Microwave-assisted simple and efficient ligand free copper nanoparticle catalyzed aryl-sulfur bond formation

Article abstract of DOI:10.1002/adsc.200700289

A new protocol for the coupling of aryl iodides with thiophenols and alkanethiols catalyzed by copper nanoparticles under ligand-free condition has been developed. A variety of functionalized aryl sulfides are prepared in excellent yields under microwave irradiation for 5-7 min. A plausible radical mechanism has been suggested.

Full text of DOI:10.1002/adsc.200700289

FULL PAPERS
DOI: 10.1002/adsc.200700289
Microwave-Assisted Simple and Efficient Ligand Free Copper
Nanoparticle Catalyzed Aryl-Sulfur Bond Formation
a,
a
a
Brindaban C. Ranu, * Amit Saha, and Ranjan Jana
a
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata – 700032, India
Fax : (+91)-33-2473-2805; e-mail: ocbcr@iacs.res.in
Received: June 13, 2007; Revised: August 31, 2007; Published online: November 21, 2007
Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: A new protocolfor the coup il ng of arylio-
wave irradiation for 5–7 min. A plausible radical
dides with thiophenols and alkanethiols catalyzed by mechanism has been suggested.
copper nanoparticles under ligand-free condition has
been developed. A variety of functionalized aryl sul- Keywords: aryl-sulfur bond; catalysis; copper nano-
fides are prepared in excellent yields under micro- particles; microwave heating; thioethers; thiols
Introduction
The formation of the aryl-sulfur bond is of much im-
portance because of the prevalence of this bond in
many molecules of pharmaceutical and material inter-
[
1]
est and the utility of aryl sulfides as intermediates in
Scheme 1.
[2]
organic synthesis. The classical method for the syn-
thesis of aryl sulfides involved condensation of aryl
[
6e]
halides with thiols requiring strongly basic and harsh high temperature (>2008C) and long reaction time.
[
3]
reaction conditions. However, such methods are not Hence, there is a need for improved procedures for
desirable for molecules containing sensitive functional this important reaction. We report here a novel
groups. The development of transition metal-cata- ligand-free protocol for the condensation of aryl io-
lyzed coupling has overcome these difficulties to a dides with thiols using nano copper (20 mol%) under
[4]
great extent. A number of methods have been re- microwave irradiation in the presence of a base
ported for the synthesis of arylaryland aryla kl ylsu -l
fides using palladium, copper, cobalt and other
(Scheme 1).
[
5]
[6]
[7]
A few ligand-free processes were also reported,
metal catalysts. The various palladium compounds such as coupling of arylboronic acid with thiopheno-
[
5a]
[8a]
[8b]
used are Pd
A
C
H
T
R
E
U
N
G
(OAc) /CyPF-t-Bu (Josiphos ligand),
l
and N-thioimides, catalyzed by Cu(OAc) , and
A
T
E
N
2
2
[
5b]
Pd (dba) /xantphos,
A
C
H
T
R
E
U
N
G
[Pd
A
H
R
U
G
2
3
2
[5c]
[5d]
[8c]
ligand,
Pd
A
C
H
T
R
E
U
N
G
(dba) /DPE-phos
among others. The microwave heating (2–6 h).
2
3
prominent copper catalysts include CuI/1,1,1-tris(hy-
[
6a]
[6b]
droxymethyl)ethane, CuI/amino acid, CuI/neocu-
[6c]
[6d]
[6e,f]
proine, CuI/HOCH CH OH, metallic Cu,
A cobalt-catalyzed reaction in the
presence of a ligand, Col (dppe) and Zn have also The experimentalprocedure is very simp el and conven-
2
been reported recently. In general, all these methods ient. A mixture of an aryl iodide and thiophenol/alkane-
involved a metal salt and a ligand other than a base thiolin DMF was treated under microwave irradiation
and solvent. Moverover, the high cost and air sensitiv- with K CO and Cu nanoparticles (4–6 nm, Figure 1 and
ity of Pd catalyst systems and often tedious proce- Figure 2). Usualwork-up provided the product. In ab-
dures for the preparation of ligands restrict their ap- sence of a base, the progress of the reaction was only
plications in large-scale processes. On the other hand, marginal. Although any conventional base such as
Cu-mediated reactions sometimes require the use of Na CO , K CO , K PO , NaOH may be used, K CO
3
and Results and Discussion
2
2
[6g]
CuBr/P -Et.
2
A
H
R
U
G
[
7]
2
3
[
9]
2
3
2
3
3
4
2
copper salts in a more than stoichiometric amount, was chosen giving better results in terms of yields.
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Ligand Free Copper Nanoparticle Catalyzed Aryl-Sulfur Bond Formation
FULL PAPERS
alkyl sulfides. The results are summarized in Table 1.
Both electron-donating and electron-withdrawing
group-substituted aryliodides participated in this re-
action with similar efficiency. The substitution at the
ortho position (entries 4, 6, 8, 17, Table 1) did not
affect the reaction. The coupling also proceeded well
with substituted thiophenols and alkanethiols. This re-
action is also very chemoselective. Aryl iodides cou-
pled with thiols without affecting bromo and chloro
groups present in the arylring (entries 8, 11, Tab el 1).
However, in coupling of p-nitroiodobenzene (entry 7,
Table 1) a small amount (5%) of product with the
nitro group reduced to amino was obtained.
In general, the reactions were very clean and high
yielding. However, in several reactions (entries 6, 8,
13–16) small amounts (2–5%) of diaryl/dialkyl disul-
fides were isolated, which were easily separated
during purification by column chromatography. In the
absence of Cu nanoparticles the coupling reaction
was not initiated at all. It was found that 20 mol% of
Cu nanopaticles provided the best results in terms of
reaction time and yield. When the reaction was car-
ried out at 1208C by conventionalheating, it required
Figure 1. TEM image of Cu nanoparticles.
1
2–15 h to be completed, whereas under microwave
irradiation the reactions were complete within 5–
min. DMF was found to be the solvent of choice
7
furnishing best results among other solvents such as
toluene and THF. The reaction medium is mild
enough to tolerate a variety of functional groups such
as OMe, OH, Cl, Br, NH etc.
2
To check the efficiency of this reaction catalyzed by
copper nanoparticles, a comparison of results of a few
representative reactions by other similar Cu-mediated
procedures is presented in Table 2. It was found that
the reactions which were carried out by using 300
mol% of metallic copper in an autoclave at 2408C for
[
6e]
6
h
were accomplished by the present procedure
using 20 mol% of Cu nanoparticles at 120 8C under
microwave heating for 5 min in better yields (en-
tries 1–3, Table 2). Another reaction (entry 4, Table 2)
took 2 h under microwave heating at 1958C using 10
[
8c]
mol% of CuI, whereas nano Cu (20 mol%) accom-
plished it in 5 min under microwave heating at 1208C
in improved yield. The coupling of m-methoxyiodo-
benzene with p-chlorothiophenol was achieved at
8
08C in the presence of 5 mol% CuI and 2 equiva-
[
6d]
lents of ethylene glycol for 18 h; however the same
reaction was carried out at 1208C under microwave
heating in 5 min by 20 mol% of Cu nanoparticles
without the requirement of any ligand or additive. A
comparison of results of a few representative reac-
tions using Cu powder with those using nano Cu
under microwave irradiation, as presented in Table 3,
showed significant increases in yields of products in
Figure 2. Energy dispersive X-ray spectra of Cu nanoparti-
cles.
Severaldiverse yl substituted aryliodides underwent
reactions with a variety of substituted thiophenols, nano Cu-catalyzed reactions compared to those cata-
benzylmercaptan, butane- and dodecanethio sl by this lyzed by Cu powder, indicating a key role of Cu at
procedure to produce the corresponding diaryl/aryl the nano stage.
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Brindaban C. Ranu et al.
FULL PAPERS
[a]
Table 1. Cross-coupling reaction of aryl iodides with thiols catalyzed by Cu nanoparticles.
[
a]
General reaction conditions: aryl iodide (1 mmol) and thiophenol (1.1 mmol) in DMF (0.8 mL) were subjected to micro-
wave irradiation at 1208C in presence of K CO (2 mmol) and nano Cu (20 mol%, optimized to give best yields).
Yields refer to those of purified products characterized by IR, H, and C NMR spectroscopic data.
Diaryl/dialkyl disulfides (2–5%) were isolated together with the desired product, the aryl sulfide.
The amino derivative (5%) was produced from reduction of the nitro group.
2
3
[
[
[
[
b]
c]
d]
e]
1
13
The reaction was carried out at 908C under microwave irradiation.
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Ligand Free Copper Nanoparticle Catalyzed Aryl-Sulfur Bond Formation
FULL PAPERS
Table 2. Comparison of results of reactions using metallic Cu, CuI, CuI/(CH OH) with Cu nanoparticles.
A
H
R
U
G
2 2
To provide a mechanistic rationale of this nano Cu- observed that when the reaction was carried out in
catalyzed coupling of aryl iodides and thiols, a tenta- the presence of 2,2,6,6-tetramethylpiperidine N-oxide
tive pathway was proposed based on some experimen- (TEMPO), a radicalquencher, under identialreaction
tal findings. In a metallic copper-catalyzed coupling conditions, the reaction was substantially (>60%) ar-
[
6e]
reaction of thiophenols with aryl halides Yamamoto
rested. Thus, a radicalpathway may be a possib ii lt y.
postulated an intermediate of diaryl disulfide which Two possible routes were considered (Scheme 2, paths
then led to the diaryl sulfide. To check the involve- a and b). In path a, Cu initiates the redicalchain pro-
[
11]
ment of this intermediate in our reaction, a coupling cess by transferring its one electron to ArI to form
reaction of aryliodide with diphenyldisu fl ide was car-
ried out under identicalreaction conditions. However,
an Ar radicalwhich then combines with RSH to pro-
vide the product ArSR and an H radicalwhich propa-
no reaction occurred and the starting materials re- gates the process (Scheme 2, path a). However, we
mained unaffected. Thus, the possiblity of this path- did not isolate any biaryl compound, ArÀAr or ArH
way was ruled out. It may be recalled that the pro- in any amount from this reaction, which is usually ex-
gressive decrease in size of metalpartic el s having a
pected from this type of free radicalreaction. Our at-
diameter in the nano range is accompanied by an in- tempts to trap this Ar radicalby an e el ctron-deficient
crease in Fermi potential. Thus, a stepwise lowering unit also failed. This led us to explore the possibility
in the radox potentialv au le takes pa lce and this
makes it easier for a nano particle to transfer elec- electron to the thiol to produce the RS radical which
of an alternative path b where nano Cu transfers its
[
10]
trons to other species.
Hence, the possibility of a then, in interaction with ArI, forms the product,
single eletron transfer process is considered. It was ArSR releasing an iodo radical. The iodo radical then
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Brindaban C. Ranu et al.
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Table 3. Comparison of results of coupling reactions using Cu nanoparticles and metallic Cu powder under microwave irradi-
ation.
propagates the process forming a fresh RS radical. If methodology for the coupling of aryl iodides and thio-
the reaction takes this course CuH should be pro- phenols. To the best of our knowledge this is the first
duced in the intiale el ctron transfer reaction of Cu
report of aryl-sulfur bond formation using nano Cu.
nanoparticles. The evidence of the formation of CuH The significant improvements offered by this proce-
is now substantiated by an observation of reduction dure are operational simplicity, no involvement of
of the nitro group in the reaction of p-nitroiodoben- ligand, general applicability to both aromatic and ali-
[
12]
zene with p-methylthiophenol (entry 7, Table 1), as phatic thiols, fast reaction (5–7 min) and comparative-
mentioned earlier. The formation of CuH in this pro- ly high isolated yields of products. Moreover, this
cess is also confirmed by a reaction of thiophenol work demonstrates the potentialof Cu nanopartic el s
with m-nitrotoluene in place of iodobenzene under in carbon-heteroatom bond formation, which is less
identicalreaction conditions producing m-toluidine explored compared to CÀC bond formation involving
[
22]
and diphenyl disulfide. This route also gains support nano metals.
by isolation of 2–5% of disulfides, ArSÀSAr in sever-
alreactions (entries 6, 8, 13–16). The HI produced
during the reaction was neutralized by K CO . The Experimental Section
2
3
mechanism in path b is also supported by the fact that
the RS radicalis ol gicalto favour the formation of
RSAr through SÀC bond rather than RSSR by SÀS
IR spectra were taken as thin films for liquid compounds
and as KBr pellets for solids on a FT-8300 Shimadzu spec-
trometer. NMR spectra were recorded on a Bruker DPX
bond formation because of the greater stability of the
SÀC bond compared to the SÀS bond, as indicated by
the larger value of relative free energy for SÀC bond
1
3
00 instrument at 300 MHz for H NMR and at 75 MHz for
1
3
C NMR in CDCl solutions. A mono-mode microwave re-
3
actor, manufactured by CEM Corporation, USA was used.
scission (approx. 108 kcal/mol) in diphenyl sulfide
compared to SÀS bond scission (47 kcal/mol) in di-
[21]
phenyldisu fl ide.
In view of these findings, path b is Coupling of Iodobenzene with Thiophenol; Typical
suggested as the possible pathway.
Procedure (entry 1, Table 1)
To a solution of iodobenzene (204 mg, 1 mmol) and thiophe-
nol(121 mg, 1.1 mmo )l in DMF (0.8 mL) was added K 2CO3
Conclusions
(
276 mg, 2 mmol) and copper nanoparticles (13 mg, 20
mol%) and the mixture was subjected to irradiation in a mi-
In conclusion, the present procedure using copper crowave reactor (CEM, Discover, USA) at 1208C (250 W)
nanoparticles provides a very efficient and convenient for 5 min (as monitored by TLC). The reaction mixture was
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Ligand Free Copper Nanoparticle Catalyzed Aryl-Sulfur Bond Formation
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2
-Dodecylsulfanyl-phenylamine (entry 17, Table 1): Col-
orless liquid: R : 0.65; IR: n=2926, 2854, 1606, 1479,
f
À1
1
1
1
7
448 cm ; H NMR: d=7.39–7.36 (m, 1H), 7.14–7.09 (m,
H), 6.80–6.69 (m, 2H), 4.24 (broad, 2H), 2.74 (t, J=
.32 Hz, 2H), 1.61–1.51 (m, 2H), 1.39–1.25 (m, 18H), 0.88
1
3
(
t, J=6.92 Hz, 3H); C NMR: d=147.28, 135.68, 129.49,
1
2
2
19.29, 116.29, 115.54, 35.11, 32.06, 29.85, 29.79, 29.77, 29.73,
9.67, 29.49, 29.33, 28.86, 22.84, 14.27; HR-MS: m/z=
+
94.2247, calcd. for C H NS (M+1) : 294.2255.
1
8
32
This procedure was followed for all the reactions listed in
Table 1. Although the representative procedure is based on
mmol scale reactions, it has been scaled up to gram quanti-
ties with reproducible results.
Supporting Information
1
13
Characterization data including H NMR and C NMR
spectra of all the products listed in Table 1 are available as
Supporting Information.
Acknowledgements
We are pleased to acknolwedge the financial support from
CSIR, New Delhi [Grant No. 01(1936)/04] for this investiga-
A
H
R
U
G
tion. A.S. and R.J. are also thankful to CSIR for their fellow-
ships.
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