Checked by F. Kienzle and A. Brossi.
1. Procedure
Caution!
Thallium compounds are highly toxic.
3 However, they may be safely handled if prudent laboratory procedures are practiced. Rubber gloves and laboratory coats should be worn and reactions should be carried out in an
efficient hood. In addition,
thallium wastes should be collected and disposed of separately (Note
1).
B.
Methyl 2-hexynoate. A
1-l., round-bottomed flask equipped with a magnetic stirring bar and a reflux condenser is charged with
12.62 g. (0.1002 mole) of 3-(1-propyl)-2-pyrazolin-5-one and
500 ml. of methanol (Note
5). To this solution,
93.20 g. (0.2097 mole) of thallium(III) nitrate trihydrate (Note
6) is slowly added so as to avoid foaming. The reaction mixture is stirred for 20 minutes at room temperature and 20 minutes at reflux (Note
7) and (Note
8), then reduced to approximately half its volume by evaporation on a rotary evaporator. It is then cooled to 0–5° and filtered through
fluted filter paper, removing precipitated
thallium(I) nitrate. The filter cake is washed with
150 ml. of chloroform, and 250 ml. of water is added to the filtrate. The
chloroform layer is separated, and two additional extractions with
100 ml. of chloroform are carried out. The combined
chloroform layers are washed once with
100 ml. of 5% aqueous sodium hydrogen carbonate, twice with 100 ml. of water, and dried over anhydrous
magnesium sulfate. The
chloroform is removed on a rotary evaporator, and the residue is filtered through a
2 cm. by 12 cm. column of 100–200 mesh Florisil (Note
9) using approximately
250 ml. of chloroform as eluent. The
chloroform is removed on a rotary evaporator, and the resulting pale yellow liquid is vacuum distilled through a
19-cm., unpacked column (Note
10), yielding
8.63–9.24 g. (
68–73%) of
methyl 2-hexynoate, b.p.
47–50° (5 mm.), as a colorless to slightly yellow liquid (Note
11).
2. Notes
1. The submitters recommend collection of solid wastes in an appropriate solid waste container, and liquid wastes (filtrates containing
thallium residues, etc.) in suitably labeled bottles or cans. For the disposal of
thallium wastes, a commercial organization specializing in the disposal of toxic materials was employed.
3. This product is available from Matheson, Coleman and Bell.
4. The
pyrazolinone should be colorless. If it is not, it may be washed with a minimum of ice-cold
ethanol. This procedure is convenient and yields material of adequate purity for the subsequent reaction. Additional
pyrazolinone may be obtained by evaporating the filtrate and recrystallizing the residue from
ethanol.
5. Commercially available anhydrous
methanol was used without further treatment.
6.
Thallium(III) nitrate trihydrate is best prepared fresh by dissolving, with stirring,
200 g. (0.439 mole) of thallium(III) oxide (available from American Smelting and Refining, Denver, Colorado) in
400 ml. of concentrated nitric acid. The submitters have found the proportion of
1 g. of thallium(III) oxide to
2 ml. of nitric acid to be best. Any suspended matter is removed by suction filtration through a medium
fritted-glass funnel. The filtrate is cooled in an
ice bath with mechanical stirring, yielding
thallium(III) nitrate trihydrate as a fine white powder. The precipitate is separated by suction filtration through a medium fritted-glass funnel, pressed as dry as possible, and dried for approximately 6 hours in a
vacuum desiccator over
phosphorus pentoxide and
potassium hydroxide. Longer drying times result in
thallium(III) nitrate trihydrate of poorer quality. These crystals of
thallium(III) nitrate trihydrate often occlude a considerable amount of
nitric acid, with a consequent decrease in reactivity. To assure removal of occluded
nitric acid, the submitters recommend grinding the initially dried material to a fine powder with a
mortar and pestle and redrying in a vacuum desiccator, again over
phosphorus pentoxide and
potassium hydroxide, for an additional 6 hours. The resulting extremely reactive
thallium(III) nitrate trihydrate should be stored in a desiccator, since it rapidly turns brown upon contact with moist air.
Thallium residues may conveniently be removed with aqueous 1
N hydrochloric acid.
9. This product is available from Floridin Company, Berkley Springs, West Virginia 25411. The checkers found that this filtration was not necessary.
10. Best results were obtained with an
oil bath maintained at 80–85°. The bath temperature should never exceed 100°.
11. The spectral properties of the product are as follows; IR (film) cm.
−1: 2230 strong, 1718 strong, 1428 strong, 1261 strong, 1075 strong;
1H NMR (neat), δ (multiplicity, coupling constant
J in Hz., number of protons, assignment): 1.01 (t,
J = 7.2, 3H, C
H3), 1.63 (m, 2H, C
H2), 2.34 (t,
J = 6.8, 2H, C
H2C

C), 3.68 (s, 3H, OC
H3). GC analysis may be conveniently carried out using 10% Carbowax 20M on 60/80 Diatoport S.
3. Discussion
Methyl 2-hexynoate has been prepared by the esterification of
2-hexynoic acid, which was prepared by the carboxylation of
sodium hexynylide.
4 α,β-Alkynoic acids have generally been obtained by either carboxylation of metal alkynylides or by elimination reactions.
5 In particular, they have been prepared by the elimination of enol brosylates and tosylates,
6 an intramolecular Wittig reaction involving
triphenylphosphinecarbomethoxymethylene and carboxylic acid chlorides,
7 and the base-promoted elimination reaction of 3-substituted-4,4-dichloro-2-pyrazolin-5-ones.
8
The present method
9 affords the methyl ester directly in high yields from 2-pyrazolin-5-ones, which are readily prepared in nearly quantitative yields from readily accessible β-keto-esters. In addition, the reaction is simple to carry out, conditions are mild, and the product is easily isolated in a high state of purity. A limitation of the reaction is that only the methyl ester can be made, as other alcohols have been found to give poor yields and undesirable mixtures of products. Table I illustrates other examples of the reaction.
10
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