Dihalocarbenes from haloforms

The reaction involves the generation of dihalocarbene from haloform and a base, e.g., KOH, which then inserts into the pyrrole ring. The subsequent ring enlargement affords the pyridine derivative, as illustrated by the reaction of chloroform and pyrrole. 

Among the oldest and more spectacular applications of PTC is the generation of carbenes (mostly dihalocarbenes) from haloforms, aqueous concentrated alkaline hydrox-... 

More useful for synthetic purposes, however, is the combination of the zinc-copper couple with methylene iodide to generate carbene-zinc iodide complex, which undergoes addition to double bonds exclusively to form cyclopropanes (7). The base-catalyzed generation of halocarbenes from haloforms (2) also provides a general route to 1,1-dihalocyclopropanes via carbene addition, as does the nonbasic generation of dihalocarbenes from phenyl(trihalomethyl)mercury compounds. Details of these reactions are given below. 

However, the reaction products were not, apparently, identified20f. Trifluoro-acetate and trichloroacetate were extracted and precipitated from the acidified solution as their silver and mercurous salts, respectively, and the carbon dioxide produced by pyrolysis of these was analyzed in the mass spectrometer. So the occurrence of side-reactions leading to other carboxylate salts cannot be completely ruled out. Just one possibility is the halodecarboxylation of the anion, followed by hydrolysis of the dihalocarbene or haloform produced, to formate, viz. 

The formation of dihalocarbene is one of the most useful phase-transfer processes developed in organic chemistry. The dihalocarbenes, once generated from haloform and base, can undergo addition or insertion reactions (3, 11, 12). If the double bond is complexed to a metal, addition by the carbene will not occur, but rather insertion into a saturated carbon-hydrogen bond will take place. 

Dihalocarbenes generated from haloforms and strong bases e.g. alkoxides) or from haloforms and alkali metal hydroxides under phase transfer conditions " or organomeicuiytrihalomethanes, add to azomethines to yield 2,2-dihaloaziridines (49 equation 30). The following carbenes have been used for such purposes dichlorocarbene, " dibromocarbene, " difluorocarbene, bromochlorocar-bene and bromofluorocarbene. The addition of dihalocarbenes to azoxybenzene or azobenzene affords dihaloaziridines e.g. 50 equation 31) among other products. 

It should be stressed that this methodology is of general use for generation of other dihalocarbenes via oc-elimination of hydrogen halide from haloforms, and many other carbenes which can be generated via base-induced a-eliminations ... 

The Ciamician—Dennstedt reaction involves the addition of intermediate dihalocarbene, generated from haloforms (CHX3, X = Cl, Br, or I) and a strong base, to a pyrrole (330) to form an unstable dihalogenocyclopropane, which rearranges to a 3-halogenopyridine such as 331. The reaction was expanded for indoles to provide 3-chloroquinolines. ... 

In solution, dihalocarbenes are often produced from the basic hydrolysis of haloforms ... 

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). 

Elimination Reactions. t-BuOK is a widely used base for both a- and /3-elimination reactions. It is the most effective base in the conventional alkoxide-haloform reaction for the generation of dihalocarbenes. This procedure still finds general use (eq 19), but since it requires anhydrous conditions, it has been replaced to a degree by use of phase-transfer catalysts. Vinylidene carbenes have also been produced from the reaction of a-halo allenes with f-BuOK. ... 

Under PTC conditions, all other dihalocarbenes can be generated from appropriate haloforms via a-elimination and trapped with alkenes with the formation of corresponding dihalocyclopropane derivatives, with one exception. 

Another wide area of application of this two-phase system is the generation of dihalocarbenes, particularly dichloro- and dibro-mocarbenes via the a-elimination of hydrogen halide from the corresponding haloforms(5). 

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