First synthesis of 3-mercapto-2(1H)-pyridinone, a simple disubstituted pyridine useful for synthesis of the 4-azaphenoxathiine ring system and its novel diazaphenoxathiine analogs: 1,6-Diazaphenoxathiine and 2,6-diazaphenoxathiine

Article abstract of DOI:10.1021/jo951254j

3-Mercapto-2(1H)-pyridinone (1) can be synthesized in three simple high-yielding steps from readily available 2-tert-butylthiazolo[4,5-b]pyridine (2). Its disodium salt condenses with o-chloronitrobenzene, 2-chloro-3-nitropyridine, and 3-chloro-4-nitropyridine 1-oxide to give respectively 4-azaphenoxathiine (10), 1,6-diazaphenoxathiine (12), and 2,6-diazaphenoxathiine 2-oxide (14) which reduces to 2,6-diazaphenoxathiine (15). The structures of these previously unreported azaphenoxathiine systems were confirmed by assignment of their respective ¹³C NMR spectra.

Full text of DOI:10.1021/jo951254j

6
62
J . Org. Chem. 1996, 61, 662-665
F ir st Syn th esis of 3-Mer ca p to-2(1H)-p yr id in on e, a Sim p le
Disu bstitu ted P yr id in e Usefu l for Syn th esis of th e
4
-Aza p h en oxa th iin e Rin g System a n d Its Novel
Dia za p h en oxa th iin e An a logs: 1,6-Dia za p h en oxa th iin e a n d
,6-Dia za p h en oxa th iin e1
2
Keith Smith,* Dorian Anderson, and Ian Matthews
†
Department of Chemistry, University of Wales Swansea, Swansea SA2 8PP, U.K.
Received J uly 13, 1995X
3
-Mercapto-2(1H)-pyridinone (1) can be synthesized in three simple high-yielding steps from readily
available 2-tert-butylthiazolo[4,5-b]pyridine (2). Its disodium salt condenses with o-chloronitroben-
zene, 2-chloro-3-nitropyridine, and 3-chloro-4-nitropyridine 1-oxide to give respectively 4-azaphe-
noxathiine (10), 1,6-diazaphenoxathiine (12), and 2,6-diazaphenoxathiine 2-oxide (14) which reduces
to 2,6-diazaphenoxathiine (15). The structures of these previously unreported azaphenoxathiine
systems were confirmed by assignment of their respective 13C NMR spectra.
In tr od u ction
Since the initial synthesis of 1-azaphenoxathiine2,3 was
reported in 1977, there has been considerable interest
in the synthesis of substituted 1-azaphenoxathiines and
isosterically related systems. Some unsubstituted 1-aza-
phenoxathiines have shown central nervous system
depressant activity,3 and the influence of azasubstitu-
tion in the benzenoid rings on the shape and biological
activity of these systems has encouraged the synthesis
We have recently reported the synthesis and applica-
tions of 2-tert-butylthiazolo[4,5-b]pyridine (2).1 In this
paper we describe the conversion of 2 into 1 and the use
of this novel pyridinone in the syntheses of 10, 12, and
2
,4
1
5, thereby rendering these systems readily available for
5
-8
of several other monoazaphenoxathiines
and diaza-
the first time.
phenoxathiines.9 It transpires that azaphenoxathiines
1
0
are essentially planar, in contrast to the phenoxathiine
parent ring system.11
Resu lts a n d Discu ssion
Despite the synthesis of several additional members
of this interesting group of ring systems in recent years,
until now there are no reports of the parent 4-azaphe-
noxathiine (10), 1,6-diazaphenoxathiine (12), or 2,6-
diazaphenoxathiine (15) ring systems. One substituted
Syn t h esis of 3-Mer ca p t o-2(1H)-p yr id in on e (1).
2-tert-Butylthiazolo[4,5-b]pyridine (2) has been obtained
from 2-aminopyridine (3) in three high-yielding steps
1
2
according to Scheme 1.
The thiazole 2 was readily hydrolyzed in alkaline
6
12,13
derivative of 4-azaphenoxathiine has been obtained via
conditions
to give bis(2-amino-3-pyridyl) disulfide (6)
a complex route which is not general. However, a more
general approach would require the availability of 3-mer-
capto-2(1H)-pyridinone (1), a key intermediate which has
never been prepared before.
in 95% yield. This was formed by autoxidation of the
free thiol during the process.
Diazotization14 of 6 gave bis(2-oxo-3(1H)-pyridyl) di-
sulfide (7) which, upon reduction of the disulfide bond
with hydrazine,15 yielded 3-mercapto-2(1H)-pyridinone
†
Formerly known as the University College of Swansea.
Abstract published in Advance ACS Abstracts, November 15, 1995.
(
1) (Scheme 2), the predominant tautomer of such sys-
X
1
6,17
tems.
(1) Part 40 in the series Novel Heterocyclic Systems. For part 39,
see: Smith, K.; El-Hiti, G. A.; Abdel-Megeed, M. F.; Abdo, M. A. J .
Org. Chem. 1995, 60, 656.
The disulfide 6 was not reduced to the corresponding
free thiol, though this should be a simple procedure under
(2) A tetrahydro derivative of 3-azaphenoxathiine was reported
reducing conditions,1
5,18
because it was felt that the
several years prior to the first synthesis of a fully aromatic azaphe-
noxathiine analog by Martin, A. R.; Caputo, J . F. J . Org. Chem. 1974,
disulfide would stand up better to the conditions of
diazotization. Interestingly the only occasion that 2-ami-
nopyridine-3-thiol has been reported is in a patent as an
intermediate for production of an array of pharmacologi-
3
9, 1811.
3) Martin, G. E.; Turley, J . C.; Williams, L.; Steenberg, M. L.;
Buckley, J . P. J . Heterocycl. Chem. 1977, 14, 1067.
4) Elliott, A. J .; Eisenstein, N.; Iorio, L. C. J . Med. Chem. 1980,
3, 333.
(
(
2
19
cally active compounds.
(5) Martin, G. E.; Turley, J . C.; Williams, L. J . Heterocycl. Chem.
1
(12) Smith, K.; Anderson, D.; Matthews, I. Sulfur Lett. 1995, 18,
79.
(13) Ueda, K. Pharm. Bull. Tokyo 1956, 4, 396. Smith, K.; Lindsay,
C. M.; Morris, I. K.; Matthews, I.; Pritchard, G. J . Sulfur Lett. 1994,
17, 197.
(14) Vogel’s Textbook of Practical Organic Chemistry, 4th ed.;
Longman: New York, 1978; p 687.
J . A. J . Heterocycl. Chem. 1982, 19, 879. (b) Martin, G. E.; Turley, J .
C. Ibid. 1978, 15, 609. (c) Caldwell, S. R.; Martin, G. E. Ibid. 1980, 17,
9
89.
7) Caldwell, S. R.; Martin, G. E.; Simonsen, S. H.; Inners, R. R.;
Willcott, M. R., III J . Heterocycl. Chem. 1981, 18, 479.
(
9) (a) Caldwell, S. R.; Turley, J . C.; Martin, G. E. J . Heterocycl.
(15) Katz, L.; Karger, L. S.; Schroeder, W.; Cohen, M. S. J . Org.
Chem. 1953, 18, 1380.
(16) Takeuchi, Y.; Dennis, N. Org. Magn. Reson. 1975, 7, 244.
(17) Katritzky, A. R.; Lagonsky, J . M. Adv. Heterocycl. Chem. 1963,
1, 339.
(18) Wardell, J . L. In The Chemistry of the Thiol Group, Part 1;
Patai, S., Ed.; Wiley: New York, 1974; pp 163-269 (notably p 221).
Chem. 1980, 17, 1153. (b) Davies, J . S.; Smith, K.; Turner, J . R.; Gymer,
G. Tetrahedron Lett. 1979, 5035. (c) Lindsay, C. M.; Smith, K.; Martin,
G. E. J . Heterocycl. Chem. 1987, 24, 211.
(
10) Martin, G. E.; Turley, J . C.; Korp, J . D.; Bernal, I. J . Heterocycl.
Chem. 1978, 15, 721.
11) Hosoya, S. Acta Crystallogr. 1966, 20, 429.
(
0
022-3263/96/1961-0662$12.00/0 © 1996 American Chemical Society

First Synthesis of 3-Mercapto-2(1H)-pyridinone
J . Org. Chem., Vol. 61, No. 2, 1996 663
Sch em e 1
Sch em e 4
Sch em e 2
Sch em e 3
ring systems having a nitrogen at position 4/6. Only one
special example of such a ring system has ever been made
before.6 The present method should be readily adaptable
for the synthesis of substituted examples.
a
1
3
C NMR Sp ectr a of th e Aza p h en oxa th iin es 10, 12,
4, a n d 15. The characterization of the molecular
1
structures of the tricyclic systems synthesized here
presents a challenge. The mass spectra of the compounds
are very simple, being dominated by the molecular ion
or its protonated form, and the absence of functional
Syn th esis of Aza p h en oxa th iin es 10, 12, 14, An d
5. For the syntheses of azaphenoxathiines, the diso-
dium salt of 1 was condensed with the appropriate
aromatic substrate. Thus the dianion 8 was generated
using sodium methoxide in methanol and reacted with
1
1
groups limits the utility of IR spectra. H NMR spectra
can be useful for analysis of the aromatic protons but are
1
(
-chloro-2-nitrobenzene to give 4-azaphenoxathiine (10)
1
3
Scheme 3). This method of dianion generation20 proved
not always well defined.
C NMR spectroscopy has
therefore become the most useful analytical technique
in confirming the structures of mono- and diazaphenox-
athiines.
to be superior to the alternative method involving
overnight metalation of the mercaptopyridinone using
sodium hydride in dimethylformamide, which has been
Martin and co-workers have fully assigned the 13C
used in the synthesis of diazaphenoxaselenines21 and also
5
in the synthesis of some 1-azaphenoxathiine analogues.4
NMR spectra of 1-azaphenoxathiine, 2-azaphenoxa-
thiine,6 and 3-azaphenoxathiine.7 They have also char-
c
Compound 10 was obtained in 41% yield after bulb-to-
bulb distillation.
The syntheses of 1,6-diazaphenoxathiine (12) and 2,6-
diazaphenoxathiine (15) by similar procedures are il-
lustrated in Scheme 4.
Compound 12 could be synthesized by the direct
reaction of dianion 8 with 2-chloro-3-nitropyridine (11),
because the more nucleophilic thiolate center displaces
the more easily replaced 2-chloro substituent of 11 in the
initial step, leaving an intermediate requiring only ring
closure for formation of the product.
6
a
acterized 6,7,9-trimethyl-4-azaphenoxathiine. The ab-
sence of 13C data on the parent 4-azaphenoxathiine
isomer is a significant gap in the literature, however, and
limits the confidence with which the NMR spectra of
related phenoxathiines can be assigned. It was therefore
important to attempt the assignment of the 1 C NMR
spectra of 4-azaphenoxathiine (10), 1,6-diazaphenoxathi-
ine (12), 2,6-diazaphenoxathiine (15), and 2,6-diazaphe-
noxathiine 2-oxide (14) (see Table 1).
3
4
-Aza p h en oxa th iin e (10). The assignment of the 13C
NMR spectrum of 4-azaphenoxathiine (10) was based
upon a comparison of calculated and observed 13C chemi-
cal shifts and coupling constant behavior. Chemical
The synthesis of compound 14 could not be achieved
by direct reaction of 8 with 3,4-dichloropyridine or
-chloro-3-nitropyridine because the 4-chloro substituent
4
1
3
shifts were calculated by incrementation of the C NMR
chemical shifts of phenoxathiine22 using additives for
annular nitrogen insertion drawn from the differences
in these compounds is displaced by the more nucleophilic
thiolate group of 8 to give 1,8-diazaphenoxathiine. There-
fore, 8 was initially reacted with 3-chloro-4-nitropyridine
N-oxide (13), in which the 3-chloro substituent is the
more easily displaced.
Compound 14 was readily reduced with phosphorus
trichloride to give 15. Thus, the availability of 3-mer-
capto-2(1H)-pyridinone (1) by a simple procedure renders
possible the synthesis of a variety of azaphenoxathiine
5
between phenoxathiine and 1-azaphenoxathiine assum-
ing that the effect of aza substitution on proximal carbon
atoms is the same whether the substitution is at the 1-
or 4-position.
For 10 it can be seen that the largest discrepancy
between the calculated and observed chemical shifts is
for C-4a, the carbon atom bridging the oxygen and
nitrogen heteroatoms. The other values match very well,
though it could possibly be argued that C-2 and C-6, and
C-7 and C-8, are permutable pairs.
(
19) Klausener, A.; Fengler, G. Ger. Offen. DE 3,545,124; Chem.
Abstr. 1987, 107, 134219q.
20) (a) Womack, C. H.; Martin, G. E. J . Heterocycl. Chem. 1981,
8, 1165. (b) Womack, C. H.; Turley, J . C.; Martin, G. E.; Kimura, M.;
Simonsen, S. H. J . Heterocycl. Chem. 1981, 18, 1173.
21) Smith, K.; Matthews, I.; Martin, G. E. J . Chem. Soc., Perkin
Trans. 1 1987, 2839.
(
1
(
(22) Isenbrandt, L. R.; J ensen, R. K.; Petrakis, L. J . Magn. Reson.
1973, 12, 143.

6
64 J . Org. Chem., Vol. 61, No. 2, 1996
Smith et al.
1
3
Ta ble 1.
C NMR Ca lcu la ted vs Obser ved Ch em ica l
heterocyclic synthesis has been demonstrated by the
production of three novel azaphenoxathiine ring systems.
a
Sh ift Da ta of 10, 12, 14, a n d 15
1
0
12 14
15
carbon
Exp er im en ta l Section
atom calcd obsd calcd obsd calcd obsd calcd obsd
Melting points are uncorrected. 1H NMR and 13C NMR
spectra were at 250 MHz for 1H and 62.9 MHz for C. IR
spectra were recorded as KBr discs. Low-resolution mass
spectra were measured at 70 eV (EI) and CI by NH . Where
3
indicated mass spectra were recorded by alternate chemical
ionization/electron impact (ACE).
1
2
3
4
6
7
8
9
4
5
9
134.6 135.7
119.9 121.0* 145.6 145.5*
147.0 145.7 122.0 122.8 135.5 135.6 146.3 146.8
125.7 124.7 115.1 115.0 113.3 113.1
117.8 118.5*
125.9 126.3 146.1 145.9* 146.0 146.3 146.0 146.0
124.6 125.1 120.4 121.3 121.9 122.4 121.9 121.9
127.3 128.1 136.0 136.2 136.3 137.2 136.1 136.3
175.5 157.5 147.5 147.8 147.0 147.4 157.6 157.7
138.5 138.5 149.4 149.8
13
†
b
†
b
Materials were generally obtained from Aldrich or BDH and
b
were purified by standard literature procedures.1
4,25
3-Chloro-
c
c
c
c
a
a
a
4
-nitropyridine 1-oxide was prepared by the method of Talik
b
151.0 151.5 155.6 155.7 155.7 155.0 155.4 155.7
118.0 118.2 114.9 115.7 114.4 112.3 113.2 114.4*
115.9 115.8 141.8 142.0 117.7 118.4 115.5 115.7*
2
6
b
and Talik. Column chromatography was carried out using
BDH Kieselgel 60 (230-400 mesh).
1
0a
Bis(2-a m in o-3-p yr id yl) Disu lfid e (6). A mixture of 2-tert-
a
12
Recorded in CDCl3, except for 14 which was recorded in
butylthiazolo[4,5-b]pyridine (2) (2.63 g, 13.7 mmol) and 10%
DMSO-d6; possibly permutable sets of assignments within any
given spectrum are indicated with * or †. Observed chemical
shifts of the C-5a to C-9a ring of 15 because N-oxide incremen-
tation values can only be applied to the N-oxide-bearing ring. c The
numbering system avoids the confusion sometimes resulting from
the inconsistent use of designations for these carbon atoms.
aqueous NaOH (44 mL, 0.11 mol) was heated under reflux for
b
6
h. After this time the starting material was still visible as
an oil on the surface and so further NaOH pellets (4.44 g, 0.11
mol) were added and the reflux was continued for another 6
h. The cooled solution was washed with CH Cl (50 mL) and
2 2
then neutralized with concd HCl. Continuous extraction of
the aqueous solution with EtOAc yielded the product (0.93 g,
54%) after 2 days. Further product was collected after filtering
the aqueous suspension to remove the insoluble white solid,
evaporation of the filtrate to dryness, and extraction with
boiling EtOAc. Removal of the solvent after several extrac-
1
,6-Dia za p h en oxa th iin e (12) a n d 2,6-Dia za p h e-
1
3
n oxth iin e (15). The assignment of the C NMR spec-
trum of 10 complements the existing literature data on
the other monoazaphenoxathiines and makes it possible
to draw up a more accurate set of incremental23 values
tions gave further disulfide (0.70 g), bringing the total yield
1
of 6 to 95%: mp 158 °C; H NMR (DMSO-d
6
) δ 6.35 (br s, 4H),
for 4-aza substitution on the basis of the observed values
for 10 and phenoxathiine.22 These values were used in
conjunction with those obtained for the effect of 1-aza
substitution and of 2-aza substitution to predict the
NMR chemical shifts of 12 and 15 (Table 1).
6
7
1
.47 (dd, J ) 4.8, 7.5 Hz, 2H), 7.27 (dd, J ) 1.8, 7.5 Hz, 2H),
13
.99 (dd, J ) 1.8, 4.8 Hz, 2H); C NMR (DMSO-d
6
) δ 111.5,
12.6, 143.1, 149.9, 159.4; IR 3470, 3300, 3160, 1630, 1580,
5
6
13
-1
+
C
1560 cm ; MS m/z (relative intensity) 250 (M , 23), 125 (100),
98 (42); HRMS calcd for C10 250.0347, found 250.0336.
Anal. Calcd for C10 (250.03): C, 47.98; H, 4.03; N,
2.38. Found: C, 47.69; H, 3.96; N, 22.09.
Bis(2-oxo-3(1H)-p yr id yl) Disu lfid e (7). A solution of 6
10 4 2
N N S
10 4 2
H N S
The agreement between the calculated and observed
chemical shifts for 12 is very good, the largest discrep-
ancy being only 1 ppm for the C-4 resonance. The shifts
for the C-2 and C-7 carbon atoms are very close and are
possibly permutable. The agreement between the cal-
culated and observed values would be significantly poorer
if the possible alternative assignments for 10 had been
used for the calculation, which tends to confirm the given
assignments. The agreement between the calculated and
observed chemical shifts for compound 15 is generally
very good, within a margin of 0.5 ppm. The only
exception is the discrepancy of 1.2 ppm for C-9a. The
assignments of C-9a and C-10a may be permuted.
However, the calculated values would again be poorer if
the alternative assignments were used for 10.
2
(
(
(
1.28 g, 5.1 mmol) in distilled H
2.8 mL) was carefully treated at 0 °C with aqueous NaNO
1.8 g in 3 mL). After stirring at 0 °C for 1 h, room
2
O (15 mL) and 98% H
2
SO
4
2
temperature for 1 h, and then 70 °C for 2 h to decompose the
diazonium compound, the resulting suspension was cooled and
1
filtered to give 7 (0.92 g, 71%): mp 225 °C; H NMR (DMSO-
d
6
6
) δ 6.26 (apparent t, J ) 6.8 Hz, 2H), 7.33 (dd, J ) ca. 1.7,
13
.4 Hz, 2H), 7.44 (dd, J ) 1.7, 7.1 Hz, 2H), 12.03 (br, 2H);
C
NMR (DMSO-d ) δ 105.7, 126.1, 132.8, 134.9, 160.0; IR 3440,
3
2
6
-1
100, 3000, 1640, 1610, 1530 cm ; MS m/z (relative intensity)
+
52 (M , 21), 127 (100), 99 (42); HRMS calcd for C10
8 2 2 2
H N O S
252.0027, found 252.0025.
3-Mer ca p to-2(1H)-p yr id in on e (1). A mixture of the di-
sulfide 7 (0.435 g, 1.7 mmol) and NH NH (1 mL) in EtOH (3
2
2
,6-Diazaph en oxath iin e 2-Oxide (14). The 13C NMR
mL) was refluxed for 1 h under Ar. The cooled mixture was
filtered to collect the product which was washed with EtOH
2
spectrum of 14 was predicted by incrementation of the
assigned spectrum of 15 with additives due to the effect
of the N-oxide function at the 2-position.24 The observed
and calculated resonances are shown in Table 1, and
although only one aromatic ring could be calculated for
the effect of N-oxidation, the figures can be seen to be in
very good agreement. The largest discrepancy (1.9 ppm)
is for C-9a, the carbon within the ring for which no
incrementation has been made and that is closest to the
N-oxide function.
1
and dried to give 1 (0.37 g, 84%): mp 175-176 °C; H NMR
[
All peaks were very broad and could not really be assigned
13
properly due to solubility problems. The C NMR spectrum
could not be measured.] (DMSO-d ) δ 6.27 (br, 3H), 6.87 (br,
6
1H), 7.35 (br, 1H); IR 2260-3400 (br, SH, NH), 1640, 1610,
-
1
+
1520 cm ; MS m/z (relative intensity) 127 (M , 100), 99 (18);
HRMS calcd for C
5 5
H NOS 127.0092, found 127.0089.
4
-Aza p h en oxa th iin e (10). A mixture of 1 (0.370 g, 2.9
mmol) and NaOMe (0.370 g, 6.85 mmol) in dry MeOH (30 mL)
was heated under reflux for 48 h. The solvent was removed
by rotary evaporation, and the resulting pale brown solid (mp
>
300 °C) was dissolved in dry DMF (35 mL) to which was
added the 1-chloro-2-nitrobenzene (9) (0.460 g, 2.9 mmol). The
Su m m a r y
mixture darkened and was heated under reflux for 6 h under
3
-Mercapto-2(1H)-pyridinone (1) has been prepared for
Ar. On cooling, distilled H
solution was extracted with CHCl
MgSO ). The extracts were evaporated under high vacuum
2
O (10 mL) was added, and the
the first time, and its importance as a precursor in
3
(4 × 80 mL) and dried
(
4
(
23) Kalinowski, H. O.; Berger, S.; Braun, S. Carbon-13 NMR
Spectroscopy; Wiley: New York, 1988; p 396.
24) Sojka, S. A.; Dinan, F. J .; Kolarczyk, R. J . Org. Chem. 1979,
4, 307.
(25) Perrin, D. D.; Armarego, W. L. F. Purification of Laboratory
Chemicals; Pergamon Press: Oxford, 1988.
(26) Talik, T.; Talik, Z. Rocz. Chem. 1962, 36, 539.
(
4

First Synthesis of 3-Mercapto-2(1H)-pyridinone
J . Org. Chem., Vol. 61, No. 2, 1996 665
218.0150, found 218.0163. Anal. Calcd for C10
to ensure complete removal of DMF. Purification by bulb-to-
6 2 2
H N O S
bulb distillation at 125 °C/0.2 mmHg gave 10 (0.239, 41%):
(218.02): C, 55.03; H, 2.77; N, 12.84. Found: C, 55.13; H, 2.89;
N, 12.74.
1
H NMR (CDCl ) δ 6.97 (dd, J ) 4.9, 7.6 Hz, 1H), 7.00-7.18
3
(
m, 4H), 7.39 (dd, J ) 1.8, 7.6 Hz, 1H), 8.02 (dd, J ) 1.8, 4.9
2
,6-Dia za p h en oxa th iin e (15). A solution of 14 (0.280 g,
.3 mmol) and PCl (0.2 mL, excess) in CHCl (20 mL) was
heated under reflux for 2 h. The mixture was cooled, distilled
O (40 mL) was cautiously added, and the mixture was
13
-1
Hz, 1H); C NMR (see Table 1); IR 3070, 1590 cm ; MS ACE
1
3
3
+
EI m/z (relative intensity) 201 (M , 100), 172 (73), 169 (68),
57 (81); CI m/z (relative intensity) 202 ((M+H) , 100), 169
+
1
H
2
(
11), 157 (9), 146 (5), 129 (3), 102 (7), 82 (3), 69 (8), 63 (10);
HRMS calcd for C11 NOS 201.0248, found 201.0284.
,6-Dia za p h en oxa th iin e (12). The procedure described
above for the synthesis of 10 was used, except that 2-chloro-
neutralized with a cold NaOH solution. The organic layer was
removed, and the aqueous solution was further extracted with
H
7
1
CHCl
MgSO
3
(3 × 80 mL). The combined extracts were dried
(
4
) and concentrated to yield 15 (0.20 g, 77%) which was
3
-nitropyridine (11) (0.460 g, 2.9 mmol) was used instead of
sublimed at 105 °C/0.1 mmHg to an off-white solid which
9
. The crude product was purified by column chromatography
1
softens and then melts at 92.5-93.5 °C: H NMR (CDCl ) δ
3
(SiO
2
, 25% Et
2 2
O in hexane). After recrystallization from Et O,
6
.95 (d, J ) 5 Hz, 1H), 7.04 (dd, J ) ca. 4.8, 7.5 Hz, 1H), 7.43
1
1
2 (0.258g, 44%) was obtained as off-white needles: mp 112-
(
(
d, J ) 7.5 Hz, 1H), 8.04 (d, J ) 5 Hz, 1H), 8.23 (s, 1H), 8.32
1
14 °C; H NMR (CDCl
3
) δ 7.02 (dd, J ) 4.9, 7.6 Hz, 1H), 7.08
13
d, J ) 4.8 Hz, 1H); C NMR (see Table 1); IR 3060, 1590,
(
7
1
dd, J ) ca. 4.7, 8.2 Hz, 1H), 7.28 (dd, J ) 1.5, 8.2 Hz, 1H),
-1
1
580, 1560, 1555, 1485 cm ; MS ACE EI m/z (relative
.45 (dd, J ) 1.8, 7.6 Hz, 1H), 8.04 (dd, J ) ca. 1.8, 4.9 Hz,
+
intensity) 202 (M , 100), 175 (36); CI m/z (relative intensity)
03 ((M + H ), 100), 175 (5); HRMS calcd for C10
02.0201, found 202.0226. Anal. Calcd for
1
3
H), 8.15 (dd, J ) ca. 1.5, 4.7 Hz, 1H); C NMR (see Table 1);
+
2
2
H
H
6
N
N
2
OS
OS
-
1
IR 3060, 1580, 1570 cm ; MS ACE EI m/z (relative intensity)
C
10
6
2
+
2
2
02 (M , 100), 174 (12), 158 (38); CI m/z (relative intensity)
(202.02): C, 59.39; H, 2.99; N, 13.86. Found: C, 59.42; H, 3.06;
+
03 ((M + H) , 100); HRMS (CI) calcd for C10
H
H N
6 2
6
N
2
OS 202.0201,
OS (202.02): C,
9.39; H, 2.99; N, 13.86. Found: C, 59.55; H, 3.07; N, 13.70.
,6-Dia za p h en oxa th iin e 2-Oxid e (14). The procedure
described above for the synthesis of 10 was used, except that
-chloro-4-nitropyridine 1-oxide (13) (0.506 g, 2.9 mmol) was
N, 13.66.
found 202.0201. Anal. Calcd for C10
5
Ack n ow led gm en t. We thank the Science and En-
gineering Research Council (now EPSRC) for a student-
ship to D. Anderson.
2
3
used instead of 9. The product (0.328 g, 52%) was isolated by
continuous extraction of the neutralized aqueous reaction
mixture with EtOAc. Recrystallization from EtOAc gave buff-
Su p p or tin g In for m a tion Ava ila ble: Full experimental
details including compound characterization data, complete
with NMR peak assignments (5 pages). This material is
contained in libraries on microfiche, immediately follows this
article in the microfilm version of the journal, and can be
ordered from the ACS; see any current masthead page for
ordering information.
1
colored needles: mp 223 °C; H NMR (DMSO-d
)
6
) δ 7.18 (d, J
7.1 Hz, 1H), 7.21 (dd, J ) 4.8, 7.6 Hz, 1H), 7.82 (dd, J )
1
1
1
2
2
.8, 7.6 Hz, 1H) 8.01 (dd, J ) 2.1, 7.1 Hz, 1H), 8.08 (dd, J )
1
3
.8, 4.8 Hz, 1H), 8.34 (d, J ) 2.1 Hz, 1H); C NMR (see Table
-
1
); IR 1585, 1475 cm ; MS ACE EI m/z (relative intensity)
+
18 (M , 100), 202 (89), 175 (31); CI m/z (relative intensity)
19 ((M + H ), 100), 203 (80); HRMS calcd for C10
+
H
6
N
2
O
2
S
J O951254J