J . Chem. Tech. Biotechnol. 1990, 47. 209-218
Synthesis and Biological Activity of Some New 2Chlorophenothiazine Derivatives S. R. El-Ezbawy* Department of Chemistry, Faculty of Science, Assiut University, Assiut, Egypt
M. A. Alshaikh Department of Chemistry, Girl’s College, Jeddah, Saudi Arabia (Received 22 September 1988; revised version received 29 March 1989; accepted 18 April 1989)
ABSTRACT
IO-(Hetero/arylthio)acetyl-2-chlorophenothiazines I1 have been synthesized via interaction of I0-chloroacetyl-2-chlorophenothiazine I with heterocyclic andlor aromatic potassium mercaptide in ethanol. Oxidation of I I using H 2 0 2 / C H 3 C O O Hmixture was studied. Structures of the products were verijed by elemental and spectral analyses. Some compounds were screened in vitro for their antibacterial activities. K e y words: synthesis, antibacterial activity, 2chlorophenothiazine, sulphides, sulphones. 1 INTRODUCI‘ION
2-Chlorophenothiazine derivatives have drawn the attention of chemists due to their pharmacological activities and application in the therapy of functional diseases such as nausea and vomiting, mental and emotional disturbances and drug addiction. Moreover, some phenothiazine derivatives are used as anthelmintics and antihistaminics and were found to be bacteri~static.’.~Also, the diverse biological activities for various diary1 sulphides and sulphones are well known.’Incorporation of sulphide or sulphone moieties into 2chlorophenothiazine is therefore expected to produce new compounds with anticipated biological activities. ‘v2
* Present address: Chemistry Department, Faculty of Science, Bani Suef, Egypt. 209 J . Chem. Tech. Biotechnol. 0268-2575/90/$03.50 0 1990 Society of Chemical Industry. Printed in Great Britain
S. R . El-Ezbawy, M . A . Alshaikh
210
2 EXPERIMENTAL Melting points were uncorrected. IR spectra were recorded on a Perkin-Elmer 137B spectrophotometer using the KBr wafer technique. Ultraviolet spectra were determined on a Carl-Zeiss VS U2-P spectrophotometer. 'H NMR spectra were recorded on a Varian A-60 spectrometer using TMS as internal standard and chemical shifts are expressed in p.p.m. Mass spectra were determined on a Finnigan MAT 8230 spectrometer. The purity of the prepared compounds was traced by TLC. 2.1 10-Chloroacet y l-2-chlorophenothiazine (I)
This was prepared as described before.'
2.2 1O-(Hetero/arylthio)acetyl-2chlorophenothiazine (11) Heterocyclic and/or aromatic mercaptan (0.001 mol) was dissolved in absolute ethanol (10ml) and was added to I (0.001 mol) in 20ml absolute ethanol. The reaction mixture was refluxed gently for 3-6 h, cooled and poured on iced water. The formed precipitate was filtered and crystallized from the proper solvent to give 11. Table 1 presents the data.
2.3 Oxidation of I1 (a) A solution of I1 (0.001 mol) in acetic acid (20ml) was treated with 3 ml 30% H,Oz. The mixture was kept at room temperature for 5 days. The deposited crystalline sulphone was collected and purified as usual. In some cases the reaction mixture was poured on water and the formed precipitate was filtered off and crystallized from the proper solvent to give 111. Table 2 presents the data. (b) The previously mentioned procedure was conducted under reflux for 4-1 h. The mixture was left overnight and the formed precipitate was separated as before to give compounds IV. Table 2 shows the data. 3 DISCUSSION The present work reports a simple and efficient synthesis of the hitherto unreported 10-(hetero/arylthio)acetyl-2chlorophenothiazine11. This was accomplished by the interaction of 10chloroacetyl-2chlorophenothiazine I with some selected heterocyclic and/or aromatic potassium mercaptide. The products were identified on the basis of their microanalytical data. Table 1 presents the data. IR spectra showed absorption bands at 1675-1670cm-' for CO and 67M50 cm-' qOCH,SAr
Some new 2-chlorophenothiuzine derioutiues
21 I
corresponding to C-S stretching. UV and visible spectra of several derivatives were determined. All studied compounds were found to exhibit a unique absorption pattern with two maxima. The dependence of the second band on the solvent polarity was studied in order to determine the nature of this band. The solvent polarity did not show any detectable change in A,,,,,, though it showed some intensity dependence. This and the numerical value of the molar extinction coefficients of the two bands indicate that both bands are due to n-n* transition. Table 3 presents the data. For more confirmation of the structure, N M R spectrum for 10[2-(benzthiazolyIthio)-acetyl]-2chlorophenothiazineIIa was recorded. The spectrum shows a singlet at 6 4.4 ppm (2H, -CH,-) and a multiplet at 6 7.17.8 ppm (1 lH, aromatic, 4-benzthiazole ring and 7-phenothiazine ring). Also, the mass spectrum for IIa was studied. The spectrum of this phenothiazine derivative revealed a peculiar behavior. The peak for molecular ion m/e 440 is rather small (2 reflecting the instability of the derivative. The base peak at m/e 208 may be attributed to ion V formed by simple cleavage ofthe H X bond. The appearance ofa peak at m/e VI confirms this type of cleavage. Another peak was observed at m/e 233 which may be attributed to VII. The process of its formation might involve rearrangement of an a-hydrogen and cleavage to give 2chlorophenothiazine ion. Similar pattern was observed for N-acetyl- and N-formylphenothiazine under electron impact. Another significant peak at m/e 166for ion VIII, may be formed by sulfur atom extrusion from phenothiazine ion IX. Also a peak at m/e 154 is present; this may be assigned to ion X formed by loss of the CS fragment. On the other hand, the peak at m/e 180, ion XI, could be attributed to loss of CO. The one at m/e 108 (ion XII) might be due to cleavage of the 1,2-and 3,4-bonds in the benzthiazole ring. Clarke et aL9 reported similar results for 2-substituted thiazoles. Scheme I illustrates the fragmentation pattern. Oxidation of the prepared derivatives was studied. This was accomplished by using H,O, in acetic acid at room temperature or under reflux to give compounds 111 and IV. The structures of these compounds were established on the basis of elemental and spectral analyses. Table 2 shows the data. IR spectra for 111 showed a band at 1685-1675cm-' for CO, at 1326-1315and 1150-1140cm-' attributed to the sulphone group. UV spectra were studied also to provide more evidence for the elucidated structure. The spectra of IIIa and IIIc revealed the presence of two bands. It can be concluded that oxidation occurred at the sulfur atom of the side chain, since the presence of 5,5dioxide-phenothiazinegreatly modifies UV spectra and a characteristic pattern with four maxima is shown.l0 Table 3 shows the data. When the reaction was performed under reflux, oxidation occurred at both sulfur atoms. This could be established on the basis of correct elemental analyses. Table 2 presents the data. The elucidated structure was verified also by electronic spectra which showed four absorption bands. Table 3 presents the data.
x)
4 RESULTS OF BIOLOGICAL SCREENING Several selected compounds were tested in vitro for their growth inhibitory activity against a variety of Gram positive and Gram negative strains of bacteria: Bacillus
TABLE 1 Physical Data of Compounds I1
~
d
~~
Ar
Q
~~
M.p. ("C)
Yield" ( %)
Molecular formula
Analysis ( %) calculated (foun C
H
N
101
68
C21H1 3N20S3C1
57.21 (57.24)
2.95 (2.85)
6-35 (6.40)
2 (2
139
576
c l FJH12N30S2C1
56.03 (56.20)
3.11 (3.23)
10-89 (10.99)
1 (1
55.74 (55.83)
3-61 (3.76)
( 10.89)
(1
60.22 (60.43)
3.76 (3.85)
7.02 (7.15)
1 (1
59.29 (59.39)
3.38 (3.41)
7.28 (7.30)
1 (1
192-3
10.83
1
CJi
52.24 (52.38)
2.81 (2.79)
7.17 (7.31)
24 (24
60.22 (6040)
3.76 (3.83)
7.02 (7.14)
1 (16
58.95 (59.20)
3.27 (3.29)
3.27 (3-20)
14 (14
C2,H,,N0 SzCl
63.39 (6352)
4.02 (4.20)
3-52 (3.60)
16 (16
C21H13N2O2S2CI
59.36 (59.48)
3.06 (3.07)
6.60 (6.59)
1 (15
59.50 (59.55)
3.31 (3.40)
9.87 (9-99)
1 (1
57.8 (57.9)
3.21 (3.26)
3.74 (3.79)
1 (1
188-190
33'
190
lowb
182
sob
cZ 1
178
48'
149
38'
138
29 '
c2 1
140
30'
Cl,Hl2NO2S2C~
C17H11N20S3C1
C20H15N2OS2Cl
Y N H ,
Q
14N03S2C1
'COOH
14N,0S2C1
H
o f crystallization; *ethanol; ' acetone.
d
TABLE 2 Physical Data of Compounds 111 and IV Ar
Yield"
(%I
M.p. ("C)
Molecular formula
Analysis ( %) calculated (foun
H
N
C21H13N203S3C1 53.33 (53.52)
2.75 (2.78)
5.92 (6.83)
20 (2
C
Q QNHz
40
239
75b
205 (cham.)
Cl,H13N203S2Cl
54.74 (54.79)
3.12 (3.23)
6.72 (6.74)
1 (1
62'
208
C2,HISN2O3S2C1
55.74 (55.83)
3-48 (3.42)
6.50 (6.52)
1 (1
60'
201
C2,HI3N,O4S2C1
55.20 (55.29)
2-85 (2.88)
6.13
1
(6.15)
(1
55.32 (55.42)
3.07 (3.06)
9.22 (9.24)
1 (1
49 H
195
C21H14N303S2Cl
@
1N203S3C1
48.98 (49.14)
2.64 (2.64)
6.72 (6.74)
23 (2
1 4N0,S2C1
54.84 (54.93)
3.04 (3.08)
3.04 (3.05)
1 (1
224 (charr.)
C21H13N205S3C1
49.95 (49.99)
2-57 (2.59)
5.55
(5.59)
1 (19
240 (charr.)
C19H13N20SS2C1
50.83 (50.93)
289 (2.92)
624 (6.26)
1 (1
40*
186
C17H11N205S3C1
45.48 (45.52)
2-45 (2-48)
6.24 (6.25)
21 (2
45 '
194
C 2 1 H 1 3N206S2C1
51.58 (51.62)
2.66 (2.68)
5.73 (5.75)
1 (1
39'
188
c2 l H 1 4N30SS2C1
51-69 (51.71)
2.87 (2.89)
862 (8.66)
1 (1
50d
200
C17H1
65'
221
c2 1
'COOH
Q
50'
aOJ H
of crystallization: *acetic acid; 'ethanol; dacetone.
S. R . El-Erbawy, M . A . Alshoikh
216
TABLE 3 UV Spectra of Compounds 11, 111 and I V
IIb IIf IIe IIg IId IIIa IIIC IVa 1vc
254,319 257, 320 256, 322 252, 325 252, 282 (sh) 244, 283 242, 280 244,278, 304, 328 242,279, 304, 327
16761, 1730 16 964, 1786 20 779, 1740 18 888, 2951 19 186, 12 298 17 660, 17 061 19 760, 18 634 12 878, 15 909, 6818, 3030 16 018, 13 272, 6407, 4348
(VI) m/e 232 (47%) (234 isotope ion)
I
(V) m/e 208 (100%)
I
m/e 440 (2%)
(VII) m/e 233 (66%) (235 isotope ion)
--co
(XI) m/e 180 (55%)
(XII) m/e 108 (4.4%)
(IX) m/e 198 (12.9%)
(X) m/e 154 (6%)
(VIII) m/e 166 (6%)
Scheme 1
COCH,SO,Ar
FOCH,SAr
TABLE 4 Antibacterial Activities Aaeruge inhibition zone diameters (mm)
Conipoirnd no.
~-
B. subtilis
S. aureus
E. coli
P. fluorescens
6 13
9 15 17
16 14 18
13 14 16
15 15 11
13 8 12 21 20 20 20
13 8 12 22
~~
tlb Ilc Ild Ile 14% Ilh IIIa IIIb I Va IVb
15
13 13 10
12 II 12 13
17 15 18 18
15
16 20
subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas fluorexens. The antibacterial activity was evaluated by using the filter paper disc technique" at a concentration of 100 pg per disc. The data are presented in Table 4.Results show that all tested compounds exhibit fair to high activity. Compounds I11 and IV were the strongest inhibitors.
REFERENCES 1. Shemisa, 0. A. & Fahien, L. A., Modification of glutamate dehydrogenase by various
drugs which affect behavior. Molec. Pharmacol., 7 (1971) 8-25. 2. Kuribara, H. & Tadokoro, S., Comparison of susceptibilities to the effects of antipsychotic drugs on lever-press avoidance responses between mice and rats. Jpn. J. Phurmucol., 33 (1983) 1127-33. 3. Tozer, T. N.. Tuck, L. D. & Craig, J. C., Activity of phenothiazine anthelmintics as related to semiquinone formation. J . Med. Chem., 12 (1969) 294-9. 4. Molnar, J. & Scheider, B., Plasmid curing and antibacterial effects of some chlorpromoazine derivatives in relation to their molecule orbitals. Acta Microbiol. Acud. Sci. Hung., 25 (1978) 291-8. 5. El-Ezbawy, S. R., Abdel-Wahab, A. A. & Khalaf, A. A., Synthesis and biological activities of some new 2-aminopyridine derivatives. Rev. Roumaine Chim.,27 (1982) 53744.
S. R . El-Ezhawy, M . A . Alshuikh
218
M.,El-Ezbawy, S. R., Abdel-Wahab, A. A. & El-Sherief, H. A., Synthesis of some new aryl and alkylmercaptobenzoxaole, benzimidazoles and benzthiazoles of biological interest. Acta Pharm. Jugosl., 32 (1982) 45-51. Abbady, M. A., El-Kashef, H. S., Abol-Alla, M. A. & Kandeel, M.M.,Synthesis and antibacterial activity of some new diarylsulphides and diarylsulphones containing azetidin-2-one and/or diazetidin-2-onyl moieties. J. Chem. Tech. Biotechnol., 32 (1984) 62-72. Dahlbom, R. & Ekstrand, T., 10-Aminoacylphenothiazines. 1-Amino-acetyl and aminopropionyl derivatives. Acta Chem. Scand., 5 (1951) 102-14. Clarke, G. M.,Grigg, R. & Williams, D. H.,Studies in mass spectrometry. Part VII. Mass spectra of thiazoles. J . Chem. Soc. ( B ) (1966) 339-43. Wechsler, M. B. & Forrest, I. S., Determination of chloroprornazine in tissues. Neurochem., 4 (1959) 36671. British Pharmacopoeia. Biological assay of antibiotics. The Pharmaceutical Press, London, 1968, pp. 1313-17.
6. Mahmoud, A.
7.
8. 9.
10. 1 1.
Synthesis and Biological Activity of Some New 2Chlorophenothiazine Derivatives S. R. El-Ezbawy* Department of Chemistry, Faculty of Science, Assiut University, Assiut, Egypt
M. A. Alshaikh Department of Chemistry, Girl’s College, Jeddah, Saudi Arabia (Received 22 September 1988; revised version received 29 March 1989; accepted 18 April 1989)
ABSTRACT
IO-(Hetero/arylthio)acetyl-2-chlorophenothiazines I1 have been synthesized via interaction of I0-chloroacetyl-2-chlorophenothiazine I with heterocyclic andlor aromatic potassium mercaptide in ethanol. Oxidation of I I using H 2 0 2 / C H 3 C O O Hmixture was studied. Structures of the products were verijed by elemental and spectral analyses. Some compounds were screened in vitro for their antibacterial activities. K e y words: synthesis, antibacterial activity, 2chlorophenothiazine, sulphides, sulphones. 1 INTRODUCI‘ION
2-Chlorophenothiazine derivatives have drawn the attention of chemists due to their pharmacological activities and application in the therapy of functional diseases such as nausea and vomiting, mental and emotional disturbances and drug addiction. Moreover, some phenothiazine derivatives are used as anthelmintics and antihistaminics and were found to be bacteri~static.’.~Also, the diverse biological activities for various diary1 sulphides and sulphones are well known.’Incorporation of sulphide or sulphone moieties into 2chlorophenothiazine is therefore expected to produce new compounds with anticipated biological activities. ‘v2
* Present address: Chemistry Department, Faculty of Science, Bani Suef, Egypt. 209 J . Chem. Tech. Biotechnol. 0268-2575/90/$03.50 0 1990 Society of Chemical Industry. Printed in Great Britain
S. R . El-Ezbawy, M . A . Alshaikh
210
2 EXPERIMENTAL Melting points were uncorrected. IR spectra were recorded on a Perkin-Elmer 137B spectrophotometer using the KBr wafer technique. Ultraviolet spectra were determined on a Carl-Zeiss VS U2-P spectrophotometer. 'H NMR spectra were recorded on a Varian A-60 spectrometer using TMS as internal standard and chemical shifts are expressed in p.p.m. Mass spectra were determined on a Finnigan MAT 8230 spectrometer. The purity of the prepared compounds was traced by TLC. 2.1 10-Chloroacet y l-2-chlorophenothiazine (I)
This was prepared as described before.'
2.2 1O-(Hetero/arylthio)acetyl-2chlorophenothiazine (11) Heterocyclic and/or aromatic mercaptan (0.001 mol) was dissolved in absolute ethanol (10ml) and was added to I (0.001 mol) in 20ml absolute ethanol. The reaction mixture was refluxed gently for 3-6 h, cooled and poured on iced water. The formed precipitate was filtered and crystallized from the proper solvent to give 11. Table 1 presents the data.
2.3 Oxidation of I1 (a) A solution of I1 (0.001 mol) in acetic acid (20ml) was treated with 3 ml 30% H,Oz. The mixture was kept at room temperature for 5 days. The deposited crystalline sulphone was collected and purified as usual. In some cases the reaction mixture was poured on water and the formed precipitate was filtered off and crystallized from the proper solvent to give 111. Table 2 presents the data. (b) The previously mentioned procedure was conducted under reflux for 4-1 h. The mixture was left overnight and the formed precipitate was separated as before to give compounds IV. Table 2 shows the data. 3 DISCUSSION The present work reports a simple and efficient synthesis of the hitherto unreported 10-(hetero/arylthio)acetyl-2chlorophenothiazine11. This was accomplished by the interaction of 10chloroacetyl-2chlorophenothiazine I with some selected heterocyclic and/or aromatic potassium mercaptide. The products were identified on the basis of their microanalytical data. Table 1 presents the data. IR spectra showed absorption bands at 1675-1670cm-' for CO and 67M50 cm-' qOCH,SAr
Some new 2-chlorophenothiuzine derioutiues
21 I
corresponding to C-S stretching. UV and visible spectra of several derivatives were determined. All studied compounds were found to exhibit a unique absorption pattern with two maxima. The dependence of the second band on the solvent polarity was studied in order to determine the nature of this band. The solvent polarity did not show any detectable change in A,,,,,, though it showed some intensity dependence. This and the numerical value of the molar extinction coefficients of the two bands indicate that both bands are due to n-n* transition. Table 3 presents the data. For more confirmation of the structure, N M R spectrum for 10[2-(benzthiazolyIthio)-acetyl]-2chlorophenothiazineIIa was recorded. The spectrum shows a singlet at 6 4.4 ppm (2H, -CH,-) and a multiplet at 6 7.17.8 ppm (1 lH, aromatic, 4-benzthiazole ring and 7-phenothiazine ring). Also, the mass spectrum for IIa was studied. The spectrum of this phenothiazine derivative revealed a peculiar behavior. The peak for molecular ion m/e 440 is rather small (2 reflecting the instability of the derivative. The base peak at m/e 208 may be attributed to ion V formed by simple cleavage ofthe H X bond. The appearance ofa peak at m/e VI confirms this type of cleavage. Another peak was observed at m/e 233 which may be attributed to VII. The process of its formation might involve rearrangement of an a-hydrogen and cleavage to give 2chlorophenothiazine ion. Similar pattern was observed for N-acetyl- and N-formylphenothiazine under electron impact. Another significant peak at m/e 166for ion VIII, may be formed by sulfur atom extrusion from phenothiazine ion IX. Also a peak at m/e 154 is present; this may be assigned to ion X formed by loss of the CS fragment. On the other hand, the peak at m/e 180, ion XI, could be attributed to loss of CO. The one at m/e 108 (ion XII) might be due to cleavage of the 1,2-and 3,4-bonds in the benzthiazole ring. Clarke et aL9 reported similar results for 2-substituted thiazoles. Scheme I illustrates the fragmentation pattern. Oxidation of the prepared derivatives was studied. This was accomplished by using H,O, in acetic acid at room temperature or under reflux to give compounds 111 and IV. The structures of these compounds were established on the basis of elemental and spectral analyses. Table 2 shows the data. IR spectra for 111 showed a band at 1685-1675cm-' for CO, at 1326-1315and 1150-1140cm-' attributed to the sulphone group. UV spectra were studied also to provide more evidence for the elucidated structure. The spectra of IIIa and IIIc revealed the presence of two bands. It can be concluded that oxidation occurred at the sulfur atom of the side chain, since the presence of 5,5dioxide-phenothiazinegreatly modifies UV spectra and a characteristic pattern with four maxima is shown.l0 Table 3 shows the data. When the reaction was performed under reflux, oxidation occurred at both sulfur atoms. This could be established on the basis of correct elemental analyses. Table 2 presents the data. The elucidated structure was verified also by electronic spectra which showed four absorption bands. Table 3 presents the data.
x)
4 RESULTS OF BIOLOGICAL SCREENING Several selected compounds were tested in vitro for their growth inhibitory activity against a variety of Gram positive and Gram negative strains of bacteria: Bacillus
TABLE 1 Physical Data of Compounds I1
~
d
~~
Ar
Q
~~
M.p. ("C)
Yield" ( %)
Molecular formula
Analysis ( %) calculated (foun C
H
N
101
68
C21H1 3N20S3C1
57.21 (57.24)
2.95 (2.85)
6-35 (6.40)
2 (2
139
576
c l FJH12N30S2C1
56.03 (56.20)
3.11 (3.23)
10-89 (10.99)
1 (1
55.74 (55.83)
3-61 (3.76)
( 10.89)
(1
60.22 (60.43)
3.76 (3.85)
7.02 (7.15)
1 (1
59.29 (59.39)
3.38 (3.41)
7.28 (7.30)
1 (1
192-3
10.83
1
CJi
52.24 (52.38)
2.81 (2.79)
7.17 (7.31)
24 (24
60.22 (6040)
3.76 (3.83)
7.02 (7.14)
1 (16
58.95 (59.20)
3.27 (3.29)
3.27 (3-20)
14 (14
C2,H,,N0 SzCl
63.39 (6352)
4.02 (4.20)
3-52 (3.60)
16 (16
C21H13N2O2S2CI
59.36 (59.48)
3.06 (3.07)
6.60 (6.59)
1 (15
59.50 (59.55)
3.31 (3.40)
9.87 (9-99)
1 (1
57.8 (57.9)
3.21 (3.26)
3.74 (3.79)
1 (1
188-190
33'
190
lowb
182
sob
cZ 1
178
48'
149
38'
138
29 '
c2 1
140
30'
Cl,Hl2NO2S2C~
C17H11N20S3C1
C20H15N2OS2Cl
Y N H ,
Q
14N03S2C1
'COOH
14N,0S2C1
H
o f crystallization; *ethanol; ' acetone.
d
TABLE 2 Physical Data of Compounds 111 and IV Ar
Yield"
(%I
M.p. ("C)
Molecular formula
Analysis ( %) calculated (foun
H
N
C21H13N203S3C1 53.33 (53.52)
2.75 (2.78)
5.92 (6.83)
20 (2
C
Q QNHz
40
239
75b
205 (cham.)
Cl,H13N203S2Cl
54.74 (54.79)
3.12 (3.23)
6.72 (6.74)
1 (1
62'
208
C2,HISN2O3S2C1
55.74 (55.83)
3-48 (3.42)
6.50 (6.52)
1 (1
60'
201
C2,HI3N,O4S2C1
55.20 (55.29)
2-85 (2.88)
6.13
1
(6.15)
(1
55.32 (55.42)
3.07 (3.06)
9.22 (9.24)
1 (1
49 H
195
C21H14N303S2Cl
@
1N203S3C1
48.98 (49.14)
2.64 (2.64)
6.72 (6.74)
23 (2
1 4N0,S2C1
54.84 (54.93)
3.04 (3.08)
3.04 (3.05)
1 (1
224 (charr.)
C21H13N205S3C1
49.95 (49.99)
2-57 (2.59)
5.55
(5.59)
1 (19
240 (charr.)
C19H13N20SS2C1
50.83 (50.93)
289 (2.92)
624 (6.26)
1 (1
40*
186
C17H11N205S3C1
45.48 (45.52)
2-45 (2-48)
6.24 (6.25)
21 (2
45 '
194
C 2 1 H 1 3N206S2C1
51.58 (51.62)
2.66 (2.68)
5.73 (5.75)
1 (1
39'
188
c2 l H 1 4N30SS2C1
51-69 (51.71)
2.87 (2.89)
862 (8.66)
1 (1
50d
200
C17H1
65'
221
c2 1
'COOH
Q
50'
aOJ H
of crystallization: *acetic acid; 'ethanol; dacetone.
S. R . El-Erbawy, M . A . Alshoikh
216
TABLE 3 UV Spectra of Compounds 11, 111 and I V
IIb IIf IIe IIg IId IIIa IIIC IVa 1vc
254,319 257, 320 256, 322 252, 325 252, 282 (sh) 244, 283 242, 280 244,278, 304, 328 242,279, 304, 327
16761, 1730 16 964, 1786 20 779, 1740 18 888, 2951 19 186, 12 298 17 660, 17 061 19 760, 18 634 12 878, 15 909, 6818, 3030 16 018, 13 272, 6407, 4348
(VI) m/e 232 (47%) (234 isotope ion)
I
(V) m/e 208 (100%)
I
m/e 440 (2%)
(VII) m/e 233 (66%) (235 isotope ion)
--co
(XI) m/e 180 (55%)
(XII) m/e 108 (4.4%)
(IX) m/e 198 (12.9%)
(X) m/e 154 (6%)
(VIII) m/e 166 (6%)
Scheme 1
COCH,SO,Ar
FOCH,SAr
TABLE 4 Antibacterial Activities Aaeruge inhibition zone diameters (mm)
Conipoirnd no.
~-
B. subtilis
S. aureus
E. coli
P. fluorescens
6 13
9 15 17
16 14 18
13 14 16
15 15 11
13 8 12 21 20 20 20
13 8 12 22
~~
tlb Ilc Ild Ile 14% Ilh IIIa IIIb I Va IVb
15
13 13 10
12 II 12 13
17 15 18 18
15
16 20
subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas fluorexens. The antibacterial activity was evaluated by using the filter paper disc technique" at a concentration of 100 pg per disc. The data are presented in Table 4.Results show that all tested compounds exhibit fair to high activity. Compounds I11 and IV were the strongest inhibitors.
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