Convenient and efficient synthesis of 1,1-bis-(4-alkylthiophenyl)-1-alkenes via tandem Friedel-Crafts acylation and alkylation of sulfides and acyl chlorides

Article abstract of DOI:10.1080/00397910500187373

1,1-Bis(4-alkylthiophenyl)-1-alkenes were conveniently and efficiently prepared from alkyl phenyl sulfides and acyl chlorides via a tandem Friedel-Crafts acylation and alkylation in the presence of anhydrous aluminum chloride. The scope, limitation, and mechanism of the tandem reaction were also discussed. Copyright Taylor & Francis, Inc.

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Convenient and
Efficient Synthesis of
1,1‐Bis‐(4‐alkylthiophenyl)‐1‐alken
via Tandem Friedel–Crafts
Acylation and Alkylation of
Sulfides and Acyl Chlorides
Jiaxi Xu a , Jiakun Xia a & Yu Lan a
a Key Laboratory of Bioorganic Chemistry and
Molecular Engineering of Ministry of Education,
College of Chemistry and Molecular Engineering,
Peking University, Beijing, China
Published online: 18 Aug 2006.
To cite this article: Jiaxi Xu , Jiakun Xia & Yu Lan (2005): Convenient and Efficient
Synthesis of 1,1‐Bis‐(4‐alkylthiophenyl)‐1‐alkenes via Tandem Friedel–Crafts Acylation
and Alkylation of Sulfides and Acyl Chlorides, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 35:17,
2347-2353
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Synthetic Communicationsw, 35: 2347–2353, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500187373
Convenient and Efficient Synthesis of
1,1-Bis-(4-alkylthiophenyl)-1-alkenes via
Tandem Friedel–Crafts Acylation and
Alkylation of Sulfides and Acyl Chlorides
Jiaxi Xu, Jiakun Xia, and Yu Lan
Key Laboratory of Bioorganic Chemistry and Molecular Engineering of
Ministry of Education, College of Chemistry and Molecular Engineering,
Peking University, Beijing, China
Abstract: 1,1-Bis(4-alkylthiophenyl)-1-alkenes were conveniently and efficiently
prepared from alkyl phenyl sulfides and acyl chlorides via a tandem Friedel–Crafts
acylation and alkylation in the presence of anhydrous aluminum chloride. The
scope, limitation, and mechanism of the tandem reaction were also discussed.
Keywords: Acylation, alkene, alkylation, Friedel–Crafts reaction, sulfide, tandem
reaction
INTRODUCTION
Friedel–Crafts acylation is one of important, convenient, and efficient
reactions used in the preparation of aromatic ketones.[1] However, in some
cases, certain abnormal products have been obtained as major products with
or without the corresponding ketones.[2,3] Recently we prepared a series of
alkyl para-alkylthiophenyl ketones via Friedel–Crafts acylation of alkyl
phenyl sulfides with acyl chlorides.[4] When acyl chlorides were added into
alkyl phenyl sulfides in the presence of anhydrous aluminum chloride,
Received in Japan February 28, 2005
Address correspondence to Jiaxi Xu, Key Laboratory of Bioorganic Chemistry and
Molecular Engineering of Ministry of Education, College of Chemistry and Molecular
Engineering, Peking University, Beijing 100871, China. E-mail: jxxu@pku.edu.cn
2347

2348
J. Xu, J. Xia, and Y. Lan
instead of the corresponding ketones, 1,1-bis(4-alkylthiophenyl)-1-alkenes
were obtained as major products in good yields. Herein, we report this
reaction and discuss its scope, limitation, and mechanism.
RESULTS AND DISCUSSION
As part of a program to synthesize chiral secondary alcohols with a variety of
functional groups via asymmetric borane reduction,[4,5] we need to synthesize
ketones with a variety of functional groups first. Friedel–Crafts acylation is a
convenient method for the preparation of aromatic ketones. Thus, it was
chosen to prepare alkyl phenyl sulfides. When acetyl chloride was added
into the solution of anhydrous aluminum chloride in thioanisole, instead of
the corresponding p-methylthioacetophenone, 1,1-bis(4-methylthiophenyl)-1
ethene was obtained as major product in high yield without any ketone.
This prompted us to investigate this reaction. A series of alkyl phenyl
sulfides were attempted. The results indicated that the reaction of acyl
chlorides and alkyl phenyl sulfides yielded alkyl p-alkylthiophenyl ketones
when acyl chlorides were added to a solution of alkyl phenyl sulfide in
carbon disulfide under a slow addition mode at 0–58C,[4] whereas it
produced 1,1-bis(4-alkylthiophenyl)-1-alkenes when acyl chlorides were
added to pure alkyl phenyl sulfide under a relative faster addition mode in
the presence of anhydrous aluminum chloride at the same or higher tempera-
tures. The results are summarized in Table 1 (entries 1–7) (Scheme 1).
Table 1. Reaction of acyl chlorides and arenes
Entry
R1
R2
Olefin 3 (Yield %)
Ketone 4 (Yield %)
1
2
MeS
EtS
H
3a (89)
3b (86)
3c (88)
3d (83)
3e (84)
3f (86)
3g (91)
3h (63)a
3i (59)b
3i (68)a
3j (75)a
H
3
MeS
EtS
Me
Me
Me
Me
Ph
4
5
n-PrS
n-BuS
MeS
MeO
MeO
MeO
MeO
Me
6
7
8
H
9
Me
Me
Ph
4i (34)b
10
11
12
13
14
Me
Me
Me
4k (76)
4l (78)
4m (74)
H
Cl
aThe reaction was run at 508C to refluxing.
bThe reaction was run at 0–58C.

1,1-Bis(4-alkylthiophenyl)-1-alkenes
2349
Scheme 1. Reaction of acyl chlorides and arenes in the presence of aluminum
chloride.
After searching the literature, some similar reactions, such as the
reactions of anisole with propionyl chloride,[6] mesitylene and tetramethyl-
benzenes with acetyl and propionyl chloride, respectively,[7,8] and so forth,
were reported previously. However, different mechanisms on this reaction
were assumed.[3,6,8] The first assumption is that the reaction of an arene
with an acyl chloride produced an aromatic ketone first, followed by the con-
densation of the newly formed ketone with a second molecule of the arene to
give 1,1-bisaryl-1-alkene.[6,8] Another rationale suggested that the newly
formed ketone enolizated into an enol under catalysis of aluminum chloride
first, and then the enol, as an alkene, underwent a Friedel–Crafts alkylation
with a second molecule of the arene.[3] However, it has been well known
that formaldehyde, which cannot form an enol, still could undergo a
Friedel–Crafts reaction with benzene to yield benzyl alcohol and to further
form benzyl chloride in the presence of anhydrous zinc chloride and
hydrogen chloride, which is called the chloromethylation reaction. It is also
known that the reaction of benzaldehyde and benzene produce diphenyl-
methanol, which could further yield triphenylmethane under the catalysis of
anhydrous aluminum chloride.[9] Thus, the enol mechanism seems to be
unreasonable.
To further understand and confirm the mechanism of this reaction,
4-ethylthiophenyl-1-propanone reacted with ethyl phenyl sulfide in the
presence of aluminum chloride to produce 1,1-bis(4-ethylthiophenyl)-1-
propene 3d. The reaction of thioanisole with benzaldehyde gave rise to
a mixture of 4-methylthiophenyl phenylmethanol and bis(4-methylthio-
phenyl) phenylmethane (shown in Scheme 2). Now, the mechanism could be
rationalized and confirmed as the following: first, an acyl chloride and an
alkyl phenyl sulfide underwent a Friedel–Crafts acylation to yield an alkyl
p-alkylthiophenyl ketone, and the formed ketone and a second molecule of
the sulfide further underwent a Friedel–Crafts alkylation because the
oxyatom of the ketone, which coordinated with aluminum chloride,
activated the carbon atom of the carbonyl group into Friedel-Crafts alkylation
with a sulfide and an elimination of HoAlCl2. In the reaction, electron-

2350
J. Xu, J. Xia, and Y. Lan
Scheme 2. Reactions of sulfides with ketone and aldehyde.
donating alkylthio groups RS could also stabilize the addition intermediates
via the formation of octet structural intermediates B because of the
existence of the sulfur-donating conjugative effect. Our results indicate that
the enol mechanism is incorrect. Our results also indicate that sulfides are
more active than ethers in the tandem reaction because alkylthio groups are
more electron donating than alkoxy groups.
CONCLUSION
In summary, 1,1-bis(4-alkylthiophenyl)-1-alkenes were conveniently and effi-
ciently prepared from sulfides and acyl chlorides via a tandem Friedel–Crafts
acylation and alkylation in the presence of anhydrous aluminum chloride. The
scope, limitation, and mechanism of the reaction were discussed on the basis
of the designed experiments. The results indicate that sulfides are more active
than ethers in the tandem reaction because alkylthio groups are more electron
donating than alkoxy groups.
EXPERIMENTAL
Melting points were measured on a Yanaco MP-500 melting-point
apparatus and are uncorrected. 1H NMR and 13C NMR spectra were
recorded on a Mercury Plus 300 (300 MHz) spectrometer in CDCl3 with
TMS as an internal standard. Mass spectra were obtained on a VG-ZAB-
HS mass spectrometer. CHN analyses were recorded on an Elementar

1,1-Bis(4-alkylthiophenyl)-1-alkenes
2351
Scheme 3. Suggested mechanism on the reaction of acyl chlorides and alkyl phenyl
sulfides in the presence of aluminum chloride.
Vario EL analyzer. The analytical data of all known compounds are
identical to those earlier reported in the literatures.[10–12]
Preparation of 1,1-Diaryl-1-alkene (3), General Procedure
Acyl chloride (10 mmol) was added dropwise to a mixture of anhydrous
aluminum chloride (1.47 g, 11 mmol) and alkyl phenyl ether or sulfide
(20 mmol) in an ice-water bath. The resulting mixture was kept stirring for
3 h and allowed to warm to room temperature. It was carefully decomposed
with water and extracted with ether. Upon evaporation of the dried ether,

2352
J. Xu, J. Xia, and Y. Lan
the residue was recrystallized from petroleum ether or ethanol to afford
colorless plates.
1,1-Bis(4-methylthiophenyl)ethene (3a): Colorless crystals, mp 126–1278C,
yield 89%; lit.[10]: mp 123–1268C.
1,1-Bis(4-ethylthiophenyl)ethene (3b): Colorless crystals, mp 117–1188C,
yield 86%; lit.[11]: mp 1188C.
1,1-Bis(4-methylthiophenyl)-1-propene(3c):Colorlesscrystals, mp86–878C,
yield 89%; Lit.[10]: mp 85.5–87.58C.
1,1-Bis(4-ethylthiophenyl)-1-propene (3d): Colorless crystals, mp 68–698C,
yield 83%; 1H NMR (300 MHz, CDCl3) d: 1.30 (t, J ¼ 7.5 Hz, 3H, CH3), 1.35
(t, J ¼ 7.2 Hz, 3H, CH3), 1.75 (d, J ¼ 6.9 Hz, 3H, CH3), 2.91 (q, J ¼ 7.2 Hz,
2H, CH2), 2.97 (q, J ¼ 7.5 Hz, 2H, CH2), 6.14 (q, J ¼ 6.9 Hz, 1H, CH¼),
7.07–7.33 (m, 8H, ArH). 13C NMR (75.5 MHz, CDCl3) d 14.34, 15.70,
27.42, 27.61, 124.06, 127.57, 128.35, 128.62, 130.47, 134.91, 135.22,
137.15, 140.42, 141.18. EI-MS m/z: 314 (Mþ, 100), 285 (Mþ–Et, 5), 253
(Mþ–EtS, 17), 192 (Mþ–2EtS, 29). Anal. calcd. for C19H22S2 (314.51): C,
72.56; H, 7.05. Found: C, 72.42; H, 6.98%
1,1-Bis(4-propylthiophenyl)-1-propene(3e):Colorlesscrystals, mp44–458C,
yield 84%. 1H NMR (300 MHz, CDCl3) d 1.01 (t, J ¼ 7.2 Hz, 3H, CH3), 1.05
(t, J ¼ 7.2 Hz, 3H, CH3), 1.65 (quintet, J ¼ 7.2 Hz, 2H, CH2), 1.73 (quintet,
J ¼ 7.2 Hz, 2H, CH2), 1.76 (d, J ¼ 7.2 Hz, 3H, CH3), 2.87 (t, J ¼ 7.2 Hz,
2H, CH2), 2.94 (t, J ¼ 7.2 Hz, 2H, CH2), 6.13 (q, J ¼ 7.2 Hz, 1H, CH¼),
7.06–7.33 (m, 8H, ArH). 13C NMR (75.5 MHz, CDCl3) d 13.43, 13.49,
22.51, 35.40, 35.61, 124.06, 127.59, 128.29, 128.60, 130.51, 135.22,
135.54, 137.08, 140.39, 141.22. EI-MS m/z: 342 (Mþ, 23), 314 (Mþ–
2CH2, 100), 192 (Mþ–2PrS, 32). Anal. calcd. for C21H26S2 (342.56): C,
73.63; H, 7.65. Found: C, 73.72; H, 7.71%.
1,1-Bis(4-butylthiophenyl)-1-propene (3f): Colorless crystals, mp 54–558C,
yield 86%. 1H NMR (300 MHz, CDCl3) d 0.91 (t, J ¼ 7.2 Hz, 3H, CH3), 0.94
(t, J ¼ 7.2 Hz, 3H, CH3), 1.40–1.54 (m, 4H, 2CH2), 1.57–1.73 (m, 4H,
2CH2), 1.75 (d, J ¼ 6.9 Hz, 3H, CH3), 2.89 (t, J ¼ 7.2 Hz, 2H, CH2), 2.96
(t, J ¼ 7.2 Hz, 2H, CH2), 6.13 (q, J ¼ 6.9 Hz, 1H, CH¼), 7.07–7.32
(m, 8H, ArH). 13C NMR (75.5 MHz, CDCl3) d 13.31, 13.62, 21.94, 31.21,
33.06, 33.26, 124.02, 127.59, 128.17, 128.47, 130.49, 135.34, 135.68,
137.08, 140.34, 141.22. EI-MS m/z: 370 (Mþ, 92), 314 (Mþ–4CH2, 100),
281 (Mþ–BuS, 8), 192 (Mþ–2BuS, 33). Anal. calcd. for C23H30S2 (370.61):
C, 74.54; H, 8.16. Found: C, 74.32; H, 8.17%.
1,1-Bis(4-methylthiophenyl)-2-phenylethene (3g): Colorless crystals, mp
111–1128C, yield 91%; lit.[12]: mp 1128C.

1,1-Bis(4-alkylthiophenyl)-1-alkenes
2353
1,1-Bis(4-methoxyphenyl)ethane (3h): Colorless crystals, mp 143–1448C,
yield 73%; lit.[10]: mp 142–1448C.
1,1-Bis(4-methoxyphenyl)-1-propene(3i):Colorlesscrystals, mp100–1018C,
yield 78%; lit.[10]: mp 100–1018C.
1,1-Bis(4-methoxyphenyl)-2-phenylethene (3j): Colorless crystals, mp
63–658C, yield 85%; lit.[10]: mp 61–658C.
ACKNOWLEDGMENT
The project was supported partly by National Natural Science Foundation of
China (Nos. 20272002 and 20472005), Ministry of Education of P.R. China
(EYTP), and Peking University (President Grant).
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