Isomerization and ring-closing metathesis for the synthesis of 6-, 7- and 8-membered benzo- and pyrido-fused N,N-, N,O- and N,S-heterocycles

Article abstract of DOI:10.1016/j.tetlet.2004.10.108

An isomerization-ring-closing metathesis (RCM) strategy afforded N-substituted 4H-1,4-benzoxazines from the protected N-allyl-2-(allyloxy) anilines. In addition, RCM was used to synthesize the N-substituted, 8-membered benzo-fused heterocycles from the re

Full text of DOI:10.1016/j.tetlet.2004.10.108

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 9171–9175
Isomerization and ring-closing metathesis for the
synthesis of 6-, 7- and 8-membered benzo- and pyrido-fused
N,N-, N,O- and N,S-heterocycles
Willem A. L. van Otterlo,* Garreth L. Morgans, Setshaba D. Khanye,
Blessing A. A. Aderibigbe, Joseph P. Michael and David G. Billing
Molecular Sciences Institute, School of Chemistry, University of the Witwatersrand, PO Wits, 2050 Johannesburg, South Africa
Received 9 September 2004; revised 11 October 2004; accepted 20 October 2004
Abstract—An isomerization–ring-closing metathesis (RCM) strategy afforded N-substituted 4H-1,4-benzoxazines from the pro-
tected N-allyl-2-(allyloxy)anilines. In addition, RCM was used to synthesize the N-substituted, 8-membered benzo-fused hetero-
cycles from the respective diallyl compounds: 1,2,5,6-tetrahydro-1,6-benzodiazocine, 5,6-dihydro-2H-1,6-benzoxazocine, 5,6,9,
10-tetrahydropyrido[2,3-b][1,4]diazocine and 5,6-dihydro-2H-1,6-benzothiazocine 1,1-dioxide. The isomerization–RCM approach
also afforded the 7-membered ring system, 2,5-dihydro-1,5-benzothiazepine 1,1-dioxide, from the protected N-allyl-2-(allylsulfonyl)-
aniline. Furthermore, the structure of 1,6-bis[(4-methylphenyl)sulfonyl]-1,2,5,6-tetrahydro-1,6-benzodiazocine was confirmed by a
single crystal X-ray determination.
ꢀ 2004 Elsevier Ltd. All rights reserved.
R1
R2
O
O
R1
R2
O
O
1. Introduction
i, ii
Ring-closing metathesis has seen a tremendous increase
in synthetic applications over the last decade. The num-
ber of recent reviews covering this topic signifies that
this reaction has become a valuable synthetic method
for forming cyclic systems.1 Our research group has
been involved in the application of RCM to the synthe-
sis of benzo-fused bicyclic molecules2 in particular. Re-
cently we have reported the use of a novel one-pot
isomerization–RCM strategy to afford a number of
these compounds, including the substituted benzodiox-
ene 1, dihydroisoquinoline 2 and benzofuran 3 as shown
in Figure 1.3 Although the number of examples in the
literature describing isomerization reactions followed
by RCM are limited,3,4 this concept has been included
in an in-depth review.5
R1,R2 = H, OMe, benzene
1
Ts
Ts
N
N
i, ii
MeO
MeO
OiPr
OiPr
2
i, ii
O
O
3
Figure 1. Examples of the application of an isomerization–RCM
strategy: (i) isomerization and (ii) RCM.
cycles.6 These types of bicyclic molecules are potential
pharmacological scaffolds with interesting biological
activities.7 An interesting paper by Guillaumet and co-
workers highlighted their approach to the 2H-1,5-benzo-
dioxepin and 2,5-dihydro-1,6-benzodioxocin skeletons
utilizing a RCM approach.8 This paper prompted us
to publish the successes we have enjoyed in our labora-
tories concerning the syntheses of N,N-, N,O- and N,S-
6-, 7- and 8-membered benzo-fused heterocycles using
RCM and isomerization–RCM strategies.9
In recent years several research groups have reported
RCM approaches to benzo-fused 8-membered hetero-
Keywords: Isomerization; Ring-closing metathesis; Benzo-fused hetero-
cycles; 1,4-Benzoxazines; 1,6-Benzodiazocine; 1,6-Benzoxazocine; 1,6-
Benzothiazocine; 1,5-Benzothiazepine.
*
Corresponding author. Tel.: +27 11 717 6707; fax: +27 11 717
6749; e-mail: willem@aurum.wits.ac.za
Crystallographic correspondence: dave@aurum.wits.ac.za
0040-4039/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.10.108

9172
W. A. L. van Otterlo et al. / Tetrahedron Letters 45 (2004) 9171–9175
R
N
2. N-Substituted 1,2,5,6-tetrahydro-1,6-benzodiazocines
and 5,6,9,10-tetrahydropyrido[2,3-b][1,4]diazocine
R
N
i
N
R
N
R
o-Phenylenediamine 4a (X = CH) and 2,3-diaminopyri-
dine 4b (X = N) were initially protected as their bis-(4-
methylphenyl)-sulfonamides. These compounds were
then alkylated with an excess of allyl bromide and
K2CO3 to afford compounds 5a and 5b in acceptable
yields (Scheme 1). Subsequent treatment of these sub-
strates with GrubbsÕ second generation catalyst 7 grati-
fyingly afforded the 8-membered 1,6-benzo-6a10 and 1,6-
pyrido-diazocine 6b11 ring systems in excellent yield.12
Furthermore, to confirm the structure of product 6a
unambiguously, a single crystal X-ray structural deter-
mination was performed (see Fig. 2).13
5a,c
8a,c
iii
ii
Boc
R
N
N
N
R
N
6c
9a,c
Boc
Scheme 2. Reagents and conditions: (i) for R = Ts: 5% [RuClH-
(CO)(PPh3)3], d8-toluene, 105ꢁC, N2, 3–4h (8a observed by NMR
spectroscopy but not isolated), for R = Boc: 4% [RuClH(CO)(PPh3)3],
toluene, 95ꢁC, N2, 98h (96%); (ii) for R = Ts: 5% catalyst 7, toluene,
110ꢁC, 5h (only compound 8a recovered), for R = Boc: 2 · 5% catalyst
7, toluene, 80ꢁC, 18h (only compound 8c recovered in 63%); (iii) 5%
catalyst 7, toluene, 110ꢁC, N2, 3h (64%).
At this point we attempted to use the isomerization–
RCM approach that we have successfully applied to
the synthesis of dioxenes.3a To this end, treatment of
diallyl compound 5a (X = CH) with the isomerization
catalyst [RuClH(CO)(PPh3)3]14,15 afforded the isomer-
ized compound 8a, which was not isolated (Scheme 2).
However, much to our disappointment, treatment of
8a with catalyst 7 did not afford the expected 1,4-
dihydroquinoxaline 9a and only starting material was
recovered.
(PPh3)3] and readily underwent the bis-isomerization
process to give compound 8c (Scheme 2). However,
when this compound was subjected to catalyst 7, no
RCM process was evident from TLC analysis of the
reaction mixture. Treatment of 5c with catalyst 7, how-
ever, once again readily afforded the 8-membered benzo-
fused compound 6c in a yield of 64%.
We wondered if the steric size of the two tosyl groups
was preventing the two enamines in 8a from reacting
in a metathetic manner. To investigate this proposal
the Boc-protected analogue of 4a was synthesized and
allylated to afford compound 5c (56% over two steps
from 4a). This compound was exposed to [RuClH(CO)-
3. N-Substituted 5,6-dihydro-2H-1,6-benzoxazocines and
4H-1,4-benzoxazines
We also decided to synthesize the N,O-diallyl compound
analogous to 5a to test whether this compound would
undergo the isomerization–RCM sequence. 2-Amino-
phenol 10 was therefore protected as its bis-tosyl equiv-
alent to afford compound 11a (Scheme 3). The phenolic
tosyl group was then selectively hydrolyzed using a litera-
ture procedure16 and the resultant compound was then
allylated to give product 12a in excellent yield. Once
again the isomerization catalyst [RuClH(CO)(PPh3)3]
proved highly successful in mediating the bis-isomeriza-
tion to afford compound 13a in quantitative yield. Satis-
fyingly, addition of GrubbsÕ second generation catalyst
7 to compound 13a cleanly afforded the substituted
4H-benzo[1,4]oxazine 14a17 in high yield.18 RCM using
GrubbsÕ catalysts on substrates containing electron-rich
vinylic olefins is known to be potentially problematic2a
Ts
N
NH2
NH2
i,ii
X
N
Ts
X
4a,b
5a,b
Ts
N
N
Mes N
Cl
Mes
iii
Ru
Cl
X
N
Ph
7
PCy3
6a,b
Ts
Scheme 1. Reagents and conditions: (i) TsCl, pyridine, 60ꢁC, N2, 20–
23h; (ii) K2CO3, allyl bromide, acetone, 60ꢁC, N2, 20–23h, 5a,
X = CH (44% over two steps), 5b, X = N (24% over two steps); (iii) 5%
catalyst 7, toluene, N2, 5h, rt, 6a, X = CH (96%), 6b, X = N (94%).
Figure 2. ORTEP diagram of the X-ray crystal structure of compound 6a with thermal ellipsoids at 50% probability.

W. A. L. van Otterlo et al. / Tetrahedron Letters 45 (2004) 9171–9175
9173
OR2
SH
NH2
S
OH
i,ii
i
NHR1
11a,b
NHTs
NH2
10
15a,b
14a,b
17
16
iii
v
ii,iii
S
O
S
O
iv
vi
v
N
Ts
N
N
N
R1
R1
O
12a,b
19
21
18
20
22
Ts
O
iv
O
S
O O
S
O
vi
N
R1
N
R1
N
Ts
N
13a,b
Ts
O
vii
O
S
O
Scheme 3. Reagents and conditions: (i) for R1, R2 = Ts: TsCl,
pyridine, 60ꢁC, N2, 20–23h, 11a (87%); for R1 = Boc and R2 = H:
Boc2O, THF, rt, N2, 12h, 11b (64%); (ii) for R1, R2 = Ts: Mg, MeOH,
rt, 8h (93%); (iii) K2CO3, allyl bromide, acetone, 60ꢁC, N2, 18h, 12a
(99%), for R1 = Boc: K2CO3, allyl bromide, acetone, 60ꢁC, N2, 23h,
12b (92%); (iv) for R1 = Ts: 1% [RuClH(CO)(PPh3)3], toluene, 95ꢁC,
N2, 2h, 13a (quantitative), for R1 = Boc: 3% [RuClH(CO)(PPh3)3], d8-
toluene, 95ꢁC, N2, 98h, 13b (quantitative by NMR spectroscopy, 81%
isolated); (v) for R1 = Ts: 5% catalyst 7, toluene, 45ꢁC, N2, 2.5h, 14a
(90%), for R1 = Boc: 2 · 5% catalyst 7, toluene, 60ꢁC, N2, 24h, 14b
(71%); (vi) 5% catalyst 7, toluene, rt, N2, 5h, 15a, R1 = Ts (69%), 15b,
R1 = Boc (70%).
O
S
viii
N
Ts
N
Ts
23
Scheme 4. Reagents and conditions: (i) allyl bromide, MeOH, NaOH,
H2O, rt, 2h; (71%); (ii) TsCl, pyridine, CH2Cl2, 45ꢁC, N2, 24h (97%);
(iii) K2CO3, allyl bromide, acetone, rt, 24h; (99%); (iv) 5% catalyst 7,
toluene, 50ꢁC, N2, 48h, complex mixture; (v) MCPBA (2.2equiv),
CH2Cl2, À5ꢁC, 48h; (71%); (vi) 5% catalyst 7, CHCl3, rt, 24h, then
45ꢁC, 24h (95%); (vii) 10% [RuClH(CO)(PPh3)3], toluene, 105ꢁC, 24h
(84%); (viii) 5% catalyst 7, toluene, 50ꢁC, 24h, then further 5% catalyst
7, 80ꢁC, 24h, 23 (41%) and 22 (59%).
and to our knowledge these results are the first examples
of high-yielding metathesis reactions between a phenolic
vinyl ether and an enamine alkene.19
the desired product 2125 in good yield although the reac-
tion was quite sluggish (Scheme 4). The phenomenon of
the oxidized substrate more readily engaging in metath-
esis has been observed before, in particular by Hanson
and co-workers.23b Finally, we attempted to apply the
sequential isomerization–RCM strategy on compound
20 and were rather surprised to isolate compound 22
in which only the N-allyl group had been isomerized.
Kuz´nik et al.14c have shown that allyl sulfones can be
isomerized to the thermodynamically more stable com-
pounds but in our hands we were unable to obtain the
bis-isomerized product. Subsequently, when compound
22 was treated with GrubbsÕ catalyst 7, the 7-membered
1,5-benzothiazepine 23 was obtained although the reac-
tion was particularly slow.26,27
To enable facile deprotection of the nitrogen functional
group, the Boc-protected precursor 12b was also synthe-
sized as described in Scheme 3. Application of the
isomerization–RCM approach readily afforded the
Boc-protected 3,4-dihydro-2H-1,4-benzoxazine com-
pound 14b.20 Satisfyingly, in addition, both precursors
12a and 12b afforded the expected 8-membered benzo-
fused oxazocine ring systems 15a21 and 15b in accepta-
ble yields of 69% and 70%, respectively, when treated
with GrubbsÕ second generation catalyst 7.
4. N-Substituted 5,6-dihydro-2H-1,6-benzothiazocine 1,1-
dioxide and 2,5-dihydro-1,5-benzothiazepine 1,1-dioxide
We have thus shown that the versatile RCM reaction,
with the GrubbsÕ second-generation catalyst 7, can be
applied to the synthesis of a number of bicyclic com-
pounds, namely N,N-, N,O- and N,S-8-membered benzo-
fused heterocycles. In addition the application of a
sequential isomerization–RCM strategy afforded the
respective N-,O-6-membered benzo-fused bicyclic com-
pounds in a novel manner although this strategy was
not successful on the N-,N-substrates. Finally, a 7-mem-
bered benzothiazepine system was synthesized by a
selective isomerization, followed by RCM. The exten-
sion of this work to the synthesis of other interesting sys-
tems is currently under investigation.
RCM of substrates containing sulfur atoms has also
seen a recent surge of interest.22 However the applica-
tion of RCM to synthesize benzo-fused S-containing
heterocycles has seldom been done.23 We thus decided
to test whether we could synthesize the 8- and 6-mem-
bered benzo-fused ring systems containing the hetero-
atoms nitrogen and sulfur. Aminothiol 16 was thus
monoalkylated with allyl bromide24 and the amine sub-
sequently protected with a tosyl group to afford com-
pound 17 (Scheme 4). Furthermore, an allylation
readily afforded compound 18. Surprisingly, RCM on
this substrate did not give the expected 8-membered
benzothiazocine compound 19 and attempted isomeriza-
tion of the same substrate was also unsuccessful.14c
Acknowledgements
Substrate 18 was thus oxidized to the corresponding
sulfone 20 and this time the RCM successfully afforded
This work was supported by the National Research
Foundation (NRF, GUN 2053652), Pretoria, and the

9174
W. A. L. van Otterlo et al. / Tetrahedron Letters 45 (2004) 9171–9175
Kishuku, H.; Shindo, M.; Shishido, K. Chem. Commun.
2003, 23, 350–351; (c) Miller, S. J.; Kim, S.-H.; Chen,
Z.-R.; Grubbs, R. H. J. Am. Chem. Soc. 1995, 117, 2108–
2109.
University of the Witwatersrand (University and Science
Faculty Research Councils). Professor C. B. de Koning
is thanked for comments regarding the manuscript. Mr.
R. Mampa and Mr. T. van der Merwe are also thanked
for providing the NMR and MS spectroscopy services,
respectively.
13. Crystallographic data for compound 6a: C24H24N2O4S2,
crystal size 0.5 · 0.5 · 0.5mm3, crystal system monoclinic,
space group P21/c, Z = 4, unit cell dimensions: a =
˚
˚
3
˚
3
13.036(5)A,
b = 11.033(5)A,
c = 16.489(5)A,
b =
˚
106.115(5)ꢁ, V = 2278.4(15)A , Dx = 1.366mg/m , collec-
tion temperature 293(2)K; hmax = 28.29ꢁ; 15,395 reflec-
tions collected with 5604 independent reflections
(Rint = 0.0201); 291 parameters; maximum residual elec-
References and notes
1. (a) Schmalz, H.-G. Angew. Chem., Int. Ed. Engl. 1995, 34,
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Tetrahedron Lett. 2003, 44, 6483–6486; (b) van Otterlo, W.
A. L.; Pathak, R.; de Koning, C. B. Synlett 2003, 1859–
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tron density 0.299 and À0.286eAÀ3; final R indices:
˚
R1 = 0.0434, wR2 = 0.1134. CCDC-249593 contains the
supplementary crystallographic data for this paper. These
data can be obtained free of charge at www.ccdc.cam.
ac.uk/conts/retrieving.html [or from the Cambridge Crys-
tallographic Data Centre, 12, Union Road, Cambridge
CB2 1EZ, UK; fax: (internat.) +44-1223/336-033; E-mail:
deposit@ccdc.cam.ac.uk].
14. (a) Krompiec, S.; Kuz´nik, N.; Penczek, R.; Rzepa, J.;
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wiak, T. Tetrahedron Lett. 2001, 42, 7095–7098; (f)
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6. For representative examples see: (a) Maishal, T. K.;
Sarkar, A. Synlett 2002, 1925–1927; For an ene-yne RCM
approach to O,O-, O,N- and N,N-8-membered benzo-
fused heterocycles see: (b) Mori, M.; Kitamura, T.;
Sakakibara, N.; Sato, Y. Org. Lett. 2000, 2, 543–545; (c)
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17. 4-[(4-Methylphenyl)sulfonyl]-4H-1,4-benzoxazine
14a:
8. Mamouni, R.; Soukri, M.; Lazar, S.; Akssira, M.;
Guillaumet, G. Tetrahedron Lett. 2004, 45, 2631–2633.
9. Taken from the ongoing Ph.D. project of Mr. G. L.
Morgans, the ongoing M.Sc. project of Blessing A. A.
Aderibigbe and the Honours project of Mr. (Rambo) S. D.
Khanye.
mp: 101–103ꢁC; Found: M+, 287.0633; C15H13NO3S
requires 287.0616; mmax (thin film/cmÀ1): 1666, 1599,
1357, 1171; 1H NMR (300MHz; CDCl3; Me4Si): 7.63–
7.60 (m, 1H, ArH), 7.43 (d, 2H, J = 8.2, 2 · ArH), 7.19 (d,
2H, J = 8.2, 2 · ArH), 7.07–7.03 (m, 2H, 2 · ArH), 6.61–
6.57 (m, 1H, ArH), 6.18 (d, 1H, J = 4.1, –HC@CH), 5.97
(d, 1H, J = 4.1, –HC@CH), 2.39 (s, 3H, ArCH3); 13C
NMR (75MHz; CDCl3): d 149.2 (ArC), 144.4 (ArC),
137.3 (ArCH), 132.3 (ArC), 129.3 (2 · ArCH), 128.0
(2 · ArCH), 127.8 (ArCH), 125.3 (ArC), 125.2 (ArCH),
124.3 (ArCH), 116.4 (OCH), 109.9 (NCH), 21.6 (ArCH3);
m/z (EI): 287.1 (M+, 13%), 132.1 (100), 91.1 (8), 77 (21), 65
(7), 51 (7).
10. Kleinpeter, E.; Ga¨bler, M.; Schroth, W. Monatsh. Chem.
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11. 5,10-Bis-[(4-methylphenyl)sulfonyl)-5,6,9,10-tetrahydro-
pyrido[2,3-b][1,4]diazocine 6b: mp: 176–178ꢁC; Found:
M+: 469.11281; C23H23N3O4S2 requires 469.11300; mmax
1
(thin film/cmÀ1): 1595, 1569, 1377, 1344, 1159; H NMR
(300MHz; CDCl3; Me4Si): 8.26 (dd, 1H, J = 4.5 and 1.5,
ArH), 8.01 (dd, 1H, J = 8.1 and 1.5, ArH), 7.84 (d, 2H,
J = 8.2, 2 · ArH), 7.74 (d, 2H, J = 8.2, 2 · ArH), 7.33-7.28
(m, 4H, 4 · ArH), 7.22 (dd, 1H, J = 8.1 and 4.5, ArH),
5.70–5.64 (m, 1H, –HC@CH), 5.57–5.53 (m, 1H,
–HC@CH), 4.53 (d, 2H, J = 7.3, CH2–CH), 3.99 (d, 2H,
J = 4.8, CH2–CH), 2.42 (s, 3H, ArCH3), 2.41 (s, 3H,
ArCH3); 13C NMR (75MHz; CDCl3): d 147.8 (ArC),
146.7 (C-2), 144.2 (ArC), 143.7 (ArC), 138.8 (ArCH),
136.1 (ArC), 134.9 (ArC), 132.8 (ArC), 129.9 (ArCH),
129.8 (2 · ArCH), 129.2 (2 · ArCH), 129.0 (2 · ArCH),
128.1 (2 · ArCH), 126.9 (C@C), 122.9 (C@C), 48.0 (CH2),
46.1 (CH2), 21.6 (ArCH3), 21.5 (ArCH3); m/z (EI): 469.1
(M+, 18%), 315.1 (20), 314.1 (78), 250.1 (100), 159 (98),
91.1 (57), 69.1 (34), 41.1 (20).
18. For a review on 1,4-benzoxazines see: Sainsbury, M.
(Part c)—1,4-oxazines, 1,4-benzoxazines and reduced
forms. In Second Supplement to the 2nd Edition of RoddÕs
Chemistry of Carbon Compounds; Sainsbury, M., Ed.;
Heterocyclic Compounds, Pts G and H; Elsevier:
Amsterdam, 1998; Vol. IV, pp 465–511.
19. For the first published work on the RCM of enamides see:
Kinderman, S. S.; van Maarseveen, J. H.; Schoemaker, H.
E.; Hiemstra, H.; Rutjes, F. P. J. T. Org. Lett. 2001, 3,
2045–2048.
20. Buon, C.; Chacun-Lefe`vre, L.; Rabot, R.; Bouyssou, P.;
Coudert, G. Tetrahedron 2000, 56, 605–614.
21. Ibrahim, Y. A.; Behbehani, H.; Ibrahim, M. R. Tetrahe-
dron Lett. 2002, 43, 4207–4210, Compound 15a has been
synthesized before by Ibrahim and co-workers but our
product appeared to be exclusively the Z-isomer in
contrast to the 2:1 E/Z ratio described in this reference.
12. For representative examples see: (a) Fellows, I. M.;
Kaelin, D. E.; Martin, S. F. J. Am. Chem. Soc. 2000,
122, 10781–10787, and earlier references cited therein; (b)

W. A. L. van Otterlo et al. / Tetrahedron Letters 45 (2004) 9171–9175
9175
22. For an informative review see: McReynolds, M. D.;
Dougherty, J. M.; Hanson, P. R. Chem. Rev. 2004, 104,
2239–2258.
(C@C)a, 122.5 (C@C), 56.0 (CH2), 50.3 (CH2), 21.7
(ArCH3); m/z (EI): 363 (M+, 9%), 256 (35), 243 (15), 220
(22), 185 (16), 129 (31), 83 (40), 69 (88), 41 (100).
23. See for example, (a) Lane, C.; Snieckus, V. Synlett 2000,
1294–1296; (b) Whitehead, A.; Moore, J. D.; Hanson, P.
R. Tetrahedron Lett. 2003, 44, 4275–4277.
24. Uchida, M.; Otsubo, K.; Matsubara, J.; Ohtani, T.;
Morita, S.; Yamasaki, K. Chem. Pharm. Bull. 1995, 43,
693–698.
25. 6-[(4-Methylphenyl)sulfonyl]-5,6-dihydro-2H-1,6-benzo-
thiazocine 1,1-dioxide 21: mp: >230ꢁC; Found: M+,
363.0626; C17H17NO4S2 requires 363.0599; mmax (thin
film/cmÀ1): 1521, 1313, 1142; 1H NMR (300MHz;
CDCl3; Me4Si, assignments with the same superscript
may be interchanged): 8.10–8.07 (m, 1H, ArH), 7.90 (d,
2H, J = 8.2, 2 · ArH), 7.60–7.57 (m, 2H, 2 · ArH), 7.40
(d, 2H, J = 8.2, 2 · ArH), 7.18–7.15 (m, 1H, ArH), 5.83–
5.74 (m, 1H, –HC@CH), 5.65–5.59 (m, 1H, –HC@CH),
4.72–4.48 (br m, 2H, CH2–CH), 3.88–3.60 (br m, 2H,
CH2–CH), 2.48 (s, 3H, ArCH3); 13C NMR (75MHz;
CDCl3): d 145.0 (ArC), 139.8 (ArC), 135.2 (ArC), 134.8
(ArC), 134.2 (ArCH), 131.7 (ArCH), 130.3 (ArCH), 130.1
(2 · ArCH), 128.8 (2 · ArCH), 128.3 (ArCH)a, 127.8
26. 5-[(4-Methylphenyl)sulfonyl]-2,5-dihydro-1,5-benzothiaze-
pine 1,1-dioxide 23: mp: 191–192ꢁC with decomposition;
Found: M+, 349.0446; C16H15NO4S2 requires 349.0442;
mmax (thin film/cmÀ1): 1663, 1598, 1328, 1170; 1H NMR
(300MHz; CDCl3; Me4Si): 8.01 (d, 1H, J = 7.8, ArH), 7.86
(d, 1H, J = 8.0, ArH), 7.75–7.70 (m, 1H, ArH), 7.64 (d,
2H, J = 8.2, 2 · ArH), 7.56–7.51 (m, 1H, ArH), 7.26 (d,
2H, J = 8.2, 2 · ArH), 6.95 (d, 1H, J = 9.8, N–H C@CH),
5.03–4.97 (m, 1H, –HC@CHCH2), 3.70 (dd, 2H, J = 4.7
and 1.4, –HC@CHCH2), 2.41 (s, 3H, ArCH3); 13C NMR
(75MHz; CDCl3): d 144.7 (ArC), 136.5 (ArC), 135.5
(ArC), 134.8 (ArC), 134.4 (ArCH), 131.3 (ArCH), 129.3
(2 · ArCH), 128.5 (4 · ArCH), 127.8 (NCH), 104.1
(HC=CHCH2), 53.6 (CH2), 21.7 (ArCH3); m/z (EI): 349
(M+, 6%), 285 (38), 221 (23), 194 (18), 155 (5), 130 (100),
91 (30), 65 (11), 39 (8).
27. For reviews on 1,5-benzothiazepines see: (a) Levai, A. J.
Heterocycl. Chem. 2000, 37, 199–214; (b) Chimirri, A.;
Gitto, R.; Grasso, S.; Monforte, A. M.; Zappala, M. Adv.
Heterocycl. Chem. 1995, 63, 62–101.