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Lieben Iodoform Reaction

A. GENERAL DESCRIPTION OF THE REACTION

This reaction was first reported by Lieben in 1870.1 It is an alkaline degradation of

compounds with acetyl or methylcarbinol groups by means of iodine treatment to form
volatile iodoform. This reaction has been widely used to test the presence of acetyl or
methylcarbinol groups and is known as the Lieben reaction,2 Lieben iodoform reaction,2d,3
iodoform test of Lieben,4 or Lieben test.5 It is believed that the positive test of methylcarbinol
group is because of the oxidation of such groups by hypoiodite generated in situ from the
alkaline disproportionation of iodine.2d Similarly, other compounds that can generate the
acetyl group under the test conditions also give a positive result,2a such as the retro Aldol
Reaction of α,β-unsaturated compounds.6 In addition, compounds with groups capable of
exerting excessively high steric hindrance have also been reported to be positive toward
the Lieben test.2d Unfortunately, some ketones, such as α-chloroacetophenone, acetome-
sitylene, propiophenone,5b pinacolone, and similar compounds involving steric hindrance7
result in a negative test. While the original procedure involves the treatment of compounds
with iodine and excess of base5b and can detect compounds at concentrations as low as
1 part in 2000,1 it often gives ambiguous results because of the anesthetic action of the
iodoform on the olfactory nerve.8

B. GENERAL REACTION SCHEME

Comprehensive Organic Name Reactions and Reagents, by Zerong Wang

Copyright © 2010 John Wiley & Sons, Inc.

1750
 RELATED REACTIONS 1751

C. PROPOSED MECHANISMS

A mechanism including the disproportionation of iodine, oxidation of methylcarbinol

into acetyl group, and the final formation of iodoform is illustrated below.

D. MODIFICATION

Because of the importance of this reaction for structural identification in the early days, it
has been modified to occur in dioxane with a slight excess of iodine-potassium iodide solu-
tion at 60◦ C to test water-insoluble compounds.4a In addition, this test has been improved
from being an older test to a color test by the addition of pyridine, quinoline, or their
homologs to the alkali hypochlorite or hypobromite solution, by which a carmine red or pink
color develops immediately if an acetyl or methylcarbinol group exists.8 Further improve-
ment has been done to differentiate between the acetyl and the methylcarbinol groups by the
addition of ortho-nitrobenzaldehyde in the alkaline solution, by which methyl ketone can
undergo the Baeyer-Drewson Indigo Synthesis, whereas compounds with methylcarbinol
groups won’t. Under these conditions, the negative Lieben test indicates the absence of
acetyl and methylcarbinol groups, whereas a positive Lieben test but negative indigo reaction
shows the presence of methylcarbinol group, and both positive tests from Lieben iodoform
reaction and the indigo reaction implies the presence of methyl ketones.2d

E. APPLICATIONS

This reaction had wide application in the structural elucidation of organic compounds
before the modern spectroscopy. In addition, this reaction has been used to prepare α-
monoiodo and α-diiodoketones by using a less than theoretical amount of iodine.9

F. RELATED REACTIONS

N/A
1752 LIEBEN IODOFORM REACTION

G. CITED EXPERIMENTAL EXAMPLES

O O
I2 (0.4 eq.) /KI
I
NaOH/H2O

Reference 9.

A mixture of 80 g pinacolone and 800 mL 5% NaOH solution was cooled in an ice and
salt mixture, and 80 g iodine, dissolved in aqueous potassium iodide, was added through
a rapidly revolving hollow stirrer. The addition was complete in 2 h. The solution was
immediately shaken with ether, and the resulting ether solution was washed with water. The
solution was dried over Na2 SO4 , and the ether was removed. The strongly lachrymatory
liquid thus obtained was distilled at 92–98◦ C (20 mmHg) to afforded 6 mL α-iodopinacolone
as a liquid, which was shaken with mercury to remove the iodine color and redistilled twice
at 48–49◦ C (2 mmHg). (No yield was given for the original experiment.)

O 1) NaOH/dioxane
CHI3
R 2) I2-KI
3) NaOH
Reference 2d.

About 100 mg of the compound being tested was dissolved in 5 mL dioxane in a 150 ×
16 mm test tube, followed by the addition of 1 mL 10% NaOH. The iodine reagent was
added dropwise with shaking until a slight excess of iodine caused a definite dark color that
did not disappear on standing. The test tube was then placed in a water bath maintained at
60◦ C, and the dropwise addition of the iodine reagent was continued until the definite dark
color persisted as before; but the warming at 60◦ C should not last > 2 min. The excess
of iodine was removed with a few drops of 10% NaOH solution, and the test tube was
filled with cold water, allowed to stand for 15 min, and filtered. The characteristic odor of
iodoform was readily distinguishable. As a confirmation, the crystals collected on the filter
paper were dried at 100◦ C for 1 h and identified by their melting point. (Iodoform melts at
114–121◦ C).

Other references related to the Lieben iodoform reaction are cited in the literature.10

H. REFERENCES

1. Lieben, A., Ann. (Suppl.), 1870, 7, 218.

2. (a) Gillis, B. T., J. Org. Chem., 1959, 24, 1027. (b) Kamen, K., Chemicky Prumysl, 1957, 7, 472.
(c) Poggi, A. R.; Biffoli, R. and Stella, C., Gazz. Chim. Ital., 1947, 77, 536. (d) Kamlet, J., Ind.
Eng. Chem., 1944, 16, 362. (e) Poggi, R., Gazz. Chim. Ital., 1940, 70, 328. (f) Lorber, L., Biochem.
Zeitsch., 1927, 181, 375.
3. van der Haar, A. W., Rec. Trav. Chim. Pays-Bas Belg., 1922, 41, 784. Kunz, R., Zeitsch. Anal.
Chem., 1920, 59, 302.
 REFERENCES 1753

4. (a) Fuson, R. C. and Tullock, C. W., J. Am. Chem. Soc., 1934, 56, 1638. (b) Baskerville, C. and
Hamor, W. A., J. Ind. Eng. Chem., 1912, 362.
5. (a) Asahina, Y. and Ukita, T., Ber., 1941, 74B, 952. (b) Fuson, R. C. and Bull, B. A., Chem. Rev.,
1935, 15, 275.
6. Esafov, V. I. and Stafeeva, N. M., Zh. Anal. Khim., 1951, 6, 195. [Chem. Abstr., 1951, 45, 8404].
7. Delange, L., Bull. Soc. Chim., 1908, [4]3, 910.
8. Adachi, J., Anal. Chem., 1951, 23, 1491.
9. Johnson, R. and Fuson, R. C., J. Am. Chem. Soc., 1935, 57, 919.
10. (a) Seelye, R. N. and Turney, T. A., J. Chem. Edu., 1959, 36, 572. (b) McElvain, S. M., The
Characterization of Organic Compounds, Macmillan., New York, 1949, p. 137. (c) Hans, M.,
Analyse und Konstitutionsermittlung Organischer Verbindungen, Julius Springer, Berlin, 1938,
pp. 305–306. (d) Baskerville, C. and Hamor, W. A., J. Ind. Eng. Chem., 1912, 499. (e) Porcher,
C. and Hervieux, C., Compt. Rend. Seances Soc. Biol. Ses Filiales, 1907, 62, 651. (f) Lieben, A.,
Ann. (Suppl.), 1870, 7, 377.