Efficient syntheses of thiophenol derivatives

Article abstract of DOI:10.1055/s-0030-1258058

The photochemical bromination of 4-methylthiophenol with N-bromosuccinimide is reported. Depending on the amount of NBS, mono or bis bromination of the methyl group was obtained. Conversion of brominated derivatives to dialdehydes is also discussed. Impro

Full text of DOI:10.1055/s-0030-1258058

LETTER
2477
Efficient Syntheses of Thiophenol Derivatives
erivativeséric Dumur,*a,b Valérie Roubaud, Eddy Dumas, Cédric R. Mayer
c
b
b
E
F
fficient
S
ynth
r
eses of
éT hiophenol
d
D
a
Laboratoire Chimie Provence, Faculté des Sciences et Techniques, Universités d’Aix-Marseille I, II, III-CNRS UMR 6264,
Equipe CROPS, campus de Saint Jérôme, avenue Escadrille Normandie-Niemen, Case 542, 13397 Marseille Cedex 20, France
Fax +33(4)91288758; E-mail: frederic.dumur@univ-provence.fr
b
c
Institut Lavoisier de Versailles, Université de Versailles Saint Quentin en Yvelines, CNRS UMR 8180,
45 avenue des Etats Unis, 78035 Versailles Cedex, France
Laboratoire Chimie Provence, Faculté des Sciences et Techniques, Universités d’Aix-Marseille I, II, III-CNRS UMR 6264,
Equipe SREP, campus de Saint Jérôme, avenue Escadrille Normandie-Niemen, Case 521, 13397 Marseille Cedex 20, France
Received 16 June 2010
6
cleave. These conditions can suffer from incompatibility
with the stability of the other substituents. On the other
hand, the S-acetyl protection represents an easily cleav-
Abstract: The photochemical bromination of 4-methylthiophenol
with N-bromosuccinimide is reported. Depending on the amount of
NBS, mono or bis bromination of the methyl group was obtained.
Conversion of brominated derivatives to dialdehydes is also dis- able group for thiols. Recently, S-acetyl thioester 1 was
cussed. Improvement of synthetic routes towards thiophenol deriv- successfully used by our group for the grafting of MRI
7
atives is motivated by their key role for the functionalization of
contrast agents onto gold nanoparticles. However, such
protection can suffer from undesired cleavage even when
metal nanoparticles and surfaces.
Key words: photochemistry, halogenation, bromine, thiols, oxida- the thioester protection is exposed to relatively mild acidic
or basic media.6 In this context, a possible alternative
b,8
tion
for the protection of the thiol function is the formation of
the corresponding symmetric disulfide under oxidative
9
conditions. For the functionalization of gold nanoparti-
cles (NPs), the main interest of this strategy is that the
Aromatic thiols are versatile synthetic intermediates in or-
cleavage of disulfides to thiols occurs during the synthesis
ganic chemistry and constitute precursors for the synthe-
10
sis of herbicides, dyes and pharmaceuticals.3
1
2
of the nanoparticles (NPs). Both aliphatic and aromatic
disulfides4 can be employed, even if the use of aromatic
spacers has the advantage of maintaining the functionaliz-
ing agent at known distance from the surface of the parti-
cles. The nature of the linker is also of crucial importance
for the nanocomposites as it determines the possibility of
an electronic communication between the functionalizing
agent and the nanoparticle. In all cases, the most conve-
a,11
Thiophenol derivatives are also extensively used for the
4
5
functionalization of gold nanoparticles, nanorods and
6
surfaces. In these fields, a large variety of protecting
groups have been tested, and the thiol function was nota-
bly protected with tert-butyl, benzoyl or acetyl groups.6,7
If the tert-butyl group provides an efficient protection to
the thiol function, it also requires harsh conditions to
Br
S
O
S
1
2
O
N R
R
i
ii
S
S
2
2
2
R
Br
P(O)OEt2
v
iii
S
S
N
2
2
S
3
2
iv
R
S
2
+
Scheme 1 Possible uses of 2 and 3. Reagents and conditions: (i) HWE reaction, base, RP(O)OEt ; (ii) RNH , catalytic H ; (iii) Arbuzov
2
2
reaction P(OEt) ; (iv) HWE reaction, base, RCHO; (v) R-pyr, heating.
3
SYNLETT 2010, No. 16, pp 2477–2481
x
x
.x
x
.2
0
1
0
Advanced online publication: 19.08.2010
DOI: 10.1055/s-0030-1258058; Art ID: G16910ST
©
Georg Thieme Verlag Stuttgart · New York

2
478
F. Dumur et al.
LETTER
nient functionalization of the thiophenol ring is on the 4- of dialdehyde 2. The simplicity and efficiency of the pro-
position as it reduces the steric hindrance around the thiol cedures presented in this letter to obtain the halogenated
function. Thus, 1,2-bis[4-(formyl)phenyl]disulfane (2) derivatives 3 and 5 and the dialdehyde 2 in one and two
can be used as precursor to generate a conjugated spacer steps, respectively, from 4-methylthiophenol is of partic-
via Horner–Wadsworth–Emmons reaction or imine for- ular interest compared to the multistep procedures of the
mation and 1,2-bis[4-(bromomethyl)phenyl]disulfane (3) literature.
is a versatile intermediate that can be indifferently used as
precursor to generate conjugated or nonconjugated spac-
ers (Scheme 1).
Br
AcS
To date, only few articles describe the synthesis of 1,2-
1
1
2
O
bis[4-(formyl)phenyl]disulfane (2) or 1,2-bis[4-(bro-
S
1
3
momethyl)phenyl]disulfane (3). Thiophenol derivatives
and 3 are indeed suitable intermediates which could be
S
2
O
2
easily used for the functionalization of gold NPs or gold
surfaces but all existing procedures suffer from excessive
synthetic lengths and low overall yields, thus limiting
their use. The synthesis of diformyl disulfide 2 is only re-
ported according to two strategies whose synthetic path-
Br
S
S
Br
3
1
2
ways are outlined in Scheme 2. Notably, the synthesis of
S
dialdehyde 2 in four steps has been reported by Stoddart
S
1
2a
et al. with an overall yield lower than 30%. Previously,
similar strategy investigated by Coombs et al. provided
4
Br
Br
1
2c
Br
Br
S
dialdehyde 2 in 75% yield. Concerning dibromide 3,
S
only one procedure reports its synthesis in low yield
1
3
(
25%) and with tedious purifications.
5
In this context, we developed a simple and efficient one-
Figure 1 Molecules investigated in this letter
pot synthesis to obtain dibromide 3 and tetrabromide 5
(
Figure 1) directly from 4-methylthiophenol using N-bro-
1
,2-Bis[4-(methyl)phenyl]disulfane 4 was generated in
mosuccinimide as oxidizing agent for the formation of the
disulfide and as bromination agent under irradiation. In-
terest of the procedures reported herein is that bromide
compounds 3 and 5 have been obtained as pure com-
pounds simply by recrystallization. Molecules 3 and 5
have been then used as precursors for a one-step synthesis
the first step of the synthesis (Scheme 3). Among the ap-
14
proaches described for the synthesis of disulfides, reac-
tions with DMSO13 or iodine in ethanol are the most
straightforward methods. However, N-bromosuccinimide
15
(
NBS) is also reported as an oxidant for thiols16 and the
synthetic pathway 1:
O
O
O
O
i
ii
S
S
O
S
Me
Me
F3C
iii
O
O
iv
S
HS
S
O
2
synthetic pathway 2:
S
O
O
v
S
S
O
2
synthetic pathway 3:
SH
vi
vii
S
S
Br
S
Br
S
4
3
Scheme 2 Reported synthesis of 2 and 3. Reagents and conditions: (i) (1) m-CPBA; (2) Ca(OH) , 59% overall yield for steps 1 and 2; (ii)
2
Pummerer rearrangement; (1) triflic anhydride; (2) MeOH–Et N; (iii) NH Cl; (iv) I , CH Cl , 50% overall yield for steps 3 and 4; (v) HBr,
3
4
2
2
2
DMSO, 92% yield; (vi) DMSO; (vii) NBS, AIBN, CCl , 25% yield.
4
Synlett 2010, No. 16, 2477–2481 © Thieme Stuttgart · New York

LETTER
Efficient Syntheses of Thiophenol Derivatives
2479
use of one equivalent of NBS converted 4-methylthiophe-
nol to disulfide 5 within a few minutes at room tempera-
ture. This known method of oxidation has the advantages
that the oxidant employed for the dimerization step, NBS,
is the reagent also further used for the bromination step
and that intermediate 4 is not isolated before the synthesis
of 3 or 5.
i
S
SH
S
4
iii
ii
Br
Br
Br
S
Dibromide 3 was selectively prepared by photochemical
bromination of disulfide 4 (Scheme 3). The total amount
of NBS added as well as the addition procedure are among
the parameters that have been optimized for this synthesis
S
Br
Br
5
S
S
Br
(
Table 1). The irradiation time was also adjusted accord-
3
ing to the total amount of NBS added and therefore varied
between one hour and five hours. When the reaction was
carried out by addition of one equivalent of NBS (ratio of yield; (ii) see Table 1, entry 4, 0.3 equiv of NBS added per portion of
Scheme 3 Photochemical synthesis of 3 and 5. Reagents and condi-
tions: (i) NBS (1 equiv), benzene, 20 °C, 20 min, argon, quantitative
the amount of NBS to the amount of 4-methylthiophenol) 0.1 equiv, benzene, reflux under argon, 3 h irradiation, 37%; (iii) see
Table 2, entry 1, 2 equiv of NBS added in one portion, benzene, reflux
under argon, 1 h irradiation, 72%.
in one portion, the desired product 3 and the side product
5
1
were obtained in the same proportions (Table 1, entry
). It should be noted that, despite repeated attempts, we
NBS used for the reaction of dimerization, tetrabromide 5
and dibromide 3 were obtained as a mixture in a ratio of
were unable to separate dibromide 3 and tetrabromide 5
by column chromatography or fractional crystallization.
When the reaction was carried out by four successive ad-
ditions of 0.25 equivalent of NBS, one per hour, followed
by an irradiation of one hour, the proportion of the side
product 5 drastically dropped to 20% (Table 1, entry 2). It
was not possible to markedly further increase the selectiv-
ity of dibromide 3 against tetrabromide 5 by reducing the
total amount of NBS added, by fractioning or slowing the
addition of NBS. By using a different approach, the for-
mation of the side product 5 was reduced when the reac-
tion was ended before the complete conversion of 3. The
reaction was monitored by NMR spectroscopy in order to
optimize the conversion of 3 while maintaining the per-
centage of 5 below 10%. Finally, purification of 3 was
achieved by simple recrystallization from ethanol afford-
9
0:10, after one hour of irradiation (Table 2, entry 1). De-
spite extensive synthetic efforts we were not able to im-
prove the 5:3 ratio. For example, increase of the
irradiation time did not modify this ratio (Table 2, entry 2)
and addition of more equivalents of NBS afforded numer-
ous side products (Table 2, entry 3). Therefore, the best
results were obtained when the reaction was performed
according to the conditions summarized in the Scheme 2.
Finally, after extraction, tetrabromide 5 was readily ob-
tained as a pure compound in 72% yield by recrystalliza-
tion from ethanol.18
Table 2 Optimization of the Reaction Conditions for the Synthesis
of 5
1
7
NBSa
Number of Ratio 3/5c
additions
Conversion
(%)
ing dibromide 3 in 37% yield, without any contamina- Entry
b
d
tion of tetrabromide 5 or disulfide 4.
1
2 equiv
2 equiv
3 equiv
1
1
1
10:90
10:90
100
100
Table 1 Optimization of the Reaction Conditions for the Synthesis
of 3
2b
Entry NBSa
Number of Amount per
additions addition
Ratioc
3/5
Conv.
(%)
3
side-products 100
b
d
a
Amount of NBS added after generation of the disulfide. Reaction
1
2
3
1 equiv
1
4
5
3
1 equiv
50:50
80:20
82:18
92:8
100
100
100
60
was performed in benzene.
b
Irradiation was maintained four hours after addition of NBS.
Ratios were determined by integration of the NMR spectra, before
1 equiv
0.25 equiv
0.10 equiv
0.10 equiv
c
recrystallization from EtOH (see text).
0.5 equiv
0.3 equiv
d
Conversion of 4 determined by integration of the NMR spectra.
4
a
Amount of NBS added after generation of the disulfide. Reaction
Then, dibromide 3 and tetrabromide 5 were used as start-
ing reagents for the synthesis of dialdehyde 2 (Scheme 4).
Oxidation of aryl halide compounds to the corresponding
carbonyl compounds are well documented in the literature
and two of these procedures were tested with 3, namely
the Sommelet reaction with hexamethylenetetramine and
was performed in benzene.
b
One addition every hour followed by one hour of irradiation.
Ratios were determined by integration of the NMR spectra, before
c
recrystallization from EtOH (see text).
d
Conversion of 4 was determined by integration of the NMR spectra.
the oxidation with dimethyl sulfoxide (DMSO) and
The tetrabromination of 4 was also studied (Scheme 3 and
Table 2). When the reaction was carried out using two
equivalents of NBS, in addition to the initial equivalent of
19
NaHCO as auxiliary agent. The mild conversion of 5 in
3
DMSO was also studied as an alternative approach for the
20
synthesis of 2. Among all the different procedures inves-
Synlett 2010, No. 16, 2477–2481 © Thieme Stuttgart · New York

2
480
F. Dumur et al.
LETTER
Br
C. T.; Zhang, Y. X.; Li, R. J.; Li, X. Y.; Jiang, J. Z. J. Org.
Chem. 2007, 72, 2402.
S
S
(3) (a) Hughes, I.; Harper, G. P.; Karran, E. H.; Markwell, R. E.;
Miles-Williams, A. J. Bioorg. Med. Chem. Lett. 1995, 5,
Br
3
3039. (b) Pankratov, A.; Shalabai, A. J. Struct. Chem. 2004,
45, 756. (c) Dubinskii, R. A.; Krivtsova, I. Y.; Grigor’ev, N.
i or ii
B.; Degterev, E. V.; Filimonova, L. D.; Kalinkina, M. A.
Pharm. Chem. J. 1994, 28, 942. (d) Dong, C.-Z.; Ahamada-
Himidi, A.; Plocki, S.; Aoun, D.; Touaibia, M.; Meddad-
Bel Habich, N.; Huet, J.; Redeuilh, C.; Ombetta, J.-E.;
Godfroid, J.-J.; Massicot, F.; Heymans, F. Bioorg. Med.
Chem. 2005, 13, 1989 .
O
S
S
O
2
(
4) (a) Mayer, C. R.; Cucchiaro, G.; Jullien, J.; Dumur, F.;
iii
Marrot, J.; Dumas, E.; Sécheresse, F. Eur. J. Inorg. Chem.
2
008, 3614. (b) Krüger, C.; Agarwal, S.; Greiner, A. J. Am.
Br
Br
Chem. Soc. 2008, 130, 2710. (c) Dumur, F.; Mayer, C. R.;
Hoang-Thi, K.; Ledoux-Rak, I.; Miomandre, F.; Clavier, G.;
Dumas, E.; Méallet-Renault, R.; Frigoli, M.; Zyss, J.;
Sécheresse, F. Inorg. Chem. 2009, 48, 8120.
Br
Br
S
S
5
(
(
5) Nikoobakht, B.; Jianping, W.; El-Sayed, M. A. Chem. Phys.
Lett. 2002, 366, 17.
6) (a) Garg, N.; Carrasquillo-Molina, E.; Lee, T. R. Langmuir
Scheme 4 Synthesis of dialdehyde 2 from 3 and 5. Reagents and
conditions: (i) NaHCO , DMSO, 115 °C, argon, 30 min, 61%; (ii)
3
hexamethylenetetramine, THF–aq AcOH, reflux, 16 h, 75%; (iii)
DMSO, 120 °C, 12 h, 53%.
2
002, 18, 2717. (b) Weibel, N.; Blazczyk, A.; von Hänisch,
C.; Mayor, M.; Pobelov, I.; Wandlowski, T.; Chen, F.; Tao,
N. Eur. J. Org. Chem. 2008, 136.
tigated, the Sommelet reaction proved to be the most effi-
(
7) (a) Moriggi, L.; Cannizzo, C.; Dumas, E.; Mayer, C. R.;
Ulianov, A.; Helm, L. J. Am. Chem. Soc. 2009, 131, 10828.
(b) Gurbhele-Tupkar, M. C.; Perez, L. R.; Silva, Y.; Lees,
W. J. Bioorg. Med. Chem. 2006, 16, 2579.
cient and afforded 2 in 75% yield, after purification by
2
1
column chromatography.
For higher simplicity and applicability of our procedures,
all reactions of conversion of 3 and 5 to dialdehyde 2 were
tested without purification of dibromide 3 and tetrabro-
mide 5, directly after aqueous workups, thus rendering the
synthesis of 2 more straightforward.
(8) (a) Pearson, D. L.; Tour, J. M. J. Org. Chem. 1997, 62,
1376. (b) Dumur, F.; Dumas, E.; Mayer, C. R. unpublished
results.
(9) (a) Joshi, A. V.; Bhusare, S.; Baidossi, M.; Qafisheh, N.;
Sasson, Y. Tetrahedron Lett. 2005, 46, 3583. (b) Kosmrlj,
J.; Kocevar, M.; Polanc, S. J. Chem. Soc., Perkin Trans. 1
In summary, we have developed a convenient and effi-
cient approach to synthesize disulfides 2, 3 and 5 from 4-
methylthiophenol. NBS was used both as the oxidizing
agent for the formation of the disulfide bond and as the
bromination agent. By controlling the total amount of
NBS added and the addition rate of NBS dibromide 3 and
new compound tetrabromide 5 were selectively prepared
in a straightforward procedure. Compounds 3 and 5 were
then successfully used to obtain dialdehyde disulfide 2 in
a one-step synthesis and the most efficient approach
proved to be the Sommelet reaction starting from dibro-
mide 3. These results, combined with the simplicity of the
isolation and of the purification procedures, make these
approaches competitive with the multistep syntheses de-
scribed in the literature.
1
998, 3917. (c) Shinkai, S.; Yamada, S.; Kunitake, T.
J. Polym. Sci: Polym. Lett. Ed. 1977, 16, 137.
(10) (a) Ionita, P.; Caragheorgheopol, A.; Gilbert, B. C.; Chechik,
V. J. Am. Chem. Soc. 2002, 124, 9048. (b) Werts, M. H. V.;
Zaim, H.; Blanchard-Desce, M. Photochem. Photobiol. Sci.
2
004, 3, 29. (c) Ionita, P.; Caragheorgheopol, A.; Gilbert, B.
C.; Chechik, V. Langmuir 2004, 20, 11536. (d) Garg, N.;
Carrasquillo-Molina, E.; Randall Lee, T. Langmuir 2002,
18, 2717.
(11) (a) Kruger, C.; Agarwal, S.; Greiner, A. J. Am. Chem. Soc.
2008, 130, 2710. (b) Nikoobakht, B.; Wang, J.; El-Sayed,
M. A. Chem. Phys. Lett. 2002, 366, 17.
(
12) (a) Lowe, J. N.; Fulton, D. A.; Chiu, S.-H.; Elizarov, A. M.;
Cantrill, S. J.; Rowan, S. J.; Fraser Stoddart, J. J. Org. Chem.
2
004, 69, 4390. (b) Dickman, D. A.; Chemburkar, S.;
Konopacki, D. B.; Elisseou, E. M. Synthesis 1993, 573.
c) Young, R. N.; Gaultier, J. Y.; Coombs, W. Tetrahedron
(
Lett. 1984, 25, 1753.
13) Miao, Z.; Liu, J.; Norman, T.; Driver, R. Int. Patent,
(
Acknowledgment
WO 2006069246, 2006.
(
(
14) Witt, D. Synthesis 2008, 2491.
Authors would like to thank Prof. Sylvain R. A. Marque for helpful
discussions about photochemistry, the C’NANO IdF, CNRS, and
the ANR agency (ANR-07-JCJC-040, AURUS program) for finan-
cial support.
15) De Martino, G.; La Regina, G.; Coluccia, A.; Edler, M. C.;
Barbera, M. C.; Brancale, A.; Wilcox, E.; Hamel, E.; Artico,
M.; Silvestri, R. J. Med. Chem. 2004, 47, 6120.
16) Bagheri, M.; Azizi, N.; Saidi, M. R. Can. J. Chem. 2005, 83,
(
146.
References and Notes
(17) Procedure for the Synthesis of 1,2-Bis[4-(bromomethyl)-
phenyl]disulfane (3; Table 1, Entry 4): NBS (0.8 g, 4.49
mmol) was added to a solution of 4-methylthiophenol (0.56
g, 4.49 mmol) in benzene (5 mL). The solution was
(
1) Yang, G. F.; Lu, R. J.; Fei, X. N.; Yang, H. Z. Chin. J. Chem.
000, 18, 435.
2
(
2) (a) Jiang, W.; Fu, Q.; Fan, H.; Ho, J.; Wang, W. Angew.
Chem. Int. Ed. 2007, 46, 8445. (b) Rohr, H.; Trieflinger, C.;
Rurack, K.; Daub, J. Chem. Eur. J. 2006, 12, 689. (c) Zhao,
deaerated with argon for 20 min during which time p-tolyl
disulfide (4) formed. NBS (0.08 g, 0.449 mmol, 0.1 equiv)
Synlett 2010, No. 16, 2477–2481 © Thieme Stuttgart · New York

LETTER
was added and the reaction mixture was irradiated for 1 h
Efficient Syntheses of Thiophenol Derivatives
2481
of bromine disappeared. The organic phase was washed
with a 250-W tungsten lamp, placed next to the flask, which
provided sufficient energy to reflux the solvent. Two other
portions of NBS (0.08 g, 0.449 mmol) were successively
added followed by 1 h of irradiation after each addition.
After cooling, succinimide precipitated and was removed by
filtration. The filtrate was then concentrated under reduced
pressure. The residue was diluted with CH Cl (100 mL) and
twice with H O (2 × 20 mL), dried over MgSO and the
2
4
solvent was removed under reduced pressure. NMR
spectrum of the crude reaction mixture showed a mixture of
5:3 in the ratio 90:10. The residue was then purified by
recrystallization from EtOH. Tetrabromide 5 was isolated
1
pure as a light-brown solid (0.908 g, 72% yield). H NMR
(400 MHz, CDCl ): d = 6.61 (s, 2 H), 7.47 (d, 4 H, J = 8.6
2
2
3
1
3
the organic phase was washed with diluted sodium
Hz), 7.52 (d, 4 H, J = 8.6 Hz). C NMR (100 MHz, CDCl ):
3
thiosulfate until the brown color of bromine disappeared.
d = 39.9, 126.8, 127.3, 138.6, 140.8. Anal. Calcd for
The organic phase was washed twice with H O (2 × 20 mL),
C H Br S : C, 29.92; H, 1.79; S, 11.41. Found: C, 30.19;
2
14 10
4 2
dried over MgSO and the solvent was removed under
H, 2.16; S, 11.61.
4
reduced pressure. NMR spectrum of the brownish solid
showed a mixture of 3 and 5 in a ratio of 92:8.
(19) (a) Jin, J.-Y.; Jin, Z.-Z.; Xia, Y.; Zhou, Z.-Y.; Wu, X.; Zhu,
D.-X.; Su, Z.-M. Polymer 2007, 48, 4028. (b) Shao, P.; Li,
Z.; Luo, J.; Wang, H.; Qin, J. Synth. Commun. 2005, 35, 49.
(20) Li, W.; Li, J.; DeVincentis, D.; Mansour, T. S. Tetrahedron
Lett. 2004, 45, 1071.
(21) Procedure for the Synthesis of 1,2-Bis[4-(formyl)-
phenyl]disulfane (2; Sommelet Reaction): aq AcOH
(50%, 20 mL) was added to a mixture of 3 (0.50 g, 1.24
mmol), and hexamethylenetetramine (0.69 g, 4.8 mmol) in
THF (10 mL). The mixture was refluxed overnight. The
Recrystallization from EtOH yielded 3 pure as a white solid
1
(
334 mg, 37% yield). H NMR (400 MHz, CDCl ): d = 4.46
3
(
s, 4 H), 7.33 (d, 4 H, J = 8.3 Hz), 7.45 (d, 4 H, J = 8.3 Hz).
C NMR (100 MHz, CDCl ): d = 32.7, 127.5, 129.8, 136.9,
37.2. Anal. Calcd for C H Br S : C, 41.60; H, 2.99; S,
1
3
3
1
14 12 2 2
15.87. Found: C, 41.58; H, 3.10; S, 16.18.
(
18) Procedure for the Synthesis of 1,2-Bis[4-(dibromo-
methyl)phenyl]disulfane (5; Table 2, Entry 1): NBS (0.8
g, 4.49 mmol) was added to a solution of 4-methylthiophenol
solution was then diluted with H O (20 mL) and extracted
2
(
0.56 g, 4.49 mmol) in benzene (5 mL). The solution was
with CH Cl (2 × 20 mL). The organic phases were
2
2
deaerated with argon for 20 min during which time p-tolyl
disulfide 4 formed. Then NBS (1.6 g, 8.98 mmol, 2 equiv)
was added in one portion and the reaction mixture was
irradiated for 1 h. After cooling, succinimide precipitated
and was removed by filtration. The filtrate was then
concentrated under reduced pressure. The residue was
diluted with CH Cl (100 mL) and the organic phase was
combined, dried over MgSO and the solvent was finally
4
removed under reduced pressure. Purification by column
chromatography (silica gel, CH Cl ) afforded dialdehyde 2
2
2
as a colorless solid (0.254 g, 75% yield). NMR
characterizations were consistent with the literature (see
1
2
1
ref. ). H NMR (400 MHz, CDCl ): d = 7.61 (d, 4 H, J = 8.4
3
1
3
Hz), 7.81 (d, 4 H, J = 8.4 Hz), 9.95 (s, 2 H, CHO). C NMR
2
2
washed with diluted sodium thiosulfate until the brown color
(100 MHz, CDCl ): d = 126.2, 130.3, 135.1, 143.7, 190.9.
3
Synlett 2010, No. 16, 2477–2481 © Thieme Stuttgart · New York