Synthesis and reactions of some tetrahydrobenzothieno[2,3-d]pyrimidine derivatives with biological interest

Article abstract of DOI:10.1080/10426500307912

Hetetrocyclic substituted rings were prepared from 1-amino-2-carboxamido-4,5,6,7-tetrahydrobenzothiophene and carbon disulphide, chloroacetic acid, or arylidene with different active methylene groups. The antimicrobial activity of synthesized compounds is discussed.

Full text of DOI:10.1080/10426500307912

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Phosphorus, Sulfur, and Silicon and the Related
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Synthesis and Reactions of Some
Tetrahydrobenzothieno[2,3- d ]Pyrimidine Derivatives
with Biological Interest
A. M. Sh. El-Sharief a , J. A. A. Micky a , N. A. M. M. Shmeiss a & G. El-Gharieb a
a Al-Azhar University , Nasr City-Cairo, Egypt
Published online: 27 Oct 2010.
To cite this article: A. M. Sh. El-Sharief , J. A. A. Micky , N. A. M. M. Shmeiss & G. El-Gharieb (2003) Synthesis and Reactions
of Some Tetrahydrobenzothieno[2,3- d ]Pyrimidine Derivatives with Biological Interest, Phosphorus, Sulfur, and Silicon and the
Related Elements, 178:3, 439-451
To link to this article: http://dx.doi.org/10.1080/10426500307912
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Phosphorus, Sulfur and Silicon, 2003, Vol. 178:439–451
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Copyright 2003 Taylor & Francis
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DOI: 10.1080/10426500390170589
SYNTHESIS AND REACTIONS OF SOME
TETRAHYDROBENZOTHIENO[2,3-d ]PYRIMIDINE
DERIVATIVES WITH BIOLOGICAL INTEREST
A. M. Sh. El-Sharief, J. A. A. Micky, N. A. M. M. Shmeiss,
and G. El-Gharieb
Al-Azhar University, Nasr City-Cairo, Egypt
(Received May 25, 2002; accepted July 25, 2002)
Hetetrocyclic substituted rings were prepared from 1-amino-2-
carboxamido-4,5,6,7-tetrahydrobenzothiophene and carbon disul-
phide, chloroacetic acid, or arylidene with different active methy-
lene groups. The antimicrobial activity of synthesized compounds is
discussed.
INTRODUCTION
Many tetrahydrobenzothiophenes possess a wide span of medical
activities including hypoglycemic,1 antifibrillatory,2 and antitumor
characteristics.3 Furthermore, divers biological properties have been
associated with numerous thienopyrimidines and thiazolothienopyrim-
idines comprising hypnotic,4 antivirol,5,6 and plant bactericidal effects.7
Based on the foregoing, the synthesis of certain novel thieopyrim-
idines and thiazolothienopyrimidines were undertaken in and endeavor
to produce heterocylic compounds of possible pharmacological activity.
Results and Discussion
Condensation of cyclohexanone with cyano(thio)acetamide and ele-
mental sulfur in presence of morpholine afforded 2-amino-4,5,6,7-
terahydrobenzothiophen-3-[carbo(thio)oxamide] 1a,b. The reaction
with cyanothioacetamide proceeded via a Gewald reaction,8 followed
by a condensation with another mole of cyclohexanone to yield 1a. This
structure was indicated via its mass spectrum where a molecular ion
appeared at m/z 292 [M+, 73.8%].
Address correspondence to N. A. M. M. Shmeiss, Chemistry Department, Faculty of
Science, Al-Azhar University (Girls), Nasr City-Cairo, Egypt.
439

440
A. M. Sh. El-Sharief et al.
SCHEME 1
Interaction (Scheme 1) of 2-(N-cyclohexyl)-4,5,6,7-tetrahydrobenzo-
thiophen-3-carbothioamide 1a with thiosemicarbazide or 2,4-dinitro-
phenyl-hydrazine in the presence of alcoholic potassium hydroxide
generated an adduct from which H2S evolved to produce compounds
2a,b. The infrared spectra showed the appearance of cyano group at
1
2199 cm
.
While the reaction 1a with benzoyl hydrazide under the same con-
ditions caused an evolution of H2S to form the carbonitrile 3 as the

Tetrahydrobenzothieno[2,3-d]Pyrimidine Derivatives
441
intermediate, the latter lost one molecule of water to form triazolo
derivative 4. The IR spectrum of 4 showed the disappearance of the car-
bonyl group of benzoyl hydrazide and the appearance of a cyano group.
On the other hand, fusion of thioamide derivative 1a with hydrazine hy-
drate caused a loss of H2S to yield the carbonitrile intermediate 5, which
underwent intermolecular cyclization to yield triazepine derivative 6
(Scheme 1).
Interaction of 2-amino-4,5,6,7-tetrahydrobenzothiophen-3-carbox-
amide 1b with a equivalent of chloroacetic acid or acetic anhydride
afforded N,N-disubstituted derivatives 7a,b. However in the case of
acetic anhydride, dehydration took place to give carbonitrile deriva-
tive 7b, which was in agreement with spectral data where the mass
spectrum of 7a showed a molecular ion peak at 312. This was compat-
ible with molecular formula C13H16N2O5S, and the IR spectrum of 7b
1
showed a cyano group at 2213 cm
.
The Schiff’s base 8a,b were obtained through the condensation
of 1b with p-chlorobenzaldehyde in presence of triethylamine or tri-
ethylorthoformate in dimethylformamide respectively. Structures were
assigned from mass spectral analysis. For example 8a exhibited a
1
molecular ion peak at m/z 318. The H-NMR spectrum of 8a showed
a singlet at 7.8 which revealed a CH N group and peaks of ethoxy
at 1.0 (t, 3H, CH3) and 3.6 (q, 2H, CH2). Treatment of 1b with
SCHEME 2

442
A. M. Sh. El-Sharief et al.
carbon disulphide yielded 2-thioxo-5,6,7-8-tetrahydrobenzothieno-
[2,3-d]pyrimidin-4-(3H)one, either 9 or the possible isomer 10. The
mass spectrum of 9 revealed a molecular ion peak at m/z 238
[M+, 100%] and this was compatible with the molecular formula
C10H10N2OS2which was analogous to previous work.9
Condensation of 2-mercaptothieno[2,3-d]pyrimidin-4-one 10 with
chloroacetic acid in presence of alcoholic potassium hydroxide caused
alkylation of the thiol group to give thienopyrimidine derivative 11.
The interaction of 10 with chloroacetic acid in acetic anhydride in
presence of anhydrous sodium acetate alkylation occurred, followed by
cyclodehydration to produce thiazolopyrmidine derivative 12. The IR
spectrum of 11 showed a broad band of an OH, and a C O of a carboxylic
acid. The 1H-NMR spectrum of 12 showed the presence of a CH2 group
of the thiazolidinone moiety at 4.0. Interaction of 2-mercaptothieno-
[2,3-d]pyrimidin-4-(3H)one 10 with arylidene malonnitrile or ethyl-
cyanoacetate led to the formation of the corresponding 2-amino-
4-(aryl)-6-oxo-7,8,9,10-tetrahydro-1,3-thiazino-[3,2-a]-thieno-[2,3-d]-
pyrimidine–3-carbonitrile (or carbethoxy, 13a–c, Scheme 3).
SCHEME 3

Tetrahydrobenzothieno[2,3-d]Pyrimidine Derivatives
443
Compound 12 that contained an active methylene group con-
densed with benzaldehyde to yield 2-(phenylmethylene)–3,5-dioxo-
6,7,8,9-tetrahydrobenzo-1,3 thiazolo[3,2-a]thieno[2,3-d]pyrmidine 14.
The latter also could be conveniently prepared through reaction of 10
with chloroacetic acid and benzaldehyde in acetic anhydride in presence
of anhydrous sodium acetate (Scheme 4).
SCHEME 4
On the other hand, reaction of 12 with arylidene malononitrle or
ethylcyanoacetate afforded 15a,b or the possible isomer 16a,b. The
structure of 15a was confirmed by elementary analysis and spectro-
1
scopic data wherein the H-NMR spectrum showed signals at 5.6 (s,
1H, H4 pyran moiety) and 7.3–7.6 (m, 7H, Ar H + NH2). The mass
spectrum exhibited a molecular ion peak at 432 which is compatible
1
with the molecular formula C22H16N4O2S2. The H-NMR spectrumof
15b revealed a signal for the ethoxy group at 1.3 (t, 3H, CH3) and 4.4
(q, 2H, CH2) (Scheme 5).
EXPERIMENTAL
All melting points were uncorrected. The IR spectra were recorded
1
in KBr on a unicam SP200 spectrophotometer. The H-NMR (CDCl3
or DMSO) spectra were obtained using a Geol DFF 100 (270 NH2) with
TMS as an internal reference. Mass spectra were recorded on a Varian
mat. CH-48 spectrometer.
2-(N-Cyclohexyl)-4,5,6,7-tetrahydrobenzothiophene–
3-thioamide (1a)
A mixture of cyclohexanone (0.1 mmol) cyanothioacetamide (0.1 mmol)
and sulfur (0.1 mmol) in ethanol (30 ml) and morpholine (5 ml) was

444
A. M. Sh. El-Sharief et al.
SCHEME 5
refluxed for 4 h. The reaction mixture was left to cool, and the solid
formed was recrystallized from ethanol (Tables I and II). The 1b was
previously prepared.9,10
Mass spectrum of 1a: m/z 292 (M+ 73.8%), 263 (22%), 259 (33.4%)
with base peak 249.
2-N-Cyclohexyl-4,5,6,7-tetrahydrobenzothiophene
Hydrazide Derivatives (2a,b)
Compound 1a (0.01 mmol) was refluxed with thiosemicarbazide or 2,4
dinitrophenylhydrazine (0.01 mmol) in ethanol for 6 h. The reaction
mixture was left to cool, and the precipitate formed was filtered off and
crystallized from a suitable solvent to give derivatives 2a,b respectively.
2a Mass: m/z 349 [M+, 1.05%], 300 [M+-17(NH3)], 259 (M+-HCNS
59%), 236 (M+-96 ( N)).
2b 1H-NMR:
4.7(DMSO) (br. s, 1H, NH2), 2.6–1.2 (2m, 18H, two cyclohexyl H’s).
8.3 (s, 1H, NH), 7.8–7.0 (m, 8H, aromatic H’s),

Tetrahydrobenzothieno[2,3-d]Pyrimidine Derivatives
TABLE I Physical Properties of New Compounds
445
Cl
Analysis calcd/found
Comp.
no.
Solvent Yield
Mol.
m.p.
C
color
%
form./m.wt.
C
H
N
S
1a
2a
230 EtOH
White
200 EtOH
Gray
170 EtOH
Green
165 EtOH
Orange
265 EtOH
Brown
210 EtOH
Brown
140 EtOH
Gray
235 EtOH
Green
240 EtOH
Yellow
245 EtOH
Brown
200 EtOH
Brown
165 EtOH
Brown
200 EtOH
Green
90 EtOH
Brown
170 EtOH
Brown
>300 EtOH
Brown
60
C15H20N2S2
292.44
C16H23N5S2
349.49
C21H25N6O4S
457.50
C22H24N4S
376.50
61.60 6.89 9.57 21.92
61.71 6.95 9.62 22.00
54.98 6.63 20.03 18.34
54.78 6.43 19.99 18.21
55.12 5.50 18.36 17.00
55.25 5.62 18.43 7.13
70.17 6.42 14.88 8.51
70.27 6.51 14.91 8.61
62.03 7.63 19.29 11.03
62.13 7.72 19.35 11.18
49.99 5.16 8.96 10.26
50.1 5.22 9.10 10.35
59.52 5.37 10.67 12.22
59.61 5.45 10.72 12.33
60.27 4.74 8.78 10.65 11.12
60.11 4.62 8.77 10.55 11.00
57.11 6.39 11.10 12.70
57.25 6.45 11.21 12.82
50.39 4.21 11.75 26.90
50.31 4.31 11.82 26.91
48.63 4.08 9.45 21.63
48.69 4.17 9.60 21.72
51.78 3.62 10.06 23.04
51.81 3.72 10.14 23.16
61.20 41.6 14.27 16.33
61.15 4.14 14.20 16.23
65
60
50
55
70
70
60
90
70
75
60
75
60
60
85
75
60
2b
4
6
C15H22N4S
290.41
C13H16N2O5S
312.32
7a
7b
8a
C13H14N2O2S
262.31
C16H15N2OSCl
318.79
8b
10
C12H16N2O2S
252.32
C
10H10N2OS2
238.30
11
C12H12N2O3S2
296.32
12
C
12H10N2O2S2
278.33
13a
13b
13c
14
C
20H16N4OS2
392.46
C22H20N3O3S2Cl 55.74 4.25 8.86 13.52 7.48
473.94
23H23N3O4S2
469.50
55.54 4.20 8.66 13.42 7.38
58.83 4.93 8.95 13.65
58.91 5.07 9.10 13.72
62.27 3.85 7.64 17.49
62.15 3.96 7.73 17.54
61.09 3.72 12.95 14.82
61.20 3.61 13.00 14.72
58.92 4.55 8.24 12.60
59.05 4.61 8.30 12.52
C
C19H14N2O2S2
366.43
15a
15b
200 EtOH
Green
90 EtOH
Orange
C
22H16N4O2S2
432.47
C25H23N3O5S2
509.57
2-(N-Cyclohexyl)-4,5,6,7-tetrahydrobenzothiophene-
3-(2-phenyl-1,2,4-triazol) (4)
Compound 1a (0.01 mmol) was refluxed with benzoylhydrazide
(0.01 mmol) for 4 h. The reaction mixture was left to cool. The crys-
tals formed was recrystallized from a suitable solvent.
1H-NMR: 8.2 (s, 1H, NH), 7.5–7.2 (m, 5H, aromatic H’s), 3–1.8
(m, 18H, two cyclohexyl H’s).

446
A. M. Sh. El-Sharief et al.
TABLE II IR Spectroscopic Data for the Prepared Compounds
Comp.
no.
1
IR (KBr) cm
1a
2a
3141 (NH), 2923, 2844 (CH-aliphatic), 1539 (C N) and 1224 (C S)
Broad band at 3189 (NH2/NH), 2926, 2852 (CH-aliphatic 2199 (C N) and
1221 (C S)
2b
4
6
Strong broad band at 3143 (NH), 2928, 2851 (CH-aliphatic and 2199 (C N)
3140 (NH), 2920, 2848 (CH-aliphatic), 2197 (C N) and 1521(C N)
3378, 3299, 3176 (H2N/NH), 2931, 2853 (CH-aliphatic) and 1623 (C N)
Broad band 3405 (HO/NH2), 2930 (CH-aliphatic) and very strong band at 1657
(C O)
7a
7b
8a
8b
2934 (CH-aliphatic), 2213 (C N) and 1743, 1693 (C O)
Broad band 3100 (NH2), 2924 (CH-aliphatic) and 1654 (C O)
2931 (CH-aliphatic) and 1631 (C O)
10
3427 (NH), 1664 (C O) and 1205 (C S)
11
12
Broad band (3226–2300) OH of carboxylic) and 1689 (C O)
3433 (OH), 2928 (CH-aliphatic) and 1663 (C O)
13a
13b
13c
15a
15b
3320, 3181 (NH2), 2931 (CH-aliphatic), 2195 (C N) and 1653 (C O)
3373, 3182 (NH2), 2930 (CH-aliphatic) and 1637 (C O)
3371, 3186 (NH2), 2931 (CH-aliphatic) and 1635 (C O)
3385 (NH), 2933, 2855 (CH-aliphatic), 2205 (C N) and 1686 (C O)
3373, 3182 (NH2), 2930, 2855 (CH-aliphatic) and 1637 (C O)
2-Cyclohexyl-4amino-6,7,8,9,-
tetrahydrobenzothiophene-1,3,4-triazepine (6)
A mixture of 1a (0.1 mmol) and excess hydrazine hydrate was fused for
1/2 h. The solid obtained was crystallized from suitable solvent (Tables I
and II).
2-N-Diacetic Acid-3 Carboxamido-4,5,6,7-
tetrahydrobenzothiophene (7a)
Compound 1b (0.01 mmol) was refluxed with chloroacetic acid
(0.01 mmol) in the presence of alcoholic KOH (20 ml) for 6 h. The
mixture was cooled, and then acidified with dilute hydrochloric acid.
The crystals formed were washed with water and crystallized from a
suitable solvent.
Mass: m/z at 312 (M+), 314 (M+ + 2, 29.6%), 254 (51.9%), and a base
peak at 192.
2-N-Diacetyl-3-cyano-4,5,6,7-
tetrahydrobenzothiophene (7b)
Acetic anhydride (20 mmol) and compound 1b (0.01 mmol) were re-
fluxed for 8 h. The reaction mixture was allowed to cool, and then poured

Tetrahydrobenzothieno[2,3-d]Pyrimidine Derivatives
447
into water, the solid was filtered off, washed with H2O, and recrystal-
lized from a suitable solvent.
Mass: m/z at 262 (M+, 3%), 220 [(M+-43 (COCH3), 90.4%], 197
(75.5%), and a base peak at 192.
SCHIFF’S BASES 8a,b
8a: p-Chlorobenzaldehyde (0.01 mmol) and compound 1b (0.01 mmol)
in ethanol (20 ml) and two drops of triethylamine were refluxed for 6 h.
The reaction was cooled and acidified with dilute HCl. The solid formed
was filtered and washed with water and recrystallized from a suitable
solvent.
Mass: m/z at 318 (M+, 1%), 283 (24%), and base peak at 62.
8b: Triethylorthoformate (0.04 mmol) in acetic anhydride (20 ml)
and compound 1b (0.01 mmol) were refluxed for 4 h. Cooling the reac-
tion gave a solid which was filtered and recrystallized from a suitable
solvent.
Mass: m/z at 252 (M+, 4.861%) and a base peal at 62.
(CDCl3)
1H-NMR: 7.8 (s, 1H, CH N), 3.6 (q, 2H, CH2), 2.8, 2.4, 1.4
(m, 10H, tetrahydrobenzo + NH2) 1.0 (t, 3H, CH3).
13C: 170 (C O), 143, 133, 131, 127, 125, 120 (4 thiophen C’S + 1
(DMSO)
CH N), 36,27 (2-aliphatic C’S) 26, 25, 23, 22 (4 tetrahydrobenzo
C’S).
2-Thioxo-4,5,6,7-tetrahydrobenzothieno-
(2,3,d)pyrimidine-4-(3H) one (10)
A mixture of compound 1b (0.01 mmol), carbon disulphide (10 ml), and
KOH (3.6 gm) in ethanol (50 ml) was refluxed in a water bath at 60–
80 C for 24 h. The reaction mixture was acidified with dilute acetic acid,
the solid formed was washed with water, filtered off, and recrystallized
from a suitable solvent.
Mass: m/z at 238 (M+ 100%), 210 (18,97%), 178 (62.4%) 151
(44.0 %).
2-S-Acetic-4-oxo-4H-4,5,6,7-tetrahydrobenzothiopheno-
[3,2-e)pyrmidine (11)
A mixture of compound 10 (0.01 mmol) and chloroacetic acid (0.01 mmol)
in acetic acid (20 ml) in presence of sodium acetate (0.01 mmol) were
refluxed for 6 h. The reaction was cooled and the solid obtained was
washed with water and recrystallized from a suitable solvent.

448
A. M. Sh. El-Sharief et al.
Mass: m/z at 296 (M+,15.8%), 278 [(M-18 (H2O), 100%].
Tetrahydrobenzothien(1,3)thiazolo(5,1- b)pyrimidine-
3,4-dione (12)
A mixture of compound 10 (0.01 mmol) and chloroacetic acid
(0.01 mmol) in acetic anhydride (30 m) in presence of sodium acetate
(0.01 mmol were refluxed for 4–6 h. The mixture was cooled and then a
poured into H2O. The solid obtained was filtered and washed with H2O
several times and crystallized from a proper solvent.
Mass: m/z at 277 (M+, 1%) and base peak at 238.
13C: 169, 167(2C O), 131, 126, 125, 124, 123, 120 [4-thiophene C’S +
(DMSO)
(1-pyrimidine + 1 thiazole C’S)], 26, 25, 24, 23, 22 (4-tetra-
hydrobenzo C’S).
1H-NMR: 4.0–1.8 ppm (m, 10H, tetrahydrobenzo + CH2 of
(DMSO)
thiazolidinone moiety).
2-Amino-4-(4-aryl)-6-oxo-7,8,9,10-tetrahydrobenzo-
1,3-thiazine[3,2-a]-thieno[2,3-d]pyrimidin-3-carbonitrile
or carboxylate (13a–c)
Compound 10 (0.01 mmol) and benzylidene malononitrile or p-chloro
(p-methoxy)benzylidene ethylcyanoacetate (0.01 mmol) in ethanol
(20 ml) and 2 drops of piperidine were refluxed for 8–10 h. The solid
obtained was recrystallized from a suitable solvent to give 13a–c.
13a: mass: m/z at 392 (M+, 5.6%) 368 (9.05%), 320 (15.09%), 302
(38.79%).
13b: mass: m/z at 473 (M+, 1.74%), 399 [M-73 (COOEt)] and a base
peak at 318.
13c: 1H-NMR 12.2 (s, 2H, NH2, D2O exchangeable), 8.3 (d, 1H, H3
of thiazine moiety), 8.1–7.1 [d-d (A-B), 4H, aromatic] 4.2 (q, 2H, CH2),
3.8 (s, 3H, OCH3), 3.4 (d, 1H, H4 of thiazine moiety), 2.7–1.6 (m, 8H,
cyclohexyl H’s), 1.2 (t, 3H, CH3).
2-(Phenylmethylen)-3,5,dioxo-6,7,8,9-tetrahydrobenzo-
1,3-thizolo[3,2-a]-thieno[2,3-d]pyrimidine (14)
Compound 12 (0.01 mmol) and benzaldehyde (0.01 mmol) in acetic an-
hydride and acetic acid (20 ml) were refluxed for 6 h. The mixture was
cooled and poured into water. The solid obtained was filtered and was
crystallized from a suitable solvent to give compound 14.
Mass: m/z at 366 (M+, 1.0%), 277 (2.5%), 238 (100%), 210 (14.3%).

Tetrahydrobenzothieno[2,3-d]Pyrimidine Derivatives
449
2-Amino-4-(4-chlorophenyl)-12-oxo-8,9,10,11-
tetrahydrobenzo-pyrano[2,3:4,5]thiazolo[3,2- a]thieno-
[2,3-d]pyrimidine-3-carbonitril or Carboxylate (15a,b)
Compound 12 (0.01 mmol) was refluxed with benzylidene malononitir-
ile of p-methoxybenzylidene ethylcyanoacetate (0.01 mmol) in ethanol
(20 ml) in presence of piperidine for 6 h. The mixture was cooled and
acidified with dilute hydrochloric acid. The solid formed was filtered
and washed with water and recrysallized from a proper solvent to give
15a,b respectively.
Compound 15a also was obtained by refluxing compound 14
(0.01 mmol) with malononitrile (0.01 mmol) in presence of piperidine
in ethanole (20 ml) for 4 h. The solid formed was recrystalized from
ethanol (m.p. and mixed m.p.).
15a: Mass : m/z at 432 (M+ , 25%), 369 (43.75%), 312 (35.5%), 257
(89.58%), 5.1 and base peak at 119.
(DMSO)
1H-NMR: 7.6–7.2 (m, 7H, aromatic H’s + NH2), 5.1 (s, 1H, H4
pyran moiety, 2.8–1.4 (m, 8H, cyclohexyl H’S).
1
15b: H-NMR 7.2–7.5 (m, 6H, aromatic H’S + NH2), 5.4 (s, 1H,
(DMSO)
H4
pyran moiety), 4.4. (q, 2H, CH2), 4.0 (d, 1H, H4 pyran
moiety), 3.8 (s, 3H, OCH3), 2.8–1.8 (m, 8H, cyclohexyl H’s), 1.3 (t, 3H,
CH3).
TABLE III Gram (+ve)
Comp.
no.
Slaphylococcus
aureus
Bacillus
subtillis
Conc.
1b
2a
8a
8b
10
5
2.5
1
5
2.5
1
5
2.5
1
5
2.5
1
5
2.5
1
5
2.5
1
+++
++
++
+
++
++
++
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
++
++
+
+
+
12
+
+
+
+
+
+

450
A. M. Sh. El-Sharief et al.
TABLE IV Gram ( ve)
Comp.
no.
Pseudomonas
aeruginosa
Escherichia
coli
Conc.
1b
2a
8a
8b
10
5
2.5
1
5
2.5
1
5
2.5
1
5
2.5
1
5
2.5
1
5
2.5
1
++
++
++
++
++
++
+
+
+
+
+
+
+
++
++
+
+
++
+++
++
++
++
+
+
++
+
+
+
+
+
12
+
+
+
+
+
+
+: less activity (0.1–0.5 cm).
++: moderate activity (0.6–1.0 cm).
+++: high activity (1.1–1.5).
: no activity.
ANTIBACTERIAL ACTIVITY
Compounds 1b, 2a, 8a, 8b, 10, and 12 were tested for their antimi-
crobial activity using the gram positive bacteria Staphylococcus aureus
and Bacillus subrllis and gram negative bacteria Escherichia coli and
Pseudomonas aeruginosa at different concentrations of the sample.
The test was done using the diffusion agar technique.11
The relation of the different concentrations of the active compounds
against the growth of bacteria was recorded in Tables III and IV.
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Tetrahydrobenzothieno[2,3-d]Pyrimidine Derivatives
451
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