Synthesis and structural characterisation of 927 4H-1,3-benzothiazine derivatives

Article abstract of DOI:10.1002/jhet.5570390512

The ring-closure reactions of N-arylthiomethylaroylamide derivatives (1a-g) in the presence of phosphorus oxychloride gave 2-aryl-4H-1,3-benzo-thiazines (2a-g). 2-(3-Chlorophenyl)-6-methyl-4H-1,3-benzothiazine (2b) was reduced with Zn to obtain the corres

Full text of DOI:10.1002/jhet.5570390512

Sep-Oct 2002
Synthesis and Structural Characterisation of
927
4H-1,3-Benzothiazine Derivatives
Lajos Fodor , Gábor Bernáth , Jari Sinkkonen and Kalevi Pihlaja *
a,b
b
c
c
a
Research Group for Heterocyclic Chemistry of the Hungarian Academy of Sciences, Institute of
Pharmaceutical Chemistry, University of Szeged,
H-6701 Szeged, PO Box 121, Hungary
Central Laboratory, County Hospital, H-5701 Gyula, PO Box 46, Hungary
b
c
Structural Chemistry Group, Department of Chemistry, University of Turku, FIN-20014 Turku, Finland
Received January 17, 2002
The ring-closure reactions of N-arylthiomethylaroylamide derivatives (1a-g) in the presence of phospho-
rus oxychloride gave 2-aryl-4H-1,3-benzo-thiazines (2a-g). 2-(3-Chlorophenyl)-6-methyl-4H-1,3-benzoth-
iazine (2b) was reduced with Zn to obtain the corresponding 2,3-dihydro derivative (3b). Potassium per-
manganate oxidation of 2-(4-chlorophenyl)-2,3-diethoxy-4H- (2e) and 2-(2-fluorophenyl)-6,7-diethoxy-4H-
1,3-benzo-thiazines (2g) gave the corresponding 4-ones (4e,g). The reactions of 2-(4-chlorophenyl)-6-
methyl-4H-1,3-benzothiazine (2c) with substituted acetyl chlorides led to linearly condensed ß-lactams
1
(5a,b). The structures of the compounds studied were confirmed by H and 13C NMR and by their charac-
teristic mass spectrometric fragmentations.
J. Heterocyclic Chem., 39, 927(2002).
Introduction.
Subsequently, certain chemical reactions of the new ben-
zothiazines were investigated. The reduction of 2b with Zn
afforded the 2,3-dihydro derivative (3b) (Scheme 2).
Potassium permanganate oxidation of 2e,g in acetone solu-
tion furnished the corresponding 4-oxo derivatives 4e,g in
good yields. Analogously to the cycloaddition reactions of
imines with acid chlorides, 2c reacted with chloroacetyl
chloride or dichloroacetyl chloride to give the linearly con-
densed ß-lactam derivatives 5a,b (Scheme 2).
1,3-Benzothiazine derivatives were first described in
1947. However, since numerous biologically active com-
pounds have subsequently been found among these com-
pounds [1-7], research on the methods of synthesising this
heterocyclic system has developed intensively during
recent decades [2,4,5,7,8,-15]. In earlier work [13,15], we
studied the ring-closure reactions of a number of N-arylth-
iomethylaroylamides in the presence of phosphorus oxy-
chloride, leading to 4H-1,3-benzothiazines. It was proved
that these cyclizations occur through an acid-catalysed
intermolecular rearrangement. Some of the substituted 4H-
1,3-benzothiazines prepared [1] displayed fungicidal
activity. On this basis, it seemed logical to prepare and
characterise various new, related 4H-1,3-benzothiazine
derivatives.
Scheme 2
Synthetic routes and structures of 3b, 4e,g and 5a,b including the
numbering system of studied compounds.
Results and Discussion.
4-Methylphenylthioaroylamides (1a-d) or 3,4
diethoxyphenylthiomethyl-aroylamides (1e-g) were
cyclized in acid medium with phosphorus oxychloride to
obtain 4H-1,3-benzothiazine derivatives (2a-g)
(Scheme 1).
Scheme 1
The structures of 1a-g and 2a-g.
1
13
H and C NMR Spectra.
1
The H NMR chemical shifts of 2e-g, 3b, 4e,g and 5a,b
are shown in Table 3. They are consistent with the pro-
posed structures of the prepared compounds. Only 3b and
5a,b exhibit a resolved doublet for the protons on C4 (J
~
44
- 17 Hz), in agreement with their non-symmetric struc-
tures. As expected, 3b also gives a signal for the proton on
C2 (5.64 ppm).

928
L. Fodor, G. Bernáth, J. Sinkkonen and K. Pihlaja
Vol. 39
Table 1
Physical and Analytical Data on Compounds 1a-g.
Table 2
Physical and Analytical Data on Compounds 2a-g, 4e,g and 5a,b
Compound Yield
%
M.p.
°C
Formula
M.w.
Analysis (%)Calcd/Found
Compound Yield M.p.
°C
Formula
M.w.
Analysis (%)Calcd/Found
C
H
N
S
%
C
H
N
S
2a
2b
2c
2d
2e
2f
9.2 123-124
8.1 134-135
10.3 137-138
8.7 143-144
41.4 152-153
C
H NOS
269.36
71.34 5.61 5.20 11.90
71.43 5.70 5.09 11.79
16 15
1a
1b
1c
1d
1e
1f
91 106-107 C H NO S 66.87 5.96 4.87 11.16
16 17 2
287.38
66.71 5.87 4.98 11.28
C
H ClNS 65.80 4.42 5.12 11.71
273.78
15 12
88 111-112
92 108-109
84 119-120
93 131-132
86 140-141
92 119-120
C
C
H ClNOS 61.74 4.84 4.80 10.99
15 14
65.69 4.49 5.21 11.60
291.80
61.85 4.76 4.86 10.84
C
H
ClNS 65.80 4.42 5.12 11.71
15 12
H
ClNOS 61.74 4.84 4.80 10.99
15 14
273.78
65.92 4.37 5.02 11.87
291.80
61.68 4.76 4.73 11.06
C
H
NO S 68.20 5.72 4.68 10.71
17 17
2
C
H
NO S 64.33 6.03 4.41 10.10
17 19
3
299.39
68.31 5.83 4.59 10.79
317.40
64.22 6.11 4.50 10.01
C
H ClNO S 62.15 5.22 4.03 9.22
18 18
2
C
H ClNO S 59.09 5.51 3.83 8.76
18 20
3
347.86
62.24 5.17 4.11 9.34
365.88
59.16 5.42 3.90 8.61
36.3 146-147 C H NO S 64.32 6.21 3.75 8.59
20 23
4
C
H
NO S 61.36 6.44 3.58 8.19
20 25
5
373.47
C H FNO S 62.24 5.47 4.23 9.68
18 18
64.21 6.30 3.68 8.70
391.48
C H FNO S 61.87 5.77 4.01 9.18
18 20
61.43 6.32 3.67 8.07
2g
3b
4e
4g
5a
5b
38.7 130-131
69.0 92- 93
2
1g
3
331.41
62.33 5.38 4.30 9.77
349.42
61.99 5.66 4.08 9.29
C
H
ClNS 65.32 5.12 5.08 11.63
15 14
275.80
C H ClNO S 59.75 4.46 3.87 8.86
18 16
65.46 5.03 5.19 11.49
13
79.1 183-184
74.3 192-193
87.2 165-166
91.3 145-146
3
The C spectra of the compounds studied were likewise
found to correspond to their expected structures (Table 4).
Compounds 2g and 4g yield typical (and similar) CF cou-
pling patterns, and 3b and 5a,b furnish the typical signals
of CH and CH groups for C2 and C4, respectively. For
4e,g the C4 chemical shifts are typical for C=O carbons,
again as expected.
361.84
59.67 4,52 3.80 8.97
C
H FNO S 62.59 4.67 4.06 9.28
18 16
3
345.39
62.67 4.58 4.12 9.40
C
H Cl NOS 58.29 3.74 4.00 9.15
17 13
2
350.26
58.37 3.62 4.11 9.02
2
C
H Cl NOS 53.07 3.14 3.64 8.34
17 12
3
384.71
53.18 3.07 3.72 8.44
It is interesting to note that for compounds2a-2d, which
differ from each other only in respect of the substituent(s)
on the aryl ring, the C-2, C-4a, C-8a and C-1' chemical
shifts, despite the relatively small ranges, show very good
Mass Spectra.
The mass spectra of the compounds studied also nicely
confirmed the proposed structures. The stabilities of the
molecular ions of all compounds (Table 5) are relatively
close to each other, except for 3b, in which the saturation
of the C-N bond makes it appreciably more stable. The
fragmentation of all compounds leads first to the base
+
linear correlations to Hammett s parameters [16] the cor-
relation coefficients being 0.995, 0.989, 0.9997, and 0.974,
respectively. This shows that a certain amount of conjuga-
tion is exerted also through C-S-C-moiety.
Scheme 3
Mass spectrometric fragmentation of 2a-g, 3b, 4e,g and 5a,b.

Sep-Oct 2002
Synthesis and Structural Characterisation of 4H-1,3-Benzothiazine Derivatives
929
Table 3
1
H Chemical Shifts (ppm from TMS) of 2a-g, 3b, 4e,g and 5a,b
Compound
H4
H5
H7
H8
CH on C6 H2'
H3'
H4'
H5'
H6'
OR
3
2a
2b
2c
2d
4.72
4.75
4.74
4.72
7.15
7.15
7.15
7.13
7.10
7.11
7.11
7.09
7.26
7.25
7.25
7.26
2.37
2.36
2.36
2.35
7.95
7.99
7.93
7.57
6.92
-
7.39
-
-
6.92
7.34
7.39
6.87
7.95
7.87
7.93
7.62
CH O 3.86 at C4'
-
-
3
7.43
-
-
CH O 3.95 at C3',
3
CH O 3.91 at C4'
3
2e
2f
4.70
4.69
6.85
6.85
-
-
6.87
6.89
-
-
7.93
7.57
7.39
-
-
-
7.39
6.89
7.93
7.62
CH O 4.09 & 4.10,
2
CH CH 1.46 at C6/7
3
2
CH O 4.09 & 4.10,
2
CH CH 1.45 at C6/7,
3
2
CH O 3.93 at C3',
3
CH O 3.96 at C4'
3
2g
4.74
6.85
6.88
7.95
7.97
7.005
7.06
-
6.83
7.00
6.88
6.89
7.10
7.18
-
-
7.13
-
7.40
7.15
7.31
7.49
7.30
7.355
7.37
7.69
7.38
8.13
8.18
7.375
7.38
CH O 4.07 & 4.11,
2
CH CH 1.45/6 at C6/7
3
2
3b[a]
4e
4.13
4.20
-
6.96
-
2.29
-
7.51
8.13
-
7.30
-
7.49
7.22
7.355
7.37
-
CH O 4.20 & 4.24,
2
CH CH 1.52/5 at C6/7
3
2
4g
-
-
-
7.55
CH O 4.20 & 4.25,
2
CH CH 1.52/4 at C6/7
3
2
5a[b]
5b[c]
4.28
4.94
4.22
4.90
6.995
7.04
2.28
2.31
7.375
7.38
-
-
-
-
[a] H2 5.64; J - 16.9 Hz; [b] H11 5.11; J - 16.5 Hz; [c] J - 16.1Hz.
44
44
44
Table 4
C Chemical Shifts (ppm from TMS) of 2a-g, 3b, 4e,g and 5a,b
13
Compound C2
C4
C4a
C5
C6
C7
C8
C8a
C1'
C2'
C3'
C4'
C5'
C6'
6-CH
3
2a[a]
2b
2c
161.3
56.6 131.67 127.5 137.4 128.2 126.4
56.8 130.95 127.6 137.7 128.4 126.4
56.8 131.1 127.6 137.7 128.4 126.4
56.6 131.7 127.5 137.4 128.2 126.3
56.5 123.3 112.2 148.8 148.5 111.6
56.4 124.0 112.3 148.6 148.4 111.7
56.6 122.7 112.2 148.7 148.5 111.3
49.4 130.1 127.8 134.4 128.0 127.5
169.0 115.5 111.9 150.7 153.4 107.7
168.6 115.6 111.7 150.8 153.4 107.4
43.3 129.4 128.9 137.2 129.2 129.6
44.3 132.05 129.0 137.5 129.7 129.9
127.7
127.0
127.1
127.6
121.3
121.9
121.8
130.0
128.2
129.3
125.7
127.8
138.8
135.5
129.9
135.5
129.9
126.2
142.1
135.3
125.0
135.3
129.4
127.8
129.0
110.0
129.0
110.0
160.2
127.0
128.7
160.9
128.4
129.0
113.8
134.6
128.7
148.9
128.7
148.9
116.2
134.6
129.3
116.7
128.7
127.15
162.0 113.8
131.0 129.7
137.2 128.7
151.6 110.3
137.2 128.7
151.6 110.3
131.7 124.1
128.5 130.0
139.7 129.3
134.0 124.7
135.0 128.7
129.4
125.8
129.0
121.4
129.0
121.4
129.9
124.9
128.7
130.3
128.4
21.06
21.06
21.06
21.05
-
-
-
20.90
-
-
21.00
21.05
160.7
160.8
161.4
160.9
161.5
158.1
64.4
170.7
168.1
70.9
2d[b]
2e[a]
2f[c]
2g[d,e]
3b
4e[f]
4g[f,g]
5a[h]
5b[i]
81.8
126.85 136.2
135.3 127.15 129.0
3.6 Hz, J 2.3
C8a,F
[a] CH O 55.4; [b] 2CH O 55.9; [c] 2CH O 56.0; 2CH CH O 64.9; 2CH CH O 14.8. [d] 2CH CH O 64.9; 2CH CH O 14.8; [e] J
3
3
3
3
2
3
2
3
2
3
2
C2,F
Hz, J
11.4 Hz, J
252.9 Hz, J
21.9 Hz, J
8.8 Hz, J
3.6 Hz, J
2.3 Hz; [f] CH CH O 65.1 (C6) & 64.9 (C7); 2CH CH O 14.5; [g]
C1',F
C2',F
C3',F
C4',F
C5',F
C8a',F 3 2 3 2
J
5.0 Hz, J
5.9 Hz, J
10.5 Hz, J
255.3 Hz, J
22.4 Hz, J
9.1 Hz, J
3.7 Hz, J
1.3 Hz; [h] C10 164.3; C11 68.3; [i] C10
C2,F
C8a,F
C1',F
C2',F
C3',F
C4',F
C5',F
C6',F
163.0; C11 89.7.
(2e-g) and 168 (4e,g) give the ion with m/z 85, and the for-
mer also the ion with m/z 67 (Table 5 and Scheme 3).
+·
peak, that of ion A , at m/z 136 (Scheme 3); for 2a-d, 3b
+
and 5a,b, this leads further to the ions [A-H] , m/z 136,
and [A-H ] , m/z 135 (Table 5). The ions with m/z 121, 92
+·
2
and 91 correspond to the loss of methyl, CS and CHS,
respectively, from [A-H] (Scheme 3). In contrast, 2e-g
EXPERIMENTAL
+
and 4e,g (Table 5) lose C H , C H , 2xC H and (C H +
General Procedure for Preparing 1a-g.
2
4
2
5
2
4
2 4
+·
C H ), respectively, from ion A (m/z 210 for 2e-g and
2
5
A solution of 3,4-dimethoxythiophenol (0.1 mol) and the N-
hydroxymethyl-substituted acid amide in 30 mL of ethanol was
treated with 10 mL of a saturated solution of HCl in ethanol. The
mixture was kept at room temperature for 3 hours, after which the
crystalline product was separated by filtration and recrystallized
m/z 224 for 4e,g) (Scheme 3). Compounds 4e,g further
+·
lose CO from [A-2C H ] , m/z 168, and [A-C H -
2
4
2 4
+
C H ] , m/z 167, leading to the ions with m/z 140 and 139,
respectively (Table 5). Finally, the ions with m/z 154/153
2
5

930
L. Fodor, G. Bernáth, J. Sinkkonen and K. Pihlaja
Vol. 39
Table 5
Electron Ionisation Mass Spectra of 2a-g, 3b, 4e,g and 5a,b at 70 eV
Compound
Ion m/z (% R. A.)
+·
+·
+
+·
+
+·
+
M
A
[A-H]
[A-H ]
C H S
C H
C H
7 7
2
7
5
7
8
2a
2b
269(31)
273(22)
275(8)
136(100)
136(100)
135(32)
135(34)
134(7)
134(5)
121(4)
121(5)
92(7)
92(8)
91(14)
91(16)
2c
273(21)
275(8)
136(100)
135(33)
134(4)
121(4)
92(7)
92(7)
92(13)
92(6)
91(14)
2d[a]
3b[b]
5a[c]
299(34)
275(94.5)
349(17)
351(12
383(16)
385(16)
387(6)
136(100)
136(100)
136(100)
135(28)
135(55)
135(30)
134(3.5)
134(7)
134(5)
121(3)
121(8)
121(4)
91(10.5)
91(30)
91(13)
5b[d]
136(100)
135(32)
134(4)
121(5)
92(7)
91(15)
+•
+
+•
+
+
+
[A-C H ]
[A-C H ]
[A-2C H ]
[A-C H -C H ]
C HOS
C H O
4 3
2
4
2
5
2
4
2
4
2
5
3
2e
347(19)
349(7)
210(100)
182(14)
181(26)
154(14)
153(63)
85(9)
67(12)
2f
2g
373(24)
331(24)
210(100)
210(100)
182(12)
182(15)
181(23)
181(27)
154(12)
154(15)
153(51)
153(71)
85(6)
85(11)
67(9)
67(14)
+•
+
+
C H O S
C H O S
C H OS
6
4
2
6
3
2
3 3
4e[e]
4g[e]
361(12)
345(15)
224(100)
224(100)
196(15)
196(15.5)
195(7)
195(8)
168(21)
168(25)
167(25) 140(7)[f]
167(30) 140(6)[f]
139(4)[g]
139(3.5)[g] 85(14)
85(17)
+
+
+
+
+
+
+
[a] [M-A] : 163(2.5); [b] [M-CH ] : 260(6.5); [M-HS] : 242(14); [M-C H Cl] : 164(6); [M-C H Cl] : 150(56); C H Cl : 125(7); C H
:
3
6
+
4
7
6
7
+
6
8
7
+·
+
+
103(6); C H : 102(6); C H : 89(10); 77(11.5); 65(6); 63(5); 51(6); CHS : 45(16); [c] [M-H] : 350(6), 348(4); [M-Cl] : 316(11),314(28); [M-
8
6
7 5
+·
+·
+
+
+
HCl] : 315(7), 313(6); [M-2Cl] : 279(6); [M-C HOCl] : 273(5); [M-C H OCl]: 272(4); C H NS : 150 (6); [d] [M-Cl] : 352(3), 350(14),
348(20.5); [M-HCl] : 351(4), 349(13), 347(13); [M-2Cl] 315(4), 313(9); [M-C H Cl] 274(6), 272(15); C H NS : 150 (5); [e] C H OS :
111(4); [f] [A-2C H -CO] ; [g][A-C H -C H -CO] .
2
2
2
8 8
+·
+·
+
+
+
6
5
8
8
5 3
+·
+
2
4
2
4
2 5
from ethanol. The physical constants and analytical data are
given in Table 1.
with stirring and cooling in ice water. Stirring was continued for
3 hours. Thereafter, CHCl3 (100 mL) was added, and the precipi-
tated MnO2 removed by filtration with suction, and washed with
CHCl3. The solvent was evaporated off and the residue was crys-
tallized from ethanol, to give light-yellow crystals of 4e or 4g.
The physical constants and analytical and spectral data are given
in Tables 2-5.
General Procedure for Preparing 2a-g.
A mixture of 1 (0.1 mol) and phosphorus oxychloride (30 mL)
was heated on a boiling water bath for 1 hour. It was then cooled
to room temperature and ice was added to decompose the excess
phosphorus oxychloride. The solution was neutralized with
Na2CO3 and extracted with benzene. The extract was dried over
anhydrous Na2SO4, filtered, and evaporated to dryness, and the
residue was crystallized from ethanol. The physical constants and
analytical and spectral data are given in Tables 2-5.
Preparation of 5a,b.
Compound 2c (10 mmol) and chloroacetyl chloride or
dichloroacetyl chloride (10 mmol) were dissolved in benzene,
and triethylamine (10 mmol) was added dropwise, with stirring
during 1 hour. The crystalline Et3N•HCl formed was removed by
filtration, the benzene solution was evaporated to dryness and the
residue was crystallized from ethanol, to yield colourless crystals
of 5a or 5b. The physical constants and analytical and spectral
data are given in Tables 2-5.
Preparation of 2-(3-Chlorophenyl)-6-methyl-2,3-dihydro-4H-
1,3-benzothiazine (3b).
2-(3-Chlorophenyl)-6-methyl-4H-1,3-benzothiazine (2b)
(0.54 g, 2 mmol) was dissolved in 20 mL of ethanol, and 1 mL of
conc. HCl and 0.3 g of Zn were added to the ice-cooled solution.
The mixture was shaken until it became colourless, the excess Zn
was immediately removed by filtration, and the filtrate was trans-
ferred to ice-cold K2CO3 solution. The resulting mixture, con-
taining a precipitate, was extracted with benzene, and the ben-
zene layer was washed with water and dried over anhydrous
Na2SO4, followed by removal of the solvent by distillation. The
residue was crystallized from ethanol, to give 0.38 g (69%) of
colourless needles. The physical constants and analytical and
spectral data are given in Tables 2-5.
1H and 13C NMR Spectra.
NMR spectra were acquired by using a JEOL JNM-A-500
spectrometer operating at 500.16 MHz for 1H, and at 125.78 MHz
for 13C, or a JEOL JNM-L-400 spectrometer operating at 399.78
MHz for 1H, and 100.54 MHz for 13C. All spectra were recorded
at 25 °C in CDCl3. Proton and carbon spectra were referenced
internally to the tetramethylsilane (TMS) signal at 0.00 ppm.
1D proton spectra were acquired with normal single-pulse exci-
tation, 45° flip-angle consisting of 32K data points. 1D carbon
spectra were acquired with normal single-pulse excitation, broad-
band proton decoupling, 45° flip-angle and with spectral widths of
30 kHz consisting of 65K data points and with 0.3–0.5 Hz expo-
nential weighting applied prior to Fourier transformation. 2D het-
KMnO4 Oxidation of 2e,g.
KMnO4 (4.24 g) was dissolved in acetone (200 mL) and a
solution of 2e or 2g (10 mmol) in acetone (50 mL) was added,

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[1] E. Vinkler, J. Szabó and I. Varga Acta Pharm. Hung. 36,
155 (1966).
[2] M. G. Vigorita, M. Basile and A. Chimirri Atti Soc.
Peloritana Sci. Fis. Mat. Natur.16, 293 (1970).
[3] Fr. Demande Patent no. FR 2047871 B1 19730316; Chem.
Abstr. 76, 3878 (1972).
[4] K. I. Lopatina, G. N. Artemenko, T. V. Sokolova, R. M.
Salimov, Yu. I. Vikhlyaev and V. A. Zagorevskii Khim.-Farm. Zh. 12,
65 (1978).
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A1 19861215; Chem. Abstr.107, 217641 (1987).
[7] A. Garofalo, G. Campiani, I. Fiorini and V. Nacci Il
Farmaco, 48, 275 (1993).
eronuclear one-bond correlation experiments were acquired using
carbon detected CH-shift correlation with partial homonuclear
decoupling in the f1 dimension. Long-range heteronuclear corre-
lation experiments included either carbon detected COLOC or
proton detected HMBC with gradient selection. One-bond cou-
pling constant was 145 Hz and the long-range coupling constants
were 5- 12 Hz in proton-carbon correlation spectra. 2D homonu-
clear H,H-correlation experiments were acquired using phase-sen-
sitive double quantum filtered COSY. The spectral widths of 2D
spectra were optimised from 1D spectra.
Mass Spectra.
The electron ionisation mass spectra (cf. Table 5 and Scheme
3) of 2a-g, 3b, 4e,g and 5a,b were recorded at 70 eV on an MM
7070E mass spectrometer (VG Analytical Ltd, Manchester, UK)
equipped with an OPUS data system. The samples were intro-
duced into the mass spectrometer through the solid-inlet system
at ambient temperature (~323 K) for low-resolution (R = 1000),
accurate mass (peak matching method in HR mode) and
metastable (B/E) measurements.
[8] J. Szabó, I. Varga and E. Vinkler Acta Chim. Acad. Sci.
Hung., 71, 363 (1972).
[9] J. Szabó, I. Varga, E. Vinkler and E. Barthos Acta Chim.
Acad. Sci. Hung., 70, 71 (1971) and 72, 213 (1972).
[10] V. A. Zagorevskii, K. I. Lopatina, T. V. Sokolova and S.
M. Lyuev Khim. Geterotsikl. Soedin., 1437 (1974).
[11] J. Szabó, L. Fodor, I. Varga, E. Vinkler and P. Sohár Acta
Chim. Acad. Sci. Hung., 92, 317 (1977).
[12] L. Fodor, J. Szabó and P. Sohár Tetrahedron, 37, 963
(1981).
[13] J. Szabó, L. Fodor, E. Szu´´cs, G. Bernáth and P. Sohár
Pharmazie, 39, 426 (1984).
Acknowledgements.
We express our thanks to the Hungarian Research Foundation
(OTKA) for grants OTKA T030647 and T034422, to the
Hungarian Ministry of Health for grant ETT 556/2000, and to the
Academy of Finland (Grant: no 4284).
[14] P. Sohár, L. Fodor, J. Szabó and G. Bernáth Tetrahedron,
40, 4387 (1984).
REFERENCES AND NOTES
[15] J. Szabó, E. Bani-Akoto, Gy. Dombi, G. Günther, G.
Bernáth and L. Fodor J. Heterocyclic Chem., 29, 1321 (1992).
[16] I. P. Hammett Advances in Linear Free Energy
Relationships, Plenum Publishing Company Ltd, New York, 1972.
*
Correspondence to: Prof. Kalevi Pihlaja, Department of
Chemistry, University of Turku, Vatselankatu 2, FIN-20014 Turku,
Finland, email: kpihlaja@utu.fi, phone: 358-(2)-3336767, fax:358-