Haloforms bromoform

This carbanion is capable of leaving because its negative charge is stabilized by the combined inductive effects of the three halogen atoms. It is still a moderately strong base with a pA., in the mid-teens. Proton transfer between this anion and the carboxylic acid gives the final products of the reaction, the salt of the acid and the haloform. bromoform (CHBrs). The same process occurs with trichloro- and triiodo-substituted methyl ketones, to give chloroform and iodoform, respectively. 

This IS called the haloform reaction because the trihalomethane produced is chloroform (CHCI3) bromoform (CHBrj) or iodoform (CHI3) depending on the halogen used... 

The structure of the adducts obtained (addition resulted from homolysis of C-Br bond) is an indirect evidence for radical character of the process. Ionic addition of haloforms is known to occur at C-H bond (ref. 11), this leads to adducts with CX3 group. The highest yield of the adduct with bromoform was obtained for... 

This sequence is called the haloform reaction because it results in the production of chloroform, bromoform, or iodoform, depending upon the halogen used. The haloform reaction is a useful method for identification of methyl ketones, particularly when iodine is used, because iodoform is a highly insoluble, bright-yellow solid. The reaction also is very effective for the synthesis of carboxylic... 

When a base is used with a methy] ketone, the alpha carbon will become completely halogenated. This trihalo product reacts further with the base to produce a carboxylic acid and a haloform (chloroform, CHCI j bromoform, CHBr, or iodoform, CHIj). This is called the Haloform Reaction. 

Consequently, for the haloform case (Table 4.10), since repulsion for chlorine is less than that for fluorine, chlorine as a substituent facilitates carbanion formation much more than fluorine. The enhanced acidities of bromoform and iodoform have been attributed to the release of steric strain on deprotonation, while the increased availability of [Pg.110]

A trihalo compound may be formed from the halogenation of a methyl ketone. The electron-withdrawing effect of the trihalomethyl group makes the carbonyl group very sensitive to nucleophilic addition. Consequently, in the presence of a mild base the trihalomethyl compound easily decomposes with the formation of chloroform, bromoform or iodoform, depending on the halogen. The other product of the haloform reaction is a carboxylic acid (Scheme 3.86). 

Aldehydes may be converted to ( )-alkenyl halides by the reaction of CrCh with a haloform in THF. The highest overall yields for the conversion were with iodoform, but somewhat higher (E) (Z) ratios were observed with bromoform or chloroform. Other low-valent metals, such as tin, zinc, manganese and vanadium, were ineffective. As the examples in Table 19 indicate, the reaction is selective for the ( )-isomer, except in the case of an a,3-unsaturated aldehyde. In addition, the reaction with ketones is sufficiently slow for chemoselectivity to be observed for mixed substrates. 

Study carefully the pKgS for the haloform series, CHX3— they may not do what you think they should Chloroform is much more acidic than fluoroform even though fluorine is more electronegative (likewise with bromoform and chloroform). The anion CFamust be slightly destabilized because of some backdonation of electrons. The anion from chloroform and bromoform may also be stabilized by some interaction with the d orbitals (there aren t any on fluorine). The conjugate base anion of bromoform is relatively stable— you will meet this again in the bromoform/iodoform reaction (Chapter 21). 

If excess base and halogen are used, a methyl ketone is triply halogenated and then cleaved by base in the haloform reaction. The products are a carboxylic acid plus a so-called haloform (chloroform, CHCI3 bromoform. 

Haloform test. A modification of a test devised by Fujiwara permits detection of fluoroform, chloroform, bromoform, or iodoform or of any precursor of a haloform or of a dihalocarbene. A few drops of a mixture suspected of containing a haloform or a precursor is added to a mixture of 3 ml. of 10% sodium hydroxide and 2 ml. of pyridine. If the mixture turns pink to bright blue-red within one or two minutes of vigorous shaking at room temperature, a haloform is present. If the color change occurs not at room temperature but when the solution is heated on the steam bath for one minute, a precursor of a haloform or a dichlorocarbene is indicated. The intensity of the color is proportional to the concentration of haloform or of precursor. 

For example, the reaction of methyllithium (from bromomethane) with dibromomethane and cyclohexene gave 7-bromobicyclo[4.1.0]heptane in 0.35-1% yield only. Alternatively, the reaction of bromoform with methyllithium (from chloromethane) and cyclohexene gave a mixture of 7,7-dibromo- (7%) and 7-bromobicyclo[4.1.0]heptane (1%). There are many competitive reactions observed in the dihalomethane or haloform and alkyllithium systems deprotonation, halogen-metal exchange in substrates and in intermediates, alkylation etc. (for examples see refs 28 and 29). These processes are described in detail in Houben-Weyl, Vol. 4/3, pp 225-228 and Vol. E19b, pp 1601-1602. Therefore, the reaction of dibromomethane or bromoform with an alkyllithium and an alkene cannot be seriously considered as a viable preparative synthesis of bromocyclopropanes. 

The haloform reaction, using iodine, was once used as an analytical test in which the formation of a yellow precipitate of iodoform was taken as evidence that a substance was a methyl ketone. This application has been superseded by spectroscopic methods of structure determination. Interest in the haloform reaction has returned with the realization that chloroform and bromoform occur naturally and are biosynthesized by an analogous process. (See the boxed essay The Haloform Reaction and the Biosynthesis of Trihalomethanes. )... 

Alumina-potassium hydroxide can be used for the generation of dichlorocarbene or dibromocarbene from chloroform or bromoform. respectively.3 A 3 1 molar mixture of cyclohexene and the haloform is adsorbed on basic alumina and kept at room temperature for 4 days and then eluted with ether. The 7,7-dihalonorcarane was obtained in 12-15% yield (calculated on the basis of the base in the alumina). 

No discussion of the Haloform reaction is complete without mention of Nature s role in the production of haloform, especially chloroform and bromoform.66 It is estimated that 90% of atmospheric chloroform has a biogenic origin while only 10% is anthropogenic.67... 

Sodium hypobromite and sodium hypoiodite solutions react in an analogous manner and yield bromoform (CHBrj) and iodoform (CHI,) respectively. The smooth production of the trihalomethanes by the use of the appropriate hypohalides is termed the haloform reaction. It is applicable to all compounds containing the —COCH3 group or which yield a substance containing this group by oxidation (e.gr., acetaldehyde from ethyl alcohol). Iodoform is a stable, crystalline, yellow solid, m.p. 119°, with a characteristic odour it is only sparingly soluble in water and hence will separate, even in very minute quantity, from an aqueous solution and can easUy be identified by m.p. and mixed m.p. determinations. 

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