Haloform reaction

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Haloform reaction
Named after Adolf Lieben
Reaction type Substitution reaction
Identifiers
Organic Chemistry Portal haloform-reaction
RSC ontology ID RXNO:0000689

In

carboxyl groups (R−C(=O)OH) or to produce chloroform (CHCl3), bromoform (CHBr3), or iodoform (CHI3). Note that fluoroform
(CHF3) can't be prepared in this way.

Haloform reaction scheme
Haloform reaction scheme

Mechanism

In the first step, the halogen dis-proportionates in the presence of hydroxide to give the halide and hypohalite.

If a secondary alcohol is present, it is oxidized to a ketone by the hypohalite:

If a methyl ketone is present, it reacts with the hypohalite in a three-step process:

1. Under basic conditions, the ketone undergoes keto-enol tautomerisation. The enolate undergoes electrophilic attack by the hypohalite (containing a halogen with a formal +1 charge).

2. When the α(alpha) position has been exhaustively halogenated, the molecule undergoes a nucleophilic acyl substitution by hydroxide, with −CX3 being the leaving group stabilized by three electron-withdrawing groups. In the third step the −CX3 anion abstracts a proton from either the solvent or the carboxylic acid formed in the previous step, and forms the haloform. At least in some cases (chloral hydrate) the reaction may stop and the intermediate product isolated if conditions are acidic and hypohalite is used.

Scope

Substrates are broadly limited to methyl ketones and secondary

hypofluorite
ion. However ketones with the structure RCOCF3 do cleave upon treatment with base to produce fluoroform; this is equivalent to the second and third steps in the process shown above.

Applications

Laboratory scale

Negative and positive iodoform test

This reaction forms the basis of the iodoform test which was commonly used in history as a chemical test to determine the presence of a methyl ketone, or a secondary alcohol oxidizable to a methyl ketone. When iodine and sodium hydroxide are used as the reagents a positive reaction gives iodoform, which is a solid at room temperature and tends to precipitate out of solution causing a distinctive cloudiness.

In organic chemistry, this reaction may be used to convert a terminal methyl ketone into the analogous carboxylic acid.

Industrially

It was formerly used to produce iodoform, bromoform, and even chloroform industrially.[citation needed]

As a by-product of water chlorination

humic acid).[5][6] There is a concern that such reactions may lead to the presence of carcinogenic compounds in drinking water.[7]

History

The haloform reaction is one of the oldest organic reactions known.[8] In 1822, Georges-Simon Serullas added potassium metal to a solution of iodine in ethanol and water to form potassium formate and iodoform, called in the language of that time hydroiodide of carbon.[9] In 1832, Justus von Liebig reported the reaction of chloral with calcium hydroxide to form chloroform and calcium formate.[10] The reaction was rediscovered by Adolf Lieben in 1870.[11] The iodoform test is also called the Lieben haloform reaction. A review of the haloform reaction with a history section was published in 1934.[2]

References

  1. ISBN 9780470084946
    .
  2. ^
    doi:10.1021/cr60052a001
    .
  3. ^ Chakrabartty, in Trahanovsky, Oxidation in Organic Chemistry, pp. 343–370, Academic Press, New York, 1978
  4. ISSN 0021-9584
    .
  5. ISSN 0013-936X
    .
  6. ISSN 0013-936X
    .
  7. PMID 10229719
    .
  8. ISBN 0-12-429785-4
    .
  9. ^ Surellas, Georges-Simon (May 1822). Notes sur l'Hydriodate de potasse et l'Acide hydriodique. – Hydriodure de carbone; moyen d'obtenir, à l'instant, ce composé triple [Notes on the hydroiodide of potassium and on hydroiodic acid – hydroiodide of carbon; means of obtaining instantly this compound of three elements] (in French). Metz, France: Antoine. On pages 17–20, Surellas produced iodoform by passing a mixture of iodine vapor and steam over red-hot coals. However, later, on pages 28–29, he produced iodoform by adding potassium metal to a solution of iodine in ethanol (which also contained some water).
  10. doi:10.1002/andp.18321000206.
    On pages 259–265, Liebig describes Chlorkohlenstoff ("carbon chloride", chloroform), but on p. 264, Liebig incorrectly states that the empirical formula
    of chloroform is C2Cl5. From p. 259: "Chlorkohlenstoff. Man erhält diese neue Verbindung, wenn man Chloral mit ätzenden Alkalien, Kalkmilch oder Barytwasser in Ueberschuss vermischt und das Gemenge destillirt." (Chloroform. One obtains this new compound when one mixes chloral with an excess of caustic alkalies, milk of lime [solution of calcium hydroxide] or barite water [solution of barium hydroxide], and [then] distills the mixture.)
  11. ^ See:
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