5b). White solid, mp
202e203 ꢀC; yield: 18% (ethyl acetate/petroleum ether: 1/2); 1H
ArH), 7.35e7.23 (m, 7H, ArH), 6.44 (d, J¼16.0 Hz, 1H, CH), 6.09e6.04
(m, 1H, CH), 5.45 (s, 1H, CH), 4.64 (dd, J¼15.0 Hz, 5.0 Hz, 1H, CH2),
3.53 (dd, J¼16.0 Hz, 8.0 Hz, 1H, CH2), 2.45e2.12 (m, 4H, 2CH2), 1.10
NMR (400 MHz, CDCl3)
d
¼9.40 (br, 1H, NH), 8.24 (s, 1H, ArH), 8.15
(s, 3H, CH3), 0.94 (s, 3H, CH2); 13C NMR (100 MHz, CDCl3)
d¼193.6,
(d, J¼8.0 Hz, 1H, ArH), 7.78 (d, J¼8.0 Hz, 1H, ArH), 7.54 (t, J¼8.0 Hz,
1H, ArH), 5.52 (s, 1H, CH), 4.46 (d, J¼16.0 Hz, 1H, CH), 4.18e4.17 (q,
2H, CH2), 3.55 (d, J¼16.0 Hz, 1H, CH), 2.48e2.11 (m, 4H, 2CH2), 1.25
(t, J¼8.0 Hz, 3H, CH3), 1.12 (s, 3H, CH3), 0.95 (s, 3H, CH3); 13C NMR
153.0, 149.9, 141.2, 134.9, 133.4, 132.4, 128.7, 128.6, 128.0, 127.6,
127.2, 124.3, 109.4, 57.5, 50.3, 46.9, 39.9, 32.8, 29.2, 27.2; HRMS
[MþH]þ calcd for C25H25ClN2O2 421.1677, found 421.1683.
(100 MHz, CDCl3)
129.7, 123.2, 122.3, 108.4, 61.5, 59.5, 50.2, 47.0, 39.8, 32.8, 29.2, 27.2,
d
¼193.5, 168.1, 152.7, 150.6, 148.5, 142.8, 133.7,
4.2.15. (E)-7,7-Dimethyl-4-phenyl-3-(3-(p-bromophenyl)allyl)-3,4,
7,8-tetrahydroquinazoline-2,5(1H,6H)-dione (6f). White solid, mp
Please cite this article in press as: Zhang, Z.; et al., Tetrahedron (2014), http://dx.doi.org/10.1016/j.tet.2014.10.006

Z. Zhang et al. / Tetrahedron xxx (2014) 1e6
5
209e210 ꢀC; yield: 56% (ethyl acetate/petroleum ether: 1/4); 1H
NMR (400 MHz, CDCl3)
ArH), 7.34e7.24 (m, 3H, ArH), 7.17 (d, J¼8.0 Hz, 2H, ArH), 6.41 (d,
J¼16.0 Hz, 1H, CH), 6.09e6.02 (m, 1H, CH), 5.44 (s, 1H, CH), 4.62 (dd,
J¼16.0 Hz, 4.0 Hz, 1H, CH2), 3.45 (dd, J¼16.0 Hz, 8.0 Hz, 1H, CH2),
2.43e2.11 (m, 4H, 2CH2), 1.08 (s, 3H, CH3), 0.92 (s, 3H, CH3); 13C
(m, 1H, CH), 5.43 (s, 1H, CH), 4.67 (dd, J¼16.0 Hz, 4.0 Hz, 1H, CH2),
3.45 (dd, J¼15.2 Hz, 8.0 Hz, 1H, CH2), 2.44e2.10 (m, 4H, 2CH2), 1.09
d
¼9.33 (br, 1H, NH), 7.40 (t, J¼8.6 Hz, 4H,
(s, 3H, CH3), 0.92 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3)
d¼193.5,
152.9, 150.1, 140.3, 136.2, 134.0, 131.8, 128.9, 128.6, 127.9, 126.4,
123.1, 121.9, 108.9, 56.9, 50.3, 46.9, 39.8, 32.8, 29.2, 27.2; HRMS
[MþH]þ calcd for C25H25BrN2O2 465.1172, found 465.1179.
NMR (100 MHz, CDCl3)
d
¼193.6, 153.0, 150.0, 141.2, 135.3, 132.4,
131.6, 128.6, 128.0, 127.9, 127.1, 124.5, 121.5, 109.3, 57.5, 50.3, 46.9,
39.8, 32.8, 29.2, 27.2; HRMS [MþH]þ calcd for C25H25BrN2O2
465.1172, found 465.1180.
4.2.21. (E)-3-Cinnamyl-7,7-dimethyl-4-(4-nitrophenyl)-3,4,7,8-te-
trahydroquinazoline-2,5(1H,6H)-dione (6l). White solid, mp
231e233 ꢀC; yield: 60% (ethyl acetate/petroleum ether: 1/2); 1H
NMR (400 MHz, CDCl3)
d
¼9.50 (br, 1H, NH), 8.20e8.17 (m, 2H,
4.2.16. (E)-7,7-Dimethyl-4-phenyl-3-(3-(p-tolyl)allyl)-3,4,7,8-tetr-ahy-
droquinazoline-2,5(1H,6H)-dione (6g). White solid, mp 216e218 ꢀC;
yield: 41% (ethyl acetate/petroleum ether: 1/3); 1H NMR (400 MHz,
ArH), 7.61e7.58 (m, 2H, ArH), 7.32e7.25 (m, 5H, ArH), 6.46 (d,
J¼16.0 Hz, 1H, CH), 6.08e6.02 (m, 1H, CH), 5.60 (s, 1H, CH), 4.70
(dd, J¼15.0 Hz, 4.6 Hz, 1H, CH2), 3.49 (dd, J¼15.2 Hz, 8.0 Hz, 1H,
CH2), 2.48e2.11 (m, 4H, 2CH2), 1.11 (s, 3H, CH3), 0.91 (s, 3H, CH3);
CDCl3)
d
¼9.72 (br, 1H, NH), 7.41 (d, J¼8.0 Hz, 2H, ArH),7.34e7.21 (m,
5H, ArH), 7.11 (d, J¼8.0 Hz, 2H, ArH), 6.46 (d, J¼16.0 Hz, 1H, CH),
6.07e6.00 (m, 1H, CH), 5.46 (s, 1H, CH), 4.69 (dd, J¼16.0 Hz, 4.0 Hz,
1H, CH2), 3.45 (dd, J¼16.0 Hz, 8.0 Hz,1H, CH2), 2.44e2.09 (m, 7H, CH3,
2CH2), 1.08 (s, 3H, CH3), 0.92 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3)
13C NMR (100 MHz, CDCl3)
d
¼193.4, 152.9, 150.7, 148.4, 147.5,
136.0, 134.4, 128.6, 128.1, 128.1, 126.4, 124.0, 122.7, 108.3, 57.0,
50.2, 47.5, 39.9, 32.8, 29.2, 27.1; HRMS [MþH]þ calcd for
C
25H25N3O4 432.1918, found 432.1923.
d
¼193.6, 153.2, 150.2, 141.3, 137.6, 133.7, 133.6, 129.2, 128.6, 127.8,
127.2, 126.3, 122.3, 109.2, 57.3, 50.3, 46.8, 39.7, 32.7, 27.1, 21.1; HRMS
4.2.22. (E)-7,7-Dimethyl-4-(4-nitrophenyl)-3-(3-(p-tolyl)allyl)-3,4,
7,8-tetrahydroquinazoline-2,5(1H,6H)-dione (6m). White solid, mp
243e245 ꢀC; yield: 42% (ethyl acetate/petroleum ether: 1/3); 1H
[MþH]þ calcd for C26H28N2O2 401.2224, found 401.2230.
4.2.17. (E)-7,7-Dimethyl-4-p-tolyl-3-(3-(p-tolyl)allyl)-3,4,7,8-tetr-ahy-
droquinazoline-2,5(1H,6H)-dione (6h). White solid, mp 222e223 ꢀC;
yield: 39% (ethyl acetate/petroleum ether: 1/4); 1H NMR (400 MHz,
NMR (400 MHz, CDCl3)
d
¼9.43 (br, 1H, NH), 8.18 (t, J¼4.0 Hz, 2H,
ArH), 7.59 (t, J¼4.0 Hz, 2H, ArH), 7.19 (d, J¼8.0 Hz, 2H, ArH), 7.11 (d,
J¼8.0 Hz, 2H, ArH), 6.42 (d, J¼16.0 Hz, 1H, CH), 6.01e5.97 (m, 1H,
CH), 5.60 (s, 1H, CH), 4.67 (dd, J¼16.0 Hz, 4.0 Hz, 1H, CH2), 3.47 (dd,
J¼15.4 Hz, 8.0 Hz,1H, CH2), 2.47e2.11 (m, 7H, CH3, 2CH2),1.10 (s, 3H,
CDCl3)
d
¼9.63 (br, 1H, NH), 7.29 (d, J¼8.0 Hz, 2H, ArH), 7.23 (t,
J¼6.0 Hz, 2H, ArH), 7.11 (t, J¼8.0 Hz, 4H, ArH), 6.45 (d, J¼16.0 Hz, 1H,
CH), 6.06e5.99 (m, 1H, CH), 5.42 (s, 1H, CH), 4.66 (dd, J¼15.2 Hz,
4.8 Hz, 1H, CH2), 3.45 (dd, J¼16.0 Hz, 8.0 Hz, 1H, CH2), 2.43e2.09 (m,
10H, 2CH3, 2CH2), 1.07 (s, 3H, CH3), 0.93 (s, 3H, CH3); 13C NMR
CH3), 0.91 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3)
d
¼193.4, 152.9,
150.7, 148.4, 147.5, 138.0, 134.4, 133.2, 129.3, 128.1, 126.3, 123.9,
121.6, 108.3, 56.9, 50.2, 47.5, 39.8, 32.8, 29.2, 27.1, 21.1; HRMS
[MþH]þ calcd for C26H27N3O4 446.2074, found 446.2081.
(100 MHz, CDCl3)
d
¼193.6,153.2,153.1,150.1,150.0,138.4,137.5,137.5,
133.7,133.6,129.2,129.1,127.2,126.3,122.4,109.3, 57.1, 50.4, 46.7, 39.7,
32.7, 29.2, 27.2, 21.1, 21.0; HRMS [MþH]þ calcd for C27H30N2O2
415.2380, found 415.2386.
4.2.23. (E)-7,7-Dimethyl-4-(4-nitrophenyl)-3-(3-(p-chlorophenyl)-
allyl)-3,4,7,8-tetrahydroquinazoline-2,5(1H,6H)-dione (6n). White
solid, mp 253e255 ꢀC; yield: 53% (ethyl acetate/petroleum ether: 1/
4.2.18. (E)-7,7-Dimethyl-4-p-tolyl-3-(3-(p-chlorophenyl)allyl)-
3,4,7,8-tetrahydroquinazoline-2,5(1H,6H)-dione (6i). White solid,
mp 228e230 ꢀC; yield: 51% (ethyl acetate/petroleum ether: 1/3); 1H
3); 1H NMR (400 MHz, CDCl3)
d
¼9.21 (br, 1H, NH), 8.19 (d, J¼8.0 Hz,
2H, ArH), 7.58 (d, J¼8.0 Hz, 2H, ArH), 7.29e7.21 (q, 4H, ArH), 6.41 (d,
J¼16.0 Hz, 1H, CH), 6.07e6.00 (m, 1H, CH), 5.58 (s, 1H, CH), 4.68 (dd,
J¼15.2 Hz, 5.2 Hz, 1H, CH2), 3.47 (dd, J¼15.2 Hz, 7.6 Hz, 1H, CH2),
2.47e2.12 (m, 4H, 2CH2),1.11 (s, 3H, CH3), 0.91 (s, 3H, CH3); 13C NMR
NMR (400 MHz, CDCl3)
d
¼9.30 (br, 1H, NH), 7.28e7.21 (m, 6H, ArH),
7.12 (d, J¼4.0 Hz, 2H, ArH), 6.41 (d, J¼16.0 Hz, 1H, CH), 6.07e6.00
(m, 1H, CH), 5.40 (s, 1H, CH), 4.61 (dd, J¼15.4 Hz, 4.8 Hz, 1H, CH2),
3.51 (dd, J¼16.0 Hz, 8.0 Hz, 1H, CH2), 2.42e2.10 (m, 7H, 2CH2, CH3),
1.08 (s, 3H, CH3), 0.93 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3)
(100 MHz, DMSO-d6)
d
¼192.5, 152.1, 151.0, 149.3, 146.7, 135.0, 131.9,
131.2, 128.4, 128.1, 127.8, 125.2, 123.7, 106.7, 56.4, 49.5, 46.5, 40.0,
32.2, 28.7, 26.3; HRMS [MþH]þ calcd for C25H24ClN3O4 466.1528,
found 466.1532.
d
¼193.6, 153.0, 150.0, 138.2, 137.7, 134.9, 133.4, 132.2, 129.3, 128.6,
127.6, 127.1, 124.4, 109.4, 57.3, 50.3, 46.7, 39.8, 32.8, 29.2, 27.2, 21.1;
HRMS [MþH]þ calcd for C26H27ClN2O2 435.1834, found 435.1838.
4.2.24. (E)-7,7-Dimethyl-4-(3-nitrophenyl)-3-(3-(p-bromophenyl)
allyl)-3,4,7,8-tetrahydroquinazoline-2,5(1H,6H)-dione (6o). White
solid, mp 242e244 ꢀC; yield: 61% (ethyl acetate/petroleum ether: 1/
4.2.19. (E)-3-Cinnamyl-7,7-dimethyl-4-(4-fluorophenyl)-3,4,7,8-
tetrahydroquinazoline-2,5(1H,6H)-dione (6j). White solid, mp
215e217 ꢀC; yield: 64% (ethyl acetate/petroleum ether: 1/3); 1H
3); 1H NMR (400 MHz, CDCl3)
d¼9.32 (br, 1H, NH), 8.24 (s, 1H, ArH),
8.12 (d, J¼8.0 Hz, 1H, ArH) 7.77 (d, J¼8.0 Hz, 1H, ArH) 7.51 (t,
J¼8.0 Hz, 1H, ArH), 7.43 (d, J¼8.0 Hz, 2H, ArH), 7.17 (d, J¼8.0 Hz, 2H,
ArH), 6.40 (d, J¼16.0 Hz, 1H, CH), 6.10e6.03 (m, 1H, CH), 5.58 (s, 1H,
CH), 4.65 (dd, J¼16.0 Hz, 8.0 Hz, 1H, CH2), 3.52 (dd, J¼16.0 Hz,
8.0 Hz, 1H, CH2), 2.48e2.12 (m, 4H, 2CH2), 1.11 (s, 3H, CH3), 0.93 (s,
NMR (400 MHz, CDCl3)
d
¼9.44 (br, 1H, NH), 7.40e7.23 (m, 7H, ArH),
7.04e6.98 (q, 2H, ArH), 6.48 (d, J¼16.0 Hz, 1H, CH), 6.11e6.05 (m,
1H, CH), 5.45 (s, 1H, CH), 4.69 (dd, J¼15.4 Hz, 5.0 Hz, 1H, CH2), 3.45
(dd, J¼16.0 Hz, 8.0 Hz, 1H, CH2), 2.44e2.10 (m, 4H, 2CH2), 1.09 (s,
3H, CH3), 0.92 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3)
d¼193.6,
3H, CH3); 13C NMR (100 MHz, CDCl3)
d¼193.5, 152.6, 150.7, 148.6,
163.5, 161.1, 153.0, 150.0, 137.2, 136.3, 133.9, 128.9, 128.8, 128.6,
127.9, 126.4, 123.3, 115.6, 115.4, 109.3, 56.8, 50.3, 46.9, 39.8, 32.8,
29.2, 27.1; HRMS [MþH]þ calcd for C25H25FN2O2 405.1973, found
405.1979.
143.4, 134.9, 133.5, 133.1, 131.7, 129.7, 127.9, 123.7, 123.1, 122.0, 121.9,
108.3, 57.2, 50.2, 47.3, 39.8, 32.9, 29.2, 27.2; HRMS [MþH]þ calcd for
C25H24BrN3O4 510.1023, found 510.1029.
4.2.25. (E)-3-Cinnamyl-7,7-dimethyl-4-(2-chlorophenyl)-3,4,7,8-
tetrahydroquinazoline-2,5(1H,6H)-dione (6p). White solid, mp
97e99 ꢀC; yield: 65% (ethyl acetate/petroleum ether: 1/4); 1H NMR
4.2.20. (E)-3-Cinnamyl-7,7-dimethyl-4-(p-bromophenyl)-3,4,7,8-
tetrahydroquinazoline-2,5(1H,6H)-dione (6k). White solid, mp
213e214 ꢀC; yield: 63% (ethyl acetate/petroleum ether: 1/4); 1H
(400 MHz, CDCl3)
d¼9.57 (br, 1H, NH), 7.47 (t, J¼4.0 Hz, 1H, ArH)
NMR (400 MHz, CDCl3)
d
¼9.35 (br, 1H, NH), 7.45 (d, J¼8.0 Hz, 2H,
7.34e7.16 (m, 8H, ArH), 6.50 (d, J¼16.0 Hz, 1H, CH), 6.10e6.03 (m,
1H, CH), 5.89 (s, 1H, CH), 4.47 (dd, J¼16.0 Hz, 4.0 Hz, 1H, CH2), 3.56
ArH), 7.32e7.24 (m, 7H, ArH), 6.46 (d, J¼16.0 Hz, 1H, CH), 6.09e6.02
Please cite this article in press as: Zhang, Z.; et al., Tetrahedron (2014), http://dx.doi.org/10.1016/j.tet.2014.10.006

6
Z. Zhang et al. / Tetrahedron xxx (2014) 1e6
4. (a) Trost, B. M.; Vranken, D. L. V. J. Am. Chem. Soc. 1993, 115, 444e458; (b)
Burgess, K.; Liu, L. T.; Pal, B. J. Org. Chem. 1993, 58, 4758e4763; (c) Paquette, L.
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2012, 51, 150e154.
(dd, J¼16.0 Hz, 8.0 Hz, 1H, CH2), 2.45e2.08 (m, 4H, 2CH2), 1.08 (s,
3H, CH3), 0.98 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3)
152.4, 150.7, 138.5, 136.5, 133.6, 133.3, 130.6, 129.9, 129.3, 128.4,
127.7, 127.2,126.4,123.3,107.9, 56.2, 50.3, 46.9, 39.8, 32.7, 29.2, 27.3;
HRMS [MþH]þ calcd for C25H25ClN2O2 421.1677, found 421.1682.
d¼193.6,
4.2.26. (E)-7,7-Dimethyl-3-(3-(2-naphthalenyl)allyl)-4-phenyl-
3,4,7,8-tetrahydroquinazoline-2,5(1H,6H)-dione (6q). White solid,
mp 221e223 ꢀC; yield: 64% (ethyl acetate/petroleum ether: 1/4); 1H
NMR (400 MHz, CDCl3)
d
¼9.50 (br, 1H, NH), 7.73 (d, J¼40.0 Hz, 4H,
ArH), 7.53e7.27 (m, 8H, ArH), 6.65 (d, J¼16.0 Hz, 1H, CH), 6.23e6.19
(m, 1H, CH), 5.50 (s, 1H, CH), 4.72 (d, J¼16.0 Hz, 1H, CH2), 3.56 (dd,
J¼16.0 Hz, 8.0 Hz,1H, CH2), 2.45e2.09 (m, 4H, 2CH2),1.08 (s, 3H, CH3),
6. (a) Ohmura, T. J.; Hartwig, F. J. Am. Chem. Soc. 2002, 124, 15164e15165; (b) Trost,
B. M.; Bunt, R. C. J. Am. Chem. Soc. 1994, 116, 4089e4090.
0.92 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3)
d¼193.6, 153.1, 150.1,
7. (a) Stanley, L. M.; Hartwig, J. F. J. Am. Chem. Soc. 2009, 131, 8971e8983; (b)
Spiess, S.; Welter, C.; Frank, G.; Taquet, J. P.; Helmchen, G. Angew. Chem., Int. Ed.
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141.3, 133.9, 133.7, 133.5, 133.0, 128.6, 128.2, 127.9, 127.6, 127.2, 126.4,
126.3, 125.9, 123.9, 123.5, 109.3, 57.5, 50.3, 47.0, 39.8, 32.8, 29.2, 27.1;
HRMS [MþH]þ calcd for C29H28N2O2 437.2224, found 437.2228.
4.2.27. (E)-4-(4-Chlorophenyl)-7,7-dimethyl-3-(3-(2-naphthaleny-l)
allyl)-3,4,7,8-tetrahydroquinazoline-2,5(1H,6H)-dione (6r). White
solid, mp 249e250 ꢀC; yield: 60% (ethyl acetate/petroleum ether: 1/
8. Ye, K. Y.; He, H.; Liu, W. B.; Dai, L. X.; Helmchen, G.; You, S. L. J. Am. Chem. Soc.
2011, 133, 19006e19014.
9. (a) Weihofen, R.; Tverskoy, O.; Helmchen, G. Angew. Chem., Int. Ed. 2006, 45,
5546e5549; (b) Kuhn, O.; Mayr, H. Angew. Chem., Int. Ed. 1999, 38, 343e345; (c)
Molander, G. A.; Gormisky, P. E.; Sandrock, D. L. J. Org. Chem. 2008, 73,
2052e2057; (e) Baruah, J. B.; Samuelson, A. G. Tetrahedron 1991, 47,
9449e9454.
10. (a) Lee, O. Y.; Law, K. L.; Yang, D. Org. Lett. 2009, 11, 3302e3305; (b) Lee, O. Y.;
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12. Ramachandran, P. V.; Sakavuyi, P. D. K.; Clark, P. Tetrahedron Lett. 2010, 51,
3167e3169.
4); 1H NMR (400 MHz, CDCl3)
d
¼9.54 (br, 1H, NH), 7.78e7.67 (m,
4H, ArH), 7.52e7.30 (m, 7H, ArH), 6.63 (d, J¼16.0 Hz, 1H, CH),
6.22e6.15 (m, 1H, CH), 5.49 (s, 1H, CH), 4.71 (dd, J¼16.0 Hz, 4.0 Hz,
1H, CH2), 3.55 (dd, J¼15.2 Hz, 8.0 Hz, 1H, CH2), 2.45e2.10 (m, 4H,
2CH2), 1.08 (s, 3H, CH3), 0.92 (s, 3H, CH3); 13C NMR (100 MHz,
CDCl3)
d
¼193.6, 153.0, 150.2, 139.9, 134.0, 133.7, 133.7, 133.5, 133.1,
128.8, 128.6, 128.2, 127.9, 127.6, 126.5, 126.3, 126.0, 123.6, 123.4,
109.0, 57.0, 50.3, 47.1, 39.8, 32.8, 29.2, 27.1; HRMS [MþH]þ calcd for
13. (a) Wipf, P.; Kendal, C.; Stephenson, C. R. J. J. Am. Chem. Soc. 2003, 125, 761e768;
(b) Wipf, P.; Stephenson, C. R. J. Org. Lett. 2003, 5, 2449e2452; (c) Patel, S. J.;
Jamison, T. F. Angew. Chem., Int. Ed. 2004, 43, 3941e3944; (d) Boezio, A. A.;
Charette, A. B. J. Am. Chem. Soc. 2003, 125, 1692e1693.
C
29H27ClN2O2 472.1912, found 472.1917.
4.2.28. (E)-Ethyl 4-(4-chlorophenyl)-3-(1-ethoxy-1-oxo-4-phenyl-3-
buten-2-yl)-6-methyl-2-oxo-1,2,3,4,-tetrahydropyrimidine-5-
carboxylate (7a). Colorless oil; yield: 41% (acetic acid/petrole-um
14. (a) Prediger, P.; Barbosa, L. F.; Gnisson, Y.; Correia, C. R. D. J. Org. Chem. 2011, 76,
7737e7749; (b) Wu, J.; Marcoux, J. F.; Davies, I. W.; Reider, P. J. Tetrahedron Lett.
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M. J.; Haw-kins, J.; Johnson, P. J.; Massett, S. S.; Neumsnn, K.; Phil-lips, J.;
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G.; Wei, L. Org. Process Res. Dev. 2005, 9, 440e450; (e) Olofsson, K.; Sahlin, H.;
Larhed, M.; Hallberg, A. J. Org. Chem. 2001, 66, 544e549; (f) Olofsson, K.;
Larhed, M.; Hallberg, A. J. Org. Chem. 2000, 65, 7235e7239; (g) Alvisi, D.; Blart,
E.; Bonini, B. F.; Mazzanti, G.; Ricci, A.; Zani, P. J. Org. Chem. 1996, 61, 7139e7146;
(h) Reddington, M. V.; Bryant, D. C. Tetrahedron Lett. 2011, 52, 181e183; (i)
Cacchi, S.; Fabrizi, G.; Goggiamani, A.; Sferrazza, A. Org. Biomol. Chem. 2011, 9,
1727e1730.
ether: 1/45); 1H NMR (400 MHz, CDCl3)
d¼8.96 (br, 1H, NH),
7.24e7.14 (m, 9H, ArH), 6.42 (d, J¼16.0 Hz,1H, CH), 6.12e6.06 (q,1H,
CH), 5.42 (s, 1H, CH), 4.76 (d, J¼8.0 Hz, 1H, CH), 4.09e4.01 (m, 4H,
2CH2), 2.23 (s, 3H, CH3), 1.16e1.11 (m, 6H, 2CH3); 13C NMR
(100 MHz, CDCl3)
d
¼169.2, 165.3, 153.2, 146.1, 140.8, 135.7, 135.5,
133.6, 129.0, 128.8, 128.5, 128.3, 126.6, 121.9, 102.2, 61.4, 61.1, 60.1,
59.3, 18.4, 14.2, 14.0; HRMS [MþH]þ calcd for C26H27ClN2O5
483.1681, found 483.1688.
15. (a) Xie, Y. J.; Hu, J. H.; Wang, Y. Y.; Xia, C. G.; Huang, H. M. J. Am. Chem. Soc. 2012,
134, 20613e20616; Hu, J. H.; Xie, Y. J.; Huang, H. M. Angew. Chem., Int. Ed. 2014,
53, 7272e7276.
16. (a) Qin, H.; Yamagiwa, N.; Matsunaga, S.; Shibasaki, M. J. Am. Chem. Soc. 2006,
128, 1611e1614; (b) Banerjee, D.; Jagadeesh, R. V.; Junge, K.; Junge, H.; Beller, M.
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sunaga, S.; Shibasaki, M. Angew. Chem., Int. Ed. 2007, 46, 409e413.
17. (a) Banerjee, D.; Junge, K.; Beller, M. Angew. Chem., Int. Ed. 2014, 53, 1630e1635;
(b) Banerjee, D.; Junge, K.; Beller, M. Org. Chem. Front. 2014, 1, 368e372.
18. Quan, Z. J.; Hu, W. H.; Zhang, Z.; Da, Y. X.; Jia, X. D.; Wang, X. C. Adv. Synth. Catal.
2013, 355, 891e900.
Acknowledgements
We are thankful for the financial support from the National
Natural Science Foundation of China (Nos. 21362032, and
21362031), Gansu Provincial Departmentof Finance, Natural Science
Foundation of Gansu Province (Nos. 1208RJYA083, 1308RJZA299).
19. (a) Yamamoto, Y.; Hayashi, H.; Saigoku, T.; Nishiyama, H. J. Am. Chem. Soc. 2005,
127, 10804e10805; (b) Luo, Y.; Lu, X.; Ye, Y.; Guo, Y.; Jiang, H.; Zeng, W. Org. Lett.
2012, 14, 5640e5643.
20. In addition, the reaction between 3,4-dihydropyrimidinone (DHPMs, 1i) with
ethyl glyoxylate (2a) and styrene (3a) under the optimal conditions was tested,
and the desired product 7a was obtained.
Supplementary data
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2014.10.006.
References and notes
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Please cite this article in press as: Zhang, Z.; et al., Tetrahedron (2014), http://dx.doi.org/10.1016/j.tet.2014.10.006