Synthesis of new benzylpyridines as potential photochromic compounds

Article abstract of DOI:10.1002/jhet.5570380332

Photoinduced proton transfer systems such as 2-(2′,4′-dinitrobenzyl)pyridine derivatives have been developed in an attempt to apply the compounds to variable optical transmission materials. However their fatigue resistance property is a limitation for the

Full text of DOI:10.1002/jhet.5570380332

May-Jun 2001
Synthesis of New Benzylpyridines as
Potential Photochromic Compounds
737
Arnault Heynderickx, André Samat * and Robert Guglielmetti
Université de la Méditerranée, Faculté des Sciences de Luminy, UMR 6114 CNRS Case 901,
13288 Marseille Cedex 9, France
Received December 18, 2000
Photoinduced proton transfer systems such as 2-(2',4'-dinitrobenzyl)pyridine derivatives have been devel-
oped in an attempt to apply the compounds to variable optical transmission materials. However their fatigue
resistance property is a limitation for these applications. New benzylpyridines have been synthesized and
tested. 2-(2',4'-Diphenylsulfonybenzyl)pyridine was found to be photochromic in the crystalline state and in
ethanolic solution (λ = 485 nm) upon UV flash photolysis.
max
J. Heterocyclic Chem., 38, 737 (2001).
Introduction.
coloration-fading. As part of our effort to bypass the
fatigue resistance of such compounds, we decided to
investigate the PIPT of new benzylpyridines substituted by
electron withdrawing groups other than the o-nitro group.
We first tried to establish if either a sulfoxide or a sulfone
group could be used for that aim. Prompted by the litera-
ture, we attempted to design and synthesize compounds
with the pyridine or pyridine-1-oxide ring (Figure 2).
In recent years, the photoinduced proton transfer (PIPT)
reaction occurring in 2-(2',4'-dinitrobenzyl)pyridine (α-
DNBP) and in some of its derivatives has drawn much
attention due to the potential applications of these com-
pounds as optically bistable systems for optical data stor-
age, in holography, and as optical switching devices[1].
For these applications, a lot of effort has been focused on
the optimization of the efficiency of the photoreaction, the
increase of the lifetime of the metastable form and a best
understanding of the PIPT mechanism. The pathways lead-
ing to the phototautomers of α-DNBP and the structure of
the different tautomers [1c] are presented in Figure 1.
Synthesis.
Only one versatile synthetic route was employed for the
preparation of the compounds used in this study and the
experimental conditions were not optimized. 2-Lithio pyri-
dine, derived from the reaction of 2-bromopyridine [5]
with n-butyllithium, was coupled with substituted benzal-
dehydes 1-4 to give expected 2-(α-hydroxybenzyl)-
pyridines 5-8 in moderate to good yield. In the next step,
treatment of alcohols 5-8 with thionyl chloride provided
1
chloromethylene derivatives as determined by their H-
Photochromism takes place in solution [2], in polymer
matrix [1a], and in the pure crystal [3].
NMR spectrum. Then, reduction of these intermediates
with Zn powder in acetic acid afforded 2-benzylpyridines
9-12 [6] (Scheme I, Table I).
Finally, sulfoxide 13 was prepared from the correspond-
ing thioether 9 by selective oxidation with m-chloroper-
oxybenzoic acid (m-CPBA) in chloroform and the sulfones
14-17 were provided using either the same methodology or
by treating the thioether with an excess of hydrogen
peroxide in acetic acid ( Scheme II, Table II).
Obviously, the ortho-nitro group, which acidifies the
hydrogen atom of the methylene group, plays an important
role in the photochemical reaction. Regarding literature
data, this structural requirement appears to be a sine qua
non condition to observe PIPT.
The major inconvenient property of these PIPT systems
is the degradation [4] of the material after several cycles of

738
A. Heynderickx, A. Samat, and R. Guglielmetti
Vol. 38
Table I
Synthesis of 2-benzylpyridines
1
2
R
R
Product
Yield (%)
Product
Yield (%)
SPh
H
H
H
SPh
5
6
7
8
95
40
88
96
9
10
11
12
92
90
85
60
SO Ph
2
SEt
SPh
Scheme I
Photochromic Properties.
We observed that only crystals of 2-(2',4'-diphenylsul-
fonybenzyl)pyridine 17, grown by slow evaporation of an
ethanolic solution in the dark, were photochromic. A pur-
ple color is developed under sunlight irradiation and fad-
ing occured after several hours in the dark.
According to earlier reports, the PIPT process has been
found to be strongly dependent on the crystal packing [8].
Thus, we tried to obtain different polymorphs of the new
molecules under different crystallisation conditions, but
the resulting crystals were still photoinert.
The UV absorption spectrum of the unexposed 2-(2',4'-
diphenylsulfonybenzyl)pyridine 17 is quite similar to
those of (α-DNBP). UV flash photolysis of its ethanolic
-5
solution (2.5 10 M) gives rise to photoinduced absorption
in the visible region (λ = 485 nm, colorability A =
max
0
Table II
Oxidation of thioethers into sulfoxides or sulfones groups
0.035) [9]. The rate constant for the reverse decoloration of
-1
the metastable form is about 0.27 s (Figure 3).
1
2
Product Heterocycle
n
R
R
Yield (%)
13
14
15
16
17
Pyridine
1
2
2
2
2
Ph
Ph
H
H
90
57
31
80
46
Pyridine-1-oxide
Pyridine-1-oxide [a]
Pyridine
Ph SO Ph
Et
Ph SO Ph
2
H
Pyridine
2
[a] Products 15 and 17 were isolated from the same reactions.
In view of tracking the impact of a nitro substituent in
such structure, the nitration of compound 16, at the 4' posi-
tion has been accomplished [7]. Derivatives 19 and 20
were obtained from 18, by hydrogenation on Pd/C and by
oxidation with hydrogen peroxide in acetic acid, respec-
tively (Scheme III).
(nm).
Figure 3

May-Jun 2001
Synthesis of New Benzylpyridines as Potentiel Photochromic Compounds
739
QP-5000 spectrometer. Microanalyses were performed by the
Microanalytical Centre of the University of Aix-Marseille III.
Photoirradiation was carried out by using a xenon lamp (150
W) or a mercury lamp (500 W). UV flash photolysis was per-
formed with a xenon lamp (60 J) by the Institute of Topology and
Dynamics of Systems (ITODYS, Paris-Jussieu)
Solvents (SDS Company, France) were used without further
purification and were dried over sieves if necessary.
Tetrahydrofuran was distilled under nitrogen from sodium ben-
zophenone ketyl and used immediately. Metalation were per-
formed under an argon atmosphere and reagents were handled
with syringes through septa.
We have assigned this photogenerated metastable form
to the enamine "NH" form . The main support for this
assignment came from the similarity of its visible absorp-
tion with the spectrum of the molecule 21 (λ = 485 nm
max
in ethanolic solution) usually called "N-methyl enamine"
in the literature [1c,2c], which has an isoelectronic struc-
ture to the "NH" quinoid form (Figure 4). The presence of
another short-lived species has not been excluded but has
not been demonstrated yet.
The substituted benzaldehydes 1-4 were prepared according to
modified literature procedures [10-13].
2-(Phenylthio)benzaldehyde (1).
To a stirred solution of benzenethiol (29.4 g, 0.27 mole) and
anhydride sodium carbonate (37.3 g) in dry DMF (80 ml), at 80-
90°, was added slowly 2-chlorobenzaldehyde (30 g, 0.213 mole)
during 10 minutes. The resulting mixture was stirred at the same
temperature for 3 hours. After cooling, the reaction mixture was
poured into 200 ml of water and extracted with ether. The extract
was washed with water, dried over anhydrous magnesium sulfate,
and concentrated to afford an oil that crystallized by adding
hexane. Recrystallisation from hexane gave colorless prisms
17
1
(34.2 g, 75%), mp 50° (lit. mp 47°-48°); H nmr (deuteriochloro-
form): δ 7.03 (dd, 1H, J = 1.0, 7.8 Hz), 7.18-7.45 (m, 7H), 7.82
(dd, 1H, J = 1.8, 7.4 Hz), 10.32 (s, 1H, CHO).
Anal. Calcd.. for C
72.83; H, 4.62.
H OS: C, 72.87; H, 4.70. Found: C,
13 10
These preliminary results demonstrate that, contrarily to
the opinion expressed previously, the presence of a nitro
group in the ortho position of the benzyl group is not a
necessary requirement to observe PIPT.
2-(Phenylsulfonyl)benzaldehyde (2).
To a solution of 2-(phenylthio)benzaldehyde 1 (2.67 g, 12.4
mmoles) in acetic anhydride (25 ml) was added, slowly, concen-
trated sulphuric acid (0.1 ml). After being stirred for 4 hours, the
mixture was poured into 100 ml of cold water, neutralized by
adding solid sodium carbonate and extracted with ethyl acetate. The
extracts were dried over magnesium sulfate and concentrated in
vacuo to afford 2-(phenylthio)benzylidene diacetate (3 g) as a oil.
To a solution of this crude product (3 g, 9.5 mmoles) in glacial
acetic acid (100 ml) was added, slowly at 0° with stirring, a solution
of hydrogen peroxide (36%, 15 ml). After 24 hours at room temper-
ature, the reaction mixture was poured into cold water (100 ml). The
resulting precipitate was collected by filtration and heated during 30
minutes under reflux with diluted sulfuric acid (6 N, 50 ml) and
acetic acid (40 ml). The mixture was poured into water (100 ml) and
cooled by a ice bath. The precipitate was collected by filtration and
dried. The product obtained was recrystallized from toluene-pen-
tane to afford 2-(phenylsulfonyl)benzaldehyde 2 (1,75 g, 75%), mp
Conclusion.
New benzylpyridines, substituted either by a sulfoxide
or sulfone group in ortho position to the benzyl hydrogen,
have been synthesized starting from 2-lithiopyridine. It has
been observed that 2-(2',4'-diphenylsulfonyl)pyridine 17
underwent a reversible photoinduced proton transfer reac-
tion in the crystalline phase as well as in ethanolic solution
at ambient temperature. The metastable coloured form was
attribued to a "NH" quinoid tautomer.
It has also been concluded that contrarily to what was
generally assumed, the presence of a nitro group at the
ortho position of the benzyl group is not a necessary con-
dition to provide proton transfer upon UV irradiation.
1
91°; H nmr (deuteriochloroform): δ 7.42-7.64 (m, 3H), 7.65-7.99
(m, 2H), 7.84 (dd, 2H, J = 1.4, 8.3 Hz), 7.97 (dd, 1H, J = 1.8, 7.1
Hz), 8.36 (dd, 1H, J = 1.9, 8.9 Hz), 10.79 (s, 1H, CHO).
EXPERIMENTAL
Melting points were determined on a Buchi 510 apparatus in
Anal. Calcd. for C
63.38; H, 3.96.
H O S: C, 63.40; H, 4.09. Found: C,
13 10 3
1
13
capillary tubes and are uncorrected. The H nmr and C nmr
spectra were recorded in deuteriochloroform on a Brüker AM
250 spectrometer (250 and 62.5 MHz, respectively) using tetram-
ethylsilane as the internal standard. Column liquid chromatogra-
phy were carried out on silica gel Merck 60 (70-230 mesh). The
infrared spectral data (ir) were recorded on a Avatar 320 spec-
trometer and were performed in potassium bromide pellets. The
electron impact mass spectra (ms) were obtained on a Shimadzu
2-(Ethylthio)benzaldehyde (3).
This was prepared in the same manner as described for the
2-(phenylthio)benzaldehyde 1, starting from ethanethiol (16.7 g,
0.27 mole). The reaction was conducted at 100° for 24 hours. The
crude material was purified by vacuum distillation to afford
colourless liquid of 2-(ethylthio)benzaldehyde in 80% yield

740
A. Heynderickx, A. Samat, and R. Guglielmetti
Vol. 38
1
Anal. Calcd. for C
Found: C, 64.32; H, 4.56; N, 4.20.
H
NO S: C, 64.44; H, 4.65; N, 4.30.
(35.8 g, 0.216 mole), bp 150° (15 mmHg); H nmr (deuteriochlo-
roform): δ 1.41 (t, 3H, J = 7.4 Hz), 3.03 (q, 2H, J = 7.4), 7.31-
7.60 (m, 3H), 7.88 (dd, 1H, J = 1.5, 7.6 Hz), 10.41 (s, 1H, CHO).
18 15
3
2-[α-Hydroxy-2-(ethylthio)benzyl]pyridine (7).
Anal. Calcd. for C H OS: C, 65.02; H, 6.06. Found: C, 65.14;
9
10
This compound was prepared employing the general procedure
described above, and starting from 2-(ethylthio)benzaldehyde 3
(13.8 mmoles, 2.29 g). The crude product was purified by col-
umn chromatography (silica gel, eluted by dichloromethane-
ethyl acetate 5:2, gradient) to provide 2.72 g (88 % overall) of 7
H, 6.10.
2,4-Di(phenylthio)benzaldehyde (4).
A solution of commercial 2,4-dichlorobenzaldehyde (50 g,
0.285 mole), benzenethiol (78.7 g, 0.714 mole) and NaOH (28.6
g, 0.715 mole) in ethanol (200 ml) was refluxed for 16 hours with
stirring. After evaporation of the solvent in vacuo, the residue
1
as yellow solid, mp 89°; H nmr (deuteriochloroform): δ 1.15 (t,
3H, J = 7.4 Hz, CH ), 2.89 (q, 2H, J = 7.4 Hz, CH ), 5.39 (s, 1H,
3
2
OH), 6.33 (s, 1H, CH), 7.05-7.23 (m, 5H), 7.33 (dd, 1H, J = 1.7,
7.7 Hz), 7.51 (dt, 1H, J = 1.7, 7.9 Hz), 8.47 (d, 1H, J = 4.7 Hz).
was triturated with dichloromethane (200 ml) and H O (100 ml).
2
The aqueous layer was extracted with dichloromethane (50 ml).
The extract was dried over magnesium sulfate and removed on a
rotary evaporation. The product obtained was recrystallized from
ethanol-hexane to afford 2,4-di(phenylthio)benzaldehyde 4 (90.9
g, 99%) as a white solid, mp 91°; H nmr (deuteriochloroform): δ
6.54 (d, 1H, J = 1.7 Hz), 6.94 (dd, 1H, J = 1.8, 8.1 Hz), 7.20-
7.35 (m, 10H), 7.62 (d, 1H, J = 8.1 Hz), 10.15 (s, 1H, CHO).
Anal. Calcd. for C
H NOS: C, 68.54; H, 6.16; N, 5.71
14 15
Found: C, 68.55; H, 6.27; N, 5.59.
2-[α-Hydroxy-2,4-di(phenylthio)benzyl]pyridine (8).
1
This compound was prepared by a modification of the general
procedure described above, starting from 2,4-di(phenylthio)ben-
zaldehyde 4 (13.8 mmoles, 4.44 g). After complete addition of
the aldehyde, the reaction mixture was allowed to warm to 0° for
1 hour before quenching. The crude product was purified by col-
umn chromatography (silica gel, eluted by dichloromethane-
ether 6:1, gradient) to provide 4.86 g (96 % overall) of 8 as oil;
Anal. Calcd. for C
70.63 H, 4.31.
H OS : C, 70.77; H, 4.38. Found: C,
19 14 2
General Procedure for the Synthesis of Substituted 2-(α-
Hydroxybenzyl)pyridines 5-8.
1
H nmr (deuteriochloroform): δ 5.39 (s, 1H, OH), 6.30 (s, 1H,
To a solution of 2-lithiopyridine (12.6 mmoles) prepared by
bromo-lithium exchange reaction [5], in THF (75 ml), at –78°
under N atmosphere, was slowly added a solution of substituted
CH), 7.05-7.27 (m, 15H), 7.52 (dt, 1H, J = 1.8, 7.8 Hz), 8.54 (d,
1H, J= 5.0 Hz).
2
Anal. Calcd. for C
H NOS : C, 71.79; H, 4.77; N, 3.49.
benzaldehydes (13.8 mmoles) in THF (50 ml), with the tempera-
ture of the reaction mixture being maintained at –78°. The stir-
ring was continued for 1 hour at –78° and hydrolysis was then
carried out using a mixture of 35% aqueous hydrochloric acid (4
ml), ethanol (4 ml) and THF (16 ml). The solution was gently
warmed to room temperature, made slightly basic with saturated
sodium hydrogenocarbonate solution and evaporated nearly to
dryness under vacuum. The residue was extracted with
dichloromethane (4 x 40 ml). The organic extract was dried over
magnesium sulfate and evaporated to dryness.
24 19 2
Found: C, 71.70; H, 4.77; N, 3.45.
General Procedure for Reduction of Alcohols to Substituted 2-
(Benzyl)pyridines 9-12 [6].
To a stirred, cooled solution (5°) of substituted 2-(α-hydroxy-
benzyl)pyridine 5-8 (12 mmoles) in chloroform (30 ml) was
added dropwise thionyl chloride (2.2 g, 18 mmoles) at such a rate
that the temperature did not exceed 20°. The red mixture was
then stirred for 3 hours at ambient temperature. After cooling at
5°, water (15 ml) was poured slowly into the reaction mixture and
adjusted to pH 8 with aqueous sodium carbonate solution. The
layers were separated and the aqueous layer extracted twice with
dichloromethane (2 x 10 ml). The combined organic layers were
dried over magnesium sulfate, filtered, and concentrated in vacuo
to give 2-(α-chlorobenzyl)pyridine.
This product was taken on without further purification, dis-
solved in glacial acetic acid (30 ml), and refluxed with stirring.
Zinc dust (3.9 g, 60 mmoles) was added over the period of one
hour. The heating was maintained 6 hours, then the insoluble
material was filtered and the acetic acid removed in vacuo. The
residue was treated with a mixture of dichloromethane (20 ml)
and water (20 ml). The resulting solution was adjusted to pH 8
with potassium carbonate. The layers were separated and the
aqueous layer extracted twice with dichloromethane (2 x 10 ml).
The combined organic layers were washed with brine (10 ml),
dried over magnesium sulfate, filtered, and concentrated in vacuo
to give the reduced product 9-12.
2-[α-Hydroxy-2-(phenylthio)benzyl]pyridine (5).
This compound was prepared employing the general procedure
described above, starting from 2-(phenylthio)benzaldehyde 1
(13.8 mmoles, 2.95 g). The crude product was purified by col-
umn chromatography (silica gel, eluted by pentane-ether 1:1) to
1
provide 3.51 g (95% overall) of 5 as oil; H nmr (deuteriochloro-
form): δ 5.68 (s, 1H, OH), 6.41 (s, 1H, CH), 7.15-7.25 (m, 9H),
7.28 (dd, 1H, J = 1.4, 7.6 Hz), 7.36-7.42 (m, 2H), 8.45 (d, 1H, J =
4.8 Hz).
Anal. Calcd. for C
Found: C, 73.81; H, 5.10, N, 4.85.
H NOS: C, 73.69; H, 5.15; N, 4.77.
18 15
2-[α-Hydroxy-2-(ph'enylsulfonyl)benzyl]pyridine (6).
This compound was prepared employing the general procedure
described above, starting from 2-(phenylsulfonyl) benzaldehyde
2 (3.39 g). The crude product was purified by column chromatog-
raphy (silica gel, eluted by dichloromethane-ethyl acetate, gradi-
ent 1:1) and recrystallized from benzene-pentane to provide 1.64
2-[2'-(Phenylthio)benzyl]pyridine (9).
1
g (40% overall) of 6 as white solid, mp 171°; H nmr (deuteri-
ochloroform): δ 5.65 (s, 1H, OH), 6.61 (s, 1H, CH), 7.13 (t, 1H, J
= 6.6 Hz), 7.21 (d, 1H, J = 7.2 Hz), 7.28 (dd, 1H, J = 1.4, 7.6
Hz), 7.35-7.56 (m, 6H, m), 7.87 (dd, 2H, J = 1.3, 7.0 Hz), 8.15
(dd, 1H, J = 1.5, 7.9 Hz), 8.45 (dd, 1H, J = 1.0, 5.0 Hz).
The title product was analogously prepared from 5 (3.52 g).
Purification by chromatography (silica gel, eluted by pentane-
1
ether 1:1) afforded 3.06 g (11 mmoles, 92%) of 9 as an oil; H
nmr (deuteriochloroform): δ 4.35 (s, 2H, CH ), 6.97-7.07 (m,
2

May-Jun 2001
Synthesis of New Benzylpyridines as Potentiel Photochromic Compounds
741
2H), 7.09-7.38 (m, 9H), 7.45 (dt, 1H, J = 1.8, 7.6 Hz), 8.52 (d,
1H, J = 4.8 Hz).
2-[2'-(Phenylsulfinyl)benzyl]pyridine (13).
This compound was prepared by oxidation of 9 (5.55 g)
according to the method A with m-CPBA (3.80 g, 1.1 eq.), T =
20°, and t = 24 hours. Purification by column chromatography
(silica gel, eluted by ether) provided 13 (5.28 g, 18 mmoles, 90%)
Anal. Calcd for C
H NS: C, 77.94; H, 5.45; N, 5.05 Found:
18 15
C, 77.87; H, 5.38; N, 4.97.
2-[2'-(Phenylsulfonyl)benzyl]pyridine (10).
1
as a solid, mp 59°; H nmr (deuteriochloroform): δ 4.26 (s, 2H,
The title product was analogously prepared from 6 (3.90 g).
Purification by chromatography (silica gel, eluted by ether)
afforded 3.34 g (10.8 mmoles, 90%) of 10 as a white solid, mp
CH ), 6.80 (d, 1H, J = 8 Hz), 7.00 (dd, 1H, J = 5.0, 6.7 Hz), 7.14
2
(dd, 1H, J = 2.2, 7.4 Hz), 7.20-7.50 (m, 8H), 7.86 (dd, 1H, J = 2.3,
7.0 Hz), 8.42 (dd, 1H, J = 1.0, 5.0 Hz).
1
99°; H nmr (deuteriochloroform): δ 4.40 (s, 2H, CH ), 6.72 (d,
2
Anal. Calcd. for C
H NOS: C, 73.69; H, 5.15; N, 4.77.
18 15
1H, J = 7.8 Hz), 6.98 (dd, 1H, J = 5.0, 6.7 Hz), 7.16 (dd, 1H, J =
1.0, 7.6 Hz), 7.28-7.48 (m, 6H), 7.74 (dd, 2H, J = 1.2, 7 Hz),
8.20 (dd, 1H, J = 1.7, 7.6 Hz), 8.37 (dd, 1H, J = 1.0, 5.0 Hz).
Found: C, 73.58; H, 5.26; N, 4.51.
2-[2'-(Phenylsulfonyl)benzyl]pyridine-1-oxide (14).
Anal. Calcd. for C
Found: C, 69.75; H, 4.90; N, 4.49.
H NO S: C, 69.88; H, 4.89 N, 4.53.
18 15 2
This compound was prepared by oxidation of 9 (6.19 g)
according to the method B, T = 100°, and t = 0.75 hours. The
crude product was recrystallised from benzene-hexane to provide
2-[2'-(Ethylthio)benzyl]pyridine (11).
1
14 (3.71 g, 11 mmoles, 57%) as a solid, mp 161° ; H nmr (deu-
The title product was analogously prepared from 7 (2.94 g).
Purification by chromatography (silica gel, eluted by
dichloromethane) afforded 2.34 g (10.2 mmoles, 85%) of 11 as a
teriochloroform): δ 4.48 (s, 2H, CH ), 6.53 (dd, 1H, J = 2.0, 7.8
2
Hz), 7.01 (t, 1H, J = 7 Hz), 7.06 (dt, 1H, J = 2.0, 7.9 Hz), 7.20-
7.54 (m, 6H), 7.79 (dd, 2H, J = 1.1, 7 Hz), 8.19 (d, 1H, J = 6.2
Hz), 8.27 (dd, 1H, J = 2.0, 7.6 Hz).
1
colorless oil; H nmr (deuteriochloroform): δ 1.19 (t, 3H, J = 7.4
Hz, CH ), 2.82 (q, 2H, J = 7.4 Hz, SCH ), 4.26 (s, 2H, CH ),
3
2
2
Anal. Calcd. for C
H NO S: C, 66.44; H, 4.65; N, 4.30.
18 15 3
6.93-7.28 (m, 6H), 7.46 (dt, 1H, J = 1.7, 8.0 Hz), 8.49 (d, 1H, J
= 5 Hz).
Found: C, 66.33; H, 4.86; N, 4.09.
Anal. Calcd. for C
H NS: C, 73.32; H, 6.59; N, 6.11. Found:
2-[2',4'-Di(phenylsulfonyl)benzyl]pyridine-1-oxide (15).
14 15
C, 73.27; H, 6.48; N, 6.23.
This compound was prepared by oxidation of 12 (7.71 g)
according to the method B, T= 20°, and t= 72 h. Purification by
chromatography (silica gel, eluted by ethyl acetate-ethanol, gra-
dient) afforded 2.88 g (6.2 mmoles, 31%) of 15 as a solid, mp
2-[2',4'-Di(phenylthio)benzyl]pyridine (12).
The title product was analogously prepared from 8 (4.82 g).
Purification by chromatography (silica gel, eluted by
dichloromethane) afforded 2.77 g (7.2 mmoles, 60%) of 12 as a
1
208°; H nmr (deuteriochloroform): δ 4.45 (s, 2H, CH ), 6.52 (d,
2
1H, J = 7.8 Hz), 6.91 (t, 1H, J = 7.8 Hz), 7.02 (t, 1H, J = 7.4
Hz), 7.27-7.54 (m, 7H), 7.70 (dd, 2H, J = 1.5, 6.9 Hz), 7.85 (dd,
2H, J = 1.5, 6.9 Hz), 7.95 (dd, 1H, J = 2, 8 Hz), 8.09 (d, 1H, J =
6.3 Hz), 8.71 (d, 1H, J = 2 Hz).
1
yellow oil; H nmr (deuteriochloroform): δ 4.25 (s, 2H, CH ),
2
6.90-7.26 (m, 15H), 7.48 (dt, 1H, J = 1.8, 7.8 Hz), 8.48 (dd, 1H,
J = 1.0, 5.0 Hz).
Anal. Calcd. for C
H NS : C, 74.77; H, 4.97; N, 3.63 Found:
24 19 2
Anal. Calcd. for C
H NO S : C, 61.92; H, 4.11; N, 3.01.
24 19 5 2
C, 74.70; H, 4.89, N, 3.52.
Found: C, 61.93; H, 4.23; N, 2.97.
General Procedure to Oxidize Sulfides to Sulfoxides and
Sulfones.
2-[2'-(Ethylsulfonyl)benzyl]pyridine (16).
This was prepared by oxidation of 11 (4.59 g) according to the
method B, T = 20°, and t = 12 hours. Purification by column chro-
matography (silica gel, eluted by dichloromethane-ether 5:2) pro-
Method A.
To a stirred solution of sulfide (20 mmoles) in chloroform (100
ml) at 0° was added a solution of m-chloroperoxybenzoic acid (
1.1, 2.1, or 4.1 equivalents) in chloroform (50 ml). The mixture
was maintained at T° for t hours. At ambient temperature, the
resulting solid was separated by filtration, and the filtrate poured
into water (30 ml). The resulting solution was made slightly basic
with sodium carbonate. The layers were separated and the aque-
ous layer extracted twice with dichloromethane (2 x 15 ml). The
combined organic layers were dried over magnesium sulfate, fil-
tered, and evaporated under reduce pressure to afford crude sul-
foxide, or sulfone.
1
vided 16 (4.18 g, 16 mmoles, 80%) as an oil; H nmr (deuteriochlo-
roform): δ 1.17 (t, 3H, J = 7.4 Hz, CH ), 3.09 (q, 2H, J = 7.4 Hz,
3
SO CH ), 4.60 (s, 2H, CH ), 7.08 (dd, 1H, J = 5.0, 6.6 Hz), 7.18 (d,
2
2
2
1H, J = 8.8 Hz), 7.29 (d, 1H, J = 8.5 Hz), 7.36 (d, 1H, J = 7.7 Hz),
7.48 (dt, 1H, J = 1.4, 7.5 Hz), 7.56 (dt, 1H, J = 1.8, 7.7 Hz), 7.99
(dd, 1H, J = 1.3, 7.9 Hz), 8.44 (d, 1H, J = 4.6 Hz).
Anal. Calcd. for C
H NO S: C, 64.34; H, 5.79; N, 5.36.
14 15 2
Found: C, 64.41; H, 5.82; N, 5.40.
2-[2',4'-Di(phenylsulfonyl)benzyl]pyridine (17).
The title product was isolated from the reaction leading to 15.
Purification by column chromatography (silica gel, eluted by
ether-ethyl acetate, gradient) provided 17 (4.13 g, 9.2 mmoles,
Method B.
To a solution of sulfide (20 mmoles) in acetic acid (100 ml)
was added dropwise a solution of 35% hydrogen peroxide (100
ml). The mixture was warmed at T° for t hours. After cooling, the
solution was reduced in vacuo and time to time diluted with
water. The concentrated solution was adjusted to pH 8 with
sodium hydrogenocarbonate, and extracted with dichloro
methane. The combined organic extracts were dried over magne-
sium sulfate and concentratred in vacuo to provide crude sulfone.
1
46%) as a solid, mp 150°; H nmr (deuteriochloroform): δ 4.39
(s, 2H, CH ), 6.77 (d, 1H, J = 7.8 Hz), 7.00 (dd, 1H, J = 5.0, 6.6
2
Hz), 7.31-7.56 (m, 8H), 7.74 (dd, 2H, J = 1.5, 7.2 Hz), 7.88 (dd,
2H, J = 1.6, 6.9 Hz), 7.95 (dd, 1H, J = 2.0, 8.1 Hz), 8.32 (m,
1H), 8.74 (d, 1H, J = 2 Hz).
Anal. Calcd. for C
H NO S : C, 64.12; H, 4.26; N, 3.12.
24 19 4 2
Found: C, 64.15; H, 4.36; N, 3.07.

742
A. Heynderickx, A. Samat, and R. Guglielmetti
Vol. 38
2-[2'-(Ethylsulfonyl)-4'-nitrobenzyl]pyridine (18).
Synthesis of the "N-Methylenamine" (21).
This product was prepared according to a modified procedure
reported in the literature for the synthesis of 2,4-dinitroben-
zylpyridine [7]. To a cooled (-5°) and well-stirred concentrated
sulfuric acid (96%) (12 ml) was added gradually 16 (4.00 g, 15.3
mmoles). Then red fuming nitric acid (density = 1.5 g / ml, 0.7
ml, 16.8 mmoles) was added dropwise over a period of about 10
minutes. After complete addition, the mixture was stirred at 100°
for 0.5 hours, and then poured onto about 100 g of ice. The result-
ing solution was basified (pH 10) by adding a saturated aqueous
solution of sodium hydroxide, and extracted with ether (3 x 50
ml). The combined ethereal extracts were dried over magnesium
sulfate, filtered, and concentrated in vacuo. The crude product
was purified by recrystallisation from benzene-cyclohexane or
from ethanol to afford 3.51 g (11.4 mmoles, 75% overall) of 18 as
This compound was prepared according to published procedure
[2c] from the product 17 (100 mg, 0.7 mmole). After purification,
the title product was obtained in 72% yield (222 mg, 0.48 mmole)
1
as an orange-red solid, mp 206°; H nmr (deuteriochloroform): δ
3.11 (s, 3H), 5.20 (s, 1H), 5.66 (t, 1H, J = 6.6 Hz), 6.53 (t, 1H, J =
8 Hz), 6.81 (d, 1H, J = 6.7 Hz), 6.92 (d, 1H, J = 9.4 Hz), 7.27-7.56
(m, 7H), 7.66 (dd, 1H, J = 2.0, 8.6 Hz), 7.72 (dd, 2H, J = 2.0, 8.5
Hz), 7.89 (dd, 2H, J = 2.0, 8.0 Hz), 8.62 (d, 1H, J = 2 Hz).
Anal. Calcd. for C
H NO S : C, 64.77; H, 4.57; N, 3.02.
25 21 4 2
Found: C, 64.61; H, 4.53; N, 3.00.
REFERENCES AND NOTES
[*] E-mail: samat@lum.univ-mrs.fr; Fax: (33) 4 91 82 93 01;
Telephone: (33) 4 91 82 94 05
1
white needless, mp 79°; H nmr (deuteriochloroform): δ 1.18 (t,
3H, J = 7.4 Hz, CH ), 3.21 (q, 2H, J = 7.4 Hz, SO CH ), 4.67 (s,
3
2
2
[1a] S. Shinohara, J. Takeda, T. Ooike and S. Kurita, J. Phys.
Soc. Jpn., 68(5), 1725 (1999); [b] S. Houbrechts, K. Clays, A.
Persoons, Z. Pikramenou and J. M. Lehn, Chem. Phys. Lett., 258, 485
(1996); [c] A. Corval, K. Kuldova, Y. Eichen, Z. Pikramenou, J. M.
Lehn and H. P. Trommsdorff, J. Phys. Chem., 100, 19315 (1996).
[2a] E. Klemm, D. Klemm, A. Graness and J. Kleinschmidt,
Chem. Phys. Lett., 55, 113 (1978); [b] E. Klemm, D. Klemm, A.
Graness and J. Kleinschmidt, Chem. Phys. Lett., 55, 503 (1978); [c]
E. Klemm and D. Klemm, J. Prackt. Chem., 321, 407 (1979); [d] E.
Klemm, D. Klemm, J. Kleinschmidt and A.Graness, Z. Phys. Chem.,
262, 621 (1981); [e] K. Yokoyama and T. Kobayashi, Chem. Phys.
Lett., 85, 175, (1982); [f] H. Takahashi, S. Hirukawa, S. Suzuki, Y.
Torii and H. Isaka, J. Mol. Struct., 146, 91 (1986).
[3] R. Casalegno, A. Corval, K. Kuldova, O. Ziane and H. P.
Trommsdorff, J. Lumin., 72-74, 78 (1997).
2H, CH benzylic), 7.10 (dd, 1H, J = 4.9, 7.4 Hz, H ), 7.27 (d,
2
5
1H, J = 7.7 Hz, H ), 7.53 (d, 1H, J = 8.5 Hz, H ), 7.60 (dt, 1H,
3
6'
J = 1.8, 7.9 Hz, H ), 8.28 (dd, 1H, J = 2.5, 8.45 Hz, H ), 8.38 (d,
4
5'
13
1H, J = 4.1 Hz, H ), 8.81 (d, 1H, J = 2.5 Hz, H ). C nmr (deu-
6
3'
teriochloroform): 7.2; 40.5; 50.8; 122.2; 124.0; 126.1; 127.8;
134.6; 137.2; 138.8; 146.5; 147.2; 149.7;158.2
'
Anal. Calcd. for C
H N O S: C, 54.89; H, 4.61; N, 9.14
14 14 2 4
Found: C, 54.89; H, 4.64; N, 9.15.
The structure of 18 was confirmed by RX diffraction [14].
2-[4'-Amino-2'-(ethylsulfonyl)benzyl]pyridine (19).
A stirred solution of 18 (2.3 g, 7.5 mmoles) in absolute
methanol (20 ml) was hydrogenated over 10% Pd-C (0.5 g) at
room temperature under atmospheric pressure of H for 2 hours.
2
[4a] R. Hardwick, H. S. Mosher and P. Passailaigue, J. Chem.
Soc., Faraday Trans., 56, 44 (1960); [b] D. Klemm, E. Klemm, J.
Prackt. Chem., 320, 551 (1978).
[5] G. Queguiner, F. Marsais, V. Snieckus and J. Epsztajn,
Adv. Heterocycl. Chem., 52, 187 (1991).
[6] N. Sperber, D. Papa, E. Schwenk and M. Sherlock, M. J.
Am. Chem. Soc., 73, 3856 (1951).
[7] A. J. Nunn and K. Schofield, J. Chem. Soc., 583 (1952).
[8] Y. Eichen, J. M. Lehn, M. Scherl, D. Haarer, J. Fischer, A.
DeCian, A. Corval and H. P. Trommsdorff, Angew. Chem. Int. Ed.
Engl., 34(22), 2530 (1995).
After removal of the catalyst by filtration on celite, the solution
was concentrated in vacuo. The residue was purified by column
chromatography (silica gel, eluted by dichloromethane-ether 1:1)
to give 19 (1.97 g, 7.1 mmoles, 95%) as a white solid crystal, mp
1
107°; H nmr (deuteriochloroform): δ 1.15 (t, 3H, J = 7.4 Hz,
CH ), 3.04 (q, 2H, J = 7.4 Hz, SO CH ), 3.89 (s, 2H, NH ), 4.42
3
2
2
2
(s, 2H, CH ), 6.73 (dd, 1H, J = 2.5, 8.2 Hz), 7.03 (m, 2H), 7.11
2
(d, 1H, J = 7.8 Hz), 7.25 (d, 1H, J = 2.5 Hz), 7.50 (dt, 1H, J =
1.8, 7.7 Hz), 8.42 (d, 1H, J = 4.8 Hz).
Anal. Calcd. for C
H N O S: C, 60.85; H, 5.84; N, 10.14.
14 16 2 2
Found: C, 60.87; H, 5.84; N, 10.10.
[9] J. J. Meyer, P. Levoir and R. Dubest, Analyst, 120,447
(1995).
2-[2'-(Ethylsulfonyl)-4'-nitrobenzyl]pyridine-1-oxide (20).
[10a] S. Sivasubramanian and K. Ravichandran, Indian J.
Chem., 30B, 1148 (1991); [b] S. Ohno, H. Shimizu, T. Kataoka and
M. Hori, J. Org. Chem., 49(13), 2472 (1984).
[11] R. Lüdersdorf and K. Praecke, Z. Naturforsch. B., 3, 1658
(1976).
This compound was prepared by oxidation of 18 (6.12 g)
according to the method B, T = 70°,and t = 8 hours.
Recrystallisation from ethanol of the crude product give 20 (4.83
1
g, 15 mmoles, 75%) as a white solid, mp 188°; H nmr (deuterio-
chloroform): δ 1.17 (t, 3H, J = 7.4 Hz, CH ), 3.53 (q, 2H, J = 7.4
3
[12] J. D. Loudon and D. M. Smith, J. Chem. Soc., 2801
(1964).
Hz, SO CH ), 4.65 (s, 2H, CH ), 7.15-7.35 (m, 3H), 7.41 (d, 1H,
2
2
2
J = 1.0, 6.8 Hz), 8.17 (dd, 1H, J = 1, 5 Hz), 8.24 (dd, 1H, J = 2.4,
8.4 Hz), 8.86 (d, 1H, J = 2.4 Hz).
[13] C. V. T. Campbell, A. Dick, J. Ferguson and J. D. Loudon,
J. Chem. Soc., 747 (1941).
Anal. Calcd. for C
Found: C, 52.16; H, 4.55; N, 8.52.
H N O S: C, 52.17; H, 4.38; N, 8.69
[14] A. Heynderickx, V. Lokshin, V., A. Samat, R. Guglielmetti
and G. Pèpe Z. Kristallogr., 215, 553 (2000).
14 14 2 5