4-Hydroxy-2-quinolinones 128. Bromination of N-allyl-4-hydroxy-2-oxo-1,2- dihydroquinolines and pyridines unsubstituted in position 3

Article abstract of DOI:10.1007/s10593-007-0178-7

Bromination of N-allyl-4-hydroxy-2-oxo-1,2-dihydroquinoline and N-allyl-5-ethoxycarbonyl-4-hydroxy-6-methyl-2-oxo-1,2-dihydropyridine is accompanied not only by closing of a five membered oxazole ring but also by a second bromination of the 2-bromomethyl-5-oxo-1,2-dihydro-5H-oxazolo[3,2-a]- derivatives formed at position 4.

Full text of DOI:10.1007/s10593-007-0178-7

Chemistry of Heterocyclic Compounds, Vol. 43, No. 9, 2007
4-HYDROXY-2-QUINOLINONES
128.* BROMINATION OF N-ALLYL-
4-HYDROXY-2-OXO-1,2-DIHYDRO-
QUINOLINES AND PYRIDINES
UNSUBSTITUTED IN POSITION 3
I. V. Ukrainets1, N. L. Bereznyakova1, A. V. Turov2, and S. V. Slobodzian3
Bromination of N-allyl-4-hydroxy-2-oxo-1,2-dihydroquinoline and N-allyl-5-ethoxycarbonyl-4-hydroxy-
6-methyl-2-oxo-1,2-dihydropyridine is accompanied not only by closing of a five membered oxazole ring
but also by a second bromination of the 2-bromomethyl-5-oxo-1,2-dihydro-5H-oxazolo[3,2-a]-derivatives
formed at position 4.
Keywords: oxazolo[3,2-a]pyridines, oxazolo[3,2-a]quinolines, bromination, heterocyclization, X-ray
structural analysis.
The treatment of N-allyl-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acids, their esters, and
analogs hydrogenated in the benzene part of the molecule with molecular bromine is a convenient and efficient
method for preparing the corresponding 2-bromomethyl-5-oxo-1,2-dihydro-5H-oxazolo[3,2-a]quinolines [2, 3]. It
would be logical for the 3H-derivatives to behave in the same way. However, as our experiments have shown,
bromination of N-allyl-4-hydroxy-2-oxo-1,2-dihydroquinoline (1) and the structurally related N-allyl-
5-ethoxycarbonyl-4-hydroxy-6-methyl-2-oxo-1,2-dihydropyridine (2) does not occur in this particular way
although it is accompanied by closure of the five membered oxazole ring.
The 4-hydroxy-2-oxoquinoline 1 was prepared by decarboxylation of acid 3. The synthesis of the
4-hydroxy-2-oxopyridine 2 involved formation of the pyridine ring in several stages starting from acetoacetic
ester (4) and allylamine using a known scheme [4].
The N-allyl-substituted 3H-azaheterocycles 1 and 2 were apparently brominated without an anomaly, an
introduced equimolar amount of bromine being decolorized almost instantaneously. In both cases, however, it
was noted that they consist of two substances in the ratio 1:1 (1H NMR spectroscopic data) which differ markedly
in their solubility in organic solvents. After separation of the reaction mixture it was found that the compounds
readily soluble in ether, against expectations, did not contain bromine in their structure and more detailed analysis
showed them to be the starting N-allyl-substituted 3H-azaheterocycles 1 and 2.
_______
* For Communication 127 see [1].
__________________________________________________________________________________________
1National University of Pharmacy, Kharkiv 61002, Ukraine; e-mail: uiv@kharkov.ua. 2Taras Shevchenko
National University, Kiev 01033, Ukraine; e-mail: nmrlab@univ.kiev.ua. 3Ohio Northern University, Ada 45810,
Ohio, USA; e-mail: s-slobodzian@onu.edu. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp.
1365-1373, September, 2007. Original article submitted May 18, 2006.
0009-3122/07/4309-1159©2007 Springer Science+Business Media, Inc.
1159

OH
N
OH
N
O
N
CO2H
O
Br
O
DMF,
boiling
Br2
1
+
– СО2
O
1
7
3
Br
O
OH
Br
EtO2C
Me
EtO2C
Me
EtO2C
CO2Et
EtO2C
EtO2C
Me
H2N
Br2
ClOCCH2CO2Et
EtONa
2
+
N
N
O
Me
NH
Me
N
O
O
O
4
5
6
8
2
Br
Bromine was found in the materials insoluble in ether. The results of the investigation of their structures
by NMR showed that a five membered oxazole ring had closed upon bromination. Along with this, however, the
unusual feature noted was the absence of singlet signals for the H-4 protons in the 1H NMR spectra.
Scheme 1
8.11
O
H
w
126.6
172.7
Br
H
7.38
7.72
124.3
81.9
123.2
135.7
132.9
158.8
O
H
N
116.4
50.8
4.73
H
7.47
80.8
4.06
H
H
H
4.34
H
35.0
H
5.59
4.01
Br
TABLE 1. Full Correlation List for the Oxazoloquinolone 7
Bond
l, Å
Bond
l, Å
Bond
l, Å
N(1A)–C(1A)
N(1A)–C(13A)
O(2A)–C(7A)
O(4A)–C(10A)
C(1A)–C(6A)
C(2A)–C(3A)
C(4A)–C(5A)
C(6A)–C(7A)
C(8A)–C(9A)
C(11A)–C(12A)
N(1B)–C(1B)
N(1B)–C(13B)
O(2B)–C(7B)
O(4B)–C(10B)
1.394(3)
1.466(3)
1.330(3)
1.315(3)
1.393(3)
1.370(3)
1.373(3)
1.434(3)
1.456(3)
1.496(3)
1.391(3)
1.466(3)
1.333(3)
1.321(3)
C(1B)–C(6B)
C(2B)–C(3B)
C(4B)–C(5B)
C(6B)–C(7B)
C(8B)–C(9B)
C(11B)–C(12B)
N(1A)–C(9A)
O(1A)–C(9A)
O(3A)–C(10A)
O(4A)–C(11A)
C(1A)–C(2A)
C(3A)–C(4A)
C(5A)–C(6A)
C(7A)–C(8A)
1.402(3)
1.381(3)
1.371(3)
1.429(3)
1.467(3)
1.499(3)
1.407(3)
1.227(2)
1.236(3)
1.459(3)
1.408(3)
1.378(4)
1.402(3)
1.383(3)
C(8A)–C(10A)
C(13A)–C(14A)
N(1B)–C(9B)
O(1B)–C(9B)
O(3B)–C(10B)
O(4B)–C(11B)
C(1B)–C(2B)
C(3B)–C(4B)
C(5B)–C(6B)
C(7B)–C(8B)
C(8B)–C(10B)
C(13B)–C(14B)
1.468(3)
1.515(3)
1.405(3)
1.221(3)
1.234(3)
1.457(3)
1.408(3)
1.379(4)
1.408(3)
1.378(3)
1.470(3)
1.514(3)
1160

13
13C NMR spectra and heteronuclear C–1H correlations were carried out to establish the structure of the
reaction products. Analysis of the carbon signals showed that they have the expected number of carbon atoms.
However, one of these had an unexpected chemical shift of 81.9 ppm for compound 7 and 87.2 ppm for
compound 8. Measurement of the DEPT spectra showed that two methyl, three methylene groups and one
methine proton were present in the molecule 8. Hence it was found that a quaternary carbon atom with chemical
shift of 87.2 ppm is present instead of that with an aromatic proton at position 4. In addition heteronuclear
correlation experiments involving one chemical bond (HMQC) and 2-3 chemical bonds (HMBC) were carried out
which allowed a full assignment of all of the carbon atom signals.
1
Scheme 1 shows the assignments of the H and 13C signals for the oxazoloquinolone 7. The spin
connections in the proton multiplets were determined from COSY-90 spectra. Assignment of the protonated
carbon atoms was made on the basis of the correlation through one bond in the HMQC spectrum, The arrows
indicate the important correlations in the HMBC spectra which served as the basis for assigning the quaternary
carbon atoms.
As is evident from the scheme presented the assignment of all of the quaternary carbon atoms can be
made on the basis of the correlation in the HMBC spectrum. Thus the carbonyl C(5) atom of the quinolone
fragment correlates with proton H-6 absorbing at 8.11 ppm. The bridging atoms C(5a) and C(9a) can be assigned on
the basis of the correlations with H-7 and H-8 respectively. The C(3a) signal correlates with the signals of all of the
protons of the oxazolidine ring. Finally, the C(4) atom absorbing at 81.9 ppm and bearing the bromine atom in our
proposal has a weak correlation through 5 bonds with the H-7 proton (ω-interaction). All of the heteronuclear
correlations found for the oxazoloquinolone 7 are given in Table 1.
Scheme 2
O
O
4.20
H2
171.1
C
61.5
Br
87.2
119.4
1.22
166.5
H3C
14.7
O
157.4
O
141.4
N
2.20
H3C
16.7
51.7
80.2
3.89
3.96
4.58
H
H
H
H
H
5.41
34.5
Br
4.20
TABLE 2. Full Correlation List for the Oxazolopyridone 8
δ, ppm
НМQC
80.2
HMBC
5.41
34.5; 157.4
157.4; 80.2; 34.5
4.58
51.7
4.20
61.5; 51.7
34.5
157.4; 166.5; 80.2; 34.5; 14.7
80.2; 51.7
3.89; 3.96
2.20
1.22
16.7
14.7
141.4; 119.4; 171.1
61.5
1161

Analysis of the 2D heteronuclear 13C–1H correlated spectra for the oxazolopyridone 8 showed that the
majority have the correlations recorded for compound 7. This indicated the closely analogous structures of the
compounds studied. Assignment of the signals in the proton and carbon spectra was carried out similarly. The
HMBC chemical shift values and correlations which served as the basis for assigning the quaternary carbon atoms
are given in Scheme 2.
Hence the signal for the carbonyl carbon atom of the ethoxycarbonyl group was assigned from its
correlation with the methylene protons at 4.20 ppm. The signal for the 7-CH3 methyl group protons has a
correlation with the signals for the carbon atoms at 141.4 and 119.4 ppm. This allowed us to assign these signals
to C(7) and C(6) respectively. The presence of a weak, ω-type correlation between the 7-CH3 signal and that at
171.1 ppm led us to assign this signal to the carbonyl C(5) atom. The C(3a) signal was assigned from the presence
of a correlation with all of the oxazolidine ring protons. The full list of the heteronuclear correlations for the
oxazolopyridone 8 is given in Table 2.
From the overall NMR data we came to the conclusion that the bromination products of the
N-allyl-substituted 3H-azaheterocycles 1 and 2 are the 4-bromo-2-bromomethyl-1,2-dihydrooxazolo[3,2-a]-
quinolin-5-one (5) and 4-bromo-2-bromomethyl-6-ethoxycarbonyl-7-methyl-1,2-dihydrooxazolo[3,2-a]pyridin-
5-one (8) respectively. This was confirmed by their chromato mass spectra, distinguishing features of which for
dibromo-substituted compound [5] are the triplet peaks for the molecular ions in the intensity ratio 1:2:1.
A conclusive argument for the proposed structures was the X-ray structural investigation of one of these,
the dibromo-substituted oxazoloquinolone 7 (Fig. 1).
Fig. 1. Structure of the dibromo-substituted oxazoloquinolone 7 with atomic numbering.
It was found that the quinoline fragment and the O(2), Br(1), O(1), and C(11) atoms lie in a single plane to an
accuracy of 0.02 Å. The O(2)–C(7) 1.242(6) and C(8)–C(9) 1.361(6) Å bonds are lengthened when compared with
their mean values [6] of 1.210 and 1.326 Å respectively and the C(7)–C(8) 1.405(7) and C(9)–O(1) 1.319(6) are
shortened (mean values 1.455 and 1.354 Å). This change in bond lengths suggest that the structure of the
molecule examined is a superposition of two resonance structures, the 5-oxo form 7 predominating.
1162

The five-membered heterocycle is randomized in two envelope conformations (A and B) in the ratio
45: 55%. The C(10) atom deviates from the mean plane of the remaining ring atoms in conformer A by -0.42 and in
conformed B by 0.30 Å. The bromomethyl has a pseudoequatorial orientation in both conformers (torsional angle
N(1)–C(11)–C(10)–C(12) 135(1) in A and -133.0(8)º in B). The bromine atom is not randomized and is found in an
ap-conformation relative to C(11)–C(10) bond in both conformers (torsional angle C(11)–C(10)–C(12)–Br(2) 177.7(8) in
A and -176.3(6)º in B). A shortened intramolecular contact H(2)···C(11) of 2.69 Å is observed in the tricyclic
fragment (sum of van der Waal radii 2.87 Å [7]).
–
O
O
Br
Br
O
N
+
N
O
Br
Br
7
7a
The shortened intermolecular contacts found between the oxazoloquinolone molecules 7 in the crystal
are: H(2)···C(12a') (-1-x, -1-y, -0.5+z) 2.78 (2.87), H(3)···Br(1') (-0.5-x, 1+y, -0.5+z) 3.02 (3.23), H(10a)···Br(1') (-0.5-x, y,
-0.5+z) 2.84 (3.23), H(10b)···Br(1') (-0.5-x, y, 0.5+z) 3.14 (3.23), Br(1)···H(12b') (-0.5-x, y, -0.5+z) 3.01 (3.23),
Br(1)···H(12c') (-0.5-x, y, 0.5+z) 3.11 (3.23), and Br(2)···H(12c') (-1-x, -2-y, 0.5+z) 3.18 Å (3.23 Å).
Hence the bromination by an equimolar amount of molecular bromine of the N-allyl-4-hydroxy-2-oxo-
1,2-dihydroquinoline (1) and N-allyl-5-ethoxycarbonyl-4-hydroxy-6-methyl-2-oxo-1,2-dihydropyridine (2) which
are unsubstituted in position 3 gives the corresponding 4-bromo-2-bromomethyl-1,2-dihydrooxazolo[3,2-a]-
hetaryl-5-ones 7 and 8. Moreover, half of the starting N-allyl derivatives do not take part in the reaction.
It follows from this that the initially formed 4H-2-bromomethyloxazoles 9 immediately undergo a second
bromination, the rate of this process being significantly greater than the rate of bromination of the N-allyl
heterocycles 1 or 2. The reason for this effect is undoubtedly due to structural features of the oxazolopyridones of
general formula 9. Because in the resonance hybrid of the final dibromo-substituted oxazoloquinolone 7 the form
7a makes a marked contribution a second bromination of the intermediate 4H-2-bromomethyloxazoles 9 in the
analogous bipolar form 10 seems very likely. The high nucleophilicity of the C(4) atom in such compounds is
evidently linked with the fact that it simultaneously behaves as enamine and vinyl ether, as a result of which the
corresponding mesomeric forms 11 or 12 can be brominated considerably faster than the OH forms 1, 2
(analogous to phenols and phenoxide ions [8]).
TABLE 3. Bond Lengths (l) in the Dibromo-substituted Oxazoloquinolone 7
Bond
l, Å
Bond
C(6)–C(7)
l, Å
Bond
O(2)–C(7)
l, Å
Br(1)–C(8)
Br(2)–C(12A)
N(1)–C(1)
O(1)–C(9)
O(1)–C(10B)
C(1)–C(6)
C(2)–C(3)
C(4)–C(5)
1.879(5)
1.99(1)
1.472(7)
1.361(6)
1.55(1)
1.48(2)
1.90(1)
1.358(6)
1.454(6)
1.49(2)
1.242(6)
1.400(7)
1.361(9)
1.396(8)
1.405(7)
1.54(2)
C(8)–C(9)
C(1)–C(2)
1.383(6)
1.319(6)
1.50(1)
C(11)–C(10B)
C(10B)–C(12B)
Br(2)–C(12B)
N(1)–C(9)
C(3)–C(4)
C(5)–C(6)
C(7)–C(8)
1.398(7)
1.362(8)
1.359(8)
C(11)–C(10A)
C(10A)–C(12A)
N(1)–C(11)
O(1)–C(10A)
1.48(2)
1163

–
O
N
O
N
OH
N
Br2
+
O
O
O
1, 2
Br
10 Br
9
O
O
O
Br
O
–
–
Br2
+
+
N
N
N
O
O
Br
7, 8
Br
Br
11
12
In conclusion and based on the results of this investigation it should be stressed that the bromination of
1-N-allyl-substituted 3H-4-hydroxy-2-oxoazaheterocycles should be carried out with a two fold amount of
molecular bromine in order to avoid the formation of reaction mixtures.
EXPERIMENTAL
The 1H and 13C NMR spectra of the dibromo-substituted oxazoloheterocycles 7 and 8, 2D COSY spectra,
and the heteronuclear HMQC and HMBC correlations were recorded on a Varian Mercury-400 (400 and 100
MHz respectively). All of the 2D experiments were carried out with gradient selection of useful signals. The
TABLE 4. Valence Angles (ω) in the Dibromo-substituted Oxazoloquinolone 7
Angle
ω, deg
Angle
ω, deg
C(12B)–Br(2)–C(12A)
C(9)–N(1)–C(11)
C(9)–O(1)–C(10A)
N(1)–C(1)–C(6)
30.8(5)
110.9(4)
107.6(7)
118.7(5)
119.8(5)
120.3(6)
121.4(5)
122.3(5)
123.1(5)
116.4(4)
118.0(4)
111.6(4)
121.5(5)
102.0(6)
110(1)
C(9)–N(1)–C(1)
C(1)–N(1)–C(11)
C(9)–O(1)–C(10B)
N(1)–C(1)–C(2)
C(3)–C(2)–C(1)
C(5)–C(4)–C(3)
C(5)–C(6)–C(1)
C(1)–C(6)–C(7)
O(2)–C(7)–C(6)
C(9)–C(8)–C(7)
C(7)–C(8)–Br(1)
O(1)–C(9)–C(8)
N(1)–C(11)–C(10A)
C(12A)–C(10A)–O(1)
O(1)–C(10A)–C(11)
C(12B)–C(10B)–O(1)
O(1)–C(10B)–C(11)
121.9(4)
127.2(4)
109.2(6)
121.5(4)
120.2(5)
120.7(6)
117.6(5)
120.1(5)
120.5(5)
121.3(5)
120.7(3)
126.8(5)
101.2(7)
107(1)
C(6)–C(1)–C(2)
C(4)–C(3)–C(2)
C(4)–C(5)–C(6)
C(5)–C(6)–C(7)
O(2)–C(7)–C(8)
C(8)–C(7)–C(6)
C(9)–C(8)–Br(1)
O(1)–C(9)–N(1)
N(1)–C(9)–C(8)
N(1)–C(11)–C(10B)
C(12A)–C(10A)–C(11)
C(10A)–C(12A)–Br(2)
C(12B)–C(10B)–C(11)
C(10B)–C(12B)–Br(2)
103(1)
110.1(9)
114(1)
106.0(8)
101.9(7)
113.2(8)
1164

mixing times in the pulse sequences were respectively 1JCH = 140 and 2-3JCH = 8 Hz. The number of increments in
1
the COSY and HMQC experiments were 128 and 400 respectively. The H NMR spectra of the starting N-allyl
derivatives 1 and 2 were taken on a Varian Mercury-VX-200 instrument (200 MHz). In all of the experiments
DMSO-d6 was used as solvent and TMS as internal standard. Chromato-mass spectra of the dibromo-substituted 7
and 8 were recorded on an Agilent 1100 LC/MSD spectrometer using the APCI ionization method (atmospheric
pressure chemical ionization). The chromatographic column parameters were: length 50 mm, diameter 4.6 mm,
stationary phase ZORBAX Eclipse XDB-C18, solvent aqueous acetonitrile, acidifier 0.1% trifluoroacetic acid,
gradient elution, and solvent flow rate 2.4 ml/min.
1-Allyl-4-hydroxy-2-oxo-1,2-dihydroquinoline (1). A solution of 1-allyl-4-hydroxy-2-oxo-1,2-dihydro-
quinoline-3-carboxylic acid (3, [2]) (2.45 g, 0.01 mol) in DMF (15 ml) was refluxed for 10 min, cooled, and
diluted with cold water. The precipitated derivative 1 was filtered off, washed with water, and dried. Yield 1.87 g
(93%); mp 224-226ºC (ethanol). 1H NMR spectrum, δ, ppm (J, Hz): 11.42 (1H, s, OH); 7.88 (1H, dd, J = 7.9, 1.4,
H-5); 7.56 (1H, td, J = 7.7, 1.7, H-7); 7.35 (1H, d, J = 8.4, H-8); 7.19 (1H, t, J = 7.3, H-6); 5.88 (1H, s, H-3); 5.83
(1H, m, CH=CH2); 5.07 (1H, dd, J = 10.3, 1.4, NCH2CH=CH-cis); 4.89 (1H, dd, J = 17.4, 1.4, NCH2CH=CH-
trans); 4.80 (2H, d, J = 4.7, NCH2). Found, %: C 71.72; H 5.64; N 6.88. C12H11NO2. Calculated, %: C 71.63,
5.51; N 6.96.
Ethyl 1-Allyl-4-hydroxy-6-methyl-2-oxo-1,2-dihydropyridine-5-carboxylate (2). Allylamine (11.3 ml,
0.15 mol) was added to acetoacetic ester (12.7 ml, 0.1 mol) and left for 3 days with periodic stirring at room
temperature. Hexane (50 ml) was added, thoroughly stirred, the water separated in the reaction process was
removed, and the allylamine and solvent were removed in vacuo. The residue of ethyl N-allylaminocrotonate 5
was dissolved in CH2Cl2 (200 ml). Triethylamine (15.4 ml, 0.11 mol) was added and then ethoxymalonyl chloride
(16.6 g, 0.11 mol) dropwise with vigorous stirring and the product was allowed to stand at room temperature for
4-5 h. It was then diluted with water and the organic layer was separated and dried using anhydrous CaCl2.
Solvent was removed in vacuo. A solution of sodium ethylate [prepared from metallic sodium (2.3 g, 0.1 mol)
and absolute ethanol (100 ml)] was added to the residue of diester 6, refluxed for 1 h, and the alcohol distilled off.
The product was cooled, diluted with water, and acidified with dilute HCl (1:1) to pH 4-4.5. The precipitate of
1
ester 2 was filtered, washed with water, and dried. Yield 18.9 g (80%); mp 121-123ºC (aqueous ethanol). H
NMR spectrum, δ, ppm (J, Hz): 10.99 (1H, s, OH); 5.85 (1H, m, CH=CH2); 5.59 (1H, s, H-3); 5.09 (1H, dd,
J = 10.5, 1.5, NCH2CH=CH-cis); 4.85 (1H, dd, J = 17.2, 1.5, NCH2CH=CH-trans); 4.57 (2H, d, J = 4.8, NCH2);
4.20 (2H, q, J = 7.0, OCH2); 2.24 (3H, s, 6-CH3); 1.22 (3H, t, J = 7.0, OCH2CH3). Found, %: C 60.61; H 6.26; N
5.81. C12H15NO4. Calculated, %: C 60.75; H 6.37; N 5.90.
4-Bromo-2-bromomethyl-1,2-dihydrooxazolo[3,2-a]quinolin-5-one (7). Bromine (1.04 ml, 0.02 mol)
was added with stirring to a solution of compound 1 (2.01 g, 0.01 mol) in acetic acid (20 ml) and it immediately
decolorized. The reaction mixture was diluted with cold water. The precipitate formed was filtered off, washed
with water, and dried. Yield 3.41 g (95%); mp 218-220ºC (ethanol). 1H NMR spectrum, δ, ppm (J, Hz): 8.11 (1H,
d, J = 7.9, H-6); 7.72 (1H, t, J = 7.4, H-8); 7.47 (1H, d, J = 8.1, H-9); 7.38 (1H, t, J = 7.4, H-7); 5.59 (1H, m,
CHO); 4.73 (1H, t, J = 9.5, NCH); 4.34 (1H, dd, J = 8.7, 6.6, NCH); 4.06 (1H, dd, J = 11.2, 4.3, CHBr); 4.01 (1H,
13
dd, J = 11.2, 3.5, CHBr). C NMR spectrum, δ, ppm: 172.7 (C=O), 158.8 (C3a), 135.7 (C9a), 132.9 (C(8)), 126.6
(C(6)), 124.3 (C(7)), 123.2 (C(5a)), 116.4 (C(9)), 81.9 (C(4)), 80.8 (CHO), 50.8 (NCH2), 35.0 (CH2Br). Mass spectrum,
m/z (Irel, %): 358 [M+H]+ (100), value only given for the 79Br isotope. Found, %: C 40.24; H 2.47; N 3.83.
C12H9Br2NO2. Calculated, %: C 40.15; H 2.53; N 3.90.
X-ray Structural Investigation. Crystals of the dibromo-substituted oxazoloquinolone 7 are rhombic, at
20ºC: a = 16.929(3), b = 9.252(2), c = 7.538(1) Å, V = 1180.6(4) Å3, Mr = 359.02, Z = 4, space group Pca21,
d
calc = 2.020 g/cm3, µ(MoKα) = 6.853 mm-1, F(000) = 696. The unit cell parameters and intensities of 12,601
reflections (3,288 independent, Rint = 0.089) were measured on an Xcalibur-3, four circle automatic diffractometer
(MoKα radiation, CCD detector, graphite monochromator, ω-scanning, 2θmax =60º). Absorption was included
analytically (Tmin = 0.400, Tmax = 0.933).
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The structure was solved by a direct method using the SHELXTL [9] program package. The positions of
the hydrogen atoms were calculated geometrically and refined using the "riding" model with Uiso = 1.2×Ueq for a
non-hydrogen atom bound with the given hydrogen. The structure was refined by F2 full matrix least squares
analysis in the anisotropic approximation for non-hydrogen atoms to wR2 = 0.095 for 3261 reflections (R1 = 0.047
for 2086 reflections with F>4σ(F), S = 0.975). The complete crystallographic data have been placed in the
Cambridge structural data base, reference CCDC 608698. The interatomic distances and valence angles are given
in Tables 3 and 4.
4-Bromo-2-bromomethyl-6-ethoxycarbonyl-7-methyl-1,2-dihdrooxazolo[3,2-a]pyridin-5-one (8) was
prepared similarly to oxazoloquinolone 7 from the ethyl ester 2. Yield 3.63 g (92%); mp 167-169ºC (ethanol). 1H
NMR spectrum, δ, ppm (J, Hz): 5.41 (1H, m, CHO); 4.58 (1H, t, J = 9.4, NCH); 4.20 (3H, m, NCH + COOCH2);
3.96 (1H, dd, J = 11.4, 5.6, CHBr); 3.89 (1H, dd, J = 11.4, 4.5, CHBr); 2.20 (3H, s, 7-CH3); 1.22 (3H, t, J = 7.5,
COOCH2CH3). 13C NMR spectrum, δ, ppm: 171.1 (C=O), 166.5 (COO), 157.4 (C(3a)), 141.4 (C(7)), 119.4 (C(6)),
87.2 (C(4)), 80.2 (CHO), 61.5 (OCH2), 51.7 (NCH2), 34.5 (CH2Br), 16.7 (7-CH3), 14.7 (CH2CH3). Mass spectrum,
m/z (Irel, %): 394 [M+H]+ (100), value only given for the 79Br isotope. Found, %: C 36.37; H 3.40; N 3.63.
C12H13Br2NO4. Calculated, %: C 36.48; H 3.32; N 3.55.
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