Novel formation of iodobenzene derivatives from 1-(methylthio)-3-tosylhexa- 1,3-dien-5-ynes via iodine-induced intramolecular cyclization

Article abstract of DOI:10.1021/jo701976q

(Chemical Equation Presented) The reaction of (1E,3E)-1-(methylthio)-3- tosylhexa-1,3-dien-5-ynes (3) with iodine to form iodine-substituted benzenes (4) is reported. The reaction of 3 with iodine proceeded very slowly, but UV irradiation accelerates the

Full text of DOI:10.1021/jo701976q

Novel Formation of Iodobenzene Derivatives from
1-(Methylthio)-3-tosylhexa-1,3-dien-5-ynes via Iodine-Induced
Intramolecular Cyclization
Shoji Matsumoto, Kenji Takase, and Katsuyuki Ogura*
Department of Applied Chemistry and Biotechnology, Graduate School of Engineering, Chiba UniVersity,
1-33 Yayoicho, Inageku, Chiba 263-8522, Japan
katsuyuki@faculty.chiba-u.jp
ReceiVed September 8, 2007
The reaction of (1E,3E)-1-(methylthio)-3-tosylhexa-1,3-dien-5-ynes (3) with iodine to form iodine-
substituted benzenes (4) is reported. The reaction of 3 with iodine proceeded very slowly, but UV irradiation
accelerates the reaction to give 4 in high-to-excellent yields. Irradiation induces the cis-trans isomerization
of the C1-C2 double bond, leading to the (1Z,3E)-geometric isomer (3′), which easily reacts with iodine
to afford 4. This reaction is applicable to 3-(methoxycarbonyl)-1-(methylthio)-6-phenylhexa-1,3-dien-
5-yne (11), which is synthesized as a geometric mixture. Interestingly, this mixture can be used as the
starting material. Irradiation of the mixture (the geometric isomer ratio ) 50:28:5:17) with iodine resulted
in the formation of methyl 3-iodo-4-phenylbenzoate (12) in 80% yield.
Introduction
of iodinated polyenyne derivatives,5-7 and (4) 6-endo-dig
electrophilic cyclization of alkyne derivatives (eq 1).8
Haloarenes constitute an important class of molecules in
synthetic organic chemistry. Especially, iodoarenes form a
carbon-carbon bond via a catalytic cross-coupling reaction1 so
efficiently that they are used as potential intermediates for
synthesizing naturally occurring products, biologically active
compounds, and functional materials.2 Various reactions leading
to iodoarenes have been reported: (1) direct iodination of
aromatic precursors,3 (2) light-induced cyclization of 1-aryl-1-
alken-3-ynes in the presence of iodine,4 (3) catalytic cyclizations
We were interested in the fourth reaction (eq 1) from the
viewpoint that an iodonium intermediate reacts intramolecularly
(3) Review: (a) Merkushev, E. B. Synthesis 1988, 923-937. Recent
reports: (b) Yang, S. G.; Kim, Y. H. Tetrahedron Lett. 1999, 40, 6051-
6054. (c) Branytska, O. V.; Neumann, R. J. Org. Chem. 2003, 68, 9510-
9512. (d) Adimurthy, S.; Ramachandraiah, G.; Ghosh, P. K.; Bedekar, A.
V. Tetrahedron Lett. 2003, 44, 5099-5101. (e) Ghorbani-Vaghei, R.
Tetrahedron Lett. 2003, 44, 7529-7532. (f) Alexander, V. M.; Khandekar,
A. C.; Samant, S. D. Synlett 2003, 1895-1897. (g) Iskra, J.; Stavber, S.;
Zupan, M. Synthesis 2004, 1869-1873. (h) Wan, S.; Wang, S. R.; Lu, W.
J. Org. Chem. 2006, 71, 4349-4352.
(4) Tinnemans, A. H. A.; Laarhoven, W. H. Tetrahedron Lett. 1973,
817-820.
(5) Miura, T.; Iwasawa, N. J. Am. Chem. Soc. 2002, 124, 518-519.
(6) Shen, H.-C.; Pal, S.; Lian, J.-J.; Liu, R.-S. J. Am. Chem. Soc. 2003,
125, 15762-15763.
(1) (a) Tsuji, J. Palladium Reagents and Catalysts; John Wiley & Sons:
Chichester, UK, 1999. (b) Suzuki, A.; Brown H. C. Organic Synthesis Via
Boranes: Suzuki Coupling; Aldrich Chemical Co. Inc.: Milwaukee, WI,
2003; Vol. 3. (c) Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457-
2483. (d) Hassan, J.; Se´vignon, M.; Gozzi, C.; Schulz, E.; Lemaire, M.
Chem. ReV. 2002, 102, 1359-1469. (e) Corbet, J. -P.; Mignani, G. Chem.
ReV. 2006, 106, 2651-2710.
(2) (a) Seevers, R. H.; Counsell, R. E. Chem. ReV. 1982, 82, 575-590.
(b) Larock, R. C.; Lee, N. H. J. Org. Chem. 1991, 56, 6253-6254. (c)
Swenton, J. S.; Callinan, A.; Wang, S. J. Org. Chem. 1992, 57, 78-85. (d)
Nicolaou, K. C. Angew. Chem., Int. Ed. Engl. 1993, 32, 1377-1385. (e)
Tatko, C. D.; Waters, M. L. Org. Lett. 2004, 6, 3969-3972.
10.1021/jo701976q CCC: $40.75 © 2008 American Chemical Society
Published on Web 02/02/2008
1726
J. Org. Chem. 2008, 73, 1726-1731

NoVel Formation of Iodobenzene DeriVatiVes
SCHEME 1. Strategy for Iodobenzene Formation
SCHEME 2. Preparation of Dienyne Compound 3a
with a benzene ring as a nucleophile to give various iodinated
polyarenes. The iodonium intermediate is formed by the attack
of iodonium ion on the triple bond. We would obtain iodoben-
zene derivatives (II) that have substituent(s) at the optional
position(s) if this reaction were extended to a 1,3-alkadien-5-
yne system (I). To achieve the expected reaction, a few problems
must be overcome: the first is how to synthesize the starting I.
In addition, it is important to force I to adopt the conformation
around the C-C single bond that is suitable for cyclization
(Scheme 1).
Recently, we reported the cyclization reaction of 4-aryl-1-
(methylthio)-3-tosylbuta-1,3-dienes (1) with iodine to give the
corresponding naphthalenes (2) (eq 2).9 In this cyclization, the
methylthio group acts as a leaving group and the tosyl group
compels the geometry of the C3-C4 double bond to be E.9,10
Herein, we wish to report the first example for the iodine-
induced cyclization of 1-(methylthio)-3-tosylhexa-1,3-dien-5-
ynes (3) and its related compounds (eq 3).
TABLE 1. Iodobenzene Ring Formation of 3a with Iodine under
Thermal Conditions
molar
equiv
entry
of I2
solvent
conditions
yield (%)
1
2
3
4
5
0.5
0.5
1.0
1.0
1.0
CH3CN rt, 17 h
CH3CN 40 °C, 6 days f reflux, 3 days
CH3CN 40 °C, 22 h
trace
6
trace
33
CHCl3
toluene
rt, 2 days f reflux, 4 days
80 °C, 5 days
53
SCHEME 3. Reaction of 3a with Iodine under UV
Irradiation
Results and Discussion
sequence, 3a was obtained as a single geometric isomer. Using
the analogy of the previous results, the geometry of 3a was
assigned as E,E.9,10
First, we investigated the iodine-induced reaction of 6-phenyl-
1-(methylthio)-3-tosylhexa-1,3-dien-5-yne (3a), which was pre-
pared by a procedure similar to the synthesis of 1:9 the
condensation of (E)-1-(methylthio)-3-tosylpropene (5) with
3-phenylpropynal (6), as shown in Scheme 2. After the lithiated
5 was added to 6, acetylation with acetic anhydride and the
subsequent treatment with triethylamine gave 3a. In this reaction
The thus-obtained 3a was subjected to reaction with iodine.
The expected reaction to form 2-iodo-4-tosyl-1,1′-biphenyl (4a)
took place at an elevated temperature (40-80 °C). The yield
of 4a was low in all cases examined (Table 1). The best yield
of 53% was attained using the reaction in toluene at 80 °C for
5 days (entry 5). The spectroscopic data (1H NMR and IR) and
elemental analysis were consistent with the structure of 4a.
Finally, the structure 4a was confirmed by single-crystal X-ray
crystallography.
It is noteworthy that the reaction of 3a under thermal
conditions required a long period of reaction time. This is
probably true because 3a mainly adopts the conformation that
disfavors the cyclization. Next, we irradiated the solution of 3a
and iodine in expectation either that the excitation of 3a would
assist the cyclization reaction or that isomerization of the olefinic
linkage(s) would occur photochemically to form the geometric
isomer suitable to the cyclization. To our delight, 4a was formed
quantitatively when a solution of 3a and iodine (1.0 molar equiv)
(7) Yamamoto, Y.; Hattori, K.; Nishiyama, H. J. Am. Chem. Soc. 2006,
128, 8336-8340.
(8) (a) Goldfinger, M. B.; Swager, T. M. J. Am. Chem. Soc. 1994, 116,
7895-7896. (b) Goldfinger, M. B.; Crawford, K. B.; Swager, T. M. J. Am.
Chem. Soc. 1997, 119, 4578-4593. (c) Yao, T.; Campo, M. A.; Larock, R.
C. J. Org. Chem. 2005, 70, 3511-3517. (d) Zhang, X.; Sarkar, S.; Larock,
R. C. J. Org. Chem. 2006, 71, 236-243. (e) Barluenga, J.; Va´zquez-Villa,
H.; Merino, I.; Ballesteros, A.; Gonza´lez, J. M. Chem.sEur. J. 2006, 12,
5790-5805. (f) Yue, D.; Ca´, N. D.; Larock, R. C. J. Org. Chem. 2006, 71,
3381-3388.
(9) (a) Matsumoto, S.; Takahashi, S.; Ogura, K. Heteroat. Chem. 2001,
12, 385-391. (b) Matsumoto, S.; Kumazawa, K.; Ogura, K. Bull. Chem.
Soc. Jpn. 2003, 76, 2179-2182.
(10) Ogura, K.; Takeda, M.; Xie, J. R.; Akazome, M.; Matsumoto, S.
Tetrahedron Lett. 2001, 42, 1923-1925.
J. Org. Chem, Vol. 73, No. 5, 2008 1727

Matsumoto et al.
FIGURE 1. 1H NMR analysis of the reaction of 3a in CDCl3: (a) before and (b) after the external irradiation for 15 min with a high-pressure
mercury lamp through a Pyrex filter. (c) Addition of I2 (1 molar equiv) into spectrum b in the dark (after 5 min).
SCHEME 4. Reaction Sequence of the Formation of 4a
SCHEME 5. Reaction of 8 with Iodine
in toluene was irradiated using a high-pressure mercury lamp
through a Pyrex filter (Scheme 3). The reaction was tolerant of
the polarity of the employed solvent. The smooth reaction
occurred not only in nonpolar toluene but also in polar CH3CN
and MeOH. Interestingly, 4a was obtained in 84% yield on
irradiation using 0.5 molar equiv of iodine, although a prolonged
reaction time was required.
The methylthio group of 3a plays an important role in the
present reaction because 1-chloro-6-phenyl-3-tosylhexa-1,3-dien-
5-yne (7), which has a chlorine atom instead of the methylthio
group, gave 4a in 26% yield under similar conditions (irradiation
in toluene for 5 h).
accelerates the cyclization reaction with iodine. Consequently,
we also synthesized 1-methyl-1-(methylthio)-6-phenyl-3-tosyl-
hexa-1,3-dien-5-yne (8),11 which was subjected to the reaction
with iodine (Scheme 5). As anticipated, the desired tetrasub-
stituted benzene derivative, 2-iodo-6-methyl-4-tosyl-1,1′-biphen-
yl (9), was obtained in almost quantitative yield on irradiation
in toluene containing iodine (1.0 molar equiv). The reaction of
8 with iodine in CH3CN proceeded smoothly at room temper-
ature in the dark, and the biphenyl (9) was formed quantitatively
after 4 h.
Next, we would like to describe the reaction mechanism for
leading from the starting 3 to the final 4. The UV irradiation
brings about the cis-trans isomerization of the C1-C2 double
bond of 3 to form the (1Z,3E)-geometric isomer (3′). The
intermediary 3′ was shown to easily react with iodine and afford
4 in a high yield (Figure 1). Hitherto, the iodine-induced
cyclization of conjugated diene-yne systems has been reported
to be initiated by the attack of an iodonium ion8 or an iodine
atom (radical).4 Since the iodine molecule splits into iodine
To gain insight into the role of irradiation in this system, the
1
reaction was followed using H NMR. The results are sum-
marized in Figure 1. When a solution of 3a in CDCl3 was
externally irradiated with a high-pressure arc lamp, a new set
of proton signals [δ 6.18 (d, 1H, J ) 10.6 Hz), 6.49 (d, 1H, J
) 10.6 Hz), and 7.04 (s, 1H)] (Figure 1b) appeared instead of
those [δ 6.24 (d, 1H, J ) 15.6 Hz), 6.82 (s, 1H), and 7.58 (d,
1H, J ) 15.6 Hz)] of 3a (Figure 1a). Upon treatment of the
resulting solution with iodine in the dark, 4a was formed imme-
diately at room temperature (Figure 1c). In an alternative run,
the new product was isolated and the geometry of its C1-C2
double bond was assigned from the coupling constant (10.6 Hz)
between H1 and H2 to be Z. Consequently, the irradiation was
shown to hasten the transformation of 3a to 4a via the 1Z-isomer
(3a′), which easily cyclizes with iodine (Scheme 4).
(11) The geometry of the C-C double bond at the 1,2-position in 8 was
determined using NOE measurements.
These facts seem to imply that the substituent at the 1Z
position of 1-(methylthio)-3-tosylhexa-1,3-dien-5-yne system
1728 J. Org. Chem., Vol. 73, No. 5, 2008

NoVel Formation of Iodobenzene DeriVatiVes
FIGURE 2. The most stable conformations of 3a, 3a′, and 8 calculated using the PM3 theory.
SCHEME 6. Plausible Reaction Mechanisms
SCHEME 7. Reaction of 8 with Iodine Monochloride
iodonium ion is bound to the triple bond or the terminal double
bond, intramolecular cyclization takes place to form a cationic
intermediate (A2 or B2), which reacts with the iodide ion. The
subsequent aromatization through the removal of methanesulfe-
nyl iodide forms 4 or 9. At present, we cannot eliminate the
possibility that the aromatization of the intermediary A2 is
directly achieved by the attack of an iodide ion on its sulfur
atom. Because methanesulfenyl iodide is so unstable that it is
converted immediately to dimethyl disulfide and iodine, one-
half of the iodine used at the initial stage is reproduced.16 For
that reason, a high yield was attained even with 0.5 molar equiv
of iodine (Scheme 3).
We examined the reaction of 8 with iodine monochloride,
which releases iodonium ion and chloride ion smoothly, to
clarify the attacking position of the iodonium ion. The inter-
mediate (B2; X ) Me, Y ) SMe) would react with a chloride
ion to form 2-chloro-6-methyl-4-tosyl-1,1′-biphenyl (10) if the
reaction proceeds through Path B. In contrast, the reaction via
Path A would form compound 9. The fact is that 9 was formed
in the reaction of 8 with iodine monochloride (Scheme 7), which
supports Path A for the reaction of 3 and 8 with iodine.
At present, the reason why the 1Z-isomer (3a′) of 3a reacts
with iodine much more rapidly than 3a (1E-isomer) remains
atoms (radicals) photochemically, we cannot eliminate the
possibility that the reaction of 3′ with iodine under the UV
irradiation involves an iodine radical. Here, the mechanism for
the reaction of 3a′ with iodine in the dark is discussed. In
Scheme 3, the reaction was shown to occur efficiently in toluene,
CH3CN, and MeOH. This does not suggest that the reactions
of the Z-isomer (3a′) with iodine in these solvents take place at
the same rate. We compared the reaction rate in benzene-d6
with that in acetonitrile-d3. In an NMR tube, the compound (3a)
was externally irradiated in benzene-d6 or acetonitrile-d3 to
obtain 3a′ mainly, and then, after addition of iodine, the reaction
in the dark was pursued by 1H NMR (see the Supporting
Information). The reaction of 3a′ with iodine in acetonitrile-d3
was much faster than that in benzene-d6. In the reaction in
acetonitrile-d3, the starting 3a′ disappeared completely within
4 min. In contrast, 24 and 5% of the starting 3a′ remained
unchanged after 4.5 and 10 min, respectively, in benzene-d6.
This result supports the idea that the reaction of 3a′ in the dark
proceeds via an ionic mechanism. Possibly, the iodonium ion
attacks either on the triple bond (Path A)8,12-15 or on the terminal
double bond (Path B),9a as depicted in Scheme 6. After the
(12) Yue, D.; Yao, T.; Larock, R. C. J. Org. Chem. 2005, 70, 10292-
10296.
(13) (a) Barluenga, J.; Trincado, M.; Rubio, E.; Gonza´lez, J. M. Angew.
Chem., Int. Ed. 2003, 42, 2406-2409. (b) Amjad, M.; Knight, D. W.
Tetrahedron Lett. 2004, 45, 539-541. (c) Yue, D.; Yao, T.; Larock, R. C.
J. Org. Chem. 2006, 71, 62-69. (d) Hessian, K. O.; Flynn, B. L. Org. Lett.
2006, 8, 243-246.
(14) (a) Flynn, B. L.; Verdier-Pinard, P.; Hamel, E. Org. Lett. 2001, 3,
651-654. (b) Yue, D.; Larock, R. C. J. Org. Chem. 2002, 67, 1905-1909.
(c) Hessian, K. O.; Flynn, B. L. Org. Lett. 2003, 5, 4377-4380.
(15) (a) Huang, Q.; Hunter, J. A.; Larock, R. C. J. Org. Chem. 2002,
67, 3437-3444. (b) Zhang, X.; Campo, M. A.; Yao, T.; Larock, R. C. Org.
Lett. 2005, 7, 763-766. (c) Kesharwani, T.; Worlikar, S. A.; Larock, R. C.
J. Org. Chem. 2006, 71, 2307-2312. (d) Fischer, D.; Tomeba, H.; Pahadi,
N. K.; Patil, N. T.; Yamamoto, Y. Angew. Chem., Int. Ed. 2007, 46, 4764-
4766.
(16) Field, L.; Vanhorne, J. L.; Cunningham, L. W. J. Org. Chem. 1970,
35, 3267-3273.
J. Org. Chem, Vol. 73, No. 5, 2008 1729

Matsumoto et al.
TABLE 2. Iodobenzene Ring Formation of 3 with Iodine under
Photoirradiationa
SCHEME 9. Formation of 12 from a Geometric Mixture of
11
time
(h)
yield (%)
of 4
entry
R
1
2
3
4
p-MeOC6H4 (3b)
p-BrC6H4 (3c)
p-MeOC(O)C6H4 (3d)
n-C12H25 (3e)
1
1
1.5
1
100
83b
86c
91
a Reaction conditions: 3 and I2 (1.0 molar equiv) in toluene (0.01 M)
under a high-pressure Hg lamp. b Starting material was recovered in 17%
yield. c Starting material was recovered in 10% yield.
SCHEME 8. Reaction of Compound (E,E)-11 Having a
Methoxycarbonyl Group with Iodine
brings about geometric isomerization around the C-C double
bonds, suggesting that the geometric mixture of 11 is suitably
used as the starting material. Indeed, the reaction of a geometric
mixture (E,E:E,Z:Z,E:Z,Z ) 50:28:5:17) of 11 gave 12 in 80%
yield (as determined by NMR analysis) (Scheme 9).
In conclusion, results of this study demonstrated the efficient
formation of iodobenzene derivatives (4) using iodonium-
induced cyclization of 1-(methylthio)-3-tosylhexa-1,3-dien-5-
ynes (3). In this reaction, UV irradiation accelerates the reaction
to form 4 in high-to-excellent yields. The irradiation causes the
cis-trans isomerization of the C-C double bond of 3 to produce
the corresponding (1Z)-geometric isomer, which easily reacts
with iodine to form 4. The present reaction system is applicable
to 3-(methoxycarbonyl)-1-(methylthio)-6-phenylhexa-1,3-dien-
5-yne (11). In this case, a geometric mixture of 11 is used as a
starting material. Because the irradiation of the geometric
isomers in the presence of iodine gives the corresponding
iodobenzene derivative (12) in a high yield, the present reaction
is regarded as an efficient procedure for synthesizing the
iodinated arenes.
questionable. Although the complete answer remains elusive,
some comments are presented. As described in the Introduction,
it is likely that, if the molecule adopts a conformation suitable
to the cyclization, it would react with iodine smoothly. For that
reason, we calculated the most stable conformations (Figure 2)
of 3a, 3a′, and 8 with the PM3 theory of MOPAC.17 Apparently,
the distance (d) between the carbons that are bound in the
reaction does not seem to be related to the reactivity because
the less reactive 3a has the shortest distance. We noticed that
the dihedral angle between the adjacent double bonds of the
reactive 3a′ and 8 is approximately 90°, whereas that of the
less reactive 3a is 42°, which suggests that the reactive
compound (3a′ or 8) has the p orbital of the terminal double
bond facing the triple bond. Therefore, it is reasonably rational-
ized that, in the reaction of 3a′ or 8, the triple bond reacts
smoothly with the terminal double bond after it undergoes the
attack of the iodonium ion.
Furthermore, we prepared various 6-substituted 1-(meth-
ylthio)-3-tosylhexa-1,3-dien-5-ynes (3) according to procedures
similar to that shown in Scheme 2 and examined the reaction
with iodine. As portrayed in Table 2, the corresponding
1-substituted 2-iodo-4-tosylbenzenes (4) were formed in high-
to-excellent yields on the irradiation in the presence of iodine.
It should be noted that a 6-dodecyl derivative (3e) was also
transformed into the corresponding 4e in 91% yield.
Finally, we present an example implying that the reaction of
3 with iodine is widely applicable. The corresponding methyl
4-phenyl-3-iodobenzoate (12) was isolated in 75% yield when
the compound (E,E)-11, having a methoxycarbonyl group
instead of a tosyl group, was subjected to the reaction with
iodine under irradiation (Scheme 8).
The starting compound (11) was synthesized from methyl
γ-(methylthio)crotonate using a method similar to the prepara-
tion of 3. Using this method, the 1,3-alkadien-5-yne system was
formed as a geometric mixture, which was separated by
chromatography to yield 11. As described above, the irradiation
Experimental Section
General Procedure for Preparation of (1E,3E)-1-(Meth-
ylthio)-3-tosylhexa-1,3-dien-5-ynes. (1E,3E)-1-(Methylthio)-6-
phenyl-3-tosylhexa-1,3-dien-5-yne (3a): To a solution of (E)-1-
(methylthio)-3-tosyl-1-propene (5)18 (1.939 g, 8.00 mmol) in THF
(50 mL) was added n-butyllithium (1.54 M in hexane; 5.5 mL, 8.5
mmol), and the resulting mixture was stirred for 10 min at -78
°C. 3-Phenylpropynal (6) (1.10 mL, 8.99 mmol) was added to the
mixture at the same temperature, and the reaction mixture was
stirred for 2 h. Then, acetic anhydride (0.84 mL, 8.9 mmol) was
added at that temperature, and the mixture was additionally stirred
for 1 h. The usual workup (quenching with saturated NH4Cl
solution, extraction with Et2O, and evaporation) gave yellow oil
(3.678 g). To a solution of that oil in undistilled CH3CN (20 mL)
was added triethylamine (1.65 mL, 11.8 mmol) at room temperature
in air. The reaction was monitored by using TLC, and the resulting
mixture was stirred for 5 h. The reaction mixture was evaporated
and was subjected to column chromatography on SiO2 (hexane/
ethyl acetate ) 3:1) to give 3a (2.349 g, 6.63 mmol) in 83% yield
as yellow solid. To use for the reaction, it was furthermore purified
by recrystallization from hexane to give yellow plate crystals: mp
112.5-113.2 °C; 1H NMR (CDCl3, 300 MHz) δ 2.32 (s, 3H), 2.43
(s, 3H), 6.24 (d, 1H, J ) 15.6 Hz), 6.82 (s, 1H), 7.29 (d, 2H, J )
8.5 Hz), 7.35-7.39 (m, 3H), 7.45 (diffused d, 2H, J ) 7.8 Hz),
(17) With MOPAC 97; Stewart, J. J. P. J. Comput. Chem. 1989, 10, 209-
220.
(18) Ogura, K.; Iihama, T.; Takahashi, K.; Iida, H. Bull. Chem. Soc.
Jpn. 1984, 57, 3347-3348.
1730 J. Org. Chem., Vol. 73, No. 5, 2008

NoVel Formation of Iodobenzene DeriVatiVes
1
7.58 (d, 1H, J ) 15.6 Hz), 7.76 (d, 2H, J ) 8.4 Hz); IR (KBr)
3059, 2920, 2185, 1595, 1576, 1319, 1157, 1122, 723, 660, 600
cm-1. Anal. Calcd for C20H18O2S2: C, 67.76; H, 5.12. Found: C,
67.73; H, 5.14.
using dibenzyl as an internal standard. The peaks in the H NMR
spectrum were in good agreement with those of the isolated 9.
Reaction of a Geometric Mixture of 11: To a solution of
lithium diisopropylamide (1.0 mmol, prepared from diisopropyl-
amine (0.11 mL, 1.0 mmol) and n-butyllithium (1.59 M in hexane,
0.64 mL, 1.0 mmol)) in THF (6 mL) was added methyl 4-(meth-
ylthio)crotonate (0.1562 g, 1.0 mmol) at -78 °C, and the resulting
mixture was stirred for 10 min at that temperature. 3-Phenylpropynal
(0.1191 g, 1.0 mmol) was added to the mixture at the same
temperature, and the reaction mixture was stirred for 1 h. Then,
acetic anhydride (0.42 mL, 1.2 mmol) was added at that temper-
ature, and the mixture was gradually warmed up to room temper-
ature. After being stirred for 1 h, DBU (0.2 mL, 1.3 mmol) and
THF (2 mL) were added to the mixture and stirred for 30 min. The
usual workup (quenching with saturated NH4Cl solution, extraction
with Et2O, and evaporation) gave yellow oil (0.3317 g). This oil
was subjected to short-path column chromatography on SiO2
(hexane/ethyl acetate ) 4:1) to give yellow oil (0.1927 g). The
ratio and yield of 11 and its geometric isomers were determined
The Reaction of 3a with Iodine under Thermal Conditions:
To a solution of 3a (0.177 g, 0.50 mmol) in toluene (12.5 mL)
was added iodine (0.127 g, 0.50 mmol), and the resulting mixture
was refluxed for 5 days. To the reaction mixture was added ethyl
acetate (10 mL) and washed with saturated Na2S2O3 solution (10
mL × 4). The organic layer was dried with MgSO4, evaporated,
and subjected to column chromatography on SiO2 (chloroform/
hexane ) 6:1) to give 2-iodo-4-tosyl-1,1′-biphenyl (4a) (0.115 g,
0.265 mmol) in 53% yield as white solid. 4a was further purified
by recrystallization from hexane and chloroform to obtain as
1
colorless plate crystals: mp 128.1-128.7 °C; H NMR (CDCl3,
300 MHz) δ 2.43 (s, 3H), 7.27 (m, 2H), 7.35 (d, 2H, J ) 8.5 Hz),
7.39 (d, 1H, J ) 8.1 Hz), 7.42-7.44 (m, 3H), 7.87 (d, 2H, J ) 8.4
Hz), 7.92 (dd, 1H, J ) 1.9 and 8.0 Hz), 8.47 (d, 1H, J ) 1.9 Hz);
IR (KBr) 3060, 2979, 2929, 1595, 1315, 1153, 1109, 800, 661,
580 cm-1. Anal. Calcd for C19H15IO2S: C, 52.55; H, 3.48. Found:
C, 52.54; H, 3.52.
1
by H NMR analysis with the internal method using triphenyl-
methane as a standard: 0.41 mmol, 41% yield; (1E,3E):(1E,3Z):
(1Z,3E):(1Z,3Z) ) 50:28:5:17. The obtained mixture (0.1905 g, 0.41
mmol) was dissolved in toluene (50 mL), and the solution was
bubbled by nitrogen gas for 20 min. Iodine (0.2530 g, 1.0 mmol)
was added to that solution, and the resulting mixture was irradiated
with a high-pressure mercury lamp through a Pyrex vessel for 1.5
h. The usual workup and short-path column chromatography was
achieved to give yellow oil (0.2113 g). The yield (0.33 mmol, 80%)
of 12 was determined by 1H NMR analysis with the internal method
using triphenylmethane as a standard.
General Procedure for Reaction of 3a with Iodine under
Photoirradiation: 3a (52.9 mg, 0.15 mmol) and iodine (39.0 mg,
0.15 mmol) in toluene (15 mL) were irradiated with a high-pressure
mercury lamp through a Pyrex vessel to be bubbled by nitrogen
gas for 1 h. To the reaction mixture was added ethyl acetate (10
mL) and washed with saturated Na2S2O3 solution (10 mL × 4).
The organic layer was dried with MgSO4, evaporated, and subjected
to column chromatography on SiO2 (chloroform) to give 4a (65.8
mg, 0.15 mmol) in 100% yield as pale yellow solid.
Reaction of 8 with Iodine Monochloride: To a solution of 8
(18.6 mg, 0.05 mmol) in toluene (5 mL) was added iodine
monochloride (16.1 mg, 0.10 mmol), and the resulting mixture was
stirred at -20 °C. After being stirred for 19 h, to the reaction
mixture was added ethyl acetate (5 mL) and washed with saturated
Na2S2O3 solution (5 mL × 2). The organic layer was dried with
MgSO4 and evaporated to give the brown solid (25.7 mg). The
Supporting Information Available: Procedures, spectral data
1
1
of H NMR and IR, elemental analytical data, the copies of H
NMR spectra for 3a, 3a′, 3b, 3c, 3d, 3e, 7, 8, 11, 4a, 4b, 4c, 4d,
4e, 9, and 12, and crystallographic data of 4a (CIF). This material
is available free of charge via the Internet at http://pubs.acs.org.
1
yield (83%) of 9 was determined by the integration of H NMR
JO701976Q
J. Org. Chem, Vol. 73, No. 5, 2008 1731