One-step synthesis of aromatic terminal alkynes from their corresponding ketones under microwave irradiation

Article abstract of DOI:10.1080/00397910600634100

One-step microwave-assisted synthesis of phenylacetylenes 2a-j from the corresponding ketones 1a-j in the presence of a new reagent, PCl 5 -pyridine, is described. The reaction is carried out under a simple operational and experimental procedure, avoiding the use of the complicated and harsh multistep reaction. Copyright Taylor & Francis Group, LLC.

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One‐Step Synthesis of Aromatic Terminal
Alkynes from Their Corresponding Ketones
under Microwave Irradiation
Mohammad Ghaffarzadeh a , Mohammad Bolourtchian a , Zohreh
Hassanzadeh Fard a , Mohammad Reza Halvagar a & Farshid Mohsenzadeh a
a Chemistry and Chemical Engineering Research Center of Iran, Tehran, Iran
Version of record first published: 20 Aug 2006
To cite this article: Mohammad Ghaffarzadeh, Mohammad Bolourtchian, Zohreh Hassanzadeh Fard,
Mohammad Reza Halvagar & Farshid Mohsenzadeh (2006): One‐Step Synthesis of Aromatic Terminal Alkynes
from Their Corresponding Ketones under Microwave Irradiation, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 36:14, 1973-1981
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Synthetic Communicationsw, 36: 1973–1981, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910600634100
One-Step Synthesis of Aromatic Terminal
Alkynes from Their Corresponding Ketones
under Microwave Irradiation
Mohammad Ghaffarzadeh, Mohammad Bolourtchian,
Zohreh Hassanzadeh Fard, Mohammad Reza Halvagar,
and Farshid Mohsenzadeh
Chemistry and Chemical Engineering Research Center of Iran,
Tehran, Iran
Abstract: One-step microwave-assisted synthesis of phenylacetylenes 2a–j from the
corresponding ketones 1a–j in the presence of a new reagent, PCl5–pyridine, is
described. The reaction is carried out under a simple operational and experimental
procedure, avoiding the use of the complicated and harsh multistep reaction.
Keywords: Microwave activation, One-step synthesis, PCl5–pyridine reagent,
Phenylacetylene derivatives
INTRODUCTION
Acetylenic groups are important targets for organic chemists because of their
applications and rich chemistry.[1] Conventional synthetic methods suggested
in the literature for preparing these compounds[2] require multistep procedures
with complicated preparation conditions, demanding vigilance during the
whole reaction.[3] Although these methods are suitable for many synthetic
routes, most of them have drawbacks such as applying sensitive chemicals
(e.g., butyl lithium) and very low temperature (ca. 2788C) under an inert
atmosphere.[4] Recently, novel procedures have been developed in which
Received in Poland December 12, 2005
Address correspondence to Mohammad Ghaffarzadeh, Chemistry and Chemical
Engineering Research Center of Iran, P.O. Box 14335-186, Tehran, Iran.
Fax: þ98(21)88037185; E-mail: ghaffarzadeh_m@ccerci.ac.ir
1973

1974
M. Ghaffarzadeh et al.
the use of a proper co-catalyst under phase-transfer catalysis conditions,[5]
supported reagent[6] and a prepared in situ reagent have been reported.[7]
a
Besides, multistep preparations and multiple isolation processes cause
low yields and high labor time. Thus, a direct synthesis of these compounds
by a one-step reaction of a common substrate with a new and efficient
reagent remains a great challenge for organic chemists.
RESULTS AND DISCUSSION
During the past few years, the one-pot syntheses of interesting target molecules
that require multistep procedures have gained increasing attention. In this
context, the use of the microwave irradiation method is one of the most
promising approaches.[8] On the other hand, the unique property of phosphorus
reagents facilitates diverse organic reactions.[9] One of the most common
methods is the conversion of a-dihalo carbonyls to the corresponding acetyle-
nics in the presence of a strong base. Although this method is an economical
process because of its cheap starting materials (ketones), it suffers from some
drawbacks such as long labor time, a multistep procedure, and low yields.
In the development of new methods for functional group transformations
in our laboratory, we were especially interested in improving the scope of the
reaction. Considering the recent progresses in rapid synthesis methodologies
such as the microwave method,[10] we were keen to carry out the conversion
of the mentioned ketones to their corresponding acetylenics in a one-step
reaction. Use of a new reagent based on phosphorus and the microwave
irradiation technique (as a rapid process) allowed us to obtain 40 to 82%
yields in a short period of time.
.
Our recent work on phosphorus based reagents (using PCl3 3Py for con-
verting hydroxyl-containing carboxylic acids to arylanilides)[11] prompted us
to investigate on the appetite of PCl5 and pyridine adduct for reactions that
consisted of preparing acetylenic compounds from ketones. In continuation
of our earlier activities on using microwave methods in organic synthesis[12]
and significant effects of this method on the rate of reactions, we were inter-
ested to apply it for preparing acetylenic compounds (Scheme 1).
[14]
PCl5/KOH[13] or PCl5/NaNH2
are known reagents in the two-step
reaction of ketones. We tried the use of PCl5/KOH or PCl5/NaNH2 in a
one-step reaction; nevertheless, it led to an unusable reagent. This observation
Scheme 1.

Aromatic Terminal Alkynes
Table 1. Optimization of time of the reaction for preparing 2d
under microwave irradiation
1975
Pyridine/ PCl5
(mol ratio)
Time
(s)
Yield
(%)
5
5
5
5
5
5
5
60
90
40
42
42
44
48
50
50
120
150
180
210
240
made us study the effects of PCl5/pyridine in this reaction. This stable reagent
is relatively mild to convert ketones to acetylenics under microwave
irradiation. Initially, we carried out the same reaction under classical exper-
imental conditions using a refluxing utility for 2.5 h which resulted in a very
low yield (from 5 to 15%). In contrast, the reaction progressed easier under
microwave irradiation to confirm the nonthermal effects of microwave
irradiation in this reaction.[10]
As shown in Tables 1 and 2, the best reaction time found for preparing 2d is
at 210 s, and the best molar ratio of PCl5 to pyridine for this product is (1 : 9).
The strong affinity of phosphorus for oxygen atoms caused the initial bond
between oxygen of the carbonyl group and phosphorus. At these conditions,
a-hydrogen atoms become more acidic and are abstracted readily by a weak
base such as pyridine, and eventually acetylenic compound is produced.
The optimizations made in Tables 1 and 2 are for all acetylenic
compounds reported in this paper except for 2i and j. For these products the
reaction time was optimized to 60 s, and the best ratio found for the molar
ratio of PCl5 to pyridine was 1 : 18 instead of 1 : 9.
The crude reaction mixtures were directly analyzed by GC-MS and/or
subjected to column chromatography. The reaction conditions and yields of
Table 2. Optimization of the molar ratio of pyridine to
PCl5 for preparing 2d under microwave irradiation
Pyridine/ PCl5
(mol ratio)
Time
(s)
Yield
(%)
6
7
210
210
210
210
210
52
60
72
82
80
8
9
10

1976
M. Ghaffarzadeh et al.
.
Table 3. Synthesis of phenylacetylene derivatives using (PCl5 Py) reagent under
microwave activation
Irradiation Yielda 3d,b
Entry
Substrate 1
Product 2
time (s)
(%)
(%)
a
210
74b (61)c
3
b
210
58 (50) 36
c
d
e
210
210
210
59 (52) 39
88 (82) 12
90 (82) 10
f
210
67 (54) 33
g
210
210
87 (77) 13
h
77 (72)
2
(continued)

Aromatic Terminal Alkynes
1977
Table 3. Continued
Irradiation Yielda 3d,b
Entry
Substrate 1
Product 2
time (s)
(%)
(%)
i
60
57 (40) 29
j
60
69 (51)
9
1
aAll products were characterized by GC-MS and H NMR.
bGC yield.
cIsolated yield.
dBy-product 3: a-chlorostyrene derivative.
the products (i.e., phenylacetylene derivatives 2) are given in Table 3. These
results indicate that 2a–j were directly synthesized in a one-step reaction from
.
1a–j using PCl5 9Py as reagent.
Our observation showed that the presence of electron-donating groups on
the aromatic nuclei enhanced the rate of reaction. The presence of oxygen-
bearing functional groups such as methoxy group on the aromatic ring,
because of its complexation with phosphorus and its conversion to a
Figure 1.

1978
M. Ghaffarzadeh et al.
negative induction group, diminished the yield. With respect to this obser-
vation the following mechanism was proposed for this reaction.
Our studies showed that a few a-chlorostyrene (3) was produced. To
overcome this issue, the time of irradiation and the ratio of the reagent to ketone
were tested, and increasing the ratio of pyridine to PCl5 was more effective. The
excess of pyridine trapped the liberated HCl and caused the abstraction of
hydrogen from a-position to be easier. It is important to note that when pyridine
.
had a low ratio (PCl5 5Py), the excess of liberated HCl produced an additional
amount of a-chlorostyrene (3) because of the absence of an effective base.
CONCLUSION
In summary, we have introduced a novel reagent for the one-step conversion
of aromatic terminal alkynes from their corresponding ketones (entirely
available chemicals) within a few minutes under microwave activation.
EXPERIMENTAL
Ketones, pyridine, and PCl5 are commercially available.
1HNMR(80 MHz)spectra wererecordedonaBruker80-MHzspectrometer
in CDCl3 using TMS as internal standard. A GC-MS method for the analysis of
mixtures was applied. A Fisons instruments gas chromatograph 8000 connected
to a mass detector (Trio 1000) with 70eV was used. A 30m ꢀ 0.25mm column
packed with Wall Coated Open Tabular (WCOT) fused silica CP-sil 5CB-MS
(from CHROMPAC in which MS shows the high quality of capillary column
for the designed GC-MS and has a low bleeding) was employed. Column temp-
erature was programmed from 80 to 2708C at 108C/min. Injection was
performed at 2808C. The carrier gas was helium, and the inlet pressure was
10psi. A modified domestic microwave oven, equipped with a refluxing utility
and a temperature controller, from Panasonic (model NN-C781JF operating at
2450MHz) was used for all syntheses carried out in a monomode cavity.
General Experimental Procedure
Preparation of Reagent
(CAUTION: PCl5 is very corrosive and pyridine is highly toxic). In a 100-ml
beaker, 9 mmol (0.725 ml) [18 mmol (1.45 ml) for 1i–j] of dry and freshly
distilled pyridine were placed. While stirring, 1 mmol (0.208 g) of phosphorus
.
pentachloride was added gradually to make PCl5 Py reagent.

Aromatic Terminal Alkynes
1979
General Procedure
It is essential to work under a powerful hood to minimize the inhalation of
chemicals.
Synthesis of 2a, 2d–h
A mixture of ketone 1a, 1d–h (1 mmol), and PCl5 Py reagent (1 mmol)
.
was refluxed at 1108C in a 50-ml flask for 210 s in microwave oven. After
cooling in air, the mixture was washed with HCl (2%) to remove the
pyridine and then extracted by dichloromethane (3 ꢀ 20 ml). The organic
layer was separated and dried over anhydrous Na2SO4. After filtration, the
solvent was evaporated and the crude product was analyzed by GC-MS.
The residue was purified from the by-product (a–chlorostyrene derivatives)
and starting ketone (if existing) by fractional distillation apparatus. The identi-
fication of the isolated products was generally performed by 1H NMR and MS
spectral analyses.
Synthesis of 2b–c
A mixture of ketone 1b and c (1 mmol) and PCl5 Py reagent (1 mmol)
.
was refluxed at 1108C in a 50-ml flask for 210 s in microwave oven. After
cooling in air, the crude product was analysed by GC-MS. Silica gel (1 g,
100 mesh) was added to the mixture, which became a free-flowing powder.
The powder was separated, and the residue was purified by flash chromato-
graphy on dry silica gel (5 g, 100 mesh) using a short column (eluent: light
petroleum ether).
Synthesis of 2i and j
A mixture of ketone 1i and j (1 mmol) and PCl5 Py reagent (0.5 mmol)
.
was refluxed at 1108C in a 50-ml flask for 60 s in microwave oven. After
cooling in air, the crude product was analysed by GC-MS. Silica gel (1 g, 100
mesh) was added to the mixture, which became a free-flowing powder. The
powder was separated, and the residue was purified by flash chromatography
on dry silica gel (5 g, 100 mesh) using a short column (eluent: light
petroleum ether).
Phenylacetylene (Table 3, entry 2a): Oil.[15a] 1H-NMR (80 MHz, CDCl3):
d ¼ 7–8 (m, 5H), 3.20 (s, 1H). MS (EI, 70 eV): m/z (%) ¼ 103 (Mþ þ 1,
9), 102 (Mþ, 100), 76 (20), 51 (7), 50 (8).
(2-Naphythyl)acetylene (Table 3, entry 2b): Oil.[15a] 1H-NMR (80 MHz,
CDCl3):d ¼ 7–8.5 (m, 7H), 3.29 (s, 1H). MS (EI, 70 eV): m/z (%) ¼ 152
(Mþ, 100), 98 (30), 78 (62), 64 (40), 53 (30).

1980
M. Ghaffarzadeh et al.
(1-Naphthyl)acetylene (Table 3, entry 2c): Oil.[15a] 1H-NMR (80 MHz,
CDCl3): d ¼ 7–8.5 (m, 7H), 3.29 (s, 1H). MS (EI, 70 eV): m/z (%) ¼ 153
(Mþ þ 1, 28), 152 (Mþ, 100), 98 (20), 76 (60), 63 (40), 50 (30).
(4-Bromophenyl)acetylene (Table 3, entry 2d): mp 648C.[15a,d] 1H-NMR
(80MHz, CDCl3): d ¼ 7.2–7.5 (AA0 BB0, 4H, JAB ¼ 5.47 Hz) 3.05 (s, 1H).
MS (EI, 70 eV): m/z (%) ¼ 182 (Mþ þ 2, 97), 180 (Mþ, 100), 101 (89), 75
(78), 50 (30).
(2-Bromophenyl)acetylene (Table 3, entry 2e): Oil.[15a,d] 1H-NMR
(80 MHz, CDCl3): d ¼ 7.6 (d, 1H), 7.5 (d, 1H), 7.2 (t, 1H), 7.1 (t, 1H), 3.3
(s, 1H). MS (EI, 70 eV): m/z (%) ¼ 182 (Mþ þ 2, 98), 180 (Mþ, 100), 101
(55), 75 (70), 50 (35), 37 (15).
(3-Bromophenyl)acetylene (Table 3, entry 2f): Oil.[15a,d] 1H-NMR
(80 MHz, CDCl3): d ¼ 7.7 (s, 1H), 7.5 (d, 1H), 7.4 (d, 1H), 7.2 (t, 1H),
3.29 (s, 1H). MS (EI, 70 eV): m/z (%) ¼ 182 (Mþ þ 2, 98), 180 (Mþ, 100),
101 (73), 75 (60), 50 (80).
(4-Chlorophenyl)acetylene (Table 3, entry 2g): mp 458C.[15b,c,d] 1H-NMR
(80 MHz, CDCl3): d ¼ 7.3–7.6 (AA0BB0, 4H, JAB ¼ 6.27 Hz) 3.05 (s, 1H).
MS (EI, 70 eV): m/z (%) ¼ 138 (Mþ þ 2, 30), 136 (Mþ, 100), 101 (30), 74
(60), 50 (65).
(2-Chlorophenyl)acetylene (Table 3, entry 2h): Oil.[15b,c,d] 1H-NMR
(80 MHz, CDCl3): d ¼ 7.5 (d, 1H), 7.4 (d, 1H), 7.3 (t, 1H), 7.2 (t, 1H), 3.30
(s, 1H). MS (EI, 70 eV): m/z (%) ¼ 138 (Mþ þ 2, 25), 136 (Mþ, 100), 101
(68), 74 (99), 50 (98).
(4-Methoxyphenyl)acetylene (Table 3, entry 2i): Oil.[15e] 1H-NMR
(80 MHz, CDCl3): d ¼ 6.8.–7.6 (AA0BB0, 4H, JAB ¼ 9.99 Hz) 3.79 (s, 3H),
3.30 (s, 1H). MS (EI, 70 eV): m/z (%) ¼ 132 (Mþ, 90), 117 (48), 89 (100),
63 (75), 62 (48), 39 (26).
(3-Methoxyphenyl)acetylene (Table 3, entry 2j): Oil.[15e] 1H-NMR
(80 MHz, CDCl3): d ¼ 6.5–7.4 (m, 4H) 3.79 (s, 3H), 3.20 (s, 1H). MS (EI,
70 eV): m/z (%) ¼ 132 (Mþ, 100), 102 (80), 89 (65), 63 (40), 62 (38), 39 (33).
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