One pot synthesis of [1,3]-oxazine and [1,3]-thiazine derivatives under thermal and microwave conditions

Article abstract of DOI:10.1002/jhet.280

(Chemical Equation Presented) A simple and efficient synthesis of substituted benzo [1,3] oxazine and benzo [1,3] thiazine derivatives under conventional heating, as well as microwave irradiation is reported. The compounds were obtained by the reaction of electron rich phenols, formaldehyde, and aromatic amines in methanol. Reactions which take 12-16 hr under conventional heating were successfully completed within a few minutes under microwave irradiation (solventless) with moderate to excellent yields.

Full text of DOI:10.1002/jhet.280

January 2010
One Pot Synthesis of [1,3]-Oxazine and [1,3]-Thiazine
Derivatives Under Thermal and Microwave Conditions
125
S. Tumtin,a I. T. Phucho,a A. Nongpiur,a R. Nongrum,a J. N. Vishwakarma,b
B. Myrboh,a and R. L. Nongkhlawa*
aDepartment of Chemistry, North-Eastern Hill University, Shillong, Meghalaya 793022, India
bOrganic Chemistry Research Laboratory, Department of Chemistry, St Anthony’s College,
Shillong, Meghalaya 793001, India
*E-mail: rlnongkhlaw@nehu.ac.in
Received June 8, 2009
DOI 10.1002/jhet.280
Published online 5 January 2010 in Wiley InterScience (www.interscience.wiley.com).
A simple and efficient synthesis of substituted benzo [1,3] oxazine and benzo [1,3] thiazine deriva-
tives under conventional heating, as well as microwave irradiation is reported. The compounds were
obtained by the reaction of electron rich phenols, formaldehyde, and aromatic amines in methanol.
Reactions which take 12–16 hr under conventional heating were successfully completed within a few
minutes under microwave irradiation (solventless) with moderate to excellent yields.
J. Heterocyclic Chem., 47, 125 (2010).
INTRODUCTION
be attractive scaffolds for exploiting chemical diversity.
Previously, napth-1, 3-oxazine derivatives have been
reported using 2-napthol and various substituted aryl
and heteroaryl aldehydes in the presence of dry metha-
nolic ammonia [18–20]. In view of the importance of
substituted [1,3]-oxazines and [1,3]-thiazines, we have
initiated a programme for the development of simpler
and more convenient methods for preparing heterocyclic
systems with high efficacy.
Development of novel synthetic methods for the con-
struction of new analogs of bioactive heterocyclic com-
pounds represents a major challenge in synthetic organic
and medicinal chemistry. The importance of [1,3]-oxa-
zines and [1,3]-thiazines in biological systems has
attracted great interest because of their medicinal and
pharmacological characteristics [1]. Many compounds
containing [1,3]-oxazine moiety have found wide bio-
logical activities such as being anticancer [2], analgesic
[3], antifungal [3], antitubercular [4], antihypertensive
[5], antithromobotic [6], antiulcer [7], anticonvulsant,
and antibacterial [8]. Moreover, certain kinds of [1,3]-
oxazines are of interest as photochromic compounds [9].
It is well known that the presence of a thiol function
in many enzymes (‘–SH enzymes’) is essential for their
enzyme activity. Likewise, incorporation of a thiol func-
tion in heterocycles, nucleosides or nucleotides has led
to a number of analogues possessing interesting biologi-
cal and therapeutic properties [10–17]. The [1,3]-thia-
zine nucleus is the active core of cephalosporins, which
are among the most widely used b-lactam antibiotics.
Owing to their chemical and biological interest, synthe-
sis of various unsubstituted and substituted 1,3-oxazine
and 1,3-thiazine derivatives is reported as they appear to
RESULTS AND DISCUSSION
Our present study mainly focuses on the synthesis of
various substituted [1,3]-oxazines and [1,3]-thiazines
(Scheme 1) and their relative comparison with micro-
1
wave assisted synthesis. H and 13C NMR spectra show
that the products were obtained in good purity. The sub-
stituents on benzyl ring did not have significant influ-
ence on the reaction time and yields. All reactions
which take many hours under conventional heating were
completed in 3–8 min under microwave irradiation with
enhanced yields. The results are presented in Table 1.
For these one-pot reactions of phenol, formaldehyde,
and aromatic amines, it is noteworthy that simultaneous
mixing resulted in poor yields [21]; however good
C
V
2010 HeteroCorporation

126
S. Tumtin, I. T. Phucho, A. Nongpiur, R. Nongrum, J. N. Vishwakarma, B. Myrboh,
and R. L. Nongkhlaw
Vol 47
Scheme 1
yields were obtained by the pretreatment of formalde-
hyde with the aromatic amines to form Schiff bases,
which upon treatment with phenol yielded the required
1,3-oxazines. Also it has been found that this reaction
worked well with formaldehyde but failed with other
aldehydes. Here we presume that steric hindrance stops
Table 1
Comparison between microwave irradiation (MWI) and conventional heating in the synthesis of compounds 2 (a–y).
2 (a-y)
MWI
Thermal
Products
R
H
Ar
X
O
Mp (ꢀC)
48
Time (hr)
14
Yield (%)
62
Press. (bar)
5
Power (watt)
80
Time (sec)
180
Yield (%)
71
2a
2b
2c
2d
2e
2f
H
O
O
O
O
O
O
O
O
O
O
O
52
55
66
69
42
54
57
68
67
54
63
14
16
15
15
15
16
16
15
14
15
16
66
57
63
59
62
64
63
65
66
65
60
5
6
6
8
6
5
7
7
8
6
7
80
85
200
180
180
210
180
180
225
185
180
220
200
72
68
70
68
70
73
70
71
72
73
68
H
H
90
H
80
2-CH3
2-CH3
2-CH3
2-CH3
2-CH3
3-CH3
3-CH3
90
2g
2h
2i
100
90
110
110
90
2j
2k
2l
90
(Continued)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

January 2010
One Pot Synthesis of [1,3]-Oxazine and [1,3]-Thiazine Derivatives under Thermal
and Microwave Conditions
127
Table 1
(Continued)
MWI
Thermal
Products
R
Ar
X
O
Mp (ꢀC)
75
Time (hr)
Yield (%)
Press. (bar)
7
Power (watt)
120
Time (sec)
180
Yield (%)
2m
2n
2o
2p
2q
2r
2s
3-CH3
3-CH3
3-CH3
4-CH3
4-CH3
4-CH3
4-CH3
4-CH3
H
15
66
72
71
69
70
71
72
72
68
67
68
68
71
67
O
O
O
O
O
O
O
S
78
72
40
62
68
65
66
38
43
45
56
58
16
15
16
15
16
16
16
15
16
16
16
16
65
62
62
63
64
64
60
58
59
61
63
58
8
9
120
90
185
250
190
195
190
200
210
180
200
210
215
240
7
90
6
80
7
90
8
100
120
100
110
100
110
120
2t
10
8
2u
2v
2w
2x
2y
H
S
8
H
S
9
H
S
9
H
S
10
the reaction at the open-chain Schiff bases without pro-
ceeding further to the cyclocondensation products. Reac-
tions with other aromatic aldehydes gave same results
[18,22]. Mcdonagh and Smith [23] reported the ring-
chain tautomerism of the condensation products of o-
hydroxybenzylamine with a number of aldehydes where
aliphatic aldehydes tend to give predominantly or exclu-
sively 1, 3-oxazines whereas aromatic aldehydes tend to
give predominantly open chain structures (Schiff bases).
Hence, it suggests that the Schiff bases formed are quite
stable and do not react further even with increasing
reaction time as well as temperature. In course of our
study, it has been found that electron donating substitu-
ents on the alcohol, as well as the aromatic primary
amines favour the reactions to give the desired products.
All the observations in both conventional as well as
microwave synthesis are similar except in the reaction
time and yield. This clearly indicates the advantages of
microwave chemistry which is fast developing as a con-
venient and ecofriendly mode of synthesis.
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128
S. Tumtin, I. T. Phucho, A. Nongpiur, R. Nongrum, J. N. Vishwakarma, B. Myrboh,
and R. L. Nongkhlaw
Vol 47
3,4-Dihydro-3-o-tolyl-2H-benzo[e][1,3]oxazine
(2b). mp
In summary, the aforementioned protocol reports the
52ꢀC, IR (KBr): 3037 (ArACAH), 1596 (C¼¼C), 1227
conventional and microwave synthesis of 1, 3-oxazines,
as well as a few numbers of 1, 3-thiazines from simple
and easily available starting materials in which micro-
wave synthesis is preferred as an alternative mode of
reactions. This microwave induced procedure offers sev-
eral advantages including operational simplicity, high
yields, simple work up and reactions are completed
within short time.
(ArACAO), 1084 (ACH2AO), 1372 (ArACAN) cmꢁ1 1H
.
NMR (CDCl3): d 2.24 (s, 3H, CH3), 4.55 (s, 2H, CH2), 5.33
(s, 2H, CH2), 6.65–7.11 (m, 8H, ArH). 13C NMR (CDCl3): d
18.7, 58.3, 79.6, 115.1, 115.9, 118.5, 121.3, 122.7, 127.4,
127.9, 128.6, 129.8, 130.6, 148.0, 157.6. MS: m/z ¼225 (Mþ).
Anal. Calcd. For C15H15NO: C, 79.97; H, 6.71; N, 6.22%.
Found: C, 79.99; H, 6.75; N, 6.18%.
3,4-Dihydro-3-m-tolyl-2H-benzo[e][1,3]oxazine
(2c). mp
55ꢀC, IR (KBr): 3035 (ArACAH), 1597 (C¼¼C), 1226
(ArACAO), 1079 (ACH2AO), 1373 (ArACAN) cmꢁ1 1H
.
NMR (CDCl3): d 2.34 (s, 3H, CH3), 4.60 (s, 2H, CH2), 5.41
(s, 2H, CH2), 6.39–7.02 (m, 8H, ArH). 13C NMR (CDCl3): d
18.4, 55.1, 78.9, 110.7, 115.2, 115.8, 118.4, 120.7, 123.0,
127.8, 129.8, 130.2, 138.8, 147.9, 157.4. MS: m/z ¼225 (Mþ).
Anal. Calcd. For C15H15NO: C, 79.97; H, 6.71; N, 6.22%.
Found: C, 79.98; H, 6.74; N, 6.19%.
EXPERIMENTAL SECTION
Microwave reactions were carried out in a CEM Discover
Benchmate microwave digester. Melting points were deter-
mined in open capillary tubes with a Thomas-Hoover appara-
tus and are uncorrected. Infrared spectra were recorded on a
BOMEM DA-8 FTIR instrument and the frequencies are
3,4-Dihydro-3-p-tolyl-2H-benzo[e][1,3]oxazine
(2d). mp
66ꢀC, IR (KBr): 3037 (ArACAH), 1597 (C¼¼C), 1228
(ArACAO), 1088 (ACH2AO), 1371 (ArACAN) cmꢁ1 1H
.
1
expressed in cmꢁ1. H and 13C NMR (400 MHz) spectra were
NMR (CDCl3): d 2.35 (s, 3H, CH3), 4.55 (s, 2H, CH2), 5.40
(s, 2H, CH2), 6.47–7.10 (m, 8H, ArH). 13C NMR (CDCl3): d
23.2, 55.7, 79.2, 113.7, 114.6, 114.8, 120.4, 123.7, 126.0,
128.4, 129.6, 130.7, 132.8, 145.9, 155.4. MS: m/z ¼225 (Mþ).
Anal. Calcd. For C15H15NO: C, 79.97; H, 6.71; N, 6.22%.
Found: C, 80.01; H, 6.67; N, 6.26%.
recorded on a Bruker Avance II-400 spectrometer using CDCl3
as the solvent. Chemical shifts are reported in ppm downfield
from internal tetramethylsilane and are given on the d scale.
Mass spectral data were obtained with a JEOL D-300 (EI)
mass spectrometer. Elemental analyses were carried out on a
Heraeus CHN-O-Rapid analyzer. All compounds give satisfac-
tory elemental analyses within 6 0.4% of the theoretical val-
ues. All reactions were monitored by TLC using precoated alu-
minum sheets (silica gel 60 F 254 0.2 mm thickness) and
developed in an iodine chamber or under UVGL-15 mineral
light 254 lamp. Column chromatographic separations were car-
ried out using ACME silica gel (60–120 mesh).
General procedure for conventional synthesis. To a well
stirred solution of the amine (1 mmol) in 5 mL of methanol,
formaldehyde (2 mmol) was added dropwise upon which a
thick white precipitate was formed. After stirring at room tem-
perature for about 15–20 min, phenol (1 mmol) dissolved in
methanol was added dropwise. The reaction mixture was then
refluxed at 70ꢀC for 14–16 hr. After the reaction was com-
pleted (monitored by TLC), the solvent was evaporated under
reduced pressure and the resultant mixture was purified by col-
umn chromatography to afford the pure compound.
3-(4-ethylphenyl)-3,4-dihydro-2H-benzo[e][1,3]oxazine (2e).
mp 69ꢀC, IR (KBr): 3036 (ArACAH), 1596 (C¼¼C), 1225
(ArACAO), 1087 (ACH2AO), 1368 (ArACAN) cmꢁ1 1H
.
NMR (CDCl3): d 1.26 (s, 3H, CH3), 2.63 (q, 2H, CH2), 4.60
(s, 2H, CH2), 5.42 (s, 2H, CH2), 6.54–7.02 (m, 8H, ArH). 13C
NMR (CDCl3): d 16.1, 35.2, 54.3, 88.9, 113.8, 114.2, 114.6,
120.5, 123.3, 127.1, 127.9, 128.7, 129.2, 129.7, 147.4, 156.8.
MS: m/z ¼239 (Mþ). Anal. Calcd. For C16H17NO: C, 80.30;
H, 7.16; N, 5.85%. Found: C, 80.34; H, 7.14; N, 5.88%.
3,4-Dihydro-8-methyl-3-phenyl-2H-benzo[e][1,3]oxazine
(2f). mp 42ꢀC, IR (KBr): 3024 (ArACAH), 1609 (C¼¼C),
1223 (ArACAO), 1085 (ACH2AO), 1336 (ArACAN) cmꢁ1
.
1H NMR (CDCl3): d 2.33 (s, 3H, CH3), 4.58 (s, 2H, CH2),
5.34 (s, 2H, CH2), 6.56–7.13 (m, 8H, ArH). 13C NMR
(CDCl3): d 15.3, 56.3, 79.9, 114.2, 114.6, 118.5, 121.3, 122.1,
124.9, 126.7, 128.2, 129.1, 129.7, 148.4, 157.6. MS: m/z ¼225
(Mþ). Anal. Calcd. For C15H15NO: C, 79.97; H, 6.71; N,
6.22%. Found: C, 80.00; H, 6.68; N, 6.24%.
General procedure for microwave assisted synthesis. A
mixture of the amine (1 mmol), formaldehyde (2 mmol) and
phenol (1 mmol) was irradiated in a microwave digester at 5–
10 bar, 80–120 W, 180–250 seconds without the use of sol-
vent. After the reaction was completed (monitored by TLC)
the resultant mixture was purified by column chromatography
to afford the pure compound.
3,4-Dihydro-8-methyl-3-o-tolyl-2H-benzo[e][1,3]oxazine
(2g). mp 54ꢀC, IR (KBr): 3025 (ArACAH), 1583 (C¼¼C),
1227 (ArACAO), 1085 (ACH2AO), 1367 (ArACAN) cmꢁ1
.
1H NMR (CDCl3): d 2.34 (s, 6H, CH3), 4.62 (s, 2H, CH2),
5.35 (s, 2H, CH2), 6.47–7.02 (m, 7H, ArH). 13C NMR
(CDCl3): d 15.3, 16.4, 58.3, 79.7, 114.7, 118.5, 120.5, 124.5,
126.3, 126.5, 127.4, 128.9, 126.7, 128.2, 146.6, 156.6. MS: m/
z ¼239 (Mþ). Anal. Calcd. For C16H17NO: C, 80.30; H, 7.16;
N, 5.85%. Found: C, 80.33; H, 7.13; N, 5.81%.
The physical and spectral data of the products are as
follows:
3,4-Dihydro-3-phenyl-2H-benzo[e][1,3]oxazine
(2a). mp
48ꢀC, IR (KBr): 3036 (ArACAH), 1597 (C¼¼C), 1227
(ArACAO), 1087 (ACH2AO), 1370 (ArACAN) cmꢁ1 1H
.
3,4-Dihydro-8-methyl-3-m-tolyl-2H-benzo[e][1,3]oxazine
(2h). mp 57ꢀC, IR (KBr): 3027 (ArACAH), 1590 (C¼¼C),
NMR (CDCl3): d 4.61 (s, 2H, CH2), 5.34 (s, 2H, CH2), 6.77–
7.02 (m, 9H, ArH). 13C NMR (CDCl3): d 49.9, 79.0, 115.4,
116.1, 117.9, 120.3, 125.4, 127.4, 128.8, 128.9, 128.9, 129.4,
147.9, 153.9. MS: m/z ¼211 (Mþ). Anal. Calcd. For
C14H13NO: C, 79.59; H, 6.20; N, 6.63%. Found: C, 79.63; H,
6.18; N, 6.67%.
1223 (ArACAO), 1087 (ACH2AO), 1375 (ArACAN) cmꢁ1
.
1H NMR (CDCl3): d 2.36 (s, 6H, CH3), 4.62 (s, 2H, CH2),
5.41 (s, 2H, CH2), 6.39–7.11 (m, 7H, ArH). 13C NMR
(CDCl3): d 15.7, 23.7, 58.3, 79.3, 111.4, 114.4, 118.7, 120.2,
121.4, 123.5, 126.6, 128.3, 129.4, 138.9, 148.6, 156.8. MS: m/
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

January 2010
One Pot Synthesis of [1,3]-Oxazine and [1,3]-Thiazine Derivatives under Thermal
and Microwave Conditions
129
z ¼ 239 (Mþ). Anal. Calcd. For C16H17NO: C, 80.30; H, 7.16;
N, 5.85%. Found: C, 80.34; H, 7.12; N, 5.82%.
4.62 (s, 2H, CH2), 5.38 (s, 2H, CH2), 6.54–7.02 (m, 7H, ArH).
13C NMR (CDCl3): d 14.1, 25.2, 32.6, 53.3, 78.9, 113.8, 114.2,
114.7, 120.5, 121.3, 127.1, 128.5, 128.7, 129.1, 137.7, 147.4,
156.8. MS: m/z ¼253 (Mþ). Anal. Calcd. For C17H19NO: C,
80.60; H, 7.56; N, 5.53%. Found: C, 80.64; H, 7.52; N, 5.55%.
3,4-Dihydro-6-methyl-3-phenyl-2H-benzo[e][1,3]oxazine
(2p). mp 40ꢀC, IR (KBr): 3110 (ArACAH), 1585 (C¼¼C),
1H NMR (CDCl3): d 2.34 (s, 3H, CH3), 4.59 (s, 2H, CH2),
5.34 (s, 2H, CH2), 6.62–7.11 (m, 8H, ArH). 13C NMR
(CDCl3): d 24.1, 53.2, 79.7, 114.6, 114.2, 115.7, 118.1, 122.2,
128.3, 129.0, 129.2, 129.8, 130.2, 148.5, 154.2. MS: m/z ¼225
(Mþ). Anal. Calcd. For C15H15NO: C, 79.97; H, 6.71; N,
6.22%. Found: C, 79.99; H, 6.75; N, 6.18%.
3,4-Dihydro-8-methyl-3-p-tolyl-2H-benzo[e][1,3]oxazine
(2i). mp 68ꢀC, IR (KBr): 3027 (ArACAH), 1581 (C¼¼C),
1220 (ArACAO), 1085 (ACH2AO), 1360 (ArACAN) cmꢁ1
.
1H NMR (CDCl3): d 2.32 (s, 6H, CH3), 4.58 (s, 2H, CH2),
5.40 (s, 2H, CH2), 6.47–7.10 (m, 7H, ArH). 13C NMR
(CDCl3): d 14.7, 25.7, 58.2, 78.9, 115.4, 115.4, 120.6, 122.4,
124.5, 126.7, 127.7, 128.6, 129.4, 130.8, 147.6, 155.8. MS: m/
z ¼ 239 (Mþ). Anal. Calcd. For C16H17NO: C, 80.30; H, 7.16;
N, 5.85%. Found: C, 80.34; H, 7.13; N, 5.87%.
1230 (ArACAO), 1085 (ACH2AO), 1366 (ArACAN) cmꢁ1
.
3-(4-ethylphenyl-3,4-dihydro-8-methyl-2H-benzo[e][1,3]
oxazine (2j). mp 67ꢀC, IR (KBr): 3024 (ArACAH), 1582
(C¼¼C), 1266 (ArACAO), 1087 (ACH2AO), 1362 (ArACAN)
cmꢁ1
.
1H NMR (CDCl3): d 1.26 (s, 3H, CH3), 2.33 (s, 3H,
3,4-Dihydro-6-methyl-3-o-tolyl-2H-benzo[e][1,3]oxazine
(2q). mp 62ꢀC, IR (KBr): 3037 (ArACAH), 1598 (C¼¼C),
CH3), 2.60 (q, 2H, CH2), 4.60 (s, 2H, CH2), 5.37 (s, 2H, CH2),
6.74–7.18 (m, 7H, ArH). 13C NMR (CDCl3): d 14.1, 15.2,
33.7, 56.9, 78.6, 114.5, 114.6, 120.5, 123.3, 126.1, 127.9,
129.7, 129.7, 130.1, 132.9, 147.4, 157.8. MS: m/z ¼253 (Mþ).
Anal. Calcd. For C17H19NO: C, 80.60; H, 7.56; N, 5.53%.
Found: C, 80.64; H, 7.57; N, 5.51%.
1228 (ArACAO), 1087 (ACH2AO), 1370 (ArACAN) cmꢁ1
.
1H NMR (CDCl3): d 2.34 (s, 6H, CH3), 4.41 (s, 2H, CH2),
5.32 (s, 2H, CH2), 6.71–7.10 (m, 7H, ArH). 13C NMR
(CDCl3): d 15.6, 24.1, 56.2, 79.2, 114.7, 114.9, 118.7, 122.4,
126.6, 127.3, 128.0, 129.2, 130.9, 130.8, 146.5, 155.1. Anal.
MS: m/z ¼239 (Mþ). Calcd. For C16H17NO: C, 80.30; H,
7.16; N, 5.85%. Found: C, 80.34; H, 7.13; N, 5.81%.
3,4-Dihydro-7-methyl-3-phenyl-2H-benzo[e][1,3]oxazine
(2k). mp 54ꢀC, IR (KBr): 3027 (ArACAH), 1601 (C¼¼C),
1227 (ArACAO), 1084 (ACH2AO), 1327 (ArACAN) cmꢁ1
.
3,4-Dihydro-6-methyl-3-m-tolyl-2H-benzo[e][1,3]oxazine
(2r). mp 68ꢀC, IR (KBr): 3041 (ArACAH), 1600 (C¼¼C),
1H NMR (CDCl3): d 2.64 (s, 3H, CH3), 4.59 (s, 2H, CH2),
5.34 (s, 2H, CH2), 6.62–7.09 (m, 8H, ArH). 13C NMR
(CDCl3): d 21.1, 50.2, 79.4, 114.6, 117.2, 117.7, 118.1, 118.2,
121.3, 126.0, 129.2, 129.2, 137.8, 148.4, 154.1. MS: m/z ¼225
(Mþ). Anal. Calcd. For C15H15NO: C, 79.97; H, 6.71; N,
6.22%. Found: C, 79.99; H, 6.75; N, 6.18%.
1237 (ArACAO), 1081 (ACH2AO), 1372 (ArACAN) cmꢁ1
.
1H NMR (CDCl3): d 2.34 (s, 6H, CH3), 4.51 (s, 2H, CH2),
5.33 (s, 2H, CH2), 6.68–7.10 (m, 7H, ArH). 13C NMR
(CDCl3): d 24.1, 24.1, 56.2, 79.6, 111.7, 114.7, 114.9, 118.4,
122.6, 128.5, 129.5, 130.3, 130.8, 139.0, 148.4, 155.1. MS: m/
z ¼239 (Mþ). Anal. Calcd. For C16H17NO: C, 80.30; H, 7.16;
N, 5.85%. Found: C, 80.33; H, 7.14; N, 5.82%.
3,4-Dihydro-7-methyl-3-o-tolyl-2H-benzo[e][1,3]oxazine
(2l). mp 63ꢀC, IR (KBr): 3026 (ArACAH), 1589 (C¼¼C),
1223 (ArACAO), 1087 (ACH2AO), 1351 (ArACAN) cmꢁ1
.
3,4-Dihydro-6-methyl-3-p-tolyl-2H-benzo[e][1,3]oxazine
(2s). mp 65ꢀC, IR (KBr): 3126 (ArACAH), 1580 (C¼¼C),
1H NMR (CDCl3): d 2.34 (s, 6H, CH3), 4.35 (s, 2H, CH2),
5.32 (s, 2H, CH2), 6.77–7.01 (m, 7H, ArH). 13C NMR
(CDCl3): d 15.6, 25.1, 56.2, 79.4, 112.6, 114.2, 117.7, 119.1,
126.2, 127.3, 128.5, 129.2, 136.2, 137.8, 148.4, 154.1. MS: m/
z ¼239 (Mþ). Anal. Calcd. For C16H17NO: C, 80.30; H, 7.16;
N, 5.85%. Found: C, 80.33; H, 7.13; N, 5.82%.
1227 (ArACAO), 1087 (ACH2AO), 1380 (ArACAN) cmꢁ1
.
1H NMR (CDCl3): d 2.23 (s, 6H, CH3), 4.55 (s, 2H, CH2),
5.29 (s, 2H, CH2), 6.61–7.02 (m, 7H, ArH). 13C NMR
(CDCl3): d 20.5, 21.1, 50.7, 116.8, 117.3, 117.7, 118.6, 119.0,
121.4, 126.5, 127.0, 128.4, 129.7, 129.9, 146.8, 152.8. MS: m/
z ¼238 (Mþ). Anal. Calcd. For C16H17NO: C, 80.30; H, 7.16;
N, 5.85%. Found: C, 80.34; H, 7.14; N, 5.81%.
3,4-Dihydro-7-methyl-3-m-tolyl-2H-benzo[e][1,3]oxazine
(2m). mp 75ꢀC, IR (KBr): 3023 (ArACAH), 1576 (C¼¼C),
1225 (ArACAO), 1084 (ACH2AO), 1327 (ArACAN) cmꢁ1
.
3-(4-ethylphenyl)-3,4-dihydro-6-methyl-2H-benzo[e][1,3]
oxazine (2t). mp 66ꢀC, IR (KBr): 3036 (ArACAH), 1599
(C¼¼C), 1227 (ArACAO), 1082 (ACH2AO), 1373 (ArACAN)
cmꢁ1. 1H NMR (CDCl3): d 1.25 (s, 3H, CH3), 2.60 (q, 2H, CH2),
1H NMR (CDCl3): d 2.34 (s, 6H, CH3), 4.45 (s, 2H, CH2),
5.33 (s, 2H, CH2), 6.65–7.00 (m, 7H, ArH). 13C NMR
(CDCl3): d 24.6, 25.1, 56.2, 79.2, 111.6, 112.2, 114.7, 119.1,
119.2, 121.3, 128.5, 129.2, 136.9, 139.8, 148.5, 156.1. MS: m/
z ¼239 (Mþ). Anal. Calcd. For C16H17NO: C, 80.30; H, 7.16;
N, 5.85%. Found: C, 80.34; H, 7.14; N, 5.81%.
4.62 (s, 2H, CH2), 5.32 (s, 2H, CH2), 6.54–7.01 (m, 7H, ArH). 13
C
NMR (CDCl3): d 14.8, 25.2, 32.5, 53.7, 78.0, 113.9, 114.2, 114.6,
122.5, 128.3, 128.6, 128.8, 129.7, 130.2, 130.7, 147.4, 156.8. MS:
m/z ¼253 (Mþ). Anal. Calcd. For C17H19NO: C, 80.60; H, 7.56;
N, 5.53%. Found: C, 80.64; H, 7.52; N, 5.55%.
3,4-Dihydro-7-methyl-3-p-tolyl-2H-benzo[e][1,3]oxazine
(2n). mp 78ꢀC, IR (KBr): 3036 (ArACAH), 1597 (C¼¼C),
1229 (ArACAO), 1082 (ACH2AO), 1370 (ArACAN) cmꢁ1
.
3,4-Dihydro-3-phenyl-2H-benzo[e][1,3]thiazine
(2u). mp
1H NMR (CDCl3): d 2.34 (s, 6H, CH3), 4.52 (s, 2H, CH2),
5.34 (s, 2H, CH2), 6.67–7.10 (m, 7H, ArH). 13C NMR
(CDCl3): d 24.6, 24.1, 56.2, 79.2, 112.2, 113.6, 114.7, 119.3,
121.2, 127.3, 128.5, 129.2, 130.2, 137.8, 146.4, 157.2. MS: m/
z ¼239 (Mþ). Anal. Calcd. For C16H17NO: C, 80.30; H, 7.16;
N, 5.85%. Found: C, 80.32; H, 7.15; N, 5.81%.
38ꢀC, IR (KBr): 3036 (ArACAH), 1596 (C¼¼C), 756 (C-S),
1367 (ArACAN) cmꢁ1 1H NMR (CDCl3): d 4.63 (s, 2H,
.
CH2), 4.88 (s, 2H, CH2), 6.81–7.03 (m, 9H, ArH). 13C NMR
(CDCl3): d 49.5, 61.7, 115.8, 116.1, 117.7, 120.3, 125.4,
127.4, 128.8, 128.9, 128.9, 129.4, 147.9, 153.9. MS: m/z ¼227
(Mþ). Anal. Calcd. For C14H13NS: C, 73.97; H, 5.76; N,
6.16%. Found: C, 74.01; H, 5.72; N, 6.18%.
3-(4-ethylphenyl)-3,4-dihydro-7-methyl-2H-benzo[e][1,3]
oxazine (2o). mp 72ꢀC, IR (KBr): 3041 (ArACAH), 1604
(C¼¼C), 1231 (ArACAO), 1085 (ACH2AO), 1365 (ArACAN)
cmꢁ1. 1H NMR (CDCl3): d 1.25 (s, 3H, CH3), 2.60 (q, 2H, CH2),
3,4-Dihydro-3-o-tolyl-2H-benzo[e][1,3]thiazine
(2v). mp
43ꢀC, IR (KBr): 3035 (ArACAH), 1597 (C¼¼C), 745 (CAS),
1391 (ArACAN) cmꢁ1 1H NMR (CDCl3): d 2.36 (s, 3H,
.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

130
S. Tumtin, I. T. Phucho, A. Nongpiur, R. Nongrum, J. N. Vishwakarma, B. Myrboh,
and R. L. Nongkhlaw
Vol 47
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deh, H. R. Tetrahedron 2006, 62, 3435.
CH3), 4.50 (s, 2H, CH2), 4.81 (s, 2H, CH2), 6.67–7.06 (m, 8H,
ArH). 13C NMR (CDCl3): d 14.9, 56.3, 62.7, 114.90 118.1,
125.0, 126.6, 126.9, 127.0, 127.8, 128.9, 130.1, 130.2, 147.3,
148.3. MS: m/z ¼241 (Mþ). Anal. Calcd. For C15H15NS: C,
74.65; H, 6.26; N, 5.80%. Found: C, 74.68; H, 6.24; N,
5.78%.
3,4-Dihydro-3-m-tolyl-2H-benzo[e][1,3]thiazine (2w). mp
45ꢀC, IR (KBr): 3041 (ArACAH), 1596 (C¼¼C), 756 (CAS),
1365 (ArACAN) cmꢁ1. 1H NMR (CDCl3): d 2.32 (s, 3H, CH3),
4.57 (s, 2H, CH2), 4.81 (s, 2H, CH2), 6.49–7.06 (m, 8H, ArH).
13C NMR (CDCl3): d 24.9, 57.3, 63.0, 111.9, 114.1, 118.0,
125.6, 126.9, 127.0, 128.1, 129.6, 130.1, 131.2, 139.3, 148.3.
MS: m/z ¼241 (Mþ). Anal. Calcd. For C15H15NS: C, 74.65; H,
6.26; N, 5.80%. Found: C, 74.68; H, 6.23; N, 5.76%.
3,4-Dihydro-3-p-tolyl-2H-benzo[e][1,3]thiazine (2x). mp
56ꢀC, IR (KBr): 3037 (ArACAH), 1597 (C¼¼C), 750 (CAS),
1385 (ArACAN) cmꢁ1. 1H NMR (CDCl3): d 2.38 (s, 3H, CH3),
4.59 (s, 2H, CH2), 4.86 (s, 2H, CH2), 6.81–7.03 (m, 8H, ArH).
13C NMR (CDCl3): d 22.1, 56.3, 67.7, 116.9, 120.1, 121.6,
124.9, 125.0, 126.8, 127.6, 128.6, 129.1, 132.2, 147.3, 150.3.
MS: m/z ¼241 (Mþ). Anal. Calcd. For C15H15NS: C, 74.65; H,
6.26; N, 5.80%. Found: C, 74.69; H, 6.23; N, 5.77%.
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walker, P. K. J Med Chem 1971, 14, 335.
3-(4-ethylphenyl)-3,4-dihydro-2H-benzo[e][1,3]thiazine
(2y). mp 58ꢀC, IR (KBr): 3035 (ArACAH), 1597 (C¼¼C), 748
[13] Holla, B. S.; Poojary, K. N.; Kalluraya, B.; Gowda, P. V. Il
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(CAS), 1367 (ArACAN) cmꢁ1 1H NMR (CDCl3): d 1.26 (t,
.
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3H, CH3), 2.56 (q, 2H, CH2), 4.59 (s, 2H, CH2), 4.82 (s, 2H,
CH2), 6.51–7.03 (m, 8H, ArH). 13C NMR (CDCl3): d 14.6,
32.1, 57.3, 66.7, 114.9, 115.1, 125.6, 126.9, 127.0, 128.2,
128.6, 128.9, 129.2, 130.3, 131.3, 146.7. MS: m/z ¼255 (Mþ).
Anal. Calcd. For C16H17NS: C, 75.25; H, 6.71; N, 5.48%.
Found: C, 75.29; H, 6.68; N, 5.49%.
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Acknowledgments. The authors thank UGC for the award of
Rajiv Gandhi National Fellowship and SAIF, NEHU, Shillong
for the spectral analysis.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet