Carbon-sulfur and carbon-selenium double bond formation through thiolysis and selenolysis of 4-methylsulfanyl-substituted pyridinium and quinolinium halides

Article abstract of DOI:10.1055/s-1998-2002

4-Methylsulfurylpyridinium and -quinolinium salts 3 and 4 with alkyl groups such as methyl, allyl, benzyl, ethoxycarbonylmethyl, benzoylmethyl on the nitrogen atom were prepared by the Menschutkin-type reaction and some of them caused to react under either the thiolysis or selenolysis reaction conditions. N-Substituted pyridine-4-thiones 5a-c and quinoline-4-thiones 6a-e were formed at different rates in high isolated yield. On the other hand, two N-alkyl-4-selenopyridone 7a,b together with three 4-selenoquinolones 8a,b,c were also produced in high chemical purity and characterized spectroscopically. In addition, 4-sulfanylpyridone 12 and 4-selenopyridone 13 with a N-tert-butyl group were obtained via Zincke' s salt 9. The overall process provides a useful alternative to the otherwise difficult direct N-alkylation of thioxo- and selenoxopyridine systems.

Full text of DOI:10.1055/s-1998-2002

January 1998
SYNTHESIS
99
Carbon–Sulfur and Carbon–Selenium Double Bond Formation Through Thiolysis and
Selenolysis of 4-Methylsulfanyl-Substituted Pyridinium and Quinolinium Halides
Jocelyne Levillain,a Daniel Paquer,b Aboubacary Sene,c Michel Vazeux*a
a Laboratoire de Chimie Moléculaire et Thioorgarnique, UMR 6507 ISMRA, Université de Caen, 6 Bd Maréchal Juin, F-14050 Caen Cedex, France
b Laboratoire de Chimie Organique, Université de Metz, Ile du Saulcy, F-57045 Metz Cedex, France
c Faculté des Sciences et techniques, Université Cheikh Anta DIOP, Dakar, Sénégal
Received 24 July 1997; revised 9 September 1997
4-Methylsulfanylpyridinium and -quinolinium salts 3 and 4 with al-
kyl groups such as methyl, allyl, benzyl, ethoxycarbonylmethyl, ben-
zoylmethyl on the nitrogen atom were prepared by the Menschutkin-
type reaction and some of them caused to react under either the thio-
lysis or selenolysis reaction conditions. N-Substituted pyridine-4-
thiones 5a–c and quinoline-4-thiones 6a–e were formed at different
rates in high isolated yield. On the other hand, two N-alkyl-4-seleno-
pyridones 7a,b together with three 4-selenoquinolones 8a,b,c were
also produced in high chemical purity and characterized spectrosco-
pically. In addition, 4-sulfanylpyridone 12 and 4-selenopyridone 13
Nitrogen–carbon bond forming reactions15 from 4-sulfa-
with a N-tert-butyl group were obtained via Zincke’s salt 9. The over-
all process provides a useful alternative to the otherwise difficult di-
nylpyridine and ring transformations16 apart, synthetic
rect N-alkylation of thioxo- and selenoxopyridine systems.
ways to N-substituted-4-pyridinethiones, including their
benzo-analogues, can be classified into two major routes.
The first path is best illustrated by the selective N-alkyla-
tion of ambident anions of 4(1H)-pyridone itself17 fol-
lowed by the thionation of the resulting N-alkyl-4-
pyridones with phosphorus(V) based reagents.18 This
classical approach, however, may suffer from the requi-
site high selectivity of the first step and the rather drastic
reaction conditions of the second which may preclude the
introduction of sensitive functional groups on the nitrogen
side chain. The second pathway may be viewed as being
able to somewhat overcome these disadvantages. The
thiolysis with sodium hydrogen sulfide or thiourea of
preformed pyridinium salts19 having nucleofugal substit-
uents, usually halogeno and to a lesser extent oxygen, sul-
fur- and nitrogen-containing groups at the 4-position,
provides an alternative method to the thiation procedure
and may be the preferred route. With regard to the synthe-
sis of selenoamides, this seems particularly true for the se-
lenolysis method if compared to the selenation
approach.20 Mechanistically, these two types of reactions
are nucleophilic substitution and occur via a two-stage
process involving addition and elimination through the in-
termediary of a so-called s-adduct.21 The ease with which
4-methylsulfanylpyridinium cations can be prepared, to-
gether with their long shelf life and their inherent high re-
activity towards heteronucleophiles, made us feel
confident that the second procedure could satisfy our goal.
It is believed that a methylsulfanyl substituent possessing
electron-donating properties and having a high leaving
group ability would facilitate both the Menschutkin and
the chalcogenolysis reactions.
The 4-pyrone and its sulfur- and nitrogen-containing
ring systems are important constituents of many mole-
cules with biological significance.1 Thiocarbonyl and se-
lenocarbonyl derivatives, as members of this interesting
family, are also of particular importance. Spectroscopic2
and electrochemical3 studies have been reported for a
number of these species, as well as for their mono and
dibenzo counterparts. They have also been shown to act
as efficient traps4 for a variety of free radicals. The great
interest of such closely related molecules lies in the va-
riety of reactions available to them and can be under-
stood in terms of a more or less efficient electron
delocalization between the C=O/S/Se p-bond and the
nonbonding electron pair(s) on the heterocyclic hetero-
atom. Compounds of the pyridone class are obviously
the more challenging and promising targets because of
the additional functionality on the nitrogen atom. They
exhibit a marked amphoteric character, as suggested by
a significant contribution of the dipolar formula II to the
resonance hybride. Besides reactions involving Diels–
Alder cycloadditions5 and conjugate additions,6 they
also undergo tandem elec-trophilic–nucleophilic addi-
tions, the combination of these two types of reactions has
been used in a number of syntheses of nitrogen-contain-
ing heptafulvenes7 and dihydropyridone derivatives.8
Members of the 2- and 4-series have recently found
many applications in the field of cyanin dyes,9 b-lactam-
ic antibiotics10 and sugar nucleosides,11 with much em-
phasis being placed on the thiocarbonyl chromophore.
Specific important uses of the 2-pyridinethiones are as
synthetic intermediates12 and in heterocyclic synthesis.13
In connection with our studies on the alkylidenation of
suitably 4-sulfanyl-functionalized pyridinium and quin-
olinium cations via the sulfur contraction process,14 and
in view of the possibilities of employing thiocarbonyl
and selenocarbonyl pyridine systems as potential radical
scavengers and as chemical intermediates, we have un-
dertaken a study of their preparation.
The overall process developed for the synthesis of some
sulfanyl- and selenocarbonyl derivatives in the 4-pyridine
and quinoline series is outlined in Scheme 1 and uses 4-
methylsulfanylpyridinium and -quinolinium halides as
key synthetic intermediates. These simple saIts are almost
quantitatively prepared by a three-step sequence of reac-
tions commencing from the corresponding and readily

100
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SYNTHESIS
available (1H)-4-thioxopyridine and -quinoline 1 and 2 On the other hand, some 4-methylsulfanylpyridinium and
themselves. The transformation includes in succession S- -quinolinium salts were found to undergo nucleophilic
methylation with methyl iodide in ethanolic solution, de- displacement with the sodium hydrogen selenide reagent,
hydroiodination of the resulting N-protonated azinium io- produced in situ from a degassed ethanolic solution of
dides under aqueous basic conditions22 and quaternization NaBH4 with powdered Se according to the procedure de-
of the 4-methylsulfanylpyridine and -quinoline base inter- veloped by Klayman and Griffin.26 Related reactions
mediates with reactive halides in acetonitrile. The pale leading to simple N-alkyl g-selenolutidones and sele-
yellow coloured pyridinium and quinolinium salts 3a–c noacridones from the corresponding chloro azinium cat-
and 4a–e precipitated from the solution and were collect- ions as well as the selenolysis of 4-methoxy and 4-
ed and purified (Table 1). In most cases, however, the re- methylsulfanyl (thia)pyrilium salts were earlier report-
action mixture was concentrated to dryness and the solid ed.27 As far as we are aware, however, little is known about
residue, first free from soluble materials in diethyl ether, the isolation of N-substituted selenopyridones and -quino-
was in sufficient purity for further reaction. This very sim- lones28 and there are virtually no reports of NMR analysis
ple procedure allows the use of an excess of halide to drive on these types of compounds. A direct extension of these
the Menschutkin reaction23 to completion.
studies is provided by the results collected in Table 5.
Thus, the reactions of N-methyl and N-allyl pyridinium
and quinolinium cations 3a,b and 4a,b with 2 equimolar
amounts of “NaSeH” under nitrogen atmosphere at 25 °C
for 2 hours followed by an aqueous workup gave the de-
sired selenocarbonyl derivatives 7a,b and 8a,b, respec-
tively. These heterocyclic vinylogous selenoamides, as
reddish orange compounds, are produced in high chemical
purity as judged by 1H NMR. In an analogous fashion, N-
ethoxycarbonylmethylquinoline-4-selenone (8c) was also
obtained from salt 4c. Besides prevailing 8c, however,
ethyl1-(1,2-dihydro-4-methylsulfanylquinolyl)acetatewas
formed as a byproduct to some extent, its formation being
in part prevented by not exceeding the amount of NaBH4
necessary for the generation in situ of 2 molar equivalents
of hydrogen selenide anion. The N-substituted g-sele-
nopyridones and -quinolones thus obtained can be stored in
a refrigerator for extended periods of time under nitrogen
atmosphere but, on exposure to the air, they undergo slow
oxidation to the corresponding carbonyl derivatives and
1
selenium. The H and 13C NMR spectra of these se-
lenocarbonyl compounds are also summarized in Table 5
and may be compared to those of their thiocarbonyl an-
alogs in Table 4. As a general trend, the ring b-protons and
b-carbons upon substitution of C=S by C=Se are sig-
nificantly shifted downfield and this can be attributed in
part to an enhanced electron delocalisation round the se-
lenium atom. A parallel but much higher effect is also pro-
duced by replacement of a C=O by a C=S group.2
In an effort to make the synthetic pathway outlined in
Scheme 1 more attractive, we have developed, via the
Zinckes reaction, a practical entry to the previously un-
Scheme 1
When 4-methylsulfanylquinolinium halides 4a–e were known pyridine systems functionalized with a 4-C=Y
stirred with 2 molar equivalents of sodium hydrogen sul- group (Y = O, S, Se) in which a tert-butyl substituent is
fide in a mixture ethanol–water (1:1) at room temperature, linked to the ring nitrogen atom. According to Scheme 2,
the thiolysis reaction proceeded rapidly to produce the treatment of 4-methylsulfanylpyridine base with 1.2 equiv
corresponding N-substituted-quinoline-4-thiones 6a–e in of 1-chloro-2,4-dinitrobenzene afforded the Zinckes salt 9
high chemical yield as shown in Table 2. In a similar man- (N-DNB) in 73% isolated yield. Previous reports29 have
ner, the pyridine-4-thiones 5a–c were formed albeit in a pointed out that the pyridinium nucleus with a strong elec-
longer reaction time. As has been observed already for the tron-withdrawing group on the nitrogen atom is prone to
reaction of N-methyl salts 3a and 4a with hydroxide be nucleophilically attacked in sequence at the C-2 and C-
ions,24 this strongly suggests that annelation with a ben- 6 position by a primary amine thus allowing exchanges of
zene ring weakens the S–C(4) bond thus making attrac- the amine moiety in the pyridinium ring. As another ex-
tion between the cationic substrate and the anionic ample, salt 9 was easily converted into 1-tert-butyl-4-me-
nucleophile more efficient. Moreover, the consumption of thylsulfanylpyridinium chloride (10) by reaction with
2 moles of sodium hydrogen sulfide per mole of salt fa- tert-butylamine in refluxing dichloromethane. The main
vors regular kinetics for the reaction.25
NMR features in DMSO-d6 of 10 are close to those of 9,

January 1998
SYNTHESIS
101
Table 1. 4-Methylsulfanylpyridinium and 4-Methylsulfanylquinolinium Halides Prepared
Salta
Yieldb
(%)
mp (°C)
(solvent)
Molecularc
Formula
IR (KBr)
n cm–1
3a
95
182–184 (185–18625)
(EtOH)
C7H10INS
3100–2900, 1620, 1540, 1490, 1450,
1105
3b
3c
95
65
124–125d
C9H12BrNS
C10H14BrNO2S
3100–2900, 1620, 1540, 1460, 1100
3000–2940, 1740, 1625, 1120, 1100,
1020
193
(EtOH)
252–253 (247–24824)
(EtOH)
4a
4b
4c
92
91
88
95
92
55
C11H12INS
1610, 1600, 1550, 1525, 1420, 1380,
1210
210
C13H14BrNS
C14H16BrNO2S
C17H16BrNS
C18H16BrNOS
C10H16ClNS
1610, 1595, 1555, 1530, 1390, 1245,
1205, 1160
3070–2850, 1736, 1598, 1552, 1390,
1262, 1248, 1208
(CH3CN/EtOAc)
194
(CH3CN/EtOAc)
4d
4e
226
(EtOH)
222
(EtOH)
3064–2978, 1654, 1610, 1596, 1554,
1530, 1488, 1396
3022–2950, 1694, 1602, 1578, 1552,
1532, 1480, 1448, 1392, 1340, 1216
10e
111 (decomp.)
(EtOAc/Et2O)
3483–3408, 3104–2984, 1622, 1558, 1540,
1493, 1478, 1456, 1446, 1406, 1376, 1318
a Salts as bromides except 3a, 4a as iodides and 10 as chloride.
b All yields were based on isolated product.
c Satisfactory microanalysis were obtained 3b,c, 4e: C±0.34; H±0.16; N±0.14; O±0.21; S±0.41; for 4b–d and 10: S±0.36.
d This salt was not recrystallyzed.
e Overall yield via the Zincke’s salt 9.
Table 2. N-Substituted Pyridine-4-thiones 5a–c, 12 and Quinoline-4-thiones 6a–e Prepared
Prod- Yielda mp (°C)
Molecularb
Formula
MS (70 eV)
m/z (%)
IR (KBr)
uct
5a
5b
5cc
6a
6b
6c
(%)
86
97
53
91
86
92
(solvent)
n (cm-1)
159–l61 (161–16218a
(EtOH)
64–65
(Toluene/light petroleum)
122
)
C6H7NS
125 (M+, 100), 81 (50), 42 (34)
2940, 1630, 1514, 1466, 1414,
1208, 1110, 1024
C8H9NS
151 (M+, 100), 119 (13), 102 (24) 1616, 1508, 1466, 1420, 1282,
1206, 1108, 1026
C9H11NO2S
3070–2852, 1736, 1598, 1552,
1528, 1390, 1262, 1248, 1012
1595, 1530, 1515, 1370, 1150,
1095
3070–2850, 1590, 1533, 1390,
1235, 1158, 1131
3070–2852, 1736, 1598, 1552,
1528, 1390, 1362, 1262, 1248,
1208
210–211 (209–11,22 210–21230) C10H9NS
(CH3CN/isopropyl ether)
97
(Toluene/light petroleum)
169
175 (M+, 100), 131 (45), 130
(47)
C12H11NS
201 (M+, 61), 160 (10), 89 (21),
41 (100)
C13H13NO2S
247 (M+, 21, 219 (10), 174 (30),
84 (64), 73 (7), 49 (100)
(EtOAc/light petroleum)
6d
6e
12
92
89
65
157
C16H13NS
C17H13NOS
C9H13NS
251 (M+, 10), 160 (7), 91 (30), 55 3000, 1614, 1606, 1538, 1508,
(100)
(Toluene/light petroleum)
168
(Toluene/light petroleum)
148 (decomp.)
1386, 1228, 1162
2922, 1684, 1596, 1540, 1386,
1228, 1164
3102–2968, 1622, 1610, 1458,
1192, 1140, 1132, 1088
167 (M+, 10), 166 (50), 151 (12),
111 (100), 110 (14), 57 (72)
(Toluene/light petroleum)
a All yields were based on isolated product.
b The microanalyses were in satisfactory agreement with the calculated values: for 5b, 6b, c and 12: C±0.44; H±0.22; H±0.24; S±0.32; for com-
pounds 5c, 6d: S±0.33; for 5c and 6e HRMS: ±0.0045.
c Isolated by chromatography.
in particular the chemical shift of heterocyclic carbons
(C2,6 at d = 139.8, C3,5 at d = 122.6 and C4 at d = 162.6
for 10; C2,6 at d = 142.6, C3,5 at d = 122.0 and C4 at d =
167.8 for 9). Submitted to the thiolysis and selenolysis
standard conditions, cation 10 was found to deliver the
sulfanyl- and selenocarbonyl derivatives 12 and 13, re-
spectively, in a very satisfactory manner. Hydrolytic
cleavage of the C–S bond also proceeded smoothly in
aqueous sodium hydroxide at 40°C to give after usual
workup 1-tert-butyl-4-pyridone (11) in 71% yield (exper-
imental section).
A very convenient and high-yielding four-step reaction
sequence which includes a blocking and deblocking pro-

102
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SYNTHESIS
Table 3. 1H NMR and 13C NMR Spectral Data of Selected 4-Methylsulfanylpyridinium and -quinolinium Salts (CDCl3/TMS)
Salt
1H NMR
13C NMR
d J (Hz)
d
3b
2.7 (3 H, s), 5.5 (3 H, m), 5.62 (1 H, d, J = 16.8), 6.12 (1H, ddt,
J = 16.8, 10.1, 6.5), 7.8 (2H, d, J = 7.1), 9.15 (2 H, d,
J = 7.1)
s: 164.6
d: 122.7, 130.4, 142.6
t: 61.9, 123.8
q: 15.1
3c
1.3 (3 H, t, J = 7.1), 2.78 (3 H, s), 4.3 (2 H, q, J = 7.1), 6.0 (2 H,
s), 7.76 (2 H, d, J = 7.2), 9.03 (2 H, d, J = 7.2)
s: 165.5, 166.3
d: 121.9, 144.0
t: 59.7, 63.3
q: 14.2, 15.0
4b
4c
2.87 (3 H, s), 5.38 (1 H, d, J = 17.4), 5.45 (1 H, d, J = 10.7), 5.87 s: 126.5, 135.8, 165.2
(2 H, d, J = 5.5), 6.15 (1 H, m), 7.87 (1 H, ddt, J = 17.4, 10.7,
5.5), 7.94 (1 H, d, J = 6.7), 8.09 (1 H, ddd, J = 8.5, 6.7,
1.5), 8.4 (2 H, m), 10.35 (1 H, d, J = 6.7)
d: 115.8, 119.8, 125.4, 129.5, 130.1, 135.8, 147.3
t: 58.8, 121.4
q: 15.4
1.3 (3 H, t, J = 7.1), 2.89 (3 H, s), 4.39 (2 H, q, J = 7.1), 6.35
(2 H, s), 7.7–7.8 (2 H, m), 8.0–8.2 (2 H, m), 8.4 (1 H, m), 10.18
(1 H, d, J = 6.8)
s: 125.5, 135.7, 165.8, 166.3
d: 115.2, 118.4, 126.3, 136.2, 136.6
t: 56.9, 63.2
q: 14.1, 15.3
s: 126.2, 134.2, 146.9, 164.9
4da
4ea
10
2.94 (3 H, s), 6.26 (2 H, s), 7.3 (5 H, m), 7.95 (1 H, m), 8.04
(1 H, d, J = 6.7), 8.15 (1 H, m), 8.4 (2 H, m), 9.5 (1 H, d, J = 6.7) d: 115.9, 120.1, 125.1, 127.1, 128.6, 129.1, 129.7, 134.4, 135.4
t: 58.7
q: 14.6
2.95 (3 H, s), 6.9 (2 H, s), 7.65 (2 H, m), 7.78 (1 H, m), 7.9–8.0
(2 H, m), 8.0 (1 H, d, J = 6.7), 8.07 (1 H, m), 8.16 (1 H, dd,
J = 7.2, 1.3), 8.31 (1 H, d, J = 8.8), 8.47 (1 H, d, J = 8.4), 9.3
(1 H, d, J = 6.7)
1.47 (9 H, s), 2.74 (3 H, s), 7.92 (2 H, d, J = 7.1), 9.13 (2 H, d,
J = 7.1)
s: 125.8, 133.6, 136.4, 165.6, 190.5
d: 115.3, 119.7, 124.7, 128.5, 128.8, 129.3, 134.5, 135.2, 147.2
t: 61.9
q: 14.8
s: 52.7, 164.3
d: 123.2, 139.7
q: 15.0, 27.8
a In DMSO-d6.
(70 eV) spectrometer. Microanalyses were obtained from the “Lab-
oratoire central de microanalyse du CNRS” (Lyon). Analyses of sul-
fur were performed at Caen following Debal and Levy’s method (Bull.
Chem. Soc. Fr., 1968, 426), TLC plastic sheets silica gel 60 F254
(0.2 mm layer thickness) and PLC plates silica gel 60 F254 (1 mm layer
thickness) were used for chromatography.
All commercially available bromides and MeI were used as received
from the suppliers. Purification of solvents was effected according to
standards methods. All reactions were conducted under N2. (1H)-Py-
ridine-4-thione (1) and (1H)-quinoline-4-thione (2) were prepared by
the procedure developed by Albert and Barlin.22 The syntheses of 4-
methylsulfanylpyridine and -quinoline bases and their methiodides 3a
and 4a were also described by these authors.
Scheme 2
N-Alkylation of 4-Methylsulfanylpyridine and -quinoline; Gener-
al Procedure:
cess and allows the introduction of functionalized carbon
side chains on the nitrogen atom of (1H)-pyridine-4-
thione and its mono-benzoanalogue has been developed.
It was further applied to the syntheses of some N-substi-
tuted-4-selenopyridones and -quinolones. Although the
reducing conditions of the thiolysis and selenolysis step
could be a limiting factor, the synthetic versatility of the
N-quarternization reaction is believed to make this proce-
dure reliable for the synthesis of varied N-functionalized
sulfanyl- and selenocarbonyl pyridine and quinoline de-
rivatives in the 4- but also in the 2-series.
The appropriate a-activated bromide (1.5 mmol) was added in one al-
iquot to a solution of 4-methylsulfanylpyridine or 4-methylsulfa-
nylquinoline (1 mmol) in anhyd MeCN (5 mL). The mixture was
stirred at r.t. or at 50°C, respectively. The reaction was monitored by
TLC (elution with CH2Cl2). After completion, the precipitate was fil-
tered off and washed well with anhyd Et2O. The pyridinium and quin-
olinium bromides were obtained in almost quantitative yields and
were of sufficient purity for further reactions. For analysis, these salts
were recrystallized as pale yellow needles (solvents given in Table 1).
Salt 4e was isolated as purple squares.
Thiolysis of 4-Methylsulfanylpyridinium and -quinolinium Ha-
lides; General Procedure:
Melting points were determined with a Gallenkamp apparatus and
were uncorrected. 1H NMR and 13C NMR spectra were recorded on
a Brucker AC 250 instrument operating at 250.13 MHz for 1H, 62.89
for 13C. IR spectra were taken with a Perkin-Elmer 16 PC FTIR spec-
trophotometer. Mass spectra were performed with a Nermag Riber
Rl0 spectrometer (70 eV). HRMS were recorded on a DM 300 GEOL
To a solution of sodium hydrogen sulfide (0.12 g, 2.1 mmol) in EtOH/
H2O (5 mL, 1/1 : v/v) was added pyridinium or quinolinium salts
(1 mmol). The mixture was stirred at r.t. for 5–10 min (quinoline se-
ries) or 1–2 h (pyridine series). The resulting mixture was extracted
with CH2Cl2 (3 ´ 5 mL) and the combined CH2Cl2 layers were

January 1998
SYNTHESIS
103
Table 4. 1H NMR and 13C NMR Spectral Data of Selected N-Substituted Pyridine-4-thiones and Quinoline-4-thiones (CDCl3/TMS)
Prod-
uct
1H NMR
d, J (Hz)
13C NMR
d
5b
5c
4.47 (2 H, d, J = 5.8), 5.3 (1 H, d, J = 16.9), 5.45 (1 H, d, J = 10.3),
5.94 (1 H, ddt, J = 16.9, 10.3, 5.8), 7.13 (2 H, d, J = 7.1), 7.46
(2 H, d, J = 7.1)
1.24 (3 H, t, J = 7.1), 4.22 (2 H, q, J = 7.1), 4.44 (2 H, s), 6.92 (2 H,
d, J = 7.1), 7.31 (2 H, d, J = 7.1)
s: 191.8
d: 130.8, 131.7, 134.6
t: 59.8, 121.4
s: 165.8, 184.1
d: 131.6, 135.1
t: 57.5, 63.l
q: 14.2
6b
6c
4.75 (2 H, d, J = 5.7), 5.07 (1 H, d, J = 17.2), 5.26 (1 H, d, J = 10.5),
5.91 (1 H, ddt, J = 17.2, 10.5, 5.7), 7.2 (1 H, d, J = 7.1), 7.3–7.4
(3 H, m), 7.6 (1 H, m), 8.9 (1 H, m)
s: 125.6, 133.9, 194.7
d: 116.7, 125.5, 130.5, 130.6, 132.7,
136.0, 136.1
t: 56.0, 119.2
1.26 (3 h, t, J = 7.1), 4.27 (2 H, q, J = 7.1), 4.85 (2 H, s), 7.22 (1 H, d,
J = 7.2), 7.28 (1 H, m), 7.47 (1 H, d, J = 7.2), 7.5 (1 H, m), 7.7 (1 H,
m), 9.02 (1 H, dd, J = 8.3, 1.5)
s: 125.9, 134.0, 164.5, 186.5
d: 115.3, 125.8, 131.2, 133.3, 136.2,
136.3
t: 54.9, 62.8
q: 14.2
6e
12
5.6 (2 H, s), 7.03 (1 H, d, J = 8.4), 7.27 (1 H, d, J = 6.9), 7.3–7.7 (6 H, m),
7.99 (2 H, dd, J = 7.8, 1.4), 8.94 (1 H, d, J = 8.3)
1.61 (9 H, s), 7.41 (2 H, d, J = 7.5), 7.49 (2 H, d, J = 7.5)
s: 62.5, 190.3
d: 131.2, 131.6
q: 29.9
Table 5. 1H NMR and 13C NMR Spectral Data of N-Substituted Pyridine-4-Selenones 7a, b, 13 and Quinoline-4-Selenones 8a–c (CDCl3/TMS)
Prod- Chemical Molecularc
1H NMR
d, J (Hz)
13C NMR
d
uct
Puritya
Formula
7a
95%
C6H7NSe
4.35 (3 H, s), 7.19 (2 H, d, J = 7.0), 7.77 (2 H, d, J = 7.0)
s: 184.8
d: 135.3, 136.8
q: 45.5
7b
8a
8b
94%
94%
85%
C8H9NSe
C10H9NSe
C12H11NSe
4.45 (2 H, d, J = 5.1), 5.40 (1 H, d, J = 10.0), 5.52 (1 H, d,
J = 17,1), 6,01 (1 H, m), 7.20 (2 H, d, J = 7.0), 7.82
(2 H, d, J = 7.0)
3.82 (3 H, s), 7.31 (1 H, d, J = 6.8), 7.5 (2 H, m), 7.78 (1 H, m), s: 126.8, 128.9, 194.4
7.97 (1 H, d, J = 6.8), 9.09 (1 H, m)
s: 186.5
d: 130.3, 132.6, 136.5
t: 60.0, 121.8
d: 116.2, 131.0, 131.7, 133.4, 134.2, 135.4,
q: 42.5
4.8 (2 H, d, J = 5.1), 5.15 (1 H, J = 17.1), 5.35 (1 H, d, J = 10.0),
6.01 (1 H, m), 7.38 (1 H, d, J = 6.9), 7.6 (1 H, m), 7.7–7.8 (2 H,
m), 7.97 (1 H, d, J = 6.9), 9.06 (1 H, m)
8cb
13
70%
C13H13NO2Se 1.25 (3 H, t, J = 7.1), 4.26 (2 H, q, J = 7.1), 4.8 (2 H, s), 7.35
(1 H, d, J = 7.0), 9.00 (1 H, m)
C9H13NSe
> 95%
1.56 (9 H, s), 7.37 (2 H, d, J = 7.2), 7.82 (2 H, d, J = 7.2)
s: 62.1, 184.5
d: 129.6, 135.4
q: 28.7
a Estimated from 1H NMR Spectra.
b Significant amount of ethyl 1-(1,2-dihydro-4-methylsulfanylquinolyl)acetate is present.
c The HRMS were in satisfactory agreement with the calculated values: ± 0.0033 except for 8c.
washed with brine and dried (MgSO4). The removal of the solvent un- bled through the mixture for 1 h to remove H2Se (bleach trap) and
der reduced pressure yielded the desired yellow thiocarbonyl deriva- deoxygenated H2O (3 mL) was added. The solution was extracted
tives which was further recrystallized (solvents given in Table 2).
with oxygen free CH2Cl2 (3 ´ 5 mL). The combined CH2Cl2 layer
was dried (MgSO4) and concentrated under reduced pressure, giving
Selenolysis of 4-Methylsulfanylpyridinium and -quinolinium Ha- an orange crude solid which was analyzed by spectroscopic means
lides; General Procedure:
(Table 5).
A nearly colorless ethanolic solution of sodium hydrogen selenide
was first prepared according to Klayman and Griffin:26 Deoxy- Synthesis and Hydrolysis of 1-tert-Butyl-4-methylsulfanylpyri-
genated absolute EtOH (3 mL) was added with magnetic stirring to dinium Chloride (10):
gray powder selenium (0.08 g, 1 mmol) and anhyd NaBH4 (0.04 g, A solution of 4-methylsulfanylpyridine (0.625 g, 5 mmol) and freshly
1.05 mmol) cooled in an ice bath. After being stirred for 10–30 min, distilled 1-chloro-2,4-dinitrobenzene (1.21 g, 6 mmol) in MeOH
pyridinium or quinolinium halide (0.5 mmol) was carefully added (3 mL) was refluxed for 24 h with stirring. After removal of the sol-
and the reaction was allowed to stand at r.t. for ca. 2 h. N2 was bub- vent under reduced pressure, Et2O (10 mL) was added. Salt 9 was ob-

104
Papers
SYNTHESIS
(10) Katano, K.; Ogino, H.; Iwamatsu, K.; Nakabayashi, S.; Yo-
shida, T.; Komiya, I.; Tsuruoka, T.; Inouye S.; Kondo, S. J. An-
tibiot. 1990, 43, 1150.
tained by filtration and washing with Et2O (3 ´ 5 mL) as white
crystals (1.20 g, 3.65 mmol, 73 %, mp = 211 °C).
1H NMR (DMSO-d6 / TMS): d = 3.34 (3 H, s), 8.19 (2 H, d, J = 7.1
Hz), 8.37 (1 H, d, J = 8.7 Hz), 8.92 (1 H, dd, J = 8.7, 2.5 Hz), 9.07 (2
H, d, J = 7.1 Hz), 9.09 (1 H, d, J = 2.5 Hz).
Hamashima, Y.; Minami, K.; Ishikura, K.; Ishitobi, H.; Onoe,
H. Jpn Patent 05148272, 1993; Chem. Abstr. 1994, 120, 134
140.
13C NMR (DMSO-d6 / TMS): d = 14.5 (q), 121.5 (d), 122.0 (d), 130.2
(d), 132.2 (d), 138.5 (s), 142.6 (d), 143.4 (s), 148.9 (s), 167.8 (s)
tert-Butylamine (200 mL, 2.5 mmol) was added dropwise to a stirred
suspension of 9 (0.66 g, 2 mmol) in anhyd CH2Cl2 (5 mL). The mix-
ture was stirred 1 h at r.t. and turned to a deep red color. After the so-
lution was refluxed for 36 h, the solvent was removed under reduced
pressure and the crude product was dissolved in a mixture of H2O and
EtOAc (l/1 v/v). The aqueous layer was separated and the EtOAc lay-
er was washed twice with H2O. The H2O extracts were combined,
washed with CH2Cl2, and concentrated in vacuo to give salt 10
(0.32 g, 1.5 mmol, 75 %) as a pale yellow solid. White crystals were
obtained from anhyd EtOAc–Et2O (Table 1).
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Hydrolysis of salt 10 (0.22 g, 1 mmol) was performed in 1M aq NaOH
(2 mL) with stirring at 40°C for 2h. After cooling to r.t., the mixture
was acidified to pH 6–7 by sat. aq NH4Cl. The aqueous layer was ex-
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1H NMR (CDCl3/TMS): d = 1.59 (9 H, s), 6.41 (2 H, d, J = 7.9 Hz),
7.59 (2 H, d, J = 7.9 Hz).
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