Haloform reaction
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The '''haloform reaction''' is a chemical reaction where a haloform (CHX<sub>3</sub>, where X is a [[halogen]]) is produced by the multiple [[halogenation]] of a methyl [[ketone]] (a molecule containing the R-CO-CH<sub>3</sub> group) in the presence of a [[Base (chemistry)|base]] <ref>Chakrabartty, in Trahanovsky, ''Oxidation in Organic Chemistry'', pp 343-370, Academic Press, New York, '''1978'''</ref>
. R may be {{Hydrogen}}, [[alkyl]] or [[aryl]]. The reaction can be used to produce [[Chloroform|CHCl<sub>3</sub>]], [[Bromoform|CHBr<sub>3</sub>]] or [[Iodoform|CHI<sub>3</sub>]].
==Uses==
In [[analytical chemistry]], this reaction was traditionally used to determine the presence of a methyl ketone, or a [[secondary alcohol]] oxidizable to a methyl ketone through the the [[#iodoform test|iodoform test]]. Nowadays, spectroscopic techniques such as [[NMR spectroscopy|NMR]] and [[infrared spectroscopy]] are preferred because they require small samples, may be non-destructive (for NMR) and are easy and quick to perform.
Formerly, it was used to produce [[iodoform]] and [[bromoform]] and even [[chloroform]] industrially.{{Fact|date=September 2007}}
In [[organic chemistry]], this reaction may be used to convert a terminal methyl ketone into the appropriate carboxylic acid.
===Iodoform test===
[[Image:Jodoformprobe.jpg|thumb|150px|negative and positive iodoform test]]
The '''iodoform test''' or '''iodoform reaction''' is a qualitative [[chemical test]] for the detection of [[ketone]]s and [[aldehyde]]s carrying an alpha [[methyl]] group. The reagents are [[iodine]] and [[sodium hydroxide]].
Only methyl [[alcohol]]s with the feature
:CH<sub>3</sub>CH(OH)R
or methyl [[ketone]]s with the feature
:CH<sub>3</sub>C(=O)R
may undergo this reaction.
There are three steps to the iodoform reaction when starting from an [[alcohol]]. If the reaction starts from a methyl ketone, the first step is not needed.
*Addition of [[Iodine|I<sub>2]]</sub>(aq) (usually I<sub>2</sub> dissolved in [[Potassium iodide|KI]], shown here reacting with [[isopropanol|2-propanol]])
:2 [[Sodium hydroxide|NaOH]] + I<sub>2</sub> + CH<sub>3</sub>CH(OH)CH<sub>3</sub> → 2 NaI + [[Acetone|CH<sub>3</sub>COCH<sub>3</sub>]] + 2 H<sub>2</sub>O
oxidizes the hydroxyl group to a ketone,
*The [[ketone]] formed reacts with the I<sub>2(aq)</sub> in a [[substitution reaction]] to produce a triiodoketone, for example triiodoacetone.
:CH<sub>3</sub>COCH<sub>3</sub> + 3I<sub>2</sub> → CH<sub>3</sub>COCI<sub>3</sub> + 3HI
(Thus, [[ketone]] and [[aldehyde]] with structure -COCH<sub>3</sub> also show positive results). Ethanal is the only aldehyde to give the iodoform reaction.
*Finally, [[Hydroxide|OH<sup>-</sup>]] (aqueous) is added, which reacts with, for example, the triiodoacetone.
:CH<sub>3</sub>COCI<sub>3</sub> + OH<sup>-</sup> → CHI<sub>3</sub> + CH<sub>3</sub>COO<sup>-</sup>
[[Image:Iodoform reaction.png]]
[[Iodoform]], or triiodomethane (CHI<sub>3</sub>) is a pale yellow substance with a relatively high [[molar mass]] due to the [[iodine]] atoms. It is therefore a solid at [[room temperature]]. It is [[insoluble]] in water and has an [[antiseptic]] smell. A visible precipitate of this compound will form from a sample only when a methyl ketone is present.
==Reaction mechanism==
First, the halogen disproportionates in the basic solution to give halide and hypohalite (= halate (I)) anions. In the case of [[chlorine]], this can be shown:
[[Chlorine|Cl<sub>2</sub>]] + 2[[hydroxide|OH<sup>−</sup>]] → [[chloride|Cl<sup>−</sup>]] + [[hypochlorite|OCl<sup>−</sup>]] + H<sub>2</sub>O
The [[reaction mechanism]] for the reaction of a methyl ketone with [[hypochlorite]] is then a three step process:
:(1) R-CO-CH<sub>3</sub> + 3[[hypochlorite|OCl<sup>-</sup>]] → R-CO-CCl<sub>3</sub> + 3 [[hydroxide|OH<sup>−</sup>]]
:(2) R-CO-CCl<sub>3</sub> + OH<sup>−</sup> → [[Carboxylic acid|RCOOH]] + <sup>−</sup>CCl<sub>3</sub>
:(3) [[Carboxylic acid|RCOOH]] + <sup>−</sup>CCl<sub>3</sub> → [[carboxylate|RCOO<sup>−</sup>]] + [[Chloroform|CHCl<sub>3</sub>]]
an exhaustive [[halogenation|chlorination]] (actually an [[electrophile|electrophilic]] substitution of H by Cl<sup>+</sup>) replacing all the hydrogen atoms on the methyl group with chlorine followed by a [[nucleophilic acyl substitution]] of the hydroxide [[anion]] with the chloromethyl anion as the [[leaving group]] and finally proton transfer from the [[carboxylic acid]] to get to chloroform. Note that the latter two steps can be combined as an alkaline [[hydrolysis]] of the trihaloketone intermediate.
The graphical depiction of the reaction of a methyl ketone with a [[hypobromite]]:
[[Image:Haloform-reaction-chemical.png|600px|center|Haloform reaction with hypobromite]]
where the first step displays a [[keto-enol tautomerism]].
Haloforms can also be prepared directly from any secondary alcohol containing the CH3-CHOH- group (such as [[isopropyl alcohol]]), since this is oxidised under the reaction conditions to the corresponding methyl ketone, which can then undergo the haloform reaction.
With [[chlorine]], it is possible to use [[sodium hypochlorite]] as a convenient source of both base and chlorine.
[[Fluoroform]] (CHF<sub>3</sub>) cannot be prepared from a methyl ketone by the haloform reaction due to the instability of hypofluorite, but compounds of the type RCOCF<sub>3</sub> do cleave with base to produce CHF<sub>3</sub>; this is equivalent to the second and third steps in the process shown above. The [[iodoform test]] is a laboratory test for the presence of a methyl ketone or the related alcohol, by formation of a pale yellow precipitate of iodoform.
==History==
The haloform reaction is one of the oldest [[organic reaction]]s around <ref>{{cite book | title = Strategic Applications of Named Reactions in Organic Synthesis | author = László Kürti and Barbara Czakó | publisher = Elsevier | location = Amsterdam | year = 2005 | isbn = 0-12-429785-4}}</ref>. In 1822 Serullas reacted [[ethanol]] with [[iodine]] and [[sodium hydroxide]] in water to [[sodium formate]] and iodoform, called in the language of that time ''hydroiodide of carbon''. In 1831 [[Justus Liebig]] reported the reaction of [[chloral]] with [[calcium hydroxide]] to [[chloroform]] and calcium formate. The reaction was rediscovered by [[Adolf Lieben]] in 1870. The [[iodoform test]] is also called the '''Lieben haloform reaction'''. A review of the Haloform reaction with a history section was published 1934.<ref>{{cite journal|title =The Haloform Reaction|author=Reynold C. Fuson and Benton A. Bull|journal=Chemical Reviews
|volume= 15|issue= 3|year= 1934|pages= 275–309|doi= 10.1021/cr60052a001}}</ref>
== References ==
<references/>
[[Category:chemical tests]]
[[Category:Chemical tests]]
[[Category:Organic redox reactions]]
[[Category:Carbon-heteroatom bond forming reactions]]
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[[ja:ハロホルム反応]]
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