Conversion of alkynes into α,α-dichloro ketones and α,α-dichlorodimethyl ketals using trichloroisocyanuric acid

Article abstract of DOI:10.1081/SCC-120021025

Trichloroisocyanuric acid reacts with alkynes in the presence of water in acetone or acetonitrile to form α,α-dichloro ketones and in methanol to form α,α-dichlorodimethyl ketals.

Full text of DOI:10.1081/SCC-120021025

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Conversion of Alkynes into α,α-Dichloro Ketones and
α,α-Dichlorodimethyl Ketals Using Trichloroisocyanuric
Acid
a
a
a
Prof. Gene A. Hiegel , Christopher D. Bayne & Brendt Ridley
a
Department of Chemistry and Biochemistry, California State University, Fullerton,
California, USA
Published online: 17 Aug 2006.
To cite this article: Prof. Gene A. Hiegel , Christopher D. Bayne & Brendt Ridley (2003): Conversion of Alkynes into
α,α-Dichloro Ketones and α,α-Dichlorodimethyl Ketals Using Trichloroisocyanuric Acid, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 33:12, 1997-2002
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Õ
SYNTHETIC COMMUNICATIONS
Vol. 33, No. 12, pp. 1997–2002, 2003
Conversion of Alkynes into a,a-Dichloro Ketones
and a,a-Dichlorodimethyl Ketals Using
Trichloroisocyanuric Acid
Gene A. Hiegel,* Christopher D. Bayne, and Brendt Ridley
Department of Chemistry and Biochemistry,
California State University, Fullerton,
California, USA
ABSTRACT
Trichloroisocyanuric acid reacts with alkynes in the presence of
water in acetone or acetonitrile to form a,a-dichloro ketones and
in methanol to form a,a-dichlorodimethyl ketals.
Key Words: Alkynes; Oxidation; Addition; Ketones; a,a-Dichloro-
ketones, ketals, a,a-Dichlorodimethylketals; Synthesis; Preparation.
*
Correspondence: Prof. Gene A. Hiegel, Department of Chemistry and
Biochemistry, California State University, 800 N. State College Blvd.,
Fullerton, California 92834, USA; Fax: 714-278-5316; E-mail: ghiegel@
fullerton.edu.
1
997
DOI: 10.1081/SCC-120021025
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
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1
998
Hiegel, Bayne, and Ridley
Alkynes can be converted into a,a-dichloro ketones by the action
[
1]
potassiummonoperoxysulfate with 1 M HCl in DMF.
N-chlorosuccini-
mide in methanol converts alkynes into a,a-dichlorodimethyl ketals which
[
2]
can be hydrolyzed in acid to the corresponding a,a-dichloroketones.
We wish to report that trichoroisocyanuric acid (1) [1,3,5-trichloro-
[
3]
,3,5-triazine-2,4,6-(1H,3H,5H)-trione; TCICA] reacts with alkynes in
1
the presence of water to form a,a-dichloro ketones and in methanol to
form a,a-dichlorodimethyl ketals as the major products (Eqs. (1) and (2)).
Although the product mixtures were quite complex, the desired com-
pound was the major component and could be isolated in reasonable
yield and purity. The results are summarized in the Table 1.
ð1Þ
ð2Þ
Because the reactions are exothermic and a higher temperature
promotes the formation of byproducts, the reaction mixtures were kept
ꢀ
below 40 C by means of a room temperature water bath and the slow
addition of solid 1. Acetone and acetonitrile are suitable solvents for the
preparation of the ketones, but acetone generally gave higher yields. The
product from1-octyne with 1 in methanol appeared to decompose during
distillation and gave an impure product.
It has been proposed that addition of chlorine gives a vinyl cation
which then reacts with water to give the enol or with methanol to give the
[2]
enol ether. These intermediates would be expected chlorinate rapidly a
second time leading to the major isolated products. Terminal, phenyl,
and symmetrical alkynes gave one major product. Unsymmetrical dialkyl
[
2]
alkynes are expected to give two major products.
EXPERIMENTAL
All reagents were used as received. Reagent grade acetone,
anhydrous methanol, 1-hexyne, 1-phenyl-1-butyne, 1-phenyl-1-hexyne,
and phenylacetylene were obtained fromAldrich. 1 was obtained from
ChemLab Products (99%, 89% available chlorine). 1-Octyne and
4-octyne were obtained fromFarchan. All liquid products were distilled

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Conversion of Alkynes into a,a-Dichloro Ketones
1999
Table 1.
Yield
(%)
GC purity
(%)
Entry
1
Alkyne
Product
61
64
62
92
93
91
2
3
4
5
6
79
59
73
95
99
96
7
8
9
52
62
80
99
96
99
through a concentric tube column except for 2,2-dichloro-1,1-dimethoxy-
1-phenylbutane, which was purified by simple vacuum distillation.
1
H NMR spectra were recorded in CDCl using a Brucker AC 200.
3
FT-IR spectra were recorded using Perkin Elmer 1650. GC analyses were
obtained using modified Varian 3700 with a 30 m DB-5 capillary column
or a Hewlet-Packard 5890 Series II with either a 5 mHP-1 capillary
column or a 6 ft 1/8 in 10% Carbowax 20 M packed column.

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2
000
Hiegel, Bayne, and Ridley
2
,2-Dichloro-1-phenyl-1-hexanone (Entry 6)
-Phenyl-1-hexyne (15.02 g, 0.0949 mol, 0.1898 ꢀ bond eq), water
20.39 g, 1.132 mol), acetone (92 mL), and a magnetic stir bar were
1
(
added to a 200 mL three-neck round-bottomed flask fitted with a thermo-
meter reaching into the liquid, a condenser, and a solid addition funnel.
The flask was placed in a roomte mp erature water bath. In the solid
addition funnel was placed 1 (19.22 g, 0.0827 mol, 0.2481 eq). A gentle
streamof N 2 was passed through the addition funnel and out the con-
denser to prevent caking in the tip of the funnel. The 1 was added at 1 min
intervals over a period of 35 min, and the temperature of the reaction did
ꢀ
not exceed 36 C. After the addition, 15 mL of acetone was used to wash
the last traces of 1 into the flask, and stirring was continued for 42 min
[
4]
more. Saturated NaHSO solution was added to destroy remaining 1,
3
and the mixture was filtered to remove the cyanuric acid precipitate. The
solution was concentrated on a rotary evaporator, and the residue
extracted with ether (2 Â 75 mL). The combined ether layers were
washed with 1 N NaOH (50 mL) and saturated NaCl (40 mL), and
dried over MgSO . After filtration and concentration, the residue was
4
distilled through a concentric tube column to give 17.01 g (73%, 96%
ꢀ
pure by GC, b.p. 130.0–132.2 C (1.0 torr)) of 2,2-dichloro-1-phenyl-1-
À1
hexanone: IR (film) 1701, 1608, 1456, 1259, 1248, 831, 695 cm
;
1
H NMR ꢁ 8.29 (m, 2H, ArH), 7.50 (m, 3H, ArH), 2.50 (m, 2H,
CH CCl ), 1.70 (m, 2H, CH CH CCl ), 1.44 (sextet, J ¼ 7.4, 2H,
2
2
2
2
2
2
CH CH ), 0.97 (t, J ¼ 7.4, 3H, CH ); HRMS calcd. for C H OCl
2
3
3
12 15
(
M þ H) 245.04999, found 245.04990.
,2-Dichloro-1,1-dimethoxy-1-phenylethane (Entry 7)
Phenylacetyl-ene (9.30 g, 0.09105 mol, 0.1821 ꢀ bond eq), methanol
100.0 mL, 2.469 mol), and a magnetic stir bar were added to a 200 mL
2
(
three-neck round-bottomed flask fitted with a thermometer reaching into
the liquid, a condenser, and a solid addition funnel. The flask was placed
in a roomtemperature water bath. In the solid addition funnel was placed
1 (10.60 g, 0.04561 mol, 0.1368 eq). A gentle stream of N was passed
2
through the addition funnel and out the condenser to prevent caking in
the tip of the funnel. The 1 was added over a period of 15 min, and the
ꢀ
temperature of the reaction did not exceed 39 C. Stirring was continued
for 2 h more. Saturated NaHSO solution was added to destroy remain-
3
[4]
ing 1, and the mixture was filtered to remove the cyanuric acid preci-
pitate. The solvent was removed on a rotary evaporator and 30 mL of
ether was added. More cyanuric acid precipitated and the sample was
filtered again. After adding 20 mL more ether, the solution was washed
with saturated NaCl (2 Â 20 mL), and dried over MgSO . After filtration
4

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Conversion of Alkynes into a,a-Dichloro Ketones
2001
and solvent removal under vacuum, the solid residue was recrystallized
fromethanol:water (85:15) to give 11.07 g (52%, 99% pure by GC, m.p.
ꢀ
[5]
6.1–66.3 C) of 2,2-dichloro-1,1-dimethoxy-1-phenylethane: IR (mull)
6
1
6
1
1
462, 1451, 1305, 1104, 1075, 1044, 1031, 992, 806, 777, 769, 709,
À1
1
61 cm ; H NMR ꢁ 7.60 (m, 2H, ArH), 7.33 (m, 3H, ArH), 5.96 (s,
H, CHCl ), 3.31 (s, 6H, OCH ); HRMS calcd. for C H O Cl (M À Cl)
2
3
10 12
2
99.05258, found 199.05260.
1,1-Dichloro-2-hexanone (Entry 1)
Mole ratio alkyne:1:H O 1.20:1:14.34, yield 61% (92% pure by GC),
2
ꢀ
À1
;
b.p. 131.1–132.0 C (171 torr): IR (film) 1733, 1218, 1149, 793, 736 cm
1
H NMR ꢁ 5.82 (s, 1H, CHCl ), 2.84 (t, J ¼ 7.5, 2H, CH CO), 1.66
2
2
(
0
1
quintet, J ¼ 7.5, 2H, CH CH CO), 1.38 (sextet, J ¼ 7.5, 2H, CH CH ),
2
2
2
3
.94 (t, J ¼ 7.5, 3H, CH ); HRMS calcd. for C H OCl (M þ H)
3
6
11
2
69.01869, found 169.01870.
1
,1-Dichloro-2-octanone (Entry 2)
Mole ratio alkyne:1:H O 1.25:1: 13.74, yield 64% (93% pure by GC),
2
ꢀ
À1
b.p. 133.8–136.7 C (54 torr): IR (film) 1735, 1217, 1142, 791, 735 cm
1
;
H NMR ꢁ 5.82 (s, 1H, CHCl ), 2.82 (t, J ¼ 7.3, 2H, CH CO), 1.68 (m,
2
2
2
H, CH CH CO), 1.33 (m, 6H, CH CH CH CH ), 0.90 (t, J ¼ 6.4, 3H,
2
2
2
2
2
3
CH ); HRMS calcd. for C H OCl (M þ H) 197.04999, found
3
8
15
2
197.05000.
5
,5-Dichloro-4-octanone (Entry 3)
Mole ratio alkyne:1:H O 1.31:1: 13.90, yield 62% (91% pure by GC),
2
ꢀ
b.p. 115.0–118.1 C (54 torr): IR (film) 1733, 1155, 1122, 1112, 1010, 894,
À1
1
7
60, 670 cm ; H NMR ꢁ 2.93 (t, J ¼ 7.0, 2H, CH CO), 2.33 (m, 2H,
2
CH CCl ), 1.53, (m, 4H, CH CH CO and CH CH CCl ), 0.90–1.11 (m,
2 2 2 2 2 2 2
6
H, CH and CH ); HRMS calcd. for C H OCl (M þ H) 197.04999,
3
3
8
15
2
found 197.04997.
a,a-Dichloroacetophenone (Entry 4)
Mole ratio alkyne:1:H O 1.15: 1:13.70, yield 79% (95% pure by GC),
b.p. 96.5–117.7 C (1.5–2.5 torr): IR and H NMR spectra were identical
to those of an authentic sample.
2
ꢀ
1
2
,2-Chloro-1-phenyl-1-butanone (Entry 5)
Mole ratio alkyne:1:H O 1.32:1:15.63, yield 59% (99% pure by GC),
2
ꢀ
b.p. 111.2–112.0 C (2.3 torr): IR (film) 1724, 1252, 1241, 1186, 1106,
À1
1
020, 920, 837, 826, 812, 724, 689, 662 cm ; H NMR ꢁ 8.29 (m, 2H,
1
ArH), 7.52 (m, 3H, ArH), 2.53 (q, J ¼ 7.0, 2H, CH ), 1.24 (t, J ¼ 7.0, 3H,
2
CH ); HRMS calcd. for C H OCl (M þ H) 217.01869, found
3
10 11
2
217.01860.

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2
002
Hiegel, Bayne, and Ridley
2
,2-Dichloro-1,1-dimethoxy-1-phenylbutane (Entry 8)
Mole ratio alkyne:1:CH OH 1.33:1:35.55, yield 62% (96% pure by
3
ꢀ
GC), b.p. 100.0–102.0 C (0.25 torr): IR (film) 1450, 1235, 1192, 1181,
À1
1
124, 1085, 1064, 918, 837, 831, 803, 755, 709, 680, 668 cm ; H NMR
1
ꢁ
7.60 (m, 2H, ArH), 7.33 (m, 3H, ArH), 3.50 (s, 6, OCH ), 1.98 (q,
3
J ¼ 7.0, CH ), 1.14 (t, J ¼ 7.0, CH ); HRMS calcd. for C H O Cl
2
3
12 16
2
(
M À Cl) 227.08388, found 227.08390.
,2-Dichloro-1,1-dimethoxy-1-phenylhexane (Entry 9)
Mole ratio alkyne:1:CH OH 1.25:1:32.40, yield 80% (99% pure by
2
3
ꢀ
GC), m.p. 44.3–45.1 C (recrystallized from95% ethanol): IR ( mu ll)
1
7
230, 1190, 1180, 1127, 1111, 1063, 1035, 1020, 943, 820, 800, 760, 741,
À1
1
18, 709, 678, 652 cm ; H NMR ꢁ 7.64 (m, 2H, ArH), 7.36 (m, 3H,
ArH), 3.52 (s, 6H, OCH ), 1.87 (m, 2H, CH CCl ), 1.70 (m, 2H,
3
2
2
CH CH CCl ), 1.28 (sextet, J ¼ 7.4, 2H, CH CH ), 0.89 (t, J ¼ 7.4, 3H,
2
2
2
2
3
CH ); HRMS calcd. for C H OCl (M–OCH ) 259.06564, found
3
13 17
2
3
259.06560.
ACKNOWLEDGMENT
HRMS data was provided courtesy of John R. Carney. This research
was supported in part by NSF-REU programgrants.
REFERENCES
1
. Kim, K.K.; Kim, J.N.; Kim, K.M.; Kim, H.R.; Ryu, E.K. One-pot
synthesis of a,a-dichloroketones with alkynes using the
N,N-dimethylformamide/hydrogen chloride/potassium monoperoxy-
sulfate system. Chemistry Letters 1992, 603–604, and references
therein for other less effective methods.
2. Reed, S.F., Jr. The preparation of a,a-dichloroketones. J. Org. Chem.
1965, 30 (7), 2195–2198.
3
. For synthetic applications of 1 see Hiegel, G.A. Trichloroisocyanuric
acid. In Encyclopedia of Reagents for Organic Synthesis; Paquette,
L.A., Ed.; Wiley: Chichester, Sussex, England, 1995; Vol. 7,
5072–5073.
4
5
. Wet iodide-starch test paper was used to test for the presence of
oxidizing power.
. Reported m.p. 66–67.5 C, Ref.
ꢀ
[2]
Received in the USA October 17, 2002