Synthesis and study of isomeric benzo[1,4]oxazines and benzothiazolines by NMR spectroscopy and X-ray crystallography

Article abstract of DOI:10.1007/s007060050307

Reaction of 2-aminophenol and 2-aminothiophenol with 1-phenyl-1,2-propanedione yields a mixture of both possible isomeric benzo[1,4]oxazines and benzothiazolines which were characterized by NMR spectroscopy. In addition, the structures for 3-methyl-2-phenyl-2H-benzo[1,4]-oxazin-2-oI and 1-(2-phenyl-2,3-dihydro-benzothiazol-2-yl)-ethanone were established by X-ray diffraction analysis.

Full text of DOI:10.1007/s007060050307

Monatshefte fuÈr Chemie 130, 1481±1486 (1999)
Synthesis and Study of Isomeric
Benzo[1,4]oxazines and Benzothiazolines by
NMR Spectroscopy and X-Ray Crystallography
Ã
 Â
Departamento de Quõmica, Centro de Investigacion y de Estudios Avanzados del IPN, 07000 Mexico
Â
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Võctor Santes , Susana Rojas-Lima, Rosa L. Santillan, and Norberto Farfan
Â
Â
D. F., Mexico
Summary. Reaction of 2-aminophenol and 2-aminothiophenol with 1-phenyl-1,2-propanedione
yields a mixture of both possible isomeric benzo[1,4]oxazines and benzothiazolines which were
characterized by NMR spectroscopy. In addition, the structures for 3-methyl-2-phenyl-2H-
benzo[1,4]-oxazin-2-ol and 1-(2-phenyl-2,3-dihydro-benzothiazol-2-yl)-ethanone were established
by X-ray diffraction analysis.
Keywords. NMR; X-Ray; Benzo[1,4]oxazine; Benzothiazoline.
Synthese und Studium der isomeren Benzo[1,4]oxazine und Benzothiazine mit Hilfe
È
von NMR-Spektroskopie und Rontgenstrukturanalyse
Zusammenfassung. Reaktion von 2-Aminophenol und 2-Aminothiophenol mit 1-Phenyl-1,2-
È
propandion gibt eine Mischung der beiden moglichen isomeren Benzo[1,4]oxazine und
Benzothiazoline, die durch NMR-Spektroskopie charakterisiert wurden. DaruÈber hinaus wurden
die Strukturen von 3-Methyl-2-phenyl-2H-benzo[1,4]oxazin-2-ol und 1-(2-Phenyl-2,3-dihydro-
È
benzothiazol-2-yl)-ethanon durch Rontgenstrukturanalyse gesichert.
Introduction
It is well known that the condensation reaction of 2-aminothiophenol with glyoxal
or 2,3-butanedione affords 2,20-dibenzothiazolidines [1±2], whereas benzil yields
2-benzoyl-2-phenylbenzothiazolines [3]. Studies concerning various aspects of the
synthesis and chemistry of this interesting class of compounds have been
undertaken recently [4±11].
We now report a study concerning 3-methyl-2-phenyl-2H-benzo[1,4]-oxazin-2-
ol (1a), 2-methyl-3-phenyl-2H-benzo[1,4]-oxazin-2-ol (1b), (2-methyl-2,3-dihy-
dro-benzothiazol-2-yl)-phenyl-methanone (2a), and 1-(2-phenyl-2,3-dihydro-ben-
zothiazol-2-yl)-ethanone (2b) obtained from 2-aminophenol and 2-amino-
thiophenol with 1-phenyl-1,2-propanedione. In contrast to results described in
Ã
Corresponding author

1482
V. Santes et al.
the literature [5] it is shown that the reaction provides a mixture of isomers, the
major product being derived from an attack at the more reactive acetyl group.
Results and Discussion
The reaction of 2-aminophenol with 1-phenyl-1,2-propanedione led to a mixture of
the isomers 1a and 1b in a 3:2 ratio which was separated by crystallization
(Scheme 1). The 13C NMR spectra of 1a and 1b show that the chemical shifts for
the two compounds are very similar; however, the signals for C-4a, C-2, and CH3
in 1a are at 141.0, 94.0 and 22.3 ppm, whereas those for 1b are found at 136.2,
92.9, and 26.6 ppm. In the 1H NMR spectra the signals for the methyl groups are at
1
1.87 and 1.66 ppm for 1a and 1b. Unequivocal H and 13C spectroscopic assign-
ments for 1a and 1b was achieved by 2D correlated experiments. Although 1b has
1
been described in the literature [5], neither its H nor its 13C NMR spectra have
been reported. The structure for 1a was established by X-ray diffraction analysis
(Fig. 1) which shows that the molecule is present in a pseudo-chair conformation
where the phenyl group occupies a pseudo-equatorial and the hydroxyl group a
pseudo-axial position as expected for this kind of compounds [10].
Reaction of 2-aminothiophenol with 1-phenyl-1,2-propanedione provides a
mixture of (2-methyl-2,3-dihydro-benzothiazol-2-yl)-phenyl-methanone (2a) and
1-(2-phenyl-2,3-dihydro-benzothiazol-2-yl)-ethanone (2b) in a 6:1 ratio as shown
1
by H NMR (Scheme 2). Compound 2a could not be separated neither by
crystallization nor by columm chromatography; it was therefore characterized from
the spectrum of the reaction mixture. On the other hand, compound 2b was
obtained in quantitative yield by isomerization of 2a (Scheme 2).
It is interesting to note that the signals for CO, C-2, and the methyl group in the
13C NMR spectrum of 2a are at 197.4, 78.4, and 30.5 ppm, whereas those for 2b
are shifted to 202.7, 86.3, and 24.4 ppm. Complete assignment was achieved by 2D
correlated experiments and comparison with analogues described in a previous
work [6]. In addition, the mass spectra show the ion m/z ˆ 212 and m/z ˆ 150
corresponding to loss of CH3CO and PhCO groups in 2b and 2a. Examination of
Scheme 1

Isomeric Benzo[1,4]oxazines
1483
Scheme 2
Fig. 1. X-Ray structures of 1a and 2b
2b by single crystal X-ray crystallographic analysis con®rmed the proposed
structure (Fig. 1).
We conclude that, in contrast to the high stereoselectivity observed in
norephedrines and phenylglycinol, the reaction of 2-aminophenol and 2-
aminothiophenol with 1-phenyl-1,2-propanedione is not stereoselective, since the
two possible diastereomers are obtained. As expected, the major products for 2-
aminophenol derivatives correspond to imine formation at the methyl ketone as
observed in previous studies [9, 10]. In the case of 2-aminothiophenol, the

1484
V. Santes et al.
preferred products are of the benzothiazoline type structures. Nevertheless, (2-
methyl-2,3-dihydro-benzothiazol-2-yl)-phenyl-methanone (2a) was found to be
unstable, and after 24 hours it isomerizes to 1-(2-phenyl-2,3-dihydro-benzothiazol-
2-yl)-ethanone (2b) which is thermodynamically more stable.
Experimental
1H and 13C NMR spectra were recorded on Jeol-270 and Jeol Eclipse ‡400 spectrometers. Chemical
shifts (ppm) are relative to internal TMS, coupling constants are quoted in Hz. The HETCOR
standard pulse sequence, which incorporates quadrature detection in both domains, was used.
Infrared spectra were recorded on a Perkin Elmer 16F-PC FT-IR spectrophotometer. Mass spectra
were obtained with an HP 5989A mass spectrometer. Melting points were measured on a
Gallenkamp MFB-595 apparatus and are uncorrected. Elemental analyses were found to be in good
agreement with the calculated values. The X-ray crystallographic studies were done on an Enraf
Ê
Nonius CAD4 diffractometer, ꢀ(MoKꢁ) ˆ 0.71 A, graphite monochromator, T ˆ 293 K, !/2ꢂ scan,
range 2 < ꢂ < 25ꢀ. Corrections were made for Lorentz and polarization effects. The structures were
solved by direct methods using SHELXS-86 [12] and MOLEN. All nonhydrogen atoms were re®ned
anisotropically using full-matrix least squares (MOLEN [13] for 1a and CRYSTALS [14] for 2b),
and hydrogen atoms were found by difference Fourier maps and re®ned with an overall isotropic
thermal parameter. Crystal data, collection, and re®nement parameters are given in Table 1.
Additional information has been deposited at the Cambridge Crystallographic Data Centre (CCDC
120973 for 1a, CCDC 120974 for 2b).
Preparation of compounds 1a and 1b
To a solution of 0.5 g 2-aminophenol (4.58 mmol) in 20 cm3 of THF, 0.61 cm3 1-phenyl-1,2-
propanedione (4.58 mmol) were added. After stirring at 78 ꢀC for 8 h the solvent was removed
Table 1. Crystallographic data for 1a and 2b.
1a
2b
Formula
C15H13NO2
239.28
0.50Â0.30Â0.20
monoclinic
P 21/c
C15H13NOS
255.33
1
Fw (g Á mol
)
Crystal size (mm)
Crystal system
Space group
0.25Â0.15Â0.10
monoclinic
P 21/n
Ê
a (A)
Ê
b (A)
Ê
c (A)
8.849(1)
12.305(1)
11.474(1)
96.55(7)
1241.2(2)
4
11.865(2)
7.3778(4)
14.202(2)
103.82(1)
1266.2(3)
4
ꢃ (deg)
Ê 3
V (A )
Z
Dcalcd (g/cm3)
No. collecd. r¯ns.
No. of ind. r¯ns.
No. of obsd. r¯ns.
No. of parameters
R
1.28
1.40
2158
2783
2158
2474
1299
1610
216
204
0.037
0.035
Rw
0.048
0.032

Isomeric Benzo[1,4]oxazines
1485
under vacuum. The resulting precipitate was washed with ethanol to give 0.75 g (80%) of a mixture
of 1a and 1b in a 3:2 ratio. Separation was carried out by recrystallization using a mixture of
methanol/hexane.
3-Methyl-2-phenyl-2H-benzo[1,4]-oxazin-2-ol (1a; C15H13NO2)
M.p.: 170±172ꢀC; 1H NMR (270 MHz, ꢄ, DMSO-d6): 8.01 (1H, s, OH), 7.54 (1H, dd, J ˆ 7.9,
1.3 Hz, H-o), 7.49±7.40 (3H, m, H-m,p), 7.37 (1H, dd, J ˆ 7.9, 1.3 Hz, H-5), 7.20 (1H, td, J ˆ 7.9,
1.3 Hz, H-7), 7.03 (1H, td, J ˆ 7.9, 1.3 Hz, H-6), 6.96 (1H, dd, J ˆ 7.9, 1.3 Hz, H-8), 1.87 (3H, s,
CH3) ppm; 13C NMR (67.80 MHz, ꢄ, DMSO-d6): 162.3 (C-3), 145.0 (C-8a), 141.0 (C-4a), 131.0 (C-
i), 128.7 (C-p), 128.2 (C-7), 128.1 (C-m), 126.6 (C-5), 126.1 (C-o), 121.5 (C-6), 115.9 (C-8), 94.0
‡
(C-2), 22.3 (C-CH3) ppm; MS: m/z (%) ˆ 239 (M , 7), 224 (1), 211 (3), 196 (100), 167 (4), 134 (30),
104 (13), 103 (2), 91 (2), 90 (1), 89(1), 78 (3), 77 (19), 65 (25), 64 (4); IR (KBr): ꢅ~ˆ 3654, 3442
1
(OH), 3350, 3000, 2788, 2000, 1700, 1652 (C=N), 1595, 1575, 1470, 1125, 1200, 1075, 1020 cm
.
2-Methyl-3-phenyl-2H-benzo[1,4]-oxazin-2-ol (1b; C15H13NO2)
1
M.p.: 120±123ꢀC (Ref. [5]: 120±122ꢀC; H NMR (270 MHz, ꢄ, DMSO-d6): 7.86 (1H, s, OH), 7.84
(1H, dd, J ˆ 6.59, 1.3 Hz, H-o), 7.47±7.49 (3H, m, H-m, p), 7.44 (1H, dd, J ˆ 7.9, 1.3 Hz, H-5), 7.24
(1H, td, J ˆ 7.9, 1.3 Hz, H-7), 7.04 (1H, td, J ˆ 7.9, 1.3 Hz, H-6), 6.99 (1H, dd, J ˆ 7.9, 1.3 Hz, H-8),
1.66 (3H, s, CH3) ppm; 13C NMR (67.80 MHz, ꢄ, DMSO-d6): 161.6 (C-3), 145.1 (C-8a), 136.2 (C-
4a), 132.0 (C-i), 129.9 (C-p), 128.8 (C-7), 128.2 (C-o), 128.0 (C-m), 127.3 (C-5), 121.6 (C-6), 116.1
‡
(C-8), 92.9 (C-2), 26.6 (C-CH3) ppm; MS: m/z (%) ˆ 239 (M , 6), 222 (3), 196 (100), 167 (4), 104
(11), 103 (1), 93 (10), 92 (1), 77 (12), 65 (20), 64 (3); IR (KBr): ꢅ~ˆ 3628 (OH), 3158, 1670, 1616,
1
1576, 1456, 1254 cm
.
Preparation of compounds 2a and 2b
To a solution of 1.07 cm3 2-aminothiophenol (10 mmol) in 10 cm3 THF, 1.3 cm3 1-phenyl-1,2-
propanedione (10 mmol) were added at 0ꢀC. After being stirring for 3 h, the solvent was removed
1
under vacuum affording 2.42 g (95%) of a mixture of 2a and 2b in a 6:1 ratio as determined by H
NMR.
(2-Methyl-2,3-dihydro-benzothiazol-2-yl)-phenyl-methanone (2a; C15H12NSO)
1H NMR (400 MHz, ꢄ, CDCl3): 8.07 (1H, d, J ˆ 7.3, Hz, H-o), 7.58 (1H, t, J ˆ 7.3 Hz, H-m), 7.48
(1H, t, J ˆ 7.3 Hz, H-p), 7.05 (1H, d, J ˆ 7.8, Hz, H-4), 7.01 (1H, t, J ˆ 7.3 Hz, H-5), 6.83 (1H, d,
J ˆ 7.3 Hz, H-6), 6.80 (1H, d, J ˆ 7.3 Hz, H-7), 2.05 (3H, s, CH3) ppm; 13C NMR (100.5 MHz, ꢄ,
CDCl3): 197.4 (C=O), 145.5 (C-3a), 136.9 (C-i), 131.9 (C-p), 131.6 (C-7a),129.9 (C-o), 128.5 (C-m),
126.0 (C-5), 121.5 (C-7), 121.3 (C-6), 112.1 (C-4), 78.4 (C-2), 30.5 (C-CH3) ppm; MS: m/z
‡
(%) ˆ 255 (M , 1), 150 (100), 109 (30).
1-(2-Phenyl-2,3-dihydro-benzothiazol-2-yl)-ethanone (2b; C15H12NSO)
M.p.: 153±155ꢀC; 1H NMR (270 MHz, ꢄ, CDCl3): 7.59 (1H, dt, J ˆ 7.6, 1 Hz, H-o), 7.44±7.32 (3H,
m, H-m,p), 7.08 (1H, dd, J ˆ 8, 1 Hz, H-4), 6.97 (1H, td, J ˆ 8, 1 Hz, H-5), 6.80 (1H, td, J ˆ 8, 1, Hz,
H-6), 6.79 (1H, dd, J ˆ 8, 1 Hz, H-7), 2.21 (3H, s, CH3) ppm; 13C NMR (67.8 MHz, ꢄ, CDCl3): 202.7
(C=O), 145.9 (C-3a), 138.8 (C-i), 128.9 (C-m, p), 127.0 (C-o), 126.1 (C-5), 125.0 (C-7a), 121.7 (C-
‡
7), 121.4 (C-6), 112.0 (C-4), 86.3 (C-2), 24.4, (C-CH3) ppm; MS: m/z (%) ˆ 255 (M , 1), 212 (100),
1
109 (21), 135 (7), 77 (7); IR (KBr) ꢅ~ˆ 3338, 1460, 1580, 1702, 1446, 1178, 724, 640 cm
.

1486
V. Santes et al.: Isomeric Benzo[1,4]oxazines
Acknowledgements
È
We are grateful to CONACYT for ®nancial support and to Prof. Dr. H. Noth for elemental analyses.
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Received April 7, 1999. Accepted (revised) May 20, 1999