α-Chlorination of Carboxylic Acids Using Trichloroisocyanuric Acid

Article abstract of DOI:10.1081/SCC-120028361

Carboxylic acids are chlorinated in the a position by heating with trichloroisocyanuric acid after formation of a small amount of the acid chloride using phosphorus trichloride.

Full text of DOI:10.1081/SCC-120028361

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α‐Chlorination of Carboxylic Acids Using
Trichloroisocyanuric Acid
a
a
a
a
Gene A. Hiegel , Diane Dutton Faher , Justin C. Lewis , Tan Duc Tran , Gregory G.
a
a
Hobson & Farhad Farokhi
a
Department of Chemistry and Biochemistry, California State University, Fullerton,
California, 92834, USA
Available online: 20 Aug 2006
To cite this article: Gene A. Hiegel, Diane Dutton Faher, Justin C. Lewis, Tan Duc Tran, Gregory G. Hobson & Farhad
Farokhi (2004): α‐Chlorination of Carboxylic Acids Using Trichloroisocyanuric Acid, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 34:5, 889-893
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SYNTHETIC COMMUNICATIONS
Vol. 34, No. 5, pp. 889–893, 2004
a-Chlorination of Carboxylic Acids Using
Trichloroisocyanuric Acid
*
Gene A. Hiegel, Diane Dutton Faher, Justin C. Lewis,
Tan Duc Tran, Gregory G. Hobson, and Farhad Farokhi
Department of Chemistry and Biochemistry, California State University,
Fullerton, California, USA
ABSTRACT
Carboxylic acids are chlorinated in the a position by heating with
trichloroisocyanuric acid after formation of a small amount of the acid
chloride using phosphorus trichloride.
Key Words: Chlorination; a-Chlorination; a-Chloro acids; 2-Chloro
acids; Carboxylic acids; Chloro acids; Substitution; Synthesis; Prep-
aration; Trichloroisocyanuric acid.
a-Halogenation of carboxylic acids is generally known as the Hell–
Volhard–Zelinsky reaction
[1,2]
and involves the conversion of the carboxylic
*
Correspondence: Gene A. Hiegel, Department of Chemistry and Biochemistry,
California State University, Fullerton, CA 92834, USA; Fax: 714-278-5316; E-mail:
ghiegel@fullerton.edu.
8
89
DOI: 10.1081/SCC-120028361
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

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90
Hiegel et al.
acid partially or completely into an acid halide followed by reaction with a
suitable halogenating agent. The synthesis of a-chloro carboxylic acids
[
3]
has been accomplished using a variety of reagents including chlorine,
[
4]
[5]
[6]
sulfuryl chloride, thionyl chloride, and LDA with CCl4. We wish to
report that trichloroisocyanuric acid (1) [1,3,5-trichloro-1,3,5-triazine-2,4,6-
(1H,3H,5H)-trione; TCICA], a stable, easily handled solid, is also a suitable
reagent for the chlorination reaction.
Our initial studies using thionyl chloride to generate a small amount of the
acid chloride led to unpredictable results. Some of these reactions gave mainly
the a-isomer and others gave a complex mixture of products, presumably
through radical chlorination. A by-product from using thionyl chloride is
[7]
hydrogen chloride, and hydrogen chloride reacts with 1 to form chlorine
which could then take part in a radical chain reaction. However, when
phosphorus trichloride was used to generate the acid chloride, the reaction
proceeded smoothly to give the a-chloro acid.
Two satisfactory procedures were developed. One in which 1 was the
limiting reagent and the carboxylic acid was in excess, and the other in
which a slight excess of 1 was used. After warming the carboxylic acid with
PCl to convert a portion to the acid chloride, 1 was added slowly using a
3
solid addition funnel while warming the reaction mixture. If 1 was added too
rapidly, the reaction became excessively exothermic and splashing took
place. In a previously reported study on the effect of reaction temperature on
the chlorination reaction of cyclohexanecarboxylic acid using chlorine, it
[8]
was shown that the optimum reaction temperature was about 1608C. Low
temperatures resulted in radical chlorination and higher temperatures
resulted in elimination of hydrogen chloride. Our results are shown in
Table 1.
Table 1. Conversion of carboxylic acids to a-chloro acids.
Bath
temperature
GC
purity
a-Chloro acid
Procedure
Yield
2
2
2
2
2
2
-Chloroacetic acid
Excess 1
Excess 1
1308C
1608C
1608C
1788C
1408C
1408C
88%
76%
52%
48%
67%
73%
99.4%
98.4%
97.7%
96.2%
95.8%
94.5%
-Chloropropanoic acid
-Chloropropanoic acid
-Chlorobutanoic acid
-Chlorobutanoic acid
-Chlorobutanoic acid
Excess acid
Excess acid
Excess 1
Excess 1

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a-Chlorination of Carboxylic Acids
891
EXPERIMENTAL
Gas chromatography was performed using a Hewlet-Paackard 5890
Series II instrument with a 6 ft  1/8 in 10% Carbowax 20 M column. FT-IR
1
spectra were recorded using a Perkin Elmer 1650. H-NMR spectra were
recorded on an Anasazi-modified Varian EFT 90 MHz instrument in CDCl or
3
CCl . All reagents were used as received except for pentane which was
4
distilled. 1, 99%, was obtained from Chem Lab Products. Acetic acid, 99%,
was from Fisher. Propanoic acid, 99%, and hexanoic acid, 99%, were from
MCB. Butanoic acid, 99%, phorphorous trichloride, 99%, and methylene
chloride were from Aldrich. All products were distilled.
Preparation of 2-Chloroacetic Acid with an Excess of 1
In a 100 mL three-neck round-bottom flask were placed a magnetic stir
bar, 10.196 g (0.1698 mol; 0.1698 eq) acetic acid and 0.611 g (0.0044 mol;
0.0133 eq) PCl . The flask was flushed with N and two stoppers and a
condenser fitted with a drying tube were added. The flask was heated in a
3
2
1308C oil bath for 10 min. GC analysis indicated that 2.1% acid chloride was
present. Then the center stopper was replaced with a solid addition funnel with
a N inlet at the top and containing 16.113 g (0.06930 mol; 0.2079 eq) 1. A
2
gentle flow of N through the funnel kept acid vapor and 1 from collecting at
2
the tip of the funnel. After wrapping the apparatus with foil and turning off the
lights, 1 was added at a slow rate over 10 min while heating was continued.
The addition funnel was then replaced with a stopper.
After 19 hr, the flask was removed from the heating bath and mixture
crystallized. Diethyl ether was added to dissolve the chloro acid and excess 1
was destroyed by the slow addition of solid NaHSO until a wet iodide-starch
3
paper test was negative. The cyanuric acid by-product was filtered and washed
with ether, and the ether was removed with a rotary evaporator. The crude
product was vacuum distilled through a Vigreux column to give 14.023 g
(
88%) 2-chloroacetic acid, b.p. 103.8–104.88C (27.3–29.5 torr), 99.4% pure
1
by GC. The GC retention time, FT-IR, and HNMR were identical to those of
an authentic sample.
Preparation of 2-Chloropropanoic Acid with an Excess of
Propanoic Acid
In a 100 mL three-neck round-bottom flask were placed a magnetic stir
bar, 16.769 g (0.2264 mol; 0.2264 eq) acetic acid and 1.486 g (0.01081 mol;

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8
92
Hiegel et al.
0
.03243 eq) PCl . The flask was flushed with N and two stoppers and a
2
3
condenser fitted with a drying tube were added. The flask was heated in a
608C oil bath for 10 min. GC analysis indicated that 3.4% acid chloride was
present. Then the center stopper was replaced with a solid addition funnel with
1
a N inlet at the top and containing 4.997 g (0.0215 mol; 0.0645 eq) 1. A gentle
2
flow of N through the funnel kept acid vapor and 1 from collecting at the tip
2
of the funnel. After wrapping the apparatus with foil and turning off the lights,
1 was added at a slow rate over 40 min while heating was continued. The
addition funnel was then replaced with a stopper.
After 23 hr, the flask was removed from the heating bath and excess 1 was
destroyed by the slow addition of solid NaHSO until a wet iodide-starch
3
paper test was negative. Diethyl ether was added, the cyanuric acid by-product
was filtered and washed with ether, and the ether was removed with a rotary
evaporator. The crude product was vacuum distilled through a concentric tube
column to give 3.659 g (52%) 2-chloropropanoic acid, b.p. 82.0–84.58C
(
1
10.3–10.5 torr), 97.7% pure by GC. The GC retention time, FT-IR, and
HNMR were identical to those of an authentic sample.
2-Chlorobutanoic Acid
Equivalent ratio of 1 : butanoic acid 1.260, yield 67% (95.8% pure by
GC), b.p. 104.0–105.88C (16.6–17.0 torr): FT-IR (film) 3703–2352, 2695,
2
1
1
1724 cm
;
H NMR (CDCl ) d 10.42 (s, 1, OH), 4.29 (ABX, J
þ
3
ax
Jbx ¼ 13.4 Hz, 1, þ CH), 2.00 (m, 2, CH ), 1.09 (t, J ¼ 7.2 Hz, CH ). Anal.
2
3
calcd. for C H O Cl: C, 39.20; H, 5.76; found: C, 39.16; H, 6.05%.
7 2
4
2-Chlorohexanoic Acid
Equivalent ratio of 1 : hexanoic acid 1.301, yield 73% (94.5% pure by
GC), b.p. 89.0–91.48C (0.5–0.9 torr): FT-IR (film) 3649–2380, 2695,
2
1
1
1
724 cm
;
H NMR (CDCl ) d 10.19 (s, 1, OH), 4.32 (ABX, J
þ
3
ax
Jbx ¼ 13.6 Hz, 1, CH), 2.01 (m, 2, CH CH), 1.42 (m, 4, CH CH CH ), 0.93
2
3
2
2
(
m, 3, CH ). HRMS calcd. for C H O Cl (M þ H) 151.05258; found:
3
6 11 2
1
51.05269.
REFERENCES
1. Sonntag, N.O.V. The reactions of aliphatic acid chlorides. Chem. Rev.
1953, 52, 237–416.

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893
2
3
4
5
6
. Harwood, H.J. Reactions of the hydrocarbon chain of fatty acids. Chem.
Rev. 1962, 62, 99–154.
. Crawford, R.J. An improved a-chlorination of carboxylic acids. J. Org.
Chem. 1983, 48, 1364–1366.
. Galat, A. An improved synthesis of dl-lysine. J. Amer. Chem. Soc. 1947,
69, 86.
. Rodin, R.L.; Gershon, H. Photochemical a-chlorination of fatty acid
chlorides by thionyl chloride. J. Org. Chem. 1973, 38, 3919–3921.
. Snider, B.B.; Kulkarni, Y.S. Preparation of unsaturated a-chloro acids and
intramolecular [2 þ 2] cycloadditions of chloroketenes derived from them.
J. Org. Chem. 1987, 52, 307–310.
7
8
. Hiegel, G.A.; Abdala, M.H.; Burke, S.V.; Beard, D.P. Methods for
preparing aqueous solutions of chlorine and bromine for halogen displace-
ment reactions. J. Chem. Educ. 1987, 64, 156.
. Little, J.C.; Sexton, A.R.; Tong, Y.C.; Zurawic, T.E. Chlorination II. Free
radical vs. Hell-Volhard-Zelinsky chlorination of cyclohexanecarboxylic
acid. J. Amer. Chem. Soc. 1969, 91, 7098–7103.
Received in the USA August 28, 2003

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