Title studies on the reaction of N-(3-carbethoxy-4,5,6,7-tetrahydrobenzo[b] thien-2-yl)-N′-phenylthiourea with hydrazine hydrate (Part 1)

Article abstract of DOI:10.1002/jhet.5570450226

(Chemical Equation Presented) The reaction of N-(3-carbethoxy-4,5,6,7- tetrahydrobenzo[b]thien-2-yl)-N′-phenylthiourea (1) with hydrazine hydrate in 1-butanol afforded a mixture of compounds 2, 3 and 4. Treatment of 3 and 4 with nitrous acid gave 6 and 8 respectively, while reactions of 3 with acetylacetone gave 7. Synthesis of tetracyclic compounds 9a-f and 11 from the reactions of 3 with ethyl orthoformate or appropriate acids, acid chloride, carbon disulphide and/or ethyl chloroformate. Also its reaction with isothiocyanate derivatives gave the corresponding thiosemicarbzides 12a,b which on, refluxing in alcoholic KOH gave the unexpected tetracyclic products 14a,b. Similarly the tetracyclic compounds 16a-e and 19 were obtained by cyclization of 4 and 18 respectively.

Full text of DOI:10.1002/jhet.5570450226

Mar-Apr 2008
467
Title Studies on the Reaction of N-(3-Carbethoxy-4,5,6,7-
tetrahydrobenzo[b]thien-2-yl)-N'-phenylthiourea with Hydrazine
Hydrate (Part 1)
Hassan A. H. El-Sherief, Galal M. El-Naggar, Zeinab A. Hozien and
Suliman M. El-Sawaisi*
Chemistry Department, Faculty of Science, Assiut University, Assiut, Egypt
*Chemistry Department, Faculty of Science, 7th October University, Misurata, Libya.
Received June 12, 2006
3+4
NH2NH2
O
N
O
N
O
N
COOC2H5
NH2NH2
NH2
C6H5
C6H5
N
N
N
+
+
NHC6H5
S
SH
NHNH2
NHCSNHC6H5
S
S
S
1
2
3
4
The reaction of N-(3-carbethoxy-4,5,6,7-tetrahydrobenzo[b]thien-2-yl)-N'-phenylthiourea (1) with
hydrazine hydrate in 1-butanol afforded a mixture of compounds 2, 3 and 4. Treatment of 3 and 4 with
nitrous acid gave 6 and 8 respectively, while reactions of 3 with acetylacetone gave 7. Synthesis of
tetracyclic compounds 9a-f and 11 from the reactions of 3 with ethyl orthoformate or appropriate acids,
acid chloride, carbon disulphide and/or ethyl chloroformate. Also its reaction with isothiocyanate
derivatives gave the corresponding thiosemicarbzides 12a,b which on, refluxing in alcoholic KOH gave
the unexpected tetracyclic products 14a,b. Similarly the tetracyclic compounds 16a-e and 19 were obtained
by cyclization of 4 and 18 respectively.
J. Heterocyclic Chem., 45, 467 (2008).
INTRODUCTION
RESULTS AND DISCUSSION
Thienopyrimidines, have been evaluated pharm-
acologically as anti-malarial [1] antibacterial [1,6], anal-
gesic and anti-inflammatory [7,11], diuretic activity in
rats [12], antiviral [13], antifungal effect [14], herbicidal
activity and antimycotoxigenic activity [15]. Besides the
synthetic methods of 3-amino-3,4-dihydro-2-arylamino-
The starting compound 1 was prepared by treatment of
2-amino-3-carbethoxy-4,5,6,7-tetrahydrobenzo[b]thiophene
with phenylisothiocyanate in boiling ethanol. Refluxing of
1 with hydrazine hydrate in ethanol for 12 hours gave a
solid crystalline product with mp. 205-207 °C in 50%
yield as previously reported [16]. A tlc of the reaction
products showed the presence of two compounds which
could be separated by recrystallization and identified as
the two isomeric products 2-hydrazino-3-phenyl-5,6,7,8-
tetrahydrobenzo[b]thieno[2,3-d]pyrimidin-4(3H)-one (3)
and 3-amino-2-phenylamino-5,6,7,8-tetrahydrobenzo[b]-
thieno[2,3-d] pyrimidin-4(3H)-one (4).
thieno[2,3-d]pyrimidin-4(3H)-ones,
a new route has
appeared in the literature by refluxing of N-(3-carbethoxy-
thien-2-yl)-N'-arylthiourea 1 with neat hydrazine hydrate
[16-18], or in ethanol. Investigation of the reported results
show different melting points for the same compound
besides the low yield of reaction products aroused our
interst in reinvestigation of these reactions and their
cyclization reactions.
Further, the product obtained by dilution and neutral-
ization of the basic filtrate was characterized as 2-
Scheme 1
O
C6H5
SH
N
N
NH2NH2
3 +4
N
O
S
2
C6H5
COOC2H5
N
NHNH2
S
NHCSNHC6H5
S
3
1
O
NH2
N
N
NHC6H5
S
4

468
H. A. H. El-Sherief, G. M. El-Naggar, Z. A. Hozien and S. M. El-Sawaisi
Vol 45
mercapto-3-phenyl-5,6,7,8-tetrahydrobenzo[b]thieno[2,3-
d]pyrimidin-4(3H)-one 2 in 42% yield (Scheme 1).
However the yield, of the latter compound was decreased
either by using 1-butanol instead of ethanol as a solvent,
or by increasing the reaction time.
This behaviour may be due to the conversion of 2 to 3
and 4, which was formed at first then reacted with
hydrazine (Scheme 1).
Scheme 3
O
N
O
N
C6H5
C6H5
N
N
N
HNO2
NHNH2
CH3COOH
S
S
S
N
3
N
N
6
AcAc
O
N
O
N
C6H5
C6H5
The conversion of 2 to 3 and 4 may be explained by
nucleophilic attacking of hydrazine on the electrophilic
centers C2 and C4 respectively (Scheme 2).
N
N
N
S
7
N3
H3C
CH3
Scheme 2
O
5,6,7,8-tetrahydrobenzo[b]thieno[2,3-d]pyrimidin-4(3H)-
one 8, as previously reported with similar compounds
[20].
-H2S
NH2
N
N
NHC6H5
S
4
O
H
O
O
HNO2
.. ..
NH-NH2
NH
NHC6H5
..
N
NH2
4
CH3COOH
..
N
NHC6H5
S
NH-CNHC6H5
S
N
H
S
S
S
8
.. ..
NH2NH2
In continuation of our earlier work [21-24] on the
cyclization reactions of heterocyclic hydrazines with
different carbonyl compounds, it was of interest to
investigate the susceptibility of 2-hydrazino-3-phenyl-
thienopyrimidine 3 towards ring closure reactions with
O
O
C6H5
S
C6H5
N
N
N
SH
N
H
S
2
S
different reagents. Refluxing of
3
with triethyl
..
..
NH2NH2
orthoformate or with either formic acid or formamide
afforded the same product 4-phenyl-6,7,8,9-tetrahydro-
benzo[b]thieno[3,2-e]-1,2,4-triazolo[4,3-a]pyrimidin-5-one
9a. It appears that when boiling formic acid or formamide
is used for the cyclization of compound 3, the [4,3-
a]triazolo derivative 9a does not undergo rearrangement
to its [2,3-a] isomer 9a' as previously reported [25,26].
Similarly the 2-hydrazino compound 3 was reacted with
acetic acid or acetic anhydride, propionic acid, and lactic
acid to give the corresponding 1-substituted triazolo[4,3-
a]thienopyrimidine derivatives 9b-d. While refluxing with
benzoyl chloride afforded 1,4-diphenyl triazolo[4,3-a]-
thienopyrimidine 9e. Further, the reaction with carbon
disulfide in boiling alcoholic KOH gave 1-mercapto-4-
phenyltirazolo [4,3-a]thienopyrimidine 9f. The hydrazino
compound 3 was also reacted with ethyl chloroformate to
give 2-ethoxycarbonylhydrazino-4-phenylthienopyrimid-
ine derivative 10, which was cyclized to 4-phenyltriazole-
[4,3-a]thienopyrimidin-1,5-dione 11 on heating over its
melting temperature (Scheme 4).
O
N
O
C6H5
C6H5
N
N
-H2S
NHNH2
N
S
N
NH2
S
3
HS
H
O
C6H5
NH2NH2
C2H5OH
Dimroth rearrangement
N
4
N
SC2H5
S
5
On the other hand, it may be assumed that 3 was
formed at the beginning of the reaction as a kinetic
product then transformed to 4 as a thermodynamic
product through the Dimroth [19] rearrangement. This
assumption was clarified as the 2-hydrazino derivative 3
was obtained in 90% yield when 5 was reacted with
hydrazine hydrate (Scheme 2). Further, the conversion of
3 to the tetrazolo derivative 6 via its reaction with HNO2,
and the formation of 2-[3,5-dimethylpyrazol-1-yl]-3-
phenyl-5,6,7,8-tetrahydrabenzo[b]thieno[2,3-d]pyrimidin-
4(3H)-one (7) via its condensation with acetylacetone, are
considered as additional evidence of its structure as 2-
hydrazino derivative 3 (Scheme 3).
Treatment of the hydrazino derivative 3 with ethyliso-
thiocyanate in boiling 1-butanol afforded the thiosemi-
carbazide derivative 12a. Refluxing of 12a in alcoholic
KOH to prepare 1-ethylamino-1,2,4-triazolo[4,3-a]thieno-
pyrimidine 13 as previously reported with similar systems
[27], afforded an unexpected product in which aromatic
Also, the structure of 4 was chemically confirmed via
its reactions with HNO2, which yielded 2-phenylamino-

Mar-Apr 2008
N-(3-Carbethoxy-4,5,6,7-tetrahydrobenzo[b]thien-2-yl)-N'-phenylthiourea
469
proton resonances were not observed in its NMR
spectrum. On the basis of elemental analysis, IR, 1H NMR
The formation of 14a,b could be explained as shown in
(Scheme 6 ).
Scheme 4
O
N
O
C6H5
C6H5
N
N
S
N
N
S
N
N
N
9a
HCOOH or
HCOONH4
9'a
O
C6H5
N
ClCOOC2H5
(i)RCOOH,C6H5COCl
or (ii)CS2/KOH
NHNH2
N
S
O
N
3
O
N
C6H5
N
C6H5
S
N
N
NHNHCOOC2H5
S
S
N
10
9b-f
R
R=CH3, C2H5, CH(OH)CH3, C6H5, SH
O
N
O
N
C6H5
C6H5
N
N
N
S
N
N
NH
11
HO
O
and mass spectra data, the reaction product was charac-
terized as 3-ethyl-2-mercapto-1,2,4-triazolo-[1,5-a]-6,7,8,
9-tetrahydrobenzo[b]thieno[2,3-d]pyrimidin-10-one (14a),
similarly, treatment of 3 with phenylisothiocyanate
afforded the corresponding thiosemicarbazide derivative
12b, which on refluxing with alcoholic KOH afforded 2-
mercapto-3-phenyl-1,2,4-triazolo[1,5-a]-6,7,8,9-tetra-
hydro[b]thieno[2,3-d]pyrimidin-10-one (14b) (Scheme 5).
Scheme 6
O
O
C6H5
C6H5
OH
N
N
H
..
H2O
NHCONHNHCSNHR
N
S
S
NHNHCSNHR
1
12a,b
H
O
..
NHC6H5
HN
O
N
H
-C6H5-NH2
N
N
C=S
S
..
..
O
HN
R
O
HN
N
H
N
H
S
S
R
Scheme 5
O
N
O
H
N
H
N
O
N
O
N
C6H5
-H2O
C6H5
N
N
N
N
S
S
..
N
R
N
N
S
S
NHNH2
..
S
R
S
N
OH
H
3
14a,b
N
13
RHN
RNCS
O
On the other hand, refluxing of 3-amino-2-phenyl-
C6H5
amino-5,6,7,8-tetrahydrobenzo[b]thieno[2,3-d]pyrim-
idin-4-one (4) with triethyl orthoformate gave 3-
phenyltriazole[1,5-a]-6,7,8,9-tetrahydrobenzo[b]thieno-
[2,3-d]pyrimidin-10-one (16a). The same product was
obtained on refluxing of 4 with formic acid or
formamide. Further, refluxing of 4 with acetic acid and
acetic anhydride afforded 16b and 17 respectively.
Refluxing of 17 in AcOH gave 16b in good yield.
Similarly, refluxing of 4 with propionic acid, lactic
acid, benzoyl chloride gave the tetracyclic products
16c-e respectively. While with ethyl chloroformate
gave 3-ethoxycarbonylamino-2-phenylamino-5,6,7,8-
KOH alc.
N
O
1
9
6
S
N
8
7
N
2
N
NHNHCNHR
S
SH
12a,b
N
3
N
S
5
4
R
C2H5I/KOH
alc.
C2H5I/KOH
alc.
O
O
H
N
N
N
N
SC2H5
S
N
N
S
N
N
S
R
R
15a,b
14a,b
12,13,14,15,a;R=C2H5,b;R=C6H5

470
H. A. H. El-Sherief, G. M. El-Naggar, Z. A. Hozien and S. M. El-Sawaisi
Vol 45
315°C [29] ; Rf 0.83 (EA/B 3:7).
tetrahydro-benzo[b]thieno-[2,3-d]pyrimidin-4-one (18),
which was cyclized to 3-phenyl-triazolo[1,5-a]-6,7,
8,9-tetrahydrobenzo[b]thieno[2,3-d]pyrimidin-2,10-
dione 19 on heating over its melting (Scheme 7).
2-Hydrazino-3-phenyl-5,6,7,8-tetrahydrobenzo[b]thieno-
[2,3-d]pyrimidin-4(3H)-one (3). Mp. 250°C (DMF), (reported)
250°C [30] (benzene). Rf 0.37 (EA/B 3:7). IR (KBr) ν 3200
(NH2, NH), 2920-2810 (C-H aliphatic), 1660 (C=O), 1535 (C =
N) cm-1. 1H NMR (CDCl3) δ 1.85 (m, 4H, H6, H7), 2.85 (m, 4H,
H5, H8), 3.85 (s, 2H,NH2), 5.55 (s, 1H, NH exchangeable by
deuteration), 7.40 (m, 5H, C6H5) ppm. MS m/z (%) [M.+ , 312
(100)], 296 (0.7), 281 (33.1). Elemental analysis for C16H16N4OS
(312), calcd: C; 61.52, H; 5.16, N; 17.93, S; 10.26. Found: C;
61.42, H; 5.38, N; 17.74, S; 10.12.
Scheme 7
O
N
O
N
NHCOCH3
NHC6H5
N
N
N
N
AcOH
CH3
S
17
S
C6H5
3-Amino-2-phenylamino-5,6,7,8-tetrahydrobenzo[b]-thieno-
[2,3-d]pyrimidin-4(3H)-one (4). Mp 197°C (ethanol) (reported)
205-208 °C [16] ,230-32 °C [17] , 227-29 °C [31] . Rf 0.57
(EA/B 3:7). IR (KBr)/ν 3300-3200 (NH), 2920-2840 (C-H
16b
Ac2O
O
O
1
aliphatic), 1650 (C=O) cm-1. H NMR (CDCl3): δ 1.77 (m, 4H,
NH2
N
N
N
A,B,C,D,E
R
H6, H7), 2.48 (m, 2H, H5), 2.74 (m, 2H, H8), 4.52 (s, 2H, NH2
exchangeable by deuteration), 7.25 (m, 5H, C6H5), 8.43 (s, 1H,
NH exchangeable by deuteration) ppm. Ms m/z (%) [M.+ , 312
(100%)]. Elemental analysis for C16H16N4OS (312), Calcd: C;
61.52, H; 5.16, N; 17.93, S; 10.26%. Found: C; 62.04, H; 4.59,
N; 18.06, S; 10.28%.
N
NHC6H5
N
N
S
S
4
16a-e
C6H5
a;R=H, b;R=CH3, c;R=C2H5
d;R=CHOHCH3.e;R=C6H5
ClCOOC2H5
O
O
H
N
NHCOOC2H5
N
2-Ethylthio-3-phenyl-5,6,7,8-tetrahydrobenzo[b]thieno-[2,
3-d]pyrimidin-4(3H)-one (5). Compound 5 was obtained by
refluxing 2 (0.3 g 0.001 mol) with ethyl iodide (excess) in 20 ml
alcoholic KOH (3%) for 4 hours. The separated product was
crystallized from ethanol. Yellowish crystals, mp 186°C
N
O
-EtOH
N
NHC6H5
S
N
N
S
18
19
C6H5
A;HC(OC2H5)3, HCOOH,HCONH2. B;CH3COOH, C,C2H5COOH.
d;CH3CH(OH)COOH .E ;C6H5COCl.
1
(reported) 194°C [32]. H NMR (CDCl3) δ 1.28 (t, 3H, CH3),
1.82 (m, 4H, H7, H8), 2.71 (m, 4H, H6, H9), 3.22 (q, 2H, -SCH2-),
7.23 (m, 5H, C6H5) ppm. Rf 0.83 (EA/B 1:1). Elemental
analysis for C18H18N4OS2 (338): S; 18.75. Found S; 18.70).
4-Phenyl-1,2,3,4-tetrazolo[1,5-a]-6,7,8,9-tetrahydrobenzo-
[b]thieno-[3,2-e]pyrimidin-5-one (6). Stirring of 3 (1 g, 0.003
mol) with 50 ml acetic acid at 0°C, 3 ml saturated solution of
NaNO2 was added dropwise at 15 min. to the reaction mixture.
Stirring was continued for about 3 hours, then the product was
extracted using benzene which was evaporated under reduced
pressure and crystallized from petroleum ether, mp 205°C; Rf
0.72 (EA/B 1:1). The IR (KBr) spectra lacked the NHNH2
absorption at 3300-3100 cm-1 and the azide absorption in the
EXPERIMENTAL
General. Melting points were measured on a Gallen-Kamp
melting point apparatus and are uncorrected. The ultraviolet
spectra were recorded using UV-2011 PC, UV-Vis scanning
spectrophotometer-shimadzu. The infrared spectra were
recorded on IR-470, IR spectrophotometer-shimadzu-using KBr
1
and CCl4. The H-NMR spectra were recorded by either varian
1
EM-390 (90 MHz) or by H NMR LA 400 MHz (Jeol) Assiut
University. Elemental analysis was carried out by Elemental
analyzer system CmbH vario El at Assiut University. Ethyl
acetate (EA), Benzene (B) mixture was used as an eleuent in tlc
chromatography.
N-(3-Carbethoxy-4,5,6,7-tetrahydrobenzo[b]thien-2-yl-N'-
phenylthiourea (1). A mixture of 2-amino-3-carbethoxy-4,5,
6,7-tetrahydrobenzo[b]thiophene (11.25 g 0.05 mol) and phenyl
isothiocyanate (7 g, 0.052 mol) was refluxed 5 hours in ethanol
(25 ml). A crude solid product formed while hot and was
collected by filtration and recrystallized from ethanol. Yield
95%; mp 192°C (ethanol) (reported) 184-187°C [28].
2,3-Disubstituted-5,6,7,8-tetrahydrobenzo[b]thieno[2,3-d]-
pyrimidin-4(3H)-ones (2-4). A mixture of thiourea derivative 1
(10.8 g, 0.03 mmol) and excess of hydrazine hydrate in ethanol
or 1-butanol was refluxed for about 10-50 hours. Separated solid
product was collected by filtration, washed several times with
KOH solution (2.5%), then with water and dried. The crude
product was recrystallized from DMF several times to isolate 3
and 4 in pure state.
2-Mercapto-3-phenyl-5,6,7,8-tetrahydrobenzo[b]thieno-[2,
3-d]pyrimidin-4(3H)-one (2). Was obtained by neutralization of
the reaction filtrate with dilute iced HCl then collection by
filtration and recrystallized from ethanol. Mp. 330°C (reported)
1
region 2200-2100 cm-1. H NMR (CDCl3): δ 1.80 (m, 4H, H7,
H8), 2.70 (s, 2H, H6), 2.85 (s, 2H, H9), 7.20 (m, 5H, aromatic
protons) ppm. MS m/z (%) [M+., 323 (52)], 295 (76), 267 (100).
Elemental analysis for C16H13N5OS (323), Calcd: C, 59.43 H;
4.05, N; 21.66, S; 9.92%. Found: C; 59.79, H; 4.51, N: 20.90, S;
9.67%.
2-[3,5-Dimethylpyrazol-1-yl]-3-phenyl-5,6,7,8-tetrahydro-
benzo[b]thieno[2,3-d]pyrimidin-4(3H)-one (7). 2-Hydrazino
derivative 3 (1 g 0.003 mol) was refluxed in 10 ml acetylacetone
for 7 hours. The excess acetylacetone was evaporated on a water
bath. The separated product was crystallized from benzene-
petroleum ether mixture, mp 156 °C. Rf 0.76 (EA/B 3:7). UV:
1
λmax 325.5, (1.254), 243.5 (1.246). H NMR (CDCl3) δ 1.85 (m,
4H, H6, H7), two singlets at 2.00, 2.20 (6H, two CH3 groups),
2.80 (s, 2H, H5), 3.00 (s, 2H, H8), 5.60, (s, 1H, CH), 7.25 (m,
5H, C6H5) ppm. MS m/z (%) [M.+ , 376 (85.3)]. Elemental
analysis for C21H20N4OS (376), Calcd: C; 67.00, H; 5.35, N;
14.88, S; 8.52%. Found: C; 66.84, H; 5.60, N; 14.54, S; 8.24%.
2-Phenylamino-5,6,7,8-tetrahydrobenzo[b]thieno[2,3-d]pyr-
imidin-4(3H)-one (8). Using the same method as for the
synthesis of compound 6; mp 286°C from cyclohexane
(reported) 284-286 °C [33]. Rf 0.54 (EA/B 1:1). IR (KBr) ν

Mar-Apr 2008
N-(3-Carbethoxy-4,5,6,7-tetrahydrobenzo[b]thien-2-yl)-N'-phenylthiourea
471
3350 (NH) cm-1. MS m/z (%) [M.+ , 297 (100)]. Elemental
analysis for C16H15N3OS (297), Calcd: C; 64.62, H; 5.08, N;
14.13, S; 10.78. Found: C; 64.40, H; 4.55, N; 14.01, S; 9.72%.
1,4-Disubstituted-6,7,8,9-tetrahydrobenzo[b]thieno[3,2-e]-
NH) ppm. MS m/z [M.+, 354 (100)], 326 (31.9), 321 (14.8), 296
(57.8). Elemental analysis for C17H14N4OS2 (354), calcd: C;
57.61, H; 3.98, N; 15.81, S; 18.09. Found: C; 57.56, H; 4.40, N;
15.90, S; 18.33.
[1,2,4]triazolo[4,3-a]pyrimidin-5-ones (9a-d). General.
A
2-Ethoxycarbonylhydrazino-4-phenyl-5,6,7,8-tetrahydro-
benzo[b]thieno[2,3-d]pyrimidin-4(3H)-one (10) and 4-phenyl-
6,7,8,9-tetrahydrobenzo[b]thieno[3,2-e]-1,2,4-triazolo[4,3-a]-
pyrimidin-1,5-dione (11). A mixture of 3 (1 g, 0.003 mol) with
ethyl chloroformate (10 mol) was refluxed for 12 hours and/or in
the presence of anhydrous K2CO3. The excess of ester removed
by evaporation on water bath, after cooling the solid crude
product obtained washed with ammonia solution, then with
water and crystallized from ethanol to give the uncyclized
product 10. The cyclized product 11 was obtained by heating 10
over its melting point for 5 min and crystallized from ethanol.
10. Yield 84%, mp 190°C (ethanol), Rf 0.52 (EA/B 4:6). IR
(KBr)ν, 3300 (NH), 3090 (C-H aromatic), 2910, 2820(C-H
mixture of 3 (1 g, 0.003 mol) with the appropriate acid, ethyl
orthoformate, acetic anhydride, was refluxed for about 6-8
hours. A white ppt formed and was washed with iced ammonia.
The crud product was crystallized from an ethanol-benzene
mixture in 90-96% yield.
9a. Yield (90%); mp. 302 °C (reported) 298-300 °C [30] Rf
0.83 (EA/B 6:4). IR (KBr) ν 1680 (C=O), 3030 (C-H aromatic),
2960-2940 (C-H aliphatic) cm-1. 1H NMR (CDCl3) δ 8.44 (s, 1H,
triazole-H), 7.49 (m, 5H, aromatic-H), 2.90 (m, 4H, H6, H9),
1.88 (d, 4H, H7, H8). Elemental analysis for C17H14N4OS (302),
Calcd: C; 63.33, H; 4.38, N; 17.38, S; 9.95. Found: C; 63.60, H;
5.00, N; 17.55, S; 10.31.
1
aliphatic), 1725 (C= O of ester), 1680 (C=O) cm-1. H NMR
9b. Yield (91%), mp 290 °C (reported) 290-92°C [30] . Rf
0.53 (EA/B 6:4). IR (KBr) ν 1670 (C= O), 3030 (C-H aromatic),
(CDCl3) δ 1.18 (t, 3H, CH3), 1.64 (m, 4H, H6, H7), 2.60 (m, 4H,
H5, H8), 4.2 (q, 2H, CH2), 7.20 (m, 5H, C6H5), 7.8, 9.1 (d, 2H,
NH) ppm. MS m/z (%) [M.+, 384 (23.6)], 383 (100), 356 (6.0),
338 (35.1). Elemental analysis for C19H20N4O3S (384), Calcd: C;
59.36, H; 5.24, N; 14.57, S; 8.34(%). Found: C; 60.01, H; 5.17,
N; 14.82, S; 7.91(%).
1
2960-2940 (C–H aliphatic) cm-1. H NMR (CDCl3) δ 1.85 (m,
2H, H7), 1.91 (m, 2H, H8), 2.80 (m, 5H, CH3 and H6), 3.00 (m,
2H, H9), 7.50 (m, 5H, C6H5) ppm. Elemental analysis for
C18H16N4OS (336), Calcd: C; 64.26, H; 4.79, N; 16.65, S;
9.53%. Found: C; 64.07, H; 5.12, N; 16.76, S; 9.25%.
9c. Yield (92%) mp 275 °C (reported) 270-72°C [30], Rf 0.51
(EA/B 6:4), IR (KBr) ν 1680 (C=O), 3030 (C-H aromatic),
11. Yield 76%, mp 360°C (ethanol) (reported) 282-84°C [30],
Rf 0.76 (EA/B 4:6). IR (KBr) ν lacked the C=O at 1725 cm-1. 1H
NMR (DMSO-d6) δ 1.70 (m, 4H, H6, H7), 2.68 (s, 2H, H5), 2.78
(s, 2H, H8), 7.50 (m, 5H, C6H5), 12.1 (s, 1H, NH) ppm. MS m/z
(%) [M+., 338 (100)].
3-Alkyl-2-mercapto/ethylthio-1,2,4-triazolo[1,5-a]-6,7,8,9-
tetrahydrobenzo[b]thieno[2,3-d]pyrimidin-10-one (14a,b, 15a,b).
General. Refluxing of the thiourea derivatives 12a,b (0.01 mol)
in (50 ml) alcoholic KOH (3%) for 7 hours followed by
acidification by HCl afforded the corresponding 14a,b.
Refluxing of 12a,b with alcoholic KOH in the presence of ethyl
iodide for about 7-9 hours gave 15a,b. Treatment of 14a,b with
ethyl iodide in alcoholic KOH afforded 15a,b.
1
2960-2940 (C-H aliphatic) cm-1. H NMR, (CDCl3) δ 1.6 (t,
3H,CH3), 3.1 (q, 2H,CH2) 1.77 (m, 4H, H7, H8), 2.78 (m, 2H,
H6), 2.85 (m, 2H, H9), 7.50 ppm (m, 5H, C6H5);, MS m/z (%)
[M+. , 350 (65.7)]. Elemental analysis for C19H18N4OS (350),
Calcd: C; 65.12, H; 5.18, N; 15.99, S; 9.15%. Found: C; 65.04,
H; 5.16, N; 15.82; H; 8.36%).
9d. Yield (96%), mp. 319°C, Rf 0.43 (EA/B 6:4); IR (KBr) ν
1680 (C=O), 3300 (OH), 3030 (C-H aromatic), 2960-2940 (C-H
aliphatic) cm-1; 1H NMR (CHCl3) δ 1.6 (d,3H,CH3) ,5.1
(m,1H,CH) , 4.6 (br,1H,OH), 1.77 (m, 4H H7, H8), 2.78 (m, 2H,
H6), 2.85 (m, 2H, H9), 7.50 ppm (m, 5H, C6H5) ; MS: m/z (%)
[M+. , 366 (100)]., Elemental analysis for C19H18N4O2S (366),
Calcd: C; 62.30, H; 4.96, N; 15.30, S; 8.74. Found: C; 61.94, H;
5.16, N; 14.96, S; 8.98.
1,4-Diphenyl-1,2,4-triazolo[4,3-a]-6,7,8,9-tetrahydrobenzo-
[b]thieno[3,2-e]pyrimidin-5-one (9e). A mixture of 3 (1 g,
0.003 mol) and benzoyl chloride (10 ml) was refluxed for 8
hours, filtered, cooled and poured into ammonia solution. The
white precipitate thus formed was collected by filtration, washed
with water, dried and recrystallized from benzene to give 9e in
81% yield. Mp 338°C (reported) 242-44°C [30], Rf 0.25 (EA/B
1:1) 1H NMR (CDCl3) δ 1.85 (m, 2H, H7), 1.91 (m, 2H, H8), 2.80
(m, 2H, CH2, H6), 3.00 (m, 2H, H9), 7.30 (m, 10H,2 C6H5) ppm.
MS m/z (%) [M.+, 398 (12)]. Elemental analysis for C23H18N4OS
(398), Calcd: C; 69.32, H; 4.55, N; 14.06, S; 8.05%. Found: C;
68.82, H; 5.03, N; 14.05, S, 8.18%.
14a. Yield 81%, mp 336°C. IR (KBr) ν 3300 (NH) cm-1. 1H
NMR (CDCl3) δ 1.18 (t, 3H, CH3), 1.64 (m, 4H, H6, H7), 2.60
(m, 4H, H5, H8), 4.2 (q, 2H, CH2), 12.1(s, 1H, NH) ppm, MS m/z
(%) [M+., 306 (60.4)], 290 (100), 262 (56.5). Elemental analysis
for C13H14N4OS2 (306), Calcd: C; 50.96, H; 4.61, N; 18.29, S;
20.93(%). Found: C; 51.56, H; 5.21, N; 18.20, S; 20.70(%).
14b. Yield 77%, mp 354°C (reported) 294-96°C [31]. IR
(KBr) ν 3370 (NH), 3100 (C-H aromatic), 2950, 2870 (C-H
aliphatic), 1690 (C=O) cm-1. 1H NMR (CDCl3): δ 1.80 (m, 4H,
H7, H8), 2.70 (m, 2H, H6), 2.85 (m, 2H, H9), 7.20 (m, 5H, C6H5),
12.2 (s,1H,NH) ppm. MS m/z (%) [M.+, 354 (100)], 325 (35.50),
296 (65). Elemental analysis for C17H14N4OS2 (354), Calcd: C;
57.61, H; 3.98, N; 15.81, S; 18.09%. Found: C; 57.53, H; 4.58,
N; 15.92, S; 17.50%.
1
15a. Yield 72% mp 208°C. H NMR (CDCl3) δ 1.24 (t, 3H,
1-Mercapto-4-phenyl-1,2,4-triazolo[4,3-a]-6,7,8,9-tetrahy-
drobenzo[b]thieno[3,2-e]pyrimidin-5-one (9f). To a solution
of 3 (1 g, 0.003 mmol) in 10 ml (3%) alcoholic KOH, CS2 (1.5
ml) was added. The mixture was refluxed for 16 hours. The
precipitate formed on acidification with dilute HCl was collected
and crystallized from ethanol in 68% yield. mp. 360°C
(reported) 342-44 °C [30], Rf 0.83 (EA/B 1:1). IR (KBr) ν 3300
(NH), 3090 (C-H aromatic), 2920-2850 (C-H aliphatic), 1680
CH3), 1.31 (t, 3H, CH3), 1.77 (m, 4H, H7, H8), 2.76 (m, 4H, H6,
H9), 3.73 (q, 2H, CH2S), 4.14 (q, 2H, CH2N) ppm. MS m/z (%)
[M+., 334 (100%)], 306 (64). Elemental analysis for C15H18N4OS2
(334), Calcd: C; 53.87, H; 5.42, N; 16.75, S; 19.17%; Found: C;
54.34, H; 4.88, N; 15.54, S; 18.45%.
15b. Yield 76% mp 202°C, IR (KBr) ν 3370 (NH), 3050 (C-H
aromatic) 2920, 2820 (C-H aliphatic), 1670 (C=O) cm-1. 1H
NMR δ 1.28 (t, 3H, CH3), 1.8 (m, 4H, H7, H8), 2.7 (m, 4H, H6,
H9), 3.0 (q, 2H, -CH2S-), 7.5 (m, 5H, C6H5). MS m/z (%) [M+.,
382 (100)]. Elemental analysis for C19H18N4OS2 (382), Calcd: C;
1
(C=O) cm-1. H NMR (DMSO-d6) δ 1.77 (m, 4H, H7, H8), 2.78
(m, 2H, H6), 2.85 (m, 2H, H9), 7.50 (m, 5H, C6H5), 3.97 (s, 1H,

472
H. A. H. El-Sherief, G. M. El-Naggar, Z. A. Hozien and S. M. El-Sawaisi
Vol 45
59.66, H; 4.74, N; 14.65, S; 16.77%. Found: C; 59.52, H; 5.30,
N; 13.97, S; 16.59%.
filtration, washed with ethanol and recrystallized from ethanol as
a colorless crystals of 18 in 93.2%, yield.
3-Phenyl-2-substituted-1,2,4-triazolo[1,5-a]-6,7,8,9-tetra-
hydrobenzo[b]thieno[2,3-d]pyrimidin-10-ones (16a-e). A
mixture of 4 (1 g, 0.003 mol) and triethyl orthoformate, appropriate
aliphatic acid, benzoyl chloride and/or ethyl chloroformate (15 ml)
was refluxed for 8 hours. The product thus formed by cooling was
collected by filtration, washed with ammonia, then with water
several times and recrystallized from ethanol-benzene mixture to
give the compounds 16a-e in variant yields.
Method B. A mixture of 4 (1 g 0.003 mole) and ethyl
chloroformate (5 ml) in dry acetone (20 ml) in the presence of
anhydrous K2CO3 was refluxed for 3 hours on water both,
filtered, the solvent evaporated on water bath, compound 18
filtered and crystallized from ethanol in 87% yield. Heating of
18 over its mp for 5 minutes gave 19 in high yield.
18. mp 222°C (ethanol), IR (KBr) ν 3310 (NH), 1725, 1660
(2 C=O). 1H NMR (CDCl3) δ 1.20 (t, 3H, CH3), 1.74 (m, 4H, H6,
H7), 2.59 (m, 2H, H5), 2.80 (m, 2H, H8), 4.19 (q, 2H, CH2), 7.35
(m, 5H, C6H5), 8.10 (s, 1H, NH), 9.420 (s, 1H, NH) ppm. MS
m/z (%) [M.+ , 384 (100)]. Elemental analysis of C19H20N4O3S
(384), Calcd: C; 59.36, H; 5.24, N; 14.57, S; 8.34%. Found: C;
59.98, H; 4.81, N; 15.06, S; 8.59%.
16a. Yield 97%, mp 241°C (reported) 242-44 °C [16], 254-
56°C [17] . IR (KBr) ν 3050 (C-H aromatic), 2920-2820 (C-H
aliphatic), 1680 (C=O), 1570 (C=N), lacked the NH2 bands at
1
3400-3100 cm-1. H NMR (CDCl3) δ 1.74 (m, 4H, H7, H8), 2.58
(s, 2H, H9), 2.80 (s, 2H, H6), 7.24 (m, 5H, C6H5), 9.05 (s, 1H,
CH: triazole ring) ppm; MS m/z (%) [M.+, 322 (100)]. Elemental
analysis for C17H14N4OS (322), Calcd: C; 63.33, H; 4.38, N;
17.38, S; 9.95%. Found: C; 63.60, H; 4.07, N; 17.50, S; 9.31%.
16b. Yield 88%, mp 230°C (reported) 279-80°C [17,31]. IR
19. mp over 360°C. IR (KBr) ν 3300 (NH), 1750 (C=O)
1
of triazole ring, 1670 (C=O) cm-1. H NMR (CDCl3) δ
1.74 (m, 4H, H6, H7), 2.59 (m, 2H, H5), 2.80 (m, 2H, H8),
7.35 (m, 5H, C6H5), 8.22 (s, 1H, NH) ppm MS m/z (%)
[M+. , 338 (100)]. Elemental analysis for C17H14 N4O2S
(338), Calcd: C; 60.34, H; 4.17, N; 16.56, S; 9.48. Found:
C; 60.79, H; 4.23, N; 17.19, S; 9.86.
1
(KBr) ν lacked any bands at 3400-3100 cm-1. H NMR (CDCl3)
δ 1.85 (m, 4H, H7, H8), 2.42 (s, 3H, CH3), 2.67 (m, 2H, H9), 3.00
(m, 2H, H6), 7.53 (m, 5H, C6H5) ppm. MS m/z (%) [M.+ , 336
(63)]. Elemental analysis for C18H16N4OS (336), Calcd: C;
64.26, H; 4.79, N; 16.65, S; 9.53%. Found: C; 64.88, H; 4.31, N;
16.79, S; 9.32%.
REFERENCES
1
16c. Yield 91%, mp 242°C; H NMR (CDCl3) δ 1.6 (t, 3H,
CH3), 3.1 (q, 2H, CH2 ) 1.77 (m, 4H, H7, H8), 2.78 (m, 2H, H6),
2.85 (m, 2H, H9), 7.50 ppm (m, 5H, C6H5); MS m/z (%) [M+.,
350 (100)]. Elemental analysis for C19H18N4OS (350), Calcd: C;
65.12, H; 5.18, N; 15.99, S; 9.15%. Found: C; 64.95, H; 5.90, N;
16.04, S; 9.00%.
16d. Yield 92%, mp 262°C; 1H NMR (CHCl3) δ 1.6 (d, 3H,
CH3), 1.77 (m, 4H H7, H8), 2.78 (m, 2H, H6), 2.85 (m, 2H, H9),
5.1 (m, 1H, CH), 4.6 (br, 1H, OH), 7.50 ppm (m, 5H, C6H5);
MS m/z (%) [M.+, 66 (100)]. Elemental analysis for C19H18N4O2S
(366), calcd: C; 62.28, H; 4.95, N; 15.29, S; 8.75%. Found: C;
61.88, H; 5.36, N; 15.07, S; 8.72%.
16e. Yield 87%, mp 342°C (reported) >300 °C[31] . 1H NMR
(CDCl3) δ 1.85 (m, 2H, H7), 1.91 (m, 2H, H8), 2.80 (m, 2H,H6),
3.00 (m, 2H, H9), 7.50 (m, 10H, 2C6H5) pp. MS m/z (%) [M.+, 98
(100)]. Elemental analysis for C23H18N4OS (398), Calcd: C;
69.32, H; 4.55, N; 14.06, S; 8.05%. Found: C; 68.82, H; 5.03, N;
14.06, S; 8.18%.
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(1 g 0.003 mol) was refluxed in acetic anhydride (10 ml) for 8
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17 in 97% yield, mp 252°C. IR (KBr) ν 3300 (NH), 2900, 2850
(C-H aliphatic) 1685 (C=O), 1665 (CONH) cm-1. 1H NMR
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