Selective preparation of α,α-dichloroketones with copper(II) chloride

Article abstract of DOI:10.1081/SCC-120015383

Aryl and enolizable alkyl ketones react with copper(II) chloride in dimethylformamide to produce the corresponding α,α-dichloroketone in high yields. Remarkable qualities of the process are high selectivity towards these substrates, undetected polychlorinated by-products, easy work-up, commercially available reagents and HCl as the only waste stream.

Full text of DOI:10.1081/SCC-120015383

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SELECTIVE PREPARATION OF α,α-DICHLOROKETONES
WITH COPPER(II) CHLORIDE
José Arimateia Nobrega a , Simone Maria C. Gonçalves a & Clovis Peppe b
a Departamento de Química Fundamental, Universidade Federal de Pernambuco, UFPE,
Recife, PE, 50670-901, Brazil
b Laboratório de Materiais Inorgânicos, Departamento de Química, Universidade Federal de
Santa Maria, UFSM, Santa Maria, RS, 97105-900, Brazil
Version of record first published: 23 Aug 2006.
To cite this article: José Arimateia Nobrega , Simone Maria C. Gonçalves & Clovis Peppe (2002): SELECTIVE PREPARATION
OF α,α-DICHLOROKETONES WITH COPPER(II) CHLORIDE, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 32:24, 3711-3717
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SYNTHETIC COMMUNICATIONS
Vol. 32, No. 24, pp. 3711–3717, 2002
SELECTIVE PREPARATION OF
a,a-DICHLOROKETONES WITH
COPPER(II) CHLORIDE
Jose Arimateia Nobrega,1
Simone Maria C. Goncalves,1 and Clovis Peppe2,
*
1Departamento de Quımica Fundamental, Universidade
Federal de Pernambuco, UFPE,
Recife-PE, Brazil, 50670-901
2Laboratorio de Materiais Inorganicos, Departamento
de Quımica, Universidade Federal de Santa Maria,
UFSM, Santa Maria-RS, Brazil, 97105-900
ABSTRACT
Aryl and enolizable alkyl ketones react with copper(II) chlor-
ide in dimethylformamide to produce the corresponding
a,a-dichloroketone in high yields. Remarkable qualities of
the process are high selectivity towards these substrates,
undetected polychlorinated by-products, easy work-up, com-
mercially available reagents and HCl as the only waste stream.
Key Words: Dichloroketones; Dichlorination; Copper(II)
chloride
*Corresponding author. E-mail: peppe@quimica.ufsm.br
3711
DOI: 10.1081/SCC-120015383
Copyright & 2002 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
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3712
NOBREGA, GONCALVES, AND PEPPE
The use of a,a-dihalogenoketones as building blocks in organic syn-
thesis has been investigated scarcely. A few reports[1,2] established that these
compounds present very interesting chemical properties. The electrochemical
reduction of a,a-dibromoacetophenone led to the simultaneous production of
(E)-4,4-dibromo-1,3-diphenyl-2,3-epoxybutan-1-one and trans-1,2,3-triben-
zoylcyclopropane, via anionic and carbene intermediates, respectively. The
reaction of a,a-dichloroacetophenone with substituted benzaldehydes, under
the Darzens conditions, produced the corresponding 1-phenyl-2-chloro-
3-aryl-2,3-epoxy-1-propanone and 1-phenyl-3-aryl-3-chloro-1,2-propane-
dione, the latter as the result of the epoxide ring-opening.[2]
Despite the relevance of these results, the use of a,a-dihalogeno-
ketones in organic synthesis still remains unexplored. This is probably due
to the lack of a convenient synthetic protocol to prepare them, particularly
the a,a-dichloro compounds, which have been synthesized from acetylenes
and N-chlorosuccinimide.[3] Alternative procedures starting with carbonyl
precursors, are controlled addition of gaseous Cl2, in formic acid containing
HCl as catalyst;[4] reaction with sulfuryl chloride;[5] and with an ammonium
salt of tetrachloroiodate.[6] Simultaneous formation of polychlorinated
by-products seems to be the major limitation associated with some[4,5] of
the latter methods.
CuX2 (X ¼ Cl, Br) compounds have been used to produce the corre-
sponding monohalogeno derivatives of silyl enol ethers,[7] enol esters,[8] and
ketones.[9,10] The latter reaction is known as the Kosower method. We now
report that it is possible to adjust the condition of the Kosower reaction to
produce a,a-dichloroketones from the corresponding ketones,[11,12] with
no signs of polychlorinated by-products, overcoming the major limitation
associated to some of the synthetic routes discussed above.
Table 1 shows that a variety of aryl and enolizable alkyl ketones were
selectively transformed into their a,a-dichloro derivatives in good to excel-
lent yields. An insight on the scope and generality of the present method was
obtained by studying the reactions with substituted acetophenones at the
aryl and alkyl portions of the molecules. We have observed that there is no
significant difference in reactivity between acetophenone (Entry 1) and its
derivatives containing electron donating (Entries 2–6) or electron withdraw-
ing groups (Entries 7–8). Substitution at the alkyl portion produced similar

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a,a-DICHLOROKETONES
3713
Table 1. Selective Preparation of a,a-Dichloroketones with Copper(II) Chloride
Time
(h)
Yield
(%)
Entry
R
R0
1
2
3
4
5
6
7
8
9
10
11
12
13
C6H5
H
H
H
H
H
H
H
H
CH3
4
5
5
4
4
5
4
4
6
5
2
2
28
76
70
71
82
80
74
86
90
70
80
65
94
4-CH3-C6H5
4-C6H5-C6H4
4-MeO-C6H5
3,4-OCH2O-C6H5
2-C4H3Sb
4-Cl-C6H5
4-F-C6H5
C6H5
a
C6H5
CH3
CH3CH2O
C6H5
C6H5
C(¼O)CH3
(CH2)c
N.R.
a30,40-(Methylenedioxy)acetophenone; b20-Acetyl-thiophene; cCyclohexanone, N.R ¼
No reaction was observed.
results. Thus, propiophenone (Entry 9) and 2-phenylacetophenone
(Entry 10) produced comparable yields than acetophenone, under similar
reaction conditions.
We have examined also the reaction between CuCl2 with alkyl ketones.
We first note that we fail to observe the formation of the a,a-dichloro
derivative from cyclohexanone (Entry 13), even after a long period of
reflux. But, the highly enolizable 1-phenyl-propan-2-one (Entry 11) and
methyl acetoacetate react considerably faster than their aryl analogues,
and no chlorination on the methyl groups of the molecules was observed.
We, therefore, conclude that this modification introduced in
the Kosower method is highly efficient for the selective preparation of
a,a-dichloroketones directly from their aryl and highly enolizable alkyl
carbonyl precursors. Special advantages associated with it when compared
to the previous methodologies are the use of non-toxic and commercially
available starting materials, easy work-up and high yields.
Selective preparation of a,a-dichloroketones with copper(II) chloride.
Experimental procedure: CuCl2 Á 2H2O (2.00 g, 11.73 mmol) and LiCl (0.50 g,
11.73 mmol) were dissolved in DMF (9 mL) in a two-neck round-bottomed
flask equipped with a reflux condenser. To this solution, the corresponding
ketone (1.95 mmol) was added and the mixture heated (90ꢀC) under
magnetic stirring for the appropriated time (Table 1). The mixture was

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3714
NOBREGA, GONCALVES, AND PEPPE
cooled to room temperature, CH2Cl2 (50 mL) added, and the organic sol-
ution washed with H2O (40 mL). The phases were separated; the aqueous
phase was washed with CH2Cl2 (50 mL). The two CH2Cl2 portions were
combined and washed with H2O (40 mL) to ensure complete removal of
DMF. The organic extract was dried (MgSO4), filtered and evaporated to
dryness to leave the a,a-dichloroketone, which was purified by column
chromatography on silica gel (hexane:ethyl acetate), and characterized by:
NMR (1H, 300 MHzin CDCl
solutions and 13C, 75.4 MHz, CDCl3
3
solutions) in a VARIAN Unityplus 300 instrument; IR spectroscopy (neat
samples between KBr plates) in a BOMEN 1,45 instrument; mass
spectrometry (CHCl3 solutions) obtained on a FINNIGAN GCQ instru-
ment operating at 70 eV; and microanalysis obtained on a CHNS-O 1110
from CE Instruments. Melting points were determined with a Micro
Quimica MQAPF-301 instrument and are uncorrected. Boiling points are
uncorrected. Yields and other conditions are given in Table 1.
Entry
1
(2,2-dichloro-acetophenone): Boiling point: 58–60ꢀC
calculated (found) for
(1.1 mm Hg), Lit.[6] 243ꢀC (760 mm Hg);
%
1
C8H6Cl2O: C, 50.82 (50.69); H, 3.19 (3.11); H NMR: 6.67 (1H, s, CHCl2),
8.1–7.5 (5H, m, Arom.); 13C NMR: 67.75 (CHCl2), 128.90 (CarH.), 129.71
(CarH), 131.30 (C10ar.), 134.53 (C20arH and C50arH), 185.88 (C¼O); MS,
m/z [ion, %]: 189/191/193 [(M þ 1)þ, 10], 153/155 [(M ꢁ Cl)þ, 5], 105
[(M ꢁ CHCl2)þ, 100]; IR (cmꢁ1): 3064.64, 2922.97, 1707.32, 1596.29, 1449.46,
814.31, 686.26.
Entry 2 (2,2-dichloro-40-methyl-acetophenone): Melting point: 52–53ꢀC,
Lit.[6] 53.5–54ꢀC; % calculated (found) for C9H8Cl2O: C, 53.23 (53.38); H,
1
3.97 (3.81); H NMR: 2.42 (3H, s, CH3), 6.66 (1H,s, CHCl2), 7.30 (2H, d,
J ¼ 8.2 Hz, CHar), 7.95 (2H, d, J ¼ 8.2 Hz, CHar); 13C NMR: 21.80 (ArCH3),
67.79 (CHCl2), 128.70 (C10ar), 129.60 (CarH), 129.82 (CarH), 145.83 (C40ar),
185.54 (C¼O); MS, m/z [ion, %]: 202/204/206 [MþÁ, 10], 167/169 [(M ꢁ Cl)þ,
5], 119 [(M ꢁ CHCl2)þ, 100], 91 [C7H7þ, 42]; IR (cmꢁ1): 3044.34, 2928.67,
1710.32, 1591.22, 1453.45, 817.32, 680.35.
Entry 3 (2,2-dichloro-40-phenyl-acetophenone): Melting point: 85–87ꢀC;
% calculated (found) for C14H10Cl2O: C, 63.42 (63.58); H, 3.80 (3.72);
1H NMR: 6.70 (1H, s, CHCl2), 7.44–8.17 (9H, m, CHar); 13C NMR: 67.86
(CHCl2), 127.29 (CarH), 127.46 (CarH), 128.66 (CarH), 129.05 (CarH),
129.88 (Car), 130.36 (CarH), 139.33 (Car), 147.25 (Car), 185.52 (C¼O); MS,
m/z[ion,%]:264/266/268[MþÁ,5],229/231[(M ꢁ Cl)þ,7],181[(M ꢁ CHCl2)þ,
100], 153 [C6H5-C6H4þ, 26]; IR (cmꢁ1): 3011.36, 1691.79, 1602.04, 1406.42,
1235.97, 855.19.
Entry
4
(2,2-dichloro-40-methoxy-acetophenone): Melting point:
77–79ꢀC, Lit.[6] 77–78ꢀC; % calculated (found) for C9H8Cl2O2: C, 49.34
(49.26); H, 3.68 (3.59); 1H NMR: 3.87 (3H, s, OCH3), 6.63 (1H, s,

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a,a-DICHLOROKETONES
3715
0
CHCl2), 6.95 (2H, d, J ¼ 9 Hz , C2arH and C60arH), 8.04 (2H, d, J ¼ 9 Hz ,
C30arH and C50arH); 13C NMR: 55.61 (OCH3), 67.82 (CHCl2), 114.16
(C20arH and C60arH), 123.83 (C10ar), 132.23 (C30arH and C50arH), 164.57
(C40ar-OMe), 188.55 (C¼O); MS, m/z [ion, %]: 218/220/222 [MþÁ, 3], 135
[(M ꢁ CHCl2)þ, 100], 107 [CH3OC6H4þ, 10]; IR (cmꢁ1): 3029.81, 2980.86,
1682.93, 1237.60, 1177.63, 847.91, 604.08.
Entry
5
(2,2-dichloro-30,40-methylenedioxy-acetophenone): Melting
point: 82–84ꢀC; % calculated (found) for C9H6Cl2O3: C, 46.38 (46.32); H,
2.59 (2.41); 1H NMR: 6.06 (2H, s, O-CH2-O), 6.60 (1H, s, CHCl2), 6.87 (1H,
d, J ¼ 8.2 Hz, C50arH), 7.51 (1H, d, J ¼ 2 Hz , C2arH), 7.69 (1H, dd,
0
J ¼ 8.2 Hz, 2 Hz, C60arH); 13C NMR: 67.27 (CHCl2), 102.25 (O-CH2-O),
109.31 (C20arH), 108.22 (C50arH), 125.59 (C10ar), 126.50 (C60arH), 148.42
(C30ar-O), 153.07 (C40ar-O), 184.24 (C¼O); MS, m/z [ion, %]: 232/234/236
þ
[MþÁ,10],197/199[(M ꢁ Cl)þ,2],149[(M ꢁ CHCl2)þ,100],121[CH2O2C6H3
,
15]; IR (cmꢁ1): 3023.42, 2920.86, 1681.65, 1601.65, 1446.18, 1251.35,
1034.63, 656.88.
Entry 6 (20-acetyl-2,2-dichloro-thiophene): Boiling point: 85–87ꢀC
(0.7 mm Hg); % calculated (found) for C6H4Cl2OS: C, 36.94 (36.83); H,
1
2.05 (2.02); S, 16.44 (16.39); H NMR: 6.52 (1H, s, CHCl2), 7.14 (1H, dd,
0
0
J ¼ 4 Hz , J ¼ 5 Hz , C4arH), 7.74 (1H, d, J ¼ 5 Hz , C3arH), 7.92 (1H, d,
J ¼ 4 Hz , C5arH); 13C NMR: 67.76 (CHCl2), 128.54 (C40arH), 134.77
0
(C30arH), 136.45 (C50arH), 136.93 (C20ar), 179.53 (C¼O); IR (cmꢁ1):
3102.40, 1682.41, 1515.16, 1411.28, 1356.71, 1244.15, 1217.88, 1066.41,
804.93, 727.10, 667.61.
Entry 7 (2,2,40-trichloro-acetophenone): Melting point: 61–63ꢀC, Lit.[6]
60–61.5ꢀC; % calculated (found) for C8H5Cl3O: C, 42.99 (42.88); H, 2.25
(2.31); H NMR: 6.58 (1H, s, CHCl2), 7.47 (2H, d, J ¼ 8.8 Hz, C20arH and
1
C60arH), 8.02 (2H, d, J ¼ 8.8 Hz, C30arH and C50arH); 13C NMR: 67.76
(CHCl2), 129.25 (CarH), 129.42 (C10ar), 131.20 (CarH), 141.19 (C40arCl),
184.86 (C¼O); MS, m/z [ion, %]: 223/225/227/229 [(M þ 1)þ, 5], 187/189/
191 [(M ꢁ Cl)þ, 3], 139/141 [(M ꢁ CHCl2)þ, 100]; IR (cmꢁ1): 3027.57,
1706.30, 1592.32, 1402.64, 1092.93, 848.78, 786.85.
Entry 8 (2,2-dichloro-40-fluoro-acetophenone): Boiling point: 82–84ꢀC
(1.9 mm Hg); % calculated (found) for C8H5Cl2FO: C, 46.41 (46.49); H,
1
2.43 (2.34); H NMR: 6.59 (1H, s, CHCl2), 7.18 (2H, dd, JH–F ¼ 8.2 Hz,
JH–H ¼ 8.6 Hz, C30ar
H
and C50arH), 8.13 (2H, dd, JH–F ¼ 5.4 Hz,
JH–H ¼ 8.6 Hz, C20arH and C60arH); 13C NMR: 67.78 (CHCl2), 116.22
(d, J ¼ 22 Hz, C30ar and C50ar), 132.90 (d, J ¼ 9.5 Hz, C20ar and C60ar), 127.52
(C10ar), 166.41 (d, J ¼ 257 Hz, C40ar), 184.54 (C¼O); MS, m/z [ion, %]:
207/209/211 [(M þ 1)þ, 6], 171/173 [(M ꢁ Cl)þ, 3], 123 [(M ꢁ CHCl2)þ,
100], 95 [FC6H4þ, 36]; IR (cmꢁ1): 3009.10, 1708.58, 1598.45, 1411.64,
1224.73, 853.42.

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3716
NOBREGA, GONCALVES, AND PEPPE
Entry
9
(2,2-dichloro-propiophenone): Boiling point: 69–71ꢀC
(2.6 mm Hg); % calculated (found) for C9H8Cl2O: C, 53.23 (53.38); H,
3.97 (3.85); 1H NMR: 2.34 (3H, s, CH3), 7.37–7.58 (3H, m), 8.29–8.34
(2H, m); 13C NMR: 34.24 (CH3), 82.68 (CCl2), 128.01 (CarH), 131.15
(CarH), 132.05 (C10ar), 133.57 (C40arH), 188.05 (C¼O); MS, m/z [ion, %]:
202/204/206 [MþÁ, 12], 167/169 [(M ꢁ Cl)þ, 7], 105 [(M ꢁ C(CH3)Cl2)þ, 100],
77 [C6H5þ, 46]; IR (cmꢁ1): 3064.40, 2996.53, 1693.32, 1598.72, 1448.27,
1258.71, 668.72.
Entry 10 (2,2-dicloro-2-phenyl-acetophenone): Melting point: 70–72ꢀC;
% calculated (found) for C14H10Cl2O: C, 63.42 (63.36); H, 3.80 (3.85);
1H NMR: 7.28–7.81 (m); 13C NMR: 89.89 (CCl2Ph), 125.93 (CarH), 128.06
(CarH), 128.93 (CarH), 129.82 (CarH), 131.05 (CarH), 131.62 (Car-CO), 133.24
(CarH), 139.44 (Car-CCl2), 186.59 (C¼O); MS, m/z [ion, %]: 229/231
[(M ꢁ Cl)þ, 25], 194 [(M ꢁ Cl2)þÁ, 12], 105 [(M ꢁ CCl2Ph)þ, 100], 77
[C6H5þ, 45]; IR (cmꢁ1): 3071.18, 1701.64, 1594.93, 1446.63, 1232.21, 732.17.
Entry 11 (2,2-dichloro-2-phenyl-propanone): Boiling point: 52–54ꢀC
(0.7 mm Hg); % calculated (found) for C9H8Cl2O: C, 53.23 (53.15); H,
3.97 (3.89); 1H NMR: 2.31 (3H, s, CH3), 7.39–7.63 (5H, m); 13C NMR:
23.64 (CH3), 90.40 (CCl2Ph), 126.63 (CarH), 128.66 (CarH), 129.83 (CarH),
137.33 (C10ar), 193.52 (C¼O); IR (cmꢁ1): 3058.72, 2986.76, 1737.42,
1447.51, 1169.82, 746.33.
Entry 12 (ethyl-2,2-dichloro-acetoacetate): Boiling point: 52–54ꢀC
(0.8 mm Hg); % calculated (found) for C6H8Cl2O3: C, 36.21 (36.16); H,
1
4.02 (3.95); H NMR: 1.27 (3H, t, J ¼ 7 Hz , CH CH3), 2.45 (3H, s, CH3),
2
4.35 (2H, q, J ¼ 7 Hz , CH2CH3); 13C NMR: 13.72 (CH2-CH3), 23.41
(CH3-CO), 64.60 (O-CH2), 81.83 (CCl2), 163.25 (CO2CH2CH3), 191.30
(CH3-C¼O); IR (cmꢁ1): 2988.45, 1740.37, 1360.42, 1299.88, 1241.16,
1166.31, 1040.94.
ACKNOWLEDGMENTS
C.P. thanks CAPES and FAPERGS for financial support. J.A.N.
thanks CNPq for the award of a scholarship.
REFERENCES
1. Batanero, B.; Pastor, G.; Barba, F. Electrochemical Reduction of
2,2-Dibromoacetophenone. Acta Chem. Scand. 1999, 53, 910–912.
2. Mamedov, V.A.; Litvinov, I.A.; Kataeva, O.N.; Rizvanov, I.K.;
Nuretdinov, I.A. Darzens Reaction as a Convenient Method for the

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a,a-DICHLOROKETONES
3717
Synthesis of a-Chloroketones, a-Chloroepoxides, and Symmetrically
Substituted Dioxines. Monatsh Chem. 1994, 125, 1427–1435.
3. Reed, S.F. The Preparation of a,a-Dichloro Ketones. J. Org. Chem.
1965, 30, 2195–2198.
4. Falbe, J.; Schulzesteinen, J. a-Chlorinated Acetophenones. Ger. Patent
1,223,824, Sept. 1, 1966; Chem. Abstr. 1966, 65, 15277c.
5. Wyman, D.P.; Kaufman, P.R. The Chlorination of Active Hydrogen
Compounds with Sulfuryl Chloride. J. Org. Chem. 1964, 29,
1956–1958.
6. Kakinami, T.; Urabe, Y.; Hermawan, I.; Yamanishi, H.; Okamoto, T.;
Kajigaeshi, S. Halogenation Using Quaternary Ammonium Poly-
halides. Dichlorination of Aromatic Acetyl Derivatives with Benzyl-
trimethylammonium Tetrachloroiodate. Bull. Chem. Soc. Jpn. 1992,
65, 2549–2551.
7. Larock, R.C. Comprehensive Organic Transformations; VCH
Publishers: New York, 1989; 369–380.
8. Shi, X.X.; Dai, L.X. Mild Halogenation of Stabilized Ester Enolates by
Cupric Halides. J. Org. Chem. 1993, 58, 4596–4598.
9. Kosower, E.M.; Cole, W.J.; Wu, G.S.; Cardy, D.E.; Meisters, G.J.
Halogenation with Copper(II). Saturated Ketones and Phenol. J. Org.
Chem. 1963, 28, 630–633.
10. (a) King, L.C.; Ostrum, G.K. Selective Bromination with Copper(II)
Bromide. J. Org. Chem. 1964, 29, 3459–3461; (b) Doifode, K.B.;
Marathey, M.G. Reactions of Cupric Bromide in Dioxane. Formation
of o-Bromo-o-hydroxyacetophenone. J. Org. Chem. 1964, 29,
2025–2026.
11. Best yields were obtained in experiments conducted in the molar ratio
CuCl2 : ketone of 6 : 1.
12. The choice of DMF as the solvent was crucial. Reactions do not occur
in acetonitrile and 1,4-dioxane.
Received in the USA November 25, 2001

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