Solvent-free addition of ethynylbenzene to ketones

Article abstract of DOI:10.1246/bcsj.74.185

The addition of ethynylbenzene to ketones proceeded efficiently in the absence of a solvent to give tertiary alkynols in good yields.

Full text of DOI:10.1246/bcsj.74.185

Short Articles
185
Bull. Chem. Soc. Jpn., 74, 185–186 (2001)
hexanone 1k using potassium t-butoxide in the absence of a
solvent gave the corresponding tertiary alkynol in low yield.
This solvent-free method is much simpler and the yield of
the product is higher than that of a solution reaction. For exam-
ple, a mixture of cyclohexanone 1k (1.0 g, 10.2 mmol), ethy-
nylbenzene 2 (1.0 g, 10.2 mmol), and potassium t-butoxide
(0.22 g, 2.0 mmol) was stirred in DMSO (10 mL) at room tem-
perature for 15 h. Also, the reaction product was mixed with
10% aqueous sodium chloride to give 1-(phenylethynyl)cyclo-
hexanol (3k)2 as colorless crystals (1.7 g, 83% yield). We
found that these reactions proceed more efficiently in the ab-
sence of a solvent than in a DMSO solution (Table 1).
Solvent-Free Addition of
Ethynylbenzene to Ketones
HisakazuMiyamoto,* ShunpeiYasaka, and
Koichi Tanaka
Department of Applied Chemistry, Faculty of Engineering,
Ehime University, Matsuyama, Ehime 790-8577
(Received August 28, 2000)
The addition of ethynylbenzene to ketones using potassium
hydroxide in solution, which give tertiary alkynols, had been
reported by Favorskii.3 This reaction is known as the Favorskii
reaction.3 Tertiary alkynols 3 were also obtained using potassi-
um hydroxide instead of potassium t-butoxide. For example,
after cyclohexanone 1k (1.0 g, 10.2 mmol), ethynylbenzene 2
(1.1 g, 10.2 mmol), and potassium hydroxide (1.1 g, 10.2
mmol) were well-mixed with agate mortar and pestle, the mix-
ture was kept at room temperature for 20 min. Also, the reac-
tion product was mixed with 10% aqueous sodium chloride to
give 1-(phenylethynyl)cyclohexanol (3k) as colorless crystals
(1.34 g, 66% yield). The addition of ethynylbenzene to 2-bu-
tanone (1b) using potassium hydroxide in the absence of a sol-
vent also gave the corresponding tertiary alkynols (3b) in 76%
The addition of ethynylbenzene to ketones proceeded
efficiently in the absence of a solvent to give tertiary alkynols
in good yields.
The alkoxide-catalyzed addition of terminal alkynes to ke-
tones, which proceeds in DMSO, has been known.1 Recently,
Tzalis et al. reported that CsOH·H2O allowed a catalytic C−H
activation of various alkynes in solution that leads, in the pres-
ence of aliphatic aldehydes or ketones, to propargylic alco-
hols.2 We found that the solvent-free addition of ethynyl-
benzene to ketones using potassium t-butoxide or potassium
hydroxide proceed efficiently at room temperature. We now
report on an ecologically and economically valuable formation
of new carbon−carbon bonds by the solvent-free addition of
ethynylbenzene to ketones.
For example, after cyclohexanone 1k (1.0 g, 10.2 mmol),
ethynylbenzene 2 (1.1 g, 10.2 mmol), and potassium t-butoxide
(1.1 g, 10.2 mmol) were well-mixed with agate mortar and pes-
tle, the mixture was kept at room temperature for 20 min.
When 1k, 2, and potassium t-butoxide were well-mixed in the
air, the reaction occurred immediately. After 20 min, the mix-
ture was kept in the crystalline state. Also, the reaction product
was mixed with 10% aqueous sodium chloride to give 1-(phe-
nylethynyl)cyclohexanol (3k)2 as colorless crystals (1.9 g, 93%
yield). A similar treatment of dialkyl ketones (1a−e), alkyl
phenyl ketones (1f−i), and cyclic ketones (1j and 1l) in the ab-
sence of a solvent gave the corresponding tertiary alkynols 3a−
j and 3l (Table 1). The addition of ethynylbenzene to 2-cyclo-
hexenone (1m) using potassium t-butoxide did not occur either
in the absence of a solvent or in solution (Scheme 1, Table 1).
The addition of 1-hexyne as another terminal alkynes to cyclo-
Table 1. Yield of Tertiary Alkynols (3) at Room Temper-
ature in the Absence of a Solvent and Solutiona)
Ketone
Product and yield/%
product
1
R1
R2
3
solvent-free solutiona)
a
b
c
d
e
f
g
h
i
M
M
e
e
M
Et
e
a
b
c
d
e
f
g
h
i
94
93
87
83
70
65
68
96
72
91
78
73
69
58
43
51
39
43
Me nPr
Et
iPr
Ph
Ph
Ph nPr
Ph iPr
Et
iPr
Me
Et
j
40
93
35
83
k
l
84
b)
46
b)
m
a) All reaction in solution were carried out in DMSO.
b) No reaction occurred.
Scheme 1.

186 Bull. Chem. Soc. Jpn., 74, No. 1 (2001)
© 2001 The Chemical Society of Japan
tracted twice with ether 10 mL. The ether solution was dried over
yield.
MgSO4, evaporated to give 3b as colorless oil (2.2 g, 93% yield).
The solvent-free addition of alkyne to carbonyl compounds
with diastereotopic faces, such as 2-methylcyclohexanone
(1n), gave a 1:1 mixture of diastereomeric propargyl alcohols
(3n)2 in 70% yield.
Various organic reactions have also been found to proceed
efficiently in the solid state.4
1
3b: IR (Neat) 3370 cm–1; H NMR δ 1.13 (m, 3H), 1.58 (s, 3H),
1.78 (m, 2H), 2.06 (s, 1H), 7.26−7.48 (m, 5H). Calcd for C12H14O:
C, 82.72; H, 8.10%. Found: C, 82.72; H, 8.10%. By the same pro-
cedure, the following compounds 3c, 3d,1,6 3g, and 3j as colorless
oil were prepared, in the yields shown in Table 1. 3c: IR (Neat)
1
3360 cm–1; H NMR δ 1.02 (m, 3H), 1.56 (s, 3H), 1.63 (m, 2H),
In summary, we have found that the addition of ethynylben-
zene to ketones is very useful and proceeds more efficiently in
the absence of a solvent than in a DMSO solution at room tem-
perature.
1.75 (m, 1H), 2.06 (s, 1H), 7.30−7.43 (m, 5H). Calcd for C13H16O:
C, 82.94; H, 8.57%. Found: C, 82.65; H, 8.67%. 3d: IR (Neat)
1
3380 cm–1; H NMR δ 1.11 (m, 6H), 1.76 (m, 4H), 1.99 (s, 1H),
7.31−7.42 (m, 5H). Calcd for C13H16O: C, 82.94; H, 8.57%.
Found: C, 82.54; H, 8.72%. 3g: IR (Neat) 3380 cm–1; 1H NMR δ
1.01 (m, 3H), 2.08 (m, 2H), 2.59 (s, 1H), 7.28−7.69 (m, 10H). Cal-
cd for C17H16O: C, 86.40; H, 6.82%. Found: C, 86.08; H, 6.82%.
Experimental
General Methods. IR spectra were measured with a JASCO
FT/IR-350 IR spectrometer, using Nujol mulls. 1H NMR spectra
were recorded in CDCl3 on a JEOL JNM-LA300 (300 MHz) spec-
trometer.
1
3j: IR (Neat) 3350 cm–1; H NMR δ 1.75−2.08 (m, 8H), 1.87 (s,
1H), 7.30−7.12 (m, 5H). Calcd for C13H14O: C, 83.83; H, 7.58%.
Found: C, 83.39; H, 7.70%.
Preparation of 1-(Phenylethynyl)cyclohexanol (3k)2 in the
Absence of a Solvent. Using potassium hydroxide as a base,
after cyclohexanone 1k (1.0 g, 10.2 mmol), ethynylbenzene 2 (1.0
g, 10.2 mmol), and potassium hydroxide (1.1 g, 10.2 mmol) were
well-mixed with agate mortar and pestle, the mixture was kept at
room temperature for 20 min. The reaction product was mixed
with 10% aqueous sodium chloride, filtered, washed with water,
and dried to give 1-(phenylethynyl)cyclohexanol (3k) as colorless
crystals (1.34 g, 66% yield).
Typical procedure in DMSO: Preparation of 1-(Phenylethy-
nyl)cyclohexanol (3k) in DMSO. A mixture of cyclohexanone
1k (1.0 g, 10.2 mmol), ethynylbenzene 2 (1.0 g, 10.2 mmol), and
potassium t-butoxide (0.22 g, 2.0 mmol) was stirred in DMSO 10
mL at room temperature for 15 h. The reaction product was mixed
with 10% aqueous sodium chloride, filtered, and washed with wa-
ter, and dried to give 1-(phenylethynyl)cyclohexanol (3k) as color-
less crystals (1.7 g, 83% yield).
Typical Procedure in the Absence of a Solvent: Preparation
of 2-Methyl-4-phenyl-3-butyn-2-ol (3a)5 in the Absence of a
Solvent. After acetone 1a (1.0 g, 17.2 mmol), ethynylbenzene 2
(1.8 g, 17.2 mmol), and potassium t-butoxide (1.9 g, 17.2 mmol)
were well-mixed with agate mortar and pestle, the mixture was
kept at room temperature for 20 min. The reaction product was
mixed with 10% aqueous sodium chloride, filtered, washed with
water, and dried to give 3a as colorless crystals (2.6 g, 94% yield).
3a: mp 41–43 °C; IR (Nujol) 3270 cm–1; 1H NMR δ 1.64 (s, 6H),
2.03 (s, 1H), 7.31−7.42 (m, 5H). Calcd for C11H12O: C, 82.46; H,
7.55%. Found: C, 82.59; H, 7.73%. By the same procedure, the
following compounds 3e,2 3f, 3h, 3i,2 3k,2 3l, and 3n2 as colorless
crystals were prepared, in the yields shown in Table 1. 3e: mp 39−
1
41 °C; IR (Nujol) 3350 cm–1; H NMR δ 1.05 (d, 6H), 1.09 (d,
6H), 1.81 (s, 1H), 2.04 (m, 2H), 7.32−7.43 (m, 5H). Calcd for
C15H20O: C, 83.28; H, 9.37%. Found: C, 83.12; H, 9.37%. 3f: mp
57−58 °C; IR (Nujol) 3300 cm–1; 1H NMR δ 1.92 (s, 3H), 2.42 (s,
1H), 7.36−7.74 (m, 10H). Calcd for C16H14O: C, 86.45; H, 6.35%.
Found: C, 86.61; H, 6.40%. 3h: mp 59−61 °C; IR (Nujol) 3300
cm–1; 1H NMR δ 0.92 (m, 3H), 1.48 (m, 2H), 1.98 (m, 2H), 2.41 (s,
1H), 7.34−7.70 (m, 10H). Calcd for C18H18O: C, 83.36; H, 7.25%.
Found: C, 86.21; H, 7.27%. 3i2: mp 54−56 °C; IR (Nujol) 3310
cm–1; 1H NMR δ 0.88 (d, 3H), 1.21 (d, 3H), 2.17 (m, 1H), 2.41 (s,
1H), 7.30−7.70 (m, 10H). Calcd for C18H18O: C, 86.36; H, 7.25%.
Found: C, 86.42; H, 7.32%. 3k2: mp 49−50 °C; IR (Nujol) 3220
This work was supported by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Science and Culture,
Japanese Government, and by Mitsubishi Chemical Corpora-
tion Fund (to H.M.). Elemental analyses were performed at the
Advanced Instrumentation Center for Chemical Analysis,
Ehime University. Technical assistance from Taku Kimura is
gratefully acknowledged.
1
cm–1; H NMR δ 1.27−2.02 (m, 10H), 2.03 (s, 1H), 7.30 (t, 3H),
7.44 (d, 2H). Calcd for C14H16O: C, 83.96; H, 8.05%. Found: C,
84.06; H, 8.20%. 3l: mp 38−40 °C; IR (Nujol) 3270 cm–1;
1H NMR δ 1.56−2.15 (m, 12H), 1.96 (s, 1H), 7.31−7.43 (m, 5H).
Calcd for C15H18O: C, 84.07; H, 8.47%. Found: C, 84.08; H,
8.62%. 3n: mp 80−82 °C; IR (Nujol) 3370 cm–1; 1H NMR δ 1.12
(d, 3H), 1.22−1.78 (m, 9H), 2.17 (s, 1H), 7.26−7.47 (m, 5H). Cal-
cd for C15H18O: C, 84.07; H, 8.47%. Found: C, 84.07; H, 8.47%.
Preparation of 3-Methyl-1-phenyl-1-pentyn-3-ol (3b)6 in the
Absence of a Solvent. After 2-butanone 1b (1.0 g, 13.9 mmol),
ethynylbenzene 2 (1.4 g, 13.9 mmol), and potassium t-butoxide
(1.6 g, 13.9 mmol) were well-mixed with agate mortar and pestle,
the mixture was kept at room temperature for 20 min. The reaction
product was mixed with 10% aqueous sodium chloride and ex-
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