Na2S2O4-mediated cyclocondensations of 2,2′-disulfanediyldi- anilines with aldehydes: A facile and inexpensive method for the synthesis of 2-substituted benzothiazoles

Article abstract of DOI:10.1002/cjoc.201190084

A facile and inexpensive method for the synthesis of 2-substituted benzothiazoles has been developed by Na₂S₂O ₄-mediated cyclocondensations of 2,2′-disulfanediyldianilines with aldehydes. In the presence of Na₂S₂O₄ and 4 A molecular sieves, a variety of 2-substituted benzothiazoles were obtained from the reaction of 2,2′-disulfanediyldianilines with aldehydes in moderate to high yields. Copyright

Full text of DOI:10.1002/cjoc.201190084

FULL PAPER
Na2S2O4-Mediated Cyclocondensations of 2,2'-Disulfanediyldi-
anilines with Aldehydes: A Facile and Inexpensive Method for
the Synthesis of 2-Substituted Benzothiazoles
*(李金恒)
Wang, Zhanglin(王章林)
Tang, Riyuan*(汤日元)
Li, Jinheng
a College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou, Zhejiang 325035, China
A facile and inexpensive method for the synthesis of 2-substituted benzothiazoles has been developed by
Na2S2O4-mediated cyclocondensations of 2,2'-disulfanediyldianilines with aldehydes. In the presence of Na2S2O4
and 4 Å molecular sieves, a variety of 2-substituted benzothiazoles were obtained from the reaction of
2,2'-disulfanediyldianilines with aldehydes in moderate to high yields.
Keywords Na2S2O4, cyclocondensation, 2,2'-disulfanediyldianiline, aldehyde, benzothiazole
Introduction
Recently, we found that the cheap and secure rongalite7
could promote the reaction of disulfides with terminal
alkynes for the synthesis of vinylarylsulfides.8 As a con-
tinuing interest in the application of rongalite in organic
synthesis, we report herein a novel route to the synthesis
of 2-substituted benzothiazole by cyclocondensation of
2,2'-disulfanediyldianiline with aldehydes in the pres-
ence of Na2S2O4 and 4 Å molecular sieves under air (Eq.
1).
Benzothiazoles are valuable synthetic intermediates
as well as prevalent structural units in many naturally
occurring and biologically active compounds.1 The im-
portance of benzothiazoles has resulted in the develop-
ment of numerous methods for their preparation. Tradi-
tional synthetic methods include: (1) S-arylation cycli-
zations of N-phenylthioamides via a cross-coupling or a
radical cyclization or transition metal-catalyzed cycliza-
tion process,2-4 and (2) cyclocondensation-dehydrations
of o-aminothiophenol with carboxylic acids1,5 or alde-
hydes under oxidative conditions (Scheme 1).1a-1c,6
However, the first methods suffer from inaccessible
substrates, expensive radical promoters and transition
metal/ligand catalytic systems. The second methods are
limited to aromatic aldehydes, and aliphatic aldehydes
are not suitable substrates for this transformations. For
example, Bahrami and co-workers6e have reported a
mild and efficient cyclocondensation method for the
synthesis of 2-substituted benzothiazoles using
H2O2/CAN oxidative system, but the reactions of ali-
phatic aldehydes give low yields. Recently, Han and
co-workers6f have developed a novel and efficient ap-
proach for the synthesis of 2-substituted benzothiazoles
catalyzed by 4-methoxy-TEMPO radical/oxygen system.
However, 4-methoxy-TEMPO radical is highly expen-
sive besides the restriction of benzenethiols’ foul smell
and pungent flavor. Alternatively, few papers have re-
ported the use of diaryl disulfides instead of ben-
zenethiols reacted with arylaldehydes to prepare ben-
zothiazoles using PPh3/p-TsOH system.1c,1g,6i-6j In view
of economy and environment, to develop a new route
using an inexpensive catalytic system is still desirable.
Scheme 1 Two routes to the synthesis of benzothiazoles
Experimental
NMR spectroscopy was performed on a Bruker
spectrometer operating at 300 MHz (1H NMR) or 500
MHz (1H NMR) and 75 MHz (13C NMR) or 125 MHz
(13C NMR). TMS (tetramethylsilane) was used as an
*
E-mail: try@wzu.edu.cn, jhli@hunnu.edu.cn; Fax: 0086-577-86689372
Received March 23, 2010; revised August 23, 2010; accepted October 14, 2010.
Project supported by the National Natural Science Foundation of China (No. 20872112), Zhejiang Provincial Natural Science Foundation of China
(Nos. Y407116 and Y4080169), and the Natural Science Foundation of Wenzhou University (No. 2007L004).
314
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2011, 29, 314— 320

A Facile and Inexpensive Method for the Synthesis of 2-Substituted Benzothiazoles
internal standard. Mass spectrometric analysis was per-
formed on GC-MS analysis (SHIMADZU GCMS-
QP2010 plus).
2-(4-Chlorophenyl)benzo[d]thiazole (7)3c White
1
solid, m.p. 111.5—112.3 ℃ (Lit.6 110—115 ℃); H
NMR (CDCl3, 300 MHz) δ: 8.09—8.01 (m, 3H), 7.90 (d,
J＝7.9 Hz, 1H), 7.53— 7.40 (m, 4H); 13C NMR (CDCl3,
75 MHz) δ: 166.6, 154.1, 137.0, 135.0, 132.1, 129.3
(2C), 128.7 (2C), 126.5, 125.4, 123.3, 121.6; IR (KBr) v:
3052, 2919, 1797,－1631, 1470, 1310, 1238, 1088, 966,
General procedure
A mixture of 2,2'-disulfanediyldianiline (1) (0.2
mmol), aldehyde 2 (0.4 mmol), Na2S2O4 (0.8 mmol), 4
Å molecular sieves (200 mg), and DMSO (2 mL) was
added in a Schelenk tube. The mixture was stirred at 80
℃ for the indicated time until complete consumption of
starting material as monitored by TLC and GC-MS
analysis. Then the mixture was washed with saturated
brine and extracted with EtOAc. The organic layers
were dried with anhydrous Na2SO4 and evaporated un-
der vacuum, and the residue was purified by flash col-
umn chromatography (hexane/ethyl acetate) to afford
the desired products.
1
825, 753, 616 cm ; LRMS (EI, 70 eV) m/z (%): 245
(M＋, 100).
2-(3-Chlorophenyl)benzo[d]thiazole (8)10 White
1
solid, m.p. 95.7—96.5 ℃ (Lit.5 96—97 ℃); H NMR
(CDCl3, 300 MHz) δ: 8.12 (s, 1H), 8.09 (d, J＝8.2 Hz,
1H), 7.96—7.90 (m, 2H), 7.54—7.39 (m, 4H); 13C
NMR (CDCl3, 75 MHz) δ: 166.3, 154.0, 135.3, 135.2,
135.1, 13－0.8, 130.2, 127.4, 126.6, 125.7, 125.6, 123.4,
1
121.7 cm ; IR (KBr) v: 1583, 1425, 1234, 1073, 882,
738, 673; LRMS (EI, 70 eV) m/z (%): 245 (M＋, 100).
2-(4-Fluorophenyl)benzo[d]thiazole (9)9 Light-
yellow solid, m.p. 96.7—98.3 ℃ (Lit.2 98—99 ℃);
1H NMR (CDCl3, 300 MHz) δ: 8.11—8.06 (m, 3H),
7.89 (d, J＝8.0 Hz, 1H), 7.49 (t, J＝7.6 Hz, 1H), 7.40 (t,
J＝7.5 Hz, 1H), 7.18 (t, J＝8.6 Hz, 2H); 13C NMR
(CDCl3, 75 MHz) δ: 166.7, 164.4 (d, J＝250.2 Hz, 1C),
154.1, 135.0, 129.9, 129.5 (d, J＝8.6, 2C), 126.4, 125.2,
123.2, 121.6, 116.1 (d, J＝22.7, 2C); IR (KBr) v: 3057,
2-Phenylbenzo[d]thiazole (3)3f Colorless solid,
1
m.p. 111.4—111.9 ℃ (Lit.1 110—111 ℃); H NMR
(CDCl3, 300 MHz) δ: 8.13—8.09 (m, 3H), 7.92 (d, J＝
7.6 Hz, 1H), 7.53—7.49 (m, 4H), 7.40 (t, J＝7.0 Hz,
1H); 13C NMR (CDCl3, 75 MHz) δ: 168.1, 154.1, 135.1,
133.6, 131.0, 129.0 (2C), 127.6 (2C), 126.3, 125.2,
123.2, 121.6; IR (KBr) v: 306－1, 1897, 1597, 1306, 1228,
1
1067, 958, 7＋56, 684, 552 cm ; LRMS (EI, 70 eV) m/z
－1
(%): 211 (M , 100).
2925, 1788, 1528, 1234, 1094, 966,＋836, 747, 598 cm ;
2-(4-Bromophenyl)benzo[d]thiazole (4)9 Light-
yellow solid, m.p. 128.7—129.9 ℃ (Lit.2 130—131
℃); 1H NMR (CDCl3, 300 MHz) δ: 8.07 (d, J＝7.9 Hz,
1H), 7.97—7.89 (m, 3H), 7.64—7.61 (dd, J＝6.9, 1.7
Hz , 2H), 7.51 (t, J＝7.5 Hz, 1H), 7.40 (t, J＝7.5 Hz,
1H); 13C NMR (CDCl3, 75 MHz) δ: 166.6, 154.0, 135.0,
132.5, 132.2 (2C), 128.8 (2C), 126.5, 125.4 (2C), 123.3,
121.6; IR (KBr) v: 2917, 1591, 1234, 1068, 965, 824,
LRMS (EI, 70 eV) m/z (%): 229 (M , 100).
4-(Benzo[d]thiazol-2-yl)benzonitrile (10)11 White
solid, m.p. 165.8—166.7 ℃ (Lit.11 166.5—167.5 ℃);
1H NMR (CDCl3, 300 MHz) δ: 8.19 (d, J＝7.6 Hz, 2H),
8.11 (d, J＝8.0 Hz, 1H), 7.93 (d, J＝8.0 Hz, 1H), 7.77
(d, J＝7.6 Hz, 2H), 7.55 (t, J＝8.2 Hz, 1H), 7.46 (t, J＝
8.2 Hz, 1H); 13C NMR (CDCl3, 75 MHz) δ: 165.3,
154.0, 137.4, 135.3, 132.7 (2C), 127.9 (2C), 126.8,
－1
－1
748, 55＋2 cm ; LRMS (EI, 70 eV) m/z (%): 291 (100),
126.1, 123.8, 121.8, 118.3, 114.1 cm ; IR (KBr) v:
289 (M , 96), 210 (Br, 28).
3062, 1603, 1245, 1061,＋834, 679, 618, 553; LRMS (EI,
2-(3-Bromophenyl)benzo[d]thiazole (5) Light-
70 eV) m/z (%): 236 (M , 100).
(Lit.4
2-(4-Nitrophenyl)benzo[d]thiazole (11)9
Light-
yellow solid, m.p. 120.2—121.8 ℃
123.1—124.5 ℃ ); 1H NMR (CDCl3, 300 MHz) δ: 8.28
(s, 1H), 8.09 (d, J＝8.1, 1H), 8.0 (d, J＝7.8, 1H), 7.87
(d, J＝7.6 Hz, 1H), 7.61—7.33 (m, 4H); 13C NMR
(CDCl3, 75 MHz) δ: 166.1, 154.0, 135.5, 135.1, 133.8,
130.5, 130.3, 126.5, 126.1, 125.6, 123.4, 123.2, 121.7;
IR (KB－r) v: 2914, 1660, 1593, 1413, 1222, 1065, 734,
yellow solid, m.p. 228.1—229.6 ℃ (Lit.2 229—230
℃); 1H NMR (CDCl3, 300 MHz) δ: 8.35 (d, J＝8.8 Hz,
2H), 8.27 (d, J＝8.8 Hz, 2H), 8.14 (d, J＝8.1 Hz, 1H),
7.96 (d, J＝7.9 Hz, 1H), 7.56 (t, J＝7.2 Hz, 1H), 7.47 (t,
J＝7.5 Hz, 1H); 13C NMR (CDCl3, 75 MHz) δ: 164.8,
154.1, 149.0, 139.1, 135.5,－128.2 (2C), 126.9, 126.2,
1
1
673＋cm ; LRMS (EI, 70 eV) m/z (%): 291 (100), 289
124.3 (2C), 123.9, 121.8 cm ; IR (KBr) v: 2918, 2853,
(M , 95), 210 (Br, 49); HRMS (EI) calcd for
1597, 1515, 1054, 853, 753, 675; LRMS (EI, 70 eV) m/z
C13H879BrNS 288.9561, found 288.9560.
(%): 256 (M＋, 100).
2-(2-Bromophenyl)benzo[d]thiazole (6)6d Yellow
2-(4-(Trifluoromethyl)phenyl)benzo[d]thiazole
(12)12 White solid, m.p. 129.8—131.5 ℃ (uncorre-
solid, m.p. 63.3—65.1 ℃ (Lit.3 66—68 ℃); H NMR
1
1
(CDCl3, 300 MHz) δ: 8.17 (d, J＝8.1 Hz, 1H), 8.02 (dd,
J＝7.8, 1.7 Hz, 1H), 7.92 (d, J＝7.9 Hz, 1H), 7.71 (d,
J＝7.5 Hz, 1H), 7.53 (t, J＝7.8 Hz, 1H), 7.45—7.40 (m,
2H), 7.30 (t, J＝7.6 Hz, 1H); 13C NMR (CDCl3, 75
MHz) δ: 165.5, 152.7, 136.1, 134.4, 134.0, 132.1, 131.2,
cted); H NMR (CDCl3, 300 MHz) δ: 8.21 (d, J＝8.2
Hz, 2H), 8.12 (d, J＝8.2 Hz, 1H), 7.93 (d, J＝7.9 Hz,
1H), 7.76 (d, J＝8.2 Hz, 2H), 7.54 (t, J＝8.5 Hz, 1H),
7.46 (t, J＝8.5 Hz, 1H); 13C NMR (CDCl3, 75 MHz) δ:
166.0, 154.0, 136.7, 135.2, 132.4 (q, J＝32.5, 1C),
127.7 (2C), 126.6, 125.8 (2C), －125.6, 123.8 (q, J＝
－1
127.5, 126.3, 125.5, 123.5, 122.0, 121.4 cm ; IR (KBr)
1
v: 3061, 1717, 1582, 1433, 1267, 1026, 962, 754, 445;
LRMS (EI, 70 eV) m/z (%): 291 (100), 289 (M＋, 97),
210 (73).
271.0 Hz, 1C), 123.6, 121.7 cm ; IR (KBr) v: 3056,
1806, 1608, 1320, 1114, 842, 757, 614; LRMS (EI, 70
eV) m/z (%): 279 (M＋, 100).
Chin. J. Chem. 2011, 29, 314— 320
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
315

Wang, Tang & Li
FULL PAPER
2-p-Tolylbenzo[d]thiazole (13)13
Light-yellow
(M＋－1, 100).
solid, m.p. 79.3—81.2 ℃ (Lit.15 81—82 ℃); 1H NMR
(CDCl3, 300 MHz) δ: 8.16 (d, J＝8.0 Hz, 1H), 7.93 (d,
J＝8.0 Hz, 1H), 7.80 (d, J＝7.4 Hz, 1H), 7.54 (t, 1H),
7.43—7.34 (m, 4H), 2.71 (s, 3H); 13C NMR (CDCl3, 75
MHz) δ: 153.8, 137.3, 135.6, 133.1, 131.6, 130.6, 130.0,
126.1, 125.1, 123.4, 121.4, 21.4; IR (KBr) v: 3056, 2954,
2-(Furan-2-yl)benzo[d]thiazole (19)16
Light-
yellow solid, m.p. 100.9—101.7 ℃ (Lit.14 101—103
℃); 1H NMR (CDCl3, 300 MHz) δ: 8.06 (d, J＝8.2 Hz,
1H), 7.87 (d, J＝8.1 Hz, 1H), 7.61—7.59 (m, 1H), 7.49
(t, J＝8.0 Hz, 1H), 7.37 (t, 1H), 7.20—7.19 (m, 1H),
6.60—6.58 (m, 1H); 13C NMR (CDCl3, 75 MHz) δ:
157.5, 153.7, 148.7, 144.7, 134.3, 126.5, 125.2, 123.1,
121.5, 112.5, 111.4; IR (KBr)－v: 3058, 2986, 1730, 1589,
－1
1591, 1447, 1217, 955, 751, 447 cm ; LRMS (EI, 70
eV) m/z (%): 225 (M＋, 86), 224 (M＋－1, 100).
4-(Benzo[d]thiazol-2-yl)phenol (14)14
Light-
1248, 1013, ＋892, 746, 591 cm ; LRMS (EI, 70 eV) m/z
1
yellow solid, m.p. 215.8—217.3 ℃ (Lit.8 214—216
(%): 201 (M , 100).
1
℃); H NMR (CD3COCD3, 300 MHz) δ: 9.08 (s, 1H),
2-Benzylbenzo[d]thiazole (20)17 Light-yellow oil;
1H NMR (CDCl3, 300 MHz) δ: 8.03 (d, J＝8.1 Hz, 1H),
7.80 (d, J＝7.9 Hz, 1H), 7.47 (t, J＝8.2 Hz, 1H),
7.41—7.31 (m, 6H), 4.46 (s, 2H); 13C NMR (CDCl3, 75
MHz) δ: 171.2, 153.3, 137.2, 135.7, 129.2 (2C), 128.9
(2C), 127.4, 126.0, 124.8, 122.8, 121.5, 40.6;－IR (KBr)
8.02—7.95 (m, 4H), 7.50 (t, J＝7.3 Hz, 1H), 7.39 (t,
J＝7.6 Hz, 1H), 7.01 (d, J＝8.6 Hz, 2H); 13C NMR
(CD3COCD3, 75 MHz) δ: 167.5, 160.3, 154.4, 134.7,
129.1 (2C), 126.2, 125.3, 124.8, 122.5, 121.7, 115.9
(2C); IR (KBr) v: 3207, 2921, 1671, 1601, 1455, 1084,
945, 830, 710, 566; LRMS (EI, 70 eV) m/z (%): 227
(M＋, 100).
1
v: 3060, 2921, 1590, 1454, 1＋068, 870, 704 ＋cm ; LRMS
(EI, 70 eV) m/z (%): 225 (M , 86), 224 (M －1, 100).
2-Propylbenzo[d]thiazole (21)16 Light-yellow oil;
1H NMR (CDCl3, 300 MHz) δ: 7.97 (d, J＝8.1 Hz, 1H),
7.80 (d, J＝7.9 Hz, 1H), 7.42 (t, J＝7.6 Hz, 1H), 7.30 (t,
J＝7.5 Hz, 1H), 3.07 (t, J＝7.5 Hz, 2H), 1.96—1.83 (m,
2H), 1.04 (t, J＝7.5 Hz, 3H); 13C NMR (CDCl3, 75
MHz) δ: 172.1, 153.2, 135.1, 125.8, 124.6, 122.5, 121.4,
36.2, 23.1, 13.7; IR (KBr) v: 3062, 2958, 2873, 1518,
4-(Benzo[d]thiazol-2-yl)-N,N-dimethylaniline
(15)6c Yellow solid, m.p. 171.3—172.2 ℃ (Lit.7
1
170—171 ℃); H NMR (CDCl3, 300 MHz) δ: 8.02—
7.96 (m, 3H), 7.85 (d, J＝7.6 Hz, 1H), 7.43 (t, J＝8.0
Hz, 1H), 7.33 (t, J＝7.8 Hz, 1H), 6.75 (dd, J＝7.1, 1.9
Hz, 2H), 3.05 (s, 6H); 13C NMR (CDCl3, 75 MHz) δ:
168.8, 154.4, 152.2, 134.5, 128.9 (2C), 126.0,
124.2,122.3, 121.3 (2C), 111.7 (2C), 40.1 (2C); IR (KBr)
v: 2915, 1607, 1468, 1310, 1231, 1059, ＋814, 738,623
－1
1443, 1＋164, 756, 652 cm ; LRMS (EI, 70 eV) m/z (%):
177 (M , 9), 162 (CH3, 17), 149 (100).
－1
cm ; LRMS (EI, 70 eV) m/z (%): 254 (M , 100).
2-Pentylbenzo[d]thiazole (22)18 Light-yellow oil;
1H NMR (CDCl3, 500 MHz) δ: 7.96 (d, J＝8.0 Hz, 1H),
7.82 (d, J＝8.0 Hz, 1H), 7.43 (t, J＝7.5 Hz, 1H), 7.33 (t,
J＝7.5 Hz, 1H), 3.10 (t, J＝7.5 Hz, 2H), 1.91—1.86 (m,
2H), 1.40—1.31 (m, 4H), 0.89 (t, J＝7.5 Hz, 3H); 13C
NMR (CDCl3, 125 MHz) δ: 172.4, 153.2, 135.1, 125.8,
124.6, 122.5, 121.4, 34.3, 31.3, 29.4, 22.3, 13.9; IR
(KBr) v: 2955, 2926, 2856, 1519, 14＋56, 1435, 756, 728;
LRMS (EI, 70 eV) m/z (%): 205 (M , 8), 162 (33), 149
(100).
2-(4-Methoxyphenyl)benzo[d]thiazole
(16)3f
White solid, m.p. 119.7—120.9 ℃ (Lit.1 120—121
℃); 1H NMR (CDCl3, 300 MHz) δ: 8.06—8.03 (m, 3H),
7.88 (d, J＝8.0 Hz, 1H), 7.47 (t, J＝7.5 Hz, 1H), 7.37 (t,
J＝8.0 Hz, 1H), 7.01 (dd, J＝6.8, 2.1 Hz, 2H), 3.89 (s,
3H); 13C NMR (CDCl3, 75 MHz) δ: 167.9, 161.9, 154.2,
134.9, 129.1 (2C), 126.4, 126.2, 124.8, 122.8, 121.5,
114.4 (2C), 55.4; IR (KBr) v: 3069, 2923, 1658, 1598,
－1
1465, 1250, 1028, 829, 754, 626 cm ; LRMS (EI, 70
eV) m/z (%): 241 (M＋, 100), 226 (CH3, 36).
2-Isopropylbenzo[d]thiazole (23)19 Light-yellow
1
2-(Benzo[d][1,3]dioxol-5-yl)benzo[d]thiazole
oil; H NMR (CDCl3, 500 MHz) δ: 7.97 (d, J＝8.0 Hz,
(17)11 White solid, m.p. 125.5—127.3 ℃ (Lit.10
1H), 7.84 (d, J＝8.0 Hz, 1H), 7.44 (t, J＝8.0 Hz, 1H),
7.32 (t, J＝8.0 Hz, 1H), 3.49—3.36 (m, 1H), 1.48 (d,
J＝7.0 Hz, 6H); 13C NMR (CDCl3, 125 MHz) δ: 178.6,
153.1, 134.7, 125.8, 124.5, 122.6, 121.5, 34.1, 22.9; －IR
1
127—128 ℃); H NMR (CDCl3, 300 MHz) δ: 8.03 (d,
J＝8.1Hz, 1H), 7.87 (d, J＝8.0 Hz, 1H), 7.62—7.58 (m,
2H), 7.46 (t, J＝7.5 Hz, 1H), 7.38 (t, J＝7.5 Hz, 1H),
6.90 (d, J＝7.9 Hz, 1H), 6.05 (s, 2H); 13C NMR (CDCl3,
75 MHz) δ: 167.6, 154.1, 150.1, 148.4, 134.9, 128.0,
126.2, 124.9, 122.9, 122.5, 121.5, 108.6, 107.5, 101.7;
IR (KB－r) v: 2980, 2907, 1610, 1468, 1252, 1＋036, 875,
1
(KBr) v: 2965, 2928, 2866, 1516, 145＋6, 757, 728 cm ;
LRMS (EI, 70 eV) m/z (%): 177 (M , 32), 162 (CH3,
100).
2-Cyclohexylbenzo[d]thiazole (24)18
Light-
1
1
687 cm ; LRMS (EI, 70 eV) m/z (%): 255 (M , 100).
yellow oil; H NMR (CDCl3, 500 MHz) δ: 7.97 (d, J＝
8.0 Hz, 1H), 7.84 (d, J＝8.0 Hz, 1H), 7.44 (t, J＝8.0 Hz,
1H), 7.33 (t, J＝8.0 Hz, 1H), 3.14—3.06 (m, 1H),
2.21—2.17 (m, 2H), 1.92—1.86 (m, 2H), 1.69—1.62
(m, 2H), 1.48—1.42 (m, 2H), 1.45—1.39 (m, 2H); 13C
NMR (CDCl3, 125 MHz) δ: 176.6, 152.1, 133.5, 124.8,
123.5, 121.5, 120.5, 42.4, 32.4, 25.1, 24.8; IR (KBr)－v:
2-(Naphthalen-1-yl)benzo[d]thiazole
(18)15
Light-yellow oil; 1H NMR (CDCl3, 300 MHz) δ: 9.13 (d,
J＝7.9 Hz, 1H), 8.25 (d, J＝8.0 Hz, 1H), 7.99—7.95 (m,
4H), 7.60—7.57 (m, 4H), 7.47 (t, J＝7.8 Hz, 1H); 13C
NMR (CDCl3, 75 MHz) δ: 167.7, 154.2, 135.5, 134.1,
131.1, 130.9, 130.7, 129.5, 128.5, 127.7, 126.6, 126.3,
126.0, 125.3, 125.0, 123.6, 121.5; IR (KBr) v: 3054,
2930, 1936, 1692, 1503, 1437, 1231, 1092, 776, 522
1
2924, 2851, 1512, 1448, 1437, 90＋7, 757, 727 cm ;
LRMS (EI, 70 eV) m/z (%): 217 (M , 8), 162 (84), 149
－1
＋
cm ; LRMS (EI, 70 eV) m/z (%): 261 (M , 53), 260
(100).
316
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Chin. J. Chem. 2011, 29, 314— 320

A Facile and Inexpensive Method for the Synthesis of 2-Substituted Benzothiazoles
5-Chloro-2-phenylbenzo[d]thiazole
(25)18
nitrogen and oxygen disfavored the reaction, giving the
product 3 in 73% and 67% yield, respectively (Entries
12 and 13).
Yellow solid, m.p. 135.5—136.7 ℃ (Lit.18 138—139
℃); 1H NMR (CDCl3, 300 MHz) δ: 8.07—8.04 (m, 3H),
7.77 (d, J＝8.5 Hz, 1H), 7.51—7.47 (m, 3H), 7.33 (d,
J＝8.5 Hz, 1H); 13C NMR (CDCl3, 75 MHz) δ: 169.9,
154.9, 133.3, 133.2, 132.3, 131.3, 129.1, 127.6, 125.6,
123.0, 122.3; IR (KBr) v－: 3068, 2921, 1893, 1603, 1445,
Table 1 Screening optimal conditionsa
1
1161, 9＋62, 759, 673 cm ; LRMS (EI, 70 eV) m/z (%):
245 (M , 100).
5-Chloro-2-(furan-2-yl)benzo[d]thiazole
(26)20
1
Yellow solid, m.p. 106.8—108.1 ℃ (uncorrected); H
NMR (CDCl3, 300 MHz) δ: 7.99 (s, 1H), 7.76 (d, J＝
8.5 Hz, 1H), 7.60—7.59 (m, 1H), 7.32 (d, J＝8.5 Hz,
1H), 7.19—7.18 (m, 1H), 6.60—6.58 (m, 1H); 13C
NMR (CDCl3, 75 MHz) δ: 159.2, 154.6, 148.3, 145.0,
132.5, 132.4, 125.6, 122.8, 122.2, 112.6, 112.0; IR (KBr)
v: 2986, 2912, 1615, 1471, 1257, 1045, 875, 759, 653
Catalyst
(equiv.)
Isolated
yield/%
Entry
Solvent
T/℃
1
Na2S2O4 (4)
Na2S2O4 (4)
Na2S2O4 (4)
Na2S2O4 (4)
Na2S2O4 (4)
Na2S2O4 (4)
Na2S2O4 (4)
Na2S2O4 (3)
Na2S2O4 (2)
⎯
DMF
80
80
59
62
72
81
77
77
92
81
76
0
＋
－1
cm ; LRMS (EI, 70 eV) m/z (%): 235 (M , 100).
2
CH3CN
5-Chloro-2-propylbenzo[d]thiazole (27)
Light-
3
DMSO
80
yellow solid, m.p. 30.9—32.5 ℃ (uncorrected); 1H
NMR (CDCl3, 300 MHz) δ: 6.91 (d, J＝8.1 Hz, 1H),
6.65 (dd, J＝8.1, 2.0 Hz, 1H), 6.56 (s, 1H), 1.87—1.79
(m, 2H), 1.46—1.39 (m, 2H), 0.95 (t, J＝7.5 Hz, 3H);
13C NMR (CDCl3, 75 MHz) δ: 147.8, 130.5, 125.4,
122.3, 122.1, 120.0, 110.1, 40.8, 19.1, 13.7; IR (KBr)－v:
4
DMSO/H2O (20∶1)
DMSO/H2O (20∶1)
DMSO/H2O (20∶1)
DMSO/H2O (20∶1)
DMSO/H2O (20∶1)
DMSO/H2O (20∶1)
DMSO/H2O (20∶1)
DMSO
80
5
100
120
80
6
7b
8b
9b
10b
11b
12b,c
13b,d
80
1
3066, 2961, 1591, 1447, 1149, 1069, 759, 653 cm ;
80
LRMS (EI, 70 eV) m/z (%): 211 (M＋, 20),＋183 (100);
HRMS (ESI) calcd for C10H10ClNS (M＋H) 212.0295,
found 212.0290.
80
Na2S2O4 (4)
Na2S2O4 (4)
Na2S2O4 (4)
80
97
73
67
DMSO
80
Results and discussion
DMSO
80
a Reaction conditions: 1a (0.2 mmol), 2a (0.4 mmol), Na2S2O4 (4
equiv.) and solvent (2 mL) for 4 h under air atmosphere. 4 Å
molecular sieves (200 mg) were added. Under N2 atmosphere.
d Under O2 atmosphere.
The reaction of 2,2'-disulfanediyldianiline (1a) with
benzaldehyde (2a) was conducted to screen the optimal
reaction conditions, and the results are summarized in
Table 1. Initially, the effect of solvents was investigated.
We found that the target product 3 was isolated in 59%
yield from the reaction of 2,2'-disulfanediyldianiline (1a)
with benzaldehyde (2a) and Na2S2O4 in DMF at 80 ℃
for 4 h (Entry 1). The yield of 3 was enhanced to some
extent when the reaction was conducted in other sol-
vents inculding MeCN, DMSO and DMSO/H2O.
Among these solvent, the reaction in DMSO/H2O gave
the highest yield in the presence of Na2S2O4 (Entries
2—4). Subsequently, the reaction temperature was also
examined. The results showed that reaction at 80 ℃
was most efficient (Entries 4—6). Interestingly, the
yield of product 3 was increased to 92% when 4 Å mo-
lecular sieves are added to the reaction system (Entry 7).
Encouraged by these results, the amount of Na2S2O4
was also evaluated. A lower yield was observed when
decreased the amount of Na2S2O4 (Entries 7—9). No
target product was observed in the absence of Na2S2O4
(Entry 10). We found that treated disulfide 1a with 2a in
DMSO using Na2S2O4 (4 equiv.) combined with 4 Å
molecular sieves gave the desired product 3 in 97%
yield (Entry 11). Finally, the effect of nitrogen and
oxygen were tested. The results demonstrated that both
b
c
With the optimal reaction condition in hand, we now
explored the scope of both disulfides and aldehydes re-
activity. As listed in Table 2, a variety of substituted
arylaldehydes 2b—2q were treated with disulfide 1a
(Entries 1—16). We were pleased to observe that a se-
ries of functional group such as bromo, 4-chloro, fluoro,
cyano, trifluoromethyl, methyl, methoxy, hydroxy and
dimethylamino groups on the aromatic ring were toler-
ated well under the standard conditions, giving the cor-
responding products in good yields (Entries 1—4, 5—7
and 9—14). However, the reaction of substrate having a
3-chloro or a 4-nitro group showed less effective, giving
the corresponding product in 33% and 29%, respec-
tively (Entries 5 and 8). It is due to the effect of strong
electron-withdrawing group or the chemical properties
of the substrates. Gratifyingly, aldehyde 2l with a hy-
droxy group was suitable for the cyclocondensation re-
action (Entry 11). Excellent yield was obtained from the
reaction of naphthaldehyde 2o with disulfide 1a (Entry
15). To our delight, the cyclocondensation reaction of
furan-2-carbaldehyde 2p, with disulfide 1a afforded the
corresponding product in good yield (Entry 16). Subse-
Chin. J. Chem. 2011, 29, 314— 320
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317

Wang, Tang & Li
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Table 2 Synthesis of 2-substituted benzothiazolesa
Entry
1
ArSSAr 1
Aldehyde 2
t/h
Yieldb/%
Entry
13
ArSSAr 1
Aldehyde 2
t/h
Yieldb/%
1
70 (4)
1a
6
67 (16)
2
3
1a
1a
4
4
61 (5)
87 (6)
14
15
1a
1a
6
4
73 (17)
97 (18)
4
5
1a
1a
1a
1a
1a
1a
1a
1a
6
8
54 (7)
33 (8)
16
17
18
19
20
21
22
23
1a
1a
1a
1a
1a
1a
1b
1b
10
10
10
10
10
10
4
72 (19)
56 (20)
71 (21)
73 (22)
60 (23)
75 (24)
85 (25)
71 (26)
6
4
90 (9)
7
4
80 (10)
29 (11)
71 (12)
65 (13)
77 (14)
8
6
9
6
10
11
10
6
4
12
1a
6
38 (15)
24
1b
4
65 (27)
a
Reaction conditions: 1 (0.2 mmol), 2 (0.4 mmol), 4 Å molecular sieves (200 mg) and DMSO (2 mL) at 80 ℃ under air atmosphere.
b Isolated yield.
318
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Chin. J. Chem. 2011, 29, 314— 320

A Facile and Inexpensive Method for the Synthesis of 2-Substituted Benzothiazoles
quently, aliphatic aldehydes including 2-phenylacetalde-
hyde 2r, butyraldehyde 2s, hexanal 2t, isobutyraldehyde
2u and cyclohexanecarbaldehyde 2v were examined.
The results showed that these aliphatic aldehydes were
suitable substrates for the reaction, giving the corres-
ponding product in moderate to good yields (Entries 17
—21). Finally, aldehydes 2a, 2q and 2s were selected to
react with 6,6'-disulfanediylbis(3-chloroaniline), and
these reactions were carried out smoothly to give the
corresponding product in moderate to good yields (En-
tries 19—21).
lecular sieves could improve the reaction because of its
component such as SiO2/Al2O3 which was used as cata-
lyst for dehydration reaction21 and addition reaction.22
Molecular sieves probablely played a role of Lewis acid
to promote the cyclocondensation reaction.
Conclusion
In summary, we have developed a facile and inex-
pensive protocol for the synthesis of 2-substituted ben-
zothiazoles. In the presence of Na2S2O4, air and 4 Å
molecular sieves, a variety of aldehydes, including aro-
matic aldehydes and aliphatic aldehydes, underwent the
reactions with 2,2'-disulfanediyldianilines successfully
to afford the corresponding 2-substituted benzothiazoles
in moderate to excellent yields. Although 4 equiv. of
Na2S2O4 was used in the reaction, Na2S2O4 is much
cheaper and securer,7 which is potential for the indus-
trial preparation of benzothiazoles in comparison with
the reported catalytic systems such as H2O2/CAN,
4-methoxy-TEMPO radical/O2 and PPh3/p-TsOH sys-
tems.6
A possible mechanism as outlined in Scheme 2 for
the cyclocondensation reaction is proposed on the basis
of the present results and the previously reported
mechanisms.1,5,6 The Schiff base A is readily generated
by condensation of an amine with an aldehyde. Subse-
quently, the S—S bond is cleaved by the radical anion B
generated from S2O24－ , to afford intermediates C and D.
Intermediate C is reoxidized to disulfide 4, and inter-
mediate D undergoes the intramolecular cyclocondensa-
tion with imine to give the corresponding aminyl radical
intermediate E. Finally, intermediate E is oxidized by
air to afford the target product. We deduced that mo-
Scheme 2 A possible mechanism
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