SnCl4-catalyzed aza-acetalization of aromatic aldehydes: Synthesis of aryl substituted 3,4-dihydro-2H-1,3-benzoxazines

Article abstract of DOI:10.1080/00397911.2010.540691

Stannic tetrachloride was an efficient Lewis acid catalyst for the aza-acetalization of aromatic aldehydes with o-arylaminomethyl phenols, and a series of novel aryl substituted 3,4-dihydro-2H-1,3-benzoxazines were prepared in good yields under mild condi

Full text of DOI:10.1080/00397911.2010.540691

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SnCl4-Catalyzed Aza-Acetalization
of Aromatic Aldehydes: Synthesis of
Aryl Substituted 3,4-Dihydro-2H-1,3-
benzoxazines
Zilong Tang a b , Weiwen Chen a , Zhonghua Zhu a & Hanwen Liu a b
a School of Chemistry and Chemical Engineering, Hunan University of
Science and Technology, Xiangtan, China
b Key Laboratory of Theoretical Chemistry and Molecular Simulation
of Ministry of Education, Hunan University of Science and
Technology, Xiangtan, China
Accepted author version posted online: 21 Oct 2011. Version of
record first published: 11 Jan 2012
To cite this article: Zilong Tang, Weiwen Chen, Zhonghua Zhu & Hanwen Liu (2012): SnCl4-Catalyzed
Aza-Acetalization of Aromatic Aldehydes: Synthesis of Aryl Substituted 3,4-Dihydro-2H-1,3-
benzoxazines, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 42:9, 1372-1383
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Synthetic Communications1, 42: 1372–1383, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.540691
SnCl4-CATALYZED AZA-ACETALIZATION OF
AROMATIC ALDEHYDES: SYNTHESIS OF ARYL
SUBSTITUTED 3,4-DIHYDRO-2H-1,3-BENZOXAZINES
Zilong Tang,1,2 Weiwen Chen,1 Zhonghua Zhu,1 and
Hanwen Liu1,2
1School of Chemistry and Chemical Engineering, Hunan University of
Science and Technology, Xiangtan, China
2Key Laboratory of Theoretical Chemistry and Molecular Simulation of
Ministry of Education, Hunan University of Science and Technology,
Xiangtan, China
GRAPHICAL ABSTRACT
Abstract Stannic tetrachloride was an efficient Lewis acid catalyst for the aza-acetalization
of aromatic aldehydes with o-arylaminomethyl phenols, and a series of novel aryl substi-
tuted 3,4-dihydro-2H-1,3-benzoxazines were prepared in good yields under mild conditions.
SnCl4 was a more efficient catalyst for the reaction than p-toluenesulfonic acid, sulfuric
acid, and aluminium chloride.
Keywords 1,3-Benzoxazine; catalyst; Lewis acid; SnCl4; synthesis
INTRODUCTION
Since 3,4-dihydro-2H-1,3-benzoxazines and 3,4-dihydro-2H-1,3-oxazine-con-
taining compounds were reported to show different antimicrobial properties,[1] such
as bactericidal, fungicidal, and many pharmacological features[2] such as antitumor,
antituberculosis, and anthelmintic activities, this type of compounds has been an
important subject of research. In addition, N-substituted 3,4-dihydro-2H-1,3-ben-
zoxazines are potential intermediates for the preparation of phenol-formaldehyde
resins.[3] Therefore, the synthesis of these compounds, including the synthesis of ben-
zoxazine monomers containing a special functional group, has attracted great interest.
Several elegant methods for the preparation of these compounds have been docu-
mented in the literature.[4–7] The most important method disclosed by Burke et al.[4]
Received February 21, 2010.
Address correspondence to Zilong Tang, School of Chemistry and Chemical Engineering, Hunan
University of Science and Technology, Xiangtan 411201, China. E-mail: zltang67@yahoo.com.cn
1372

ARYL SUBSTITUTED 3,4-DIHYDRO-2H-1,3-BENZOXAZINES
1373
Scheme 1. Synthesis of 3,4-dihydro-2H-1,3-benzoxazines 1.
involved Mannich-type condensation of phenols with primary amines and two
equivalents of formaldehyde and was often used for the preparation of
2-unsubstituted 3,4-dihydro-2H-1,3-benzoxazines. Condensations of o-aminomethyl-
phenol with aliphatic aldehydes or ketones provided another route to 3,4-dihydro-2H-
1,3-benzoxazines, while reactions with aromatic aldehydes gave benzoxazines together
with Schiff bases and sometimes only Schiff bases.[5] The condensations could be oper-
ated without catalyst, but sometimes catalysts such as TsOH or triethyl amine were
necessary. Because some drawbacks existed in these synthetic methods, the search
for more efficient methods for the preparation of 3,4-dihydro-2H-1,3-benzoxazines
is still of great importance. In the search for new pesticide compounds, we planned
to prepare aryl substituted 3,4-dihydro-2H-1,3-benzoxazines. We found TsOH was
inefficient to catalyze the condensation of o-arylmethylphenols with aromatic
aldehydes, and neither was triethyl amine. In contrast, SnCl4 could effectively promote
the reaction. To the best of our knowledge, there is no report about SnCl4-mediated
aza-acetalization reactions of aromatic aldehydes with o-arylaminomethyl phenols
to prepare aryl substituted 3,4-dihydro-2H-1,3-benzoxazines (Scheme 1). Therefore,
we present these new findings.
RESULTS AND DISCUSSION
According to the synthetic scheme, we chose the reaction of o-aminomethyl
phenol 4a resulting from the reduction of Schiff base 3[8] with m-nitrobenzaldehyde
5a as the model reaction to prepare 3,4-dihydro-2H-1,3-benzoxazines 1a. Initially,
we carried out the reaction in chloroform under reflux without catalyst, but the
reaction did not work (Table 1, entry 1). Then, we used TsOH[2e,9] as catalyst, and
the reaction was performed in chloroform by azeotropically removing condensation
water under reflux. The reaction gave the desired product in only 11% yield along
with an unknown white solid (Table 1, entry 2). Taking into account the high azeo-
tropic ability of cyclohexane, we carried out the reaction in a mixed solvent of
chloroform and cyclohexane (v=v ¼ 1:7), and the yield raised to 18% (entry 3). Here,
it should be noted that the addition of chloroform was essential to increase the solu-
bility of reactants. To further enhance the yield, sulfuric acid was used as catalyst

1374
Z. TANG ET AL.
Table 1. Results of the preparation of compound 1aa
Entry
Conditionsb
Yieldc (%)
1
2
CHCl3, reflux, 5 h, no catalyst
—
11d
18
TsOH (20 mol%), CHCl3, reflux, 5 h
3
TsOH (20 mol%), 85 ꢀC, 5 h, CHCl3=C6H12
H2SO4 (20 mol%), 85 ꢀC, 5 h, CHCl3=C6H12
Et3N (20 mol%), 85 ꢀC, 5 h, CHCl3=C6H12
4
28
—
5
6
AlCl3 (20 mol%), 85 ꢀC, 5 h, CHCl3=C6H12
trace
95
7
SnCl4 (20 mol%), 85 ꢀC, 5 h, CHCl3=C6H12 (n 4=n 5 ¼ 1:1.3)
8
SnCl4 (10 mol%), 85 ꢀC, 5 h, CHCl3=C6H12
87
85
9
SnCl4 (25 mol%), 85 ꢀC, 5 h, CHCl3=C6H12
10
11
12
13
14
15
SnCl4 (30 mol%), 85 ꢀC, 5 h, CHCl3=C6H12
78
95
SnCl4 (20 mol%), 85 ꢀC, 5 h, CHCl3=C6H12 (v:v ¼ 1:1)
SnCl4 (20 mol%), 85 ꢀC, 5 h, CHCl3=C6H12 (v:v ¼ 7:1)
SnCl4 (20 mol%), 85 ꢀC, 5 h, CHCl3=C6H12 (n 4=n 5 ¼ 1:1)
SnCl4 (20 mol%), 85 ꢀC, 5 h, CHCl3=C6H12 (n 4=n 5 ¼ 1:1.2)
SnCl4 (20 mol%), 85 ꢀC, 5 h, CHCl3=C6H12 (n 4=n 5 ¼ 1:1.4)
94
85
91
92
aCompound 1a: R ¼ 4-CH3, R1 ¼ 3-NO2C6H4.
bUnless noted, the molar ratio of n(4a)=n(5a) ¼ 1:1.3. The amount of SnCl4 (20 mol%) is based on ami-
nomethyl phenol except for the cases marked in the table. C6H12, cyclohexane; CHCl3=C6H12 ¼ 1:7 (v=v).
cIsolated yield.
dAn unknown white solid also formed.
and the yield of 1a was raised to 28% (entry 4). However, this modification was still
unacceptable. We next tried organic base triethyl amine (20 mol%),[5c] but the reac-
tion did not work at all (entry 5). We then turned to the rescue of Lewis acid SnCl4
because in literature it was reported to be an effective catalyst for many reactions
such as acetalization and ketalization of aldehydes or ketones.[10] We used SnCl4
(20 mol%, based on 4a) as catalyst, and to our delight, it turned out that the reaction
of 4a with 5a in chloroform=cyclohexane gave product 1a in 95% yield at 85ꢀC (entry
7). To the best of our knowledge, this is the first time to adopt SnCl4 as catalyst for
aza-acetalization of aromatic aldehyde with o-aminomethylphenol to prepare aryl
substituted dihydro-1,3-benzoxazine. It was observed the yield decreased with
increasing or decreasing the amount of catalyst (entries 8–10). Varying the volume
ratio of the two solvents did not have effect on the reaction efficiency. Considering
the toxicity of chloroform, we adopted a mixed solvent of chloroform=cyclohexane
(v=v ¼ 1:7) for the following reactions. The influence of the molar ratio of the reac-
tants on the reaction was also explored, and the results showed the great yield (95%)
was obtained with n(4)=n(5) ¼ 1:1.3 (entry 7 vs. entries 13–15), while the yield
decreased to 85% at the ratio of n(4)=n(5) ¼ 1:1 (entry 13). Encouraged by these
results, we also attempted to use similar Lewis acid AlCl3 as a catalyst. Surprisingly,
the reaction gave only a trace of product (entry 6). From the mechanistic point of
view, it can be understood that the yield of the reaction in the presence of SnCl4
is greater than that of the reaction catalyzed by TsOH or H2SO4. Although TsOH
and H2SO4 can activate the carbonyl group of the aromatic aldehyde, they can also
easily protonate the nitrogen atom of the aminomethyl phenol and thus lower the
nucleophilicity of the nitrogen atom. Hence, the yield of the reaction is very low.
In contrast, because of its oxophilicity SnCl4 is more liable to coordinate with the

ARYL SUBSTITUTED 3,4-DIHYDRO-2H-1,3-BENZOXAZINES
Table 2. Results of the preparation of compound 1a
1375
Entry
R
R1
Product
Yieldb (%)
1
2
4-CH3
3-CH3
3-CH3
2-CH3
2-CH3
4-Cl
2-NO2C6H4
2-NO2C6H4
3-NO2C6H4
2-NO2C6H4
3-NO2C6H4
2-NO2C6H4
4-NO2C6H4
2-NO2C6H4
3-NO2C6H4
2-NO2C6H4
3-NO2C6H4
4-NO2C6H4
Hc
1b
1c
1d
1e
1f
80
69
68
63
65
69
60
66
61
73
70
76
73
63
71
68
3
4
5
6
1g
1h
1i
7
4-Cl
H
8
9
H
1j
10
11
12
13
14
15
16
4-CH3O
4-CH3O
4-CH3O
4-CH3O
4-CH3
4-Cl
1k
1l
1m
1n
1o
1p
1q
Hc
Hc
Hc
3-CH3
aThe molar ratio of n (aldehyde 5)=n (aminomethyl phenol 4) ¼ 1:1.3 for all reactions. The amount of
SnCl4 (20 mol%) is based on aminomethyl phenol. CHCl3=C6H12 ¼ 1:7 (v=v).
bIsolated yield.
cFormaldehyde used.
oxygen atom of the carbonyl group of the aromatic aldehyde compared to the nitro-
gen, it can increase the reactivity of the aldehyde and lead to good yields. However,
the reason why the Lewis acid AlCl3 could not catalyze the reaction is not clear at the
current stage.
Under the optimized conditions, compounds 1b–1q were prepared in 60–80%
yields (Table 2). It can be seen from Table 2, in general, that the reactions with aro-
matic aldehydes and aminomethylphenols possessing an electron-releasing group on
the phenyl group bond to the nitrogen atom gave better yields than those with an
electron-withdrawing group. An electron-releasing group increases the electron den-
sity of the nitrogen and therefore increases its nucleophilicity. For reactions with for-
maldehyde, substituents impacted a little effect on the yields (entries 13–16). It was
further observed that for compounds containing a methyl group on the benzene ring
connected with the nitrogen atom, the yields depended mainly on the position of the
methyl group in the order of para > meta > ortho regardless of the nature of the aryl
group at position 2 of the oxazine ring. The last two cases may be attributed to the
steric hindrace. In addition, there was no apparent difference in yields with aromatic
aldehydes or formaldehyde as reactants.
In summary, we have demonstrated that SnCl4 is an effective Lewis acid cata-
lyst for the aza-acetalization of aromatic aldehydes with o-arylaminomethyl phenols,
and thereby a series of novel aryl substituted 3,4-dihydro-2H-1,3-benzoxazine deri-
vatives except for 1n–1p were prepared in good yields from o-arylaminomethylphe-
nols and aromatic aldehydes. It was found that SnCl4 was a more efficient catalyst
than p-toluenesulfonic acid, sulfuric acid, and aluminium chloride.
All solvents were dried by standard procedure. Aromatic aldehydes and substi-
tuted anilines were commercially available. Infrared (IR) spectra were recorded on a

1376
Z. TANG ET AL.
1
PE-2000 Fourier transform (FT)–IR instrument. H and 13C NMR spectra were
recorded on Bruker Avance 500-MHz spectrometer. Chemical shifts (d) are given
1
relative to Me4Si (0, H) or CDCl3 (77.0, 13C). Mass spectra were obtained with a
Thermo Finnigan LCQ Advantage spectrometer. Elemental analysis was measured
on PE 2400 II CHNS instrument. Melting points were determined on a WRS-1B
digital melting-point instrument. Thin-layer chromatography (TLC) was run on pre-
coated silica-gel phates (Merck 60 F254). Column chromatography was carried out
using flash silica gel.
General Procedure for the Synthesis of 3,4-Dihydro-2H-
1,3-benzoxazines 1a–1q
Under nitrogen, 2-((p-toluidino)methyl)phenol 4a (1.07 g, 5 mmol), 3-nitroben-
zaldehyde (0.98 g, 6.5 mmol), mixed solvent of chloroform and cyclohexane (150 mL,
v=v ¼ 1:7), and SnCl4 (0.26 g, 20 mol%) were added with stirring to a 250 mL
three-necked flask equipped with a Dean–stark trap. The solution was heated at
85 ꢀC for 5 h (checked by thin-layer chromatography, TLC), and the condensation
water was removed by azeotropic distillation of most of the solvent. Then, triethyl
amine was added to bring the solution to pH 8, followed by addition of ethyl acetate
(100 mL). The solution was washed sequentially with water (2 ꢁ 100 mL) and
saturated brine (2 ꢁ 100 mL). The organic phase was dried over MgSO4 and evapo-
rated under reduced pressure. The obtained yellow oil was purified by flash column
chromatography (silica gel, PE-EtOAc) to give the product 1a (1.64 g, 95% yield) as a
yellow solid.
2-(3-Nitrophenyl)-3-p-tolyl-3,4-dihydro-2H-benzo[e][1,3]oxazine (1a)
Yield 95%, mp 123.6–125.5 ꢀC. IR (KBr): 3093, 3070, 3022, 2978, 2857, 1611,
1583, 1528, 1513, 1490, 1457, 1380, 1346, 1272, 1265, 1227, 1197, 1149, 1127, 1108,
1083, 1033, 995, 956, 941, 923, 893, 821, 811, 805, 752, 734, 711, 694, 670, 594 cmꢂ1
.
1H NMR (CDCl3, 500 MHz): d ¼ 2.27 (s, 3H, CH3), 4.25 (d, J ¼ 17.0 Hz, 1H, CH2),
4.35 (d, J ¼ 17.0 Hz, 1H, CH2), 6.56 (s, 1H, CH), 6.86 (d, J ¼ 8.0 Hz, 2H), 7.02–7.03
(m, 1H), 7.07–7.12 (m, 4H), 7.16 (d, J ¼ 2.5 Hz, 1H), 7.51 (t, J ¼ 8.0 Hz, 1H), 7.90 (d,
J ¼ 8.5 Hz, 1H), 8.15–8.17 (m, 1H), 8.45 (s, 1H). 13C NMR (CDCl3, 125 MHz):
d ¼ 20.68, 47.20, 87.61, 117.09, 120.14, 121.01 (2C), 121.16, 122.29, 123.23, 126.67,
128.37, 129.69, 129.91 (2C), 132.58, 133.09, 141.64, 146.95, 148.70, 152.39. MS
(EI, 70 ev) m=z (%): 346 (30) [Mþ], 240 (100), 223 (6), 193 (8), 165 (4), 118 (14),
107 (4), 91 (25), 77 (9), 65 (9), 51 (4). Anal. calcd. for C21H18N2O3: C, 72.82; H,
5.24; N 8.09. Found: C, 72.53; H, 5.22; N. 8.06.
2-(2-Nitrophenyl)-3-p-tolyl-3,4-dihydro-2H-benzo[e][1,3]oxazine (1b)
Yield 80%, mp 152.6–153.0 ꢀC. IR (KBr): 3083, 3021, 2972, 2920, 1610, 1585,
1530, 1513, 1486, 1456, 1437, 1386, 1363, 1337, 1292, 1276, 1268, 1224, 1198, 1144,
1109, 1034, 1024, 1015, 978, 961, 935, 852, 839, 820, 782, 757, 736, 714, 687, 679, 632,
1
589 cmꢂ1. H NMR (CDCl3, 500 MHz): d ¼ 2.25 (s, 3H, CH3), 4.00 (d, J ¼ 17.0 Hz,
1H, CH2), 4.19 (d, J ¼ 17.0 Hz, 1H, CH2), 6.85 (s, 1H, CH), 6.86–6.88 (m, 1H),

ARYL SUBSTITUTED 3,4-DIHYDRO-2H-1,3-BENZOXAZINES
1377
7.00–7.06 (m, 6H), 7.17–7.20 (m, 1H), 7.44–7.47 (m, 2H), 7.61–7.63 (m, 1H),
7.72–7.74 (m, 1H). 13C NMR (CDCl3, 125 MHz): d ¼ 20.74, 47.12, 85.52, 116.72,
120.45, 120.86 (2C), 121.13, 124.45, 126.72, 128.41, 128.76, 129.21, 129.80 (2C),
131.84, 132.76, 132.99, 146.74, 149.08, 152.60. MS (ESI): 347 [M þ H]þ. Anal. calcd.
for C21H18N2O3: C, 72.82; H, 5.24; N, 8.09. Found: C, 73.11; H, 5.26; N, 8.05.
2-(2-Nitrophenyl)-3-m-tolyl-3,4-dihydro-2H-benzo[e][1,3]oxazine (1c)
Yield 69%, mp 138.1–139.0 ꢀC. IR (KBr): 3072, 2947, 2906, 2862, 1606, 1586,
1535, 1489, 1456, 1445, 1378, 1340, 1301, 1273, 1236, 1216, 1199, 1169, 1140, 1109,
1
1036, 983, 958, 937, 852, 837, 782, 772, 756, 737, 690, 634, 597 cmꢂ1. H NMR
(CDCl3, 500 MHz): d ¼ 2.30 (s, 3H, CH3), 4.01 (d, J ¼ 17.0 Hz, 1H, CH2), 4.23
(dd, J ¼ 1.0 Hz, J ¼ 1.0 Hz, 1H, CH2), 6.80 (d, J ¼ 7.5 Hz, 1H), 6.85–6.87 (m, 2H),
6.93–6.95 (m, 1H), 6.98 (s, 1H, CH), 7.01 (d, J ¼ 8.0 Hz, 1H), 7.08 (s, 1H), 7.11
(t, J ¼ 8.0 Hz, 1H), 7.17–7.20 (m, 1H), 7.43–7.48 (m, 2H), 7.61–7.62 (m, 1H),
7.73–7.74 (m, 1H). 13C NMR (CDCl3, 125 MHz): d ¼ 21.72, 46.79, 85.03, 116.76,
117.27, 120.41, 121.05 (2C), 121.13, 123.91, 124.47, 126.66, 128.41, 128.78, 129.02,
129.22, 131.83, 132.99, 139.02, 149.10, 152.44. MS (ESI): 347 [M þ H]þ. Anal. calcd.
for C21H18N2O3: C, 72.82; H, 5.24; N, 8.09. Found: C, 73.12; H, 5.28; N, 8.06.
2-(3-Nitrophenyl)-3-m-tolyl-3,4-dihydro-2H-benzo[e][1,3]oxazine (1d)
Yield 68%, mp 101.3–102.0 ꢀC. IR (KBr): 3092, 3025, 2979, 2918, 1602, 1585,
1529, 1488, 1475, 1380, 1348, 1314, 1271, 1238, 1219, 1181, 1123, 1113, 1087, 1046,
1
1032, 994, 958, 970, 942, 899, 891, 806, 776, 753, 735, 696, 688, 671, 599 cmꢂ1. H
NMR (CDCl3, 500 MHz): d ¼ 2.32 (s, 3H, CH3), 4.26 (d, J ¼ 17.0 Hz, 1H, CH2),
4.37 (d, J ¼ 17.0 Hz, 1H, CH2), 6.63 (s, 1H, CH), 6.82–6.89 (m, 3H), 7.00–7.04 (m,
3H), 7.15–7.19 (m, 2H), 7.51 (t, J ¼ 8.0 Hz, 1H), 7.89–7.91 (m, 1H), 8.15–8.17 (m.
1H), 8.44 (s, 1H). 13C NMR (CDCl3, 125 MHz): d ¼ 21.65, 46.56, 86.98, 117.11,
117.24, 120.05, 121.07, 121.13, 122.20, 123.22, 123.54, 126.60, 128.35, 129.17,
129.72, 133.04, 139.24, 141.60, 148.64, 149.36, 152.15. MS (ESI): 347 [M þ H]þ.
Anal. calcd. for C21H18N2O3: C, 72.82; H, 5.24; N, 8.09. Found: C, 72.53; H,
5.20; N, 8.05.
2-(2-Nitrophenyl)-3-o-tolyl-3,4-dihydro-2H-benzo[e][1,3]oxazine (1e)
Yield 63%, mp 164.3–165.3 ꢀC. IR (KBr): 3079, 3025, 2948, 2913, 1608, 1597,
1588, 1527, 1458, 1439, 1365, 1338, 1300, 1274, 1228, 1207, 1187, 1142, 1118, 1057,
1035, 1021, 977, 955, 937, 855, 841, 827, 780, 760, 737, 725, 714, 684, 663, 634,
1
592 cmꢂ1. H NMR (CDCl3, 500 MHz): d ¼ 2.20 (s, 3H, CH3), 3.93 (s, 2H, CH2),
6.76 (d, J ¼ 12.0 Hz, 1H), 6.83–6.86 (m, 1H), 6.98 (s, 1H, CH), 6.99–7.01 (dd,
J ¼ 7.4 Hz, J ¼ 0.9 Hz, 1H), 7.03 (t, J ¼ 8.0 Hz, 1H), 7.09 (d, J ¼ 8.0 Hz, 1H), 7.14
(d, J ¼ 7.0 Hz, 1H), 7.20–7.23 (m, 1H), 7.43–7.51 (m, 3H), 7.72 (d, J ¼ 7.5 Hz, 1H),
7.78 (dd, J ¼ 1.5 Hz, J ¼ 1.0 Hz, 1H). 13C NMR (CDCl3, 125 MHz): d ¼ 17.93,
47.84, 85.79, 116.61, 119.57, 121.08, 122.95, 124.92 (2C), 126.64, 127.06, 128.47,
128.77, 129.13, 131.19, 132.11, 133.17, 133.37, 148.11, 148.79, 152.44. MS (ESI):

1378
Z. TANG ET AL.
347[M þ H]þ. Anal. calcd. for C21H18N2O3: C, 72.82; H, 5.24; N, 8.09. Found: C,
72.51; H, 5.21; N, 8.05.
2-(3-Nitrophenyl)-3-o-tolyl-3,4-dihydro-2H-benzo[e][1,3]oxazine (1f)
Yield 65%, mp 85.0–86.1 ꢀC. IR (KBr): 3023, 2933, 2885, 1598, 1585, 1533,
1490, 1456, 1434, 1386, 1380, 1349, 1336, 1227, 1215, 1188, 1149, 1082, 1033, 986,
959, 893, 807, 764, 755, 742 724, 695, 673, 588 cmꢂ1
.
1H NMR (CDCl3,
500 MHz): d ¼ 2.51 (s, 3H, CH3), 4.14 (d, J ¼ 17.0 Hz, 1H, CH2), 4.25 (d, J ¼ 17.0 Hz,
Hz, 1H, CH2), 6.34 (s, 1H, CH), 6.86–6.92 (m, 2H), 7.05–7.13 (m, 3H), 7.20–7.25 (m,
2H), 7.36 (d, J ¼ 7.5 Hz, 1H), 7.53 (t, J ¼ 8.0 Hz, 1H), 7.99 (d, J ¼ 2.5 Hz, 1H),
8.16–8.18 (m, 1H), 8.54–8.55 (m, 1H). 13C NMR (CDCl3, 125 MHz): d ¼ 18.59,
47.37, 87.92, 117.08, 119.86, 121.15, 122.35, 123.10, 123.31, 125.03, 126.69, 126.86,
128.23, 129.57, 131.07, 133.13, 133.17, 141.43, 148.11, 148.52, 152.28. MS (ESI):
347 [M þ H]þ. Anal. calcd. for C21H18N2O3: C, 72.82; H, 5.24; N, 8.09%. Found:
C, 73.12; H, 5.28; N, 8.06.
3-(4-Chlorophenyl)-2-(2-nitrophenyl)-3,4-dihydro-2H-
benzo[e][1,3]oxazine (1g)
Yield 69%, mp 140.7–141.3 ꢀC. IR (KBr): 3035, 2936, 2875, 1609, 1592, 1522,
1494, 1457, 1384, 1361, 1342, 1304, 1276, 1224, 1203, 1113, 1098, 1034, 1020, 1008,
.
980, 949, 936, 855, 826, 782 750, 740, 727, 645, 596 cmꢂ1 1H NMR (CDCl3,
500 MHz): d ¼ 3.99 (d, J ¼ 17.0 Hz, 1H, CH2), 4.22 (d, J ¼ 17.0 Hz, 1H, CH2), 6.85
(s, 1H, CH), 6.87–6.91 (m, 1H), 7.00 (d, J ¼ 9.5 Hz, 2H), 7.06–7.09 (m, 2H),
7.17–7.22 (m, 3H), 7.44–7.49 (m, 2H), 7.59–7.62 (m, 1H), 7.73–7.77 (m, 1H). 13C
NMR (CDCl3, 125 MHz): d ¼ 46.95, 85.09, 116.67, 119.81, 121.28, 121.98 (2C),
124.49, 126.60, 128.25, 128.57, 128.61, 129.14 (2C), 129.33, 131.94, 132.40, 147.54,
148.77, 152.28. MS (ESI): 367 [M þ H]þ. Anal. calcd. for C20H15ClN2O3: C, 65.49;
H, 4.12; N, 7.64. Found: C, 65.75; H, 4.10; N, 7.68.
3-(4-Chlorophenyl)-2-(4-nitrophenyl)-3,4-dihydro-2H-
benzo[e][1,3]oxazine (1h)
Yield 60%, mp 135.9–137.6 ꢀC. IR (KBr): 3075, 3057, 2938, 2973, 2891, 2851,
1605, 1593, 1583, 1516, 1496, 1487, 1455, 1373, 1348, 1331, 1288, 1224, 1199, 1182,
1131, 1112, 1034, 1005, 963, 930, 902, 855, 830, 819, 800, 753, 743, 724, 711, 642, 624,
602, 559 cmꢂ1. 1H NMR (CDCl3, 500 MHz): d ¼ 4.24 (d, J ¼ 17.0 Hz, 1H, CH2), 4.34
(d, J ¼ 1 7.0 Hz, 1H, CH2), 6.56 (s, 1H, CH), 6.89–6.94 (m, 2H), 7.00 (d, J ¼ 8.0 Hz,
1H), 7.11–7.12 (m, 2H), 7.17–7.19 (m, 1H), 7.20–7.24 (m, 2H), 7.72–7.74 (m, 2H),
8.19–8.21 (m, 2H). 13C NMR (CDCl3, 125 MHz): d ¼ 47.24, 87.23, 117.02, 119.61,
121.39, 121.90 (3C), 123.90 (2C), 126.66, 127.84, 127.90 (2C), 128.53, 129.29 (2C),
145.83, 147.78, 152.12. MS (EI, 70 ev) m=z (%): 366 (35) [Mþ], 260 (100), 213 (17),
178 (4%), 138 (10), 111 (12), 78 (7), 51 (5). Anal. calcd. for C20H15ClN2O3: C,
65.49; H, 4.12; N, 7.64. Found: C, 65.15; H, 4.08; N, 7.60.

ARYL SUBSTITUTED 3,4-DIHYDRO-2H-1,3-BENZOXAZINES
1379
2-(2-Nitrophenyl)-3-phenyl-3,4-dihydro-2H-benzo[e][1,3]oxazine (1i)
Yield 66%, mp 130.9–131.7 ꢀC. IR (KBr): 3023, 2948, 2860, 1598, 1585, 1535,
1496, 1486, 1455, 1396, 1365, 1273, 1223, 1136, 1110, 1036, 981, 957, 853, 783, 756,
1
735, 717, 694, 591 cmꢂ1. H NMR (CDCl3, 500 MHz): d ¼ 4.04 (d, J ¼ 17.0 Hz, 1H,
CH2), 4.26 (d, J ¼ 17.0 Hz, 1H, CH2), 6.89 (s, 1H, CH), 6.92–6.94 (m, 1H), 6.96–7.03
(m, 2H), 7.11 (s, 1H), 7.16–7.23 (m, 3H), 7.25–7.28 (m, 2H), 7.46–7.49 (m, 2H),
7.63–7.65 (m, 1H), 7.75–7.77 (m, 1H). 13C NMR (CDCl3, 125 MHz): d ¼ 46.78,
85.24, 116.75, 120.36, 120.55 (3C), 121.20, 123.12, 124.50, 126.69, 128.47, 128.79,
129.26 (3C), 131.88, 132.87, 149.08, 152.50. MS (EI, 70 ev) m=z (%) ¼ 332 (29)
[Mþ], 315 (22), 284 (4), 226 (10), 209 (72), 196 (12), 181 (12), 179 (28), 151 (19),
152 (36), 134 (7), 120 (6), 104 (20), 92 (23), 77 (100), 65 (9), 51 (41). Anal. calcd.
for C20H16N2O3: C, 72.28; H, 4.85; N, 8.43. Found: C, 71.95; H, 4.82; N, 8.39.
2-(3-Nitrophenyl)-3-phenyl-3,4-dihydro-2H-benzo[e][1,3]oxazine (1j)
Yield 61%, m.p. 90.3–91.8 ꢀC. IR (KBr): 3030, 2962, 2875, 1605, 1502, 1488,
1456, 1398, 1364, 1252, 1227, 1138, 1127, 1085, 994, 957, 893, 783, 757, 735, 713,
1
694, 592 cmꢂ1. H NMR (CDCl3, 500 MHz): d ¼ 4.04 (d, J ¼ 17.0 Hz, 1H, CH2),
4.26 (d, J ¼ 17.0 Hz, 1H, CH2), 6.62 (s, 1H, CH), 6.82–6.92 (m, 3H), 7.02–7.06 (m,
3H), 7.16–7.20 (m, 2H), 7.25–7.28 (m, 1H), 7.51–7.55 (m, 2H), 7.66–7.76 (m, 2H).
13C NMR (CDCl3, 125 MHz): d ¼ 47.02, 87.23, 116.90, 120.45, 120.62 (3C),
121.41, 123.22, 125.00, 126.73, 128.51, 129.02, 129.28 (3C), 132.11, 132.90, 149.09,
152.78. MS (ESI): 333 [M þ H]þ. Anal. calcd. for C20H16N2O3: C, 72.28; H, 4.85;
N, 8.43. Found: C, 72.65; H, 4.81; N, 8.38.
3-(4-Methoxyphenyl)-2-(2-nitrophenyl)-3,4-dihydro-2H-
benzo[e][1,3]oxazine (1k)
Yield 73%, mp 165.9–166.9 ꢀC. IR (KBr): 3076, 2968, 1607, 1579, 1531, 1509,
1488, 1456, 1388, 1364, 1299, 1270, 1242, 1225, 1199, 1145, 1108, 1034, 1022, 975,
1
960, 854, 830, 783, 758, 737, 685, 631, 589 cmꢂ1. H NMR (CDCl3, 500 MHz):
d ¼ 3.75 (s, 3H, OCH3), 4.01 (d, J ¼ 17.0 Hz, 1H, CH2), 4.17 (d, J ¼ 17.0 Hz, 1H,
CH2), 6.77–6.79 (m, 2H), 6.87–6.92 (m, 2H), 6.94 (s, 1H, CH), 7.04 (d, J ¼ 8.0 Hz,
1H), 7.09–7.11 (m, 2H), 7.21–7.25 (m, 1H), 7.46–7.48 (m, 2H), 7.64–7.66 (m, 1H),
7.75–7.76 (m, 1H). 13C NMR (CDCl3, 125 MHz): d ¼ 47.48, 55.29, 85.96, 114.17
(2C), 116.59, 120.41, 121.06, 123.18 (2C), 124.28, 126.64, 128.27, 128.59, 129.06,
131.75, 132.77, 142.48, 148.95, 152.63, 155.92. MS (ESI): 363 [M þ H]þ. Anal. calcd.
for C21H18N2O3: C, 69.60; H, 5.01; N, 7.73. Found: C, 69.31; H, 4.98; N, 7.69.
3-(4-Methoxyphenyl)-2-(3-nitrophenyl)-3,4-dihydro-2h-
benzo[e][1,3]oxazine (1l)
Yield 70%, m.p. 103.2–106.1 ꢀC. IR (KBr): 3070, 3093, 2950, 2832, 1610, 1582,
1528, 1512, 1488, 1456, 1345, 1252, 1227, 1197, 1179, 1127, 1085, 1038, 994, 957, 893,
826, 783, 757, 735, 712, 694, 670 cmꢂ1. 1H NMR (CDCl3, 500 MHz): d ¼ 3.77 (s, 3H,
OCH3), 4.26 (d, J ¼ 17.0 Hz, 1H, CH2), 4.34 (d, J ¼ 17.0 Hz, 1H, CH2), 6.48 (s, 1H,

1380
Z. TANG ET AL.
CH), 6.81–6.83 (m, 2H), 6.90–6.91 (m, 2H), 7.05 (d, J ¼ 8.0 Hz, 1H), 7.16–7.18 (m,
2H), 7.20–7.23 (m, 1H), 7.53 (t, J ¼ 8.0 Hz, 1H), 7.94 (d, J ¼ 8.0 Hz, 1H), 8.17–8.1
9(m, 1H), 8.49 (s, 1H). 13C NMR (CDCl3, 125 MHz): d ¼ 47.99, 55.36, 88.17,
114.31(2C), 116.96, 120.10, 121.10, 122.22, 123.12, 123.34 (2C), 126.60, 128.25,
129.54, 133.07, 141.41, 142.61, 148.50, 152.44, 155.77. MS (EI, 70 ev) m=z (%) ¼ 362
(72) [Mþ], 345 (17), 256 (100), 239 (38), 227 (7), 209 (11), 196 (19), 183 (8), 168 (48),
152 (10), 140 (19), 135 (30), 122 (51), 106 (25), 92 (20), 77 (41), 64 (19). Anal. calcd.
for C21H18N2O3: C, 69.60; H, 5.01; N, 7.73. Found: C, 69.85; H, 5.05; N, 7.69.
3-(4-Methoxyphenyl)-2-(4-nitrophenyl)-3,4-dihydro-2H-
benzo[e][1,3]oxazine (1m)
Yield 76%, mp 84.3–86.1 ꢀC. IR (KBr): 3014, 2968, 2945,2937, 2860, 1607,
1583, 1512, 1487, 1466, 1457, 1438, 1380, 1319, 1300, 1266, 1245, 1226, 1201,
1188, 1138, 1107, 1037, 1024, 1012, 974, 965, 950, 939, 855, 834, 822, 767, 739,
1
713, 695, 590 cmꢂ1. H NMR (CDCl3, 500 MHz): d ¼ 3.74 (s, 3H, OCH3), 4.21
(d, J ¼ 17.0 Hz, 1H, CH2), 4.31 (d, J ¼ 17.0 Hz, 1H, CH2), 6.46 (s, 1H, CH),
6.77–6.80 (m, 2H), 6.86–6.88 (m, 2H), 7.00 (d, J ¼ 8.0 Hz, 1H), 7.11–7.14 (m, 2H),
7.17–7.20 (m, 1H), 7.75 (d, J ¼ 8.5 Hz, 2H), 8.18–8.19 (m, 2H). 13C NMR (CDCl3,
125 MHz): d ¼ 48.05, 55.41, 88.42, 114.35 (2C), 116.91, 120.17, 121.17, 123.20
(2C), 123.76 (2C), 126.68, 127.97 (2C), 128.27, 142.63, 146.30, 147.66, 152.56,
155.76. MS (ESI): 363 [M þ H]þ. Anal. calcd. for C21H18N2O3: C, 69.60; H, 5.01;
N, 7.73. Found: C, 69.25; H, 4.97; N, 7.68.
3-(4-Methoxyphenyl)-3,4-dihydro-2H-benzo[e][1,3]oxazine (1n)
Yield 73%, mp 75.7–76.8 ꢀC. IR (KBr): 3032, 2997, 2948, 2834, 1607, 1582,
1554, 1541, 1511, 1488, 1464, 1455, 1438, 1386, 1360, 1339, 1299, 1253, 1243,
1228, 1208, 1188, 1141, 1105, 1085, 1031, 971, 943, 934, 830, 771, 758, 730,
591 cmꢂ1
.
1H NMR (CDCl3, 500 MHz): d ¼ 3.74 (s, 3H, OCH3), 4.55 (s, 2H,
CH2), 5.29 (s, 2H, CH2), 6.79–6.82 (m, 3H), 6.86–6.89 (m, 1H), 6.99 (d, J ¼ 2.5 Hz,
Hz, 1H), 7.05–7.08 (m, 2H), 7.10–7.13 (m, 1H). 13C NMR (CDCl3, 125 MHz):
d ¼ 51.08, 55.46, 80.71, 114.43 (2C), 116.83, 120.70, 120.74 (2C), 120.86, 126.75,
127.83, 142.28, 154.29, 154.87. MS (EI, 70 ev) m=z (%) ¼ 241 (32) [Mþ], 135 (100),
120 (52), 107 (2), 92 (9), 77 (8), 65 (9), 51 (6). Anal. calcd. for C15H15NO2: C,
74.67; H, 6.27; N, 5.81. Found: C, 74.29; H, 6.24; N, 5.85.
3-p-Tolyl-3,4-dihydro-2H-benzo[e][1,3]oxazine (1o)
Yield 63%, mp 82.0–83.2 ꢀC. IR (KBr): 3064, 3027, 2969, 2861, 1609, 1581,
1513, 1489, 1455, 1390, 1377, 1362, 1336, 1252, 1223, 1196, 1187, 1152, 1113,
1083, 1033, 982, 972, 939, 841, 817, 752, 728, 704, 672, 590 cmꢂ1. 1H NMR (CDCl3,
500 MHz): d ¼ 2.27 (s, 3H, CH3), 4.61 (s, 2H, CH2), 5.34 (s, 2H, CH2), 6.80 (d,
J ¼ 8.0 Hz, 1H), 6.87 (t, J ¼ 7.5 Hz, 1H), 7.01 (t, J ¼ 8.5 Hz, 3H), 7.07 (d, J ¼ 8.0 Hz,
Hz, 2H), 7.10 (t, J ¼ 8.0 Hz, 1H). 13C NMR (CDCl3, 125 MHz): d ¼ 20.60, 50.68,
80.02, 116.94, 118.69 (2C), 120.78, 120.97, 126.80, 127.88, 129.85 (2C), 131.12,
146.14, 154.41. MS (EI, 70 ev) m=z (%) ¼ 225 (20) [Mþ], 119 (100), 105 (3), 91 (38),

ARYL SUBSTITUTED 3,4-DIHYDRO-2H-1,3-BENZOXAZINES
1381
77 (5), 65 (10), 51 (6). Anal. calcd. for C15H15NO: C, 79.97; H, 6.71; N, 6.22. Found:
C, 79.46; H, 6.75; N, 6.19.
3-(4-Chlorophenyl)-3,4-dihydro-2H-benzo[e][1,3]oxazine (1p)
Yield 71%, mp 61.1–61.7 ꢀC. IR (KBr): 3071, 2911, 1606, 1595, 1578, 1498,
1487, 1454, 1365, 1336, 1248, 1222, 1191, 1153, 1113, 1083, 1035, 1004, 983, 969,
1
945, 822, 807, 782, 754, 739, 612, 586 cmꢂ1. H NMR (CDCl3, 500 MHz): d ¼ 4.63
(s, 2H, CH2), 5.35 (s, 2H, CH2), 6.82 (d, J ¼ 8.0 Hz, 1H), 6.90 (t, J ¼ 7.4 Hz, 1H),
7.02-7.07 (m, 3H), 7.13 (t, J ¼ 7.4 Hz, 1H), 7.22–7.24 (m, 2H). 13C NMR (CDCl3,
125 MHz): d ¼ 50.67, 79.38, 117.03, 119.67 (2C), 120.56, 121.03, 126.49, 126.80,
128.09, 129.23 (2C), 147.09, 154.22. MS (EI, 70 ev) m=z (%) ¼ 245 (34) [Mþ], 139
(100), 111 (14), 77 (7), 51 (9). Anal. calcd. for C14H12ClNO: C, 68.44; H, 4.92; N,
5.70. Found: C, 68.39; H, 4.89; N, 5.74.
3-m-Tolyl-3,4-dihydro-2H-benzo[e][1,3]oxazine (1q)
Yield 68%, mp 60.0–61.5 ꢀC. IR (KBr): 3002, 2964, 1601, 1581, 1488, 1473,
1455, 1367, 1339, 1257, 1227, 1177, 1156, 1114, 1092, 1034, 999, 983, 973, 943,
.
896, 883, 856, 837, 787, 751, 728, 700, 653, 598 cmꢂ1 1H NMR (CDCl3,
500 MHz): d ¼ 2.34 (s, 3H, CH3), 4.66 (s, 2H, CH2), 5.39 (s, 2H, CH2), 6.77 (d,
J ¼ 7.45 Hz, 1H), 6.83 (d, J ¼ 8.2 Hz, 1H), 6.90–6.96 (m, 3H), 7.03 (d, J ¼ 7.5 Hz,
1H), 7.12–7.19 (m, 2H). 13C NMR (CDCl3, 125 MHz): d ¼ 21.76, 50.47, 79.48,
115.30, 117.03, 118.96, 120.85, 121.06, 122.34, 126.81, 127.88, 129.16, 139.14,
148.43, 154.45. MS (ESI): 226 [M þ H]þ. Anal. calcd. for C15H15NO: C, 79.97; H,
6.71; N, 6.22. Found: C, 79.44; N, 6.67; H, 6.25.
ACKNOWLEDGMENTS
The authors thank the Natural Science Foundation of Hunan Province (No.
06JJ50016) and the Scientific Research Foundation for the Returned Overseas Chi-
nese Scholars of the State Education Ministry for the financial support of this work.
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