Sodium reaction + haloforms

The cuprate-mediated reaction of l-phenoxy-(2i ,7)-octadiene with propylmag-nesium chloride leads to undeca-l,6-diene, which may be selectively oxidised at the terminal double bond in a Wacker oxidation. Further oxidation with sodium hypobromite (haloform reaction) and reduction with lithium aluminium hydride then lead to (5 )-decenol, which can be esterified with acetic anhydride. The alcohol and the acetate are then mixed corresponding to their ratio in the natural pheromone composition. [187]... 

Efaloform Reaetion. Ethyl alcohol reacts with sodium hypochlorite to give chloroform [67-66-3] (haloform reaction). 

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... 

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. 

Hi) Oxidation of methyl ketones by haloform reaction Aldehydes and ketones having at least one methyl group linked to the carbonyl carbon atom (methyl ketones) are oxidised by sodium hypohalite to sodium salts of O corresponding carboxylic... 

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 ... 

Exercise 17-12 Trichloromethane (chloroform) at one time was synthesized commercially by the action of sodium hypochlorite on ethanol. Formulate the reactions that may reasonably be involved. What other types of alcohols may be expected to give haloforms with halogens and base ... 

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. 

Exercise 17-14 The Haller-Bauer cleavage of 2,2-dimethyl-1-phenyl-1-propanone with sodium amide forms benzenecarboxamide and 2-methylpropane. Write a mechanism for the Haller-Bauer reaction analogous to the haloform cleavage reaction. 

Rothenberg, G. and Sasson, Y. (1996) Extending the haloform reaction to nonmethyl ketones oxidative cleavage of cydoalkanones to dicarboxylic adds using sodium hypochlorite under phase transfer catalysis conditions. Tetrahedron, 52, 13641. 

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 hypohalite oxidations are easy to carry out. The methyl ketones, pure or dissolved in dioxane, are added to cooled or warm solutions of hypohalites in water. The reverse order of addition has also been used [736], An exothermic reaction ensues, and the haloform starts forming a heavy organic layer. The excess hypohalite is destroyed by sodium bisulfite, the heavy layer is separated, the residual haloform is removed by steam distillation, and the aqueous solution of the alkaline salt of the carboxylic acid is treated with sulfuric or hydrochloric acid (equation 420). 

The rearrangement of pyrroles to 3-halo-pyridines upon treatment with haloforms (CHX3 where X = Cl, Br, I) in the presence of a strong base was first described by G.L. Ciamician. Its synthetic utility was later extended by M. Dennstedt to the sodium methoxide catalyzed reaction of pyrrole with methylene iodide to give pyridine. Soon after the initial discovery, the methodology was also extended for the indole series to prepare substituted quinolines. The reaction is known as the Ciamician-Dennstedt rearrangement, but it is also referred to as the abnormal Relmer-Tiemann reaction. 

The biomimetic total synthesis of (+)-20-epiervatamine was accomplished by J. Bosch et al. The authors used the addition of 2-acetylindole enolate to a 3-acylpyridinium salt as akey step to connect the two main fragments. The in situ formed 1,4-dihydropyridine was trapped with trichloroacetic anhydride to afford the corresponding trichloroacetyl-substituted 1,4-dihydropyridine derivative. The conversion of the trichloroacetyl group to a methyl ester was achieved by treatment with sodium methoxide. This transformation can be regarded as the second step of the haloform reaction. 

This sensitive test permits use of the readily available sodium hypochlorite in place of sodium hypoiodite for recognition of methyl carbonyl or methylcarbinol structures. It is useful also when detection of a haloform by infrared spectroscopy or gas-liquid chromatography is unsatisfactory, as may happen in certain reactions in which haloform-type cleavage occurs to a slight extent. ... 

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). 

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... 

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