The synthesis of some new 7-methyl-3-substituted-1,2,4-triazolo[3,4-b]benzothiazoles

Article abstract of DOI:10.1002/jccs.200100111

New 7-Methyl-3-substituted-1,2,4-triazolo[3,4-b]benzothiazoles were synthesized from p-methylaniline to 5 with various aromatic carbonic acids. The yielded product 6a-j was investigated with Elemental analyses, NMR, MS and IR techniques.

Full text of DOI:10.1002/jccs.200100111

JournaloftheChineseChemicalSociety, 2001, 48, 783-786
783
The Syn the sis of Some New
7-Methyl-3-substituted-1,2,4-triazolo[3,4-b]benzothiazoles
a
a
a
Heng-Shan Dong * (
), Ji-Yong Zhang (
), Yan-Bo Tang (
),
b
b
Xue-Rong Mao (
) and Bin Quan (
)
a
NationalLaboratoryofAppliedOrganicChemistry,InstituteofOrganicChemistry,Colege of Chem is try and
ChemicalEngineering, LanzhouUniversity, Lanzhou, Gansu730000, P. R. China
b
DepartmentofChemistry,GuansuEducationCollege,Lanzhou,Gansu730000,P.R.China
New 7-Methyl-3-substituted-1,2,4-triazolo[3,4-b]benzothiazoles were syn the sized from p-methyl-
aniline to 5 withvariousaromaticcarbonicacids. Theyieldedproduct6a-j wasinvestigatedwithElemental
analyses, NMR, MSandIRtechniques.
INTRODUCTION
Tricyclazole is one of the benzothiazole de riv a tives,
b]benzothiazolederivativesareofinterestbecauseoftheir
broadspectraofbiologicalactivities.Therefore,itwasplanned
toinvestigateasystemwhichcombinesthesethreebiologic
components in a molecule to give a compact system for
screeningtheirbiologicactivities.Recently,wehavesynthe-
sized some new 7-methyl-3-substituted-1,2,4- triazolo [3,4-
b]benzothiazolesfromp-methylaniline to 5withvariousaro-
matic carboxylic ac ids in the pres ence of phos pho rus oxy-
which are well known for de vel op ing this syn the sis as many
compoundswiththisringsystemareassociatedwithdiverse
biologicalactivitiessuchasapplicationaspotentantibacte-
1
,2
rials and as fun gi cides for the con trol of Piricularia oryzae
3
in the pre ven tion of rice blast. Inparticular,s-triazolo[3,4-
Scheme I
COOH
N
N
N3
N2 CI
CH3
NH2
N
NaN3
CH3COCH2COOEt
EtONa,EtOH
NaNO2,HCI
o
0
~5 C
CH3
CH3
CH3
CH3
S
.
NH
C
NH2
Br2
NH2 HCl
NH2
N
S
KSCN
NH2.HBr
HCl
CH3
CH3
2
CH3
3
4
CH3
1
Ar
H2NNH2
N
S
ArCOOH
POCl 3
N
S
N
NHNH2
N
CH3
CH3
5
6
Ar = 6a 5-methyl-1-(4-chlorophenyl)-1,2,3-triazol-4-yl; 6b 2,4-dichlorophoxymethylene; 6c 2-phenylquinolino-
-yl;6d 5-methyl-1-(4-methylphenyl)-1,2,3-triazol-4-yl; 6e 5-methyl-1-(2-methylphenyl)-1,2,3-triazol-4-yl; 6f
-furyl; 6g 1-C10 CH -; 6h 1-C10 OCH -; 6i 2-C10 OCH -; 6j 3-bromopyridyl.
4
2
H
7
2
H
7
2
H
7
2

784 J. Chin. Chem. Soc., Vol. 48, No. 4, 2001
Dong et al.
chloride.Thestructuresofthesecompoundswereestablished
byelementalanalysis,NMR,MSandIRtechniques.Thesyn-
thesispathwayofcompound6a-j is shown inScheme I.
gave the triazolo[3,4-b]benzothiadiazole 6a-j (Table 1). The
spec tral data of6a-j are pre sented in Tables 2-4. IR ab sorp-
-
1
tion peaks of 5 at 3167, 3203 cm are as signed to its NHNH
group ings. When 5 is con verted 6, the NHNH peak dis ap-
pears but a new peak char ac ter is tic of C=N ap pears at 1588-
2
2
-
1
4
RESULTSANDDISCUSSION
1626cm .Likethealliedsystem, com pound 6a-j shows ab-
-
1
sorp tion peaks for C-S-C in the re gion of 693-702 cm .
1
Thenew7-methyl-3-substituted-1,2,4-triazolo[3,4-b]-
benzothiazoles were synthesized from p-methylaniline to 5
with var i ous ar o matic carboxylic ac ids in the pres ence of
phosphorusoxychloride.The2-Hydrazino-6-methylbenzo-
thiazole 5 (mp 225-226 C) was pre pared in 93% yield from
In H NMR spec tra of 5 with 6a-j, we found that af ter
cyclization the ev i dent change is that the sig nals of -NHNH
2
pro tons are at 3.11ppm. Thechemicalshiftsofthearomatic
5
,6
methyl group show in the range of 2.36-2.52 ppm.
In the mass spec tra of6a-j, the mo lec u lar ion peaks of
6bareweak(theirrelativeintensitieswereabout1%)andthe
oth ers are strong. All the mem bers of6a-j ex hibit some im-
por tant ion peaks atm/z 190, 189, 163, 162, 121, 110, 91, 77,
4
(
,thelatterbeingpreparedfrom1 to 2 (mp 195-196 C) and3
mp 254-255 C). Com pound 5on treat ment with ar o matic
car boxylic acid in the pres ence of phos pho rus oxychloride
Table 1. Structures, Yields and Melting Points of the Compounds 6a-j
Compound
Yield (%)
M.p. (°C)
Formula
Found (required) (%)
H
C
N
6
6
6
6
6
6
6
6
6
6
7
a
b
c
d
e
f
g
h
I
39
53
58
50
45
39
41
41
33
65
52
289-290
278-279
253-254
195-196
175-176
155-156
203-204
194-195
190-191
228-229
226-227
C
C
18
H
H
13ClN
6
S
56.54 (56.77)
52.80 (52.76)
73.39 (73.45)
63.41 (63.31)
63.30 (63.31)
61.05 (61.16)
73.01 (72.92)
69.48 (69.54)
69.55 (69.54)
49.28 (49.28)
66.22 (66.10)
3.40 (3.44)
3.01 (3.04)
4.08 (4.11)
4.45 (4.47)
4.45 (4.47)
3.49 (3.55)
4.55 (4.59)
4.36 (4.38)
4.39 (4.38)
2.58 (2.66)
4.85 (4.71)
22.14 (22.07)
11.40 (11.54)
13.40 (13.26)
23.55 (23.32)
23.30 (23.32)
16.60 (16.46)
12.85 (12.76)
12.33 (12.17)
12.08 (12.17)
15.30 (15.25)
11.67 (11.56)
16
11Cl N OS
2
3
C H N S
2
4
16
16
16
4
6
6
C
C
19
H
H
N
N
S
S
19
C H N OS
1
3
9
3
C
C
20
H
H
15
N
3
S
20
15
N
3
OS
C H N OS
2
0
15
3
j
i
C
C
14
H
H
9 4
BrN S
N O S
17 3 2
20
Table 2. IR Spectral Data for Compounds 6a-j
-
1
Compound
IR (cm ) (KBr disc)
1593, 1492, 1461,
1605, 1582, 1492, 1375,
262, 1240,
6
6
a
b
3058,
3099, 3031,
2915,
1610,
972.3, 861, 823,
862, 798,
693.5
710.4
2957, 2922, 2855, 1614,
1
6
6
6
6
c
d
e
f
3027,
3104, 3003,
3044,
2915,
2920, 2852,
2921,
1600,
1610,
1610,
1597,
1600, 1492, 1446, 1377,
1593, 1492, 1456, 1372,
1593, 1492, 1456, 1368,
1593, 1493, 1458, 1368,
861, 807, 764, 696.1
972.6, 860, 815,
972.9, 824, 762,
692.9
698.1
3112,
2917,
888, 808, 759, 701.5
1
256, 1188,
6
6
g
h
3046,
3055, 3003,
2918,
2968, 2896,
1597,
1610,
1586, 1495, 1461, 1377,
1578, 1491, 1462, 1399,
807, 788, 768, 697.2
811, 789, 768, 705.7
1
261, 1100,
1600, 1499, 1462, 1394,
254, 1217, 1181,
1504, 1482, 1429, 1370,
6
i
3098, 3058,
3037,
2952, 2920, 2852, 1629,
2952, 2924, 2861, 1588, 1546,
839, 801, 740, 693.5
1
6
7
j
i
807, 781,
836, 812,
703.3
695,
3203, 3058, 3023, 2980, 2911, 2844, 1686, 1666, 1627, 1602, 1546, 1511, 1467,
393, 1257, 1216, 1179,
1

Some New 7-Methyl-3-substituted-1,2,4-triazolo[3,4-b]benzothiazoles
J. Chin. Chem. Soc., Vol. 48, No. 4, 2001 785
1
Table 3. H NMR Spectral Data for Compounds 6a-j
1
Compound
H NMR (CDCl -d) (ppm), J (Hz)
3
6
a
6 4 6 4
8.96-9.06 (d, 2H, J = 8.5, Bti-4,7H), 7.28-7.37 (d, 2H, J = 8.5, p-ClC H -), 7.37-7.60 (m, 3H, Bti-5H, p-ClC H -), 2.51
(
s, 3H, Ph-CH
7.99-8.09 (d, 1H, J = 8.4, Bti-4H), 7.26-7.52 (m, 5H, Bti-5, 7H, 2,4-diClC
CH
6.72-8.43 (m, 13H, Bti-H, Ar-H), 2.42 (s, 3H, Ph-CH
9.10-9.14 (d, 1H, J = 8.4, Bti-4H), 7.54 (m, 1H, Bti-7H), 7.33-7.37 (m, 1H, J = 8.4, Bti-5H), 7.44 (s, 4H, Ph-CH
s, 3H, Tazo-CH ), 2.51 (s, 3H, Ph-CH
3 3
), 2.79 (s, 3H, Tazo-CH )
6
b
6 3 2
H ), 5.74 (s, 2H, -OCH -), 2.52 (s, 3H, Ph-
3
)
6
6
c
d
3
)
3
), 2.74
(
3
3
)
6
6
e
f
9.10-9.15 (d, 1H, J = 8.4, Bti-4H), 7.31-7.36 (m, 2H, J = 8.4, Bti-5,7H), 7.44-7.54 (m, 4H, Ph-H), 2.59 (s, 3H, Tazo-
CH ), 2.50 (s,3H, Ph-CH ), 2.15 (s, 3H, o-Ph-CH )
3
3
3
8.06-8.10 (d, 1H, J = 8.4, Bti-4H), 7.49-7.50 (d, 1H, J = 1.0, Bti-7H), 7.24-7.29 (q or 2d, 1H, J = 8.4, J = 1.0, Bti-5H),
.75-7.76 (2d, 1H, J = 1.8, J = 0.8, F-5H), 7.22-7.24 (2d, 1H, J = 3.5, J = 0.8, F-3H), 6.68-6.71 (2d, 1H, J = 3.5, J = 1.8,
F-4H), 2.50 (s, 3H, CH ), 2.49 (s, 3H, Ph-CH
8.22-8.18 (d, 1H, J = 8.4, Bti-4H), 7.58-7.66, (m, 2H, Bti-5, 7H), 7.76-7.95, 7.29-7.44, 6.95-7.02 (m, 7H, -C10
s, 2H, -CH -), 2.36 (s, 3H, Ph-CH
8.11-8.15 (d, 1H, J = 8.2, Bti-4H), 7.16-7.21 (m, 2H, Bti-5, 7H), 7.36-7.86 (m, 7H, -C10
s, 3H, Ph-CH
7.82-7.92 (d, 1H, J = 8.2, Bti-4H), 7.16-7.21 (m, 2H, Bti-5, 7H), 7.23-7.92 (m, 7H, -C10
s, 3H, Ph-CH
9.00-8.92 (t, 1H, J = 8.4, Bti-4H), 7.38-7.42 (d, 1H, Bti-7H), 7.19-7.22 (m, 2H, Bti-5H), 9.00 (s, 1H, Py-2H), 8.33-8.35
t, 1H, J = 2, Py-4H), 7.55 (s, 1H, Py-6H), 2.48 (s, 3H, Ph-CH3)
7
3
3
)
6
6
6
6
7
g
h
i
H
7
), 5.04
-), 2.44
-), 2.46
(
2
3
)
H
7
), 5.79 (s, 2H, -OCH
2
(
3
)
H
7
), 5.77 (s, 2H, -OCH
2
(
3
)
j
(
i
7.06-8.92 (m, 10H, Bti-H, -C10
H
7
-H), 4.87 (s, 2H, -CH
2
3
-), 3.09 (b, 2H, -NHNH-), 2.35 (s, 3H, Ph-CH )
Bti = benzothiazole; Tazo = 1,2,3-triazol; F = 2-furyl; Py = 3-bromopyridyl
Table 4. MS Spectral Data for Compounds 6a-j
No
M &
m/z (%)
6
6
6
6
6
a
b
c
380(19)
353(15) 352(51) 323(20) 317(18) 289(7) 274(3) 219(2) 197(10) 190(22) 189(20) 163(100) 162(26) 161(17)
44(8) 136(12) 121(28) 111(8) 89(15) 77(28) 75(77) 65(10) 51(24)
330(8) 329(3) 328(17) 237(2) 203(12) 202(100) 174(7) 173(6) 163(4) 159(24) 135(11) 133(16) 130(18)
21(8) 111(7) 103(6) 89(6) 77(11) 63(18) 51(6)
391(100) 376(1) 362(1) 334(2) 315(2) 289(2) 261(3) 230(36) 229(59) 203(8) 190(1) 189(1) 163(7) 162(48)
61(25) 134(17) 121(21) 111(4) 110(21) 77(27) 65(10)
333(24) 332(100) 317(6) 303(25) 289(4) 214(3) 198(5) 197(5) 190(1) 170(34) 169(39) 163(72) 143(21)
21(13) 110(6) 102(8) 91(36) 77(15) 65(33) 51(7)
333(21) 332(93) 317(6) 303(22) 289(4) 262(3) 247(2) 214(3) 198(3) 197(4) 190(4) 170(38) 169(100)
63(64) 143(33) 121(18) 110(10) 91(41) 77(18) 65(46) 51(10)
1
363(1)
1
392(52)
360(49)
360(41)
1
d
e
1
1
6
6
f
g
255(100)
329(69)
218(1) 202(1) 198(1) 190(1) 163(8) 162(62) 147(5) 136(4) 135(3) 121(5) 111(3) 110(6) 95(4) 77(5) 65(3)
328(100) 301(2) 300(2) 287(3) 256(1) 202(2) 181(4) 167(28) 166(53) 152(11) 141(13) 140(11) 139(140)
1
27(3) 121(3) 115(12) 91(2) 77(6) 65(3)
203(14) 202(100) 174(4) 173(3) 163(1) 162(2) 159(12) 147(3) 143(3) 130(9) 127(2) 115(15) 110(2) 89(4)
7(3) 65(2)
317(1) 220(1) 203(14) 202(100) 192(1) 174(4) 173(3) 163(1) 162(2) 159(10) 143(1) 130(8) 127(3) 115(12)
10(2) 89(3) 77(3) 65(2)
344(38) 265(8) 238(3) 202(1) 184(2) 182(2) 163(12) 162(100) 147(8) 143(1) 136(8) 135(50) 121(6) 111(2)
10(13) 103(12) 91(6) 77(9) 65(6)
221(13) 220(100) 206(13) 201(1) 193(11) 192(93) 185(1) 178(15) 177(17) 170(10) 164(55) 163(32) 157(7)
50(38) 144(47) 128(15) 127(73) 115(35) 111(2) 77(19)
6
6
6
7
h
i
345(12)
345(17)
346(37)
363(35)
7
1
j
i
1
1
6
5, 45. Compound 6a had m/z 219 (2%), 192 (8%), 111
these re ac tions yield the cyclized prod ucts un der neu tral re-
ac tion con di tions. We claim that the re ac tion mech a nism is
the fol low ing for ma tion un der the neu tral re ac tion con di-
tions.
(
81%). 6b has m/z 202 (100%). 6d and 6e had m/z 197, 170,
1
43, 91.6g-i hadm/z 141, 127.
We iso lated one uncyclized prod uct7i when most of

786 J. Chin. Chem. Soc., Vol. 48, No. 4, 2001
Dong et al.
Scheme II
N
N
O
ArCOOH
POCl 3
NHNH2
NHNH
CCH2 O
S
S
CH 3
CH3
5
7i
CH2 O
POCl3
H 2O
N
N
N
-
S
CH 3
6i
EXPERIMENTAL
ACKNOWLEDGEMENTS
Melting points were de ter mined on a Kofler melt ing
pointapparatusandareuncorrected. Themassspectrumwas
per formed on a HP-5988A spec trom e ter (EI at 70 eV). IR
spec tra were ob tained in KBr discs us ing a Nicolet 170SX
The au thors wish to ac knowl edge this pro ject is sup-
ported by a Gansu NSFC (ZS991-A25-003-Z) and Lanzhou
Univ. NLAOC grant.
1
FT-IRspectrometer. HNMRspectroscopywererecordedat
room tem per a ture at 200.13 MHz on a Avorce DRX 200 in-
strument. ElementalanalyseswerecarriedoutonaYanaco
CHNCorderMT-3analyzer.
Received November 13, 2000.
Key Words
Phos pho rus oxychloride was redistilled (bp 105 C).
Synthesis; 1,2,4-Triazolo[3,4-b]benzothiazole;
Benzothiazole derivative.
5
-Methyl-1-(4-methylphenyl)-1,2,3-triazol-4-carbox-
ylic acid, 5-Methyl-1-(2-methylphenyl)-1,2,3-triazol-4- car-
boxylic acid and 5-Methyl-1-(4-cholophenyl)-1,2,3-triazol-
4
- carboxylic acid were pre pared by the method re ported in
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7
-methyl-3-substituted-1,2,4-triazolo[3,4-b]benzothiazole
6
a-j. The re sults are given inTable 1.