Synthesis of propargylic alcohols by base promoted alkynylation of ketones with ethynylbenzene using ionic liquid [(bmim) PF6]

Article abstract of DOI:10.3184/030823407X225509

A mild and efficient addition of ethynylbenzene with ketones using KOH in ionic liquid 1-butyl-3-methylimidazolium hexaflurophosphate [(bmim) PF ₆] gives propargylic alcohols in high yields.

Full text of DOI:10.3184/030823407X225509

370 RESEARCH PAPER
JUNE, 370–372
JOURNAL OF CHEMICAL RESEARCH 2007
Synthesis of propargylic alcohols by base promoted alkynylation of
ketones with ethynylbenzene using ionic liquid [(bmim) PF6]
Sachin R. Jagtap and Bhalchandra M. Bhanage*
Department of Chemistry, Institute of Chemical Technology (Autonomous), University of Mumbai, N. Parekh Marg, Matunga,
Mumbai – 400 019, India
A mild and efficient addition of ethynylbenzene with ketones using KOH in ionic liquid 1-butyl-3-methylimidazolium
hexaflurophosphate [(bmim) PF6] gives propargylic alcohols in high yields.
Keywords: alkynylation, ionic liquid, base, propargylic alcohols, reuse
HO
Propargylic alcohols are well known as a versatile building
block for the synthesis of many natural products such as
C
prostaglandins, steroids, carotenoids, etc.1 They are generally
C
Ionic liquid
C
CH
+
O
prepared by the addition of alkynylmetals to aldehydes and
ketones using catalytic/stoichiometric amount of Lewis acd or
base. High acdity and strong basicty of many alkynylmetals
including alkynyl-Li, Na, K and Mg, also causes undesired
side reactions.2 Recently, a considerable progress has been
made in the alkynylation of carbonyl compounds using Lewis
Base (C)
D
A
B
Scheme 1 Alkynylation of cyclohexanone.
6b
acd e.g. SnCl4,3 GaI3,4 Sn(OTf)25 and Zn(OTf)26a and ZnCl2
Table 1 Reaction of cyclohexanone with ethynylbenzene
catalysed by various bases under different conditions using
ionic liquid [(bmim) PF6]
in combination with a base. Various bases such as quaternary
ammoniumhydroxide,7 KF/Al2O3,8 CsOH.H2O9 andt-BuOK10
have also been reported for the alkynylation of carbonyl
compounds. However, t-BuOK catalysed alkynylation of
enolisable carbonyl compounds leads to a complex mixture
of products,10 Cs-catalysed alkynylation gave solution to this
problem but have a limitation that they cannot be used for the
alkynylation of aromatic carbonyl compounds.9 Therefore,
a versatile method for the synthesis of propargylic alcohols
with a wider range of substrates, including both aldehyde or
ketones and aromatic carbonyl compounds, is highly desirable.
Despite a number of Lewis acd and Lewis base systems have
been developed for the alkynylation of carbonyl compounds,
no attention was paid to carry out the reaction in ionic liquid
as a solvent media and using inexpensive base.
Entry Base
Mol.ratio of Time/min Temp/0C aYield/%
A : B : C
1
KOH
KOH
KOH
KOH
KOH
KOH
NaOH
1 : 1 : 0.2
1 : 1 : 0.5
1 : 1 : 1
1 : 1 : 1.5
1 : 1 : 1
1 : 1 : 1
1 : 1 : 1
10
10
10
10
90
30
10
10
10
10
10
70
70
70
70
R.T.
45
70
70
70
70
70
34
67
92
78
48
70
74
27
25
0
2
3
4
5
6
7
8
NaOMe 1 : 1 : 1
9
NaOEt
K2CO3
1 : 1 : 1
1 : 1 : 1
10
11
Na2CO3 1 : 1 : 1
0
aIsolated yield.
Within a past few years the area of ionic liquids have
emerged as a new class of ‘green’ solvents for the variety
of chemical transformations and have attracted considerable
attention. The nonvolatile nature of ionic liquids gives them
significant advantage in minimising VOC’s and solvent
consumption. Their polarity renders them good solvents
for homogeneous catalysis11. In many applications ionic
base leads to decrease in the yield of D (Table 1, entry 4).
The higher yield of D was obtained when the A: B: C are
in the ratio 1:1:1 at 70°C and the reaction was completed
within shorter reaction time of 10 min giving 92% yield of D.
In order to study the effect of temperature the reaction was
carried out at various temperature (Table 1, entries 3 and 5,
6). At room temperature the yield of D was found to be very
low 48% and it requires 90 min. However, with increase in
the temperature, enhancement in the rate of reaction and
yield was observed. Thus, at 45°C the yield of D was found
to be 70% in 30 min and the higher yield of D (92%) was
obtained at 70°C in 10 min. The effect of various bases on the
reaction was also studied as shown in the entry 3 and 7–11
(Table 1) and among them potassium hydroxide was found to
give best result i.e. 92% yield of D in 10 min at 70°C. The
enhancement in the rate and the yield of reaction obtained
is because of the solvent effect of the ionic liquid. When
the same reaction is carried out using conventional organic
solvents like DMSO, NMP and DMF, which gives only 15%,
13%, 13% yield of the D respectively. It indicates the role of
ionic liquid in enhancement of rate and yield of reaction. After
the completion of the reaction the product was extracted using
diethyl ether. The ionic liquid recovered after the extraction
was reused under identical reaction conditions with addition
of fresh base. The recycling studies were performed for four
times which gives identical results indicating reusability
of ionic liquid. Thus our approach using ionic liquid has
-
liquids with weakly coordinating anions, such as BF4 and
-
PF6 , together with suitably substituted cations often results
in an altered chemical reactivity and selectivity. Among the
commonly used ionic liquids, 1-butyl-3-methylimidiazolium
hexafluorophosphate [(bmim) PF6] is a common reaction
medium for the various organic transformations such as
hydrogenation,12 hydroformylation,13 oxidation,14 etc.
We now report the alkynylation of ketones promoted by
potassium hydroxide in ionic liquid [(bmim) PF6] as a solvent
furnishing propargylic alcohol in moderate to high yields.
Using cyclohexanone as a typical representative of ketones,
we investigated the addition reaction under various conditions
using [(bmim) PF6] in the presence of different bases and
reaction conditions were optimised (Scheme 1). The typical
results are summarised in Table 1.
It can be seen from entries 1–4 (Table 1) that with increase
in the amount of potassium hydroxide from 0.2 equivalents
to 1 equivalent the yield of D increases from 34 to 92%
(Table 1, entries 1–3). Further increase in the molar ratio of
* Correspondent. Email: bhalchandra_bhanage@yahoo.com;
bmb@udct.org
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JOURNAL OF CHEMICAL RESEARCH 2007 371
Table 2 Alkynylation of ketones in presence of potassium hydroxide in ionic liquid
Entry
A
B
D
Time/min
aIsolated yield/%
HO
O
C
C
1
10
92
HO
O
C
C
2
10
10
10
10
10
10
20
25
20
30
30
90
85
90
90
92
95
75
72
70
68
65
OH
C
O
CH
3
C
C
C
CH3
CH3
3
HO
CH3
O
C
C
H3C
CH
CH3
C
H3
C
CH3
O
4
HO
CH3
C
C
CH3
C
H3C
CH3
5
HO
CH3
C
CH3
O
CH3
C
CH2
CH
C
CH3
H3C
CH3
6
HO
CH3
O
C
CH3
H3
C
C
C
C
CH3
CH3
H3
C
H3C
CH3
7
OH
C
O
CH3
C
C
C
CH3
8
HO
CH3
C
C
O
C
C
CH3
9
HO
Cl
Cl
CH3
O
C
C
C
C
CH3
MeO
MeO
10
11
12
OMe
OMe
HO
CH3
OMe
O
C
C
C
C
CH3
OMe
O
C
C
OH
Reaction conditions: Phenylacetylene 2 mmol, ketone 2 mmol, KOH 2 mmol, 1 gm [(bmim) PF6] temperature 70˚C.
aIsolated yield.
following advantages; shorter reaction time, high yield,
low cost and environmentally friendly.
Therefore in the following investigations, we discussed
the addition of ethynylbenzene to different ketones under all
the above optimum conditions (Scheme 2). All the results
HO
C
R2
C
O
R1
C
[(bmim) PF6]
KOH, 700C
C
CH
+
C
obtained are listed in Table 2.
R2
R1
It is clearly observed from the Table 2, that the reaction of
aliphatic acyclic or cyclic ketones proceeds very efficently
within short time of 10 min giving excellent yield of product
(entries 1–7). While the addition of aromatic ketones with
ethynylbenzene required longer reaction time and result in
C
D
A
B
Scheme 2 Alkynylation of various ketones using
ethylylbenzene
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372 JOURNAL OF CHEMICAL RESEARCH 2007
1
D7: IR (film) 3458, 2228 cm-1; H NMR δ 1.10 (s, 9 H), 1.58
lower yield of expected product (entries 8–11).
(s, 3H), 2.0 (s, 1H), 7.30 (t, 3H, J = 4.7 Hz), 7.40 (d, 2H, J = 1.6 Hz);
Mass EI-MS m/z (rel. intensity) M+ 202 (2), 187 (7), 172 (2), 159 (3),
145 (100), 129 (10), 115 (8), 102 (5), 91 (2), 77 (3), 57 (9), 43 (41).
In conclusion, potassium hydroxide mediated synthesis
of propargylic alcohols via addition of ethynylbenzene to
ketones gives excellent yield in [(bmim) PF6].
D815: IR (film) 3302, 2250 cm-1; H NMR δ 2.20 (s, 3H), 2.45
1
(s, 1H), 7.30–7.78 (m, 10H); Mass EI-MS m/z (rel. intensity) M+ 222
(35), 221 (100), 207 (95), 189 (9), 179 (75), 165 (5), 145 (8), 129
(78), 115 (10), 105 (35), 89 (7), 77 (40), 63 (8), 43 (28).
D9: IR (film) 3379, 2234 cm-1, 1H NMR δ 2.80 (s, 3H), 2.90
(s, 1H), 7.30–7.62 (m, 9H); Mass CI-MS (M + 1)+ 257.5 (50), 239
(100), 204 (22), 179 (15), 170 (33), 144 (5), 126 (20), 113 (6), 103
(22).
Experimental
A solution of KOH (2 mmol) in ethanol (3 ml) was added to 1 g of
[(bmim) PF6]. The clear solution was kept under vacuum at 50°C for
12 h. To this basic solution ethynylbenzene (2 mmol) was added and
the reaction mixture was stirred for 5 min at room temperature then the
ketone (2 mmol) was added to the reaction mixture and the reaction
mixture was heated at 70°C with continuous stirring for the specfic
reaction time as mentioned in Table 1. The progress of the reaction
is monitored by TLC. After completion of the reaction mixture the
viscous solution was submitted to continuous liquid–liquid extraction
with diethyl ether until no further product recovery was obtained.
The organic extract were then concentrated in vacuum and the crude
product obtained was subjected to column chromatography for
further purification and all the products were analysed by GC–MS
(SHIMADZU QB 2010), MS Thermo Finnigan LCQ Advantage
Max, NMR (Varian 400 MHz) and IR (Perkin Elmer FTIR Spectrum
100) Spectroscopy. After the diethyl ether extraction the ionic liquid
was kept at 40°C under reduced pressure for 12 h and a second run
was performed under identical reaction conditions. Reuse of the ionic
liquid was carried out four times successively.
D11: IR (film) 3491, 2290 cm-1, 1H NMR δ 1.84 (s,3H), 2.01
(s, 3H), 3.90 (m, 6H), 6.85 (t, 3H, J = 5.6 Hz), 7.25–7.60 (m, 5H);
Mass CI-MS (M + 1)+ 283 (15), 265 (20), 234 (93), 219 (100), 204
(45), 181 (32), 153 (18), 137 (30), 126 (58).
D12: IR (film) 3368, 2230 cm-1, 1H NMR δ 3.0 (s, 1H), 7.20–7.80
(m, 15H); Mass CI-MS (M + 1)+ 285 (12), 267 (100), 183 (7), 165
(10).
We thank the Technical Education Quality Improvement
Program (TEQIP) grant from Government of India for
financal support.
Received 1 May 2007; accepted 25 June 2007
Paper 07/4627 doi: 10.3184/030823407X225509
Spectroscopic data of propargylic alcohols
References
1
D115: IR (film) 3257, 2258 cm-1; H NMR δ 1.44–1.70 (m, 10H),
1
2
(a) J. Fried, C. Lin, M. Mehro, W. Kao and P. Dahren, Ann. N. Y. Acad.
Sc., 1971, 180, 38; (b) W.S. Johnson, R.S. Brinkmeyer, U.M. Kapoor
and T.L. Yarnell, J. Am. Chem. Soc., 1977, 99, 8341; (c) K.K. Chan,
N.C. Cohen, J.P. Denoble, A.C. Specan and G. Saucy, J. Org. Chem.,
1976, 41, 3497.
(a) K. Fridrich, In The Chemistry of Triple-bonded Functional Groups,
Supplement C; S. Patai and Z. Rappoport, (eds.); John Wiley & Sons, New
York, 1983; Chap. 28; (b) L. Brandsma and H.D. Verkruijsse, Synthesis of
Acetylenes, Allenes and Cumulenes; Elsevier: Amsterdam, 1981, p.3.
M. Yagamuchi, A. Hayashi and M. Hirama, Chem. Lett., 1992, 2479.
Y. Han and Y.Z. Huang, Tetrahedron Lett., 1995, 36, 7277.
M. Yagamuchi, A. Hayashi and T. Minami, J. Org. Chem., 1991, 56,
4091.
2.50 (s, 1H), 7.30 (t, 3H, J = 3.1 Hz), 7.43 (d, 2H, J = 2 Hz); Mass
EI-MS m/z (rel. intensity) M+199 (79), 185 (9), 171 (15), 157 (100),
144 (28), 129 (52), 115 (30), 102 (26), 91 (10), 81 (27).
1
D215: IR (film) 3381, 2225 cm-1; H NMR δ 1.70–1.90 (m, 8H),
2.10 (s, 1H), 7.30 (t, 3H, J = 6 Hz), 7.43 (d, 2H, J = 3.9 Hz); Mass EI-
MS m/z (rel. intensity) M+ 186 (20), 185 (100), 171 (2), 157 (30), 143
(8), 129 (50), 115 (26), 102 (20), 91 (9), 77 (10), 67 (20), 55 (20).
1
D3: IR (film) 3404, 2232 cm-1; H NMR δ 0.45 (m, 4H), 0.65
3
4
5
(s, 1H), 1.01 (s,3H), 2.0 (s, 1H), 7.31 (t, 3H, J = 4.3 Hz), 7.43 (d, 2H,
J = 2.8 Hz); Mass EI-MS m/z (rel. intensity) M+186 (7), 171 (35),
158 (80), 145 (20), 129 (45), 115 (25), 102 (18), 91 940, 77 (12), 69
(10), 43 (100).
6
7
8
9
(a) N.K. Anand and E.M. Carreira, J. Am. Chem. Soc., 2001, 123, 9687;
(b) J. Biao and Y.G. Si, Tetrahedron Lett., 2002, 43, 8323.
I. Teruhiko, M. Tomohiro, H. Kumiko, A. Toshiaki, K. Takayuki and
S. Seiki, J. Org. Chem., 2003, 68, 3702.
A. Sharifi, M. Mirzaei and M. Jamal, Synthetic Commun., 2005, 35,
1039.
1
D416: IR (film) 3406, 2230 cm-1; H NMR δ 1.16–1.19 (m, 6H),
1.70 (s, 3H), 2.21 (s, 3H), 7.30 (t, 3H, J = 6 Hz), 7.42 (d, 2H, J = 2.1
Hz); Mass EI-MS m/z (rel. intensity) M+188 (2), 173 (5), 155 (2), 145
(100), 129 (9), 115 (4), 102 (7), 91 (2), 77 (4), 63 (2), 43 (55).
D. Tazils and P. Knochel, Angew.Chem., Int. Ed., 1999, 38, 1463.
1
D515: IR (film) 3361, 2229 cm-1; H NMR δ 1.60 (s, 6H), 2.90
10 J.H. Babler, V.P. Liptak and N. Phan. J. Org. Chem., 1996, 61, 416.
11 P. Wasserscheid and W. Keim, Angew. Chem., Int. Ed., 2000, 39, 3772.
12 S. Steines, B. Drieben-Holscher and P. Wasserscheid, J. Prakt. Chem.,
2000, 342, 348.
13 Y. Chauvin, H. Oliver and L. Mubamann, FR 95/14, 147, 1995; [Chem.
Abstr. 1997, 127, P 341298k].
14 C.E. Song and E.J. Roh, Chem. Commun., 2000, 837.
15 H. Miyamoto, S. Yasaka and K. Tanaka, Bull Chem. Soc., 2001, 74, 185.
16 T. Ishikawa, T. Mizuta, K. Hagiwara, T. Aikawa, T. Kudo and S. Saito.,
J. Org. Chem., 2003, 68, 3702.
(s, 1H), 7.30 (t, 3H, J = 6.4 Hz), 7.42 (d, 2H, J = 3.2 Hz); Mass EI-
MS m/z (rel. intensity) M+160 (27), 145 (100), 129 (9), 115 (15), 102
(10), 91 (7), 72 (10), 63 (5), 43 (85).
D6: IR (film) 3396, 2229 cm-1; 1H NMR δ 1.05(m, 6H), 1.60
(s, 3H), 1.70 (d, 2H, J = 1.8 Hz), 2.10 (s, 1H), 7.30 (t, 3H, J = 4.6
Hz), 7.42 (d, 2H, J = 5.9 Hz); Mass EI-MS m/z (rel. intensity) M+ 202
(2), 201 (2), 187 (10), 169 (2), 159 (3), 145 (100), 129 (10), 115 (8),
102 (9), 91 (2), 77 (4), 57 (2), 43 (50).
PAPER: 07/4627