Synthesis and structure determination of 2,3-diphenyl-2H-1,4-benzoxazin-2- ol

Article abstract of DOI:10.3184/030823407X247776

A stable hemiacetal, 2,3-diphenyl-2H-1,4-benzoxazin-2-ol, was isolated as the main product from the reaction of benzil and o-aminophenol in THF. The structure of the product is confirmed by elemental analysis, common spectroscopic methods, and X-ray cryst

Full text of DOI:10.3184/030823407X247776

548 RESEARCH PAPER
SEPTEMBER, 548–551
JOURNAL OF CHEMICAL RESEARCH 2007
Synthesis and structure determination of 2,3-diphenyl-2H-1,4-benzoxazin-2-ol
Katayoun Marjani, Jafar Asgarian and Mohsen Mousavi*
Faculty of Chemistry, Teacher Training University, 49 Dr Mofatteh St., Tehran-15614, Iran
A stable hemiacetal, 2,3-diphenyl-2H-1,4-benzoxazin-2-ol, was isolated as the main product from the reaction
of benzil and o-aminophenol in THF. The structure of the product is confirmed by elemental analysis, common
spectroscopic methods, and X-ray crystallographic analysis.
Keywords: benzoxazine, hemiacetal, crystal structure, Schiff-base
Condensation of α-diketones and primary amines is an
Ph
Ph
interesting synthetic subject, especially in coordination
chemistry1 since the resulting products, α-diSchiff-bases,
are potentially bidentate ligands providing various options to
modify electronic and steric effect and coordination properties
of nitrogen atoms. Such ligands may be more interesting when
having other N, O or S atoms in the suitable position on amine
molecule for coordination to the metal ions simultaneously
with N atoms of Schiff-base. Therefore, condensation of
o-aminophenol, 2-aminoethanol and their related compound,
possessing S or N atoms instead of O, with α-diketones has
often been the subject of synthetic works.2-6
However, there have always been uncertainties in the
structure determination of products in these reactions. Some
researchers have identified the products of these reactions
as open chain Schiff-bases, and have even reported some of
their complexes with metal ions,3-5 but others have considered
the product of the same or very similar reactions as five
or six membered heterocyclic compounds.6-9 These later
identifications are more reliable since they often were based
on more detailed spectroscopic studies and even sometimes on
X-ray crystallography.7,9 Note that some researchers believed
in a kind of tautomeric equilibration in solution between these
heterocyclic structures and their related open chain Schiff-
bases, especially in the presence of metal ions or in alkaline
media.5-8
Ph
O
HN
HN
N
N
O
Ph
OH
HO
1
2
Ph
O
H
N
Ph
Ph
N
O
N
H
O
Ph
OH
4
3
Scheme 1
O
H
N
H
R
R
O
O
O
N
H
O
N
5, R=H or CH3
6
In the case of condensation of benzil and o-aminophenol
itself, previous researchers have been reported different
products 1,10 2,3 3,4 and 47 (Scheme 1).
Scheme 2
Then the solvent was reduced to half, giving a yellowish crystalline
product that was collected by filtration, washed with cold THF
(3 cm3), and dried in vacuo to give 6 (3 g, 73%), m.p. = 142–144°C.
Method (b): A solution of 2.1 g (10 mmol) benzil and 2.18 g
(20 mmol) o-aminophenol in THF (50 cm3) was refluxed for a week.
The solvent was evaporated and a dark precipitate was washed
several times with petroleum ether. The product was extracted from
the residue by chloroform and recrystalised from THF, and gave 6
(2.7 g, 66%).
The alternative structure 5, shown in Scheme 2, is also
suggested for the product of some closely related reactions.6
Here we report a completely different result; a hemiacetal
hydrogen bonded to THF in equimolar ratio (structure 6
shown in Scheme 2) which was isolated as main product of
the reaction between benzil and o-aminophenol in THF and
identified by elemental analysis, IR, 1H NMR, 13C NMR, and
mass spectroscopy, as well as X-ray crystallographic analysis.
Spectroscopy
Elemental analysis: found
Experimental
General method
C
77.11,
H
6.08,
N
3.75,
C24H23NO3(373.17) requires C 77.19, H 6.21, N 3.75; IR (KBr):
3140 cm-1, broad (OH), 1610 (C=N), 1047 (C–O); Mass m/z (%):
molecular ion was not observed, 196(94) [Ph–C=N–o–C6H4–OH]+,
105(14) [Ph–C=O]+, 43(100) [CH3C=O]+(this fragment probably
originated from THF); 13C NMR(acetone-d6): δ 160.5 ppm (for C
double bonded to N), 145.4, 142.4, 137.3, 132.7, 130.3, 129.9, 129.7,
129.3, 128.8, 128.7, 128.4, 127.2, 122.7, 116.9 ppm (14 peaks for
Benzil and THF were purchased from Merck and used without
further purification; o-aminophenol was also purchased from Merck
and purified either by sublimation or several recrystallisations from
toluene before use. Elemental analysis (CHN) was obtained on
Heraeus CHN–O– Rapid Analyser. IR spectrum was recorded with
a Perkin-Elmer 843 spectrometer. The mass spectrum was recorded
by Finingan-MAT8430 70eV. H NMR and 13C NMR spectra were
1
1
carbons of aromatic rings), and 116.9 ppm (for hemiacetalic C); H
recorded on a Bruker Avance-300 MHz spectrometer employing
NMR(acetone-d6): δ 7.83(d, 2H), 7.62(d, 2H), 7.53(d, 1H), 7.45(s,
1H), 7.3(m, 7H), 7.1(t, 1H), 6.9(d, 1H), and THF peaks at δ 1.75 and
3.6 ppm; 13C NMR(CDCl3): the same spectrum as in acetone, except
six additional small peaks at 27°C which increases to 16 additional
peaks at 60°C in the aromatic region from δ 115 to 152 ppm; 1H
NMR(CDCl3): the same spectrum as in acetone, except for a shift for
hydroxyl protons to δ 5 ppm and its broadness, and some additional
small peaks beginning at δ 8.23 ppm, ending at δ 6.6 ppm whose area
percent increases in higher temperatures (approximately from 20 to
30% from hole under peaks area at 27 and 60°C, respectively.
tetramethylsilane as an internal reference.
Synthesis of 2,3-diphenyl-2H-1,4-benzoxazin-2-ol, 6
Method (a):Asolution of 2.1 g (10 mmol) benzil and 2.18 g (20 mmol)
o-aminophenol in THF (20 cm3) was placed in an Erlenmeyer flask
(100 cm3) fitted by a simple glass funnel and irradiated in a domestic
microwave oven under 100 W power for 30 h (From time to time
some solvent was added to save the approximate volume of solvent).
* Correspondent. E-mail address: moooosavi@yahoo.com
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JOURNAL OF CHEMICAL RESEARCH 2007 549
X-ray crystallography
Crystals of 6 were grown by slow evaporation from THF. Diffraction
data were collected on a Bruker SMART 1000 CCD area detector
diffractometer with graphite monochromated MoKα. radiation.
The structure was solved and refined with the SHELXTL version
5.1 programs. Crystallographic data and selected geometry parameters
are presented in Tables 1 and 2, respectively. An ORTEP plot and
atom numbering is given in Fig. 1.
The structure of compound 6 is composed of three planar aromatic
rings, attached to a six membered oxazine ring, which deviates from
planarity due to the presence of a hemiacetal sp3 carbon atom and
also an oxygen atom in this ring (Fig. 1). As a result the oxazine
ring, at the centre of the molecule, has a half chair conformation
(Fig. 2). In this ring, hemiacetal carbon atom retained its tetrahedral
geometry. Bond angles around this atom are close to normal sp3
bond angles. The benzoxazine is nearly planar, but the plane of the
two phenyl substituents bonded to the imine and hemiacetal carbon
atoms are rotated from this plane by angles of about –34° and 77.8°,
respectively (Table 2).
The crystal structure of 6 in the solid state is stabilised by
strong intermolecular hydrogen bonding between the O–H
group of hemiacetal and the oxygen atom of THF molecules (Fig. 3).
The packing of the molecules in the solid state is also stabilised by
C–H…π intermolecular interactions (Fig. 4). Details of hydrogen
bonding and C–H…π interactions are summarised in Tables 3 and 4,
respectively.
Fig.1 ORTEP plot of 6 by ellipsoids at 50% probability.
Result and discussion
Reaction of benzil and o-aminophenol in THF was a clean
reaction, either in microwave oven under 100 w radiation
power or in reflux condition at 70°C or lower, and product
was isolated in a simple way. However, raising either radiation
power, or refluxing temperature, in each case respectively,
was resulted to a mixture of products. Furthermore, applying
the same reaction condition for condensation of benzil and
Table 1 Crystal data and structure refinement
Empirical formula
Formula weight
Temperature
C24H23NO3
373.43
120(2) K
0.71073 Å
Monoclinic
P 21/c
Wavelength
Crystal system
Space group
Unit cell dimensions
a = 10.2545(8) Å
b = 10.7973(8) Å
a = 90°
b = 101.408(6)°
c = 17.7458(14) Å g = 90°
volume
1926.0(3) Å3
Z
4
Density (calculated)
Absorption coefficient
F(000)
Crystal size
Theta range for data collection
Index ranges
1.288 Mg/m3
0.085 mm-1
792
0.3 x 0.25 x 0.25 mm
2.03 to 27.00°
–13 < = h< = 12, –13< = k< = 13, –22< = 1< = 22
18027
4177 [R(int) = 0.0469]
99.3%
Reflections collected
Independent reflections
Completeness to theta = 27.00°
Absorption correction
Refinement method
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [for 2477 rfln with I>2 sigma (I)]
R indices (all data)
semi-empirical from equivalents
Full-matrix least-squares on F2
4177/0/253
1.003
R1 = 0.0590, wR2 = 0.1314
R1 = 0.0968, wR2 = 0.1461
0.896 and -0.295 e. Å-3
Largest diff. peak and hole
Table 2 selected bond lengths [Å] and bond angles [°]
O(1)–C(8)
1.355(3)
1.517(3)
1.412(3)
1.518(3)
1.386(3)
102.78(17)
109.38(18)
116.9(2)
23.0(3)
N(1)–C(2)
O(1)–C(1)
C(1)–C(9)
C(3)–C(8)
1.273(3)
1.468(3)
1.511(3)
1.406(3)
C(1)–C(2)
N(1)–C(3)
C(2)–C(15)
O(2)–C(1)
O(1)–C(1)–C(9)
O(1)–C(1)–C(2)
C(2)–N(1)–C(3)
O(1)–C(1)–C(2)–N(1)
O(1)–C(1)–C(9)–C(14)
C(8)–O(1)–C(1)
O(2)–C(1)–C(9)
N(1)–C(2)–C(1)
118.70(17)
110.77(18)
125.9(2)
–34.0(3)
–160.67(19)
N(1)–C(2(–C(15)–C(20)
C(1)–O(1)–C(8)–C(7)
77.8(2)
Table 3 Hydrogen bonds for 6 [Å and°]
D-H…A
O(2)-H(2O)…O(1S)
d(D-H)
0.97
d(D…A)
1.70
d(D…A)
2.653(2)
<(DHA)
170
Symmetry transformations used to generate equivalent atoms: x-1,y,z.
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550 JOURNAL OF CHEMICAL RESEARCH 2007
Table 4 X–H...Cg (Pi-ring) interactions for 6 [Å and °]
X–H (I)…Cg (J)
d (H…Cg)
<(X-H…Cg)
141
d(X…Cg)
3.797(3)
3.678(2)
3.774(3)
C (1S)–H (1SB)…Cg (2) (ii)
C (12)–H (12A)…Cg (2) (iii)
C (18)–H (18A)…Cg (3) (IV)
3.00
2.92
2.95
139
148
Symmetry transformations used to generate equivalent atoms: (ii) 1 + X, Y, Z; (iii) 1–X, 1/2 + Y, 1/2–Z; (IV) X, 3/2–Y,–1/2 + Z
The Cg (J) refers to the ring centre-of-gravity.
aromatic amines possessing general formula 7 (Scheme 3),
led to dark oil mixtures, which was not precipitated after the
usual solvent treatments.
On the other hand, the reaction between benzil and
o-aminophenol either in benzene, toluene, or chloroform
resulted in complex mixtures.
As a simple view, condensation of primary amines with α-
diketones has two potential products, mono-imine and di-imine,
and depends on the molar ratio of of starting material. Thus,
in the condensation of benzil and o-aminophenol, either Schiff
base 2 or 3 is expected to be the main product of the reaction.
But it has been shown earlier5-9 in similar reactions that the
first hypothetically formed imines will be issued to further
cyclisation reaction by inter-molecular nucleophilic attack of
phenolic oxygen on carbon atom of imine group, so one of
the heterocyclic compounds 4 or 6 may be isolated. However,
when we have run the reaction in THF either in 1:1, 2:1 or even
higher molar ratio of o-aminophenol to benzil, we only isolated
the hemiacetal 6. This observation was rather unexpected
because earlier researchers have not reported this product,
and also hemiacetals are usually considered as unstable and
unseparateable products; however, more investigation revealed
that Murase6 and Belgodere8 had earlier obtained some similar
hemiacetal products in condensation of o-aminophenol and
some α-dicarbonyl compounds.
Fig. 2 Half chair conformation of benzoxazine ring and
tetrahedral geometry of sp3 carbon.
Conclusion
These observations lead us to assume that the cyclisation of
imine to benzoxazine, which could not take place in amines
7 (Scheme 3) except for o-aminophenol, is the motivational
force of the reaction. Furthermore formation of 4 or 6, beyond
the molar ratio of starting materials, strongly depends on the
nature of solvent. THF, capable of hydrogen bonding with
hydroxyl group, may stabilise the hemiacetalin structure
of monobenzoxazine 6 and prevent it from further reaction
to form 4, because formation of hemiacetal inactivates the
carbonyl group against nucleophilic attack by o-aminophenol.
This is unless an equilibrium, as shown in Scheme 4, opens
the benzoxazine ring and liberates the carbonyl group for
further reaction.
Fig. 3 A view of molecular packing, hydrogen bonds are
shown in dashed lines.
THF, by stabilisation of hemiacetal, prevents the equilibrium
proceeding and consequently hemiacetal 6 becomes the final
product. Solvents such as benzene, toluene and chloroform are
not capable of behaving like this. Therefore in such solvents,
unstable hemiacetal falls in equilibration with open chain
keto-imine and the carbonyl group becomes free for further
nucleophilic attack by o-aminophenol; so with a proper molar
ratio of the starting material, the final product would be
benzoxazinobenzoxazine 4. The mechanism of stabilisation
of hemiacetal by THF apparently occurs mainly through
hydrogen bonding between lone pair electrons of solvent and
acidic hydrogen of hemiacetal (Fig. 3).
Fig. 4 C-H… π interactions in the solid state of 6.
NH2
X= m-OH, P-OH, o-OMe, m-OMe, o-COOH,o-OCOCH3
X
7
Scheme 3
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JOURNAL OF CHEMICAL RESEARCH 2007 551
from the Cambridge Crystallographic Data Centre via www.
ccdc.cam.ac.uk/data-request/cif.
OH
Ph
OH
O
Ph
O
N
The authors wish to thank their Teacher Training University
for financial support.
Ph
N
Ph
not condensing
condensing
Received 26 June 2007; accepted 20 September 2007
Paper 07/4716 doi: 10.3184/030823407X247776
Scheme 4
Evidence for this conception, beyond X-ray crystallography,
arises from experiments and spectroscopy. When the reaction
runs in THF, the yield of mono-benzoxazine 6 has such
predominance that it simply crystallises from the mixture;
while in benzene, toluene and chloroform, the product is more
complicated and chromatographic methods must be applied to
separate the product. Furthermore, when NMR experiments
were run in acetone, a solvent capable of hydrogen bonding,
the resulting proton and carbon spectra are fully in accord
with the mono-benzoxazine structure 6. On the other hand,
in chloroform, the spectra are rather complicated and some
additional small peaks appear which follow a regular pattern
and their area percentage increases at elevated temperatures
as was mentioned in the spectroscopy section. These
observations indicate the conversion of hemiacetal 6 to
another equilibrating structure in chloroform. Although we do
not have enough evidence to assign the second equilibrating
structure, but this conversion is an evidence of the instability
of 6 in chloroform.
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Supplementary data
CCDC 643815 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
9
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