Hydroxide reaction + haloforms

The catalytic conditions (aqueous concentrated sodium hydroxide and tetraalkylammonium catalyst) are very useful in generating dihalo-carbenes from the corresponding haloforms. Dichlorocarbene thus generated reacts with alkenes to give high yields of dichlorocyclopropane derivatives,16 even in cases where other methods have failed,17 and with some hydrocarbons to yield dicholromethyl derivatives.18 Similar conditions are suited for the formation and reactions of dibromocar-benc,19 bromofluoro- and chlorofluorocarbene,20 and chlorothiophenoxy carbene,21 as well as the Michael addition of trichloromethyl carbanion to unsaturated nitriles, esters, and sulfones.22... 

In the haloform reaction, methyl ketones (and the only methyl aldehyde, acetaldehyde) are cleaved with halogen and a base. The halogen can be bromine, chlorine, or iodine. What takes place is actually a combination of two reactions. The first is an example of 12-4, in which, under the basic conditions employed, the methyl group is trihalogenated. Then the resulting trihalo ketone is attacked by hydroxide ion ... 

It is exactly the same with the haloform reaction. If chloroform is poured onto the acetone/sodium hydroxide mixture, there can be an explosion whereas incorporating hydroxide in the other two substances would not be dangerous. In this case the risk factor is the high hydroxide concentration. 

In general, ketones don t undergo oxidation however, methyl ketones undergo a haloform reaction. In a haloform reaction, the oxidation converts the methyl group to a haloform molecule (usually iodoform (CHI3)), which leaves the Ccirbon backbone one carbon atom shorter. The oxidant in a haloform reaction is sodium hypohalite (NaOX), which forms by the reaction of sodium hydroxide (NaOH) with a halogen (X, where X = Cl, Br, or 1). 

A reaction somewhat similar to the cleavage of haloforms with hydroxide occurs with ketones that do not have a-hydrogens through the action of sodium amide ... 

Explain why the first, but not the second, reaction proceeds rapidly with the aid of sodium hydroxide. Would you expect ethanoic acid to undergo the haloform reaction Explain. 

A second type of elimination reaction for some halocarbons is the 1,1 elimination. For example, hydrolysis of the halogenated methanes or haloforms is thought to occur by proton abstraction and subsequent formation of a carbene that reacts with water or hydroxide to form carbon monoxide and water (Equations (9)-(ll)). 

The conclusion of the haloform reaction is a nucleophilic acyl substitution, with hydroxide as the nucleophile and -CX3 as the leaving group. 

In the first studies of isotope exchange of the haloforms, general base catalysis could not be clearly observed [164]. In more recent studies of the detritiation of chloroform in aqueous morpholine and piperidine buffers, general base catalysis could not be detected and the reaction was dominated by hydroxide ion catalysis [114]. In this latter study it was assumed that the mechanism of isotope exchange consisted of a slow triton transfer to base (99), viz. 

A value of kH/kD = 1.4 was obtained [114] for the rate of proton transfer compared with deuteron transfer from chloroform to hydroxide ion and this result is similar to the values determined earlier for several haloforms [164, 166]. In the most recent work [171(b)] a value kH /kD = 1.11 0.05 was determined for chloroform. These values are close to those observed for reaction of cyanocarbon acids (though a different base catalyst is involved) and in Sect. 4.3 it was argued that isotope effects as low as these are expected for a transition state in which proton transfer is almost complete. The isotope effect for proton transfer from chloroform was measured using a new and useful method [114]. It can be shown that the ratio of initial rates of uptake of tritium for the first ten per cent of reaction from tritiated water into CHC13 and CDC13 is identical to the primary isotope effect for proton loss (feH /fcD). The procedure can be used for measuring isotope effects on proton transfer from carbon acids to hydroxide ion or buffer catalysts and is more convenient than other methods. Other methods which have been used, for example, involve the comparison of rates of detritiation and dedeuteration or the comparison of rates of bromination for isotopically different acids (RCH and RCD) [113]. 

Methyl aryl ketones react with iodine in the presence of excess pyridine to give pyridinium salts. Cleavage of the salts is readily accomplished by heating with aqueous-alcoholic sodium hydroxide. Over-all yields of 60-83% are reported. This two-step procedure affords a method similar to the haloform reaction for degradation of certain methyl ketones to acids with one less carbon-atom. 

The cleavage stage of the haloform reaction may be regarded as a hydroxide ion displacement reaction at the keto group, although again w e cannot be sure that preliminary addition at the carbonyl group does not take place (p. 90) ... 

Same measures of stereocontrol had previously been observed in approaches to pyrethroid acids involving intramolecular enolate alkylation. As outlined in Figure 3, workers at Sumitomo have investigated the cyclization of a methyl ketone enolate (5). They obtained a 9 1 ratio of cis trans products upon ring closure initiated by sodium hydroxide. The methyl ketone was subsequently converted to the corresponding carboxylic acid via the haloform reaction. 

A reaction of haloforms with a base, which generates dihalocarbenes (a-elimination) and their addition to alkenes is an efficient method for the preparation of 1,1-dihalocyclopropanes, with the exception of 1,1-difluoro derivatives (Houben-Weyl, Vol.E19b, pp 1464-1466). When chlorodifluoromethane and an alkene are treated with methyllithium, potassium tcrt-butox-ide, powdered sodium hydroxide in tetraglyme or a concentrated aqueous solution of alkali metal hydroxide and a phase-transfer catalyst, the expected 1,1-difluorocyclopropanes are formed in low yields. Comparable low yields of these products result, if dichlorodi-fluoromethane and an alkene are treated with methyllithium. " The main products formed are those that result from reaction of difluorocarbene (carbenoid), and its precursor, with the base or the solvent present in the system (for examples, see refs 10-12). Therefore, the reaction of chlorodifluoromethane with base and an alkene lacks preparative value. The difficulties mentioned above are circumvented in the method using chlorodifluoromethane, oxirane (or chloromethyloxirane), with tetraalkylammonium halide as a catalyst and an alkene (Houben-eyl, Vol. 4/3, p 380 and Vol. E19b, pp 1468-1469). 

The reaction of methyl ketones with excess hydroxide and chlorine, bromine or iodine leads to the formation of a carboxylic acid together with CHX3 in a haloform reaction. The use of iodine gives CHI3 (iodoform), which is the basis of a functional group test for methyl ketones. 

Trichloromethyl)-l,2-dihydro-l,3,5-triazines 3. or the hydrochlorides, can also be converted to 1,3,5-triazines 4 in a haloform reaction. Thus, treatment of the dihydrotriazines with a solution of sodium hydroxide in ethanol under reflux for a short time affords the 1,3,5-triazines in 30 to 95% yield.5... 

Only a few departures from the basic Haloform reaction conditions (Section 7.3.5) have been developed. Both sodium bromite23 and benzyltrimethylammonium tribromide24 in aqueous sodium hydroxide are convenient alternatives to the use of bromine in the Haloform reaction (e.g., 13 to 14,23 15 to 1624). Both reagents also effect conversion of methyl carbinols to carboxylic acids. 

Undecanoic acid may be obtained from the product of part (g) by use of the haloform reaction followed by treatment with acid. Upon the addition of iodine and sodium hydroxide (to form sodium hypoiodite, NaOT), methyl... 

The replacement of an a hydrogen of an alkyl halide by halogen decreases Sn2 reactivity. Chloroform, however, is about one thousandfold more reactive in basic hydrolysis than methylene chloride . Every bromine-containing halo-form studied (Table 7) is at least 600 times as reactive toward hydroxide ions in 66.7% aqueous dioxan as methylene bromide ". Toward weakly basic nucleophiles, such as thiophenoxide ion, the predicted reactivity order is obeyed haloforms have been found to be less reactive than the corresponding methylene halides . The reaction of haloforms with sodium thiophenoxide is strongly accelerated, however, by the presence of hydroxide ions - . These observations are quite unexplainable in terms of scheme (22). 

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