Dibenzo[b,h][1,4,7]thiadiazonines: Examples of a novel ring system

Article abstract of DOI:10.1021/jo010318p

Acetanilides la-e react with 1,1′-sulfinylbis(benzotriazole)/trimethylchlorosilane at 45-65 °C to form 1,2-di(benzotriazol-1-yl)-2-arylimino-l-ethanethiones 3a-e, while heating the same reagents at 110 °C results in dibenzo[b, h][1,4,7]thiadiazonines 5a,c,d, and 6. X-ray crystal structures are reported for three representative examples.

Full text of DOI:10.1021/jo010318p

J . Org. Chem. 2001, 66, 5601-5605
5601
Diben zo[b,h ][1,4,7]th ia d ia zon in es: Exa m p les of a Novel Rin g
System
Alan R. Katritzky* and Tian-Bao Huang
Department of Chemistry, Center for Heterocyclic Compounds, University of Florida,
Gainesville, Florida 32611-7200
Peter J . Steel*
Department of Chemistry, University of Canterbury, Christchurch, New Zealand
katritzky@chem.ufl.edu
Received March 23, 2001
Acetanilides 1a -e react with 1,1′-sulfinylbis(benzotriazole)/trimethylchlorosilane at 45-65 °C to
form 1,2-di(benzotriazol-1-yl)-2-arylimino-1-ethanethiones 3a -e, while heating the same reagents
at 110 °C results in dibenzo[b,h][1,4,7]thiadiazonines 5a ,c,d , and 6. X-ray crystal structures are
reported for three representative examples.
Sch em e 1
In tr od u ction
Short routes for the efficient construction of medium-
ring heterocycles are currently a major challenge in syn-
thetic organic chemistry. Until now, few representatives
of 1-thia-4,7-diazacyclononanes have been reported, and
those are almost exclusively simple derivatives of the par-
ent saturated heterocycle1 or peptide-like analogues.2 To
the best of our knowledge, no 1,4,7-thiadiazonines, form-
ally representing a 10π Hu¨ckel aromatic ring, have pre-
viously been synthesized. We now disclose that acetan-
ilides 1a -e and the 1,1′-sulfinylbis(benzotriazole)/chloro-
trimethylsilane reagent, heated over 50 °C, form 1,2-di-
(benzotriazol-1-yl)-2-arylimino-1-ethanethiones 3a -e and
dibenzo[b,h][1,4,7]thiadiazonines 5a ,c,d and 6, the first
representatives of fully unsaturated 1-thia-4,7-diazacy-
clononanes, along with the corresponding imidoylbenzo-
triazoles 2.
Secondary amides have previously been converted into
imidoylbenzotriazoles by treatment with (1) 1,1′-sulfi-
nylbis(benzotriazole), prepared in situ from benzotriazole
and thionyl chloride,3 or (2) benzotriazole and phosphorus
oxychloride under basic conditions.4 Imidoylbenzotriaz-
oles, stable analogues of imidoyl chlorides, were demon-
strated to be important precursors for the preparation
of imidates and thioimidates3a and guanidines,5 as well
as ketones4 and various heteroaromatics.3b,6
Resu lts a n d Discu ssion
P r ep a r a tion of Im in oth ion es 3. The 1,1′-sulfinylbis-
(benzotriazole)/trimethylchlorosilane (BtSOBt/TMSCl) re-
agent was prepared in situ by treatment of 1-trimethyl-
silylbenzotriazole with thionyl chloride as described
previously,3a except that, considering the high sensitivity
of the BtSOBt/TMSCl reagent to atmospheric moisture,
this reaction was carried out in a solvent (THF, CH2Cl2,
or toluene) appropriate for the further transformations.
We found that heating acetanilides 1a -e with a 3-fold
excess of the BtSOBt/TMSCl reagent in methylene chlor-
ide under reflux for 6-12 h gave iminothiones 3a -e in
41-88% yields (Scheme 1). The intermediacy of the
* To whom correspondence should be addressed. E-mail: (P.J .S.)
p.steel@chem.canterbury.ac.nz.
(1) (a) Hart, S. M.; Boeyens, J . C. A.; Michael, J . P.; Hancock, R. D.
J . Chem. Soc., Dalton Trans. 1983, 1601. (b) Hoffmann, P.; Steinhoff,
A.; Mattes, R. Z. Naturforsch. 1987, 42B, 867. (c) Wambeke, D. M.;
Lippens, W.; Herman, G. G.; Goeminne, A. M. Bull. Soc. Chim. Belg.
1989, 98, 307. (d) Blake, A. J .; Danks, J . P.; Harrison, A.; Parsons, S.;
Schooler, P.; Whittaker, G.; Schroder, M. J . Chem. Soc., Dalton Trans.
1998, 2335. (e) Lippolis, V.; Blake, A. J .; Cooke, P. A.; Isaia, F.; Li,
W.-S.; Schroder, M. Chem. Eur. J . 1999, 5, 1987.
(2) (a) Virgilio, A. A.; Ellman, J . A. J . Am. Chem. Soc. 1994, 116,
11580. (b) Virgilio, A. A.; Schu¨rer, S. C.; Ellman, J . A. Tetrahedron
Lett. 1996, 37, 6961. (c) Virgilio, A. A.; Bray, A. A.; Zhang, W.; Trinh,
L.; Snyder, M.; Morrissey, M. M.; Ellman, J . A. Tetrahedron 1997, 53,
6635. (d) Souers, A. J .; Virgilio, A. A.; Schu¨rer, S. S.; Ellman, J . A.;
Kogan, T. P.; West, H. E.; Ankener, W.; Vanderslice, P. Bioorg. Med.
Chem. Lett. 1998, 8, 2297. (e) Souers, A. J .; Virgilio, A. A.; Rosenquist,
A.; Fenuik, W.; Ellman, J . A. J . Am. Chem. Soc. 1999, 121, 1817. (f)
Haskell-Luevano, C.; Rosenquist, A.; Souers, A.; Khong, K. C.; Ellman,
J . A.; Cone, R. D. J . Med. Chem. 1999, 42, 4380.
(4) Katritzky, A. R.; Rachwal, S.; Offerman, R. J .; Najzarek, Z.;
Yagoub, A. K.; Zhang, Y. Chem. Ber. 1990, 123, 1545.
(5) Katritzky, A. R.; Rogovoy, B.; Klein, C.; Insuasty, H.; Vvedensky,
V.; Insuasty, B. J . Org. Chem. 2001, 66, 2854.
(6) Katritzky, A. R.; Huang, T.-B.; Voronkov, M. V. J . Org. Chem.
2000, 65, 8069.
(3) (a) Katritzky, A. R.; Stevens, C. V.; Zhang, G.-F.; J iang, J .; De
Kimpe, N. Heterocycles 1995, 40, 231. (b) Katritzky, A. R.; Yang, B.;
Abonia, R.; Insuasty, B. J . Chem. Res., Synop. 1996, 540.
10.1021/jo010318p CCC: $20.00 © 2001 American Chemical Society
Published on Web 07/18/2001

5602 J . Org. Chem., Vol. 66, No. 16, 2001
Katritzky et al.
F igu r e 2. Perspective view of the crystal structure of 5a . The
solvate molecule is not shown.
of 3a-e: in THF, concurrent benzotriazolation of tetrahy-
drofuran led to 2-(benzotriazol-1-yl)- (4a ) and 2-(benzo-
triazol-2-yl)tetrahydrofuran (4b) (Scheme 1). Analogous
benzotriazolation of tetrahydrofuran was previously ob-
served with N-chlorobenzotriazole under Lewis acid
catalysis.7
P r ep a r a tion of Th ia d ia zon in es 5. Heating aceta-
nilides 1a ,c,d with excess BtSOBt/TMSCl reagent under
reflux in toluene for 6-12 h formed dibenzo[b,h][1,4,7]-
thiadiazonines 5a ,c,d as shown in Scheme 1. The nature
and the position of the substituent R in the starting
acetanilide influence the reaction significantly: a chlorine
at the meta position decreases the yield of the desired
product to 15% (compare with 65% for the p-chloro
derivative), while p-nitroacetanilide gave no thiadiazo-
nine 5.
Surprisingly, reaction of ethoxy-substituted acetanilide
1e (R3 ) H, R4 ) EtO) with the BtSOBt/TMSCl reagent
under the aforementioned conditions occurred with an
unexpected ethoxy group cleavage to afford the unsym-
metrically substituted thiadiazonine 6 in 49% yield.
However, when 4,5-dimethylbenzotriazole was used in
place of benzotriazole, this cleavage did not occur and
thiadiazonine 8 resulted.
F igu r e 1. Perspective view of one of the two independent
molecules in the crystal structure of 3b.
corresponding imidoylbenzotriazoles was supported by (1)
independent preparation of imidoylbenzotriazole 2b from
N-(4-methylphenyl)acetamide 1b at 0 °C (all the other
conditions being the same) and (2) the presence of traces
of compounds 2 in the NMR spectra of the reaction
mixtures even after a prolonged reaction time (up to 3
days). The formation of 3a -e from acetamides 1a -e may
involve intermediates of type 7.
The structures of compounds 5a ,c,d and 6 were
1
initially assigned on the basis of their H and 13C NMR
spectra and confirmed by X-ray structure determinations
for 5a and 6. Perspective views of the crystal structures
of 5a and 6 are displayed in Figures 2 and 3, respectively.
Compounds 5 structurally possess C2 symmetry, which
1
explains the simplified sets of signals in both H and 13C
NMR spectra. The absence of C2 or Cs symmetry in 6
leads to a more complicated pattern. As shown by X-ray
analysis, the [1,4,7]thiadiazonine ring of both 5a and 6
is twisted and therefore not aromatic. Kinetic as well as
thermodynamic factors appear to enhance the stability
of 5a ,c,d , 6, and 8. The two bulky benzotriazolyl groups
and two benzo substituents shield the internal imidoyl
groups from nucleophilic attack. Further, as is apparent
from Figures 2 and 3, the molecules of 5a and 6 adopt
very similar conformations, which have the two imine
components in approximately orthogonal orientations
(N-C-C-N torsional angles ) 85.7-88.4°) within each
molecule. In all cases, the plane of the benzotriazole ring
is almost exactly coplanar with the plane of its attached
imine functionality.
1
Structure 3b, suggested by H and 13C NMR spectra,
was confirmed by X-ray crystallography. This compound
crystallizes with two independent molecules in the asym-
metric unit, which adopt very similar conformations. As
shown in Figure 1, the planes of the imine and thiocar-
bonyl functionalities are approximately orthogonal [N-C-
C-S torsional angles ) 69.5 and 74.2° for the two
independent molecules]. In contrast, each of the benzo-
triazole groups is approximately coplanar with the
adjacent functional group. The structures of compounds
3a ,c-e were assigned by analogy and by spectroscopic
1
data comparisons. In the H NMR spectra of compounds
3a -e, the 4- and 7-benzotriazole aromatic protons signals
are significantly shifted downfield, probably because of
deshielding by the adjacent functional groups. Methylene
chloride was an advantageous solvent for the preparation
(7) Katritzky, A. R.; Voronkov, M. V.; Pastor, A.; Tatham, D.
Heterocycles 1999, 51, 1877.

Dibenzo[b,h][1,4,7]thiadiazonines
J . Org. Chem., Vol. 66, No. 16, 2001 5603
in CDCl3 (if not stated otherwise) with tetramethylsilane as
the internal standard for 1H (300 MHz) or a solvent as the
internal standard for 13C (75 MHz). Tetrahydrofuran, benzene,
and toluene were distilled from sodium/benzophenone (THF)
or from sodium under nitrogen immediately prior to use. All
reactions with air-sensitive compounds were carried out under
argon atmosphere. Column chromatography was conducted
with silica gel 230-400 mesh.
1,1′-Su lfin ylbis(ben zotr ia zole)/tr im eth ylch lor osila n e
r ea gen t (BtSOBt/TMSCl) was prepared by treatment of
1-trimethylsilyl benzotriazole (BtTMS) with thionyl chloride
in dichloromethane, THF, or toluene at 20 °C following the
reported procedure.3a
N-(4-Tolyl)a cetoim id oyl-1-ben zotr ia zole (2b). A solution
of N-(4-methylphenyl)acetamide 1b (0.3 g, 2 mmol) and of 1,1′-
sulfinylbis(benzotriazole) (3 mmol), prepared in situ as de-
scribed above, in dry dichloromethane was stirred at 0 °C for
4 h. Then the solvent was removed under reduced pressure
and the residue obtained was subjected to column chromatog-
raphy using hexane/ethyl acetate (15:1) as eluent to afford
N-(4-tolyl)acetoimidoyl-1-benzotriazole (2) in 39% yield as
orange needles. Analytically pure product was obtained as
yellow crystals by recrystallization from methylene chloride-
ethanol: mp 111-112 °C (lit.3a mp 108 °C); 1H NMR δ 2.39 (s,
3H), 2.75 (s, 3H), 6.85 (d, J ) 8.2 Hz, 2H), 7.22 (d, J ) 8.1 Hz,
2H), 7.47 (t, J ) 7.6 Hz, 1H), 7.59 (t, J ) 7.7 Hz, 1H), 8.12 (d,
J ) 8.4 Hz, 1H), 8.54 (d, J ) 8.2 Hz, 1H); 13C NMR δ 16.5,
21.1, 116.0, 120.0, 120.4, 125.6, 129.4, 130.0, 134.1, 145.0,
146.8, 154.2.
F igu r e 3. Perspective view of one of the two independent
molecules in the crystal structure of 6.
The mechanism of formation of [1,4,7]thiadiazonines
5a ,c,d , 6, and 8 may involve intermediates of type 9.
Indeed, bis(imidoylbenzotriazole) 9, prepared by reaction
of oxalic dianilide with BtSOBt/TMSCl in 86% yield, on
further treatment with an additional 2 equiv of the
BtSOBt/TMSCl reagent gave [1,4,7]thiadiazonine 5a in
71% yield.
Gen er a l P r oced u r e for th e P r ep a r a tion of Com p ou n d s
3. A solution of an acetanilide (2 mmol) and BtSOBt/TMSCl
reagent (6-7 mmol) in dry dichloromethane (25 mL) was
heated under reflux for 6-12 h. Then the solvent was removed
under reduced pressure and the residue was subjected to
purification by column chromatography using hexane/ethyl
acetate (15:1) as an eluent to afford the corresponding 1,2-di-
(benzotriazol-1-yl)-2-arylimino-1-ethanethione (3). Analytically
pure product was obtained by recrystallization from methylene
chloride-ethanol.
1,2-Di(1H-1,2,3-benzotriazol-1-yl)-2-arylimino-1-ethane-
thione 3b reacted with o-benzenediamine to give 10
(11%). Reactions of 6,7-di(1,2,3-benzotriazol-1-yl)dibenzo-
When THF was used as a solvent, the similar reactions gave
compounds 3 in 11-35% yields (compared to 41-69% in
dichloromethane) as well as 4a and 4b in 25% yield each.
1,2-Di(ben zotr ia zol-1-yl)-2-[(ph en yl)im in o]-1-eth a n eth -
ion e (3a ): orange prisms (from dichloromethane-ethanol);
yield 65%; mp 167-168 °C; 1H NMR δ 6.97 (d, J ) 7.5 Hz,
2H), 7.04 (t, J ) 7.5 Hz, 1H), 7.18-7.25 (m, 1H), 7.51-7.62
(m, 2H), 7.67-7.73 (m, 2H), 8.12 (d, J ) 8.2 Hz, 1H), 8.14 (d,
J ) 8.1 Hz, 1H), 8.58 (d, J ) 8.2 Hz, 1H), 8.62 (d, J ) 8.2 Hz,
1H); 13C NMR δ 115.3, 115.4, 120.3, 120.4, 121.2, 125.3, 126.4,
128.2, 129.2, 130.1, 130.8, 131.5, 132.2, 145.9, 146.3, 147.0,
147.6, 187.0. Anal. Calcd for C20H13N7S: C, 62.65; H, 3.42; N,
25.57. Found: C, 62.36; H, 3.34; N, 25.41.
[b,h][1,4,7]thiadiazonine (5a ) with 2 equiv of 4-chloroa-
niline in benzene in the presence of a catalytic amount
of DBU afforded 6,7-di(4-chlorophenylamino)dibenzo[b,h]-
[1,4,7]thiadiazonine (11) in excellent yield. The readiness
of this benzotriazolyl group substitution with a strong
nucleophile could provide a plausible explanation for the
formation of unsymmetrical thiadiazonine 12 as a major
product on treatment of N-(3,4,5-trimethoxyphenyl)-
acetamide (1f) with the BtSOBt/TMSCl reagent.
In summary, we have developed preparatively useful
procedures for the synthesis of novel 1,2-di(benzotriazol-
1-yl)-2-arylimino-1-ethanethiones (3a -e) and dibenzo-
[b,h]-[1,4,7]thiadiazonines (5a ,c,d , 6, and 8) stemming
from one-pot reactions of acetanilides with the 1,1′-
sulfinylbis(benzotriazole)/trimethylchlorosilane reagent
under different conditions.
1,2-Di(ben zotr ia zol-1-yl)-2-[(4-m eth ylp h en yl)im in o]-1-
eth a n eth ion e (3b): orange hexagons (from dichloromethane-
1
ethanol); yield 86%; mp 155-156 °C; H NMR δ 2.21 (s, 3H),
6.87 (d, J ) 8.2 Hz, 2H), 7.00 (d, J ) 8.2 Hz, 2H), 7.47-7.58
(m, 2H), 7.63-7.70 (m, 2H), 8.10 (d, J ) 8.1 Hz, 1H), 8.11 (d,
J ) 7.8 Hz, 1H), 8.57 (d, J ) 8.4 Hz, 1H), 8.63 (d, J ) 8.2 Hz,
1H); 13C NMR δ 20.8, 115.1, 115.2, 119.9, 120.1, 120.9, 126.0,
128.0, 129.6, 129.8, 130.5, 131.2, 131.9, 134.8, 143.0, 145.9,
146.7, 147.1, 187.2. Anal. Calcd for C21H15N7S: C, 63.46; H,
3.80; N, 24.67. Found: C, 63.41; H, 3.63; N, 24.74.
Cr ysta l d a ta for 3b: C21H15N7S, MW 379.46, monoclinic,
space group P21/c, a ) 14.466(5) Å, b ) 9.489(4) Å, c ) 28.115-
(10) Å, â ) 95.708(5)°, V ) 3846(2) Å3, F(000) ) 1648, Z ) 8,
T ) -110 °C, µ(Mo KR) ) 0.191 mm-1, Dcalcd ) 1.373 g‚cm-3
,
2θmax 53° (CCD area detector, Mo KR radiation, 47 627
reflections collected, R(int) ) 0.028, 99.2% completeness), GOF
) 1.04, wR(F2) ) 0.1028 (all 7860 data), R ) 0.0374 (6592 data
with I > 2σI).
1,2-Di(ben zotr ia zol-1-yl)-2-[(3-ch lor op h en yl)im in o]-1-
eth a n eth ion e (3c): yellow prisms (from dichloromethane-
Exp er im en ta l Section
1
Gen er a l Meth od s. Melting points were determined on a
capillary melting point apparatus equipped with a digital
thermometer and are uncorrected. NMR spectra were recorded
ethanol); yield 88%; mp 111-112 °C; H NMR δ 6.83 (d, J )
7.9 Hz, 1H), 6.97-7.10 (m, 3H), 7.47 (d, J ) 7.9 Hz, 1H), 7.52
(d, J ) 8.6 Hz, 1H), 7.63 (t, J ) 7.3 Hz, 1H), 7.64 (t, J ) 7.7

5604 J . Org. Chem., Vol. 66, No. 16, 2001
Katritzky et al.
Hz, 1H), 8.08 (d, J ) 8.2 Hz, 2H), 8.49 (d, J ) 8.2 Hz, 1H),
8.55 (d, J ) 8.2 Hz, 1H); 13C NMR δ 115.0, 115.2, 118.3, 120.2,
120.8, 121.1, 125.2, 126.4, 128.3, 130.2, 130.5, 131.2, 132.2,
129.9, 134.1, 138.2, 139.3, 154.4, 158.2. Anal. Calcd for C26H14
Cl2N8S: C, 57.68; H, 2.61. Found: C, 57.94; H, 2.95.
-
2,11-Dich lor o-6,7-d i(b en zot r ia zol-1-yl)d ib en zo[b,h ]-
[1,4,7]th iadiazon in e (5d): red needles (from dichloromethane-
134.8, 146.1, 146.8, 146.9, 148.1, 186.0. Anal. Calcd for C20H12
-
1
ClN7S: C, 57.49; H, 2.89; N, 23.46. Found: C, 57.23; H, 2.72;
N 23.40.
ethanol); yield 65%; mp 159-160 °C; H NMR δ 7.51 (t, J )
7.6 Hz, 2H), 7.65 (t, J ) 7.6 Hz, 2H), 7.91 (d, J ) 8.4 Hz, 2H),
8.20 (d, J ) 8.2 Hz, 2H), 8.26 (s, 4H), 8.40 (s, 2H); 13C NMR δ
110.5, 112.9, 120.9, 123.3, 125.2, 125.7, 129.2, 132.2, 138.2,
147.0, 154.0, 154.6. Anal. Calcd for C26H14Cl2N8S: C, 57.68;
H, 2.61. Found: C, 57.38; H, 2.73.
1,2-Di(ben zotr ia zol-1-yl)-2-[(4-ch lor op h en yl)im in o]-1-
eth a n eth ion e (3d ): red prisms (from dichloromethane-
1
ethanol); yield 68%; mp 180-181 °C; H NMR δ 6.92 (d, J )
8.8 Hz, 2H), 7.18 (d, J ) 8.8 Hz, 2H), 7.53-7.78 (m, 4H), 8.15
(t, J ) 8.1 Hz, 2H), 8.55 (d, J ) 8.3 Hz, 1H), 8.67 (d, J ) 8.3
Hz, 1H); 13C NMR δ 115.3, 115.5, 120.4, 121.3, 121.8, 126.5,
128.5, 129.4, 130.3, 130.8, 131.4, 132.4, 144.5, 146.3, 147.1,
148.1, 186.6. Anal. Calcd for C20H12ClN7S: C, 57.49; H, 2.89;
N, 23.46. Found: C, 57.84; H, 2.91; N, 23.61.
2-E t h oxy-6,7-d i(b en zot r ia zol-1-yl)d iben zo[b,h ][1,4,7]-
th ia d ia zon in e (6): yellow plates (from dichloromethane-
1
ethanol); yield 49%; mp 213-214 °C; H NMR (DMSO-d6) δ
1.10 (t, J ) 6.9 Hz, 3H), 3.75-3.80 (m, 2H), 6.50 (dd, J ) 8.8,
2.7 Hz, 1H), 6.71 (d, J ) 8.8 Hz, 1H), 6.78 (dd, J ) 7.5, 1.6 Hz,
1H), 6.85-6.94 (m, 3H), 7.40 (dd, J ) 7.6, 1.4 Hz, 1H), 7.60-
7.68 (m, 2H), 7.74-7.84 (m, 2H), 8.16-8.28 (m, 4H); 13C NMR
δ 14.2, 63.4, 113.7, 113.8, 114.1, 120.3, 120.4, 121.4, 122.1,
122.7, 123.7, 126.2, 127.1, 127.2, 127.4, 129.3, 129.4, 130.1,
131.1, 131.2, 136.7, 144.7, 145.4, 145.5, 147.0, 147.7, 155.8.
Anal. Calcd for C28H20N8OS: C, 65.10; H, 3.90; N, 21.69.
Found: C, 64.56; H, 3.98; N, 21.35.
1,2-Di(ben zotr ia zol-1-yl)-2-[(4-eth oxyp h en yl)im in o]-1-
eth a n eth ion e (3e): orange prisms (from dichloromethane-
1
ethanol); yield 41%; mp 128-129 °C; H NMR δ 1.34 (t, J )
7.0 Hz, 3H), 3.92 (q, J ) 7.0 Hz, 2H), 6.73 (d, J ) 8.9 Hz, 2H),
6.92 (d, J ) 9.1 Hz, 2H), 7.51-7.78 (m, 4H), 8.12 (d, J ) 8.3
Hz, 1H), 8.16 (d, J ) 8.1 Hz, 1H), 8.60 (d, J ) 8.3 Hz, 1H),
8.71 (d, J ) 8.3 Hz, 1H); 13C NMR δ 15.0, 63.8, 110.3, 115.1,
115.5, 115.6, 120.3, 121.3, 122.1, 126.3, 128.3, 130.0, 130.9,
131.6, 132.3, 138.7, 146.3, 147.1, 156.9, 188.1. Anal. Calcd for
Cr ysta l d a ta for 6: C28H20N8OS, MW 516.58, monoclinic,
space group P21/c, a ) 21.005(7) Å, b ) 18.076(6) Å, c ) 13.811-
(5) Å, â ) 106.960(5)°, V ) 5016(3) Å3, F(000) ) 2144, Z ) 8,
C
22H17N7OS: C, 61.81; H, 4.01; N, 22.94. Found: C, 61.77; H,
T ) -105 °C, µ(Mo KR) ) 0.168 mm-1, Dcalcd ) 1.368 g‚cm-3
,
3.90; N, 22.64.
1-(2-Tetr a h yd r ofu r yl)ben zotr ia zole (4a ):8 colorless oil;
2θmax 45° (CCD area detector, Mo KR radiation, 47 338
reflections collected, R(int) ) 0.1017, 99.9% completeness),
GOF ) 1.09, wR(F2) ) 0.1166 (all 6564 data), R ) 0.0537 (4680
data with I > 2σI).
1
yield 25%; H NMR δ 2.15-2.23 (m, 1H), 2.35-2.59 (m, 2H),
3.12-3.21 (m, 1H), 4.00-4.14 (m, 2H), 6.51 (dd, J ) 6.7, 2.3
Hz, 1H), 7.37 (dt, J ) 7.7, 1.0 Hz, 1H), 7.50 (dt, J ) 7.7, 1.2
Hz, 1H), 7.71 (d, J ) 8.3 Hz, 1H), 8.07 (d, J ) 8.3 Hz, 1H); 13
C
2,11-Diet h oxy-6,7-d i(5,6-d im et h ylb en zot r ia zol-1-yl)-
d iben zo[b,h ][1,4,7]th ia d ia zon in e 8. A solution of N-(4-
ethoxyphenyl)acetamide (0.36 g, 2 mmol) and DMBt-SO-
DMBt/TMSCl reagent (7 mmol) in dry toluene (25 mL) was
heated at 100 °C for 12 h. The solvent was removed under
reduced pressure, and the residue was subjected to column
chromatography using hexane/ethyl acetate (9:1) as an eluent
to afford dibenzo[b,h][1,4,7]thiadiazonine 8 in 59% yield. The
analytically pure product was obtained by recrystallization
from dichloromethane-ethanol: purple needles; mp 193-194
NMR δ 24.6, 31.0, 69.5, 88.1, 110.6, 120.1, 124.3, 127.7, 133.0,
146.6.
2-(2-Tetr a h yd r ofu r yl)ben zotr ia zole (4b):8 colorless oil;
1
yield 25%; H NMR δ 2.11-2.18 (m, 1H), 2.45-2.57 (m, 2H),
2.72-2.77 (m, 1H), 4.14 (dd, J ) 14.1, 8.1 Hz, 1H), 4.34 (dd, J
) 13.9, 8.1 Hz, 1H), 6.60 (dd, J ) 6.3, 2.4 Hz, 1H), 7.36-7.42
(m, 2H), 7.85-7.91 (m, 2H); 13C NMR δ 24.5, 32.6, 70.5, 94.4,
118.7, 126.8, 144.5.
Gen er a l P r oced u r e for th e P r ep a r a tion of Com p ou n d s
5 a n d 6. A solution of an acetanilide (2 mmol) and BtSOBt/
TMSCl reagent (6-7 mmol) in dry toluene (25 mL) was heated
under reflux for 12 h. The solvent was removed under reduced
pressure, and the residue was subjected to purification by
column chromatography using hexane/ethyl acetate (6:1) as
an eluent to afford the corresponding dibenzo[b,h][1,4,7]-
thiadiazonine (5 or 6). Analytically pure product was obtained
by recrystallization from dichloromethane-ethanol.
6,7-Di(ben zotr ia zol-1-yl)d iben zo[b,h ][1,4,7]th ia d ia zo-
n in e (5a ): pale yellow prisms (from dichloromethane-etha-
nol); yield 78%; mp 232-233 °C; 1H NMR δ 6.71-6.78 (m, 2H),
6.81-6.83 (m, 4H), 7.28 (d, J ) 7.6 Hz, 2H), 7.45 (t, J ) 7.5
Hz, 2H), 7.57 (t, J ) 7.5 Hz, 2H), 8.02 (d, J ) 8.2 Hz, 2H),
8.27 (d, J ) 8.2 Hz, 2H); 13C NMR δ 114.5, 120.2, 122.5, 122.8,
125.7, 126.5, 126.9, 130.0, 130.2, 130.4, 145.0, 146.3, 147.4.
Anal. Calcd for C26H16N8S.0.5C2H6O (ethanol solvate): N,
22.61. Found: N, 22.86.
Cr ysta l d a ta for 5a : C26H16N8S.0.5C2H6O, FW 495.56,
monoclinic, space group C2/c, a ) 14.557(11) Å, b ) 11.785(9)
Å, c ) 28.21(2) Å, V ) 4740(6) Å3, F(000) ) 2056, Z ) 8, T )
-105 °C, µ(Mo KR) ) 0.173 mm-1, Dcalcd ) 1.389 g‚cm-3, 2θmax
53° (CCD area detector, Mo KR radiation, 29 914 reflections
collected, R(int) ) 0.025, 98.4% completeness), GOF ) 1.04,
wR(F2) ) 0.1289 (all 4807 data), R ) 0.0471 (3867 data with
I > 2σI).
1
°C; H NMR δ 1.48 (t, J ) 7.0 Hz, 6H), 2.43 (s, 12H), 4.17 (q,
J ) 7.0 Hz, 4H), 7.19 (dd, J ) 8.4, 2.6 Hz, 2H), 7.49 (s, 2H),
7.54 (d, J ) 8.5 Hz, 2H), 7.73 (d, J ) 2.3 Hz, 2H), 7.95 (s, 2H);
13C NMR δ 15.2, 19.8, 20.3, 64.5, 108.0, 119.6, 119.9, 120.5,
127.3, 134.0, 136.2, 137.0, 139.9, 151.1, 151.6, 152.5, 156.5;
HRMS (FAB) calcd for C34H33N8O2S (M + 1) 617.2447, found
617.2444.
Bis(p h en ylim id oyl-1-ben zotr ia zole) (9). A mixture of
oxalic anilide (0.24 g, 1 mmol) and BtSOBt/TMSCl reagent (3
mmol) in benzene (10 mL) was heated under reflux for 4 h.
Then the solvent was removed under reduced pressure, and
the residue was subjected to column chromatography using
hexane/ethyl acetate (5:1) as an eluent to afford the product 9
in 86% yield as orange needles. Analytically pure product was
obtained as yellow crystals by recrystallization from dichlo-
1
romethane-ethanol: mp 85-86 °C; H NMR δ 7.05 (dd, J )
8.5, 1.2 Hz, 4H), 7.17-7.22 (m, 2H), 7.33-7.41 (m, 6H), 7.50-
7.55 (m, 2H), 7.91 (d, J ) 8.3 Hz, 2H), 8.14 (d, J ) 8.3 Hz,
2H); 13C NMR δ 114.7, 119.9, 120.7, 125.9, 126.1, 129.3, 129.9,
131.3, 142.0, 146.0, 146.4; HRMS (FAB) calcd for C13H9N4 (1/2
M) 221.0827, found 221.0835.
P r oced u r e for th e P r ep a r a tion of Im id oyl Ben zotr ia -
zole 10. A solution of 1,2-di(benzotriazol-1-yl)-2-[(4-meth-
ylphenyl)imino]-1-ethanethione (3b) (0.40 g, 1 mmol) and
o-phenylenediamine (0.11 g, 1 mmol) in dry benzene (10 mL)
was heated under reflux for 2 h. The solvent was removed
under reduced pressure, and the residue was subjected to
purification by column chromatography using hexane/ethyl
acetate (9:1) as an eluent to afford product 10 in 11% yield.
When THF was used as a solvent, the reaction gave compounds
4a and 4b in 30-40% yields; only traces of 10 were observed
by NMR spectra.
1,12-Dich lor o-6,7-d i(b en zot r ia zol-1-yl)d ib en zo[b,h ]-
[1,4,7]th iadiazon in e (5c): red needles (from dichloromethane-
ethanol); yield 15%; mp 155-156 °C; 1H NMR δ 7.38 (dd, J )
8.0, 1.6 Hz, 2H), 7.60-7.72 (m, 6H), 7.79 (dd, J ) 7.6, 1.7 Hz,
2H), 8.16 (d, J ) 8.1 Hz, 2H), 8.23 (dd, J ) 7.5, 1.8 Hz, 2H);
13C NMR δ 120.1, 122.2, 123.7, 124.1, 124.6, 127.2, 128.1,
N -[Be n zim id a zol-2-yl(1,2,3-b e n zot r ia zol-1-yl)m e t h -
ylid en e]-4-m eth yla n ilin e (10): orange needles; yield 11%;
mp 154-155 °C; 1H NMR (CD2Cl2) δ 2.39 (s, 3H), 7.23 (m, 2H),
(8) Katritzky, A. R.; Rachwal, S.; Rachwal, B. J . Chem. Soc., Perkin
Trans. 1 1990, 1717.

Dibenzo[b,h][1,4,7]thiadiazonines
J . Org. Chem., Vol. 66, No. 16, 2001 5605
7.51-7.78 (m, 5H), 7.87 (m, 3H), 7.99 (d, J ) 8.1 Hz, 1H), 8.24
toluene (25 mL) was heated under reflux for 12 h. The solvent
was removed under reduced pressure, and the residue was
subjected to purification by column chromatography using
hexane/ethyl acetate (9:1) as an eluent to afford dibenzo[b,h]-
[1,4,7]thiadiazonine 12 in 27% yield. The analytically pure
product was obtained by recrystallization from methylene
chloride-ethanol: yellow needles; yield 39%; mp 77-78 °C; 1H
NMR δ 3.86 (s, 3H), 3.88 (s, 3H), 3.93 (s, 3H), 6.89 (s, 1H),
7.06 (t, J ) 7.3 Hz, 1H), 7.30-7.39 (m, 5H), 7.44 (dt, J ) 7.8,
1.4 Hz, 1H), 7.61 (dt, J ) 7.8, 1.2 Hz, 1H), 7.76 (d, J ) 7.7 Hz,
2H), 7.83-7.88 (m, 2H), 8.09 (dd, J ) 8.1, 1.2 Hz, 1H), 8.87 (s,
1H); 13C NMR δ 56.4, 61.2, 61.4, 105.2, 107.4, 107.5, 118.6,
120.2, 120.8, 123.2, 126.1, 126.7, 127.0, 127.2, 129.0, 130.8,
134.4, 139.4, 142.2, 143.8, 145.1, 153.0, 154.2; HRMS (FAB)
calcd for C29H25N6O3S (M + 1) 537.1660, found 537.1769.
(d, J ) 8.2 Hz, 1H), 8.86 (d, J ) 8.4 Hz, 1H), 10.52 (s, 1H); 13
C
NMR δ 21.2, 30.2, 116.5, 120.7, 121.6, 126.5, 126.6, 126.7,
128.4, 129.9, 130.4, 130.8, 134.0, 135.1, 136.1, 137.1, 140.4,
143.0, 146.0. HRMS (FAB) Calcd for
353.1515; found 353.1514.
C21H17N6 (M + 1)
P r ep a r a tion of 6,7-Di(4-ch lor op h en yla m in o)d iben zo-
[b,h ][1,4,7]th ia d ia zon in e 11. A solution of a mixture of 6,7-
di(benzotriazol-1-yl)dibenzo[b,h][1,4,7]thiadiazonine (5a ) (0.24
g, 0.5 mmol), DBU (a catalytic amount), and 4-chloroaniline
(0.14 g, 1.10 mmol) in dry benzene (10 mL) was stirred at 20
°C for 6 h. Then the solvent was removed under reduced
pressure, and the residue was subjected to column chroma-
tography using hexane/ethyl acetate (5:1) as an eluent to afford
the thiadiazonine 11 as red needles. The analytically pure
product was obtained as yellow crystals by recrystallization
from methylene chloride-ethanol: yield 97%; mp 96-97 °C;
1H NMR δ 7.27 (d, J ) 8.7 Hz, 4H), 7.53 (t, J ) 7.7 Hz, 2H),
7.65-7.70 (m, 6H), 8.15 (d, J ) 8.2 Hz, 2H)), 8.48 (d, J ) 8.2
Hz, 2H), 9.85 (s, 2H); 13C NMR δ 114.0, 119.3, 120.4, 126.4,
127.7, 129.2, 130.3, 132.0, 138.3, 145.2, 147.0. Anal. Calcd for
Ack n ow led gm en t. We thank Dr. Olga Denisko for
her valuable help in the preparation of this paper.
Su p p or tin g In for m a tion Ava ila ble: Crystal data collec-
tion and refinement parameters, full tables of atom coordi-
nates, bond lengths and angles, and thermal displacement
parameters (Tables S1-S15) for X-ray crystal structures of
3b, 5a , and 6. This material is available free of charge via the
Internet at http://pubs.acs.org.
C
26H18Cl2N8S: C, 63.81; H, 3.71; N, 11.45. Found: C, 63.35;
H, 4.37; N, 11.33.
P r ep a r a tion of 6-(4,5,6-Tr im eth oxa n ilin o)-7-(ben zot-
r ia zol-1-yl)d iben zo[b,h ][1,4,7]th ia d ia zon in e (12). A solu-
tion of N-(3,4,5-trimethoxyphenyl)acetamide 1f (0.45 g, 2
mmol) and DMBt-SO-DMBt/TMSCl reagent (7 mmol) in dry
J O010318P