Org. Synth. 1971, 51, 73
DOI: 10.15227/orgsyn.051.0073
3-CHLOROCYCLOBUTANECARBOXYLIC ACID
[Cyclobutanecarboxylic acid, 3-chloro-]
Submitted by Gary M. Lampman and James C. Aumiller
1.
Checked by G. Nelson and K. B. Wiberg.
1. Procedure
Caution! Benzene has been identified as a carcinogen; OSHA has issued emergency standards on its use. All procedures involving benzene should be carried out in a well-ventilated hood, and glove protection is required.
A 2-l., three-necked, round-bottomed flask equipped with a Trubore stirrer and paddle is charged with 172.8 g. (1.200 moles) of 1,1-cyclobutanedicarboxylic acid (Note 1) and 1500 ml. of benzene. The mixture is stirred and heated at reflux, and 200 ml. of benzene and benzene-water azeotrope is removed by distillation to ensure anhydrous conditions. The flask is then fitted with an addition funnel and a reflux condenser attached to a drying tube. Stirring and heating are continued, and over a 40-minute period, 170 g. (102 ml., 1.26 moles) of sulfuryl chloride (Note 2) is added from the funnel, while 4.0 g. of benzoyl peroxide (Note 3) is added simultaneously in small portions through the top of the condenser. After a short induction period, hydrogen chloride and sulfur dioxide are evolved. After the addition is complete, heating at reflux is maintained for 22 hours. The solid is dissolved after 1 hour, leaving a light brown solution. After the heating period is complete, the benzene is removed by distillation, and the residue is heated to 190–210° for 45 minutes to effect decarboxylation. The black residue is transferred to a small flask and distilled under vacuum through a 6-cm. Vigreux column. After a forerun of about 25–30 g. (Note 4), 65–79 g. (40–49%) of cis- and trans-3-chlorocyclobutanecarboxylic acid is collected as a light yellow liquid, b.p. 131–137° (15 mm.) nD24 1.4790 (Note 5). A black residue remains in the distillation flask.
2. Notes
1.
Diethyl 1,1-cyclobutanedicarboxylate is prepared by the method in
Org. Synth., Coll. Vol. 4, 288 (1963). The diester is isolated in 55% yield, b.p.
111–114° (16 mm.). The diester can be saponified by the method in
Org. Synth., Coll. Vol. 3, 213 (1955), but omitting the
barium chloride step, to give the diacid. This material upon recrystallization from
ethyl acetate gives the diacid in high purity. The diacid may also be purchased from Aldrich Chemical Company, Inc.
2.
Eastman Organic Chemicals or Matheson, Coleman and Bell practical grade material was distilled before use. Since
hydrogen chloride and
sulfur dioxide are evolved, the preparation should be carried out in an efficient hood.
3.
Eastman Organic Chemicals white label material was used.
4.
The forerun contains
cyclobutanecarboxylic acid and
3-chlorocyclobutanecarboxylic acid, b.p.
100–130° (15 mm.) nD24 1.4623. The presence of
cyclobutanecarboxylic acid indicates that some of the diacid was not chlorinated. Attempts were made to reduce the amount of unchlorinated product by increasing the amount of
sulfuryl chloride. Instead, this increased the amount of a dichlorinated impurity which is difficult to separate from the desired product.
5.
The product is analyzed by GC at 190° on a Beckman GC-2 chromatograph equipped with a
180 cm. × 6 mm. column (Beckman 17449) containing 42/60 Johns-Manville C-22 firebrick coated with Dow-Corning 550 silicone oil. The retention times are 8 and 9 minutes for the
trans- and
cis- compounds, respectively.
3. Discussion
3-Chlorocyclobutanecarboxylic acid has been prepared from the rather inaccessible
3-hydroxy-1,1-cyclobutanedicarboxylic acid.
2 The related
3-bromocyclobutanecarboxylic acid has also been prepared by an eight-step synthetic scheme.
3 The present method, based upon the procedure of Nevill, Frank, and Trepka,
4 affords the 3-chloro acid in high yield in one step. Thus this method provides a compound which cannot be easily made by other methods.
The use of
sulfuryl chloride for free radical chlorination of aliphatic carboxylic acids gives mixtures of positional isomers;
5 however, with the
cyclobutane ring, the attack is much more selective. The present method provides a procedure for free radical halogenation of a cyclobutane ring.
The conversion of
3-chlorocyclobutanecarboxylic acid to
1-bromo-3-chlorocyclobutane is described in
Organic Syntheses.6This preparation is referenced from:
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
hydrogen chloride (7647-01-0)
Benzene (71-43-2)
ethyl acetate (141-78-6)
sulfur dioxide (7446-09-5)
barium chloride (10361-37-2)
sulfuryl chloride (7791-25-5)
Diethyl 1,1-cyclobutanedicarboxylate (3779-29-1)
benzoyl peroxide (94-36-0)
1,1-Cyclobutanedicarboxylic acid (5445-51-2)
Cyclobutanecarboxylic acid (3721-95-7)
cyclobutane (287-23-0)
1-Bromo-3-chlorocyclobutane (4935-03-9)
3-Chlorocyclobutanecarboxylic acid,
Cyclobutanecarboxylic acid, 3-chloro-,
cis- and trans-3-chlorocyclobutanecarboxylic acid (35207-71-7)
3-bromocyclobutanecarboxylic acid
3-hydroxy-1,1-cyclobutanedicarboxylic acid
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